[Pickled food, fish, seafood intakes and oral squamous cell carcinoma: a case-control study].

PubMed

Huang, J F; Qiu, Y; Cai, L; Liu, F P; Chen, F; Yan, L J; Wu, J F; Bao, X D; Liu, F Q; Zheng, X Y; Lin, L S; He, B C

2017-08-06

Objective: To investigate the effects between fish, seafood and pickled food intakes on oral squamous cell carcinoma (OSCC). Methods: A case-control study was carried out in Fujian area during September 2010 to December 2016, in which 604 newly diagnosed primary OSCC cases confirmed by pathological diagnosis were collected from hospital and 1 343 control subjects were enrolled from community and healthy hospital population. Demographic data, history of smoking drinking and tea drinking, oral hygiene status and dietary behaviors (fish, seafood and pickled food intakes) were collected by in-person interviews using a standard questionnaire.Using unconditional logistic regression to estimate adjusted odds ratios ( ORs ) and corresponding 95% confidence intervals ( CIs ) to assess the effects of fish, seafood and pickled food intakes on OSCC. Analysis stratified by smoking, alcohol drinking and bad prosthesis to explore the possible difference in association between subgroups. Multiplicative interactions and additive interactions between fish and bad prosthesis, seafood and alcohol drinking, pickled food and bad prosthesis were assessed by unconditional logistic regression, relative excess risk due to interaction ( RERI ), attributable proportion due to interaction ( AP ) and synergy index (S). Results: The average age of case group and control group were separately (58.69±13.92) years old and (59.27±11.37) years old (χ(2)=4.75, P= 0.191). The people whose fish and seafood intakes ≥3 times/week had the lower risk of OSCC, the adjusted OR (95 %CI ) values were 0.63 (0.52-0.77) and 0.51 (0.41-0.64); The stratified analysis indicated that the people having bad prosthesis had the lower risk of OSCC if they eating fish ≥3 times/week, and the adjusted OR (95 %CI ) values was 0.53 (0.39-0.71); the people having bad prosthesis had the higher risk of OSCC if they eating pickled food ≥3 times/week, the adjusted OR (95 %CI ) values was 1.37 (1.02-1.88). Regularly eating seafood can decrease the risk of OSCC for non-smokers, smokers, non-drinkers, drinkers, people without bad prosthesis and had bad prosthesis, the adjusted OR (95 %CI ) values were 0.49 (0.36-0.68), 0.52 (0.37-0.73), 0.41 (0.31-0.55), 0.77 (0.51-0.96), 0.49 (0.36-0.67), 0.59 (0.42-0.83). Crossover analysis showed fish and bad prosthesis exist multiplication interaction relationship (adjusted OR= 0.66, 95 %CI: 0.44-0.97) and additional interaction relationship ( RERI =-0.81, 95 %CI: -1.43--0.19; AP= -0.76, 95 %CI: -1.35--0.17; S =0.08, 95 %CI: 0.01-0.98); pickled food and bad prosthesis exist multiplication interaction relationship (adjusted OR= 1.63, 95 %CI: 1.06-2.51) and addition interaction relationship ( RERI =0.65, 95 %CI: 0.08-1.22; AP= 0.36, 95 %CI: 0.10-0.62; S =5.19, 95 %CI: 1.32-54.49). Conclusion: Reducing the consumption of pickled food, quitting smoking and limiting alcohol consumption, and regularly eating fish and seafood can prevent the occurrence of OSCC.

Identification of New Genetic Susceptibility Loci for Breast Cancer Through Consideration of Gene-Environment Interactions

PubMed Central

Schoeps, Anja; Rudolph, Anja; Seibold, Petra; Dunning, Alison M.; Milne, Roger L.; Bojesen, Stig E.; Swerdlow, Anthony; Andrulis, Irene; Brenner, Hermann; Behrens, Sabine; Orr, Nicholas; Jones, Michael; Ashworth, Alan; Li, Jingmei; Cramp, Helen; Connley, Dan; Czene, Kamila; Darabi, Hatef; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Knight, Julia; Glendon, Gord; Mulligan, Anna M.; Dumont, Martine; Severi, Gianluca; Baglietto, Laura; Olson, Janet; Vachon, Celine; Purrington, Kristen; Moisse, Matthieu; Neven, Patrick; Wildiers, Hans; Spurdle, Amanda; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana M.; Hamann, Ute; Ko, Yon-Dschun; Dieffenbach, Aida K.; Arndt, Volker; Stegmaier, Christa; Malats, Núria; Arias Perez, JoséI.; Benítez, Javier; Flyger, Henrik; Nordestgaard, Børge G.; Truong, Théresè; Cordina-Duverger, Emilie; Menegaux, Florence; Silva, Isabel dos Santos; Fletcher, Olivia; Johnson, Nichola; Häberle, Lothar; Beckmann, Matthias W.; Ekici, Arif B.; Braaf, Linde; Atsma, Femke; van den Broek, Alexandra J.; Makalic, Enes; Schmidt, Daniel F.; Southey, Melissa C.; Cox, Angela; Simard, Jacques; Giles, Graham G.; Lambrechts, Diether; Mannermaa, Arto; Brauch, Hiltrud; Guénel, Pascal; Peto, Julian; Fasching, Peter A.; Hopper, John; Flesch-Janys, Dieter; Couch, Fergus; Chenevix-Trench, Georgia; Pharoah, Paul D. P.; Garcia-Closas, Montserrat; Schmidt, Marjanka K.; Hall, Per; Easton, Douglas F.; Chang-Claude, Jenny

2014-01-01

Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10−07), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m2 (OR = 1.26, 95% CI 1.15–1.38) but not in women with a BMI of 30 kg/m2 or higher (OR = 0.89, 95% CI 0.72–1.11, P for interaction = 3.2 × 10−05). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci. PMID:24248812

Sugar-Sweetened Beverages and Genetic Risk of Obesity

PubMed Central

Qi, Qibin; Chu, Audrey Y.; Kang, Jae H.; Jensen, Majken K.; Curhan, Gary C.; Pasquale, Louis R.; Ridker, Paul M.; Hunter, David J.; Willett, Walter C.; Rimm, Eric B.; Chasman, Daniel I.; Hu, Frank B.; Qi, Lu

2012-01-01

BACKGROUND Temporal increases in the consumption of sugar-sweetened beverages have paralleled the rise in obesity prevalence, but whether the intake of such beverages interacts with the genetic predisposition to adiposity is unknown. METHODS We analyzed the interaction between genetic predisposition and the intake of sugar-sweetened beverages in relation to body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) and obesity risk in 6934 women from the Nurses’ Health Study (NHS) and in 4423 men from the Health Professionals Follow-up Study (HPFS) and also in a replication cohort of 21,740 women from the Women’s Genome Health Study (WGHS). The genetic-predisposition score was calculated on the basis of 32 BMI-associated loci. The intake of sugar-sweetened beverages was examined prospectively in relation to BMI. RESULTS In the NHS and HPFS cohorts, the genetic association with BMI was stronger among participants with higher intake of sugar-sweetened beverages than among those with lower intake. In the combined cohorts, the increases in BMI per increment of 10 risk alleles were 1.00 for an intake of less than one serving per month, 1.12 for one to four servings per month, 1.38 for two to six servings per week, and 1.78 for one or more servings per day (P<0.001 for interaction). For the same categories of intake, the relative risks of incident obesity per increment of 10 risk alleles were 1.19 (95% confidence interval [CI], 0.90 to 1.59), 1.67 (95% CI, 1.28 to 2.16), 1.58 (95% CI, 1.01 to 2.47), and 5.06 (95% CI, 1.66 to 15.5) (P = 0.02 for interaction). In the WGHS cohort, the increases in BMI per increment of 10 risk alleles were 1.39, 1.64, 1.90, and 2.53 across the four categories of intake (P = 0.001 for interaction); the relative risks for incident obesity were 1.40 (95% CI, 1.19 to 1.64), 1.50 (95% CI, 1.16 to 1.93), 1.54 (95% CI, 1.21 to 1.94), and 3.16 (95% CI, 2.03 to 4.92), respectively (P = 0.007 for interaction). CONCLUSIONS The genetic association with adiposity appeared to be more pronounced with greater intake of sugar-sweetened beverages. PMID:22998338

Cigarette smoking and postmenopausal breast cancer risk in a prospective cohort

PubMed Central

Nyante, S J; Gierach, G L; Dallal, C M; Freedman, N D; Park, Y; Danforth, K N; Hollenbeck, A R; Brinton, L A

2014-01-01

Background: The relationship between cigarette smoking and breast cancer risk has been inconsistent, potentially due to modification by other factors or confounding. Methods: We examined smoking and breast cancer risk in a prospective cohort of 186 150 female AARP (formerly American Association of Retired Persons) members, ages 50–71 years, who joined the study in 1995–96 by responding to a questionnaire. Through 2006, 7481 breast cancers were diagnosed. Multivariable-adjusted hazard ratios (HRs) were estimated, overall and stratified by breast cancer risk factors, using Cox proportional hazards regression. Multiplicative interactions were evaluated using the likelihood ratio test. Results: Increased breast cancer risk was associated with current (HR 1.19, 95% confidence interval (CI) 1.10–1.28) and former (HR 1.07, CI 1.01–1.13) smoking. The current smoking association was stronger among women without (HR 1.24, CI 1.15–1.35) as compared to those with a family history of breast cancer (HR 0.94, CI 0.78–1.13) (P-interaction=0.03). The current smoking association was also stronger among those with later (⩾15 years: HR 1.52, CI 1.20–1.94) as compared with earlier (⩽12 years: HR 1.14, CI 1.03–1.27; 13–14 years: HR 1.18, CI 1.05–1.32) ages at menarche (P-interaction=0.03). Conclusions: Risk was elevated in smokers, particularly in those without a family history or late menarche. Research into smoking's effects on the genome and breast development may clarify these relationships. PMID:24642621

Low-lying π∗ resonances associated with cyano groups: A CAP/SAC-CI study

NASA Astrophysics Data System (ADS)

Ehara, Masahiro; Kanazawa, Yuki; Sommerfeld, Thomas

2017-01-01

The complex absorbing potential (CAP)/symmetry-adapted cluster-configuration interaction (SAC-CI) method is applied to low-lying π∗ resonance states of molecules containing one or two cyano (CN) groups. Benchmark calculations are carried out comparing the non-variational and approximate variational approach of SAC-CI and studying the selection threshold of operators. Experimental resonance positions from electron transmission spectroscopy (ETS) are reproduced provided the anticipated deviations due to vibronic effects are taken into account. Moreover, the calculated positions and widths agree well with those obtained in previous electron scattering calculations for HCN, CH3CN and their isonitriles. Based on our results, we suggest a reassignment of the experimental ETS of fumaronitrile and malononitrile. Our present results demonstrate again that the CAP/SAC-CI method reliably predicts low-lying π∗ resonances, and regarding the total numbers of molecules and resonances investigated, it is fair to say that it is presently the most extensively used high-level method in the temporary anion field.

Tobacco control environment in the United States and individual consumer characteristics in relation to continued smoking: Differential responses among menthol smokers?

PubMed Central

Lewis, Michael; Wang, Yanwen; Berg, Carla J.

2014-01-01

Objective We used a consumer panel augmented with state-specific measures of tobacco control activities to examine main effects and interactions among consumer behaviors, particularly menthol cigarette smoking, and tobacco control environment on cessation over a six-year period. Methods We used the Nielson Homescan Panel, which tracks consumer purchasing behaviors, and tobacco control information matched to panelist zip code. We focused on 1,582 households purchasing ≥20 packs from 2004–2009. Our analysis included demographics; purchasing behavior including menthol versus nonmenthol use (≥80% of cigarettes purchased being menthol), quality preferences (average price/pack), purchase recency, and nicotine intake (nicotine levels of cigarettes purchased); and tobacco control metrics (taxation, anti-tobacco advertising, smoke-free policies). Results Menthol smoking (Hazards Ratio [HR]=0.79, 95% Confidence Interval [CI] 0.64, 0.99), being African American (HR=0.67, CI 0.46, 0.98), being male (HR=0.46; CI 0.28, 0.74), higher quality premium preferences (HR=0.80, CI0.77, 0.91), lower recency (HR=1.04, CI 1.02, 1.05), and higher nicotine intake rates (HR=0.99, CI 0.99, 0.99) were related to continued smoking. No significant interactions were found. Conclusion While there were no interactions between menthol use and effects of tobacco control activities, we did find additional support for the decreased cessation rates among menthol cigarette smokers, particularly in the African American population. PMID:24780527

Case-Only Gene–Environment Interaction Between ALAD tagSNPs and Occupational Lead Exposure in Prostate Cancer

PubMed Central

Neslund-Dudas, Christine; Levin, Albert M.; Rundle, Andrew; Beebe-Dimmer, Jennifer; Bock, Cathryn H.; Nock, Nora L.; Jankowski, Michelle; Datta, Indrani; Krajenta, Richard; Dou, Q. Ping; Mitra, Bharati; Tang, Deliang; Rybicki, Benjamin A.

2014-01-01

BACKGROUND Black men have historically had higher blood lead levels than white men in the U.S. and have the highest incidence of prostate cancer in the world. Inorganic lead has been classified as a probable human carcinogen. Lead (Pb) inhibits delta-aminolevulinic acid dehydratase (ALAD), a gene recently implicated in other genitourinary cancers. The ALAD enzyme is involved in the second step of heme biosynthesis and is an endogenous inhibitor of the 26S proteasome, a master system for protein degradation and a current target of cancer therapy. METHODS Using a case-only study design, we assessed potential gene–environment (G × E) interactions between lifetime occupational Pb exposure and 11 tagSNPs within ALAD in black (N = 260) and white (N = 343) prostate cancer cases. RESULTS Two ALAD tagSNPs in high linkage disequilibrium showed significant interaction with high Pb exposure among black cases (rs818684 interaction odds ratio or IOR = 2.73, 95% CI 1.43–5.22, P = 0.002; rs818689 IOR = 2.20, 95% CI 1.15–4.21, P = 0.017) and an additional tagSNP, rs2761016, showed G × E interaction with low Pb exposure (IOR = 2.08, 95% CI 1.13– 3.84, P = 0.019). Further, the variant allele of rs818684 was associated with a higher Gleason grade in those with high Pb exposure among both blacks (OR 3.96, 95% CI 1.01–15.46, P = 0.048) and whites (OR 2.95, 95% CI 1.18–7.39, P = 0.020). CONCLUSIONS Genetic variation in ALAD may modify associations between Pb and prostate cancer. Additional studies of ALAD, Pb, and prostate cancer are warranted and should include black men. PMID:24500903

Correlation of interactions between NOS3 polymorphisms and oxygen therapy with retinopathy of prematurity susceptibility

PubMed Central

Yu, Chunhong; Yi, Jinglin; Yin, Xiaolong; Deng, Yan; Liao, Yujun; Li, Xiaobing

2015-01-01

Aim: This study was aimed to detect the correlation of nitric oxide synthase 3 (NOS3) gene polymorphisms (T-786C and G894T) and retinopathy of prematurity (ROP) susceptibility. Interaction between NOS3 gene polymorphisms and the duration of oxygen therapy was also explored in ROP babies. Methods: Genotypes of NOS3 gene polymorphisms were genotyped by MassArray method. Hardy-Weinberg equilibrium (HWE) was used to calculate the representativeness of the cases and controls. Crossover analysis was utilized to explore the gene environment interactions. Relative risk of ROP was presented by odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs). Results: Among the subject features, oxygen therapy had obvious difference between case and control groups (P<0.05). There existed significant association between-786C allele and ROP susceptibility (P=0.049, OR=0.669, 95% CI=0.447-0.999). Genotypes of T-786C polymorphism and genotypes and alleles of G894T polymorphism did not related to the susceptibility of ROP. Interactions were existed between NOS3 gene polymorphisms and oxygen therapy duration. When the duration of oxygen therapy was less than 17 days, both -786CC genotype and 894GT genotype were correlated with ROP susceptibility (P=0.020, OR=0.115, 95% CI=0.014-0.960; P=0.011, OR=0.294, 95% CI=0.100-0.784). Conclusion: -786C allele might have a protective effect for ROP. Interactions of -786CC and 894GT genotype with oxygen therapy duration (less than 17 days) were both protection factors of ROP. PMID:26823875

On the extension of the MCSCF/CI method

NASA Technical Reports Server (NTRS)

Bauschlicher, C., Jr.; Nelin, C. J.; Komornicki, A.

1984-01-01

Research conducted during this period was focused on two main areas: (1) bonding in transition metal oxides; and (2) adsorption of CO on Al and Ni. In both of these theoretical studies a major interest was to obtain a better understanding of the nature of the bonding in transition metal containing systems. The studies used self consistent field (SCF), multi-configuration self cosistent field (MCSCF) and configuration interaction (CI) methods in the treatment of the transition metal oxides and only the SCF method in the adsorption studies. The reports of three principle investigators who contributed to this work during the tenure of the project are presented along with associated published papers.

Xenobiotic metabolizing gene variants, pesticide use, and risk of prostate cancer

PubMed Central

Koutros, Stella; Andreotti, Gabriella; Berndt, Sonja I.; Barry, Kathryn Hughes; Lubin, Jay H.; Hoppin, Jane A.; Kamel, Freya; Sandler, Dale P.; Burdette, Laurie A.; Yuenger, Jeffrey; Yeager, Meredith; Alavanja, Michael C.R.; Beane Freeman, Laura E.

2011-01-01

Background To explore associations with prostate cancer and farming, it is important to investigate the relationship between pesticide use and single nucleotide polymorphisms (SNPs) in xenobiotic metabolic enzyme (XME) genes. Objectives We evaluated pesticide-SNP interactions between 45 pesticides and 1,913 XME SNPs with respect to prostate cancer among 776 cases and 1,444 controls in the Agricultural Health Study. Methods We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. Results A positive monotonic interaction was observed between petroleum oil/petroleum distillate use and rs1883633 in the oxidative stress gene glutamate-cysteine ligase (GCLC) (p-interaction=1.0×10−4); men carrying at least one variant allele (minor allele) experienced an increased prostate cancer risk (OR=3.7, 95% CI: 1.9–7.3). Among men carrying the variant allele for thioredoxin reductase 2 (TXNRD2) rs4485648, microsomal epoxide hyrdolase 1 (EPHX1) rs17309872, or myeloperoxidase (MPO) rs11079344, increased prostate cancer risk was observed with high compared to no petroleum oil/petroleum distillate (OR=1.9, 95% CI: 1.1–3.2, p-interaction=0.01), (OR=2.1, 95% CI: 1.1–4.0, p-interaction=0.01), or terbufos (OR=3.0, 95% CI: 1.5–6.0 p-interaction=2.0×10−3) use, respectively. No interactions were deemed noteworthy at the false discovery rate = 0.20 level; the number of observed interactions in XMEs was comparable to the number expected by chance alone. Conclusions We observed several pesticide-SNP interactions in oxidative stress and phase I/phase II enzyme genes and risk of prostate cancer. Additional work is needed to explain the joint contribution of genetic variation in XMEs, pesticide use, and prostate cancer risk. PMID:21716162

Negative exchange interactions in coupled few-electron quantum dots

NASA Astrophysics Data System (ADS)

Deng, Kuangyin; Calderon-Vargas, F. A.; Mayhall, Nicholas J.; Barnes, Edwin

2018-06-01

It has been experimentally shown that negative exchange interactions can arise in a linear three-dot system when a two-electron double quantum dot is exchange coupled to a larger quantum dot containing on the order of one hundred electrons. The origin of this negative exchange can be traced to the larger quantum dot exhibiting a spin tripletlike rather than singletlike ground state. Here we show using a microscopic model based on the configuration interaction (CI) method that both tripletlike and singletlike ground states are realized depending on the number of electrons. In the case of only four electrons, a full CI calculation reveals that tripletlike ground states occur for sufficiently large dots. These results hold for symmetric and asymmetric quantum dots in both Si and GaAs, showing that negative exchange interactions are robust in few-electron double quantum dots and do not require large numbers of electrons.

Relationship of polymorphisms and haplotype in interleukin-16 and adiponectin gene with late-onset Alzheimer’s disease risk

PubMed Central

Yin, Honglei; Zhang, Yuzhen; Hua, Linlin; Li, Jinfeng; Zeng, Zhilei; Yang, Xiaopeng; Gong, Bin; Geng, Shuang; Liu, Yajun; Zhang, Hui; Liu, Yanqiu; Zhao, Jing; Wang, Yunliang

2017-01-01

Aims To investigate the impact of Interleukin-16 (IL- 16) and Adiponectin (ANP) gene single nucleotide polymorphisms (SNPs), gene- gene interactions and haplotype on late-onset Alzheimer’s disease (LOAD) risk. Methods Hardy-Weinberg equilibrium (HWE), haplotype and pairwise linkage disequilibrium (LD) analysis were investigated by using SNPstats (available online at http://bioinfo.iconcologia.net/SNPstats). Generalized multifactor dimensionality reduction (GMDR) was used to examine interaction among 4 SNPs, odds ratio (OR) and 95% confident interval (95%CI) were calculated by logistic regression model. Results LOAD risk was significantly higher in carriers of rs266729- G allele than those with CC genotype (CG+ GG versus CC), OR (95%CI) =1.61 (1.26-1.96), and higher in carriers of rs1501299- T allele, OR (95%CI) = 1.62 (1.32-2.12), lower in carriers of rs4072111- T allele, adjusted OR (95%CI) =0.65 (0.44-0.93). We also found a significant gene- gene interaction between rs266729 and rs4072111. Participants with CG or GG of rs266729 and CC of rs4072111 genotype have the highest LOAD risk, OR (95%CI) = 2.62 (1.64 -3.58). Haplotype containing the rs266729- G and rs1501299- T alleles were associated with increased LOAD risk, OR (95%CI)= 1.83 (1.32- 2.43), and haplotype containing the rs1131445- C and rs4072111- T alleles were associated with decreased LOAD risk, OR (95%CI)= 0.53 (0.18- 0.95). Conclusions We concluded that rs266729 and rs1501299 minor alleles were associated with increased LOAD risk, but rs4072111 minor allele was associated with decreased LOAD risk. We also found that interaction involving rs266729 and rs4072111, and haplotype combinations were associated with LOAD risk. PMID:29108295

Gene-gene interactions of CYP2A6 and MAOA polymorphisms on smoking behavior in Chinese male population.

PubMed

Tang, Xun; Guo, Song; Sun, Hongqiang; Song, Xuemei; Jiang, Zuonin; Sheng, Lixiang; Zhou, Dongfeng; Hu, Yonghua; Chen, Dafang

2009-05-01

Nicotine is the major psychoactive ingredient in tobacco, and is responsible for dependence through the nicotine-stimulated reward pathway mediated by the central dopaminergic system. Consequently, genetic polymorphisms in both nicotine metabolism and dopamine catabolism genes may influence smoking behavior, and interact with each other resulting in risk modulation. In this study, we investigated the association and multilocus gene-gene interactions of cytochrome P450 2A6 (CYP2A6), dopamine beta-hydroxylase (DBH), catechol O-methyl transferase (COMT), and monoamine oxidase A (MAOA) polymorphisms with smoking behavior in a community-based Chinese male population. The polymorphisms were genotyped in 203 current smokers, 66 former smokers, and 102 never smokers. Multivariate logistic regression models and the multifactor dimensionality reduction method were used to analyze the association and multilocus gene-gene interactions. Statistically significant trends were shown for increased risk of smoking initiation in participants with CYP2A6*1B/CYP2A6*1B genotypes compared with those with CYP2A6*1A/CYP2A6*1A genotypes [odds ratio (OR)=3.5, 95% confidence interval (CI)= 1.5-8.1], and participants with CYP2A6*1/CYP2A6*1 genotypes were at higher risk of smoking initiation (OR=2.4, 95% CI=1.2-4.5) and smoking persistence (OR=4.0, 95% CI=1.5-10.3) than those who have CYP2A6*4C genotypes. Moreover, the best model involved a gene-gene interaction between MAOA and CYP2A6 was characterized by the multifactor dimensionality reduction method (64.11% accuracy, P<0.001), and indicated that carriers of the combined 1460 T/O genotype for MAOA EcoRV and CYP2A6*1/CYP2A6*1 genotypes were at higher risk of smoking (OR=15.4, 95% CI=4.5-52.5). These findings suggested a substantial influence of CYP2A6 polymorphism as well as the interaction with MAOA resulting in risk modulation on smoking behavior in Chinese male population.

Gene-environment interactions associated with CYP1A1 MspI and GST polymorphisms and the risk of upper aerodigestive tract cancers in an Indian population.

PubMed

Sam, Soya Sisy; Thomas, Vinod; Reddy, K S; Surianarayanan, Gopalakrishnan; Chandrasekaran, Adithan

2010-06-01

Genetic risk to tobacco related cancers are associated with polymorphisms in CYP1A1 and GST, which are involved in the metabolic activation and detoxification of carcinogens. The genetic variations in these drug-metabolizing enzymes may alter the susceptibility to UADT cancers triggered by environmental exposures. The hospital-based case-control study evaluated the impact of combined CYP1A1 MspI and GST (M1 & T1) polymorphisms among the individuals exposed to environmental risk factors as modulators in the risk of UADT cancers in Tamilians, a population of south India. The unrelated histopathologically confirmed 408 cases and 220 population-based controls matched by age and gender were genotyped for CYP1A1 MspI, GSTM1 and GSTT1 polymorphisms using PCR based methods. To investigate the potential gene-environment interactions, analyses were carried out stratifying by smoking and tobacco chewing status using SPSS software. The combination of genes and environment interactions by stratified analyses revealed significant interactions among the habitual tobacco smokers (CYP1A1 MspI & GSTM1 null: OR 14.06; 95% CI 3.90-50.68, CYP1A1 MspI & GSTT1 null: OR 33.28; 95% CI 4.24-261.19) and tobacco chewers (CYP1A1 MspI & GSTM1 null: OR 20.51; 95% CI 6.77-62.13, CYP1A1 MspI & GSTT1 null: OR 79.35; 95% CI 10.40-605.55) on the multiplicative scale. Our findings have indicated that the individuals polymorphic for CYP1A1 MspI either with GSTM1 null or with GSTT1 null genotypes revealed an increased risk for UADT cancers than that ascribed to a single susceptible gene among the tobacco users in the population [single gene risk among smokers and chewers, respectively, for CYP1A1 MspI (OR 6.43; 95% CI 3.69-11.21); (OR 10.24; 95% CI 5.95-17.60), GSTM1*0 (OR 3.77; 95% CI 1.94-7.37); (OR 7.97 95% CI 4.10-15.76) and GSTT1*0 (OR 6.95 95% CI 2.88-16.77); (OR 25.83 95% CI 7.78-85.76).

CI-KNOW: Cyberinfrastructure Knowledge Networks on the Web. A Social Network Enabled Recommender System for Locating Resources in Cyberinfrastructures

NASA Astrophysics Data System (ADS)

Green, H. D.; Contractor, N. S.; Yao, Y.

2006-12-01

A knowledge network is a multi-dimensional network created from the interactions and interconnections among the scientists, documents, data, analytic tools, and interactive collaboration spaces (like forums and wikis) associated with a collaborative environment. CI-KNOW is a suite of software tools that leverages automated data collection, social network theories, analysis techniques and algorithms to infer an individual's interests and expertise based on their interactions and activities within a knowledge network. The CI-KNOW recommender system mines the knowledge network associated with a scientific community's use of cyberinfrastructure tools and uses relational metadata to record connections among entities in the knowledge network. Recent developments in social network theories and methods provide the backbone for a modular system that creates recommendations from relational metadata. A network navigation portlet allows users to locate colleagues, documents, data or analytic tools in the knowledge network and to explore their networks through a visual, step-wise process. An internal auditing portlet offers administrators diagnostics to assess the growth and health of the entire knowledge network. The first instantiation of the prototype CI-KNOW system is part of the Environmental Cyberinfrastructure Demonstration project at the National Center for Supercomputing Applications, which supports the activities of hydrologic and environmental science communities (CLEANER and CUAHSI) under the umbrella of the WATERS network environmental observatory planning activities (http://cleaner.ncsa.uiuc.edu). This poster summarizes the key aspects of the CI-KNOW system, highlighting the key inputs, calculation mechanisms, and output modalities.

General transfer matrix formalism to calculate DNA–protein–drug binding in gene regulation: application to OR operator of phage λ

PubMed Central

Teif, Vladimir B.

2007-01-01

The transfer matrix methodology is proposed as a systematic tool for the statistical–mechanical description of DNA–protein–drug binding involved in gene regulation. We show that a genetic system of several cis-regulatory modules is calculable using this method, considering explicitly the site-overlapping, competitive, cooperative binding of regulatory proteins, their multilayer assembly and DNA looping. In the methodological section, the matrix models are solved for the basic types of short- and long-range interactions between DNA-bound proteins, drugs and nucleosomes. We apply the matrix method to gene regulation at the OR operator of phage λ. The transfer matrix formalism allowed the description of the λ-switch at a single-nucleotide resolution, taking into account the effects of a range of inter-protein distances. Our calculations confirm previously established roles of the contact CI–Cro–RNAP interactions. Concerning long-range interactions, we show that while the DNA loop between the OR and OL operators is important at the lysogenic CI concentrations, the interference between the adjacent promoters PR and PRM becomes more important at small CI concentrations. A large change in the expression pattern may arise in this regime due to anticooperative interactions between DNA-bound RNA polymerases. The applicability of the matrix method to more complex systems is discussed. PMID:17526526

Serious Bleeding Events due to Warfarin and Antibiotic Co-prescription In a Cohort of Veterans

PubMed Central

Lane, Michael A.; Zeringue, Angelique; McDonald, Jay R.

2014-01-01

Background Antibiotics may interact with warfarin, increasing the risk for significant bleeding events. Methods Retrospective cohort study of veterans prescribed warfarin for ≥ 30 days without interruption through the VA between October 1, 2002 and September 1, 2008. Antibiotics considered to be high-risk for interaction with warfarin include: trimethoprim/sulfamethoxazole (TMP/SMX), ciprofloxacin, levofloxacin, metronidazole, fluiconazole, azithromycin, and clarithromycin. Low-risk antibiotics include: clindamycin and cephalexin. Risk of bleeding event within 30 days of antibiotic exposure was measured using Cox proportional hazards regression, adjusted for demographic characteristics, comorbid conditions and receipt of other medications interacting with warfarin. Results A total of 22,272 patients met inclusion criteria with 14,078 and 8,194 receiving high- and low-risk antibiotics, respectively. There were 93 and 36 bleeding events in the high- and low-risk groups, respectively. Receipt of a high-risk antibiotic (HR 1.48, 95% CI 1.00-2.19) and azithromycin (HR 1.93, 95% CI 1.13-3.30) were associated with increased risk of bleeding as a primary diagnosis. TMP/SMX (HR 2.09, 95% CI 1.45-3.02), ciprofloxacin (HR 1.87, 95% CI 1.42-2.50), levofloxacin (HR 1.77, 95% CI 1.22-2.50), azithromycin (HR 1.64, 95% CI 1.16-2.33), and clarithromycin (HR 2.40, 95% CI 1.16-4.94) were associated with serious bleeding as a primary or secondary diagnosis. INR alterations were common; 9.7% of patients prescribed fluconazole had INR value >6. Patients who had INR performed 3-14 days of co-prescription were at a decrease risk of serious bleeding (HR 0.61, 95% CI 0.42-0.88). Conclusions Warfarin users who are prescribed high-risk antibiotics are at higher risk for serious bleeding events. Early INR evaluation may mitigate this risk. PMID:24657899

HoPaCI-DB: host-Pseudomonas and Coxiella interaction database

PubMed Central

Bleves, Sophie; Dunger, Irmtraud; Walter, Mathias C.; Frangoulidis, Dimitrios; Kastenmüller, Gabi; Voulhoux, Romé; Ruepp, Andreas

2014-01-01

Bacterial infectious diseases are the result of multifactorial processes affected by the interplay between virulence factors and host targets. The host-Pseudomonas and Coxiella interaction database (HoPaCI-DB) is a publicly available manually curated integrative database (http://mips.helmholtz-muenchen.de/HoPaCI/) of host–pathogen interaction data from Pseudomonas aeruginosa and Coxiella burnetii. The resource provides structured information on 3585 experimentally validated interactions between molecules, bioprocesses and cellular structures extracted from the scientific literature. Systematic annotation and interactive graphical representation of disease networks make HoPaCI-DB a versatile knowledge base for biologists and network biology approaches. PMID:24137008

Occupational exposure to textile dust increases the risk of rheumatoid arthritis: results from a Malaysian population-based case–control study

PubMed Central

Too, Chun Lai; Muhamad, Nor Asiah; Ilar, Anna; Padyukov, Leonid; Alfredsson, Lars; Klareskog, Lars; Murad, Shahnaz; Bengtsson, Camilla

2016-01-01

Objectives Lung exposures including cigarette smoking and silica exposure are associated with the risk of rheumatoid arthritis (RA). We investigated the association between textile dust exposure and the risk of RA in the Malaysian population, with a focus on women who rarely smoke. Methods Data from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis population-based case–control study involving 910 female early RA cases and 910 female age-matched controls were analysed. Self-reported information on ever/never occupationally exposed to textile dust was used to estimate the risk of developing anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA. Interaction between textile dust and the human leucocyte antigen DR β-1 (HLA-DRB1) shared epitope (SE) was evaluated by calculating the attributable proportion due to interaction (AP), with 95% CI. Results Occupational exposure to textile dust was significantly associated with an increased risk of developing RA in the Malaysian female population (OR 2.8, 95% CI 1.6 to 5.2). The association between occupational exposure to textile dust and risk of RA was uniformly observed for the ACPA-positive RA (OR 2.5, 95% CI 1.3 to 4.8) and ACPA-negative RA (OR 3.5, 95% CI 1.7 to 7.0) subsets, respectively. We observed a significant interaction between exposure to occupational textile dust and HLA-DRB1 SE alleles regarding the risk of ACPA-positive RA (OR for double exposed: 39.1, 95% CI 5.1 to 297.5; AP: 0.8, 95% CI 0.5 to 1.2). Conclusions This is the first study demonstrating that textile dust exposure is associated with an increased risk for RA. In addition, a gene–environment interaction between HLA-DRB1 SE and textile dust exposure provides a high risk for ACPA-positive RA. PMID:26681695

Dopamine Transporter Genetic Variants and Pesticides in Parkinson’s Disease

PubMed Central

Ritz, Beate R.; Manthripragada, Angelika D.; Costello, Sadie; Lincoln, Sarah J.; Farrer, Matthew J.; Cockburn, Myles; Bronstein, Jeff

2009-01-01

Background Research suggests that independent and joint effects of genetic variability in the dopamine transporter (DAT) locus and pesticides may influence Parkinson’s disease (PD) risk. Materials Methods: In 324 incident PD patients and 334 population controls from our rural California case–control study, we genotyped rs2652510, rs2550956 (for the DAT 5′ clades), and the 3′ variable number of tandem repeats (VNTR). Using geographic information system methods, we determined residential exposure to agricultural maneb and paraquat applications. We also collected occupational pesticide use data. Employing logistic regression, we calculated odds ratios (ORs) for clade diplotypes, VNTR genotype, and number of susceptibility (A clade and 9-repeat) alleles and assessed susceptibility allele–pesticide interactions. Results PD risk was increased separately in DAT A clade diplotype carriers [AA vs. BB: OR = 1.66; 95% confidence interval (CI), 1.08–2.57] and 3′ VNTR 9/9 carriers (9/9 vs. 10/10: OR = 1.8; 95% CI, 0.96–3.57), and our data suggest a gene dosing effect. Importantly, high exposure to paraquat and maneb in carriers of one susceptibility allele increased PD risk 3-fold (OR = 2.99; 95% CI, 0.88–10.2), and in carriers of two or more alleles more than 4-fold (OR = 4.53; 95% CI, 1.70–12.1). We obtained similar results for occupational pesticide measures. Discussion Using two independent pesticide measures, we a) replicated previously reported gene–environment interactions between DAT genetic variants and occupational pesticide exposure in men and b) overcame previous limitations of nonspecific pesticide measures and potential recall bias by employing state records and computer models to estimate residential pesticide exposure. Conclusion Our results suggest that DAT genetic variability and pesticide exposure interact to increase PD risk. PMID:19590691

Effect of Interaction Between Noise and A1166C Site of AT1R Gene Polymorphism on Essential Hypertension in an Iron and Steel Enterprise Workers

PubMed Central

Tong, Junwang; Wang, Ying; Yuan, Juxiang; Yang, Jingbo; Wang, Zhaoyang; Zheng, Yao; Chai, Feng; Li, Xiangwen

2017-01-01

Objective: This study aimed to analyze the interaction of Angiotensin II type 1 receptor (AT1R) gene polymorphism and occupational noise on the occurrence of essential hypertension (EH) in steel and iron enterprise men workers. Methods: A case control study of 935 iron and steel enterprise men workers was conducted, which included 312 cases of hypertension and 623 cases without hypertension. The noise at the workplace was assessed. Polymorphism of AT1R of the workers was examined using polymerase chain reaction - restriction fragment length polymorphism. Results: Polymorphism of AT1R (AC+CC vs. AA, odds ratio [OR] = 1.760, 95% confidence interval [CI]: 1.061∼2.920) and noise (greater than or equal to 85 dB(A),OR = 1.641, 95%CI: 1.225∼2.198) were independent determinants of EH using multivariate Logistic regression. Compared with AA carriers without noise, AC+CC interacted with noise (OR = 2.519, 95%CI: 1.254∼5.062) based on the multiplied model. Conclusions: AC+CC genotype of AT1R and noise were the risky factors of EH. These factors also interacted with each other. PMID:28157766

Systematic Expansion of Active Spaces beyond the CASSCF Limit: A GASSCF/SplitGAS Benchmark Study.

PubMed

Vogiatzis, Konstantinos D; Li Manni, Giovanni; Stoneburner, Samuel J; Ma, Dongxia; Gagliardi, Laura

2015-07-14

The applicability and accuracy of the generalized active space self-consistent field, (GASSCF), and (SplitGAS) methods are presented. The GASSCF method enables the exploration of larger active spaces than with the conventional complete active space SCF, (CASSCF), by fragmentation of a large space into subspaces and by controlling the interspace excitations. In the SplitGAS method, the GAS configuration interaction, CI, expansion is further partitioned in two parts: the principal, which includes the most important configuration state functions, and an extended, containing less relevant but not negligible ones. An effective Hamiltonian is then generated, with the extended part acting as a perturbation to the principal space. Excitation energies of ozone, furan, pyrrole, nickel dioxide, and copper tetrachloride dianion are reported. Various partitioning schemes of the GASSCF and SplitGAS CI expansions are considered and compared with the complete active space followed by second-order perturbation theory, (CASPT2), and multireference CI method, (MRCI), or available experimental data. General guidelines for the optimum applicability of these methods are discussed together with their current limitations.

ABCB1 genetic polymorphism and risk of upper aerodigestive tract cancers among smokers, tobacco chewers and alcoholics in an Indian population.

PubMed

Sam, Soya Sisy; Thomas, Vinod; Sivagnanam, Kumaran; Reddy, Kanipakapatanam Sathyanarayana; Surianarayanan, Gopalakrishnan; Chandrasekaran, Adithan

2007-10-01

Upper aerodigestive tract (UADT) cancers are associated with the tobacco use and alcohol consumption. Certain toxins and carcinogens causing UADT cancers are found to be substrates of polymorphic ABCB1 gene encoded P-glycoprotein efflux pump. This study investigates the association between ABCB1 gene polymorphism at exon 26 (3435C>T) and risk to UADT cancers in Tamilians, a population of south India. The study included 219 unrelated histopathologically confirmed cases and 210 population-based controls. Genomic DNA was extracted from peripheral leukocytes and genotyped for ABCB1 3435C>T polymorphism by PCR-restriction fragment length polymorphism method. The multivariate logistic regression analyses demonstrated that the homozygous ABCB1 TT genotype was significantly associated with an overall increased risk for developing UADT cancers [odds ratio (OR): 2.53; 95% confidence interval (CI): 1.28-5.02]. Further, the determination of gene-environment interaction by stratified analyses have revealed a significant interaction between the smoking and homozygous TT genotype [(OR: 7.52; CI: 1.50-37.70) and (OR: 16.89; CI: 3.87-73.79) for 11-20 and >20 pack-years, respectively]. The strongest interaction was observed among the regular tobacco chewers (OR: 45.29; CI: 8.94-130.56) homozygous for TT genotype. No suggestion, however, of an interaction between the genotypes and the alcohol consumption on the multiplicative scale was made. The ABCB1 gene polymorphism at exon 26 (3435C>T) may be one of the risk factors for susceptibility to UADT cancers. Furthermore, the significant interaction among habitual smokers and tobacco chewers, homozygous for TT genotype modulates the risk to UADT cancers in the Tamilian population of south India.

Effects of Primary Care Team Social Networks on Quality of Care and Costs for Patients With Cardiovascular Disease

PubMed Central

Mundt, Marlon P.; Gilchrist, Valerie J.; Fleming, Michael F.; Zakletskaia, Larissa I.; Tuan, Wen-Jan; Beasley, John W.

2015-01-01

PURPOSE Cardiovascular disease is the leading cause of mortality and morbidity in the United States. Primary care teams can be best suited to improve quality of care and lower costs for patients with cardiovascular disease. This study evaluates the associations between primary care team communication, interaction, and coordination (ie, social networks); quality of care; and costs for patients with cardiovascular disease. METHODS Using a sociometric survey, 155 health professionals from 31 teams at 6 primary care clinics identified with whom they interact daily about patient care. Social network analysis calculated variables of density and centralization representing team interaction structures. Three-level hierarchical modeling evaluated the link between team network density, centralization, and number of patients with a diagnosis of cardiovascular disease for controlled blood pressure and cholesterol, counts of urgent care visits, emergency department visits, hospital days, and medical care costs in the previous 12 months. RESULTS Teams with dense interactions among all team members were associated with fewer hospital days (rate ratio [RR] = 0.62; 95% CI, 0.50–0.77) and lower medical care costs (−$556; 95% CI, −$781 to −$331) for patients with cardiovascular disease. Conversely, teams with interactions revolving around a few central individuals were associated with increased hospital days (RR = 1.45; 95% CI, 1.09–1.94) and greater costs ($506; 95% CI, $202–$810). Team-shared vision about goals and expectations mediated the relationship between social network structures and patient quality of care outcomes. CONCLUSIONS Primary care teams that are more interconnected and less centralized and that have a shared team vision are better positioned to deliver high-quality cardiovascular disease care at a lower cost. PMID:25755035

Effects of external electrical and magnetic fields on pacemakers and defibrillators: from engineering principles to clinical practice.

PubMed

Beinart, Roy; Nazarian, Saman

2013-12-24

The overall risk of clinically significant adverse events related to EMI in recipients of CIEDs is very low. Therefore, no special precautions are needed when household appliances are used. Environmental and industrial sources of EMI are relatively safe when the exposure time is limited and distance from the CIEDs is maximized. The risk of EMI-induced events is highest within the hospital environment. Physician awareness of the possible interactions and methods to minimize them is warranted.

Interactions of central obesity with rs3918242 on risk of non-alcoholic fat liver disease: a preliminary case-control study.

PubMed

Wu, Pengbo; Hua, Yonglong; Tan, Shiyun; Li, Ming; Shu, Yongxiang; Fang, Guo

2015-01-01

NAFLD is a complex disease characterized by inflammation and insulin resistance which is determined by an interaction of genetics and environmental factors. MMP gene has been implicated in relation to inflammation and insulin resistance. The preliminary case-control study aimed to investigate the association between Matrix metalloproteinase (MMP)-9-1562C/T (rs3918242), MMP-2-1306C/T (rs243865) and risk of NAFLD and to further evaluate the interactions of central obesity with rs3918242 and rs243865. Two variants, rs3918242 and rs243865, were genotyped by polymerase chain reaction -restriction fragment length polymorphism. Gene-environment interactions on risk of NAFLD was preliminarily investigated by generalized multifactor dimensionality reduction (GMDR) and further confirmed by unconditional logistic regression methods. After adjusting for covariates, increased risk of NAFLD were observed in subjects carrying TT/CT genotypes in rs3918242 ((Adjust)OR=1.64, 95% CI: 1.24, 2.11, P=0.006). However, decreased risk of non-alcoholic fat liver disease was found when MMP-2 rs243865 (TT/CT) genotype carriers compared with CC carrier ((Adjust)OR=0.65, 95% CI: 0.47, 0.72, P=0.000).Interactions of central obesity with rs3918242 was preliminarily found by GMDR, with a maximum prediction accuracy (67.61%) and a maximum Cross-validation Consistency (10/10).The unconditional logistic regression method indicated central obesity-positive subject with genotype TT/CT had 4.54 times risk of NAFLD compared to central obesity-negative subjects with genotype CC (OR(add)(a)=4.54, 95% CI: 2.81, 7.21, P(add)(a)=0.000), which further confirmed the interactions. The results indicate that both rs3918242 and rs243865 is associated with risk of NAFLD. Furthermore, rs3918242 and central obesity have synergistic effects on risk of NAFLD.

Genetic Variation in Selenoprotein Genes, Lifestyle, and Risk of Colon and Rectal Cancer

PubMed Central

Slattery, Martha L.; Lundgreen, Abbie; Welbourn, Bill; Corcoran, Christopher; Wolff, Roger K.

2012-01-01

Background Associations between selenium and cancer have directed attention to role of selenoproteins in the carcinogenic process. Methods We used data from two population-based case-control studies of colon (n = 1555 cases, 1956 controls) and rectal (n = 754 cases, 959 controls) cancer. We evaluated the association between genetic variation in TXNRD1, TXNRD2, TXNRD3, C11orf31 (SelH), SelW, SelN1, SelS, SepX, and SeP15 with colorectal cancer risk. Results After adjustment for multiple comparisons, several associations were observed. Two SNPs in TXNRD3 were associated with rectal cancer (rs11718498 dominant OR 1.42 95% CI 1.16,1.74 pACT 0.0036 and rs9637365 recessive 0.70 95% CI 0.55,0.90 pACT 0.0208). Four SNPs in SepN1 were associated with rectal cancer (rs11247735 recessive OR 1.30 95% CI 1.04,1.63 pACT 0.0410; rs2072749 GGvsAA OR 0.53 95% CI 0.36,0.80 pACT 0.0159; rs4659382 recessive OR 0.58 95% CI 0.39,0.86 pACT 0.0247; rs718391 dominant OR 0.76 95% CI 0.62,0.94 pACT 0.0300). Interaction between these genes and exposures that could influence these genes showed numerous significant associations after adjustment for multiple comparisons. Two SNPs in TXNRD1 and four SNPs in TXNRD2 interacted with aspirin/NSAID to influence colon cancer; one SNP in TXNRD1, two SNPs in TXNRD2, and one SNP in TXNRD3 interacted with aspirin/NSAIDs to influence rectal cancer. Five SNPs in TXNRD2 and one in SelS, SeP15, and SelW1 interacted with estrogen to modify colon cancer risk; one SNP in SelW1 interacted with estrogen to alter rectal cancer risk. Several SNPs in this candidate pathway influenced survival after diagnosis with colon cancer (SeP15 and SepX1 increased HRR) and rectal cancer (SepX1 increased HRR). Conclusions Findings support an association between selenoprotein genes and colon and rectal cancer development and survival after diagnosis. Given the interactions observed, it is likely that the impact of cancer susceptibility from genotype is modified by lifestyle. PMID:22615972

[Expression of Dengue virus type 2 nonstructural protein 3 and isolation of host proteins interacting with it].

PubMed

Weng, Daihui; Lei, Yingfeng; Dong, Yangchao; Han, Peijun; Ye, Chuantao; Yang, Jing; Wang, Yuan; Yin, Wen

2015-12-01

To construct the plasmid expressing the fusion protein of Dengue virus type 2 (DENV2) nonstructural protein 3 (NS3) with affinity tag, and isolate the cellular proteins interacting with NS3 protein using tandem affinity purification (TAP) assay. Primers for amplifying NS3 gene were designed according to the sequence of DENV2 genome and chemically synthesized. The NS3 fragments, after amplified by PCR with DENV2 cDNA as template, were digested and cloned into the mammalian eukaryotic expression vector pCI-SF with the tandem affinity tag (FLAG-StrepII). The recombinant pCI-NS3-SF was transiently transformed by Lipofectamine(TM) 2000 into HEK293T cells, and the expression of the fusion protein was confirmed by Western blotting. Cellular proteins that interacted with NS3 were isolated and purified by TAP assay. The eukaryotic expression vector expressing NS3 protein was successfully constructed. The host proteins interacting with NS3 protein were isolated by TAP system. TAP is an efficient method to isolate the cellular proteins interacting with DENV2 NS3.

Neighborhood Ethnic Diversity and Behavioral and Emotional Problems in 3 Year Olds: Results from the Generation R Study

PubMed Central

Flink, Ilse J. E.; Prins, Rick G.; Mackenbach, Johan J. P.; Jaddoe, Vincent W.; Hofman, Albert; Verhulst, Frank C.; Tiemeier, Henning; Raat, Hein

2013-01-01

Background Studies suggest that neighborhood ethnic diversity may be important when it comes to understanding ethnic inequalities in mental health. The primary aim of this study was to investigate whether neighborhood ethnic diversity moderated the association between the ethnic minority status and child behavioral and emotional problems. Methods We included 3076 preschoolers participating in the Generation R Study, a birth cohort study in Rotterdam, the Netherlands. At child age 3-years, parents completed the Child Behavior Checklist (CBCL/1,5-5). Individual-level data, assessed with questionnaires, was combined with neighborhood-level data. Multi-level logistic regression models predicted the Odds Ratios for the CBCL total problems score as a function of maternal ethnic background and neighborhood ethnic diversity, computed with the Racial Diversity Index and categorized into tertiles. Interaction on the additive scale was assessed using Relative Access Risk due to Interaction. Results Being from an ethnic minority was associated with child behavioral and emotional problems in unadjusted (OR 2.76, 95% CI 1.88–4.04) and adjusted models (OR 2.64, 95% CI 1.79–3.92). Residing in a high diversity neighborhood was associated with child behavioral and emotional problems in unadjusted (OR 2.03, 95% CI 1.13–3.64) but not in adjusted models (OR 0.89, 95% CI 0.51–1.57). When stratifying by the three levels of neighborhood ethnic diversity, ethnic inequalities in behavioral and emotional problems were greatest in low diversity neighborhoods (OR 5.24, 95%CI 2.47–11.14), smaller in high diversity neighborhoods (OR 3.15, 95% CI 1.66–5.99) and smallest in medium diversity neighborhoods (OR 1.59, 95% CI 0.90–2.82). Tests for interaction (when comparing medium to low diversity neighborhoods) trended towards negative on both the additive and multiplicative scale for the maternal-report (RERI: −3.22, 95% CI −0.70–0.59; Ratio of ORs: 0.30, 95% CI 0.12–0.76). Conclusion This study suggests that ethnic inequalities in child behavioral and emotional problems may be greatest in ethnically homogeneous neighborhoods. PMID:23967068

Interaction of maternal smoking and preterm birth on future risk of maternal cardiovascular disease: A population-based record linkage study.

PubMed

Ngo, Anh D; Roberts, Christine L; Chen, Jian S; Figtree, Gemma

2016-04-01

While associations of smoking and preterm birth (PTB) with maternal cardiovascular disease (CVD) risks have been established, it is unknown whether the coexistence of these two conditions could synergistically increase the risks. We linked birth records of 902,008 mothers with singleton infants during 1994-2011 in New South Wales, Australia to the mothers' subsequent CVD hospitalisation or death. Multiplicative interaction was tested through an interaction term in a multivariate Cox-proportional hazard regression model, while additive interaction was assessed by calculating the synergy index. Relative to never-smokers with term babies, the CVD risk in ever-smokers with PTBs (hazard ratio (HR) 3.35, 95% confidence interval (CI) 2.96-3.80) was significantly greater than the sum of risks in ever-smokers with term babies (HR 2.10, 95% CI 1.96-2.24) and in never-smokers with PTBs (HR 1.73, 95% CI 1.55-1.93), indicating an additive interaction (synergy index = 1.29, 95% CI 1.05-1.58). In ever-smokers, the association was stronger for extremely PTB (HR 3.83, 95% CI 3.23-4.69) than moderately PTB (HR 3.18, 95% CI 2.76-3.66), and for ≥2 PTB (HR 4.47, 95% CI 3.39-5.88) than one PTB (HR 3.20, 95% CI 2.81-3.64). Maternal smoking and PTB interact on the additive scale to synergistically increase maternal CVD risks. The interaction was dose-dependent according to both the severity and number of PTBs. © The European Society of Cardiology 2015.

Combined endosulfan and cypermethrin-induced toxicity to embryo-larval development of Rhinella arenarum.

PubMed

Svartz, Gabriela V; Aronzon, Carolina M; Pérez Coll, Cristina S

2016-01-01

The combined effects of two widely used pesticides, endosulfan and cypermethrin, on survival of embryo-larval development of the South American toad (Rhinella arenarum) were examined. The toxicity bioassays were performed according to the AMPHITOX test. Embryos and larvae were exposed to mixtures of these pesticides at equitoxic ratios from acute or chronic exposure to evaluate interaction effects. The results were analyzed using both Marking's additive index and combination index (CI)-isobologram methods. Acute (96-h) and intermediate (168-h) toxicity of endosulfan-cypermethrin mixtures remained almost constant for larvae and embryos, but when exposure duration was increased, there was a significant elevation in toxicity, obtaining chronic (240-h) no-observed-effect concentrations (NOEC) values of 0.045 and 0.16 mg/L for embryos and larvae, respectively. These are environmentally relevant concentrations that reflect a realistic risk of this pesticide mixture to this native amphibian species. The toxicity increment with the exposure duration was coincident with the central nervous system development on embryos reaching the larval period, the main target organ of these pesticides. The interactions of the pesticide mixtures at acute and chronic exposure were antagonistic for embryo development (CI > 1), and additive (CI = 1) for larvae, while chronic exposure interactions were synergistic (CI < 1) for both developmental periods. Data indicated that endosulfan-cypermethrin mixtures resulted in different interaction types depending on duration and developmental stage exposed. As a general pattern and considering conditions of overall developmental period and chronic exposure, this pesticide mixture usually applied in Argentine crop fields is synergistic with respect to toxicity for this native amphibian species.

Crossmodal interactions during non-linguistic auditory processing in cochlear-implanted deaf patients.

PubMed

Barone, Pascal; Chambaudie, Laure; Strelnikov, Kuzma; Fraysse, Bernard; Marx, Mathieu; Belin, Pascal; Deguine, Olivier

2016-10-01

Due to signal distortion, speech comprehension in cochlear-implanted (CI) patients relies strongly on visual information, a compensatory strategy supported by important cortical crossmodal reorganisations. Though crossmodal interactions are evident for speech processing, it is unclear whether a visual influence is observed in CI patients during non-linguistic visual-auditory processing, such as face-voice interactions, which are important in social communication. We analyse and compare visual-auditory interactions in CI patients and normal-hearing subjects (NHS) at equivalent auditory performance levels. Proficient CI patients and NHS performed a voice-gender categorisation in the visual-auditory modality from a morphing-generated voice continuum between male and female speakers, while ignoring the presentation of a male or female visual face. Our data show that during the face-voice interaction, CI deaf patients are strongly influenced by visual information when performing an auditory gender categorisation task, in spite of maximum recovery of auditory speech. No such effect is observed in NHS, even in situations of CI simulation. Our hypothesis is that the functional crossmodal reorganisation that occurs in deafness could influence nonverbal processing, such as face-voice interaction; this is important for patient internal supramodal representation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantitative Assessment of Combination Antimicrobial Therapy against Multidrug-Resistant Acinetobacter baumannii▿

PubMed Central

Lim, Tze-Peng; Ledesma, Kimberly R.; Chang, Kai-Tai; Hou, Jing-Guo; Kwa, Andrea L.; Nikolaou, Michael; Quinn, John P.; Prince, Randall A.; Tam, Vincent H.

2008-01-01

Treatment of multidrug-resistant bacterial infections poses a therapeutic challenge to clinicians; combination therapy is often the only viable option for multidrug-resistant infections. A quantitative method was developed to assess the combined killing abilities of antimicrobial agents. Time-kill studies (TKS) were performed using a multidrug-resistant clinical isolate of Acinetobacter baumannii with escalating concentrations of cefepime (0 to 512 mg/liter), amikacin (0 to 256 mg/liter), and levofloxacin (0 to 64 mg/liter). The bacterial burden data in single and combined (two of the three agents with clinically achievable concentrations in serum) TKS at 24 h were mathematically modeled to provide an objective basis for comparing various antimicrobial agent combinations. Synergy and antagonism were defined as interaction indices of <1 and >1, respectively. A hollow-fiber infection model (HFIM) simulating various clinical (fluctuating concentrations over time) dosing exposures was used to selectively validate our quantitative assessment of the combined killing effect. Model fits in all single-agent TKS were satisfactory (r2 > 0.97). An enhanced combined overall killing effect was seen in the cefepime-amikacin combination (interactive index, 0.698; 95% confidence interval [CI], 0.675 to 0.722) and the cefepime-levofloxacin combination (interactive index, 0.929; 95% CI, 0.903 to 0.956), but no significant difference in the combined overall killing effect for the levofloxacin-amikacin combination was observed (interactive index, 0.994; 95% CI, 0.982 to 1.005). These assessments were consistent with observations in HFIM validation studies. Our method could be used to objectively rank the combined killing activities of two antimicrobial agents when used together against a multidrug-resistant A. baumannii isolate. It may offer better insights into the effectiveness of various antimicrobial combinations and warrants further investigations. PMID:18505848

Electrocardiographic J Wave and Cardiovascular Outcomes in the General Population (from the Atherosclerosis Risk In Communities Study).

PubMed

O'Neal, Wesley T; Wang, Yi Grace; Wu, Hau-Tieng; Zhang, Zhu-Ming; Li, Yabing; Tereshchenko, Larisa G; Estes, E Harvey; Daubechies, Ingrid; Soliman, Elsayed Z

2016-09-15

The association between the J wave, a key component of the early repolarization pattern, and adverse cardiovascular outcomes remains unclear. Inconsistencies have stemmed from the different methods used to measure the J wave. We examined the association between the J wave, detected by an automated method, and adverse cardiovascular outcomes in 14,592 (mean age = 54 ± 5.8 years; 56% women; 26% black) participants from the Atherosclerosis Risk In Communities (ARIC) study. The J wave was detected at baseline (1987 to 1989) and during follow-up study visits (1990 to 1992, 1993 to 1995, and 1996 to 1998) using a fully automated method. Sudden cardiac death, coronary heart disease death, and cardiovascular mortality were ascertained from hospital discharge records, death certificates, and autopsy data through December 31, 2010. A total of 278 participants (1.9%) had evidence of a J wave. Over a median follow-up of 22 years, 4,376 of the participants (30%) died. In a multivariable Cox regression analysis adjusted for demographics, cardiovascular risk factors, and potential confounders, the J wave was not associated with an increased risk of sudden cardiac death (hazard ratio [HR] 0.74, 95% CI 0.36 to 1.50), coronary heart disease death (HR 0.72, 95% CI 0.40 to 1.32), or cardiovascular mortality (HR 1.16, 95% CI 0.87 to 1.56). An interaction was detected for cardiovascular mortality by gender with men (HR 1.54, 95% CI 1.09 to 2.19) having a stronger association than women (HR 0.74, 95% CI 0.43 to 1.25; P-interaction = 0.030). In conclusion, our findings suggest that the J wave is a benign entity that is not associated with an increased risk for sudden cardiac arrest in middle-aged adults in the United States. Copyright © 2016 Elsevier Inc. All rights reserved.

Separated-pair independent particle model and the generalized Brillouin theorem: ab initio calculations on the dissociation of polyatomic molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sundberg, Kenneth Randall

1976-01-01

A method is developed to optimize the separated-pair independent particle (SPIP) wave function; it is a special case of the separated-pair theory obtained by using two-term natural expansions of the geminals. The orbitals are optimized by a theory based on the generalized Brillouin theorem and iterative configuration interaction (CI) calculations in the space of the SPIP function and its single excitations. The geminal expansion coefficients are optimized by serial 2 x 2 CI calculations. Formulas are derived for the matrix elements. An algorithm to implement the method is presented, and the work needed to evaluate the molecular integrals is discussed.

Low serum uric acid concentration augments insulin effects on the prevalence of metabolic syndrome.

PubMed

Porchia, Leonardo M; Gonzalez-Mejia, M Elba; Torres-Rasgado, Enrique; Ruiz-Vivanco, Guadalupe; Pérez-Fuentes, Ricardo

2018-05-01

Insulin and uric acid were shown affect the prevalence of Metabolic Syndrome (MetS), but no studies examine their interaction. Therefore, we conducted this study to determine their biological interaction in subjects from central Mexico. 433 subjects were enrolled for a cross-sectional study. MetS was defined according to the Harmonizing Definition. Hyperuricemia was defined as ≥7.0 mg/dL in males and ≥5.8 mg/dL in females. Hyperinsulinemia was defined as ≥11.0 μU/mL. Pearson correlation coefficient (r) was calculated to determine the association between uric acid or insulin and MetS. Logistic regression was used to determine the risk (odds ratio) of developing MetS. Biological interactions were determined by the PROCESS Macro and Anderson's method. Insulin and uric acid levels were elevated in MetS positive group (p < .05) and correlated with the number of MetS components (r = 0.276 and r = 0.166, p < .001, respectively). The interaction between uric acid and insulin was associated with the number of MetS components (PROCESS Model 1, interaction coefficient = -0.009, 95%CI: -0.017 to -0.001, p = .036). Johnson-Neyman analysis suggests the interaction is lost when uric acid concentration increased >7.0 mg/dL. When the cohort was separated by hyperinsulinemia and hyperuricemia, there was a significant risk of developing MetS for subjects with hyperuricemia (odds ratio = 2.3; 95%CI: 1.1-4.8, p < .05), hyperinsulinemia (odds ratio = 3.1; 95%CI: 1.9-4.9, p < .05), or both (odds ratio = 7.4; 95%CI: 3.2-17.2, p < .05); however, there was no multiplicative or additive interaction. Here, we show that uric acid and insulin augments the prevalence of MetS; however, no biological interaction was determined for hyperuricemia and hyperinsulinemia. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Association and interaction between triglyceride-glucose index and obesity on risk of hypertension in middle-aged and elderly adults.

PubMed

Jian, Song; Su-Mei, Nie; Xue, Chen; Jie, Zhang; Xue-Sen, Wu

2017-01-01

To investigate the association between triglyceride-glucose(TyG) index and the risk of hypertension. A cross-sectional study was conducted in Bengbu, China. The participants received relevant questionnaire survey, anthropometric tests, and laboratory examination. Multivariate logistic regression analysis was performed to estimate the possible association between TyG index and hypertension risk. The additive interaction evaluated by the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index(SI) was calculated. A total of 1777 participants (748 men and 1029 women) were investigated. There was a significant increase in the risk of hypertension and isolated systolic hypertension (ISH) when comparing the highest TyG index (the fourth quartile) to the lowest TyG index (the first quartile) and corresponding ORs were 2.446 (95% CI: 1.746-3.426) and 2.621(95%CI: 1.627-4.224), respectively. However, no significant relationship was observed between TyG index and isolated diastolic hypertension (IDH). In males, significant interactions between TyG index and WHtR (RERI:1.978, 95%CI: 0.162-3.792; AP: 0.359, 0.113-0.605; SI:1.782, 1.017-3.122), smoking (AP: 0.437, 95%CI: 0.048-0.825), family history of hypertension (AP:0.433, 95%CI: 0.203-0.662; SI:2.248, 95%CI: 1.333-3.791) were observed. As for females, there were also significant interactions between TyG index and WHtR (RERI:1.415, 95%CI: 0.693-2.136; AP: 0.198, 95%CI: 0.104-0.291; SI:1.298, 95%CI:1.101-1.530), family history of hypertension (RERI:1.744, 95%CI: 0.221-3.267; AP:0.405, 95%CI: 0.113-0.697) on risk of hypertension. Increased TyG index was significantly associated with higher risk of hypertension and ISH, but not for IDH in middle-aged and elderly adults. Our results also demonstrated interactions of TyG index and abdominal obesity and family history of hypertension on hypertension risk.

Electrophysiological channel interactions using focused multipolar stimulation for cochlear implants

NASA Astrophysics Data System (ADS)

George, Shefin S.; Shivdasani, Mohit N.; Wise, Andrew K.; Shepherd, Robert K.; Fallon, James B.

2015-12-01

Objective. Speech intelligibility with existing multichannel cochlear implants (CIs) is thought to be limited by poor spatial selectivity and interactions between CI channels caused by overlapping activation with monopolar (MP) stimulation. Our previous studies have shown that focused multipolar (FMP) and tripolar (TP) stimulation produce more restricted neural activation in the inferior colliculus (IC), compared to MP stimulation. Approach. This study explored interactions in the IC produced by simultaneous stimulation of two CI channels. We recorded multi-unit neural activity in the IC of anaesthetized cats with normal and severely degenerated spiral ganglion neuron populations in response to FMP, TP and MP stimulation from a 14 channel CI. Stimuli were applied to a ‘fixed’ CI channel, chosen toward the middle of the cochlear electrode array, and the effects of simultaneously stimulating a more apical ‘test’ CI channel were measured as a function of spatial separation between the two stimulation channels and stimulus level of the fixed channel. Channel interactions were quantified by changes in neural responses and IC threshold (i.e., threshold shift) elicited by simultaneous stimulation of two CI channels, compared to stimulation of the test channel alone. Main results. Channel interactions were significantly lower for FMP and TP than for MP stimulation (p < 0.001), whereas no significant difference was observed between FMP and TP stimulation. With MP stimulation, threshold shifts increased with decreased inter-electrode spacing and increased stimulus levels of the fixed channel. For FMP and TP stimulation, channel interactions were found to be similar for different inter-electrode spacing and stimulus levels of the fixed channel. Significance. The present study demonstrates how the degree of channel interactions in a CI can be controlled using stimulation configurations such as FMP and TP; such knowledge is essential in enhancing CI function in complex acoustic environments.

Adaptive multiconfigurational wave functions.

PubMed

Evangelista, Francesco A

2014-03-28

A method is suggested to build simple multiconfigurational wave functions specified uniquely by an energy cutoff Λ. These are constructed from a model space containing determinants with energy relative to that of the most stable determinant no greater than Λ. The resulting Λ-CI wave function is adaptive, being able to represent both single-reference and multireference electronic states. We also consider a more compact wave function parameterization (Λ+SD-CI), which is based on a small Λ-CI reference and adds a selection of all the singly and doubly excited determinants generated from it. We report two heuristic algorithms to build Λ-CI wave functions. The first is based on an approximate prescreening of the full configuration interaction space, while the second performs a breadth-first search coupled with pruning. The Λ-CI and Λ+SD-CI approaches are used to compute the dissociation curve of N2 and the potential energy curves for the first three singlet states of C2. Special attention is paid to the issue of energy discontinuities caused by changes in the size of the Λ-CI wave function along the potential energy curve. This problem is shown to be solvable by smoothing the matrix elements of the Hamiltonian. Our last example, involving the Cu2O2(2+) core, illustrates an alternative use of the Λ-CI method: as a tool to both estimate the multireference character of a wave function and to create a compact model space to be used in subsequent high-level multireference coupled cluster computations.

Diketo modification of curcumin affects its interaction with human serum albumin.

PubMed

Shaikh, Shaukat Ali M; Singh, Beena G; Barik, Atanu; Ramani, Modukuri V; Balaji, Neduri V; Subbaraju, Gottumukkala V; Naik, Devidas B; Indira Priyadarsini, K

2018-06-15

Curcumin isoxazole (CI) and Curcumin pyrazole (CP), the diketo modified derivatives of Curcumin (CU) are metabolically more stable and are being explored for pharmacological properties. One of the requirements in such activities is their interaction with circulatory proteins like human serum albumin (HSA). To understand this, the interactions of CI and CP with HSA have been investigated employing absorption and fluorescence spectroscopy and the results are compared with that of CU. The respective binding constants of CP, CI and CU with HSA were estimated to be 9.3×10 5 , 8.4×10 5 and 2.5×10 5 M -1 , which decreased with increasing salt concentration in the medium. The extent of decrease in the binding constant was the highest in CP followed by CI and CU. This revealed that along with hydrophobic interaction other binding modes like electrostatic interactions operate between CP/CI/CU with HSA. Fluorescence quenching studies of HSA with these compounds suggested that both static and dynamic quenching mechanisms operate, where the contribution of static quenching is higher for CP and CI than that for CU. From fluorescence resonance energy transfer studies, the binding site of CU, CI and CP was found to be in domain IIA of HSA. CU was found to bind in closer proximity with Trp214 as compared to CI and CP and the same was responsible for efficient energy transfer and the same was also established by fluorescence anisotropy measurements. Furthermore docking simulation complemented the experimental observation, where both electrostatic as well as hydrophobic interactions were indicated between HSA and CP, CI and CU. This study is useful in designing more stable CU derivatives having suitable binding properties with proteins like HSA. Copyright © 2018 Elsevier B.V. All rights reserved.

Diketo modification of curcumin affects its interaction with human serum albumin

NASA Astrophysics Data System (ADS)

Shaikh, Shaukat Ali M.; Singh, Beena G.; Barik, Atanu; Ramani, Modukuri V.; Balaji, Neduri V.; Subbaraju, Gottumukkala V.; Naik, Devidas B.; Indira Priyadarsini, K.

2018-06-01

Curcumin isoxazole (CI) and Curcumin pyrazole (CP), the diketo modified derivatives of Curcumin (CU) are metabolically more stable and are being explored for pharmacological properties. One of the requirements in such activities is their interaction with circulatory proteins like human serum albumin (HSA). To understand this, the interactions of CI and CP with HSA have been investigated employing absorption and fluorescence spectroscopy and the results are compared with that of CU. The respective binding constants of CP, CI and CU with HSA were estimated to be 9.3 × 105, 8.4 × 105 and 2.5 × 105 M-1, which decreased with increasing salt concentration in the medium. The extent of decrease in the binding constant was the highest in CP followed by CI and CU. This revealed that along with hydrophobic interaction other binding modes like electrostatic interactions operate between CP/CI/CU with HSA. Fluorescence quenching studies of HSA with these compounds suggested that both static and dynamic quenching mechanisms operate, where the contribution of static quenching is higher for CP and CI than that for CU. From fluorescence resonance energy transfer studies, the binding site of CU, CI and CP was found to be in domain IIA of HSA. CU was found to bind in closer proximity with Trp214 as compared to CI and CP and the same was responsible for efficient energy transfer and the same was also established by fluorescence anisotropy measurements. Furthermore docking simulation complemented the experimental observation, where both electrostatic as well as hydrophobic interactions were indicated between HSA and CP, CI and CU. This study is useful in designing more stable CU derivatives having suitable binding properties with proteins like HSA.

Can model Hamiltonians describe the electron-electron interaction in π-conjugated systems?: PAH and graphene

NASA Astrophysics Data System (ADS)

Chiappe, G.; Louis, E.; San-Fabián, E.; Vergés, J. A.

2015-11-01

Model Hamiltonians have been, and still are, a valuable tool for investigating the electronic structure of systems for which mean field theories work poorly. This review will concentrate on the application of Pariser-Parr-Pople (PPP) and Hubbard Hamiltonians to investigate some relevant properties of polycyclic aromatic hydrocarbons (PAH) and graphene. When presenting these two Hamiltonians we will resort to second quantisation which, although not the way chosen in its original proposal of the former, is much clearer. We will not attempt to be comprehensive, but rather our objective will be to try to provide the reader with information on what kinds of problems they will encounter and what tools they will need to solve them. One of the key issues concerning model Hamiltonians that will be treated in detail is the choice of model parameters. Although model Hamiltonians reduce the complexity of the original Hamiltonian, they cannot be solved in most cases exactly. So, we shall first consider the Hartree-Fock approximation, still the only tool for handling large systems, besides density functional theory (DFT) approaches. We proceed by discussing to what extent one may exactly solve model Hamiltonians and the Lanczos approach. We shall describe the configuration interaction (CI) method, a common technology in quantum chemistry but one rarely used to solve model Hamiltonians. In particular, we propose a variant of the Lanczos method, inspired by CI, that has the novelty of using as the seed of the Lanczos process a mean field (Hartree-Fock) determinant (the method will be named LCI). Two questions of interest related to model Hamiltonians will be discussed: (i) when including long-range interactions, how crucial is including in the Hamiltonian the electronic charge that compensates ion charges? (ii) Is it possible to reduce a Hamiltonian incorporating Coulomb interactions (PPP) to an ‘effective’ Hamiltonian including only on-site interactions (Hubbard)? The performance of CI will be checked on small molecules. The electronic structure of azulene and fused azulene will be used to illustrate several aspects of the method. As regards graphene, several questions will be considered: (i) paramagnetic versus antiferromagnetic solutions, (ii) forbidden gap versus dot size, (iii) graphene nano-ribbons, and (iv) optical properties.

Association between rs2981582 polymorphism in the FGFR2 gene and the risk of breast cancer in Mexican women

PubMed Central

Murillo-Zamora, Efrén; Moreno-Macías, Hortensia; Ziv, Elad; Romieu, Isabelle; Lazcano-Ponce, Eduardo; Ángeles-Llerenas, Angélica; Pérez-Rodríguez, Edelmiro; Vidal-Millán, Silvia; Fejerman, Laura; Torres-Mejía, Gabriela

2014-01-01

Background and Aims The rs2981582 single nucleotide polymorphism in the Fibroblast Growth Factor Receptor 2 gene has been consistently associated with an increased risk of breast cancer. We evaluated the effect of rs2981582 polymorphism in the FGFR2 gene on the risk of breast cancer and its interaction with non-genetic risk factors. Methods A population based case control study was conducted in Mexico. Data from 687 cases and 907 controls were analyzed. Results The T allele of the rs2981582 polymorphism was associated with an increased risk of breast cancer (OR per allele =1.24, 95% CI 1.06 – 1.46). There was also an interaction between this polymorphism and alcohol consumption (p = 0.043); the effect of alcohol consumption on the risk of breast cancer varied according to the allelic variants of the rs2981582 polymorphism in the FGFR2 gene: OR = 3.97 (95% CI 2.10 – 7.49), OR = 2.01 (95% CI 1.23 − 3.29) and OR = 1.21 (95% CI 0.48 − 3.05) for genotypes CC, CT and TT, respectively. Conclusions This is the first study exploring the association between rs2981582 polymorphism in the FGFR2 gene and breast cancer risk in Mexican women. The interaction found may be of great public health interest, since alcohol consumption is a modifiable breast cancer risk factor. Therefore, replication of this finding is of foremost importance. PMID:24054997

Simultaneous analytical optimization of variational parameters in Gaussian-type functions with full configuration interaction of multicomponent molecular orbital method by elimination of translational and rotational motions: application to isotopomers of the hydrogen molecule.

PubMed

Ishimoto, Takayoshi; Tachikawa, Masanori; Nagashima, Umpei

2008-04-28

We have extended the multicomponent molecular orbital (MCMO) method to the full-configuration interaction (full-CI) fully variational molecular orbital method by elimination of translational and rotational motion components from total Hamiltonian. In the MCMO scheme, the quantum effects of protons and deuterons as well as electrons can be directly taken into account. All variational parameters in the full-CI scheme, i.e., exponents and centers (alpha and R) in the Gaussian-type function (GTF) basis set as well as the CI coefficients, are simultaneously optimized by using their analytical gradients. The total energy of the H(2) molecule calculated using the electronic [6s3p2d1f] and nuclear [1s1p1d1f] GTFs is -1.161 726 hartree, which can be compared to the energy of -1.164 025 hartree reported using a 512 term-explicitly correlated GTF calculation. Although the d- and f-type nuclear GTFs contribute to the improvement of energy convergence, the convergence of electron-nucleus correlation energy is slower than that of electron-electron one. The nuclear wave functions are delocalized due to the electron-nucleus correlation effect compared to the result of Hartree-Fock level of MCMO method. In addition, the average internuclear distances of all diatomic molecules are within 0.001 A of the previously reported experimental results. The dipole moment of the HD molecule estimated by our method is 8.4 x 10(-4) D, which is in excellent agreement with the experimental result of (8-10) x 10(-4) D.

Warfarin - Fluoroquinolones, Sulfonamides, or Azole Antifungals Interactions and the Risk of Hospitalization for Gastrointestinal Bleeding

PubMed Central

Schelleman, Hedi; Bilker, Warren B.; Brensinger, Colleen M.; Han, Xiaoyan; Kimmel, Stephen E.; Hennessy, Sean

2008-01-01

Objective To determine whether a potential pharmacokinetic interaction between warfarin and orally administered anti-infectives increases the risk of hospitalization for gastrointestinal (GI) bleeding in warfarin users. Methods We conducted a nested case-control and case-crossover study in US Medicaid data. Logistic regression was used to determine the association between GI bleeding and prior use of ciprofloxacin, levofloxacin, gatifloxacin, cotrimoxazole, or fluconazole, all versus no exposure and versus cephalexin, which would not be expected to interact with warfarin. Results All anti-infectives examined exhibited an elevated odds ratio (OR) vs. no exposure. Using cephalexin as the reference category, ORs for cotrimoxazole (OR:1.68 [95% CI:1.21–2.33] in the prior 6–10 days) and fluconazole (OR:2.09 [95% CI:1.34–3.26] in the prior 11–15 days) were significantly elevated. Conclusions Warfarin users who had received an anti-infective agent showed a substantially increased risk of GI bleeding. Nonetheless, a drug-drug interaction with warfarin was evident only for cotrimoxazole and fluconazole. PMID:18685566

Interactive eBooks in Educating Patients and their Families About Head Injury Regardless of Age

PubMed Central

Sahyouni, Ronald; Mahmoodi, Amin; Mahmoodi, Amir; Huang, Melissa; Tran, Diem Kieu; Chen, Jefferson W.

2017-01-01

Objectives Traumatic Brain Injury (TBI) is a common and debilitating injury that is particularly prevalent in patients over 60. Given the influence of head injury on dementia (and vice versa), and the increased likelihood of ground-level falls, elderly patients are vulnerable to TBI. Educational interventions can increase knowledge and influence preventative activity to decrease the likelihood of further TBI. We sought to determine the efficacy of interactive tablet-based educational interventions in elderly patients on self-reported knowledge. Patients and Methods Patients and family members, ages 20–90, presenting to a NeuroTrauma clinic completed a pre-survey to assess baseline TBI or concussion knowledge, depending on their diagnosis. Participants then received an interactive electronic book (eBook), or a text-based pamphlet with identical information, and completed a post-survey to test interim knowledge improvement. Results All participants (n = 180), regardless of age, had significantly higher post-survey scores (p<.01, 95% CI). Elderly participants who received the eBook (n=39) scored lower than their younger counterparts despite higher pre-survey scores (p<0.01, 95% CI). All participants who received the eBook (n=20, 90) significantly improved on the post-survey (p<0.01, 95% CI) when compared to participants who received the paper pamphlets (n=10, 31). All participants significantly preferred the eBook (p<0.01, 95% CI). Conclusions We demonstrated that interactive educational interventions are effective in the elderly TBI population. Enhanced educational awareness in the elderly population, especially patients at risk or with prior TBI, may prevent further head injury by educating patients on the importance of avoiding further head injury and taking precautionary measures to decrease the likelihood of further injury. PMID:28324787

Gastric atrophy and oesophageal squamous cell carcinoma: possible interaction with dental health and oral hygiene habit

PubMed Central

Nasrollahzadeh, D; Malekzadeh, R; Aghcheli, K; Sotoudeh, M; Merat, S; Islami, F; Kamangar, F; Abnet, C C; Shakeri, R; Pourshams, A; Semnani, S; Boffetta, P; Dawsey, S M; Ye, W

2012-01-01

Background: Gastric fundal atrophy has been hypothesised to increase the risk of oesophageal squamous cell carcinoma (OSCC), but studies have shown inconsistent results. Methods: We measured serum pepsinogen I (PGI) and pepsinogen II (PGII) among 293 incident cases and 524 matched neighbourhood controls in a high-risk area of Northern Iran. Conditional logistic regression model was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs). Results: After controlling for age, sex, residence area and other potential confounders, gastric atrophy (defined by a validated criterion, PGI <55 μg dl−1) was associated with a two-fold increased risk (OR=2.01, 95% CI: 1.18, 3.45) of OSCC in the absence of nonatrophic pangastritis (defined as PGII <11.8 μg dl−1). Stratification by PGII decreased the misclassification errors due to cancer-induced gastritis. Presence of both poor dental health, indicated by higher than median sum of decayed, missing, and filled teeth (DMFT score), and gastric atrophy further increased the risk of OSCC (OR=4.15, 95% CI: 2.04, 8.42) with relative excess risk due to interaction (RERI) of 1.47 (95% CI: −1.15, 4.1). Coexistence of poor oral hygiene habit with gastric atrophy elevated OSCC risk eight times (OR=8.65, 95% CI: 3.65, 20.46) and the additive interaction index was marginally statistically significant (RERI=4.34, 95% CI: −1.07, 9.76). Conclusion: Gastric atrophy is a risk factor for OSCC, and poor dental health and oral hygiene habit may act synergistically in increasing the risk. PMID:22814581

Coincident Alcohol Dependence and Depression Increases Risk of Suicidal Ideation among Army National Guard Soldiers

PubMed Central

Fink, David; Sampson, Laura; Tamburrino, Marijo; Liberzon, Israel; Calabrese, Joseph R.; Galea, Sandro

2017-01-01

Purpose Suicide rates among military service members have risen dramatically, while drivers remain poorly understood. We aimed to examine the relationship between coincident alcohol dependence and depression in shaping subsequent risk of suicidal ideation among National Guard forces. Methods We performed a longitudinal analysis using a randomly selected, population-based sample of Ohio Army National Guard soldiers. Telephone-based surveys of 1582 soldiers who participated in both wave 1 (data collected 2008–2009) and wave 2 (data collected 2009– 2010) were analyzed. Results Incident suicidal ideation was present among 2.47% of soldiers at follow-up. Odds ratios (ORs) for suicidal ideation among those with vs. without alcohol dependence were similar among non-depressed [OR=3.85 (95% Confidence Intervals(CI) = 1.18–12.52)] and depressed individuals [OR = 3.13 (95% CI = 0.88–11.14)]; a logistic model cross-product term confirmed an absence of multiplicative interaction (beta coefficient=−0.21, p=0.82). In contrast, the risk differences (RD) for suicidal ideation among those with vs. without alcohol dependence diverged for those without depression [RD = 0.04 (95% CI = 0.02–0.07)] compared to those with depression [RD 0.11(95% CI=0.06–0.18)]; strong evidence of additive interaction was observed - [Relative Excess Risk of Interaction (RERI) = 5.978(95% CI=0.364–11.591)]. Conclusions We found that alcohol dependence and depression worked together to shape risk for incident suicidal ideation among Army National Guard service members. Because coincident alcohol dependence and depression is relatively rare, a high-risk prevention approach is recommended. Population-based screening for suicidality among patients with alcohol dependence, depression, and particularly those with both conditions is warranted in military populations. PMID:28139369

Non-Hodgkin lymphoma, body mass index and cytokine polymorphisms: a pooled analysis from the InterLymph consortium

PubMed Central

Kane, Eleanor; Skibola, Christine F.; Bracci, Paige M.; Cerhan, James R.; Costas, Laura; Smedby, Karin Ekström; Holly, Elizabeth A.; Maynadié, Marc; Novak, Anne J.; Lightfoot, Tracy J.; Ansell, Stephen M.; Smith, Alex G.; Liebow, Mark; Melbye, Mads; Morton, Lindsay; de Sanjosé, Silvia; Slager, Susan L.; Wang, Sophia S.; Zhang, Yawei; Zheng, Tongzhang; Roman, Eve

2015-01-01

Background Excess adiposity has been associated with lymphomagenesis, possibly mediated by increased cytokine production causing a chronic inflammatory state. The relationship between obesity, cytokine polymorphisms and selected mature B-cell neoplasms is reported. Method Data on 4979 cases and 4752 controls from nine American/European studies from the InterLymph consortium (1988–2008) were pooled. For diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), joint associations of body mass index (from self-reported height and weight) and 12 polymorphisms in cytokines IL1A (rs1800587), IL1B (rs16944, rs1143627), IL1RN (rs454078), IL2 (rs2069762), IL6 (rs1800795, rs1800797), IL10 (rs1800890, rs1800896), TNF (rs1800629), LTA (rs909253), and CARD15 (rs2066847) were investigated using unconditional logistic regression. BMI-polymorphism interaction effects were estimated using the relative excess risk due to interaction (RERI). Results Obesity (BMI≥30kg m−2) was associated with DLBCL risk (OR=1.33, 95%CI 1.02–1.73), as was TNF-308GA+AA (OR=1.24, 95%CI 1.07–1.44). Together, being obese and TNF-308GA+AA increased DLBCL risk almost two-fold relative to those of normal weight and TNF-308GG (OR=1.93 95%CI 1.27–2.94), with a RERI of 0.41 (95%CI −0.05,0.84, P(interaction)=0.13). For FL and CLL/SLL, no associations with obesity or TNF-308GA+AA, either singly or jointly, were observed. No evidence of interactions between obesity and the other polymorphisms were detected. Conclusions Our results suggest that cytokine polymorphisms do not generally interact with BMI to increase lymphoma risk but obesity and TNF-308GA+AA may interact to increase DLBCL risk. Impact Studies using better measures of adiposity are needed to further investigate the interactions between obesity and TNF-308G>A in the pathogenesis of lymphoma. PMID:25962811

Adaptive multiconfigurational wave functions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Evangelista, Francesco A., E-mail: francesco.evangelista@emory.edu

2014-03-28

A method is suggested to build simple multiconfigurational wave functions specified uniquely by an energy cutoff Λ. These are constructed from a model space containing determinants with energy relative to that of the most stable determinant no greater than Λ. The resulting Λ-CI wave function is adaptive, being able to represent both single-reference and multireference electronic states. We also consider a more compact wave function parameterization (Λ+SD-CI), which is based on a small Λ-CI reference and adds a selection of all the singly and doubly excited determinants generated from it. We report two heuristic algorithms to build Λ-CI wave functions.more » The first is based on an approximate prescreening of the full configuration interaction space, while the second performs a breadth-first search coupled with pruning. The Λ-CI and Λ+SD-CI approaches are used to compute the dissociation curve of N{sub 2} and the potential energy curves for the first three singlet states of C{sub 2}. Special attention is paid to the issue of energy discontinuities caused by changes in the size of the Λ-CI wave function along the potential energy curve. This problem is shown to be solvable by smoothing the matrix elements of the Hamiltonian. Our last example, involving the Cu{sub 2}O{sub 2}{sup 2+} core, illustrates an alternative use of the Λ-CI method: as a tool to both estimate the multireference character of a wave function and to create a compact model space to be used in subsequent high-level multireference coupled cluster computations.« less

Self-reported Violence-related Outcomes for Adolescents Within Eight Weeks Of Emergency Department Treatment For Assault Injury

PubMed Central

Blackstone, Mercedes M.; Mollen, Cynthia J.; Culyba, Alison J.; Fein, Joel A.

2011-01-01

Purpose To estimate, using a novel interactive voice response (IVR) survey, the incidence of self-reported violence-related experiences of adolescent assault-injured patients in the weeks following Emergency Department (ED) discharge. Methods In an urban ED, a prospective cohort study with eight week follow-up IVR survey either weekly, bi-weekly or monthly after discharge was conducted with patients aged 12-19 years presenting with assault-related injuries. Survival analysis methods were used to estimate cumulative risks of self-reported violence experience within four and eight weeks. Results Ninety-five patients were enrolled; 42 (44.2%) reported to the IVR survey. As a result of the ED index event, an estimated 18.2% (CI=9.1-34.6%) reported being assaulted (no weapon), 2.9% (CI=0.4-19.1%) had been shot or stabbed, 20.7% (CI=10.9-37.3%) had assaulted someone else (no weapon), and 2.9% (CI=0.4-19.1%) shot or stabbed someone else. Additionally, 54.6% (CI=39.6-70.9%) had avoided going certain places, 47.0% (CI=32.5-64.1%) considered retaliating, 38.1% (CI=24.3-56.3%) had been threatened, and 27.0% (CI=15.4-44.6%) had carried a weapon. Most outcome occurrences happened within four weeks. There was evidence that intent to retaliate when asked at baseline was associated with an elevated risk of several outcomes. Conclusions The risk for subsequent violence among assault-injured adolescent ED patients appears high within weeks of discharge. PMID:22031979

Computational intelligence in bioinformatics: SNP/haplotype data in genetic association study for common diseases.

PubMed

Kelemen, Arpad; Vasilakos, Athanasios V; Liang, Yulan

2009-09-01

Comprehensive evaluation of common genetic variations through association of single-nucleotide polymorphism (SNP) structure with common complex disease in the genome-wide scale is currently a hot area in human genome research due to the recent development of the Human Genome Project and HapMap Project. Computational science, which includes computational intelligence (CI), has recently become the third method of scientific enquiry besides theory and experimentation. There have been fast growing interests in developing and applying CI in disease mapping using SNP and haplotype data. Some of the recent studies have demonstrated the promise and importance of CI for common complex diseases in genomic association study using SNP/haplotype data, especially for tackling challenges, such as gene-gene and gene-environment interactions, and the notorious "curse of dimensionality" problem. This review provides coverage of recent developments of CI approaches for complex diseases in genetic association study with SNP/haplotype data.

The Combined Effect of Long Working Hours and Low Job Control on Self-Rated Health

PubMed Central

Cho, Seong-Sik; Ju, Young-Su; Paek, Domyung; Kim, Hyunjoo; Jung-Choi, Kyunghee

2018-01-01

Objectives: The aim of this study was to investigate the combined effects of long working hours and low job control on self-rated health. Methods: We analyzed employees’ data obtained from the third Korean Working Conditions Survey (KWCS). Multiple survey logistic analysis and postestimation commands were employed to estimate the relative excess risk due to interaction (RERI). Results: The odds ratio (OR) for poor self-rated health was 1.24 [95% confidence interval (95% CI): 1.13 to 1.35] for long working hours, 1.04 (95% CI: 0.97 to 1.13) for low job control, and 1.47 (95% CI: 1.33 to 1.62) for both long working hours and low job control. The RERI was 0.18 (95% CI: 0.02 to 0.34). Conclusion: These results imply that low job control may increase the negative influence of long working hours on self-rated health. PMID:29200187

Identification and localization of the sperm CRISP family protein CiUrabin involved in gamete interaction in the ascidian Ciona intestinalis.

PubMed

Yamaguchi, Akira; Saito, Takako; Yamada, Lixy; Taniguchi, Hisaaki; Harada, Yoshito; Sawada, Hitoshi

2011-07-01

Ascidians are hermaphrodites, and most release sperm and eggs nearly simultaneously. Many species, including Halocynthia roretzi and Ciona intestinalis, are self-sterile. We previously reported that the interaction between a 12 EGF-like repeat-containing vitelline-coat (VC) protein, HrVC70, and a sperm GPI-anchored CRISP, HrUrabin, in lipid rafts plays a key role in self-/nonself-recognizable gamete interaction in H. roretzi. On the other hand, we recently identified two pairs of polymorphic genes responsible for self-incompatibility in C. intestinalis by positional cloning: The sperm polycystin 1-like receptors s-Themis-A/B and its fibrinogen-like ligand v-Themis-A/B on the VC. However, it is not known if the orthologs of HrVC70 and HrUrabin also participate in gamete interaction in C. intestinalis since they are from different orders. Here, we tested for a C. intestinalis ortholog (CiUrabin) of HrUrabin by searching the genome database and proteomes of sperm lipid rafts. The identified CiUrabin belongs to the CRISP family, with a PR domain and a GPI-anchor-attachment site. CiUrabin appears to be specifically expressed in the testis and localized at the surface of the sperm head, as revealed by Northern blotting and immunocytochemistry, respectively. The specific interaction between CiVC57, a C. intestinalis ortholog of HrVC70, and CiUrabin was confirmed by Far Western analysis, similarly to the interaction between HrVC70 and HrUrabin. The molecular interaction between CiVC57 and CiUrabin may be involved in the primary binding of sperm to the VC prior to the allorecognition process, mediated by v-Themis-A/B and s-Themis-A/B, during fertilization of C. intestinalis. Copyright © 2011 Wiley-Liss, Inc.

Electron Capture in Slow Collisions of Si4+ With Atomic Hydrogen

NASA Astrophysics Data System (ADS)

Joseph, D. C.; Gu, J. P.; Saha, B. C.

2009-10-01

In recent years the charge transfer involving Si4+ and H at low energies has drawn considerable attention both theoretically and experimentally due to its importance not only in astronomical environments but also in modern semiconductor industries. Accurate information regarding its molecular structures and interactions are essential to understand the low energy collision dynamics. Ab initio calculations are performed using the multireference single- and double-excitation configuration-interaction (MRD-CI) method to evaluate potential energies. State selective cross sections are calculate using fully quantum and semi-classical molecular-orbital close coupling (MOCC) methods in the adiabatic representation. Detail results will be presented in the conference.

Cross-sectional interactions between quality of the physical and social environment and self-reported physical activity in adults living in income-deprived communities.

PubMed

Sawyer, Alexia D M; Jones, Russell; Ucci, Marcella; Smith, Lee; Kearns, Ade; Fisher, Abi

2017-01-01

Understanding the environmental determinants of physical activity in populations at high risk of inactivity could contribute to the development of effective interventions. Socioecological models of activity propose that environmental factors have independent and interactive effects of physical activity but there is a lack of research into interactive effects. This study aimed to explore independent and interactive effects of social and physical environmental factors on self-reported physical activity in income-deprived communities. Participants were 5,923 adults in Glasgow, United Kingdom. Features of the social environment were self-reported. Quality of the physical environment was objectively-measured. Neighbourhood walking and participation in moderate physical activity [MPA] on ≥5 days/week was self-reported. Multilevel multivariate logistic regression models tested independent and interactive effects of environmental factors on activity. 'Social support' (walking: OR:1.22,95%CI = 1.06-1.41,p<0.01; MPA: OR:0.79,95%CI = 0.67-0.94,p<0.01), 'social interaction' (walking: OR:1.25,95%CI = 1.10-1.42,p<0.01; MPA: OR:6.16,95%CI = 5.14-7.37,p<0.001) and 'cohesion and safety' (walking: OR:1.78,95%CI = 1.56-2.03,p<0.001; MPA: OR:1.93,95%CI = 1.65-2.27,p<0.001), but not 'trust and empowerment', had independent effects on physical activity. 'Aesthetics of built form' (OR:1.47,95%CI = 1.22-1.77,p<0.001) and 'aesthetics and maintenance of open space' (OR:1.32, 95%CI = 1.13-1.54,p<0.01) were related to walking. 'Physical disorder' (OR:1.63,95%CI = 1.31-2.03,p<0.001) had an independent effect on MPA. Interactive effects of social and physical factors on walking and MPA were revealed. Findings suggest that intervening to create activity-supportive environments in deprived communities may be most effective when simultaneously targeting the social and physical neighbourhood environment.

Association of Medical Students' Reports of Interactions with the Pharmaceutical and Medical Device Industries and Medical School Policies and Characteristics: A Cross-Sectional Study

PubMed Central

Yeh, James S.; Austad, Kirsten E.; Franklin, Jessica M.; Chimonas, Susan; Campbell, Eric G.; Avorn, Jerry; Kesselheim, Aaron S.

2014-01-01

Background Professional societies use metrics to evaluate medical schools' policies regarding interactions of students and faculty with the pharmaceutical and medical device industries. We compared these metrics and determined which US medical schools' industry interaction policies were associated with student behaviors. Methods and Findings Using survey responses from a national sample of 1,610 US medical students, we compared their reported industry interactions with their schools' American Medical Student Association (AMSA) PharmFree Scorecard and average Institute on Medicine as a Profession (IMAP) Conflicts of Interest Policy Database score. We used hierarchical logistic regression models to determine the association between policies and students' gift acceptance, interactions with marketing representatives, and perceived adequacy of faculty–industry separation. We adjusted for year in training, medical school size, and level of US National Institutes of Health (NIH) funding. We used LASSO regression models to identify specific policies associated with the outcomes. We found that IMAP and AMSA scores had similar median values (1.75 [interquartile range 1.50–2.00] versus 1.77 [1.50–2.18], adjusted to compare scores on the same scale). Scores on AMSA and IMAP shared policy dimensions were not closely correlated (gift policies, r = 0.28, 95% CI 0.11–0.44; marketing representative access policies, r = 0.51, 95% CI 0.36–0.63). Students from schools with the most stringent industry interaction policies were less likely to report receiving gifts (AMSA score, odds ratio [OR]: 0.37, 95% CI 0.19–0.72; IMAP score, OR 0.45, 95% CI 0.19–1.04) and less likely to interact with marketing representatives (AMSA score, OR 0.33, 95% CI 0.15–0.69; IMAP score, OR 0.37, 95% CI 0.14–0.95) than students from schools with the lowest ranked policy scores. The association became nonsignificant when fully adjusted for NIH funding level, whereas adjusting for year of education, size of school, and publicly versus privately funded school did not alter the association. Policies limiting gifts, meals, and speaking bureaus were associated with students reporting having not received gifts and having not interacted with marketing representatives. Policy dimensions reflecting the regulation of industry involvement in educational activities (e.g., continuing medical education, travel compensation, and scholarships) were associated with perceived separation between faculty and industry. The study is limited by potential for recall bias and the cross-sectional nature of the survey, as school curricula and industry interaction policies may have changed since the time of the survey administration and study analysis. Conclusions As medical schools review policies regulating medical students' industry interactions, limitations on receipt of gifts and meals and participation of faculty in speaking bureaus should be emphasized, and policy makers should pay greater attention to less research-intensive institutions. Please see later in the article for the Editors' Summary PMID:25314155

Comparing Cognitive Interviewing and Online Probing: Do They Find Similar Results?

ERIC Educational Resources Information Center

Meitinger, Katharina; Behr, Dorothée

2016-01-01

This study compares the application of probing techniques in cognitive interviewing (CI) and online probing (OP). Even though the probing is similar, the methods differ regarding typical mode setting, sample size, level of interactivity, and goals. We analyzed probing answers to the International Social Survey Programme item battery on specific…

Methods for using clinical laboratory test results as baseline confounders in multi-site observational database studies when missing data are expected.

PubMed

Raebel, Marsha A; Shetterly, Susan; Lu, Christine Y; Flory, James; Gagne, Joshua J; Harrell, Frank E; Haynes, Kevin; Herrinton, Lisa J; Patorno, Elisabetta; Popovic, Jennifer; Selvan, Mano; Shoaibi, Azadeh; Wang, Xingmei; Roy, Jason

2016-07-01

Our purpose was to quantify missing baseline laboratory results, assess predictors of missingness, and examine performance of missing data methods. Using the Mini-Sentinel Distributed Database from three sites, we selected three exposure-outcome scenarios with laboratory results as baseline confounders. We compared hazard ratios (HRs) or risk differences (RDs) and 95% confidence intervals (CIs) from models that omitted laboratory results, included only available results (complete cases), and included results after applying missing data methods (multiple imputation [MI] regression, MI predictive mean matching [PMM] indicator). Scenario 1 considered glucose among second-generation antipsychotic users and diabetes. Across sites, glucose was available for 27.7-58.9%. Results differed between complete case and missing data models (e.g., olanzapine: HR 0.92 [CI 0.73, 1.12] vs 1.02 [0.90, 1.16]). Across-site models employing different MI approaches provided similar HR and CI; site-specific models provided differing estimates. Scenario 2 evaluated creatinine among individuals starting high versus low dose lisinopril and hyperkalemia. Creatinine availability: 44.5-79.0%. Results differed between complete case and missing data models (e.g., HR 0.84 [CI 0.77, 0.92] vs. 0.88 [0.83, 0.94]). HR and CI were identical across MI methods. Scenario 3 examined international normalized ratio (INR) among warfarin users starting interacting versus noninteracting antimicrobials and bleeding. INR availability: 20.0-92.9%. Results differed between ignoring INR versus including INR using missing data methods (e.g., RD 0.05 [CI -0.03, 0.13] vs 0.09 [0.00, 0.18]). Indicator and PMM methods gave similar estimates. Multi-site studies must consider site variability in missing data. Different missing data methods performed similarly. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A systematic review and meta-analysis of online versus alternative methods for training licensed health care professionals to deliver clinical interventions.

PubMed

Richmond, Helen; Copsey, Bethan; Hall, Amanda M; Davies, David; Lamb, Sarah E

2017-11-23

Online training is growing in popularity and yet its effectiveness for training licensed health professionals (HCPs) in clinical interventions is not clear. We aimed to systematically review the literature on the effectiveness of online versus alternative training methods in clinical interventions for licensed Health Care Professionals (HCPs) on outcomes of knowledge acquisition, practical skills, clinical behaviour, self-efficacy and satisfaction. Seven databases were searched for randomised controlled trials (RCTs) from January 2000 to June 2015. Two independent reviewers rated trial quality and extracted trial data. Comparative effects were summarised as standardised mean differences (SMD) and 95% confidence intervals. Pooled effect sizes were calculated using a random-effects model for three contrasts of online versus (i) interactive workshops (ii) taught lectures and (iii) written/electronic manuals. We included 14 studies with a total of 1089 participants. Most trials studied medical professionals, used a workshop or lecture comparison, were of high risk of bias and had small sample sizes (range 21-183). Using the GRADE approach, we found low quality evidence that there was no difference between online training and an interactive workshop for clinical behaviour SMD 0.12 (95% CI -0.13 to 0.37). We found very low quality evidence of no difference between online methods and both a workshop and lecture for knowledge (workshop: SMD 0.04 (95% CI -0.28 to 0.36); lecture: SMD 0.22 (95% CI: -0.08, 0.51)). Lastly, compared to a manual (n = 3/14), we found very low quality evidence that online methods were superior for knowledge SMD 0.99 (95% CI 0.02 to 1.96). There were too few studies to draw any conclusions on the effects of online training for practical skills, self-efficacy, and satisfaction across all contrasts. It is likely that online methods may be as effective as alternative methods for training HCPs in clinical interventions for the outcomes of knowledge and clinical behaviour. However, the low quality of the evidence precludes drawing firm conclusions on the relative effectiveness of these training methods. Moreover, the confidence intervals around our effect sizes were large and could encompass important differences in effectiveness. More robust, adequately powered RCTs are needed.

XPS of oxygen atoms on Ag(111) and Ag(110) surfaces: accurate study with SAC/SAC-CI combined with dipped adcluster model.

PubMed

Ishikawa, Atsushi; Nakatsuji, Hiroshi

2013-08-05

O1s core-electron binding energies (CEBE) of the atomic oxygens on different Ag surfaces were investigated by the symmetry adapted cluster-configuration interaction (SAC-CI) method combined with the dipped adcluster model, in which the electron exchange between bulk metal and adsorbate is taken into account properly. Electrophilic and nucleophilic oxygens (O(elec) and O(nuc)) that might be important for olefin epoxidation in a low-oxygen coverage condition were focused here. We consider the O1s CEBE as a key property to distinguish the surface oxygen states, and series of calculation was carried out by the Hartree-Fock, Density functional theory, and SAC/SAC-CI methods. The experimental information and our SAC/SAC-CI results indicate that O(elec) is the atomic oxygen adsorbed on the fcc site of Ag(111) and that O(nuc) is the one on the reconstructed added-row site of Ag(110) and that one- and two-electron transfers occur, respectively, to the O(elec) and O(nuc) adclusters from the silver surface. Copyright © 2013 Wiley Periodicals, Inc.

Detection of plum pox potyviral protein-protein interactions in planta using an optimized mRFP-based bimolecular fluorescence complementation system.

PubMed

Zilian, Eva; Maiss, Edgar

2011-12-01

In previous studies, protein interaction maps of different potyviruses have been generated using yeast two-hybrid (YTH) systems, and these maps have demonstrated a high diversity of interactions of potyviral proteins. Using an optimized bimolecular fluorescence complementation (BiFC) system, a complete interaction matrix for proteins of a potyvirus was developed for the first time under in planta conditions with ten proteins from plum pox virus (PPV). In total, 52 of 100 possible interactions were detected, including the self-interactions of CI, 6K2, VPg, NIa-Pro, NIb and CP, which is more interactions than have ever been detected for any other potyvirus in a YTH approach. Moreover, the BiFC system was shown to be able to localize the protein interactions, which was typified for the protein self-interactions indicated above. Additionally, experiments were carried out with the P3N-PIPO protein, revealing an interaction with CI but not with CP and supporting the involvement of P3N-PIPO in the cell-to-cell movement of potyviruses. No self-interaction of the PPV helper component-proteinase (HC-Pro) was detected using BiFC in planta. Therefore, additional experiments with turnip mosaic virus (TuMV) HC-Pro, PPV_HC-Pro and their mutants were conducted. The self-interaction of TuMV_HCpro, as recently demonstrated, and the self-interaction of the TuMV_ and PPV_HC-Pro mutants were shown by BiFC in planta, indicating that HC-Pro self-interactions may be species-specific. BiFC is a very useful and reliable method for the detection and localization of protein interactions in planta, thus enabling investigations under more natural conditions than studies in yeast cells.

Relativistic many-body calculation of energies, multipole transition rates, and lifetimes in tungsten ions

NASA Astrophysics Data System (ADS)

Safronova, U. I.; Safronova, M. S.; Nakamura, N.

2017-04-01

Atomic properties of Cd-like W26 +, In-like W25 +, and Sn-like W24 + ions are evaluated by using a relativistic CI+all -order approach that combines configuration-interaction and the coupled-cluster methods. The energies, transition rates, and lifetimes of low-lying levels are calculated and compared with available theoretical and experimental values. The magnetic-dipole transition rates are calculated to determine the branching ratios and lifetimes for the 4 f3 states in W25 + and for the 4 f4 states in W24 + ions. Excellent agreement of the CI+all -order values provided a benchmark test of this method for the 4 fn configurations validating the recommended values of tungsten ion properties calculated in this work.

Suitability of the Binaural Interaction Component for Interaural Electrode Pairing of Bilateral Cochlear Implants.

PubMed

Hu, Hongmei; Kollmeier, Birger; Dietz, Mathias

2016-01-01

Although bilateral cochlear implants (BiCIs) have succeeded in improving the spatial hearing performance of bilateral CI users, the overall performance is still not comparable with normal hearing listeners. Limited success can be partially caused by an interaural mismatch of the place-of-stimulation in each cochlea. Pairing matched interaural CI electrodes and stimulating them with the same frequency band is expected to facilitate binaural functions such as binaural fusion, localization, or spatial release from masking. It has been shown in animal experiments that the magnitude of the binaural interaction component (BIC) derived from the wave-eV decreases for increasing interaural place of stimulation mismatch. This motivated the investigation of the suitability of an electroencephalography-based objective electrode-frequency fitting procedure based on the BIC for BiCI users. A 61 channel monaural and binaural electrically evoked auditory brainstem response (eABR) recording was performed in 7 MED-EL BiCI subjects so far. These BiCI subjects were directly stimulated at 60% dynamic range with 19.9 pulses per second via a research platform provided by the University of Innsbruck (RIB II). The BIC was derived for several interaural electrode pairs by subtracting the response from binaural stimulation from their summed monaural responses. The BIC based pairing results are compared with two psychoacoustic pairing methods: interaural pulse time difference sensitivity and interaural pitch matching. The results for all three methods analyzed as a function of probe electrode allow for determining a matched pair in more than half of the subjects, with a typical accuracy of ± 1 electrode. This includes evidence for statistically significant tuning of the BIC as a function of probe electrode in human subjects. However, results across the three conditions were sometimes not consistent. These discrepancies will be discussed in the light of pitch plasticity versus less plastic brainstem processing.

Select-divide-and-conquer method for large-scale configuration interaction

NASA Astrophysics Data System (ADS)

Bunge, Carlos F.; Carbó-Dorca, Ramon

2006-07-01

A select-divide-and-conquer variational method to approximate configuration interaction (CI) is presented. Given an orthonormal set made up of occupied orbitals (Hartree-Fock or similar) and suitable correlation orbitals (natural or localized orbitals), a large N-electron target space S is split into subspaces S0,S1,S2,…,SR. S0, of dimension d0, contains all configurations K with attributes (energy contributions, etc.) above thresholds T0≡{T0egy,T0etc.}; the CI coefficients in S0 remain always free to vary. S1 accommodates Ks with attributes above T1⩽T0. An eigenproblem of dimension d0+d1 for S0+S1 is solved first, after which the last d1 rows and columns are contracted into a single row and column, thus freezing the last d1 CI coefficients hereinafter. The process is repeated with successive Sj(j ⩾2) chosen so that corresponding CI matrices fit random access memory (RAM). Davidson's eigensolver is used R times. The final energy eigenvalue (lowest or excited one) is always above the corresponding exact eigenvalue in S. Threshold values {Tj;j=0,1,2,…,R} regulate accuracy; for large-dimensional S, high accuracy requires S0+S1 to be solved outside RAM. From there on, however, usually a few Davidson iterations in RAM are needed for each step, so that Hamiltonian matrix-element evaluation becomes rate determining. One μhartree accuracy is achieved for an eigenproblem of order 24×106, involving 1.2×1012 nonzero matrix elements, and 8.4×109 Slater determinants.

Red meat intake, NAT2, and risk of colorectal cancer: A pooled analysis of 11 studies

PubMed Central

Ananthakrishnan, Ashwin N.; Du, Mengmeng; Berndt, Sonja I.; Brenner, Hermann; Caan, Bette J.; Casey, Graham; Chang-Claude, Jenny; Duggan, David; Fuchs, Charles S.; Gallinger, Steven; Giovannucci, Edward L.; Harrison, Tabitha A.; Hayes, Richard B.; Hoffmeister, Michael; Hopper, John L.; Hou, Lifang; Hsu, Li; Jenkins, Mark A.; Kraft, Peter; Ma, Jing; Nan, Hongmei; Newcomb, Polly A.; Ogino, Shuji; Potter, John D.; Seminara, Daniela; Slattery, Martha L.; Thornquist, Mark; White, Emily; Wu, Kana; Peters, Ulrike; Chan, Andrew T.

2014-01-01

Background Red meat intake has been associated with risk of colorectal cancer (CRC), potentially mediated through heterocyclic amines. The metabolic efficiency of N-acetyltransferase 2 (NAT2) required for the metabolic activation of such amines is influenced by genetic variation. The interaction between red meat intake, NAT2 genotype, and CRC has been inconsistently reported. Methods We used pooled individual-level data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Red meat intake was collected by each study. We inferred NAT2 phenotype based on polymorphism at rs1495741, highly predictive of enzyme activity. Interaction was assessed using multiplicative interaction terms in multivariate-adjusted models. Results From 11 studies, 8,290 CRC cases and 9,115 controls were included. The highest quartile of red meat intake was associated with increased risk of CRC compared to the lowest quartile (OR 1.41, 95%CI 1.29 – 1.55). However, a significant association was observed only for studies with retrospective diet data, not for studies with diet prospectively assessed before cancer diagnosis. Combining all studies, high red meat intake was similarly associated with CRC in those with a rapid/intermediate NAT2 genotype (OR 1.38, 95%CI 1.20 – 1.59) as with a slow genotype (OR 1.43, 95%CI 1.28 – 1.61) (p- interaction=0.9). Conclusion We found that high red meat intake was associated with increased risk of CRC only from retrospective case-control studies and not modified by NAT2 enzyme activity. Impact Our results suggest no interaction between NAT2 genotype and red-meat intake in mediating risk of CRC. PMID:25342387

Potential drug-drug and drug-disease interactions in well-functioning community-dwelling older adults.

PubMed

Hanlon, J T; Perera, S; Newman, A B; Thorpe, J M; Donohue, J M; Simonsick, E M; Shorr, R I; Bauer, D C; Marcum, Z A

2017-04-01

There are few studies examining both drug-drug and drug-disease interactions in older adults. Therefore, the objective of this study was to describe the prevalence of potential drug-drug and drug-disease interactions and associated factors in community-dwelling older adults. This cross-sectional study included 3055 adults aged 70-79 without mobility limitations at their baseline visit in the Health Aging and Body Composition Study conducted in the communities of Pittsburgh PA and Memphis TN, USA. The outcome factors were potential drug-drug and drug-disease interactions as per the application of explicit criteria drawn from a number of sources to self-reported prescription and non-prescription medication use. Over one-third of participants had at least one type of interaction. Approximately one quarter (25·1%) had evidence of had one or more drug-drug interactions. Nearly 10·7% of the participants had a drug-drug interaction that involved a non-prescription medication. % The most common drug-drug interaction was non-steroidal anti-inflammatory drugs (NSAIDs) affecting antihypertensives. Additionally, 16·0% had a potential drug-disease interaction with 3·7% participants having one involving non-prescription medications. The most common drug-disease interaction was aspirin/NSAID use in those with history of peptic ulcer disease without gastroprotection. Over one-third (34·0%) had at least one type of drug interaction. Each prescription medication increased the odds of having at least one type of drug interaction by 35-40% [drug-drug interaction adjusted odds ratio (AOR) = 1·35, 95% confidence interval (CI) = 1·27-1·42; drug-disease interaction AOR = 1·30; CI = 1·21-1·40; and both AOR = 1·45; CI = 1·34-1·57]. A prior hospitalization increased the odds of having at least one type of drug interaction by 49-84% compared with those not hospitalized (drug-drug interaction AOR = 1·49, 95% CI = 1·11-2·01; drug-disease interaction AOR = 1·69, CI = 1·15-2·49; and both AOR = 1·84, CI = 1·20-2·84). Drug interactions are common among community-dwelling older adults and are associated with the number of medications and hospitalization in the previous year. Longitudinal studies are needed to evaluate the impact of drug interactions on health-related outcomes. © 2017 John Wiley & Sons Ltd.

Reducing Anxiety in the Pediatric Emergency Department: A Comparative Trial

PubMed Central

Heilbrunn, Benjamin R.; Wittern, Rachael E.; Lee, Justin B.; Pham, Phung K.; Hamilton, Anita H.; Nager, Alan L.

2014-01-01

Background Anxiety among patients in a Pediatric Emergency Department (PED) can be significant but often goes unaddressed. Objective To determine whether exposure to Child Life (CL) or Hospital Clowning (HC) can reduce anxiety in children presenting to a PED. Methods Patients were randomized to CL, HC or control and assessed upon: entry to examination room (T1), prior to physician arrival (T2) and during physician examination (T3), using the modified Yale Preoperative Anxiety Scale (m-YPAS). CL and HC interventions occurred for 5–10 minutes prior to physician entry. Effects were analyzed using mixed ANOVA. Results m-YPAS scores ranged from 23 to 59, with a higher score indicating increased anxiety. Mixed ANOVA on the study sample (n=113) showed a significant interaction between groups (CL, HC, control) and time, p = .02. Further analyses indicated effect of group only at T2 (MCL = 23.8, 95% CI 23.2–24.5; MHC = 25.2, 95% CI 24.2–26.2; Mcontrol = 26.1, 95% CI 24.2–27.9), p = .02. Sub-analysis of patients with T1 m-YPAS score ≥ 28 (n=56) showed a significant interaction between group and time, p = .01. Further analysis showed effect of group only at T2 (MCL = 24.4, 95% CI 23.3–25.6; MHC = 27.0, 95% CI 25.2–28.7; Mcontrol = 29.2, 95% CI 25.6–32.7), p = .003. Conclusion CL services can reduce SA for patients presenting to a PED with heightened anxiety at baseline. This reduction occurred immediately following CL intervention, but was not observed in patients exposed to HC or during physician examination. PMID:25271180

Maternal Body Mass Index Moderates the Influence of Smoking Cessation on Breast Feeding

PubMed Central

2014-01-01

Introduction: Smoking cessation is associated with greater breast feeding in newly postpartum women, while being overweight or obese is associated with lower rates of breast feeding. The purpose of this study is to examine whether the increases in breast feeding associated with smoking cessation are moderated by maternal body mass index (BMI). To our knowledge, the interaction of maternal smoking status and overweight/obesity on breast feeding has not been previously reported. Methods: Participants (N = 370) were current or recent smokers at the start of prenatal care who participated in controlled trials on smoking cessation or relapse prevention during/after pregnancy. Study participants were followed from the start of prenatal care through 24 weeks postpartum. Smoking status was biochemically verified, and maternal reports of breast feeding were collected at 2-, 4-, 8-, 12-, and 24-week postpartum assessments. Results: Women who reported postpartum smoking abstinence or had a normal/underweight prepregnancy BMI (<25) were more likely to be breast feeding at the time that smoking status was ascertained (odds ratio [OR] = 3.02, confidence interval [CI] = 2.09–4.36, and OR = 2.07, CI = 1.37–3.12, respectively). However, smoking status and BMI interacted such that (a) normal/underweight women showed a stronger association between smoking abstinence and breast feeding (OR = 4.58, CI = 2.73–7.66) than overweight/obese women (OR = 1.89, CI = 1.11–3.23), and (b) abstainers showed an association between normal/underweight BMI and breast feeding (OR = 3.53, CI = 1.96–6.37), but smokers did not (OR = 1.46, CI = 0.88–2.44). Conclusions: Overweight/obesity attenuates the positive relationship between smoking abstinence and greater breast feeding among newly postpartum women. PMID:24203932

Serum Uric Acid and the Risk of Mortality During 23 Years Follow-up in the Scottish Heart Health Extended Cohort Study

PubMed Central

Juraschek, Stephen P.; Tunstall-Pedoe, Hugh; Woodward, Mark

2017-01-01

Background Elevated uric acid is a prevalent condition with controversial health consequences. Observational studies disagree with regard to the relationship of uric acid with mortality, and with factors modifying this relationship. Objective We examined the association of serum uric acid with mortality in 15,083 participants in the Scottish Heart Health Extended Cohort (SHHEC) Study. Methods Serum uric acid measured at study enrollment. Death was ascertained using both the Scottish death register and record linkage. Results During a median follow-up of 23 years, there were 3,980 deaths. In Cox proportional hazards models with sexes combined, those in the highest fifth of uric acid had significantly greater mortality (HR 1.18, 95% CI: 1.06, 1.31) compared with the second fifth, after adjustment for traditional cardiovascular risk factors. This relationship was modified by sex (P-interaction = 0.002) with adjusted HRs of 1.69 (95% CI: 1.40, 2.04) and 0.99 (95% CI: 0.86, 1.14) in women and men, respectively. Compared with the second fifth, the highest fifth of uric acid was most associated with kidney-related death (HR: 2.08, 95% CI: 1.31, 3.32). Conclusion Elevated uric acid is associated with earlier mortality, especially in women. Future studies should evaluate mechanisms for these interactions and explore the strong association with renal-related mortality. PMID:24534458

Social Support and Thriving Health: A New Approach to Understanding the Health of Indigenous Canadians

PubMed Central

Richmond, Chantelle A.M.; Ross, Nancy A.; Egeland, Grace M.

2007-01-01

Objectives. We examined the importance of social support in promoting thriving health among indigenous Canadians, a disadvantaged population. Methods. We categorized the self-reported health status of 31625 adult indigenous Canadians as thriving (excellent, very good) or nonthriving (good, fair, poor). We measured social support with indices of positive interaction, emotional support, tangible support, and affection and intimacy. We used multivariable logistic regression analyses to estimate odds of reporting thriving health, using social support as the key independent variable, and we controlled for educational attainment and labor force status. Results. Compared with women reporting low levels of social support, those reporting high levels of positive interaction (odds ratio [OR]=1.4; 95% confidence interval [CI]=1.2, 1.6), emotional support (OR=2.1; 95% CI=1.8, 2.4), and tangible support (OR = 1.4; 95% CI = 1.2, 1.5) were significantly more likely to report thriving health. Among men, only emotional support was significantly related to thriving health (OR=1.7; 95% CI=1.5, 1.9). Thriving health status was also significantly mediated by age, aboriginal status (First Nations, Métis, or Inuit), educational attainment, and labor force status. Conclusions. Social support is a strong determinant of thriving health, particularly among women. Research that emphasizes thriving represents a positive and necessary turn in the indigenous health discourse. PMID:17761564

[Interaction between HLA-DRB1 gene polymorphism and environmental risk factors in the development of gestational diabetes mellitus].

PubMed

Wang, Ming; Zhang, Li; Liu, Xinghui

2014-04-01

To explore the interactions between human leukocyte antigen (HLA) -DRB1 gene polymorphism and environmental risk factors in gestational diabetes mellitus (GDM) pathogenesis. Pregnant women who had prenatal cares in Obstetric Department, West China Second Hospital of Sichuan University were recruited from January 1(st) to December 31(st) in 2011. A prospective cohort study was conducted in the women who had a glucose challenge test (GCT) or 75 g oral glucose tolerance test (OGTT) during 24-28 gestational weeks. A total of 104 women diagnosed with GDM were randomly included in GDM group while another 103 normal women fell into the control group. The HLA-DRB1 polymorphism was detected by Polymerase Chain Reaction - Sequence Specific Primers (PCR-SSP) method in both groups. The interactions between HLA-DRB1 polymorphism and environmental risk factors were analyzed based on the simple-case-study method. (1) There were 712 pregnant women with complete perinatal information during January 1(st) to December 31(st) , 2011, among whom 175 (24.6%) women were diagnosed with GDM. A logistic regression analysis showed that advanced maternal age (OR = 1.081, 95%CI: 1.027- 1.138), imbalanced diet (OR = 3.329, 95%CI: 2.167-5.116), high body mass index (BMI ≥ 24.0 kg/m(2)) before pregnancy (OR = 1.095, 95%CI:1.008-1.190), HBsAg carrier status (OR = 3.173, 95%CI: 1.387-7.260) and family history of diabetes mellitus (DM) (OR = 1.798, 95%CI: 1.063-3.041) were risk factors of GDM. (2) There were 49 HLA-DRB1 genotypes and 51 HLA-DRB1 genotypes in GDM group and the control group, respectively. We further compared the genotypes that occurred in over 3 cases in either group and found that HLA-DRB1*12, 16 was only detected in 5 cases (5/103, 4.9%) in control group, and the difference was significant between the two groups (P = 0.029). HLA-DRB1*11, 16 and HLA-DRB1*09,09 were only detected in 4 cases (3.8%, 4/104) and 5 cases (4.8%, 5/104) in GDM group respectively, but without significant differences between the two groups (P > 0.05). No significant difference was found in other genotype frequencies between the two groups (P > 0.05). (3) Thirteen types of HLA-DRB1 allele were detected but no significant differences were observed in their frequencies between two groups (P > 0.05). (4) A positive interaction was detected between HLA-DRB1*07 polymorphism and advanced maternal ages (OR = 5.952, 95%CI:1.314-26.970, P = 0.022), while no interaction was found between HLA-DRB polymorphisms to other risk factors such as imbalanced diet, high body mass index (BMI ≥ 24.0 kg/m(2)), HBsAg carrier status or DM family history. Advanced maternal age, unbalanced diet, high body mass index (BMI ≥ 24.0 kg/m(2)), HBsAg carrier status and DM family history are environmental risk factors of GDM in Chengdu. While HLA-DRB1*12, 16 genotype may be a protective genotype for GDM. There is a positive interaction between HLA-DRB1*07 polymorphism and advanced maternal age which may play a critic role in GDM development.

Association of genetic polymorphism of glutathione S-transferase (GSTM1, GSTT1, GSTP1) with bladder cancer susceptibility.

PubMed

Safarinejad, Mohammad Reza; Safarinejad, Saba; Shafiei, Nayyer; Safarinejad, Shiva

2013-10-01

The glutathione-S-transferases (GSTs) comprise a class of enzymes that detoxify carcinogenic compounds by conjugating glutathione to facilitate their removal. Polymorphisms in GSTM1, GSTT1, and GSTP1 genes have been related to risk for bladder cancer. Studies focusing on GSTs gene variants relationship with the risk of bladder cancer have produced conflicting and inconsistent results. We examine the association between genetic polymorphism of glutathione S-transferase P1, GSTM1, GSTT1 genes and development of bladder transitional cell carcinoma (TCC). The study population consisted of 166 histologically confirmed male bladder TCC cases and 332 healthy male controls. Genotyping was done using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method and also investigated combined gene interactions. The GSTP1 Val/Val genotype was significantly associated with bladder cancer (OR = 4.32, 95% CI: 2.64-6.34), whereas the association observed for GSTM1 null (OR = 1.32, 95% CI: 0.82-2.62; P = 0.67) and GSTT1 null genotype (OR = 1.18, 95% CI: 0.79-1.67; P = 0.74) did not reach statistical significance. There was a significant multiple interaction between GSTM1, GSTT1, and GSTP1 genotypes in risk of bladder cancer (P for interaction = 0.02). The risk associated with the concurrent presence of GSTM1 positive and GSTP1 Ile/Val or Val/Val (OR = 3.71, 95% CI: 2.34-5.54) and GSTT1 positive and GSTP1 Ile/Val or Val/Val (OR = 2.66, 95% CI: 1.54-4.72) was statistically significant. Patients carrying GSTP1 Val/Val genotype were at increased risk for developing high-grade (OR = 7.68, 95% CI: 4.73-19.25) and muscle invasive (OR = 10.67, 95% CI: 6.34-21.75) bladder cancer. High risk for bladder TCC also was observed with respect to combined GSTT1 null/GSTP1 Ile/Val or Val/Val (OR = 4.76, 95% CI: 2.68-18.72) and GSTM1 null/GSTT1 null/GSTP1 Ile/Val or Val/Val (OR = 6.42, 95% CI: 4.76-14.72) genotype variant. This study suggests that the GSTP1 polymorphism and its combination with GSTM1, and GSTT1 may be associated with bladder cancer susceptibility in the Iranian population. Further confirmation in large population-based studies is needed. Copyright © 2013 Elsevier Inc. All rights reserved.

CHA2DS2-VASc score and risk of thromboembolism and bleeding in patients with atrial fibrillation and recent cancer.

PubMed

D'Souza, Maria; Carlson, Nicholas; Fosbøl, Emil; Lamberts, Morten; Smedegaard, Lærke; Nielsen, Dorte; Torp-Pedersen, Christian; Gislason, Gunnar; Schou, Morten

2018-04-01

Background Cancer may influence the risk of thromboembolism and bleeding associated with the CHA 2 DS 2 -VASc score. We examined the risk of thromboembolism and bleeding associated with the CHA 2 DS 2 -VASc score in atrial fibrillation patients with and without recent cancer. Methods and results Using nationwide registers all patients diagnosed with atrial fibrillation from 2000 to 2015 and not on oral anticoagulation or heparin therapy were included and followed for 2 years. Recent cancer was defined by a cancer diagnosis 5 years or fewer earlier. Risks of thromboembolism and bleeding were estimated in cumulative incidence curves and Cox regression models. We included 122,053 patients with incident atrial fibrillation, 12,014 (10%) had recent cancer. The 2-year cumulative incidence of thromboembolism and bleeding in patients with versus without recent cancer was 1.7% (95% confidence interval (CI) 0.5-2.8) and 4.3% (95% CI 2.4-6.2) versus 1.2% (95% CI 0.9-1.5) and 1.7% (95% CI 1.4-2.0) for CHA 2 DS 2 -VASc score 0; 3.2% (95%CI 2.2-4.3) and 4.4% (95%CI 3.2-5.6) versus 1.8% (95%CI 1.6-2.1) and 3.0% (95% CI 2.7-3.3) for CHA 2 DS 2 -VASc score 1; and 7.1% (95% CI 6.6-7.7) and 6.8% (95% CI 6.3-7.2) versus 10.9% (95% CI 10.7-11.1) and 6.2% (95% CI 6.1-6.4) for CHA 2 DS 2 -VASc score 2 or greater. Although the CHA 2 DS 2 -VASc score was associated with thromboembolism and bleeding in both patients with and without cancer, the association differed between the groups for thromboembolism (test for interaction, p < 0.001) and bleeding (test for interaction, p < 0.001). Conclusion The association of the CHA 2 DS 2 -VASc score and risk of thromboembolism and bleeding differed between atrial fibrillation patients with and without recent cancer. Therefore, the CHA 2 DS 2 -VASc score should be used with caution in patients with recent cancer.

Acute kidney injury during concomitant use of valacyclovir and loxoprofen: detecting drug-drug interactions in a spontaneous reporting system.

PubMed

Yue, Zhihua; Shi, Jinhai; Jiang, Pengli; Sun, He

2014-11-01

Little is known about the effects of drug-drug interactions between valacyclovir and non-steroidal anti-inflammatory drugs (NSAIDs). In this study, we analysed the adverse event 'acute kidney injury (AKI)' resulting from a possible interaction between loxoprofen (a non-selective NSAID) and valacyclovir in reports received by FDA Adverse Event Reporting System (AERS) database between January 2004 and June 2012. Adverse event reports of elderly patients aged ≥65 years old were included in the study. Exposure categories were divided into three index groups (only valacyclovir or loxoprofen was used, and both drugs were concomitantly used) and a reference group (neither valacyclovir nor loxoprofen were used). Case/non-case AKI reports associated with these drugs were recorded and analysed by the reporting odds ratio (ROR). In total, 447 002 reports were included in the study. The ROR, adjusted for year of reporting, age and sex, for an AKI in elderly patients who used only valacyclovir or loxoprofen compared with elderly patients who used neither valacyclovir nor loxoprofen was 4.6 (95%CI: 4.1-5.2) and 1.4 (95%CI: 1.2-1.6), respectively, while the adjusted ROR was 26.0 (95%CI: 19.2-35.3) when both drugs were concomitantly used. Case reports in AERS are suggestive that interactions between valacyclovir and loxoprofen resulting in AKI may occur, while this association needs to be analysed by other methods in more detail in order to determine the real strength of the relationship. Copyright © 2014 John Wiley & Sons, Ltd.

Genetic polymorphisms involved in dopaminergic neurotransmission and risk for Parkinson's disease in a Japanese population

PubMed Central

2011-01-01

Background Parkinson's disease (PD) is characterized by alterations in dopaminergic neurotransmission. Genetic polymorphisms involved in dopaminergic neurotransmission may influence susceptibility to PD. Methods We investigated the relationship of catechol-O-methyltransferase (COMT), monoamine oxidase B (MAOB), dopamine receptor (DR) D2 and DRD4 polymorphisms and PD risk with special attention to the interaction with cigarette smoking among 238 patients with PD and 369 controls in a Japanese population. Results Subjects with the AA genotype of MAOB rs1799836 showed a significantly increased risk of PD (odds ratio (OR) = 1.70, 95% confidence interval (CI) = 1.12 - 2.58) compared with the AG and GG genotypes combined. The AA genotype of COMT rs4680 was marginally associated with an increased risk of PD (OR = 1.86, 95% CI = 0.98 - 3.50) compared with the GG genotype. The DRD2 rs1800497 and DRD4 rs1800955 polymorphisms showed no association with PD. A COMT -smoking interaction was suggested, with the combined GA and AA genotypes of rs4680 and non-smoking conferring significantly higher risk (OR = 3.97, 95% CI = 2.13 - 7.41) than the AA genotype and a history of smoking (P for interaction = 0.061). No interactions of smoking with other polymorphisms were observed. Conclusions The COMT rs4680 and MAOB rs1799836 polymorphisms may increase susceptibility to PD risk among Japanese. Future studies involving larger control and case populations and better pesticide exposure histories will undoubtedly lead to a more thorough understanding of the role of the polymorphisms involved in the dopamine pathway in PD. PMID:21781348

Platelet Count Mediates the Contribution of a Genetic Variant in LRRC16A to ARDS Risk

PubMed Central

Wei, Yongyue; Wang, Zhaoxi; Su, Li; Chen, Feng; Tejera, Paula; Bajwa, Ednan K.; Wurfel, Mark M.; Lin, Xihong

2015-01-01

BACKGROUND: Platelets are believed to be critical in pulmonary-origin ARDS as mediators of endothelial damage through their interactions with fibrinogen and multiple signal transduction pathways. A prior meta-analysis identified five loci for platelet count (PLT): BAD, LRRC16A, CD36, JMJD1C, and SLMO2. This study aims to validate the quantitative trait loci (QTLs) of PLT within BAD, LRRC16A, CD36, JMJD1C, and SLMO2 among critically ill patients and to investigate the associations of these QTLs with ARDS risk that may be mediated through PLT. METHODS: ARDS cases and at-risk control subjects were recruited from the intensive care unit of the Massachusetts General Hospital. Exome-wide genotyping data of 629 ARDS cases and 1,026 at-risk control subjects and genome-wide gene expression profiles of 18 at-risk control subjects were generated for analysis. RESULTS: Single-nucleotide polymorphism (SNP) rs7766874 within LRRC16A was a significant locus for PLT among at-risk control subjects (β = −13.00; 95% CI, −23.22 to −2.77; P = .013). This association was validated using LRRC16A gene expression data from at-risk control subjects (β = 77.03 per 1 SD increase of log2-transformed expression; 95% CI, 27.26-126.80; P = .005). Further, rs7766874 was associated with ARDS risk conditioned on PLT (OR = 0.68; 95% CI, 0.51-0.90; P = .007), interacting with PLT (OR = 1.15 per effect allele per 100 × 103/μL of PLT; 95% CI, 1.03-1.30; P = .015), and mediated through PLT (indirect OR = 1.045; 95% CI, 1.007-1.085; P = .021). CONCLUSIONS: Our findings support the role of LRRC16A in platelet formation and suggest the importance of LRRC16A in ARDS pathophysiology by interacting with, and being mediated through, platelets. PMID:25254322

Polymorphisms in ABC Transporter Genes and Concentrations of Mercury in Newborns – Evidence from Two Mediterranean Birth Cohorts

PubMed Central

Llop, Sabrina; Engström, Karin; Ballester, Ferran; Franforte, Elisa; Alhamdow, Ayman; Pisa, Federica; Tratnik, Janja Snoj; Mazej, Datja; Murcia, Mario; Rebagliato, Marisa; Bustamante, Mariona; Sunyer, Jordi; Sofianou-Katsoulis, Αikaterini; Prasouli, Alexia; Antonopoulou, Eleni; Antoniadou, Ioanna; Nakou, Sheena; Barbone, Fabio; Horvat, Milena; Broberg, Karin

2014-01-01

Background The genetic background may influence methylmercury (MeHg) metabolism and neurotoxicity. ATP binding cassette (ABC) transporters actively transport various xenobiotics across biological membranes. Objective To investigate the role of ABC polymorphisms as modifiers of prenatal exposure to MeHg. Methods The study population consisted of participants (n = 1651) in two birth cohorts, one in Italy and Greece (PHIME) and the other in Spain (INMA). Women were recruited during pregnancy in Italy and Spain, and during the perinatal period in Greece. Total mercury concentrations were measured in cord blood samples by atomic absorption spectrometry. Maternal fish intake during pregnancy was determined from questionnaires. Polymorphisms (n = 5) in the ABC genes ABCA1, ABCB1, ABCC1 and ABCC2 were analysed in both cohorts. Results ABCB1 rs2032582, ABCC1 rs11075290, and ABCC2 rs2273697 modified the associations between maternal fish intake and cord blood mercury concentrations. The overall interaction coefficient between rs2032582 and log2-transformed fish intake was negative for carriers of GT (β = −0.29, 95%CI −0.47, −0.12) and TT (β = −0.49, 95%CI −0.71, −0.26) versus GG, meaning that for a doubling in fish intake of the mothers, children with the rs2032582 GG genotype accumulated 35% more mercury than children with TT. For rs11075290, the interaction coefficient was negative for carriers of TC (β = −0.12, 95%CI −0.33, 0.09), and TT (β = −0.28, 95%CI −0.51, −0.06) versus CC. For rs2273697, the interaction coefficient was positive when combining GA+AA (β = 0.16, 95%CI 0.01, 0.32) versus GG. Conclusion The ABC transporters appear to play a role in accumulation of MeHg during early development. PMID:24831289

Exponentially more precise quantum simulation of fermions in the configuration interaction representation

NASA Astrophysics Data System (ADS)

Babbush, Ryan; Berry, Dominic W.; Sanders, Yuval R.; Kivlichan, Ian D.; Scherer, Artur; Wei, Annie Y.; Love, Peter J.; Aspuru-Guzik, Alán

2018-01-01

We present a quantum algorithm for the simulation of molecular systems that is asymptotically more efficient than all previous algorithms in the literature in terms of the main problem parameters. As in Babbush et al (2016 New Journal of Physics 18, 033032), we employ a recently developed technique for simulating Hamiltonian evolution using a truncated Taylor series to obtain logarithmic scaling with the inverse of the desired precision. The algorithm of this paper involves simulation under an oracle for the sparse, first-quantized representation of the molecular Hamiltonian known as the configuration interaction (CI) matrix. We construct and query the CI matrix oracle to allow for on-the-fly computation of molecular integrals in a way that is exponentially more efficient than classical numerical methods. Whereas second-quantized representations of the wavefunction require \\widetilde{{ O }}(N) qubits, where N is the number of single-particle spin-orbitals, the CI matrix representation requires \\widetilde{{ O }}(η ) qubits, where η \\ll N is the number of electrons in the molecule of interest. We show that the gate count of our algorithm scales at most as \\widetilde{{ O }}({η }2{N}3t).

Grass Roots Design for the Ocean Science of Tomorrow

NASA Astrophysics Data System (ADS)

Jul, S.; Peach, C. L.; Kilb, D. L.; Schofield, O.; Fisher, C.; Quintana, C.; Keen, C. S.

2010-12-01

Current technologies offer the opportunity for ocean science to expand its traditional expeditionary base by embracing e-science methods of continuous interactive real-time research. The Ocean Observatories Initiative Cyberinfrastructure (OOI CI) is an NSF-funded effort to develop a national cyberinfrastructure that will allow researchers, educators and others to share in this new type of oceanography. The OOI is an environmental observatory spanning coastal waters to the deep ocean, enabled by the CI to offer scientists continuous interactive access to instruments in the ocean, and allow them to search, subscribe to and access real-time or archival data streams. It will also supply interactive analysis and visualization tools, and a virtual social environment for discovering and realizing collaborative opportunities. Most importantly, it provides an extensible open-access cyberinfrastructure that supports integration of new technologies and observatories, and which will allow adoption of its tools elsewhere, such as by the Integrated Ocean Observing System (IOOS). The eventual success of such a large and flexible system requires the input of a large number of people, and user-centered design has been a driving philosophy of the OOI CI from its beginning. Support for users’ real needs cannot be designed as an add-on or casual afterthought, but must be deeply embedded in all aspects of a project, from inception through architecture, implementation, and deployment. The OOI CI strategy is to employ the skills and knowledge of a small number of user experience professionals to channel and guide a very large collective effort to deliver tools, interfaces and interactions that are intellectually stimulating, scientifically productive, and conducive to innovation. Participation from all parts of the user community early in the design process is vital to meeting these goals. The OOI user experience team will be on hand to meet members of the Earth and ocean sciences community, and invites them to become partners in the design of the Ocean Observatory by offering their thoughts, ideas and observations.

A Randomized Factorial Trial of Vitamins C, E, and Beta-Carotene in the Secondary Prevention of Cardiovascular Events in Women

PubMed Central

Cook, Nancy R.; Albert, Christine M.; Gaziano, J. Michael; Zaharris, Elaine; MacFadyen, Jean; Danielson, Eleanor; Buring, Julie E.; Manson, JoAnn E.

2007-01-01

Background Randomized trials have largely failed to support an effect of antioxidant vitamins on risk of cardiovascular disease (CVD). Few trials have examined interactions among antioxidants, and no previous trial has examined the individual effect of vitamin C on CVD. Methods WACS tested the effects of vitamins C (500 mg daily), E (600 IU every other day), and beta-carotene (50 mg every other day) on the combined outcome of myocardial infarction (MI), stroke, coronary revascularization, or CVD death among 8,171 female health professionals at increased risk in a 2×2×2 factorial design. Participants were 40 years or older with a prior history of CVD or three or more CVD risk factors, and were followed an average 9.4 years, from 1995-96 to 2005. Results 1,450 women experienced one or more CVD outcomes. There was no overall effect of vitamin C (RR=1.02, 95% CI=0.92-1.13, p=0.71), vitamin E (RR=0.94, 95% CI=0.85-1.04, p=0.23), or beta-carotene (RR=1.02, 95% CI=0.92-1.13, p=0.71) on the primary combined endpoint, or on the individual secondary outcomes of MI, stroke, coronary revascularization, or CVD death. A marginally significant reduction in the primary outcome with active vitamin E was observed among the pre-specified subgroup of women with prior CVD (RR=0.89, 95% CI=0.79-1.00, p=0.04; p-interaction=0.07). There were no significant interactions between agents for the primary endpoint, but those randomized to both active vitamin C and E experienced fewer strokes (p for interaction=0.03). Conclusion There were no overall effects of vitamins C, E or beta-carotene on cardiovascular events among women at high risk for CVD. Trial Registration clinicaltrials.gov Identifier: NCT00000541 PMID:17698683

[Potential interaction effect on attention-deficit/hyperactivity disorder between mother's educational level and preschoolers' dietary pattern].

PubMed

Yan, S Q; Cao, H; Gu, C L; Gao, G P; Ni, L L; Tao, H H; Shao, T; Xu, Y Q; Tao, F B

2018-04-10

Objective: To explore the interaction effect between mother's educational level and preschoolers' dietary pattern on attention-deficit/hyperactivity disorder (ADHD). Methods: In 2014, there were 16 439 children aged 3-6 years old from 91 kindergartens in Ma'anshan municipality of China. A semi-quantitative food frequency questionnaire and the 10-item Chinese version of the Conners' Abbreviated Symptom Questionnaire (C-ASQ) were administered to assess the usual dietary intake and symptoms on ADHD. Social-demographic information was collected through questionnaires. Unconditional logistic regression was used to analyze the multiplication interaction effect between mother's educational level and preschoolers' dietary pattern on ADHD. Excel software was used to analyze the additive interaction effect of mother's educational level and preschoolers'dietary pattern on ADHD. Results: Results showed that factors as: mother's low educational level[a OR =1.31 (1.13-1.52)], scores related to preschoolers in the top quintile of "food processing" [a OR =1.31 (1.16-1.48)] and "snack" [a OR =1.45 (1.29-1.63)]patterns showed greater odds while preschoolers in the top quintile of "vegetarian" [a OR =0.80 (0.71-0.90)]showed less odds for having ADHD symptoms. Both multiplication and additive interactions were observed between mothers with less education. The processed dietary patterns ( OR =1.17, 95% CI : 1.11-1.25), relative excess risk of interaction ( RERI ), attributable proportion ( AP ) and the interaction index ( SI ) appeared as 0.21, 0.13 and 1.47, respectively. Multiplication interaction was observed between levels of mother's low education and the snack dietary pattern ( OR =1.21, 95% CI : 1.14-1.29), with RERI , AP and SI as 0.49, 0.26 and 2.36, respectively. However, neither multiplication interaction or additive interaction was noticed between levels of mother's low education and the vegetarian dietary pattern ( OR =0.97, 95% CI : 0.92-1.03), with RERI , AP and SI as 0.09, 0.05 and 1.15, respectively. Conclusions: Levels of mother's low education presented a risk factor for ADHD symptoms in preschool children. Both multiplication interaction and additive interaction were observed between mother's low education levels and the processed dietary pattern. Multiplication interaction was noticed between mother's education levels and the snack dietary pattern but not with the vegetarian dietary pattern.

Sex-dependent difference in the effect of metformin on colorectal cancer-specific mortality of diabetic colorectal cancer patients

PubMed Central

Park, Jung Won; Lee, Jin Ha; Park, Ye Hyun; Park, Soo Jung; Cheon, Jae Hee; Kim, Won Ho; Kim, Tae Il

2017-01-01

AIM To assess factors associated with the higher effect of metformin on mortality in diabetic colorectal cancer (CRC) patients, since the factors related to the effectiveness of metformin have not been identified yet. METHODS Between January 2000 and December 2010, 413 patients diagnosed with both stage 3/4 CRC and diabetes mellitus were identified. Patients’ demographics and clinical characteristics were analyzed. The effect of metformin on CRC-specific mortality and the interactions between metformin and each adjusted factor were evaluated. RESULTS Total follow-up duration was median 50 mo (range: 1-218 mo). There were 85 deaths (45.9%) and 72 CRC-specific deaths (38.9%) among 185 patients who used metformin, compared to 130 total deaths (57.0%) and 107 CRC-specific deaths (46.9%) among 228 patients who did not use metformin. In multivariate analysis, survival benefit associated with metformin administration was identified (HR = 0.985, 95%CI: 0.974-0.997, P = 0.012). Interaction test between metformin and sex after adjustment for relevant factors revealed that female CRC patients taking metformin exhibited a significantly lower CRC-specific mortality rate than male CRC patients taking metformin (HR = 0.369, 95%CI: 0.155-0.881, P = 0.025). Furthermore, subgroup analysis revealed significant differences in CRC-specific mortality between the metformin and non-metformin groups in female patients (HR = 0.501, 95%CI: 0.286-0.879, P = 0.013) but not male patients (HR = 0.848, 95%CI: 0.594-1.211, P = 0.365). There were no significant interactions between metformin and other adjusted factors on CRC-specific mortality. CONCLUSION We showed a strong sex-dependent difference in the effect of metformin on CRC-specific mortality in advanced stage CRC patients with diabetes. PMID:28811714

Conditional cash transfers improve retention in PMTCT services by mitigating the negative effect of not having money to come to the clinic

PubMed Central

Yotebieng, Marcel; Moracco, Kathryn E.; Thirumurthy, Harsha; Edmonds, Andrew; Tabala, Martine; Kawende, Bienvenu; Wenzi, Landry Kipula; Okitolonda, Emile W.; Behets, Frieda

2016-01-01

Objective To elucidate the mechanisms by which a cash incentive intervention increases retention in prevention of mother-to-child transmission (PMTCT) services. Methods We used data from a randomized controlled trial in Kinshasa, Democratic Republic of Congo. Perceptual factors associated with loss-to-follow-up (LTFU) through six weeks postpartum were first identified. Then, binomial models were used to assess interactions between LTFU and identified factors, and the cash incentive intervention. Results Participants were less likely to be LTFU if they perceived HIV as a “very serious” health problem for their baby vs. not (risk difference [RD], −0.13; 95% confidence interval [CI], −0.30, 0.04), if they believed it would be “very likely” to pass HIV on to their baby if they did not take any HIV drug vs. not (RD, −0.15; 95% CI, −0.32, 0.02), and if they anticipated that not having money would make it difficult for them to come to clinic vs. not (RD, 0.12; 95% CI, −0.07, 0.30). The effect of each of the three factors on LTFU was antagonistic to that of receiving the cash incentive intervention. The excess risk due to interaction between the cash incentive intervention and the anticipated difficulty of “not having money” to come to clinic was exactly equal to the effect of removing this perceived barrier (excess risk due to interaction, −0.12; 95% CI, −0.35, 0.10). Conclusions Our analyses show that cash transfers improve retention in PMTCT services mainly by mitigating the negative effect of not having money to come to the clinic. PMID:27787342

Black–White Blood Pressure Disparities: Depressive Symptoms and Differential Vulnerability to Blood Lead

PubMed Central

Gee, Gilbert C.; Connell, Cathleen; Snow, Rachel C.; Morenoff, Jeffrey; Hu, Howard

2012-01-01

Background: Blacks have higher hypertension rates than whites, but the reasons for these disparities are unknown. Differential vulnerability, through which stress alters vulnerability to the effects of environmental hazards, is an emergent notion in environmental health that may contribute to these disparities. Objectives: We examined whether blacks and whites exhibit different associations between blood lead (BPb) and blood pressure (BP) and whether depressive symptoms may play a role. Methods: Using the National Health and Nutrition Examination Survey 2005–2008, we regressed BP on the three-way interaction among race/ethnicity, BPb, and depressive symptoms in blacks and whites ≥ 20 years of age. Results: Blacks but not whites showed a positive association between BPb and systolic blood pressure (SBP). The disparity in this association between blacks and whites appeared to be specific to the high depressive symptoms group. In the low depressive symptoms group, there was no significant black–white disparity (βinteraction = 0.9 mmHg; 95% CI: –0.9, 2.7). However, of those with high depressive symptoms, blacks and whites had 5.6 mmHg (95% CI: 2.0, 9.2) and 1.2 mmHg (95% CI: –0.5, 2.9) increases in SBP, respectively, in association with each doubling of BPb (βinteraction = 4.4 mmHg; 95% CI: 0.5, 8.3). The pattern of results was similar for diastolic blood pressure. Conclusions: Our results suggest that depressive symptoms may contribute to the black–white disparity in the association between BPb and BP. Depressive symptoms may result, in part, from psychosocial stress. Our results support the notion that stress increases vulnerability to the health effects of environmental hazards and suggest that stress-related vulnerability may be an important determinant of racial/ethnic health disparities. PMID:23127977

Household responsibilities, income, and ambulatory blood pressure among working men and women

PubMed Central

Thurston, Rebecca C.; Sherwood, Andrew; Matthews, Karen A.; Blumenthal, James A.

2011-01-01

Objective To test the hypothesis that a greater perceived responsibility for household tasks and a greater number of hours spent doing these tasks would be associated with elevated ambulatory systolic (SBP) and diastolic blood pressure (DBP). The connection between job characteristics and cardiovascular outcomes has been widely studied. However, less is known about links between household work characteristics and cardiovascular health. Methods 113 employed unmedicated hypertensive men and women underwent one day of ambulatory blood pressure (ABP) monitoring. Participants provided information on 1) the number of hours spent doing and 2) their degree of responsibility for seven household tasks (child care, pet care, caring for ill/elderly, household chores, house/car repair, yardwork, finances). Associations between task hours and responsibility ratings in relation to SBP and DBP were estimated using generalized estimating equations, with covariates age, race, gender, body mass index, location, posture. Interactions with gender and socioeconomic position were assessed. Results A greater perceived responsibility for household tasks, but not the hours spent doing these tasks, was associated with higher ambulatory SBP (b(95% confidence interval (CI))=0.93(0.29–1.56), p=0.004) and DBP (b(95%CI)=0.30(0.10–0.51), p=0.003)). Significant interactions with income indicated that associations between household responsibilities and ABP were most pronounced among low income participants (SBP: b(95%CI)=1.40(0.58–2.21), p<0.001; DBP: b(95%CI)=0.48(0.18–0.78), p<0.01). The task most strongly associated with BP was household chores. No interactions with gender were observed. Conclusions Greater perceived responsibility for household tasks was associated with elevated ABP, particularly for lower income participants. Household obligations may have important implications for cardiovascular health, meriting further empirical attention. PMID:21217097

Evaluating the Impact of Guessing and Its Interactions With Other Test Characteristics on Confidence Interval Procedures for Coefficient Alpha

PubMed Central

Paek, Insu

2015-01-01

The effect of guessing on the point estimate of coefficient alpha has been studied in the literature, but the impact of guessing and its interactions with other test characteristics on the interval estimators for coefficient alpha has not been fully investigated. This study examined the impact of guessing and its interactions with other test characteristics on four confidence interval (CI) procedures for coefficient alpha in terms of coverage rate (CR), length, and the degree of asymmetry of CI estimates. In addition, interval estimates of coefficient alpha when data follow the essentially tau-equivalent condition were investigated as a supplement to the case of dichotomous data with examinee guessing. For dichotomous data with guessing, the results did not reveal salient negative effects of guessing and its interactions with other test characteristics (sample size, test length, coefficient alpha levels) on CR and the degree of asymmetry, but the effect of guessing was salient as a main effect and an interaction effect with sample size on the length of the CI estimates, making longer CI estimates as guessing increases, especially when combined with a small sample size. Other important effects (e.g., CI procedures on CR) are also discussed. PMID:29795863

Excited state electron affinity calculations for aluminum

NASA Astrophysics Data System (ADS)

Hussein, Adnan Yousif

2017-08-01

Excited states of negative aluminum ion are reviewed, and calculations of electron affinities of the states (3s^23p^2)^1D and (3s3p^3){^5}{S}° relative to the (3s^23p)^2P° and (3s3p^2)^4P respectively of the neutral aluminum atom are reported in the framework of nonrelativistic configuration interaction (CI) method. A priori selected CI (SCI) with truncation energy error (Bunge in J Chem Phys 125:014107, 2006) and CI by parts (Bunge and Carbó-Dorca in J Chem Phys 125:014108, 2006) are used to approximate the valence nonrelativistic energy. Systematic studies of convergence of electron affinity with respect to the CI excitation level are reported. The calculated value of the electron affinity for ^1D state is 78.675(3) meV. Detailed Calculations on the ^5S°c state reveals that is 1216.8166(3) meV below the ^4P state.

Does emergency presentation of cancer represent poor performance in primary care? Insights from a novel analysis of linked primary and secondary care data

PubMed Central

Murchie, Peter; Smith, Sarah M; Yule, Michael S; Adam, Rosalind; Turner, Melanie E; Lee, Amanda J; Fielding, Shona

2017-01-01

Background: People diagnosed with cancer following emergency presentation have poorer short-term survival. To what extent this signifies a missed opportunity for earlier diagnosis in primary care remains unclear as little detailed data exist on the patient/general practitioner interaction beforehand. Methods: Analysis of primary care and regional data for 1802 cancer patients from Northeast Scotland. Adjusted odds ratios (OR) and 95% confidence intervals (CIs) for patient and GP practice predictors of emergency presentation. Qualitative context coding of primary care interaction before emergency presentation. Results: Emergency presentations equalled 20% (n=365). Twenty-eight per cent had no relevant prior GP contact. Of those with prior GP contact 30% were admitted while waiting to be seen in secondary care, and 19% were missed opportunities for earlier diagnosis. Associated predictors: no prior GP contact (OR=3.89; CI 95% 2.14–7.09); having lung (OR=23.24; 95% CI 7.92–68.21), colorectal (OR=18.49; CI 95% 6.60–51.82) and upper GI cancer (OR=18.97; CI 95% 6.08–59.23); ethnicity (OR=2.78; CI 95% 1.27–6.06). Conclusions: Our novel approach has revealed that emergency cancer presentation is more complex than previously thought. Patient delay, prolonged referral pathways and missed opportunities by GPs all contribute, but emergency presentation can also represent effective care. Resources should be used proportionately to raise public and GP awareness and improve post-referral pathways. PMID:28334728

[Gene-gene interaction on central obesity in school-aged children in China].

PubMed

Fu, L W; Zhang, M X; Wu, L J; Gao, L W; Mi, J

2017-07-10

Objective: To investigate possible effect of 6 obesity-associated SNPs in contribution to central obesity and examine whether there is an interaction in the 6 SNPs in the cause of central obesity in school-aged children in China. Methods: A total of 3 502 school-aged children who were included in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) Study were selected, and based on the age and sex specific waist circumference (WC) standards in the BCAMS study, 1 196 central obese cases and 2 306 controls were identified. Genomic DNA was extracted from peripheral blood white cells using the salt fractionation method. A total of 6 single nucleotide polymorphisms ( FTO rs9939609, MC4R rs17782313, BDNF rs6265, PCSK1 rs6235, SH2B1 rs4788102, and CSK rs1378942) were genotyped by TaqMan allelic discrimination assays with the GeneAmp 7900 sequence detection system (Applied Biosystems, Foster City, CA, USA). Logistic regression model was used to investigate the association between 6 SNPs and central obesity. Gene-gene interactions among 6 polymorphic loci were analyzed by using the Generalized Multifactor Dimensionality Reduction (GMDR) method, and then logistic regression model was constructed to confirm the best combination of loci identified in the GMDR. Results: After adjusting gender, age, Tanner stage, physical activity and family history of obesity, the FTO rs9939609-A, MC4R rs17782313-C and BDNF rs6265-G alleles were associated with central obesity under additive genetic model ( OR =1.24, 95 %CI : 1.06-1.45, P =0.008; OR =1.26, 95 %CI : 1.11-1.43, P =2.98×10(-4); OR =1.18, 95 % CI : 1.06-1.32, P =0.003). GMDR analysis showed a significant gene-gene interaction between MC4R rs17782313 and BDNF rs6265 ( P =0.001). The best two-locus combination showed the cross-validation consistency of 10/10 and testing accuracy of 0.539. This interaction showed the maximum consistency and minimum prediction error among all gene-gene interaction models evaluated. Moreover, the combination of MC4R rs17782313-C and BDNF rs6265-G was associated with an increased risk of central obesity after adjustment for gender, age, Tanner stage, physical activity and family history of obesity. Conclusions: Our study showed that FTO rs9939609-A, MC4R rs17782313-C and BDNF rs6265-G alleles were associated with central obesity, and statistical interaction between MC4R rs17782313-C and BDNF rs6265-G increased risk of central obesity in school-aged children in China.

Preferential interactions in pigmented, polymer blends - C.I. Pigment Blue 15:4 and C.I. Pigment Red 122 - as used in a poly(carbonate)-poly(butylene terephthalate) polymer blend.

PubMed

Fagelman, K E; Guthrie, J T

2005-11-18

Some important characteristics of selected pigments have been evaluated, using the inverse gas chromatography (IGC) technique, that indicate the occurrence of preferential interactions in pigmented polymer blends. Attention has been given to copper phthalocyanine pigments and to quinacridone pigments incorporated in polycarbonate-poly(butylene terephthalate) blends. Selected supporting techniques were used to provide supplementary information concerning the pigments of interest, C.I. Pigment Blue 15:4 and C.I. Pigment Red 122. For C.I. Pigment Red 122 and for C.I. Pigment Blue, the dispersive component of the surface free energy decreases as the temperature increases, indicating the relative ease with which the molecules can be removed from the surface.

Effectiveness of a diet and physical activity promotion strategy on the prevention of obesity in Mexican school children

PubMed Central

2012-01-01

Background Overweight and obesity in children in Mexico was among the countries with the highest prevalence's in the world. Mexico currently has few innovative and comprehensive experiences to help curb the growth of this serious public health problem. Therefore, the aim of this study is to assess the effectiveness of a nutrition and physical activity strategy, called "Nutrition on the Go" ("nutrición en movimiento") in maintaining the BMI values of school children in the State of Mexico. Methods A two-stage cluster trial was carried out. Sixty schools were selected in the State of Mexico, of which 30 were randomly assigned to the intervention group (IG) and 30 to the control group (CG). A total of 1020 fifth grade school children participated. The intervention strategy aimed to decrease the energy content of school breakfasts and include fruits and vegetables, as well as increase physical activity and the consumption of water during the time spent at school. The strategy was implemented over a 6-month period. Results The estimated probability (EP) of obesity between baseline and the final stage for the IG decreased 1% (Initial EP = 11.8%, 95%CI 9.0, 15.2, final EP = 10.8, 95%CI 8.4, 13.) For the CG, the probability increased 0.9% (baseline EP = 10.6%; 95%CI 8.1, 13.7; final EP = 11.5, 95%CI 9.0, 14.6). The interaction between the intervention and the stage is the average odd time corrected treatment effect, which is statistically significant (p = 0.01) (OR = 0.68, 95%CI 0.52, 091). This represents the interaction between intervention and stage, which is highly significant (p = 0.01) (OR = 0.68; 95%CI 0.52, 091). In addition, girls had a protective effect on obesity (OR = 0.56; 95%CI 0.39, 0.80). Conclusions The intervention strategy is effective in maintaining the BMI of school children. PMID:22381137

Exploring the Nature of the H[subscript 2] Bond. 1. Using Spreadsheet Calculations to Examine the Valence Bond and Molecular Orbital Methods

ERIC Educational Resources Information Center

Halpern, Arthur M.; Glendening, Eric D.

2013-01-01

A three-part project for students in physical chemistry, computational chemistry, or independent study is described in which they explore applications of valence bond (VB) and molecular orbital-configuration interaction (MO-CI) treatments of H[subscript 2]. Using a scientific spreadsheet, students construct potential-energy (PE) curves for several…

Additive Interaction of MTHFR C677T and MTRR A66G Polymorphisms with Being Overweight/Obesity on the Risk of Type 2 Diabetes.

PubMed

Zhi, Xueyuan; Yang, Boyi; Fan, Shujun; Li, Yongfang; He, Miao; Wang, Da; Wang, Yanxun; Wei, Jian; Zheng, Quanmei; Sun, Guifan

2016-12-15

Although both methylenetetrahydrofolate reductase ( MTHFR ) C677T and methionine synthase reductase ( MTRR ) A66G polymorphisms have been associated with type 2 diabetes (T2D), their interactions with being overweight/obesity on T2D risk remain unclear. To evaluate the associations of the two polymorphisms with T2D and their interactions with being overweight/obesity on T2D risk, a case-control study of 180 T2D patients and 350 healthy controls was conducted in northern China. Additive interaction was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S). After adjustments for age and gender, borderline significant associations of the MTHFR C677T and MTRR A66G polymorphisms with T2D were observed under recessive (OR = 1.43, 95% CI: 0.98-2.10) and dominant (OR = 1.43, 95% CI: 1.00-2.06) models, respectively. There was a significant interaction between the MTHFR 677TT genotype and being overweight/obesity on T2D risk (AP = 0.404, 95% CI: 0.047-0.761), in addition to the MTRR 66AG/GG genotypes (RERI = 1.703, 95% CI: 0.401-3.004; AP = 0.528, 95% CI: 0.223-0.834). Our findings suggest that individuals with the MTHFR 677TT or MTRR 66AG/GG genotypes are more susceptible to the detrimental effect of being overweight/obesity on T2D. Further large-scale studies are still needed to confirm our findings.

Bayesian logistic regression in detection of gene-steroid interaction for cancer at PDLIM5 locus.

PubMed

Wang, Ke-Sheng; Owusu, Daniel; Pan, Yue; Xie, Changchun

2016-06-01

The PDZ and LIM domain 5 (PDLIM5) gene may play a role in cancer, bipolar disorder, major depression, alcohol dependence and schizophrenia; however, little is known about the interaction effect of steroid and PDLIM5 gene on cancer. This study examined 47 single-nucleotide polymorphisms (SNPs) within the PDLIM5 gene in the Marshfield sample with 716 cancer patients (any diagnosed cancer, excluding minor skin cancer) and 2848 noncancer controls. Multiple logistic regression model in PLINK software was used to examine the association of each SNP with cancer. Bayesian logistic regression in PROC GENMOD in SAS statistical software, ver. 9.4 was used to detect gene- steroid interactions influencing cancer. Single marker analysis using PLINK identified 12 SNPs associated with cancer (P< 0.05); especially, SNP rs6532496 revealed the strongest association with cancer (P = 6.84 × 10⁻³); while the next best signal was rs951613 (P = 7.46 × 10⁻³). Classic logistic regression in PROC GENMOD showed that both rs6532496 and rs951613 revealed strong gene-steroid interaction effects (OR=2.18, 95% CI=1.31-3.63 with P = 2.9 × 10⁻³ for rs6532496 and OR=2.07, 95% CI=1.24-3.45 with P = 5.43 × 10⁻³ for rs951613, respectively). Results from Bayesian logistic regression showed stronger interaction effects (OR=2.26, 95% CI=1.2-3.38 for rs6532496 and OR=2.14, 95% CI=1.14-3.2 for rs951613, respectively). All the 12 SNPs associated with cancer revealed significant gene-steroid interaction effects (P < 0.05); whereas 13 SNPs showed gene-steroid interaction effects without main effect on cancer. SNP rs4634230 revealed the strongest gene-steroid interaction effect (OR=2.49, 95% CI=1.5-4.13 with P = 4.0 × 10⁻⁴ based on the classic logistic regression and OR=2.59, 95% CI=1.4-3.97 from Bayesian logistic regression; respectively). This study provides evidence of common genetic variants within the PDLIM5 gene and interactions between PLDIM5 gene polymorphisms and steroid use influencing cancer.

News, social capital and health in the context of Katrina.

PubMed

Beaudoin, Christopher E

2007-05-01

This study assesses the public health functions played by news information and social capital in the context of Hurricane Katrina. In-depth interviews were conducted with 57 hurricane shelter residents between 4 and 6 weeks after the hurricane. Depression was more common for participants who relied more on news information than for other participants after the hurricane (adjusted odds ratio [AOR], 5.49; 95% CI, 1.29 to 23.35; p=.021). Depression was more common for participants with relatively low levels of pre-hurricane positive social interactions (AOR, .16; 95% CI, .02 to 1.83; p=.046) and post-hurricane positive social interactions (AOR, .02; 95% CI, .00 to .74; p=.033) and high levels of post-hurricane negative social interactions (AOR, 17.05; 95% CI, .92 to 315.64; p=.047). Illness and injury were more common for participants who had relied more on news information than for other participants after the hurricane (AOR, 1.13; 95% CI, 1.02 to 2.77; p=.046).

Trends in survival and early functional outcomes from hospitalized severe adult traumatic brain injuries, Pennsylvania, 1998–2007

PubMed Central

Sánchez, Álvaro I; Krafty, Robert T; Weiss, Harold B; Rubiano, Andrés M; Peitzman, Andrew B; Puyana, Juan Carlos

2011-01-01

Objective To determine trends for in-hospital survival and functional outcomes at acute care hospital discharge for severe adult traumatic brain injury (SATBI) patients in Pennsylvania, during 1998–2007. Methods Secondary analysis of the Pennsylvania trauma outcome study database. Main Outcome Measures Survival and functional status scores of five domains (feeding, locomotion, expression, transfer mobility, and social interaction) fitted into logistic regression models adjusted for age, sex, race, co-morbidities, injury mechanism, extra-cranial injuries, severity scores, hospital stay, trauma center, and hospital level. Sensitivity analyses for functional outcomes were performed. Results There were 26,234 SATBI patients. Annual numbers of SATBI increased from 1,757 to 3,808 during 1998–2007. Falls accounted for 47.7% of all SATBI. Survival increased significantly from 72.5% to 82.7% (OR 1.10, 95%CI 1.08–1.11, P<0.001). In sensitivity analyses, trends of complete independence in functional outcomes increased significantly for expression (OR 1.01, 95%CI 1.00–1.02, P=0.011) and social interaction (OR 1.01, 95%CI 1.00–1.03, P=0.002). There were no significant variations over time for feeding, locomotion, and transfer mobility. Conclusions Trends for SATBI served by Pennsylvania’s established trauma system showed increases in rates but substantial reductions in mortality and significant improvements in functional outcomes at discharge for expression and social interaction. PMID:21386713

“Polio Eradication” Game May Increase Public Interest in Global Health

PubMed Central

Barnabas, Ruanne V.; Rue, Tessa; Weisman, Jordan; Harris, Nathan A.; Orenstein, Walter A.

2015-01-01

Abstract Background: Interactive games that highlight global health challenges and solutions are a potential tool for increasing interest in global health. To test this hypothesis, we developed an interactive “Polio Eradication” (PE) game and evaluated whether playing or watching was associated with increased public interest in global health. Materials and Methods: The PE game is a life-size, human board game that simulates PE efforts. Four players—a researcher, a transportation expert, a local community coordinator, and a healthcare worker—collaborate as an interdisciplinary team to help limit ongoing and future polio outbreaks in Pakistan, represented on the game board. Participants who played or observed the game and those who did not participate in the game, but visited noninteractive global health exhibits, completed a survey on participation outcomes. We used relative risk regression to examine associations between cofactors and change in global health interest. Results: Three variables predicted increased global health interest among the game participants: Having little or no previous global health knowledge prior to playing the game (risk ratio [RR]=1.28; 95 percent confidence interval [CI], 1.13–1.45), not currently being involved in global health (RR=1.41; 95 percent CI, 1.07–1.85), and visiting Seattle (RR=1.25; 95 percent CI, 1.04–1.51). Conclusions: Our results suggest that a hands-on, interactive game may increase the public's interest in global health, particularly among those with minimal previous knowledge of or involvement in global health activities. PMID:26182064

[Four sessions of the work of a teacher of deaf at the initial stage of rehabilitation of a child with a cochlear implant].

PubMed

Sataeva, A I

To present the system of the teacher of the deaf work with a child with CI and their family at the initial rehabilitation stage aimed at reorganization of interaction between the child with CI and his family and transition of the child to the way of natural development. The paper presents a brief description of the teacher of the deaf systematic work at the initial rehabilitation stage, which includes four work sessions of the teacher, during which the logic of normal development of a hearing child during the first year of their life is reproduced. The main difficulties in interaction with a child with CI, faced by their parents are described. Indicators of completion of each session with a child with CI and their parents are specified. There is noted that 90 children passed to the way of natural development of communication and speech with their relatives and parents sought to improve their interaction with the children. The system of the teacher of the deaf work with children after CI surgery, developed in the Institute of Special Education of the Russian Academy of Education, allows to reconstruct interaction between the child and their parents on a normal sensory basis and for a child with CI to pass to the way of natural development of their communication and speech as early age hearing children do.

Racial disparities in advanced stage colorectal cancer survival

PubMed Central

Wallace, Kristin; Hill, Elizabeth G.; Lewin, David N.; Williamson, Grace; Oppenheimer, Stephanie; Ford, Marvella E.; Wargovich, Michael J.; Berger, Franklin G.; Bolick, Susan W.; Thomas, Melanie B.; Alberg, Anthony J.

2013-01-01

Purpose African Americans (AA) have a higher incidence and lower survival from colorectal cancer (CRC) compared to European Americans (EA). In the present study, statewide, population-based data from South Carolina Central Cancer Registry (SCCCR) is used to investigate the relationship between race and age on advanced stage CRC survival. Methods The study population was comprised of 3865 advanced pathologically documented colon and rectal adenocarcinoma cases diagnosed between 01 January 1996 and 31 December 2006: 2673 (69%) EA and 1192 (31%) AA. Kaplan-Meier methods were used to generate median survival time and corresponding 95% confidence intervals (CI) by race, age, and gender. Factors associated with survival were evaluated by fitting Cox proportional hazards (CPH) regression models to generate Hazard Ratios (HR) and 95% CI. Results We observed a significant interaction between race and age on CRC survival (p = 0.04). Among younger patients (< 50 years), AA race was associated with a 1.34 (95% CI 1.06-1.71) higher risk of death compared to EA. Among older patients, we observed a modest increase risk of death among AA men compared to EA (HR 1.16 (95% CI 1.01-1.32) but no difference by race among women (HR 0.94 (95% CI 0.82-1.08)). Moreover, we observed that the disparity in survival has worsened over the past 15 years. Conclusions Future studies that integrate clinical, molecular, and treatment-related data are needed for advancing understanding of the racial disparity in CRC survival, especially for those < 50 years old. PMID:23296454

Women’s Health Initiative Clinical Trials: Interaction of calcium plus vitamin D and Hormone Therapy

PubMed Central

Robbins, John A; Aragaki, Aaron; Crandall, Carolyn J; Manson, Joann E; Carbone, Laura; Jackson, Rebecca; Lewis, Cora E.; Johnson, Karen C.; Sarto, Gloria; Stefanick, Marcia L; Wactawski-Wende, Jean

2013-01-01

Objective To test the added value of Calcium and vitamin D (CaD) for fracture prevention among women taking postmenopausal hormone therapy (HT). Methods A prospective, partial-factorial design, randomized controlled double blind trial amongst Women’s Health Initiative post-menopausal participants, ages 50–79, at 40 centers in the US, with 7.1 years average follow-up. 27,347 women were randomized to HT (conjugated estrogen 0.625 mg alone, or CEE 0.625 mg daily plus medroxyprogesterone acetate 2.5mg) and 36,282 women randomized to either 1000mg elemental calcium (carbonate) plus 400 IU of vitamin D3 daily each compared to placebo. A total of 16,089 women were in both arms. The predefined outcomes were adjudicated hip fractures and measured bone mineral density. Results Interaction between HT and CaD on hip fracture (P-interaction = 0.01) was shown. The effect of CaD was stronger among women assigned to HT (HR, 0.59; 95%CI, 0.38–0.93) than placebo (HR, 1.20; 95%CI, 0.85, 1.69). The effect of HT on hip fracture was stronger among women assigned to active CaD (HR, 0.43; 0.28–0.66) than placebo (HR, 0.87; 95%CI, 0.60–1.26). CaD supplementation enhanced the anti-fracture effect of the HT at all levels of personal calcium intake. There was no interaction of HT and CaD on change in hip or spine BMD. Conclusions Postmenopausal women at normal risk of hip fracture on HT, supplementation with CaD significantly reduced incident hip fracture beyond HT alone; at all levels of personal baseline total calcium intake. PMID:23799356

A partitioned correlation function interaction approach for describing electron correlation in atoms

NASA Astrophysics Data System (ADS)

Verdebout, S.; Rynkun, P.; Jönsson, P.; Gaigalas, G.; Froese Fischer, C.; Godefroid, M.

2013-04-01

The traditional multiconfiguration Hartree-Fock (MCHF) and configuration interaction (CI) methods are based on a single orthonormal orbital basis. For atoms with many closed core shells, or complicated shell structures, a large orbital basis is needed to saturate the different electron correlation effects such as valence, core-valence and correlation within the core shells. The large orbital basis leads to massive configuration state function (CSF) expansions that are difficult to handle, even on large computer systems. We show that it is possible to relax the orthonormality restriction on the orbital basis and break down the originally very large calculations into a series of smaller calculations that can be run in parallel. Each calculation determines a partitioned correlation function (PCF) that accounts for a specific correlation effect. The PCFs are built on optimally localized orbital sets and are added to a zero-order multireference (MR) function to form a total wave function. The expansion coefficients of the PCFs are determined from a low dimensional generalized eigenvalue problem. The interaction and overlap matrices are computed using a biorthonormal transformation technique (Verdebout et al 2010 J. Phys. B: At. Mol. Phys. 43 074017). The new method, called partitioned correlation function interaction (PCFI), converges rapidly with respect to the orbital basis and gives total energies that are lower than the ones from ordinary MCHF and CI calculations. The PCFI method is also very flexible when it comes to targeting different electron correlation effects. Focusing our attention on neutral lithium, we show that by dedicating a PCF to the single excitations from the core, spin- and orbital-polarization effects can be captured very efficiently, leading to highly improved convergence patterns for hyperfine parameters compared with MCHF calculations based on a single orthogonal radial orbital basis. By collecting separately optimized PCFs to correct the MR function, the variational degrees of freedom in the relative mixing coefficients of the CSFs building the PCFs are inhibited. The constraints on the mixing coefficients lead to small off-sets in computed properties such as hyperfine structure, isotope shift and transition rates, with respect to the correct values. By (partially) deconstraining the mixing coefficients one converges to the correct limits and keeps the tremendous advantage of improved convergence rates that comes from the use of several orbital sets. Reducing ultimately each PCF to a single CSF with its own orbital basis leads to a non-orthogonal CI approach. Various perspectives of the new method are given.

Gender-specific differences of interaction between cadmium exposure and obesity on prediabetes in the NHANES 2007-2012 population.

PubMed

Jiang, Fei; Zhi, Xueyuan; Xu, Miao; Li, Bingyan; Zhang, Zengli

2018-05-30

Data from National Health and Nutrition Examination Survey (NHANES) for the years 2007-2012 were used to evaluate the interactions of cadmium (Cd) exposure with being overweight/obesity on the risk of prediabetes among adults 20 years older. A total of 3552 subjects were included in the analysis. Urinary cadmium levels (UCd) was used as a biomarker for long-term exposure to Cd. Additive interaction was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S). Following covariates adjustments, we found significant associations of UCd with higher prediabetes prevalence, and this association was more apparent in males (Q4 vs Q1: OR = 1.95, 95%CI: 1.34-2.84); while overweight/obesity was associated with prediabetes both in males and in females. Additionally, there was a significant interaction between Cd exposure and being overweight/obesity on prediabetes risk among males (RERI = 1.18, 95% CI: 0.42-1.93; AP = 0.35, 95% CI: 0.12-0.58; S = 2.00, 95% CI: 0.92-4.34). Our results suggest that being overweight/obesity may substantially amplify the adverse effects of long-term cadmium exposure on prediabetes risk, and this interaction is more severe in male adults. Further studies are needed to confirm these findings.

Genome-wide interaction study of smoking and bladder cancer risk

PubMed Central

Figueroa, Jonine D.; Han, Summer S.; Garcia-Closas, Montserrat; Baris, Dalsu; Jacobs, Eric J.; Kogevinas, Manolis; Schwenn, Molly; Malats, Nuria; Johnson, Alison; Purdue, Mark P.; Caporaso, Neil; Landi, Maria Teresa; Prokunina-Olsson, Ludmila; Wang, Zhaoming; Hutchinson, Amy; Burdette, Laurie; Wheeler, William; Vineis, Paolo; Siddiq, Afshan; Cortessis, Victoria K.; Kooperberg, Charles; Cussenot, Olivier; Benhamou, Simone; Prescott, Jennifer; Porru, Stefano; Bueno-de-Mesquita, H.Bas; Trichopoulos, Dimitrios; Ljungberg, Börje; Clavel-Chapelon, Françoise; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth; Tjønneland, Anne; Brenan, Paul; Chang-Claude, Jenny; Riboli, Elio; Conti, David; Gago-Dominguez, Manuela; Stern, Mariana C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Hohensee, Chancellor; Rodabough, Rebecca; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Chen, Constance; De Vivo, Immaculata; Giovannucci, Edward; Hunter, David J.; Kraft, Peter; Lindstrom, Sara; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Karagas, Margaret R.; Schned, Alan; Armenti, Karla R.; Hosain, G.M.Monawar; Haiman, Chris A.; Fraumeni, Joseph F.; Chanock, Stephen J.; Chatterjee, Nilanjan; Rothman, Nathaniel; Silverman, Debra T.

2014-01-01

Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study (GWAS) of smoking and bladder cancer risk based on primary scan data from 3002 cases and 4411 controls from the National Cancer Institute Bladder Cancer GWAS. Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with interaction P values < 5 × 10− 5 were evaluated further in an independent dataset of 2422 bladder cancer cases and 5751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial dataset and in the combined dataset, providing evidence of interaction with tobacco use. Further, two of these novel SNPs showed strong evidence of association with bladder cancer in tobacco use subgroups that approached genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never smokers [combined odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.20–1.50, P value = 5.18 × 10− 7]; and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility SNP for ever smokers (combined OR = 0.75, 95% CI = 0.67–0.84, P value = 6.35 × 10− 7). In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, whereas the additive interaction analysis identified more loci with associations among smokers—including the known smoking and NAT2 acetylation interaction. Our findings provide additional evidence of gene–environment interactions for tobacco and bladder cancer. PMID:24662972

Using genetics to test the causal relationship of total adiposity and periodontitis: Mendelian randomization analyses in the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium

PubMed Central

Shungin, Dmitry; Cornelis, Marilyn C; Divaris, Kimon; Holtfreter, Birte; Shaffer, John R; Yu, Yau-Hua; Barros, Silvana P; Beck, James D; Biffar, Reiner; Boerwinkle, Eric A; Crout, Richard J.; Ganna, Andrea; Hallmans, Goran; Hindy, George; Hu, Frank B; Kraft, Peter; McNeil, Daniel W; Melander, Olle; Moss, Kevin L; North, Kari E; Orho-Melander, Marju; Pedersen, Nancy L; Ridker, Paul M; Rimm, Eric B; Rose, Lynda M; Rukh, Gull; Teumer, Alexander; Weyant, Robert J; Chasman, Daniel I; Joshipura, Kaumudi; Kocher, Thomas; Magnusson, Patrik KE; Marazita, Mary L; Nilsson, Peter; Offenbacher, Steve; Davey Smith, George; Lundberg, Pernilla; Palmer, Tom M; Timpson, Nicholas J; Johansson, Ingegerd; Franks, Paul W

2015-01-01

Background: The observational relationship between obesity and periodontitis is widely known, yet causal evidence is lacking. Our objective was to investigate causal associations between periodontitis and body mass index (BMI). Methods: We performed Mendelian randomization analyses with BMI-associated loci combined in a genetic risk score (GRS) as the instrument for BMI. All analyses were conducted within the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium in 13 studies from Europe and the USA, including 49 066 participants with clinically assessed (seven studies, 42.1% of participants) and self-reported (six studies, 57.9% of participants) periodontitis and genotype data (17 672/31 394 with/without periodontitis); 68 761 participants with BMI and genotype data; and 57 871 participants (18 881/38 990 with/without periodontitis) with data on BMI and periodontitis. Results: In the observational meta-analysis of all participants, the pooled crude observational odds ratio (OR) for periodontitis was 1.13 [95% confidence interval (CI): 1.03, 1.24] per standard deviation increase of BMI. Controlling for potential confounders attenuated this estimate (OR = 1.08; 95% CI:1.03, 1.12). For clinically assessed periodontitis, corresponding ORs were 1.25 (95% CI: 1.10, 1.42) and 1.13 (95% CI: 1.10, 1.17), respectively. In the genetic association meta-analysis, the OR for periodontitis was 1.01 (95% CI: 0.99, 1.03) per GRS unit (per one effect allele) in all participants and 1.00 (95% CI: 0.97, 1.03) in participants with clinically assessed periodontitis. The instrumental variable meta-analysis of all participants yielded an OR of 1.05 (95% CI: 0.80, 1.38) per BMI standard deviation, and 0.90 (95% CI: 0.56, 1.46) in participants with clinical data. Conclusions: Our study does not support total adiposity as a causal risk factor for periodontitis, as the point estimate is very close to the null in the causal inference analysis, with wide confidence intervals. PMID:26050256

The Relationship of Adverse Childhood Events To Smoking, Overweight, Obesity and Binge Drinking Among Women In Hawaii

PubMed Central

Remigio-Baker, Rosemay A.; Hayes, Donald K.; Reyes-Salvail, Florentina

2016-01-01

OBJECTIVES To evaluate how the associations of adverse childhood events (ACEs) with smoking, overweight, obesity and binge drinking differ by race/ethnicity among women, including a large, understudied cohort of Asians and Native Hawaiians/Pacific Islanders (NHOPIs). METHODS The number and type (household dysfunction, and physical, verbal and sexual abuse) of ACEs were examined in relation to adulthood smoking, overweight, obesity and binge drinking among 3,354 women in Hawaii using the 2010 Behavioral Risk Factor Surveillance System data using Poisson regression. We additionally investigated for interaction by race/ethnicity. Covariates included age, race/ethnicity, education, emotional support, healthcare coverage, and the other health outcomes. RESULTS Overall, 54.9% reported at least 1 ACE. The prevalence of smoking (Prevalence Ratio [PR]=1.40 [1 ACE] to PR=2.55 [5+ ACEs]), overweight (PR=1.22 [1 ACE] to PR=1.31 [5+ ACEs]) and obesity (PR=1.00 [1 ACE] to PR=1.85 [5+ ACEs]) increased with increasing ACE count. Smoking was associated with household dysfunction (PR=1.67, CI=1.26–2.22), and physical (PR=2.04, CI=1.50–2.78) and verbal (PR=1.62, CI=1.25–2.10) abuse. Obesity was also significantly related to household dysfunction (PR=1.22, CI=1.01–1.48), and physical (PR=1.36, CI=1.10–1.70), verbal (PR=1.35, CI=1.11–1.64) and sexual (PR=1.53, CI=1.25–1.88) abuse. Among Asians, sexual abuse was associated with a lower prevalence of binge drinking (PR=0.26, CI=0.07, 0.93), which was significantly different from the null association among Whites (interaction p=0.02). CONCLUSION Preventing/addressing ACEs may help optimize childhood health, and reduce the likelihood of smoking/obesity among women including Asians/NHOPIs. Further studies are warranted to evaluate the sexual abuse-binge drinking association among Asians, which may support the need for culturally-tailored programs to address ACEs. PMID:27449778

[Association and interaction of heat shock proteins B1 gene and tumor-suppressor protein p53 gene with chromosome damage levels among coke oven workers].

PubMed

Li, X L; Deng, Q F; Zhang, X; Wang, T; Chen, Z W; Bai, Y S; Wang, S H; Wu, T C; Guo, H

2016-10-06

Objective: To investigate the association and interaction of heat shock proteins B1(HSPB1)gene rs2868371 and tumor-suppressor protein p53(TP53)gene rs1042522 polymorphisms with chromosome damage levels among coke oven workers. Methods: We recruited 1 333 male workers from a state-run coke oven plant in Wuhan in September-October 2010. Among them, 949 who had worked in coke oven workplaces, including auxiliary facilities and bottom, side, and top ovens, were nominated as coke oven workers(i.e., exposed), and 384 administrative or medical staff whose workplaces were offices were used as controls. General characteristics and 5 ml of venous blood were collected from each participant. The plasma concentrations of benzo[a]pyrene-diolepoxide(BPDE)-albumin adducts and the lymphocytic micronucleus(MN)frequencies for each individual were detected by ELISA and cytokinesis-block micronucleus assay, respectively. Gene polymorphisms were genotyped using TaqMan assays via quantitative PCR(ABI Prism 7900HT), and the corresponding frequency ratios( FR )with 95% confidence intervals( CI )were computed for all assays. Results: In the exposed group, the MN frequencies were higher in HSPB1 rs2868371 GC, CC, and GC+ CC genotype carriers((3.88 ± 2.88)‰,(4.00 ± 2.66)‰, and(3.91 ± 2.83)‰, respectively)than in rs2868371 GG genotype carriers((3.52±2.67)‰; FR =1.10, 1.13, and 1.11; 95% CI : 1.02-1.19, 1.02-1.25, and 1.03-1.19, respectively), and the HSPB1 rs2868371C allele was associated with increased MN frequency( P trend =0.006). Further, in the exposed group, the MN frequencies were lower in TP53 rs1042522 CG and CG+GG genotype carriers((3.63±2.61)‰ and(3.66±2.61)‰, respectively)than in TP53 rs1042522 CC genotype carriers(3.95±3.06)‰( FR =0.87 and 0.90; 95% CI : 0.83-0.96 and 0.84-0.97, respectively). The effect of gene-gene interaction between HSPB1, rs2868371, and TP53 rs1042522 on MN frequency was significant among coke oven workers( P= 0.001). Further stratified analyses showed that the effects of the HSPB1 rs2868371C allele in increasing MN frequencies were robust in subjects aged >40 years( FR =1.07, 95% CI : 1.01-1.12), those working >20 years( FR =1.08, 95% CI : 1.02-1.14), those with BMI ≤24 kg/m 2 ( FR =1.07, 95% CI : 1.01-1.13), drinkers( FR =1.09, 95% CI : 1.02-1.16), and workers with higher BPDE-albumin adduct levels( FR =1.07, 95% CI : 1.01-1.13)( P trend =0.023, 0.013, 0.029, and 0.020, respectively). The decreasing effect of the TP53 rs1042522 G allele on MN frequencies was robust in subjects aged >40 years( FR =0.94, 95% CI : 0.89-0.99), those with BMI ≤24 kg/m 2 ( FR =0.94, 95% CI : 0.88-0.99), and drinkers( FR =0.94, 95% CI : 0.88-1.00)( P trend =0.031, 0.023, and 0.038, respectively). In addition, there were interactions between HSPB1 rs2868371 and age and between HSPB1 rs2868371 and working years in terms of MN frequency( P= 0.030 and 0.013, respectively). Conclusion: In coke oven workers, the HSPB1 rs2868371 C and TP53 rs1042522 G alleles were associated with increased and decreased chromosome damage levels, respectively, and their interaction effect on chromosome damage levels was significant.

ARE HEALTH VISITORS' OBSERVATIONS OF EARLY PARENT-INFANT INTERACTIONS RELIABLE? A CROSS-SECTIONAL DESIGN.

PubMed

Kristensen, Ingeborg H; Trillingsgaard, Tea; Simonsen, Marianne; Kronborg, Hanne

2017-03-01

Health visitors need competences to promote healthy early parent-infant relationships. The aims of this study were to explore whether there are differences between groups of health visitors with and without additional parenting program education in terms of their knowledge of infant-parent interaction and their observation and assessment skills of such interactions. The cross-sectional study included 36 health visitors' certified Marte Meo therapists and 85 health visitors without additional parenting program education. Health visitors' observation skills were measured assessing five video-recorded mother-infant interactions. A questionnaire was used to measure their intention, self-efficacy, and knowledge. More certified Marte Meo therapists than health visitors without additional parenting program education reported a significantly higher mean level of knowledge of the early relationship, 6.42 (95% CI; 6.18-6.66) versus 5.05 (95% CI; 4.86-6.10), p = .04; and more certified Marte Meo therapists than health visitors without additional parenting program education reported a higher mean level of knowledge of infant self-regulation, 2.44 (95% CI; 2.18-2.71) versus 1.83 (95% CI; 1.62-2.03), p < .001. In the latter group, 54% (95% CI; 0.43-0.64) reported a significantly higher need for further education versus 22% (95% CI; 0.11-0.39), p = .001. Compared to health visitors without any parenting program education, health visitors certified as Marte Meo therapists reported a significantly higher frequency of correct assessment of mothers' sensitivity in two of five video-recordings, with 77.78% (95% CI; 0.61-0.87) compared to 45.88% (95% CI; 0.35-0.57) in Video 3, p = .001, and 69.44% (95% CI; 0.52-0.82) compared to 49.41% (95% CI; 0.39-0.60) in Video 4, p = .04, respectively. The results of the present study support the use of video-based education of health visitors to increase their knowledge of and skills in assessing parent-infant interactions. Randomized controlled trials are needed to determine whether the improved level of health visitors' knowledge and observation skills may be assigned to participation in the Marte Meo education program. © 2017 Michigan Association for Infant Mental Health.

Interaction between adolescent obesity and HLA risk genes in the etiology of multiple sclerosis

PubMed Central

Lima Bomfim, Izaura; Barcellos, Lisa; Gianfrancesco, Milena; Schaefer, Catherine; Kockum, Ingrid; Olsson, Tomas; Alfredsson, Lars

2014-01-01

Objective: We investigated potential interactions between human leukocyte antigen (HLA) genotype and body mass index (BMI) status in relation to the risk of developing multiple sclerosis (MS). Methods: We used 2 case-control studies, one with incident cases (1,510 cases, 2,017 controls) and one with prevalent cases (937 cases, 609 controls). Subjects with different genotypes and BMI were compared with regard to incidence of MS by calculating odds ratios (ORs) with 95% confidence intervals (CIs) employing logistic regression. Potential interactions between genotypes and BMI were evaluated by calculating the attributable proportion due to interaction. Results: In both cohorts, a significant interaction was observed between HLA-DRB1*15 and obesity, regardless of HLA-A*02 status. Similarly, there was a significant interaction between absence of A*02 and obesity, regardless of DRB1*15 status. In the incident cohort, obese subjects with the most susceptible genotype (carriage of DRB1*15 and absence of A*02) had an OR of 16.2 (95% CI 7.5–35.2) compared to nonobese subjects without the genetic risk factors. The corresponding OR in the prevalent study was 13.8 (95% CI 4.1–46.8). Conclusions: We observed striking interactions between BMI status and HLA genotype with regard to MS risk. Hypothetically, a low-grade inflammatory response inherent to obesity synergizes with the adaptive, HLA molecule–restricted arm of the immune system, causing MS. Prevention of adolescent obesity may thus lower the risk of developing MS, predominantly among people with a genetic susceptibility to the disease. PMID:24500647

MSMB gene variant alters the association between prostate cancer and number of sexual partners

PubMed Central

Stott-Miller, Marni; Wright, Jonathan L.; Stanford, Janet L.

2014-01-01

Background Recently, a genetic variant (rs10993994) in the MSMB gene associated with prostate cancer (PCa) risk was shown to correlate with reduced prostate secretory protein of 94 amino acids (PSP94) levels. Although the biological activity of PSP94 is unclear, one of its hypothesized functions is to protect prostatic cells from pathogens. Number of sexual partners and a history of sexually transmitted infections (STIs) have been positively associated with PCa risk, and these associations may be related to pathogen-induced chronic prostatic inflammation. Based on these observations, we investigated whether MSMB genotype modifies the PCa-sexual history association. Methods We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between number of sexual partners and PCa by fitting logistic regression models, stratified by MSMB genotype, and adjusted for age, family history of PCa, and PCa screening history among 1,239 incident cases and 1,232 controls. Results Compared with 1–4 female sexual partners, men with ≥15 such partners who carried the variant T allele of rs10993994 were at increased risk for PCa (OR=1.32; 95% CI, 1.03–1.71); no association was observed in men with the CC genotype (OR=1.03; 95% CI, 0.73–1.46; p=0.05 for interaction). Similar estimates were observed for total sexual partners (any T allele OR=1.37; 95% CI, 1.07–1.77; CC genotype OR=1.11; 95% CI, 0.79–1.55; p=0.06 for interaction). Conclusions The rs10993994 genotype in the MSMB gene modifies the association between number of sexual partners and PCa risk. These findings support a hypothesized biological mechanism whereby prostatic infection/inflammation may enhance risk of PCa. PMID:24037734

Pre- and postnatal stress and asthma in children: Temporal- and sex-specific associations

PubMed Central

Lee, Alison; Chiu, Yueh-Hsiu Mathilda; Rosa, Maria José; Jara, Calvin; Wright, Robert O.; Coull, Brent A.; Wright, Rosalind J.

2016-01-01

BACKGROUND Temporal- and sex-specific effects of perinatal stress have not been examined for childhood asthma. OBJECTIVES We examined associations between pre- and/or postnatal stress and children's asthma (n=765) and effect modification by sex in a prospective cohort study. METHODS Maternal negative life events (NLEs) were ascertained prenatally and postpartum. NLEs scores were categorized as 0, 1-2, 3-4, or ≥5 to assess exposure-response relationships. We examined effects of pre- and postnatal stress on children's asthma by age 6 years modeling each as independent predictors; mutually adjusting for prenatal and postnatal stress; and finally considering interactions between pre- and postnatal stress. Effect modification by sex was examined in stratified analyses and by fitting interaction terms. RESULTS When considering stress in each period independently, among boys a dose-response relationship was evident for each level increase on the ordinal scale prenatally (OR=1.38, 95% CI 1.06, 1.79; p-for-trend=0.03) and postnatally (OR=1.53, 95% CI 1.16, 2.01; p-for-trend=0.001); among girls only the postnatal trend was significant (OR=1.60, 95% CI 1.14, 2.22; p-for-trend=0.005). Higher stress in both the pre- and postnatal periods was associated with increased odds of being diagnosed with asthma in girls [OR=1.37, 95% CI 0.98, 1.91 (pinteraction=0.07)] but not boys [OR=1.08, 95% CI 0.82, 1.42 (pinteraction=0.61)]. CONCLUSIONS While boys were more vulnerable to stress during the prenatal period, girls were more impacted by postnatal stress and cumulative stress across both periods in relation to asthma. Understanding sex and temporal differences in response to early life stress may provide unique insight into asthma etiology and natural history. PMID:26953156

Vitamin D and calcium supplementation and one-year change in mammographic density in the Women’s Health Initiative Calcium and Vitamin D Trial

PubMed Central

Bertone-Johnson, Elizabeth R.; McTiernan, Anne; Thomson, Cynthia A.; Wactawski-Wende, Jean; Aragaki, Aaron K.; Rohan, Thomas E.; Vitolins, Mara Z.; Tamimi, Rulla M.; Johnson, Karen C.; Lane, Dorothy; Rexrode, Kathryn M.; Peck, Jennifer D.; Chlebowski, Rowan T.; Sarto, Gloria; Manson, JoAnn E.

2012-01-01

Background Calcium and vitamin D may be inversely related to breast cancer risk, in part by affecting mammographic density. However, results from previous, mostly cross-sectional studies have been mixed, and there have been few randomized clinical trials of the effect of calcium and vitamin D supplementation on change in mammographic density. Methods We assessed the effect of one year of supplementation on mammographic density in 330 postmenopausal women enrolled in the Women’s Health Initiative Hormone Therapy (HT) and Calcium and Vitamin D (CaD) trials. Women were randomized to receive 1000 mg/day of elemental calcium carbonate plus 400 IU/day of vitamin D3 or placebo. Results After approximately one year, mammographic density decreased 2% in the CaD supplementation group and increased 1% in the placebo group (ratio of means = 0.97; 95% confidence interval (CI) = 0.81–1.17). Results suggested potential interaction by HT use (P = 0.08). Among women randomized to HT placebo, the ratio of mean density comparing CaD supplementation and placebo groups was 0.82 (95%CI = 0.61–1.11) vs. 1.16 (95%CI = 0.92–1.45) in women randomized to active HT. In sensitivity analyses limited to women taking ≥80% of study supplements, ratios were 0.67 (95%CI = 0.41–1.07) in women not assigned to HT and 1.07 (95%CI = 0.79–1.47) women assigned to HT. Conclusions We observed no overall effect of vitamin D and calcium supplementation on mammographic density after one year. Impact Potential interaction between these nutrients and estrogen as related to mammographic density warrants further study. PMID:22253296

HHEX_23 AA Genotype Exacerbates Effect of Diabetes on Dementia and Alzheimer Disease: A Population-Based Longitudinal Study

PubMed Central

Xu, Wei-Li; Pedersen, Nancy L.; Keller, Lina; Kalpouzos, Grégoria; Wang, Hui-Xin; Graff, Caroline; Winblad, Bengt; Bäckman, Lars; Fratiglioni, Laura

2015-01-01

Background Research has suggested that variations within the IDE/HHEX gene region may underlie the association of type 2 diabetes with Alzheimer disease (AD). We sought to explore whether IDE genes play a role in the association of diabetes with dementia, AD, and structural brain changes using data from two community-based cohorts of older adults and a subsample with structural MRI. Methods and Findings The first cohort, which included dementia-free adults aged ≥75 y (n = 970) at baseline, was followed for 9 y to detect incident dementia (n = 358) and AD (n = 271) cases. The second cohort (for replication), which included 2,060 dementia-free participants aged ≥60 y at baseline, was followed for 6 y to identify incident dementia (n = 166) and AD (n = 121) cases. A subsample (n = 338) of dementia-free participants from the second cohort underwent MRI. HHEX_23 and IDE_9 were genotyped, and diabetes (here including type 2 diabetes and prediabetes) was assessed. In the first cohort, diabetes led to an adjusted hazard ratio (HR) of 1.73 (95% CI 1.19–2.32) and 1.66 (95% CI 1.06–2.40) for dementia and AD, respectively, among all participants. Compared to people carrying the GG genotype without diabetes, AA genotype carriers with diabetes had an adjusted HR of 5.54 (95% CI 2.40–7.18) and 4.81 (95% CI 1.88–8.50) for dementia and AD, respectively. There was a significant interaction between HHEX_23-AA and diabetes on dementia (HR 4.79, 95% CI 1.63–8.90, p = 0.013) and AD (HR 3.55, 95% CI 1.45–9.91, p = 0.025) compared to the GG genotype without diabetes. In the second cohort, the HRs were 1.68 (95% CI 1.04–2.99) and 1.64 (1.02–2.33) for the diabetes–AD and dementia–AD associations, respectively, and 4.06 (95% CI 1.06–7.58, p = 0.039) and 3.29 (95% CI 1.02–8.33, p = 0.044) for the interactions, respectively. MRI data showed that HHEX_23-AA carriers with diabetes had significant structural brain changes compared to HHEX_23-GG carriers without diabetes. No joint effects of IDE_9 and diabetes on dementia were shown. As a limitation, the sample sizes were small for certain subgroups. Conclusions A variant in the HHEX_23 gene interacts with diabetes to be associated with a substantially increased risk of dementia and AD, and with structural brain changes among dementia-free elderly people. PMID:26173052

Low plasma selenium concentrations in critically ill children: the interaction effect between inflammation and selenium deficiency

PubMed Central

2014-01-01

Introduction Low plasma selenium concentrations are frequent in critically ill patients. However, whether this is due to systemic inflammation, a deficient nutritional state or both is still not clear. We aimed to determine the factors associated with low plasma selenium in critically ill children while considering the inflammatory response and nutritional status. Method A prospective study was conducted in 173 children (median age 34 months) with systemic inflammatory response who had plasma selenium concentrations assessed 48 hours after admission and on the 5th day of ICU stay. The normal reference range was 0.58 μmol/L to 1.6 μmol/L. The outcome variable was ‘low plasma selenium’, which was defined as plasma selenium values below the distribution median during this period. The main explanatory variables were age, malnutrition, sepsis, C-reactive protein (CRP), and clinical severity scores. The data were analyzed using a Binomial Generalized Estimating Equations model, which includes the correlation between admission and 5th day responses. Results Malnutrition and CRP were associated with low plasma selenium. The interaction effect between these two variables was significant. When CRP values were less than or equal to 40 mg/L, malnutrition was associated with low plasma selenium levels (odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.39 to 7.63, P = 0.007; OR = 2.98, 95% CI 1.26 to 7.06, P = 0.013; OR = 2.49, 95% CI 1.01 to 6.17, P = 0.049, for CRP = 10, 20 and 40 mg/L, respectively). This effect decreased as CRP concentrations increased and there was loose significance when CRP values were >40 mg/L. Similarly, the effect of CRP on low plasma selenium was significant for well-nourished patients (OR = 1.13; 95% CI 1.06 to 1.22, P <0.001) but not for the malnourished (OR = 1.03; 95% CI 0.99 to 1.08, P = 0.16). Conclusions There is a significant interaction between the magnitude of the inflammatory response and malnutrition on low plasma selenium. This interaction should be considered when interpreting plasma concentrations as an index of selenium status in patients with systemic inflammation as well as in the decision on selenium supplementation. PMID:24886623

Polymorphism in COX-2 modifies the inverse association between Helicobacter pylori seropositivity and esophageal squamous cell carcinoma risk in Taiwan: a case control study

PubMed Central

2009-01-01

Background Overexpression of Cyclooxygenase-2 (COX-2) was observed in many types of cancers, including esophageal squamous cell carcinoma (ESCC). One functional SNP, COX-2 -1195G/A, has been reported to mediate susceptibility of ESCC in Chinese populations. In our previous study, the presence of Helicobacter pylori (H. pylori) was found to play a protective role in development of ESCC. The interaction of COX-2 and H. pylori in gastric cancer was well investigated. However, literature on their interaction in ESCC risk is scarce. The purpose of this study was to evaluate the association and interaction between COX-2 single nucleotide polymorphism (SNP), H. pylori infection and the risk of developing ESCC. Methods One hundred and eighty patients with ESCC and 194 controls were enrolled in this study. Personal data regarding related risk factors, including alcohol consumption, smoking habits and betel quid chewing, were collected via questionnaire. Genotypes of the COX-2 -1195 polymorphism were determined by PCR-based restriction fragment length polymorphism. H. pylori seropositivity was defined by immunochromatographic screening test. Data was analyzed by chi-squared tests and polytomous logistics regression. Results In analysis adjusting for the covariates and confounders, H. pylori seropositivity was found to be inversely association with the ESCC development (adjusted OR: 0.5, 95% CI: 0.3 – 0.9). COX-2 -1195 AA homozygous was associated with an increased risk of contracting ESCC in comparison with the non-AA group, especially among patients with H. pylori seronegative (adjusted OR ratio: 2.9, 95% CI: 1.2 – 7.3). The effect was strengthened among patients with lower third ESCC (adjusted OR ratio: 6.9, 95% CI 2.1 – 22.5). Besides, H. pylori seropositivity conveyed a notably inverse effect among patients with COX-2 AA polymorphism (AOR ratio: 0.3, 95% CI: 0.1 – 0.9), and the effect was observed to be enhanced for the lower third ESCC patients (AOR ratio: 0.09, 95% CI: 0.02 – 0.47, p for multiplicative interaction 0.008) Conclusion H. pylori seropositivity is inversely associated with the risk of ESCC in Taiwan, and COX-2 -1195 polymorphism plays a role in modifying the influence between H. pylori and ESCC, especially in lower third esophagus. PMID:19463183

Synergistic interaction of benign prostatic hyperplasia and prostatitis on prostate cancer risk

PubMed Central

Hung, S-C; Lai, S-W; Tsai, P-Y; Chen, P-C; Wu, H-C; Lin, W-H; Sung, F-C

2013-01-01

Background: The incidence of prostate cancer is much lower in Asian men than in Western men. This study investigated whether prostate cancer is associated with prostatitis, benign prostatic hyperplasia (BPH), and other medical conditions in the low-incidence population. Methods: From the claims data obtained from the universal National Health Insurance of Taiwan, we identified 1184 patients with prostate cancer diagnosed from 1997 to 2008. Controls comprised 4736 men randomly selected from a cancer-free population. Both groups were 50 years of age or above. Medical histories between the two groups were compared. Results: Multivariate logistic regression analysis showed that prostatitis and BPH had stronger association with prostate cancer than the other medical conditions tested. Compared with men without prostatitis and BPH, a higher odds ratio (OR) for prostate cancer was associated with BPH (26.2, 95% confidence interval (CI) 20.8–33.0) than with prostatitis (10.5, 95% CI=3.36–32.7). Men with both conditions had an OR of 49.2 (95% CI=34.7–69.9). Conclusion: Men with prostate cancer have strong association with prostatitis and/or BPH. Prostatitis interacts with BPH, resulting in higher estimated relative risk of prostate cancer in men suffering from both conditions. PMID:23612451

Diabetes is more lethal in Mexicans and Mexican Americans compared to non-Hispanic Whites

PubMed Central

Hunt, Kelly J; Gonzalez, Maria Elena; Lopez, Ruy; Haffner, Steve M; Stern, Michael P; Gonzalez-Villalpando, Clicerio

2012-01-01

Purpose To examine the mortality risk associated with diabetes in the Mexico City Diabetes Study (MCDS) and the San Antonio Heart Study (SAHS). Methods Prospective cohorts conducted 1990-2007 in MCDS and 1979-2000 in SAHS. Mortality risk was examined using Cox proportional hazard models in 1,402 non-Hispanic whites (NHW), 1,907 U.S.-born Mexican Americans (MA), 444 Mexican-born MA, 2,281 Mexico City residents (MCR) between the ages of 35 and 64. Results Age- and sex-adjusted mortality HRs comparing U.S.-born MA, Mexican-born MA and MCR to NHW were 1.09 (95% CI: 0.86, 1.37), 1.23 (95% CI: 0.86, 1.76) and 0.97 (95% CI: 0.77, 1.23), respectively, in non-diabetic individuals; in contrast, mortality risk varied in diabetic individuals with respective HRs of 1.77 (95% CI: 1.20, 2.61), 1.08 (95% CI: 0.59, 1.97) and 2.27 (95% CI: 1.53, 3.35) (interaction p-value=0.0003). Excluding Mexican-born MA and non-diabetic individuals, controlling for medication use, insulin use, fasting glucose levels and duration of diabetes explained a significant proportion of the mortality differential (HRs relative to NHW were 1.31 (95% CI: 0.87, 1.98) in U.S.-born MA and 1.38 (95% CI: 0.89, 2.12) in MCR). Conclusions This study provides evidence that diabetes is more lethal in U.S.-born MA and MCR than in NHW. PMID:21840730

Genome-wide analysis of the interaction between the endosymbiotic bacterium Wolbachia and its Drosophila host.

PubMed

Xi, Zhiyong; Gavotte, Laurent; Xie, Yan; Dobson, Stephen L

2008-01-02

Intracellular Wolbachia bacteria are obligate, maternally-inherited, endosymbionts found frequently in insects and other invertebrates. The success of Wolbachia can be attributed in part to an ability to alter host reproduction via mechanisms including cytoplasmic incompatibility (CI), parthenogenesis, feminization and male killing. Despite substantial scientific effort, the molecular mechanisms underlying the Wolbachia/host interaction are unknown. Here, an in vitro Wolbachia infection was generated in the Drosophila S2 cell line, and transcription profiles of infected and uninfected cells were compared by microarray. Differentially-expressed patterns related to reproduction, immune response and heat stress response are observed, including multiple genes that have been previously reported to be involved in the Wolbachia/host interaction. Subsequent in vivo characterization of differentially-expressed products in gonads demonstrates that Angiotensin Converting Enzyme (Ance) varies between Wolbachia infected and uninfected flies and that the variation occurs in a sex-specific manner. Consistent with expectations for the conserved CI mechanism, the observed Ance expression pattern is repeatable in different Drosophila species and with different Wolbachia types. To examine Ance involvement in the CI phenotype, compatible and incompatible crosses of Ance mutant flies were conducted. Significant differences are observed in the egg hatch rate resulting from incompatible crosses, providing support for additional experiments examining for an interaction of Ance with the CI mechanism. Wolbachia infection is shown to affect the expression of multiple host genes, including Ance. Evidence for potential Ance involvement in the CI mechanism is described, including the prior report of Ance in spermatid differentiation, Wolbachia-induced sex-specific effects on Ance expression and an Ance mutation effect on CI levels. The results support the use of Wolbachia infected cell cultures as an appropriate model for predicting in vivo host/Wolbachia interactions.

Effect of educational interventions and medical school policies on medical students' attitudes toward pharmaceutical marketing practices: a multi-institutional study.

PubMed

Kao, Audiey C; Braddock, Clarence; Clay, Maria; Elliott, Donna; Epstein, Scott K; Filstead, William; Hotze, Tim; May, Win; Reenan, Jennifer

2011-11-01

To determine the effect of educational interventions on medical students' attitudes toward pharmaceutical industry marketing practices and whether restrictive medical school policies governing medicine-industry interactions are associated with student support for banning such interactions. Prospective cohort study involving the graduating classes of 2009 (intervention, n=474) and 2010 (control, n=459) at four U.S. medical schools. Intervention students experienced a former pharmaceutical representative's presentation, faculty debate, and a Web-based course. Both groups completed baseline and follow-up attitude surveys about pharmaceutical marketing. A total of 482 students (51.6%) completed both surveys. In regression analyses, intervention students were more likely than control students to think that physicians are strongly or moderately influenced by pharmaceutical marketing (OR, 2.29; 95% CI, 1.46-3.59) and believed they would be more likely to prescribe a company's drug if they accepted that company's gifts and food (OR, 1.68; 95% CI, 1.12-2.52). Intervention students were more likely to support banning interactions between pharmaceutical representatives and students (OR, 4.82; 95% CI, 3.02-7.68) and with physicians (OR, 6.88; 95% CI, 4.04-11.70). Students from schools with more restrictive policies were more likely to support banning interactions between pharmaceutical representatives and students (OR, 1.99; 95% CI, 1.26-3.16) and with physicians (OR, 3.44; 95% CI, 2.05-5.79). Education about pharmaceutical marketing practices and more restrictive policies governing medicine-industry interactions seem to increase medical students' skepticism about the appropriateness of such marketing practices and disapproval of pharmaceutical representatives in the learning environment.

Drug interactions with phenprocoumon and the risk of serious haemorrhage: a nested case-control study in a large population-based German database.

PubMed

Jobski, Kathrin; Behr, Sigrid; Garbe, Edeltraut

2011-09-01

Phenprocoumon is the most frequently used vitamin K antagonist in Germany. The aim of this study was to estimate the risk of serious bleeding as a result of the use of drugs with potential interaction with phenprocoumon. We conducted a nested case-control study in a cohort of 246,220 phenprocoumon users in the German Pharmacoepidemiological Research Database. Cases were patients hospitalised for haemorrhage of different kinds. Ten controls were matched to each case by health insurance, birth year and sex using incidence density sampling. Odds ratios (OR) with 95% confidence intervals (CI) of the risk of serious bleeding associated with combined use of phenprocoumon and potentially interacting drugs versus phenprocoumon alone were estimated using conditional logistic regression analysis. Our analyses considered multiple risk factors, such as bleeding history, other comorbidities or co-medication. Our study included 2,553 cases and 25,348 matched controls. An increased risk of bleeding was observed for the combined use of phenprocoumon and clopidogrel vs phenprocoumon use alone (OR: 1.83, 95% CI: 1.41-2.36). Antibiotic drugs associated with an increased risk of haemorrhage in the population of phenprocoumon users included the group of quinolones with ORs ranging from 2.74 (95% CI: 1.80-4.18) for ciprofloxacin to 4.40 (95% CI: 2.45-7.89) for levofloxacin, amoxicillin plus clavulanic acid (OR: 2.99, 95% CI: 1.39-6.42) and cotrimoxazole (OR 3.57, 95% CI: 2.36-5.40). Among non-steroidal anti-inflammatory drugs (NSAIDs), ketoprofen and naproxen were associated with the highest risks. Significantly elevated risks of major bleeding were mainly observed for drugs with known pharmacodynamic interaction with phenprocoumon, and less for drugs with possible pharmacokinetic interaction.

Genome-wide analysis of the interaction between the endosymbiotic bacterium Wolbachia and its Drosophila host

PubMed Central

Xi, Zhiyong; Gavotte, Laurent; Xie, Yan; Dobson, Stephen L

2008-01-01

Background Intracellular Wolbachia bacteria are obligate, maternally-inherited, endosymbionts found frequently in insects and other invertebrates. The success of Wolbachia can be attributed in part to an ability to alter host reproduction via mechanisms including cytoplasmic incompatibility (CI), parthenogenesis, feminization and male killing. Despite substantial scientific effort, the molecular mechanisms underlying the Wolbachia/host interaction are unknown. Results Here, an in vitro Wolbachia infection was generated in the Drosophila S2 cell line, and transcription profiles of infected and uninfected cells were compared by microarray. Differentially-expressed patterns related to reproduction, immune response and heat stress response are observed, including multiple genes that have been previously reported to be involved in the Wolbachia/host interaction. Subsequent in vivo characterization of differentially-expressed products in gonads demonstrates that Angiotensin Converting Enzyme (Ance) varies between Wolbachia infected and uninfected flies and that the variation occurs in a sex-specific manner. Consistent with expectations for the conserved CI mechanism, the observed Ance expression pattern is repeatable in different Drosophila species and with different Wolbachia types. To examine Ance involvement in the CI phenotype, compatible and incompatible crosses of Ance mutant flies were conducted. Significant differences are observed in the egg hatch rate resulting from incompatible crosses, providing support for additional experiments examining for an interaction of Ance with the CI mechanism. Conclusion Wolbachia infection is shown to affect the expression of multiple host genes, including Ance. Evidence for potential Ance involvement in the CI mechanism is described, including the prior report of Ance in spermatid differentiation, Wolbachia-induced sex-specific effects on Ance expression and an Ance mutation effect on CI levels. The results support the use of Wolbachia infected cell cultures as an appropriate model for predicting in vivo host/Wolbachia interactions. PMID:18171476

CREB1 gene polymorphisms combined with environmental risk factors increase susceptibility to major depressive disorder (MDD)

PubMed Central

Wang, Peng; Yang, Yanjie; Yang, Xiuxian; Qiu, Xiaohui; Qiao, Zhengxue; Wang, Lin; Zhu, Xiongzhao; Sui, Hong; Ma, Jingsong

2015-01-01

Major depressive disorder (MDD) is one of the most severe psychiatric disorders. The objective of this study was to explore the effects of CREB1 gene polymorphisms on risk of developing MDD and the joint effects of gene-environment interactions. Genotyping was performed by Taqman allelic discrimination assay among 586 patients and 586 healthy controls. A significant impact on rs6740584 genotype distribution was found for childhood trauma (P = 0.015). We did not find an association of CREB1 polymorphisms with MDD susceptibility. However, we found a significantly increased risk associated with the interactions of CREB1 polymorphisms and drinking (OR = 11.67, 95% CI = 2.52-54.18; OR = 11.52, 95% CI = 2.55-51.95 for rs11904814; OR = 4.18, 95% CI = 1.87-9.38; OR = 5.02, 95% CI = 2.27-11.14 for rs6740584; OR = 7.58, 95% CI = 2.05-27.98; OR = 7.59, 95% CI = 2.12-27.14 for rs2553206; OR = 8.37, 95% CI = 3.02-23.23; OR = 7.84, 95% CI = 2.93-20.98 for rs2551941). We also noted that CREB polymorphisms combined with family harmony and childhood trauma conferred increased susceptibility for MDD. In conclusion, polymorphisms in the CREB gene may not be independently associated with MDD risk, but they are likely to confer increased susceptibility by interacting with environmental risk factors in the Chinese population. PMID:25755794

Sugar-sweetened beverages and genetic risk of obesity.

PubMed

Qi, Qibin; Chu, Audrey Y; Kang, Jae H; Jensen, Majken K; Curhan, Gary C; Pasquale, Louis R; Ridker, Paul M; Hunter, David J; Willett, Walter C; Rimm, Eric B; Chasman, Daniel I; Hu, Frank B; Qi, Lu

2012-10-11

Temporal increases in the consumption of sugar-sweetened beverages have paralleled the rise in obesity prevalence, but whether the intake of such beverages interacts with the genetic predisposition to adiposity is unknown. We analyzed the interaction between genetic predisposition and the intake of sugar-sweetened beverages in relation to body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) and obesity risk in 6934 women from the Nurses' Health Study (NHS) and in 4423 men from the Health Professionals Follow-up Study (HPFS) and also in a replication cohort of 21,740 women from the Women's Genome Health Study (WGHS). The genetic-predisposition score was calculated on the basis of 32 BMI-associated loci. The intake of sugar-sweetened beverages was examined prospectively in relation to BMI. In the NHS and HPFS cohorts, the genetic association with BMI was stronger among participants with higher intake of sugar-sweetened beverages than among those with lower intake. In the combined cohorts, the increases in BMI per increment of 10 risk alleles were 1.00 for an intake of less than one serving per month, 1.12 for one to four servings per month, 1.38 for two to six servings per week, and 1.78 for one or more servings per day (P<0.001 for interaction). For the same categories of intake, the relative risks of incident obesity per increment of 10 risk alleles were 1.19 (95% confidence interval [CI], 0.90 to 1.59), 1.67 (95% CI, 1.28 to 2.16), 1.58 (95% CI, 1.01 to 2.47), and 5.06 (95% CI, 1.66 to 15.5) (P=0.02 for interaction). In the WGHS cohort, the increases in BMI per increment of 10 risk alleles were 1.39, 1.64, 1.90, and 2.53 across the four categories of intake (P=0.001 for interaction); the relative risks for incident obesity were 1.40 (95% CI, 1.19 to 1.64), 1.50 (95% CI, 1.16 to 1.93), 1.54 (95% CI, 1.21 to 1.94), and 3.16 (95% CI, 2.03 to 4.92), respectively (P=0.007 for interaction). The genetic association with adiposity appeared to be more pronounced with greater intake of sugar-sweetened beverages. (Funded by the National Institutes of Health and others.).

Outcomes in Black Patients With Early Breast Cancer Treated With Breast Conservation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nichols, Michael A.; Mell, Loren K.; Hasselle, Michael D.

Background: The race-specific impact of prognostic variables for early breast cancer is unknown for black patients undergoing breast conservation. Methods and Materials: This was a retrospective study of 1,231 consecutive patients {>=}40 years of age with Stage I-II invasive breast cancer treated with lumpectomy and radiation therapy at the University of Chicago Hospitals and affiliates between 1986 and 2004. Patients were classified as either black or nonblack. Cox proportional hazards regression was used to model the effects of known prognostic factors and interactions with race. Results: Median follow-up for surviving patients was 82 months. Thirty-four percent of patients were black,more » and 66% were nonblack (Caucasian, Hispanic, and Asian). Black patients had a poorer 10-year overall survival (64.6% vs. 80.8%; adjusted hazard ratio [HR], 1.59; 95% confidence interval [CI], 1.23-2.06) and 10-year disease-free survival (58.1% vs. 75.4%; HR 1.49; 95% CI, 1.18-1.89) compared with nonblack patients. Tumor sizes were similar between nonblack and black patients with mammographically detected tumors (1.29 cm vs. 1.20 cm, p = 0.20, respectively). Tumor size was significantly associated with overall survival (HR 1.48; 95% CI, 1.12-1.96) in black patients with mammographically detected tumors but not in nonblack patients (HR 1.09; 95% CI, 0.78-1.53), suggesting that survival in black patients depends more strongly on tumor size in this subgroup. Tests for race-size method of detection interactions were statistically significant for overall survival (p = 0.049), locoregional control (p = 0.036), and distant control (p = 0.032) and borderline significant for disease-free survival (p = 0.067). Conclusion: Despite detection at comparable sizes, the prognostic effect of tumor size in patients with mammographically detected tumors is greater for black than in nonblack patients.« less

Pubertal stage and the prevalence of violence and social relational aggression

PubMed Central

Hemphill, Sheryl A.; Kotevski, Aneta; Herrenkohl, Todd I.; Toumbourou, John W.; Carlin, John B.; Catalano, Richard F.; Patton, George C.

2010-01-01

Objective Violence and social relational aggression are global problems that become prominent in early adolescence. This study examines associations between pubertal stage and adolescent violent behavior and social relational aggression. Methods This paper draws on cross-sectional data from the International Youth Development Study (IYDS), which comprised two state-wide representative samples of students in grades 5, 7 and 9 (N = 5,769) in Washington State in the United States and Victoria, Australia, drawn as a 2-stage cluster sample in each state. The study used carefully matched methods to conduct a school-administered, self-report student survey measuring behavioral outcomes including past year violent behavior (measured as attacking or beating up another person) and social relational aggression (excluding peers from the group, threatening to spread lies or rumors), as well as a comprehensive range of risk and protective factors and pubertal development. Results Compared with early puberty, the odds of violent behavior were approximately three-fold higher in mid-puberty (odds ratio [OR]: 2.87; 95% confidence interval [CI]: 1.81,4.55) and late puberty (OR: 3.79; 95% CI: 2.25,6.39), after adjustment for age, gender, state, and state by gender interaction. For social relational aggression, there were weaker overall associations after adjustment but these included an interaction between pubertal stage and age, showing stronger associations with pubertal stage at younger age (p = .003; mid-puberty OR 1.78; 95% CI 1.20,2.63; late puberty OR 3.00; 95% CI 1.95,4.63. Associations between pubertal stage and violent behavior and social relational aggression remained (although the magnitude of effects was reduced), after the inclusion of social contextual mediators in the analyses. Conclusions Pubertal stage was associated with higher rates of violent behavior and social relational aggression, with the latter association seen only at younger ages. Puberty may be an important phase for interventions aimed at preventing the adolescent rise in violent and antisocial behaviors. PMID:20624807

Reduction in early stroke risk in carotid stenosis with transient ischemic attack associated with statin treatment

PubMed Central

Merwick, Áine; Albers, Gregory W; Arsava, Ethem M; Ay, Hakan; Calvet, David; Coutts, Shelagh B; Cucchiara, Brett L; Demchuk, Andrew M; Giles, Matthew F; Mas, Jean-Louis; Olivot, Jean Marc; Purroy, Francisco; Rothwell, Peter M; Saver, Jeffrey L; Sharma, Vijay K; Tsivgoulis, Georgios; Kelly, Peter J

2013-01-01

Background and Purpose Statins reduce stroke risk when initiated months after TIA/stroke and reduce early vascular events in acute coronary syndromes, possibly via pleiotropic plaque-stabilisation. Few data exist regarding acute statin use in TIA. We aimed to determine if statin pre-treatment at TIA onset modified early stroke risk in carotid stenosis. Methods We analyzed data from 2770 TIA patients from 11 centres, 387 with ipsilateral carotid stenosis. ABCD2 score, abnormal DWI, medication pre-treatment, and early stroke were recorded. Results In patients with carotid stenosis, 7-day stroke risk was 8.3% (95% confidence interval [CI] 5.7–11.1) compared with 2.7% [CI 2.0–3.4%] without stenosis (p<0.0001) (90-day risks 17.8% and 5.7% [p<0.0001]). Among carotid stenosis patients, non-procedural 7-day stroke risk was 3.8% [CI 1.2–9.7%] with statin treatment at TIA onset, compared to 13.2% [CI 8.5–19.8%] in those not statin pre-treated (p=0.01) (90-day risks 8.9% versus 20.8% [p=0.01]). Statin pre-treatment was associated with reduced stroke risk in carotid stenosis patients (OR for 90-day stroke 0.37, CI 0.17–0.82), but not non-stenosis patients (OR 1.3, CI 0.8–2.24) (p for interaction 0.008). On multivariable logistic regression, the association remained after adjustment for ABCD2 score, smoking, antiplatelet treatment, recent TIA, and DWI hyperintensity (adjusted p for interaction 0.054). Conclusion In acute symptomatic carotid stenosis, statin pre-treatment was associated with reduced stroke risk, consistent with findings from randomized trials in acute coronary syndromes. These data support the hypothesis that statins started acutely after TIA symptom onset may also be beneficial to prevent early stroke. Randomized trials addressing this question are required. PMID:23908061

iCI: Iterative CI toward full CI.

PubMed

Liu, Wenjian; Hoffmann, Mark R

2016-03-08

It is shown both theoretically and numerically that the minimal multireference configuration interaction (CI) approach [Liu, W.; Hoffmann, M. R. Theor. Chem. Acc. 2014, 133, 1481] converges quickly and monotonically from above to full CI by updating the primary, external, and secondary states that describe the respective static, dynamic, and again static components of correlation iteratively, even when starting with a rather poor description of a strongly correlated system. In short, the iterative CI (iCI) is a very effective means toward highly correlated wave functions and, ultimately, full CI.

What Do High-Risk Patients Value? Perspectives on a Care Management Program.

PubMed

Ganguli, Ishani; Orav, E John; Weil, Eric; Ferris, Timothy G; Vogeli, Christine

2018-01-01

There is growing interest in coordinating care for high-risk patients through care management programs despite inconsistent results on cost reduction. Early evidence suggests patient-centered benefits, but we know little about how participants engage with the programs and what aspects they value. To explore care management program participants' awareness and perceived utility of program offerings. Cross-sectional telephone survey administered December 2015-January 2016. Patients enrolled in a Boston-area primary care-based care management program. Our main outcome was the number of topics in which patients reported having "very helpful" interactions with their care team in the past year. We analyzed awareness of one's care manager as an intermediate outcome, and then as a primary predictor of the main outcome, along with patient demographics, years in the program, attitudes, and worries as secondary predictors. The survey response rate was 45.8% (n = 1220); non-respondents were similar to respondents. More respondents reported worrying about family (72.8%) or financial issues (52.5%) than about their own health (41.6%). Seventy-four percent reported care manager awareness, particularly women (OR 1.33, 95% CI 1.01-1.77) and those with more years in the program (OR 1.16, 95% CI 1.03-1.30). While interaction rates ranged from 19.8% to 72.4% across topics, 81.3% rated at least one interaction as very helpful. Those who were aware of their care manager reported very helpful interactions on more topics (OR 2.77, 95% CI 2.15-3.56), as did women (OR 1.25, 95% CI 1.00-1.55), younger respondents (OR 0.98 for older age, 95% CI 0.97-0.99), and those with higher risk scores (OR 1.04, 95% CI 1.02-1.06), preference for deferring treatment decisions to doctors (OR 2.00, 95% CI 1.60-2.50), and reported control over their health (OR 1.67, 95% CI 1.33-2.10). High-risk patients reported helpful interactions with their care team around medical and social determinants of health, particularly those who knew their care manager. Promoting care manager awareness may help participants make better use of the program.

Genetic and environmental factors affecting self-esteem from age 14 to 17: a longitudinal study of Finnish twins

PubMed Central

Raevuori, Anu; Dick, Danielle M.; Keski-Rahkonen, Anna; Pulkkinen, Lea; Rose, Richard J.; Rissanen, Aila; Kaprio, Jaakko; Viken, Richard J.; Silventoinen, Karri

2007-01-01

Background We analysed genetic and environmental influences on self-esteem and its stability across adolescence. Methods Finnish twins born in 1983–1987 were assessed by questionnaire at ages 14y (N= 4132 twin individuals) and 17y (N=3841 twin individuals). Self esteem was measured using the Rosenberg global self-esteem scale and analyzed using quantitative genetic methods for twin data in the Mx statistical package. Results The heritability of self-esteem was 0.62 (95% CI 0.56–0.68) in 14-y-old boys and 0.40 (95% CI 0.26–0.54) in 14-y-old girls, while the corresponding estimates at age 17y were 0.48 (95% CI 0.39–0.56) and 0.29 (95% CI 0.11–0.45). Rosenberg self-esteem scores at age 14 y and 17 y were modestly correlated (r=0.44 in boys, r=0.46 in girls). In boys, the correlation was mainly (82%) due to genetic factors, with residual co-variation due to unique environment. In girls, genetic (31%) and common environmental (61%) factors largely explained the correlation. Conclusions In adolescence, self-esteem seems to be differently regulated in boys versus girls. A key challenge for future research is to identify environmental influences contributing to self-esteem during adolescence and how these factors interact with genetic influences. PMID:17537282

TIMMDC1/C3orf1 functions as a membrane-embedded mitochondrial complex I assembly factor through association with the MCIA complex.

PubMed

Guarani, Virginia; Paulo, Joao; Zhai, Bo; Huttlin, Edward L; Gygi, Steven P; Harper, J Wade

2014-03-01

Complex I (CI) of the electron transport chain, a large membrane-embedded NADH dehydrogenase, couples electron transfer to the release of protons into the mitochondrial inner membrane space to promote ATP production through ATP synthase. In addition to being a central conduit for ATP production, CI activity has been linked to neurodegenerative disorders, including Parkinson's disease. CI is built in a stepwise fashion through the actions of several assembly factors. We employed interaction proteomics to interrogate the molecular associations of 15 core subunits and assembly factors previously linked to human CI deficiency, resulting in a network of 101 proteins and 335 interactions (edges). TIMMDC1, a predicted 4-pass membrane protein, reciprocally associated with multiple members of the MCIA CI assembly factor complex and core CI subunits and was localized in the mitochondrial inner membrane, and its depletion resulted in reduced CI activity and cellular respiration. Quantitative proteomics demonstrated a role for TIMMDC1 in assembly of membrane-embedded and soluble arms of the complex. This study defines a new membrane-embedded CI assembly factor and provides a resource for further analysis of CI biology.

Dietary fiber, kidney function, inflammation, and mortality risk.

PubMed

Xu, Hong; Huang, Xiaoyan; Risérus, Ulf; Krishnamurthy, Vidya M; Cederholm, Tommy; Arnlöv, Johan; Lindholm, Bengt; Sjögren, Per; Carrero, Juan Jesús

2014-12-05

In the United States population, high dietary fiber intake has been associated with a lower risk of inflammation and mortality in individuals with kidney dysfunction. This study aimed to expand such findings to a Northern European population. Dietary fiber intake was calculated from 7-day dietary records in 1110 participants aged 70-71 years from the Uppsala Longitudinal Study of Adult Men (examinations performed during 1991-1995). Dietary fiber was adjusted for total energy intake by the residual method. Renal function was estimated from the concentration of serum cystatin C, and deaths were registered prospectively during a median follow-up of 10.0 years. Dietary fiber independently and directly associated with eGFR (adjusted difference, 2.6 ml/min per 1.73 m(2) per 10 g/d higher; 95% confidence interval [95% CI], 0.3 to 4.9). The odds of C-reactive protein >3 mg/L were lower (linear trend, P=0.002) with higher fiber quartiles. During follow-up, 300 participants died (incidence rate of 2.87 per 100 person-years at risk). Multiplicative interactions were observed between dietary fiber intake and kidney dysfunction in the prediction of mortality. Higher dietary fiber was associated with lower mortality in unadjusted analysis. These associations were stronger in participants with kidney dysfunction (eGFR<60 ml/min per 1.73 m(2)) (hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.98) than in those without (HR, 1.30; 95% CI, 0.76 to 2.22; P value for interaction, P=0.04), and were mainly explained by a lower incidence of cancer-related deaths (0.25; 95% CI, 0.10 to 0.65) in individuals with kidney dysfunction versus individuals with an eGFR≥60 ml/min per 1.73 m(2) (1.61; 95% CI, 0.69 to 3.74; P value for interaction, P=0.01). High dietary fiber was associated with better kidney function and lower inflammation in community-dwelling elderly men from Sweden. High dietary fiber was also associated with lower (cancer) mortality risk, especially in individuals with kidney dysfunction. Copyright © 2014 by the American Society of Nephrology.

Dietary Fiber, Kidney Function, Inflammation, and Mortality Risk

PubMed Central

Xu, Hong; Huang, Xiaoyan; Risérus, Ulf; Krishnamurthy, Vidya M.; Cederholm, Tommy; Ärnlöv, Johan; Lindholm, Bengt; Sjögren, Per

2014-01-01

Background and objectives In the United States population, high dietary fiber intake has been associated with a lower risk of inflammation and mortality in individuals with kidney dysfunction. This study aimed to expand such findings to a Northern European population. Design, setting, participants, & measurements Dietary fiber intake was calculated from 7-day dietary records in 1110 participants aged 70–71 years from the Uppsala Longitudinal Study of Adult Men (examinations performed during 1991–1995). Dietary fiber was adjusted for total energy intake by the residual method. Renal function was estimated from the concentration of serum cystatin C, and deaths were registered prospectively during a median follow-up of 10.0 years. Results Dietary fiber independently and directly associated with eGFR (adjusted difference, 2.6 ml/min per 1.73 m2 per 10 g/d higher; 95% confidence interval [95% CI], 0.3 to 4.9). The odds of C-reactive protein >3 mg/L were lower (linear trend, P=0.002) with higher fiber quartiles. During follow-up, 300 participants died (incidence rate of 2.87 per 100 person-years at risk). Multiplicative interactions were observed between dietary fiber intake and kidney dysfunction in the prediction of mortality. Higher dietary fiber was associated with lower mortality in unadjusted analysis. These associations were stronger in participants with kidney dysfunction (eGFR<60 ml/min per 1.73 m2) (hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.98) than in those without (HR, 1.30; 95% CI, 0.76 to 2.22; P value for interaction, P=0.04), and were mainly explained by a lower incidence of cancer-related deaths (0.25; 95% CI, 0.10 to 0.65) in individuals with kidney dysfunction versus individuals with an eGFR≥60 ml/min per 1.73 m2 (1.61; 95% CI, 0.69 to 3.74; P value for interaction, P=0.01). Conclusions High dietary fiber was associated with better kidney function and lower inflammation in community-dwelling elderly men from Sweden. High dietary fiber was also associated with lower (cancer) mortality risk, especially in individuals with kidney dysfunction. PMID:25280496

Genome-wide gene-asbestos exposure interaction association study identifies a common susceptibility variant on 22q13.31 associated with lung cancer risk

PubMed Central

Liu, Chen-yu; Stücker, Isabelle; Chen, Chu; Goodman, Gary; McHugh, Michelle K.; D’Amelio, Anthony M.; Etzel, Carol J.; Li, Su; Lin, Xihong; Christiani, David C.

2015-01-01

Background Occupational asbestos exposure has been found to increase lung cancer risk in epidemiological studies. Methods We conducted an asbestos exposure-gene interaction analyses among several Caucasian populations who were current or ex-smokers. The discovery phase included 833 Caucasian cases and 739 Caucasian controls, and used a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) with gene-asbestos interaction effects. The top ranked SNPs from the discovery phase were replicated within the International Lung and Cancer Consortium (ILCCO). First, in silico replication was conducted in those groups that had GWAS and asbestos exposure data, including 1,548 cases and 1,527 controls. This step was followed by de novo genotyping to replicate the results from the in silico replication, and included 1,539 cases and 1,761 controls. Multiple logistic regression was used to assess the SNP-asbestos exposure interaction effects on lung cancer risk. Results We observed significantly increased lung cancer risk among MIRLET7BHG (MIRLET7B host gene located at 22q13.31) polymorphisms rs13053856, rs11090910, rs11703832, and rs12170325 heterozygous and homozygous variant allele(s) carriers [p<5×10−7 by likelihood ratio test; df=1]. Among the heterozygous and homozygous variant allele(s) carriers of polymorphisms rs13053856, rs11090910, rs11703832, and rs12170325, each unit increase in the natural log-transformed asbestos exposure score was associated with age-, sex-, smoking status- and center-adjusted ORs of 1.34 (95%CI=1.18–1.51), 1.24 (95%CI=1.14–1.35), 1.28 (95%CI=1.17–1.40), and 1.26 (95%CI=1.15–1.38), respectively for lung cancer risk. Conclusion Our findings suggest that MIRLET7BHG polymorphisms may be important predictive markers for asbestos exposure-related lung cancer. Impact To our knowledge, our study is the first report using a systematic genome-wide analysis in combination with detailed asbestos exposure data and replication to evaluate asbestos-associated lung cancer risk. PMID:26199339

Harnessing Neuroplasticity to Promote Rehabilitation: CI Therapy for TBI

DTIC Science & Technology

2016-10-01

scheduled plus 33 to be enrolled, because we assume that the proportion of withdrawals will be the same as experienced to date, i.e., 24%. This plan will...period? Victor Mark, Investigator Interactive Immersive Virtual Reality Walking for SCI Neuropathic Pain (Trost) 0.24 calendar months Kim Cerise...Direct Costs: $149,999 This project designs and test an immersive virtual reality treatment method to control neuropathic pain following traumatic spinal

Change over Time in Police Interactions and HIV Risk Behavior Among Female Sex Workers in Andhra Pradesh, India.

PubMed

Erausquin, Jennifer Toller; Reed, Elizabeth; Blankenship, Kim M

2015-06-01

Little is known about the effectiveness of intervening to change interactions between female sex workers (FSWs) and police in order to reduce HIV risk. Using data collected in the context of a HIV prevention intervention that included components to change policing practices (n = 1,680), we examine the association of FSWs' reports of negative police interactions and HIV risk behaviors and whether these associations varied over time. Results show negative police interactions declined significantly over time. FSWs who had more than one negative police interaction were more likely to experience STI symptoms (AOR 2.97 [95 % CI 2.27-3.89]), inconsistently use condoms with their clients (AOR 1.36 [95 % CI 1.03-1.79]), and accept more money for condomless sex (AOR 2.37 [95 % CI 1.76-3.21]). Over time, these associations were stable or increased. Even where interventions have reduced the number of police incidents experienced by FSWs, stakeholders in HIV prevention must remain vigilant in challenging these incidents.

Maternal Smoking during Pregnancy, Prematurity and Recurrent Wheezing in Early Childhood

PubMed Central

Robison, Rachel G; Kumar, Rajesh; Arguelles, Lester M; Hong, Xiumei; Wang, Guoying; Apollon, Stephanie; Bonzagni, Anthony; Ortiz, Kathryn; Pearson, Colleen; Pongracic, Jacqueline A; Wang, Xiaobin

2013-01-01

Summary Background Prenatal maternal smoking and prematurity independently affect wheezing and asthma in childhood. Objective We sought to evaluate the interactive effects of maternal smoking and prematurity upon the development of early childhood wheezing. Methods We evaluated 1448 children with smoke exposure data from a prospective urban birth cohort in Boston. Maternal antenatal and postnatal exposure was determined from standardized questionnaires. Gestational age was assessed by the first day of the last menstrual period and early prenatal ultrasound (preterm<37 weeks gestation). Wheezing episodes were determined from medical record extraction of well and ill/unscheduled visits. The primary outcome was recurrent wheezing, defined as ≥ 4 episodes of physician documented wheezing. Logistic regression models and zero inflated negative binomial regression (for number of episodes of wheeze) assessed the independent and joint association of prematurity and maternal antenatal smoking on recurrent wheeze, controlling for relevant covariates. Results In the cohort, 90 (6%) children had recurrent wheezing, 147 (10%) were exposed to in utero maternal smoke and 419 (29%) were premature. Prematurity (odds ratio [OR] 2.0; 95% CI, 1.3-3.1) was associated with an increased risk of recurrent wheezing, but in utero maternal smoking was not (OR 1.1, 95% CI 0.5-2.4). Jointly, maternal smoke exposure and prematurity caused an increased risk of recurrent wheezing (OR 3.8, 95% CI 1.8-8.0). There was an interaction between prematurity and maternal smoking upon episodes of wheezing (p=0.049). Conclusions We demonstrated an interaction between maternal smoking during pregnancy and prematurity on childhood wheezing in this urban, multiethnic birth cohort. PMID:22290763

Effect of breastfeeding on obesity of schoolchildren: influence of maternal education

PubMed Central

Pudla, Katia Jakovljevic; Gonzaléz-Chica, David Alejandro; de Vasconcelos, Francisco de Assis Guedes

2015-01-01

Abstract Objective: To evaluate the association between duration of breastfeeding (BF) and obesity in schoolchildren of Florianópolis (SC), and the role of possible effect modifiers. Methods: Cross-sectional study with a random sample of 2826 schoolchildren (7-14 years). Weight and height were measured according to standardized procedures. Data concerning BF and sociodemographic variables were obtained from a questionnaire sent to parents/guardians. Children's nutritional status was evaluated by BMI-for-age z-score for gender (WHO reference curves). Adjusted analyses were performed through logistic regression, considering a possible interaction among variables. Results: Prevalence of obesity was 8.6% (95% CI: 7.6-9.7%) and 55.7% (95% CI: 53.8-57.6%) received breastmilk for ≥6 months. BF was not associated with obesity, even in the adjusted analysis. Stratified analysis according to maternal schooling showed that, in children aged 7-10 years and children whose mothers had 0-8 years of schooling, the chance of obesity was lower among those breastfeed for >1 month, especially among those who received breastmilk for 1-5 months (OR=0.22; 95% CI 0.08-0.62). Among children of women with higher schooling (>8 years), the chance of obesity was 44% lower in those who were breastfed for >12 months (p-value for interaction <0.01). This interaction was not found in older children (11-14 years). Conclusions: Among children of women with lower schooling, BF for any period longer than 1 month is protective against obesity; however, for a higher maternal schooling, BF for less than 12 months increases the odds of obesity. PMID:26100592

Interaction between HLA-B60 and HLA-B27 as a Better Predictor of Ankylosing Spondylitis in a Taiwanese Population

PubMed Central

Hsu, Yu-Wen; Wen, Ya-Feng; Wang, Wen-Chang; Wong, Ruey-Hong; Lu, Hsing-Fang; van Gaalen, Floris A.; Chang, Wei-Chiao

2015-01-01

Objective Ankylosing spondylitis (AS) is a form of chronic inflammatory spondyloarthritis (SpA) that causes pain and stiffness in spines or joints. Human leukocyte antigen B27 (HLA-B27) and B60 (HLA-B60) have been reported as major genetic risk factors of AS. In addition, rs13202464, located on major histocompatibility complex (MHC) region, showed high sensitivity (98.7%) and specificity (98.0%) for HLA-B27. Design The aim of our study is to test whether the interaction between HLA-B60 and HLA-B27 (rs13202464) can serve as a better predictor of AS. We have genotyped HLA-B60 and rs13202464 among 471 patients with AS and 557 healthy subjects. Combined risk factors were investigated to test the biological interaction. Results Our results indicated that the relative risk (RR) for HLA-B27+/HLA-B60− was 152 (95% CI 91 to 255) and it increased to 201 (95% CI 85 to 475) in HLA-B27+/HLA-B60+ patients (with HLA-B27−/HLA-B60− as reference). Combinational analysis of two risk factors (HLA-B27+/HLA-B60+) showed a relative excess risk due to interaction (RERI) of 46.79 (95% CI: -117.58 to 211.16), attributable proportion (AP) of 0.23 (95% CI: -0.41 to 0.88) and a synergy index (S) of 1.31 (95% CI: 0.56 to 3.04). Conclusion In conclusion, genetic interaction analysis revealed that the interaction between HLA-B60 and HLA-B27 is a better marker for the risk of AS susceptibility in a Taiwanese population. PMID:26469786

Interaction between HLA-B60 and HLA-B27 as a Better Predictor of Ankylosing Spondylitis in a Taiwanese Population.

PubMed

Wei, James Cheng-Chung; Sung-Ching, Henry Wong; Hsu, Yu-Wen; Wen, Ya-Feng; Wang, Wen-Chang; Wong, Ruey-Hong; Lu, Hsing-Fang; Gaalen, Floris A van; Chang, Wei-Chiao

2015-01-01

Ankylosing spondylitis (AS) is a form of chronic inflammatory spondyloarthritis (SpA) that causes pain and stiffness in spines or joints. Human leukocyte antigen B27 (HLA-B27) and B60 (HLA-B60) have been reported as major genetic risk factors of AS. In addition, rs13202464, located on major histocompatibility complex (MHC) region, showed high sensitivity (98.7%) and specificity (98.0%) for HLA-B27. The aim of our study is to test whether the interaction between HLA-B60 and HLA-B27 (rs13202464) can serve as a better predictor of AS. We have genotyped HLA-B60 and rs13202464 among 471 patients with AS and 557 healthy subjects. Combined risk factors were investigated to test the biological interaction. Our results indicated that the relative risk (RR) for HLA-B27+/HLA-B60- was 152 (95% CI 91 to 255) and it increased to 201 (95% CI 85 to 475) in HLA-B27+/HLA-B60+ patients (with HLA-B27-/HLA-B60- as reference). Combinational analysis of two risk factors (HLA-B27+/HLA-B60+) showed a relative excess risk due to interaction (RERI) of 46.79 (95% CI: -117.58 to 211.16), attributable proportion (AP) of 0.23 (95% CI: -0.41 to 0.88) and a synergy index (S) of 1.31 (95% CI: 0.56 to 3.04). In conclusion, genetic interaction analysis revealed that the interaction between HLA-B60 and HLA-B27 is a better marker for the risk of AS susceptibility in a Taiwanese population.

Fast food price, diet behavior, and cardiometabolic health: Differential associations by neighborhood SES and neighborhood fast food restaurant availability in the CARDIA study.

PubMed

Rummo, Pasquale E; Meyer, Katie A; Green Howard, Annie; Shikany, James M; Guilkey, David K; Gordon-Larsen, Penny

2015-09-01

Little research has addressed whether neighborhood context influences associations between fast food price, diet, and cardiometabolic health. We investigated these associations using 25 years of Coronary Artery Risk Development in Young Adults (CARDIA) study data (n=4,469, observations=21,134). We found a negative association between fast food price and consumption, with stronger inverse associations in more (vs. less) deprived neighborhoods [3rd tertile: β=-0.68 (95% CI: (-0.85, -0.51); 1st tertile: β=-0.22 (95% CI: -0.42, -0.02); p-interaction-0.002], and a similar association for BMI [3rd tertile: β=-1.34 (95% CI: -1.54, -1.14); 1st tertile: β=-0.45 (95% CI: -0.66, -0.25); p-interaction<0.001], but not insulin resistance [3rd tertile: β=-0.07 (95% CI: -0.24, 0.09); 1st tertile: β=0.09 (95% CI: -0.08, 0.26); p-interaction=0.40]. We observed no modification of fast food price by fast food availability. Future research on obesity disparities should consider potential differences in the association between fast food prices and health outcomes across neighborhood socioeconomic levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fast food price, diet behavior, and cardiometabolic health: differential associations by neighborhood SES and neighborhood fast food restaurants in the CARDIA Study

PubMed Central

Gordon-Larsen, Penny; Rummo, Pasquale E.; Meyer, Katie A.; Howard, Annie Green; Shikany, James M.; Guilkey, David K.

2015-01-01

Little research has addressed whether neighborhood context influences associations between fast food price, diet, and cardiometabolic health. We investigated these associations using 25 years of Coronary Artery Risk Development in Young Adults (CARDIA) study data (n=4,469, observations=21,134). We found a negative association between fast food price and consumption, with stronger inverse associations in more (vs. less) deprived neighborhoods [3rd tertile: β=−0.68 (95% CI: (−0.85, −0.51); 1st tertile: β=−0.22 (95% CI: −0.42, −0.02) ; p-interaction-0.002], and a similar association for BMI [3rd tertile: β=−1.34 (95% CI: −1.54, −1.14); 1st tertile: β=−0.45 (95% CI: −0.66, −0.25); p-interaction<0.001], but not insulin resistance [3rd tertile: β=− 0.07 (95% CI: −0.24, 0.09); 1st tertile: β=0.09 (95% CI: −0.08, 0.26); p-interaction=0.40]. We observed no modification of fast food price by fast food availability. Future research on obesity disparities should consider potential differences in the association between fast food prices and health outcomes across neighborhood socioeconomic levels. PMID:26319447

Relationship between channel interaction and spectral-ripple discrimination in cochlear implant usersa

PubMed Central

Jones, Gary L.; Ho Won, Jong; Drennan, Ward R.; Rubinstein, Jay T.

2013-01-01

Cochlear implant (CI) users can achieve remarkable speech understanding, but there is great variability in outcomes that is only partially accounted for by age, residual hearing, and duration of deafness. Results might be improved with the use of psychophysical tests to predict which sound processing strategies offer the best potential outcomes. In particular, the spectral-ripple discrimination test offers a time-efficient, nonlinguistic measure that is correlated with perception of both speech and music by CI users. Features that make this “one-point” test time-efficient, and thus potentially clinically useful, are also connected to controversy within the CI field about what the test measures. The current work examined the relationship between thresholds in the one-point spectral-ripple test, in which stimuli are presented acoustically, and interaction indices measured under the controlled conditions afforded by direct stimulation with a research processor. Results of these studies include the following: (1) within individual subjects there were large variations in the interaction index along the electrode array, (2) interaction indices generally decreased with increasing electrode separation, and (3) spectral-ripple discrimination improved with decreasing mean interaction index at electrode separations of one, three, and five electrodes. These results indicate that spectral-ripple discrimination thresholds can provide a useful metric of the spectral resolution of CI users. PMID:23297914

Relationship between channel interaction and spectral-ripple discrimination in cochlear implant users.

PubMed

Jones, Gary L; Won, Jong Ho; Drennan, Ward R; Rubinstein, Jay T

2013-01-01

Cochlear implant (CI) users can achieve remarkable speech understanding, but there is great variability in outcomes that is only partially accounted for by age, residual hearing, and duration of deafness. Results might be improved with the use of psychophysical tests to predict which sound processing strategies offer the best potential outcomes. In particular, the spectral-ripple discrimination test offers a time-efficient, nonlinguistic measure that is correlated with perception of both speech and music by CI users. Features that make this "one-point" test time-efficient, and thus potentially clinically useful, are also connected to controversy within the CI field about what the test measures. The current work examined the relationship between thresholds in the one-point spectral-ripple test, in which stimuli are presented acoustically, and interaction indices measured under the controlled conditions afforded by direct stimulation with a research processor. Results of these studies include the following: (1) within individual subjects there were large variations in the interaction index along the electrode array, (2) interaction indices generally decreased with increasing electrode separation, and (3) spectral-ripple discrimination improved with decreasing mean interaction index at electrode separations of one, three, and five electrodes. These results indicate that spectral-ripple discrimination thresholds can provide a useful metric of the spectral resolution of CI users.

Ciona intestinalis Noto4 contains a phosphotyrosine interaction domain and is involved in the midline intercalation of notochord cells.

PubMed

Yamada, Shigehiro; Ueno, Naoto; Satoh, Nori; Takahashi, Hiroki

2011-01-01

Brachyury plays a pivotal role in the notochord formation in ascidian embryos. Ciona intestinalis Noto4 (Ci-Noto4) was isolated as a gene downstream of Ci-Bra. This gene encodes a 307 amino-acid protein with a C-terminal phosphotyrosine interaction domain (PTB/PID). Expression of Ci-Noto4 commences at the neural plate stage and is specific to notochord cells. Suppression of Ci-Noto4 levels with specific antisense morpholino oligonucleotides resulted in the formation of two rows of notochord cells owing to a lack of midline intercalation between the bilateral populations of progenitor cells. In contrast, overexpression of Ci-Noto4 by injection of a Ci-Bra(promoter):Ci-Noto4-EGFP construct into fertilized eggs disrupted the localization of notochord cells. Ci-Noto4 overexpression did not affect cellular differentiation in the notochord, muscle, mesenchyme, or nervous system. Analysis of Ci-Noto4 regions that are responsible for its function suggested significant roles for the PTB/PID and a central region, an area with no obvious sequence similarity to other known proteins. These results suggested that PTB/PID-containing Ci-Noto4 is essential for midline intercalation of notochord cells in chordate embryos.

Obesity interacts with infectious mononucleosis in risk of multiple sclerosis.

PubMed

Hedström, A K; Lima Bomfim, I; Hillert, J; Olsson, T; Alfredsson, L

2015-03-01

The possible interaction between adolescent obesity and past infectious mononucleosis (IM) was investigated with regard to multiple sclerosis (MS) risk. This report is based on two population-based case-control studies, one with incident cases (1780 cases, 3885 controls) and one with prevalent cases (4502 cases, 4039 controls). Subjects were categorized based on adolescent body mass index (BMI) and past IM and compared with regard to occurrence of MS by calculating odds ratios with 95% confidence intervals (CIs) employing logistic regression. A potential interaction between adolescent BMI and past IM was evaluated by calculating the attributable proportion due to interaction. Regardless of human leukocyte antigen (HLA) status, a substantial interaction was observed between adolescent obesity and past IM with regard to MS risk. The interaction was most evident when IM after the age of 10 was considered (attributable proportion due to interaction 0.8, 95% CI 0.6-1.0 in the incident study, and attributable proportion due to interaction 0.7, 95% CI 0.5-1.0 in the prevalent study). In the incident study, the odds ratio of MS was 14.7 (95% CI 5.9-36.6) amongst subjects with adolescent obesity and past IM after the age of 10, compared with subjects with none of these exposures. The corresponding odds ratio in the prevalent study was 13.2 (95% CI 5.2-33.6). An obese state both impacts the cellular immune response to infections and induces a state of chronic immune-mediated inflammation which may contribute to explain our finding of an interaction between adolescent BMI and past IM. Measures taken against adolescent obesity may thus be a preventive strategy against MS. © 2014 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

Randomized Phase II Study of Clofarabine-Based Consolidation for Younger Adults With Acute Myeloid Leukemia in First Remission.

PubMed

Thomas, Xavier; de Botton, Stéphane; Chevret, Sylvie; Caillot, Denis; Raffoux, Emmanuel; Lemasle, Emilie; Marolleau, Jean-Pierre; Berthon, Céline; Pigneux, Arnaud; Vey, Norbert; Reman, Oumedaly; Simon, Marc; Recher, Christian; Cahn, Jean-Yves; Hermine, Olivier; Castaigne, Sylvie; Celli-Lebras, Karine; Ifrah, Norbert; Preudhomme, Claude; Terré, Christine; Dombret, Hervé

2017-04-10

Purpose To evaluate the efficacy and safety of a clofarabine-based combination (CLARA) versus conventional high-dose cytarabine (HDAC) as postremission chemotherapy in younger patients with acute myeloid leukemia (AML). Patients and Methods Patients age 18 to 59 years old with intermediate- or unfavorable-risk AML in first remission and no identified donor for allogeneic stem-cell transplantation (SCT) were eligible. Two hundred twenty-one patients were randomly assigned to receive three CLARA or three HDAC consolidation cycles. The primary end point was relapse-free survival (RFS). To handle the confounding effect of SCT that could occur in patients with late donor identification, hazard ratios (HRs) of events were adjusted on the time-dependent treatment × SCT interaction term. Results At 2 years, RFS was 58.5% (95% CI, 49% to 67%) in the CLARA arm and 46.5% (95% CI, 37% to 55%) in the HDAC arm. Overall, 110 patients (55 in each arm) received SCT in first remission. On the basis of a multivariable Cox-adjusted treatment × SCT interaction, the HR of CLARA over HDAC before or in absence of SCT was 0.65 (95% CI, 0.43 to 0.98; P = .041). In a sensitivity analysis, when patients who received SCT in first remission were censored at SCT time, 2-year RFS was 53.3% (95% CI, 39% to 66%) in the CLARA arm and 31.0% (95% CI, 19% to 43%) in the HDAC arm (HR, 0.63; 95% CI, 0.41 to 0.98; P = .043). Gain in RFS could be related to the lower cumulative incidence of relapse observed in the CLARA arm versus the HDAC arm (33.9% v 46.4% at 2 years, respectively; cause-specific HR, 0.61; 95% CI, 0.40 to 0.94; P = .025). CLARA cycles were associated with higher hematologic and nonhematologic toxicity than HDAC cycles. Conclusion These results suggest that CLARA might be considered as a new chemotherapy option in younger patients with AML in first remission.

Enhanced audio-visual interactions in the auditory cortex of elderly cochlear-implant users.

PubMed

Schierholz, Irina; Finke, Mareike; Schulte, Svenja; Hauthal, Nadine; Kantzke, Christoph; Rach, Stefan; Büchner, Andreas; Dengler, Reinhard; Sandmann, Pascale

2015-10-01

Auditory deprivation and the restoration of hearing via a cochlear implant (CI) can induce functional plasticity in auditory cortical areas. How these plastic changes affect the ability to integrate combined auditory (A) and visual (V) information is not yet well understood. In the present study, we used electroencephalography (EEG) to examine whether age, temporary deafness and altered sensory experience with a CI can affect audio-visual (AV) interactions in post-lingually deafened CI users. Young and elderly CI users and age-matched NH listeners performed a speeded response task on basic auditory, visual and audio-visual stimuli. Regarding the behavioral results, a redundant signals effect, that is, faster response times to cross-modal (AV) than to both of the two modality-specific stimuli (A, V), was revealed for all groups of participants. Moreover, in all four groups, we found evidence for audio-visual integration. Regarding event-related responses (ERPs), we observed a more pronounced visual modulation of the cortical auditory response at N1 latency (approximately 100 ms after stimulus onset) in the elderly CI users when compared with young CI users and elderly NH listeners. Thus, elderly CI users showed enhanced audio-visual binding which may be a consequence of compensatory strategies developed due to temporary deafness and/or degraded sensory input after implantation. These results indicate that the combination of aging, sensory deprivation and CI facilitates the coupling between the auditory and the visual modality. We suggest that this enhancement in multisensory interactions could be used to optimize auditory rehabilitation, especially in elderly CI users, by the application of strong audio-visually based rehabilitation strategies after implant switch-on. Copyright © 2015 Elsevier B.V. All rights reserved.

Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19,268 Children

PubMed Central

Kilpeläinen, Tuomas O.; Qi, Lu; Brage, Soren; Sharp, Stephen J.; Sonestedt, Emily; Demerath, Ellen; Ahmad, Tariq; Mora, Samia; Kaakinen, Marika; Sandholt, Camilla Helene; Holzapfel, Christina; Autenrieth, Christine S.; Hyppönen, Elina; Cauchi, Stéphane; He, Meian; Kutalik, Zoltan; Kumari, Meena; Stančáková, Alena; Meidtner, Karina; Balkau, Beverley; Tan, Jonathan T.; Mangino, Massimo; Timpson, Nicholas J.; Song, Yiqing; Zillikens, M. Carola; Jablonski, Kathleen A.; Garcia, Melissa E.; Johansson, Stefan; Bragg-Gresham, Jennifer L.; Wu, Ying; van Vliet-Ostaptchouk, Jana V.; Onland-Moret, N. Charlotte; Zimmermann, Esther; Rivera, Natalia V.; Tanaka, Toshiko; Stringham, Heather M.; Silbernagel, Günther; Kanoni, Stavroula; Feitosa, Mary F.; Snitker, Soren; Ruiz, Jonatan R.; Metter, Jeffery; Larrad, Maria Teresa Martinez; Atalay, Mustafa; Hakanen, Maarit; Amin, Najaf; Cavalcanti-Proença, Christine; Grøntved, Anders; Hallmans, Göran; Jansson, John-Olov; Kuusisto, Johanna; Kähönen, Mika; Lutsey, Pamela L.; Nolan, John J.; Palla, Luigi; Pedersen, Oluf; Pérusse, Louis; Renström, Frida; Scott, Robert A.; Shungin, Dmitry; Sovio, Ulla; Tammelin, Tuija H.; Rönnemaa, Tapani; Lakka, Timo A.; Uusitupa, Matti; Rios, Manuel Serrano; Ferrucci, Luigi; Bouchard, Claude; Meirhaeghe, Aline; Fu, Mao; Walker, Mark; Borecki, Ingrid B.; Dedoussis, George V.; Fritsche, Andreas; Ohlsson, Claes; Boehnke, Michael; Bandinelli, Stefania; van Duijn, Cornelia M.; Ebrahim, Shah; Lawlor, Debbie A.; Gudnason, Vilmundur; Harris, Tamara B.; Sørensen, Thorkild I. A.; Mohlke, Karen L.; Hofman, Albert; Uitterlinden, André G.; Tuomilehto, Jaakko; Lehtimäki, Terho; Raitakari, Olli; Isomaa, Bo; Njølstad, Pål R.; Florez, Jose C.; Liu, Simin; Ness, Andy; Spector, Timothy D.; Tai, E. Shyong; Froguel, Philippe; Boeing, Heiner; Laakso, Markku; Marmot, Michael; Bergmann, Sven; Power, Chris; Khaw, Kay-Tee; Chasman, Daniel; Ridker, Paul; Hansen, Torben; Monda, Keri L.; Illig, Thomas; Järvelin, Marjo-Riitta; Wareham, Nicholas J.; Hu, Frank B.; Groop, Leif C.; Orho-Melander, Marju; Ekelund, Ulf; Franks, Paul W.; Loos, Ruth J. F.

2011-01-01

Background The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268). Methods and Findings All studies identified to have data on the FTO rs9939609 variant (or any proxy [r 2>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A−) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20–1.26), but PA attenuated this effect (p interaction  = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio  = 1.22/allele, 95% CI 1.19–1.25) than in the inactive group (odds ratio  = 1.30/allele, 95% CI 1.24–1.36). No such interaction was found in children and adolescents. Conclusions The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity. Please see later in the article for the Editors' Summary PMID:22069379

Risk of unsafe abortion associated with long-term contraception behaviour: a case control study from Sri Lanka.

PubMed

Arambepola, Carukshi; Rajapaksa, Lalini C

2017-06-29

When faced with an unintended pregnancy, some women choose to undergo an unsafe abortion, while others do not. This choice may depend on long-term contraception that shapes the fertility goals of women, along with many other risk factors. We assessed the risk for unsafe abortion associated with contraceptive practices based on women's long-term behaviour, and its likely modification by the use of different types of contraceptives among women in Sri Lanka. An unmatched case-control study was conducted in nine hospitals among 171 women admitted for care following an unsafe abortion (Cases) and 600 women admitted to same hospitals for delivery of an unintended term pregnancy (Controls). Interviewer-administered-questionnaires assessed their socio-economic, reproductive and fertility (decisions on family size, family completion) characteristics, contraceptive method last used (traditional, modern), reasons for discontinuation/never-use, and contraceptive practices assessed at different time points. Using several regression models, the risk of abortion was assessed for 'non-use' of contraception against 'ineffective use' at conception; for non-use further categorised as 'never-use', 'early-discontinuation' (discontinued before last birth interval) and 'late-discontinuation' (discontinued during last birth interval); and for any interaction between the contraceptive practice and contraceptive method last used among the ever-users of contraception. At conception, 'non-use' of contraception imparted a two-fold risk for abortion against ineffective use (adjusted-OR = 2.0; 95% CI: 1.2-3.2). The abortion risk on 'non-use' varied further according to 'early' (adjusted-OR = 1.7; 95% CI: 1.1-3.1) and 'late' (adjusted-OR = 2.3; 95% CI: 1.5-3.6) discontinuation of contraception, but not with 'never-use' (crude-OR = 1.1; 95% CI: 0.6-2.3). Among the ever-users, the risk of abortion varied within each contraceptive practice by their last used contraceptive method and reasons for discontinuation. A significant interaction between modern contraceptives and early discontinuation (adjusted-OR = 1.4; 95% CI = 1.1-3.1) demonstrated a seven-fold abortion risk for early discontinuation of modern methods against its ineffective use. In particular, hormonal methods seemed to be responsible for this risk (51.1% cases versus 42.5% controls). Long-term contraceptive practices showed varying risk for abortion, and was further modified by early discontinuation of modern contraceptives. This knowledge should be applied during postnatal visits by public-health staff.

Pushing configuration-interaction to the limit: Towards massively parallel MCSCF calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vogiatzis, Konstantinos D.; Ma, Dongxia; Olsen, Jeppe

A new large-scale parallel multiconfigurational self-consistent field (MCSCF) implementation in the open-source NWChem computational chemistry code is presented. The generalized active space approach is used to partition large configuration interaction (CI) vectors and generate a sufficient number of batches that can be distributed to the available cores. Massively parallel CI calculations with large active spaces can be performed. The new parallel MCSCF implementation is tested for the chromium trimer and for an active space of 20 electrons in 20 orbitals, which can now routinely be performed. Unprecedented CI calculations with an active space of 22 electrons in 22 orbitals formore » the pentacene systems were performed and a single CI iteration calculation with an active space of 24 electrons in 24 orbitals for the chromium tetramer was possible. In conclusion, the chromium tetramer corresponds to a CI expansion of one trillion Slater determinants (914 058 513 424) and is the largest conventional CI calculation attempted up to date.« less

Pushing configuration-interaction to the limit: Towards massively parallel MCSCF calculations

DOE PAGES

Vogiatzis, Konstantinos D.; Ma, Dongxia; Olsen, Jeppe; ...

2017-11-14

A new large-scale parallel multiconfigurational self-consistent field (MCSCF) implementation in the open-source NWChem computational chemistry code is presented. The generalized active space approach is used to partition large configuration interaction (CI) vectors and generate a sufficient number of batches that can be distributed to the available cores. Massively parallel CI calculations with large active spaces can be performed. The new parallel MCSCF implementation is tested for the chromium trimer and for an active space of 20 electrons in 20 orbitals, which can now routinely be performed. Unprecedented CI calculations with an active space of 22 electrons in 22 orbitals formore » the pentacene systems were performed and a single CI iteration calculation with an active space of 24 electrons in 24 orbitals for the chromium tetramer was possible. In conclusion, the chromium tetramer corresponds to a CI expansion of one trillion Slater determinants (914 058 513 424) and is the largest conventional CI calculation attempted up to date.« less

Pushing configuration-interaction to the limit: Towards massively parallel MCSCF calculations

NASA Astrophysics Data System (ADS)

Vogiatzis, Konstantinos D.; Ma, Dongxia; Olsen, Jeppe; Gagliardi, Laura; de Jong, Wibe A.

2017-11-01

A new large-scale parallel multiconfigurational self-consistent field (MCSCF) implementation in the open-source NWChem computational chemistry code is presented. The generalized active space approach is used to partition large configuration interaction (CI) vectors and generate a sufficient number of batches that can be distributed to the available cores. Massively parallel CI calculations with large active spaces can be performed. The new parallel MCSCF implementation is tested for the chromium trimer and for an active space of 20 electrons in 20 orbitals, which can now routinely be performed. Unprecedented CI calculations with an active space of 22 electrons in 22 orbitals for the pentacene systems were performed and a single CI iteration calculation with an active space of 24 electrons in 24 orbitals for the chromium tetramer was possible. The chromium tetramer corresponds to a CI expansion of one trillion Slater determinants (914 058 513 424) and is the largest conventional CI calculation attempted up to date.

Increasing water productivity, nitrogen economy, and grain yield of rice by water saving irrigation and fertilizer-N management.

PubMed

Aziz, Omar; Hussain, Saddam; Rizwan, Muhammad; Riaz, Muhammad; Bashir, Saqib; Lin, Lirong; Mehmood, Sajid; Imran, Muhammad; Yaseen, Rizwan; Lu, Guoan

2018-06-01

The looming water resources worldwide necessitate the development of water-saving technologies in rice production. An open greenhouse experiment was conducted on rice during the summer season of 2016 at Huazhong Agricultural University, Wuhan, China, in order to study the influence of irrigation methods and nitrogen (N) inputs on water productivity, N economy, and grain yield of rice. Two irrigation methods, viz. conventional irrigation (CI) and "thin-shallow-moist-dry" irrigation (TSMDI), and three levels of nitrogen, viz. 0 kg N ha -1 (N 0 ), 90 kg N ha -1 (N 1 ), and 180 kg N ha -1 (N 2 ), were examined with three replications. Study data indicated that no significant water by nitrogen interaction on grain yield, biomass, water productivity, N uptake, NUE, and fertilizer N balance was observed. Results revealed that TSMDI method showed significantly higher water productivity and irrigation water applications were reduced by 17.49% in TSMDI compared to CI. Thus, TSMDI enhanced root growth and offered significantly greater water saving along with getting more grain yield compared to CI. Nitrogen tracer ( 15 N) technique accurately assessed the absorption and distribution of added N in the soil crop environment and divulge higher nitrogen use efficiency (NUE) influenced by TSMDI. At the same N inputs, the TSMDI was the optimal method to minimize nitrogen leaching loss by decreasing water leakage about 18.63%, which are beneficial for the ecological environment.

Interaction between physical activity, PITX1 rs647161 genetic polymorphism and colorectal cancer risk in a Korean population: a case-control study

PubMed Central

Gunathilake, Madhawa Neranjan; Lee, Jeonghee; Cho, Young Ae; Oh, Jae Hwan; Chang, Hee Jin; Sohn, Dae Kyung; Shin, Aesun; Kim, Jeongseon

2018-01-01

This study assessed the interaction between physical activity and colorectal cancer (CRC) risk based on a polymorphism in the paired-like homeodomain 1 (PITX1) gene in Koreans. In total, 923 cases and 1,846 controls were enrolled at the National Cancer Center, Korea. Subjects who did regular exercise showed a significantly reduced risk of CRC than those did not exercise regularly (OR = 0.37, 95% CI = 0.30–0.45). Subjects in the highest tertile of metabolic equivalents of task (MET)-minutes per week showed a significantly lower risk of CRC (OR = 0.62, 95% CI = 0.48–0.79, p-trend < 0.001). In the dominant model, minor allele carriers showed a significantly higher risk of CRC than subjects homozygous for the major allele (OR = 1.46, 95% CI = 1.18–1.80). The PITX1 genetic variant showed significant interactions with regular exercise and CRC risk (p-interaction = 0.018) and colon cancer risk (p-interaction = 0.029) among all subjects. Subjects who carried at least one minor allele and did not regularly exercise showed a greater risk of CRC (OR = 1.81, 95% CI = 1.37–2.41). Subjects who were homozygous for the major allele with high physical activity showed a significantly reduced risk of CRC (OR = 0.56, 95% CI = 0.38–0.82). Thus, individuals with PITX1 genetic variants can have benefit from physical activity regarding prevention of CRC risk in a Korean population. PMID:29484135

Are neighbourhood social capital and availability of sports facilities related to sports participation among Dutch adolescents?

PubMed Central

2012-01-01

Background The aim of this study is to explore whether availability of sports facilities, parks, and neighbourhood social capital (NSC) and their interaction are associated with leisure time sports participation among Dutch adolescents. Methods Cross-sectional analyses were conducted on complete data from the last wave of the YouRAction evaluation trial. Adolescents (n = 852) completed a questionnaire asking for sports participation, perceived NSC and demographics. Ecometric methods were used to aggregate perceived NSC to zip code level. Availability of sports facilities and parks was assessed by means of geographic information systems within the zip-code area and within a 1600 meter buffer. Multilevel logistic regression analyses, with neighborhood and individual as levels, were conducted to examine associations between physical and social environmental factors and leisure time sports participation. Simple slopes analysis was conducted to decompose interaction effects. Results NSC was significantly associated with sports participation (OR: 3.51 (95%CI: 1.18;10.41)) after adjustment for potential confounders. Availability of sports facilities and availability of parks were not associated with sports participation. A significant interaction between NSC and density of parks within the neighbourhood area (OR: 1.22 (90%CI: 1.01;1.34)) was found. Decomposition of the interaction term showed that adolescents were most likely to engage in leisure time sports when both availability of parks and NSC were highest. Conclusions The results of this study indicate that leisure time sports participation is associated with levels of NSC, but not with availability of parks or sports facilities. In addition, NSC and availability of parks in the zip code area interacted in such a way that leisure time sports participation is most likely among adolescents living in zip code areas with higher levels of NSC, and higher availability of parks. Hence, availability of parks appears only to be important for leisure time sports participation when NSC is high. PMID:22849512

Can shoulder range of movement be measured accurately using the Microsoft Kinect sensor plus Medical Interactive Recovery Assistant (MIRA) software?

PubMed

Wilson, James D; Khan-Perez, Jennifer; Marley, Dominic; Buttress, Susan; Walton, Michael; Li, Baihua; Roy, Bibhas

2017-12-01

This study compared the accuracy of measuring shoulder range of movement (ROM) with a simple laptop-sensor combination vs. trained observers (shoulder physiotherapists and shoulder surgeons) using motion capture (MoCap) laboratory equipment as the gold standard. The Microsoft Kinect sensor (Microsoft Corp., Redmond, WA, USA) tracks 3-dimensional human motion. Ordinarily used with an Xbox (Microsoft Corp.) video game console, Medical Interactive Recovery Assistant (MIRA) software (MIRA Rehab Ltd., London, UK) allows this small sensor to measure shoulder movement with a standard computer. Shoulder movements of 49 healthy volunteers were simultaneously measured by trained observers, MoCap, and the MIRA device. Internal rotation was assessed with the shoulder abducted 90° and external rotation with the shoulder adducted. Visual estimation and MIRA measurements were compared with gold standard MoCap measurements for agreement using Bland-Altman methods. There were 1670 measurements analyzed. The MIRA evaluations of all 4 cardinal shoulder movements were significantly more precise, with narrower limits of agreement, than the measurements of trained observers. MIRA achieved ±11° (95% confidence interval [CI], 8.7°-12.6°) for forward flexion vs. ±16° (95% CI, 14.6°-17.6°) by trained observers. For abduction, MIRA showed ±11° (95% CI, 8.7°-12.8°) against ±15° (95% CI, 13.4°-16.2°) for trained observers. MIRA attained ±10° (95% CI, 8.1°-11.9°) during external rotation measurement, whereas trained observers only reached ±21° (95% CI, 18.7°-22.6°). For internal rotation, MIRA achieved ±9° (95% CI, 7.2°-10.4°), which was again better than TOs at ±18° (95% CI, 16.0°-19.3°). A laptop combined with a Microsoft Kinect sensor and the MIRA software can measure shoulder movements with acceptable levels of accuracy. This technology, which can be easily set up, may also allow precise shoulder ROM measurement outside the clinic setting. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

The Relationship Between Metabolic Risk Factors and Incident Cardiovascular Disease in Europeans, South Asians, and African Caribbeans

PubMed Central

Tillin, Therese; Hughes, Alun D.; Mayet, Jamil; Whincup, Peter; Sattar, Naveed; Forouhi, Nita G.; McKeigue, Paul M.; Chaturvedi, Nish

2013-01-01

Objectives This study sought to determine whether ethnic differences in diabetes, dyslipidemia, and ectopic fat deposition account for ethnic differences in incident cardiovascular disease. Background Coronary heart disease risks are elevated in South Asians and are lower in African Caribbeans compared with Europeans. These ethnic differences map to lipid patterns and ectopic fat deposition. Methods Cardiovascular risk factors were assessed in 2,049 Europeans, 1,517 South Asians, and 630 African Caribbeans from 1988 through 1991 (mean age: 52.4 ± 6.9 years). Fatal and nonfatal events were captured over a median 20.5-year follow-up. Subhazard ratios (SHR) were calculated using competing risks regression. Results Baseline diabetes prevalence was more than 3 times greater in South Asians and African Caribbeans than in Europeans. South Asians were more and African Caribbeans were less centrally obese and dyslipidemic than Europeans. Compared with Europeans, coronary heart disease incidence was greater in South Asians and less in African Caribbeans. The age- and sex-adjusted South Asian versus European SHR was 1.70 (95% confidence interval [CI]: 1.52 to 1.91, p < 0.001) and remained significant (1.45, 95% CI: 1.28 to 1.64, p < 0.001) when adjusted for waist-to-hip ratio. The African Caribbean versus European age- and sex-adjusted SHR of 0.64 (95% CI: 0.52 to 0.79, p < 0.001) remained significant when adjusted for high-density lipoprotein and low-density lipoprotein cholesterol (0.74, 95% CI: 0.60 to 0.92, p = 0.008). Compared with Europeans, South Asians and African Caribbeans experienced more strokes (age- and sex-adjusted SHR: 1.45 [95% CI: 1.17 to 1.80, p = 0.001] and 1.50 [95% CI: 1.13 to 2.00, p = 0.005], respectively), and this differential was more marked in those with diabetes (age-adjusted SHR: 1.97 [95% CI: 1.16 to 3.35, p = 0.038 for interaction] and 2.21 [95% CI: 1.14 to 4.30, p = 0.019 for interaction]). Conclusions Ethnic differences in measured metabolic risk factors did not explain differences in coronary heart disease incidence. The apparently greater association between diabetes and stroke risk in South Asians and African Caribbeans compared with Europeans merits further study. PMID:23500273

Pharmacokinetic Evaluation of the Interactions of Amenamevir (ASP2151) with Ketoconazole, Rifampicin, Midazolam, and Warfarin in Healthy Adults.

PubMed

Kusawake, Tomohiro; den Adel, Martin; Groenendaal-van de Meent, Dorien; Garcia-Hernandez, Alberto; Takada, Akitsugu; Kato, Kota; Ohtsu, Yoshiaki; Katashima, Masataka

2017-11-01

Amenamevir is a nonnucleoside antiherpes virus compound available for treating herpes zoster infections. Four studies aimed to determine any potential interactions between amenamevir and ketoconazole, rifampicin, midazolam, or warfarin in healthy male participants. Two studies were open-label studies that evaluated the effects of multiple doses of ketoconazole (400 mg) and rifampicin (600 mg) on the pharmacokinetics of a single oral dose of amenamevir. The other two studies were randomized, double-blind, parallel-group studies that evaluated the effects of multiple doses of amenamevir on the pharmacokinetics of a single dose of midazolam (7.5 mg) and warfarin (25 mg). A drug interaction was considered to occur if the 90% confidence interval (CI) of the least squares geometric mean ratio (GMR) of amenamevir to the comparator was outside the prespecified interval of 0.80-1.25. Interactions were observed between amenamevir and ketoconazole, rifampicin, and midazolam, but not between amenamevir and warfarin. After a single 400-mg dose of amenamevir, the GMRs of amenamevir plus ketoconazole or rifampicin versus amenamevir alone for C max and the area under the plasma concentration-time curve from time zero to infinity (AUC inf ) were 1.30 (90% CI 1.17-1.45) and 2.58 (90% CI 2.32-2.87), respectively, for ketoconazole and 0.42 (90% CI 0.37-0.49) and 0.17 (90% CI 0.15-0.19), respectively, for rifampicin. Following multiple doses of amenamevir (400 mg), the GMRs of midazolam plus amenamevir versus midazolam alone for AUC inf and C max were 0.53 (90% CI 0.47-0.61) and 0.63 (90% CI 0.50-0.80), respectively. After a single dose of warfarin, the (S)-warfarin and (R)-warfarin mean C max increased and mean AUC inf decreased in the presence of amenamevir; however, the 90% CIs of the GMRs for these parameters remained within the predefined limits. These findings confirm that amenamevir (as a cytochrome P450 3A4 substrate) can interact with ketoconazole or rifampicin, and (as a cytochrome P450 3A4 inducer) can interact with midazolam; however, no interaction between amenamevir and (S)-warfarin was observed, indicating that amenamevir is not an inducer of cytochrome P450 2C9. Astellas Pharma. EudraCT2007-002227-33 (study 15L-CL-008), EudraCT2007-002228-14 (study 15L-CL-009), EudraCT2007-002761-13 (study 15L-CL-010), and EudraCT2007-002779-14 (study 15L-CL-018).

Consumption of herbal remedies and dietary supplements amongst patients hospitalized in medical wards

PubMed Central

Goldstein, Lee H; Elias, Mazen; Ron-Avraham, Gilat; Biniaurishvili, Ben Zion; Madjar, Magali; Kamargash, Irena; Braunstein, Rony; Berkovitch, Matitiahu; Golik, Ahuva

2007-01-01

What is already known about this subject In general, use of herbal remedies and supplements is constantly rising in the western population and this may be potentially dangerous due to adverse effects and drug–herb interactions. All information up to now has been derived from the general population or outpatients. There are no publications on the rate of consumption of herbals in inpatients, or the awareness of the medical team of this fact. What this study adds Approximately 25% of patients hospitalized in internal medicine wards consume some kind of herbal or dietary supplement.Consumption is associated with higher income, nonsmoking and benign prostatic hypertrophy.The medical team was aware of the consumption in only 23% of the cases, and all drug–herbal interactions which we discovered were missed by the medical team. Aims Herbal remedies may have adverse effects and potentially serious interactions with some commonly prescribed conventional medications. Little is known about consumption of herbal remedies and dietary supplements by hospitalized patients. The aim was to evaluate the rate of consumption and characterize the patients hospitalized in internal medicine departments who consume herbal remedies and dietary supplements. Also, to assess the medical teams' awareness and assess the percentage of patients with possible drug–herb interactions. Methods Patients hospitalized in the medical wards of two hospitals in Israel were interviewed about their use of herbal remedies or dietary supplements. The medical records were searched for evidence that the medical team had knowledge of the use of herbal remedies or dietary supplements. Results Two hundred and ninety-nine hospitalized medical patients were interviewed. Of the participants, 26.8% were herbal or dietary supplement consumers (HC). On multivariate analysis the only variates associated with herbal or dietary supplement consumption were the hospital [odds ratio (OR) 2.97, 95% confidence interval (CI) 1.29, 6.52], income (OR 0.39, 95% CI 0.15, 1.05), smoking habits (OR 0.17, 95% CI 0.05, 0.55) and benign prostatic hypertrophy (OR 4.64, 95% CI 1.3, 16.5). Ninety-four percent of the patients had not been asked specifically of herbal consumption by the medical team. Only 23% of the hospital's medical files of the HC patients had any record of the use of herbal or dietary supplements. Seven possible drug–herbal interactions were encountered (7.1%). The most serious was an interaction between camomile tea and ciclosporin. Conclusions Herbal remedy consumption is common amongst patients hospitalized in internal medicine wards and is often overlooked by the medical team. Patients and doctors should be more aware of the possible adverse effects and of the potential of herb–drug interactions. PMID:17425631

The interaction between impaired acute insulin response and insulin resistance predict type 2 diabetes and impairment of fasting glucose.

PubMed

Zethelius, Björn; Berglund, Lars; Hänni, Arvo; Berne, Christian

2008-01-01

Impaired acute insulin response (AIR) and insulin resistance (IR) are characteristics of Type 2 diabetes (T2DM). The aim was to develop risk models for T2DM and impaired fasting glucose (IFG), reflecting estimates both of AIR and IR, and of their interaction, as predictors over 20 years of follow-up. We developed predictive models using hierarchic multiple regression analyses in a population-based cohort of 1227 men with normal fasting blood glucose at baseline (1970-73) and were reinvestigated after 10 and after 20 years. Using IVGTT-variables correlated either to AIR or to IR, separate models were developed. Combined models were also estimated from which prediction scores, representing individual risk, were calculated. In combined models, interaction between prediction scores reflecting AIR and IR predicted T2DM and IFG. Lowest tertile of AIR and the highest tertile of IR showed a relative risk (RR) of 15.3 (95%-CI=5.58-41.84) for T2DM compared to the contrast group (high AIR and low IR). Corresponding RR for IFG was 13.23 (95%-CI=6.53-26.78). C-statistic increased from 0.76 to 0.79 (p=0.018) for T2DM and from 0.77 to 0.80 for IFG (p=0.062) taking interaction into account. Main effects of lowest tertile of AIR and highest tertile of IR versus best were: RR for T2DM, 8.80 (95%-CI=4.25-18.21) and 6.31 (95%-CI=3.26-12.21); for IFG, 9.07, (95%-CI=5.38-15.29) and 4.49 (95%-CI=2.98-6-76). The interaction between low AIR and high IR revealed a high relative risk for T2DM or IFG reflecting the interplay between these factors over long time on worsening glucose tolerance and development of manifest disease.

Investigating multiple candidate genes and nutrients in the folate metabolism pathway to detect genetic and nutritional risk factors for lung cancer.

PubMed

Swartz, Michael D; Peterson, Christine B; Lupo, Philip J; Wu, Xifeng; Forman, Michele R; Spitz, Margaret R; Hernandez, Ladia M; Vannucci, Marina; Shete, Sanjay

2013-01-01

Folate metabolism, with its importance to DNA repair, provides a promising region for genetic investigation of lung cancer risk. This project investigates genes (MTHFR, MTR, MTRR, CBS, SHMT1, TYMS), folate metabolism related nutrients (B vitamins, methionine, choline, and betaine) and their gene-nutrient interactions. We analyzed 115 tag single nucleotide polymorphisms (SNPs) and 15 nutrients from 1239 and 1692 non-Hispanic white, histologically-confirmed lung cancer cases and controls, respectively, using stochastic search variable selection (a Bayesian model averaging approach). Analyses were stratified by current, former, and never smoking status. Rs6893114 in MTRR (odds ratio [OR] = 2.10; 95% credible interval [CI]: 1.20-3.48) and alcohol (drinkers vs. non-drinkers, OR = 0.48; 95% CI: 0.26-0.84) were associated with lung cancer risk in current smokers. Rs13170530 in MTRR (OR = 1.70; 95% CI: 1.10-2.87) and two SNP*nutrient interactions [betaine*rs2658161 (OR = 0.42; 95% CI: 0.19-0.88) and betaine*rs16948305 (OR = 0.54; 95% CI: 0.30-0.91)] were associated with lung cancer risk in former smokers. SNPs in MTRR (rs13162612; OR = 0.25; 95% CI: 0.11-0.58; rs10512948; OR = 0.61; 95% CI: 0.41-0.90; rs2924471; OR = 3.31; 95% CI: 1.66-6.59), and MTHFR (rs9651118; OR = 0.63; 95% CI: 0.43-0.95) and three SNP*nutrient interactions (choline*rs10475407; OR = 1.62; 95% CI: 1.11-2.42; choline*rs11134290; OR = 0.51; 95% CI: 0.27-0.92; and riboflavin*rs8767412; OR = 0.40; 95% CI: 0.15-0.95) were associated with lung cancer risk in never smokers. This study identified possible nutrient and genetic factors related to folate metabolism associated with lung cancer risk, which could potentially lead to nutritional interventions tailored by smoking status to reduce lung cancer risk.

Canonical-ensemble state-averaged complete active space self-consistent field (SA-CASSCF) strategy for problems with more diabatic than adiabatic states: Charge-bond resonance in monomethine cyanines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olsen, Seth, E-mail: seth.olsen@uq.edu.au

2015-01-28

This paper reviews basic results from a theory of the a priori classical probabilities (weights) in state-averaged complete active space self-consistent field (SA-CASSCF) models. It addresses how the classical probabilities limit the invariance of the self-consistency condition to transformations of the complete active space configuration interaction (CAS-CI) problem. Such transformations are of interest for choosing representations of the SA-CASSCF solution that are diabatic with respect to some interaction. I achieve the known result that a SA-CASSCF can be self-consistently transformed only within degenerate subspaces of the CAS-CI ensemble density matrix. For uniformly distributed (“microcanonical”) SA-CASSCF ensembles, self-consistency is invariant tomore » any unitary CAS-CI transformation that acts locally on the ensemble support. Most SA-CASSCF applications in current literature are microcanonical. A problem with microcanonical SA-CASSCF models for problems with “more diabatic than adiabatic” states is described. The problem is that not all diabatic energies and couplings are self-consistently resolvable. A canonical-ensemble SA-CASSCF strategy is proposed to solve the problem. For canonical-ensemble SA-CASSCF, the equilibrated ensemble is a Boltzmann density matrix parametrized by its own CAS-CI Hamiltonian and a Lagrange multiplier acting as an inverse “temperature,” unrelated to the physical temperature. Like the convergence criterion for microcanonical-ensemble SA-CASSCF, the equilibration condition for canonical-ensemble SA-CASSCF is invariant to transformations that act locally on the ensemble CAS-CI density matrix. The advantage of a canonical-ensemble description is that more adiabatic states can be included in the support of the ensemble without running into convergence problems. The constraint on the dimensionality of the problem is relieved by the introduction of an energy constraint. The method is illustrated with a complete active space valence-bond (CASVB) analysis of the charge/bond resonance electronic structure of a monomethine cyanine: Michler’s hydrol blue. The diabatic CASVB representation is shown to vary weakly for “temperatures” corresponding to visible photon energies. Canonical-ensemble SA-CASSCF enables the resolution of energies and couplings for all covalent and ionic CASVB structures contributing to the SA-CASSCF ensemble. The CASVB solution describes resonance of charge- and bond-localized electronic structures interacting via bridge resonance superexchange. The resonance couplings can be separated into channels associated with either covalent charge delocalization or chemical bonding interactions, with the latter significantly stronger than the former.« less

Canonical-ensemble state-averaged complete active space self-consistent field (SA-CASSCF) strategy for problems with more diabatic than adiabatic states: charge-bond resonance in monomethine cyanines.

PubMed

Olsen, Seth

2015-01-28

This paper reviews basic results from a theory of the a priori classical probabilities (weights) in state-averaged complete active space self-consistent field (SA-CASSCF) models. It addresses how the classical probabilities limit the invariance of the self-consistency condition to transformations of the complete active space configuration interaction (CAS-CI) problem. Such transformations are of interest for choosing representations of the SA-CASSCF solution that are diabatic with respect to some interaction. I achieve the known result that a SA-CASSCF can be self-consistently transformed only within degenerate subspaces of the CAS-CI ensemble density matrix. For uniformly distributed ("microcanonical") SA-CASSCF ensembles, self-consistency is invariant to any unitary CAS-CI transformation that acts locally on the ensemble support. Most SA-CASSCF applications in current literature are microcanonical. A problem with microcanonical SA-CASSCF models for problems with "more diabatic than adiabatic" states is described. The problem is that not all diabatic energies and couplings are self-consistently resolvable. A canonical-ensemble SA-CASSCF strategy is proposed to solve the problem. For canonical-ensemble SA-CASSCF, the equilibrated ensemble is a Boltzmann density matrix parametrized by its own CAS-CI Hamiltonian and a Lagrange multiplier acting as an inverse "temperature," unrelated to the physical temperature. Like the convergence criterion for microcanonical-ensemble SA-CASSCF, the equilibration condition for canonical-ensemble SA-CASSCF is invariant to transformations that act locally on the ensemble CAS-CI density matrix. The advantage of a canonical-ensemble description is that more adiabatic states can be included in the support of the ensemble without running into convergence problems. The constraint on the dimensionality of the problem is relieved by the introduction of an energy constraint. The method is illustrated with a complete active space valence-bond (CASVB) analysis of the charge/bond resonance electronic structure of a monomethine cyanine: Michler's hydrol blue. The diabatic CASVB representation is shown to vary weakly for "temperatures" corresponding to visible photon energies. Canonical-ensemble SA-CASSCF enables the resolution of energies and couplings for all covalent and ionic CASVB structures contributing to the SA-CASSCF ensemble. The CASVB solution describes resonance of charge- and bond-localized electronic structures interacting via bridge resonance superexchange. The resonance couplings can be separated into channels associated with either covalent charge delocalization or chemical bonding interactions, with the latter significantly stronger than the former.

[Association of peripheral and central systolic blood pressure with urinary albumin-to-creatinine ratio in a community-based population in Beijing].

PubMed

Fan, F F; Li, Y X; Jia, J; Li, H X; Qi, L T; Huo, Y; Zhang, Y

2017-03-06

Objective: The aim of this study was to investigate the association of both peripheral and central systolic blood pressure (pSBP and cSBP) with urinary albumin-to-creatinine ratio (UACR) in a community-based population in Beijing. Methods: A total of 3 479 Chinese subjects with questionnaire, UACR, pSBP, and cSBP data available were included from an atherosclerosis cohort of Peking University First Hospital in Shijingshan District, Beijing followed up from April to July in 2014. Multivariate linear regression analyses were used to examine the effect of pSBP and cSBP on lnUACR, and further tests for interactions were performed according to associated covariates. Results: Subjects were (59.0±8.6) years old, 36.2% ( n= 1 260) were male, 46.0% ( n= 1 595) had hypertension, and 20.2% ( n= 700) had diabetes. The pSBP and cSBP was (126.9 ± 16.4) mmHg (1 mmHg=0.133 kPa), and (136.3 ± 16.7) mmHg, respectively. P (50) ( P (25)- P (75)) of UACR was 6.2 (4.2-11.1) mg/g. Both pSBP and cSBP were linearly associated with lnUACR adjusted for age, sex, body mass index, smoking status, drinking status, triglyceride, HDL-C, LDL-C, fasting glucose, creatinine, history of cardiovascular disease, antihypertensive and hypoglycemic agents (every 10 mmHg increase for pSBP: β=0.12, 95 %CI: 0.10-0.15, P< 0.001; for cSBP: β=0.11, 95 %CI: 0.09-0.14, P< 0.001). The relationships were remained in subgroups such as non-hypertension group, non-diabetes group, normal UACR group, and 3-combination group (every 10 mmHg increase for pSBP: β=0.09, 95 %CI: 0.05-0.13; β=0.12, 95 %CI: 0.10-0.15; β=0.07, 95 %CI: 0.06-0.09; β=0.08, 95 %CI: 0.05-0.12. for cSBP: β=0.07, 95 %CI: 0.04-0.11; β=0.11, 95 %CI: 0.08-0.13; β=0.07, 95 %CI: 0.05-0.08; β=0.06, 95 %CI: 0.03-0.09, all P< 0.001). Furthermore, analyses for interaction found that both pSBP and cSBP were more strongly associated with lnUACR in males, current smokers and subjects with high serum creatinine level (≥87 µmol/L) when compared with females, non-current smokers and subjects with low serum creatinine level (<87 µmol/L), respectively (all P for interaction<0.05). Conclusion: The results showed that both pSBP and cSBP were independently associated with UACR in this Chinese community-based population even in low risk population suggesting well-controlled both peripheral and central blood pressure may reduce urinary albumin. Males, current smokers and subjects with higher serum creatinine should pay more attention to the impacts of pSBP and cSBP on UACR.

Change over Time in Police Interactions and HIV Risk Behavior Among Female Sex Workers in Andhra Pradesh, India

PubMed Central

Reed, Elizabeth; Blankenship, Kim M.

2015-01-01

Little is known about the effectiveness of intervening to change interactions between female sex workers (FSWs) and police in order to reduce HIV risk. Using data collected in the context of a HIV prevention intervention that included components to change policing practices (n = 1,680), we examine the association of FSWs’ reports of negative police interactions and HIV risk behaviors and whether these associations varied over time. Results show negative police interactions declined significantly over time. FSWs who had more than one negative police interaction were more likely to experience STI symptoms (AOR 2.97 [95 % CI 2.27–3.89]), inconsistently use condoms with their clients (AOR 1.36 [95 % CI 1.03–1.79]), and accept more money for condomless sex (AOR 2.37 [95 % CI 1.76–3.21]). Over time, these associations were stable or increased. Even where interventions have reduced the number of police incidents experienced by FSWs, stakeholders in HIV prevention must remain vigilant in challenging these incidents. PMID:25354735

Tuning of few-electron states and optical absorption anisotropy in GaAs quantum rings.

PubMed

Wu, Zhenhua; Li, Jian; Li, Jun; Yin, Huaxiang; Liu, Yu

2017-11-15

The electronic and optical properties of a GaAs quantum ring (QR) with few electrons in the presence of the Rashba spin-orbit interaction (RSOI) and the Dresselhaus spin-orbit interaction (DSOI) have been investigated theoretically. The configuration interaction (CI) method is employed to calculate the eigenvalues and eigenstates of the multiple-electron QR accurately. Our numerical results demonstrate that the symmetry breaking induced by the RSOI and DSOI leads to an anisotropic distribution of multi-electron states. The Coulomb interaction offers additional modulation of the electron distribution and thus the optical absorption indices in the quantum rings. By tuning the magnetic/electric fields and/or electron numbers in a quantum ring, one can change its optical properties significantly. Our theory provides a new way to control the multi-electron states and optical properties of a QR by hybrid modulations or by electrical means only.

The kangaroo cation-independent mannose 6-phosphate receptor binds insulin-like growth factor II with low affinity.

PubMed

Yandell, C A; Dunbar, A J; Wheldrake, J F; Upton, Z

1999-09-17

The mammalian cation-independent mannose 6-phosphate receptor (CI-MPR) binds mannose 6-phosphate-bearing glycoproteins and insulin-like growth factor (IGF)-II. However, the CI-MPR from the opossum has been reported to bind bovine IGF-II with low affinity (Dahms, N. M., Brzycki-Wessell, M. A., Ramanujam, K. S., and Seetharam, B. (1993) Endocrinology 133, 440-446). This may reflect the use of a heterologous ligand, or it may represent the intrinsic binding affinity of this receptor. To examine the binding of IGF-II to a marsupial CI-MPR in a homologous system, we have previously purified kangaroo IGF-II (Yandell, C. A., Francis, G. L., Wheldrake, J. F., and Upton, Z. (1998) J. Endocrinol. 156, 195-204), and we now report the purification and characterization of the CI-MPR from kangaroo liver. The interaction of the kangaroo CI-MPR with IGF-II has been examined by ligand blotting, radioreceptor assay, and real-time biomolecular interaction analysis. Using both a heterologous and homologous approach, we have demonstrated that the kangaroo CI-MPR has a lower binding affinity for IGF-II than its eutherian (placental mammal) counterparts. Furthermore, real-time biomolecular interaction analysis revealed that the kangaroo CI-MPR has a higher affinity for kangaroo IGF-II than for human IGF-II. The cDNA sequence of the kangaroo CI-MPR indicates that there is considerable divergence in the area corresponding to the IGF-II binding site of the eutherian receptor. Thus, the acquisition of a high-affinity binding site for regulating IGF-II appears to be a recent event specific to the eutherian lineage.

Factors affecting quality of care in family planning clinics: a study from Iran.

PubMed

Shahidzadeh-Mahani, Ali; Omidvari, Sepideh; Baradaran, Hamid-Reza; Azin, Seyyed-Ali

2008-08-01

Despite good contraceptive coverage rates, recent studies in Iran have shown an alarmingly high incidence of unplanned pregnancy. To determine factors affecting quality of family planning services, a cross-sectional study was performed from June to August 2006 on women visiting urban Primary Health Care clinics in a provincial capital in western Iran. The primary focus of the study was on provider-client interaction. We used a slightly edited version of a UNICEF checklist and a convenient sampling method to assess quality of care in 396 visits to the family planning sections at 25 delivery points. Poor performance was observed notably in Counselling and Choice of method sections. In logistic regression analysis, the following factors were found to be associated with higher quality of care: provider experience [OR (odds ratio)=1.9, CI(0.95) (confidence interval)=1.2-3.0], low provider education (OR=6.7, CI(0.95)=4.0-10.8), smaller workload at the clinic (OR=3.7, CI(0.95)=2.0-6.7), and 'new client' status (OR=4.2, CI(0.95)=2.6-6.7). This study identified the issues of counselling and information exchange as the quality domains in serious need of improvement; these areas are expected to be the focus of future training programmes for care providers. Also, priority should be given to devising effective supervision mechanisms and on-the-job training of senior nursing and midwifery graduates to make them more competent in delivering basic family planning services.

Interaction of Sleep Duration and Sleep Quality on Hypertension Prevalence in Adult Chinese Males.

PubMed

Lu, Kai; Chen, Jia; Wu, Shouling; Chen, Ji; Hu, Dayi

2015-01-01

Previous studies demonstrated conflicting results about the association of sleep duration and hypertension. Given the potential relationship between sleep quality and hypertension, this study aimed to investigate the interaction of self-reported sleep duration and sleep quality on hypertension prevalence in adult Chinese males. We undertook a cross-sectional analysis of 4144 male subjects. Sleep duration were measured by self-reported average sleep time during the past month. Sleep quality was evaluated using the standard Pittsburgh Sleep Quality Index. Hypertension was defined as blood pressure level ≥140/90 mm Hg or current antihypertensive treatment. The association between hypertension prevalence, sleep duration, and sleep quality was analyzed using logistic regression after adjusting for basic cardiovascular characteristics. Sleep duration shorter than 8 hours was found to be associated with increased hypertension, with odds ratios and 95% confidence intervals (CIs) of 1.25 (95% CI, 1.03-1.52) for 7 hours, 1.41 (95% CI, 1.14-1.73) for 6 hours, and 2.38 (95% CI, 1.81-3.11) for <6 hours. Using very good sleep quality as the reference, good, poor, and very poor sleep quality were associated with hypertension, with odds ratios of 1.20 (95% CI, 1.01-1.42), 1.67 (95% CI, 1.32-2.11), and 2.32 (95% CI, 1.67-3.21), respectively. More importantly, further investigation of the association of different combinations of sleep duration and quality in relation to hypertension indicated an additive interaction. There is an additive interaction of poor sleep quality and short sleep duration on hypertension prevalence. More comprehensive measurement of sleep should be performed in future studies.

Uric acid predicts mortality and ischaemic stroke in subjects with diastolic dysfunction: the Tromsø Study 1994-2013.

PubMed

Norvik, Jon V; Schirmer, Henrik; Ytrehus, Kirsti; Storhaug, Hilde M; Jenssen, Trond G; Eriksen, Bjørn O; Mathiesen, Ellisiv B; Løchen, Maja-Lisa; Wilsgaard, Tom; Solbu, Marit D

2017-05-01

To investigate whether serum uric acid predicts adverse outcomes in persons with indices of diastolic dysfunction in a general population. We performed a prospective cohort study among 1460 women and 1480 men from 1994 to 2013. Endpoints were all-cause mortality, incident myocardial infarction, and incident ischaemic stroke. We stratified the analyses by echocardiographic markers of diastolic dysfunction, and uric acid was the independent variable of interest. Hazard ratios (HR) were estimated per 59 μmol/L increase in baseline uric acid. Multivariable adjusted Cox proportional hazards models showed that uric acid predicted all-cause mortality in subjects with E/A ratio <0.75 (HR 1.12, 95% confidence interval [CI] 1.00-1.25) or E/A ratio >1.5 (HR 1.51, 95% CI 1.09-2.09, P for interaction between E/A ratio category and uric acid = 0.02). Elevated uric acid increased mortality risk in persons with E-wave deceleration time <140 ms or >220 ms (HR 1.46, 95% CI 1.01-2.12 and HR 1.13, 95% CI 1.02-1.26, respectively; P for interaction = 0.04). Furthermore, in participants with isovolumetric relaxation time ≤60 ms, mortality risk was higher with increasing uric acid (HR 4.98, 95% CI 2.02-12.26, P for interaction = 0.004). Finally, elevated uric acid predicted ischaemic stroke in subjects with severely enlarged left atria (HR 1.62, 95% CI 1.03-2.53, P for interaction = 0.047). Increased uric acid was associated with higher all-cause mortality risk in subjects with echocardiographic indices of diastolic dysfunction, and with higher ischaemic stroke risk in persons with severely enlarged left atria.

Minimizing variability of cascade impaction measurements in inhalers and nebulizers.

PubMed

Bonam, Matthew; Christopher, David; Cipolla, David; Donovan, Brent; Goodwin, David; Holmes, Susan; Lyapustina, Svetlana; Mitchell, Jolyon; Nichols, Steve; Pettersson, Gunilla; Quale, Chris; Rao, Nagaraja; Singh, Dilraj; Tougas, Terrence; Van Oort, Mike; Walther, Bernd; Wyka, Bruce

2008-01-01

The purpose of this article is to catalogue in a systematic way the available information about factors that may influence the outcome and variability of cascade impactor (CI) measurements of pharmaceutical aerosols for inhalation, such as those obtained from metered dose inhalers (MDIs), dry powder inhalers (DPIs) or products for nebulization; and to suggest ways to minimize the influence of such factors. To accomplish this task, the authors constructed a cause-and-effect Ishikawa diagram for a CI measurement and considered the influence of each root cause based on industry experience and thorough literature review. The results illustrate the intricate network of underlying causes of CI variability, with the potential for several multi-way statistical interactions. It was also found that significantly more quantitative information exists about impactor-related causes than about operator-derived influences, the contribution of drug assay methodology and product-related causes, suggesting a need for further research in those areas. The understanding and awareness of all these factors should aid in the development of optimized CI methods and appropriate quality control measures for aerodynamic particle size distribution (APSD) of pharmaceutical aerosols, in line with the current regulatory initiatives involving quality-by-design (QbD).

Interaction between parental psychosis and early motor development and the risk of schizophrenia in a general population birth cohort

PubMed Central

Keskinen, E.; Marttila, A.; Marttila, R.; Jones, P.B.; Murray, G.K.; Moilanen, K.; Koivumaa-Honkanen, H.; Mäki, P.; Isohanni, M.; Jääskeläinen, E.; Miettunen, J.

2015-01-01

Background Delayed motor development in infancy and family history of psychosis are both associated with increased risk of schizophrenia, but their interaction is largely unstudied. Aim To investigate the association of the age of achieving motor milestones and parental psychosis and their interaction in respect to risk of schizophrenia. Methods We used data from the general population-based prospective Northern Finland Birth Cohort 1966 (n = 10,283). Developmental information of the cohort members was gathered during regular visits to Finnish child welfare clinics. Several registers were used to determine the diagnosis of schizophrenia among the cohort members and psychosis among the parents. Altogether 152 (1.5%) individuals had schizophrenia by the age of 46 years, with 23 (15.1%) of them having a parent with psychosis. Cox regression analysis was used in analyses. Results Parental psychosis was associated (P < 0.05) with later achievement of holding the head up, grabbing an object, and walking without support. In the parental psychosis group, the risk for schizophrenia was increased if holding the head up (hazard ratio [HR]: 2.46; degrees of freedom [df] = 1; 95% confidence interval [95% CI]: 1.07–5.66) and touching the thumb with the index finger (HR: 1.84; df = 1; 95% CI: 1.11–3.06) was later. In the group without parental psychosis, a delay in the following milestones increased the risk of schizophrenia: standing without support and walking without support. Parental psychosis had an interaction with delayed touching thumb with index finger (HR: 1.87; df = 1; 95% CI: 1.08–3.25) when risk of schizophrenia was investigated. Conclusions Parental psychosis was associated with achieving motor milestones later in infancy, particularly the milestones that appear early in a child's life. Parental psychosis and touching the thumb with the index finger had a significant interaction on risk of schizophrenia. Genetic risk for psychosis may interact with delayed development to raise future risk of schizophrenia, or delayed development may be a marker of other risk processes that interact with genetic liability to cause later schizophrenia. PMID:26070841

Water solvent effects using continuum and discrete models: The nitromethane molecule, CH3NO2.

PubMed

Modesto-Costa, Lucas; Uhl, Elmar; Borges, Itamar

2015-11-15

The first three valence transitions of the two nitromethane conformers (CH3NO2) are two dark n → π* transitions and a very intense π → π* transition. In this work, these transitions in gas-phase and solvated in water of both conformers were investigated theoretically. The polarizable continuum model (PCM), two conductor-like screening (COSMO) models, and the discrete sequential quantum mechanics/molecular mechanics (S-QM/MM) method were used to describe the solvation effect on the electronic spectra. Time dependent density functional theory (TDDFT), configuration interaction including all single substitutions and perturbed double excitations (CIS(D)), the symmetry-adapted-cluster CI (SAC-CI), the multistate complete active space second order perturbation theory (CASPT2), and the algebraic-diagrammatic construction (ADC(2)) electronic structure methods were used. Gas-phase CASPT2, SAC-CI, and ADC(2) results are in very good agreement with published experimental and theoretical spectra. Among the continuum models, PCM combined either with CASPT2, SAC-CI, or B3LYP provided good agreement with available experimental data. COSMO combined with ADC(2) described the overall trends of the transition energy shifts. The effect of increasing the number of explicit water molecules in the S-QM/MM approach was discussed and the formation of hydrogen bonds was clearly established. By including explicitly 24 water molecules corresponding to the complete first solvation shell in the S-QM/MM approach, the ADC(2) method gives more accurate results as compared to the TDDFT approach and with similar computational demands. The ADC(2) with S-QM/MM model is, therefore, the best compromise for accurate solvent calculations in a polar environment. © 2015 Wiley Periodicals, Inc.

Estimating the mediating effect of different biomarkers on the relation of alcohol consumption with the risk of type 2 diabetes.

PubMed

Beulens, Joline W J; van der Schouw, Yvonne T; Moons, Karel G M; Boshuizen, Hendriek C; van der A, Daphne L; Groenwold, Rolf H H

2013-04-01

Moderate alcohol consumption is associated with a reduced type 2 diabetes risk, but the biomarkers that explain this relation are unknown. The most commonly used method to estimate the proportion explained by a biomarker is the difference method. However, influence of alcohol-biomarker interaction on its results is unclear. G-estimation method is proposed to accurately assess proportion explained, but how this method compares with the difference method is unknown. In a case-cohort study of 2498 controls and 919 incident diabetes cases, we estimated the proportion explained by different biomarkers on the relation between alcohol consumption and diabetes using the difference method and sequential G-estimation method. Using the difference method, high-density lipoprotein cholesterol explained the relation between alcohol and diabetes by 78% (95% confidence interval [CI], 41-243), whereas high-sensitivity C-reactive protein (-7.5%; -36.4 to 1.8) or blood pressure (-6.9; -26.3 to -0.6) did not explain the relation. Interaction between alcohol and liver enzymes led to bias in proportion explained with different outcomes for different levels of liver enzymes. G-estimation method showed comparable results, but proportions explained were lower. The relation between alcohol consumption and diabetes may be largely explained by increased high-density lipoprotein cholesterol but not by other biomarkers. Ignoring exposure-mediator interactions may result in bias. The difference and G-estimation methods provide similar results. Copyright © 2013 Elsevier Inc. All rights reserved.

Endotoxin exposure, serum vitamin D, asthma and wheeze outcomes.

PubMed

Mendy, Angelico; Cohn, Richard D; Thorne, Peter S

2016-05-01

Endotoxin has been shown to induce neutrophilic asthma and wheeze after binding toll-like receptor 4 to produce pro-inflammatory cytokines. Animal models have demonstrated that vitamin D might inhibit lipopolysaccharide-induced cytokines. However, whether endotoxin exposure and serum vitamin D deficiency interact to affect asthma and wheeze in humans has never been investigated in an epidemiological study. Joint associations of house dust endotoxin and vitamin D with asthma and wheeze were examined using logistic regression adjusted for covariates in 5924 US participants of the National Health and Nutrition Examination Survey (NHANES). Interactions were assessed on the multiplicative as well as additive scale using the relative excess risk, the attributable portion due to additive interaction, and the synergy index. The median endotoxin concentration was 19.1 EU/mg. Prevalence of vitamin D inadequacy (20-30 ng/ml) and deficiency (<20 ng/ml) were respectively 42.9 and 33.4%. The combination of high endotoxin and low vitamin D was associated with current asthma (OR: 1.56, 95% CI: 1.09, 2.23), wheeze in the past 12 months (OR: 1.72, 95% CI: 1.10, 3.71), recurrent wheeze (OR: 1.97, 95% CI: 1.00, 4.00), asthma diagnosis or recurrent wheeze (OR: 1.88, 95% CI: 1.33, 2.66), and current asthma or recurrent wheeze (OR:1.81, 95% CI: 1.23, 2.68) when compared to low endotoxin and normal vitamin D. The interactions between the exposures were not significant on the multiplicative or additive scale for any of the outcomes. Combination of high endotoxin exposure and low vitamin D increases the odds of asthma and wheeze, but the exposures do not interact or modify each other's effect in the NHANES cohort. Copyright © 2016 Elsevier Ltd. All rights reserved.

Interactive Effectiveness of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers or Their Combination on Survival of Hemodialysis Patients

PubMed Central

Kido, Ryo; Akizawa, Tadao; Fukagawa, Masafumi; Onishi, Yoshihiro; Yamaguchi, Takuhiro; Fukuhara, Shunichi

2018-01-01

Background Does the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers individually or as a combination confer a survival benefit in hemodialysis patients? The answer to this question is yet unclear. Methods We performed a case-cohort study using data from the Mineral and Bone Disorder Outcomes Study for Japanese CKD stage 5D patients (MBD-5D), a 3-year multicenter prospective case-cohort study, including 8,229 hemodialysis patients registered from 86 facilities in Japan. All patients had secondary hyperparathyroidism, a condition defined as a parathyroid hormone level ≥180 pg/mL and/or receiving vitamin D receptor activators. We compared all-cause mortality rates between those receiving ACEI, ARB, and their combination and non-users with interaction testing. We used marginal structural Poisson regression (causal model) to estimate the causal effect and interaction adjusted for possible time-dependent confounding. Cardiovascular mortality was also evaluated. Results Among 3,762 randomly sampled subcohort patients, those taking ACEI, ARB, and their combination at baseline accounted for 4.0, 31.6, and 3.8%, respectively. Over 3 years, 1,226 all-cause and 462 cardiovascular deaths occurred. Compared to non-users, ARB-alone users had a lower all-cause mortality rate (adjusted incident rate ratio [aIRR] 0.62, 95% CI 0.50–0.76), whereas ACEI-alone users showed a statistically similar rate (aIRR 1.01, 95% CI 0.57–1.77). On the contrary, combination users had a greater mortality rate (aIRR 2.56, 95% CI 1.22–5.37), showing significant interaction (p = 0.03). Analysis for cardiovascular mortality showed similar results. Conclusion Among hemodialysis patients with secondary hyperparathyroidism, unlike ACEI use, ARB use was associated with greater survival than non-use. Conversely, combination use was associated with greater mortality. Controlled trials are warranted to verify the causality factors of these associations. PMID:29161689

House Dust Endotoxin Levels Are Associated with Adult Asthma in a U.S. Farming Population

PubMed Central

Carnes, Megan Ulmer; Hoppin, Jane A.; Metwali, Nervana; Wyss, Annah B.; Hankinson, John L.; O’Connell, Elizabeth Long; Richards, Marie; Long, Stuart; Freeman, Laura E. Beane; Sandler, Dale P.; Henneberger, Paul K.; Barker-Cummings, Christie; Umbach, David M.; Thorne, Peter S.

2017-01-01

Rationale: Endotoxin initiates a proinflammatory response from the innate immune system. Studies in children suggest that endotoxin exposure from house dust may be an important risk factor for asthma, but few studies have been conducted in adult populations. Objectives: To investigate the association of house dust endotoxin levels with asthma and related phenotypes (wheeze, atopy, and pulmonary function) in a large U.S. farming population. Methods: Dust was collected from the bedrooms (n = 2,485) of participants enrolled in a case–control study of current asthma (927 cases) nested within the Agricultural Health Study. Dust endotoxin was measured by Limulus amebocyte lysate assay. Outcomes were measured by questionnaire, spirometry, and blood draw. We evaluated associations using linear and logistic regression. Measurements and Main Results: Endotoxin was significantly associated with current asthma (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.14–1.47), and this relationship was modified by early-life farm exposure (born on a farm: OR, 1.18; 95% CI, 1.02–1.37; not born on a farm: OR, 1.67; 95% CI, 1.26–2.20; Interaction P = 0.05). Significant positive associations were seen with both atopic and nonatopic asthma. Endotoxin was not related to either atopy or wheeze. Higher endotoxin was related to lower FEV1/FVC in asthma cases only (Interaction P = 0.01). For asthma, there was suggestive evidence of a gene-by-environment interaction for the CD14 variant rs2569190 (Interaction P = 0.16) but not for the TLR4 variants rs4986790 and rs4986791. Conclusions: House dust endotoxin was associated with current atopic and nonatopic asthma in a U.S. farming population. The degree of the association with asthma depended on early-life farm exposures. Furthermore, endotoxin was associated with lower pulmonary function in patients with asthma. PMID:27977294

Does age modify the association between physical work demands and deterioration of self-rated general health?

PubMed

Burr, Hermann; Pohrt, Anne; Rugulies, Reiner; Holtermann, Andreas; Hasselhorn, Hans Martin

2017-05-01

Objective Due to the growing proportion of older employees in the work force in several countries, the importance of age in the association between work and health is becoming increasingly relevant. Few studies have investigated whether age modifies the association of physical work demands with health. We hypothesized that the association of demanding body postures with deteriorated self-rated health (SRH) is stronger among older employees than among younger employees. Method We analyzed three 5-year cohorts in the Danish Work Environment Cohort Study comprising 8318 observations from 5204 employees (follow-up participation rate 83%) with good baseline SRH. Physical work demands were assessed as demanding body postures. Age was divided into tertiles; young (18-32 years), middle-aged (33-43 years) and old (44-59 among men and 44-54 years among women). Poor SRH ("fairly good", "poor", and "very poor") was measured with a single item. Log binomial regressions were stratified by gender. Effect modification (ie, interaction) was defined as deviation from additivity and examined by calculating the relative excess risk due to interaction (RERI). The reference group was employees aged 18-32 years with low physical exposure. Results When predicting deterioration of SRH, an interaction between demanding body postures and age was found among men [RERI: 0.75, 95% confidence interval (95% CI) 0.16-1.34, regarding the age group 44-59 years] and among women (RERI: 0.84, 95% CI 0.19-1.34, for the age group 33-43 years; and 1.17, 95% CI 0.42-1.93, for the age group 44-54 years). Conclusion The study findings suggest that demanding body postures have a stronger impact on health among older compared to younger employees.

Race, exercise training, and outcomes in chronic heart failure: Findings from Heart Failure - A Controlled Trial Investigating Outcomes in Exercise TraiNing (HF-ACTION)

PubMed Central

Mentz, Robert J.; Bittner, Vera; Schulte, Phillip J.; Fleg, Jerome L.; Piña, Ileana L.; Keteyian, Steven J.; Moe, Gordon; Nigam, Anil; Swank, Ann M.; Onwuanyi, Anekwe E.; Fitz-Gerald, Meredith; Kao, Andrew; Ellis, Stephen J.; Kraus, William E.; Whellan, David J.; O'Connor, Christopher M.

2014-01-01

Background The strength of race as an independent predictor of long-term outcomes in a contemporary chronic heart failure (HF) population and its association with exercise training response have not been well established. We aimed to investigate the association between race and outcomes and to explore interactions with exercise training in patients with ambulatory HF. Methods We performed an analysis of HF-ACTION, which randomized 2331 patients with HF having an ejection fraction ≤35% to usual care with or without exercise training. We examined characteristics and outcomes (mortality/hospitalization, mortality, and cardiovascular mortality/HF hospitalization) by race using adjusted Cox models and explored an interaction with exercise training. Results There were 749 self-identified black patients (33%). Blacks were younger with significantly more hypertension and diabetes, less ischemic etiology, and lower socioeconomic status versus whites. Blacks had shorter 6-minute walk distance and lower peak VO2 at baseline. Over a median follow-up of 2.5 years, black race was associated with increased risk for all outcomes except mortality. After multivariable adjustment, black race was associated with increased mortality/hospitalization (hazard ratio [HR] 1.16, 95% CI 1.01–1.33) and cardiovascular mortality/HF hospitalization (HR 1.46, 95% CI 1.20–1.77). The hazard associated with black race was largely caused by increased HF hospitalization (HR 1.58, 95% CI 1.27–1.96), given similar cardiovascular mortality. There was no interaction between race and exercise training on outcomes (P >.5). Conclusions Black race in patients with chronic HF was associated with increased prevalence of modifiable risk factors, lower exercise performance, and increased HF hospitalization, but not increased mortality or a differential response to exercise training. PMID:24016498

Early life family conflict, Social interactions and Carotid Artery Intima-Media Thickness in Adulthood

PubMed Central

John-Henderson, Neha A.; Kamarck, Thomas W.; Muldoon, Matthew F.; Manuck, Stephen B.

2015-01-01

Objective Conflict in early life family environments is known to affect psychosocial functioning and coping styles into adulthood and is reported to negatively affect access to psychosocial resources that are critical to the management of stress. However, it remains unknown whether early life family conflict similarly affects subclinical cardiovascular disease (CVD) in adulthood. We predicted that family conflict in early life would be associated with greater mean Intima-Media thickness (IMT), a subclinical marker of CVD risk, in adulthood. Methods Data were collected in a community sample of 503 adults (47.4 % male, mean age: 42.8 years [SD=7.3]). Associations between family conflict in early life with IMT (assessed using B-mode ultrasound) in adulthood were examined using regression analysis. We also tested for indirect effects of early life family conflict on mean IMT through ecological momentary assessment (EMA) reports of social interactions, diversity of social roles, and perceived social support. Results Linear regression analyses adjusted for demographics and physiological risk factors showed conflict in early life associated with greater mean IMT (β=0.08, t(447)=2.13, p=0.034, R2=0.46). Early life conflict was significantly related to diversity of social roles, perceived social support, and EMA reports of pleasant and social conflict interactions. Significant indirect effects of early life conflict on mean IMT were observed through fewer pleasant social interactions and more frequent social conflict interactions in adulthood (β = 0.001, 95% CI, 0.0001–0.0014 and β=0.001, 95% CI, 0.0002–0.0015, respectively). Conclusions These findings provide initial evidence that family conflict in early life heightens CVD risk in adulthood, in part by shaping the quality of adulthood social interactions. PMID:26809109

What People "Like": Analysis of Social Media Strategies Used by Food Industry Brands, Lifestyle Brands, and Health Promotion Organizations on Facebook and Instagram.

PubMed

Klassen, Karen Michelle; Borleis, Emily S; Brennan, Linda; Reid, Mike; McCaffrey, Tracy A; Lim, Megan Sc

2018-06-14

Health campaigns have struggled to gain traction with young adults using social media, even though more than 80% of young adults are using social media at least once per day. Many food industry and lifestyle brands have been successful in achieving high levels of user engagement and promoting their messages; therefore, there may be lessons to be learned by examining the successful strategies commercial brands employ. This study aims to identify and quantify social media strategies used by the food industry and lifestyle brands, and health promotion organizations across the social networking sites Facebook and Instagram. The six most engaging posts from the 10 most popular food industry and lifestyle brands and six health promotion organizations were included in this study. A coding framework was developed to categorize social media strategies, and engagement metrics were collected. Exploratory linear regression models were used to examine associations between strategies used and interactions on Facebook and Instagram. Posts from Facebook (143/227, 63.0%) and Instagram (84/227, 37.0%) were included. Photos (64%) and videos (34%) were used to enhance most posts. Different strategies were most effective for Facebook and Instagram. Strategies associated with higher Facebook interactions included links to purchasable items (beta=0.81, 95% CI 0.50 to 1.13, P<.001) featuring body image messages compared with food content (beta=1.96, 95% CI 1.29 to 2.64, P<.001), and where the content induced positive emotions (beta=0.31, 95% CI 0.04 to 0.57, P=.02). Facebook interactions were negatively associated with using pop culture (beta=-0.67, 95% CI -0.99 to -0.34, P<.001), storytelling (beta=-0.86, 95% CI -1.29 to -0.43, P<.001) or visually appealing graphics (beta=-0.53, 95% CI -0.78 to -0.28, P<.001) in their posts compared with other strategies. Posting relatable content was negatively associated with interactions on Facebook (beta=-0.29, 95% CI -0.53 to -0.06, P=.01), but positively associated on Instagram (beta=0.50, 95% CI 0.05 to 0.95, P=.03). Instagram interactions were negatively associated with weight loss (beta=-1.45, 95% CI -2.69 to -0.21, P=.02) and other content (beta=-0.81, 95% CI -1.57 to -.06, P=.04) compared with food content. Health promotion professionals and organizations can improve engagement using positive messaging and tailoring posts appropriate for different social media channels. ©Karen Michelle Klassen, Emily S Borleis, Linda Brennan, Mike Reid, Tracy A McCaffrey, Megan SC Lim. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 14.06.2018.

The interaction of C.I. acid red 27 with human hemoglobin in solution.

PubMed

Wang, Yan-Qing; Zhang, Hong-Mei; Tang, Bo-Ping

2010-08-02

The nature of the interaction between human hemoglobin and C.I. acid red 27 was investigated systematically by ultraviolet-vis absorbance, circular dichroism, fluorescence, synchronous fluorescence, and three-dimensional fluorescence spectra techniques at pH 7.40. The quenching mechanism, binding constants, and the number of binding sites were determined by the quenching of human hemoglobin fluorescence in presence of C.I. acid red 27. The results showed that the nature of the quenching was of static type and the process of binding acid red 27 on human hemoglobin was a spontaneous molecular interaction procedure. The electrostatic and hydrophobic interactions played a major role in stabilizing the complex; The distance r between donor and acceptor was obtained to be 4.40 nm according to Förster's theory; The effect of acid red 27 on the conformation of human hemoglobin was analyzed using synchronous fluorescence, circular dichroism and three-dimensional fluorescence spectra. 2010 Elsevier B.V. All rights reserved.

Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function.

PubMed

Floyd, Brendan J; Wilkerson, Emily M; Veling, Mike T; Minogue, Catie E; Xia, Chuanwu; Beebe, Emily T; Wrobel, Russell L; Cho, Holly; Kremer, Laura S; Alston, Charlotte L; Gromek, Katarzyna A; Dolan, Brendan K; Ulbrich, Arne; Stefely, Jonathan A; Bohl, Sarah L; Werner, Kelly M; Jochem, Adam; Westphall, Michael S; Rensvold, Jarred W; Taylor, Robert W; Prokisch, Holger; Kim, Jung-Ja P; Coon, Joshua J; Pagliarini, David J

2016-08-18

Mitochondria are essential for numerous cellular processes, yet hundreds of their proteins lack robust functional annotation. To reveal functions for these proteins (termed MXPs), we assessed condition-specific protein-protein interactions for 50 select MXPs using affinity enrichment mass spectrometry. Our data connect MXPs to diverse mitochondrial processes, including multiple aspects of respiratory chain function. Building upon these observations, we validated C17orf89 as a complex I (CI) assembly factor. Disruption of C17orf89 markedly reduced CI activity, and its depletion is found in an unresolved case of CI deficiency. We likewise discovered that LYRM5 interacts with and deflavinates the electron-transferring flavoprotein that shuttles electrons to coenzyme Q (CoQ). Finally, we identified a dynamic human CoQ biosynthetic complex involving multiple MXPs whose topology we map using purified components. Collectively, our data lend mechanistic insight into respiratory chain-related activities and prioritize hundreds of additional interactions for further exploration of mitochondrial protein function. Copyright © 2016 Elsevier Inc. All rights reserved.

Additive Interaction between Heterogeneous Environmental Quality Domains (Air, Water, Land, Sociodemographic, and Built Environment) on Preterm Birth.

PubMed

Grabich, Shannon C; Rappazzo, Kristen M; Gray, Christine L; Jagai, Jyotsna S; Jian, Yun; Messer, Lynne C; Lobdell, Danelle T

2016-01-01

Environmental exposures often occur in tandem; however, epidemiological research often focuses on singular exposures. Statistical interactions among broad, well-characterized environmental domains have not yet been evaluated in association with health. We address this gap by conducting a county-level cross-sectional analysis of interactions between Environmental Quality Index (EQI) domain indices on preterm birth in the Unites States from 2000 to 2005. The EQI, a county-level index constructed for the 2000-2005 time period, was constructed from five domain-specific indices (air, water, land, built, and sociodemographic) using principal component analyses. County-level preterm birth rates ( n  = 3141) were estimated using live births from the National Center for Health Statistics. Linear regression was used to estimate prevalence differences (PDs) and 95% confidence intervals (CIs) comparing worse environmental quality to the better quality for each model for (a) each individual domain main effect, (b) the interaction contrast, and (c) the two main effects plus interaction effect (i.e., the "net effect") to show departure from additivity for the all U.S. counties. Analyses were also performed for subgroupings by four urban/rural strata. We found the suggestion of antagonistic interactions but no synergism, along with several purely additive (i.e., no interaction) associations. In the non-stratified model, we observed antagonistic interactions, between the sociodemographic/air domains [net effect (i.e., the association, including main effects and interaction effects) PD: -0.004 (95% CI: -0.007, 0.000), interaction contrast: -0.013 (95% CI: -0.020, -0.007)] and built/air domains [net effect PD: 0.008 (95% CI 0.004, 0.011), interaction contrast: -0.008 (95% CI: -0.015, -0.002)]. Most interactions were between the air domain and other respective domains. Interactions differed by urbanicity, with more interactions observed in non-metropolitan regions. Observed antagonistic associations may indicate that those living in areas with multiple detrimental domains may have other interfering factors reducing the burden of environmental exposure. This study is the first to explore interactions across different environmental domains and demonstrates the utility of the EQI to examine the relationship between environmental domain interactions and human health. While we did observe some departures from additivity, many observed effects were additive. This study demonstrated that interactions between environmental domains should be considered in future analyses.

Electronic health record use, intensity of hospital care, and patient outcomes.

PubMed

Blecker, Saul; Goldfeld, Keith; Park, Naeun; Shine, Daniel; Austrian, Jonathan S; Braithwaite, R Scott; Radford, Martha J; Gourevitch, Marc N

2014-03-01

Previous studies have suggested that weekend hospital care is inferior to weekday care and that this difference may be related to diminished care intensity. The purpose of this study was to determine whether a metric for measuring intensity of hospital care based on use of the electronic health record was associated with patient-level outcomes. We performed a cohort study of hospitalizations at an academic medical center. Intensity of care was defined as the hourly number of provider accessions of the electronic health record, termed "electronic health record interactions." Hospitalizations were categorized on the basis of the mean difference in electronic health record interactions between the first Friday and the first Saturday of hospitalization. We used regression models to determine the association of these categories with patient outcomes after adjusting for covariates. Electronic health record interactions decreased from Friday to Saturday in 77% of the 9051 hospitalizations included in the study. Compared with hospitalizations with no change in Friday to Saturday electronic health record interactions, the relative lengths of stay for hospitalizations with a small, moderate, and large decrease in electronic health record interactions were 1.05 (95% confidence interval [CI], 1.00-1.10), 1.11 (95% CI, 1.05-1.17), and 1.25 (95% CI, 1.15-1.35), respectively. Although a large decrease in electronic health record interactions was associated with in-hospital mortality, these findings were not significant after risk adjustment (odds ratio 1.74, 95% CI, 0.93-3.25). Intensity of inpatient care, measured by electronic health record interactions, significantly diminished from Friday to Saturday, and this decrease was associated with length of stay. Hospitals should consider monitoring and correcting temporal fluctuations in care intensity. Copyright © 2014 Elsevier Inc. All rights reserved.

Serum Vitamin D, Vitamin D Binding Protein, and Risk of Colorectal Cancer

PubMed Central

Anic, Gabriella M.; Weinstein, Stephanie J.; Mondul, Alison M.; Männistö, Satu; Albanes, Demetrius

2014-01-01

Background We previously reported a positive association between serum 25-hydroxyvitamin D (25(OH)D) and colorectal cancer risk. To further elucidate this association, we examined the molar ratio of 25(OH)D to vitamin D binding protein (DBP), the primary 25(OH)D transport protein, and whether DBP modified the association between 25(OH)D and colorectal cancer risk. Methods In a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, controls were 1∶1 matched to 416 colorectal cancer cases based on age and date of blood collection. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for quartiles of 25(OH)D, DBP, and the molar ratio of 25(OH)D:DBP, a proxy for free, unbound circulating 25(OH)D. Results Comparing highest to lowest quartiles, DBP was not associated with colorectal cancer risk (OR = 0.91; 95% CI: 0.58, 1.42, p for trend  = 0.58); however, a positive risk association was observed for the molar ratio of 25(OH)D:DBP (OR = 1.44; 95% CI: 0.92, 2.26, p for trend  = 0.04). In stratified analyses, the positive association between 25(OH)D and colorectal cancer was stronger among men with DBP levels above the median (OR = 1.89; 95% CI: 1.07, 3.36, p for trend  = 0.01) than below the median (OR = 1.20; 95% CI: 0.68, 2.12, p for trend  = 0.87), although the interaction was not statistically significant (p for interaction  = 0.24). Conclusion Circulating DBP may influence the association between 25(OH)D and colorectal cancer in male smokers, with the suggestion of a stronger positive association in men with higher DBP concentrations. This finding should be examined in other populations, especially those that include women and non-smokers. PMID:25036524

Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal Crohn’s disease

PubMed Central

Gathungu, Grace; Zhang, Yuanhao; Tian, Xinyu; Bonkowski, Erin; Rowehl, Leahana; Krumsiek, Julia; Nix, Billy; Chalk, Claudia; Trapnell, Bruce; Zhu, Wei; Newberry, Rodney; Denson, Lee; Li, Ellen

2018-01-01

AIM To examine the relationship between elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) auto-antibodies (Ab) level and time to surgical recurrence after initial surgery for Crohn’s disease (CD). METHODS We reviewed 412 charts from a clinical database at tertiary academic hospital. Patients included in the study had ileal or ileocolonic CD and surgical resection of small bowel or ileocecal region for management of disease. Serum samples were analyzed for serological assays including GM-CSF cytokine, GM-CSF Ab, ASCA IgG and IgA, and genetic markers including SNPs rs2066843, rs2066844, rs2066845, rs2076756 and rs2066847 in NOD2, rs2241880 in ATG16L1, and rs13361189 in IRGM. Cox proportional-hazards models were used to assess the predictors of surgical recurrence. RESULTS Ninety six percent of patients underwent initial ileocecal resection (ICR) or ileal resection (IR) and subsequently 40% of patients required a second ICR/IR for CD. GM-CSF Ab level was elevated at a median of 3.81 mcg/mL. Factors predicting faster time to a second surgery included elevated GM-CSF Ab [hazard ratio (HR) 3.52, 95%CI: 1.45-8.53, P = 0.005] and elevated GM-CSF cytokine (HR = 2.48, 95%CI: 1.31-4.70, P = 0.005). Factors predicting longer duration between first and second surgery included use of Immunomodulators (HR = 0.49, 95%CI: 0.31-0.77, P = 0.002), the interaction effect of low GM-CSF Ab levels and smoking (HR = 0.60, 95%CI: 0.45-0.81, P = 0.001) and the interaction effect of low GM-CSF cytokine levels and ATG16L1 (HR = 0.65, 95%CI: 0.49-0.88, P = 0.006). CONCLUSION GM-CSF bioavailability plays a critical role in maintaining intestinal homeostasis. Decreased bioavailability coupled with the genetic risk markers and/or smoking results in aggressive CD behavior. PMID:29434451

Cumulative Effects of Neighborhood Social Adversity and Personal Crime Victimization on Adolescent Psychotic Experiences

PubMed Central

Newbury, Joanne; Arseneault, Louise; Caspi, Avshalom; Moffitt, Terrie E; Odgers, Candice L

2018-01-01

Abstract Background: Little is known about the impact of urbanicity, adverse neighborhood conditions and violent crime victimization on the emergence of adolescent psychotic experiences. Methods: Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 British twins who were interviewed about adolescent psychotic experiences at age 18. Urbanicity, neighborhood characteristics, and personal victimization by violent crime were measured during childhood and adolescence via geocoded census data, surveys of over 5000 immediate neighbors of the E-Risk participants, and interviews with participants themselves. Results: Adolescents raised in urban vs rural neighborhoods were significantly more likely to have psychotic experiences (OR = 1.67, 95% CI = 1.21–2.30, P = .002). This association remained significant after considering potential confounders including family socioeconomic status, family psychiatric history, and adolescent substance problems (OR = 1.43, 95% CI = 1.01–2.03, P = .042), but became nonsignificant after considering adverse social conditions in urban neighborhoods such as low social cohesion and high neighborhood disorder (OR = 1.35, 95% CI = 0.94–1.92, P = .102). The combined association of adverse neighborhood social conditions and personal crime victimization with adolescent psychotic experiences (adjusted OR = 4.86, 95% CI = 3.28–7.20, P < .001) was substantially greater than for either exposure alone, highlighting a potential interaction between neighborhood conditions and crime victimization (interaction contrast ratio = 1.81, 95% CI = −0.03 to 3.65) that was significant at the P = .054 level. Conclusions: Cumulative effects of adverse neighborhood social conditions and personal victimization by violent crime during upbringing partly explain why adolescents in urban settings are more likely to report psychotic experiences. Early intervention efforts for psychosis could be targeted towards victimized youth living in urban and socially adverse neighborhoods. PMID:28535284

Effect of Zinc Supplementation on Growth Outcomes in Children under 5 Years of Age.

PubMed

Liu, Enju; Pimpin, Laura; Shulkin, Masha; Kranz, Sarah; Duggan, Christopher P; Mozaffarian, Dariush; Fawzi, Wafaie W

2018-03-20

(1) Background: The effects of zinc supplementation on child growth, and prior reviews of these studies, have shown mixed results. We aim to systematically review and meta-analyze randomized controlled trials evaluating effects of preventive zinc supplementation for 3 months or longer during pregnancy or in children up to age 5 years on pregnancy outcomes and child growth; (2) Methods: We searched PubMed, EMBASE, Cochrane Library, Web of Science, and trial registries for eligible trials up to October 10, 2017. Inclusion selection and data extractions were performed independently and in duplicate. Study quality was evaluated by the Cochrane Risk of Bias tool. Findings were pooled using random effects meta-analysis, with heterogeneity assessed by I ² and τ² statistic, stratified analyses, and meta-regression, and publication bias by Egger's and Begg's tests; (3) Results: Seventy-eight trials with 34,352 unique participants were identified, including 24 during pregnancy and 54 in infancy/childhood. Maternal zinc supplementation did not significantly increase birth weight (weighted mean difference (WMD) = 0.08 kg, 95%CI: -0.05, 0.22) or decrease the risk of low birth weight (RR = 0.76, 95%CI: 0.52-1.11). Zinc supplementation after birth increased height (WMD = 0.23 cm, 95%CI: 0.09-0.38), weight (WMD = 0.14 kg, 95%CI: 0.07-0.21), and weight-for-age Z -score (WMD = 0.04, 95%CI: 0.001-0.087), but not height-for-age Z -score (WMD = 0.02, 95%CI: -0.01-0.06) or weight-for-height Z score (WMD = 0.02, 95%CI: -0.03-0.06). Child age at zinc supplementation appeared to modify the effects on height ( P -interaction = 0.002) and HAZ ( P -interaction = 0.06), with larger effects of supplementation starting at age ≥2 years (WMD for height = 1.37 cm, 95%CI: 0.50-2.25; WMD for HAZ = 0.12, 95%CI: 0.05-0.19). No significant effects of supplementation were found on the risk of stunting, underweight or wasting; (4) Conclusion: Although the possibility of publication bias and small study effect could not be excluded, the current meta-analysis indicates that zinc supplementation in infants and early childhood, but not pregnancy, increases specific growth outcomes, with evidence for a potentially stronger effect after 2 years of age. These findings inform recommendation and policy development for zinc supplementation to improve growth among young children.

Frailty and quality of life among older people with and without a cancer diagnosis: Findings from TOPICS-MDS

PubMed Central

Schoon, Yvonne; van Goor, Harry; Olde Rikkert, Marcel; Melis, René

2017-01-01

Background The number of older cancer patients is rising. Especially in older people, treatment considerations should balance the impact of disease and treatment on quality of life (QOL) and survival. How a cancer diagnosis in older people interacts with concomitant frailty to impact on QOL is largely unknown. We aimed to determine the association between frailty and QOL among community-dwelling older people aged 65 years or above with and without a cancer diagnosis cross-sectionally and at 12 months follow-up. Methods Data were derived from the TOPICS-MDS database. Frailty was quantified by a frailty index (FI). QOL was measured with the subjective Cantril’s Self Anchoring Ladder (CSAL, range: 0–10) and the health-related EuroQol-5D (EQ-5D, range:-0.33–1.00) at baseline and after 12 months. To determine associations, linear mixed models were used. Results 7493 older people (78.6±6.4 years, 58.4% female) were included. Dealing with a cancer diagnosis (n = 751) was associated with worse QOL both at baseline (CSAL:-0.25 (95%-CI:-0.36;-0.14), EQ-5D:-0.03 (95%-CI:-0.05;-0.02)) and at follow-up (CSAL:-0.13 (95%-CI:-0.24;-0.02), EQ-5D:-0.02 (95%-CI:-0.03;-0.00)). A ten percent increase in frailty was also associated with a decrease in QOL at baseline (CSAL:-0.35 (95%-CI:-0.38;-0.32), EQ-5D:-0.12 (95%-CI:-0.12;-0.11)) and follow-up (CSAL:-0.27 (95%-CI:-0.30;-0.24), EQ-5D:-0.07 (95%-CI:-0.07;-0.06)). When mutually adjusting for frailty and a cancer diagnosis, associations between a cancer diagnosis and QOL only remained significant for CSAL at baseline (-0.14 (95%-CI:-0.25;-0.03)), whereas associations between frailty and QOL remained significant for all QOL outcomes at baseline and follow-up. No statistical interactions between cancer and frailty in their combined impact on QOL were found. Conclusions Cancer diagnosis and frailty were associated with worse health-related and self-perceived QOL both at baseline and at follow-up. Differences in QOL between older people with and without a cancer diagnosis were explained to a large extent by differences in frailty levels. This stresses the importance to take into account frailty in routine oncologic care. PMID:29244837

Effects of cognitive impairment on prosodic parameters of speech production planning in multiple sclerosis.

PubMed

De Looze, Céline; Moreau, Noémie; Renié, Laurent; Kelly, Finnian; Ghio, Alain; Rico, Audrey; Audoin, Bertrand; Viallet, François; Pelletier, Jean; Petrone, Caterina

2017-05-24

Cognitive impairment (CI) affects 40-65% of patients with multiple sclerosis (MS). CI can have a negative impact on a patient's everyday activities, such as engaging in conversations. Speech production planning ability is crucial for successful verbal interactions and thus for preserving social and occupational skills. This study investigates the effect of cognitive-linguistic demand and CI on speech production planning in MS, as reflected in speech prosody. A secondary aim is to explore the clinical potential of prosodic features for the prediction of an individual's cognitive status in MS. A total of 45 subjects, that is 22 healthy controls (HC) and 23 patients in early stages of relapsing-remitting MS, underwent neuropsychological tests probing specific cognitive processes involved in speech production planning. All subjects also performed a read speech task, in which they had to read isolated sentences manipulated as for phonological length. Results show that the speech of MS patients with CI is mainly affected at the temporal level (articulation and speech rate, pause duration). Regression analyses further indicate that rate measures are correlated with working memory scores. In addition, linear discriminant analysis shows the ROC AUC of identifying MS patients with CI is 0.70 (95% confidence interval: 0.68-0.73). Our findings indicate that prosodic planning is deficient in patients with MS-CI and that the scope of planning depends on patients' cognitive abilities. We discuss how speech-based approaches could be used as an ecological method for the assessment and monitoring of CI in MS. © 2017 The British Psychological Society.

Parents' reported preference scores for childhood atopic dermatitis disease states

PubMed Central

Friedman, Joëlle Y; Reed, Shelby D; Weinfurt, Kevin P; Kahler, Kristijan H; Walter, Emmanuel B; Schulman, Kevin A

2004-01-01

Background We sought to elicit preference weights from parents for health states corresponding to children with various levels of severity of atopic dermatitis. We also evaluated the hypothesis that parents with children who had been diagnosed with atopic dermatitis would assign different preferences to the health state scenarios compared with parents who did not have a child with atopic dermatitis. Methods Subjects were parents of children aged 3 months to 18 years. The sample was derived from the General Panel, Mommies Sub-Panel, and Chronic Illness Sub-Panel of Harris Interactive. Participants rated health scenarios for atopic dermatitis, asthma, and eyeglasses on a visual analog scale, imagining a child was experiencing the described state. Results A total of 3539 parents completed the survey. Twenty-nine percent had a child with a history of atopic dermatitis. Mean preference scores for atopic dermatitis were as follows: mild, 91 (95% confidence interval [CI], 90.7 to 91.5); mild/moderate, 84 (95%CI, 83.5 to 84.4); moderate, 73 (95%CI, 72.5 to 73.6); moderate/severe, 61 (95%CI, 60.6 to 61.8); severe, 49 (95% CI, 48.7 to 50.1); asthma, 58 (95%CI, 57.4 to 58.8); and eyeglasses, 87(95%CI, 86.3 to 87.4). Conclusions Parents perceive that atopic dermatitis has a negative effect on quality of life that increases with disease severity. Estimates of parents' preferences can provide physicians with insight into the value that parents place on their children's treatment and can be used to evaluate new medical therapies for atopic dermatitis. PMID:15491500

Epidemiology of Drug-Disease Interactions in Older Veteran Nursing Home Residents

PubMed Central

Aspinall, Sherrie L.; Zhao, Xinhua; Semla, Todd P.; Cunningham, Francesca E.; Paquin, Allison M.; Pugh, Mary Jo; Schmader, Kenneth E.; Stone, Roslyn A.; Hanlon, Joseph T.

2014-01-01

Objectives Few studies have examined drug-disease interactions (DDIs) in older nursing home residents. Therefore, the objective is to describe the prevalence of, and factors associated with, DDIs according to The American Geriatrics Society 2012 Beers Criteria. Design Cross-sectional study. Setting Fifteen Veterans Affairs Community Living Centers. Participants Patients≥65 years old with a diagnosis of dementia/cognitive impairment, history of falls/hip fractures, heart failure (HF), history of peptic ulcer disease (PUD) and/or stage IV or V chronic kidney disease (CKD). Measurements Prevalence of medications that could exacerbate the above conditions (i.e., DDIs). Results Overall, 361 of 696 (51.9%) eligible residents had ≥1 DDI. None involved those with a history of PUD; one involved a resident with CKD, and four occurred in those with HF. In residents with dementia/cognitive impairment (N=540), 50.7% took a drug that could exacerbate these conditions; the most commonly involved medications were antipsychotics (35.4%) and benzodiazepines (14.4%). In those with a history of falls/hip fractures (N=267), 67.8% received an interacting medication, with SSRIs (33.1%), antipsychotics (30.7%) and anticonvulsants (25.1%) being most commonly involved. Using separate multivariable logistic regression models, factors associated with DDIs in both dementia/cognitive impairment and falls/fractures included: age 85+ (Adjusted Odds Ratio [aOR] and 95% confidence interval [CI] of 0.38; 0.24–0.60 and aOR 0.48; 95%CI 0.24–0.96, respectively); taking 5–8 medications (aOR 2.06; 95%CI 1.02–4.16 and aOR 4.76; 95%CI 1.68–13.5, respectively) and ≥9 medications (aOR 1.99; 95%CI 1.03–3.85 and aOR 3.68; 95%CI 1.41–9.61, respectively), and being a long stay patient (aOR 1.80; 95%CI 1.04–3.12 and aOR 2.35; 95%CI 1.12–4.91, respectively). Conclusion Drug-disease interactions were common in older nursing home residents with dementia/cognitive impairment and/or a history of falls/fractures. PMID:25537124

The functional cytotoxic T lymphocyte-associated Protein 4 49G-to-A genetic variant and risk of pancreatic cancer.

PubMed

Yang, Ming; Sun, Tong; Zhou, Yifeng; Wang, Li; Liu, Li; Zhang, Xiaojiao; Tang, Xiaohu; Zhou, Mo; Kuang, Pengqun; Tan, Wen; Li, Hui; Yuan, Qipeng; Yu, Dianke

2012-10-01

Antitumor T lymphocytes play an essential part in immune surveillance of cancer cells. Cytotoxic T lymphocyte-associated Protein 4 (CTLA-4) is a negative regulator of T cell activation and proliferation and therefore influences immune surveillance of carcinogenesis of pancreas. Thus, this study examined the association between functional CTLA-4 49G-to-A (49G>A) single-nucleotide polymorphism and pancreatic cancer risk. Genotypes were determined in 368 patients with pancreatic cancer and 926 controls, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. A significant increased risk of pancreatic cancer was found to be associated with the CTLA-4 49G>A single-nucleotide polymorphism. Compared with noncarriers, the OR of developing pancreatic cancer for CTLA-4 49 GA or AA carriers was 1.75 (95% CI = 1.34-2.30, P = 4.83 × 10(-5) ) or 2.54 (95% CI = 1.67-3.87, P = 1.36 × 10(-5) ), respectively. In stratified analyses, the association was more pronounced in GA and AA carriers aged ≤60 years (OR = 3.10, 95% CI = 2.15-4.47, P(interaction) = .002), smokers with GA and AA genotypes (OR = 3.92, 95% CI = 2.39-6.43, P(interaction) = .037), and drinkers with GA and AA genotypes (OR = 4.55, 95% CI = 2.65-7.82, P(interaction) = .042), compared with GG carriers. Moreover, a supermultiplicative interaction between the CTLA-4 49AA genotype and smoking plus drinking was also evident in intensifying risk of pancreatic cancer (P(interaction) = 5.64 × 10(-12) ). These results suggest that CTLA-4 49G>A polymorphism is involved in susceptibility to developing pancreatic cancer, alone and in a gene-environment interaction manner. Copyright © 2012 American Cancer Society.

Maternal depression and low maternal intelligence as risk factors for malnutrition in children: a community based case-control study from South India

PubMed Central

Anoop, S; Saravanan, B; Joseph, A; Cherian, A; Jacob, K

2004-01-01

Aims: To determine whether current and postpartum maternal depression and low maternal intelligence are risk factors for malnutrition in children. Methods: In rural South India 72 children with malnutrition were identified from a central register; 72 controls were matched for age, gender, and residence. Results: Major depression in the postpartum period (OR 5.0, 95% CI 1.0 to 24.0), current major depression (OR 3.2, 95% CI 1.1 to 9.5), and low maternal intelligence (OR 3.8, 95% CI 1.3 to 11.1) were associated with malnutrition in the child. Low birth weight (OR 2.9, 95% CI 1.2 to 6.8) was also significantly associated with infant malnutrition. Conditional logistic regression adjusting for all other determinants yielded the following results: major depression during the postpartum period (OR 7.8; 95% CI 1.6 to 38.51), current major depression (OR 3.1; 95% CI 0.9 to 9.7), low maternal intelligence (OR 4.6; 95% CI 1.5 to 14.1), and low birth weight (OR 2.7; 95% CI 2.5 to 6.8). The interactions between current maternal depression and low birth weight and between postpartum depression and low maternal intelligence were statistically significant. The level of maternal intelligence was associated with nutritional status. The severity of malnutrition was also significantly associated with major depression during the postpartum period and low maternal intelligence. Conclusion: There is evidence for an association between postpartum maternal depression, low maternal intelligence, and low birth weight with malnutrition in children aged 6–12 months. PMID:15033840

Video feedback promotes relations between infants and vulnerable first-time mothers: a quasi-experimental study.

PubMed

Kristensen, Ingeborg Hedegaard; Simonsen, Marianne; Trillingsgaard, Tea; Kronborg, Hanne

2017-11-15

Supporting early mother-infant relationships to ensure infants' future health has been recommended. The aim of this study was to investigate whether video feedback using the Marte Meo method promotes a healthy early relationship between infants and vulnerable first-time mothers. Video feedback or usual care was delivered by health visitors during home visits in Danish municipalities. This quasi-experimental study included pre- and post-tests of 278 vulnerable families. Mothers were allocated to an intervention group (n = 69), a comparison group (n = 209) and an exactly matched video subsample from the comparison group (n = 63). Data consisted of self-reported questionnaires and video recordings of mother-infant interactions. Outcomes were mother-infant dyadic synchrony (CARE-Index), maternal confidence (KPCS), parental stress (PSS), maternal mood (EPDS) and infant socialemotional behaviours (ASQ:SE). The data were analysed using descriptive and linear multiple regression analysis. The levels of dyadic synchrony in the intervention group had significantly improved (p < 0.001) at follow-up with a mean score of 9.51 (95%CI;8.93-10.09) compared with 7.62 (95%CI;7.03-8.21). The intervention group also showed a higher level of maternal sensitivity with a mean score of 9.55 (95%CI;8.96-10.14) compared with 7.83 (95%CI;7.19-8.46) in the matched video subsample (p < 0.001). With respect to infant cooperation, similar improvements were found with a mean score of 9.43 (95% CI;8.88-9.99) in the intervention group compared with 7.73 (95%CI;7.13-8.33) in the matched video subsample from the comparison group (p < 0.001). Furthermore, mothers in the intervention group reported significantly lower levels of parental stress with a mean score of 32.04 (95%CI;30.13-33.94) compared with 35.29 (95%CI;34.07-36.52) in the comparison group (p = 0.03), as well as higher levels of maternal confidence with a mean score of 41.10 (95%CI;40.22-41.98) compared with 40.10 (95%CI;39.65-40.56) in the comparison group (p = 0.04). No significant differences were found in EPDS and ASQ:SE. The findings support the assumption that video feedback using the Marte Meo method early after birth may strengthen the relationship between infants and vulnerable firsttime mothers as well as improve maternal psychosocial functioning. Further research applying random assignment is needed to strengthen these conclusions; further research is also needed to assess any long term effects of the video feedback intervention using the Marte Meo method. This study was registered on 24 January 2013 in ClinicalTrials.gov with the identifier: NCT01799447 .

Early-Onset Chronic Obstructive Pulmonary Disease Is Associated with Female Sex, Maternal Factors, and African American Race in the COPDGene Study

PubMed Central

Foreman, Marilyn G.; Zhang, Lening; Murphy, James; Hansel, Nadia N.; Make, Barry; Hokanson, John E.; Washko, George; Regan, Elizabeth A.; Crapo, James D.; Silverman, Edwin K.

2011-01-01

Rationale: The characterization of young adults who develop late-onset diseases may augment the detection of novel genes and promote new pathogenic insights. Methods: We analyzed data from 2,500 individuals of African and European ancestry in the COPDGene Study. Subjects with severe, early-onset chronic obstructive pulmonary disease (COPD) (n = 70, age < 55 yr, FEV1 < 50% predicted) were compared with older subjects with COPD (n = 306, age > 64 yr, FEV1 < 50% predicted). Measurements and Main Results: Subjects with severe, early-onset COPD were predominantly females (66%), P = 0.0004. Proportionally, early-onset COPD was seen in 42% (25 of 59) of African Americans versus 14% (45 of 317) of non-Hispanic whites, P < 0.0001. Other risk factors included current smoking (56 vs. 17%, P < 0.0001) and self-report of asthma (39 vs. 25%, P = 0.008). Maternal smoking (70 vs. 44%, P = 0.0001) and maternal COPD (23 vs. 12%, P = 0.03) were reported more commonly in subjects with early-onset COPD. Multivariable regression analysis found association with African American race, odds ratio (OR), 7.5 (95% confidence interval [CI], 2.3–24; P = 0.0007); maternal COPD, OR, 4.7 (95% CI, 1.3–17; P = 0.02); female sex, OR, 3.1 (95% CI, 1.1–8.7; P = 0.03); and each pack-year of smoking, OR, 0.98 (95% CI, 0.96–1.0; P = 0.03). Conclusions: These observations support the hypothesis that severe, early-onset COPD is prevalent in females and is influenced by maternal factors. Future genetic studies should evaluate (1) gene-by-sex interactions to address sex-specific genetic contributions and (2) gene-by-race interactions. PMID:21562134

Variable association of reactive intermediate genes with systemic lupus erythematosus (SLE) in populations with different African ancestry

PubMed Central

Ramos, Paula S.; Oates, James C.; Kamen, Diane L.; Williams, Adrienne H.; Gaffney, Patrick M.; Kelly, Jennifer A.; Kaufman, Kenneth M.; Kimberly, Robert P.; Niewold, Timothy B.; Jacob, Chaim O.; Tsao, Betty P.; Alarcón, Graciela S.; Brown, Elizabeth E.; Edberg, Jeffrey C.; Petri, Michelle A.; Ramsey-Goldman, Rosalind; Reveille, John D.; Vilá, Luis M.; James, Judith A.; Guthridge, Joel M.; Merrill, Joan T.; Boackle, Susan A.; Freedman, Barry I.; Scofield, R. Hal; Stevens, Anne M.; Vyse, Timothy J.; Criswell, Lindsey A.; Moser, Kathy L.; Alarcón-Riquelme, Marta E.; Langefeld, Carl D.; Harley, John B.; Gilkeson, Gary S.

2013-01-01

Objective Little is known about the genetic etiology of systemic lupus erythematosus (SLE) in individuals of African ancestry, despite its higher prevalence and greater disease severity. Overproduction of nitric oxide (NO) and reactive oxygen species are implicated in the pathogenesis and severity of SLE, making NO synthases and other reactive intermediate related genes biological candidates for disease susceptibility. This study analyzed variation in reactive intermediate genes for association with SLE in two populations with African ancestry. Methods A total of 244 SNPs from 53 regions were analyzed in non-Gullah African Americans (AA; 1432 cases and 1687 controls) and the genetically more homogeneous Gullah of the Sea Islands of South Carolina (133 cases and 112 controls) and. Single-marker, haplotype, and two-locus interaction tests were computed for these populations. Results The glutathione reductase gene GSR (rs2253409, P=0.0014, OR [95% CI]=1.26 [1.09–1.44]) was the most significant single-SNP association in AA. In the Gullah, the NADH dehydrogenase NDUFS4 (rs381575, P=0.0065, OR [95%CI]=2.10 [1.23–3.59]) and nitric oxide synthase gene NOS1 (rs561712, P=0.0072, OR [95%CI]=0.62 [0.44–0.88]) were most strongly associated with SLE. When both populations were analyzed together, GSR remained the most significant effect (rs2253409, P=0.00072, OR [95%CI]=1.26 [1.10–1.44]). Haplotype and two-locus interaction analyses also uncovered different loci in each population. Conclusion These results suggest distinct patterns of association with SLE in African-derived populations; specific loci may be more strongly associated within select population groups. PMID:23637325

Predictors of Androgen Deprivation Therapy Efficacy Combined With Prostatic Irradiation: The Central Role of Tumor Stage and Radiation Dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Scott, E-mail: scott.williams@petermac.or; Buyyounouski, Mark; Kestin, Larry

2011-03-01

Purpose: To evaluate the response of clinically localized prostate cancer to various durations of planned androgen deprivation therapy (ADT) and to investigate subgroups predicting response. Methods and Materials: Data of 3,666 prostate cancer patients treated with either combined ADT and external beam radiotherapy (EBRT) or EBRT alone at four institutions were examined. ADT consisted of neoadjuvant, concurrent, or adjuvant ADT or combinations of these regimens. The primary endpoint was time to biochemical failure (nadir plus 2 ng/ml), assessed from the end of therapy. Factors predictive for the need for ADT were examined with interaction analyses. Results: The impact of increasingmore » ADT duration was nonlinear with, on average, 6 months of adjuvant ADT resulting in a reduction of the risk of biochemical failure by 38% (95% confidence interval [CI], 29%-46%), while 12, 24, and 36 months of ADT resulted in a 58% (95% CI, 47%-67%), 66% (95% CI, 55%-75%), and 66% (95% CI, 51%-77%) relative failure reduction, respectively. Patients with higher T stage cancers and those treated with lower radiation doses had a significantly greater benefit for increasing ADT duration (interaction, p = 0.016 and p = 0.007, respectively). Pretreatment prostate-specific antigen values, Gleason score, age, and risk group did not modify the response to ADT. Conclusions: The known ADT efficacy derived from randomized studies can be generalized to patients with different features, and individual predictions of potential benefit from ADT use and duration may be calculated to aid patient and physician decision making. Tumor stage and radiation dose variations were related to significantly different ADT duration effects. The validity of these predictive factors requires prospective evaluation.« less

Urinary cadmium concentration and the risk of ischemic stroke.

PubMed

Chen, Cheng; Xun, Pengcheng; Tsinovoi, Cari; McClure, Leslie A; Brockman, John; MacDonald, Leslie; Cushman, Mary; Cai, Jianwen; Kamendulis, Lisa; Mackey, Jason; He, Ka

2018-06-22

To examine the association between urinary cadmium levels and the incidence of ischemic stroke and to explore possible effect modifications. A case-cohort study was designed nested in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, including 680 adjudicated incident cases of ischemic stroke and 2,540 participants in a randomly selected subcohort. Urinary creatinine-corrected cadmium concentration was measured at baseline. Multivariable-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated with the Barlow weighting method for the Cox proportional hazards regression model. The median urinary cadmium concentration was 0.42 (interquartile range 0.27-0.68) μg/g creatinine. After adjustment for potential confounders, urinary cadmium was associated with increased incidence of ischemic stroke (quintile 5 vs quintile 1: HR 1.50, 95% CI 1.01-2.22, p for trend = 0.02). The observed association was more pronounced among participants in the lowest serum zinc tertile (tertile 3 vs tertile 1: HR 1.82, 95% CI 1.06-3.11, p for trend = 0.004, p for interaction = 0.05) but was attenuated and became nonsignificant among never smokers (tertile 3 vs tertile 1: never smokers: HR 1.27, 95% CI 0.80-2.03, p for trend = 0.29; ever smokers: HR 1.60, 95% CI 1.06-2.43, p for trend = 0.07, p for interaction = 0.51). Findings from this study suggest that cadmium exposure may be an independent risk factor for ischemic stroke in the US general population. Never smoking and maintaining a high serum zinc level may ameliorate the potential adverse effects of cadmium exposure. © 2018 American Academy of Neurology.

Use of standardized patients to assess quality of tuberculosis care: a pilot, cross-sectional study

PubMed Central

Das, Jishnu; Kwan, Ada; Daniels, Ben; Satyanarayana, Srinath; Subbaraman, Ramnath; Bergkvist, Sofi; Das, Ranendra K.; Das, Veena; Pai, Madhukar

2015-01-01

SUMMARY Background Existing studies on quality of tuberculosis care mostly reflect knowledge, not actual practice. Methods We conducted a validation study on the use of standardized patients (SPs) for assessing quality of TB care. Four cases, two for presumed TB and one each for confirmed TB and suspected MDR-TB, were presented by 17 SPs, with 250 SP interactions among 100 consenting providers in Delhi, including qualified (29%), alternative medicine (40%) and informal providers (31%). Validation criteria were: (1) negligible risk and ability to avoid adverse events for providers and SPs; (2) low detection rates of SPs by providers, and (3) data accuracy across SPs and audio verification of SP recall. We used medical vignettes to assess provider knowledge for presumed TB. Correct case management was benchmarked using Standards for TB Care in India (STCI). Findings SPs were deployed with low detection rates (4.7% of 232 interactions), high correlation of recall with audio recordings (r=0.63; 95% CI: 0.53 – 0.79), and no safety concerns. Average consultation length was 6 minutes with 6.2 questions/exams completed, representing 35% (95% confidence interval [CI]: 33%–38%) of essential checklist items. Across all cases, only 52 of 250 (21%; 95% CI: 16%–26%) were correctly managed. Correct management was higher among MBBS doctors (adjusted OR=2.41, 95% CI: 1.17–4.93) as compared to all others. Provider knowledge in the vignettes was markedly more consistent with STCI than their practice. Interpretation The SP methodology can be successfully implemented to assess TB care. Our data suggest a big gap between provider knowledge and practice. PMID:26268690

Organisational justice protects against the negative effect of workplace violence on teachers' sleep: a longitudinal cohort study.

PubMed

Gluschkoff, Kia; Elovainio, Marko; Hintsa, Taina; Pentti, Jaana; Salo, Paula; Kivimäki, Mika; Vahtera, Jussi

2017-07-01

This study aimed to examine the longitudinal association of workplace violence with disturbed sleep and the moderating role of organisational justice (ie, the extent to which employees are treated with fairness) in teaching. We identified 4988 teachers participating in the Finnish Public Sector study who reported encountering violence at work. Disturbed sleep was measured in three waves with 2-year intervals: the wave preceding exposure to violence, the wave of exposure and the wave following the exposure. Data on procedural and interactional justice were obtained from the wave of exposure to violence. The associations were examined using repeated measures log-binomial regression analysis with the generalised estimating equations method, adjusting for gender and age. Exposure to violence was associated with an increase in disturbed sleep (RR 1.32 (95% CI 1.15 to 1.52)) that also persisted after the exposure (RR 1.26 (95% CI 1.07 to 1.48)). The increase was higher among teachers perceiving the managerial practices as relatively unfair (RR 1.46 (95% CI 1.01 to 2.09) and RR 1.59 (95% CI 1.04 to 2.42) for interactional and procedural justice, respectively). By contrast, working in high-justice conditions seemed to protect teachers from the negative effect of violence on sleep. Our findings show an increase in sleep disturbances due to exposure to workplace violence in teaching. However, the extent to which teachers are treated with justice moderates this association. Although preventive measures for violence should be prioritised, resources aimed at promoting justice at schools can mitigate sleep problems associated with workplace violence. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effects of a walking intervention using mobile technology and interactive voice response on serum adipokines among postmenopausal women at increased breast cancer risk.

PubMed

Llanos, Adana A M; Krok, Jessica L; Peng, Juan; Pennell, Michael L; Vitolins, Mara Z; Degraffinreid, Cecilia R; Paskett, Electra D

2014-04-01

Practical methods to reduce the risk of obesity-related breast cancer among high-risk subgroups are lacking. Few studies have investigated the effects of exercise on circulating adipokines, which have been shown to be associated with obesity and breast cancer. The aim of this study was to examine the effects of a walking intervention on serum adiponectin, leptin, and the adiponectin-to-leptin ratio (A/L). Seventy-one overweight and obese postmenopausal women at increased risk of developing breast cancer were stratified by BMI (25-30 kg/m(2) or >30 kg/m(2)) and randomized to a 12-week, two-arm walking intervention administered through interactive voice response (IVR) and mobile devices. The intervention arms were IVR + coach and IVR + no-coach condition. Pre-post changes in serum adiponectin, leptin, and the A/L ratio were examined using mixed regression models, with ratio estimates (and 95 % confidence intervals [CI]) corresponding to postintervention adipokine concentrations relative to preintervention concentrations. While postintervention effects included statistically significant improvements in anthropometric measures, the observed decreases in adiponectin and leptin (ratio = 0.86, 95 % CI 0.74-1.01, and ratio = 0.94, 95 % CI 0.87-1.01, respectively) and increase in A/L ratio = 1.09, 95 % CI 0.94-1.26) were not significant. Thus, these findings do not support significant effects of the walking intervention on circulating adipokines among overweight and obese postmenopausal women. Additional studies are essential to determine the most effective and practical lifestyle interventions that can promote beneficial modification of serum adipokine concentrations, which may prove useful for obesity-related breast cancer prevention.

Effects of a walking intervention using mobile technology and interactive voice response on serum adipokines among postmenopausal women at increased breast cancer risk

PubMed Central

Llanos, Adana A.M.; Krok, Jessica L.; Peng, Juan; Pennell, Michael L.; Vitolins, Mara Z.; Degraffinreid, Cecilia R.; Paskett, Electra D.

2014-01-01

Practical methods to reduce the risk of obesity-related breast cancer among high-risk subgroups are lacking. Few studies have investigated the effects of exercise on circulating adipokines, which have been shown to be associated with obesity and breast cancer. The aim of this study was to examine the effects of a walking intervention on serum adiponectin, leptin and the adiponectin-to-leptin ratio (A/L). Seventy-one overweight and obese postmenopausal women at increased risk of developing breast cancer were stratified by BMI (25-30 kg/m2 or >30 kg/m2) and randomized to a 12-week, 2-arm walking intervention administered through interactive voice response (IVR) and mobile devices. The intervention arms were: IVR + coach and IVR + no coach condition. Pre-post changes in serum adiponectin, leptin and the A/L ratio were examined using mixed regression models, with ratio estimates (and 95% confidence intervals [CI]) corresponding to post-intervention adipokine concentrations relative to pre-intervention concentrations. While post-intervention effects included statistically significant improvements in anthropometric measures, the observed decreases in adiponectin and leptin (Ratio=0.86, 95% CI 0.74-1.01 and Ratio=0.94, 95% CI 0.87-1.01, respectively) and increase in A/L (Ratio=1.09, 95% CI 0.94-1.26) were not significant. Thus, these findings do not support significant effects of the walking intervention on circulating adipokines among overweight and obese postmenopausal women. Additional studies are essential to determine the most effective and practical lifestyle interventions that can promote beneficial modification of serum adipokine concentrations, which may prove useful for obesity-related breast cancer prevention. PMID:24435584

Serum β-Glucuronidase Activity in Response to Fruit and Vegetable Supplementation: A Controlled Feeding Study

PubMed Central

Maruti, Sonia S.; Chang, Jyh-Lurn; Prunty, JoAnn; Bigler, Jeannette; Schwarz, Yvonne; Li, Shuying S.; Li, Lin; King, Irena B.; Potter, John D.; Lampe, Johanna W.

2008-01-01

Background Fruit and vegetable intake may lower the risk of some cancers. One hypothesized, but understudied, chemopreventive mechanism is that plant food constituents inhibit β-glucuronidase, an acid hydrolase that deconjugates glucuronides. Methods We conducted a cross-over feeding trial in 63 healthy women and men aged 20−40 years, to examine the effect of diet on serum β-glucuronidase activity. Participants were randomized to 2 two-week experimental diets with an intervening washout period: a diet high in selected citrus fruit, crucifers, and soy (F&V) and a diet devoid of fruits, vegetables, and soy (basal). Serum β-glucuronidase activity was measured during the pre-intervention, F&V, and basal periods. Linear mixed models were used to obtain effect estimates and 95% confidence intervals (CI). Results We observed statistically significantly higher β-glucuronidase activity during the F&V than the basal diet (ratio, F&V versus basal diet, 1.09; 95% CI, 1.05−1.13; P <0.01). These results were probably due to decreased β-glucuronidase activity during the basal diet (ratio, basal period versus pre-intervention, 0.93; 95% CI, 0.87−0.98; P=0.01), rather than increased enzyme activity during the F&V diet (ratio, F&V period versus pre-intervention, 1.01; 95% CI, 0.96−1.06; P=0.64). The diet-enzyme activity relation did not differ by sex (P interaction=0.30), but there was a suggestion of a short-term diet effect at 8 days versus 15 days (P interaction=0.06). Conclusion This intervention of selected fruits and vegetables did not lower β-glucuronidase activity. Further investigation is needed regarding what other foods and phytochemicals may influence β-glucuronidase activity and effect modifiers of this relation PMID:18628435

Predictors and outcomes of increases in creatine phosphokinase concentrations or rhabdomyolysis risk during statin treatment

PubMed Central

van Staa, Tjeerd P; Carr, Daniel F; O’Meara, Helen; McCann, Gerry; Pirmohamed, Munir

2014-01-01

Aim The aim was to evaluate clinical risk factors associated with myotoxicity in statin users. Methods This was a cohort study of patients prescribed a statin in UK primary care practices contributing to the Clinical Practice Research Datalink. Outcomes of interest were creatine phosphokinase (CPK) concentrations and clinical records of rhabdomyolysis. Results The cohort comprised 641 703 statin users. Simvastatin was most frequently prescribed (66.3%), followed by atorvastatin (24.4%). CPK was measured in 127 209 patients: 81.4% within normal range and 0.7% above four times ULN CPK compared with normal CPK (OR 1.28, 95% CI 1.01, 1.60). Rosuvastatin users had higher risk of >four times ULN CPK (OR 1.62, 95% CI 1.22, 2.15) as did patients with larger daily doses of other statin types. A recent clinical record of myalgia was associated with an increased OR of >four times ULN CPK (OR 1.73, 95% CI 1.37, 2.18). In patients who were rechallenged to statins and had repeat CPK measurements after >four times ULN CPK abnormalities, 54.8% of the repeat CPK values were within normal range, 32.1% between one to three times and 13.0% >four times ULN. Conclusions The frequencies of substantive CPK increases and rhabdomyolysis during statin treatment were low, with highest risks seen in those on large daily doses or interacting drugs and on rosuvastatin. CPK measurements appeared to have been done in a haphazard manner and better guidance is needed. PMID:24602118

Residential Air Pollution and Associations with Wheeze and Shortness of Breath in Adults: A Combined Analysis of Cross-Sectional Data from Two Large European Cohorts

PubMed Central

de Hoogh, Kees; Probst-Hensch, Nicole; Mbatchou, Stéphane; Eeftens, Marloes; Cai, Yutong; Schindler, Christian; Fortier, Isabel; Hodgson, Susan; Gaye, Amadou; Stolk, Ronald; Hansell, Anna

2017-01-01

Background: Research examining associations between air pollution exposure and respiratory symptoms in adults has generally been inconclusive. This may be related in part to sample size issues, which also preclude analysis in potentially vulnerable subgroups. Objectives: We estimated associations between air pollution exposures and the prevalence of wheeze and shortness of breath using harmonized baseline data from two very large European cohorts, Lifelines (2006–2013) and UK Biobank (2006–2010). Our aim was also to determine whether the relationship between air pollution and respiratory symptom prevalence differed between individuals with different characteristics. Methods: Cross-sectional analyses explored associations between prevalence of self-reported wheeze and shortness of breath and annual mean particulate matter with aerodynamic diameter <2.5μm, 2.5–10μm, and <10μm (PM2.5, PMcoarse, and PM10, respectively) and nitrogen dioxide (NO2) concentrations at place of residence using logistic regression. Subgroup analyses and tests for interaction were performed for age, sex, smoking status, household income, obesity status, and asthma status. Results: All PM exposures were associated with respiratory symptoms based on single-pollutant models, with the largest associations seen for PM2.5 with prevalence of wheezing {odds ratio (OR)=1.16 per 5μg/m³ [95% confidence interval (CI): 1.11, 1.21]} and shortness of breath [OR=1.61 per 5μg/m³ (95% CI: 1.45, 1.78)]. The association between shortness of breath and a 5-μg/m³ increment in PM2.5 was significantly higher for individuals from lower-[OR=1.73 (95% CI: 1.52, 1.97)] versus higher-income households [OR=1.31 (95% CI: 1.11, 1.55); p-interaction=0.005), whereas the association between PM2.5 and wheeze was limited to lower-income participants [OR=1.30 (95% CI: 1.22, 1.38) vs. OR=1.02; (95% CI: 0.96, 1.08); p-interaction<0.001]. Exposure to NO2 also showed positive associations with wheeze and shortness of breath. Conclusion: Exposure to PM and NO2 air pollution was associated with the prevalence of wheeze and shortness of breath in this large study, with stronger associations between PM2.5 and both outcomes among lower- versus higher-income participants. https://doi.org/10.1289/EHP1353 PMID:28963089

Interaction of notochord-derived fibrinogen-like protein with Notch regulates the patterning of the central nervous system of Ciona intestinalis embryos.

PubMed

Yamada, Shigehiro; Hotta, Kohji; Yamamoto, Takamasa S; Ueno, Naoto; Satoh, Nori; Takahashi, Hiroki

2009-04-01

The midline organ the notochord and its overlying dorsal neural tube are the most prominent features of the chordate body plan. Although the molecular mechanisms involved in the formation of the central nervous system (CNS) have been studied extensively in vertebrate embryos, none of the genes that are expressed exclusively in notochord cells has been shown to function in this process. Here, we report a gene in the urochordate Ciona intestinalis encoding a fibrinogen-like protein that plays a pivotal role in the notochord-dependent positioning of neuronal cells. While this gene (Ci-fibrn) is expressed exclusively in notochord cells, its protein product is not confined to these cells but is distributed underneath the CNS as fibril-like protrusions. We demonstrated that Ci-fibrn interacts physically and functionally with Ci-Notch that is expressed in the central nervous system, and that the correct distribution of Ci-fibrn protein is dependent on Notch signaling. Disturbance of the Ci-fibrn distribution caused an abnormal positioning of neuronal cells and an abnormal track of axon extension. Therefore, it is highly likely that the interaction between the notochord-based fibrinogen-like protein and the neural tube-based Notch signaling plays an essential role in the proper patterning of CNS.

Association of Long-Duration Breastfeeding and Dental Caries Estimated with Marginal Structural Models

PubMed Central

Chaffee, Benjamin W.; Feldens, Carlos Alberto; Vítolo, Márcia Regina

2014-01-01

Purpose Estimate the association between breastfeeding ≥24 months and severe early childhood caries (ECC). Methods Within a birth cohort (n=715) from low-income families in Porto Alegre, Brazil, the age 38-month prevalence of severe-ECC (≥4 affected tooth surfaces or ≥1 affected maxillary anterior teeth) was compared over breastfeeding duration categories using marginal structural models to account for time-dependent confounding by other feeding habits and child growth. Additional analyses assessed whether daily breastfeeding frequency modified the association of breastfeeding duration and severe-ECC. Multiple imputation and censoring weights were used to address incomplete covariate information and missing outcomes, respectively. Confidence intervals (CI) were estimated using bootstrap re-sampling. Results Breastfeeding ≥24 months was associated with the highest adjusted population-average severe-ECC prevalence (0.45, 95% CI: 0.36, 0.54) compared with breastfeeding <6 months (0.22, 95% CI: 0.15, 0.28), 6–11 months (0.38, 95% CI: 0.25, 0.53), or 12–23 months (0.39, 95% CI: 0.20, 0.56). High frequency breastfeeding enhanced the association between long-duration breastfeeding and caries (excess prevalence due to interaction: 0.13, 80% CI: −0.03, 0.30). Conclusions In this population, breastfeeding ≥24 months, particularly if frequent, was associated with severe-ECC. Dental health should be one consideration, among many, in evaluating health outcomes associated with breastfeeding ≥24 months. PMID:24636616

Interaction between Education and Household Wealth on the Risk of Obesity in Women in Egypt

PubMed Central

Aitsi-Selmi, Amina; Chandola, Tarani; Friel, Sharon; Nouraei, Reza; Shipley, Martin J.; Marmot, Michael G.

2012-01-01

Background Obesity is a growing problem in lower income countries particularly among women. There are few studies exploring individual socioeconomic status indicators in depth. This study examines the interaction of education and wealth in relation to obesity, hypothesising that education protects against the obesogenic effect of wealth. Methods Four datasets of women of reproductive age from the Egyptian Demographic and Health Surveys spanning the period 1992–2008 are used to examine two distinct time periods: 1992/95 (N = 11097) and 2005/08 (N = 23178). The association in the two time periods between education level and household wealth in relation to the odds of being obese is examined, and the interaction between the two socioeconomic indicators investigated. Estimates are adjusted for age group and area of residence. Results An interaction was found between the association of education and wealth with obesity in both time periods (P-value for interaction <0.001). For women with the lowest education level, moving up one wealth quintile was associated with a 78% increase in the odds of obesity in 1992/95 (OR; 95%CI: 1.78; 1.65,1.91) and a 33% increase in 2005/08 (OR; 95%CI: 1.33; 1.26,1.39). For women with the highest level of education, there was little evidence of an association between wealth and obesity (OR; 95%CI: 0.82; 0.57,1.16 in 1992/95 and 0.95; 0.84,1.08 in 2005/08). Obesity levels increased most in women who were in the no/primary education, poorest wealth quintile and rural groups (absolute difference in prevalence percentage points between the two time periods: 20.2, 20.1, and 21.3 respectively). Conclusion In the present study, wealth appears to be a risk factor for obesity in women with lower education levels, while women with higher education are protected. The findings also suggest that a reversal in the social distribution of obesity risk is occurring which can be explained by the large increase in obesity levels in lower socioeconomic groups between the two time periods. PMID:22761807

Oral health related quality of life in pregnant and post partum women in two social network domains; predominantly home-based and work-based networks

PubMed Central

2012-01-01

Background Individuals connected to supportive social networks have better general and oral health quality of life. The objective of this study was to assess whether there were differences in oral health related quality of life (OHRQoL) between women connected to either predominantly home-based and work-based social networks. Methods A follow-up prevalence study was conducted on 1403 pregnant and post-partum women (mean age of 25.2 ± 6.3 years) living in two cities in the State of Rio de Janeiro, Brazil. Women were participants in an established cohort followed from pregnancy (baseline) to post-partum period (follow-up). All participants were allocated to two groups; 1. work-based social network group - employed women with paid work, and, 2. home-based social network group - women with no paid work, housewives or unemployed women. Measures of social support and social network were used as well as questions on sociodemographic characteristics and OHRQoL and health related behaviors. Multinomial logistic regression was performed to obtain OR of relationships between occupational contexts, affectionate support and positive social interaction on the one hand, and oral health quality of life, using the Oral Health Impacts Profile (OHIP) measure, adjusted for age, ethnicity, family income, schooling, marital status and social class. Results There was a modifying effect of positive social interaction on the odds of occupational context on OHRQoL. The odds of having a poorer OHIP score, ≥4, was significantly higher for women with home-based social networks and moderate levels of positive social interactions [OR 1.64 (95% CI: 1.08-2.48)], and for women with home-based social networks and low levels of positive social interactions [OR 2.15 (95% CI: 1.40-3.30)] compared with women with work-based social networks and high levels of positive social interactions. Black ethnicity was associated with OHIP scores ≥4 [OR 1.73 (95% CI: 1.23-2.42)]. Conclusions Pregnant and post-partum Brazilian women in paid employment outside the home and having social supports had better OHRQoL than those with home-based social networks. PMID:22244015

Objective Sedentary Time, Moderate-to-Vigorous Physical Activity, and Physical Capability in a British Cohort

PubMed Central

KEEVIL, VICTORIA L.; COOPER, ANDREW J. M.; WIJNDAELE, KATRIEN; LUBEN, ROBERT; WAREHAM, NICHOLAS J.; BRAGE, SOREN; KHAW, KAY-TEE

2016-01-01

ABSTRACT Purpose Sedentariness has been proposed as an independent risk factor for poor health. However, few studies have considered associations of sedentary time (ST) with physical functional health independent of time spent in moderate-to-vigorous physical activity (MVPA). Methods Community-based men and women (n = 8623, 48–92 yr old) in the European Prospective Investigation of Cancer—Norfolk study attended a health examination for objective measurement of physical capability, including grip strength (Smedley dynamometer (kg)), usual walking speed (UWS (cm·s−1)), and timed chair stand speed (TCSS (stands per minute)). Of these, 4051 participants wore an accelerometer (GT1M ActiGraph) for 7 d to estimate time spent in MVPA (MVPA, ≥1952 counts per minute) and ST (ST, <100 counts per minute). Relations between physical capability outcomes and both MVPA and ST were explored using linear regression. The mutual independence of associations was also tested, and ST-MVPA interactions were explored using fractional polynomial models to account for nonlinear associations. Results Men in the highest compared with those in the lowest sex-specific quartile of MVPA were stronger (1.84 kg; 95% confidence interval (CI), 0.79–2.89), had faster UWS (11.7 cm·s−1; 95% CI, 8.4–15.1) and faster TCSS (2.35 stands per minute; 95% CI, 1.11–3.59) after multivariable adjustment. Similarly, women in the highest quartile of MVPA were stronger (2.47 kg; 95% CI, 1.79–3.14) and had faster UWS (15.5 cm·s−1; 95% CI, 12.4–18.6) and faster TCSS (3.27 stands per minute; 95% CI, 2.19–4.25). Associations persisted after further adjustment for ST. Associations between higher ST and lower physical capability were also observed, but these were attenuated after accounting for MVPA. Furthermore, no MVPA–ST interactions were observed (Pinteractions > 0.05). Conclusions More time spent in MVPA was associated with higher physical capability, but there were no independent ST associations. PMID:26501232

Anxiety and Anger Immediately Prior to Myocardial Infarction and Long-term Mortality: Characteristics of High-Risk Patients

PubMed Central

Smeijers, Loes; Mostofsky, Elizabeth; Tofler, Geoffrey H.; Muller, James E.; Kop, Willem J.; Mittleman, Murray A.

2016-01-01

Objective Acute high levels of anger and anxiety are associated with an elevated risk of myocardial infarction (MI) in the following two hours. MIs preceded by these acute negative emotions may also have a poor long-term prognosis, but information about high-risk patients is lacking. We examined whether young age and female sex are associated with MIs that are preceded by negative emotions and whether age and sex moderate the subsequent increased mortality risk following MI preceded by negative emotions. Methods We conducted a secondary analysis of the Determinants of Myocardial Infarction Onset Study (N=2176, mean age=60.1±12.3 years, 29.2% women). Anxiety and anger immediately prior to (0-2 hour) MI and the day before (24-26 hour) MI were assessed using a structured interview. Subsequent 10-year all-cause mortality was determined using the US National Death Index. Results Anxiety during the 0-2 hour pre-MI period was associated with younger age (OR=0.98,95%CI=0.96-0.99 per year) and female sex (OR=1.50,95%CI=1.11-2.02). Anger in the 0-2 hour pre-MI period was also associated with younger age (OR=0.95,95%CI=0.94-0.96) but not with sex (OR=0.93,95%CI=0.67-1.28). During follow-up, 580 (26.7%) patients died. Mortality rate was higher if MI occurred immediately after high anxiety, particularly in patients ≥65 years (HR=1.80,95%CI=1.28-2.54) vs. younger patients (HR=0.87,95%CI=0.55-1.40; p-interaction=0.015). Other interactions with sex or anger were not significant. Conclusions Patients with high anxiety or anger levels in the critical 2-hour period prior to MI are younger than those without such emotional precipitants. In addition, pre-MI anxiety is associated with an elevated 10-year mortality risk in patients aged ≥65 years. PMID:28107888

Theoretical study of the electric dipole moment function of the ClO molecule

NASA Technical Reports Server (NTRS)

Pettersson, L. G. M.; Langhoff, S. R.; Chong, D. P.

1986-01-01

The potential energy function and electric dipole moment function (EDMF) are computed for ClO X 2Pi using several different techniques to include electron correlation. The EDMF is used to compute Einstein coefficients, vibrational lifetimes, and dipole moments in higher vibrational levels. The band strength of the 1-0 fundamental transition is computed to be 12 + or - 2 per sq cm atm determined from infrared heterodyne spectroscopy. The theoretical methods used include SCF, CASSCF, multireference singles plus doubles configuration interaction (MRCI) and contracted CI, coupled pair functional (CPF), and a modified version of the CPF method. The results obtained using the different methods are critically compared.

Family and home correlates of children's physical activity in a multi-ethnic population: the cross-sectional child heart and health study in england (CHASE)

PubMed Central

2011-01-01

Background The influence of the family and home environment on childhood physical activity (PA) and whether this differs between ethnic groups remains uncertain. This paper investigates associations between family and home factors and childhood PA in a multi-ethnic population and explores whether associations differ between ethnic groups. Methods Cross-sectional study of 9-10 year-old schoolchildren, in which PA was objectively measured by Actigraph GT1 M accelerometers for ≤7 days to estimate average activity counts per minute (CPM). Information on 11 family and home environmental factors were collected from questionnaires. Associations between these factors and CPM were quantified using multi-level linear regression. Interactions with ethnicity were explored using likelihood ratio tests. Results 2071 children (mean ± SD age: 9.95 ± 0.38 years; 47.8% male) participated, including 25% white European, 28% black African-Caribbean, 24% South Asian, and 24% other ethnic origin. Family PA support and having a pet were associated with higher average CPM (adjusted mean difference: 6 (95%CI:1,10) and 13 (95%CI:3,23), respectively) while car ownership and having internet access at home were associated with lower average CPM (adjusted mean difference: -19 (95%CI:-30,-8) and -10 (95%CI:-19,0), respectively). These associations did not differ by ethnicity. Although the number of siblings showed no overall association with PA, there was some evidence of interaction with ethnicity (p for ethnicity interaction = 0.04, 0.05 in a fully-adjusted model); a positive significant association with number of siblings was observed in white Europeans (per sibling CPM difference 10.3 (95% CI 1.7, 18.9)) and a positive non-significant association was observed in black African-Caribbeans (per sibling CPM difference: 3.5 (-4.2, 11.2)) while a negative, non-significant association was observed in South Asians (per sibling CPM difference -6.0 (-15.5, 3.4)). Conclusions Some family and home environmental factors have modest associations with childhood PA and these are mostly similar across different ethnic groups. This suggests that targeting these factors in an intervention to promote PA would be relevant for children in different ethnic groups. PMID:21324105

[Gender differences in stressful life events and depression in Chinese adults aged 30-79 years].

PubMed

Wu, M; Li, J C; Yu, C Q; Chen, Y P; Lyu, J; Guo, Y; Bian, Z; Tan, Y L; Pei, P; Chen, J S; Chen, Z M; Li, L M

2017-11-10

Objective: To investigate gender specific differences in the association between stressful life events (SLEs) and depression in Chinese adults aged 30-79 years. Methods: In the baseline survey during 2004-2008, the China Kadoorie Biobank (CKB) recruited 512 891 men and women aged 30-79 years from 10 areas of China. Detailed information on SLEs, including demographic and socio-economic status, smoking, alcohol drinking and history of chronic disease, as well as depression symptoms and major depressive episodes (MDEs) in preceding 12 months, was collected by using standardized questionnaire. Multinomial logistic regression model was employed to estimate the relative risk ratio ( RRR ) and 95 %CI of SLEs (3 categories, 10 items) on depression and the dose-response relationship between the number of SLEs experienced and depression. The interactions between gender and SLEs on depression were examined with likelihood ratio test. Results: Among the 512 891 participants, 35 085 (6.8%) reported family-related events, 5 972 (1.2%) reported finance-related events, and 4 453 (0.9%) reported other stressful life events. Females had a higher occurrence of family-related events, while males had a higher occurrence of finance-related and other events (all P -value <0.001). After adjusted for potential confounders, SLEs were significantly associated with MDEs ( RRR =11.99, 95 %CI : 10.49-13.71 for males; RRR =14.15, 95 %CI : 12.97-15.43 for females), and with depressive symptoms ( RRR =7.43, 95 %CI : 6.94-7.95 for males; RRR =8.30, 95 %CI : 7.91-8.72 for females). And the associations were stronger in females than in males ( P for interaction=0.049). In the three categories of SLEs, family-related events showed stronger association in female ( P for interaction <0.001), while no gender specific differences were observed for the other two categories (all P -value>0.05). Furthermore, the effect of the number of SLEs experienced increased in a dose-response manner on depressive symptoms and MDEs for both genders, but no gender specific differences were found. Conclusions: The gender modifies the association between stressful life events and depression in Chinese adults, and women experienced family-related events have a greater risk of depression. The more the stressful events experienced, the more likely to have depression.

Coumarin-indole conjugate donor-acceptor system: Synthesis, photophysical properties, anion sensing ability, theoretical and biological activity studies of two coumarin-indole based push-pull dyes

NASA Astrophysics Data System (ADS)

Aksungur, Tuğçe; Aydıner, Burcu; Seferoğlu, Nurgül; Özkütük, Müjgan; Arslan, Leyla; Reis, Yasemin; Açık, Leyla; Seferoğlu, Zeynel

2017-11-01

Two coumarin-indole conjugate fluorescent dyes having donor-acceptor-donor (D-A-D) (CI-1 and CI-2) were synthesized, and characterized using IR, 1H/13C NMR and HRMS. The absorption and emission properties of the dyes were determined in different solvents. The anion sensitivity and selectivity of the dyes were studied with some anions (CN-, F-, AcO-, Cl-, Br-, I-, HSO4- and H2PO4-) in DMSO, and their interaction mechanisms were evaluated by spectrophotometric and 1H NMR titration techniques. In addition, the molecular and electronic structures of CI-1, as well as the molecular complexes of CI-1, formed with the anions (F- and AcO-), were obtained theoretically and confirmed by DFT and TD-DFT calculations. CI-1 behaves as a colorimetric chemosensor for selective and sensitive detection of CN- in DMSO/H2O (9:1) over other competing anions such as F- and AcO-. However, only CN- interacts with chromophore CI-2 via Michael addition and the main absorption maxima shifts hypsochromically with an observed distinctive color change from orange to yellow. For using as a optic dye, the thermal stability properties of the dyes was determined by TGA (Thermal Gravimetric Analysis). Antimicrobial, antifungal and DNA-ligand interaction studies of the dyes were also examined. The dyes cause conformational changes on DNA and selectively bind to nucleotides of A/A and G/G.

Tobacco control environment in the United States and individual consumer characteristics in relation to continued smoking: differential responses among menthol smokers?

PubMed

Lewis, Michael; Wang, Yanwen; Berg, Carla J

2014-08-01

We used a consumer panel augmented with state-specific measures of tobacco control activities to examine the main effects and interactions among consumer behaviors, particularly menthol cigarette smoking, and tobacco control environment on cessation over a six-year period. We used the Nielson Homescan Panel, which tracks consumer purchasing behaviors, and tobacco control information matched to panelist zip code. We focused on 1582 households purchasing ≥20 packs from 2004 to 2009. Our analysis included demographics; purchasing behavior including menthol versus nonmenthol use (≥80% of cigarettes purchased being menthol), quality preferences (average price/pack), purchase recency, and nicotine intake (nicotine levels of cigarettes purchased); and tobacco control metrics (taxation, anti-tobacco advertising, smoke-free policies). Menthol smoking (Hazard Ratio [HR]=0.79, 95% Confidence Interval [CI] 0.64, 0.99), being African American (HR=0.67, CI 0.46, 0.98), being male (HR=0.46, CI 0.28, 0.74), higher quality premium preferences (HR=0.80, CI 0.77, 0.91), lower recency (HR=1.04, CI 1.02, 1.05), and higher nicotine intake rates (HR=0.99, CI 0.99, 0.99) were related to continued smoking. No significant interactions were found. While there were no interactions between menthol use and effects of tobacco control activities, we did find additional support for the decreased cessation rates among menthol cigarette smokers, particularly in the African American population. Copyright © 2013 Elsevier Inc. All rights reserved.

Risk factors and psychosocial characteristics of potential problematic and problematic internet use among adolescents: A cross-sectional study

PubMed Central

2011-01-01

Background Problematic internet use (PIU) is associated with a plethora of psychosocial adversities. The study objectives were to assess the determinants and psychosocial implications associated with potential PIU and PIU among adolescents. Methods A cross-sectional study design was applied among a random sample (n = 866) of Greek adolescents (mean age: 14.7 years). Self-completed questionnaires, including internet use characteristics, Young Internet Addiction Test, and Strengths and Difficulties Questionnaire, were utilized to examine the study objectives. Results Among the study population, the prevalence rates of potential PIU and PIU were 19.4% and 1.5%, respectively. Multinomial logistic regression indicated that male gender (Odds Ratio, OR: 2.01; 95% Confidence Interval, 95% CI: 1.35-3.00), as well as utilizing the internet for retrieving sexual information (OR: 2.52; 95% CI: 1.53-4.12), interactive game playing (OR: 1.85; 95% CI: 1.21-2.82), and socialization, including chat-room use (OR: 1.97; 95% CI: 1.36-2.86) and email (OR: 1.53; 95% CI: 1.05-2.24), were independently associated with potential PIU and PIU. Adolescents with potential PIU had an increased likelihood of concomitantly presenting with hyperactivity (OR: 4.39; 95% CI: 2.03-9.52) and conduct (OR: 2.56; 95% CI: 1.46-4.50) problems. Moreover, adolescent PIU was significantly associated with hyperactivity (OR: 9.96; 95% CI: 1.76-56.20) and conduct (OR: 8.39; 95% CI: 2.04-34.56) problems, as well as comprehensive psychosocial maladjustment (OR: 8.08; 95% CI: 1.44-45.34). Conclusions The determinants of potential PIU and PIU include accessing the internet for the purposes of retrieving sexual information, game playing, and socialization. Furthermore, both potential PIU and PIU are adversely associated with notable behavioral and social maladjustment among adolescents. PMID:21794167

Intake of Mediterranean foods associated with positive affect and low negative affect

PubMed Central

Ford, Patricia A.; Jaceldo-Siegl, Karen; Lee, Jerry W.; Youngberg, Wes; Tonstad, Serena

2013-01-01

Objective To examine associations between consumption of foods typical of Mediterranean versus Western diets with positive and negative affect. Nutrients influence mental states yet few studies have examined whether foods protective or deleterious for cardiovascular disease affect mood. Methods Participants were 9255 Adventist church attendees in North America who completed a validated food frequency questionnaire in 2002–6. Scores for affect were obtained from the Positive and Negative Affect Schedule questionnaire in 2006–7. Multiple linear regression models controlled for age, gender, ethnicity, BMI, education, sleep, sleep squared (to account for high or low amounts), exercise, total caloric intake, alcohol and time between the questionnaires. Results Intake of vegetables (β=0.124 [95% CI 0.101, 0.147]), fruit (β=0.066 [95% CI 0.046, 0.085]), olive oil (β=0.070 [95% CI 0.029, 0.111]), nuts (β=0.054 [95% CI 0.026, 0.082]), and legumes (β=0.055 [95% CI 0.032, 0.077]) were associated with positive affect while sweets/desserts (β=−0.066 [95% CI −0.086, −0.046]), soda (β=−0.025 [95% CI −0.037, −0.013]) and fast food frequency (β=−0.046 [95% CI −0.062, −0.030]) were inversely associated with positive affect. Intake of sweets/desserts (β=0.058 [95% CI 0.037, 0.078]) and fast food frequency (β=0.052 [95% CI 0.036, 0.068]) were associated with negative affect while intake of vegetables (β=−0.076 [95% CI −0.099, −0.052]), fruit (β=−0.033 [95% CI −0.053, −0.014]) and nuts (β=−0.088 [95% CI −0.116, −0.060]) were inversely associated with negative affect. Gender interacted with red meat intake (P<.001) and fast food frequency (P<.001) such that these foods were associated with negative affect in females only. Conclusions Foods typical of Mediterranean diets were associated with positive affect as well as lower negative affect while Western foods were associated with low positive affect in general and negative affect in women. PMID:23332529

Social Support, Sexual Violence, and Transactional Sex Among Female Transnational Migrants to South Africa

PubMed Central

Giorgio, Margaret; Townsend, Loraine; Zembe, Yanga; Guttmacher, Sally; Kapadia, Farzana; Cheyip, Mireille; Mathews, Catherine

2018-01-01

Objectives To examine the relationship between sexual violence and transactional sex and assess the impact of social support on this relationship among female transnational migrants in Cape Town, South Africa. Methods In 2012 we administered a behavioral risk factor survey using respondent-driven sampling to transnational migrant women aged between 16 and 39 years, born outside South Africa, living in Cape Town, and speaking English, Shona, Swahili, Lingala, Kirundi, Kinyarwanda, French, or Somali. Results Controlling for study covariates, travel-phase sexual violence was positively associated with engagement in transactional sex (adjusted prevalence ratio [APR] = 1.38; 95% confidence interval [CI] = 1.07, 1.77), and social support was shown to be a protective factor (APR = 0.84; 95% CI = 0.75, 0.95). The interaction of experienced sexual violence during migration and social support score was APR = 0.85 (95% CI = 0.66, 1.10). In the stratified analysis, we found an increased risk of transactional sex among the low social support group (APR = 1.56; 95% CI = 1.22, 2.00). This relationship was not statistically significant among the moderate or high social support group (APR = 1.04; 95% CI = 0.58, 1.87). Conclusions Programs designed to strengthen social support may reduce transactional sex among migrant women after they have settled in their receiving communities. PMID:29417089

Providing prenatal care to pregnant women with overweight or obesity: Differences in provider communication and ratings of the patient-provider relationship by patient body weight

PubMed Central

Washington Cole, Katie O.; Gudzune, Kimberly A.; Bleich, Sara N.; Cheskin, Lawrence J.; Bennett, Wendy L.; Cooper, Lisa A.; Roter, Debra L.

2017-01-01

Objective To examine the association of women’s body weight with provider communication during prenatal care. Methods We coded audio recordings of prenatal visits between 22 providers and 117 of their patients using the Roter Interaction Analysis System. Multivariate, multilevel Poisson models were used to examine the relationship between patient pre-pregnancy body mass index and provider communication. Results Compared to women with normal weight, providers asked fewer lifestyle questions (IRR 0.66, 95% CI 0.44 – 0.99, p = 0.04) and gave less lifestyle information (IRR 0.51, 95% CI 0.32 – 0.82, p = 0.01) to women with overweight and obesity, respectively. Providers used fewer approval (IRR 0.68, 95% CI 0.51 – 0.91, p = 0.01) and concern statements (IRR 0.68, 95% CI 0.53 – 0.86, p = 0.002) when caring for women with overweight and fewer self-disclosure statements caring for women with obesity (IRR 0.40, 95% CI 0.19 – 0.84 p = 0.02). Conclusion Less lifestyle and rapport building communication for women with obesity may weaken patient-provider relationship during routine prenatal care. Practice implications Interventions to increase use of patient-centered communication – especially for women with overweight and obesity – may improve prenatal care quality. PMID:28062155

A Locality-Based Threading Algorithm for the Configuration-Interaction Method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shan, Hongzhang; Williams, Samuel; Johnson, Calvin

The Configuration Interaction (CI) method has been widely used to solve the non-relativistic many-body Schrodinger equation. One great challenge to implementing it efficiently on manycore architectures is its immense memory and data movement requirements. To address this issue, within each node, we exploit a hybrid MPI+OpenMP programming model in lieu of the traditional flat MPI programming model. Here in this paper, we develop optimizations that partition the workloads among OpenMP threads based on data locality,-which is essential in ensuring applications with complex data access patterns scale well on manycore architectures. The new algorithm scales to 256 threadson the 64-core Intelmore » Knights Landing (KNL) manycore processor and 24 threads on dual-socket Ivy Bridge (Xeon) nodes. Compared with the original implementation, the performance has been improved by up to 7× on theKnights Landing processor and 3× on the dual-socket Ivy Bridge node.« less

A Locality-Based Threading Algorithm for the Configuration-Interaction Method

DOE PAGES

Shan, Hongzhang; Williams, Samuel; Johnson, Calvin; ...

2017-07-03

The Configuration Interaction (CI) method has been widely used to solve the non-relativistic many-body Schrodinger equation. One great challenge to implementing it efficiently on manycore architectures is its immense memory and data movement requirements. To address this issue, within each node, we exploit a hybrid MPI+OpenMP programming model in lieu of the traditional flat MPI programming model. Here in this paper, we develop optimizations that partition the workloads among OpenMP threads based on data locality,-which is essential in ensuring applications with complex data access patterns scale well on manycore architectures. The new algorithm scales to 256 threadson the 64-core Intelmore » Knights Landing (KNL) manycore processor and 24 threads on dual-socket Ivy Bridge (Xeon) nodes. Compared with the original implementation, the performance has been improved by up to 7× on theKnights Landing processor and 3× on the dual-socket Ivy Bridge node.« less

[The effect of pre-pregnancy weight and the increase of gestational weight on fetal growth restriction: a cohort study].

PubMed

Shi, M Y; Wang, Y F; Huang, K; Yan, S Q; Ge, X; Chen, M L; Hao, J H; Tong, S L; Tao, F B

2017-12-06

Objective: To investigate the effect of pre-pregnancy weight and the increase of gestational weight on fetal growth restriction. Methods: From May 2013 to September 2014, a total of 3 474 pregnant women who took their first antenatal care and willing to undergo their prenatal care and delivery in Ma 'anshan Maternity and Child Care Centers were recruited in the cohort study. Excluding subjects without weight data before delivery ( n= 54), pregnancy termination ( n= 162), twins live births ( n= 39), without fetal birth weight data ( n= 7), 3 212 maternal-singleton pairs were enrolled for the final data analysis. Demographic information of pregnant woman, pregnancy history, disease history, height and weight were collected. In the 24(th)-28(th), 32(nd)-36(th) gestational week and childbirth, three follow-up visits were undertaken to collect data of pregnancy weight, pregnancy vomiting, gestational hypertension, gestational diabetes mellitus, newborn gender and birth weight. χ(2) test was used to compare the detection rate of fetal growth restriction in different groups. Multivariate unconditional logistic regression model and spreadsheet were used to analyze the independent and interaction effect of pre-pregnancy weight and the increase of gestational weight on fetal growth restriction. Results: The incidence of fetal growth restriction was 9.7%(311/3 212). The incidence of fetal growth restriction in pre-pregnancy underweight group was 14.9% (90/603), higher than that in normal pre-pregnancy weight group (8.7% (194/2 226)) (χ(2)=24.37, P< 0.001). The incidence of fetal growth restriction in inadequate increase of gestational weight group was 17.9% (50/279), higher than the appropriate increase of weight group (11.8% (110/932)) (χ(2)=36.89, P< 0.001). Multivariate unconditional logistic regression analysis showed that compared with normal pre-pregnancy weight group, pre-pregnancy underweightwas a risk factor for fetal growth restriction, with RR (95 %CI ) at 1.76 (1.34-2.32); Compared with the appropriate increase of gestational weight group, inadequate weight increase during pregnancy was a risk factor for fetal growth restriction, with the RR (95 %CI ) at 1.70 (1.17-2.48). No additive model interaction [relative excess risk of interaction, attributable proportions of interaction, the synergy index and their 95 %CI were 0.75 (-2.14-3.63), 0.21 (-0.43-0.86) and 1.43 (0.45-4.53), respectively] or multiplication model interaction ( RR (95 %CI ): 1.00 (0.44-2.29)) existed between pre-pregnancy underweight and inadequate increase of gestational weight on fetal growth restriction. Conclusion: Pre-pregnancy underweight and inadequate increase of gestational weight would increase the risk of fetal growth restriction without interaction.

Prasugrel versus clopidogrel in patients with ST-segment elevation myocardial infarction according to timing of percutaneous coronary intervention: a TRITON-TIMI 38 subgroup analysis (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infarction 38).

PubMed

Udell, Jacob A; Braunwald, Eugene; Antman, Elliott M; Antman, Elliot M; Murphy, Sabina A; Montalescot, Gilles; Wiviott, Stephen D

2014-06-01

This study sought to evaluate the efficacy of prasugrel versus clopidogrel in ST-segment elevation myocardial infarction (STEMI) by the timing of percutaneous coronary intervention (PCI). Treatment strategies and outcomes for patients with STEMI may differ when treated with primary compared with secondary PCI. STEMI patients in the TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infarction 38) were randomized to prasugrel or clopidogrel on presentation if primary PCI was intended or later during secondary PCI. Primary PCI was defined as within 12 h of symptom onset. The primary endpoint was cardiovascular death, myocardial infarction (MI), or stroke. Because periprocedural MI is difficult to assess in the setting of STEMI, we performed analyses excluding these events. Reductions in the primary endpoint with prasugrel versus clopidogrel (hazard ratio [HR]: 0.79; 95% confidence interval [CI]: 0.65 to 0.97; p = 0.022) were consistent between primary and secondary PCI patients at 15 months (HR: 0.89; 95% CI: 0.69 to 1.13 vs. HR: 0.65; 95% CI: 0.46 to 0.93; p interaction = 0.15). However, a tendency toward a difference in treatment effect at 30 days (HR: 0.68; 95% CI: 0.54 to 0.87; p = 0.002) was observed between primary and secondary PCI patients (HR: 0.81; 95% CI: 0.60 to 1.09 vs. HR: 0.51; 95% CI: 0.34 to 0.76; p interaction = 0.06). When periprocedural MI was excluded, the efficacy of prasugrel remained consistent among primary and secondary PCI patients at 30 days (HR: 0.53; 95% CI: 0.34 to 0.81 vs. HR: 0.44; 95% CI: 0.22 to 0.88; p interaction = 0.68) and 15 months (HR: 0.76; 95% CI: 0.56 to 1.03 vs. HR: 0.75; 95% CI: 0.46 to 1.21; p interaction = 0.96). The efficacy of prasugrel versus clopidogrel was consistent irrespective of the timing of PCI, particularly in preventing nonprocedural events. (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38; NCT00097591). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Glucagon gene polymorphism modifies the effects of smoking and physical activity on risk of type 2 diabetes mellitus in Han Chinese.

PubMed

Li, Linlin; Gao, Kaiping; Zhao, Jingzhi; Feng, Tianping; Yin, Lei; Wang, Jinjin; Wang, Chongjian; Li, Chunyang; Wang, Yan; Wang, Qian; Zhai, Yujia; You, Haifei; Ren, Yongcheng; Wang, Bingyuan; Hu, Dongsheng

2014-01-25

Few genome-wide association studies have considered interactions between multiple genetic variants and environmental factors associated with disease. The interaction was examined between a glucagon gene (GCG) polymorphism and smoking, alcohol consumption and physical activity and the association with risk of type 2 diabetes mellitus (T2DM) in a case-control study of Chinese Han subjects. The rs12104705 polymorphism of GCG and interactions with environmental variables were analyzed for 9619 participants by binary multiple logistic regression. Smoking with the C-C haplotype of rs12104705 was associated with increased risk of T2DM (OR=1.174, 95% CI=1.013-1.361). Moderate and high physical activity with the C-C genotype was associated with decreased risk of T2DM as compared with low physical activity with the genotype (OR=0.251, 95% CI=0.206-0.306 and OR=0.190, 95% CI=0.164-0.220). However, the interaction of drinking and genotype was not associated with risk of T2DM. Genetic polymorphism in rs12104705 of GCG may interact with smoking and physical activity to modify the risk of T2DM. © 2013.

Early social-communicative and cognitive development of younger siblings of children with autism spectrum disorders.

PubMed

Stone, Wendy L; McMahon, Caitlin R; Yoder, Paul J; Walden, Tedra A

2007-04-01

To compare the early social-communicative development of younger siblings of children with autism spectrum disorders (ASDs) with that of younger siblings of children with typical development, using parental report and child-based measures. Group comparison. Vanderbilt University, between July 1, 2003, and July 31, 2006. Younger siblings of children with ASD (n = 64) and younger siblings of children with typical development (n = 42) between the ages of 12 and 23 months (mean, 16 months). Main Exposure Having a sibling with an ASD. Child-based measures included a cognitive assessment; an interactive screening tool assessing play, imitation, and communication; and a rating of autism symptoms. Parental report measures were an interview of social-communicative interactions and a questionnaire assessing language and communication skills. Younger siblings of children with ASD demonstrated weaker performance in nonverbal problem solving (mean difference [MD], 5.91; 95% confidence interval [CI], 2.48-9.34), directing attention (MD, 0.52; 95% CI, 0.07-0.97), understanding words (MD, 33.30; 95% CI, 3.11-63.48), understanding phrases (MD, 4.56; 95% CI, 1.85-7.27), gesture use (MD, 1.49; 95% CI, 0.51-2.47), and social-communicative interactions with parents (MD, 1.32; 95% CI, 0.27-2.37), and had increased autism symptoms (MD, 2.54; 95% CI, 1.05-4.03), relative to control siblings. A substantial minority of the ASD sibling group exhibited lower performance relative to controls. Significant correlations between child-based measures and parental reports assessing similar constructs were found (r = -0.74 to 0.53; P range, .000-.002). The weaker performance found for children in the ASD sibling group may represent early-emerging features of the broader autism phenotype, thus highlighting the importance of developmental surveillance for younger siblings.

Evaluation of the pharmacokinetic and pharmacodynamic drug interactions between cilnidipine and valsartan, in healthy volunteers

PubMed Central

Lee, Jieon; Lee, Howard; Jang, Kyungho; Lim, Kyoung Soo; Shin, Dongseong; Yu, Kyung-Sang

2014-01-01

Purpose Although cilnidipine and valsartan are widely coadministered to patients with hypertension, their drug–drug interaction potential has not been investigated. This study compared the pharmacokinetic (PK), pharmacodynamic (PD), and tolerability profiles of cilnidipine and valsartan, both alone and in combination, in healthy male subjects. Patients and methods Fifty-four subjects, enrolled into an open-label, single-dose, three-treatment, three-period crossover study, randomly received cilnidipine (10 mg), valsartan (160 mg), or both according to one of six sequences. Blood samples were collected at baseline and up to 24 hours after drug administration in each period. Plasma concentrations of cilnidipine and valsartan were determined by liquid chromatography with tandem mass spectrometry. Maximum plasma concentration (Cmax) and area under the concentration-time curve from 0 to the last measurable time (AUClast) were estimated using a noncompartmental method. Tolerability was evaluated by assessing adverse events (AEs), vital signs, electrocardiograms, and clinical laboratory tests. Blood pressure was also measured for PD assessment. Results A total of 51 subjects completed the study. The PK profile of cilnidipine was not significantly affected by coadministered valsartan; the geometric mean ratio and 90% confidence interval (90% CI) of AUClast for cilnidipine with and without valsartan was 1.04 (0.98–1.10). Likewise, cilnidipine did not affect the PK of valsartan; the geometric mean ratio (90% CI) of AUClast for valsartan with and without cilnidipine was 0.94 (0.83–1.07). Coadministration of cilnidipine and valsartan reduced blood pressure in an additive way. No serious AEs were reported, and both cilnidipine and valsartan were well tolerated. Conclusion Coadministered cilnidipine and valsartan do not cause a significant PK or PD interaction, and they are well tolerated. PMID:25336921

CARCINOGEN METABOLISM GENES, RED MEAT AND POULTRY INTAKE, AND COLORECTAL CANCER RISK

PubMed Central

Wang, Jun; Joshi, Amit D.; Corral, Román; Siegmund, Kimberly D.; Le Marchand, Loïc; Martinez, Maria Elena; Haile, Robert W.; Ahnen, Dennis J.; Sandler, Robert S.; Lance, Peter; Stern, Mariana C.

2011-01-01

Diets high in red meat are established risk factors for colorectal cancer (CRC). Carcinogenic compounds generated during meat cooking have been implicated as causal agents. We conducted a family-based case-control study to investigate the association between polymorphisms in carcinogen metabolism genes (CYP1A2 -154A>C, CYP1B1 Leu432Val, CYP2E1 -1054C>T, GSTP1 Ile105Val, PTGS2 5UTR -765, EPHX1 Tyr113His, NAT2 Ile114Thr, NAT2 Arg197Gln and NAT2 Gly286Glu) and CRC risk. We tested for gene-environment interactions using case-only analyses (N = 577) and compared statistically significant results to those obtained using case-unaffected sibling comparisons (N = 307 sibships). Our results suggested that CYP1A2 -154A>C might modify the association between intake of red meat cooked using high temperature methods and well done on the inside and CRC risk (case-only interaction OR = 1.53; 95% CI = 1.19-1.97; p = 0.0008) and the association between intake of red meat heavily browned on the outside and rectal cancer risk (case-only interaction OR = 0.65; 95% CI = 0.48-0.86; p = 0.003). We also found that GSTP1 Ile105Val might modify the association between intake of poultry cooked with high temperature methods and CRC risk (p = 0.0035), a finding that was stronger among rectal cancer cases. Our results support a role for heterocyclic amines that form in red meat as a potential explanation for the observed association between diets high in red meat and CRC. Our findings also suggest a possible role for diets high in poultry cooked at high temperatures in CRC risk. PMID:21618522

Magnesium for treatment of acute lacunar stroke syndromes: further analysis of the IMAGES trial.

PubMed

Aslanyan, Stella; Weir, Christopher J; Muir, Keith W; Lees, Kennedy R

2007-04-01

A prespecified interaction analysis of the neutral Intravenous Magnesium Efficacy in Stroke (IMAGES) trial revealed significant benefit from magnesium (Mg) in patients with noncortical stroke. Post hoc analysis indicated that this effect was seen in lacunar clinical syndromes (LACS), interaction P=0.005. We have now examined whether this interaction could be explained by confounding baseline factors. LACS was defined on the basis of neurological signs and did not include imaging. We investigated the interaction between baseline variables and Mg treatment on global outcome. We used logistic-regression models to test whether the Mg-LACS interaction remained significant after adjusting for stratification variables, sex, a novel stroke severity score, and baseline variables that had an interaction with treatment (P<0.1). The Mg (n=383) and placebo (n=382) groups of LACS patients were well matched on baseline factors. In addition to LACS, we found an interaction between beneficial Mg treatment effect and younger age (P=0.003), higher baseline diastolic blood pressure (P=0.02), higher mean blood pressure (P=0.02), and absence of ischemic heart disease (P=0.07). Even so, the adjusted Mg-LACS interaction remained significant (odds ratio [OR] 0.57; 95% CI, 0.39 to 0.83; P=0.003). In the LACS subgroup, Mg improved Barthel Index <95 (OR 0.73; 95% CI, 0.55 to 0.98), modified Rankin Scale >1 (OR 0.67; 95% CI, 0.50 to 0.91), and global outcome (OR 0.70; 95% CI, 0.53 to 0.92) but not Barthel Index <60 or mortality. The positive treatment effect of Mg in LACS cannot be ascribed to general issues of severity, time to treatment, blood pressure, or other baseline factors; equally, this finding may be due to chance. A large trial of Mg treatment in LACS appears justified.

Ginger phytochemicals exhibit synergy to inhibit prostate cancer cell proliferation

PubMed Central

Brahmbhatt, Meera; Gundala, Sushma R.; Asif, Ghazia; Shamsi, Shahab A; Aneja, Ritu

2014-01-01

Dietary phytochemicals offer non-toxic therapeutic management as well as chemopreventive intervention for slow-growing prostate cancers. However, the limited success of several single-agent clinical trials suggest a paradigm shift that the health benefits of fruits and vegetables are not ascribable due to individual phytochemicals rather may be ascribed to but to synergistic interactions among them. We recently reported growth-inhibiting and apoptosis-inducing properties of ginger extract (GE) in in vitro and in vivo prostate cancer models. Nevertheless, the nature of interactions among the constituent ginger biophenolics, viz. 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogoal, remains elusive. Here we show antiproliferative efficacy of the most-active GE biophenolics as single-agents and in binary combinations, and investigate the nature of their interactions using the Chou-Talalay combination-index (CI) method. Our data demonstrate that binary combinations of ginger phytochemicals synergistically inhibit proliferation of PC-3 cells with CI values ranging from 0.03-0.88. To appreciate synergy among phytochemicals present in GE, the natural abundance of ginger biophenolics was quantitated using LC-UV/MS. Interestingly, combining GE with its constituents (in particular, 6-gingerol) resulted in significant augmentation of GE’s antiproliferative activity. These data generate compelling grounds for further preclinical evaluation of GE alone and in combination with individual ginger biophenols for prostate cancer management. PMID:23441614

Maternal Malaria and Gravidity Interact to Modify Infant Susceptibility to Malaria

PubMed Central

Mutabingwa, Theonest K; Bolla, Melissa C; Li, Jin-Long; Domingo, Gonzalo J; Li, Xiaohong; Fried, Michal; Duffy, Patrick E

2005-01-01

Background In endemic areas, placental malaria due to Plasmodium falciparum is most frequent and severe in first-time mothers, and increases the risk of infant mortality in their offspring. Placental malaria may increase the susceptibility of infants to malaria parasitemia, but evidence for this effect is inconclusive. Methods and Findings During 2002–2004, we monitored parasitemia in 453 infants, including 69 who were born to mothers with placental malaria, in a region of northeastern Tanzania where malaria transmission is intense. We used a Cox proportional hazards model to evaluate the time from birth to first parasitemia, and a generalized estimating equations logistic regression model to evaluate risk of any parasitemia throughout the first year of life. Compared with infants whose mothers did not have placental malaria at delivery (“PM-negative”), offspring of mothers with placental malaria at delivery (“PM-positive”) were 41% more likely to experience their first parasitemia at a younger age (adjusted hazard ratio [AHR] = 1.41, 95% confidence interval [CI] 1.01–1.99). The odds of parasitemia throughout infancy were strongly modified by the interaction between placental malaria and gravidity (p for interaction = 0.008, Type 3 likelihood ratio test). Offspring of PM-negative primigravidae had lower odds of parasitemia during infancy (adjusted odds ratio [AOR] = 0.67, 95% CI 0.50–0.91) than offspring of PM-negative multigravidae, and offspring of PM-positive primigravidae had the lowest odds (AOR = 0.21, 95% CI 0.09–0.47). In contrast, offspring of PM-positive multigravidae had significantly higher odds of parasitemia (AOR = 1.59, 95% CI 1.16–2.17). Conclusion Although parasitemia is more frequent in primigravid than multigravid women, the converse is true in their offspring, especially in offspring of PM-positive women. While placental malaria is known to increase mortality risk for first-born infants, it surprisingly reduced their risk of parasitemia in this study. Placental malaria of multigravidae, on the other hand, is a strong risk factor for parasitemia during infancy, and therefore preventive antimalarial chemotherapy administered to multigravid women close to term may reduce the frequency of parasitemia in their offspring. PMID:16259531

HLA Class II Antigens and Their Interactive Effect on Perinatal Mother-To-Child HIV-1 Transmission

PubMed Central

Luo, Ma; Embree, Joanne; Ramdahin, Suzie; Bielawny, Thomas; Laycock, Tyler; Tuff, Jeffrey; Haber, Darren; Plummer, Mariel; Plummer, Francis A.

2015-01-01

HLA class II antigens are central in initiating antigen-specific CD4+ T cell responses to HIV-1. Specific alleles have been associated with differential responses to HIV-1 infection and disease among adults. This study aims to determine the influence of HLA class II genes and their interactive effect on mother-child perinatal transmission in a drug naïve, Mother-Child HIV transmission cohort established in Kenya, Africa in 1986. Our study showed that DRB concordance between mother and child increased risk of perinatal HIV transmission by three fold (P = 0.00035/Pc = 0.0014, OR: 3.09, 95%CI, 1.64-5.83). Whereas, DPA1, DPB1 and DQB1 concordance between mother and child had no significant influence on perinatal HIV transmission. In addition, stratified analysis showed that DRB1*15:03+ phenotype (mother or child) significantly increases the risk of perinatal HIV-1 transmission. Without DRB1*15:03, DRB1 discordance between mother and child provided 5 fold protection (P = 0.00008, OR: 0.186, 95%CI: 0.081-0.427). However, the protective effect of DRB discordance was diminished if either the mother or the child was DRB1*15:03+ phenotype (P = 0.49-0.98, OR: 0.7-0.99, 95%CI: 0.246-2.956). DRB3+ children were less likely to be infected perinatally (P = 0.0006, Pc = 0.014; OR:0.343, 95%CI:0.183-0.642). However, there is a 4 fold increase in risk of being infected at birth if DRB3+ children were born to DRB1*15:03+ mother compared to those with DRB1*15:03- mother. Our study showed that DRB concordance/discordance, DRB1*15:03, children’s DRB3 phenotype and their interactions play an important role in perinatal HIV transmission. Identification of genetic factors associated with protection or increased risk in perinatal transmission will help develop alternative prevention and treatment methods in the event of increases in drug resistance of ARV. PMID:25945792

Associations between breakfast frequency and adiposity indicators in children from 12 countries

PubMed Central

Zakrzewski, J K; Gillison, F B; Cumming, S; Church, T S; Katzmarzyk, P T; Broyles, S T; Champagne, C M; Chaput, J-P; Denstel, K D; Fogelholm, M; Hu, G; Kuriyan, R; Kurpad, A; Lambert, E V; Maher, C; Maia, J; Matsudo, V; Mire, E F; Olds, T; Onywera, V; Sarmiento, O L; Tremblay, M S; Tudor-Locke, C; Zhao, P; Standage, M

2015-01-01

OBJECTIVES: Reports of inverse associations between breakfast frequency and indices of obesity are predominantly based on samples of children from high-income countries with limited socioeconomic diversity. Using data from the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE), the present study examined associations between breakfast frequency and adiposity in a sample of 9–11-year-old children from 12 countries representing a wide range of geographic and socio-cultural variability. METHODS: Multilevel statistical models were used to examine associations between breakfast frequency (independent variable) and adiposity indicators (dependent variables: body mass index (BMI) z-score and body fat percentage (BF%)), adjusting for age, sex, and parental education in 6941 children from 12 ISCOLE study sites. Associations were also adjusted for moderate-to-vigorous physical activity, healthy and unhealthy dietary patterns and sleep time in a sub-sample (n=5710). Where interactions with site were significant, results were stratified by site. RESULTS: Adjusted mean BMI z-score and BF% for frequent breakfast consumers were 0.45 and 20.5%, respectively. Frequent breakfast consumption was associated with lower BMI z-scores compared with occasional (P<0.0001, 95% confidence intervals (CI): 0.10–0.29) and rare (P<0.0001, 95% CI: 0.18–0.46) consumption, as well as lower BF% compared with occasional (P<0.0001, 95% CI: 0.86–1.99) and rare (P<0.0001, 95% CI: 1.07–2.76). Associations with BMI z-score varied by site (breakfast by site interaction; P=0.033): associations were non-significant in three sites (Australia, Finland and Kenya), and occasional (not rare) consumption was associated with higher BMI z-scores compared with frequent consumption in three sites (Canada, Portugal and South Africa). Sub-sample analyses adjusting for additional covariates showed similar associations between breakfast and adiposity indicators, but lacked site interactions. CONCLUSIONS: In a multinational sample of children, more frequent breakfast consumption was associated with lower BMI z-scores and BF% compared with occasional and rare consumption. Associations were not consistent across all 12 countries. Further research is required to understand global differences in the observed associations. PMID:27152190

Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial

PubMed Central

Breithardt, Günter; Baumgartner, Helmut; Berkowitz, Scott D.; Hellkamp, Anne S.; Piccini, Jonathan P.; Stevens, Susanna R.; Lokhnygina, Yuliya; Patel, Manesh R.; Halperin, Jonathan L.; Singer, Daniel E.; Hankey, Graeme J.; Hacke, Werner; Becker, Richard C.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

2014-01-01

Aims We investigated clinical characteristics and outcomes of patients with significant valvular disease (SVD) in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial. Methods and results ROCKET AF excluded patients with mitral stenosis or artificial valve prostheses. We used Cox regression to adjust comparisons for potential confounders. Among 14 171 patients, 2003 (14.1%) had SVD; they were older and had more comorbidities than patients without SVD. The rate of stroke or systemic embolism with rivaroxaban vs. warfarin was consistent among patients with SVD [2.01 vs. 2.43%; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.55–1.27] and without SVD (1.96 vs. 2.22%; HR 0.89, 95% CI 0.75–1.07; interaction P = 0.76). However, rates of major and non-major clinically relevant bleeding with rivaroxaban vs. warfarin were higher in patients with SVD (19.8% rivaroxaban vs. 16.8% warfarin; HR 1.25, 95% CI 1.05–1.49) vs. those without (14.2% rivaroxaban vs. 14.1% warfarin; HR 1.01, 95% CI 0.94–1.10; interaction P = 0.034), even when controlling for risk factors and potential confounders. In intracranial haemorrhage, there was no interaction between patients with and without SVD where the overall rate was lower among those randomized to rivaroxaban. Conclusions Many patients with ‘non-valvular atrial fibrillation’ have significant valve lesions. Their risk of stroke is similar to that of patients without SVD after controlling for stroke risk factors. Efficacy of rivaroxaban vs. warfarin was similar in patients with and without SVD; however, the observed risk of bleeding was higher with rivaroxaban in patients with SVD but was the same among those without SVD. Atrial fibrillation patients with and without SVD experience the same stroke-preventive benefit of oral anticoagulants. PMID:25148838

A prospective study of common variants in the RAR-related orphan receptor alpha (RORalpha) gene and risk of neovascular age-related macular degeneration

PubMed Central

Schaumberg, Debra A.; Chasman, Daniel; Morrison, Margaux A.; Adams, Scott M.; Guo, Qun; Hunter, David J.; Hankinson, Susan E.; DeAngelis, Margaret M.

2010-01-01

Objectives The RAR-related orphan receptor alpha (RORalpha) gene is implicated as a candidate for age-related macular degeneration (AMD) through a previous microarray expression study, linkage data, biological plausibility, and two clinic-based cross sectional studies. We aimed to determine if common variants in RORalpha predict future risk of neovascular AMD. Methods We measured genotypes for 18 variants in intron 1 of the RORalpha gene among 164 cases who developed neovascular AMD and 485 age- and sex-matched controls in a prospective nested case-control study within the Nurses’ Health Study and the Health Professionals Follow-up Study. We determined the incidence rate ratios (IRR) and 95% confidence intervals (CI) for neovascular AMD for each variant, and examined interactions with other AMD-associated variants and modifiable risk factors. Results We identified a single SNP (rs12900948) that was significantly associated with increased incidence of neovascular AMD. Participants with one and two copies of the “G” allele were 1.73 (CI= 1.32–2.27) and 2.99 (CI=1.74–5.14) times more likely to develop neovascular AMD. Individuals homozygous for both the “G” allele of rs12900948 and ARMS2 A69S had a 40.8-fold increased risk of neovascular AMD (CI=10.1–164; P for interaction=0.017). Cigarette smokers who carried two copies of the “G” allele had a 9.89-fold risk of neovascular AMD, but the interaction was not significant (P=0.08). We identified a significant AMD-associated haplotype block containing SNPs rs730754, rs8034864, and rs12900948, with P-values for ACA=1.16 × 10−9, ACG=5.85 × 10−12, and GAA=0.0001 when compared to all other haplotypes. Conclusion Common variants and haplotypes within the RORalpha gene appear to act synergistically with the ARMS2 A69S polymorphism to increase risk of neovascular AMD. These data add further evidence of a high level of complexity linking genetic and modifiable risk factors to AMD development and should help efforts at risk prediction. PMID:21060049

Association of medical students' reports of interactions with the pharmaceutical and medical device industries and medical school policies and characteristics: a cross-sectional study.

PubMed

Yeh, James S; Austad, Kirsten E; Franklin, Jessica M; Chimonas, Susan; Campbell, Eric G; Avorn, Jerry; Kesselheim, Aaron S

2014-10-01

Professional societies use metrics to evaluate medical schools' policies regarding interactions of students and faculty with the pharmaceutical and medical device industries. We compared these metrics and determined which US medical schools' industry interaction policies were associated with student behaviors. Using survey responses from a national sample of 1,610 US medical students, we compared their reported industry interactions with their schools' American Medical Student Association (AMSA) PharmFree Scorecard and average Institute on Medicine as a Profession (IMAP) Conflicts of Interest Policy Database score. We used hierarchical logistic regression models to determine the association between policies and students' gift acceptance, interactions with marketing representatives, and perceived adequacy of faculty-industry separation. We adjusted for year in training, medical school size, and level of US National Institutes of Health (NIH) funding. We used LASSO regression models to identify specific policies associated with the outcomes. We found that IMAP and AMSA scores had similar median values (1.75 [interquartile range 1.50-2.00] versus 1.77 [1.50-2.18], adjusted to compare scores on the same scale). Scores on AMSA and IMAP shared policy dimensions were not closely correlated (gift policies, r = 0.28, 95% CI 0.11-0.44; marketing representative access policies, r = 0.51, 95% CI 0.36-0.63). Students from schools with the most stringent industry interaction policies were less likely to report receiving gifts (AMSA score, odds ratio [OR]: 0.37, 95% CI 0.19-0.72; IMAP score, OR 0.45, 95% CI 0.19-1.04) and less likely to interact with marketing representatives (AMSA score, OR 0.33, 95% CI 0.15-0.69; IMAP score, OR 0.37, 95% CI 0.14-0.95) than students from schools with the lowest ranked policy scores. The association became nonsignificant when fully adjusted for NIH funding level, whereas adjusting for year of education, size of school, and publicly versus privately funded school did not alter the association. Policies limiting gifts, meals, and speaking bureaus were associated with students reporting having not received gifts and having not interacted with marketing representatives. Policy dimensions reflecting the regulation of industry involvement in educational activities (e.g., continuing medical education, travel compensation, and scholarships) were associated with perceived separation between faculty and industry. The study is limited by potential for recall bias and the cross-sectional nature of the survey, as school curricula and industry interaction policies may have changed since the time of the survey administration and study analysis. As medical schools review policies regulating medical students' industry interactions, limitations on receipt of gifts and meals and participation of faculty in speaking bureaus should be emphasized, and policy makers should pay greater attention to less research-intensive institutions. Please see later in the article for the Editors' Summary.

The FEM-R-Matrix Approach: Use of Mixed Finite Element and Gaussian Basis Sets for Electron Molecule Collisions

NASA Technical Reports Server (NTRS)

Thuemmel, Helmar T.; Huo, Winifred M.; Langhoff, Stephen R. (Technical Monitor)

1995-01-01

For the calculation of electron molecule collision cross sections R-matrix methods automatically take advantage of the division of configuration space into an inner region (I) bounded by radius tau b, where the scattered electron is within the molecular charge cloud and the system is described by an correlated Configuration Interaction (CI) treatment in close analogy to bound state calculations, and an outer region (II) where the scattered electron moves in the long-range multipole potential of the target and efficient analytic methods can be used for solving the asymptotic Schroedinger equation plus boundary conditions.

Factors limiting vocal-tract length discrimination in cochlear implant simulations.

PubMed

Gaudrain, Etienne; Başkent, Deniz

2015-03-01

Perception of voice characteristics allows normal hearing listeners to identify the gender of a speaker, and to better segregate speakers from each other in cocktail party situations. This benefit is largely driven by the perception of two vocal characteristics of the speaker: The fundamental frequency (F0) and the vocal-tract length (VTL). Previous studies have suggested that cochlear implant (CI) users have difficulties in perceiving these cues. The aim of the present study was to investigate possible causes for limited sensitivity to VTL differences in CI users. Different acoustic simulations of CI stimulation were implemented to characterize the role of spectral resolution on VTL, both in terms of number of channels and amount of channel interaction. The results indicate that with 12 channels, channel interaction caused by current spread is likely to prevent CI users from perceiving VTL differences typically found between male and female speakers.

The Combined Effect of Long Working Hours and Low Job Control on Self-Rated Health: An Interaction Analysis.

PubMed

Cho, Seong-Sik; Ju, Young-Su; Paek, Domyung; Kim, Hyunjoo; Jung-Choi, Kyunghee

2018-05-01

The aim of this study was to investigate the combined effects of long working hours and low job control on self-rated health. We analyzed employees' data obtained from the third Korean Working Conditions Survey (KWCS). Multiple survey logistic analysis and postestimation commands were employed to estimate the relative excess risk due to interaction (RERI). The odds ratio (OR) for poor self-rated health was 1.24 [95% confidence interval (95% CI): 1.13 to 1.35] for long working hours, 1.04 (95% CI: 0.97 to 1.13) for low job control, and 1.47 (95% CI: 1.33 to 1.62) for both long working hours and low job control. The RERI was 0.18 (95% CI: 0.02 to 0.34). These results imply that low job control may increase the negative influence of long working hours on self-rated health.

Marital status, labour force activity and mortality: A study of the United States and 6 European countries

PubMed Central

van Hedel, Karen; van Lenthe, Frank J; Avendano, Mauricio; Bopp, Matthias; Esnaola, Santiago; Kovács, Katalin; Martikainen, Pekka; Regidor, Enrique; Mackenbach, Johan P

2015-01-01

Aims Labour force activity and marriage share some of the pathways through which they potentially influence health. In this paper, we examine whether marriage and labour force participation interact in the way they influence mortality in the United States and six European countries. Methods We used data from the US National Health Interview Survey linked to the National Death Index, and national mortality registry data for Austria, England/Wales, Finland, Hungary, Norway and Spain (Basque country) during 1999-2007 for men and women aged 30-59 at baseline. Poisson regression was used to estimate both additive (the relative excess risk due to interaction) and multiplicative interactions between marriage and labour force activity on mortality. Results Labour force inactivity was associated with higher mortality, but this association was stronger for unmarried than married individuals. Likewise, being unmarried was associated with higher mortality, but this association was stronger for inactive than for active individuals. To illustrate, among US women out of the labour force, being unmarried was associated with a 3.98 (95%CI:3.28-4.82) times higher risk of dying than being married, whereas the relative risk was 2.49 (95%CI:2.10-2.94) for women active in the labour market. Although this interaction between marriage and labour force activity was only significant for women on a multiplicative scale, there was a significant additive interaction for both men and women. The pattern was similar across all countries. Conclusions Marriage attenuates the increased mortality risk associated with labour force inactivity, while labour force activity attenuates the mortality risk associated with being unmarried. Our study emphasizes the importance of public health and social policies that improve the health and well-being of men and women who are both unmarried and inactive. PMID:25868643

Quantitative model for the blood pressure‐lowering interaction of valsartan and amlodipine

PubMed Central

Heo, Young‐A; Holford, Nick; Kim, Yukyung; Son, Mijeong

2016-01-01

Aims The objective of this study was to develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model to quantitatively describe the antihypertensive effect of combined therapy with amlodipine and valsartan. Methods PK modelling was used with data collected from 48 healthy volunteers receiving a single dose of combined formulation of 10 mg amlodipine and 160 mg valsartan. Systolic (SBP) and diastolic blood pressure (DBP) were recorded during combined administration. SBP and DBP data for each drug alone were gathered from the literature. PKPD models of each drug and for combined administration were built with NONMEM 7.3. Results A two‐compartment model with zero order absorption best described the PK data of both drugs. Amlodipine and valsartan monotherapy effects on SBP and DBP were best described by an I max model with an effect compartment delay. Combined therapy was described using a proportional interaction term as follows: (D1 + D2) +ALPHA×(D1 × D2). D1 and D2 are the predicted drug effects of amlodipine and valsartan monotherapy respectively. ALPHA is the interaction term for combined therapy. Quantitative estimates of ALPHA were −0.171 (95% CI: −0.218, −0.143) for SBP and −0.0312 (95% CI: −0.07739, −0.00283) for DBP. These infra‐additive interaction terms for both SBP and DBP were consistent with literature results for combined administration of drugs in these classes. Conclusion PKPD models for SBP and DBP successfully described the time course of the antihypertensive effects of amlodipine and valsartan. An infra‐additive interaction between amlodipine and valsartan when used in combined administration was confirmed and quantified. PMID:27504853

Comparison of Combined Aerobic and High-Force Eccentric Resistance Exercise With Aerobic Exercise Only for People With Type 2 Diabetes Mellitus

PubMed Central

Marcus, Robin L; Smith, Sheldon; Morrell, Glen; Addison, Odessa; Dibble, Leland E; Wahoff-Stice, Donna; LaStayo, Paul C

2008-01-01

Background and Purpose: The purpose of this study was to compare the outcomes between a diabetes exercise training program using combined aerobic and high-force eccentric resistance exercise and a program of aerobic exercise only. Subjects and Methods: Fifteen participants with type 2 diabetes mellitus (T2DM) participated in a 16-week supervised exercise training program: 7 (mean age=50.7 years, SD=6.9) in a combined aerobic and eccentric resistance exercise program (AE/RE group) and 8 (mean age=58.5 years, SD=6.2) in a program of aerobic exercise only (AE group). Outcome measures included thigh lean tissue and intramuscular fat (IMF), glycosylated hemoglobin, body mass index (BMI), and 6-minute walk distance. Results: Both groups experienced decreases in mean glycosylated hemoglobin after training (AE/RE group: −0.59% [95% confidence interval (CI)=−1.5 to 0.28]; AE group: −0.31% [95% CI=−0.60 to −0.03]), with no significant between-group differences. There was an interaction between group and time with respect to change in thigh lean tissue cross-sectional area, with the AE/RE group gaining more lean tissue (AE/RE group: 15.1 cm2 [95% CI=7.6 to 22.5]; AE group: −5.6 cm2 [95% CI=−10.4 to 0.76]). Both groups experienced decreases in mean thigh IMF cross-sectional area (AE/RE group: −1.2 cm2 [95% CI=−2.6 to 0.26]; AE group: −2.2 cm2 [95% CI=−3.5 to −0.84]) and increases in 6-minute walk distance (AE/RE group: 45.5 m [95% CI=7.5 to 83.6]; AE group: 29.9 m [95% CI=−7.7 to 67.5]) after training, with no between-group differences. There was an interaction between group and time with respect to change in BMI, with the AE/RE group experiencing a greater decrease in BMI. Discussion and Conclusion: Significant improvements in long-term glycemic control, thigh composition, and physical performance were demonstrated in both groups after participating in a 16-week exercise program. Subjects in the AE/RE group demonstrated additional improvements in thigh lean tissue and BMI. Improvements in thigh lean tissue may be important in this population as a means to increase resting metabolic rate, protein reserve, exercise tolerance, and functional mobility. PMID:18801851

Psychological violence against pregnant women in a prenatal care cohort: rates and associated factors in São Luís, Brazil

PubMed Central

2014-01-01

Background Violence against pregnant women has been associated with gestational and perinatal disorders. Psychological violence is the type least investigated and its associated factors have been little studied. The present study was conducted in order to estimate prevalence rates and analyze the factors associated with exclusive and recurrent psychological violence in the municipality of São Luís, Brazil. Methods Data regarding 982 pregnant women, aged from 14 to 45 years, interviewed in 2010 and 2011 in a prenatal cohort were used. A self-applied questionnaire was used to screen for violence. Pregnant women submitted to physical and sexual violence were excluded from the analysis of factors associated with exclusive psychological violence. Prevalence ratios and 95% confidence intervals were estimated by a Poisson regression model with a hierarchical approach at three levels. At level 1 of the theoretical-conceptual model, we analyzed demographic and socioeconomic characteristics and variables that express gender inequalities; at level 2, we analyzed social support received by the women, and at level 3, the life experiences of the pregnant women. Results Prevalence rate of exclusive psychological violence was 41.6% and of recurrent violence was 32.6%. Exclusive psychological violence was associated with pregnant women’s age of 14 to 18 years (PR: 1.32 95% CI: 1.04 – 1.70), pregnant women’s schooling superior to that of her intimate partner (PR: 1.54 95% CI: 1.09 – 2.16), inadequate social affective support/positive social interaction (PR: 1.34 95% CI: 1.11 – 1.62), use of illicit drugs by the pregnant women (PR: 1.80 95% CI: 1.16 – 2.81) and having had six or more intimate partners in life (PR: 1.52 95% CI: 1.18 – 1.96). Recurrent exclusive psychological violence was associated with inadequate social affective support/positive social interaction (PR: 1.47 95% CI: 1.15 – 1.87), use of illicit drugs by the pregnant women (PR: 2,28 95% CI: 1,40 - 3,71) and having had six or more intimate partners in life (PR: 1.47 95% CI: 1.06 – 2.03). Conclusions Psychological violence was a common phenomenon in this population of pregnant women that was associated with gender inequalities, inadequate social support and illicit drug use and should be routinely investigated during prenatal visits at health care services. PMID:24521235

The low-lying electronic excitations in long polyenes: A PPP-MRD-CI study

NASA Astrophysics Data System (ADS)

Tavan, Paul; Schulten, Klaus

1986-12-01

A correct description of the electronic excitations in polyenes demands that electron correlation is accounted for correctly. Very large expansions are necessary including many-electron configurations with at least one, two, three, and four electrons promoted from the Hartree-Fock ground state. The enormous size of such expansions had prohibited accurate computations of the spectra for polyenes with more than ten π electrons. We present a multireference double excitation configuration interaction method (MRD-CI) which allows such computations for polyenes with up to 16 π electrons. We employ a Pariser-Parr-Pople (PPP) model Hamiltonian. For short polyenes with up to ten π electrons our calculations reproduce the excitation energies resulting from full-CI calculations. We extend our calculations to study the low-lying electronic excitations of the longer polyenes, in particular, the gap between the first optically forbidden and the first optically allowed excited singlet state. The size of this gap is shown to depend strongly on the degree of bond alternation and on the dielectric shielding of the Coulomb repulsion between the π electrons.

Pharmacokinetic Interactions between the Hormonal Emergency Contraception, Levonorgestrel (Plan B), and Efavirenz

PubMed Central

Carten, Monica L.; Kiser, Jennifer J.; Kwara, Awewura; Mawhinney, Samantha; Cu-Uvin, Susan

2012-01-01

Objectives. Compare the Plan B levonorgestrel (LNG) area under the concentration- time curve (AUC12) prior to and with efavirenz (EFV). Design. Prospective, open-label, single-arm, equivalence study. Methods. Healthy HIV-negative subjects underwent 12 hr intensive pharmacokinetic (PK) sampling following single dose LNG alone and after 14 days of EFV. Geometric means, Geometric Mean Ratios, and 90% confidence intervals (CI) are reported for PK Parameters. T-tests were utilized. Clinical parameters and liver function tests (LFTs) were assessed. Results. 24 women enrolled and 21 completed the study. With EFV, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) from 42.9 to 17.8 ng∗hr/mL, and maximum concentration (Cmax⁡) was reduced 41% (95% CI: 33%, 50%) from 8.4 to 4.6 ng/mL. LNG was well tolerated with no grade 3 or 4 treatment-related toxicities. Conclusions. EFV significantly reduced LNG exposures. Higher LNG doses may be required with EFV. These results reinforce the importance of effective contraception in women taking EFV. PMID:22536010

Caffeine Consumption and Risk of Breast Cancer in a Large Prospective Cohort of Women

PubMed Central

Ishitani, Ken; Lin, Jennifer; Manson, JoAnn E.; Buring, Julie E.; Zhang, Shumin M.

2008-01-01

Background Prospective data relating caffeine consumption to breast cancer risk are limited. We evaluated the association among women enrolled in a completed cancer prevention trial. Methods Detailed dietary information was obtained at baseline (1992–1995) among 38,432 women aged ≥45 years and free of cancer. During an average of 10 years of follow-up, we identified 1188 invasive breast cancer cases. Results Consumption of caffeine and caffeinated beverages and foods was not statistically significantly associated with overall risk of breast cancer. The multivariable relative risks (RRs) of breast cancer were 1.02 (95% confidence interval [CI], 0.84–1.22) for caffeine (top vs. bottom quintile), 1.08 (95% CI, 0.89–1.30) for coffee (≥4 cups/day vs. almost never), and 1.03 (95% CI, 0.85–1.25) for tea (≥2 cups/day vs. almost never). However, among women with benign breast disease, a borderline significant positive association with breast cancer risk was observed for the highest quintile of caffeine (RR = 1.32; 95% CI, 0.99–1.76) and for the highest category of coffee (≥4 cups/day) (RR = 1.35; 95% CI, 1.01–1.80); tests for interaction were marginally significant. Caffeine consumption was also significantly positively associated with risk of developing ER−PR−breast cancer (RR = 1.68; 95% CI, 1.01–2.81) and breast tumors of >2 cm in size (RR = 1.79; 95% CI, 1.18–2.72). Conclusions Data show no overall association between caffeine consumption and breast cancer risk. The possibility of an increased risk among women with benign breast disease or for tumors that are ER−PR− or greater than 2 cm in size warrants further study. PMID:18852405

Predictors of stroke recurrence in patients with recent lacunar stroke and response to interventions according to risk status: Secondary Prevention of Small Subcortical Strokes (SPS3) trial

PubMed Central

Hart, Robert G.; Pearce, Lesly A.; Bakheet, Majid F.; Benavente, Oscar; Conwit, Robin A.; McClure, Leslie A.; Talbert, Robert L.; Anderson, David C.

2013-01-01

Background Among participants in the Secondary Prevention of Small Subcortical Strokes randomized trial, we sought to identify patients with high vs. low rates of recurrent ischemic stroke and to assess effects of aggressive blood pressure control and dual antiplatelet therapy according to risk status. Methods Multivariable analyses of 3020 participants with recent MRI-defined lacunar strokes followed for a mean of 3.7 years with 243 recurrent ischemic strokes. Results: Prior symptomatic lacunar stroke or TIA (HR 2.2, 95%CI 1.6,2.9), diabetes (HR 2.0, 95%CI 1.5,2.5), Black race (HR 1.7, 95%CI 1.3,2.3) and male sex (HR 1.5, 95%CI 1.1,1.9) were each independently predictive of recurrent ischemic stroke. Recurrent ischemic stroke occurred at a rate of 4.3%/yr (95% CI 3.3, 5.5) in patients with prior symptomatic lacunar stroke or TIA (15% of the cohort), 3.1%/yr (95%CI 2.6, 3.9) in those with >1 of the other 3 risk factors (27% of the cohort), and 1.3%/yr (95%CI 1.0,1.7) in those with 0 to 1 risk factors (58% of the cohort). There were no significant interactions between treatment effects and stroke risk status. Conclusions In this large, carefully followed cohort of patients with recent lacunar stroke and aggressive blood pressure management, prior symptomatic lacunar ischemia, diabetes, Black race and male sex independently predicted ischemic stroke recurrence. The effects of blood pressure targets and dual antiplatelet therapy were similar across the spectrum of independent risk factors and recurrence risk. PMID:23800503

Multisensory emotion perception in congenitally, early, and late deaf CI users

PubMed Central

Nava, Elena; Villwock, Agnes K.; Büchner, Andreas; Lenarz, Thomas; Röder, Brigitte

2017-01-01

Emotions are commonly recognized by combining auditory and visual signals (i.e., vocal and facial expressions). Yet it is unknown whether the ability to link emotional signals across modalities depends on early experience with audio-visual stimuli. In the present study, we investigated the role of auditory experience at different stages of development for auditory, visual, and multisensory emotion recognition abilities in three groups of adolescent and adult cochlear implant (CI) users. CI users had a different deafness onset and were compared to three groups of age- and gender-matched hearing control participants. We hypothesized that congenitally deaf (CD) but not early deaf (ED) and late deaf (LD) CI users would show reduced multisensory interactions and a higher visual dominance in emotion perception than their hearing controls. The CD (n = 7), ED (deafness onset: <3 years of age; n = 7), and LD (deafness onset: >3 years; n = 13) CI users and the control participants performed an emotion recognition task with auditory, visual, and audio-visual emotionally congruent and incongruent nonsense speech stimuli. In different blocks, participants judged either the vocal (Voice task) or the facial expressions (Face task). In the Voice task, all three CI groups performed overall less efficiently than their respective controls and experienced higher interference from incongruent facial information. Furthermore, the ED CI users benefitted more than their controls from congruent faces and the CD CI users showed an analogous trend. In the Face task, recognition efficiency of the CI users and controls did not differ. Our results suggest that CI users acquire multisensory interactions to some degree, even after congenital deafness. When judging affective prosody they appear impaired and more strongly biased by concurrent facial information than typically hearing individuals. We speculate that limitations inherent to the CI contribute to these group differences. PMID:29023525

Multisensory emotion perception in congenitally, early, and late deaf CI users.

PubMed

Fengler, Ineke; Nava, Elena; Villwock, Agnes K; Büchner, Andreas; Lenarz, Thomas; Röder, Brigitte

2017-01-01

Emotions are commonly recognized by combining auditory and visual signals (i.e., vocal and facial expressions). Yet it is unknown whether the ability to link emotional signals across modalities depends on early experience with audio-visual stimuli. In the present study, we investigated the role of auditory experience at different stages of development for auditory, visual, and multisensory emotion recognition abilities in three groups of adolescent and adult cochlear implant (CI) users. CI users had a different deafness onset and were compared to three groups of age- and gender-matched hearing control participants. We hypothesized that congenitally deaf (CD) but not early deaf (ED) and late deaf (LD) CI users would show reduced multisensory interactions and a higher visual dominance in emotion perception than their hearing controls. The CD (n = 7), ED (deafness onset: <3 years of age; n = 7), and LD (deafness onset: >3 years; n = 13) CI users and the control participants performed an emotion recognition task with auditory, visual, and audio-visual emotionally congruent and incongruent nonsense speech stimuli. In different blocks, participants judged either the vocal (Voice task) or the facial expressions (Face task). In the Voice task, all three CI groups performed overall less efficiently than their respective controls and experienced higher interference from incongruent facial information. Furthermore, the ED CI users benefitted more than their controls from congruent faces and the CD CI users showed an analogous trend. In the Face task, recognition efficiency of the CI users and controls did not differ. Our results suggest that CI users acquire multisensory interactions to some degree, even after congenital deafness. When judging affective prosody they appear impaired and more strongly biased by concurrent facial information than typically hearing individuals. We speculate that limitations inherent to the CI contribute to these group differences.

[Implication of inverse-probability weighting method in the evaluation of diagnostic test with verification bias].

PubMed

Kang, Leni; Zhang, Shaokai; Zhao, Fanghui; Qiao, Youlin

2014-03-01

To evaluate and adjust the verification bias existed in the screening or diagnostic tests. Inverse-probability weighting method was used to adjust the sensitivity and specificity of the diagnostic tests, with an example of cervical cancer screening used to introduce the Compare Tests package in R software which could be implemented. Sensitivity and specificity calculated from the traditional method and maximum likelihood estimation method were compared to the results from Inverse-probability weighting method in the random-sampled example. The true sensitivity and specificity of the HPV self-sampling test were 83.53% (95%CI:74.23-89.93)and 85.86% (95%CI: 84.23-87.36). In the analysis of data with randomly missing verification by gold standard, the sensitivity and specificity calculated by traditional method were 90.48% (95%CI:80.74-95.56)and 71.96% (95%CI:68.71-75.00), respectively. The adjusted sensitivity and specificity under the use of Inverse-probability weighting method were 82.25% (95% CI:63.11-92.62) and 85.80% (95% CI: 85.09-86.47), respectively, whereas they were 80.13% (95%CI:66.81-93.46)and 85.80% (95%CI: 84.20-87.41) under the maximum likelihood estimation method. The inverse-probability weighting method could effectively adjust the sensitivity and specificity of a diagnostic test when verification bias existed, especially when complex sampling appeared.

Comparison of Interaural Electrode Pairing Methods for Bilateral Cochlear Implants

PubMed Central

Dietz, Mathias

2015-01-01

In patients with bilateral cochlear implants (CIs), pairing matched interaural electrodes and stimulating them with the same frequency band is expected to facilitate binaural functions such as binaural fusion, localization, and spatial release from masking. Because clinical procedures typically do not include patient-specific interaural electrode pairing, it remains the case that each electrode is allocated to a generic frequency range, based simply on the electrode number. Two psychoacoustic techniques for determining interaurally paired electrodes have been demonstrated in several studies: interaural pitch comparison and interaural time difference (ITD) sensitivity. However, these two methods are rarely, if ever, compared directly. A third, more objective method is to assess the amplitude of the binaural interaction component (BIC) derived from electrically evoked auditory brainstem responses for different electrode pairings; a method has been demonstrated to be a potential candidate for bilateral CI users. Here, we tested all three measures in the same eight CI users. We found good correspondence between the electrode pair producing the largest BIC and the electrode pair producing the maximum ITD sensitivity. The correspondence between the pairs producing the largest BIC and the pitch-matched electrode pairs was considerably weaker, supporting the previously proposed hypothesis that whilst place pitch might adapt over time to accommodate mismatched inputs, sensitivity to ITDs does not adapt to the same degree. PMID:26631108

Adsorption of C.I. Natural Red 4 onto Spongin Skeleton of Marine Demosponge

PubMed Central

Norman, Małgorzata; Bartczak, Przemysław; Zdarta, Jakub; Tylus, Włodzimierz; Szatkowski, Tomasz; Stelling, Allison L.; Ehrlich, Hermann; Jesionowski, Teofil

2014-01-01

C.I. Natural Red 4 dye, also known as carmine or cochineal, was adsorbed onto the surface of spongin-based fibrous skeleton of Hippospongia communis marine demosponge for the first time. The influence of the initial concentration of dye, the contact time, and the pH of the solution on the adsorption process was investigated. The results presented here confirm the effectiveness of the proposed method for developing a novel dye/biopolymer hybrid material. The kinetics of the adsorption of carmine onto a marine sponge were also determined. The experimental data correspond directly to a pseudo-second-order model for adsorption kinetics (r2 = 0.979–0.999). The hybrid product was subjected to various types of analysis (FT-IR, Raman, 13C CP/MAS NMR, XPS) to investigate the nature of the interactions between the spongin (adsorbent) and the dye (the adsorbate). The dominant interactions between the dye and spongin were found to be hydrogen bonds and electrostatic effects. Combining the dye with a spongin support resulted with a novel hybrid material that is potentially attractive for bioactive applications and drug delivery systems. PMID:28787926

Suicide and accidental deaths in children and adolescents in England and Wales, 2001-2010.

PubMed

Windfuhr, Kirsten; While, David; Hunt, Isabelle M; Shaw, Jenny; Appleby, Louis; Kapur, Nav

2013-12-01

To investigate the impact of narrative verdicts on suicide statistics among 10-19-year-olds; to identify the number and rate of suicide and accidental deaths, particularly in 10-14-year-olds. National cohort study. England and Wales. Mid-year population estimates from the Office for National Statistics (ONS) were used to calculate rates per 100,000 population for suicide (undetermined and suicide verdicts) and accidental deaths (poisoning, hanging) for those aged 10-14 and 15-19. Trends in rates over time (2001-2010) were investigated using Poisson regression. Interaction tests were carried out to determine differences in trends between the two time periods (2001-2005 and 2006-2010). There were 1523 suicides (2.25/100,000). Suicide rates were highest in those aged 15-19 years (4.04/100,000) and in males (3.14/100,000). Between 2001 and 2010, rates significantly decreased among those aged 15-19 years (incidence rate-ratio (IRR): 0.95; 95% CI 0.93 to 0.97), with no change in rates of accidental deaths (IRR: 1.01, 95% CI 0.95 to 1.07). However, there was a significant interaction between the two time periods for accidental poisonings (2001-2005: IRR: 0.79 (95% CI 0.69 to 0.91); 2006-2010: IRR: 1.01 (95% CI 0.89 to 1.15), interaction p=0.012) and accidental hangings (2001-2005: IRR: 0.93 (95% CI 0.76 to 1.14); 2006-2010: IRR: 1.25 (95% CI 1.04 to 1.49), interaction=0.01) Undetermined deaths significantly decreased among females aged 15-19 yeras (IRR: 0.93; 95% CI 0.88 to 0.98). There were no significant trends among 10-14-year-olds. Rates of suicide are higher among older adolescents and males. There was a significant fall in suicide rates in males aged 15-19 years that was not accounted for by changes in rates of accidental death. The absence of a significant trend in suicide or accidental deaths in those aged 10-14 years may have been the result of small numbers. However, monitoring should continue to identify longitudinal trends in all young people.

Educational Level, Underachievement, and General Mental Health Problems in 10,866 Adolescents.

PubMed

Tempelaar, Wanda M; de Vos, Nelleke; Plevier, Carolien M; van Gastel, Willemijn A; Termorshuizen, Fabian; MacCabe, James H; Boks, Marco P M

2017-08-01

Previous research suggests that cognitive functioning is associated with the risk of several adult psychiatric disorders. In this study we investigated whether adolescents who perform worse than expected at secondary school are at a higher risk for general mental health problems. In a cross-sectional survey comprising 10,866 Dutch adolescents aged 13 to 16 years, underachievement at secondary school was defined as the discrepancy between predicted school grade and actual grade 1 or 3 years later. Mental health problems were assessed using the Strengths and Difficulties Questionnaire. We investigated the association of underachievement with mental health problems using logistic regression, adjusting for potential confounders. Underachievement was associated with general psychopathology in pupils aged 13 to 14 years (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.47-2.37) and in pupils aged 15 to 16 years (OR, 2.05; 95% CI, 1.67-2.52) in a multivariate analysis including sociodemographic factors. The association between underachievement and mental health problems was attenuated when school factors such as teacher advice and interaction between underachievement and teacher advice were added, but underachievement remained significantly associated with mental health problems in adolescents in the higher educational tracks (pupils aged 13-14 years: OR, 2.22; 95% CI, 1.07-4.60 and OR, 2.41; 95% CI, 1.10-5.30, age 15-16 years: OR, 2.63; 95% CI, 1.38-5.03). In the multivariate analysis including the interaction between underachievement and teacher advice, a significant interaction effect occurs between underachievement and teacher advice in the higher tracks. Values of OR and CI are given for each significant interaction term. In the younger age group (pupils aged 13-14 years) this results in 2 sets of OR and CI. This association was most pronounced for the hyperactivity subscale of the Strengths and Difficulties Questionnaire. Underachievement at secondary school is associated with general mental health problems, especially with hyperactivity symptoms, in pupils who started at high educational tracks. Copyright © 2017 Academic Pediatric Association. All rights reserved.

The Comparative Efficacy of Lifestyle Intervention and Metformin by Educational Attainment in the Diabetes Prevention Program

PubMed Central

O’Brien, Matthew J.; Whitaker, Robert C.; Yu, Daohai; Ackermann, Ronald T.

2015-01-01

Objective Educational attainment is inversely associated with type 2 diabetes risk, but it is unknown whether education impacts individuals’ diabetes prevention efforts. We examined the comparative efficacy of intensive lifestyle intervention and metformin by educational attainment among participants in the Diabetes Prevention Program (DPP), an ongoing U.S. multi-site trial beginning in 1996. Methods We studied 2,910 DPP participants randomized to receive lifestyle intervention, metformin, or placebo. Stratifying by educational attainment, diabetes incidence and relative risk reductions by treatment assignment were estimated using Cox proportional hazards regression. Results 47% of participants had completed college and 53% had not. Compared to placebo, lifestyle participants who had completed college demonstrated a 68% reduction in diabetes incidence (95% CI=56, 77), whereas those with less education experienced a 47% risk reduction (95% CI=29, 61). For metformin participants, college graduates experienced a 49% relative risk reduction (95% CI=33, 62), compared to 23% (95% CI=1, 41) among those with lower educational attainment. There was a statistically significant education-by-treatment interaction with incident diabetes (p=0.03). Conclusions Intensive lifestyle intervention and metformin have greater efficacy among highly educated individuals. Future efforts to deliver these treatments and study their dissemination may be more effective if tailored to individuals’ educational background. PMID:26024851

Case-only gene-environment interaction between ALAD tagSNPs and occupational lead exposure in prostate cancer.

PubMed

Neslund-Dudas, Christine; Levin, Albert M; Rundle, Andrew; Beebe-Dimmer, Jennifer; Bock, Cathryn H; Nock, Nora L; Jankowski, Michelle; Datta, Indrani; Krajenta, Richard; Dou, Q Ping; Mitra, Bharati; Tang, Deliang; Rybicki, Benjamin A

2014-05-01

Black men have historically had higher blood lead levels than white men in the U.S. and have the highest incidence of prostate cancer in the world. Inorganic lead has been classified as a probable human carcinogen. Lead (Pb) inhibits delta-aminolevulinic acid dehydratase (ALAD), a gene recently implicated in other genitourinary cancers. The ALAD enzyme is involved in the second step of heme biosynthesis and is an endogenous inhibitor of the 26S proteasome, a master system for protein degradation and a current target of cancer therapy. Using a case-only study design, we assessed potential gene-environment (G × E) interactions between lifetime occupational Pb exposure and 11 tagSNPs within ALAD in black (N = 260) and white (N = 343) prostate cancer cases. Two ALAD tagSNPs in high linkage disequilibrium showed significant interaction with high Pb exposure among black cases (rs818684 interaction odds ratio or IOR = 2.73, 95% CI 1.43-5.22, P = 0.002; rs818689 IOR = 2.20, 95% CI 1.15-4.21, P = 0.017) and an additional tagSNP, rs2761016, showed G × E interaction with low Pb exposure (IOR = 2.08, 95% CI 1.13-3.84, P = 0.019). Further, the variant allele of rs818684 was associated with a higher Gleason grade in those with high Pb exposure among both blacks (OR 3.96, 95% CI 1.01-15.46, P = 0.048) and whites (OR 2.95, 95% CI 1.18-7.39, P = 0.020). Genetic variation in ALAD may modify associations between Pb and prostate cancer. Additional studies of ALAD, Pb, and prostate cancer are warranted and should include black men. Prostate 74:637-646, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Associations of cigarette smoking with rheumatoid arthritis in African Americans

PubMed Central

Mikuls, Ted R.; Sayles, Harlan; Yu, Fang; LeVan, Tricia; Gould, Karen A.; Thiele, Geoffrey M.; Conn, Doyt; Jonas, Beth L.; Callahan, Leigh F.; Smith, Edwin; Brasington, Richard; Moreland, Larry W.; Reynolds, Richard; Bridges, S. Louis

2010-01-01

Objective To examine the associations of cigarette smoking with rheumatoid arthritis (RA) in African Americans and to determine to whether this association is impacted by HLA-DRB1 shared epitope (SE). Methods Smoking status, cumulative smoking exposure, and SE status were measured in African American patients with RA and in healthy controls. Associations of smoking with RA were examined using age- and gender-adjusted logistic regression. Additive and multiplicative SE-smoking interactions were examined. Results After adjusting for age and gender, ever (OR = 1.45; 95% CI 1.07 to 1.97) and current smoking (OR = 1.56; 95% CI 1.07 to 2.26) were more common in African American RA cases (n = 605) than in controls (n = 255). The association of smoking with RA was limited to those with a cumulative exposure exceeding 10 pack-years, associations that were evident in both autoantibody positive and negative disease. There was evidence of a significant additive interaction between SE status and heavy smoking (≥ 10 pack-years) in RA risk (attributable proportion due to interaction [AP] of 0.58, p = 0.007) with an AP of 0.47 (p = 0.006) between SE status and ever smoking. There was no evidence of multiplicative interactions. Conclusion Among African Americans, cigarette smoking is associated not only with the risk of autoantibody positive RA but also with the risk of autoantibody negative disease. RA risk attributable to smoking is limited to African Americans with more than 10 pack-years of exposure and is more pronounced among individuals positive for HLA-DRB1 SE. PMID:20722010

Calculations of the excitation energies of all-trans and 11,12s-dicis retinals using localized molecular orbitals obtained by the elongation method

NASA Astrophysics Data System (ADS)

Kurihara, Youji; Aoki, Yuriko; Imamura, Akira

1997-09-01

In the present article, the excitation energies of the all-trans and the 11,12s-dicis retinals were calculated by using the elongation method. The geometries of these molecules were optimized with the 4-31G basis set by using the GAUSSIAN 92 program. The wave functions for the calculation of the excitation energies were obtained with CNDO/S approximation by the elongation method, which enables us to analyze electronic structures of aperiodic polymers in terms of the exciton-type local excitation and the charge transfer-type excitation. The excitation energies were calculated by using the single excitation configuration interaction (SECI) on the basis of localized molecular orbitals (LMOs). The LMOs were obtained in the process of the elongation method. The configuration interaction (CI) matrices were diagonalized by Davidson's method. The calculated results were in good agreement with the experimental data for absorption spectra. In order to consider the isomerization path from 11,12s-dicis to all-trans retinals, the barriers to the rotations about C11-C12 double and C12-C13 single bonds were evaluated.

A Smartphone Application for Customized Frequency Table Selection in Cochlear Implants.

PubMed

Jethanamest, Daniel; Azadpour, Mahan; Zeman, Annette M; Sagi, Elad; Svirsky, Mario A

2017-09-01

A novel smartphone-based software application can facilitate self-selection of frequency allocation tables (FAT) in postlingually deaf cochlear implant (CI) users. CIs use FATs to represent the tonotopic organization of a normal cochlea. Current CI fitting methods typically use a standard FAT for all patients regardless of individual differences in cochlear size and electrode location. In postlingually deaf patients, different amounts of mismatch can result between the frequency-place function they experienced when they had normal hearing and the frequency-place function that results from the standard FAT. For some CI users, an alternative FAT may enhance sound quality or speech perception. Currently, no widely available tools exist to aid real-time selection of different FATs. This study aims to develop a new smartphone tool for this purpose and to evaluate speech perception and sound quality measures in a pilot study of CI subjects using this application. A smartphone application for a widely available mobile platform (iOS) was developed to serve as a preprocessor of auditory input to a clinical CI speech processor and enable interactive real-time selection of FATs. The application's output was validated by measuring electrodograms for various inputs. A pilot study was conducted in six CI subjects. Speech perception was evaluated using word recognition tests. All subjects successfully used the portable application with their clinical speech processors to experience different FATs while listening to running speech. The users were all able to select one table that they judged provided the best sound quality. All subjects chose a FAT different from the standard FAT in their everyday clinical processor. Using the smartphone application, the mean consonant-nucleus-consonant score with the default FAT selection was 28.5% (SD 16.8) and 29.5% (SD 16.4) when using a self-selected FAT. A portable smartphone application enables CI users to self-select frequency allocation tables in real time. Even though the self-selected FATs that were deemed to have better sound quality were only tested acutely (i.e., without long-term experience with them), speech perception scores were not inferior to those obtained with the clinical FATs. This software application may be a valuable tool for improving future methods of CI fitting.

Assessment of pharmacokinetic interaction between piracetam and l-carnitine in healthy subjects.

PubMed

Mendes, Gustavo D; Zaffalon, Gabriela Traldi; Silveira, Antonio Sérgio; Ramacciato, Juliana Cama; Motta, Rogério Heládio Lopes; Gagliano-Jucá, Thiago; Lopes, Anibal Gil; de Almeida Magalhães, José Cássio; De Nucci, Gilberto

2016-04-01

A rapid, sensitive and specific method for quantifying piracetam in human plasma using Piracetam d-8 as the internal standard (IS) is described. The analyte and the IS were extracted from plasma by one-step precipitation of protein using an acetonitrile (100%). The extracts were analyzed by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/MS). The method had a chromatographic run time of 3.8 min and a linear calibration curve over the range 0.5-50 µg/mL (r > 0.99). This LC-MS-MS procedure was used to assess the bioavailability of two piracetam formulations: piracetam + l-carnitine (Piracar®; 270/330 mg tablet) and piracetam (Nootropil®; 800 mg tablet) in healthy volunteers of both sexes. The geometric means with corresponding 90% confidence interval (CI) for test/reference percentage ratios were 88.49% (90% CI = 81.19 - 96.46) for peak concentration/dose and 102.55% (90% CI = 100.62 - 104.51) for AUCinf /dose. The limit of quantitation of 0.5 µg/mL is well suited for pharmacokinetic studies in healthy volunteers. It was concluded that piracetam (Piracar®; 270/330 mg tablet) has a bioavailability equivalent to the piracetam (Nootropil®; 800 mg tablet) formulation with regard to both the rate and the extent of absorption. Copyright © 2015 John Wiley & Sons, Ltd.

Gene–environment interactions involving functional variants: Results from the Breast Cancer Association Consortium

PubMed Central

Barrdahl, Myrto; Rudolph, Anja; Hopper, John L.; Southey, Melissa C.; Broeks, Annegien; Fasching, Peter A.; Beckmann, Matthias W.; Gago‐Dominguez, Manuela; Castelao, J. Esteban; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E.; Gapstur, Susan M.; Gaudet, Mia M.; Brenner, Hermann; Arndt, Volker; Brauch, Hiltrud; Hamann, Ute; Mannermaa, Arto; Lambrechts, Diether; Jongen, Lynn; Flesch‐Janys, Dieter; Thoene, Kathrin; Couch, Fergus J.; Giles, Graham G.; Simard, Jacques; Goldberg, Mark S.; Figueroa, Jonine; Michailidou, Kyriaki; Bolla, Manjeet K.; Dennis, Joe; Wang, Qin; Eilber, Ursula; Behrens, Sabine; Czene, Kamila; Hall, Per; Cox, Angela; Cross, Simon; Swerdlow, Anthony; Schoemaker, Minouk J.; Dunning, Alison M.; Kaaks, Rudolf; Pharoah, Paul D.P.; Schmidt, Marjanka; Garcia‐Closas, Montserrat; Easton, Douglas F.; Milne, Roger L.

2017-01-01

Investigating the most likely causal variants identified by fine‐mapping analyses may improve the power to detect gene–environment interactions. We assessed the interplay between 70 single nucleotide polymorphisms identified by genetic fine‐scale mapping of susceptibility loci and 11 epidemiological breast cancer risk factors in relation to breast cancer. Analyses were conducted on up to 58,573 subjects (26,968 cases and 31,605 controls) from the Breast Cancer Association Consortium, in one of the largest studies of its kind. Analyses were carried out separately for estrogen receptor (ER) positive (ER+) and ER negative (ER–) disease. The Bayesian False Discovery Probability (BFDP) was computed to assess the noteworthiness of the results. Four potential gene–environment interactions were identified as noteworthy (BFDP < 0.80) when assuming a true prior interaction probability of 0.01. The strongest interaction result in relation to overall breast cancer risk was found between CFLAR‐rs7558475 and current smoking (ORint = 0.77, 95% CI: 0.67–0.88, p int = 1.8 × 10−4). The interaction with the strongest statistical evidence was found between 5q14‐rs7707921 and alcohol consumption (ORint =1.36, 95% CI: 1.16–1.59, p int = 1.9 × 10−5) in relation to ER– disease risk. The remaining two gene–environment interactions were also identified in relation to ER– breast cancer risk and were found between 3p21‐rs6796502 and age at menarche (ORint = 1.26, 95% CI: 1.12–1.43, p int =1.8 × 10−4) and between 8q23‐rs13267382 and age at first full‐term pregnancy (ORint = 0.89, 95% CI: 0.83–0.95, p int = 5.2 × 10−4). While these results do not suggest any strong gene–environment interactions, our results may still be useful to inform experimental studies. These may in turn, shed light on the potential interactions observed. PMID:28670784

Investigating the heterogeneity of alkylating agents' efficacy and toxicity between sexes: A systematic review and meta-analysis of randomized trials comparing cyclophosphamide and ifosfamide (MAIAGE study).

PubMed

Fresneau, Brice; Hackshaw, A; Hawkins, D S; Paulussen, M; Anderson, J R; Judson, I; Litière, S; Dirksen, U; Lewis, I; van den Berg, H; Gaspar, N; Gelderblom, H; Whelan, J; Boddy, A V; Wheatley, K; Pignon, J P; De Vathaire, F; Le Deley, M C; Le Teuff, G

2017-08-01

A marginal interaction between sex and the type of alkylating agent was observed for event-free survival in the Euro-EWING99-R1 randomized controlled trial (RCT) comparing cyclophosphamide and ifosfamide in Ewing sarcoma. To further evaluate this interaction, we performed an individual patient data meta-analysis of RCTs assessing cyclophosphamide versus ifosfamide in any type of cancer. A literature search produced two more eligible RCTs (EICESS92 and IRS-IV). The endpoints were progression-free survival (PFS, main endpoint) and overall survival (OS). The hazard ratios (HRs) of the treatment-by-sex interaction and their 95% confidence interval (95% CI) were assessed using stratified multivariable Cox models. Heterogeneity of the interaction across age categories and trials was explored. We also assessed this interaction for severe acute toxicity using logistic models. The meta-analysis comprised 1,528 pediatric and young adult sarcoma patients from three RCTs: Euro-EWING99-R1 (n = 856), EICESS92 (n = 155), and IRS-IV (n = 517). There were 224 PFS events in Euro-EWING99-R1 and 200 in the validation set (EICESS92 + IRS-IV), and 171 and 154 deaths in each dataset, respectively. The estimated treatment-by-sex interaction for PFS in Euro-EWING99-R1 (HR = 1.73, 95% CI = 1.00-3.00) was not replicated in the validation set (HR = 0.97, 95% CI = 0.55-1.72), without heterogeneity across trials (P = 0.62). In the pooled analysis, the treatment-by-sex interaction was not significant (HR = 1.31, 95% CI = 0.89-1.95, P = 0.17), without heterogeneity across age categories (P = 0.88) and trials (P = 0.36). Similar results were observed for OS. No significant treatment-by-sex interaction was observed for leucopenia/neutropenia (P = 0.45), infection (P = 0.64), or renal toxicity (P = 0.20). Our meta-analysis did not confirm the hypothesis of a treatment-by-sex interaction on efficacy or toxicity outcomes. © 2017 Wiley Periodicals, Inc.

Cooking methods and depressive symptoms are joint risk factors for fatigue among migrant Indonesian women working domestically in Taiwan.

PubMed

Palupi, Khairizka Citra; Shih, Chun-Kuang; Chang, Jung-Su

2017-06-01

Fatigue is a critical occupational health risk among migrant workers. Globally, more than half of migrant workers are women. However, the prevalence rate and risk factors for fatigue in domestically employed migrant women are unknown. In total, 194 Indonesian women migrants aged 20-50 years who were working in Taipei were studied. Self-perceived acculturation, dietary acculturation, BMI and haemoglobin were evaluated. Fatigue and depressive symptoms were assessed using the Brief Fatigue Inventory and Beck Depression Inventory-II, respectively. The prevalence of fatigue was 27.8%. Depressive symptoms (p<0.0001), cooking methods (p=0.027), and self-perceived feelings of sadness and weakness (p=0.003) were associated with fatigue. After adjustment for covariates, the ORs for depressive symptoms (OR: 5.40; 95% CI: 2.32-12.6), deep frying/stir frying (OR: 5.23; 95% CI: 1.27-21.5), and self-perceived feelings of sadness and weakness (OR: 3.41; 95% CI: 1.26-9.25) remained significant. An interactive analysis revealed that women without depressive symptoms who used deep frying/stir frying as a cooking method had a 3.5-fold (1-12.3) higher risk of fatigue than did those who used non-deep frying and stir frying as cooking methods (which served as the reference) for cooking. By contrast, women with depressive symptoms who used non-deep frying and stir frying had a 6.5-fold (2.8-15.3) higher risk of fatigue, and the risk increased sharply to 12.6-fold (1.26-125.8) if they used deep frying and stir frying for cooking. The risk of fatigue among migrant women working domestically is increased when they exhibit depressive symptoms and their cooking technique is frying.

Effectiveness of xenogenous-based bovine-derived platelet gel embedded within a three-dimensional collagen implant on the healing and regeneration of the Achilles tendon defect in rabbits

PubMed Central

Moshiri, Ali; Oryan, Ahmad; Meimandi-Parizi, Abdolhamid; Koohi-Hosseinabadi, Omid

2014-01-01

Background and objective: Tissue engineering is an option in reconstructing large tendon defects and managing their healing and regeneration. We designed and produced a novel xenogeneic-based bovine platelet, embedded it within a tissue-engineered collagen implant (CI) and applied it in an experimentally induced large tendon defect model in rabbits to test whether bovine platelets could stimulate tendon healing and regeneration in vivo. Methods: One hundred twenty rabbits were randomly divided into two experimental and pilot groups. In all the animals, the left Achilles tendon was surgically excised and the tendon edges were aligned by Kessler suture. Each group was then divided into three groups of control (no implant), treated with CI and treated with collagen-platelet implant. The pilot groups were euthanized at 10, 15, 30 and 40 days post-injury (DPI), and their gross and histologic characteristics were evaluated to study host–graft interaction mechanism. To study the tendon healing and its outcome, the experimental animals were tested during the experiment using hematologic, ultrasonographic and various methods of clinical examinations and then euthanized at 60 DPI and their tendons were evaluated by gross pathologic, histopathologic, scanning electron microscopic, biophysical and biochemical methods. Results: Bovine platelets embedded within a CI increased inflammation at short term while it increased the rate of implant absorption and matrix replacement compared with the controls and CI alone. Treatment also significantly increased diameter, density, amount, alignment and differentiation of the collagen fibrils and fibers and approximated the water uptake and delivery behavior of the healing tendons to normal contralaterals (p < 0.05). Treatment also improved echogenicity and homogenicity of the tendons and reduced peritendinous adhesion, muscle fibrosis and atrophy, and therefore, it improved the clinical scores and physical activity related to the injured limb when compared with the controls (p < 0.05). Conclusion: The bovine platelet gel embedded within the tissue-engineered CI was effective in healing, modeling and remodeling of the Achilles tendon in rabbit. This strategy may be a valuable option in the clinical setting. PMID:24840092

UNO DMRG CASCI calculations of effective exchange integrals for m-phenylene-bis-methylene spin clusters

NASA Astrophysics Data System (ADS)

Kawakami, Takashi; Sano, Shinsuke; Saito, Toru; Sharma, Sandeep; Shoji, Mitsuo; Yamada, Satoru; Takano, Yu; Yamanaka, Shusuke; Okumura, Mitsutaka; Nakajima, Takahito; Yamaguchi, Kizashi

2017-09-01

Theoretical examinations of the ferromagnetic coupling in the m-phenylene-bis-methylene molecule and its oligomer were carried out. These systems are good candidates for exchange-coupled systems to investigate strong electronic correlations. We studied effective exchange integrals (J), which indicated magnetic coupling between interacting spins in these species. First, theoretical calculations based on a broken-symmetry single-reference procedure, i.e. the UHF, UMP2, UMP4, UCCSD(T) and UB3LYP methods, were carried out with a GAUSSIAN program code under an SR wave function. From these results, the J value by the UHF method was largely positive because of the strong ferromagnetic spin polarisation effect. The J value by the UCCSD(T) and UB3LYP methods improved an overestimation problem by correcting the dynamical electronic correlation. Next, magnetic coupling among these spins was studied using the CAS-based method of the symmetry-adapted multireference methods procedure. Thus, the UNO DMRG CASCI (UNO, unrestricted natural orbital; DMRG, density matrix renormalised group; CASCI, complete active space configuration interaction) method was mainly employed with a combination of ORCA and BLOCK program codes. DMRG CASCI calculations in valence electron counting, which included all orbitals to full valence CI, provided the most reliable result, and support the UB3LYP method for extended systems.

In vitro testing of drug combinations employing nilotinib and alkylating agents with regard to pretransplant conditioning treatment of advanced-phase chronic myeloid leukemia.

PubMed

Radujkovic, Aleksandar; Luft, Thomas; Dreger, Peter; Ho, Anthony D; Jens Zeller, W; Fruehauf, Stefan; Topaly, Julian

2014-08-01

The prognosis of patients with advanced-phase chronic myeloid leukemia (CML) remains dismal despite the availability of targeted therapies and allogeneic stem cell transplantation (allo-SCT). Increasing the antileukemic efficacy of the pretransplant conditioning regimen may be a strategy to increase remission rates and duration. We therefore investigated the antiproliferative effects of nilotinib in combination with drugs that are usually used for conditioning: the alkylating agents mafosfamide, treosulfan, and busulfan. Drug combinations were tested in vitro in different imatinib-sensitive and imatinib-resistant BCR-ABL-positive cell lines. A tetrazolium-based MTT assay was used for the assessment and quantification of growth inhibition after exposure to alkylating agents alone or to combinations with nilotinib. Drug interaction was analyzed using the median-effect method of Chou and Talalay, and combination index (CI) values were calculated according to the classic isobologram equation. Treatment of imatinib-sensitive, BCR-ABL-positive K562 and LAMA84 cells with nilotinib in combination with mafosfamide, treosulfan, or busulfan resulted in synergistic (CI < 1), additive (CI ~ 1), and predominantly antagonistic (CI > 1) effects, respectively. In imatinib-resistant K562-R and LAMA84-R cells, all applied drug combinations were synergistic (CI < 1) at higher growth inhibition levels. Our in vitro data warrant further investigation and may provide the basis for nilotinib-supplemented conditioning regimens for allo-SCT in advanced-phase CML.

Welfare State Regimes, Gender, and Depression: A Multilevel Analysis of Middle and High Income Countries

PubMed Central

Chung, Haejoo; Ng, Edwin; Ibrahim, Selahadin; Karlsson, Björn; Benach, Joan; Espelt, Albert; Muntaner, Carles

2013-01-01

Using the 2002 World Health Survey, we examine the association between welfare state regimes, gender and mental health among 26 countries classified into seven distinct regimes: Conservative, Southeast Asian, Eastern European, Latin American, Liberal, Southern/Ex-dictatorship, and Social Democratic. A two-level hierarchical model found that the odds of experiencing a brief depressive episode in the last 12 months was significantly higher for Southern/Ex- dictatorship countries than for Southeast Asian (odds ratio (OR) = 0.12, 95% confidence interval (CI) 0.05–0.27) and Eastern European (OR = 0.36, 95% CI 0.22–0.58) regimes after controlling for gender, age, education, marital status, and economic development. In adjusted interaction models, compared to Southern/Ex-dictatorship males (reference category), the odds ratios of depression were significantly lower among Southeast Asian males (OR = 0.16, 95% CI 0.08–0.34) and females (OR = 0.23, 95% CI 0.10–0.53) and Eastern European males (OR = 0.41, 95% CI 0.26–0.63) and significantly higher among females in Liberal (OR = 2.00, 95% CI 1.14–3.49) and Southern (OR = 2.42, 95% CI 1.86–3.15) regimes. Our results highlight the importance of incorporating middle-income countries into comparative welfare regime research and testing for interactions between welfare regimes and gender on mental health. PMID:23538729

Prevalence and clinical impact of recreational drug consumption in people living with HIV on treatment: a cross-sectional study

PubMed Central

Zurita, Beatriz; Velasco, Cesar; Feliu, Anna; Gutierrez, Mar; Masip, Montserrat; Mangues, M Antonia

2017-01-01

Objectives Drug interactions, poor adherence to medication and high-risk sexual behaviour may occur in individuals with HIV using recreational drugs. Thus, we aimed to assess the prevalence of recreational drugs use and to explore its clinical impact in HIV patients on treatment. Methods Observational, cross sectional, study conducted in a 700 bed university hospital, Barcelona, Spain. A total of 208 adults living with HIV on treatment were included. A questionnaire was administered by clinical pharmacists, including evaluation of sociodemographic variables, past 12-month drug consumption, adherence to antiretrovirals (Simplified Medication Adherence Questionnaire) and high-risk sexual behaviour (condomless sex/multiple partners). Additional data were obtained from clinical records. Recreational drug-antiretroviral interactions were checked in reference databases. Prevalence was calculated for 5% precision and 95% CI. Crude and adjusted binary logistic regressions were performed to identify associations between recreational drug use and adherence problems, and between recreational drug use and high-risk sexual behaviour. Results From the overall sample, 92 participants (44.2%) consumed recreational drugs over the past 1 year. Of these, 44 (48.8%) had used different types of recreational drugs in this period. We detected 11 recreational substances, including sildenafil and nitrites. The most consumed drugs were: cannabis (68.5%), cocaine (45.5%), nitrites (31.5%), sildenafil (28.3) and ecstasy (19.6%). Relevant interactions occurred in 46 (50%) of the individuals consuming drugs. Recreational drug consumption was found to be related to adherence problems with antiretrovirals (OR: 2.51 (95% CI 1.32 to 4.77) p=0.005) and high-risk sexual behaviour (OR: 2.81 (95% CI 1.47 to 5.39) p=0.002). Conclusions Recreational drugs are frequently used by HIV patients on treatment. Classical drugs and new substances consumed in sexual context are usual. Recreational drug consumption interferes with several clinical outcomes, including potentially relevant interactions between drugs and antiretrovirals, adherence problems and high-risk sexual behaviour. Thus, there is the urgent need of implementing patient-centred care involving recreational drug consumption. PMID:28100565

Mediterranean Diet Reduces the Adverse Effect of the TCF7L2-rs7903146 Polymorphism on Cardiovascular Risk Factors and Stroke Incidence

PubMed Central

Corella, Dolores; Carrasco, Paula; Sorlí, Jose V.; Estruch, Ramón; Rico-Sanz, Jesús; Martínez-González, Miguel Ángel; Salas-Salvadó, Jordi; Covas, M. Isabel; Coltell, Oscar; Arós, Fernando; Lapetra, José; Serra-Majem, Lluís; Ruiz-Gutiérrez, Valentina; Warnberg, Julia; Fiol, Miquel; Pintó, Xavier; Ortega-Azorín, Carolina; Muñoz, Miguel Ángel; Martínez, J. Alfredo; Gómez-Gracia, Enrique; González, José I.; Ros, Emilio; Ordovás, José M.

2013-01-01

OBJECTIVE Transcription factor 7-like 2 (TCF7L2) polymorphisms are strongly associated with type 2 diabetes, but controversially with plasma lipids and cardiovascular disease. Interactions of the Mediterranean diet (MedDiet) on these associations are unknown. We investigated whether the TCF7L2-rs7903146 (C>T) polymorphism associations with type 2 diabetes, glucose, lipids, and cardiovascular disease incidence were modulated by MedDiet. RESEARCH DESIGN AND METHODS A randomized trial (two MedDiet intervention groups and a control group) with 7,018 participants in the PREvención con DIetaMEDiterránea study was undertaken and major cardiovascular events assessed. Data were analyzed at baseline and after a median follow-up of 4.8 years. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) for cardiovascular events. RESULTS The TCF7L2-rs7903146 polymorphism was associated with type 2 diabetes (odds ratio 1.87 [95% CI 1.62–2.17] for TT compared with CC). MedDiet interacted significantly with rs7903146 on fasting glucose at baseline (P interaction = 0.004). When adherence to the MedDiet was low, TT had higher fasting glucose concentrations (132.3 ± 3.5 mg/dL) than CC+CT (127.3 ± 3.2 mg/dL) individuals (P = 0.001). Nevertheless, when adherence was high, this increase was not observed (P = 0.605). This modulation was also detected for total cholesterol, LDL cholesterol, and triglycerides (P interaction < 0.05 for all). Likewise, in the randomized trial, TT subjects had a higher stroke incidence in the control group (adjusted HR 2.91 [95% CI 1.36–6.19]; P = 0.006 compared with CC), whereas dietary intervention with MedDiet reduced stroke incidence in TT homozygotes (adjusted HR 0.96 [95% CI 0.49–1.87]; P = 0.892 for TT compared with CC). CONCLUSIONS Our novel results suggest that MedDiet may not only reduce increased fasting glucose and lipids in TT individuals, but also stroke incidence. PMID:23942586

Cardiorespiratory fitness attenuates risk for major adverse cardiac events in hyperlipidemic men and women independent of statin therapy: The Henry Ford ExercIse Testing Project.

PubMed

Hung, Rupert K; Al-Mallah, Mouaz H; Qadi, Mohamud A; Shaya, Gabriel E; Blumenthal, Roger S; Nasir, Khurram; Brawner, Clinton A; Keteyian, Steven J; Blaha, Michael J

2015-08-01

We sought to evaluate the effect of cardiorespiratory fitness (CRF) in predicting mortality, myocardial infarction (MI), and revascularization in patients with hyperlipidemia after stratification by gender and statin therapy. This retrospective cohort study included 33,204 patients with hyperlipidemia (57 ± 12 years old, 56% men, 25% black) who underwent physician-referred treadmill stress testing at the Henry Ford Health System from 1991 to 2009. Patients were stratified by gender, baseline statin therapy, and estimated metabolic equivalents from stress testing. We computed hazard ratios using Cox regression models after adjusting for demographics, cardiac risk factors, comorbidities, pertinent medications, interaction terms, and indication for stress testing. There were 4,851 deaths, 1,962 MIs, and 2,686 revascularizations over a median follow-up of 10.3 years. In men and women not on statin therapy and men and women on statin therapy, each 1-metabolic equivalent increment in CRF was associated with hazard ratios of 0.86 (95% CI 0.85-0.88), 0.83 (95% CI 0.81-0.85), 0.85 (95% CI 0.83-0.87), and 0.84 (95% CI 0.81-0.87) for mortality; 0.93 (95% CI 0.90-0.96), 0.87 (95% CI 0.83-0.91), 0.89 (95% CI 0.86-0.92), and 0.90 (95% CI 0.86-0.95) for MI; and 0.91 (95% CI 0.88-0.93), 0.87 (95% CI 0.83-0.91), 0.89 (95% CI 0.87-0.92), and 0.90 (95% CI 0.86-0.94) for revascularization, respectively. No significant interactions were observed between CRF and statin therapy (P > .23). Higher CRF attenuated risk for mortality, MI, and revascularization independent of gender and statin therapy in patients with hyperlipidemia. These results reinforce the prognostic value of CRF and support greater promotion of CRF in this patient population. Copyright © 2015 Elsevier Inc. All rights reserved.

Nature of KaiB-KaiC binding in the cyanobacterial circadian oscillator

PubMed Central

Pattanayek, Rekha; Yadagiri, Kirthi Kiran; Ohi, Melanie D.; Egli, Martin

2013-01-01

In the cyanobacteria Synechococcus elongatus and Thermosynechococcus elongatus, the KaiA, KaiB and KaiC proteins in the presence of ATP generate a post-translational oscillator (PTO) that can be reconstituted in vitro. KaiC is the result of a gene duplication and resembles a double doughnut with N-terminal CI and C-terminal CII hexameric rings. Six ATPs are bound between subunits in both the CI and CII ring. CI harbors ATPase activity, and CII catalyzes phosphorylation and dephosphorylation at T432 and S431 with a ca. 24-h period. KaiA stimulates KaiC phosphorylation, and KaiB promotes KaiC subunit exchange and sequesters KaiA on the KaiB-KaiC interface in the final stage of the clock cycle. Studies of the PTO protein-protein interactions are convergent in terms of KaiA binding to CII but have led to two opposing models of the KaiB-KaiC interaction. Electron microscopy (EM) and small angle X-ray scattering (SAXS), together with native PAGE using full-length proteins and separate CI and CII rings, are consistent with binding of KaiB to CII. Conversely, NMR together with gel filtration chromatography and denatured PAGE using monomeric CI and CII domains support KaiB binding to CI. To resolve the existing controversy, we studied complexes between KaiB and gold-labeled, full-length KaiC with negative stain EM. The EM data clearly demonstrate that KaiB contacts the CII ring. Together with the outcomes of previous analyses, our work establishes that only CII participates in interactions with KaiA and KaiB as well as with the His kinase SasA involved in the clock output pathway. PMID:23388462

Potential mechanisms for the association between fall birth and food allergy.

PubMed

Keet, C A; Matsui, E C; Savage, J H; Neuman-Sunshine, D L; Skripak, J; Peng, R D; Wood, R A

2012-06-01

Season of birth has been reported as a risk factor for food allergy, but the mechanisms by which it acts are unknown. Two populations were studied: 5862 children from the National Health and Nutrition Examination Survey (NHANES) III and 1514 well-characterized food allergic children from the Johns Hopkins Pediatric Allergy Clinic (JHPAC). Food allergy was defined as self-report of an acute reaction to a food (NHANES), or as milk, egg, and peanut allergy. Logistic regression compared fall or nonfall birth between (i) food allergic and nonallergic subjects in NHANES, adjusted for ethnicity, age, income, and sex, and (ii) JHPAC subjects and the general Maryland population. For NHANES, stratification by ethnicity and for JHPAC, eczema were examined. Fall birth was more common among food allergic subjects in both NHANES (OR, 1.91; 95% CI, 1.31-2.77) and JHPAC/Maryland (OR, 1.31; 95% CI, 1.18-1.47). Ethnicity interacted with season (OR, 2.34; 95% CI, 1.43-3.82 for Caucasians; OR, 1.19; 95% CI, 0.77-1.86 for non-Caucasians; P = 0.04 for interaction), as did eczema (OR, 1.47; 95% CI, 1.29-1.67 with eczema; OR, 1.00; 95% CI, 0.80-1.23 without eczema; P = 0.002 for interaction). Fall birth is associated with increased risk of food allergy, and this risk is greatest among those most likely to have seasonal variation in vitamin D during infancy (Caucasians) and those at risk for skin barrier dysfunction (subjects with a history of eczema), suggesting that vitamin D and the skin barrier may be implicated in seasonal associations with food allergy. © 2012 John Wiley & Sons A/S.

Interactions Between Air Pollution and Obesity on Blood Pressure and Hypertension in Chinese Children.

PubMed

Dong, Guang-Hui; Wang, Jing; Zeng, Xiao-Wen; Chen, Lihua; Qin, Xiao-Di; Zhou, Yang; Li, Meng; Yang, Mingan; Zhao, Yang; Ren, Wan-Hui; Hu, Qian-Sheng

2015-09-01

Little information exists regarding the effect of interaction of obesity and long-term air pollution exposure on children's blood pressure and hypertension in areas with high levels of air pollution. The aim of this study is to assess effect modification by obesity on the association between exposure and blood pressure in Chinese children. We studied 9,354 Chinese children, ages 5-17 years old, from 24 elementary schools and 24 middle schools in the Seven Northeastern Cities during 2012-2013. Four-year average concentrations of particles with an aerodynamic diameter ≤10 µm (PM10), sulfur dioxide, nitrogen dioxides, and ozone (O3) were measured at the monitoring stations in the 24 districts. We used generalized additive models and two-level logistic regression models to examine the health effects. Consistent interactions were found between exposure and obesity on blood pressure and hypertension. The association between exposure and hypertension was consistently larger for overweight/obese children than for children with normal-weight, with odds ratios for hypertension ranging from 1.16 per 46.3μg/m for O3 (95% confidence interval [CI] = 1.12, 1.20) to 2.91 per 30.6μg/m for PM10 (95% CI = 2.32, 3.64), and estimated increases in mean systolic and diastolic blood pressure ranging from 0.57 mmHg (95% CI = 0.36, 0.78) and 0.63 mmHg (95% CI = 0.46, 0.81) per 46.3 μg/m for O3 to 4.04 mmHg (95% CI = 3.00, 5.09) and 2.02 mmHg (95% CI = 1.14, 2.89) per 23.4 μg/m for sulfur dioxide. Obesity amplifies the association of long-term air pollution exposure with blood pressure and hypertension in Chinese children.

Refuting the ticagrelor-aspirin black box warning: and proposing a ticagrelor early-PCI black box warning.

PubMed

DiNicolantonio, James J; Serebruany, Victor L; Tomek, Ales

2013-10-03

Ticagrelor, a novel reversible antiplatelet agent, has a black box warning to avoid maintenance doses of aspirin>100mg. However, a significant ticagrelor-early percutaneous coronary intervention (PCI) interaction exists. To discuss the inappropriateness of the black box warning for aspirin doses>100mg with ticagrelor and the appropriateness (and need) for a black box warning for ticagrelor patients needing early (within 24 hours of randomization) PCI. The FDA Complete Response Review for ticagrelor indicates that aspirin doses ≥ 300 mg/daily was not a significant interaction. In the ticagrelor-aspirin ≥ 300 mg cohort, all-cause mortality (through study end) and cardiovascular (CV) mortality (through study end) were not significantly increased (HR=1.27; 95% CI, 0.84-1.93, p=0.262 and HR=1.39; 95% CI:0.87-2.2, p=0.170), respectively. However, in patients treated with early (within 24 hours) PCI, ticagrelor significantly increased all-cause mortality (30 day: HR=1.89; 95% CI: 1.26-2.81, p=0.002, and through study end, HR=1.41; 95% CI,1.08-1.84, p=0.012) and increased CV mortality (30 day: HR=1.31; 95% CI: 0.97-1.77, p=0.075, and through study end, HR=1.35; 95% CI, 0.995-1.82, p=0.054) compared to clopidogrel. Early-PCI was more prevalent in the US versus outside-US regions (61% versus 49%). The black box warning for the use of maintenance aspirin doses over 100mg/daily with ticagrelor is inappropriate and ignores the more important, credible, and highly significant ticagrelor-early PCI adverse interaction in PLATO. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Impact of polyvascular disease on patients with atrial fibrillation: Insights from ROCKET AF.

PubMed

Chen, Sean T; Hellkamp, Anne S; Becker, Richard C; Berkowitz, Scott D; Breithardt, Günter; Fox, Keith A A; Hacke, Werner; Halperin, Jonathan L; Hankey, Graeme J; Mahaffey, Kenneth W; Nessel, Christopher C; Piccini, Jonathan P; Singer, Daniel E; Patel, Manesh R

2018-06-01

We investigated the impact of polyvascular disease in patients enrolled in ROCKET AF. Cox regression models were used to assess clinical outcomes and treatment effects of rivaroxaban compared with warfarin in patients with atrial fibrillation and coronary, peripheral, or carotid artery disease, or any combination of the 3. A total of 655 (4.6%) patients had polyvascular disease (≥2 disease locations), and 3,391 (23.8%) had single-arterial bed disease. Patients with polyvascular disease had similar rates of stroke/systemic embolism but higher rates of cardiovascular and bleeding events when compared with those without vascular disease. Use of rivaroxaban compared with warfarin was associated with higher rates of stroke in patients with polyvascular disease (hazard ratio [HR] 2.41, 95% CI 1.05-5.54); however, this was not seen in patients with single-bed (HR 0.90, 95% CI 0.64-1.28) or no vascular disease (HR 0.85, 95% CI 0.69-1.04; interaction P = .058). There was a significant interaction for major or nonmajor clinically relevant bleeding in patients with polyvascular (HR 1.23, 95% CI 0.91-1.65) and single-bed vascular disease (HR 1.30, 95% CI 1.13-1.49) treated with rivaroxaban compared with warfarin when compared with those without vascular disease (HR 0.95, 95% CI 0.87-1.04; interaction P = .0006). Additional antiplatelet therapy in this population did not improve stroke or cardiovascular outcomes. The use of rivaroxaban compared with warfarin was associated with a higher risk of stroke and bleeding in patients with polyvascular disease enrolled in ROCKET AF. Further studies are needed to understand the optimal management of this high-risk population. Copyright © 2018 Elsevier Inc. All rights reserved.

Comment on Mars as the Parent Body of the CI Carbonaceous Chondrites by J. E. Brandenburg

NASA Technical Reports Server (NTRS)

Treiman, Allan H.

1996-01-01

Geological and chemical data refute a martian origin for the CI carbonaceous chondrites. Here, I will first consider Brandenburg's [1996] proposal that the CI's formed as water-deposited sediments on Mars, and that these sediments had limited chemical interactions with their martian environment. Finally, I will address oxygen isotope ratios, the strongest link between the CIs and the martian meteorites.

The development of intonation in young children with cochlear implants: A preliminary study of the influence of age at implantation and length of implant experience

PubMed Central

Snow, David; Ertmer, David

2010-01-01

This study describes the development of emerging intonation in six children who had received a cochlear implant (CI) before the age of three years. At the time their implant was activated, the children ranged in age from 11 to 37 months. Spontaneous longitudinal speech samples were recorded from 30-minute sessions in which the child interacted with his or her mother. Data were collected 2 months before activation of each child's CI and at monthly intervals after activation for 6 months. The findings were compared to the typical pattern of early intonation development in children with normal hearing (NH). The results suggested that young CI recipients progress through stages similar to those observed in children with NH. However, the intonation development of children with a CI reflects a marked interaction between chronological age at implantation and amount of CI experience. That is, after 2 months of CI-assisted hearing experience, the older children demonstrated a later stage of intonation development than younger children. These preliminary results support the idea that children acquire some foundations or prerequisites of intonation production through maturation, as measured by chronological age, even without robust auditory experience. PMID:20882119

Behaviors Associated With a Risk of HIV Transmission From HIV-Positive Street Youth to Non–Street Youth in Ukraine

PubMed Central

Nerlander, Lina M.C.; Zapata, Lauren B.; Yorick, Roman; Skipalska, Halyna; Smith, Ruben A.; Kissin, Dmitry M.; Jamieson, Denise J.; Vitek, Charles R.; Hillis, Susan D.

2017-01-01

Background Little is known about the extent to which HIV-infected street youth (living part or full time on the streets) exhibit behaviors associated with HIV transmission in their interactions with youth not living on the streets (“non–street youth”). We aimed to determine prevalences and predictors of such “bridging behaviors”: inconsistent condom use and needle sharing between HIV-positive street youth and non–street youth. Methods A total of 171 street youth in 3 Ukrainian cites were identified as HIV infected after testing of eligible participants aged 15 to 24 years after random selection of venues. Using data from these youth, we calculated prevalence estimates of bridging behaviors and assessed predictors using logistic regression. Results Overall, two-thirds of HIV-infected street youth exhibited bridging behaviors; subgroups with high prevalences of bridging included females (78.3%) and those involved in transactional sex (84.2%). In multivariable analysis, inconsistent condom use with non–street youth was associated with being female (adjusted prevalence ratio [aPR], 1.2; 95% confidence interval [CI], 1.1–1.4), working (aPR, 1.2; 95% CI, 1.03–1.4), multiple partners (aPR, 1.4; 95% CI, 1.2–1.6), and “never” (aPR, 1.4; 95% CI, 1.1–1.6) or “sometimes” (aPR, 1.3; 95% CI, 1.02–1.8) versus “always” sleeping on the street. Needle sharing with non–street youth was associated with being male (aPR, 1.4; 95% CI, 1.02–2.0), orphaned (aPR, 2.3; 95% CI, 1.8–3.0), and 2 years or less living on the streets (aPR, 1.8; 95% CI, 1.5–2.1). Conclusions Bridging behaviors between HIV-infected street youth and non–street youth are common. Addressing the comprehensive needs of street and other at-risk youth is a critical prevention strategy. PMID:26267878

Ticagrelor vs. clopidogrel in patients with acute coronary syndromes and diabetes: a substudy from the PLATelet inhibition and patient Outcomes (PLATO) trial

PubMed Central

James, Stefan; Angiolillo, Dominick J.; Cornel, Jan H.; Erlinge, David; Husted, Steen; Kontny, Frederic; Maya, Juan; Nicolau, Josë C.; Spinar, Jindrich; Storey, Robert F.; Stevens, Susanna R.; Wallentin, Lars

2010-01-01

Aims Patients with diabetes mellitus (DM) have high platelet reactivity and are at increased risk of ischaemic events and bleeding post-acute coronary syndromes (ACS). In the PLATelet inhibition and patient Outcomes (PLATO) trial, ticagrelor reduced the primary composite endpoint of cardiovascular death, myocardial infarction, or stroke, but with similar rates of major bleeding compared with clopidogrel. We aimed to investigate the outcome with ticagrelor vs. clopidogrel in patients with DM or poor glycaemic control. Methods and results We analysed patients with pre-existing DM (n = 4662), including 1036 patients on insulin, those without DM (n = 13 951), and subgroups based on admission levels of haemoglobin A1c (HbA1c; n = 15 150). In patients with DM, the reduction in the primary composite endpoint (HR: 0.88, 95% CI: 0.76–1.03), all-cause mortality (HR: 0.82, 95% CI: 0.66–1.01), and stent thrombosis (HR: 0.65, 95% CI: 0.36–1.17) with no increase in major bleeding (HR: 0.95, 95% CI: 0.81–1.12) with ticagrelor was consistent with the overall cohort and without significant diabetes status-by-treatment interactions. There was no heterogeneity between patients with or without ongoing insulin treatment. Ticagrelor reduced the primary endpoint, all-cause mortality, and stent thrombosis in patients with HbA1c above the median (HR: 0.80, 95% CI: 0.70–0.91; HR: 0.78, 95% CI: 0.65–0.93; and HR: 0.62, 95% CI: 0.39–1.00, respectively) with similar bleeding rates (HR: 0.98, 95% CI: 0.86–1.12). Conclusion Ticagrelor, when compared with clopidogrel, reduced ischaemic events in ACS patients irrespective of diabetic status and glycaemic control, without an increase in major bleeding events. PMID:20802246

Semistochastic approach to many electron systems

NASA Astrophysics Data System (ADS)

Grossjean, M. K.; Grossjean, M. F.; Schulten, K.; Tavan, P.

1992-08-01

A Pariser-Parr-Pople (PPP) Hamiltonian of an 8π electron system of the molecule octatetraene, represented in a configuration-interaction basis (CI basis), is analyzed with respect to the statistical properties of its matrix elements. Based on this analysis we develop an effective Hamiltonian, which represents virtual excitations by a Gaussian orthogonal ensemble (GOE). We also examine numerical approaches which replace the original Hamiltonian by a semistochastically generated CI matrix. In that CI matrix, the matrix elements of high energy excitations are choosen randomly according to distributions reflecting the statistics of the original CI matrix.

Using Diverse Communication Strategies to Re-Engage Relapsed Tobacco Quitline Users in Treatment, New York State, 2014

PubMed Central

Miles, Lyndsay; Doyle, Suzanne; Celestino, Paula; Koutsky, James

2015-01-01

Introduction Most smoking cessation programs lack strategies to reach relapsed participants and encourage a new quit attempt. We used a multimodal intervention to encourage past quitline registry participants to recycle into services. Methods We invited 3,510 past quitline participants back to quitline services, using messages consecutively delivered through Interactive Voice Response (IVR), followed by postcard and email reminders, 2 Short Messaging Services (SMS) texts, and a final cycle of IVR. The primary study outcome was recycling into a new quitline-assisted quit attempt. We used statistical analyses to assess rates and predictors of recycling (socioeconomic, health- and tobacco-related variables) with study participants and compared the study sample with registry participants not selected for the study (comparison group). Results Quitline services were re-initiated by 12.2% of the intervention sample and 1.9% of the comparison group (z = 6.03, P < .001, effect size of 0.44). Most re-enrollments were done via direct IVR-transfer to the quitline. Predictors of re-enrollment were age (odds ratio [OR] = 1.45 for every 10 years of age; 95% confidence interval [CI], 1.34–1.57), number of years smoking (OR = 1.27; 95% CI, 1.18–1.36), and reporting cancer (OR = 2.32; 95% CI, 1.47–3.68) or chronic obstructive pulmonary disease (OR = 1.55; 95% CI, 1.16–2.10). Living with other smokers was correlated with a lower chance of recycling into treatment (OR = 0.72; 95% CI, 0.57–0.91). Conclusion Recycling previous quitline participants using a proactive, IVR-based intervention is effective in reinitiating quitline-assisted quit attempts. Older, long-term smokers reporting chronic conditions are more likely than younger smokers to re-engage in quitline support when these methods are used. PMID:26491814

Cigarettes, genetic background, and menopausal timing: the presence of single nucleotide polymorphisms in cytochrome P450 genes is associated with increased risk of natural menopause in European-American smokers

PubMed Central

Butts, Samantha F.; Sammel, Mary D.; Greer, Christine; Rebbeck, Timothy R.; Boorman, David W.; Freeman, Ellen W.

2016-01-01

Objective This study aims to evaluate associations between variations in genes involved in the metabolism of environmental chemicals and steroid hormones and risk of menopause in smokers. Methods Survival analysis was performed on 410 eligible participants from the Penn Ovarian Aging study (ongoing for 14 years), a cohort study of late-reproductive-age women. Single nucleotide polymorphisms at the following loci were studied: COMT Val158Met, CYP1B1*4 Asn452Ser, CYP1B1*3 Leu432Val, and CYP3A4*1B. Results Significant interactions between smoking and single nucleotide polymorphisms were observed in European-American carriers of CYP3A4*1B and CYP1B1*3, supporting a greater risk of menopause entry compared with those not carrying these alleles. Among CYP1B1*3 carriers, smokers had a greater risk of menopause entry than nonsmokers (adjusted hazard ratio [HR], 2.26; 95% CI, 1.4–3.67; median time to menopause, 10.42 and 11.07 y, respectively). No association between smoking and menopause was identified in CYP1B1 wild types. Among CYP3A4*1B carriers, smokers were at greater risk for menopause entry than nonsmokers (adjusted HR, 15.1; 95% CI, 3.31–69.2; median time to menopause, 11.36 and 13.91 y, respectively). Risk of menopause entry in CYP3A4 wild types who smoked was far lower (adjusted HR, 1.59; 95% CI, 1.03–2.44). Heavily smoking CYP1B1*3 carriers (adjusted HR, 3.0; 95% CI, 1.54–5.84; median time to menopause, 10.41 y) and heavily smoking CYP3A4*1B carriers (adjusted HR, 17.79; 95% CI, 3.21–98.65; median time to menopause, 5.09 y) had the greatest risk of menopause entry. Conclusions Our finding that the risk of menopause entry in European-American smokers varies depending on genetic background represents a novel gene-environment interaction in reproductive aging. PMID:24448104

The combined effects of job demand and control, effort-reward imbalance and work-family conflicts on the risk of major depressive episode: a 4-year longitudinal study.

PubMed

Nigatu, Yeshambel T; Wang, JianLi

2018-01-01

Work-related psychosocial factors may precipitate the onset of depression. In occupational mental health research, there are three widely used theoretical models, namely, job demand and control (JD-C), effort-reward imbalance (ERI) and work-family conflicts (WFC). However, the interaction between these models and their combined effect on the risk of major depression in the workplace is largely unknown. The aim of this study is to examine the longitudinal combined effects of JD-C, ERI and WFC on the risk of major depression in the working population. Longitudinal data (2008-2013) were collected on randomly selected participants (n=4200) from the working population of the province of Alberta, Canada, at baseline and 1-, 2-, 3- and 4-year follow-up. Data about JD-C, ERI, WFC and major depression were collected by trained interviewers using a computer-assisted telephone interviewing method. Generalised estimating equations for longitudinal modelling were used. There was an independent association between high ERI and high WFC at t x and major depression at t x+1 (OR 1.56, 95% CI 1.25 to 1.96; OR 1.33, 95% CI 1.16 to 1.52), respectively. The combined effects of JD-C and ERI, ERI and WFC, and WFC and JD-C on the risk of major depression were as follows: OR 1.71, 95% CI 1.22 to 2.42, OR 2.47, 95% CI 1.99 to 3.49 and OR 2.21, 95% CI 1.48 to 3.30, respectively. The relative excess risks attributable to the interactions were statistically non-significant. Work-related psychosocial factors are associated with increased risk of major depression over time, but their combined effect is not synergistic. The effects of the factors depicted in the three occupational health models on the risk of major depression appear to be additive. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Lung Cancer in Chinese Women: Evidence for an Interaction between Tobacco Smoking and Exposure to Inhalants in the Indoor Environment

PubMed Central

Tang, Li; Lim, Wei-Yen; Eng, Philip; Leong, Swan Swan; Lim, Tow Keang; Ng, Alan W.K.; Tee, Augustine; Seow, Adeline

2010-01-01

Background Epidemiologic data suggest that Chinese women have a high incidence of lung cancer in relation to their smoking prevalence. In addition to active tobacco smoke exposure, other sources of fumes and airborne particles in the indoor environment, such as cooking and burning of incense and mosquito coils, have been considered potential risk factors for lung cancer. Objectives We used a case–control study to explore effects of inhalants from combustion sources common in the domestic environment on lung cancer and their modification by active tobacco smoking. Methods We analyzed 703 primary lung cancer cases and 1,578 controls. Data on demographic background and relevant exposures were obtained by face-to-face interviews in the hospital. Results We observed a positive relationship with daily exposure to incense or mosquito coils and to cooking fumes only among smokers, and no association among lifetime nonsmokers. Interactions between smoking and frequency of cooking, or exposure to incense or mosquito coils were statistically significant and consistent with synergistic effects on lung cancer. The odds ratio (OR) comparing smokers without daily incense or mosquito coil exposure with nonsmokers without daily exposure was 2.80 [95% confidence interval (CI), 1.86–4.21], whereas the OR comparing smokers with daily exposure to the same referent group was 4.61 (95% CI, 3.41–6.24). In contrast, daily exposure to incense or mosquito coils was not associated with lung cancer among nonsmokers (OR = 0.91; 95% CI, 0.72–1.16). We observed the same pattern of associations for smokers without (OR = 2.31; 95% CI, 1.52–3.51) and with (OR = 4.50; 95% CI, 3.21–6.30) daily cooking exposure compared with nonsmokers, with no evidence of an association with daily cooking exposure among nonsmokers. Conclusion Our results suggest that active tobacco smoking not only is an important risk factor for development of lung cancer, but also may cause smokers to be more susceptible to the risk-enhancing effects of other inhalants. PMID:20472525

Exposure to intimate partner violence reduces the protective effect that women’s high education has on children’s corporal punishment: a population-based study

PubMed Central

Salazar, Mariano; Dahlblom, Kjerstin; Solórzano, Lucia; Herrera, Andrés

2014-01-01

Background Previous studies have shown that women's education is protective against corporal punishment (CP) of children. However, the effect that women's exposure to intimate partner violence (IPV) has on the association between women's education and children's CP has not been studied. Objective To understand how the interaction between women's exposure to IPV and their education level influences the occurrence of children's CP at the household level. Methods We selected 10,156 women who had at least one child less than 16 years old from cross-sectional data from the 2006–2007 Nicaraguan Demographic and Health Survey. Children's CP was defined as the punishment of children by slapping them, hitting them with a fist, or hitting them with a rope, belt, stick, or other object. IPV was measured by using a conflict tactic scale. The WHO Self-Reporting Questionnaire 20 (SRQ-20) was used to assess the women's mental health. We computed adjusted risk ratios (ARR) and 95% confidence intervals (CI) using Poisson regression with a robust variance estimator. Results Women's exposure to IPV was associated with a 10–17% increase in the risk of children's CP. IPV and children's CP were associated with impaired women's mental health. Women's lifetime exposure to emotional IPV and controlling behavior by a partner significantly decreased the protective effect from women's high education level on children's CP. When women were exposed to emotional IPV, the protective effect from having a college education decreased from ARR=0.61 (95% CI 0.47–0.80) to ARR=0.98 (95% CI 0.80–1.19). A similar pattern was found among women exposed to controlling behavior by a partner, the protective effect decreased from ARR=0.71 (95% CI 0.53–0.90) to ARR=0.86 (95% CI 0.70–1.06). Conclusion This study shows how significant gains in one positive social determinant of children's well-being can be undermined when it interacts with men's violence toward women. Policies that aim to end children's CP must include actions to end women's exposure to IPV. PMID:25226419

Use of the internet by Italian pediatricians: habits, impact on clinical practice and expectations

PubMed Central

2012-01-01

Background Medical professionals go online for literature searches and communication with families. We administered a questionnaire to members of the Italian Society of Pediatrics to assess determinants of their use of the Internet, of social platforms and of personal health records during clinical practice. Methods All the 9180 members of the Italian Society of Pediatrics were invited to fill in a questionnaire concerning use of the Internet and usefulness of Internet-based tools during clinical practice. The questionnaire was administered through the SurveyMonkey® web platform. Logistic regression analysis was used to study factors affecting use and influence of the Internet in clinical practice. Results A total of 1335 (14.5%) members returned the questionnaire. Mean age was 49.2 years, 58.6% were female. 32.3% had access to the Internet through a Smartphone. 71.9% of respondents used the Internet during clinical practice, mainly searching for guidelines and drug references. Use of the Internet during clinical practice was more frequent among younger pediatricians (OR 0.964; 95% CI 0.591-0.978), males (OR 1.602; 95% CI 1.209-2.123) and those living in Northern and Central Italy (OR 1.441; 95% CI 1.111-1.869), while it was lower among family pediatricians. 94.6% of respondents were influenced in their clinical practice by information found on the Internet, in particular younger pediatricians (OR 0.96, 95% CI 0.932-0.989), hospital pediatricians (OR 2.929, 95% CI 1.708-5.024), and other pediatric profiles (OR 6.143, 95%CI 1.848-20.423). 15.9% of respondents stated that social networks may be useful in pediatric practice. Slightly more than half (50.5%) of respondents stated that personal health records may be clinically relevant. Registrars and hospital pediatricians were more likely to perceive personal health records as useful tools for clinical practice. Additional resources pediatricians would like to access were free bibliographic databases and tools for interacting with families. Conclusions Italian pediatricians frequently use the Internet during their practice. One-third of them access the Internet through a Smartphone. Interaction with families and their empowerment can be improved by the use of Internet tools, including personal health records, toward which respondents show a significant interest. Though, they show a general resistance to the introduction of social networks in clinical practice. PMID:22455671

Outdoor Light at Night and Breast Cancer Incidence in the Nurses’ Health Study II

PubMed Central

Bertrand, Kimberly A.; Hart, Jaime E.; Schernhammer, Eva S.; Tamimi, Rulla M.; Laden, Francine

2017-01-01

Background: Animal and epidemiologic studies suggest that exposure to light at night (LAN) may disrupt circadian patterns and decrease nocturnal secretion of melatonin, which may disturb estrogen regulation, leading to increased breast cancer risk. Objectives: We examined the association between residential outdoor LAN and breast cancer incidence using data from the nationwide U.S.-based Nurses’ Health Study II cohort. Methods: We followed 109,672 women from 1989 through 2013. Cumulative LAN exposure was estimated using time-varying satellite data for a composite of persistent nighttime illumination at ∼1 km2 scale for each residence during follow-up. Incident invasive breast cancer cases were confirmed by medical record review. We used Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for anthropometric, reproductive, lifestyle, and socioeconomic risk factors. Results: Over 2,187,425 person-years, we identified 3,549 incident breast cancer cases. Based on a fully adjusted model, the estimated HR for incident breast cancer with an interquartile range (IQR) (31.6 nW/cm2/sr) increase in cumulative average outdoor LAN was 1.05 (95% CI: 1.00, 1.11). An association between LAN and breast cancer appeared to be limited to women who were premenopausal at the time of a case [HR=1.07 (95% CI: 1.01, 1.14) based on 1,973 cases vs. HR=1.00 (95% CI: 0.91, 1.09) based on 1,172 cases in postmenopausal women; p-interaction=0.08]. The LAN–breast cancer association was observed only in past and current smokers at the end of follow-up [HR=1.00 (95% CI: 0.94, 1.07) based on 2,215 cases in never smokers; HR=1.10 (95% CI: 1.01, 1.19) based on 1,034 cases in past smokers vs. HR=1.21 (95% CI: 1.07, 1.37) for 300 cases in current smokers; p-interaction=0.08]. Conclusions: Although further work is required to confirm our results and to clarify potential mechanisms, our findings suggest that exposure to residential outdoor light at night may contribute to invasive breast cancer risk. https://doi.org/10.1289/EHP935 PMID:28886600

Using Web 2.0 applications to promote health-related physical activity: findings from the WALK 2.0 randomised controlled trial

PubMed Central

Kolt, Gregory S; Rosenkranz, Richard R; Vandelanotte, Corneel; Caperchione, Cristina M; Maeder, Anthony J; Tague, Rhys; Savage, Trevor N; Van, Itallie Anetta; Mummery, W Kerry; Oldmeadow, Christopher; Duncan, Mitch J

2017-01-01

Background/Aim Web 2.0 internet technology has great potential in promoting physical activity. This trial investigated the effectiveness of a Web 2.0-based intervention on physical activity behaviour, and the impact on website usage and engagement. Methods 504 (328 women, 126 men) insufficiently active adult participants were randomly allocated to one of two web-based interventions or a paper-based Logbook group. The Web 1.0 group participated in the existing 10 000 Steps programme, while the Web 2.0 group participated in a Web 2.0-enabled physical activity intervention including user-to-user interaction through social networking capabilities. ActiGraph GT3X activity monitors were used to assess physical activity at four points across the intervention (0, 3, 12 and 18 months), and usage and engagement were assessed continuously through website usage statistics. Results Treatment groups differed significantly in trajectories of minutes/day of physical activity (p=0.0198), through a greater change at 3 months for Web 2.0 than Web 1.0 (7.3 min/day, 95% CI 2.4 to 12.3). In the Web 2.0 group, physical activity increased at 3 (mean change 6.8 min/day, 95% CI 3.9 to 9.6) and 12 months (3.8 min/day, 95% CI 0.5 to 7.0), but not 18 months. The Logbook group also increased physical activity at 3 (4.8 min/day, 95% CI 1.8 to 7.7) and 12 months (4.9 min/day, 95% CI 0.7 to 9.1), but not 18 months. The Web 1.0 group increased physical activity at 12 months only (4.9 min/day, 95% CI 0.5 to 9.3). The Web 2.0 group demonstrated higher levels of website engagement (p=0.3964). Conclusions In comparison to a Web 1.0 intervention, a more interactive Web 2.0 intervention, as well as the paper-based Logbook intervention, improved physical activity in the short term, but that effect reduced over time, despite higher levels of engagement of the Web 2.0 group. Trial registration number ACTRN12611000157976. PMID:28049624

Sex, Adiposity, and Hypertension Status Modify the Inverse Effect of Marine Food Intake on Blood Pressure in Alaska Native (Yup’ik) People123

PubMed Central

Beaulieu-Jones, Brendin R; O’Brien, Diane M; Hopkins, Scarlett E; Moore, Jason H; Boyer, Bert B; Gilbert-Diamond, Diane

2015-01-01

Background: Alaska Native people currently have a higher prevalence of hypertension than do nonnative Alaskans, although in the 1950s hypertension was rare among Alaska Native people. A novel biomarker of marine foods, the nitrogen isotope ratio (δ15N) in RBCs was shown to be negatively associated with systolic and diastolic blood pressure. Few studies have examined how individual characteristics modify the association of marine food intake with blood pressure. Objective: This exploratory analysis examined whether sex, adiposity, and hypertension modify the inverse association between marine food intake and blood pressure. Methods: We used covariate-adjusted linear models to describe the association between δ15N and blood pressure in 873 adult Alaska Native (Yup’ik) people who resided in 8 communities in southwest Alaska. We separately stratified by sex, body mass index (BMI) group, abdominal obesity, and hypertension status and assessed the interaction between δ15N and participant characteristics on blood pressure via likelihood ratio tests. Results: The association between δ15N and systolic blood pressure was modified by sex, BMI status, and abdominal obesity, with the inverse association observed only in the male (β = −1.5; 95% CI: −2.4, −0.6), nonobese BMI (β = −1.7; 95% CI: −2.5, −1.0), and non–abdominally obese (β = −1.6; 95% CI: −2.4, −0.9) strata (all P-interaction < 0.0001). A reduction in diastolic blood pressure associated with δ15N was observed in the nonobese BMI (β = −1.1; 95% CI: −1.7, −0.5) and non–abdominally obese (β = −1.1; 95% CI: −1.7, −0.5) strata, although only the interaction between BMI group and δ15N with diastolic blood pressure was significant. The inverse association between δ15N and both systolic and diastolic blood pressure was observed in nonhypertensive individuals, although the comparison had limited power. The results were consistent with those identified by using combined RBC concentrations of eicosapentaenoic acid and docosahexaenoic acid as the biomarker of marine food intake, although the associations identified by using δ15N were larger. Conclusions: Obesity status modified the inverse association between marine food intake and both systolic and diastolic blood pressure in adult Alaska Native (Yup’ik) people. The inverse association between δ15N and systolic blood pressure was also modified by sex. PMID:25788581

Environmental tobacco smoking, mutagen sensitivity, and head and neck squamous cell carcinoma.

PubMed

Zhang, Z F; Morgenstern, H; Spitz, M R; Tashkin, D P; Yu, G P; Hsu, T C; Schantz, S P

2000-10-01

Although active tobacco smoking has been considered a major risk factor for head and neck cancer, few studies have evaluated environmental tobacco smoke (ETS) and its interaction with mutagen sensitivity on the risk of head and neck cancer. We investigated the relationship between ETS and head and neck cancer in a case-control study of 173 previously untreated cases with pathologically confirmed diagnoses of squamous cell carcinoma of the head and neck and 176 cancer-free controls at Memorial Sloan-Kettering Cancer Center between 1992 and 1994. A structured questionnaire was used to collect ETS exposure and other covariates including a history of active tobacco smoking and alcohol use. ETS measures include a history of ETS exposure at home and at workplace. The associations between passive smoking and head and neck cancer were analyzed by Mantel-Haenszel methods and logistic regression models. Additive and multiplicative models were used to evaluate effect modifications between ETS and mutagen sensitivity. The crude odds ratio (OR) for ETS exposure was 2.8 [95% confidence intervals (CI), 1.3-6.0]. Controlling for age, sex, race, education, alcohol consumption, pack-years of cigarette smoking, and marijuana use, the risk of squamous cell carcinoma of the head and neck was increased with ETS (adjusted OR, 2.4; 95% CI, 0.9-6.8). Dose-response relationships were observed for the degree of ETS exposure; the adjusted ORs were 2.1 (95% CI, 0.7-6.1) for those with moderate exposure and 3.6 (95% CI, 1.1-11.5) for individuals with heavy exposure (P for trend = 0.025), in comparison with those who never had ETS exposures. These associations and the dose-response relationships were still present when the analysis was restricted to nonactive smoking cases and controls (crude OR, 2.2; 95% CI, 0.6-8.4). Crude odds ratios were 1.8 for those with moderate ETS exposure and 4.3 for individuals with heavy ETS exposure among nonsmoking cases and controls (P for trend = 0.008). More than multiplicative interaction was suggested between passive smoking and mutagen sensitivity. This study suggests that ETS exposure may increase the risk of head and neck cancer with a dose-response pattern. Our analysis indicated that passive smoking may interact with mutagen sensitivity and other risk factors to increase the risk of head and neck cancer. Our results need to be interpreted with caution because of potential residual confounding effects of active tobacco smoking and other methodological limitations. Future large-scale studies are warranted to confirm our findings.

APOA2, Dietary Fat and Body Mass Index: Replication of a Gene-Diet Interaction in Three Independent Populations

PubMed Central

Corella, Dolores; Peloso, Gina; Arnett, Donna K.; Demissie, Serkalem; Cupples, L Adrienne; Tucker, Katherine; Lai, Chao-Qiang; Parnell, Laurence D.; Coltell, Oscar; Lee, Yu-Chi; Ordovas, Jose M.

2010-01-01

Background Nutrigenetics studies the role of genetic variation on interactions between diet and health aimed at providing more personalized dietary advice. However, replication has been very low. Our aim was to study the interaction between a functional APOA2 polymorphism, food intake and body mass index (BMI) in independent populations to replicate findings and to increase their evidence level. Methods Cross-sectional, follow-up (20 years) and case-control analyses were undertaken in three independent populations. We analyzed gene-diet interactions between the APOA2 -265T>C polymorphism and saturated fat (SATFAT) intake on BMI and obesity in 3,462 subjects from three American populations: Framingham (1,454 Whites), GOLDN (1,078 Whites) and Boston-Puerto Rican studies (930 Hispanics of Caribbean origin). Results Prevalence of CC subjects ranged from 11-15%. We identified statistically significant interactions between the APOA2 -265T>C and SATFAT on BMI in all three populations. Thus, the magnitude of the difference in BMI between the CC and TT+TC subjects differed by SATFAT. A mean increase of 6.2% BMI (ranging from 4.3%-7.9%; P<0.05), was observed between genotypes with high (>=22g/d), but not with low SATFAT intake in all studies. Likewise, the CC genotype was significantly associated with higher obesity prevalence in all populations only in the high-SATFAT stratum. Meta-analysis estimations of obesity for CC compared with TT+TC subjects were: OR=1.84, 95%CI:1.38-2.47; P<0.0001 in the high-SATFAT stratum, but no association was detected in the low-SATFAT stratum (OR=0.81, 95%CI:0.59-1.11;P=0.181). Conclusions For the first time, a gene-diet interaction influencing BMI and obesity has been strongly and consistently replicated in three independent populations. PMID:19901143

Synergistic Effects of Perioperative Complications on 30-Day Mortality Following Hepatopancreatic Surgery.

PubMed

Merath, Katiuscha; Chen, Qinyu; Bagante, Fabio; Akgul, Ozgur; Idrees, Jay J; Dillhoff, Mary; Cloyd, Jordan M; Pawlik, Timothy M

2018-06-18

Data on the interaction effect of multiple concurrent postoperative complications relative to the risk of short-term mortality following hepatopancreatic surgery have not been reported. The objective of the current study was to define the interaction effect of postoperative complications among patients undergoing HP surgery on 30-day mortality. Using the ACS-NSQIP Procedure Targeted Participant Use Data File, patients who underwent HP surgery between 2014 and 2016 were identified. Hazard ratios (HRs) for 30-day mortality were estimated using Cox proportional hazard models. Two-way interaction effects assessing combinations of complications relative to 30-day mortality were calculated using the relative excess risk due to interaction (RERI) in separate adjusted Cox models. Among 26,824 patients, 10,886 (40.5%) experienced at least one complication. Mortality was higher among patients who experienced at least one complication versus patients who did not experience a complication (3.0 vs 0.1%, p < 0.001). The most common complications were blood transfusion (16.9%, n = 4519), organ space infection (12.2%, n = 3273), and sepsis/septic shock (8.2%, n = 2205). Combinations associated with additive effect on mortality included transfusion + renal dysfunction (RERI 12.3, 95% CI 5.2-19.4), pulmonary dysfunction + renal dysfunction (RERI 60.9, 95% CI 38.6-83.3), pulmonary dysfunction + cardiovascular complication (RERI 144.1, 95% CI 89.3-199.0), and sepsis/septic shock + renal dysfunction (RERI 11.5, 95% CI 4.4-18.7). Both the number and specific type of complication impacted the incidence of postoperative mortality among patients undergoing HP surgery. Certain complications interacted in a synergistic manner, leading to a greater than expected increase in the risk of short-term mortality.

Effects of primary care team social networks on quality of care and costs for patients with cardiovascular disease.

PubMed

Mundt, Marlon P; Gilchrist, Valerie J; Fleming, Michael F; Zakletskaia, Larissa I; Tuan, Wen-Jan; Beasley, John W

2015-03-01

Cardiovascular disease is the leading cause of mortality and morbidity in the United States. Primary care teams can be best suited to improve quality of care and lower costs for patients with cardiovascular disease. This study evaluates the associations between primary care team communication, interaction, and coordination (ie, social networks); quality of care; and costs for patients with cardiovascular disease. Using a sociometric survey, 155 health professionals from 31 teams at 6 primary care clinics identified with whom they interact daily about patient care. Social network analysis calculated variables of density and centralization representing team interaction structures. Three-level hierarchical modeling evaluated the link between team network density, centralization, and number of patients with a diagnosis of cardiovascular disease for controlled blood pressure and cholesterol, counts of urgent care visits, emergency department visits, hospital days, and medical care costs in the previous 12 months. Teams with dense interactions among all team members were associated with fewer hospital days (rate ratio [RR] = 0.62; 95% CI, 0.50-0.77) and lower medical care costs (-$556; 95% CI, -$781 to -$331) for patients with cardiovascular disease. Conversely, teams with interactions revolving around a few central individuals were associated with increased hospital days (RR = 1.45; 95% CI, 1.09-1.94) and greater costs ($506; 95% CI, $202-$810). Team-shared vision about goals and expectations mediated the relationship between social network structures and patient quality of care outcomes. Primary care teams that are more interconnected and less centralized and that have a shared team vision are better positioned to deliver high-quality cardiovascular disease care at a lower cost. © 2015 Annals of Family Medicine, Inc.

Alcohol intake and early-onset basal cell carcinoma in a case-control study

PubMed Central

Zhang, Y; Ferrucci, L.M.; Cartmel, B.; Molinaro, A.M.; Leffell, D.J.; Bale, A.E.; Mayne, S.T.

2014-01-01

Background Previous epidemiologic studies of overall alcohol intake and basal cell carcinoma (BCC) are inconsistent, with some evidence for differences by type of alcoholic beverage. While alcohol may enhance the carcinogenicity of ultraviolet (UV) light, this has not been evaluated in existing epidemiologic studies. Objective To evaluate alcohol intake in relation to early-onset BCC, and explore potential interactions with UV exposure. Methods BCC cases (n=380) and controls with benign skin conditions (n=390) under age 40 were identified through Yale Dermatopathology. Participants provided information on lifetime alcohol intake, including type of beverage during an in-person interview. Self-report data on indoor tanning and outdoor sunbathing were used to categorize UV exposure. We calculated odds ratios (OR) and 95% confidence intervals (CI) using unconditional multivariate logistic regression in the full sample and in women only. Results There was no statistically significant association between lifetime alcohol intake and early-onset BCC overall (above median intake vs. no regular alcohol intake OR 1.10, 95% CI 0.69-1.73) or in women only (OR 1.21, 95% CI 0.73-2.01). Similarly, intake of red wine, white wine, beer or hard liquor and mixed drinks was not associated with early-onset BCC. In exploratory analyses, we saw limited evidence for an interaction (pinteraction=0.003), with highest risk for high alcohol and high UV exposures, especially in women, but subgroup risk estimates had wide and overlapping confidence intervals. Conclusions Overall, we did not observe any clear association between lifetime alcohol intake and early-onset BCC. PMID:25059635

Risk factors for pulmonary tuberculosis in Croatia: a matched case–control study

PubMed Central

2013-01-01

Background Mycobacterium tuberculosis is a necessary, but not sufficient, cause of tuberculosis. A number of studies have addressed the issue of risk factors for tuberculosis development. Croatia is a European country with an incidence rate of 14/100 000 which is slowly decreasing. The aim of this study is to evaluate the potential demographic, socioeconomic, behavioural and biological risk factors for tuberculosis in Croatia in comparison to other high-income, low-incidence European countries. Methods A total of 300 tuberculosis patients were matched for age, sex and county of residence to 300 controls randomly selected from general practitioners’ registers. They were interviewed and their medical records were evaluated for variables broadly described as potential risk factors. Results In multiple logistic regression, the following factors were significant: parents born in a particular neighbouring county (Bosnia and Herzegovina) (OR = 3.90, 95% CI 2.01-7.58), the lowest level of education (OR = 3.44, 95% CI 1.39-8.50), poor household equipment (OR = 4.72, 95% CI 1.51-14.76), unemployment (OR = 2.69, 95% CI 1.18-6.16), contact with tuberculosis (OR = 2.19, 95% CI 1.27-3.77), former (OR = 2.27, 95% CI 1.19-4.33) and current smoking habits (OR = 2.35, 95% CI 1.27-4.36), diabetes (OR = 2.38, 95% CI 1.05-5.38), a malignant disease (OR = 5.79, 95% CI 1.49-22.42), being underweight in the previous year (OR = 13.57, 95% CI 1.21-152.38). Conclusion In our study, the identified risk groups for tuberculosis reflect a complex interaction between socioeconomic conditions, lifestyle and non-communicable diseases. Interventions focused on poverty will undoubtedly be useful, but not sufficient. Tuberculosis control would benefit from a combination of broad public health activities aimed at the prevention and control of risky lifestyles and non-communicable diseases, interventions outside the health sector, and efforts to constantly improve the Croatian national tuberculosis programme. PMID:24144113

Work environment and health in the fishing fleet: results from a survey amongst Norwegian fishers.

PubMed

Sønvisen, Signe Annie; Thorvaldsen, Trine; Holmen, Ingunn M; Øren, Anita

Fishery is an important industry in Norway. Compared to other industries the number of occupational accidents is high. Fishers are exposed to a range of unfavourable working conditions, but there is limited research-based knowledge about the interaction between working conditions and health. The aim of the article is to study fishers' 1) work-related exposures and health complaints, 2) sickness absence, 3) subjective perception of health status and 3) level of job satisfaction. Data was gathered through a telephone survey. The survey included questions about exposure, health complaints, health status and job satisfaction. Methods for analysis were descriptive statistics and relative risk (RR). A total of 830 full-time fishers were interviewed. Coastal fishers are more exposed to factors such as climatic (RR = 1.546, 95% confidence interval [CI] 1.311-1.823), ergonomic (RR = 1.539, 95% CI 1.293-1.833) and processing (RR = 2.119, 95% CI 1.847-2.431), compared to other groups of fishers. Coastal fishers are also more likely to experience musculoskeletal problems (RR = 1.623, 95% CI 1.139-2.314), sickness absence (RR = 1.337, 95% CI 1.081-1.655) and to perceive their own health as poor (RR = 2.155, 95% CI 1.119-4.152). Purse sein fishers are less exposed to climatic (RR = 0.777, 95% CI 0.633-0.953), ergonomic (RR = 0.617, 95% CI 0.487-0.783) and processing (RR = 0.292, 95% CI 0.221-0.385) factors and are less likely to experience sickness absence (RR = 0.635, 95% CI 0.479-0.840). In terms of job satisfaction, 99% if our respondents enjoy their work. Norwegian fishers have a high degree of job satisfaction and overall good health. Challenges regarding health complaints and exposures in the working environment were identified. This may be helpful for the industry, showing where measures should be implemented to prevent exposure, illness and sickness absence. Findings may also serve as a basis for future intervention studies aimed at promoting healthy working environments for fishers, especially how to improve vessels and develop user-friendly technology to reduce risk of injuries and strain.

Genetic Susceptible Locus in NOTCH2 Interacts with Arsenic in Drinking Water on Risk of Type 2 Diabetes

PubMed Central

Pan, Wen-Chi; Kile, Molly L.; Seow, Wei Jie; Lin, Xihong; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Mostofa, Golam; Lu, Quan; Christiani, David C.

2013-01-01

Background Chronic exposure to arsenic in drinking water is associated with increased risk of type 2 diabetes mellitus (T2DM) but the underlying molecular mechanism remains unclear. Objectives This study evaluated the interaction between single nucleotide polymorphisms (SNPs) in genes associated with diabetes and arsenic exposure in drinking water on the risk of developing T2DM. Methods In 2009–2011, we conducted a follow up study of 957 Bangladeshi adults who participated in a case-control study of arsenic-induced skin lesions in 2001–2003. Logistic regression models were used to evaluate the association between 38 SNPs in 18 genes and risk of T2DM measured at follow up. T2DM was defined as having a blood hemoglobin A1C level greater than or equal to 6.5% at follow-up. Arsenic exposure was characterized by drinking water samples collected from participants' tubewells. False discovery rates were applied in the analysis to control for multiple comparisons. Results Median arsenic levels in 2001–2003 were higher among diabetic participants compared with non-diabetic ones (71.6 µg/L vs. 12.5 µg/L, p-value <0.001). Three SNPs in ADAMTS9 were nominally associated with increased risk of T2DM (rs17070905, Odds Ratio (OR)  = 2.30, 95% confidence interval (CI) 1.17–4.50; rs17070967, OR = 2.02, 95%CI 1.00–4.06; rs6766801, OR = 2.33, 95%CI 1.18–4.60), but these associations did not reach the statistical significance after adjusting for multiple comparisons. A significant interaction between arsenic and NOTCH2 (rs699780) was observed which significantly increased the risk of T2DM (p for interaction = 0.003; q-value = 0.021). Further restricted analysis among participants exposed to water arsenic of less than 148 µg/L showed consistent results for interaction between the NOTCH2 variant and arsenic exposure on T2DM (p for interaction  = 0.048; q-value = 0.004). Conclusions These findings suggest that genetic variation in NOTCH2 increased susceptibility to T2DM among people exposed to inorganic arsenic. Additionally, genetic variants in ADAMTS9 may increase the risk of T2DM. PMID:23967108

Breast Cancer Adjuvant Chemotherapy Decisions in Older Women: The Role of Patient Preference and Interactions With Physicians

PubMed Central

Mandelblatt, Jeanne S.; Sheppard, Vanessa B.; Hurria, Arti; Kimmick, Gretchen; Isaacs, Claudine; Taylor, Kathryn L.; Kornblith, Alice B.; Noone, Anne-Michelle; Luta, Gheorghe; Tallarico, Michelle; Barry, William T.; Hunegs, Lisa; Zon, Robin; Naughton, Michael; Winer, Eric; Hudis, Clifford; Edge, Stephen B.; Cohen, Harvey Jay; Muss, Hyman

2010-01-01

Purpose Breast cancer chemotherapy decisions in patients ≥ 65 years old (older) are complex because of comorbidity, toxicity, and limited data on patient preference. We examined relationships between preferences and chemotherapy use. Methods Older women (n = 934) diagnosed with invasive (≥ 1 cm), nonmetastatic breast cancer from 2004 to 2008 were recruited from 53 cooperative group sites. Data were collected from patient interviews (87% complete), physician survey (93% complete), and charts. Logistic regression and multiple imputation methods were used to assess associations between chemotherapy and independent variables. Chemotherapy use was also evaluated according to the following two groups: indicated (estrogen receptor [ER] negative and/or node positive) and possibly indicated (ER positive and node negative). Results Mean patient age was 73 years (range, 65 to 100 years). Unadjusted chemotherapy rates were 69% in the indicated group and 16% in the possibly indicated group. Women who would choose chemotherapy for an increase in survival of ≤ 12 months had 3.9 times (95% CI, 2.4 to 6.3 times; P < .001) higher odds of receiving chemotherapy than women with lower preferences, controlling for covariates. Stronger preferences were seen when chemotherapy could be indicated (odds ratio [OR] = 7.7; 95% CI, 3.8 to 16; P < .001) than when treatment might be possibly indicated (OR = 1.9; 95% CI, 1.0 to 3.8; P = .06). Higher patient rating of provider communication was also related to chemotherapy use in the possibly indicated group (OR = 1.9 per 5-point increase in communication score; 95% CI, 1.4 to 2.8; P < .001) but not in the indicated group (P = .15). Conclusion Older women's preferences and communication with providers are important correlates of chemotherapy use, especially when benefits are more equivocal. PMID:20516438

Physical Activity Modifies the Effect of LPL, LIPC and CETP polymorphisms on HDL-C Levels and the Risk of Myocardial Infarction in Caucasian Women

PubMed Central

Ahmad, Tariq; Chasman, Daniel I.; Buring, Julie E.; Lee, I-Min; Ridker, Paul M; Everett, Brendan M.

2010-01-01

Background Recent genome-wide association studies have identified common variants associated with high-density lipoprotein cholesterol (HDL-C). Whether these associations are modified by physical activity, which increases HDL-C levels and reduces the risk of cardiovascular disease (CVD), is uncertain. Methods and Results In a prospective cohort study of 22,939 apparently healthy Caucasian US women, we selected 58 single nucleotide polymorphisms (SNPs) in 9 genes that demonstrated genome-wide association (P<5×10−8) with HDL-C levels and sought evidence of effect modification according to levels of physical activity (PA). PA modified the effects on HDL-C of 7 SNPs at 3 loci, and the strongest evidence of effect was observed for rs10096633 at LPL, rs1800588 at LIPC and rs1532624 at CETP (each P-interaction <0.05). The per-minor-allele increase in HDL-C for rs1800588 at LIPC and rs1532624 at CETP was greater in active than inactive women, whereas the reverse was observed for rs10096633 at LPL. Minor-allele carrier status at the LPL SNP was associated with a reduced risk of MI in active (Hazard Ratio [HR] 0.42, 95% Confidence Interval [CI] 0.23–0.76) but not amongst inactive women (HR 1.10, 95% CI 0.83–1.44; P-interaction=0.007). By contrast, carrier status at the CETP SNP was associated with a reduced risk of MI regardless of activity level (HR 0.72, 95% CI 0.57–0.92; P-interaction=0.71). No association between LIPC SNP carrier status and MI risk was noted Conclusions The effects of common variants in the LPL, LIPC and CETP genes on HDL-C levels are modified by PA. For a common variant in LPL, the impact on MI varied by activity level, while the effects of a common variant in CETP on MI risk did not. PMID:21252145

HLA-Cw*0602 associates with a twofold higher prevalence of positive streptococcal throat swab at the onset of psoriasis: a case control study

PubMed Central

Mallbris, Lotus; Wolk, Katarina; Sánchez, Fabio; Ståhle, Mona

2009-01-01

Background The influence of streptococcal infections in the pathogenesis of psoriasis is not yet understood. In vitro data suggest that streptococcal factors influence T-cell function in psoriasis in a HLA-dependent manner, but studies designed to measure the HLA-C/Streptococci interaction are lacking. In the present study, we hypothesized that there is a statistical interaction between the result of streptococcal throat cultures and the presence of the HLA-Cw*0602 allele in psoriasis patients. Methods We performed a case control study using the "Stockholm Psoriasis Cohort" consisting of patients consecutively recruited within 12 months of disease onset (Plaque psoriasis = 439, Guttate psoriasis = 143), matched to healthy controls (n = 454) randomly chosen from the Swedish Population Registry. All individuals underwent physical examination including throat swabs and DNA isolation for HLA-Cw*0602 genotyping. The prevalence of positive streptococcal throat swabs and HLA-Cw*0602 was compared between patients and controls and expressed as odds ratios with 95% confidence intervals. Associations were evaluated separately for guttate and plaque psoriasis by Fisher's exact test. Results Regardless of disease phenotype, the prevalence of positive streptococcal throat swabs in HLA-Cw*0602 positive patients was twice the prevalence among HLA-Cw*0602 negative patients (OR = 5.8 C.I. = 3.57–9.67, p < 0.001), while no difference was observed among Cw*0602 positive versus negative controls. The corresponding odds ratios for the guttate and plaque psoriasis phenotypes were 3.5 (CI = 1.5–8.7, p = 0.01) and 2.3 (CI = 1.0–5.1, p = 0.02) respectively. Conclusion These findings suggest that among HLA-Cw*0602 positive psoriasis patients, streptococci may contribute to the onset or exacerbation of the inflammatory process independent of the disease phenotype. However, studies on the functional interaction between HLA-C and streptococcal factors are needed. PMID:19480679

Difficulties with Emotion Regulation and Psychopathology Interact to Predict Early Smoking Cessation Lapse.

PubMed

Farris, Samantha G; Zvolensky, Michael J; Schmidt, Norman B

2016-06-01

There is little knowledge about how emotion regulation difficulties interplay with psychopathology in terms of smoking cessation. Participants ( n = 250; 53.2 % female, M age = 39.5, SD = 13.85) were community-recruited daily smokers (≥8 cigarettes per day) who self-reported motivation to quit smoking; 38.8 % of the sample met criteria for a current (past 12-month) psychological disorder. Emotion regulation deficits were assessed pre-quit using the Difficulties with Emotion Regulation Scale (DERS; Gratz and Roemer in J Psychopathol Behav Assess 26(1):41-54, 2004) and smoking behavior in the 28 days post-quit was assessed using the Timeline Follow-Back (TLFB; Sobell and Sobell in Measuring alcohol consumption: psychosocial and biochemical methods. Humana Press, Totowa, 1992). A Cox proportional-hazard regression analysis was used to model the effects of past-year psychopathology, DERS (total score), and their interaction, in terms of time to lapse post-quit day. After adjusting for the effects of gender, age, pre-quit level of nicotine dependence, and treatment condition, the model revealed a non-significant effect of past-year psychopathology ( OR = 1.14, CI 95 % = 0.82-1.61) and difficulties with emotion regulation ( OR = 1.01, CI 95 % = 1.00-1.01) on likelihood of lapse rate. However, the interactive effect of psychopathology status and difficulties with emotion regulation was significant ( OR = 0.98, CI 95 % = 0.97-0.99). Specifically, there was a significant conditional effect of psychopathology status on lapse rate likelihood at low, but not high, levels of emotion regulation difficulties. Plots of the cumulative survival functions indicated that for smokers without a past-year psychological disorder, those with lower DERS scores relative to elevated DERS scores had significantly lower likelihood of early smoking lapse, whereas for smokers with past-year psychopathology, DERS scores did not differentially impact lapse rate likelihood. Smokers with emotion regulation difficulties may have challenges quitting, and not having such difficulties, especially without psychopathology, decreases the potential likelihood of early lapse.

B-Type Natriuretic Peptide Assessment in Patients Undergoing Revascularization for Left Main Coronary Artery Disease: Analysis from the EXCEL Trial.

PubMed

Redfors, Björn; Chen, Shmuel; Crowley, Aaron; Ben-Yehuda, Ori; Gersh, Bernard J; Lembo, Nicholas J; Brown, W Morris; Banning, Adrian P; Taggart, David P; Serruys, Patrick W; Kappetein, Arie Pieter; Sabik, Joseph F; Stone, Gregg W

2018-04-17

Background -Elevated B-type natriuretic peptide (BNP) is reflective of impaired cardiac function and is associated with worse prognosis among patients with coronary artery disease (CAD). We sought to assess the association between baseline BNP, adverse outcomes, and the relative efficacy of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with left main (LM) CAD. Methods -The EXCEL trial randomized patients with LMCAD and low or intermediate SYNTAX scores to PCI with everolimus-eluting stents versus CABG. The primary endpoint was the composite of all-cause death, myocardial infarction (MI) or stroke. We used multivariable Cox proportional hazards regression to assess the associations between normal versus elevated BNP (≥100 pg/mL), randomized treatment, and the 3-year risk of adverse events. Results -BNP at baseline was elevated in 410 of 1037 (39.5%) patients enrolled in EXCEL. Patients with elevated BNP levels were older and more frequently had additional cardiovascular risk factors and lower LVEF than those with normal BNP, but had similar SYNTAX scores. Patients with elevated BNP had significantly higher 3-year rates of the primary endpoint (18.6% vs. 11.7%, adjusted HR 1.62, 95% CI 1.16-2.28, P=0.005), and higher mortality (11.5% vs. 3.9%, adjusted HR 2.49, 95% CI 1.48-4.19, P=0.0006), both from cardiovascular and non-cardiovascular causes. In contrast, there were no significant differences in the risks of MI, stroke, ischemia-driven revascularization, stent thrombosis, graft occlusion, or major bleeding. A significant interaction (P interaction =0.03) was present between elevated versus normal BNP and treatment with PCI versus CABG for the adjusted risk of the primary composite endpoint at 3 years among patients with elevated BNP (adjusted HR for PCI versus CABG 1.54, 95% CI 0.96-2.47) versus normal BNP (adjusted HR 0.74, 95% CI 0.46-1.20). This interaction was stronger when log(BNP) was modeled as a continuous variable (P interaction =0.002). Conclusions -In the EXCEL trial, elevated baseline BNP levels in patients with LMCAD undergoing revascularization were independently associated with long-term mortality but not non-fatal adverse ischemic or bleeding events. The relative long-term outcomes after PCI vs. CABG for revascularization of LMCAD may be conditioned by the baseline BNP level. Clinical Trial Registration -URL: http://www.clinicaltrials.gov. Unique identifier: NCT01205776.

Mobile phone-based interventions for improving contraception use.

PubMed

Smith, Chris; Gold, Judy; Ngo, Thoai D; Sumpter, Colin; Free, Caroline

2015-06-26

Contraception provides significant benefits for women's and children's health, yet an estimated 225 million women had an unmet need for modern contraceptive methods in 2014. Interventions delivered by mobile phone have been demonstrated to be effective in other health areas, but their effects on use of contraception have not been established. To assess the effects of mobile phone-based interventions for improving contraception use. We searched for randomised controlled trials (RCTs) of client-provider interventions delivered by mobile phone to improve contraception use compared with standard care or another intervention. We searched the electronic databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Global Health, PsycINFO, POPLINE, Africa-Wide Information and Latin American Caribbean Health Sciences Literature (LILACS) from January 1993 to October 2014, as well as clinical trials registries, online mHealth resources and abstracts from key conferences. Randomised controlled trials of mobile phone-based interventions to improve any form of contraception use amongst users or potential users of contraception. Outcome measures included uptake of contraception, measures of adherence, pregnancy and abortion. Two review authors independently screened titles and abstracts of studies retrieved using the search strategy and extracted data from the included studies. We calculated the Mantel-Haenszel risk ratio (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes, together with 95% confidence intervals (CIs). Differences in interventions and outcome measures did not permit us to undertake meta-analysis. Five RCTs met our inclusion criteria. Three trials aimed to improve adherence to a specific method of contraception amongst existing or new contraception users by comparing automated text message interventions versus standard care. Two trials aimed to improve both uptake and adherence, not limited to one method, in both users and non-users of contraception. No trials were at low risk of bias in all areas assessed.One trial in the USA reported improved self reported oral contraceptive (OC) continuation at six months from an intervention comprising a range of uni-directional and interactive text messages (RR 1.19, 95% CI 1.05 to 1.35). One trial in Cambodia reported increased self reported use of effective contraception at four months post abortion from an intervention comprising automated interactive voice messages and phone counsellor support (RR 1.39, 95% CI 1.17 to 1.66).One feasibility trial in the USA reported a lower mean number of days between scheduled and completed attendance for the first but not subsequent Depo-Provera appointments using clinic records from an intervention comprising reminders and healthy self management text messages (mean difference (MD) -8.60 days, 95% CI -16.74 to -0.46). Simple text message OC reminders had no effect on missed pills as assessed by electronic medication monitoring in a small trial in the USA (MD 0.5 missed pills, 95% CI -1.08 to 2.08). No effect on self reported contraception use was noted amongst isotretinoin users from an intervention that provided health information via two uni-directional text messages and mail (RR 1.26, 95% CI 0.84 to 1.89). One trial assessed potential adverse effects of the intervention and reported no evidence of road traffic accidents or domestic abuse. Our review provides limited evidence that interventions delivered by mobile phone can improve contraception use. Whilst evidence suggests that a series of interactive voice messages and counsellor support can improve post-abortion contraception, and that a mixture of uni-directional and interactive daily educational text messages can improve OC adherence, the cost-effectiveness and long-term effects of these interventions remain unknown. Further high-quality trials are required to robustly establish the effects of interventions delivered by mobile phone to improve contraception use.

Association of Genetic Markers in the BCL-2 Family of Apoptosis-Related Genes with Endometrial Cancer Risk in a Chinese Population

PubMed Central

Dorjgochoo, Tsogzolmaa; Xiang, Yong-Bing; Long, Jirong; Shi, Jiajun; Deming, Sandra; Xu, Wang-Hong; Cai, Hui; Cheng, Jiarong; Cai, Qiuyin; Zheng, Wei; Shu, Xiao-Ou

2013-01-01

Background In vitro studies have demonstrated the role of the BCL-2 family of genes in endometrial carcinogenesis. The role of genetic variants in BCL-2 genes and their interactions with non-genetic factors in the development of endometrial cancer has not been investigated in epidemiological studies. Patients and Methods We examined the relationship between BCL-2 gene family variants and endometrial cancer risk among 1,028 patients and 1,922 age-matched community controls from Shanghai, China. We also investigated possible interactions between genetic variants and established risk factors (demographic, lifestyle and clinical). Individuals were genotyped for 86 tagging single nucleotide polymorphisms (SNPs) in the BCL2, BAX, BAD and BAK1 genes. Results Significant associations with endometrial cancer risk were found for 9 SNPs in the BCL2 gene (P trend<0.05 for all). For SNPs rs17759659 and rs7243091 (minor allele for both: G), the associations were independent. The odds ratio was 1.27 (95% CI: 1.04–1.53) for women with AG genotype for the SNP rs17759659 and 1.82 (95% CI: 1.21–2.73) for women with the GG genotype for the SNP rs7243091. No interaction between these two SNPs and established non-genetic risk factors of endometrial cancer was noticed. Conclusion Genetic polymorphisms in the BCL2 gene may be associated with the risk of endometrial cancer in Chinese women. PMID:23637776

Dating Violence: Outcomes Following a Brief Motivational Interviewing Intervention Among At-risk Adolescents in an Urban Emergency Department

PubMed Central

Cunningham, Rebecca M.; Whiteside, Lauren K.; Chermack, Stephen T.; Zimmerman, Marc A.; Shope, Jean T.; Bingham, C. Raymond; Blow, Frederic C.; Walton, Maureen A.

2013-01-01

Objectives A recent study demonstrated the efficacy of the SafERteens intervention in reducing peer violence among adolescents presenting to the emergency department (ED). The objective of this study was to determine the efficacy of this ED-based brief intervention (BI) on dating violence 1 year following the ED visit among the subsample of adolescents in the original randomized controlled trial reporting past-year dating violence. Methods Patients (aged 14 to 18 years) at an ED were eligible for inclusion if they had past-year violence and alcohol use. Participants were randomized to one of three conditions (BI delivered by a computer [CBI], BI delivered by a therapist and a computer (T+CBI), or control) and completed follow-ups at 3, 6, and 12 months. In addition to content on alcohol misuse and peer violence, adolescents reporting dating violence received a tailored module on dating violence. The outcome of interest was frequency of moderate and severe dating violence victimization and aggression (baseline and 3, 6, and 12 months after ED visit). Results Among eligible adolescents, 55% (n = 397) reported dating violence and were included in these analyses. Compared to the control group (who received a resource brochure only), participants in the CBI showed reductions in moderate dating victimization at 3 months (inter-rater reliability [IRR] = 0.71; 95% confidence interval [CI] = 0.51 to 0.99; p < 0.05) and 6 months (IRR = 0.56; 95% CI = 0.38 to 0.83; p < 0.01). Models examining interaction effects were significant for the CBI on moderate dating victimization at 3 months (IRR = 0.81; 95% CI = 0.67 to 0.98; p < 0.05) and 6 months (IRR = 0.81; 95% CI = 0.66 to 0.99; p < 0.05). Significant interaction effects were found for the T+CBI on moderate dating violence victimization at 6 months (IRR = 0.81; 95% CI = 0.69 to 0.96; p < 0.01) and 12 months (IRR = 0.76; 95% CI = 0.63 to 0.90; p < 0.001) and severe dating violence victimization at 3 months (IRR = 0.76; 95% CI = 0.59 to 0.96; p < 0.05). Conclusions ED-based BIs tailored to address multiple risk behaviors (i.e., peer violence, alcohol use, and dating violence) show promise for reducing moderate and severe dating victimization for up to 1 year following an ED visit. PMID:23758302

The Relationship Between Long-Term Sunlight Radiation and Cognitive Decline in the REGARDS Cohort Study

PubMed Central

Kent, Shia T.; Kabagambe, Edmond K.; Wadley, Virginia G.; Howard, Virginia J.; Crosson, William L.; Al-Hamdan, Mohammad Z.; Judd, Suzanne E.; Peace, Fredrick; McClure, Leslie A.

2013-01-01

BACKGROUND Sunlight may be related to cognitive function through vitamin D metabolism or circadian rhythm regulation. METHODS Fifteen-year residential history merged with satellite and ground monitor data were used to determine sunlight (solar radiation) and air temperature exposure for a cohort of 19,896 cognitively intact black and white participants aged 45+ from the 48 contiguous United States. 15, 10, 5, 2, and 1-year exposures were used to predict cognitive status at the most recent assessment in logistic regression models. RESULTS 1-year insolation and maximum temperatures were chosen as exposure measures. Solar radiation interacted with temperature, age, and gender in its relationships with incident cognitive impairment. After adjustment for covariates, the odds ratios of cognitive decline for solar radiation exposure below the median vs. above the median in the 3rd tertile of maximum temperatures was 1.88 (95% CI: 1.24, 2.85), the 2nd tertile was 1.33 (95% CI: 1.09, 1.62), and 1st tertile was 1.22 (95% CI: 0.92, 1.60). We also found that participants under 60 year old had an OR=1.63 (95% CI: 1.20, 2.22), those 60 to 80 years old had an OR=1.18 (95% CI: 1.02, 1.36), and those over 80 years old had an OR=1.05 (0.80, 1.37). Lastly, we found that males had an OR=1.43 (95% CI: 1.22, 1.69), and females had an OR=1.02 (0.87, 1.20). CONCLUSIONS We found that lower levels of solar radiation were associated with increased odds of incident cognitive impairment. PMID:23340910

Co-administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects

PubMed Central

Mueck, Wolfgang; Kubitza, Dagmar; Becka, Michael

2013-01-01

Aims The anticoagulant rivaroxaban is an oral, direct Factor Xa inhibitor for the management of thromboembolic disorders. Metabolism and excretion involve cytochrome P450 3A4 (CYP3A4) and 2J2 (CYP2J2), CYP-independent mechanisms, and P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) (ABCG2). Methods The pharmacokinetic effects of substrates or inhibitors of CYP3A4, P-gp and Bcrp (ABCG2) on rivaroxaban were studied in healthy volunteers. Results Rivaroxaban did not interact with midazolam (CYP3A4 probe substrate). Exposure to rivaroxaban when co-administered with midazolam was slightly decreased by 11% (95% confidence interval [CI] −28%, 7%) compared with rivaroxaban alone. The following drugs moderately affected rivaroxaban exposure, but not to a clinically relevant extent: erythromycin (moderate CYP3A4/P-gp inhibitor; 34% increase [95% CI 23%, 46%]), clarithromycin (strong CYP3A4/moderate P-gp inhibitor; 54% increase [95% CI 44%, 64%]) and fluconazole (moderate CYP3A4, possible Bcrp [ABCG2] inhibitor; 42% increase [95% CI 29%, 56%]). A significant increase in rivaroxaban exposure was demonstrated with the strong CYP3A4, P-gp/Bcrp (ABCG2) inhibitors (and potential CYP2J2 inhibitors) ketoconazole (158% increase [95% CI 136%, 182%] for a 400 mg once daily dose) and ritonavir (153% increase [95% CI 134%, 174%]). Conclusions Results suggest that rivaroxaban may be co-administered with CYP3A4 and/or P-gp substrates/moderate inhibitors, but not with strong combined CYP3A4, P-gp and Bcrp (ABCG2) inhibitors (mainly comprising azole-antimycotics, apart from fluconazole, and HIV protease inhibitors), which are multi-pathway inhibitors of rivaroxaban clearance and elimination. PMID:23305158

Prevalence and determinants of asthma in adult male leather tannery workers in Karachi, Pakistan: A cross sectional study

PubMed Central

Shahzad, Khurram; Akhtar, Saeed; Mahmud, Sadia

2006-01-01

Background This study aimed to estimate the prevalence and to identify some risk factors of adult asthma in male leather tannery workers in Karachi, Pakistan. Methods A cross sectional study was conducted from August 2003 to March 2004 on leather tannery workers of Karachi, Pakistan. Data were collected from 641 workers engaged in 95 different tanneries in Korangi industrial area selected as sample of convenience. Face to face interviews were performed using a structured pre-tested questionnaire by trained data collectors. Results Prevalence of adult asthma was 10.8% (69/641) in this study population. The prevalence of perceived work-related asthma was 5.3% (34/641). Multivariable logistic regression model showed that after taking into account the age effect, the leather tannery worker were more likely to be asthmatic, if they were illiterate (adjusted OR = 2.13, 95% CI: 1.17–3.88), of Pathan ethnicity (adjusted OR = 2.69; 95% CI: 1.35–5.36), ever-smoked (adjusted OR = 2.22, 95% CI: 1.16–4.26), reportedly never used gloves during different tanning tasks (OR = 3.28; 95% CI : 1.72–6.26). Also, the final model showed a significant interaction between perceived allergy and duration of work. Those who perceived to have allergy were more likely to have asthma if their duration of work was 8 years (adjusted OR = 2.26; 95% CI: 1.19 – 4.29) and this relationship was even stronger if duration was 13 years (adjusted OR = 3.67; 95% CI: 1.98–6.79). Conclusion Prevalence of asthma in leather tannery workers appears to be high and is associated with educational status, ethnicity, smoking, glove use, perceived to have allergy and duration of work. PMID:17144930

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peters, Junenette L., E-mail: jpeters@hsph.harvard.edu; Perlstein, Todd S.; Perry, Melissa J.

Background: It is unclear whether environmental cadmium exposure is associated with cardiovascular disease, although recent data suggest associations with myocardial infarction and peripheral arterial disease. Objective: The objective of this study was to evaluate the association of measured cadmium exposure with stroke and heart failure (HF) in the general population. Methods: We analyzed data from 12,049 participants, aged 30 years and older, in the 1999-2006 National Health and Nutrition Examination Survey (NHANES) for whom information was available on body mass index, smoking status, alcohol consumption, and socio-demographic characteristics. Results: At their interviews, 492 persons reported a history of stroke, andmore » 471 a history of HF. After adjusting for demographic and cardiovascular risk factors, a 50% increase in blood cadmium corresponded to a 35% increased odds of prevalent stroke [OR: 1.35; 95% confidence interval (CI): 1.12-1.65] and a 50% increase in urinary cadmium corresponded to a 9% increase in prevalent stroke [OR: 1.09; 95% CI: 1.00-1.19]. This association was higher among women [OR: 1.38; 95% CI: 1.11-1.72] than men [OR: 1.30; 95% CI: 0.93-1.79] (p-value for interaction=0.05). A 50% increase in blood cadmium corresponded to a 48% increased odds of prevalent HF [OR: 1.48; 95% CI: 1.17-1.87] and a 50% increase in urinary cadmium corresponded to a 12% increase in prevalent HF [OR: 1.12; 95% CI: 1.03-1.20], with no difference in sex-specific associations. Conclusions: Environmental exposure to cadmium was associated with significantly increased stroke and heart failure prevalence. Cadmium exposure may increase these important manifestations of cardiovascular disease.« less

Black-white disparities in the association between posttraumatic stress disorder and chronic illness

PubMed Central

Nobles, Carrie J.; Valentine, Sarah E.; Borba, Christina P.C.; Gerber, Monica W.; Shtasel, Derri L.; Marques, Luana

2016-01-01

Objective Non-Latino blacks experience a higher proportion of chronic illness and associated disabilities than non-Latino whites. Posttraumatic stress disorder (PTSD) is associated with a greater risk of chronic illness, although few studies have investigated whether the interaction of PTSD with racial disparities may lead to a greater risk of chronic illness among blacks with PTSD than among whites with PTSD. Methods We evaluated data from the population-based National Survey of American Life and the National Comorbidity Survey Replication to investigate the association between race, lifetime PTSD and self-reported chronic illness. Weighted linear and Poisson regression models assessed differences in the magnitude of association between PTSD and chronic illness by race on both the additive and multiplicative scales. Results The magnitude of the association between lifetime PTSD and diabetes was greater among blacks (RD 0.07, 95% CI 0.02, 0.11; RR 1.9, 95% CI 1.4, 2.5) than whites (RD 0.004, 95% CI −0.02, 0.03; RR 1.2, 95% CI 0.7, 1.9) on the additive (p=0.017) scale. The magnitude of the association between lifetime PTSD and heart disease was greater among blacks (RD 0.09, 95% CI 0.05, 0.13) than whites (RD 0.04, 95% CI 0.01, 0.07) on the additive scale at a level approaching significance (p=0.051). Conclusion A lifetime history of PTSD was associated with a significantly greater risk of diabetes among blacks as compared to whites. These findings suggest that continuous exposure to racial inequalities may be associated with a greater risk of PTSD-related health sequela. PMID:27212665

Additive interaction between heterogeneous environmental ...

EPA Pesticide Factsheets

BACKGROUND Environmental exposures often occur in tandem; however, epidemiological research often focuses on singular exposures. Statistical interactions among broad, well-characterized environmental domains have not yet been evaluated in association with health. We address this gap by conducting a county-level cross-sectional analysis of interactions between Environmental Quality Index (EQI) domain indices on preterm birth in the Unites States from 2000-2005.METHODS: The EQI, a county-level index constructed for the 2000-2005 time period, was constructed from five domain-specific indices (air, water, land, built and sociodemographic) using principal component analyses. County-level preterm birth rates (n=3141) were estimated using live births from the National Center for Health Statistics. Linear regression was used to estimate prevalence differences (PD) and 95% confidence intervals (CI) comparing worse environmental quality to the better quality for each model for a) each individual domain main effect b) the interaction contrast and c) the two main effects plus interaction effect (i.e. the “net effect”) to show departure from additive interaction for the all U.S counties. Analyses were also performed for subgroupings by four urban/rural strata. RESULTS: We found the suggestion of antagonistic interactions but no synergism, along with several purely additive (i.e., no interaction) associations. In the non-stratified model, we observed antagonistic interac

Management of Patients with Cardiac Arrest Complicating Myocardial Infarction in New York Before and After Public Reporting Policy Changes

PubMed Central

Strom, Jordan B.; McCabe, James M.; Waldo, Stephen W.; Pinto, Duane; Kennedy, Kevin F.; Feldman, Dmitriy N.; Yeh, Robert W.

2017-01-01

Background In 2010, New York State began excluding selected patients with cardiac arrest and coma from publicly reported mortality statistics after percutaneous coronary intervention (PCI). We evaluated the effects of this exclusion on rates of coronary angiography, revascularization, and mortality among patients with acute myocardial infarction (AMI) and cardiac arrest. Methods and Results Using statewide hospitalization files, we identified discharges for AMI and cardiac arrest 1/2003–12/2013 in New York and several comparator states. A difference-in-differences approach was used to evaluate the likelihood of coronary angiography, revascularization, and in-hospital mortality before and after 2010. A total of 26,379 patients with AMI and cardiac arrest (5,619 in New York) were included. Of these, 17,141 (65%) underwent coronary angiography, 12,183 (46.2%) underwent PCI and 2,832 (10.7%) underwent CABG. Prior to 2010, cardiac arrest patients in New York were less likely to undergo PCI compared with referent states (aRR 0.79, 95% CI 0,73–0.85, p<0.001). This relationship was unchanged after the policy change (aRR 0.82, 95% CI 0.76–0.89, interaction p = 0.359). Adjusted risks of in-hospital mortality between New York and comparator states after 2010 were also similar (aRR 0.94, 95% CI 0.87–1.02, p = 0.152 for post- vs. pre-2010 in New York, aRR 0.88, 95% CI 0.84–0.92, p <0.001 for comparator states; interaction p = 0.103). Conclusions Exclusion of selected cardiac arrest cases from public reporting was not associated with changes in rates of PCI or in-hospital mortality in New York. Rates of revascularization in New York for cardiac arrest patients were lower throughout. PMID:28495895

Prognostic Importance of Early Worsening Renal Function Following Initiation of Angiotensin Converting Enzyme Inhibitor Therapy in Patients with Cardiac Dysfunction

PubMed Central

Testani, Jeffrey M.; Kimmel, Stephen E.; Dries, Daniel L.; Coca, Steven G.

2011-01-01

Background Worsening renal function (WRF) in the setting of heart failure has been associated with increased mortality. However, it is unclear if this decreased survival is a direct result of the reduction in glomerular filtration rate (GFR) or if the mechanism underlying the deterioration in GFR is driving prognosis. Given that WRF in the setting of angiotensin converting enzyme inhibitor (ACE-I) initiation is likely mechanistically distinct from spontaneously occurring WRF, we sought to investigate the relative early WRF associated mortality rates in subjects randomized to ACE-I or placebo. Methods and Results Subjects in the Studies Of Left Ventricular Dysfunction limited data set were studied (6,377 patients). The interaction between early WRF (decrease in estimated GFR ≥20% at 14 days), randomization to enalapril, and mortality was the primary endpoint. In the overall population, early WRF was associated with increased mortality (adjusted HR=1.2, 95% CI 1.0–1.4, p=0.037). When analysis was restricted to the placebo group, this association strengthened (adjusted HR=1.4, 95% CI 1.1–1.8, p=0.004). However, in the enalapril group, early WRF had no adverse prognostic significance (adjusted HR=1.0, 95% CI 0.8–1.3, p=1.0, p interaction=0.09). In patients that continued study drug despite early WRF, a survival advantage remained with enalapril therapy (adjusted HR=0.66, 95% CI 0.5–0.9, p=0.018). Conclusions These data support the notion that the mechanism underlying WRF is important in determining its prognostic significance. Specifically, early WRF in the setting of ACE-I initiation appears to represent a benign event which is not associated with a loss of benefit from continued ACE-I therapy. PMID:21903907

Drug–drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding

PubMed Central

Delaney, Joseph A.; Opatrny, Lucie; Brophy, James M.; Suissa, Samy

2007-01-01

Background Anticoagulants and antiplatelet drugs (e.g., warfarin, clopidogrel and acetylsalicylic acid) are key therapeutic agents in the treatment of cardiovascular diseases. However, drug–drug interactions may lead to a greatly increased risk of gastrointestinal bleeding when these drugs are combined. We assessed whether antithrombotic drug combinations increased the risk of such bleeding in a general practice population. Methods We conducted a population-based, retrospective case–control study using records in the United Kingdom General Practice Research Database from 2000 through 2005. Cases were identified as patients over 18 years of age with a first-ever diagnosis of gastrointestinal bleeding. They were matched with controls by physician practice, patient age and index date (date of diagnosis of bleeding). All eligible patients had to have at least 3 years of follow-up data in the database. Drug exposure was considered to be any prescription issued in the 90 days before the index date. Results There were 4028 cases with a diagnosis of gastrointestinal bleeding and 40 171 matched controls. The prescribing of acetylsalicylic acid with either clopidogrel (adjusted rate ratio [RR] 3.90, 95% confidence interval [CI] 2.78–5.47) or warfarin (adjusted RR 6.48, 95% CI 4.25–9.87) was associated with a greater risk of gastrointestinal bleeding than that observed with each drug alone. The same was true when a nonsteroidal anti-inflammatory drug was combined with either clopidogrel (adjusted RR 2.93, 95% CI 1.74–4.93) or warfarin (RR 4.60, 95% CI 2.77–7.64). Interpretation Drug combinations involving antiplatelets and anticoagulants are associated with a high risk of gastrointestinal bleeding beyond that associated with each drug used alone. Physicians should be aware of these risks to better assess their patients' therapeutic risk–benefit profiles. PMID:17698822

Moclobemide monotherapy vs. combined therapy with valproic acid or carbamazepine in depressive patients: a pharmacokinetic interaction study

PubMed Central

Ignjatovic, Anita Rakic; Miljkovic, Branislava; Todorovic, Dejan; Timotijevic, Ivana; Pokrajac, Milena

2009-01-01

AIM To assess the impact of valproic acid (VPA) and carbamazepine (CBZ) on moclobemide (MCB) pharmacokinetics (PK) and metabolism at steady state in depressive patients. METHODS Twenty-one inpatients with recurrent endogenous depression received MCB (150 mg t.i.d.), either as monotherapy or in combination with VPA (500 mg b.i.d.) or CBZ (200 mg b.i.d.) in a nonrandomized manner. Steady-state plasma PK parameters of MCB and its two metabolites, Ro 12-8095 and Ro 12-5637, were derived. Clinical assessments of treatment efficacy were performed weekly using standard depression rating scales. RESULTS CBZ, but not VPA, was associated with decreases in the MCB AUC by 35% [from 7.794 to 5.038 mg h l−1; 95% confidence interval (CI) −4.84863, −0.66194; P = 0.01] and Cmax by 28% (from 1.911 to 1.383 mg l−1; 95% CI −0.98197, −0.07518; P < 0.05), and an increase in its oral clearance by 41% (from 0.323 to 0.454 l h−1 kg−1; 95% CI 0.00086, 0.26171; P < 0.05) after 4 weeks of co-administration. MCB through concentrations were also decreased, on average by 41% (from 0.950 to 0.559 mg l−1; 95% CI −0.77479, −0.03301; P < 0.05). However, the efficacy in this group of patients was not inferior to the controls, for several possible reasons. Overall tolerability of all study medications was good. CONCLUSIONS VPA does not significantly affect PK or metabolism of MCB, whereas CBZ time-dependently decreases MCB exposure, probably by inducing metabolism of MCB and its major plasma metabolite. The actual clinical relevance of the observed MCB–CBZ PK interaction needs to be further evaluated in a more comprehensive study. PMID:19076986

Age, burnout and physical and psychological work ability among nurses.

PubMed

Hatch, D J; Freude, G; Martus, P; Rose, U; Müller, G; Potter, G G

2018-03-26

The ageing of the US labour force highlights the need to examine older adults' physical and psychological ability to work, under varying levels of occupational burnout. To examine how age and burnout interact in predicting physical and psychological work ability. Using a cohort of actively working nurses, we assessed factors on the Work Ability Index at 12-month follow-up and determined how these were related to age and exhaustion-related burnout at baseline. The study group consisted of 402 nurses aged 25-67 (mean = 41.7). Results indicated age by burnout interactions in which decrements in physical work ability with greater age were observed at all but the lowest level of burnout (1.5 SD below mean: β = -0.14, 95% CI -0.36, 0.07; 1 SD below: β = -0.23, 95% CI -0.39, -0.06; mean: β = -0.39, 95% CI -0.50, -0.29; 1 SD above: β = -0.56, 95% CI -0.70, -0.42; 1.5 SD above: β = -0.64, 95% CI -0.83, -0.46). In contrast, we observed decrements in psychological work ability with age at higher levels of burnout only (1 SD above: β = -0.20, 95% CI -0.35, -0.05; 1.5 SD above: β = -0.30, 95% CI -0.49, -0.11); at lower levels of burnout, older age was associated with improvements in this (1 SD below: β = 0.19, 95% CI 0.03, 0.35; 1.5 SD below: β = 0.29, 95% CI 0.08, 0.50). Findings indicated physical and psychological dimensions of work ability that differed by age and occupational burnout. This emphasizes the need for interventions to reduce burnout and to address age-related strengths and vulnerabilities relating to physical and psychological work ability.

Capacity and willingness of patients with chronic noncommunicable diseases to use information technology to help manage their condition: a cross-sectional study

PubMed Central

Afshar, Arash Ehteshami; Weaver, Robert G.; Lin, Meng; Allan, Michael; Ronksley, Paul E; Sanmartin, Claudia; Lewanczuk, Richard; Rosenberg, Mark; Manns, Braden; Hemmelgarn, Brenda

2014-01-01

Background Health care providers have shown considerable interest in using information technologies such as email, text messages and video conferencing to facilitate the management of chronic noncommunicable diseases such as hypertension, diabetes mellitus and vascular disease. We sought to determine whether these technologies are available and appealing to the target population. Methods We analyzed cross-sectional data from a computer-assisted telephone survey, conducted by Statistics Canada in February and March 2012, of western Canadian adults with at least 1 chronic condition. Survey respondents were asked about their capacity (e.g., “Do you own a mobile phone?”) and willingness to use each of 3 information technologies (email, text messages and video conferencing) to interact with health care providers. For all analyses, Statistics Canada’s calibrated design weights and bootstrap weights were used to obtain population-level point estimates for proportions and odds ratios. Results In total, 1849 (79.8%) of 2316 eligible people participated. Of the 1849 participants, 81.9% had hypertension, 26.2% had diabetes, 21.4% had heart disease, and 7.9% had stroke; 32.2% had more than 1 of the 4 chronic conditions of interest. High proportions of respondents owned a computer with Internet access (76.4%, 95% confidence interval [CI] 73.3%–79.3%) or a mobile phone (73.9%, 95% CI 70.7%–76.8%). About two-thirds of respondents were interested in using email to interact with a specialist (66.3%, 95% CI 63.0%–69.5%); respondents were less enthusiastic about using text messages (44.9%, 95% CI 41.2%–48.7%). Enthusiasm for video conferencing was more pronounced among those residing further from medical specialists than among those living closer. Among respondents who were potentially interested in video conferencing, almost 50% of remote dwellers would use this technology if it saved more than 60 minutes of travel time. Interpretation Many people were interested in using electronic technologies, especially video conferencing and email-based methods, to help manage their chronic condition. The effectiveness and cost implications of using email and video conferencing in the management of chronic disease deserve further consideration. PMID:25077130

Acute Cardiovascular Events after Herpes Zoster: A Self-Controlled Case Series Analysis in Vaccinated and Unvaccinated Older Residents of the United States

PubMed Central

Minassian, Caroline; Thomas, Sara L.; Smeeth, Liam; Douglas, Ian; Brauer, Ruth; Langan, Sinéad M.

2015-01-01

Background Herpes zoster is common and can have serious consequences. Additionally, emerging data suggest an increased risk of acute cardiovascular events following herpes zoster. However, to our knowledge, existing association studies compare outcomes between individuals and are therefore vulnerable to between-person confounding. In this study, we used a within-person study design to quantify any short-term increased risk of acute cardiovascular events (stroke and myocardial infarction [MI]) after zoster and to assess whether zoster vaccination modifies this association. Methods and Findings The self-controlled case series method was used to estimate rates of stroke and acute MI in defined periods after herpes zoster compared to other time periods, within individuals. Participants were fully eligible Medicare beneficiaries aged ≥65 y with a herpes zoster diagnosis and either an ischemic stroke (n = 42,954) or MI (n = 24,237) between 1 January 2006 and 31 December 2011. Age-adjusted incidence ratios (IRs) for stroke and MI during predefined periods up to 12 mo after zoster relative to unexposed time periods were calculated using conditional Poisson regression. We observed a marked increase in the rate of acute cardiovascular events in the first week after zoster diagnosis: a 2.4-fold increased ischemic stroke rate (IR 2.37, 95% CI 2.17–2.59) and a 1.7-fold increased MI rate (IR 1.68, 95% CI 1.47–1.92), followed by a gradual resolution over 6 mo. Zoster vaccination did not appear to modify the association with MI (interaction p-value = 0.44). We also found no evidence for a difference in the IR for ischemic stroke between vaccinated (IR 1.14, 95% CI 0.75–1.74) and unvaccinated (IR 1.78, 95% CI 1.68–1.88) individuals during the first 4 wk after zoster diagnosis (interaction p-value = 0.28). The relatively few vaccinated individuals limited the study’s power to assess the role of vaccination. Conclusions Stroke and MI rates are transiently increased after exposure to herpes zoster. We found no evidence for a role of zoster vaccination in these associations. These findings enhance our understanding of the temporality and magnitude of the association between zoster and acute cardiovascular events. PMID:26671338

The transition from the open minimum to the ring minimum on the ground state and on the lowest excited state of like symmetry in ozone: A configuration interaction study

DOE PAGES

Theis, Daniel; Ivanic, Joseph; Windus, Theresa L.; ...

2016-03-10

The metastable ring structure of the ozone 1 1A 1 ground state, which theoretical calculations have shown to exist, has so far eluded experimental detection. An accurate prediction for the energy difference between this isomer and the lower open structure is therefore of interest, as is a prediction for the isomerization barrier between them, which results from interactions between the lowest two 1A 1 states. In the present work, valence correlated energies of the 1 1A 1 state and the 2 1A 1 state were calculated at the 1 1A 1 open minimum, the 1 1A 1 ring minimum, themore » transition state between these two minima, the minimum of the 2 1A 1 state, and the conical intersection between the two states. The geometries were determined at the full-valence multi-configuration self-consistent-field level. Configuration interaction (CI) expansions up to quadruple excitations were calculated with triple-zeta atomic basis sets. The CI expansions based on eight different reference configuration spaces were explored. To obtain some of the quadruple excitation energies, the method of CorrelationEnergy Extrapolation by Intrinsic Scaling was generalized to the simultaneous extrapolation for two states. This extrapolation method was shown to be very accurate. On the other hand, none of the CI expansions were found to have converged to millihartree (mh) accuracy at the quadruple excitation level. The data suggest that convergence to mh accuracy is probably attained at the sextuple excitation level. On the 11A1 state, the present calculations yield the estimates of (ring minimum—open minimum) ~45–50 mh and (transition state—open minimum) ~85–90 mh. For the (2 1A 1– 1A 1) excitation energy, the estimate of ~130–170 mh is found at the open minimum and 270–310 mh at the ring minimum. At the transition state, the difference (2 1A 1– 1A 1) is found to be between 1 and 10 mh. The geometry of the transition state on the 11A1 surface and that of the minimum on the 2 1A 1 surface nearly coincide. More accurate predictions of the energydifferences also require CI expansions to at least sextuple excitations with respect to the valence space. Furthermore, for every wave function considered, the omission of the correlations of the 2s oxygen orbitals, which is a widely used approximation, was found to cause errors of about ±10 mh with respect to the energy differences.« less

The transition from the open minimum to the ring minimum on the ground state and on the lowest excited state of like symmetry in ozone: A configuration interaction study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Theis, Daniel; Ivanic, Joseph; Windus, Theresa L.

The metastable ring structure of the ozone 1 1A 1 ground state, which theoretical calculations have shown to exist, has so far eluded experimental detection. An accurate prediction for the energy difference between this isomer and the lower open structure is therefore of interest, as is a prediction for the isomerization barrier between them, which results from interactions between the lowest two 1A 1 states. In the present work, valence correlated energies of the 1 1A 1 state and the 2 1A 1 state were calculated at the 1 1A 1 open minimum, the 1 1A 1 ring minimum, themore » transition state between these two minima, the minimum of the 2 1A 1 state, and the conical intersection between the two states. The geometries were determined at the full-valence multi-configuration self-consistent-field level. Configuration interaction (CI) expansions up to quadruple excitations were calculated with triple-zeta atomic basis sets. The CI expansions based on eight different reference configuration spaces were explored. To obtain some of the quadruple excitation energies, the method of CorrelationEnergy Extrapolation by Intrinsic Scaling was generalized to the simultaneous extrapolation for two states. This extrapolation method was shown to be very accurate. On the other hand, none of the CI expansions were found to have converged to millihartree (mh) accuracy at the quadruple excitation level. The data suggest that convergence to mh accuracy is probably attained at the sextuple excitation level. On the 11A1 state, the present calculations yield the estimates of (ring minimum—open minimum) ~45–50 mh and (transition state—open minimum) ~85–90 mh. For the (2 1A 1– 1A 1) excitation energy, the estimate of ~130–170 mh is found at the open minimum and 270–310 mh at the ring minimum. At the transition state, the difference (2 1A 1– 1A 1) is found to be between 1 and 10 mh. The geometry of the transition state on the 11A1 surface and that of the minimum on the 2 1A 1 surface nearly coincide. More accurate predictions of the energydifferences also require CI expansions to at least sextuple excitations with respect to the valence space. Furthermore, for every wave function considered, the omission of the correlations of the 2s oxygen orbitals, which is a widely used approximation, was found to cause errors of about ±10 mh with respect to the energy differences.« less

Association between ALDH2 and ADH1B polymorphisms, alcohol drinking and gastric cancer: a replication and mediation analysis.

PubMed

Ishioka, Kuka; Masaoka, Hiroyuki; Ito, Hidemi; Oze, Isao; Ito, Seiji; Tajika, Masahiro; Shimizu, Yasuhiro; Niwa, Yasumasa; Nakamura, Shigeo; Matsuo, Keitaro

2018-04-03

Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms have a strong impact on carcinogenic acetaldehyde accumulation after alcohol drinking. To date, however, evidence for a significant ALDH2-alcohol drinking interaction and a mediation effect of ALDH2/ADH1B through alcohol drinking on gastric cancer have remained unclear. We conducted two case-control studies to validate the interaction and to estimate the mediation effect on gastric cancer. We calculated odds ratios (OR) and 95% confidence intervals (CI) for ALDH2/ADH1B genotypes and alcohol drinking using conditional logistic regression models after adjustment for potential confounding in the HERPACC-2 (697 cases and 1372 controls) and HERPACC-3 studies (678 cases and 678 controls). We also conducted a mediation analysis of the combination of the two studies to assess whether the effects of these polymorphisms operated through alcohol drinking or through other pathways. ALDH2 Lys alleles had a higher risk with increased alcohol consumption compared with ALDH2 Glu/Glu (OR for heavy drinking, 3.57; 95% CI 2.04-6.27; P for trend = 0.007), indicating a significant ALDH2-alcohol drinking interaction (P interaction  = 0.024). The mediation analysis indicated a significant positive direct effect (OR 1.67; 95% CI 1.38-2.03) and a protective indirect effect (OR 0.84; 95% CI 0.76-0.92) of the ALDH2 Lys alleles with the ALDH2-alcohol drinking interaction. No significant association of ADH1B with gastric cancer was observed. The observed ALDH2-alcohol drinking interaction and the direct effect of ALDH2 Lys alleles may suggest the involvement of acetaldehyde in the development of gastric cancer.

Effect of synergistic interaction between abnormal adiposity-related metabolism and prediabetes on microalbuminuria in the general population

PubMed Central

Lee, Chang Hwa

2017-01-01

Central obesity and related metabolic components are important risks for microalbuminuria. To describe the effects of interactions between central obesity and related metabolic components on microalbuminuria, we conducted a nation-wide, population-based interaction analysis using cardio-metabolic index (CMI) as a candidate indicator of central obesity and related abnormal lipid metabolism. We recruited native Koreans aged 20 years or older with no medical illness. A total of 5398 participants were divided into quintiles according to CMI with sex as a covariate factor. Participants in the highest CMI quintile had elevated blood pressure (BP), increased glycemic exposure, poor lipid profile, and increased urine albumin-to-creatinine ratio compared to other lower quintiles. Multiple logistic regression models adjusted for age, sex, systolic BP, and diastolic BP showed that CMI had an independent association with increased glycemic exposure and increased urine albumin-to-creatinine ratio. Our interaction analysis revealed a significant interaction between the highest CMI quintile and prediabetes with an increased risk of microalbuminuria (adjusted RERI = 0.473, 95% CI = 0.464–0.482; adjusted AP = 0.276, 95% CI = 0.156–0.395; adjusted SI = 2.952, 95% CI = 1.234–4.670). Our findings suggest a significant association between central obesity-related abnormal lipid metabolism and prediabetes, and their interaction may exert a synergistic effect on renal vascular endothelial dysfunction even before the appearance of full-blown diabetes mellitus. To confirm these findings, large population-based prospective studies are needed. PMID:28715448

HIV and herpes simplex virus type 2 epidemiological synergy: misguided observational evidence? A modelling study.

PubMed

Omori, Ryosuke; Nagelkerke, Nico; Abu-Raddad, Laith J

2017-12-04

To investigate whether observational studies of HIV and herpes simplex virus type 2 (HSV-2) infections have the capacity to assess the HIV/HSV-2 epidemiological synergy. An individual-based Monte Carlo model was used to simulate HIV/HSV-2 epidemics in two scenarios: no HIV/HSV-2 biological interaction and HSV-2 seropositivity enhancing HIV acquisition. Cross-sectional observational studies were simulated by sampling individuals from the population to assess resulting crude and adjusted ORs of the HIV/HSV-2 association. Meta-analyses were conducted to estimate the pooled mean ORs. Impact of under-reporting of sexual behaviour and miscapture of high-risk individuals was assessed through sensitivity analyses. Assuming no HIV/HSV-2 biological interaction, the crude HIV/HSV-2 OR ranged between 1.38 and 9.93, with a pooled mean of 6.45 (95% CI 5.81 to 7.17). Adjustment for the number of sexual partners over last year, over lifetime and for both partner numbers simultaneously reduced the mean OR to 5.45 (95% CI 4.90 to 6.06), 3.70 (95% CI 3.32 to 4.12) and 3.54 (95% CI 3.17 to 3.94), respectively. Assuming HIV/HSV-2 biological interaction, the crude OR ranged between 3.44 and 9.95, with a pooled mean of 8.05 (95% CI 7.14 to 9.07). The adjustments reduced the mean OR to 7.00 (95% CI 6.21 to 7.90), 3.76 (95% CI 3.32 to 4.25) and 3.68 (95% CI 3.25 to 4.17), respectively. Under-reporting of partners reduced the confounder-adjustment effects. Miscapture of high-risk individuals considerably lowered the estimated ORs. It is difficult to control for sexual-behaviour confounding in observational studies. The observed HIV/HSV-2 association appears more consistent with two infections sharing the same mode of transmission, rather than with HSV-2 enhancing HIV acquisition. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Methodes de calcul des forces aerodynamiques pour les etudes des interactions aeroservoelastiques

NASA Astrophysics Data System (ADS)

Biskri, Djallel Eddine

L'aeroservoelasticite est un domaine ou interagissent la structure flexible d'un avion, l'aerodynamique et la commande de vol. De son cote, la commande du vol considere l'avion comme une structure rigide et etudie l'influence du systeme de commande sur la dynamique de vol. Dans cette these, nous avons code trois nouvelles methodes d'approximation de forces aerodynamiques: Moindres carres corriges, Etat minimal corrige et Etats combines. Dans les deux premieres methodes, les erreurs d'approximation entre les forces aerodynamiques approximees par les methodes classiques et celles obtenues par les nouvelles methodes ont les memes formes analytiques que celles des forces aerodynamiques calculees par LS ou MS. Quant a la troisieme methode, celle-ci combine les formulations des forces approximees avec les methodes standards LS et MS. Les vitesses et frequences de battement et les temps d'executions calcules par les nouvelles methodes versus ceux calcules par les methodes classiques ont ete analyses.

Impact of social capital on psychological distress and interaction with house destruction and displacement after the Great East Japan Earthquake of 2011.

PubMed

Tsuchiya, Naho; Nakaya, Naoki; Nakamura, Tomohiro; Narita, Akira; Kogure, Mana; Aida, Jun; Tsuji, Ichiro; Hozawa, Atsushi; Tomita, Hiroaki

2017-01-01

Social capital has been considered an important factor affecting mental-health outcomes, such as psychological distress in post-disaster settings. Although disaster-related house condition and displacement could affect both social capital and psychological distress, limited studies have investigated interactions. This study aimed to examine the association between social capital and psychological distress, taking into consideration the interaction of disaster-related house condition after the Great East Japan Earthquake of 2011. Using data from 3793 adults living in Shichigahama, Miyagi Prefecture, Japan, we examined the association between social capital measured by generalized trust and psychological distress measured by the Kessler 6 scale. We conducted stratified analysis to investigate an interaction of house destruction and displacement. Multivariate analyses taking into consideration the interaction were performed. In the crude analysis, low social capital (odds ratio [OR] 4.46; 95% confidence interval [CI], 3.27-6.07) and large-scale house destruction (OR 1.96; 95%CI, 1.47-2.62) were significantly associated with psychological distress. Stratified analyses detected an interaction with house destruction and displacement (P for interaction = 0.04). Multivariate analysis with interaction term revealed that individuals with low social capital, large-scale house damage, and displacement were at greater risk of psychological distress, corresponding to adjusted OR of 5.78 (95%CI, 3.48-9.60). In the post-disaster setting, low social capital increased the risk of psychological distress, especially among individuals who had large-scale house destruction. Among the participants with severe disaster damage, high social capital would play an important role in protecting mental health. © 2016 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.

Coadministration of voriconazole and phenytoin: pharmacokinetic interaction, safety, and toleration

PubMed Central

Purkins, Lynn; Wood, Nolan; Ghahramani, Parviz; Love, Edward R; Eve, Malcolm D; Fielding, Anitra

2003-01-01

Aims Voriconazole is a new triazole antifungal agent, and is metabolized by the cytochrome P450 isoenzymes CYP2C9, CYP2C19, and, to a lesser extent, by CYP3A4. Phenytoin is an inducer of CYP3A4 activity, and a substrate and inducer of CYP2C9 and CYP2C19. The present studies investigated the pharmacokinetic interactions of voriconazole and phenytoin when coadministered. Methods Two placebo-controlled parallel-group studies were conducted in healthy male volunteers. Study A was an open-label study and investigated the effect of phenytoin (300 mg once daily) on the steady-state pharmacokinetics of voriconazole (200 mg and 400 mg twice daily). Study B was a double-blind randomized study to investigate the effects of voriconazole (400 mg twice daily) on the steady-state pharmacokinetics of phenytoin (300 mg once daily). Cmax and AUCτ were compared at days 7, 21, and 28 (Study A), and at days 7 and 17 (Study B). All adverse events were recorded. Results Study A: 21 subjects were evaluable (10 voriconazole + phenytoin, 11 voriconazole + placebo). For subjects receiving voriconazole (200 mg twice daily) plus phenytoin, the day 21/day 7 ratios for voriconazole Cmax and AUCτ were 60.7% [90% confidence interval (CI) 50.1, 73.6] and 35.9% (90% CI 29.7, 43.3), respectively. Adjusted for voriconazole + placebo, the ratios between the means were 50.7% (90% CI 38.8, 66.1) and 30.6% (90% CI 23.5, 39.7), respectively. When the dose of voriconazole was increased to 400 mg twice daily, the day 28/day 7 ratios for voriconazole Cmax and AUCτ were 134% (90% CI 89.2, 200) and 139% (90% CI 97.3, 199), respectively. Study B: 15 subjects were evaluable for pharmacokinetic assessments (six phenytoin + voriconazole, nine phenytoin + placebo). The ratios between the means for phenytoin + voriconazole/phenytoin + placebo on day 17 vs. day 7 were: phenytoin Cmax 167% (90% CI 144, 193) and phenytoin AUCτ 181% (90% CI 156, 210). All treatments were well tolerated: most adverse events were mild/moderate and transient. Conclusions Repeat dose administration of phenytoin decreased the mean steady-state Cmax and AUCτ of voriconazole by approximately 50% and 70%, respectively. Increasing the dose of voriconazole from 200 mg to 400 mg b.d. compensated for this effect. Repeat dose administration of 400 mg b.d. voriconazole increased the mean steady-state Cmax and AUCτ of phenytoin by approximately 70% and 80%, respectively. It is therefore recommended that plasma phenytoin concentrations are monitored and the dose adjusted as appropriate when phenytoin is coadministered with voriconazole. PMID:14616412

Detecting drug-drug interactions using a database for spontaneous adverse drug reactions: an example with diuretics and non-steroidal anti-inflammatory drugs.

PubMed

van Puijenbroek, E P; Egberts, A C; Heerdink, E R; Leufkens, H G

2000-12-01

Drug-drug interactions are relatively rarely reported to spontaneous reporting systems (SRSs) for adverse drug reactions. For this reason, the traditional approach for analysing SRS has major limitations for the detection of drug-drug interactions. We developed a method that may enable signalling of these possible interactions, which are often not explicitly reported, utilising reports of adverse drug reactions in data sets of SRS. As an example, the influence of concomitant use of diuretics and non-steroidal anti-inflammatory drugs (NSAIDs) on symptoms indicating a decreased efficacy of diuretics was examined using reports received by the Netherlands Pharmacovigilance Foundation Lareb. Reports received between 1 January 1990 and 1 January 1999 of patients older than 50 years were included in the study. Cases were defined as reports with symptoms indicating a decreased efficacy of diuretics, non-cases as all other reports. Exposure categories were the use of NSAIDs or diuretics versus the use of neither of these drugs. The influence of the combined use of both drugs was examined using logistic regression analysis. The odds ratio of the statistical interaction term of the combined use of both drugs was increased [adjusted odds ratio 2.0, 95% confidence interval (CI) 1.1-3.7], which may indicate an enhanced effect of concomitant drug use. The findings illustrate that spontaneous reporting systems have a potential for signal detection and the analysis of possible drug-drug interactions. The method described may enable a more active approach in the detection of drug-drug interactions after marketing.

Sexual Orientation-Based Discrimination, Excessive Alcohol Use, and Substance Use Disorders Among Sexual Minority Adults

PubMed Central

Godette, Dionne; Huang, Boji; Ruan, W. June; Kerridge, Bradley T.

2017-01-01

Abstract Purpose: The purpose of this study was to examine relationships between sexual orientation-based discrimination and excessive alcohol use and substance use disorders and to identify how these relationships differ by sexual identity, sex, race, Hispanic origin, and education among sexual minorities. Methods: We used logistic regression to analyze associations between discrimination and substance use measures among 1351 gay/lesbian, bisexual, or unsure adults from a nationally representative survey. Differential effects by sexual identity, sex, race, Hispanic origin, and education were assessed using interaction models followed by stratified models. Results: Discrimination was associated with increased odds of the following: exceeding weekly drinking limits [adjusted odds ratio (aOR) = 1.52, 95% confidence interval (CI): 1.12–2.08] among bisexuals, any substance use disorder (aOR = 2.04, 95% CI: 1.41–2.95) and nicotine use disorder (aOR = 1.52, 95% CI: 1.08–2.14) among Hispanic sexual minorities, and exceeding weekly drinking limits (aOR = 1.56, 95% CI: 1.08–2.26) among those with a high school degree or less. Conclusion: Sexual orientation-based discrimination was associated with select substance use outcomes, especially among bisexuals, Hispanics, and less educated sexual minority adults, highlighting potential disparities associated with experiencing discrimination. PMID:28876167

Cardiometabolic risk factors are associated with high urinary enterolactone concentration, independent of urinary enterodiol concentration and dietary fiber intake in adults.

PubMed

Frankenfeld, Cara L

2014-09-01

The study objective was to evaluate independent and interactive associations of dietary fiber intake and high urinary enterolignans with cardiometabolic risk factors. The analysis included 2260 adults (≥20 y of age) from the 2003-2010 NHANES. Logistic regression models were used to evaluate obesity and clinically defined cardiometabolic risk factors in relation to dietary fiber intake and urinary enterolignan concentrations. Three sets of models were created: 1) independent associations, 2) mutually adjusted associations, and 3) interactions. Models were adjusted for age, gender, race/ethnicity, education, smoking status, and energy intake. High concentrations were considered to be above the 90th percentile of urinary enterolignan concentrations. Increasing dietary fiber intake was associated with high blood pressure (P = 0.02) and low serum HDL cholesterol (P-trend = 0.03). High urinary enterodiol concentration was not associated with obesity or cardiometabolic risk factors. High urinary enterolactone concentration was inversely associated with obesity (OR: 0.44; 95% CI: 0.29, 0.66), abdominal obesity (OR: 0.58; 95% CI: 0.39, 0.87), high serum C-reactive protein (CRP; OR: 0.52; 95% CI: 0.37, 0.74), high serum triglycerides (OR: 0.39; 95% CI: 0.23, 0.61), low serum HDL cholesterol (OR: 0.37; 95% CI: 0.23, 0.61), and metabolic syndrome (OR: 0.47; 95% CI: 0.30, 0.74). In mutually adjusted models, enterolactone associations observed in independent models remained similar, but associations for dietary fiber intake were attenuated, with the exception of blood pressure. In interaction models, there were 2 significant interactions: between high urinary enterodiol concentration and dietary fiber intake for high serum CRP (P = 0.04) and high plasma glucose (P = 0.04). Overall, being in the highest 10% of urinary enterolactone concentration was associated with cardiometabolic risk factors, independent of dietary fiber intake and enterodiol concentration. Future studies are warranted to evaluate physiologic actions of enterolactone or aspects of the gut microbial profile responsible for lignan metabolism to enterolactone. © 2014 American Society for Nutrition.

Efficacy and safety of rivaroxaban compared with warfarin in patients with peripheral artery disease and non-valvular atrial fibrillation: insights from ROCKET AF.

PubMed

Jones, William Schuyler; Hellkamp, Anne S; Halperin, Jonathan; Piccini, Jonathan P; Breithardt, Gunter; Singer, Daniel E; Fox, Keith A A; Hankey, Graeme J; Mahaffey, Kenneth W; Califf, Robert M; Patel, Manesh R

2014-01-01

Vascular disease is included in a risk scoring system to predict stroke in patients with non-valvular atrial fibrillation (AF). This post hoc analysis of ROCKET AF aimed to determine the absolute rates of stroke and bleeding, and the relative effectiveness and safety of rivaroxaban vs. warfarin in patients with and without peripheral artery disease (PAD). Peripheral artery disease was defined on the case-report form as the presences of intermittent claudication, amputation for arterial insufficiency, vascular reconstruction, bypass surgery, or percutaneous intervention to the extremities, or previously documented abdominal aortic aneurysm. ROCKET AF was a double-blind, double-dummy, randomized-controlled trial comparing rivaroxaban and warfarin for the prevention of stroke or systemic embolism. A total of 839 (5.9%) patients in ROCKET AF had PAD. Patients with and without PAD had similar rates of stroke or systemic embolism [HR: 1.04, 95% CI (0.72, 1.50), P = 0.84] and major or non-major clinically relevant (NMCR) bleeding [HR: 1.11, 95% CI (0.96, 1.28), P = 0.17], respectively. The efficacy of rivaroxaban when compared with warfarin for the prevention of stroke or systemic embolism was similar in patients with PAD (HR: 1.19, 95% CI: 0.63-2.22) and without PAD (HR: 0.86, 95% CI: 0.73-1.02; interaction P = 0.34). There was a significant interaction for major or NMCR bleeding in patients with PAD treated with rivaroxaban compared with warfarin (HR: 1.40, 95% CI: 1.06-1.86) compared with those without PAD (HR: 1.03, 95% CI: 0.95-1.11; interaction P = 0.037). Patients with PAD in ROCKET AF did not have a statistically significant higher risk of stroke or systemic embolism than patients without PAD, and there were similar efficacy outcomes in patients treated with rivaroxaban and warfarin. In PAD patients, there was a higher risk of major bleeding or NMCR bleeding with rivaroxaban when compared with warfarin (interaction P = 0.037). Further investigation is warranted to validate this subgroup analysis and determine the optimal treatment in this high-risk cohort of AF patients with PAD.

A urate gene-by-diuretic interaction and gout risk in participants with hypertension: results from the ARIC study

PubMed Central

McAdams-DeMarco, Mara A; Maynard, Janet W; Baer, Alan N; Kao, Linda W; Kottgen, Anna; Coresh, Josef

2015-01-01

Objective To test for a urate gene-by-diuretic interaction on incident gout. Methods The Atherosclerosis Risk in Communities Study is a prospective population-based cohort of 15 792 participants recruited from four US communities (1987–1989). Participants with hypertension and available single nucleotide polymorphism (SNP) genotype data were included. A genetic urate score (GUS) was created from common urate-associated SNPs for eight genes. Gout incidence was self-reported. Using logistic regression, the authors estimated the adjusted OR of incident gout by diuretic use, stratified by GUS median. Results Of 3524 participants with hypertension, 33% used a diuretic and 3.1% developed gout. The highest 9-year cumulative incidence of gout was in those with GUS above the median and taking a thiazide or loop diuretic (6.3%). Compared with no thiazide or loop diuretic use, their use was associated with an OR of 0.40 (95% CI 0.14 to 1.15) among those with a GUS below the median and 2.13 (95% CI 1.23 to 3.67) for those with GUS above the median; interaction p=0.006. When investigating the genes separately, SLC22A11 and SLC2A9 showed a significant interaction, consistent with the former encoding an organic anion/dicarboxylate exchanger, which mediates diuretic transport in the kidney. Conclusions Participants who were genetically predisposed to hyperuricaemia were susceptible to developing gout when taking thiazide or loop diuretics, an effect not evident among those without a genetic predisposition. These findings argue for a potential benefit of genotyping individuals with hypertension to assess gout risk, relative in part to diuretic use. PMID:22753387

Postmenopausal hormone therapy, type 2 diabetes mellitus, and brain volumes

PubMed Central

Brinton, Roberta Diaz; Manson, JoAnn E.; Yaffe, Kristine; Hugenschmidt, Christina; Vaughan, Leslie; Craft, Suzanne; Edwards, Beatrice J.; Casanova, Ramon; Masaki, Kamal; Resnick, Susan M.

2015-01-01

Objective: To examine whether the effect of postmenopausal hormone therapy (HT) on brain volumes in women aged 65–79 years differs depending on type 2 diabetes status during postintervention follow-up of a randomized controlled clinical trial. Methods: The Women's Health Initiative randomized clinical trials assigned women to HT (0.625 mg/day conjugated equine estrogens with or without 2.5 mg/day medroxyprogesterone acetate) or placebo for an average of 5.6 years. A total of 1,402 trial participants underwent brain MRI 2.4 years after the trials; these were repeated in 699 women 4.7 years later. General linear models were used to assess the interaction between diabetes status and HT assignment on brain volumes. Results: Women with diabetes at baseline or during follow-up who had been assigned to HT compared to placebo had mean decrement in total brain volume of −18.6 mL (95% confidence interval [CI] −29.6, −7.6). For women without diabetes, this mean decrement was −0.4 (95% CI −3.8, 3.0) (interaction p = 0.002). This interaction was evident for total gray matter (p < 0.001) and hippocampal (p = 0.006) volumes. It was not evident for changes in brain volumes over follow-up or for ischemic lesion volumes and was not influenced by diabetes duration or oral medications. Conclusions: For women aged 65 years or older who are at increased risk for brain atrophy due to type 2 diabetes, prescription of postmenopausal HT is associated with lower gray matter (total and hippocampal) volumes. Interactions with diabetes and insulin resistance may explain divergent findings on how estrogen influences brain volume among older women. PMID:26163429

Pharmacoepidemiologic and in vitro evaluation of potential drug–drug interactions of sulfonylureas with fibrates and statins

PubMed Central

Schelleman, H; Han, X; Brensinger, C M; Quinney, S K; Bilker, W B; Flockhart, D A; Li, L; Hennessy, Sean

2014-01-01

Aims To examine whether initiation of fibrates or statins in sulfonylurea users is associated with hypoglycaemia, and examine in vitro inhibition of cytochrome P450 (CYP) enzymes by statins, fenofibrate and glipizide. Methods We used healthcare data to conduct nested case-control studies of serious hypoglycaemia (i.e. resulting in hospital admission or emergency department treatment) in persons taking glipizide or glyburide, and calculated adjusted overall and time-stratified odds ratios (ORs) and 95% confidence intervals (CIs). We also characterized the in vitro inhibition of CYP enzymes by statins, fenofibrate and glipizide using fluorometric CYP450 inhibition assays, and estimated area under the concentration–time curve ratios (AUCRs) for the drug pairs. Results We found elevated adjusted overall ORs for glyburide-fenofibrate (OR 1.84, 95% CI 1.37, 2.47) and glyburide-gemfibrozil (OR 1.57, 95% CI 1.25, 1.96). The apparent risk did decline over time as might be expected from a pharmacokinetic mechanism. Fenofibrate was a potent in vitro inhibitor of CYP2C19 (IC50 = 0.2 μm) and CYP2B6 (IC50 = 0.7 μm) and a moderate inhibitor of CYP2C9 (IC50 = 9.7 μm). The predicted CYP-based AUCRs for fenofibrate-glyburide and gemfibrozil-glyburide interactions were only 1.09 and 1.04, suggesting that CYP inhibition is unlikely to explain such an interaction. Conclusions Use of fenofibrate or gemfibrozil together with glyburide was associated with elevated overall risks of serious hypoglycaemia. CYP inhibition seems unlikely to explain this observation. We speculate that a pharmacodynamic effect of fibrates (e.g. activate peroxisome proliferator-activator receptor alpha) may contribute to these apparent interactions. PMID:24548191

[Food insecurity: associated variables and issues for public policy].

PubMed

Del Castillo, Sara E; Patiño, Gonzalo A; Herrán, Oscar F

2012-01-01

The validity of the explanations change over time according to the state of demographic, epidemiological and nutritional transitions. Five methods were compared to establish t he magnitude of food insecurity and related variables. Four hundred and thirty-two households in Colombia were classified using five methods, including (1) the scale of perceptions of food safety (EPSA),(2) the Latin American and Caribbean scale (ELCSA), (3) the usual intake of energy from the head of household, (4) the usual consumption of energy of all members of the home, and (5) an algorithm based on consumption and status of children. Binomial regression established variables associated with food insecurity. Insecurity varied between 35.9% and 87.0%. According ELCSA and method 3, households with children have a lower risk of insecurity, 0.51 (95% CI 0.25 to 0.90) and 0.72 (95% CI 0.48 to 0.96). Under the EPSA and ELCSA, increased insecurity is associated with nonpayment of utilities, 1.75 (95% CI: 1.23 to 2.28) and the head of household declared limited access to food, 1.48 (95% CI: 1, 20 to 1.68). Sporadic income was associated with the method 3, 1.34 (95% CI 1.04 to 1.53) and method 4, 1.32 (95% CI 1.03 to 1.52). Paying rent, 1.12 (95% CI: 1.01 to 1.16), time spent in the municipality, 0.59 (95% CI 0.23 to 0.93) and not having sewer, 1.13 (95% CI 1.01 to 1.16) were associated with the food insecurity using method 5. Since the country has reliable information that is obtained routinely it is not relevant or useful to use these methods with the purpose of developing social policies.

Consonant Acquisition in Young Cochlear Implant Recipients and Their Typically Developing Peers

PubMed Central

Jung, Jongmin; Ertmer, David J.

2017-01-01

Purpose Consonant acquisition was examined in 13 young cochlear implant (CI) recipients and 11 typically developing (TD) children. Method A longitudinal research design was implemented to determine the rate and nature of consonant acquisition during the first 2 years of robust hearing experience. Twenty-minute adult–child (typically a parent) interactions were video and audio recorded at 3-month intervals following implantation until 24 months of robust hearing experience was achieved. TD children were similarly recorded between 6 and 24 months of age. Consonants that were produced twice within a 50-utterance sample were considered “established” within a child's consonant inventory. Results Although the groups showed similar trajectories, the CI group produced larger consonant inventories than the TD group at each interval except for 21 and 24 months. A majority of children with CIs also showed more rapid acquisition of consonants and more diverse consonant inventories than TD children. Conclusions These results suggest that early auditory deprivation does not significantly affect consonant acquisition for most CI recipients. Tracking early consonant development appears to be a useful way to assess the effectiveness of cochlear implantation in young recipients. PMID:28474085

Communicating HIV status in sexual interactions: assessing social cognitive constructs, situational factors, and individual characteristics among South African MSM.

PubMed

Knox, Justin; Reddy, Vasu; Kaighobadi, Farnaz; Nel, Dawie; Sandfort, Theo

2013-01-01

This study assessed whether social cognitive constructs, situational factors, and individual characteristics were associated with communicating HIV status and whether communication was related to sexual risk behavior. A quota-sampling method stratified by age, race, and township was used to recruit 300 men who have sex with men to participate in a community-based survey in Pretoria in 2008. Participants reported characteristics of their last sexual encounter involving anal sex, including whether they or their partner had communicated their HIV status. Fifty-nine percent of participants reported that they or their partner had communicated their HIV status. HIV communication self-efficacy (aOR = 1.2, 95 % CI: 1.04-1.68), being with a steady partner (aOR = 0.36, 95 % CI: 0.19-0.67), and being Black (versus White; aOR = 0.08, 95 % CI: 0.03-0.27) were independently associated with communicating HIV status. Communicating HIV status was not associated with unprotected anal intercourse. HIV communication self-efficacy increases men's likelihood of communicating HIV status. Being with a steady partner and being Black reduces that likelihood. Communication about HIV status did not lead to safer sex.

Quantitative descriptions of rice plant architecture and their application

PubMed Central

Li, Xumeng; Wang, Xiaohui; Peng, Yulin; Wei, Hailin; Zhu, Xinguang; Chang, Shuoqi; Li, Ming; Li, Tao; Huang, Huang

2017-01-01

Plant architecture is an important agronomic trait, and improving plant architecture has attracted the attention of scientists for decades, particularly studies to create desirable plant architecture for high grain yields through breeding and culture practices. However, many important structural phenotypic traits still lack quantitative description and modeling on structural-functional relativity. This study defined new architecture indices (AIs) derived from the digitalized plant architecture using the virtual blade method. The influences of varieties and crop management on these indices and the influences of these indices on biomass accumulation were analyzed using field experiment data at two crop growth stages: early and late panicle initiation. The results indicated that the vertical architecture indices (LAI, PH, 90%-DRI, MDI, 90%-LI) were significantly influenced by variety, water, nitrogen management and the interaction of water and nitrogen, and compact architecture indices (H-CI, Q-CI, 90%-LI, 50%-LI) were significantly influenced by nitrogen management and the interaction of variety and water. Furthermore, there were certain trends in the influence of variety, water, and nitrogen management on AIs. Biomass accumulation has a positive linear correlation with vertical architecture indices and has a quadratic correlation with compact architecture indices, respectively. Furthermore, the combination of vertical and compact architecture indices is the indicator for evaluating the effects of plant architecture on biomass accumulation. PMID:28545144

Quantitative descriptions of rice plant architecture and their application.

PubMed

Li, Xumeng; Wang, Xiaohui; Peng, Yulin; Wei, Hailin; Zhu, Xinguang; Chang, Shuoqi; Li, Ming; Li, Tao; Huang, Huang

2017-01-01

Plant architecture is an important agronomic trait, and improving plant architecture has attracted the attention of scientists for decades, particularly studies to create desirable plant architecture for high grain yields through breeding and culture practices. However, many important structural phenotypic traits still lack quantitative description and modeling on structural-functional relativity. This study defined new architecture indices (AIs) derived from the digitalized plant architecture using the virtual blade method. The influences of varieties and crop management on these indices and the influences of these indices on biomass accumulation were analyzed using field experiment data at two crop growth stages: early and late panicle initiation. The results indicated that the vertical architecture indices (LAI, PH, 90%-DRI, MDI, 90%-LI) were significantly influenced by variety, water, nitrogen management and the interaction of water and nitrogen, and compact architecture indices (H-CI, Q-CI, 90%-LI, 50%-LI) were significantly influenced by nitrogen management and the interaction of variety and water. Furthermore, there were certain trends in the influence of variety, water, and nitrogen management on AIs. Biomass accumulation has a positive linear correlation with vertical architecture indices and has a quadratic correlation with compact architecture indices, respectively. Furthermore, the combination of vertical and compact architecture indices is the indicator for evaluating the effects of plant architecture on biomass accumulation.

Combined effect of urinary monohydroxylated polycyclic aromatic hydrocarbons and impaired lung function on diabetes.

PubMed

Hou, Jian; Sun, Huizhen; Xiao, Lili; Zhou, Yun; Yin, Wenjun; Xu, Tian; Cheng, Juan; Chen, Weihong; Yuan, Jing

2016-07-01

Associations of type 2 diabetes with exposure to polycyclic aromatic hydrocarbons and reduced lung function have been reported. The aim of the present study was to investigate effect of reduced lung function and exposure to background PAHs on diabetes. A total of 2730 individuals were drawn from the Wuhan-Zhuhai (WHZH) Cohort Study (n=3053). Participants completed physical examination, measurement of lung function and urinary monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs). Risk factors for type 2 diabetes were identified by multiple logistic regression analysis, and the presence of additive interaction between levels of urinary OH-PAHs and lower lung function was evaluated by calculation of the relative excess risk due to interaction (RERI) and attributable proportion due to interaction (AP). Urinary OH-PAHs levels was positively associated with type 2 diabetes among individuals with impaired lung function (p<0.05). Forced expiratory volume in one second (FEV1, odd ratio (OR): 0.664, 95% confidence interval (CI): 0.491-0.900) and forced vital capacity (FVC, OR: 0.693, 95% CI: 0.537-0.893) were negatively associated with diabetes among individuals. Additive interaction of higher urinary levels of OH-PAHs and lower FVC (RERI: 0.679, 95% CI: 0.120-1.238); AP: 0.427, 95% CI: 0.072-0.782) was associated with diabetes. Exposure to background PAHs was related to diabetes among individuals with lower lung function. Urinary levels of OH-PAHs and reduced lung function had an additive effect on diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

Linguistic Validation of Interactive Educational Interventions in Neurologic Trauma.

PubMed

Sahyouni, Ronald; Mahmoodi, Amin; Tran, Diem K; Tran, Peter; Chen, Jefferson W

2017-11-01

Neurological surgeons oftentimes educate patients and their families on complex medical conditions and treatment options. Time constraints and varied linguistic and cultural backgrounds limit the amount of information that can be disbursed. In this study, we assessed the linguistic validity of interactive educational interventions in non-English-speaking patients with traumatic brain injury (TBI) and concussion and their families. A total of 273 English-, Spanish-, Korean-, and Vietnamese-speaking neurotrauma patients (n =124) and family members (n =149) completed a presurvey to evaluate their incipient understanding, interacted with an iPad-based iBook (Apple) on concussion or TBI in their native language, completed a postsurvey to gauge changes in understanding, and then consulted with their neurosurgeon. All participants (124 patients and 149 family members) had significantly increased (95% confidence interval [CI], P < 0.01) postsurvey scores (average pre-iBook score, 2.810; average post-iBook score, 4.109), regardless of native language or cultural background. Caucasian participants scored significantly higher than the combination of all ethnicities on both the baseline survey (95% CI, P < 0.01) and the post-iBook survey (95% CI, P < 0.01), and Asian participants scored significantly lower (95% CI, P < 0.05) than the combination regardless of similar baseline scores. Interactive iBook-based interventions on concussion and TBI can increase participants' comprehension, improve their comfort with their medical condition and the follow-up care, and enhance communication with their physicians. These findings are linguistically valid irrespective of the participants' native language or cultural background. Copyright © 2017 Elsevier Inc. All rights reserved.

Topical Antimycotics for Oral Candidiasis in Warfarin Users.

PubMed

Hellfritzsch, Maja; Pottegård, Anton; Pedersen, Andreas James Thestrup; Burghle, Alaa; Mouaanaki, Fatima; Hallas, Jesper; Grove, Erik Lerkevang; Damkier, Per

2017-04-01

Treatment for oral candidiasis in warfarin users may be complicated by drug-drug interactions (DDIs) between warfarin and topically applied antimycotics. However, current knowledge of these putative DDIs is merely based on case series. We therefore performed a cohort cross-over study with the objective to evaluate the potential DDIs between warfarin and miconazole oral gel or nystatin oral solution. The cohort consisted of individuals using warfarin in the period of 1998-2012 (n ≈ 7400). We collected data on cohort members' measurements of the international normalized ratio (INR) from a clinical database, and obtained information on their use of topically applied miconazole and nystatin from a regional prescription register. Potential DDIs were assessed by comparing INR values before and after initiation of an antimycotic drug. Among 17 warfarin users exposed to miconazole oral gel, the mean INR increased from 2.5 (95% CI: 2.1-2.8) to 3.8 (95% CI: 2.8-4.8) after exposure, corresponding to a mean INR increase of 1.4 (95% CI: 0.3-2.4). Among 30 warfarin users exposed to nystatin oral solution, the mean INR was 2.7 (95% CI: 2.3-3.1) before and 2.5 (95% CI: 2.2-2.9) after exposure. In conclusion, we found evidence supporting a clinically relevant drug-drug interaction between warfarin and miconazole oral gel. In contrast, we did not find any indication of an interaction between warfarin and nystatin oral solution. Nystatin rather than miconazole should be preferred when treating warfarin users for oral candidiasis. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Effects of sevelamer carbonate on advanced glycation end products and antioxidant/pro-oxidant status in patients with diabetic kidney disease.

PubMed

Yubero-Serrano, Elena M; Woodward, Mark; Poretsky, Leonid; Vlassara, Helen; Striker, Gary E

2015-05-07

The primary goals were to re-examine whether sevelamer carbonate (SC) reduces advanced glycation end products (AGEs) (methylglyoxal and carboxymethyllysine [CML]), increases antioxidant defenses, reduces pro-oxidants, and improves hemoglobin A1c (HbA1c) in patients with type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). Secondary goals examined albuminuria, age, race, sex, and metformin prescription. This two-center, randomized, intention-to-treat, open-label study evaluated 117 patients with T2DM (HbA1c >6.5%) and stages 2-4 DKD (urinary albumin/creatinine ratio ≥200 mg/g) treated with SC (1600 mg) or calcium carbonate (1200 mg), three times a day, without changing medications or diet. Statistical analyses used linear mixed models adjusted for randomization levels. Preselected subgroup analyses of sex, race, age, and metformin were conducted. SC lowered serum methylglyoxal (95% confidence interval [CI], -0.72 to -0.29; P<0.001), serum CML (95% CI, -5.08 to -1.35; P≤0.001), and intracellular CML (95% CI, -1.63 to -0.28; P=0.01). SC increased anti-inflammatory defenses, including nuclear factor like-2 (95% CI, 0.58 to 1.29; P=0.001), AGE receptor 1 (95% CI, 0.23 to 0.96; P=0.001), NAD-dependent deacetylase sirtuin-1 (95% CI, 0.20 to 0.86; P=0.002), and estrogen receptor α (95% CI, 1.38 to 2.73; P ≤0.001). SC also decreased proinflammatory factors such as TNF receptor 1 (95% CI, -1.56 to -0.72; P≤0.001) and the receptor for AGEs (95% CI, -0.58 to 1.53; P≤0.001). There were no differences in HbA1c, GFR, or albuminuria in the overall group. Subanalyses showed that SC lowered HbA1c in women (95% CI, -1.71 to -0.27; P=0.01, interaction P=0.002), and reduced albuminuria in those aged <65 years (95% CI, -1.15 to -0.07; P=0.03, interaction P=0.02) and non-Caucasians (95% CI, -1.11 to -0.22; P=0.003, interaction P≤0.001), whereas albuminuria increased after SC and calcium carbonate in Caucasians. SC reduced circulating and cellular AGEs, increased antioxidants, and decreased pro-oxidants, but did not change HbA1c or the albumin/creatinine ratio overall in patients with T2DM and DKD. Because subanalyses revealed that SC may reduce HbA1c and albuminuria in some patients with T2DM with DKD, further studies may be warranted. Copyright © 2015 by the American Society of Nephrology.

The Relative Associations of β-Cell Function and Insulin Sensitivity with Glycemic Status and Incident Glycemic Progression in Migrant Asian Indians in the United States: the MASALA study

PubMed Central

Gujral, UP; Narayan, KMV; Kahn, SE; Kanaya, AM

2013-01-01

AIMS We assessed the relative associations of β-cell dysfunction and insulin sensitivity with baseline glycemic status and incident glycemic progression among Asian Indians in the United States. METHODS A 5-sample oral glucose tolerance test was obtained at baseline. Normoglycemia, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM) were defined by ADA criteria. The Matsuda Index (ISIM) estimated insulin sensitivity, and the Disposition Index (DIo) estimated β-cell function. Visceral fat was measured by abdominal CT. After 2.5 years, participants underwent a 2-sample oral glucose tolerance test. Standardized polytomous logistic regression was used to examine associations with prevalent and incident glycemia. RESULTS Mean age was 57±8 years and BMI 26.1±4.6 kg/m2. Log ISIM and log DIo were associated with prediabetes and T2DM after adjusting for age, sex, BMI, family history of diabetes, hypertension, and smoking. After adjusting for visceral fat, only DIo remained associated with prediabetes (OR per SD 0.17, 95% CI: 0.70, 0.41) and T2DM (OR 0.003, 95% CI: 0.0001, 0.03). Incidence rates (per 1,000 person-year) were: normoglycemia to IGT: 82.0, 95% CI (40, 150); to IFG: 8.4, 95% CI (0, 41); to T2DM: 8.6, 95% CI (0, 42); IGT to T2DM: 55.0, 95% CI (17, 132); IFG to T2DM: 64.0, 95% CI (3, 316). The interaction between sex and the change in waist circumference (OR 1.8, per SD 95% CI: 1.22, 2.70) and the change in log HOMA-β(OR 0.37, per SD 95% CI: 0.17, 0.81) were associated with glycemic progression. CONCLUSIONS The association of DIo with baseline glycemia after accounting for visceral fat as well as the association of the change in log HOMA-β with incident glycemic progression implies innate β-cell susceptibility in Asian Indians for glucose intolerance or dysglycemia. PMID:24211090

Quality Reporting of Multivariable Regression Models in Observational Studies: Review of a Representative Sample of Articles Published in Biomedical Journals.

PubMed

Real, Jordi; Forné, Carles; Roso-Llorach, Albert; Martínez-Sánchez, Jose M

2016-05-01

Controlling for confounders is a crucial step in analytical observational studies, and multivariable models are widely used as statistical adjustment techniques. However, the validation of the assumptions of the multivariable regression models (MRMs) should be made clear in scientific reporting. The objective of this study is to review the quality of statistical reporting of the most commonly used MRMs (logistic, linear, and Cox regression) that were applied in analytical observational studies published between 2003 and 2014 by journals indexed in MEDLINE.Review of a representative sample of articles indexed in MEDLINE (n = 428) with observational design and use of MRMs (logistic, linear, and Cox regression). We assessed the quality of reporting about: model assumptions and goodness-of-fit, interactions, sensitivity analysis, crude and adjusted effect estimate, and specification of more than 1 adjusted model.The tests of underlying assumptions or goodness-of-fit of the MRMs used were described in 26.2% (95% CI: 22.0-30.3) of the articles and 18.5% (95% CI: 14.8-22.1) reported the interaction analysis. Reporting of all items assessed was higher in articles published in journals with a higher impact factor.A low percentage of articles indexed in MEDLINE that used multivariable techniques provided information demonstrating rigorous application of the model selected as an adjustment method. Given the importance of these methods to the final results and conclusions of observational studies, greater rigor is required in reporting the use of MRMs in the scientific literature.

Racial disparities in advanced-stage colorectal cancer survival.

PubMed

Wallace, Kristin; Hill, Elizabeth G; Lewin, David N; Williamson, Grace; Oppenheimer, Stephanie; Ford, Marvella E; Wargovich, Michael J; Berger, Franklin G; Bolick, Susan W; Thomas, Melanie B; Alberg, Anthony J

2013-03-01

African-Americans (AA) have a higher incidence of and lower survival from colorectal cancer (CRC) compared with European Americans (EA). In the present study, statewide, population-based data from South Carolina Central Cancer Registry are used to investigate the relationship between race and age on advanced-stage CRC survival. The study population was comprised of 3,865 advanced pathologically documented colon and rectal adenocarcinoma cases diagnosed between 01 January 1996 and 31 December 2006: 2,673 (69 %) EA and 1,192 (31 %) AA. Kaplan-Meier methods were used to generate median survival time and corresponding 95 % confidence intervals (CI) by race, age, and gender. Factors associated with survival were evaluated by fitting Cox proportional hazards regression models to generate hazard ratios (HR) and 95 % CI. We observed a significant interaction between race and age on CRC survival (p = 0.04). Among younger patients (<50 years), AA race was associated with a 1.34 times (95 % CI 1.06-1.71) higher risk of death compared with EA. Among older patients, we observed a modest increase in risk of death among AA men compared with EA [HR 1.16 (95 % CI 1.01-1.32)] but no difference by race between women [HR 0.94 (95 % CI 0.82-1.08)]. Moreover, we observed that the disparity in survival has worsened over the past 15 years. Future studies that integrate clinical, molecular, and treatment-related data are needed for advancing understanding of the racial disparity in CRC survival, especially for those <50 years old.

Exposure and Sensitization to Pets Modify Endotoxin Association with Asthma and Wheeze.

PubMed

Mendy, Angelico; Wilkerson, Jesse; Salo, Päivi M; Cohn, Richard D; Zeldin, Darryl C; Thorne, Peter S

2018-04-21

Pets are major contributors of endotoxin in homes, but whether they influence endotoxin association with respiratory outcomes is unclear. To examine whether exposure and sensitization to dog and cat modify the relationship between endotoxin exposure and asthma and wheeze. We analyzed data from 6051 participants in the 2005-2006 cycle of the National Health and Nutrition Examination Survey (NHANES). House dust from bedroom floor and bedding was evaluated for endotoxin and for dog (Canis familiaris 1) and cat (Feline domesticus 1) allergens. The NHANES also collected data on respiratory outcomes and measured IgE specific to allergens. Associations of log-endotoxin and pet exposure with respiratory outcomes were examined, adjusting for covariates including pet avoidance. Dog and cat ownership among participants was 48.3% and 37.5%, respectively. Endotoxin geometric mean (SE) was 15.49 (0.50) EU/mg. Endotoxin and pet allergen levels were significantly higher in households with a dog or cat. Overall, endotoxin was positively associated with wheeze (odds ratio [OR], 1.30; 95% CI, 1.04-1.62), but not with asthma. However, in participants nonsensitized to dog, the odds of endotoxin association with wheeze were higher with exposure to dog allergen (OR, 1.80; 95% CI, 1.27-2.53; P interaction  = .048). In participants sensitized to cat and exposed to cat allergen, endotoxin became positively associated with asthma (OR, 1.92; 95% CI, 1.21-3.0; P interaction  = .040). With coexposure to dog and cat allergens, endotoxin association with asthma and wheeze was exacerbated (OR, 2.00; 95% CI, 1.04-3.83; P interaction  = .012 and OR, 1.88; 95% CI, 1.32-2.66; P interaction  = .016, respectively). Exposure to dog and cat allergens enhances the association of endotoxin with asthma and wheeze. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Tree Tensor Network State with Variable Tensor Order: An Efficient Multireference Method for Strongly Correlated Systems

PubMed Central

2015-01-01

We study the tree-tensor-network-state (TTNS) method with variable tensor orders for quantum chemistry. TTNS is a variational method to efficiently approximate complete active space (CAS) configuration interaction (CI) wave functions in a tensor product form. TTNS can be considered as a higher order generalization of the matrix product state (MPS) method. The MPS wave function is formulated as products of matrices in a multiparticle basis spanning a truncated Hilbert space of the original CAS-CI problem. These matrices belong to active orbitals organized in a one-dimensional array, while tensors in TTNS are defined upon a tree-like arrangement of the same orbitals. The tree-structure is advantageous since the distance between two arbitrary orbitals in the tree scales only logarithmically with the number of orbitals N, whereas the scaling is linear in the MPS array. It is found to be beneficial from the computational costs point of view to keep strongly correlated orbitals in close vicinity in both arrangements; therefore, the TTNS ansatz is better suited for multireference problems with numerous highly correlated orbitals. To exploit the advantages of TTNS a novel algorithm is designed to optimize the tree tensor network topology based on quantum information theory and entanglement. The superior performance of the TTNS method is illustrated on the ionic-neutral avoided crossing of LiF. It is also shown that the avoided crossing of LiF can be localized using only ground state properties, namely one-orbital entanglement. PMID:25844072

Fixed-node diffusion Monte Carlo potential energy curve of the fluorine molecule F{sub 2} using selected configuration interaction trial wavefunctions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giner, Emmanuel; Scemama, Anthony; Caffarel, Michel

2015-01-28

The potential energy curve of the F{sub 2} molecule is calculated with Fixed-Node Diffusion Monte Carlo (FN-DMC) using Configuration Interaction (CI)-type trial wavefunctions. To keep the number of determinants reasonable and thus make FN-DMC calculations feasible in practice, the CI expansion is restricted to those determinants that contribute the most to the total energy. The selection of the determinants is made using the CIPSI approach (Configuration Interaction using a Perturbative Selection made Iteratively). The trial wavefunction used in FN-DMC is directly issued from the deterministic CI program; no Jastrow factor is used and no preliminary multi-parameter stochastic optimization of themore » trial wavefunction is performed. The nodes of CIPSI wavefunctions are found to reduce significantly the fixed-node error and to be systematically improved upon increasing the number of selected determinants. To reduce the non-parallelism error of the potential energy curve, a scheme based on the use of a R-dependent number of determinants is introduced. Using Dunning’s cc-pVDZ basis set, the FN-DMC energy curve of F{sub 2} is found to be of a quality similar to that obtained with full configuration interaction/cc-pVQZ.« less

Effect of Interaction Between Noise and A1166C Site of AT1R Gene Polymorphism on Essential Hypertension in an Iron and Steel Enterprise Workers.

PubMed

Tong, Junwang; Wang, Ying; Yuan, Juxiang; Yang, Jingbo; Wang, Zhaoyang; Zheng, Yao; Chai, Feng; Li, Xiangwen

2017-04-01

This study aimed to analyze the interaction of Angiotensin II type 1 receptor (AT1R) gene polymorphism and occupational noise on the occurrence of essential hypertension (EH) in steel and iron enterprise men workers. A case control study of 935 iron and steel enterprise men workers was conducted, which included 312 cases of hypertension and 623 cases without hypertension. The noise at the workplace was assessed. Polymorphism of AT1R of the workers was examined using polymerase chain reaction - restriction fragment length polymorphism. Polymorphism of AT1R (AC+CC vs. AA, odds ratio [OR] = 1.760, 95% confidence interval [CI]: 1.061∼2.920) and noise (greater than or equal to 85 dB(A),OR = 1.641, 95%CI: 1.225∼2.198) were independent determinants of EH using multivariate Logistic regression. Compared with AA carriers without noise, AC+CC interacted with noise (OR = 2.519, 95%CI: 1.254∼5.062) based on the multiplied model. AC+CC genotype of AT1R and noise were the risky factors of EH. These factors also interacted with each other.

Rheumatoid Arthritis-Associated Autoantibodies and Subclinical Interstitial Lung Disease: The Multi-Ethnic Study of Atherosclerosis

PubMed Central

Bernstein, Elana J.; Barr, R. Graham; Austin, John H.M.; Kawut, Steven M.; Raghu, Ganesh; Sell, Jessica L.; Hoffman, Eric A.; Newell, John D.; Watts, Jubal R.; Nath, P. Hrudaya; Sonavane, Sushil K.; Bathon, Joan M.; Majka, Darcy S.; Lederer, David J.

2016-01-01

Background Adults with interstitial lung disease (ILD) often have serologic evidence of autoimmunity of uncertain significance without overt autoimmune disease. We examined associations of rheumatoid arthritis (RA)-associated antibodies with subclinical ILD in community-dwelling adults. Methods We measured serum rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP) and high attenuation areas (HAA; CT attenuation values between −600 and −250 HU) on cardiac CT in 6,736 community-dwelling U.S. adults enrolled in the Multi-Ethnic Study of Atherosclerosis. We measured interstitial lung abnormalities (ILA) in 2,907 full-lung CTs at 9.5-year median follow-up. We used generalized linear and additive models to examine associations between autoantibodies and both HAA and ILA, and tested for effect modification by smoking. Results In adjusted models, HAA increased by 0.49% (95% CI 0.11–0.86%) per doubling of RF IgM and by 0.95% (95% CI 0.50–1.40%) per RF IgA doubling. ILA prevalence increased by 11% (95% CI 3–20%) per RF IgA doubling. Smoking modified the associations of both RF IgM and anti-CCP with both HAA and ILA (interaction p-values varied from 0.01 to 0.09). Among ever smokers, HAA increased by 0.81% (95% CI 0.33–1.30%) and ILA prevalence increased by 14% (95% CI 5–24%,) per RF IgM doubling; and HAA increased by 1.31% (95% CI 0.45–2.18%) and ILA prevalence increased by 13% (95% CI 2–24%) per anti-CCP doubling. Among never smokers, no meaningful associations were detected. Conclusions RA-related autoimmunity is associated with both quantitative and qualitative subclinical ILD phenotypes on CT, particularly among ever smokers. PMID:27609750

Neuroblastoma Survivors are at Increased Risk for Second Malignancies: A Report from the International Neuroblastoma Risk Group Project

PubMed Central

Applebaum, Mark A.; Vaksman, Zalman; Lee, Sang Mee; Hungate, Eric A.; Henderson, Tara O.; London, Wendy B.; Pinto, Navin; Volchenboum, Samuel L.; Park, Julie R.; Naranjo, Arlene; Hero, Barbara; Pearson, Andrew D.; Stranger, Barbara E.; Cohn, Susan L.; Diskin, Sharon J.

2017-01-01

Background The incidence of SMN within the first ten years of diagnosis in high-risk neuroblastoma patients treated with modern, intensive therapy is unknown. Further, the underlying germline genetics that contribute to SMN in these survivors are not known. Methods The International Neuroblastoma Risk Group (INRG) database of patients diagnosed from 1990–2010 was analyzed. SMN risk was accessed by cumulative incidence, standardized incidence ratios (SIR), and absolute excess risk (AER). A candidate gene-based association study evaluated genetic susceptibility to SMN in neuroblastoma survivors. Results Of the 5,987 patients in the INRG database with SMN data enrolled in a clinical trial, 43 (0.72%) developed a SMN. The 10-year cumulative incidence of SMN for high-risk patients was 1.8% (95% CI 1.0–2.6%) compared to 0.38% (95% CI: 0.22–0.94%) for low-risk patients (P=0.01). High-risk patients had an almost 18-fold higher incidence of SMN compared to age and sex matched controls (SIR=17.5 (95% CI: 11.4–25.3), AER=27.6). For patients treated on high- and intermediate-risk clinical trials, the SIR of acute myelogenous leukemia (AML) was 106.8 (95% CI: 28.7–273.4) and 127.7 (95%CI: 25.7–373.3), respectively. Variants implicating DNA repair genes XRCC3 (rs861539: P=0.006; Odds Ratio: 2.04, 95%CI: 1.19–3.46) and MSH2 (rs17036651: P=0.009; Odds Ratio: 0.26, 95% CI: 0.08–0.81) were associated with SMN. Conclusion The intensive multi-modality treatment strategy currently used to treat high-risk neuroblastoma is associated with a significantly increased risk of secondary AML. Defining the interactions of treatment exposures and genetic factors that promote the development of SMN is critical for optimizing survivorship care PMID:28033528

Exploring the Driving Factors of Construction Industrialization Development in China.

PubMed

Xiahou, Xiaer; Yuan, Jingfeng; Liu, Yan; Tang, Yuchun; Li, Qiming

2018-03-03

Construction industrialization (CI) has been adopted worldwide because of its potential benefits. However, current research shows the incentives for adopting CI may differ in different regions. While the promotion of CI in China is still at the initial stage, a systematical analysis of the driving factors would help decision makers get a comprehensive understanding of CI development and select proper strategies to promote CI. This research combines qualitative and quantitative methods to explore the construction industrialization driving factors (CIDFs) in China. The grounded theory method (GTM) was employed to explore CI concepts among 182 CI-related articles published in 10 top-tier journals from 2000 to 2017. A total of 15 CIDFs were identified, including one suggested by professionals during a pre-test questionnaire survey. The analysis showed that the development of CI in China is pushed by macrodevelopment and pulled by the government and is also a self-driven process. The major driving factors for CI adoption in China are the transformation and upgrade of the conventional construction industry and the solution of development dilemmas. Our study also suggests that pilot programs are, currently, the most effective method to promote CI in China and to accumulate experience so to gain recognition by the society. This research is also of value for CI promotion in other developing countries.

Exploring the Driving Factors of Construction Industrialization Development in China

PubMed Central

Xiahou, Xiaer; Yuan, Jingfeng; Tang, Yuchun; Li, Qiming

2018-01-01

Construction industrialization (CI) has been adopted worldwide because of its potential benefits. However, current research shows the incentives for adopting CI may differ in different regions. While the promotion of CI in China is still at the initial stage, a systematical analysis of the driving factors would help decision makers get a comprehensive understanding of CI development and select proper strategies to promote CI. This research combines qualitative and quantitative methods to explore the construction industrialization driving factors (CIDFs) in China. The grounded theory method (GTM) was employed to explore CI concepts among 182 CI-related articles published in 10 top-tier journals from 2000 to 2017. A total of 15 CIDFs were identified, including one suggested by professionals during a pre-test questionnaire survey. The analysis showed that the development of CI in China is pushed by macrodevelopment and pulled by the government and is also a self-driven process. The major driving factors for CI adoption in China are the transformation and upgrade of the conventional construction industry and the solution of development dilemmas. Our study also suggests that pilot programs are, currently, the most effective method to promote CI in China and to accumulate experience so to gain recognition by the society. This research is also of value for CI promotion in other developing countries. PMID:29510507

Low-Lying π* Resonances of Standard and Rare DNA and RNA Bases Studied by the Projected CAP/SAC-CI Method.

PubMed

Kanazawa, Yuki; Ehara, Masahiro; Sommerfeld, Thomas

2016-03-10

Low-lying π* resonance states of DNA and RNA bases have been investigated by the recently developed projected complex absorbing potential (CAP)/symmetry-adapted cluster-configuration interaction (SAC-CI) method using a smooth Voronoi potential as CAP. In spite of the challenging CAP applications to higher resonance states of molecules of this size, the present calculations reproduce resonance positions observed by electron transmission spectra (ETS) provided the anticipated deviations due to vibronic effects and limited basis sets are taken into account. Moreover, for the standard nucleobases, the calculated positions and widths qualitatively agree with those obtained in previous electron scattering calculations. For guanine, both keto and enol forms were examined, and the calculated values of the keto form agree clearly better with the experimental findings. In addition to these standard bases, three modified forms of cytosine, which serve as epigenetic or biomarkers, were investigated: formylcytosine, methylcytosine, and chlorocytosine. Last, a strong correlation between the computed positions and the observed ETS values is demonstrated, clearly suggesting that the present computational protocol should be useful for predicting the π* resonances of congeners of DNA and RNA bases.

Physical and psychosocial ergonomic risk factors for low back pain in automobile manufacturing workers.

PubMed

Vandergrift, Jonathan L; Gold, Judith E; Hanlon, Alexandra; Punnett, Laura

2012-01-01

To examine the association between ergonomic physical and psychosocial exposures and the risk of prevalent and incident low back pain (LBP) in a longitudinal cohort of automobile manufacturing workers. Ergonomic exposure intensity and LBP presence were determined through questionnaires at baseline (n=1181) and to workers in the same job 1 year later (n=505). Models were constructed using log-binomial regression with special attention to interactions between ergonomic exposures. Awkward back posture (prevalence ratio (PR) 1.12, 95% CI 1.07 to 1.17), hand force (PR 1.06, 95% CI 1.02 to 1.10), physical effort (PR 1.10, 95% CI 1.04 to 1.16) and whole body vibration (PR 1.04, 95% CI 1.01 to 1.08) were each associated cross-sectionally with LBP. Awkward back posture (RR 1.13, 95% CI 0.98 to 1.31) and hand force (RR 1.07, 95% CI 0.93 to 1.22) also predicted incident LBP, although estimates were statistically less precise. Neither job control, psychological demands, nor job strain was independently related to risk of incident LBP. Among participants reporting high physical ergonomic exposures and moderate to high job control, increasing job demands was associated with a reduced LBP risk (RR 0.72, 95% CI 0.52 to 1.00). Among participants reporting high physical exposures and low job control, psychological demands was associated with an increased LBP risk (RR 1.30, 95% CI 1.02 to 1.66). Psychosocial workplace interventions for LBP should prioritise jobs in which there are high physical ergonomic exposures. Future studies of LBP should examine the interactions between physical ergonomic risk factors.

Carbon, oxygen and intrinsic defect interactions in germanium-doped silicon

NASA Astrophysics Data System (ADS)

Londos, C. A.; Sgourou, E. N.; Chroneos, A.; Emtsev, V. V.

2011-10-01

Production and annealing of oxygen-vacancy (VO) and oxygen-carbon (CiOi, CiOiI) defects in germanium-doped Czochralski-grown silicon (Cz-Si) containing carbon are investigated. All the samples were irradiated with 2 MeV fast electrons. Radiation-produced defects are studied using infrared spectroscopy by monitoring the relevant bands in optical spectra. For the VO defects, it is established that the doping with Ge affects the thermal stability of VO (830 cm-1) defects as well as their fraction converted to VO2 (888 cm-1) defects. In Ge-free samples containing carbon, it was found that carbon impurity atoms do not affect the thermal stability of VO defects, although they affect the fraction of VO defects that is converted to VO2 complexes. Considering the oxygen-carbon complexes, it is established that the annealing of the 862 cm-1 band associated with the CiOi defects is accompanied with the emergence of the 1048 cm-1 band, which has earlier been assigned to the CsO2i center. The evolution of the CiOiI bands is also traced. Ge doping does not seem to affect the thermal stability of the CiOi and CiOiI defects. Density functional theory (DFT) calculations provide insights into the stability of the defect clusters (VO, CiOi, CiOiI) at an atomic level. Both experimental and theoretical results are consistent with the viewpoint that Ge affects the stability of the VO but does not influence the stability of the oxygen-carbon clusters. DFT calculations demonstrate that C attracts both Oi and VO pairs predominately forming next nearest neighbor clusters in contrast to Ge where the interactions with Oi and VO are more energetically favorable at nearest neighbor configurations.

Pharmacokinetics and tolerability of voriconazole and a combination oral contraceptive co-administered in healthy female subjects

PubMed Central

Andrews, Emma; Damle, Bharat D; Fang, Annie; Foster, Grover; Crownover, Penelope; LaBadie, Robert; Glue, Paul

2008-01-01

AIM To assess the two-way pharmacokinetic interaction between voriconazole and Ortho-Novum® 1/35, an oral contraceptive containing norethindrone 1 mg and ethinyl oestradiol 35 μg. METHODS In this open-label, three-period, fixed-sequence study, 16 healthy females received voriconazole (400 mg q12 h, day 1; 200 mg q12 h, days 2–4) (period 1), oral contraceptive (q24 h, days 12–32) (period 2), and combination voriconazole (400 mg q12 h, day 57; 200 mg q12 h, days 58–60) and oral contraceptive (q24 h, days 40–60) (period 3). RESULTS Voriconazole geometric mean AUCτ and Cmax increased 46% (12 682–18 495 ng h ml−1; 90% confidence interval [CI] 32, 61) and 14% (2485–2840 ng ml−1; 90% CI 3, 27), respectively, when co-administered with oral contraceptive vs. voriconazole alone. Ethinyl oestradiol geometric mean AUCτ and Cmax increased 61% (1031–1657 ng h ml−1; 90% CI 50, 72) and 36% (119–161 ng ml−1; 90% CI 28, 45), respectively, and norethindrone geometric mean AUCτ and Cmax increased 53% (116–177 ng h ml−1; 90% CI 44, 64) and 15% (18–20 ng ml−1; 90% CI 3, 28), respectively, during voriconazole co-administration vs. oral contraceptive alone. Neither ethinyl oestradiol nor norethindrone levels were reduced in subjects following voriconazole co-administration. Adverse events (AEs) were generally mild, occurring less in subjects receiving voriconazole alone (36 events) vs. oral contraceptive alone (88 events) or combination treatment (68 events); four subjects experienced a severe AE. CONCLUSIONS Co-administration of voriconazole and oral contraceptive increased systemic exposures of all analytes relative to respective monotherapy. Although generally safe and well tolerated, it is recommended that patients receiving co-administered voriconazole and oral contraceptive be monitored for development of AEs commonly associated with these medications. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Voriconazole, a broad-spectrum antifungal drug, is a substrate and inhibitor of CYP2C19 and CYP3A4 isozymes.Ethinyl oestradiol and norethindrone, components of the combination oral contraceptive drug Ortho-Novum® 1/35, also are substrates of cytochrome P450 CYP2C19 and CYP3A4 isozymes.Because co-administration of voriconazole and Ortho-Novum® 1/35 could potentially result in pharmacokinetic interactions that increase systemic exposure of one or both drugs to unsafe levels, clinical studies are needed to define better the two-way pharmacokinetic interaction between these drugs. WHAT THIS STUDY ADDS Although co-administered voriconazole and oral contraceptive did result in increased systemic exposures of all three drugs relative to respective monotherapy, co-administered treatment was generally safe and well tolerated.It is recommended, however, that patients receiving co-administered voriconazole and oral contraceptives be monitored for the development of adverse events commonly associated with these medications. PMID:18294327

Short-term effects of meteorological factors on hand, foot and mouth disease among children in Shenzhen, China: Non-linearity, threshold and interaction.

PubMed

Zhang, Zhen; Xie, Xu; Chen, Xiliang; Li, Yuan; Lu, Yan; Mei, Shujiang; Liao, Yuxue; Lin, Hualiang

2016-01-01

Various meteorological factors have been associated with hand, foot and mouth disease (HFMD) among children; however, fewer studies have examined the non-linearity and interaction among the meteorological factors. A generalized additive model with a log link allowing Poisson auto-regression and over-dispersion was applied to investigate the short-term effects daily meteorological factors on children HFMD with adjustment of potential confounding factors. We found positive effects of mean temperature and wind speed, the excess relative risk (ERR) was 2.75% (95% CI: 1.98%, 3.53%) for one degree increase in daily mean temperature on lag day 6, and 3.93% (95% CI: 2.16% to 5.73%) for 1m/s increase in wind speed on lag day 3. We found a non-linear effect of relative humidity with thresholds with the low threshold at 45% and high threshold at 85%, within which there was positive effect, the ERR was 1.06% (95% CI: 0.85% to 1.27%) for 1 percent increase in relative humidity on lag day 5. No significant effect was observed for rainfall and sunshine duration. For the interactive effects, we found a weak additive interaction between mean temperature and relative humidity, and slightly antagonistic interaction between mean temperature and wind speed, and between relative humidity and wind speed in the additive models, but the interactions were not statistically significant. This study suggests that mean temperature, relative humidity and wind speed might be risk factors of children HFMD in Shenzhen, and the interaction analysis indicates that these meteorological factors might have played their roles individually. Copyright © 2015 Elsevier B.V. All rights reserved.

Specificity Rendering ‘Hot-Spots’ for Aurora Kinase Inhibitor Design: The Role of Non-Covalent Interactions and Conformational Transitions

PubMed Central

Badrinarayan, Preethi; Sastry, G. Narahari

2014-01-01

The present study examines the conformational transitions occurring among the major structural motifs of Aurora kinase (AK) concomitant with the DFG-flip and deciphers the role of non-covalent interactions in rendering specificity. Multiple sequence alignment, docking and structural analysis of a repertoire of 56 crystal structures of AK from Protein Data Bank (PDB) has been carried out. The crystal structures were systematically categorized based on the conformational disposition of the DFG-loop [in (DI) 42, out (DO) 5 and out-up (DOU) 9], G-loop [extended (GE) 53 and folded (GF) 3] and αC-helix [in (CI) 42 and out (CO) 14]. The overlapping subsets on categorization show the inter-dependency among structural motifs. Therefore, the four distinct possibilities a) 2W1C (DI, CI, GE) b) 3E5A (DI, CI, GF) c) 3DJ6 (DI, CO, GF) d) 3UNZ (DOU, CO, GF) along with their co-crystals and apo-forms were subjected to molecular dynamics simulations of 40 ns each to evaluate the variations of individual residues and their impact on forming interactions. The non-covalent interactions formed by the 157 AK co-crystals with different regions of the binding site were initially studied with the docked complexes and structure interaction fingerprints. The frequency of the most prominent interactions was gauged in the AK inhibitors from PDB and the four representative conformations during 40 ns. Based on this study, seven major non-covalent interactions and their complementary sites in AK capable of rendering specificity have been prioritized for the design of different classes of inhibitors. PMID:25485544

Effects of interactions between common genetic variants and alcohol consumption on colorectal cancer risk

PubMed Central

Song, Nan; Shin, Aesun; Oh, Jae Hwan; Kim, Jeongseon

2018-01-01

Background Genome-wide association studies (GWAS) have identified approximately 40 common genetic loci associated with colorectal cancer risk. To investigate possible gene-environment interactions (GEIs) between GWAS-identified single-nucleotide polymorphisms (SNPs) and alcohol consumption with respect to colorectal cancer, a hospital-based case-control study was conducted. Results Higher levels of alcohol consumption as calculated based on a standardized definition of a drink (1 drink=12.5g of ethanol) were associated with increased risk of colorectal cancer (OR=2.47, 95% CI=1.62-3.76 for heavy drinkers [>50g/day] compared to never drinkers; ptrend<0.01). SNP rs6687758 near the DUSP10 gene at 1q41 had a statistically significant interaction with alcohol consumption in analyses of standardized drinks (p=4.6×10-3), although this did not surpass the corrected threshold for multiple testing. When stratified by alcohol consumption levels, in an additive model the risk of colorectal cancer associated with the G allele of rs6687758 tended to increase among individuals in the heavier alcohol consumption strata. A statistically significant association between rs6687758 and colorectal cancer risk was observed among moderate alcohol drinkers who consumed between >12.5 and ≤50g of alcohol per day (OR=1.46, 95% CI=1.01-2.11). Methods A total of 2,109 subjects (703 colorectal cancer patients and 1,406 healthy controls) were recruited from the Korean National Cancer Center. For genotyping, 30 GWAS-identified SNPs were selected. A logistic regression model was used to evaluate associations of SNPs and alcohol consumption with colorectal cancer risk. We also tested GEIs between SNPs and alcohol consumption using a logistic model with multiplicative interaction terms. Conclusions Our results suggest that SNP rs6687758 at 1q41 may interact with alcohol consumption in the etiology of colorectal cancer. PMID:29464080

Schistosoma mansoni: interactive effects of irradiation and cryopreservation on parasite maturation and immunization of mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

James, E.R.; Dobinson, A.R.

1984-06-01

Mechanically transformed schistosomula of Schistosoma mansoni were irradiated with levels of 60Co irradiation between 2.5 and 54 krad, cryopreserved by the two-step addition of ethanediol and rapid cooling technique, and were injected intramuscularly into groups of mice which were perfused 40 days later. The schistosomula were either irradiated and then cryopreserved (IC) or cryopreserved and then irradiated in the frozen state (CI). Development into adult worms was prevented with 4 krad for IC schistosomula, but for CI schistosomula a small number of worms (1.6%) was recovered using 8.8 krad. A dose of 4 krad was sufficient to prevent development ofmore » unfrozen controls (I), but for schistosomula irradiated while exposed to ethanediol (EI), a dose of 7 krad was required. Using the different protocols, the peak levels of protection against a challenge infection were achieved with 9 (IC) and 16 krad (CI), compared to 20 krad for unfrozen schistosomula (I) reported previously. The highest level of protection (65%) was achieved with CI schistosomula. Possible interactions between the radioprotective and damaging effects of cryopreservation are discussed.« less

Accurate calculation and modeling of the adiabatic connection in density functional theory

NASA Astrophysics Data System (ADS)

Teale, A. M.; Coriani, S.; Helgaker, T.

2010-04-01

Using a recently implemented technique for the calculation of the adiabatic connection (AC) of density functional theory (DFT) based on Lieb maximization with respect to the external potential, the AC is studied for atoms and molecules containing up to ten electrons: the helium isoelectronic series, the hydrogen molecule, the beryllium isoelectronic series, the neon atom, and the water molecule. The calculation of AC curves by Lieb maximization at various levels of electronic-structure theory is discussed. For each system, the AC curve is calculated using Hartree-Fock (HF) theory, second-order Møller-Plesset (MP2) theory, coupled-cluster singles-and-doubles (CCSD) theory, and coupled-cluster singles-doubles-perturbative-triples [CCSD(T)] theory, expanding the molecular orbitals and the effective external potential in large Gaussian basis sets. The HF AC curve includes a small correlation-energy contribution in the context of DFT, arising from orbital relaxation as the electron-electron interaction is switched on under the constraint that the wave function is always a single determinant. The MP2 and CCSD AC curves recover the bulk of the dynamical correlation energy and their shapes can be understood in terms of a simple energy model constructed from a consideration of the doubles-energy expression at different interaction strengths. Differentiation of this energy expression with respect to the interaction strength leads to a simple two-parameter doubles model (AC-D) for the AC integrand (and hence the correlation energy of DFT) as a function of the interaction strength. The structure of the triples-energy contribution is considered in a similar fashion, leading to a quadratic model for the triples correction to the AC curve (AC-T). From a consideration of the structure of a two-level configuration-interaction (CI) energy expression of the hydrogen molecule, a simple two-parameter CI model (AC-CI) is proposed to account for the effects of static correlation on the AC. When parametrized in terms of the same input data, the AC-CI model offers improved performance over the corresponding AC-D model, which is shown to be the lowest-order contribution to the AC-CI model. The utility of the accurately calculated AC curves for the analysis of standard density functionals is demonstrated for the BLYP exchange-correlation functional and the interaction-strength-interpolation (ISI) model AC integrand. From the results of this analysis, we investigate the performance of our proposed two-parameter AC-D and AC-CI models when a simple density functional for the AC at infinite interaction strength is employed in place of information at the fully interacting point. The resulting two-parameter correlation functionals offer a qualitatively correct behavior of the AC integrand with much improved accuracy over previous attempts. The AC integrands in the present work are recommended as a basis for further work, generating functionals that avoid spurious error cancellations between exchange and correlation energies and give good accuracy for the range of densities and types of correlation contained in the systems studied here.

Effects of prenatal community violence and ambient air pollution on childhood wheeze in an urban population

PubMed Central

Mathilda Chiu, Yueh-Hsiu; Coull, Brent A.; Sternthal, Michelle J.; Kloog, Itai; Schwartz, Joel; Cohen, Sheldon; Wright, Rosalind J.

2013-01-01

Background: Prenatal exposures to stress and physical toxins influence children’s respiratory health, albeit few studies consider these factors together. Objectives: To concurrently examine effects of prenatal community-level psychosocial (exposure to community violence, ECV) and physical (air pollution) stressors on repeated wheeze in 708 urban children followed to age 2 years. Methods: Multi-item ECV reported by mothers in pregnancy was summarized into a continuous score using Rasch modeling. Prenatal black carbon (BC) exposure was estimated using land-use regression (LUR) modeling; particulate matter (PM2.5) was estimated using LUR incorporating satellite data. Mothers reported child’s wheeze every 3 months. Effects of ECV and air pollutants on repeated wheeze (≥2 episodes) were examined using logistic regression. Interactions between ECV and pollutants were examined. Results: Mothers were primarily Black (29%) and Hispanic (55%) with lower education (62% with ≤12 years); 87 children (12%) wheezed repeatedly. In models examining concurrent exposures, ECV [OR=1.95 (95% CI: 1.13-3.36), highest vs. lowest tertile] and BC [OR=1.84 (95% CI: 1.08-3.12), ≥median vs.

Serum Endotoxins and Flagellin and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

PubMed Central

Kong, So Yeon; Tran, Hao Quang; Gewirtz, Andrew T.; McKeown-Eyssen, Gail; Fedirko, Veronika; Romieu, Isabelle; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Boutron-Ruault, Marie-Christine; Bastide, Nadia; Affret, Aurélie; Kühn, Tilman; Kaaks, Rudolf; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Kritikou, Maria; Vasilopoulou, Effie; Palli, Domenico; Krogh, Vittorio; Mattiello, Amalia; Tumino, Rosario; Naccarati, Alessio; Bueno-de-Mesquita, H.Bas; Peeters, Petra H.; Weiderpass, Elisabete; Quirós, J. Ramón; Sala, Núria; Sánchez, María-José; Huerta Castaño, José María; Barricarte, Aurelio; Dorronsoro, Miren; Werner, Mårten; Wareham, Nicholas J.; Khaw, Kay-Tee; Bradbury, Kathryn E.; Freisling, Heinz; Stavropoulou, Faidra; Ferrari, Pietro; Gunter, Marc J.; Cross, Amanda J.; Riboli, Elio; Bruce, W. Robert

2017-01-01

Background Chronic inflammation and oxidative stress are thought to be involved in colorectal cancer (CRC) development. These processes may be contributed to by leakage of bacterial products, such as lipopolysaccharide (LPS) and flagellin, across the gut barrier. The objective of this study, nested within a prospective cohort, was to examine associations between circulating LPS and flagellin serum antibody levels and CRC risk. Methods 1,065 incident CRC cases (colon n=667; rectal n=398) were matched (1:1) to control subjects. Serum flagellin- and LPS-specific IgA and IgG levels were quantitated by ELISA. Multivariable conditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI), adjusting for multiple relevant confouding factors. Results Overall, elevated anti-LPS and anti-flagellin biomarker levels were not associated with CRC risk. After testing potential interactions by various factors relevant for CRC risk and anti-LPS and anti-flagellin, sex was identified as a statistically significant interaction factor (pinteraction < 0.05 for all the biomarkers). Analyses stratified by sex showed a statistically significant positive CRC risk association for men (fully-adjusted OR for highest vs. lowest quartile for total anti-LPS+flagellin = 1.66; 95% CI, 1.10-2.51; ptrend = 0.049) while a borderline statistically significant inverse association was observed for women (fully-adjusted OR= 0.70; 95%CI, 0.47-1.02; ptrend = 0.18). Conclusion In this prospective study on European populations, we found bacterial exposure levels to be positively associated to CRC risk among men while in women, a possible inverse association may exist. Impact Further studies are warranted to better clarify these preliminary observations. PMID:26823475

The association of health and voluntary early retirement pension and the modifying effect of quality of supervision: Results from a Danish register-based follow-up study

PubMed Central

de Wind, Astrid; Burr, Hermann; Pohrt, Anne; Hasselhorn, Hans Martin; Van der Beek, Allard Johan; Rugulies, Reiner

2017-01-01

Objectives: The aims of this article are to (1) determine whether and to what extent general perceived health and quality of supervision predict voluntary early retirement pension (VERP) and (2) assess whether quality of supervision modifies the association between general perceived health and VERP. Methods: Employees aged 49–64 years who participated in the Danish Work Environment Cohort Study in 2000 were selected. Their questionnaire data about health and work were linked to register data on social transfer payments, among others VERP, from 2001 to 2012 in the Danish Register for Evaluation of Marginalization (N=1167). Cox proportional hazards analyses were performed to identify the prospective association of general perceived health and quality of supervision on VERP. Relative excess risks due to interaction (RERIs) were calculated to assess whether quality of supervision modified the association between health and VERP. Results: Employees with poor health at baseline had an increased risk of VERP during follow-up (hazard ratio [HR]=1.23; 95% confidence interval [CI] 1.02–1.49). Quality of supervision at baseline was not associated to VERP during follow-up (HR=1.04; 95% CI 0.90–1.21). There was no statistically significant interaction of poor health and poor quality of supervision with regard to risk of VERP (RERI=−0.33; 95% CI −1.79 to 1.14). Conclusions: This study did not support the notion that quality of supervision buffers the association between poor health and VERP. Future research is needed to determine whether other aspects of supervision, for example supervisors’ opportunities to effectuate workplace adjustments, may modify the association of poor health and VERP. PMID:28381121

Maternal education and age: inequalities in neonatal death

PubMed Central

Fonseca, Sandra Costa; Flores, Patricia Viana Guimarães; Camargo, Kenneth Rochel; Pinheiro, Rejane Sobrino; Coeli, Claudia Medina

2017-01-01

ABSTRACT OBJECTIVE Evaluate the interaction between maternal age and education level in neonatal mortality, as well as investigate the temporal evolution of neonatal mortality in each stratum formed by the combination of these two risk factors. METHODS A nonconcurrent cohort study, resulting from a probabilistic relationship between the Mortality Information System and the Live Birth Information System. To investigate the risk of neonatal death we performed a logistic regression, with an odds ratio estimate for the combined variable of maternal education and age, as well as the evaluation of additive and multiplicative interaction. The neonatal mortality rate time series, according to maternal education and age, was estimated by the Joinpoint Regression program. RESULTS The neonatal mortality rate in the period was 8.09‰ and it was higher in newborns of mothers with low education levels: 12.7‰ (adolescent mothers) and 12.4‰ (mother 35 years old or older). Low level of education, without the age effect, increased the chance of neonatal death by 25% (OR = 1.25, 95%CI 1.14–1.36). The isolated effect of age on neonatal death was higher for adolescent mothers (OR = 1.39, 95%CI 1.33–1.46) than for mothers aged ≥ 35 years (OR = 1.16, 95%CI 1.09–1.23). In the time-trend analysis, no age group of women with low education levels presented a reduction in the neonatal mortality rate for the period, as opposed to women with intermediate or high levels of education, where the reduction was significant, around 4% annually. CONCLUSIONS Two more vulnerable groups – adolescents with low levels of education and older women with low levels of education – were identified in relation to the risk of neonatal death and inequality in reducing the mortality rate. PMID:29166446

Parent-adolescent interaction and risk of adolescent internet addiction: a population-based study in Shanghai

PubMed Central

2014-01-01

Background Family-based intervention is essential for adolescents with behavioral problems. However, limited data are available on the relationship between family-based factors and adolescent internet addiction (AIA). We aimed to examine this relationship using a representative sample of Shanghai adolescents. Methods In October 2007, a total of 5122 adolescents were investigated from 16 high schools via stratified-random sampling in Shanghai. Self-reported and anonymous questionnaires were used to assess parent-adolescent interaction and family environments. AIA was assessed by DRM-52 Scale, developed from Young’s Internet-addiction Scale, using seven subscales to evaluate psychological symptoms of AIA. Results Adjusting for adolescents’ ages, genders, socio-economic status, school performances and levels of the consumption expenditure, strong parental disapproval of internet-use was associated with AIA (vs. parental approval, OR = 2.20, 95% CI: 1.24-3.91). Worse mother-adolescent relationships were more significantly associated with AIA (OR = 3.79, 95% CI: 2.22-6.48) than worse father-adolescent relationships (OR = 1.76, 95% CI: 1.10-2.80). Marital status of “married-but-separated” and family structure of “left-behind adolescents” were associated with symptoms of some subscales. When having high monthly allowance, resident students tended to develop AIA but commuter students did not. Family social-economic status was not associated with the development of AIA. Conclusions The quality of parent-adolescent relationship/communication was closely associated with the development of AIA, and maternal factors were more significantly associated with development of AIA than paternal factors. Family social-economic status moderated adolescent internet-use levels but not the development of AIA. PMID:24731648

Gene variants as risk factors for gastroschisis

PubMed Central

Yang, Wei; Schultz, Kathleen; Tom, Lauren; Lin, Bin; Carmichael, Suzan L.; Lammer, Edward J.; Shaw, Gary M.

2016-01-01

In a population‐based case‐control study in California of 228 infants, we investigated 75 genetic variants in 20 genes and risk of gastroschisis with regard to maternal age, race/ethnicity, vitamin use, and smoking exposure. We hypothesized that genes related to vascular compromise may interact with environmental factors to affect the risk of gastroschisis. Haplotypes were constructed for 75 gene variants using the HaploView program. Risk for gastroschisis associated with each gene variant was calculated for both the homozygotes and the heterozygotes, with the homozygous wildtypes as the referent. Risks were estimated as odds ratios (ORs) with 95% confidence intervals (CIs) by logistic regression. We found 11 gene variants with increased risk and four variants with decreased risk of gastroschisis for heterozygous (ORh) or homozygous variants (ORv) genotypes. These included NOS3 (rs1036145) ORh = 0.4 (95% CI: 0.2–0.7); NOS3 (rs10277237) ORv = 2.7 (95% CI: 1.3–6.0); ADD1 (rs12503220) ORh = 2.9 (95% CI: 1.6–5.4), GNB3 (rs5443) ORh = 0.2 (95% CI: 0.1–0.5), ORv = 0.4 (95% CI: 0.2–0.9); ICAM1 (rs281428) ORv = 6.9 (95% CI: 2.1–22.9), ICAM1 (rs3093030) ORv = 2.6 (95% CI: 1.2–5.6); ICAM4 (rs281438) ORv = 4.9 (95% CI: 1.4–16.6), ICAM5 (rs281417) ORh = 2.1 (95% CI: 1.1–4.1), ORv = 4.8 (95% CI: 1.7–13.6); ICAM5 (rs281440) ORh = 23.7 (95% CI: 5.5–102.5), ORv = 20.6 (95% CI: 3.4–124.3); ICAM5 (rs2075741) ORv = 2.2 (95% CI: 1.1–4.4); NAT1 ORv = 0.3 (95% CI: 0.1–0.9). There were additional associations between several gene variants and gastroschisis among women aged 20–24 and among mothers with and without vitamin use. NOS3, ADD1, ICAM1, ICAM4, and ICAM5 warrant further investigation in additional populations and with the interaction of additional environmental exposures. © 2016 Wiley Periodicals, Inc. PMID:27616475

Interaction of sleep quality and sleep duration on impaired fasting glucose: a population-based cross-sectional survey in China.

PubMed

Lou, Peian; Chen, Peipei; Zhang, Lei; Zhang, Pan; Chang, Guiqiu; Zhang, Ning; Li, Ting; Qiao, Cheng

2014-03-13

To explore the interactions of sleep quality and sleep duration and their effects on impaired fasting glucose (IFG) in Chinese adults. Cross-sectional survey. Community-based investigation in Xuzhou, China. 15 145 Chinese men and women aged 18-75 years old who fulfilled the inclusion criteria. The Pittsburgh Sleep Quality Index was used to produce sleep quality categories of good, common and poor. Fasting blood glucose levels were assessed for IFG. Sleep duration was measured by average hours of sleep per night, with categories of <6, 6-8 and >8 h. The products of sleep and family history of diabetes, obesity and age were added to the logistic regression model to evaluate the addictive interaction and relative excess risk of interaction (RERI) on IFG. The attributable proportion (AP) of the interaction and the synergy index (S) were applied to evaluate the additive interaction of two factors. Bootstrap measures were used to calculate 95% CI of RERI, AP and S. The prevalence of IFG was greatest in those with poor sleep quality and short sleep duration (OR 6.37, 95% CI 4.66 to 8.67; p<0.001) compared with those who had good sleep quality and 6-8 h sleep duration, after adjusting for confounders. After adjusting for potential confounders RERI, AP and S values (and their 95% CI) were 1.69 (0.31 to 3.76), 0.42 (0.15 to 0.61) and 2.85 (2.14 to 3.92), respectively, for the interaction between poor sleep quality and short sleep duration, and 0.78 (0.12 to 1.43), 0.61 (0.26 to 0.87) and -65 (-0.94 to -0.27) for the interaction between good sleep quality and long sleep duration. The results suggest that there are additive interactions between poor sleep quality and short sleep duration.

Health care expenditures associated with overweight and obesity among US adults: importance of age and race.

PubMed

Wee, Christina C; Phillips, Russell S; Legedza, Anna T R; Davis, Roger B; Soukup, Jane R; Colditz, Graham A; Hamel, Mary Beth

2005-01-01

We estimated health care expenditures associated with overweight and obesity and examined the influence of age, race, and gender. Using 1998 Medical Expenditure Panel Survey data, we employed 2-stage modeling to estimate annual health care expenditures associated with high body mass index (BMI) and examine interactions between demographic factors and BMI. Overall, the mean per capita annual health care expenditure (converted to December 2003 dollars) was $3338 before adjustment. While the adjusted expenditure was $2127 (90% confidence interval [CI]=$1927, $2362) for a typical normal-weight White woman aged 35 to 44 years, expenditures were $2358 (90% CI=$2128, $2604) for women with BMIs of 25 to 29.9 kg/m(2), $2873 (90% CI=$2530, $3236) for women with BMIs of 30 to 34.9 kg/m(2), $3058 (90% CI=$2529, $3630) for women with BMIs of 35 to 39.9 kg/m(2), and $3506 (90% CI=$2912, $4228) for women with BMIs of 40 kg/m(2) or higher. Expenditures related to higher BMI rose dramatically among White and older adults but not among Blacks or those younger than 35 years. We found no interaction between BMI and gender. Health care costs associated with overweight and obesity are substantial and vary according to race and age.

Apixaban in Comparison With Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: Findings From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial.

PubMed

Avezum, Alvaro; Lopes, Renato D; Schulte, Phillip J; Lanas, Fernando; Gersh, Bernard J; Hanna, Michael; Pais, Prem; Erol, Cetin; Diaz, Rafael; Bahit, M Cecilia; Bartunek, Jozef; De Caterina, Raffaele; Goto, Shinya; Ruzyllo, Witold; Zhu, Jun; Granger, Christopher B; Alexander, John H

2015-08-25

Apixaban is approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. However, the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial included a substantial number of patients with valvular heart disease and only excluded patients with clinically significant mitral stenosis or mechanical prosthetic heart valves. We compared the effect of apixaban and warfarin on rates of stroke or systemic embolism, major bleeding, and death in patients with and without moderate or severe valvular heart disease using Cox proportional hazards modeling. Of the 18 201 patients enrolled in ARISTOTLE, 4808 (26.4%) had a history of moderate or severe valvular heart disease or previous valve surgery. Patients with valvular heart disease had higher rates of stroke or systemic embolism and bleeding than patients without valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in patients with and without valvular heart disease in reducing stroke and systemic embolism (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.51-0.97 and HR, 0.84; 95%, CI 0.67-1.04; interaction P=0.38), causing less major bleeding (HR, 0.79; 95% CI, 0.61-1.04 and HR, 0.65; 95% CI, 0.55-0.77; interaction P=0.23), and reducing mortality (HR, 1.01; 95% CI, 0.84-1.22 and HR, 0.84; 95% CI, 0.73-0.96; interaction P=0.10). More than a quarter of the patients in ARISTOTLE with nonvalvular atrial fibrillation had moderate or severe valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in reducing stroke or systemic embolism, causing less bleeding, and reducing death in patients with and without valvular heart disease. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984. © 2015 American Heart Association, Inc.

Genetic ancestry modifies the association between genetic risk variants and breast cancer risk among Hispanic and non-Hispanic white women

PubMed Central

Fejerman, Laura

2013-01-01

Hispanic women in the USA have lower breast cancer incidence than non-Hispanic white (NHW) women. Genetic factors may contribute to this difference. Breast cancer genome-wide association studies (GWAS) conducted in women of European or Asian descent have identified multiple risk variants. We tested the association between 10 previously reported single nucleotide polymorphisms (SNPs) and risk of breast cancer in a sample of 4697 Hispanic and 3077 NHW women recruited as part of three population-based case–control studies of breast cancer. We used stratified logistic regression analyses to compare the associations with different genetic variants in NHWs and Hispanics classified by their proportion of Indigenous American (IA) ancestry. Five of 10 SNPs were statistically significantly associated with breast cancer risk. Three of the five significant variants (rs17157903-RELN, rs7696175-TLR1 and rs13387042-2q35) were associated with risk among Hispanics but not in NHWs. The odds ratio (OR) for the heterozygous at 2q35 was 0.75 [95% confidence interval (CI) = 0.50–1.15] for low IA ancestry and 1.38 (95% CI = 1.04–1.82) for high IA ancestry (P interaction 0.02). The ORs for association at RELN were 0.87 (95% CI = 0.59–1.29) and 1.69 (95% CI = 1.04–2.73), respectively (P interaction 0.03). At the TLR1 locus, the ORs for women homozygous for the rare allele were 0.74 (95% CI = 0.42–1.31) and 1.73 (95% CI = 1.19–2.52) (P interaction 0.03). Our results suggest that the proportion of IA ancestry modifies the magnitude and direction of the association of 3 of the 10 previously reported variants. Genetic ancestry should be considered when assessing risk in women of mixed descent and in studies designed to discover causal mutations. PMID:23563089

Copy number variations of GSTT1 and GSTM1, colorectal cancer risk and possible effect modification of cigarette smoking and menopausal hormone therapy.

PubMed

Rudolph, Anja; Hein, Rebecca; Hoffmeister, Michael; Försti, Asta; Hemminki, Kari; Risch, Angela; Brenner, Hermann; Chang-Claude, Jenny

2012-09-01

Copy number variations (CNVs) of the glutathione-S-transferase θ-1 (GSTT1) and glutathione-S-transferase μ-1 (GSTM1) gene loci can lead to complete lack of enzyme and have been associated with colorectal cancer (CRC) risk. As GSTs are involved in the detoxification of xenobiotics, CNVs may modify CRC risk associated with smoking exposure and menopausal hormone therapy (MHT) use. We investigated CRC risk associated with GSTT1 and GSTM1 CNVs and their interaction with smoking in 1,796 cases and 1,806 age-, sex- and residence-matched controls from a German population-based case-control study (DACHS). The interaction with MHT was assessed in the subset of 684 postmenopausal female cases and 681 controls. Trimodular genotypes (0/0, 1/0 and 1/1) were determined with relative quantification based on multiplex real-time polymerase chain reaction. The associations with CRC risk as well as possible effect modifications were evaluated using conditional logistic regression analysis. CNVs of GSTT1 and GSTM1 were not significantly associated with CRC risk. Compared to the 1/1 genotype, odds ratios (ORs) for the 0/1 genotype and the 0/0 genotype were 0.89 [95% confidence interval (CI): 0.77-1.04] and 0.97 (95% CI: 0.80-1.18) for GSTT1, and 0.99 (95% CI: 0.78-1.27) and 1.03 (95% CI: 0.81-1.31) for GSTM1. Compared to the non-null genotype, ORs for the null-genotype were 1.04 (95% CI: 0.87-1.23) for GSTT1 and 1.03 (95% CI: 0.91-1.18) for GSTM1. No significant interaction with smoking and MHT use was observed. Our study does not provide evidence for a strong association between CRC risk and CNVs of GSTT1 or GSTM1 or for an effect modification of smoking or MHT use. Copyright © 2012 UICC.

Efficacy and safety of apixaban compared with warfarin for stroke prevention in patients with atrial fibrillation from East Asia: a subanalysis of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial.

PubMed

Goto, Shinya; Zhu, Jun; Liu, Lisheng; Oh, Byung-Hee; Wojdyla, Daniel M; Aylward, Philip; Bahit, M Cecilia; Gersh, Bernard J; Hanna, Michael; Horowitz, John; Lopes, Renato D; Wallentin, Lars; Xavier, Denis; Alexander, John H

2014-09-01

The perceived risk of serious bleeding is an obstacle to the use of oral anticoagulation in East Asia. The efficacy and safety of apixaban in East Asian patients with atrial fibrillation are unknown. ARISTOTLE included 18,201 patients with nonvalvular atrial fibrillation randomized to apixaban 5mg twice daily or warfarin. The efficacy and safety of apixaban and warfarin among patients recruited from East Asia (n = 1,993) were compared with those recruited from outside East Asia (n = 16,208). Compared with warfarin, apixaban resulted in a consistent reduction in stroke or systemic embolism in East Asian (hazard ratio [HR] 0.74, 95% CI 0.50-1.10) and non-East Asian (HR 0.81, 95% CI 0.66-0.99) patients (interaction P = .70). Consistent benefits of apixaban over warfarin were also seen for major bleeding in East Asian (HR 0.53, 95% CI 0.35-0.80) and non-East Asian (HR 0.72, 95% CI 0.62-0.83) patients (interaction P = .17). There was a greater reduction in major or clinically relevant nonmajor bleeding with apixaban compared with warfarin in East Asian (HR 0.49, 95% CI 0.35-0.67) than in non-East Asian (HR 0.71, 95% CI 0.63-0.79) patients (interaction P = .03). Numerically higher rates of intracranial bleeding were seen in East Asian patients with warfarin but not with apixaban. Apixaban resulted in similar reductions in stroke or systemic embolism and major bleeding and greater reductions in major or clinically relevant nonmajor bleeding in patients from East Asia. Warfarin is associated with more intracranial bleeding, particularly in patients from East Asia. Copyright © 2014 Mosby, Inc. All rights reserved.

Interaction between physical and psychosocial work risk factors for low back symptoms and its consequences amongst Indonesian coal mining workers.

PubMed

Widanarko, Baiduri; Legg, Stephen; Devereux, Jason; Stevenson, Mark

2015-01-01

This study assessed the interaction between physical and psychosocial factors for low back symptoms (LBS) and its consequences (reduced activities and absenteeism) in a developing country. A sample of 1294 Indonesian coal mining workers reported occupational exposures, LBS and its consequences using a self-administered questionnaire. Respondents were placed into one of four combination exposure groups: high physical and high psychosocial (HPhyHPsy); high physical and low psychosocial (HPhyLPsy); low physical and high psychosocial (LPhyHPsy), and; low physical and low psychosocial (LPhyLPsy). The attributable proportion due to interaction between physical and psychosocial factors was examined. Individuals in the HPhyHPsy group were most likely to report LBS (OR 5.42, 95% CI 3.30-8.89), reduced activities (OR 4.89, 95% CI 3.09-7.74), and absenteeism (OR 4.96, 95% CI 3.05-8.06). Interactions between physical and psychosocial factors were present for LBS, reduced activities, and absenteeism; although for LBS and absenteeism the interactions were not significant. Current smokers were more likely to report LBS consequences. Permanent employment and night shift work increased the odds of LBS and its consequences. We conclude that interventions aimed at reducing LBS and its consequences should address both physical and psychosocial factors, with a focus on smokers, permanent employment and night shift work. Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.

To be or not to be empathic: the combined role of empathic concern and perspective taking in understanding burnout in general practice

PubMed Central

2014-01-01

Background General practice is stressful and burnout is common among family physicians. A growing body of evidence suggests that the way physicians relate to their patients could be linked to burnout. The goal of this study was to examine how patterns of empathy explained physicians’ burnout. Methods We surveyed 294 French general practitioners (response rate 39%), measured burnout, empathic concern (EC) and perspective taking (PT) using self-reported questionnaires, and modeled burnout levels and frequencies with EC, PT and their interaction in linear and logistic regression analyses. Results Multivariate linear models for burnout prediction were associated with lower PT (β = −0.21, p < 0.001) and lower EC (β = −0.17, p < 0.05). Interestingly, the interaction (EC x PT) also predicted burnout levels (β = 0.11, p < 0.05). The investigation of interactions revealed that high scores on PT predicted lower levels of burnout independent from EC (odd ratios (OR) 0.37; 95% confidence interval (95% CI) 0.21–0.65 p < 0.001), and high scores on both EC and PT were protective against burnout: OR 0.31; 95% CI 0.15–0.63, p < 0.001). Conclusions Deficits in PT alone might be a risk factor for burnout, whereas higher PT and EC might be protective. Educators should take into account how the various components of empathy are potentially associated with emotional outcomes in physicians. PMID:24456299

The DNA Methyltransferase 3B -149 Genetic Polymorphism Modulates Lung Cancer Risk from Smoking

PubMed Central

Lai, Chung Yu; Huang, Chia Chen; Tsai, Chin Hung; Wang, Jiun Yao; Kerr, Chih Ling; Chen, Yi Yu; Cai, Yan Wei; Wong, Ruey Hong

2017-01-01

Background: Smoking can cause increase of DNA methylation and hypermethylation of tumor suppressor genes, this possible contributing to subsequent lung cancer development. DNA methyltransferase 3B (DNMT3B) is crucial in regulation of DNA methylation and it has been proposed that green tea might lower cancer risk through inhibiting its activity. Here, we designed a case-control study to investigate whether the DNMT3B -149 genetic polymorphism could modulate lung cancer risk due to smoking. Possible interactions of smoking and green tea consumption with this DNMT3B genetic polymorphism were also assessed. Materials and Methods: A total of 190 lung cancer patients and 380 healthy controls were recruited. Questionnaires were administered to obtain data on sociodemographic and lifestyle variables, as well as family history of lung cancer. Genotypes for DNMT3B -149 were identified by polymerase chain reaction. Results: Smoking, green tea consumption, exposure to cooking fumes, family history of lung cancer, and the DNMT3B -149 genotype (odds ratio (OR)=2.65; 95% confidence interval (CI) 1.15-6.10) were all significantly associated with the development of lung cancer. Smokers carrying the DNMT3B -149 TT genotype were at elevated risk compared to non-smokers carrying DNMT3B -149 (OR=7.69; 95% CI 2.55-23.14). Interaction of smoking with DNMT3B -149 genotypes was significant regarding lung cancer risk. However, interaction between green tea drinking and DNMT3B -149 genotypes was not. Conclusions: The DNMT3B -149 TT genotype might increase the smoking-associated lung cancer risk. PMID:29072397

The Kto-Skd complex can regulate ptc expression by interacting with Cubitus interruptus (Ci) in the Hedgehog signaling pathway.

PubMed

Mao, Feifei; Yang, Xiaofeng; Fu, Lin; Lv, Xiangdong; Zhang, Zhao; Wu, Wenqing; Yang, Siqi; Zhou, Zhaocai; Zhang, Lei; Zhao, Yun

2014-08-08

The hedgehog (Hh) signaling pathway plays a very important role in metazoan development by controlling pattern formation. Drosophila imaginal discs are subdivided into anterior and posterior compartments that derive from adjacent cell populations. The anterior/posterior (A/P) boundaries, which are critical to maintaining the position of organizers, are established by a complex mechanism involving Hh signaling. Here, we uncover the regulation of ptc in the Hh signaling pathway by two subunits of mediator complex, Kto and Skd, which can also regulate boundary location. Collectively, we provide further evidence that Kto-Skd affects the A/P-axial development of the whole wing disc. Kto can interact with Cubitus interruptus (Ci), bind to the Ci-binding region on ptc promoter, which are both regulated by Hh signals to down-regulate ptc expression. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Assessment of sound quality perception in cochlear implant users during music listening.

PubMed

Roy, Alexis T; Jiradejvong, Patpong; Carver, Courtney; Limb, Charles J

2012-04-01

Although cochlear implant (CI) users frequently report deterioration of sound quality when listening to music, few methods exist to quantify these subjective claims. 1) To design a novel research method for quantifying sound quality perception in CI users during music listening; 2) To validate this method by assessing one attribute of music perception, bass frequency perception, which is hypothesized to be relevant to overall musical sound quality perception. Limitations in bass frequency perception contribute to CI-mediated sound quality deteriorations. The proposed method will quantify this deterioration by measuring CI users' impaired ability to make sound quality discriminations among musical stimuli with variable amounts of bass frequency removal. A method commonly used in the audio industry (multiple stimulus with hidden reference and anchor [MUSHRA]) was adapted for CI users, referred to as CI-MUSHRA. CI users and normal hearing controls were presented with 7 sound quality versions of a musical segment: 5 high pass filter cutoff versions (200-, 400-, 600-, 800-, 1000-Hz) with decreasing amounts of bass information, an unaltered version ("hidden reference"), and a highly altered version (1,000-1,200 Hz band pass filter; "anchor"). Participants provided sound quality ratings between 0 (very poor) and 100 (excellent) for each version; ratings reflected differences in perceived sound quality among stimuli. CI users had greater difficulty making overall sound quality discriminations as a function of bass frequency loss than normal hearing controls, as demonstrated by a significantly weaker correlation between bass frequency content and sound quality ratings. In particular, CI users could not perceive sound quality difference among stimuli missing up to 400 Hz of bass frequency information. Bass frequency impairments contribute to sound quality deteriorations during music listening for CI users. CI-MUSHRA provided a systematic and quantitative assessment of this reduced sound quality. Although the effects of bass frequency removal were studied here, we advocate CI-MUSHRA as a user-friendly and versatile research tool to measure the effects of a wide range of acoustic manipulations on sound quality perception in CI users.

Frequency and severity of potential drug interactions in a cohort of HIV-infected patients Identified through a Multidisciplinary team.

PubMed

Molas, E; Luque, S; Retamero, A; Echeverría-Esnal, D; Guelar, A; Montero, M; Guerri, R; Sorli, L; Lerma, E; Villar, J; Knobel, H

2018-02-01

Interactions between antiretroviral treatment (ART) and comedications are a concern in HIV-infected patients. This study aimed to determine the frequency and severity of potential drug-drug interactions (PDDIs) with ART in our setting. Observational study by a multidisciplinary team in 1259 consecutive HIV patients (March 2015-September 2016). Data on demographics, toxic habits, comorbidities, and current ART were collected. A structured questionnaire recorded concomitant medications (including occasional and over-the-counter drugs). PDDIs were classified into four categories: (1) no interactions, (2) mild (clinically non-significant), (3) moderate (requiring close monitoring or drug modification/dose adjustment), and (4) severe (contraindicated). chi-square test, logistic regression analysis. In total, 881 (70%) patients took comedication, and 563 (44.7%) had ≥ PDDI. Forty-one comedicated patients (4.6%) had severe and 522 (59.2%) moderate PDDIs. Moderate PDDIs mainly involved cardiovascular (53.8%) and central nervous system (40.2%) drugs. Independent risk factors for PDDIs were ART containing a boosted protease inhibitor (odds ratio [OR]=9.11, 95% confidence interval [CI] 5.15-16.11; p = 0.0001) and/or non-nucleoside reverse transcriptase (NNRTI) (OR = 4.34, 95%CI 2.49-7.55; p = 0.0001), HCV co-infection (OR = 3.26, 95%CI 2.15-4.93; p = 0.0001), and use of two or more comedications (OR = 3.36, 95%CI 2.27-4.97; p = 0.0001). Adherence and effectiveness of ART were similar in patients with and without PDDIs. The team made 133 recommendations related to comedications (drug change or dose adjustment) or ART (drug switch or change in administration schedule). Systematic evaluation detected a significant percentage of PDDIs requiring an intervention in HIV patients on ART. Monitoring and advice about drug-drug interactions should be part of routine practice.

Detrimental social interactions predict loss of dignity among patients with cancer.

PubMed

Philipp, R; Mehnert, A; Lehmann, C; Oechsle, K; Bokemeyer, C; Krüll, A; Vehling, S

2016-06-01

This prospective study aimed to determine the extent to which cancer patients experience loss of dignity during primary cancer care (baseline) and at 3-month follow-up and the contribution of positive social support and detrimental social interactions on loss of dignity at follow-up. At baseline, we enrolled N = 270 cancer patients (advanced cancer 57 %) undergoing oncological treatment. At follow-up, n = 178 patients (72 %) participated. Patients completed the following questionnaires: sense of dignity item (SDI), physical problem list of the NCCN Distress Thermometer, Illness-Specific Social Support Scale (SSUK), Patient Health Questionnaire (PHQ-9), and Generalized Anxiety Disorder Questionnaire (GAD-7). We conducted ordinal regression analyses controlling for age, gender, tumor stage, number of physical symptoms, depression, and anxiety. At baseline, 18 % of the patients experienced moderate to extreme loss of dignity (follow-up 23 %, p = 0.27). Detrimental interactions significantly predicted loss of dignity (OR = 1.42, 95 % CI 1.06-1.90) in a model including positive support (OR = 1.10, 95 % CI 0.82-1.49), depression (OR = 1.55, 95 % CI 0.96-2.51), and anxiety (OR = 1.20, 95 % CI 0.83-1.74). Items in relation to detrimental interactions with significant others such as "made you feel like you couldn't take care of yourself" (r = 0.29, p < 0.001) and "felt uncomfortable in illness conversations" (r = 0.24, p = 0.002) showed the highest associations with perceived loss of dignity. Loss of dignity was a frequent problem in our mixed cancer patient sample. Detrimental interactions that weaken the sense of dignity may result from discrepancies with patients' needs for autonomy and security. Tailoring social support to attachment-related patient needs may help to conserve patients' sense of dignity.

Real-time, two-way interaction during ST-segment elevation myocardial infarction management improves door-to-balloon times.

PubMed

Sardi, Gabriel L; Loh, Joshua P; Torguson, Rebecca; Satler, Lowell F; Waksman, Ron

2014-01-01

The study aimed to determine if utilization of the CodeHeart application (CHap) reduces door-to-balloon (DTB) times of ST-segment elevation myocardial infarction (STEMI) patients. A pre-hospital electrocardiogram improves the management of patients with STEMI. Current telecommunication systems do not permit real-time interaction with the initial care providers. Our institution developed a novel telecommunications system based on a software application that permits real-time, two-way video and voice interaction over a secured network. All STEMI system activations after implementation of the CHap were prospectively entered into a database. Consecutive CHap activations were compared to routine activations as controls, during the same time period. A total of 470 STEMI system activations occurred; CHap was used in 83 cases (17.7%). DTB time was reduced by the use of CHap when compared to controls (CHap 103 minutes, 95% CI [87.0-118.3] vs. standard 149 minutes, 95% CI [134.0-164.8], p<0.0001), as was first call-to-balloon time (CHap 70 minutes, 95% CI [60.8-79.5] vs. standard 92 minutes, 95% CI [85.8-98.9], p=0.0002). The percentage of 'true positive' catheterization laboratory activations was nominally higher with the use of CHap, although this did not reach statistical significance [CHap 47/83 (56.6%) vs. routine 178/387 (45.9%), p=0.103]. The implementation of a two-way telecommunications system allowing real-time interactions between interventional cardiologists and referring practitioners improves overall DTB time. In addition, it has the potential to decrease the frequency of false activations, thereby improving the cost efficiency of a network's STEMI system. Copyright © 2014. Published by Elsevier Inc.

Interactive eBooks in educating patients and their families about head injury regardless of age.

PubMed

Sahyouni, Ronald; Mahmoodi, Amin; Mahmoodi, Amir; Huang, Melissa; Tran, Diem Kieu; Chen, Jefferson W

2017-05-01

Traumatic Brain Injury (TBI) is a common and debilitating injury that is particularly prevalent in patients over 60. Given the influence of head injury on dementia (and vice versa), and the increased likelihood of ground-level falls, elderly patients are vulnerable to TBI. Educational interventions can increase knowledge and influence preventative activity to decrease the likelihood of further TBI. We sought to determine the efficacy of interactive tablet-based educational interventions in elderly patients on self-reported knowledge. Patients and family members, ages 20-90, presenting to a NeuroTrauma clinic completed a pre-survey to assess baseline TBI or concussion knowledge, depending on their diagnosis. Participants then received an interactive electronic book (eBook), or a text-based pamphlet with identical information, and completed a post-survey to test interim knowledge improvement. All participants (n=180), regardless of age, had significantly higher post-survey scores (p<0.01, 95% CI). Elderly participants who received the eBook (n=39) scored lower than their younger counterparts despite higher pre-survey scores (p<0.01, 95% CI). All participants who received the eBook (n=20, 90) significantly improved on the post-survey (p<0.01, 95% CI) when compared to participants who received the paper pamphlets (n=10, 31). All participants significantly preferred the eBook (p<0.01, 95% CI). We demonstrated that interactive educational interventions are effective in the elderly TBI population. Enhanced educational awareness in the elderly population, especially patients at risk or with prior TBI, may prevent further head injury by educating patients on the importance of avoiding further head injury and taking precautionary measures to decrease the likelihood of further injury. Copyright © 2017 Elsevier B.V. All rights reserved.

Randomized trial of vitamin supplements in relation to transmission of HIV-1 through breastfeeding and early child mortality.

PubMed

Fawzi, Wafaie W; Msamanga, Gernard I; Hunter, David; Renjifo, Boris; Antelman, Gretchen; Bang, Heejung; Manji, Karim; Kapiga, Saidi; Mwakagile, Davis; Essex, Max; Spiegelman, Donna

2002-09-27

HIV-1 transmission through breastfeeding is a global problem and has been associated with poor maternal micronutrient status. A total of 1078 HIV-infected pregnant women from Tanzania were randomly assigned to vitamin A or multivitamins excluding A from approximately 20 weeks' gestation and throughout lactation. Multivitamins excluding A had no effect on the total risk of HIV-1 transmission (RR 1.04, 95% CI 0.82-1.32, P= 0.76). Vitamin A increased the risk of transmission (RR 1.38, 95% CI 1.09-1.76, P = 0.009). Multivitamins were associated with non-statistically significant reductions in transmission through breastfeeding, and mortality by 24 months among those alive and not infected at 6 weeks. Multivitamins significantly reduced breastfeeding transmission in infants of mothers with low baseline lymphocyte counts (RR 0.37; 95% CI 0.16-0.85, P = 0.02) compared with infants of mothers with higher counts (RR 0.99, 95% CI 0.68-1.45, P = 0.97; -for-interaction 0.03). Multivitamins also protected against transmission among mothers with a high erythrocyte sedimentation rate (P-for-interaction 0.06), low hemoglobin (P-for-interaction 0.06), and low birthweight babies (P-for-interaction 0.04). Multivitamins reduced death and prolonged HIV-free survival significantly among children born to women with low maternal immunological or nutritional status. Vitamin A alone increased breastfeeding transmission but had no effect on mortality by 24 months. Vitamin A increased the risk of HIV-1 transmission. Multivitamin (B, C, and E) supplementation of breastfeeding mothers reduced child mortality and HIV-1 transmission through breastfeeding among immunologically and nutritionally compromised women. The provision of these supplements to HIV-infected lactating women should be considered.

Individual and combined effects of maternal anemia and prenatal infection on risk for schizophrenia in offspring.

PubMed

Nielsen, Philip R; Meyer, Urs; Mortensen, Preben B

2016-04-01

Maternal iron deficiency and infection during pregnancy have individually been associated with increased risk of schizophrenia in the offspring, but possible interactions between the two remain unidentified thus far. Therefore, we determined the individual and combined effects of maternal infection during pregnancy and prepartum anemia on schizophrenia risk in the offspring. We conducted a population-based study with individual record linkage of the Danish Civil Registration System, the Danish Hospital Register, and the Central Danish Psychiatric Register. In a cohort of Danish singleton births 1,403,183 born between 1977 and 2002, 6729 developed schizophrenia between 1987 and 2012. Cohort members were considered as having a maternal history of anemia if the mother had received a diagnosis of anemia at any time during the pregnancy. Maternal infection was defined based on infections requiring hospital admission during pregnancy. Maternal anemia and infection were both associated with increased risk of schizophrenia in unadjusted analyses (1.45-fold increase for anemia, 95% CI: 1.14-1.82; 1.32-fold increase for infection, 95% CI: 1.17-1.48). The effect of maternal infection remained significant (1.16-fold increase, 95% CI: 1.03-1.31) after adjustment for possible confounding factors. Combined exposure to anemia and an infection increased the effect size to a 2.49-fold increased schizophrenia risk (95% CI: 1.29-4.27). The interaction analysis, however, failed to provide evidence for multiplicative interactions between the two factors. Our findings indicate that maternal anemia and infection have additive but not interactive effects, and therefore, they may represent two independent risk factors of schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Habitual betel quid chewing and risk for hepatocellular carcinoma complicating cirrhosis.

PubMed

Tsai, Jung-Fa; Jeng, Jen-Eing; Chuang, Lee-Yea; Ho, Mei-Shang; Ko, Ying-Chin; Lin, Zu-Yau; Hsieh, Min-Yuh; Chen, Shin-Chern; Chuang, Wan-Lung; Wang, Liang-Yen; Yu, Ming-Lung; Dai, Chia-Yen

2004-05-01

This case-control study aimed to assess the independent and interactive role of habitual betel quid chewing and known risk factors for hepatocellular carcinoma (HCC). Subjects enrolled included 210 pairs of sex- and age-matched cirrhotic patients with HCC, patients with cirrhosis alone, and healthy controls. Information on risk factors was obtained through serologic examination of hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV), and a standardized personal interview with a structured questionnaire. Multivariate analysis indicated that betel quid chewing (odds ratio [OR], 5.81; 95% confidence interval [CI], 2.26-14.94); HBsAg (OR, 37.98; 95% CI, 19.65-73.42); and anti-HCV (OR, 47.23; 95% CI, 18.86-118.25) were independent risk factors for HCC when HCC patients were compared with healthy controls. Using patients with cirrhosis alone as a reference group, multivariate analysis indicated that only betel quid chewing (OR, 1.69; 95% CI, 1.04-2.76) and HBsAg (OR, 1.54; 95% CI, l.01-2.37) were independent risk factors for HCC. There was an additive interaction between betel quid chewing and the presence of either HBsAg (synergy index, 5.22) or anti-HCV (synergy index, 1.35). Moreover, a higher risk of HCC was associated with a longer duration of betel quid chewing and a larger amount of betel quid consumed (each p(for trend) < 0.0001). In conclusion, betel quid chewing is an independent risk factor for cirrhotic HCC. There is an additive interaction between betel quid chewing and chronic hepatitis B and/or hepatitis C virus infection.

Health information technology and physician-patient interactions: impact of computers on communication during outpatient primary care visits.

PubMed

Hsu, John; Huang, Jie; Fung, Vicki; Robertson, Nan; Jimison, Holly; Frankel, Richard

2005-01-01

The aim of this study was to evaluate the impact of introducing health information technology (HIT) on physician-patient interactions during outpatient visits. This was a longitudinal pre-post study: two months before and one and seven months after introduction of examination room computers. Patient questionnaires (n = 313) after primary care visits with physicians (n = 8) within an integrated delivery system. There were three patient satisfaction domains: (1) satisfaction with visit components, (2) comprehension of the visit, and (3) perceptions of the physician's use of the computer. Patients reported that physicians used computers in 82.3% of visits. Compared with baseline, overall patient satisfaction with visits increased seven months after the introduction of computers (odds ratio [OR] = 1.50; 95% confidence interval [CI]: 1.01-2.22), as did satisfaction with physicians' familiarity with patients (OR = 1.60, 95% CI: 1.01-2.52), communication about medical issues (OR = 1.61; 95% CI: 1.05-2.47), and comprehension of decisions made during the visit (OR = 1.63; 95% CI: 1.06-2.50). In contrast, there were no significant changes in patient satisfaction with comprehension of self-care responsibilities, communication about psychosocial issues, or available visit time. Seven months post-introduction, patients were more likely to report that the computer helped the visit run in a more timely manner (OR = 1.76; 95% CI: 1.28-2.42) compared with the first month after introduction. There were no other significant changes in patient perceptions of the computer use over time. The examination room computers appeared to have positive effects on physician-patient interactions related to medical communication without significant negative effects on other areas such as time available for patient concerns. Further study is needed to better understand HIT use during outpatient visits.

Clinical outcomes of patients with diabetes and atrial fibrillation treated with apixaban: results from the ARISTOTLE trial.

PubMed

Ezekowitz, Justin A; Lewis, Basil S; Lopes, Renato D; Wojdyla, Daniel M; McMurray, John J V; Hanna, Michael; Atar, Dan; Cecilia Bahit, M; Keltai, Matyas; Lopez-Sendon, Jose L; Pais, Prem; Ruzyllo, Witold; Wallentin, Lars; Granger, Christopher B; Alexander, John H

2015-04-01

We compared clinical outcomes in patients with AF with and without diabetes in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial. The main efficacy endpoints were SSE and mortality; safety endpoints were major and major/clinically relevant non-major bleeding. A total of 4547/18 201 (24.9%) patients had diabetes who were younger (69 vs. 70 years), more had coronary artery disease (39 vs. 31%), and higher mean CHADS2 (2.9 vs. 1.9) and HAS-BLED scores (1.9 vs. 1.7) (all P < 0.0001) than patients without diabetes. Patients with diabetes receiving apixaban had lower rates of SSE [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.53-1.05), all-cause mortality (HR 0.83, 95% CI 0.67-1.02), cardiovascular mortality (HR 0.89, 95% CI 0.66-1.20), intra-cranial haemorrhage (HR 0.49, 95% CI 0.25-0.95), and a similar rate of myocardial infarction (HR 1.02, 95% CI 0.62-1.67) compared with warfarin. For major bleeding, a quantitative interaction was seen (P-interaction = 0.003) with a greater reduction in major bleeding in patients without diabetes even after multivariable adjustment. Other measures of bleeding showed a consistent reduction with apixaban compared with warfarin without a significant interaction based on diabetes status. Apixaban has similar benefits on reducing stroke, decreasing mortality, and causing less intra-cranial bleeding than warfarin in patients with and without diabetes. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Bullied Status and Physical Activity in Texas Adolescents.

PubMed

Case, Kathleen R; Pérez, Adriana; Saxton, Debra L; Hoelscher, Deanna M; Springer, Andrew E

2016-06-01

This study examined the association between having been bullied at school during the past 6 months ("bullied status") and not meeting physical activity (PA) recommendations of 60 minutes of daily PA during the past week among 8th- and 11th-grade Texas adolescents. Multiple logistic regression analysis was conducted to examine this association, adjusted for weight status, grade, race/ethnicity, and stratified by gender; furthermore, a significant interaction was found between bullied status and weight status. Results are presented by interaction status. Results indicated that overweight girls who reported never being bullied, as well as those who reported being bullied more than twice, had higher odds of not meeting PA recommendations than normal weight girls who were never bullied (adjusted odds ratio [AOR] = 2.12, 95% confidence interval [CI: 1.12, 3.99]; AOR = 9.18, 95% CI [2.26, 37.27], respectively). Obese girls who were bullied once or twice had higher odds of not meeting PA recommendations than normal weight girls who were never bullied (AOR = 2.89, 95% CI [1.06, 7.89]). Overweight boys who reported never being bullied had lower odds of not meeting PA recommendations than normal weight boys who were never bullied (AOR = 0.62, 95% CI [0.39, 0.97]). Conversely, obese boys who were bullied once or twice reported higher odds of not meeting PA recommendations than normal weight boys who were never bullied (AOR = 3.61, 95% CI [1.22, 10.67]). Findings from this study indicate that the association between bullied status and meeting PA recommendations is complex and may differ by gender and the interaction between bullied status and weight status. © 2015 Society for Public Health Education.

Meta-analysis of ADH1B and ALDH2 polymorphisms and esophageal cancer risk in China.

PubMed

Zhang, Guo-Hong; Mai, Rui-Qin; Huang, Bo

2010-12-21

To evaluate whether alcohol dehydrogenase-1B (ADH1B) His47Arg and aldehyde dehydrogenase-2 (ALDH2) Glu487Lys polymorphism is involved in the esophageal squamous cell carcinoma (ESCC) risk in Chinese Han population. Seven studies of ADH1B and ALDH2 genotypes in Chinese Han population in 1450 cases and 2459 controls were included for meta-analysis. Stratified analyses were carried out to determine the gene-alcohol and gene-gene interaction with ESCC risk. Potential sources of heterogeneity between studies were explored, and publication bias was also evaluated. Individuals with ADH1B arginine (Arg)/Arg genotype showed 3.95-fold increased ESCC risk in the recessive genetic model [Arg/Arg vs Arg/histidine (His) + His/His: odds ratio (OR) = 3.95, 95% confidence interval (CI): 2.76-5.67]. Significant association was found in the dominant model for ALDH2 lysine (Lys) allele [glutamate (Glu)/Lys + Lys/Lys vs Glu/Glu: OR = 2.00, 95% CI: 1.54-2.61]. Compared with the non-alcoholics, Arg/Arg (OR = 25.20, 95% CI: 10.87-53.44) and Glu/Lys + Lys/Lys (OR = 21.47, 95% CI: 6.44-71.59) were found to interact with alcohol drinking to increase the ESCC risk. ADH1B Arg+ and ALDH2 Lys+ had a higher risk for ESCC (OR = 7.09, 95% CI: 2.16-23.33). The genetic variations of ADH1B His47Arg and ALDH2 Glu487Lys are susceptible loci for ESCC in Chinese Han population and interact substantially with alcohol consumption. The individuals carrying both risky genotypes have a higher baseline risk of ESCC.

Association between Prediagnostic Allergy-Related Serum Cytokines and Glioma.

PubMed

Schwartzbaum, Judith; Seweryn, Michal; Holloman, Christopher; Harris, Randall; Handelman, Samuel K; Rempala, Grzegorz A; Huang, Ruo-Pan; Burkholder, Brett; Brandemihl, Adam; Kallberg, Henrik; Johannesen, Tom Borge; Ahlbom, Anders; Feychting, Maria; Grimsrud, Tom K

2015-01-01

Allergy is inversely related to glioma risk. To determine whether prediagnostic allergy-related serum proteins are associated with glioma, we conducted a nested case-control study of seven cytokines (IL4, IL13, IL5, IL6, IL10, IFNG, TGFB2), two soluble cytokine receptors (sIL4RA, sIL13RA2) and three allergy-related transcription factors (FOXP3, STAT3, STAT6) using serum specimens from the Janus Serum Bank Cohort in Oslo, Norway. Blood donors subsequently diagnosed with glioma (n = 487) were matched to controls (n = 487) on age and date of blood draw and sex. We first estimated individual effects of the 12 serum proteins and then interactions between IL4 and IL13 and their receptors using conditional logistic regression. We next tested equality of case-control inter-correlations among the 12 serum proteins. We found that TGFB2 is inversely related to glioblastoma (Odds Ratio (OR) = 0.87, 95% Confidence Interval (CI)) = 0.76, 0.98). In addition, ≤ 5 years before diagnosis, we observed associations between IL4 (OR = 0.82, 95% CI = 0.66, 1.01), sIL4RA (OR = 0.80, 95% CI = 0.65, 1.00), their interaction (OR = 1.06, 95% CI = 1.01, 1.12) and glioblastoma. This interaction was apparent > 20 years before diagnosis (IL4-sIL4RA OR = 1.20, 95% CI = 1.05, 1.37). Findings for glioma were similar. Case correlations were different from control correlations stratified on time before diagnosis. Five years or less before diagnosis, correlations among case serum proteins were weaker than were those among controls. Our findings suggest that IL4 and sIL4RA reduce glioma risk long before diagnosis and early gliomagenesis affects circulating immune function proteins.

Do Interleukin Polymorphisms Play a Role in the Prevention of Colorectal Adenoma Recurrence by Dietary Flavonols?

PubMed Central

Bobe, Gerd; Murphy, Gwen; Albert, Paul S.; Sansbury, Leah B.; Young, Matthew R.; Lanza, Elaine; Schatzkin, Arthur; Colburn, Nancy H.; Cross, Amanda J.

2010-01-01

Chemopreventive dietary compounds, such as flavonols, may inhibit colorectal carcinogenesis partly by altering cytokine expression and attenuating inflammation. Single nucleotide polymorphisms (SNPs) in the promoter regions of genes encoding cytokines may influence flavonol-induced changes in cytokine expression and consequently cancer risk. Using logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between SNPs of interleukin (IL)-1β, 6, 8, and 10, alone or combined with flavonol intake or serum IL concentration changes, and adenoma recurrence in 808 participants from the intervention arm of the Polyp Prevention Trial, a 4-year intervention study evaluating the effectiveness of a low-fat, high-fiber, high-fruit and vegetable diet on adenoma recurrence.. Overall, SNPs in genes encoding IL-1β, 6, 8, and 10 were not associated with their corresponding serum concentrations or adenoma recurrence. However, individuals homozygous for IL-10 -592 C (OR = 2.23, 95% CI: 1.07–4.66, P interaction = 0.03) or IL-10 -819 C (OR = 2.18, 95% CI: 1.05–4.51, P interaction = 0.05) had an elevated risk of high risk adenoma recurrence when their serum IL-10 concentrations increased during the trial. In addition, IL-6 -174 GG in combination with above median flavonol intake (OR = 0.14, 95% CI: 0.03–0.66) or with decreased IL 6 concentrations (OR = 0.14, 95% CI: 0.03–0.65) reduced the risk of advanced adenoma recurrence, although the interaction term was not statistically significant. In conclusion, our results suggest that IL SNPs, in combination with a flavonol-rich diet or decreased serum IL, may lower the risk of adenoma recurrence. PMID:21160427

A Review of Computational Methods for Finding Non-Coding RNA Genes

PubMed Central

Abbas, Qaisar; Raza, Syed Mansoor; Biyabani, Azizuddin Ahmed; Jaffar, Muhammad Arfan

2016-01-01

Finding non-coding RNA (ncRNA) genes has emerged over the past few years as a cutting-edge trend in bioinformatics. There are numerous computational intelligence (CI) challenges in the annotation and interpretation of ncRNAs because it requires a domain-related expert knowledge in CI techniques. Moreover, there are many classes predicted yet not experimentally verified by researchers. Recently, researchers have applied many CI methods to predict the classes of ncRNAs. However, the diverse CI approaches lack a definitive classification framework to take advantage of past studies. A few review papers have attempted to summarize CI approaches, but focused on the particular methodological viewpoints. Accordingly, in this article, we summarize in greater detail than previously available, the CI techniques for finding ncRNAs genes. We differentiate from the existing bodies of research and discuss concisely the technical merits of various techniques. Lastly, we review the limitations of ncRNA gene-finding CI methods with a point-of-view towards the development of new computational tools. PMID:27918472

External validation of scoring instruments for evaluating pediatric resuscitation.

PubMed

Levy, Arielle; Donoghue, Aaron; Bailey, Benoit; Thompson, Nathan; Jamoulle, Olivier; Gagnon, Robert; Gravel, Jocelyn

2014-12-01

Although many methods have been proposed to assess clinical performance during resuscitation, robust and generalizable metrics are still lacking. Further research is necessary to develop validated clinical performance assessment tools and show an improvement in outcomes after training. We aimed to establish evidence for validity of a previously published scoring instrument--the Clinical Performance Tool (CPT)--designed to evaluate clinical performance during simulated pediatric resuscitations. This was a prospective experimental trial performed in the simulation laboratory of a pediatric tertiary care facility, with a pretest/posttest design that assessed residents before and after pediatric advanced life support (PALS) certification. Thirteen postgraduate year 1 (PGY1) and 11 PGY3 pediatric residents completed 5 simulated pediatric resuscitation scenarios each during 2 consecutive sessions; between the 2 sessions, they completed a full PALS certification course. All sessions were video recorded. Sessions were scored by raters using the CPT; total scores were expressed as a percentage of maximum points possible for each scenario. Validity evidence was established and interpreted according to Messick's framework. Evidence regarding relations to other variables was assessed by calculating differences in scores between pre-PALS and post-PALS certification and PGY1 and PGY3 using a repeated-measures analysis of variance test. Internal structure evidence was established by assessing interrater reliability using intraclass correlation coefficients (ICCs) for each scenario, a G-study, and a variance component analysis of individual measurement facets (scenarios, raters, and occasions) and associated interactions. Overall scores for the entire study cohort improved by 10% after PALS training. Scores improved by 9.9% (95% confidence interval [CI], 4.5-15.4) for the pulseless nonshockable arrest (ICC, 0.85; 95% CI, 0.74-0.92), 14.6% (95% CI, 6.7-22.4) for the pulseless shockable arrest (ICC, 0.98; 95% CI, 0.96-0.99), 4.1% (95% CI, -4.5 to 12.8) for the dysrhythmias (ICC, 0.92; 95% CI, 0.87-0.96), 18.4% (95% CI, 9.7-27.1) for the respiratory scenario (ICC, 0.97; 95% CI, 0.95-0.98), and 5.3% (95% CI, -1.4 to 2.0) for the shock scenarios (ICC, 0.94; 95% CI, 0.90-0.97). There were no differences between PGY1 and PGY3 scores before or after the PALS course. Reliability of the instrument was acceptable as demonstrated by a mean ICC of 0.95 (95% CI, 0.94-0.96). The G-study coefficient was 0.94. Most variance could be attributed to the subject (57%). Interactions between subject and scenario and subject and occasion were 9.9% and 1.4%, respectively, and variance attributable to rater was minimal (0%). Pediatric residents improved scores on CPT after completion of a PALS course. Clinical Performance Tool scores are sensitive to the increase in skills and knowledge resulting from such a course but not to learners' levels. Validity evidence from scores for the CPT confirms implementation in new contexts and partially supports internal structure. More evidence is required to further support internal structure and especially to support relations with other variables and consequence evidence. Additional modifications should be made to the CPT before considering its use for high-stakes certification such as PALS.

Time on androgen deprivation therapy and adaptations to exercise: secondary analysis from a 12-month randomized controlled trial in men with prostate cancer.

PubMed

Taaffe, Dennis R; Buffart, Laurien M; Newton, Robert U; Spry, Nigel; Denham, James; Joseph, David; Lamb, David; Chambers, Suzanne K; Galvão, Daniel A

2018-02-01

To explore if duration of previous exposure to androgen deprivation therapy (ADT) in men with prostate cancer (PCa) undertaking a year-long exercise programme moderates the exercise response with regard to body composition and muscle performance, and also to explore the moderator effects of baseline testosterone, time since ADT, and baseline value of the outcome. In a multicentre randomized controlled trial, 100 men who had previously undergone either 6 months (short-term) or 18 months (long-term) of ADT in combination with radiotherapy, as part of the TROG 03.04 RADAR trial, were randomized to 6 months supervised exercise, followed by a 6-month home-based maintenance programme, or to printed physical activity educational material for 12 months across 13 university-affiliated exercise clinics in Australia and New Zealand. The participants were long-term survivors of PCa with a mean age of 71.7 ± 6.4 years, and were assessed for lower extremity performance (repeated chair rise), with a subset of men (n = 57) undergoing additional measures for upper and lower body muscle strength and body composition (lean mass, fat mass, appendicular skeletal muscle [ASM]) by dual X-ray absorptiometry. Data were analysed using generalized estimating equations. Time on ADT significantly moderated the exercise effects on chair rise (β interaction = -1.3 s, 95% confidence interval [CI] -2.6 to 0.0), whole-body lean mass (β interaction = 1194 g, 95% CI 234 to 2153) and ASM mass (β interaction = 562 g, 95% CI 49 to 1075), and approached significance for fat mass (β interaction = -1107 g, 95% CI -2346 to 132), with greater benefits for men previously on long-term ADT. At 6 months, the intervention effects on chair rise time -1.5 s (95% CI -2.5 to -0.5), whole-body lean mass 824 g (95% CI 8 to 1640), ASM mass 709 g (95% CI 260 to 1158), and fat mass -1377 g (95% CI -2156 to -598) were significant for men previously on long-term ADT, but not for men on short-term ADT. At 12 months, the intervention effects for men on long-term ADT remained significant for the chair rise, with improved performance (-2.0 s, 95% CI -3.0 to -1.0) and increased ASM (537 g, 95% CI 153 to 921). Time on ADT did not moderate the exercise effects on muscle strength, nor did time since ADT cessation moderate any intervention effects. Similarly, testosterone and baseline values of the outcome had negligible moderator effects. Men with PCa previously treated long-term with ADT respond more favourably to exercise in terms of lower body muscle performance and body composition (lean and fat mass, and ASM) than those with short-term ADT exposure. As a result, men who were formerly on long-term androgen suppression regimens should be especially prescribed exercise medicine interventions to alleviate residual treatment-related adverse effects. © 2017 The Authors. BJU International.

Effect of Intensive Versus Standard Blood Glucose Control in Patients With Type 2 Diabetes Mellitus in Different Regions of the World: Systematic Review and Meta-analysis of Randomized Controlled Trials.

PubMed

Sardar, Partha; Udell, Jacob A; Chatterjee, Saurav; Bansilal, Sameer; Mukherjee, Debabrata; Farkouh, Michael E

2015-05-05

Regional variation in type 2 diabetes mellitus care may affect outcomes in patients treated with intensive versus standard blood glucose control. We sought to evaluate these differences between North America and the rest of the world. Databases were searched from their inception through December 2013. Randomized controlled trials comparing the effects of intensive therapy with standard therapy for macro- and microvascular complications in adults with type 2 diabetes mellitus were selected. We calculated summary odds ratios (ORs) and 95% CIs with the random-effects model. The analysis included 34 967 patients from 17 randomized controlled trials (7 in North America and 10 in the rest of the world). There were no significant differences between intensive and standard therapy groups for all-cause mortality (OR 1.03, 95% CI 0.93 to 1.13) and cardiovascular mortality (OR 1.09, 95% CI 0.90 to 1.32). For trials conducted in North America, intensive therapy compared with standard glycemic control resulted in significantly higher all-cause mortality (OR 1.21, 95% CI 1.05 to 1.40) and cardiovascular mortality (OR 1.41, 95% CI 1.05 to 1.90) than trials conducted in the rest of the world (all-cause mortality OR 0.93, 95% CI 0.85 to 1.03; interaction P=0.006; cardiovascular mortality OR 0.89, 95% CI, 0.79 to 1.00; interaction P=0.007). Analysis of individual macro- and microvascular outcomes revealed no significant regional differences; however, the risk of severe hypoglycemia was significantly higher in trials of intensive therapy in North America (OR 3.52, 95% CI 3.07 to 4.03) compared with the rest of the world (OR 1.45, 95% CI 0.85 to 2.47; interaction P=0.001). Randomization to intensive glycemic control in type 2 diabetes mellitus patients was associated with increases in all-cause mortality, cardiovascular mortality, and severe hypoglycemia in North America compared with the rest of the world. Further investigation into the pathobiology or patient variability underlying these findings is warranted. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

The Effect of Electroencephalogram (EEG) Reference Choice on Information-Theoretic Measures of the Complexity and Integration of EEG Signals

PubMed Central

Trujillo, Logan T.; Stanfield, Candice T.; Vela, Ruben D.

2017-01-01

Converging evidence suggests that human cognition and behavior emerge from functional brain networks interacting on local and global scales. We investigated two information-theoretic measures of functional brain segregation and integration—interaction complexity CI(X), and integration I(X)—as applied to electroencephalographic (EEG) signals and how these measures are affected by choice of EEG reference. CI(X) is a statistical measure of the system entropy accounted for by interactions among its elements, whereas I(X) indexes the overall deviation from statistical independence of the individual elements of a system. We recorded 72 channels of scalp EEG from human participants who sat in a wakeful resting state (interleaved counterbalanced eyes-open and eyes-closed blocks). CI(X) and I(X) of the EEG signals were computed using four different EEG references: linked-mastoids (LM) reference, average (AVG) reference, a Laplacian (LAP) “reference-free” transformation, and an infinity (INF) reference estimated via the Reference Electrode Standardization Technique (REST). Fourier-based power spectral density (PSD), a standard measure of resting state activity, was computed for comparison and as a check of data integrity and quality. We also performed dipole source modeling in order to assess the accuracy of neural source CI(X) and I(X) estimates obtained from scalp-level EEG signals. CI(X) was largest for the LAP transformation, smallest for the LM reference, and at intermediate values for the AVG and INF references. I(X) was smallest for the LAP transformation, largest for the LM reference, and at intermediate values for the AVG and INF references. Furthermore, across all references, CI(X) and I(X) reliably distinguished between resting-state conditions (larger values for eyes-open vs. eyes-closed). These findings occurred in the context of the overall expected pattern of resting state PSD. Dipole modeling showed that simulated scalp EEG-level CI(X) and I(X) reflected changes in underlying neural source dependencies, but only for higher levels of integration and with highest accuracy for the LAP transformation. Our observations suggest that the Laplacian-transformation should be preferred for the computation of scalp-level CI(X) and I(X) due to its positive impact on EEG signal quality and statistics, reduction of volume-conduction, and the higher accuracy this provides when estimating scalp-level EEG complexity and integration. PMID:28790884

Hypertension after preeclampsia and relation to the C1114G polymorphism (rs4606) in RGS2: data from the Norwegian HUNT2 study

PubMed Central

2014-01-01

Background Preeclampsia is associated with an increased risk of hypertension later in life. The regulator of G protein signaling 2 negatively regulates several vasoconstrictors. We recently demonstrated an association between preeclampsia and the CG or GG genotype of the C1114G polymorphism (rs4606) of the regulator of G protein signaling 2 gene. Here, we examined the polymorphism with respect to the development of hypertension after pregnancy. Methods We genotyped 934 women on average 15.1 years after preeclampsia and 2011 age matched women with previous normotensive pregnancy. All women in this study were retrospectively recruited from the Nord-Trøndelag Health Study (HUNT2). Information from HUNT2 was linked to the Medical Birth Registry of Norway to identify women with a history of preeclampsia and women without a history of preeclampsia. Results No significant association was found between hypertension (blood pressure ≥140/90 mmHg and/or taking antihypertensive drugs) and the polymorphism in crude analysis (OR (95% CI): CG genotype: 1.07 (0.90-1.27); GG genotype: 1.23 (0.90-1.67)). However, in a minimally adjusted model (age and BMI adjusted), a significant association between the GG genotype and hypertension was found (OR (95% CI): 1.49 (1.05-2.11)). This association remained significant also after adjustment for a history of preeclampsia (OR (95% CI): 1.46 (1.02-2.09)), but not in a model adjusted for multiple other variables (OR (95% CI): 1.26 (0.82-1.94)). In multivariate, but not in crude, analysis, the GG genotype of rs4606 (OR (95% CI): 1.93 (1.05-3.53)) was significantly and independently associated with severe hypertension later in life, defined as systolic blood pressure ≥160 mmHg (stage 2 hypertension) and/or taking antihypertensive drugs. A significant association was also found for the merged CG and GG genotypes (OR (95% CI): 1.43 (1.02-2.00)). Moreover, an interaction with physical activity was found. A history of preeclampsia was a significant and independent predictor of either definition of hypertension, both in crude and adjusted analyses. Conclusion Women carrying the rs4606 CG or GG genotype are at elevated risk for developing hypertension after delivery. Physical activity may interact with the association. Preeclampsia remains an independent risk factor for subsequent hypertension after adjusting for this polymorphism and classical CVD risk factors. PMID:24593135

Food Insecurity, Nutritional Status, and Factors Associated with Malnutrition among People Living with HIV/AIDS Attending Antiretroviral Therapy at Public Health Facilities in West Shewa Zone, Central Ethiopia.

PubMed

Gebremichael, Delelegn Yilma; Hadush, Kokeb Tesfamariam; Kebede, Ermiyas Mulu; Zegeye, Robel Tezera

2018-01-01

In resource limited settings, HIV/AIDS patients lack access to sufficient nutritious foods, which poses challenges to the success of antiretroviral therapy. HIV/AIDS and malnutrition are still major public health problems in Ethiopia. Though measuring nutritional status is an essential part of ART program, little evidence exists on food insecurity and nutritional status of HIV/AIDS patients in Ethiopia. Hence, the study aimed to determine food insecurity and nutritional status and contextual determinants of malnutrition among HIV/AIDS patients in West Shewa Zone, Ethiopia. Institution-based cross-sectional study was conducted among HIV/ADIS patients who have been attending antiretroviral therapy at public health facilities in West Shewa Zone from April to May 2016, Ethiopia. The sample size was 512 and study participants were selected from each facilities using systematic random sampling method. Data were collected using pretested questionnaire by trained data collectors. Data were entered to Epi-Info 3.5.1 for Windows and analyzed using SPSS version 22. Logistic regression analyses were conducted to determine independent factors associated with malnutrition. Prevalence of malnutrition was 23.6% (95% CI: 19.7%-27.4%) and prevalence of household food insecurity was 35.2% (95% CI: 31.1%-39.0%). Factors significantly associated with malnutrition among HIV/AIDS patients were unemployment (AOR = 3.4; 95% CI: 1.8-5.3), WHO clinical stages III/IV (AOR = 3.3; 95% CI: 1.8-6.5), CD4 count less than 350 cells/ μ l (AOR = 2.0; 95% CI: 1.8-4.2), tuberculosis (AOR = 2.3; 95% CI: 1.3-4.9), duration on antiretroviral therapy (AOR = 1.8; 95% CI: 1.2-2.9), and household food insecurity (AOR = 5.3; 95% CI: 2.5-8.3). The findings revealed high prevalence of malnutrition and household food insecurity among HIV/AIDS patients attended ART. The negative interactive effects of undernutrition, inadequate food consumption, and HIV infection demand effective cross-sectorial integrated programs and effective management of opportunistic infections like tuberculosis.

Bullying, Depression, and Suicidal Ideation Among Adolescents in the Fujian Province of China

PubMed Central

Hong, Lingyao; Guo, Lan; Wu, Hong; Li, Pengsheng; Xu, Yan; Gao, Xue; Deng, Jianxiong; Huang, Guoliang; Huang, Jinghui; Lu, Ciyong

2016-01-01

Abstract The relationship of bullying with suicidal ideation among adolescents is controversial. Although depression has been related to bullying and suicidal ideation, little is known about the combined impacts of depression and bullying on suicidal ideation. A sample of 20,509 high school students from Fujian Province were selected randomly by multistage stratified sampling. All participants completed an adolescent health status questionnaire. Three categories of bullying were assessed: perpetration, victimization, and both (victimization and perpetration). The associations of these 3 categories of bullying with depression and their interaction with suicidal ideation were examined in logistic models. After adjustment for potential confounders, all 3 categories of bullying (perpetration, victimization, and both) were related to increased risk of suicidal ideation with odds ratios (ORs) of 1.66 (95% confidence interval [CI] 1.20–2.30), 2.74 (95% CI 2.29–3.29), and 2.83 (95% CI 2.27–3.52), respectively. There was an interaction between depression and bullying (P = 0.001). Subgroup analyses showed a stronger association between perpetration and suicidal ideation in students with depression (odds ratio [OR] 2.97; 95% CI 1.44–6.09) than in those without depression (OR 1.65; 95% CI 1.19–2.28). The association between victimization and suicidal ideation was weaker in students with depression (OR 1.49; 95% CI 1.07–2.07) than in those without (OR 2.69; 95% CI 2.24–3.23). The association of both victimization and perpetration with suicidal ideation was weaker in students with depression (OR 2.22, 95% CI 1.43–3.47) than those without (OR 2.78; 95% CI 2.23–3.47). We observed an independent association of bullying with increased risk of suicidal ideation among adolescent students, and this association was affected by depression. Prospective studies should be conducted to confirm these findings. PMID:26844460

Bullying, Depression, and Suicidal Ideation Among Adolescents in the Fujian Province of China: A Cross-sectional Study.

PubMed

Hong, Lingyao; Guo, Lan; Wu, Hong; Li, Pengsheng; Xu, Yan; Gao, Xue; Deng, Jianxiong; Huang, Guoliang; Huang, Jinghui; Lu, Ciyong

2016-02-01

The relationship of bullying with suicidal ideation among adolescents is controversial. Although depression has been related to bullying and suicidal ideation, little is known about the combined impacts of depression and bullying on suicidal ideation.A sample of 20,509 high school students from Fujian Province were selected randomly by multistage stratified sampling. All participants completed an adolescent health status questionnaire. Three categories of bullying were assessed: perpetration, victimization, and both (victimization and perpetration). The associations of these 3 categories of bullying with depression and their interaction with suicidal ideation were examined in logistic models.After adjustment for potential confounders, all 3 categories of bullying (perpetration, victimization, and both) were related to increased risk of suicidal ideation with odds ratios (ORs) of 1.66 (95% confidence interval [CI] 1.20-2.30), 2.74 (95% CI 2.29-3.29), and 2.83 (95% CI 2.27-3.52), respectively. There was an interaction between depression and bullying (P = 0.001). Subgroup analyses showed a stronger association between perpetration and suicidal ideation in students with depression (odds ratio [OR] 2.97; 95% CI 1.44-6.09) than in those without depression (OR 1.65; 95% CI 1.19-2.28). The association between victimization and suicidal ideation was weaker in students with depression (OR 1.49; 95% CI 1.07-2.07) than in those without (OR 2.69; 95% CI 2.24-3.23). The association of both victimization and perpetration with suicidal ideation was weaker in students with depression (OR 2.22, 95% CI 1.43-3.47) than those without (OR 2.78; 95% CI 2.23-3.47).We observed an independent association of bullying with increased risk of suicidal ideation among adolescent students, and this association was affected by depression. Prospective studies should be conducted to confirm these findings.

Single and combined effects of zinc and cinnamon essential oil in diet on productive performance, egg quality traits, and blood parameters of laying hens reared under cold stress condition

NASA Astrophysics Data System (ADS)

Torki, Mehran; Akbari, Mohsen; Kaviani, Keyomars

2015-09-01

This study was conducted to evaluate the effects of adding zinc (Zn), cinnamon essential oil (Ci), or their combination in diet on productive performance, egg quality, and blood parameters of laying hens reared under cold stress condition (8.8 ± 3 °C). Feed intake (FI), feed conversion ratio (FCR), egg weight (EW), egg production (EP), and egg mass (EM) were evaluated during the 56-day trial period using 120 Lohmann LSL-Lite laying hens. Significant interactions between Ci and Zn on FCR, EW, EP, or EM were observed ( P < 0.05). The EP, EM, and EW increased, whereas FCR decreased ( P < 0.05) in the hens fed the diets including Ci and Zn (as single or combined form) compared to those fed the basal diet. There were significant interactions between Ci and Zn on the serum level of glucose and triglycerides as well as plasma concentration of zinc ( P < 0.05), so that serum content of glucose and triglyceride decreased and the plasma content of zinc increased in the hens fed the diets including Ci and Zn (together) compared to those fed the basal diet. From the results of the present experiment, it can be concluded that diet supplementation by the combined form of Ci and Zn could have beneficial effects on performance and blood parameters of hens reared under cold stress condition.

Single and combined effects of zinc and cinnamon essential oil in diet on productive performance, egg quality traits, and blood parameters of laying hens reared under cold stress condition.

PubMed

Torki, Mehran; Akbari, Mohsen; Kaviani, Keyomars

2015-09-01

This study was conducted to evaluate the effects of adding zinc (Zn), cinnamon essential oil (Ci), or their combination in diet on productive performance, egg quality, and blood parameters of laying hens reared under cold stress condition (8.8 ± 3 °C). Feed intake (FI), feed conversion ratio (FCR), egg weight (EW), egg production (EP), and egg mass (EM) were evaluated during the 56-day trial period using 120 Lohmann LSL-Lite laying hens. Significant interactions between Ci and Zn on FCR, EW, EP, or EM were observed (P < 0.05). The EP, EM, and EW increased, whereas FCR decreased (P < 0.05) in the hens fed the diets including Ci and Zn (as single or combined form) compared to those fed the basal diet. There were significant interactions between Ci and Zn on the serum level of glucose and triglycerides as well as plasma concentration of zinc (P < 0.05), so that serum content of glucose and triglyceride decreased and the plasma content of zinc increased in the hens fed the diets including Ci and Zn (together) compared to those fed the basal diet. From the results of the present experiment, it can be concluded that diet supplementation by the combined form of Ci and Zn could have beneficial effects on performance and blood parameters of hens reared under cold stress condition.

Effects of Sevelamer Carbonate on Advanced Glycation End Products and Antioxidant/Pro-Oxidant Status in Patients with Diabetic Kidney Disease

PubMed Central

Yubero-Serrano, Elena M.; Woodward, Mark; Poretsky, Leonid; Vlassara, Helen

2015-01-01

Background and objectives The primary goals were to re-examine whether sevelamer carbonate (SC) reduces advanced glycation end products (AGEs) (methylglyoxal and carboxymethyllysine [CML]), increases antioxidant defenses, reduces pro-oxidants, and improves hemoglobin A1c (HbA1c) in patients with type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). Secondary goals examined albuminuria, age, race, sex, and metformin prescription. Design, setting, participants, & measurements This two-center, randomized, intention-to-treat, open-label study evaluated 117 patients with T2DM (HbA1c >6.5%) and stages 2–4 DKD (urinary albumin/creatinine ratio ≥200 mg/g) treated with SC (1600 mg) or calcium carbonate (1200 mg), three times a day, without changing medications or diet. Statistical analyses used linear mixed models adjusted for randomization levels. Preselected subgroup analyses of sex, race, age, and metformin were conducted. Results SC lowered serum methylglyoxal (95% confidence interval [CI], −0.72 to −0.29; P<0.001), serum CML (95% CI, −5.08 to −1.35; P≤0.001), and intracellular CML (95% CI, −1.63 to −0.28; P=0.01). SC increased anti-inflammatory defenses, including nuclear factor like-2 (95% CI, 0.58 to 1.29; P=0.001), AGE receptor 1 (95% CI, 0.23 to 0.96; P=0.001), NAD-dependent deacetylase sirtuin-1 (95% CI, 0.20 to 0.86; P=0.002), and estrogen receptor α (95% CI, 1.38 to 2.73; P ≤0.001). SC also decreased proinflammatory factors such as TNF receptor 1 (95% CI, −1.56 to −0.72; P≤0.001) and the receptor for AGEs (95% CI, −0.58 to 1.53; P≤0.001). There were no differences in HbA1c, GFR, or albuminuria in the overall group. Subanalyses showed that SC lowered HbA1c in women (95% CI, −1.71 to −0.27; P=0.01, interaction P=0.002), and reduced albuminuria in those aged <65 years (95% CI, −1.15 to −0.07; P=0.03, interaction P=0.02) and non-Caucasians (95% CI, −1.11 to −0.22; P=0.003, interaction P≤0.001), whereas albuminuria increased after SC and calcium carbonate in Caucasians. Conclusions SC reduced circulating and cellular AGEs, increased antioxidants, and decreased pro-oxidants, but did not change HbA1c or the albumin/creatinine ratio overall in patients with T2DM and DKD. Because subanalyses revealed that SC may reduce HbA1c and albuminuria in some patients with T2DM with DKD, further studies may be warranted. PMID:25710801

In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4 phenotypes

PubMed Central

Gardner, Stephanie F.; Hubbard, Martha A.; Williams, D. Keith; Gentry, W. Brooks; Khan, Ikhlas A.; Shah., Amit

2007-01-01

Objectives Phytochemical-mediated modulation of cytochrome P-450 activity may underlie many herb-drug interactions. Single time-point, phenotypic metabolic ratios were used to determine whether long-term supplementation of goldenseal (Hydrastis canadensis), black cohosh (Cimicifuga racemosa), kava kava (Piper methysticum), or valerian (Valeriana officinalis) extracts affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4/5 activity. Methods Twelve healthy volunteers (6 females) were randomly assigned to receive goldenseal, black cohosh, kava kava, or valerian for 28 days. For each subject, a 30-day washout period was interposed between each supplementation phase. Probe drug cocktails of midazolam and caffeine, followed 24 hours later by chlorzoxazone and debrisoquine were administered before (baseline) and at the end of supplementation. Pre- and post-supplementation phenotypic trait measurements were determined for CYP3A4/5, CYP1A2, CYP2E1, and CYP2D6 using 1-hydroxymidazolam/midazolam serum ratios (1-hour sample), paraxanthine/caffeine serum ratios (6-hour sample), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour sample), and debrisoquine urinary recovery ratios (8-hour collection), respectively. The content of purported “active” phytochemicals was determined for each supplement. Results Comparisons of pre- and post-supplementation phenotypic ratio means revealed significant inhibition (~40%) of CYP2D6 (difference = −0.228; 95% CI = −0.268 to −0.188) and CYP3A4/5 (difference = −1.501; 95% CI = −1.840 to −1.163) activity for goldenseal. Kava produced significant reductions (~40%) in CYP2E1 only (difference = −0.192; 95% CI = −0.325 to −0.060). Black cohosh also exhibited statistically significant inhibition of CYP2D6 (difference = −0.046; 95% CI = −0.085 to −0.007), but the magnitude of the effect (~7%) did not appear clinically relevant. No significant changes in phenotypic ratios were observed for valerian. Conclusions Botanical supplements containing goldenseal strongly inhibited CYP2D6 and CYP3A4/5 activity in vivo, while kava inhibited CYP2E1 and black cohosh weakly inhibited CYP2D6. Accordingly, serious adverse interactions may result from the concomitant ingestion of goldenseal supplements and drugs that are CYP2D6 and CYP3A4/5 substrates. Kava kava and black cohosh may interact with CYP2E1 and CYP2D6 substrates, respectively. Valerian appears less likely to produce CYP-mediated herb-drug interactions. PMID:15900287

Evaluation of incidence and risk factors for high-dose methotrexate-induced nephrotoxicity.

PubMed

Wiczer, Tracy; Dotson, Emily; Tuten, Amy; Phillips, Gary; Maddocks, Kami

2016-06-01

High-dose methotrexate (doses ≥1 g/m(2)) is a key component of several chemotherapy regimens used to treat patients with leukemia or lymphoma. Despite appropriate precautions with hydration, urine alkalinization, and leucovorin, nephrotoxicity remains a risk which can lead to significant morbidity and mortality. Current reports of risk factors for nephrotoxicity focus on patients with nephrotoxicity with a lack of comparison to those without toxicity. This study aimed to describe the incidence of high-dose methotrexate-induced nephrotoxicity at our institution and determined risk factors for high-dose methotrexate-induced nephrotoxicity by examining characteristics of patients with and without nephrotoxicity. This was a retrospective, single-center, chart review. Adult patients with a diagnosis of leukemia or lymphoma who received high-dose methotrexate were included. Serum creatinine values were used to evaluate nephrotoxicity according to Common Terminology Criteria for Adverse Events criteria v4.03. Data related to the following proposed risk factors were collected: age, sex, body mass index, methotrexate dose, number of high-dose methotrexate exposures, leucovorin administration route, baseline renal function, albumin, hydration status, Clostridium difficile infection, urine pH, and concomitant interacting and nephrotoxic medications. The primary endpoint was evaluated with exact binomial methods and risk factors were identified using multivariable random-effects logistic regression. Final analyses included 140 patients with 432 high-dose methotrexate exposures. There were no differences in baseline demographical characteristics. Fifty-four patients (38.6%) experienced nephrotoxicity of any grade: 27.9% with grade 1, 5.7% with grade 2, 3.6% grade 3, 0% with grade 4, and 1.4% with grade 5 toxicity. More patients in the toxicity group received doses of methotrexate ≥3 g/m(2) (58.3% versus 57.2%, p < 0.001), had an albumin level <3 g/dL (31.9% versus 15.9%, p = 0.04), and received an interacting medication during high-dose methotrexate clearance (44.4% versus 24.7%, p = 0.003). Male gender (OR 2.3, 95% CI: 1.27-4.18, p = 0.006), albumin (OR 0.44, 95% CI: 0.26-0.75, p = 0.002), number of drug interactions (OR 1.60, 95% CI: 1.15-2.21, p = 0.005), and use of furosemide (OR 2.56, 95% CI 1.46-4.48, p = 0.001) were all independent risk factors for the development of nephrotoxicity. Nephrotoxicity is a possible complication of therapy with high-dose methotrexate with most instances comprising grade 1-2 toxicity. Male gender, low albumin, and administration of interacting drugs or furosemide during high-dose methotrexate clearance may predispose patients to nephrotoxicity. © The Author(s) 2015.

Geographical segregation and IL-6: a marker of chronic inflammation in older adults.

PubMed

Purser, Jama L; Kuchibhatla, Maragatha N; Miranda, Marie L; Blazer, Dan G; Cohen, Harvey J; Fillenbaum, Gerda G

2008-01-01

AIM: To examine environmental sociodemographic risks of high IL-6, a marker of chronic inflammation in older adults. METHODS: We spatially linked 1990 USA Census tract demographic and economic measures to a prospective cohort study of representative community residents aged 71 years and older, from over 1700 of whom a cytokine protein and biological marker of chronic inflammation. IL-6, was collected. Using generalized interactive mixed models, we modeled 1989-1990 individual and census level risk factors for the dependent variable high IL-6 between 1992-1993 (high IL-6 = upper quartile: >2.96 pg/ml). RESULTS: After individual health risk adjustment, IL-6 remained elevated in communities with greater densities of poor older adults (odd ratio [OR]: 1.25 per 10% increase in exposure. 95% confidence interval [CI]: 1.05, 1.48) and in racially segregated communities (OR: 1.14 per 10% increase in exposure. 95% CI: 1.04, 1.25). CONCLUSIONS: Socially disadvantaged environments may influence IL-6, a biomarker of age-associated inflammation.

Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus.

PubMed

Kwon, H H; Bang, S Y; Won, S; Park, Y; Yi, J H; Joo, Y B; Lee, H S; Bae, S C

2018-01-01

Objectives Avascular necrosis (AVN) is one of the most common causes of organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyze their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, n = 132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20 g (odds ratio (OR) 3.62, p = 0.015) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.51, p < 0.001) remained as significant risk factors for AVN. Patients with cumulative corticosteroid dose > 20 g and immunosuppressant use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors ( p < 0.001). RERI, AP and S, which define the strength of interactions between two risk factors, were 9.01 (95% confidence interval (CI) 1.30-16.73), 0.58 (95% CI 0.36-0.81) and 2.66 (95% CI 1.42-4.99), respectively, supporting the presence of synergistic interactions in the development of symptomatic AVN in our Korean lupus cohort. Conclusions An individual risk assessment for AVN development should be made prior to and during treatment for SLE, especially in patients with high-dose corticosteroid and immunosuppressant use regardless of clinical manifestations and disease activity.

Investigating Sociodemographic Factors and HIV Risk Behaviors Associated With Social Networking Among Adolescents in Soweto, South Africa: A Cross-Sectional Survey

PubMed Central

Laher, Fatima; Hornschuh, Stefanie; Nkala, Busisiwe; Chimoyi, Lucy; Otwombe, Kennedy; Kaida, Angela; Gray, Glenda Elisabeth; Miller, Cari

2016-01-01

Background Internet access via mobile phones and computers facilitates interaction and potential health communication among individuals through social networking. Many South African adolescents own mobile phones and can access social networks via apps. Objective We investigated sociodemographic factors and HIV risk behaviors of adolescent social networking users in Soweto, South Africa. Methods We conducted an interviewer-administered, cross-sectional survey of adolescents aged 14-19 years. Independent covariates of social networking were assessed by multivariate logistic regression analysis. Results Of 830 adolescents, 57% (475/830) were females and the median age was found to be 18 years (interquartile range 17-18). Social networking was used by 60% of adolescents (494/830); more than half, that is, 87% (396/494) accessed social networks through mobile phones and 56% (275/494) spent more than 4 hours per day using their mobile phones. Social networking was independently associated with mobile usage 2-4 hours (adjusted odds ratio [AOR]: 3.06, CI: 1.69-5.51) and more than 4 hours per day (AOR: 6.16, CI: 3.46-10.9) and one (AOR: 3.35, CI: 1.79-6.27) or more sexual partner(s) (AOR: 2.58, CI: 1.05-6.36). Conclusions Mobile phone–based social networking is prevalent among sexually active adolescents living in Soweto and may be used as an entry point for health promotion and initiation of low-cost adolescent health interventions. PMID:27683173

Socio-economic status and lifestyle factors are associated with achalasia risk: A population-based case-control study

PubMed Central

Coleman, Helen G; Gray, Ronan T; Lau, Kar W; McCaughey, Conall; Coyle, Peter V; Murray, Liam J; Johnston, Brian T

2016-01-01

AIM: To evaluate the association between various lifestyle factors and achalasia risk. METHODS: A population-based case-control study was conducted in Northern Ireland, including n = 151 achalasia cases and n = 117 age- and sex-matched controls. Lifestyle factors were assessed via a face-to-face structured interview. The association between achalasia and lifestyle factors was assessed by unconditional logistic regression, to produce odds ratios (OR) and 95% confidence interval (CI). RESULTS: Individuals who had low-class occupations were at the highest risk of achalasia (OR = 1.88, 95%CI: 1.02-3.45), inferring that high-class occupation holders have a reduced risk of achalasia. A history of foreign travel, a lifestyle factor linked to upper socio-economic class, was also associated with a reduced risk of achalasia (OR = 0.59, 95%CI: 0.35-0.99). Smoking and alcohol consumption carried significantly reduced risks of achalasia, even after adjustment for socio-economic status. The presence of pets in the house was associated with a two-fold increased risk of achalasia (OR = 2.00, 95%CI: 1.17-3.42). No childhood household factors were associated with achalasia risk. CONCLUSION: Achalasia is a disease of inequality, and individuals from low socio-economic backgrounds are at highest risk. This does not appear to be due to corresponding alcohol and smoking behaviours. An observed positive association between pet ownership and achalasia risk suggests an interaction between endotoxin and viral infection exposure in achalasia aetiology. PMID:27099443

The ‘apparent clearance’ of free phenytoin in elderly vs. younger adults

PubMed Central

Wright, Daniel F B; Begg, Evan J

2010-01-01

AIMS To test the hypothesis that the ‘apparent clearance’ of free phenytoin is reduced in elderly patients. METHODS Two separate studies were conducted comparing free phenytoin ‘apparent clearance’ in elderly vs. younger adults. The first study was a retrospective analysis of free phenytoin concentrations measured at Christchurch Hospital from 1997 to 2006. In the second study free phenytoin concentrations were measured prospectively in ambulatory subjects who were taking phenytoin regularly. RESULTS In the retrospective study (n = 29), free phenytoin ‘apparent clearance’ was 0.27 ± 0.04 l kg−1 day−1 (95% CI 0.19, 0.34) in the elderly cohort vs. 0.37 ± 0.06 l kg−1 day−1 (95% CI 0.22, 0.52) in younger adults, but the difference was not statistically significant. In the prospective study, free phenytoin ‘apparent clearance’ showed a non-significant trend to being reduced in the elderly patients (0.12 ± 0.02 l kg−1 day−1, 95% CI 0.07, 0.17) compared with the younger cohort (0.18 ± 0.07 l kg−1 day−1, 95% CI 0.09, 0.26) in those not taking interacting drugs (n = 21). CONCLUSIONS This research does not prove the hypothesis that the ‘apparent clearance’ of free phenytoin is reduced in the elderly. However, the trends found in these two studies are supported by trends in the same direction in other published studies, suggesting an age effect. PMID:20642556

The FOXO1 Gene-Obesity Interaction Increases the Risk of Type 2 Diabetes Mellitus in a Chinese Han Population.

PubMed

Gong, Lilin; Li, Rong; Ren, Wei; Wang, Zengchan; Wang, Zhihong; Yang, Maosheng; Zhang, Suhua

2017-02-01

Here, we aimed to study the effect of the forkhead box O1-insulin receptor substrate 2 (FOXO1-IRS2) gene interaction and the FOXO1 and IRS2 genes-environment interaction for the risk of type 2 diabetes mellitus (T2DM) in a Chinese Han population. We genotyped 7 polymorphism sites of FOXO1 gene and IRS2 gene in 780 unrelated Chinese Han people (474 cases of T2DM, 306 cases of healthy control). The risk of T2DM in individuals with AA genotype for rs7986407 and CC genotype for rs4581585 in FOXO1 gene was 2.092 and 2.57 times higher than that with GG genotype (odds ratio [OR] = 2.092; 95% confidence interval [CI] = 1.178-3.731; P = 0.011) and TT genotype (OR = 2.571; 95% CI = 1.404-4.695; P = 0.002), respectively. The risk of T2DM in individuals with GG genotype for Gly1057Asp in IRS2 gene was 1.42 times higher than that with AA genotype (OR = 1.422; 95% CI = 1.037-1.949; P = 0.029). The other 4 single nucleotide polymorphisms (SNPs) had no significant association with T2DM (P > 0.05). Multifactor dimensionality reduction (MDR) analysis showed that the interaction between SNPs rs7986407 and rs4325426 in FOXO1 gene and waist was the best model confirmed by interaction analysis, closely associating with T2DM. There was an increased risk for T2DM in the case of non-obesity with genotype combined AA/CC, AA/AC or AG/AA for rs7986407 and rs4325426, and obesity with genotype AA for rs7986407 or AA for rs4325426 (OR = 3.976; 95% CI = 1.156-13.675; P value from sign test [P(sign)] = 0.025; P value from permutation test [P(perm)] = 0.000-0.001). Together, this study indicates an association of FOXO1 and IRS2 gene polymorphisms with T2DM in Chinese Han population, supporting FOXO1-obesity interaction as a key factor for the risk of T2DM.

The Impact of Adjuvant Radiation Therapy for High-Grade Gliomas by Histology in the United States Population

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rusthoven, Chad G., E-mail: Chad.Rusthoven@ucdenver.edu; Carlson, Julie A.; Waxweiler, Timothy V.

Purpose: To compare the survival impact of adjuvant external beam radiation therapy (RT) for malignant gliomas of glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and mixed anaplastic oligoastrocytoma (AOA) histology. Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER) database was queried from 1998 to 2007 for patients aged ≥18 years with high-grade gliomas managed with upfront surgical resection, treated with and without adjuvant RT. Results: The primary analysis totaled 14,461 patients, with 12,115 cases of GBM (83.8%), 1312 AA (9.1%), 718 AO (4.9%), and 316 AOA (2.2%). On univariate analyses, adjuvant RT was associated with significantly improved overallmore » survival (OS) for GBMs (2-year OS, 17% vs 7%, p<.001), AAs (5-year OS, 38% vs 24%, p<.001), and AOAs (5-year OS, 55% vs 44%, p=.026). No significant differences in OS were observed for AOs (5-year OS, with RT 50% vs 56% without RT, p=.277). In multivariate Cox proportional hazards models accounting for extent of resection, age, sex, race, year, marital status, and tumor registry, RT was associated with significantly improved OS for both GBMs (HR, 0.52; 95% CI, 0.50-0.55; P<.001) and AAs (HR, 0.57; 95% CI, 0.48-0.68; P<.001) but only a trend toward improved OS for AOAs (HR, 0.70; 95% CI, 0.45-1.09; P=.110). Due to the observation of nonproportional hazards, Cox regressions were not performed for AOs. A significant interaction was observed between the survival impact of RT and histology overall (interaction P<.001) and in a model limited to the anaplastic (WHO grade 3) histologies. (interaction P=.024), characterizing histology as a significant predictive factor for the impact of RT. Subgroup analyses demonstrated greater hazard reductions with RT among patients older than median age for both GBMs and AAs (all interaction P≤.001). No significant interactions were observed between RT and extent of resection. Identical patterns of significance were observed for cause-specific survival and OS across analyses. Conclusions: In this large population-based cohort, glioma histology represented a significant predictor for the survival impact of RT. Adjuvant RT was associated with improved survival for AAs, with benefits comparable to those observed for GBMs over the same 10-year interval. No survival advantage was observed with adjuvant RT for AOs.« less

Envelope Interactions in Multi-Channel Amplitude Modulation Frequency Discrimination by Cochlear Implant Users

PubMed Central

2015-01-01

Rationale Previous cochlear implant (CI) studies have shown that single-channel amplitude modulation frequency discrimination (AMFD) can be improved when coherent modulation is delivered to additional channels. It is unclear whether the multi-channel advantage is due to increased loudness, multiple envelope representations, or to component channels with better temporal processing. Measuring envelope interference may shed light on how modulated channels can be combined. Methods In this study, multi-channel AMFD was measured in CI subjects using a 3-alternative forced-choice, non-adaptive procedure (“which interval is different?”). For the reference stimulus, the reference AM (100 Hz) was delivered to all 3 channels. For the probe stimulus, the target AM (101, 102, 104, 108, 116, 132, 164, 228, or 256 Hz) was delivered to 1 of 3 channels, and the reference AM (100 Hz) delivered to the other 2 channels. The spacing between electrodes was varied to be wide or narrow to test different degrees of channel interaction. Results Results showed that CI subjects were highly sensitive to interactions between the reference and target envelopes. However, performance was non-monotonic as a function of target AM frequency. For the wide spacing, there was significantly less envelope interaction when the target AM was delivered to the basal channel. For the narrow spacing, there was no effect of target AM channel. The present data were also compared to a related previous study in which the target AM was delivered to a single channel or to all 3 channels. AMFD was much better with multiple than with single channels whether the target AM was delivered to 1 of 3 or to all 3 channels. For very small differences between the reference and target AM frequencies (2–4 Hz), there was often greater sensitivity when the target AM was delivered to 1 of 3 channels versus all 3 channels, especially for narrowly spaced electrodes. Conclusions Besides the increased loudness, the present results also suggest that multiple envelope representations may contribute to the multi-channel advantage observed in previous AMFD studies. The different patterns of results for the wide and narrow spacing suggest a peripheral contribution to multi-channel temporal processing. Because the effect of target AM frequency was non-monotonic in this study, adaptive procedures may not be suitable to measure AMFD thresholds with interfering envelopes. Envelope interactions among multiple channels may be quite complex, depending on the envelope information presented to each channel and the relative independence of the stimulated channels. PMID:26431043

Screening toll-like receptor markers to predict latent tuberculosis infection and subsequent tuberculosis disease in a Chinese population.

PubMed

Wu, Linlin; Hu, Yi; Li, Dange; Jiang, Weili; Xu, Biao

2015-04-01

We investigated whether polymorphisms in the toll-like receptor genes or gene-gene interactions are associated with susceptibility to latent tuberculosis infection (LTBI) or subsequent pulmonary tuberculosis (PTB) in a Chinese population. Two matched case-control studies were undertaken. Previously reported polymorphisms in the toll-like receptors (TLRs) were compared between 422 healthy controls (HC) and 205 LTBI patients and between 205 LTBI patients and 109 PTB patients, to assess whether these polymorphisms and their interactions are associated with LTBI or PTB. A PCR-based restriction fragment length polymorphism analysis was used to detect genetic polymorphisms in the TLR genes. Nonparametric multifactor dimensionality reduction (MDR) was used to analyze the effects of interactions between complex disease genes and other genes or environmental factors. Sixteen markers in TLR1, TLR2, TLR4, TLR6, TLR8, TLR9, and TIRAP were detected. In TLR2, the frequencies of the CC genotype (OR = 2.262; 95% CI: 1.433-3.570) and C allele (OR = 1.566; 95% CI: 1.223-1.900) in single-nucleotide polymorphism (SNP) rs3804100 were significantly higher in the LTBI group than in the HC group, whereas the GA genotype of SNP rs5743708 was associated with PTB (OR = 6.087; 95% CI: 1.687-21.968). The frequencies of the GG genotype of SNP rs7873784 in TLR4 (OR = 2.136; 95% CI: 1.312-3.478) and the CC genotype of rs3764879 in TLR8 (OR = 1.982; 95% CI: 1.292-3.042) were also significantly higher in the PTB group than in the HC group. The TC genotype frequency of SNP rs5743836 in TLR9 was significantly higher in the LTBI group than in the HC group (OR = 1.664; 95% CI: 1.201-2.306). An MDR analysis of gene-gene and gene-environment interactions identified three SNPs (rs10759932, rs7873784, and rs10759931) that predicted LTBI with 84% accuracy (p = 0.0004) and three SNPs (rs3804100, rs1898830, and rs10759931) that predicted PTB with 80% accuracy (p = 0.0001). Our results suggest that genetic variation in TLR2, 4, 8 and 9, implicating TLR-related pathways affecting the innate immunity response, modulate LTBI and PTB susceptibility in Chinese.

Outcomes Associated with Steroid Avoidance and Alemtuzumab among Kidney Transplant Recipients.

PubMed

Serrano, Oscar K; Friedmann, Patricia; Ahsanuddin, Sayeeda; Millan, Carlos; Ben-Yaacov, Almog; Kayler, Liise K

2015-11-06

Alemtuzumab is a humanized anti-CD52 monoclonal antibody used as induction in kidney transplantation (KTX) since 2003. Few studies have evaluated long-term outcomes of this agent or changes in outcomes over time. A retrospective cohort study was performed examining United States registry data from 2003 to 2014 of primary KTX recipients receiving induction with alemtuzumab (AZ; n=5521) or antithymocyte globulin (ATG; n=8504) and maintenance immunosuppression with tacrolimus and mycophenolate mofetil and early withdrawal of steroids. The primary outcome was overall death-censored graft survival (DCGS), and secondary outcomes were overall patient survival and 1-year acute rejection. Multivariate models were fit with donor, recipient, and transplant covariates. Because poorer outcomes with AZ may occur from a learning curve impact with the use of a new medication, transplant year was categorized into three time periods to evaluate outcomes over time (2003-2005, 2006-2008, ≥2009), and an interaction term of induction type with transplant year category was included in all models to test for era impacts. On multivariate analysis of DCGS there was a significant interaction between AZ and era (P<0.001). AZ was significantly associated with inferior DCGS in the earliest 2003-2005 era (adjusted hazard ratio [aHR], 2.21; 95% confidence interval [95% CI], 1.72 to 2.84) but not in the middle 2006-2008 era (aHR, 1.14; 95% CI, 0.96 to 1.36) or the most recent 2009-2014 era (aHR, 1.08; 95% CI, 0.90 to 1.29) compared with ATG. Risk-adjusted patient survival (aHR, 1.32; 95% CI, 1.08 to 1.61; aHR, 1.26; 95% CI, 1.09 to 1.46; and aHR, 1.10; 95% CI, 0.93 to 1.29 by era, respectively) and acute rejection (adjusted odds ratio [aOR], 1.17; 95% CI, 0.96 to 1.42; aOR, 0.94; 95% CI, 0.82 to 1.07; aOR, 0.89; 95% CI, 0.81 to 0.98 by era, respectively) with AZ was comparable with ATG in the most recent era; however, there was no significant interaction with time (P=0.13 and P=0.06, respectively). Current alemtuzumab utilization is associated with comparable graft and patient survival and acute rejection compared with ATG. Graft survival with alemtuzumab has improved over time. Copyright © 2015 by the American Society of Nephrology.

Outcomes Associated with Steroid Avoidance and Alemtuzumab among Kidney Transplant Recipients

PubMed Central

Serrano, Oscar K.; Friedmann, Patricia; Ahsanuddin, Sayeeda; Millan, Carlos; Ben-Yaacov, Almog

2015-01-01

Background and objectives Alemtuzumab is a humanized anti-CD52 monoclonal antibody used as induction in kidney transplantation (KTX) since 2003. Few studies have evaluated long-term outcomes of this agent or changes in outcomes over time. Design, setting, participants, & measurements A retrospective cohort study was performed examining United States registry data from 2003 to 2014 of primary KTX recipients receiving induction with alemtuzumab (AZ; n=5521) or antithymocyte globulin (ATG; n=8504) and maintenance immunosuppression with tacrolimus and mycophenolate mofetil and early withdrawal of steroids. The primary outcome was overall death-censored graft survival (DCGS), and secondary outcomes were overall patient survival and 1-year acute rejection. Multivariate models were fit with donor, recipient, and transplant covariates. Because poorer outcomes with AZ may occur from a learning curve impact with the use of a new medication, transplant year was categorized into three time periods to evaluate outcomes over time (2003–2005, 2006–2008, ≥2009), and an interaction term of induction type with transplant year category was included in all models to test for era impacts. Results On multivariate analysis of DCGS there was a significant interaction between AZ and era (P<0.001). AZ was significantly associated with inferior DCGS in the earliest 2003–2005 era (adjusted hazard ratio [aHR], 2.21; 95% confidence interval [95% CI], 1.72 to 2.84) but not in the middle 2006–2008 era (aHR, 1.14; 95% CI, 0.96 to 1.36) or the most recent 2009–2014 era (aHR, 1.08; 95% CI, 0.90 to 1.29) compared with ATG. Risk-adjusted patient survival (aHR, 1.32; 95% CI, 1.08 to 1.61; aHR, 1.26; 95% CI, 1.09 to 1.46; and aHR, 1.10; 95% CI, 0.93 to 1.29 by era, respectively) and acute rejection (adjusted odds ratio [aOR], 1.17; 95% CI, 0.96 to 1.42; aOR, 0.94; 95% CI, 0.82 to 1.07; aOR, 0.89; 95% CI, 0.81 to 0.98 by era, respectively) with AZ was comparable with ATG in the most recent era; however, there was no significant interaction with time (P=0.13 and P=0.06, respectively). Conclusions Current alemtuzumab utilization is associated with comparable graft and patient survival and acute rejection compared with ATG. Graft survival with alemtuzumab has improved over time. PMID:26342042

Comparing two anesthesia information management system user interfaces: a usability evaluation.

PubMed

Wanderer, Jonathan P; Rao, Anoop V; Rothwell, Sarah H; Ehrenfeld, Jesse M

2012-11-01

Anesthesia information management systems (AIMS) have been developed by multiple vendors and are deployed in thousands of operating rooms around the world, yet not much is known about measuring and improving AIMS usability. We developed a methodology for evaluating AIMS usability in a low-fidelity simulated clinical environment and used it to compare an existing user interface with a revised version. We hypothesized that the revised user interface would be more useable. In a low-fidelity simulated clinical environment, twenty anesthesia providers documented essential anesthetic information for the start of the case using both an existing and a revised user interface. Participants had not used the revised user interface previously and completed a brief training exercise prior to the study task. All participants completed a workload assessment and a satisfaction survey. All sessions were recorded. Multiple usability metrics were measured. The primary outcome was documentation accuracy. Secondary outcomes were perceived workload, number of documentation steps, number of user interactions, and documentation time. The interfaces were compared and design problems were identified by analyzing recorded sessions and survey results. Use of the revised user interface was shown to improve documentation accuracy from 85.1% to 92.4%, a difference of 7.3% (95% confidence interval [CI] for the difference 1.8 to 12.7). The revised user interface decreased the number of user interactions by 6.5 for intravenous documentation (95% CI 2.9 to 10.1) and by 16.1 for airway documentation (95% CI 11.1 to 21.1). The revised user interface required 3.8 fewer documentation steps (95% CI 2.3 to 5.4). Airway documentation time was reduced by 30.5 seconds with the revised workflow (95% CI 8.5 to 52.4). There were no significant time differences noted in intravenous documentation or in total task time. No difference in perceived workload was found between the user interfaces. Two user interface design problems were identified in the revised user interface. The usability of anesthesia information management systems can be evaluated using a low-fidelity simulated clinical environment. User testing of the revised user interface showed improvement in some usability metrics and highlighted areas for further revision. Vendors of AIMS and those who use them should consider adopting methods to evaluate and improve AIMS usability.

Dialyzer Reuse and Outcomes of High Flux Dialysis

PubMed Central

Argyropoulos, Christos; Roumelioti, Maria-Eleni; Sattar, Abdus; Kellum, John A.; Weissfeld, Lisa; Unruh, Mark L.

2015-01-01

Background The bulk of randomized trial evidence for the expanding use of High Flux (HF) hemodialysis worldwide comes from two randomized controlled trials, one of which (HEMODIALYSIS, HEMO) allowed, while the other (Membrane Outcomes Permeability, MPO) excluded, the reuse of membranes. It is not known whether dialyzer reuse has a differential impact on outcomes with HF vs low flyx (LF) dialyzers. Methods Proportional Hazards Models and Joint Models for longitudinal measures and survival outcomes were used in HEMO to analyze the relationship between β2-microglobulin (β2M) concentration, flux, and reuse. Meta-analysis and regression techniques were used to synthesize the evidence for HF dialysis from HEMO and MPO. Findings In HEMO, minimally reused (< 6 times) HF dialyzers were associated with a hazard ratio (HR) of 0.67 (95% confidence interval, 95%CI: 0.48–0.92, p = 0.015), 0.64 (95%CI: 0.44 – 0.95, p = 0.03), 0.61 (95%CI: 0.41 – 0.90, p = 0.012), 0.53 (95%CI: 0.28 – 1.02, p = 0.057) relative to minimally reused LF ones for all cause, cardiovascular, cardiac and infectious mortality respectively. These relationships reversed for extensively reused membranes (p for interaction between reuse and flux < 0.001, p = 0.005) for death from all cause and cardiovascular causes, while similar trends were noted for cardiac and infectious mortality (p of interaction between reuse and flux of 0.10 and 0.08 respectively). Reduction of β2M explained only 1/3 of the effect of minimally reused HF dialyzers on all cause mortality, while non-β2M related factors explained the apparent attenuation of the benefit with more extensively reused dialyzers. Meta-regression of HEMO and MPO estimated an adjusted HR of 0.63 (95% CI: 0.51–0.78) for non-reused HF dialyzers compared with non-reused LF membranes. Conclusions This secondary analysis and synthesis of two large hemodialysis trials supports the widespread use of HF dialyzers in clinical hemodialysis over the last decade. A mechanistic understanding of the effects of HF dialysis and the reuse process on dialyzers may suggest novel biomarkers for uremic toxicity and may accelerate membrane technology innovations that will improve patient outcomes. PMID:26057383

Prevention of Atrial Fibrillation by Bucindolol Is Dependent on the Beta1389 Arg/Gly Adrenergic Receptor Polymorphism

PubMed Central

Aleong, Ryan G.; Sauer, William H.; Davis, Gordon; Murphy, Guinevere A.; Port, J. David; Anand, Inder S.; Fiuzat, Mona; O’Connor, Christopher M.; Abraham, William T.; Liggett, Stephen B.; Bristow, Michael R.

2013-01-01

Objectives This study assessed the impact of bucindolol, a beta-blocker/sympatholytic agent, on the development of atrial fibrillation (AF) in advanced chronic heart failure with reduced left ventricular ejection fraction (HFREF) patients enrolled in the BEST (Beta-Blocker Evaluation of Survival Trial). Background β-Blockers have modest efficacy for AF prevention in HFREF patients. Bucindolol’s effects on HF and ventricular arrhythmic endpoints are genetically modulated by β1- and α2c-adrenergic receptor (AR) polymorphisms that can be used to subdivide HFREF populations into those with bucindolol effectiveness levels that are enhanced, unchanged, or lost. Methods BEST enrolled 2,708 New York Heart Association (NYHA) class III to IV HFREF patients. A substudy in which 1,040 patients’ DNA was genotyped for the β1-AR position 389 Arg/Gly and the α2c322–325 wild type (Wt)/deletion (Del) polymorphisms, and new-onset AF was assessed from adverse event case report forms or electrocardiograms at baseline and at 3 and 12 months. Results In the entire cohort, bucindolol reduced the rate of new-onset AF compared to placebo by 41% (hazard ratio [HR]: 0.59 [95% confidence interval (CI): 0.44 to 0.79], p = 0.0004). In the 493 β1389 arginine homozygotes (Arg/Arg) in the DNA substudy, bucindolol reduced new-onset AF by 74% (HR: 0.26 [95% CI: 0.12 to 0.57]), with no effect in β1389 Gly carriers (HR: 1.01 [95% CI: 0.56 to 1.84], interaction test = 0.008). When β1389 Gly carriers were subdivided by α2c Wt homozygotes (n = 413, HR: 0.94 [95% CI: 0.48 to 1.82], p = 0.84) or Del variant carriers (n = 134, HR: 1.33 [95% CI: 0.32 to 5.64], p = 0.70), there was a positive interaction test (p = 0.016) when analyzed with β1389 Arg homozygotes. Conclusions Bucindolol prevented new-onset AF; β1 and α2c polymorphisms predicted therapeutic response; and the 47% of patients who were β1389 Arg homozygotes had an enhanced effect size of 74%. (Beta-Blocker Evaluation in Survival Trial [BEST]; NCT00000560) PMID:24159564

L'effet Hall Quantique

NASA Astrophysics Data System (ADS)

Samson, Thomas

Nous proposons une methode permettant d'obtenir une expression pour la conductivite de Hall de structures electroniques bidimensionnelles et nous examinons celle -ci a la limite d'une temperature nulle dans le but de verifier l'effet Hall quantique. Nous allons nous interesser essentiellement a l'effet Hall quantique entier et aux effets fractionnaires inferieurs a un. Le systeme considere est forme d'un gaz d'electrons en interaction faible avec les impuretes de l'echantillon. Le modele du gaz d'electrons consiste en un gaz bidimensionnel d'electrons sans spin expose perpendiculairement a un champ magnetique uniforme. Ce dernier est decrit par le potentiel vecteur vec{rm A} defini dans la jauge de Dingle ou jauge symetrique. Conformement au formalisme de la seconde quantification, l'hamiltonien de ce gaz est represente dans la base des etats a un-corps de Dingle |n,m> et exprime ainsi en terme des operateurs de creation et d'annihilation correspondants a_sp{ rm n m}{dag} et a _{rm n m}. Nous supposons de plus que les electrons du niveau fondamental de Dingle interagissent entre eux via le potentiel coulombien. La methode utilisee fait appel a une equation mai tresse a N-corps, de nature quantique et statistique, et verifiant le second principe de la thermodynamique. A partir de celle-ci, nous obtenons un systeme d'equations differentielles appele hierarchie d'equations quantique dont la resolution nous permet de determiner une equation a un-corps, dite de Boltzmann quantique, et dictant l'evolution de la moyenne statistique de l'operateur non-diagonal a _sp{rm n m}{dag } a_{rm n}, _{rm m}, sous l'action du champ electrique applique vec{rm E}(t). C'est sa solution Tr(p(t) a _sp{rm n m}{dag} a_{rm n},_ {rm m}), qui definit la relation de convolution entre la densite courant de Hall vec{rm J}_{rm H }(t) et le champ electrique vec {rm E}(t) dont la transformee de Laplace-Fourier du noyau nous fournit l'expression de la conductivite de Hall desiree. Pour une valeur de facteur d'occupation (nombre d'electrons/degenerescence des etats de Dingle) superieure a un, c'est-a-dire en absence d'interaction electron-electron, il nous sera facile d'evaluer cette conductivite a la limite d'une temperature nulle et de demontrer qu'elle tend vers l'une des valeurs quantiques qe^2/h conformement a l'effet Hall quantique entier. Cependant, pour une valeur du facteur d'occupation inferieure a un, c'est-a-dire en presence d'interaction electron-electron, nous ne pourrons evaluer cette limite et obtenir les resultats escomptes a cause de l'impossibilite de determiner l'un des termes impliques. Neanmoins, ce dernier etant de nature statistique, il pourra etre aisement mis en fonction du propagateur du gaz d'electrons dont on doit maintenant determiner une expression en regime effet Hall quantique fractionnaire. Apres avoir demontre l'impuissance de la theorie des perturbations, basee sur le theoreme de Wick et la technique des diagrammes de Feynman, a accomplir cette tache correctement, nous proposons une seconde methode. Celle -ci fait appel au formalisme de l'integrale fonctionnelle et a l'utilisation d'une transformation de Hubbard-Stratonovich generalisee permettant de substituer a l'interaction a deux-corps une interaction effective a un-corps. L'expression finale obtenue bien que non completement resolue, devrait pouvoir etre estimee par une bonne approximation analytique ou au pire numeriquement.

Long-acting family planning method switching among revisit clients of public health facilities in Dire Dawa, Ethiopia.

PubMed

Atnafe, Meselu; Assefa, Nega; Alemayehu, Tadesse

2016-01-01

"Contraceptive switching" from one method to another is a common phenomenon. Switching from a more effective long-acting method to a less effective method exposes women for unplanned pregnancy. The aim of this study was to assess the level and factors associated with long-acting family planning method switching to other methods. A facility-based cross-sectional study was conducted from January to March 2013 on 634 women attending public health facilities in Dire Dawa City Administration, Ethiopia. Participants of the study were revisit clients of family planning service and were interviewed as they appear in the clinics. Data were analyzed using crude and adjusted logistic regression, and results were reported using OR and corresponding 95 % CI. Long-acting family planning method switching among revisit clients was 40.4 %; switching from implant was 29.8 % and from IUCD, it was 10.6 %. The main reasons for methods switching were side effects of the methods such as bleeding, weight loss, and feeling of arm numbness. The tendency of switching was less among married women (AOR = 2.41, 95 % CI: 1.01, 5.74), women who had 2-4 and 5 and more children (AOR 3.00, 95 % CI: 1.59, 5.67) and (AOR 2.07, 95 % CI: 1.17, 3.66), respectively. It was also less among women who want to stop birth (AOR 5.11, 95 % CI: 1.15, 24.8), among those who mentioned health care providers as source of information for family planning (AOR 1.88, 95 % CI: 1.18, 3.01), and among women whose husbands were aware of their use of the methods (AOR 3.05, 95 % CI: 1.88, 4.94). Method switching from long-acting contraceptives to less effective methods is high. Method switching was significant among unmarried women, who had one child, plan to postpone fertility, and whose husbands were not aware of their wive's use of the method. In the provision of family planning service, the health care providers should give adequate information about each method and risks of method switching. Appropriate family planning Information Education and Communication (IEC) and Behavioral Change Communication (BCC) strategies should be emphasized.

Responses to mental health stigma questions: the importance of social desirability and data collection method.

PubMed

Henderson, Claire; Evans-Lacko, Sara; Flach, Clare; Thornicroft, Graham

2012-03-01

To evaluate the impact on the general public of England's Time to Change program to reduce mental health-related stigma and discrimination using newly developed measures of knowledge and intended behaviour regarding people with mental health problems, and an established attitudes scale, and to investigate whether social desirability affects responses to the new measures and test whether this varies according to data collection method. The Mental Health Knowledge Schedule (MAKS) and Reported and Intended Behaviour Scale (RIBS) were administered together with the 13-item version of the Marlowe-Crowne Social Desirability Scale to 2 samples (each n = 196) drawn from the Time to Change mass media campaign target group; one group was interviewed face to face, while the other completed the measures as an online survey. After controlling for other covariates, interaction terms between collection method and social desirability were positive for each instrument. The social desirability score was associated with the RIBS score in the face-to-face group only (β = 0.35, 95% CI 0.14 to 0.57), but not with the MAKS score in either group; however, MAKS scores were more likely to be positive when data were collected face to face (β = 1.53, 95% CI 0.74 to 2.32). Behavioural intentions toward people with mental health problems may be better assessed using online self-complete methods than in-person interviews. The effect of face-to-face interviewing on knowledge requires further investigation.

Interaction of tinnitus suppression and hearing ability after cochlear implantation.

PubMed

Wang, Qian; Li, Jia-Nan; Lei, Guan-Xiong; Chen, Dai-Shi; Wang, Wei-Ze; Chen, Ai-Ting; Mong, Meng-Di; Li, Sun; Jiao, Qing-Shan; Yang, Shi-Ming

2017-10-01

To study the postoperative impact of cochlear implants (CIs) on tinnitus, as well as the impact of tinnitus on speech recognition with CI switched on. Fifty-two postlingual deafened CI recipients (21 males and 31 females) were assessed using an established Tinnitus Characteristics Questionnaire and Tinnitus Handicap Inventory (THI) before and after cochlear implantation. The tinnitus loudness was investigated when CI was switched on and off in CI recipients with persistent tinnitus. The relation between tinnitus loudness and recipients' satisfaction of cochlear implantation was analyzed by the visual analogue scale (VAS) score. With CI 'OFF', 42 CI recipients experienced tinnitus postimplant ipsilaterally and 44 contralaterally. Tinnitus was totally suppressed ipsilateral to the CI with CI 'ON' in 42.9%, partially suppressed in 42.9%, unchanged in 11.9% and aggravated in 2.4%. Tinnitus was totally suppressed contralaterally with CI 'ON' in 31.8% of CI recipients, partially suppressed in 47.7%, unchanged in 20.5%. Pearson correlation analysis showed that tinnitus loudness and the results of cochlear implant patients satisfaction was negatively correlated (r = .674, p < .001). The study suggests six-month CI activation can be effective for suppressing tinnitus. The tinnitus loudness may affect patients' satisfaction with the use of CI.

Characterization of long-term elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate beads in vitro by two distinct sample collection methods.

PubMed

Tulipan, Rachel J; Phillips, Heidi; Garrett, Laura D; Dirikolu, Levent; Mitchell, Mark A

2017-05-01

OBJECTIVE To characterize long-term elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate (CI-CSH) beads in vitro by comparing 2 distinct sample collection methods designed to mimic 2 in vivo environments. SAMPLES 162 CI-CSH beads containing 4.6 mg of carboplatin (2.4 mg of platinum/bead). PROCEDURES For method 1, which mimicked an in vivo environment with rapid and complete fluid exchange, each of 3 plastic 10-mL conical tubes contained 3 CI-CSH beads and 5 mL of PBS solution. Eluent samples were obtained by evacuation of all fluid at 1, 2, 3, 6, 9, and 12 hours and 1, 2, 3, 6, 9, 12, 15, 18, 22, 26, and 30 days. Five milliliters of fresh PBS solution was then added to each tube. For method 2, which mimicked an in vivo environment with no fluid exchange, each of 51 tubes (ie, 3 tubes/17 sample collection times) contained 3 CI-CSH beads and 5 mL of PBS solution. Eluent samples were obtained from the assigned tubes for each time point. All samples were analyzed for platinum content by inductively coupled plasma-mass spectrometry. RESULTS Platinum was released from CI-CSH beads for 22 to 30 days. Significant differences were found in platinum concentration and percentage of platinum eluted from CI-CSH beads over time for each method. Platinum concentrations and elution percentages in method 2 samples were significantly higher than those of method 1 samples, except for the first hour measurements. CONCLUSIONS AND CLINICAL RELEVANCE Sample collection methods 1 and 2 may provide estimates of the minimum and maximum platinum release, respectively, from CI-CSH beads in vivo.

Use of Dual Methods for Protection from Unintended Pregnancy and Sexually Transmitted Diseases in Adolescent African American Women.

PubMed

Kottke, Melissa; Whiteman, Maura K; Kraft, Joan Marie; Goedken, Peggy; Wiener, Jeffrey; Kourtis, Athena P; DiClemente, Ralph

2015-12-01

To characterize factors associated with dual method contraceptive use in a sample of adolescent women. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We conducted a cross-sectional survey of sexually active African American women aged 14-19 years who attended an urban Title X clinic in Georgia in 2012 (N = 350). Participants completed a computerized survey to assess contraceptive and condom use during the past 2 sexual encounters with their most recent partner. Dual method use was defined as use of a hormonal contraceptive or intrauterine device and a condom. We applied multinomial logistic regression, using generalized estimating equations, to examine the adjusted association between dual method use (vs use of no methods or less effective methods alone; eg, withdrawal) and select characteristics. Dual methods were used by 20.6% of participants at last sexual intercourse and 23.6% at next to last sexual intercourse. Having a previous sexually transmitted disease (adjusted odds ratio [aOR], 2.30; 95% confidence interval [CI], 1.26-4.18), negative attitude toward pregnancy (aOR, 2.25; 95% CI, 1.19-4.28), and a mother who gave birth as a teen (aOR, 2.34; 95% CI, 1.21-4.52) were associated with higher odds of dual method use. Having no health insurance (aOR, 0.39; 95% CI, 0.18-0.82), 4 or more lifetime sexual partners (aOR, 0.42; 95% CI, 0.22-0.78), sex at least weekly (aOR, 0.54; 95% CI, 0.29-0.99), and agreeing to monogamy with the most recent partner (aOR, 0.40; 95% CI, 0.16-0.96) were associated with decreased odds of dual method use. Dual method use was uncommon in our sample. Efforts to increase use of dual methods should address individual and relationship factors. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. All rights reserved.

Development of a multi-criteria evaluation system to assess growing pig welfare.

PubMed

Martín, P; Traulsen, I; Buxadé, C; Krieter, J

2017-03-01

The aim of this paper was to present an alternative multi-criteria evaluation model to assess animal welfare on farms based on the Welfare Quality® (WQ) project, using an example of welfare assessment of growing pigs. The WQ assessment protocol follows a three-step aggregation process. Measures are aggregated into criteria, criteria into principles and principles into an overall assessment. This study focussed on the first step of the aggregation. Multi-attribute utility theory (MAUT) was used to produce a value of welfare for each criterion. The utility functions and the aggregation function were constructed in two separated steps. The Measuring Attractiveness by a Categorical Based Evaluation Technique (MACBETH) method was used for utility function determination and the Choquet Integral (CI) was used as an aggregation operator. The WQ decision-makers' preferences were fitted in order to construct the utility functions and to determine the CI parameters. The methods were tested with generated data sets for farms of growing pigs. Using the MAUT, similar results were obtained to the ones obtained applying the WQ protocol aggregation methods. It can be concluded that due to the use of an interactive approach such as MACBETH, this alternative methodology is more transparent and more flexible than the methodology proposed by WQ, which allows the possibility to modify the model according, for instance, to new scientific knowledge.

An outbreak of cardiovascular syndromes requiring urgent medical treatment and its association with environmental factors: an ecological study

PubMed Central

Turner, Robin M; Muscatello, David J; Zheng, Wei; Willmore, Alan; Arendts, Glenn

2007-01-01

Background In April 2005, syndromic surveillance based on statistical control chart methods in Sydney, Australia, signalled increasing incidence of urgent emergency department visits for cardiovascular and chest pain syndromes compared to the preceding twelve months. This paper aimed to determine whether environmental factors could have been responsible for this 'outbreak'. Methods The outcome studied was daily counts of emergency department visits for cardiovascular or chest pain syndromes that were considered immediately or imminently life threatening on arrival at hospital. The outbreak had a mean daily count of 5.7 visits sustained for eight weeks, compared with 4.0 in the same months in previous years. Poisson regression was used to systematically assess the emergency department visits in relation to available daily weather and pollution variables by first finding the best model that explained short-term variation in the outcome over the period 25 January 2002 to 31 May 2005, and then assessing interactions of all available variables with the 'outbreak' period, April-May 2005. Rate ratios were estimated for an interquartile increase in each variable meaning that the ratio measures the relative increase (or decrease) in the emergency department visits for an interquartile increase in the weather or pollution variable. The rate ratios for the outbreak period measure the relative increase (or decrease) in the emergency department visits for an interquartile increase in the weather or pollution variable during the outbreak period only. Results The best fitting model over the whole study period included minimum temperature with a rate ratio (RR) of 0.86 (95% confidence interval (CI), 0.77–0.96), maximum relative humidity of 1.09 (95% CI 1.05–1.14) and minimum daily particulate matter less than 10 microns (PM10) of 1.05 (95% CI, 1.01–1.09). During the outbreak period, maximum temperature (RR 1.27, 95% CI 1.03–1.57), solar radiation (RR 1.44, 95% CI, 1.00–2.07) and ozone (RR 1.13, 95% CI 1.01–1.26) were associated with the outcome. Conclusion The increase may have been associated with photochemical pollution. Syndromic surveillance can identify outbreaks of non-communicable diseases associated with environmental factors. PMID:18036253

Systematic review and meta-analysis of Internet interventions for smoking cessation among adults

PubMed Central

Graham, Amanda L; Carpenter, Kelly M; Cha, Sarah; Cole, Sam; Jacobs, Megan A; Raskob, Margaret; Cole-Lewis, Heather

2016-01-01

Background The aim of this systematic review was to determine the effectiveness of Internet interventions in promoting smoking cessation among adult tobacco users relative to other forms of intervention recommended in treatment guidelines. Methods This review followed Cochrane Collaboration guidelines for systematic reviews. Combinations of “Internet,” “web-based,” and “smoking cessation intervention” and related keywords were used in both automated and manual searches. We included randomized trials published from January 1990 through to April 2015. A modified version of the Cochrane risk of bias assessment tool was used. We calculated risk ratios (RRs) for each study. Meta-analysis was conducted using random-effects method to pool RRs. Presentation of results follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Results Forty randomized trials involving 98,530 participants were included. Most trials had a low risk of bias in most domains. Pooled results comparing Internet interventions to assessment-only/waitlist control were significant (RR 1.60, 95% confidence interval [CI] 1.15–2.21, I2=51.7%; four studies). Pooled results of largely static Internet interventions compared to print materials were not significant (RR 0.83, 95% CI 0.63–1.10, I2=0%; two studies), whereas comparisons of interactive Internet interventions to print materials were significant (RR 2.10, 95% CI 1.25–3.52, I2=41.6%; two studies). No significant effects were observed in pooled results of Internet interventions compared to face-to-face counseling (RR 1.35, 95% CI 0.97–1.87, I2=0%; four studies) or to telephone counseling (RR 0.95, 95% CI 0.79–1.13, I2=0%; two studies). The majority of trials compared different Internet interventions; pooled results from 15 such trials (24 comparisons) found a significant effect in favor of experimental Internet interventions (RR 1.16, 95% CI 1.03–1.31, I2=76.7%). Conclusion Internet interventions are superior to other broad reach cessation interventions (ie, print materials), equivalent to other currently recommended treatment modes (telephone and in-person counseling), and they have an important role to play in the arsenal of tobacco-dependence treatments. PMID:27274333

Practicing Dentists’ Self-Efficacy and Associated Factors in Managing the Treatment of Adults with Mental and Physical Disabilities: An Exploratory Cross-Sectional Study in Riyadh, Saudi Arabia

PubMed Central

AlQahtani, Sakher; Zakaria Murshid, Ebtissam; Kassim, Saba

2017-01-01

Background: Provision of oral healthcare to adults with mental and physical disabilities (AMPD) remains a challenging area across various healthcare systems. The present study aimed to assess self-reported efficacy and investigate factors associated with self-efficacy in the management of AMPD among practicing dentists in Saudi Arabia. Methods: A pilot-tested, self-administered questionnaire was distributed to a convenience sample of 1000 dentists. Descriptive and inferential analyses were performed on the collected responses. Results: Among the respondents (54%), 43% were males. Only 14% described their self-efficacy in managing AMPD as “High”. Multivariable regression analyses revealed significant associations between “High” self-efficacy and male gender (Odd ratio (OR) = 2.39, 95% CI = 1.16–4.89), experience practicing dentistry for 11 years or more (OR = 2.19, 95% CI = 1.04–4.47), specialization in pediatric dentistry (OR = 3.98, 95% CI = 1.31–12.07), previous experience in managing AMPD (OR = 4.23, 95% CI = 1.59–11.22), and awareness of regulations for managing AMPD (OR = 2.62, 95% CI = 1.42–4.38). The interaction of gender x age was significantly associated (p = 0.028) with “High” self-efficacy. Gender-stratified analyses revealed a significant association between age and “High” self-efficacy among male dentists only. Conclusions: The findings of the present study highlight that a large percentage of dentists reported “Low/Moderate” self-efficacy in managing AMPD, particularly among female dentists. However, further studies are required to verify the factors associated with self-efficacy in the present study, and to identify other factors that may influence self-efficacy in managing AMPD. PMID:29232884

The Relationship of Cardiovascular Risk in Rheumatoid Arthritis Comparing TNFα Blockade with Non-Biologic DMARDs

PubMed Central

Solomon, Daniel H.; Curtis, Jeffrey R.; Saag, Kenneth G.; Lii, Joyce; Chen, Lang; Harrold, Leslie R.; Herrinton, Lisa J; Graham, David J; Kowal, Mary K.; Kuriya, Bindee; Liu, Liyan; Griffin, Marie R.; Lewis, James D.; Rassen, Jeremy A.

2015-01-01

Background Elevated TNFα likely contributes to the excess cardiovascular risk observed in rheumatoid arthritis. We compared the cardiovascular risk in rheumatoid arthritis patients starting a TNFα blocking agent versus a non-biologic disease-modifying anti-rheumatic drug (nbDMARD). Methods Subjects with rheumatoid arthritis participating in several different US insurance programs between 1998-2007 who received methotrexate were eligible. Those who added a TNFα blocking agent were compared with subjects who added a nbDMARD in Cox regression models stratified by propensity score decile and adjusted for oral glucocorticoid dosage. We examined the composite cardiovascular endpoint of myocardial infarction, stroke, or coronary re-vascularization after six months. Results We compared 8,656 new users of a nbDMARD with 11,587 new users of a TNFα blocking agent with similar baseline covariates. Incidence rates per 100 person-years for the composite cardiovascular endpoint were 3.05 (95% CI 2.54 – 3.65) for nbDMARDs and 2.52 (95% CI 2.12-2.98) for TNFα blocking agents. The hazard ratio (HR) for the TNFα blocking agent compared with nbDMARD carrying the first exposure forward was 0.80 (95% CI 0.62 - 1.04), while the HR for the as-treated analysis was 0.71 (95% CI 0.52 - 0.97). The potential cardiovascular benefit of TNFα blocking agents was strongest among persons ≥ 65 years of age (HR 0.52, 95% CI 0.34 – 0.77; p for interaction = 0.075). Conclusion Among subjects with rheumatoid arthritis, TNFα blocking agents may be associated with a reduced risk of cardiovascular events compared to a nbDMARD. Randomized controlled clinical trials should be considered to test this hypothesis. PMID:23885678

Characteristics of Plantar Loads in Maximum Forward Lunge Tasks in Badminton

PubMed Central

Hu, Xiaoyue; Li, Jing Xian; Hong, Youlian; Wang, Lin

2015-01-01

Background Badminton players often perform powerful and long-distance lunges during such competitive matches. The objective of this study is to compare the plantar loads of three one-step maximum forward lunges in badminton. Methods Fifteen right-handed male badminton players participated in the study. Each participant performed five successful maximum lunges at three directions. For each direction, the participant wore three different shoe brands. Plantar loading, including peak pressure, maximum force, and contact area, was measured by using an insole pressure measurement system. Two-way ANOVA with repeated measures was employed to determine the effects of the different lunge directions and different shoes, as well as the interaction of these two variables, on the measurements. Results The maximum force (MF) on the lateral midfoot was lower when performing left-forward lunges than when performing front-forward lunges (p = 0.006, 95% CI = −2.88 to −0.04%BW). The MF and peak pressures (PP) on the great toe region were lower for the front-forward lunge than for the right-forward lunge (MF, p = 0.047, 95% CI = −3.62 to −0.02%BW; PP, p = 0.048, 95% CI = −37.63 to −0.16 KPa) and left-forward lunge (MF, p = 0.015, 95% CI = −4.39 to −0.38%BW; PP, p = 0.008, 95% CI = −47.76 to −5.91 KPa). Conclusions These findings indicate that compared with the front-forward lunge, left and right maximum forward lunges induce greater plantar loads on the great toe region of the dominant leg of badminton players. The differences in the plantar loads of the different lunge directions may be potential risks for injuries to the lower extremities of badminton players. PMID:26367741

Using Diverse Communication Strategies to Re-Engage Relapsed Tobacco Quitline Users in Treatment, New York State, 2014.

PubMed

Carlini, Beatriz; Miles, Lyndsay; Doyle, Suzanne; Celestino, Paula; Koutsky, James

2015-10-22

Most smoking cessation programs lack strategies to reach relapsed participants and encourage a new quit attempt. We used a multimodal intervention to encourage past quitline registry participants to recycle into services. We invited 3,510 past quitline participants back to quitline services, using messages consecutively delivered through Interactive Voice Response (IVR), followed by postcard and email reminders, 2 Short Messaging Services (SMS) texts, and a final cycle of IVR. The primary study outcome was recycling into a new quitline-assisted quit attempt. We used statistical analyses to assess rates and predictors of recycling (socioeconomic, health- and tobacco-related variables) with study participants and compared the study sample with registry participants not selected for the study (comparison group). Quitline services were re-initiated by 12.2% of the intervention sample and 1.9% of the comparison group (z = 6.03, P < .001, effect size of 0.44). Most re-enrollments were done via direct IVR-transfer to the quitline. Predictors of re-enrollment were age (odds ratio [OR] = 1.45 for every 10 years of age; 95% confidence interval [CI], 1.34-1.57), number of years smoking (OR = 1.27; 95% CI, 1.18-1.36), and reporting cancer (OR = 2.32; 95% CI, 1.47-3.68) or chronic obstructive pulmonary disease (OR = 1.55; 95% CI, 1.16-2.10). Living with other smokers was correlated with a lower chance of recycling into treatment (OR = 0.72; 95% CI, 0.57-0.91). Recycling previous quitline participants using a proactive, IVR-based intervention is effective in reinitiating quitline-assisted quit attempts. Older, long-term smokers reporting chronic conditions are more likely than younger smokers to re-engage in quitline support when these methods are used.

Can machine-learning improve cardiovascular risk prediction using routine clinical data?

PubMed Central

Kai, Joe; Garibaldi, Jonathan M.; Qureshi, Nadeem

2017-01-01

Background Current approaches to predict cardiovascular risk fail to identify many people who would benefit from preventive treatment, while others receive unnecessary intervention. Machine-learning offers opportunity to improve accuracy by exploiting complex interactions between risk factors. We assessed whether machine-learning can improve cardiovascular risk prediction. Methods Prospective cohort study using routine clinical data of 378,256 patients from UK family practices, free from cardiovascular disease at outset. Four machine-learning algorithms (random forest, logistic regression, gradient boosting machines, neural networks) were compared to an established algorithm (American College of Cardiology guidelines) to predict first cardiovascular event over 10-years. Predictive accuracy was assessed by area under the ‘receiver operating curve’ (AUC); and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) to predict 7.5% cardiovascular risk (threshold for initiating statins). Findings 24,970 incident cardiovascular events (6.6%) occurred. Compared to the established risk prediction algorithm (AUC 0.728, 95% CI 0.723–0.735), machine-learning algorithms improved prediction: random forest +1.7% (AUC 0.745, 95% CI 0.739–0.750), logistic regression +3.2% (AUC 0.760, 95% CI 0.755–0.766), gradient boosting +3.3% (AUC 0.761, 95% CI 0.755–0.766), neural networks +3.6% (AUC 0.764, 95% CI 0.759–0.769). The highest achieving (neural networks) algorithm predicted 4,998/7,404 cases (sensitivity 67.5%, PPV 18.4%) and 53,458/75,585 non-cases (specificity 70.7%, NPV 95.7%), correctly predicting 355 (+7.6%) more patients who developed cardiovascular disease compared to the established algorithm. Conclusions Machine-learning significantly improves accuracy of cardiovascular risk prediction, increasing the number of patients identified who could benefit from preventive treatment, while avoiding unnecessary treatment of others. PMID:28376093

Role of Systemic Therapy in the Development of Lung Sequelae After Conformal Radiotherapy in Breast Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Varga, Zoltan; Cserhati, Adrienn; Kelemen, Gyoengyi

2011-07-15

Purpose: To analyze the risk of radiogenic lung damage in breast cancer patients after conformal radiotherapy and different forms of systemic treatment. Methods and Materials: In 328 patients receiving sequential taxane-based chemotherapy, concomitant hormone therapy (tamoxifen or aromatase inhibitors), or no adjuvant systemic therapy, symptomatic and asymptomatic lung sequelae were prospectively evaluated via the detection of visible CT abnormalities, 3 months or 1 year after the completion of the radiotherapy. Results: Significant positive associations were detected between the development of both pneumonitis and fibrosis of Grade 1 and patient age, ipsilateral mean lung dose, volume of the ipsilateral lung receivingmore » 20 Gy, and irradiation of the regional lymph nodes. In multivariate analysis, age and mean lung dose proved to be independent predictors of early (odds ratio [OR] = 1.035, 95% confidence interval [CI] 1.011-1.061 and OR = 1.113, 95% CI 1.049-1.181, respectively) and late (OR = 1.074, 95% CI 1.042-1.107 and OR = 1.207, 95% CI 1.124-1.295, respectively) radiogenic lung damage, whereas the role of systemic therapy was significant in the development of Grade 1 lung fibrosis (p = 0.01). Among the various forms of systemic therapy, tamoxifen increased the risk of late lung sequelae (OR = 2.442, 95% CI 1.120-5.326, p = 0.025). No interaction was demonstrated between the administration of systemic therapy and the other above-mentioned parameters as regards the risk of radiogenic lung damage. Conclusions: Our analyses demonstrate the independent role of concomitant tamoxifen therapy in the development of radiogenic lung fibrosis but do not suggest such an effect for the other modes of systemic treatment.« less

Parental Style and Its Association With Substance Use in Youth in Argentina

PubMed Central

Peña, Lorena; Pérez, Adriana; Morello, Paola; Lorenzo-Blanco, Elma I.; Santillan, Edna Arillo; Kollath-Cattano, Christy; Thrasher, James F.; Sargent, James; Mejia, Raúl

2017-01-01

Background In Europe and the United States, family relationships and parenting behavior can influence youth substance use, but less is known about their influence in Latin American countries. Objective To explore whether parenting behavior is associated with substance use among Latin American youth. Methods A cross-sectional, school-based survey of middle-school youth (n=3,172) in three Argentinian cities queried tobacco, alcohol, and drug use using items adapted from global youth surveys. Parenting behavior was assessed with previously validated items that tapped into demandingness and responsiveness, separately for mothers and fathers. Multilevel logistic regression models assessed associations between parenting behavior and substance use after adjusting for student characteristics, socioeconomic indicators, sensation seeking, and smoking amongst peers and family members. Results Substance use prevalence was 10% for current smoking, 32% for current drinking alcohol, 17% for past 30-day binge drinking (≥5 drinks), and 8% for previous year illicit drug use (marijuana or cocaine). Greater maternal demandingness was independently associated with lower likelihood of current smoking (AOR=0.77; 95% CI 0.64–0.92), current drinking (AOR=0.81; 95% CI 0.71 –0.92), binge drinking (AOR=0.77; 95% CI 0.66–0.99, and drug use (AOR=0.71; 95% CI 0.61–0.83). No other parenting behavior were independently associated with substance use, except for paternal demandingness and binge drinking (AOR=0.84; 95% CI 0.74–0.97). For all outcomes, no interactions were found between parenting behavior and student gender. Conclusions Among Argentine adolescents, maternal demandingness was the strongest and most consistent correlate of substance use, regardless of adolescent substance use behavior or gender. PMID:28010167

Genetic variation in C-reactive protein (CRP) in relation to colon and rectal cancer risk and survival

PubMed Central

Slattery, Martha L.; Curtin, Karen; Poole, Elizabeth M.; Duggan, David J.; Samowitz, Wade S.; Peters, Ulrike; Caan, Bette J.; Potter, John D.; Ulrich, Cornelia M.

2011-01-01

Background C-reactive protein (CRP), a biomarker of inflammation has been shown to be influenced by genetic variation in the CRP gene. Methods In this study, we test the hypothesis that genetic variation in CRP influences both the risk of developing colon and rectal cancer and survival. Two population-based studies of colon cancer (n=1574 cases, 1970 controls) and rectal (n=791 cases, 999 controls) were conducted. We evaluated four CRP tagSNPs: rs1205 (G>A, 3’ UTR); rs1417938 (T>A, intron); rs1800947 (G>C, L184L); and rs3093075 (C>A, 3’ flanking). Results The CRP rs1205 AA genotype was associated with an increased risk of colon cancer (OR 1.3, 95%CI 1.1-1.7), whereas the rs3093075 A allele was associated with a reduced risk of rectal cancer (OR 0.7, 95%CI 0.5-0.9). The strongest association for the rs1205 polymorphism and colon cancer was observed among those with KRAS2 mutations (OR 1.5, 95%CI 1.1-2.0). The CRP rs1205 AA genotype also was associated with an increased risk of CIMP+ rectal tumors (OR 2.5, 95% CI 1.2-5.3); conversely, the rs1417938 A allele was associated with a reduced risk of CIMP+ rectal tumors (OR 0.5, 95%CI 0.3-0.9). We observed interactions between CRP rs1800947 and BMI and family history of CRC in modifying risk of both colon and rectal cancer. Conclusions These data suggest that genetic variation in the CRP gene influences risk of both colon and rectal cancer development. PMID:20949557

Childhood socioeconomic factors and perinatal characteristics influence development of rheumatoid arthritis in adulthood

PubMed Central

Parks, Christine G; D’Aloisio, Aimee A; DeRoo, Lisa A; Huiber, Kirstin; Rider, Lisa G; Miller, Frederick W; Sandler, Dale P

2016-01-01

Background Rheumatoid arthritis (RA) has been associated with lower socioeconomic status (SES), but the reasons for this are not known. Objective To examine childhood SES measures, SES trajectory and other perinatal factors in relation to RA. Methods The sample included 50 884 women, aged 35–74 (84% non-Hispanic white) enrolled 2004–9 in a US national cohort study. In baseline questionnaires, cases (N=424, 0.8%) reported RA diagnosis after age 16, ever use of disease-modifying antirheumatic drugs or steroids for RA and ≥6 weeks bilateral joint swelling. Childhood SES measures are presented as OR and 95% CI adjusted for age and race/ethnicity. Analyses of perinatal factors also adjusted for childhood SES, and joint effects of childhood and adult SES and smoking exposures were evaluated. Results Patients with RA reported lower childhood household education (<12 years vs college degree; OR=1.7; 95% CI 1.1 to 2.5), food insecurity (OR=1.5, 95% CI 1.1 to 2.0) and young maternal age (<20 vs 20–34 years; OR=1.7, 95% CI 1.2 to 2.5), with a trend (p<0.0001) for increasing number of adverse factors (OR=3.0; 95% CI 1.3 to 7.0; 4 vs 0 factors) compared with non-cases. High birth weight (>4000 g) and preconception paternal smoking were independently associated with RA. Together, lower childhood SES and adult education (

Statins and risk of poststroke hemorrhagic complications

PubMed Central

MacIsaac, Rachael L.; Abdul-Rahim, Azmil H.; Siegerink, Bob; Bath, Philip M.; Endres, Matthias; Lees, Kennedy R.; Nolte, Christian H.

2016-01-01

Objective: To assess whether statin treatment before or after acute ischemic stroke (AIS) affects the risk of acute intracerebral hemorrhage (ICH), postacute ICH, and mortality within 90 days. Methods: Data were sought from the Virtual International Stroke Trials Archive, an international repository of clinical trials data. Using propensity score matching, we retrospectively compared patients with prior statin treatment and newly initiated statin within 3 days after AIS to patients without statin exposure. Outcomes of interest were acute symptomatic ICH (sICH), any acute ICH, postacute ICH, and mortality during follow-up of 3 months. Results: A total of 8,535 patients (mean age 70 years, 54% male, median baseline NIH Stroke Scale score 13) were analyzed. After propensity score matching, prior statin use was not strongly associated with sICH (adjusted odds ratio [OR] 1.33, 95% confidence interval [CI] 0.83–2.14) or any ICH (adjusted OR 1.35, 95% CI 0.92–1.98). There was no evidence of an interaction between prior statin use and thrombolysis. New initiation of statins was not associated with postacute ICH (adjusted hazard ratio [HR] 1.60, 95% CI 0.70–3.65). There was a signal towards lower 90-day mortality in patients with prior statin use (adjusted HR 0.84, 95% CI 0.70–1.00) and especially early initiation of statins (adjusted HR 0.67, 95% CI 0.46–0.97). Conclusions: Statin use prior to AIS was not associated with early hemorrhagic complications, irrespective of treatment with thrombolysis. New initiation of statin treatment early after AIS did not affect risk of postacute ICH, but might be associated with reduced mortality. PMID:27016519

The Effect of an EDTA-based Chelation Regimen on Patients with Diabetes and Prior Myocardial Infarction in TACT

PubMed Central

Escolar, Esteban; Lamas, Gervasio A.; Mark, Daniel B.; Boineau, Robin; Goertz, Christine; Rosenberg, Yves; Nahin, Richard L.; Ouyang, Pamela; Rozema, Theodore; Magaziner, Allan; Nahas, Richard; Lewis, Eldrin F.; Lindblad, Lauren; Lee, Kerry L.

2014-01-01

Background The Trial to Assess Chelation Therapy (TACT) showed clinical benefit of an ethylene diamine tetraacetic acid (EDTA-based) infusion regimen in patients 50 years or older with prior myocardial infarction (MI). Diabetes prior to enrollment was a pre-specified subgroup. Methods and Results Patients received 40 infusions of EDTA chelation or placebo. 633 (37%) had diabetes (322 EDTA, 311 placebo). EDTA reduced the primary endpoint (death, reinfarction, stroke, coronary revascularization, or hospitalization for angina) [25% vs 38%, hazard ratio (HR) 0.59, 95% confidence interval (CI) (0.44, 0.79), p<0.001] over 5 years. The result remained significant after Bonferroni adjustment for multiple subgroups (99.4% CI (0.39, 0.88), adjusted p=0.002). All-cause mortality was reduced by EDTA chelation [10% vs 16%, HR 0.57, 95% CI (0.36, 0.88) p=0.011], as was the secondary endpoint (cardiovascular death, reinfarction, or stroke) [11% vs 17% HR 0.60, 95% CI (0.39, 0.91), p=0.017]. After adjusting for multiple subgroups, however, those results were no longer significant. The number needed to treat to reduce one primary endpoint was 6.5 over 5 years (95% CI (4.4, 12.7). There was no reduction in events in non-diabetics (n=1075, p=0.877), resulting in a treatment by diabetes interaction (p=0.004). Conclusions Post-MI diabetic patients age 50 or older demonstrated a marked reduction in cardiovascular events with EDTA chelation. These findings support efforts to replicate these findings and define the mechanisms of benefit. They do not, however, constitute sufficient evidence to indicate the routine use of chelation therapy for all post-MI diabetic patients. PMID:24254885

Geographic Factors and Human Papillomavirus (HPV) Vaccination Initiation Among Adolescent Girls in the United States

PubMed Central

Henry, Kevin A.; Stroup, Antoinette M.; Warner, Echo L; Kepka, Deanna

2015-01-01

Background This study is among the first to explore geographic factors that may be associated with HPV vaccine uptake in the United States. Methods Data from the 2011 and 2012 National Immunization Survey-Teen for 20,565 female adolescents aged 13-17 years were analyzed to examine associations of HPV vaccine initiation (receipt of at least one dose) with ZIP code-level geographic factors. Logistic regression including individual and geographic factors was used to estimate the odds of HPV vaccine initiation. Results Approximately 53% of girls initiated the HPV vaccine in both years. Girls in high poverty communities had higher HPV vaccine initiation compared to those in low poverty communities (61.1% vs .52.4%; Adjusted Odds Ratio [AOR] 1.18,95%CI 1.04-1.33). Initiation was higher among girls in communities where the majority of the population was Hispanic (69.0% vs. 49.9%;AOR 1.64, 95%CI 1.43-1.87) or non-Hispanic mixed race (60.4% vs. 49.9%; AOR 1.30, 95%CI 1.17-1.44) compared to majority non-Hispanic white communities. Interactions between individual-level race/ethnicity and community racial–ethnic composition indicated significantly higher odds of initiation among Hispanic girls living in Hispanic communities compared to Hispanic girls living in predominately NHW (AOR 2.23;95%CI 1.87-2.65) or NHB (AOR 1.90; 95%CI 1.20-3.04)communities, respectively Conclusion Initiation rates of HPV vaccination among teen girls were highest in the poorest communities and among Hispanics living in communities where the racial–ethnic composition was predominantly Hispanic or mixed race. Impact Given low HPV vaccination rates in the United States, these results provide important evidence to inform public health interventions to increase HPV vaccination. PMID:26768989

Practicing Dentists' Self-Efficacy and Associated Factors in Managing the Treatment of Adults with Mental and Physical Disabilities: An Exploratory Cross-Sectional Study in Riyadh, Saudi Arabia.

PubMed

AlQahtani, Sakher; Murshid, Ebtissam Zakaria; Fadel, Hani Talal; Kassim, Saba

2017-12-11

Background: Provision of oral healthcare to adults with mental and physical disabilities (AMPD) remains a challenging area across various healthcare systems. The present study aimed to assess self-reported efficacy and investigate factors associated with self-efficacy in the management of AMPD among practicing dentists in Saudi Arabia. Methods: A pilot-tested, self-administered questionnaire was distributed to a convenience sample of 1000 dentists. Descriptive and inferential analyses were performed on the collected responses. Results: Among the respondents (54%), 43% were males. Only 14% described their self-efficacy in managing AMPD as "High". Multivariable regression analyses revealed significant associations between "High" self-efficacy and male gender (Odd ratio (OR) = 2.39, 95% CI = 1.16-4.89), experience practicing dentistry for 11 years or more (OR = 2.19, 95% CI = 1.04-4.47), specialization in pediatric dentistry (OR = 3.98, 95% CI = 1.31-12.07), previous experience in managing AMPD (OR = 4.23, 95% CI = 1.59-11.22), and awareness of regulations for managing AMPD (OR = 2.62, 95% CI = 1.42-4.38). The interaction of gender x age was significantly associated ( p = 0.028) with "High" self-efficacy. Gender-stratified analyses revealed a significant association between age and "High" self-efficacy among male dentists only. Conclusions: The findings of the present study highlight that a large percentage of dentists reported "Low/Moderate" self-efficacy in managing AMPD, particularly among female dentists. However, further studies are required to verify the factors associated with self-efficacy in the present study, and to identify other factors that may influence self-efficacy in managing AMPD.

Racial Differences in the Impact of Elevated Systolic Blood Pressure on Stroke Risk

PubMed Central

Howard, George; Lackland, Daniel T.; Kleindorfer, Dawn O.; Kissela, Brett M.; Moy, Claudia S.; Judd, Suzanne E.; Safford, Monika M.; Cushman, Mary; Glasser, Stephen P.; Howard, Virginia J.

2013-01-01

Background Between the ages 45 and 65 years, incident stroke is 2 to 3 times more common in blacks than in whites, a difference not explained by traditional stroke risk factors. Methods Stroke risk was assessed in 27 748 black and white participants recruited between 2003 and 2007, who were followed up through 2011, in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Racial differences in the impact of systolic blood pressure (SBP) was assessed using proportional hazards models. Racial differences in stroke risk were assessed in strata defined by age (<65 years, 65–74 years, and ≥75 years) and SBP (<120 mm Hg, 120–139 mm Hg, and 140–159 mm Hg). Results Over 4.5 years of follow-up, 715 incident strokes occurred. A 10–mm Hg difference in SBP was associated with an 8% (95% CI, 0%-16%) increase in stroke risk for whites, but a 24% (95% CI, 14%-35%) increase for blacks (P value for interaction, .02). For participants aged 45 to 64 years (where disparities are greatest), the black to white hazard ratio was 0.87 (95% CI, 0.48–1.57) for normotensive participants, 1.38 (95% CI, 0.94–2.02) for those with prehypertension, and 2.38 (95% CI, 1.19–4.72) for those with stage 1 hypertension. Conclusions These findings suggest racial differences in the impact of elevated blood pressure on stroke risk. When these racial differences are coupled with the previously documented higher prevalence of hypertension and poorer control of hypertension in blacks, they may account for much of the racial disparity in stroke risk. PMID:23229778

Risk Factors for Smoking in Rural Women

PubMed Central

Salsberry, Pamela J.; Ferketich, Amy K.; Ahijevych, Karen L.; Hood, Nancy E.; Paskett, Electra D.

2012-01-01

Abstract Background This study examined the association between social, demographic, and psychologic factors and smoking status among Appalachian Ohio women. A secondary aim examined whether specific factors could be identified and segmented for future tailored treatment of tobacco dependence. Methods A cross-sectional survey (n=570) obtained information about social, demographic, and psychologic factors and smoking. Logistic regression described associations between these characteristics and smoking status. Chi-square automatic interaction detection (CHAID) analyses identified subgroups at risk for smoking. Results Fifty-two percent never smoked, with 20.5% and 27.5% categorized as former and current smokers, respectively. Women with low adult socioeconomic position (SEP) were more likely to smoke (odds ratio [OR] 3.05, 95% confidence interval [CI] 1.74-5.34) compared to high SEP women. Other factors associated with current smoking included age 31–50 (OR 2.30, 95% CI 1.22-4.33), age 18–30 (OR 3.29, 95% CI 1.72-5.34), Center for Epidemiologic Studies Depression scale (CES-D) score≥16 (OR 1.99, 95% CI 1.31-3.05), and first pregnancy at age<20 (OR 1.74, 95% CI 1.14-2.66). The prevalence of smoking was 50% among those with four or more risk factors compared to 10% for those reporting no risk factors. CHAID analyses identified low adult SEP and depressive symptoms as the combination of risk factors most strongly associated with smoking; 49.3% of women in this subgroup currently smoked. Conclusions Low SEP in adulthood, maternal circumstances, and depressive symptoms are associated with current smoking. Tailored cessation interventions that address these risk factors should be developed and further evaluated in an attempt to reduce disparities in smoking prevalence among this vulnerable group of women. PMID:22360694

Improving tobacco dependence treatment outcomes for smokers of lower socioeconomic status: A randomized clinical trial.

PubMed

Sheffer, Christine E; Bickel, Warren K; Franck, Christopher T; Panissidi, Luana; Pittman, Jami C; Stayna, Helen; Evans, Shenell

2017-12-01

Evidence-based treatments for tobacco dependence are significantly less effective for smokers of lower socioeconomic status which contributes to socioeconomic disparities in smoking prevalence rates and health. We aimed to reduce the socioeconomic gradient in treatment outcomes by systematically adapting evidence-based, cognitive-behavioral treatment for tobacco dependence for diverse lower socioeconomic smokers. Participants were randomized to adapted or standard treatment, received six 1-h group treatment sessions, and were followed for six months. We examined the effectiveness of the adapted treatment to improve treatment outcomes for lower socioeconomic groups. Participants (n=227) were ethnically, racially, and socioeconomically diverse. The adapted treatment significantly reduced the days to relapse for the two lowest socioeconomic groups: SES1: M=76.6 (SD 72.9) vs. 38.3 (SD 60.1) days to relapse (RR=0.63 95% CI, 0.45, 0.88, p=0.0013); SES2: M=88.2 (SD 67.3) vs. 40.1 (SD 62.6 days to relapse (RR=0.57 95% CI, 0.18, 0.70, p=0.0024). Interactions between socioeconomic status and condition were significant for initial abstinence (OR=1.26, 95% CI 1.09, 1.46, p=0.002), approached significance for 3-month abstinence (OR=0.90, 95% CI 0.80, 1.01, p<0.071), and were not significant for 6-month abstinence (OR=0.99 95% CI 0.88, 1.10, p=0.795). No significant differences in long-term abstinence were observed. Systematic adaption of evidence-based treatment for tobacco dependence can significantly improve initial and short-term treatment outcomes for diverse lower socioeconomic smokers and reduce inequities in days to relapse. Novel methods of providing targeted extended support are needed to improve long-term outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Neonatal antecedents for cerebral palsy in extremely preterm babies and interaction with maternal factors.

PubMed

Tran, Uyen; Gray, Peter H; O'Callaghan, Michael J

2005-06-01

Preterm delivery is associated with an increased risk of cerebral palsy (CP). The greatest risk is for infants born <28 weeks' gestation. To identify significant neonatal risk factors for CP and explore the interactions between antenatal and neonatal risk factors, among extremely preterm infants of 27 weeks' gestation or less. Nested case control design. Infants born between 1989 and 1996, at 24-27 weeks' gestation, were evaluated: 30 with CP at 2 years corrected age and 120 control infants matched for gestation age. Neonatal variables were compared using matched analyses with the interaction between antenatal and neonatal factors being examined using logistic regression analyses. Risk factors for CP on matched analyses included patent ductus arteriosus requiring surgical ligation, peri-intraventricular haemorrhage, moderate to severe ventricular dilatation, periventricular leukomalacia (PVL) and need for home oxygen. Independent neonatal predictors were ventricular dilatation (OR 7.3; 95% CI 1.6, 32.3), PVL (OR 29.8; 95% CI 5.6, 159.1) and home oxygen use (OR 3.4; 95% CI 1.2, 9.4). No interaction terms in the logistic models were significant between the previously identified pregnancy risk factors of absence of antenatal steroids and intrauterine growth restriction and the neonatal risk factors. PVL is the most powerful independent predictor of CP in extremely preterm infants of 27 weeks' gestation or less and appears to be uninfluenced by antenatal factors.

Tecarfarin, a novel vitamin K reductase antagonist, is not affected by CYP2C9 and CYP3A4 inhibition following concomitant administration of fluconazole in healthy participants.

PubMed

Bavisotto, Linda M; Ellis, David J; Milner, Peter G; Combs, Daniel L; Irwin, Ian; Canafax, Daniel M

2011-04-01

Comparative pharmacokinetics of vitamin K epoxide reductase antagonists tecarfarin and warfarin were assessed before and after coadministration for 21 days of the CYP450 inhibitor fluconazole in a randomized, open-label, single-center drug interaction study. Twenty healthy adult participants were randomized 1:1 to receive approximately equipotent single oral doses of tecarfarin (50 mg) or warfarin (17.5 mg). Following 7 days of baseline serial blood level collections, each participant received oral fluconazole 400 mg daily for 21 days. A second identical single oral dose of tecarfarin or warfarin was given 14 days after starting fluconazole with serial pharmacokinetic sampling. Key pharmacokinetic parameters C(max), t(max), AUC(0-168), apparent clearance, and t(1/2) demonstrated no tecarfarin-fluconazole interaction but a strong warfarin-fluconazole interaction. The ratio of log-transformed mean AUC(0-168) with versus without fluconazole for tecarfarin was 91.2% (90% confidence interval [CI]: 83.3-99.8) and for racemic warfarin was 213% (90% CI: 202-226). The 90% CI was entirely within the standard 80% to 125% bioequivalence interval for tecarfarin but well outside the bioequivalence interval for warfarin, confirming a clinically significant pharmacokinetic interaction between warfarin and fluconazole. In contrast, tecarfarin pharmacokinetics were apparently unchanged by fluconazole.

R package to estimate intracluster correlation coefficient with confidence interval for binary data.

PubMed

Chakraborty, Hrishikesh; Hossain, Akhtar

2018-03-01

The Intracluster Correlation Coefficient (ICC) is a major parameter of interest in cluster randomized trials that measures the degree to which responses within the same cluster are correlated. There are several types of ICC estimators and its confidence intervals (CI) suggested in the literature for binary data. Studies have compared relative weaknesses and advantages of ICC estimators as well as its CI for binary data and suggested situations where one is advantageous in practical research. The commonly used statistical computing systems currently facilitate estimation of only a very few variants of ICC and its CI. To address the limitations of current statistical packages, we developed an R package, ICCbin, to facilitate estimating ICC and its CI for binary responses using different methods. The ICCbin package is designed to provide estimates of ICC in 16 different ways including analysis of variance methods, moments based estimation, direct probabilistic methods, correlation based estimation, and resampling method. CI of ICC is estimated using 5 different methods. It also generates cluster binary data using exchangeable correlation structure. ICCbin package provides two functions for users. The function rcbin() generates cluster binary data and the function iccbin() estimates ICC and it's CI. The users can choose appropriate ICC and its CI estimate from the wide selection of estimates from the outputs. The R package ICCbin presents very flexible and easy to use ways to generate cluster binary data and to estimate ICC and it's CI for binary response using different methods. The package ICCbin is freely available for use with R from the CRAN repository (https://cran.r-project.org/package=ICCbin). We believe that this package can be a very useful tool for researchers to design cluster randomized trials with binary outcome. Copyright © 2017 Elsevier B.V. All rights reserved.

CI2 for creating and comparing confidence-intervals for time-series bivariate plots.

PubMed

Mullineaux, David R

2017-02-01

Currently no method exists for calculating and comparing the confidence-intervals (CI) for the time-series of a bivariate plot. The study's aim was to develop 'CI2' as a method to calculate the CI on time-series bivariate plots, and to identify if the CI between two bivariate time-series overlap. The test data were the knee and ankle angles from 10 healthy participants running on a motorised standard-treadmill and non-motorised curved-treadmill. For a recommended 10+ trials, CI2 involved calculating 95% confidence-ellipses at each time-point, then taking as the CI the points on the ellipses that were perpendicular to the direction vector between the means of two adjacent time-points. Consecutive pairs of CI created convex quadrilaterals, and any overlap of these quadrilaterals at the same time or ±1 frame as a time-lag calculated using cross-correlations, indicated where the two time-series differed. CI2 showed no group differences between left and right legs on both treadmills, but the same legs between treadmills for all participants showed differences of less knee extension on the curved-treadmill before heel-strike. To improve and standardise the use of CI2 it is recommended to remove outlier time-series, use 95% confidence-ellipses, and scale the ellipse by the fixed Chi-square value as opposed to the sample-size dependent F-value. For practical use, and to aid in standardisation or future development of CI2, Matlab code is provided. CI2 provides an effective method to quantify the CI of bivariate plots, and to explore the differences in CI between two bivariate time-series. Copyright © 2016 Elsevier B.V. All rights reserved.

Participatory design of a music aural rehabilitation programme.

PubMed

van Besouw, Rachel M; Oliver, Benjamin R; Hodkinson, Sarah M; Polfreman, Richard; Grasmeder, Mary L

2015-09-01

Many cochlear implant (CI) users wish to enjoy music but are dissatisfied by its quality as perceived through their implant. Although there is evidence to suggest that training can improve CI users' perception and appraisal of music, availability of interactive music-based aural rehabilitation for adults is limited. In response to this need, an 'Interactive Music Awareness Programme' (IMAP) was developed with and for adult CI users. An iterative design and evaluation approach was used. The process began with identification of user needs through consultations, followed by use of mock-up applications in workshops. Feedback from these were used to develop the prototype IMAP; a programme of 24 interactive sessions, enabling users to create and manipulate music. The prototype IMAP was subsequently evaluated in a home trial with 16 adult CI users over a period of 12 weeks. Overall ratings for the prototype IMAP were positive and indicated that it met users' needs. Quantitative and qualitative feedback on the sessions and software in the prototype IMAP were used to identify aspects of the programme that worked well and aspects that required improvement. The IMAP was further developed in response to users' feedback and is freely available online. The participatory design approach used in developing the IMAP was fundamental in ensuring its relevance, and regular feedback from end users in each phase of development proved valuable for early identification of issues. Observations and feedback from end users supported a holistic approach to music aural rehabilitation.

The transition from the open minimum to the ring minimum on the ground state and on the lowest excited state of like symmetry in ozone: A configuration interaction study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Theis, Daniel; Windus, Theresa L.; Ruedenberg, Klaus

The metastable ring structure of the ozone 1{sup 1}A{sub 1} ground state, which theoretical calculations have shown to exist, has so far eluded experimental detection. An accurate prediction for the energy difference between this isomer and the lower open structure is therefore of interest, as is a prediction for the isomerization barrier between them, which results from interactions between the lowest two {sup 1}A{sub 1} states. In the present work, valence correlated energies of the 1{sup 1}A{sub 1} state and the 2{sup 1}A{sub 1} state were calculated at the 1{sup 1}A{sub 1} open minimum, the 1{sup 1}A{sub 1} ring minimum,more » the transition state between these two minima, the minimum of the 2{sup 1}A{sub 1} state, and the conical intersection between the two states. The geometries were determined at the full-valence multi-configuration self-consistent-field level. Configuration interaction (CI) expansions up to quadruple excitations were calculated with triple-zeta atomic basis sets. The CI expansions based on eight different reference configuration spaces were explored. To obtain some of the quadruple excitation energies, the method of Correlation Energy Extrapolation by Intrinsic Scaling was generalized to the simultaneous extrapolation for two states. This extrapolation method was shown to be very accurate. On the other hand, none of the CI expansions were found to have converged to millihartree (mh) accuracy at the quadruple excitation level. The data suggest that convergence to mh accuracy is probably attained at the sextuple excitation level. On the 1{sup 1}A{sub 1} state, the present calculations yield the estimates of (ring minimum—open minimum) ∼45–50 mh and (transition state—open minimum) ∼85–90 mh. For the (2{sup 1}A{sub 1}–{sup 1}A{sub 1}) excitation energy, the estimate of ∼130–170 mh is found at the open minimum and 270–310 mh at the ring minimum. At the transition state, the difference (2{sup 1}A{sub 1}–{sup 1}A{sub 1}) is found to be between 1 and 10 mh. The geometry of the transition state on the 1{sup 1}A{sub 1} surface and that of the minimum on the 2{sup 1}A{sub 1} surface nearly coincide. More accurate predictions of the energy differences also require CI expansions to at least sextuple excitations with respect to the valence space. For every wave function considered, the omission of the correlations of the 2s oxygen orbitals, which is a widely used approximation, was found to cause errors of about ±10 mh with respect to the energy differences.« less

Interactive effect of STAT6 and IL13 gene polymorphisms on eczema status: results from a longitudinal and a cross-sectional study

PubMed Central

2013-01-01

Background Eczema is a prevalent skin disease that is mainly characterized by systemic deviation of immune response and defective epidermal barrier. Th2 cytokines, such as IL-13 and transcription factor STAT6 are key elements in the inflammatory response that characterize allergic disorders, including eczema. Previous genetic association studies showed inconsistent results for the association of single nucleotide polymorphisms (SNPs) with eczema. Our aim was to investigate whether SNPs in IL13 and STAT6 genes, which share a biological pathway, have an interactive effect on eczema risk. Methods Data from two independent population-based studies were analyzed, namely the Isle of Wight birth cohort study (IOW; n = 1,456) and for the purpose of replication the Swansea PAPA (Poblogaeth Asthma Prifysgol Abertawe; n = 1,445) cross-sectional study. Log-binomial regressions were applied to (i) account for the interaction between IL13 (rs20541) and STAT6 (rs1059513) polymorphisms and (ii) estimate the combined effect, in terms of risk ratios (RRs), of both risk factors on the risk of eczema. Results Under a dominant genetic model, the interaction term [IL13 (rs20541) × STAT6 (rs1059513)] was statistically significant in both studies (IOW: adjusted Pinteraction = 0.046; PAPA: Pinteraction = 0.037). The assessment of the combined effect associated with having risk genotypes in both SNPs yielded a 1.52-fold increased risk of eczema in the IOW study (95% confidence interval (CI): 1.05 – 2.20; P = 0.028) and a 2.01-fold higher risk of eczema (95% CI: 1.29 – 3.12; P = 0.002) in the PAPA study population. Conclusions Our study adds to the current knowledge of genetic susceptibility by demonstrating for the first time an interactive effect between SNPs in IL13 (rs20541) and STAT6 (rs1059513) on the occurrence of eczema in two independent samples. Findings of this report further support the emerging evidence that points toward the existence of genetic effects that occur via complex networks involving gene-gene interactions (epistasis). PMID:23815671

Application of multicriteria decision making methods to compression ignition engine efficiency and gaseous, particulate, and greenhouse gas emissions.

PubMed

Surawski, Nicholas C; Miljevic, Branka; Bodisco, Timothy A; Brown, Richard J; Ristovski, Zoran D; Ayoko, Godwin A

2013-02-19

Compression ignition (CI) engine design is subject to many constraints, which present a multicriteria optimization problem that the engine researcher must solve. In particular, the modern CI engine must not only be efficient but must also deliver low gaseous, particulate, and life cycle greenhouse gas emissions so that its impact on urban air quality, human health, and global warming is minimized. Consequently, this study undertakes a multicriteria analysis, which seeks to identify alternative fuels, injection technologies, and combustion strategies that could potentially satisfy these CI engine design constraints. Three data sets are analyzed with the Preference Ranking Organization Method for Enrichment Evaluations and Geometrical Analysis for Interactive Aid (PROMETHEE-GAIA) algorithm to explore the impact of (1) an ethanol fumigation system, (2) alternative fuels (20% biodiesel and synthetic diesel) and alternative injection technologies (mechanical direct injection and common rail injection), and (3) various biodiesel fuels made from 3 feedstocks (i.e., soy, tallow, and canola) tested at several blend percentages (20-100%) on the resulting emissions and efficiency profile of the various test engines. The results show that moderate ethanol substitutions (~20% by energy) at moderate load, high percentage soy blends (60-100%), and alternative fuels (biodiesel and synthetic diesel) provide an efficiency and emissions profile that yields the most "preferred" solutions to this multicriteria engine design problem. Further research is, however, required to reduce reactive oxygen species (ROS) emissions with alternative fuels and to deliver technologies that do not significantly reduce the median diameter of particle emissions.

Utilization of smoking cessation informational, interactive, and online community resources as predictors of abstinence: cohort study.

PubMed

An, Lawrence C; Schillo, Barbara A; Saul, Jessie E; Wendling, Ann H; Klatt, Colleen M; Berg, Carla J; Ahulwalia, Jasjit S; Kavanaugh, Annette M; Christenson, Matthew; Luxenberg, Michael G

2008-12-20

The association between greater utilization of Web-assisted tobacco interventions and increased abstinence rates is well recognized. However, there is little information on how utilization of specific website features influences quitting. To determine the association between utilization of informational, interactive, and online community resources (eg. bulletin boards) and abstinence rates, with the broader objective to identify potential strategies for improving outcomes for Web-assisted tobacco interventions. In Spring 2004, a cohort of 607 quitplan.com users consented to participate in an evaluation of quitplan.com, a Minnesota branded version of QuitNet.com. We developed utilization measures for different site features: general information, interactive diagnostic tools and quit planning tools, online expert counseling, passive (ie, reading of bulletin boards) and active (ie, public posting) online community engagement, and one-to-one messaging with other virtual community members. Using bivariate, multivariate, and path analyses, we examined the relationship between utilization of specific site features and 30-day abstinence at 6 months. The most commonly used resources were the interactive quit planning tools (used by 77% of site users). Other informational resources (ie, quitting guides) were used more commonly (60% of users) than passive (38%) or active (24%) community features. Online community engagement through one-to-one messaging was low (11%) as was use of online counseling (5%). The 30-day abstinence rate among study participants at 6 months was 9.7% (95% Confidence Interval [CI] 7.3% - 12.1%). In the logistic regression model, neither the demographic data (eg, age, gender, education level, employment, or insurance status) nor the smoking-related data (eg, cigarettes per day, time to first morning cigarette, baseline readiness to quit) nor use of smoking cessation medications entered the model as significant predictors of abstinence. Individuals who used the interactive quit planning tools once, two to three times, or four or more times had an odds of abstinence of 0.65 (95% Confidence Interval [CI] 0.22 - 1.94), 1.87 (95% CI 0.77 - 4.56), and 2.35 (95% CI 1.0 - 5.58), respectively. The use of one-to-one messages (reference = none vs 1 or more) entered the final model as potential predictor for abstinence, though the significance of this measure was marginal (OR = 1.91, 95% CI 0.92 - 3.97, P = .083). In the path analysis, an apparent association between active online community engagement and abstinence was accounted for in large part by increased use of interactive quitting tools and one-to-one messaging. Use of interactive quitting tools, and perhaps one-to-one messaging with other members of the online community, was associated with increased abstinence rates among quitplan.com users. Designs that facilitate use of these features should be considered.

Polycyclic aromatic hydrocarbon (PAH)-DNA adducts and breast cancer: modification by gene promoter methylation in a population-based study.

PubMed

White, Alexandra J; Chen, Jia; McCullough, Lauren E; Xu, Xinran; Cho, Yoon Hee; Teitelbaum, Susan L; Neugut, Alfred I; Terry, Mary Beth; Hibshoosh, Hanina; Santella, Regina M; Gammon, Marilie D

2015-12-01

Polycyclic aromatic hydrocarbon (PAH)-DNA adducts have been associated with breast cancer incidence. Aberrant changes in DNA methylation may be an early event in carcinogenesis. However, possible relations between PAH-DNA adducts, methylation, and breast cancer are unknown. The objectives of this study were to (1) assess associations between PAH-DNA adducts, and breast cancer, stratified by DNA methylation markers and (2) examine interactions between adducts and DNA methylation in association with breast cancer and tumor subtype. In a population-based case-control study, promoter methylation of 13 breast cancer-related genes was measured in tumor tissue (n = 765-851 cases). Blood DNA from breast cancer cases (n = 873) and controls (n = 941) was used to assess PAH-DNA adducts and global methylation. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI); and the ratio of the OR (ROR) was used to assess heterogeneity. Women with detectable PAH-DNA adducts and methylated RARβ (ROR 2.69, 95% CI 1.02-7.12; p for interaction = 0.03) or APC (ROR 1.76, 95% CI 0.87-3.58; p for interaction = 0.09) genes were more likely to have hormone receptor-positive tumors than other subtypes. Interactions with other methylation markers were not apparent (p ≥ 0.10). The association between adducts and breast cancer did not vary by methylation status of the tumor nor did adducts associate with global methylation in the controls. Gene-specific methylation of RARβ, and perhaps APC, may interact with PAH-DNA adducts to increase risk of hormone receptor-positive breast cancer. There was little evidence that adducts were associated with or interacted with other methylation markers of interest.

Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial.

PubMed

LaCroix, Andrea Z; Chlebowski, Rowan T; Manson, JoAnn E; Aragaki, Aaron K; Johnson, Karen C; Martin, Lisa; Margolis, Karen L; Stefanick, Marcia L; Brzyski, Robert; Curb, J David; Howard, Barbara V; Lewis, Cora E; Wactawski-Wende, Jean

2011-04-06

The Women's Health Initiative Estrogen-Alone Trial was stopped early after a mean of 7.1 years of follow-up because of an increased risk of stroke and little likelihood of altering the balance of risk to benefit by the planned trial termination date. Postintervention health outcomes have not been reported. To examine health outcomes associated with randomization to treatment with conjugated equine estrogens (CEE) among women with prior hysterectomy after a mean of 10.7 years of follow-up through August 2009. The intervention phase was a double-blind, placebo-controlled, randomized clinical trial of 0.625 mg/d of CEE compared with placebo in 10,739 US postmenopausal women aged 50 to 79 years with prior hysterectomy. Follow-up continued after the planned trial completion date among 7645 surviving participants (78%) who provided written consent. The primary outcomes were coronary heart disease (CHD) and invasive breast cancer. A global index of risks and benefits included these primary outcomes plus stroke, pulmonary embolism, colorectal cancer, hip fracture, and death. The postintervention risk (annualized rate) for CHD among women assigned to CEE was 0.64% compared with 0.67% in the placebo group (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.75-1.25), 0.26% vs 0.34%, respectively, for breast cancer (HR, 0.75; 95% CI, 0.51-1.09), and 1.47% vs 1.48%, respectively, for total mortality (HR, 1.00; 95% CI, 0.84-1.18). The risk of stroke was no longer elevated during the postintervention follow-up period and was 0.36% among women receiving CEE compared with 0.41% in the placebo group (HR, 0.89; 95% CI, 0.64-1.24), the risk of deep vein thrombosis was lower at 0.17% vs 0.27%, respectively (HR, 0.63; 95% CI, 0.41-0.98), and the risk of hip fracture did not differ significantly and was 0.36% vs 0.28%, respectively (HR, 1.27; 95% CI, 0.88-1.82). Over the entire follow-up, lower breast cancer incidence in the CEE group persisted and was 0.27% compared with 0.35% in the placebo group (HR, 0.77; 95% CI, 0.62-0.95). Health outcomes were more favorable for younger compared with older women for CHD (P = .05 for interaction), total myocardial infarction (P = .007 for interaction), colorectal cancer (P = .04 for interaction), total mortality (P = .04 for interaction), and global index of chronic diseases (P = .009 for interaction). Among postmenopausal women with prior hysterectomy followed up for 10.7 years, CEE use for a median of 5.9 years was not associated with an increased or decreased risk of CHD, deep vein thrombosis, stroke, hip fracture, colorectal cancer, or total mortality. A decreased risk of breast cancer persisted. clinicaltrials.gov Identifier: NCT00000611.

Maternal Alcohol Consumption during Pregnancy and Early Age Leukemia Risk in Brazil.

PubMed

Ferreira, Jeniffer Dantas; Couto, Arnaldo Cézar; Emerenciano, Mariana; Pombo-de-Oliveira, Maria S; Koifman, Sergio

2015-01-01

Objectives. To investigate the association between the maternal alcohol consumption during pregnancy and early age leukemia (EAL) in offspring. Methods. Datasets were analyzed from a case-control study carried out in Brazil during 1999-2007. Data were obtained by maternal interviews using a standardized questionnaire. The present study included 675 children (193 acute lymphoid leukemia (ALL), 59 acute myeloid leukemia (AML), and 423 controls). Unconditional logistic regression was performed, and adjusted odds ratios (adj. OR) on the association between alcohol consumption and EAL were ascertained. Results. Alcohol consumption was reported by 43% of ALL and 39% of AML case mothers and 35.5% of controls'. Beer consumption before and during pregnancy was associated with ALL in crude analysis (OR = 1.54, 95% CI, 1.08-2.19), although in adjusted analysis no statistical significance was found. For weekly intake of ≤1 glass (adj. OR = 1.30, 95% CI, 0.71-2.36) and ≥1 glass/week (adj. OR = 1.47, 95% CI, 0.88-2.46) a potential dose-response was observed (P trend < 0.03). Conclusion. This study failed to support the hypothesis of an increased risk of EAL associated with maternal alcohol intake during pregnancy, neither with the interaction with tobacco nor with alcohol consumption.

Occupational activity and osteoarthritis of the knee.

PubMed Central

Cooper, C; McAlindon, T; Coggon, D; Egger, P; Dieppe, P

1994-01-01

OBJECTIVES--To test the hypothesis that specific occupational physical activities are risk factors for knee osteoarthritis (OA). METHODS--A population-based case-control study of knee osteoarthritis was carried out in which 109 men and women with painful, radiographically confirmed knee OA were compared with 218 age and sex matched controls who had not suffered knee pain and had normal radiographs. Information collected included a lifetime occupational history and details of specific workplace physical activities. RESULTS--After adjustment for obesity and Heberden's nodes, the risk of knee OA was significantly elevated in subjects whose main job entailed more than 30 minutes per day squatting (OR 6.9, 95% CI 1.8-26.4) or kneeling (OR 3.4, 95% CI 1.3-9.1), or climbing more than ten flights of stairs per day (OR 2.7, 95% CI 1.2-6.1). The increase in risk associated with kneeling or squatting appeared to be more marked in subjects whose jobs entailed heavy lifting, but the size of the study did not permit precise delineation of any such interaction. CONCLUSIONS--These data suggest that prolonged or repeated knee bending is a risk factor for knee OA, and that risk may be higher in jobs which entail both knee bending and mechanical loading. PMID:8129467

CYP1A1, GSTM1, GSTT1 and NQO1 polymorphisms and colorectal adenomas in Japanese men

PubMed Central

Hamachi, Tadamichi; Tajima, Osamu; Uezono, Kousaku; Tabata, Shinji; Abe, Hiroshi; Ohnaka, Keizo; Kono, Suminori

2013-01-01

AIM: To investigate the role of functional genetic polymorphisms of metabolic enzymes of tobacco carcinogens in the development of colorectal adenomas. METHODS: The study subjects were 455 patients with colorectal adenomas and 1052 controls with no polyps who underwent total colonoscopy in a preretirement health examination at two Self Defense Forces hospitals. The genetic polymorphisms studied were CYP1A1*2A (rs 4646903), CYP1A1*2C (rs 1048943), GSTM1 (null or non-null genotype), GSTT1 (null or non-null genotype) and NQO1 C609T (rs 1800566). Genotypes were determined by the polymerase chain reaction (PCR)-restriction fragment length polymorphism or PCR method using genomic DNA extracted from the buffy coat. Cigarette smoking and other lifestyle factors were ascertained by a self-administered questionnaire. The associations of the polymorphisms with colorectal adenomas were examined by means of OR and 95%CI, which were derived from logistic regression analysis. Statistical adjustment was made for smoking, alcohol use, body mass index and other factors. The gene-gene interaction and effect modification of smoking were evaluated by the likelihood ratio test. RESULTS: None of the five polymorphisms showed a significant association with colorectal adenomas, nor was the combination of GSTM1 and GSTT1. A borderline significant interaction was observed for the combination of CYP1A1*2C and NQO1 (P = 0.051). The OR associated with CYP1A1*2C was significantly lower than unity among individuals with the NQO1 609CC genotype. The adjusted OR for the combination of the CYP1A1*2C allele and NQO1 609CC genotype was 0.61 (95%CI: 0.42-0.91). Although the interaction was not statistically significant (P = 0.24), the OR for individuals carrying the CYP1A1*2C allele and GSTT1 null genotype decreased significantly compared with those who had neither CYP1A1*2C allele nor GSTT1 null genotype (adjusted OR: 0.69, 95%CI: 0.49-0.97). Smoking did not modify the associations of the individual polymorphisms with colorectal adenomas. There was no measurable effect modification of smoking even regarding the combination of the genetic polymorphisms of the phase I and phase II enzymes. CONCLUSION: Combination of the CYP1A1*2C and NQO1 609CC genotypes was associated with a decreased risk of colorectal adenomas regardless of smoking status. PMID:23840148

Lack of clinically relevant drug-drug interaction between empagliflozin, a sodium glucose cotransporter 2 inhibitor, and verapamil, ramipril, or digoxin in healthy volunteers.

PubMed

Macha, Sreeraj; Sennewald, Regina; Rose, Peter; Schoene, Katja; Pinnetti, Sabine; Woerle, Hans J; Broedl, Uli C

2013-03-01

Empagliflozin is a sodium glucose cotransporter 2 inhibitor in clinical development as a treatment for type 2 diabetes mellitus. The goal of this study was to investigate potential drug-drug interactions between empagliflozin and verapamil, ramipril, and digoxin in healthy volunteers. The potential drug-drug interactions were evaluated in 3 separate trials. In the first study, 16 subjects were randomized to receive single-dose empagliflozin 25 mg alone or single-dose empagliflozin 25 mg with single-dose verapamil 120 mg. In the second study, 23 subjects were randomized to receive empagliflozin 25 mg once daily (QD) for 5 days, ramipril (2.5 mg on day 1 then 5 mg QD on days 2-5) for 5 days or empagliflozin 25 mg with ramipril (2.5 mg on day 1 then 5 mg QD on days 2-5) for 5 days. In the third study, 20 subjects were randomized to receive single-dose digoxin 0.5 mg alone or empagliflozin 25 mg QD for 8 days with single-dose digoxin 0.5 mg on day 5. Exposure of empagliflozin was not affected by coadministration with verapamil (AUC0-∞: geometric mean ratio [GMR], 102.95%; 90% CI, 98.87-107.20; Cmax: GMR, 92.39%; 90% CI, 85.38-99.97) or ramipril (AUC over a uniform dosing interval τ at steady state [AUCτ,ss]: GMR, 96.55%; 90% CI, 93.05-100.18; Cmax at steady state [Cmax,ss]: GMR, 104.47%; 90% CI 97.65-111.77). Empagliflozin had no clinically relevant effect on exposure of ramipril (AUCτ,ss: GMR, 108.14%; 90% CI 100.51-116.35; Cmax,ss: GMR, 103.61%; 90% CI, 89.73-119.64) or its active metabolite ramiprilat (AUCτ,ss: GMR, 98.67%; 90% CI, 96.00-101.42; Cmax,ss: GMR, 98.29%; 90% CI, 92.67-104.25). Coadministration of empagliflozin had no clinically meaningful effect on digoxin AUC0-∞ (GMR, 106.11%; 90% CI, 96.71-116.41); however, a slight increase in Cmax was observed that was not considered clinically relevant (GMR, 113.94%; 90% CI, 99.33-130.70). All treatments were well tolerated. There were no serious adverse events or adverse events leading to discontinuation in any of the studies. No dose adjustment of empagliflozin is required when coadministered with ramipril or verapamil, and no dose adjustment of digoxin or ramipril is required when coadministered with empagliflozin. ClinicalTrials.gov identifiers: NCT01306175 (digoxin), NCT01276301 (verapamil), and NCT01284621 (ramipril). Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

Tuberculosis detection and the challenges of integrated care in rural China: A cross-sectional standardized patient study.

PubMed

Sylvia, Sean; Xue, Hao; Zhou, Chengchao; Shi, Yaojiang; Yi, Hongmei; Zhou, Huan; Rozelle, Scott; Pai, Madhukar; Das, Jishnu

2017-10-01

Despite recent reductions in prevalence, China still faces a substantial tuberculosis (TB) burden, with future progress dependent on the ability of rural providers to appropriately detect and refer TB patients for further care. This study (a) provides a baseline assessment of the ability of rural providers to correctly manage presumptive TB cases; (b) measures the gap between provider knowledge and practice and; (c) evaluates how ongoing reforms of China's health system-characterized by a movement toward "integrated care" and promotion of initial contact with grassroots providers-will affect the care of TB patients. Unannounced standardized patients (SPs) presenting with classic pulmonary TB symptoms were deployed in 3 provinces of China in July 2015. The SPs successfully completed 274 interactions across all 3 tiers of China's rural health system, interacting with providers in 46 village clinics, 207 township health centers, and 21 county hospitals. Interactions between providers and standardized patients were assessed against international and national standards of TB care. Using a lenient definition of correct management as at least a referral, chest X-ray or sputum test, 41% (111 of 274) SPs were correctly managed. Although there were no cases of empirical anti-TB treatment, antibiotics unrelated to the treatment of TB were prescribed in 168 of 274 interactions or 61.3% (95% CI: 55%-67%). Correct management proportions significantly higher at county hospitals compared to township health centers (OR 0.06, 95% CI: 0.01-0.25, p < 0.001) and village clinics (OR 0.02, 95% CI: 0.0-0.17, p < 0.001). Correct management in tests of knowledge administered to the same 274 physicians for the same case was 45 percentage points (95% CI: 37%-53%) higher with 24 percentage points (95% CI: -33% to -15%) fewer antibiotic prescriptions. Relative to the current system, where patients can choose to bypass any level of care, simulations suggest that a system of managed referral with gatekeeping at the level of village clinics would reduce proportions of correct management from 41% to 16%, while gatekeeping at the level of the township hospital would retain correct management close to current levels at 37%. The main limitations of the study are 2-fold. First, we evaluate the management of a one-time new patient presenting with presumptive TB, which may not reflect how providers manage repeat patients or more complicated TB presentations. Second, simulations under alternate policies require behavioral and statistical assumptions that should be addressed in future applications of this method. There were significant quality deficits among village clinics and township health centers in the management of a classic case of presumptive TB, with higher proportions of correct case management in county hospitals. Poor clinical performance does not arise only from a lack of knowledge, a phenomenon known as the "know-do" gap. Given significant deficits in quality of care, reforms encouraging first contact with lower tiers of the health system can improve efficiency only with concomitant improvements in appropriate management of presumptive TB patients in village clinics and township health centers.

Do mother's education and foreign born status interact to influence birth outcomes? Clarifying the epidemiological paradox and the healthy migrant effect.

PubMed

Auger, N; Luo, Z-C; Platt, R W; Daniel, M

2008-05-01

The unresolved "epidemiological paradox" concerns the association between low socioeconomic status and unexpectedly favourable birth outcomes in foreign born mothers. The "healthy migrant" effect concerns the association between foreign born status per se and birth outcomes. The epidemiological paradox and healthy migrant effect were analysed for newborns in a favourable sociopolitical environment. 98,330 live births to mothers in Montreal, Canada from 1997 to 2001 were analysed. Mothers were categorised as foreign born versus Canadian born. Outcomes were: small for gestational age (SGA) birth; low birth weight (LBW) and preterm birth (PTB). Multilevel logistic regression was used to examine the interaction between maternal education and foreign born status, adjusting for covariates. Not having a high school diploma was associated with LBW in Canadian (odds ratio (OR) 3.20; 95% CI 2.61 to 3.91) but not foreign born (OR 1.14; 95% CI 0.99 to 2.10) mothers and was more strongly associated with SGA birth in Canadian (OR 2.03; 95% CI 1.84 to 2.22) than in foreign born (OR 1.26; 95% CI 1.07 to 1.49) mothers. Foreign born status was associated with SGA birth (OR 1.37; 95% CI 1.28 to 1.47), LBW (OR 1.51; 95% CI 1.27 to 1.79) and PTB (OR 1.12; 95% CI 1.03 to 1.22) in university-educated mothers only. The epidemiological paradox associated with low educational attainment was present for SGA birth and LBW but not PTB. Foreign born status was associated with adverse birth outcomes in university-educated mothers, the opposite of the healthy migrant effect.

Bacterial expression of the phosphodiester-binding site of the cation-independent mannose 6-phosphate receptor for crystallographic and NMR studies

PubMed Central

Olson, Linda J.; Jensen, Davin R.; Volkman, Brian F.; Kim, Jung-Ja P.; Peterson, Francis C.; Gundry, Rebekah L.; Dahms, Nancy M.

2015-01-01

The cation-independent mannose 6-phosphate receptor (CI-MPR) is a multifunctional protein that interacts with diverse ligands and plays central roles in autophagy, development, and tumor suppression. By delivering newly synthesized phosphomannosyl-containing acid hydrolases from the Golgi to endosomal compartments, CI-MPR is an essential component in the generation of lysosomes that are critical for the maintenance of cellular homeostasis. The ability of CI-MPR to interact with ~60 different acid hydrolases is facilitated by its large extracellular region, with four out of its 15 domains binding phosphomannosyl residues. Although the glycan specificity of CI-MPR has been elucidated, the molecular basis of carbohydrate binding has not been determined for two out of these four carbohydrate recognition domains (CRD). Here we report expression of CI-MPR’s CRD located in domain 5 that preferentially binds phosphodiester-containing glycans. Domain 5 of CI-MPR was expressed in Escherichia coli BL21 (DE3) cells as a fusion protein containing an N-terminal histidine tag and the small ubiquitin-like modifier (SUMO) protein. The His6-SUMO-CRD construct was recovered from inclusion bodies, refolded in buffer to facilitate disulfide bond formation, and subjected to Ni-NTA affinity chromatography and size exclusion chromatography. Surface plasmon resonance analyses demonstrated that the purified protein was active and bound phosphorylated glycans. Characterization by NMR spectroscopy revealed high quality 1H–15N HSQC spectra. Additionally, crystallization conditions were identified and a crystallographic data set of the CRD was collected to 1.8 Å resolution. Together, these studies demonstrate the feasibility of producing CI-MPR’s CRD suitable for three-dimensional structure determination by NMR spectroscopic and X-ray crystallographic approaches. PMID:25863146

Severity of Vision Loss Interacts With Word-Specific Features to Impact Out-Loud Reading in Glaucoma

PubMed Central

Mathews, Priya M.; Rubin, Gary S.; McCloskey, Michael; Salek, Sherveen; Ramulu, Pradeep Y.

2015-01-01

Purpose. To assess the impact of glaucoma-related vision loss on measures of out-loud reading, including time to say individual words, interval time between consecutive words, lexical errors, skipped words, and repetitions. Methods. Glaucoma subjects (n = 63) with bilateral visual field loss and glaucoma suspect controls (n = 57) were recorded while reading a standardized passage out loud. A masked evaluator determined the start and end of each recorded word and identified reading errors. Results. Glaucoma subjects demonstrated longer durations to recite individual words (265 vs. 243 ms, P < 0.001), longer intervals between words (154 vs. 124 ms, P < 0.001), and longer word/post-word interval complexes (the time spanned by the word and the interval following the word; 419 vs. 367 ms, P < 0.001) than controls. In multivariable analyses, each 0.1 decrement in log contrast sensitivity (logCS) was associated with a 15.0 ms longer word/post-interval complex (95% confidence interval [CI] = 9.6–20.4; P < 0.001). Contrast sensitivity was found to significantly interact with word length, word frequency, and word location at the end of a line with regards to word/post-word interval complex duration (P < 0.05 for all). Glaucoma severity was also associated with more lexical errors (Odds ratio = 1.20 for every 0.1 logCS decrement; 95% CI = 1.02–1.39, P < 0.05), but not with more skipped or repeated words. Conclusions. Glaucoma patients with greater vision loss make more lexical errors, are slower in reciting longer and less frequently used words, and more slowly transition to new lines of text. These problem areas may require special attention when designing methods to rehabilitate reading in patients with glaucoma. PMID:25737150

Identification of immune correlates of protection in Shigella infection by application of machine learning.

PubMed

Arevalillo, Jorge M; Sztein, Marcelo B; Kotloff, Karen L; Levine, Myron M; Simon, Jakub K

2017-10-01

Immunologic correlates of protection are important in vaccine development because they give insight into mechanisms of protection, assist in the identification of promising vaccine candidates, and serve as endpoints in bridging clinical vaccine studies. Our goal is the development of a methodology to identify immunologic correlates of protection using the Shigella challenge as a model. The proposed methodology utilizes the Random Forests (RF) machine learning algorithm as well as Classification and Regression Trees (CART) to detect immune markers that predict protection, identify interactions between variables, and define optimal cutoffs. Logistic regression modeling is applied to estimate the probability of protection and the confidence interval (CI) for such a probability is computed by bootstrapping the logistic regression models. The results demonstrate that the combination of Classification and Regression Trees and Random Forests complements the standard logistic regression and uncovers subtle immune interactions. Specific levels of immunoglobulin IgG antibody in blood on the day of challenge predicted protection in 75% (95% CI 67-86). Of those subjects that did not have blood IgG at or above a defined threshold, 100% were protected if they had IgA antibody secreting cells above a defined threshold. Comparison with the results obtained by applying only logistic regression modeling with standard Akaike Information Criterion for model selection shows the usefulness of the proposed method. Given the complexity of the immune system, the use of machine learning methods may enhance traditional statistical approaches. When applied together, they offer a novel way to quantify important immune correlates of protection that may help the development of vaccines. Copyright © 2017 Elsevier Inc. All rights reserved.

Coefficient Alpha Bootstrap Confidence Interval under Nonnormality

ERIC Educational Resources Information Center

Padilla, Miguel A.; Divers, Jasmin; Newton, Matthew

2012-01-01

Three different bootstrap methods for estimating confidence intervals (CIs) for coefficient alpha were investigated. In addition, the bootstrap methods were compared with the most promising coefficient alpha CI estimation methods reported in the literature. The CI methods were assessed through a Monte Carlo simulation utilizing conditions…

Contribution of genome-environment interaction to pre-eclampsia in a Havana Maternity Hospital.

PubMed

Lardoeyt, Roberto; Vargas, Gerardo; Lumpuy, Jairo; García, Ramón; Torres, Yuselis

2013-07-01

Pre-eclampsia is a major cause of morbidity and mortality during pregnancy worldwide and is among the leading causes of maternal mortality in Cuba. It is a complex, multifactoral disease, in which interaction of genetic and environmental factors should not be overlooked if the goal is proper risk assessment to support personalized preventive genetic counseling and more effective prenatal care to prevent pregnancy complications. Determine the contribution to pre-eclampsia of interaction between a predisposing genome and adverse environmental factors in pregnant women in a Havana maternity hospital. This was the exploratory phase of a hospital-based case-control study, using January 2007-December 2009 patient records from the Eusebio Hernández University Hospital, a provincial maternity hospital in Havana. Eighty pregnant women diagnosed with pre-eclampsia and 160 controls were studied. The main variables were age, parity, nutritional status (measured by BMI), alcohol use, tobacco use, and history of pre-eclampsia in relatives of the pregnant woman (proband) or of her partner. Pearson chi square and Fisher exact test were used to assess statistical significance of associations between variables and odds ratio as a measure of association strength. Familial aggregation was studied and a case-control design used to assess gene-environment interaction, using multiplicative and additive models. Among the environmental risk factors studied, alcohol showed the strongest effect on pre-eclampsia risk (OR 3.87, 95% CI 1.64-9.13). Familial pre-eclampsia clustering was observed; risk was increased for both first-degree (OR 2.43, 95% CI 1.62-3.73) and second-degree (OR 1.89, 95% CI 1.34-2.68) relatives as well as for husband's relatives (OR 2.32, 95% CI 1.40-3.86). There was evidence of interaction between alcohol consumption and family history. Familial aggregation of the disorder was demonstrated, the first Cuban epidemiological evidence of genetic and enviromental contributions to pre-eclampsia risk. Familial clustering among the husband's relatives demonstrates the fetal genome's importance in genesis of pre-eclampsia. The interaction of environmental risk factors with genetic ones produces increased pre-eclampsia risk, compared to expectations based on independent action of these variables. KEYWORDS Pre-eclampsia, toxemia of pregnancy, pregnancy outcome, environment, genetics, genome-environment interaction, genetic epidemiology, Cuba.

[Interaction between quality and duration of sleep on the prevalence of type 2 diabetes].

PubMed

Zhang, Pan; Lou, Peian; Chang, Guiqiu; Zhang, Lei; Chen, Peipei; Li, Ting; Qiao, Cheng; Dong, Zongmei

2014-09-01

To explore the effects related to quality and duration of sleep and their interactions on the prevalence of type-2 diabetes (T2DM). 9 622 people aged 18 years and over were recruited for our cross-sectional study during March 2013 to May 2013. Unconditional logistic regression was used to analyze the relationship between quality and duration of sleep on T2DM. Bootstrap was used to calculate the relative excess risk of interaction (RERI), the attributable proportion (AP) of interaction and the synergy index (SI). 95% confidence intervals (CI) of RERI, AP and SI were estimated. Concerning the comparison between cases and controls on both individual and total scores, other scores were all significantly different (P < 0.01), except for two items (time for falling asleep and drugs for hypnosis). The prevalence of T2DM in volunteers with poor sleeping quality was higher than that in volunteers with good sleeping quality (P < 0.01). Individuals with sleep duration <6 hours had a higher prevalence of T2DM, when compared with individuals with sleep duration of 6-8 hours (P < 0.01). After adjusting for age, gender, level of education, occupation, family history of diabetes, status on cigarette smoking, alcohol intake, physical activities and body mass index (BMI), the prevalence of T2DM appeared the highest in those with poor sleeping quality and short duration (OR = 4.78, 95% CI:3.32-6.99; P < 0.01), when compared with those who had good sleep quality and 6-8 h sleep duration. The risk of T2DM still increased in people who had poor sleep or long duration (OR = 1.92, 95% CI:1.18-3.31; P < 0.01). Values of RERI, AP and SI (with 95% CI) were 2.33 (1.23-8.79), 0.67(0.21-0.83) and 6.87 (2.33-10.75), respectively, for the interaction between poor sleep quality and short sleep duration, while 0.33 (-0.12-1.13), 0.17 (-0.03-0.51), 1.56 (0.76-2.74) for the interaction between good sleep quality and long sleep duration. Our results suggested that there were additive interactions between poor quality and shorter duration of sleep.

Type D personality is associated with social anxiety in the general population.

PubMed

Kupper, Nina; Denollet, Johan

2014-06-01

Research on the emotional processes associated with Type D personality is important for its further conceptualization. We examined the associations of Type D personality with social and general anxiety symptoms in a large community sample. The aim of the current study was to disentangle the associations of Type D personality and its components with social anxiety and general anxiety in a large sample from the general population. A random sample of 2,475 adults from the general population filled out questionnaires to assess Type D personality (DS-14), social anxiety (SIAS(10), SPS(11), BFNE-II), and general anxiety (HADS-A, GAD-7). Type D individuals were characterized by increased levels of both social and general anxiety. The social inhibition (SI) component of Type D personality was most strongly associated with social interaction anxiety (r = .63), while negative affectivity (NA) was strongly associated with general anxiety (GAD-7: r = .70; HADS-A: r = .66). Within social anxiety, SI was more strongly associated with facets of social interaction anxiety than with social phobia. Multiple regression analysis showed that the synergistic interaction of NA and SI was a predictor of social anxiety (SIAS(10): β = .32, p < .0005; SPS(11): β = .27, p < .0005; BFNE-II: β = .11, p = .007) independent of demographics and the scores on the individual Type D components. This interaction was not a significant predictor of general anxiety. Logistic regression using the dichotomous Type D classification demonstrated a 9.1-fold (95%CI, 7.0-11.8) increased odds of a score in the highest quartile of social interaction anxiety and a 7.6-fold (95%CI, 5.8-9.8) increased odds of high social phobia. Odds ratios for clinically relevant levels of general anxiety were 8.3 (95%CI, 5.5-12.5) for GAD-7 and 6.5 (95%CI, 3.4-12.6) for HADS-A. In the general population, Type D individuals were characterized by both social and general anxiety. The SI component of Type D is strongly associated with social interaction anxiety and the synergistic interaction of NA and SI was associated with high social anxiety, above and beyond the main NA and SI effects.

Association of methylenetetrahydrofolate reductase gene-gene interaction and haplotype with susceptibility to acute lymphoblastic leukemia in Chinese children.

PubMed

Xia, Xiaojun; Duan, Yun; Cui, Jie; Jiang, Junfeng; Lin, Li; Peng, Xiaojuan; Wang, YuHong; Guo, Bingtao; Liu, Shouhai; Lei, Xudong

2017-08-01

The aim of this study was to investigate the association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and additional gene-gene interaction with acute lymphoblastic leukemia (ALL) risk. Logistic regression was performed to investigate the association between two single nucleotide polymorphisms (SNPs) within MTHFR gene and ALL risk and additional gene-gene interaction between rs1801133 and rs1801131. The minor allele of rs1801133 and rs1801131 is associated with decreased ALL risk, OR (95% CI) were 0.61 (0.38-0.89), and 0.68 (0.50-0.96), respectively. We also found a significantly interaction between the two SNPs, participants with rs1801133 - CT or TT and rs1801131 - AC or CC genotype have the lowest ALL risk, compared with participants with rs1801133 - CC and rs1801131 - AA genotype, OR (95% CI) was 0.32 (0.12-0.63). We did not find any haplotype between the rs1801133 and rs1801131 associated with ALL risk. rs1801133 and rs1801131 within MTHFR gene and their interaction were both associated with ALL risk in Chinese children.

Depressive Symptoms, Psychiatric Medication Use, and Risk of Type 2 Diabetes: Results from the Health and Retirement Study

PubMed Central

Ratliff, Scott; Mezuk, Briana

2015-01-01

Objective This prospective study investigates the relationships between depressive symptoms, psychiatric medication use, and their interaction on risk of developing type 2 diabetes. Method Data come from the 1998 – 2010 waves of the Health and Retirement Study, a U.S. nationally-representative cohort of adults aged 51 and older. Analysis is restricted to participants <65 who did not have diabetes in 1998 (N=8,704). Depressive symptoms were assessed using the 8-item Center for Epidemiologic Studies–Depression scale. Risk of diabetes over the 12-year follow-up period was assessed using Cox proportional hazard models with time-varying covariates. Results After adjusting for covariates, both depressive symptoms (hazard ratio [HR]: 1.06, 95% Confidence Interval [CI]: 1.02 – 1.09) and psychiatric medication use (HR: 1.57, 95% CI: 1.25 – 1.96) were associated with development of diabetes. The interaction between depressive symptoms and medication use was significant (beta = −0.240, p = .049), indicating that the association between elevated depressive symptoms and diabetes was higher among respondents not taking medications. The associations between depressive symptoms and medication use were also attenuated by increasing BMI. Conclusion Findings highlight the complex relationship between depressive symptoms and psychiatric medications on diabetes risk, and the need for a nuanced understanding of these factors. PMID:26094130

Polymorphisms of the TLR4 gene and risk of gastric cancer.

PubMed

Huang, Lina; Yuan, Kexin; Liu, Jingjing; Ren, Xiyun; Dong, Xiaoqun; Tian, Wenjing; Jia, Yunhe

2014-03-01

Toll-like receptor 4 (TLR4) is an important lipo-polysaccharide (LPS) receptor in gastric epithelial cell signaling transduction and plays critical roles in the development and progression of gastric cancer (GC). We investigated the effects of TLR4 gene polymorphisms and gene-environmental interactions on the risk of GC in Northeastern China. We genotyped two single-nucleotide polymorphisms (SNPs) in TLR4 (rs10116253 and rs1927911) in 217 GC patients and 294 cancer-free controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence intervals (CIs) were estimated by unconditional logistic-regression models. Individuals carrying CC genotype of rs10116253 and TT genotype of rs1927911 had a significantly decreased risk of GC (adjusted OR=0.33, 95% CI 0.18-0.60, P<0.001 and adjusted OR=0.37, 95% CI 0.21-0.67, P=0.001 respectively), compared with TT genotype of rs10116253 and CC genotype of rs1927911. In addition, the SNP effects were additive to the effects of some known environmental factors without any interaction between them in the susceptibility to GC. Our data suggested that TLR4 gene polymorphisms may be associated with a decreased risk of GC in Chinese population. And these SNPs and their combined effects with environmental factors may be associated with the risk of GC. Copyright © 2013 Elsevier B.V. All rights reserved.

[Joint effect of birth weight and obesity measures on abnormal glucose metabolism at adulthood].

PubMed

Xi, Bo; Cheng, Hong; Chen, Fangfang; Zhao, Xiaoyuan; Mi, Jie

2016-01-01

To investigate the joint effect of birth weight and each of obesity measures (body mass index (BMI) and waist circumference (WC)) on abnormal glucose metabolism (including diabetes) at adulthood. Using the historical cohort study design and the convenience sampling method, 1 921 infants who were born in Beijing Union Medical College Hospital from June 1948 to December 1954 were selected to do the follow-up in 1995 and 2001 respectively. Through Beijing Household Registration and Management System, they were invited to participate in this study. A total of 972 subjects (627 were followed up in 1995 and 345 were followed up in 2001) with complete information on genders, age, birth weight, family history of diabetes, BMI, WC, fasting plasma glucose (FPG) and 2-hour plasma glucose (2 h PG) met the study inclusion criteria at the follow-up visits. In the data analysis, they were divided into low, normal, and high birth weight, respectively. The ANOVA and Chi-squared tests were used to compare the differences in their characteristics by birth weight group. In addition, multiple binary Logistic regression model was used to investigate the single effect of birth weight, BMI, and waist circumference on abnormal glucose metabolism at adulthood. Stratification analysis was used to investigate the joint effect of birth weight and each of obesity measures (BMI and WC) on abnormal glucose metabolism. There were 972 subjects (males: 50.7%, mean age: (46.0±2.2) years) included in the final data analysis. The 2 h PG in low birth weight group was (7.6±3.2) mmol/L , which was higher than that in normal birth weight group (6.9±2.1) mmol/L and high birth weight group (6.4±1.3) mmol/L (F=3.88, P=0.021). After adjustment for genders, age, body length, gestation age, family history of diabetes, physical activity, smoking and alcohol consumption, and duration of follow-up, subjects with overweight and obesity at adulthood had 2.73 (95% confidence interval (CI) =2.06- 3.62) times risk to develop abnormal glucose metabolism when compared with norm weight ones. Likewise, subjects with central obesity were more likely to develop abnormal glucose metabolism than ones with normal waist (odds ratio (OR)=3.35, 95%CI=2.49-4.50). In addition, compared to subjects with normal birth weight and normal BMI at adulthood, ones with normal birth weight and overweight (including obesity) at adulthood were more likely to have abnormal glucose metabolism (OR= 2.60, 95%CI=1.94-3.49); subjects with low birth weight and overweight (including obesity) at adulthood had the highest risk for abnormal glucose metabolism (OR=4.70, 95% CI=1.84- 11.99). The attributable proportion of interaction between low birth weight and overweight (including obesity) at adulthood was 48.5%. In addition, compared to subjects with normal birth weight and normal WC at adulthood, one with normal birth weight and central obesity at adulthood were more likely to have abnormal glucose metabolism (OR=3.18, 95% CI=2.33- 4.32); subjects with low birth weight and central obesity at adulthood had the highest risk for abnormal glucose metabolism (OR=4.78, 95% CI=2.01- 11.38); subjects with high birth weight and central at adulthood also had high risk for abnormal glucose metabolism (OR=4.35, 95%CI=1.38- 13.65). We found that the attributable proportion of interaction between low birth weight and central obesity at adulthood was 38.5% , and was 28.3% for interaction between high weight and central obesity. There was strong interaction effect between birth weight and overweight (especially central obesity) at adulthood on abnormal glucose metabolism at adulthood. Effective measures should be adopted to prevent and control adult obesity in order to offset the adverse effect of birth weight on long-term health risk.

Clinical importance of the drug interaction between statins and CYP3A4 inhibitors: a retrospective cohort study in The Health Improvement Network

PubMed Central

Rowan, Christopher G.; Brunelli, Steven M.; Munson, Jeffrey; Flory, James; Reese, Peter P.; Hennessy, Sean; Lewis, James; Mines, Daniel; Barrett, Jeffrey S.; Bilker, Warren; Strom, Brian L.

2014-01-01

Objective To compare the relative hazard of muscle toxicity, renal dysfunction, and hepatic dysfunction associated with the drug interaction between statins and concomitant medications that inhibit the CYP3A4 isoenzyme. Background Although statins provide important clinical benefits related to mitigating the risk of cardiovascular events, this class of medications also has the potential for severe adverse reactions. The risk for adverse events may be potentiated by concomitant use of medications that interfere with statin metabolism. Methods Data from The Health Improvement Network (THIN) from 1990 to 2008 were used to conduct a retrospective cohort study. Cohorts were created to evaluate each outcome (muscle toxicity, renal dysfunction, and hepatic dysfunction) independently. Each cohort included new statin initiators and compared the relative hazard of the outcome. The interaction ratio (I*R) was the primary contrast of interest. The I*R represents the relative effect of each statin type (statin 3A4 substrate vs. statin non-3A4 substrate) with a CYP3A4 inhibitor, independent of the effect of the statin type without a CYP3A4 inhibitor. We adjusted for confounding variables using the multinomial propensity score. Results The median follow-up time per cohort was 1.5 years. There were 7889 muscle toxicity events among 362 809 patients and 792 665 person-years. The adjusted muscle toxicity I*R was 1.22 (95% confidence interval [CI] = 0.90–1.66). There were 1449 renal dysfunction events among 272,099 patients and 574 584 person-years. The adjusted renal dysfunction I*R was 0.91 (95%CI = 0.58–1.44). There were 1434 hepatic dysfunction events among 367 612 patients and 815 945 person-years. The adjusted hepatic dysfunction I*R was 0.78 (95%CI = 0.45–1.31). Conclusions Overall, this study found no difference in the relative hazard of muscle toxicity, renal dysfunction, or hepatic dysfunction for patients prescribed a statin 3A4 substrate versus a statin non-3A4 substrate with CYP3A4 inhibitor concomitancy. PMID:22422642

Difficulties with Emotion Regulation and Psychopathology Interact to Predict Early Smoking Cessation Lapse

PubMed Central

Zvolensky, Michael J.; Schmidt, Norman B.

2015-01-01

There is little knowledge about how emotion regulation difficulties interplay with psychopathology in terms of smoking cessation. Participants (n = 250; 53.2 % female, Mage = 39.5, SD = 13.85) were community-recruited daily smokers (≥8 cigarettes per day) who self-reported motivation to quit smoking; 38.8 % of the sample met criteria for a current (past 12-month) psychological disorder. Emotion regulation deficits were assessed pre-quit using the Difficulties with Emotion Regulation Scale (DERS; Gratz and Roemer in J Psychopathol Behav Assess 26(1):41–54, 2004) and smoking behavior in the 28 days post-quit was assessed using the Timeline Follow-Back (TLFB; Sobell and Sobell in Measuring alcohol consumption: psychosocial and biochemical methods. Humana Press, Totowa, 1992). A Cox proportional-hazard regression analysis was used to model the effects of past-year psychopathology, DERS (total score), and their interaction, in terms of time to lapse post-quit day. After adjusting for the effects of gender, age, pre-quit level of nicotine dependence, and treatment condition, the model revealed a non-significant effect of past-year psychopathology (OR = 1.14, CI95 % = 0.82–1.61) and difficulties with emotion regulation (OR = 1.01, CI95 % = 1.00–1.01) on likelihood of lapse rate. However, the interactive effect of psychopathology status and difficulties with emotion regulation was significant (OR = 0.98, CI95 % = 0.97–0.99). Specifically, there was a significant conditional effect of psychopathology status on lapse rate likelihood at low, but not high, levels of emotion regulation difficulties. Plots of the cumulative survival functions indicated that for smokers without a past-year psychological disorder, those with lower DERS scores relative to elevated DERS scores had significantly lower likelihood of early smoking lapse, whereas for smokers with past-year psychopathology, DERS scores did not differentially impact lapse rate likelihood. Smokers with emotion regulation difficulties may have challenges quitting, and not having such difficulties, especially without psychopathology, decreases the potential likelihood of early lapse. PMID:27239081

Instructional methods and cognitive and learning styles in web-based learning: report of two randomised trials.

PubMed

Cook, David A; Gelula, Mark H; Dupras, Denise M; Schwartz, Alan

2007-09-01

Adapting web-based (WB) instruction to learners' individual differences may enhance learning. Objectives This study aimed to investigate aptitude-treatment interactions between learning and cognitive styles and WB instructional methods. We carried out a factorial, randomised, controlled, crossover, post-test-only trial involving 89 internal medicine residents, family practice residents and medical students at 2 US medical schools. Parallel versions of a WB course in complementary medicine used either active or reflective questions and different end-of-module review activities ('create and study a summary table' or 'study an instructor-created table'). Participants were matched or mismatched to question type based on active or reflective learning style. Participants used each review activity for 1 course module (crossover design). Outcome measurements included the Index of Learning Styles, the Cognitive Styles Analysis test, knowledge post-test, course rating and preference. Post-test scores were similar for matched (mean +/- standard error of the mean 77.4 +/- 1.7) and mismatched (76.9 +/- 1.7) learners (95% confidence interval [CI] for difference - 4.3 to 5.2l, P = 0.84), as were course ratings (P = 0.16). Post-test scores did not differ between active-type questions (77.1 +/- 2.1) and reflective-type questions (77.2 +/- 1.4; P = 0.97). Post-test scores correlated with course ratings (r = 0.45). There was no difference in post-test subscores for modules completed using the 'construct table' format (78.1 +/- 1.4) or the 'table provided' format (76.1 +/- 1.4; CI - 1.1 to 5.0, P = 0.21), and wholist and analytic styles had no interaction (P = 0.75) or main effect (P = 0.18). There was no association between activity preference and wholist or analytic scores (P = 0.37). Cognitive and learning styles had no apparent influence on learning outcomes. There were no differences in outcome between these instructional methods.

A structural model of polyglutamine determined from a host-guest method combining experiments and landscape theory.

PubMed

Finke, John M; Cheung, Margaret S; Onuchic, José N

2004-09-01

Modeling the structure of natively disordered peptides has proved difficult due to the lack of structural information on these peptides. In this work, we use a novel application of the host-guest method, combining folding theory with experiments, to model the structure of natively disordered polyglutamine peptides. Initially, a minimalist molecular model (C(alpha)C(beta)) of CI2 is developed with a structurally based potential and captures many of the folding properties of CI2 determined from experiments. Next, polyglutamine "guest" inserts of increasing length are introduced into the CI2 "host" model and the polyglutamine is modeled to match the resultant change in CI2 thermodynamic stability between simulations and experiments. The polyglutamine model that best mimics the experimental changes in CI2 thermodynamic stability has 1), a beta-strand dihedral preference and 2), an attractive energy between polyglutamine atoms 0.75-times the attractive energy between the CI2 host Go-contacts. When free-energy differences in the CI2 host-guest system are correctly modeled at varying lengths of polyglutamine guest inserts, the kinetic folding rates and structural perturbation of these CI2 insert mutants are also correctly captured in simulations without any additional parameter adjustment. In agreement with experiments, the residues showing structural perturbation are located in the immediate vicinity of the loop insert. The simulated polyglutamine loop insert predominantly adopts extended random coil conformations, a structural model consistent with low resolution experimental methods. The agreement between simulation and experimental CI2 folding rates, CI2 structural perturbation, and polyglutamine insert structure show that this host-guest method can select a physically realistic model for inserted polyglutamine. If other amyloid peptides can be inserted into stable protein hosts and the stabilities of these host-guest mutants determined, this novel host-guest method may prove useful to determine structural preferences of these intractable but biologically relevant protein fragments.

Methods of learning in statistical education: Design and analysis of a randomized trial

NASA Astrophysics Data System (ADS)

Boyd, Felicity Turner

Background. Recent psychological and technological advances suggest that active learning may enhance understanding and retention of statistical principles. A randomized trial was designed to evaluate the addition of innovative instructional methods within didactic biostatistics courses for public health professionals. Aims. The primary objectives were to evaluate and compare the addition of two active learning methods (cooperative and internet) on students' performance; assess their impact on performance after adjusting for differences in students' learning style; and examine the influence of learning style on trial participation. Methods. Consenting students enrolled in a graduate introductory biostatistics course were randomized to cooperative learning, internet learning, or control after completing a pretest survey. The cooperative learning group participated in eight small group active learning sessions on key statistical concepts, while the internet learning group accessed interactive mini-applications on the same concepts. Controls received no intervention. Students completed evaluations after each session and a post-test survey. Study outcome was performance quantified by examination scores. Intervention effects were analyzed by generalized linear models using intent-to-treat analysis and marginal structural models accounting for reported participation. Results. Of 376 enrolled students, 265 (70%) consented to randomization; 69, 100, and 96 students were randomized to the cooperative, internet, and control groups, respectively. Intent-to-treat analysis showed no differences between study groups; however, 51% of students in the intervention groups had dropped out after the second session. After accounting for reported participation, expected examination scores were 2.6 points higher (of 100 points) after completing one cooperative learning session (95% CI: 0.3, 4.9) and 2.4 points higher after one internet learning session (95% CI: 0.0, 4.7), versus nonparticipants or controls, adjusting for other performance predictors. Students who preferred learning by reflective observation and active experimentation experienced improved performance through internet learning (5.9 points, 95% CI: 1.2, 10.6) and cooperative learning (2.9 points, 95% CI: 0.6, 5.2), respectively. Learning style did not influence study participation. Conclusions. No performance differences by group were observed by intent-to-treat analysis. Participation in active learning appears to improve student performance in an introductory biostatistics course and provides opportunities for enhancing understanding beyond that attained in traditional didactic classrooms.