Genetic signatures of natural selection in a model invasive ascidian

NASA Astrophysics Data System (ADS)

Lin, Yaping; Chen, Yiyong; Yi, Changho; Fong, Jonathan J.; Kim, Won; Rius, Marc; Zhan, Aibin

2017-03-01

Invasive species represent promising models to study species’ responses to rapidly changing environments. Although local adaptation frequently occurs during contemporary range expansion, the associated genetic signatures at both population and genomic levels remain largely unknown. Here, we use genome-wide gene-associated microsatellites to investigate genetic signatures of natural selection in a model invasive ascidian, Ciona robusta. Population genetic analyses of 150 individuals sampled in Korea, New Zealand, South Africa and Spain showed significant genetic differentiation among populations. Based on outlier tests, we found high incidence of signatures of directional selection at 19 loci. Hitchhiking mapping analyses identified 12 directional selective sweep regions, and all selective sweep windows on chromosomes were narrow (~8.9 kb). Further analyses indentified 132 candidate genes under selection. When we compared our genetic data and six crucial environmental variables, 16 putatively selected loci showed significant correlation with these environmental variables. This suggests that the local environmental conditions have left significant signatures of selection at both population and genomic levels. Finally, we identified “plastic” genomic regions and genes that are promising regions to investigate evolutionary responses to rapid environmental change in C. robusta.

Sonora exploratory study for the detection of wheat-leaf rust

NASA Technical Reports Server (NTRS)

Payne, R. W. (Principal Investigator)

1980-01-01

The applicability of LANDSAT remote sensing technology to the detection of a wheat-leaf-rust epidemic in Sonora, Mexico, during 1977 was investigated. LANDSAT data acquired during crop years 1975-76 and 1976-77 were clustered, classified, and analyzed in order to detect agricultural changes. Analysis of 1977 data indicates a significant proportion of the identified wheat is stressed (potentially rust-infected). Additional analyses show a significant increase in fallowing during the year, as well as a substantial decrease in reservoir levels in the Sonora agricultural region. Ground observations are required to substantiate these analyses. The possibility exists that heat-rust is not LANDSAT detectable and that the clusters identified as containing stressed signatures represent different varieties of wheat or perhaps nonwheat crops.

Detecting significant change in stream benthic macroinvertebrate communities in wilderness areas

USGS Publications Warehouse

Milner, Alexander M.; Woodward, Andrea; Freilich, Jerome E.; Black, Robert W.; Resh, Vincent H.

2016-01-01

Within a region, both MDS analyses typically identified similar years as exceeding reference condition variation, illustrating the utility of the approach for identifying wider spatial scale effects that influence more than one stream. MDS responded to both simulated water temperature stress and a pollutant event, and generally outlying years on MDS plots could be explained by environmental variables, particularly higher precipitation. Multivariate control charts successfully identified whether shifts in community structure identified by MDS were significant and whether the shift represented a press disturbance (long-term change) or a pulse disturbance. We consider a combination of TD and MDS with control charts to be a potentially powerful tool for determining years significantly outside of a reference condition variation.

Visual field progression with frequency-doubling matrix perimetry and standard automated perimetry in patients with glaucoma and in healthy controls.

PubMed

Redmond, Tony; O'Leary, Neil; Hutchison, Donna M; Nicolela, Marcelo T; Artes, Paul H; Chauhan, Balwantray C

2013-12-01

A new analysis method called permutation of pointwise linear regression measures the significance of deterioration over time at each visual field location, combines the significance values into an overall statistic, and then determines the likelihood of change in the visual field. Because the outcome is a single P value, individualized to that specific visual field and independent of the scale of the original measurement, the method is well suited for comparing techniques with different stimuli and scales. To test the hypothesis that frequency-doubling matrix perimetry (FDT2) is more sensitive than standard automated perimetry (SAP) in identifying visual field progression in glaucoma. Patients with open-angle glaucoma and healthy controls were examined by FDT2 and SAP, both with the 24-2 test pattern, on the same day at 6-month intervals in a longitudinal prospective study conducted in a hospital-based setting. Only participants with at least 5 examinations were included. Data were analyzed with permutation of pointwise linear regression. Permutation of pointwise linear regression is individualized to each participant, in contrast to current analyses in which the statistical significance is inferred from population-based approaches. Analyses were performed with both total deviation and pattern deviation. Sixty-four patients and 36 controls were included in the study. The median age, SAP mean deviation, and follow-up period were 65 years, -2.6 dB, and 5.4 years, respectively, in patients and 62 years, +0.4 dB, and 5.2 years, respectively, in controls. Using total deviation analyses, statistically significant deterioration was identified in 17% of patients with FDT2, in 34% of patients with SAP, and in 14% of patients with both techniques; in controls these percentages were 8% with FDT2, 31% with SAP, and 8% with both. Using pattern deviation analyses, statistically significant deterioration was identified in 16% of patients with FDT2, in 17% of patients with SAP, and in 3% of patients with both techniques; in controls these values were 3% with FDT2 and none with SAP. No evidence was found that FDT2 is more sensitive than SAP in identifying visual field deterioration. In about one-third of healthy controls, age-related deterioration with SAP reached statistical significance.

Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer.

PubMed

Robertson, A Gordon; Kim, Jaegil; Al-Ahmadie, Hikmat; Bellmunt, Joaquim; Guo, Guangwu; Cherniack, Andrew D; Hinoue, Toshinori; Laird, Peter W; Hoadley, Katherine A; Akbani, Rehan; Castro, Mauro A A; Gibb, Ewan A; Kanchi, Rupa S; Gordenin, Dmitry A; Shukla, Sachet A; Sanchez-Vega, Francisco; Hansel, Donna E; Czerniak, Bogdan A; Reuter, Victor E; Su, Xiaoping; de Sa Carvalho, Benilton; Chagas, Vinicius S; Mungall, Karen L; Sadeghi, Sara; Pedamallu, Chandra Sekhar; Lu, Yiling; Klimczak, Leszek J; Zhang, Jiexin; Choo, Caleb; Ojesina, Akinyemi I; Bullman, Susan; Leraas, Kristen M; Lichtenberg, Tara M; Wu, Catherine J; Schultz, Nicholaus; Getz, Gad; Meyerson, Matthew; Mills, Gordon B; McConkey, David J; Weinstein, John N; Kwiatkowski, David J; Lerner, Seth P

2017-10-19

We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations

PubMed Central

Liang, Jingjing; Le, Thu H.; Edwards, Digna R. Velez; Tayo, Bamidele O.; Gaulton, Kyle J.; Lu, Yingchang; Jensen, Richard A.; Chen, Guanjie; Schwander, Karen; McKenzie, Colin A.; Fox, Ervin; Nalls, Michael A.; Young, J. Hunter; Lane, Jacqueline M.; Zhou, Jie; Tang, Hua; Fornage, Myriam; Musani, Solomon K.; Wang, Heming; Forrester, Terrence; Chu, Pei-Lun; Evans, Michele K.; Morrison, Alanna C.; Martin, Lisa W.; Wiggins, Kerri L.; Hui, Qin; Zhao, Wei; Jackson, Rebecca D.; Faul, Jessica D.; Reiner, Alex P.; Bray, Michael; Denny, Joshua C.; Mosley, Thomas H.; Palmas, Walter; Guo, Xiuqing; Polak, Joseph F.; Taylor, Ken D.; Boerwinkle, Eric; Bottinger, Erwin P.; Liu, Kiang; Risch, Neil; Hunt, Steven C.; Kooperberg, Charles; Zonderman, Alan B.; Becker, Diane M.; Cai, Jianwen; Loos, Ruth J. F.; Psaty, Bruce M.; Weir, David R.; Kardia, Sharon L. R.; Arnett, Donna K.; Won, Sungho; Edwards, Todd L.; Redline, Susan; Cooper, Richard S.; Rao, D. C.; Rotimi, Charles; Levy, Daniel; Chakravarti, Aravinda

2017-01-01

Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10−8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension. PMID:28498854

Gene and pathway level analyses of germline DNA-repair gene variants and prostate cancer susceptibility using the iCOGS-genotyping array.

PubMed

Saunders, Edward J; Dadaev, Tokhir; Leongamornlert, Daniel A; Al Olama, Ali Amin; Benlloch, Sara; Giles, Graham G; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Borge G; Travis, Ruth C; Neal, David; Pasayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen N; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Park, Jong Y; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Pandha, Hardev; Govindasami, Koveela; Muir, Ken; Easton, Douglas F; Eeles, Rosalind A; Kote-Jarai, Zsofia

2016-04-12

Germline mutations within DNA-repair genes are implicated in susceptibility to multiple forms of cancer. For prostate cancer (PrCa), rare mutations in BRCA2 and BRCA1 give rise to moderately elevated risk, whereas two of B100 common, low-penetrance PrCa susceptibility variants identified so far by genome-wide association studies implicate RAD51B and RAD23B. Genotype data from the iCOGS array were imputed to the 1000 genomes phase 3 reference panel for 21 780 PrCa cases and 21 727 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. We subsequently performed single variant, gene and pathway-level analyses using 81 303 SNPs within 20 Kb of a panel of 179 DNA-repair genes. Single SNP analyses identified only the previously reported association with RAD51B. Gene-level analyses using the SKAT-C test from the SNP-set (Sequence) Kernel Association Test (SKAT) identified a significant association with PrCa for MSH5. Pathway-level analyses suggested a possible role for the translesion synthesis pathway in PrCa risk and Homologous recombination/Fanconi Anaemia pathway for PrCa aggressiveness, even though after adjustment for multiple testing these did not remain significant. MSH5 is a novel candidate gene warranting additional follow-up as a prospective PrCa-risk locus. MSH5 has previously been reported as a pleiotropic susceptibility locus for lung, colorectal and serous ovarian cancers.

Genome-Wide Association Study in Obsessive-Compulsive Disorder: Results from the OCGAS

PubMed Central

Mattheisen, Manuel; Samuels, Jack F.; Wang, Ying; Greenberg, Benjamin D.; Fyer, Abby J.; McCracken, James T.; Geller, Daniel A.; Murphy, Dennis L.; Knowles, James A.; Grados, Marco A.; Riddle, Mark A.; Rasmussen, Steven A.; McLaughlin, Nicole C.; Nurmi, Erica; Askland, Kathleen D.; Qin, Hai-De; Cullen, Bernadette A.; Piacentini, John; Pauls, David L.; Bienvenu, O. Joseph; Stewart, S. Evelyn; Liang, Kung-Yee; Goes, Fernando S.; Maher, Brion; Pulver, Ann E.; Shugart, Yin-Yao; Valle, David; Lange, Cristoph; Nestadt, Gerald

2014-01-01

Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients, with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1 065 families (containing 1 406 patients with OCD), combined with population-based samples (resulting in a total sample of 5 061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at SNP- and gene-levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13×10−7). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of GWAS signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2, and PTPRD. Analyses at the gene-level revealed association of IQCK and C16orf88 (both P<1×10−6, experiment-wide significant), as well as OFCC1 (P=6.29×10−5). The suggestive findings in this study await replication in larger samples. PMID:24821223

Three Psychotherapies Examined: Ellis, Rogers, Perls

ERIC Educational Resources Information Center

Stoten, J.; Goos, W.

1974-01-01

This study uses Bales' Interaction Process Analysis (I. P. A.) to identify significant process elements in counselling and psychotherapy. For this purpose, the film "Three Approaches to Psychotherapy" was analysed. (Editor)

Genetic signatures of natural selection in a model invasive ascidian

PubMed Central

Lin, Yaping; Chen, Yiyong; Yi, Changho; Fong, Jonathan J.; Kim, Won; Rius, Marc; Zhan, Aibin

2017-01-01

Invasive species represent promising models to study species’ responses to rapidly changing environments. Although local adaptation frequently occurs during contemporary range expansion, the associated genetic signatures at both population and genomic levels remain largely unknown. Here, we use genome-wide gene-associated microsatellites to investigate genetic signatures of natural selection in a model invasive ascidian, Ciona robusta. Population genetic analyses of 150 individuals sampled in Korea, New Zealand, South Africa and Spain showed significant genetic differentiation among populations. Based on outlier tests, we found high incidence of signatures of directional selection at 19 loci. Hitchhiking mapping analyses identified 12 directional selective sweep regions, and all selective sweep windows on chromosomes were narrow (~8.9 kb). Further analyses indentified 132 candidate genes under selection. When we compared our genetic data and six crucial environmental variables, 16 putatively selected loci showed significant correlation with these environmental variables. This suggests that the local environmental conditions have left significant signatures of selection at both population and genomic levels. Finally, we identified “plastic” genomic regions and genes that are promising regions to investigate evolutionary responses to rapid environmental change in C. robusta. PMID:28266616

Twenty years of meta-analyses in orthopaedic surgery: has quality kept up with quantity?

PubMed

Dijkman, Bernadette G; Abouali, Jihad A K; Kooistra, Bauke W; Conter, Henry J; Poolman, Rudolf W; Kulkarni, Abhaya V; Tornetta, Paul; Bhandari, Mohit

2010-01-01

As the number of studies in the literature is increasing, orthopaedic surgeons highly depend on meta-analyses as their primary source of scientific evidence. The objectives of this review were to assess the scientific quality and number of published meta-analyses on orthopaedics-related topics over time. We conducted, in duplicate and independently, a systematic review of published meta-analyses in orthopaedics in the years 2005 and 2008 and compared them with a previous systematic review of meta-analyses from 1969 to 1999. A search of electronic databases (MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews) was performed to identify meta-analyses published in 2005 and 2008. We searched bibliographies and contacted content experts to identify additional relevant studies. Two investigators independently assessed the quality of the studies, using the Oxman and Guyatt index, and abstracted relevant data. We included forty-five and forty-four meta-analyses from 2005 and 2008, respectively. While the number of meta-analyses increased fivefold from 1999 to 2008, the mean quality score did not change significantly over time (p = 0.067). In the later years, a significantly lower proportion of meta-analyses had methodological flaws (56% in 2005 and 68% in 2008) compared with meta-analyses published prior to 2000 (88%) (p = 0.006). In 2005 and 2008, respectively, 18% and 30% of the meta-analyses had major to extensive flaws in their methodology. Studies from 2008 with positive conclusions used and described appropriate criteria for the validity assessment less often than did those with negative results. The use of random-effects and fixed-effects models as pooling methods became more popular toward 2008. Although the methodological quality of orthopaedic meta-analyses has increased in the past twenty years, a substantial proportion continues to show major to extensive flaws. As the number of published meta-analyses is increasing, a routine checklist for scientific quality should be used in the peer-review process to ensure methodological standards for publication.

Differences in taste sensitivity between obese and non-obese children and adolescents.

PubMed

Overberg, Johanna; Hummel, Thomas; Krude, Heiko; Wiegand, Susanna

2012-12-01

Taste sensitivity varies between individuals. Several studies describe differences between obese and non-obese subjects concerning their taste perception. However, data are partly contradictory and insufficient. Therefore, in this study taste sensitivity of obese and non-obese children/adolescents was analysed. In a cross-sectional study gustatory sensitivity of n=99 obese subjects (body mass index (BMI) >97th percentile) and n=94 normal weight subjects (BMI <90th percentile), 6-18 years of age, was compared. Sensitivity for the taste qualities sweet, sour, salty, umami and bitter was analysed by means of impregnated 'taste strips' in different concentrations. A total score was determined for all taste qualities combined as well as for each separately. Furthermore, the possible influence of sex, age and ethnicity on taste perception was analysed. An intensity rating for sweet was performed on a 5-point rating scale. Obese subjects showed-compared to the control group-a significantly lower ability to identify the correct taste qualities regarding the total score (p<0.001). Regarding individual taste qualities there was a significantly lower detection rate for salty, umami and bitter by obese subjects. Furthermore, the determinants age and sex had a significant influence on taste perception: older age and female sex was associated with better ability to identify taste qualities. Concerning the sweet intensity rating obese children gave significantly lower intensity ratings to three of the four concentrations. Obese and non-obese children and adolescents differ in their taste perception. Obese subjects could identify taste qualities less precisely than children and adolescents of normal weight.

A genome-wide association study of corneal astigmatism: The CREAM Consortium

PubMed Central

Shah, Rupal L.; Li, Qing; Zhao, Wanting; Tedja, Milly S.; Tideman, J. Willem L.; Khawaja, Anthony P.; Fan, Qiao; Yazar, Seyhan; Williams, Katie M.; Verhoeven, Virginie J.M.; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J.; Pärssinen, Olavi; Wedenoja, Juho; Biino, Ginevra; Concas, Maria Pina; Uitterlinden, André; Rivadeneira, Fernando; Jaddoe, Vincent W.V.; Hysi, Pirro G.; Sim, Xueling; Tan, Nicholas; Tham, Yih-Chung; Sensaki, Sonoko; Hofman, Albert; Vingerling, Johannes R.; Jonas, Jost B.; Mitchell, Paul; Hammond, Christopher J.; Höhn, René; Baird, Paul N.; Wong, Tien-Yin; Cheng, Chinfsg-Yu; Teo, Yik Ying; Mackey, David A.; Williams, Cathy; Saw, Seang-Mei; Klaver, Caroline C.W.; Bailey-Wilson, Joan E.

2018-01-01

Purpose To identify genes and genetic markers associated with corneal astigmatism. Methods A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. Results The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08–1.16), p=5.55×10−9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans—claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). Conclusions In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism. PMID:29422769

The Distance Learning of Foreign Languages: A Research Agenda

ERIC Educational Resources Information Center

White, Cynthia

2014-01-01

Research into the distance learning of languages is now established as a significant avenue of enquiry in language teaching, with evident research trajectories in several domains. This article selects and analyses significant areas of investigation in distance language learning and teaching to identify new and emerging gaps, along with research…

Low creatinine clearance is a risk factor for D2 gastrectomy after neoadjuvant chemotherapy.

PubMed

Hayashi, Tsutomu; Aoyama, Toru; Tanabe, Kazuaki; Nishikawa, Kazuhiro; Ito, Yuichi; Ogata, Takashi; Cho, Haruhiko; Morita, Satoshi; Miyashita, Yumi; Tsuburaya, Akira; Sakamoto, Junichi; Yoshikawa, Takaki

2014-09-01

The feasibility and safety of D2 surgery following neoadjuvant chemotherapy (NAC) has not been fully evaluated in patients with gastric cancer. Moreover, risk factor for surgical complications after D2 gastrectomy following NAC is also unknown. The purpose of the present study was to identify risk factors of postoperative complications after D2 surgery following NAC. This study was conducted as an exploratory analysis of a prospective, randomized Phase II trial of NAC. The surgical complications were assessed and classified according to the Clavien-Dindo classification. A uni- and multivariate logistic regression analyses were performed to identify risk factors for morbidity. Among 83 patients who were registered to the Phase II trial, 69 patients received the NAC and D2 gastrectomy. Postoperative complications were identified in 18 patients and the overall morbidity rate was 26.1 %. The results of univariate and multivariate analyses of various factors for overall operative morbidity, creatinine clearance (CCr) ≤ 60 ml/min (P = 0.016) was identified as sole significant independent risk factor for overall morbidity. Occurrence of pancreatic fistula was significantly higher in the patients with a low CCr than in those with a high CCr. Low CCr was a significant risk factor for surgical complications in D2 gastrectomy after NAC. Careful attention is required for these patients.

Multimodal neural correlates of cognitive control in the Human Connectome Project.

PubMed

Lerman-Sinkoff, Dov B; Sui, Jing; Rachakonda, Srinivas; Kandala, Sridhar; Calhoun, Vince D; Barch, Deanna M

2017-12-01

Cognitive control is a construct that refers to the set of functions that enable decision-making and task performance through the representation of task states, goals, and rules. The neural correlates of cognitive control have been studied in humans using a wide variety of neuroimaging modalities, including structural MRI, resting-state fMRI, and task-based fMRI. The results from each of these modalities independently have implicated the involvement of a number of brain regions in cognitive control, including dorsal prefrontal cortex, and frontal parietal and cingulo-opercular brain networks. However, it is not clear how the results from a single modality relate to results in other modalities. Recent developments in multimodal image analysis methods provide an avenue for answering such questions and could yield more integrated models of the neural correlates of cognitive control. In this study, we used multiset canonical correlation analysis with joint independent component analysis (mCCA + jICA) to identify multimodal patterns of variation related to cognitive control. We used two independent cohorts of participants from the Human Connectome Project, each of which had data from four imaging modalities. We replicated the findings from the first cohort in the second cohort using both independent and predictive analyses. The independent analyses identified a component in each cohort that was highly similar to the other and significantly correlated with cognitive control performance. The replication by prediction analyses identified two independent components that were significantly correlated with cognitive control performance in the first cohort and significantly predictive of performance in the second cohort. These components identified positive relationships across the modalities in neural regions related to both dynamic and stable aspects of task control, including regions in both the frontal-parietal and cingulo-opercular networks, as well as regions hypothesized to be modulated by cognitive control signaling, such as visual cortex. Taken together, these results illustrate the potential utility of multi-modal analyses in identifying the neural correlates of cognitive control across different indicators of brain structure and function. Copyright © 2017 Elsevier Inc. All rights reserved.

Reduced Clostridium difficile Tests and Laboratory-Identified Events With a Computerized Clinical Decision Support Tool and Financial Incentive.

PubMed

Madden, Gregory R; German Mesner, Ian; Cox, Heather L; Mathers, Amy J; Lyman, Jason A; Sifri, Costi D; Enfield, Kyle B

2018-06-01

We hypothesized that a computerized clinical decision support tool for Clostridium difficile testing would reduce unnecessary inpatient tests, resulting in fewer laboratory-identified events. Census-adjusted interrupted time-series analyses demonstrated significant reductions of 41% fewer tests and 31% fewer hospital-onset C. difficile infection laboratory-identified events following this intervention.Infect Control Hosp Epidemiol 2018;39:737-740.

Polygenic risk score, genome-wide association, and gene set analyses of cognitive domain deficits in schizophrenia.

PubMed

Nakahara, Soichiro; Medland, Sarah; Turner, Jessica A; Calhoun, Vince D; Lim, Kelvin O; Mueller, Bryon A; Bustillo, Juan R; O'Leary, Daniel S; Vaidya, Jatin G; McEwen, Sarah; Voyvodic, James; Belger, Aysenil; Mathalon, Daniel H; Ford, Judith M; Guffanti, Guia; Macciardi, Fabio; Potkin, Steven G; van Erp, Theo G M

2018-06-12

This study assessed genetic contributions to six cognitive domains, identified by the MATRICS Cognitive Consensus Battery as relevant for schizophrenia, cognition-enhancing, clinical trials. Psychiatric Genomics Consortium Schizophrenia polygenic risk scores showed significant negative correlations with each cognitive domain. Genome-wide association analyses identified loci associated with attention/vigilance (rs830786 within HNF4G), verbal memory (rs67017972 near NDUFS4), and reasoning/problem solving (rs76872642 within HDAC9). Gene set analysis identified unique and shared genes across cognitive domains. These findings suggest involvement of common and unique mechanisms across cognitive domains and may contribute to the discovery of new therapeutic targets to treat cognitive deficits in schizophrenia. Copyright © 2018 Elsevier B.V. All rights reserved.

Investigation of environmental change pattern in Japan. Observation of present state of agricultural land-use by analysing LANDSAT data

NASA Technical Reports Server (NTRS)

Maruyasu, T. (Principal Investigator); Hayashi, S.

1977-01-01

The author has identified the following significant results. Species and ages of grasses in pastures were identified, and soils were classified into several types using LANDSAT data. This data could be used in a wide area of cultivation, reclamation, or management planning on agricultural land.

Identifying Personal and Contextual Factors that Contribute to Attrition Rates for Texas Public School Teachers

ERIC Educational Resources Information Center

Sass, Daniel A.; Flores, Belinda Bustos; Claeys, Lorena; Perez, Bertha

2012-01-01

Teacher attrition is a significant problem facing schools, with a large percentage of teachers leaving the profession within their first few years. Given the need to retain high-quality teachers, research is needed to identify those teachers with higher retention rates. Using survival analyses and a large state dataset, researchers examined…

Hydrothermal Liquefaction Treatment Hazard Analysis Report

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

Lowry, Peter P.; Wagner, Katie A.

Hazard analyses were performed to evaluate the modular hydrothermal liquefaction treatment system. The hazard assessment process was performed in 2 stages. An initial assessment utilizing Hazard Identification and Preliminary Hazards Analysis (PHA) techniques identified areas with significant or unique hazards (process safety-related hazards) that fall outside of the normal operating envelope of PNNL and warranted additional analysis. The subsequent assessment was based on a qualitative What-If analysis. The analysis was augmented, as necessary, by additional quantitative analysis for scenarios involving a release of hazardous material or energy with the potential for affecting the public. The following selected hazardous scenarios receivedmore » increased attention: •Scenarios involving a release of hazardous material or energy, controls were identified in the What-If analysis table that prevent the occurrence or mitigate the effects of the release. •Scenarios with significant consequences that could impact personnel outside the immediate operations area, quantitative analyses were performed to determine the potential magnitude of the scenario. The set of “critical controls” were identified for these scenarios (see Section 4) which prevent the occurrence or mitigate the effects of the release of events with significant consequences.« less

Genome Wide Analysis of Fertility and Production Traits in Italian Holstein Cattle

PubMed Central

Stella, Alessandra; Biffani, Stefano; Negrini, Riccardo; Lazzari, Barbara; Ajmone-Marsan, Paolo; Williams, John L .

2013-01-01

A genome wide scan was performed on a total of 2093 Italian Holstein proven bulls genotyped with 50K single nucleotide polymorphisms (SNPs), with the objective of identifying loci associated with fertility related traits and to test their effects on milk production traits. The analysis was carried out using estimated breeding values for the aggregate fertility index and for each trait contributing to the index: angularity, calving interval, non-return rate at 56 days, days to first service, and 305 day first parity lactation. In addition, two production traits not included in the aggregate fertility index were analysed: fat yield and protein yield. Analyses were carried out using all SNPs treated separately, further the most significant marker on BTA14 associated to milk quality located in the DGAT1 region was treated as fixed effect. Genome wide association analysis identified 61 significant SNPs and 75 significant marker-trait associations. Eight additional SNP associations were detected when SNP located near DGAT1 was included as a fixed effect. As there were no obvious common SNPs between the traits analyzed independently in this study, a network analysis was carried out to identify unforeseen relationships that may link production and fertility traits. PMID:24265800

A system biology approach for understanding the miRNA regulatory network in colon rectal cancer.

PubMed

Pradhan, Meeta; Nagulapalli, Kshithija; Ledford, Lakenvia; Pandit, Yogesh; Palakal, Mathew

2015-01-01

In this paper we present a systems biology approach to the understanding of the miRNA-regulatory network in colon rectal cancer. An initial set of significant genes in Colon Rectal Cancer (CRC) were obtained by mining relevant literature. An initial set of cancer-related miRNAs were obtained from three databases: miRBase, miRWalk, Targetscan and GEO microarray experiment. First principle methods were then used to generate the global miRNA-gene network. Significant miRNAs and associated transcription factors in the global miRNA-gene network were identified using topological and sub-graph analyses. Eleven novel miRNAs were identified and three of the novel miRNAs, hsa-miR-630, hsa-miR-100 and hsa-miR-99a, were further analysed to elucidate their role in CRC. The proposed methodology effectively made use of literature data and was able to show novel, significant miRNA-transcription associations in CRC.

A Systematic Review and Meta-Analyses Show that Carbapenem Use and Medical Devices Are the Leading Risk Factors for Carbapenem-Resistant Pseudomonas aeruginosa

PubMed Central

Voor in ‘t holt, Anne F.; Severin, Juliëtte A.; Lesaffre, Emmanuel M. E. H.

2014-01-01

A systematic review and meta-analyses were performed to identify the risk factors associated with carbapenem-resistant Pseudomonas aeruginosa and to identify sources and reservoirs for the pathogen. A systematic search of PubMed and Embase databases from 1 January 1987 until 27 January 2012 identified 1,662 articles, 53 of which were included in a systematic review and 38 in a random-effects meta-analysis study. The use of carbapenem, use of fluoroquinolones, use of vancomycin, use of other antibiotics, having medical devices, intensive care unit (ICU) admission, having underlying diseases, patient characteristics, and length of hospital stay were significant risk factors in multivariate analyses. The meta-analyses showed that carbapenem use (odds ratio [OR] = 7.09; 95% confidence interval [CI] = 5.43 to 9.25) and medical devices (OR = 5.11; 95% CI = 3.55 to 7.37) generated the highest pooled estimates. Cumulative meta-analyses showed that the pooled estimate of carbapenem use was stable and that the pooled estimate of the risk factor “having medical devices” increased with time. We conclude that our results highlight the importance of antibiotic stewardship and the thoughtful use of medical devices in helping prevent outbreaks of carbapenem-resistant P. aeruginosa. PMID:24550343

The emergence of the nanobiotechnology industry

NASA Astrophysics Data System (ADS)

Maine, Elicia; Thomas, V. J.; Bliemel, Martin; Murira, Armstrong; Utterback, James

2014-01-01

The confluence of nanotechnology and biotechnology provides significant commercial opportunities. By identifying, classifying and tracking firms with capabilities in both biotechnology and nanotechnology over time, we analyse the emergence and evolution of the global nanobiotechnology industry.

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels.

PubMed

Spracklen, Cassandra N; Chen, Peng; Kim, Young Jin; Wang, Xu; Cai, Hui; Li, Shengxu; Long, Jirong; Wu, Ying; Wang, Ya Xing; Takeuchi, Fumihiko; Wu, Jer-Yuarn; Jung, Keum-Ji; Hu, Cheng; Akiyama, Koichi; Zhang, Yonghong; Moon, Sanghoon; Johnson, Todd A; Li, Huaixing; Dorajoo, Rajkumar; He, Meian; Cannon, Maren E; Roman, Tamara S; Salfati, Elias; Lin, Keng-Hung; Guo, Xiuqing; Sheu, Wayne H H; Absher, Devin; Adair, Linda S; Assimes, Themistocles L; Aung, Tin; Cai, Qiuyin; Chang, Li-Ching; Chen, Chien-Hsiun; Chien, Li-Hsin; Chuang, Lee-Ming; Chuang, Shu-Chun; Du, Shufa; Fan, Qiao; Fann, Cathy S J; Feranil, Alan B; Friedlander, Yechiel; Gordon-Larsen, Penny; Gu, Dongfeng; Gui, Lixuan; Guo, Zhirong; Heng, Chew-Kiat; Hixson, James; Hou, Xuhong; Hsiung, Chao Agnes; Hu, Yao; Hwang, Mi Yeong; Hwu, Chii-Min; Isono, Masato; Juang, Jyh-Ming Jimmy; Khor, Chiea-Chuen; Kim, Yun Kyoung; Koh, Woon-Puay; Kubo, Michiaki; Lee, I-Te; Lee, Sun-Ju; Lee, Wen-Jane; Liang, Kae-Woei; Lim, Blanche; Lim, Sing-Hui; Liu, Jianjun; Nabika, Toru; Pan, Wen-Harn; Peng, Hao; Quertermous, Thomas; Sabanayagam, Charumathi; Sandow, Kevin; Shi, Jinxiu; Sun, Liang; Tan, Pok Chien; Tan, Shu-Pei; Taylor, Kent D; Teo, Yik-Ying; Toh, Sue-Anne; Tsunoda, Tatsuhiko; van Dam, Rob M; Wang, Aili; Wang, Feijie; Wang, Jie; Wei, Wen Bin; Xiang, Yong-Bing; Yao, Jie; Yuan, Jian-Min; Zhang, Rong; Zhao, Wanting; Chen, Yii-Der Ida; Rich, Stephen S; Rotter, Jerome I; Wang, Tzung-Dau; Wu, Tangchun; Lin, Xu; Han, Bok-Ghee; Tanaka, Toshihiro; Cho, Yoon Shin; Katsuya, Tomohiro; Jia, Weiping; Jee, Sun-Ha; Chen, Yuan-Tsong; Kato, Norihiro; Jonas, Jost B; Cheng, Ching-Yu; Shu, Xiao-Ou; He, Jiang; Zheng, Wei; Wong, Tien-Yin; Huang, Wei; Kim, Bong-Jo; Tai, E-Shyong; Mohlke, Karen L; Sim, Xueling

2017-05-01

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A Systematic Review of the Cost-Effectiveness of Biologics for Ulcerative Colitis.

PubMed

Stawowczyk, Ewa; Kawalec, Paweł

2018-04-01

Ulcerative colitis (UC) is a chronic autoimmune inflammation of the colon. The condition significantly decreases quality of life and generates a substantial economic burden for healthcare payers, patients and the society in which they live. Some patients require chronic pharmacotherapy, and access to novel biologic drugs might be crucial for long-term remission. The analyses of cost-effectiveness for biologic drugs are necessary to assess their efficiency and provide the best available drugs to patients. Our aim was to collect and assess the quality of economic analyses carried out for biologic agents used in the treatment of UC, as well as to summarize evidence on the drivers of cost-effectiveness and evaluate the transferability and generalizability of conclusions. A systematic database review was conducted using MEDLINE (via PubMed), EMBASE, Cost-Effectiveness Analysis Registry and CRD0. Both authors independently reviewed the identified articles to determine their eligibility for final review. Hand searching of references in collected papers was also performed to find any relevant articles. The reporting quality of economic analyses included was evaluated by two reviewers using the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement checklist. We reviewed the sensitivity analyses in cost-effectiveness analyses to identify the variables that may have changed the conclusions of the study. Key drivers of cost-effectiveness were selected by identifying uncertain parameters that caused the highest change of the results of the analyses compared with base-case results. Of the 576 identified records, 87 were excluded as duplicates and 16 studies were included in the final review; evaluations for Canada, the UK and Poland were mostly performed. The majority of the evaluations revealed were performed for infliximab (approximately 75% of total volume); however, some assessments were also performed for adalimumab (50%) and golimumab (31%). Only three analyses were conducted for vedolizumab, whereas no relevant studies were found for etrolizumab and tofacitinib. The reporting quality of the included economic analyses was assessed as high, with an average score of 21 points per 24 maximum possible (range 14-23 points according to the ISPOR CHEERS statement checklist). In the case of most analyses, quality-adjusted life-years were used as a clinical outcome, and endpoints such as remission, response and mucosal healing were less common. The higher clinical effectiveness (based on response rates) of biological treatment over non-biological treatments was presented in revealed analyses. The incremental cost-utility ratios for biologics, compared with standard care, varied significantly between the studies and ranged from US$36,309 to US$456,979. The lowest value was obtained for infliximab and the highest for the treatment scheme including infliximab 5 mg/kg and infliximab 10 mg/kg + adalimumab. The change of utility weights and clinical parameters had the most significant influence on the results of the analysis; the variable related to surgery was the least sensitive. Limited data on the cost-effectiveness of UC therapy were identified. In the majority of studies, the lack of cost-effectiveness was revealed for biologics, which was associated with their high costs. Clinical outcomes are transferable to other countries and could be generalized; however, cost inputs are country-specific and therefore limit the transferability and generalizability of conclusions. The key drivers and variables that showed the greatest effect on the analysis results were utility weights and clinical parameters.

A genome-wide interaction analysis of tri/tetracyclic antidepressants and RR and QT intervals: a pharmacogenomics study from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium

PubMed Central

Noordam, Raymond; Sitlani, Colleen M; Avery, Christy L; Stewart, James D; Gogarten, Stephanie M; Wiggins, Kerri L; Trompet, Stella; Warren, Helen R; Sun, Fangui; Evans, Daniel S; Li, Xiaohui; Li, Jin; Smith, Albert V; Bis, Joshua C; Brody, Jennifer A; Busch, Evan L; Caulfield, Mark J; Chen, Yii-Der I; Cummings, Steven R; Cupples, L Adrienne; Duan, Qing; Franco, Oscar H; Méndez-Giráldez, Rául; Harris, Tamara B; Heckbert, Susan R; van Heemst, Diana; Hofman, Albert; Floyd, James S; Kors, Jan A; Launer, Lenore J; Li, Yun; Li-Gao, Ruifang; Lange, Leslie A; Lin, Henry J; de Mutsert, Renée; Napier, Melanie D; Newton-Cheh, Christopher; Poulter, Neil; Reiner, Alexander P; Rice, Kenneth M; Roach, Jeffrey; Rodriguez, Carlos J; Rosendaal, Frits R; Sattar, Naveed; Sever, Peter; Seyerle, Amanda A; Slagboom, P Eline; Soliman, Elsayed Z; Sotoodehnia, Nona; Stott, David J; Stürmer, Til; Taylor, Kent D; Thornton, Timothy A; Uitterlinden, André G; Wilhelmsen, Kirk C; Wilson, James G; Gudnason, Vilmundur; Jukema, J Wouter; Laurie, Cathy C; Liu, Yongmei; Mook-Kanamori, Dennis O; Munroe, Patricia B; Rotter, Jerome I; Vasan, Ramachandran S; Psaty, Bruce M; Stricker, Bruno H; Whitsel, Eric A

2017-01-01

Background Increased heart rate and a prolonged QT interval are important risk factors for cardiovascular morbidity and mortality, and can be influenced by the use of various medications, including tri/tetracyclic antidepressants (TCAs). We aim to identify genetic loci that modify the association between TCA use and RR and QT intervals. Methods and Results We conducted race/ethnic-specific genome-wide interaction analyses (with HapMap Phase II imputed reference panel imputation) of TCAs and resting RR and QT intervals in cohorts of European (n=45,706; n=1,417 TCA users), African (n=10,235; n=296 TCA users) and Hispanic/Latino (n=13,808; n=147 TCA users) ancestry, adjusted for clinical covariates. Among the populations of European ancestry, two genome-wide significant loci were identified for RR interval: rs6737205 in BRE (β = 56.3, Pinteraction = 3.9e−9) and rs9830388 in UBE2E2 (β = 25.2, Pinteraction = 1.7e−8). In Hispanic/Latino cohorts, rs2291477 in TGFBR3 significantly modified the association between TCAs and QT intervals (β = 9.3, Pinteraction = 2.55e−8). In the meta-analyses of the other ethnicities, these loci either were excluded from the meta-analyses (as part of quality control), or their effects did not reach the level of nominal statistical significance (Pinteraction > 0.05). No new variants were identified in these ethnicities. No additional loci were identified after inverse-variance-weighted meta-analysis of the three ancestries. Conclusion Among Europeans, TCA interactions with variants in BRE and UBE2E2, were identified in relation to RR intervals. Among Hispanic/Latinos, variants in TGFBR3 modified the relation between TCAs and QT intervals. Future studies are required to confirm our results. PMID:28039329

Longitudinal analyses of the DNA methylome in deployed military servicemen identify susceptibility loci for post-traumatic stress disorder.

PubMed

Rutten, B P F; Vermetten, E; Vinkers, C H; Ursini, G; Daskalakis, N P; Pishva, E; de Nijs, L; Houtepen, L C; Eijssen, L; Jaffe, A E; Kenis, G; Viechtbauer, W; van den Hove, D; Schraut, K G; Lesch, K-P; Kleinman, J E; Hyde, T M; Weinberger, D R; Schalkwyk, L; Lunnon, K; Mill, J; Cohen, H; Yehuda, R; Baker, D G; Maihofer, A X; Nievergelt, C M; Geuze, E; Boks, M P M

2018-05-01

In order to determine the impact of the epigenetic response to traumatic stress on post-traumatic stress disorder (PTSD), this study examined longitudinal changes of genome-wide blood DNA methylation profiles in relation to the development of PTSD symptoms in two prospective military cohorts (one discovery and one replication data set). In the first cohort consisting of male Dutch military servicemen (n=93), the emergence of PTSD symptoms over a deployment period to a combat zone was significantly associated with alterations in DNA methylation levels at 17 genomic positions and 12 genomic regions. Evidence for mediation of the relation between combat trauma and PTSD symptoms by longitudinal changes in DNA methylation was observed at several positions and regions. Bioinformatic analyses of the reported associations identified significant enrichment in several pathways relevant for symptoms of PTSD. Targeted analyses of the significant findings from the discovery sample in an independent prospective cohort of male US marines (n=98) replicated the observed relation between decreases in DNA methylation levels and PTSD symptoms at genomic regions in ZFP57, RNF39 and HIST1H2APS2. Together, our study pinpoints three novel genomic regions where longitudinal decreases in DNA methylation across the period of exposure to combat trauma marks susceptibility for PTSD.

Is intramedullary fixation of displaced midshaft clavicle fracture superior to plate fixation? Evidence from a systematic review of discordant meta-analyses.

PubMed

Xu, Bin; Lin, Yongsheng; Wang, Zhihong; Cao, Junming; Yang, Yipeng; Xia, Hehuan; Zhang, Yingze

2017-07-01

An increasing number of meta-analyses comparing intramedullary fixation (IF) with plate fixation (PF) for displaced midshaft clavicle fracture have been reported, but the inconsistent results obtained might confuse decision-making. We systematically reviewed discordant meta-analyses for assisting the decision-maker in interpreting and selecting amongst discordant meta-analyses and providing surgical recommendations for displaced midshaft clavicle fracture according to currently best available evidence. Meta-analyses on IF and PF for displaced midshaft clavicle fracture were identified by searching PubMed, Emabase and the Cochrane Library. A review of meta-analysis quality and data extraction was individually conducted by two reviewers. The meta-analysis providing the best available evidence was identified using the Jadad decision algorithm. Nine studies were included, five of which were of Level-II evidence and four of which were of Level-III evidence. These meta-analyses scored from 6 to 10 according to the Assessment of Multiple Systematic Reviews instrument. With respect to the Jadad decision algorithm, the best meta-analysis was chosen depending upon publication characteristics and methodology of primary studies, language restrictions, and whether data on individual patients were analysed. A meta-analysis incorporating more randomised controlled trials was eventually selected. The best available evidence indicated that the differences between IF and PF were not significant in terms of shoulder function or the rate of treatment failure. However, IF significantly decreased the operative time and the rate of non-operative complications, especially the rate of infection. Based on the best available evidence, IF may be superior to PF for treating displaced midshaft clavicle fracture. Copyright © 2017. Published by Elsevier Ltd.

Lessons Learned During TBCC Design for the NASA-AFRL Joint System Study

NASA Technical Reports Server (NTRS)

Snyder, Christopher A.; Espinosa, A. M.

2013-01-01

NASA and the Air Force Research Laboratory are involved in a Joint System Study (JSS) on Two-Stage-to-Orbit (TSTO) vehicles. The JSS will examine the performance, operability and analysis uncertainty of unmanned, fully reusable, TSTO launch vehicle concepts. NASA is providing a vehicle concept using turbine-based combined cycle (TBCC) propulsion on the booster stage and an all-rocket orbiter. The variation in vehicle and mission requirements for different potential customers, combined with analysis uncertainties, make it problematic to define optimum vehicle types or concepts, but the study is being used by NASA for tool assessment and development, and to identify technology gaps. Preliminary analyses were performed on the entire TBCC booster concept; then higher-fidelity analyses were performed for particular areas to verify results or reduce analysis uncertainties. Preliminary TBCC system analyses indicated that there would be sufficient thrust margin over its mission portion. The higher fidelity analyses, which included inlet and nozzle performance corrections for significant area mismatches between TBCC propulsion requirements versus the vehicle design, resulted in significant performance penalties from the preliminary results. TBCC system design and vehicle operation assumptions were reviewed to identify items to mitigate these performance penalties. The most promising items were then applied and analyses rerun to update performance predictions. A study overview is given to orient the reader, quickly focusing upon the NASA TBCC booster and low speed propulsion system. Details for the TBCC concept and the analyses performed are described. Finally, a summary of "Lessons Learned" are discussed with suggestions to improve future study efforts.

Genetic susceptibility of postmenopausal osteoporosis on sulfide quinone reductase-like gene.

PubMed

Cai, X; Yi, X; Zhang, Y; Zhang, D; Zhi, L; Liu, H

2018-05-31

Postmenopausal osteoporosis is a major health problem with important genetic factors in postmenopausal women. We explored the relationship between SQRDL and osteoporosis in a cohort of 1006 patients and 2027 controls from Han Chinese postmenopausal women. Our evidence supported the significant role of SQRDL in the etiology of postmenopausal osteoporosis. Postmenopausal osteoporosis (PMOP) is a metabolic bone disease leading to progressive bone loss and the deterioration of the bone microarchitecture. The sulfide-quinone reductase-like protein is an important enzyme regulating the cellular hydrogen sulfide levels, and it can regulate bone metabolism balance in postmenopausal women. In this study, we aimed to investigate whether SQRDL is associated with susceptibility to PMOP in the Han Chinese population. A total of 3033 postmenopausal women, comprised of 1006 cases and 2027 controls, were recruited in the study. Twenty-two SNPs were selected for genotyping to evaluate the association of SQRDL gene with BMD and PMOP. Association analyses in both single marker and haplotype levels were performed for PMOP. Bone mineral density (BMD) was also utilized as a quantitative phenotype in further analyses. Bioinformatics tools were applied to predict the functional consequences of targeted polymorphisms in SQRDL. The SNP rs1044032 (P = 6.42 × 10 -5 , OR = 0.80) was identified as significantly associated with PMOP. Three SNPs (rs1044032, rs2028589, and rs12913151) were found to be significantly associated with BMD. Although limited functional significance can be obtained for these polymorphisms, significant hits for association with PMOP were found. Moreover, further association analyses with BMD identified three SNPs with significantly independent effects. Our evidence supported the significant role of SQRDL in the etiology of PMOP and suggest that it may be a genetic risk factor for BMD and osteoporosis in Han Chinese postmenopausal women.

IDENTIFICATION OF DIFFERENTIALLY EXPRESSED GENES IN THE KIDNEYS OF GROWTH HORMONE TRANSGENIC MICE

PubMed Central

Coschigano, K.T.; Wetzel, A.N.; Obichere, N.; Sharma, A.; Lee, S.; Rasch, R.; Guigneaux, M.M.; Flyvbjerg, A.; Wood, T.G.; Kopchick, J.J.

2010-01-01

Objective Bovine growth hormone (bGH) transgenic mice develop severe kidney damage. This damage may be due, at least in part, to changes in gene expression. Identification of genes with altered expression in the bGH kidney may identify mechanisms leading to damage in this system that may also be relevant to other models of kidney damage. Design cDNA subtraction libraries, northern blot analyses, microarray analyses and real-time reverse transcription polymerase chain reaction (RT/PCR) assays were used to identify and verify specific genes exhibiting differential RNA expression between kidneys of bGH mice and their non-transgenic (NT) littermates. Results Immunoglobulins were the vast majority of genes identified by the cDNA subtractions and the microarray analyses as being up-regulated in bGH. Several glycoprotein genes and inflammation-related genes also showed increased RNA expression in the bGH kidney. In contrast, only a few genes were identified as being significantly down-regulated in the bGH kidney. The most notable decrease in RNA expression was for the gene encoding kidney androgen-regulated protein. Conclusions A number of genes were identified as being differentially expressed in the bGH kidney. Inclusion of two groups, immunoglobulins and inflammation-related genes, suggests a role of the immune system in bGH kidney damage. PMID:20655258

Advertising bans as a means of tobacco control policy: a systematic literature review of time-series analyses.

PubMed

Quentin, Wilm; Neubauer, Simone; Leidl, Reiner; König, Hans-Helmut

2007-01-01

This paper reviews the international literature that employed time-series analysis to evaluate the effects of advertising bans on aggregate consumption of cigarettes or tobacco. A systematic search of the literature was conducted. Three groups of studies representing analyses of advertising bans in the U.S.A., in other countries and in 22 OECD countries were defined. The estimated effects of advertising bans and their significance were analysed. 24 studies were identified. They used a wide array of explanatory variables, models, estimating methods and data sources. 18 studies found a negative effect of an advertising ban on aggregate consumption, but only ten of these studies found a significant effect. Two studies using data from 22 OECD countries suggested that partial bans would have little or no influence on aggregate consumption, whereas complete bans would significantly reduce consumption. The results imply that advertising bans have a negative but sometimes only narrow impact on consumption. Complete bans let expect a higher effectiveness. Because of methodological restrictions of analysing advertising bans' effects by time series approaches, also different approaches should be used in the future.

Publication bias in obesity treatment trials?

PubMed

Allison, D B; Faith, M S; Gorman, B S

1996-10-01

The present investigation examined the extent of publication bias (namely the tendency to publish significant findings and file away non-significant findings) within the obesity treatment literature. Quantitative literature synthesis of four published meta-analyses from the obesity treatment literature. Interventions in these studies included pharmacological, educational, child, and couples treatments. To assess publication bias, several regression procedures (for example weighted least-squares, random-effects multi-level modeling, and robust regression methods) were used to regress effect sizes onto their standard errors, or proxies thereof, within each of the four meta-analysis. A significant positive beta weight in these analyses signified publication bias. There was evidence for publication bias within two of the four published meta-analyses, such that reviews of published studies were likely to overestimate clinical efficacy. The lack of evidence for publication bias within the two other meta-analyses might have been due to insufficient statistical power rather than the absence of selection bias. As in other disciplines, publication bias appears to exist in the obesity treatment literature. Suggestions are offered for managing publication bias once identified or reducing its likelihood in the first place.

A Combined Pathway and Regional Heritability Analysis Indicates NETRIN1 Pathway Is Associated With Major Depressive Disorder.

PubMed

Zeng, Yanni; Navarro, Pau; Fernandez-Pujals, Ana M; Hall, Lynsey S; Clarke, Toni-Kim; Thomson, Pippa A; Smith, Blair H; Hocking, Lynne J; Padmanabhan, Sandosh; Hayward, Caroline; MacIntyre, Donald J; Wray, Naomi R; Deary, Ian J; Porteous, David J; Haley, Chris S; McIntosh, Andrew M

2017-02-15

Genome-wide association studies (GWASs) of major depressive disorder (MDD) have identified few significant associations. Testing the aggregation of genetic variants, in particular biological pathways, may be more powerful. Regional heritability analysis can be used to detect genomic regions that contribute to disease risk. We integrated pathway analysis and multilevel regional heritability analyses in a pipeline designed to identify MDD-associated pathways. The pipeline was applied to two independent GWAS samples [Generation Scotland: The Scottish Family Health Study (GS:SFHS, N = 6455) and Psychiatric Genomics Consortium (PGC:MDD) (N = 18,759)]. A polygenic risk score (PRS) composed of single nucleotide polymorphisms from the pathway most consistently associated with MDD was created, and its accuracy to predict MDD, using area under the curve, logistic regression, and linear mixed model analyses, was tested. In GS:SFHS, four pathways were significantly associated with MDD, and two of these explained a significant amount of pathway-level regional heritability. In PGC:MDD, one pathway was significantly associated with MDD. Pathway-level regional heritability was significant in this pathway in one subset of PGC:MDD. For both samples the regional heritabilities were further localized to the gene and subregion levels. The NETRIN1 signaling pathway showed the most consistent association with MDD across the two samples. PRSs from this pathway showed competitive predictive accuracy compared with the whole-genome PRSs when using area under the curve statistics, logistic regression, and linear mixed model. These post-GWAS analyses highlight the value of combining multiple methods on multiple GWAS data for the identification of risk pathways for MDD. The NETRIN1 signaling pathway is identified as a candidate pathway for MDD and should be explored in further large population studies. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Ecology and geography of human monkeypox case occurrences across Africa.

PubMed

Ellis, Christine K; Carroll, Darin S; Lash, Ryan R; Peterson, A Townsend; Damon, Inger K; Malekani, Jean; Formenty, Pierre

2012-04-01

As ecologic niche modeling (ENM) evolves as a tool in spatial epidemiology and public health, selection of the most appropriate and informative environmental data sets becomes increasingly important. Here, we build on a previous ENM analysis of the potential distribution of human monkeypox in Africa by refining georeferencing criteria and using more-diverse environmental data to identify environmental parameters contributing to monkeypox distributional ecology. Significant environmental variables include annual precipitation, several temperature-related variables, primary productivity, evapotranspiration, soil moisture, and pH. The potential distribution identified with this set of variables was broader than that identified in previous analyses but does not include areas recently found to hold monkeypox in southern Sudan. Our results emphasize the importance of selecting the most appropriate and informative environmental data sets for ENM analyses in pathogen transmission mapping.

Integrative analysis for identification of shared markers from various functional cells/tissues for rheumatoid arthritis.

PubMed

Xia, Wei; Wu, Jian; Deng, Fei-Yan; Wu, Long-Fei; Zhang, Yong-Hong; Guo, Yu-Fan; Lei, Shu-Feng

2017-02-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease. So far, it is unclear whether there exist common RA-related genes shared in different tissues/cells. In this study, we conducted an integrative analysis on multiple datasets to identify potential shared genes that are significant in multiple tissues/cells for RA. Seven microarray gene expression datasets representing various RA-related tissues/cells were downloaded from the Gene Expression Omnibus (GEO). Statistical analyses, testing both marginal and joint effects, were conducted to identify significant genes shared in various samples. Followed-up analyses were conducted on functional annotation clustering analysis, protein-protein interaction (PPI) analysis, gene-based association analysis, and ELISA validation analysis in in-house samples. We identified 18 shared significant genes, which were mainly involved in the immune response and chemokine signaling pathway. Among the 18 genes, eight genes (PPBP, PF4, HLA-F, S100A8, RNASEH2A, P2RY6, JAG2, and PCBP1) interact with known RA genes. Two genes (HLA-F and PCBP1) are significant in gene-based association analysis (P = 1.03E-31, P = 1.30E-2, respectively). Additionally, PCBP1 also showed differential protein expression levels in in-house case-control plasma samples (P = 2.60E-2). This study represented the first effort to identify shared RA markers from different functional cells or tissues. The results suggested that one of the shared genes, i.e., PCBP1, is a promising biomarker for RA.

Regression Analysis to Identify Factors Associated with Household Salt Iodine Content at the Sub-National Level in Bangladesh, India, Ghana and Senegal

PubMed Central

Knowles, Jacky; Kupka, Roland; Dumble, Sam; Garrett, Greg S.; Pandav, Chandrakant S.; Yadav, Kapil; Nahar, Baitun; Touré, Ndeye Khady; Amoaful, Esi Foriwa; Gorstein, Jonathan

2018-01-01

Regression analyses of data from stratified, cluster sample, household iodine surveys in Bangladesh, India, Ghana and Senegal were conducted to identify factors associated with household access to adequately iodised salt. For all countries, in single variable analyses, household salt iodine was significantly different (p < 0.05) between strata (geographic areas with representative data, defined by survey design), and significantly higher (p < 0.05) among households: with better living standard scores, where the respondent knew about iodised salt and/or looked for iodised salt at purchase, using salt bought in a sealed package, or using refined grain salt. Other country-level associations were also found. Multiple variable analyses showed a significant association between salt iodine and strata (p < 0.001) in India, Ghana and Senegal and that salt grain type was significantly associated with estimated iodine content in all countries (p < 0.001). Salt iodine relative to the reference (coarse salt) ranged from 1.3 (95% CI 1.2, 1.5) times higher for fine salt in Senegal to 3.6 (95% CI 2.6, 4.9) times higher for washed and 6.5 (95% CI 4.9, 8.8) times higher for refined salt in India. Sub-national data are required to monitor equity of access to adequately iodised salt. Improving household access to refined iodised salt in sealed packaging, would improve iodine intake from household salt in all four countries in this analysis, particularly in areas where there is significant small-scale salt production. PMID:29671774

Alexithymia in eating disorders: Systematic review and meta-analyses of studies using the Toronto Alexithymia Scale.

PubMed

Westwood, Heather; Kerr-Gaffney, Jess; Stahl, Daniel; Tchanturia, Kate

2017-08-01

The aim of this review was to synthesise the literature on the use of the Toronto Alexithymia Scale (TAS) in eating disorder populations and Healthy Controls (HCs) and to compare TAS scores in these groups. Electronic databases were searched systematically for studies using the TAS and meta-analyses were performed to statistically compare scores on the TAS between individuals with eating disorders and HCs. Forty-eight studies using the TAS with both a clinical eating disorder group and HCs were identified. Of these, 44 were included in the meta-analyses, separated into: Anorexia Nervosa; Anorexia Nervosa, Restricting subtype; Anorexia Nervosa, Binge-Purge subtype, Bulimia Nervosa and Binge Eating Disorder. For all groups, there were significant differences with medium or large effect sizes between the clinical group and HCs, with the clinical group scoring significantly higher on the TAS, indicating greater difficulty with identifying and labelling emotions. Across the spectrum of eating disorders, individuals report having difficulties recognising or describing their emotions. Given the self-report design of the TAS, research to develop and evaluate treatments and clinician-administered assessments of alexithymia is warranted. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Exploring the facilitators and barriers to engagement in physical activity for people with multiple sclerosis.

PubMed

Kayes, Nicola M; McPherson, Kathryn M; Schluter, Philip; Taylor, Denise; Leete, Marta; Kolt, Gregory S

2011-01-01

To explore the relationship that cognitive behavioural and other previously identified variables have with physical activity engagement in people with multiple sclerosis (MS). This study adopted a cross-sectional questionnaire design. Participants were 282 individuals with MS. Outcome measures included the Physical Activity Disability Survey--Revised, Cognitive and Behavioural Responses to Symptoms Questionnaire, Barriers to Health Promoting Activities for Disabled Persons Scale, Multiple Sclerosis Self-efficacy Scale, Self-Efficacy for Chronic Diseases Scales and Chalder Fatigue Questionnaire. Multivariable stepwise regression analyses found that greater self-efficacy, greater reported mental fatigue and lower number of perceived barriers to physical activity accounted for a significant proportion of variance in physical activity behaviour, over that accounted for by illness-related variables. Although fear-avoidance beliefs accounted for a significant proportion of variance in the initial analyses, its effect was explained by other factors in the final multivariable analyses. Self-efficacy, mental fatigue and perceived barriers to physical activity are potentially modifiable variables which could be incorporated into interventions designed to improve physical activity engagement. Future research should explore whether a measurement tool tailored to capture beliefs about physical activity identified by people with MS would better predict participation in physical activity.

Environmental risk factors and Parkinson's disease: An umbrella review of meta-analyses.

PubMed

Bellou, Vanesa; Belbasis, Lazaros; Tzoulaki, Ioanna; Evangelou, Evangelos; Ioannidis, John P A

2016-02-01

Parkinson's disease is a neurological disorder with complex pathogenesis implicating both environmental and genetic factors. We aimed to summarise the environmental risk factors that have been studied for potential association with Parkinson's disease, assess the presence of diverse biases, and identify the risk factors with the strongest support. We searched PubMed from inception to September 18, 2015, to identify systematic reviews and meta-analyses of observational studies that examined associations between environmental factors and Parkinson's disease. For each meta-analysis we estimated the summary effect size by random-effects and fixed-effects models, the 95% confidence interval and the 95% prediction interval. We estimated the between-study heterogeneity expressed by I(2), evidence of small-study effects and evidence of excess significance bias. Overall, 75 unique meta-analyses on different risk factors for Parkinson's disease were examined, covering diverse biomarkers, dietary factors, drugs, medical history or comorbid diseases, exposure to toxic environmental agents and habits. 21 of 75 meta-analyses had results that were significant at p < 0.001 by random-effects. Evidence for an association was convincing (more than 1000 cases, p < 10(-6) by random-effects, not large heterogeneity, 95% prediction interval excluding the null value and absence of hints for small-study effects and excess significance bias) for constipation, and physical activity. Many environmental factors have substantial evidence of association with Parkinson's disease, but several, perhaps most, of them may reflect reverse causation, residual confounding, information bias, sponsor conflicts or other caveats. Copyright © 2016. Published by Elsevier Ltd.

Going to extremes: contrasting rates of diversification in a recent radiation of new world passerine birds.

PubMed

Barker, F Keith; Burns, Kevin J; Klicka, John; Lanyon, Scott M; Lovette, Irby J

2013-03-01

Recent analyses suggest that a few major shifts in diversification rate may be enough to explain most of the disparity in diversity among vertebrate lineages. At least one significant increase in diversification rate appears to have occurred within the birds; however, several nested lineages within birds have been identified as hyperdiverse by different studies. A clade containing the finches and relatives (within the avian order Passeriformes), including a large radiation endemic to the New World that comprises ~8% of all bird species, may be the true driver of this rate increase. Understanding the patterns and processes of diversification of this diverse lineage may go a long way toward explaining the apparently rapid diversification rates of both passerines and of birds as a whole. We present the first multilocus phylogenetic analyses of this endemic New World radiation of finch relatives that include sampling of all recognized genera, a relaxed molecular clock analysis of its divergence history, and an analysis of its broad-scale diversification patterns. These analyses recovered 5 major lineages traditionally recognized as avian families, but identified an additional 10 relatively ancient lineages worthy of recognition at the family level. Time-calibrated diversification analyses suggested that at least 3 of the 15 family-level lineages were significantly species poor given the entire group's background diversification rate, whereas at least one-the tanagers of family Thraupidae-appeared significantly more diverse. Lack of an age-diversity relationship within this clade suggests that, due to rapid initial speciation, it may have experienced density-dependent ecological limits on its overall diversity.

Prominence of scientific publications towards peri-implant complications in implantology: A bibliometric analysis using the H-classics method.

PubMed

Chiang, H-S; Huang, R-Y; Weng, P-W; Mau, L-P; Tsai, Y-W C; Chung, M-P; Chung, C-H; Yeh, H-W; Shieh, Y-S; Cheng, W-C

2018-03-01

Current bibliometric analyses of the evolving trends in research scope category across different time periods using the H-classics method in implantology are considerably limited. The purpose of this study was to identify the classic articles in implantology to analyse bibliometric characteristics and associated factors in implantology for the past four decades. H-Classics in implantology were identified within four time periods between 1977 and 2016, based on the h-index from the Scopus ® database. For each article, the principal bibliometric parameters of authorship, geographic origin, country origin, and institute origin, collaboration, centralisation, article type, scope of study and other associated factors were analysed in four time periods. A significant increase in mean numbers of authors per H-Classics was found across time. Both Europe and North America were the most productive region/country and steadily dominated this field in each time period. Collaborations of author, internationally and inter-institutionally had significantly increased across time. A significant decentralisation in authorships, institutes and journals was noted in past four decades. The journal of Clinical Oral Implant Researches has raised its importance for almost 30 years (1987-2016). Research on Complications, peri-implant infection/pathology/therapy had been increasing in production throughout each period. This is the first study to evaluate research trends in implantology in the past 40 years using the H-classics method, which through analysing via principle bibliometric characteristics reflected a historical perspective on evolutionary mainstream in the field. Prominence of research regarding complications may forecast innovative advancements in future. © 2018 John Wiley & Sons Ltd.

Genome-wide analysis of pain-, nerve- and neurotrophin -related gene expression in the degenerating human annulus

PubMed Central

2012-01-01

Background In spite of its high clinical relevance, the relationship between disc degeneration and low back pain is still not well understood. Recent studies have shown that genome-wide gene expression studies utilizing ontology searches provide an efficient and valuable methodology for identification of clinically relevant genes. Here we use this approach in analysis of pain-, nerve-, and neurotrophin-related gene expression patterns in specimens of human disc tissue. Control, non-herniated clinical, and herniated clinical specimens of human annulus tissue were studied following Institutional Review Board approval. Results Analyses were performed on more generated (Thompson grade IV and V) discs vs. less degenerated discs (grades I-III), on surgically operated discs vs. control discs, and on herniated vs. control discs. Analyses of more degenerated vs. less degenerated discs identified significant upregulation of well-recognized pain-related genes (bradykinin receptor B1, calcitonin gene-related peptide and catechol-0-methyltransferase). Nerve growth factor was significantly upregulated in surgical vs. control and in herniated vs. control discs. All three analyses also found significant changes in numerous proinflammatory cytokine- and chemokine-related genes. Nerve, neurotrophin and pain-ontology searches identified many matrix, signaling and functional genes which have known importance in the disc. Immunohistochemistry was utilized to confirm the presence of calcitonin gene-related peptide, catechol-0-methyltransferase and bradykinin receptor B1 at the protein level in the human annulus. Conclusions Findings point to the utility of microarray analyses in identification of pain-, neurotrophin and nerve-related genes in the disc, and point to the importance of future work exploring functional interactions between nerve and disc cells in vitro and in vivo. Nerve, pain and neurotrophin ontology searches identified numerous changes in proinflammatory cytokines and chemokines which also have significant relevance to disc biology. Since the degenerating human disc is primarily an avascular tissue site into which disc cells have contributed high levels of proinflammatory cytokines, these substances are not cleared from the tissue and remain there over time. We hypothesize that as nerves grow into the human annulus, they encounter a proinflammatory cytokine-rich milieu which may sensitize nociceptors and exacerbate pain production. PMID:22963171

Computational toxicology: Its essential role in reducing drug attrition.

PubMed

Naven, R T; Louise-May, S

2015-12-01

Predictive toxicology plays a critical role in reducing the failure rate of new drugs in pharmaceutical research and development. Despite recent gains in our understanding of drug-induced toxicity, however, it is urgent that the utility and limitations of our current predictive tools be determined in order to identify gaps in our understanding of mechanistic and chemical toxicology. Using recently published computational regression analyses of in vitro and in vivo toxicology data, it will be demonstrated that significant gaps remain in early safety screening paradigms. More strategic analyses of these data sets will allow for a better understanding of their domain of applicability and help identify those compounds that cause significant in vivo toxicity but which are currently mis-predicted by in silico and in vitro models. These 'outliers' and falsely predicted compounds are metaphorical lighthouses that shine light on existing toxicological knowledge gaps, and it is essential that these compounds are investigated if attrition is to be reduced significantly in the future. As such, the modern computational toxicologist is more productively engaged in understanding these gaps and driving investigative toxicology towards addressing them. © The Author(s) 2015.

Inference of combinatorial Boolean rules of synergistic gene sets from cancer microarray datasets.

PubMed

Park, Inho; Lee, Kwang H; Lee, Doheon

2010-06-15

Gene set analysis has become an important tool for the functional interpretation of high-throughput gene expression datasets. Moreover, pattern analyses based on inferred gene set activities of individual samples have shown the ability to identify more robust disease signatures than individual gene-based pattern analyses. Although a number of approaches have been proposed for gene set-based pattern analysis, the combinatorial influence of deregulated gene sets on disease phenotype classification has not been studied sufficiently. We propose a new approach for inferring combinatorial Boolean rules of gene sets for a better understanding of cancer transcriptome and cancer classification. To reduce the search space of the possible Boolean rules, we identify small groups of gene sets that synergistically contribute to the classification of samples into their corresponding phenotypic groups (such as normal and cancer). We then measure the significance of the candidate Boolean rules derived from each group of gene sets; the level of significance is based on the class entropy of the samples selected in accordance with the rules. By applying the present approach to publicly available prostate cancer datasets, we identified 72 significant Boolean rules. Finally, we discuss several identified Boolean rules, such as the rule of glutathione metabolism (down) and prostaglandin synthesis regulation (down), which are consistent with known prostate cancer biology. Scripts written in Python and R are available at http://biosoft.kaist.ac.kr/~ihpark/. The refined gene sets and the full list of the identified Boolean rules are provided in the Supplementary Material. Supplementary data are available at Bioinformatics online.

Differential gene expression analysis in glioblastoma cells and normal human brain cells based on GEO database.

PubMed

Wang, Anping; Zhang, Guibin

2017-11-01

The differentially expressed genes between glioblastoma (GBM) cells and normal human brain cells were investigated to performed pathway analysis and protein interaction network analysis for the differentially expressed genes. GSE12657 and GSE42656 gene chips, which contain gene expression profile of GBM were obtained from Gene Expression Omniub (GEO) database of National Center for Biotechnology Information (NCBI). The 'limma' data packet in 'R' software was used to analyze the differentially expressed genes in the two gene chips, and gene integration was performed using 'RobustRankAggreg' package. Finally, pheatmap software was used for heatmap analysis and Cytoscape, DAVID, STRING and KOBAS were used for protein-protein interaction, Gene Ontology (GO) and KEGG analyses. As results: i) 702 differentially expressed genes were identified in GSE12657, among those genes, 548 were significantly upregulated and 154 were significantly downregulated (p<0.01, fold-change >1), and 1,854 differentially expressed genes were identified in GSE42656, among the genes, 1,068 were significantly upregulated and 786 were significantly downregulated (p<0.01, fold-change >1). A total of 167 differentially expressed genes including 100 upregulated genes and 67 downregulated genes were identified after gene integration, and the genes showed significantly different expression levels in GBM compared with normal human brain cells (p<0.05). ii) Interactions between the protein products of 101 differentially expressed genes were identified using STRING and expression network was established. A key gene, called CALM3, was identified by Cytoscape software. iii) GO enrichment analysis showed that differentially expressed genes were mainly enriched in 'neurotransmitter:sodium symporter activity' and 'neurotransmitter transporter activity', which can affect the activity of neurotransmitter transportation. KEGG pathway analysis showed that the differentially expressed genes were mainly enriched in 'protein processing in endoplasmic reticulum', which can affect protein processing in endoplasmic reticulum. The results showed that: i) 167 differentially expressed genes were identified from two gene chips after integration; and ii) protein interaction network was established, and GO and KEGG pathway analyses were successfully performed to identify and annotate the key gene, which provide new insights for the studies on GBN at gene level.

Identifying and characterizing hepatitis C virus hotspots in Massachusetts: a spatial epidemiological approach.

PubMed

Stopka, Thomas J; Goulart, Michael A; Meyers, David J; Hutcheson, Marga; Barton, Kerri; Onofrey, Shauna; Church, Daniel; Donahue, Ashley; Chui, Kenneth K H

2017-04-20

Hepatitis C virus (HCV) infections have increased during the past decade but little is known about geographic clustering patterns. We used a unique analytical approach, combining geographic information systems (GIS), spatial epidemiology, and statistical modeling to identify and characterize HCV hotspots, statistically significant clusters of census tracts with elevated HCV counts and rates. We compiled sociodemographic and HCV surveillance data (n = 99,780 cases) for Massachusetts census tracts (n = 1464) from 2002 to 2013. We used a five-step spatial epidemiological approach, calculating incremental spatial autocorrelations and Getis-Ord Gi* statistics to identify clusters. We conducted logistic regression analyses to determine factors associated with the HCV hotspots. We identified nine HCV clusters, with the largest in Boston, New Bedford/Fall River, Worcester, and Springfield (p < 0.05). In multivariable analyses, we found that HCV hotspots were independently and positively associated with the percent of the population that was Hispanic (adjusted odds ratio [AOR]: 1.07; 95% confidence interval [CI]: 1.04, 1.09) and the percent of households receiving food stamps (AOR: 1.83; 95% CI: 1.22, 2.74). HCV hotspots were independently and negatively associated with the percent of the population that were high school graduates or higher (AOR: 0.91; 95% CI: 0.89, 0.93) and the percent of the population in the "other" race/ethnicity category (AOR: 0.88; 95% CI: 0.85, 0.91). We identified locations where HCV clusters were a concern, and where enhanced HCV prevention, treatment, and care can help combat the HCV epidemic in Massachusetts. GIS, spatial epidemiological and statistical analyses provided a rigorous approach to identify hotspot clusters of disease, which can inform public health policy and intervention targeting. Further studies that incorporate spatiotemporal cluster analyses, Bayesian spatial and geostatistical models, spatially weighted regression analyses, and assessment of associations between HCV clustering and the built environment are needed to expand upon our combined spatial epidemiological and statistical methods.

Gene-diet interaction effects on BMI levels in the Singapore Chinese population.

PubMed

Chang, Xuling; Dorajoo, Rajkumar; Sun, Ye; Han, Yi; Wang, Ling; Khor, Chiea-Chuen; Sim, Xueling; Tai, E-Shyong; Liu, Jianjun; Yuan, Jian-Min; Koh, Woon-Puay; van Dam, Rob M; Friedlander, Yechiel; Heng, Chew-Kiat

2018-02-24

Recent genome-wide association studies (GWAS) have identified 97 body-mass index (BMI) associated loci. We aimed to evaluate if dietary intake modifies BMI associations at these loci in the Singapore Chinese population. We utilized GWAS information from six data subsets from two adult Chinese population (N = 7817). Seventy-eight genotyped or imputed index BMI single nucleotide polymorphisms (SNPs) that passed quality control procedures were available in all datasets. Alternative Healthy Eating Index (AHEI)-2010 score and ten nutrient variables were evaluated. Linear regression analyses between z score transformed BMI (Z-BMI) and dietary factors were performed. Interaction analyses were performed by introducing the interaction term (diet x SNP) in the same regression model. Analysis was carried out in each cohort individually and subsequently meta-analyzed using the inverse-variance weighted method. Analyses were also evaluated with a weighted gene-risk score (wGRS) contructed by BMI index SNPs from recent large-scale GWAS studies. Nominal associations between Z-BMI and AHEI-2010 and some dietary factors were identified (P = 0.047-0.010). The BMI wGRS was robustly associated with Z-BMI (P = 1.55 × 10 - 15 ) but not with any dietary variables. Dietary variables did not significantly interact with the wGRS to modify BMI associations. When interaction analyses were repeated using individual SNPs, a significant association between cholesterol intake and rs4740619 (CCDC171) was identified (β = 0.077, adjP interaction  = 0.043). The CCDC171 gene locus may interact with cholesterol intake to increase BMI in the Singaporean Chinese population, however most known obesity risk loci were not associated with dietary intake and did not interact with diet to modify BMI levels.

Investigation of serum biomarkers in primary gout patients using iTRAQ-based screening.

PubMed

Ying, Ying; Chen, Yong; Zhang, Shun; Huang, Haiyan; Zou, Rouxin; Li, Xiaoke; Chu, Zanbo; Huang, Xianqian; Peng, Yong; Gan, Minzhi; Geng, Baoqing; Zhu, Mengya; Ying, Yinyan; Huang, Zuoan

2018-03-21

Primary gout is a major disease that affects human health; however, its pathogenesis is not well known. The purpose of this study was to identify biomarkers to explore the underlying mechanisms of primary gout. We used the isobaric tags for relative and absolute quantitation (iTRAQ) technique combined with liquid chromatography-tandem mass spectrometry to screen differentially expressed proteins between gout patients and controls. We also identified proteins potentially involved in gout pathogenesis by analysing biological processes, cellular components, molecular functions, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and protein-protein interactions. We further verified some samples using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were carried out using SPSS v. 20.0 and ROC (receiver operating characterstic) curve analyses were carried out using Medcalc software. Two-sided p-values <0.05 were deemed to be statistically significant for all analyses. We identified 95 differentially expressed proteins (50 up-regulated and 45 down-regulated), and selected nine proteins (α-enolase (ENOA), glyceraldehyde-3-phosphate dehydrogenase (G3P), complement component C9 (CO9), profilin-1 (PROF1), lipopolysaccharide-binding protein (LBP), tubulin beta-4A chain (TBB4A), phosphoglycerate kinase (PGK1), glucose-6-phosphate isomerase (G6PI), and transketolase (TKT)) for verification. This showed that the level of TBB4A was significantly higher in primary gout than in controls (p=0.023). iTRAQ technology was useful in the selection of differentially expressed proteins from proteomes, and provides a strong theoretical basis for the study of biomarkers and mechanisms in primary gout. In addition, TBB4A protein may be associated with primary gout.

Association mapping in sunflower (Helianthus annuus L.) reveals independent control of apical vs. basal branching.

PubMed

Nambeesan, Savithri U; Mandel, Jennifer R; Bowers, John E; Marek, Laura F; Ebert, Daniel; Corbi, Jonathan; Rieseberg, Loren H; Knapp, Steven J; Burke, John M

2015-03-11

Shoot branching is an important determinant of plant architecture and influences various aspects of growth and development. Selection on branching has also played an important role in the domestication of crop plants, including sunflower (Helianthus annuus L.). Here, we describe an investigation of the genetic basis of variation in branching in sunflower via association mapping in a diverse collection of cultivated sunflower lines. Detailed phenotypic analyses revealed extensive variation in the extent and type of branching within the focal population. After correcting for population structure and kinship, association analyses were performed using a genome-wide collection of SNPs to identify genomic regions that influence a variety of branching-related traits. This work resulted in the identification of multiple previously unidentified genomic regions that contribute to variation in branching. Genomic regions that were associated with apical and mid-apical branching were generally distinct from those associated with basal and mid-basal branching. Homologs of known branching genes from other study systems (i.e., Arabidopsis, rice, pea, and petunia) were also identified from the draft assembly of the sunflower genome and their map positions were compared to those of associations identified herein. Numerous candidate branching genes were found to map in close proximity to significant branching associations. In sunflower, variation in branching is genetically complex and overall branching patterns (i.e., apical vs. basal) were found to be influenced by distinct genomic regions. Moreover, numerous candidate branching genes mapped in close proximity to significant branching associations. Although the sunflower genome exhibits localized islands of elevated linkage disequilibrium (LD), these non-random associations are known to decay rapidly elsewhere. The subset of candidate genes that co-localized with significant associations in regions of low LD represents the most promising target for future functional analyses.

Common and rare genetic markers of lipid variation in subjects with type 2 diabetes from the ACCORD clinical trial.

PubMed

Marvel, Skylar W; Rotroff, Daniel M; Wagner, Michael J; Buse, John B; Havener, Tammy M; McLeod, Howard L; Motsinger-Reif, Alison A

2017-01-01

Individuals with type 2 diabetes are at an increased risk of cardiovascular disease. Alterations in circulating lipid levels, total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG) are heritable risk factors for cardiovascular disease. Here we conduct a genome-wide association study (GWAS) of common and rare variants to investigate associations with baseline lipid levels in 7,844 individuals with type 2 diabetes from the ACCORD clinical trial. DNA extracted from stored blood samples from ACCORD participants were genotyped using the Affymetrix Axiom Biobank 1 Genotyping Array. After quality control and genotype imputation, association of common genetic variants (CV), defined as minor allele frequency (MAF) ≥ 3%, with baseline levels of TC, LDL, HDL, and TG was tested using a linear model. Rare variant (RV) associations (MAF < 3%) were conducted using a suite of methods that collapse multiple RV within individual genes. Many statistically significant CV ( p  < 1 × 10 -8 ) replicate findings in large meta-analyses in non-diabetic subjects. RV analyses also confirmed findings in other studies, whereas significant RV associations with CNOT2 , HPN-AS1 , and SIRPD appear to be novel ( q  < 0.1). Here we present findings for the largest GWAS of lipid levels in people with type 2 diabetes to date. We identified 17 statistically significant ( p  < 1 × 10 -8 ) associations of CV with lipid levels in 11 genes or chromosomal regions, all of which were previously identified in meta-analyses of mostly non-diabetic cohorts. We also identified 13 associations in 11 genes based on RV, several of which represent novel findings.

Common and rare genetic markers of lipid variation in subjects with type 2 diabetes from the ACCORD clinical trial

PubMed Central

Wagner, Michael J.; Buse, John B.; Havener, Tammy M.; McLeod, Howard L.

2017-01-01

Background Individuals with type 2 diabetes are at an increased risk of cardiovascular disease. Alterations in circulating lipid levels, total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG) are heritable risk factors for cardiovascular disease. Here we conduct a genome-wide association study (GWAS) of common and rare variants to investigate associations with baseline lipid levels in 7,844 individuals with type 2 diabetes from the ACCORD clinical trial. Methods DNA extracted from stored blood samples from ACCORD participants were genotyped using the Affymetrix Axiom Biobank 1 Genotyping Array. After quality control and genotype imputation, association of common genetic variants (CV), defined as minor allele frequency (MAF) ≥ 3%, with baseline levels of TC, LDL, HDL, and TG was tested using a linear model. Rare variant (RV) associations (MAF < 3%) were conducted using a suite of methods that collapse multiple RV within individual genes. Results Many statistically significant CV (p < 1 × 10−8) replicate findings in large meta-analyses in non-diabetic subjects. RV analyses also confirmed findings in other studies, whereas significant RV associations with CNOT2, HPN-AS1, and SIRPD appear to be novel (q < 0.1). Discussion Here we present findings for the largest GWAS of lipid levels in people with type 2 diabetes to date. We identified 17 statistically significant (p < 1 × 10−8) associations of CV with lipid levels in 11 genes or chromosomal regions, all of which were previously identified in meta-analyses of mostly non-diabetic cohorts. We also identified 13 associations in 11 genes based on RV, several of which represent novel findings. PMID:28480134

Identification of Two Heritable Cross-Disorder Endophenotypes for Tourette Syndrome.

PubMed

Darrow, Sabrina M; Hirschtritt, Matthew E; Davis, Lea K; Illmann, Cornelia; Osiecki, Lisa; Grados, Marco; Sandor, Paul; Dion, Yves; King, Robert; Pauls, David; Budman, Cathy L; Cath, Danielle C; Greenberg, Erica; Lyon, Gholson J; Yu, Dongmei; McGrath, Lauren M; McMahon, William M; Lee, Paul C; Delucchi, Kevin L; Scharf, Jeremiah M; Mathews, Carol A

2017-04-01

Phenotypic heterogeneity in Tourette syndrome is partly due to complex genetic relationships among Tourette syndrome, obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD). Identifying symptom-based endophenotypes across diagnoses may aid gene-finding efforts. Assessments for Tourette syndrome, OCD, and ADHD symptoms were conducted in a discovery sample of 3,494 individuals recruited for genetic studies. Symptom-level factor and latent class analyses were conducted in Tourette syndrome families and replicated in an independent sample of 882 individuals. Classes were characterized by comorbidity rates and proportion of parents included. Heritability and polygenic load associated with Tourette syndrome, OCD, and ADHD were estimated. The authors identified two cross-disorder symptom-based phenotypes across analyses: symmetry (symmetry, evening up, checking obsessions; ordering, arranging, counting, writing-rewriting compulsions, repetitive writing tics) and disinhibition (uttering syllables/words, echolalia/palilalia, coprolalia/copropraxia, and obsessive urges to offend/mutilate/be destructive). Heritability estimates for both endophenotypes were high and statistically significant (disinhibition factor=0.35, SE=0.03; symmetry factor=0.39, SE=0.03; symmetry class=0.38, SE=0.10). Mothers of Tourette syndrome probands had high rates of symmetry (49%) but not disinhibition (5%). Polygenic risk scores derived from a Tourette syndrome genome-wide association study (GWAS) were significantly associated with symmetry, while risk scores derived from an OCD GWAS were not. OCD polygenic risk scores were significantly associated with disinhibition, while Tourette syndrome and ADHD risk scores were not. The analyses identified two heritable endophenotypes related to Tourette syndrome that cross traditional diagnostic boundaries. The symmetry phenotype correlated with Tourette syndrome polygenic load and was present in otherwise Tourette-unaffected mothers, suggesting that this phenotype may reflect additional Tourette syndrome (rather than OCD) genetic liability that is not captured by traditional DSM-based diagnoses.

Genome-wide meta-analyses identify novel loci associated with n-3 and n-6 polyunsaturated fatty acid levels in Chinese and European-ancestry populations.

PubMed

Hu, Yao; Li, Huaixing; Lu, Ling; Manichaikul, Ani; Zhu, Jingwen; Chen, Yii-Der I; Sun, Liang; Liang, Shuang; Siscovick, David S; Steffen, Lyn M; Tsai, Michael Y; Rich, Stephen S; Lemaitre, Rozenn N; Lin, Xu

2016-03-15

Epidemiological studies suggest that levels of n-3 and n-6 long-chain polyunsaturated fatty acids are associated with risk of cardio-metabolic outcomes across different ethnic groups. Recent genome-wide association studies in populations of European ancestry have identified several loci associated with plasma and/or erythrocyte polyunsaturated fatty acids. To identify additional novel loci, we carried out a genome-wide association study in two population-based cohorts consisting of 3521 Chinese participants, followed by a trans-ethnic meta-analysis with meta-analysis results from 8962 participants of European ancestry. Four novel loci (MYB, AGPAT4, DGAT2 and PPT2) reached genome-wide significance in the trans-ethnic meta-analysis (log10(Bayes Factor) ≥ 6). Of them, associations of MYB and AGPAT4 with docosatetraenoic acid (log10(Bayes Factor) = 11.5 and 8.69, respectively) also reached genome-wide significance in the Chinese-specific genome-wide association analyses (P = 4.15 × 10(-14) and 4.30 × 10(-12), respectively), while associations of DGAT2 with gamma-linolenic acid (log10(Bayes Factor) = 6.16) and of PPT2 with docosapentaenoic acid (log10(Bayes Factor) = 6.24) were nominally significant in both Chinese- and European-specific genome-wide association analyses (P ≤ 0.003). We also confirmed previously reported loci including FADS1, NTAN1, NRBF2, ELOVL2 and GCKR. Different effect sizes in FADS1 and independent association signals in ELOVL2 were observed. These results provide novel insight into the genetic background of polyunsaturated fatty acids and their differences between Chinese and European populations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Microsatellite markers identify three lineages of Phytophthora ramorum in US nurseries, yet single lineages in US forest and European nursery populations.

PubMed

Ivors, K; Garbelotto, M; Vries, I D E; Ruyter-Spira, C; Te Hekkert, B; Rosenzweig, N; Bonants, P

2006-05-01

Analysis of 12 polymorphic simple sequence repeats identified in the genome sequence of Phytophthora ramorum, causal agent of 'sudden oak death', revealed genotypic diversity to be significantly higher in nurseries (91% of total) than in forests (18% of total). Our analysis identified only two closely related genotypes in US forests, while the genetic structure of populations from European nurseries was of intermediate complexity, including multiple, closely related genotypes. Multilocus analysis determined populations in US forests reproduce clonally and are likely descendants of a single introduced individual. The 151 isolates analysed clustered in three clades. US forest and European nursery isolates clustered into two distinct clades, while one isolate from a US nursery belonged to a third novel clade. The combined microsatellite, sequencing and morphological analyses suggest the three clades represent distinct evolutionary lineages. All three clades were identified in some US nurseries, emphasizing the role of commercial plant trade in the movement of this pathogen.

Proteomic Analyses of Corneal Tissue Subjected to Alkali Exposure

PubMed Central

Parikh, Toral; Eisner, Natalie; Venugopalan, Praseeda; Yang, Qin; Lam, Byron L.

2011-01-01

Purpose. To determine whether exposure to alkaline chemicals results in predictable changes in corneal protein profile. To determine whether protein profile changes are indicative of severity and duration of alkali exposure. Methods. Enucleated bovine and porcine (n = 59 each) eyes were used for exposure to sodium, ammonium, and calcium hydroxide, respectively. Eyes were subjected to fluorescein staining, 5-bromo-2′-deoxy-uridine (BrdU) labeling. Excised cornea was subjected to protein extraction, spectrophotometric determination of protein amount, dynamic light scattering and SDS-PAGE profiling, mass spectrometric protein identification, and iTRAQ-labeled quantification. Select identified proteins were subjected to Western blot and immunohistochemical analyses. Results. Alkali exposure resulted in lower protein extractability from corneal tissue. Elevated aggregate formation was found with strong alkali exposure (sodium hydroxide>ammonium, calcium hydroxide), even with a short duration of exposure compared with controls. The protein yield after exposure varied as a function of postexposure time. Protein profiles changed because of alkali exposure. Concentration and strength of the alkali affected the profile change significantly. Mass spectrometry identified 15 proteins from different bands with relative quantification. Plexin D1 was identified for the first time in the cornea at a protein level that was further confirmed by Western blot and immunohistochemical analyses. Conclusions. Exposure to alkaline chemicals results in predictable and reproducible changes in corneal protein profile. Stronger alkali, longer durations, or both, of exposure resulted in lower yields and significant protein profile changes compared with controls. PMID:20861482

Identification of the active compounds and significant pathways of yinchenhao decoction based on network pharmacology

PubMed Central

Huang, Jihan; Cheung, Fan; Tan, Hor-Yue; Hong, Ming; Wang, Ning; Yang, Juan; Feng, Yibin; Zheng, Qingshan

2017-01-01

Yinchenhao decoction (YCHD) is a traditional Chinese medicine formulation, which has been widely used for the treatment of jaundice for 2,000 years. Currently, YCHD is used to treat various liver disorders and metabolic diseases, however its chemical/pharmacologic profiles remain to be elucidated. The present study identified the active compounds and significant pathways of YCHD based on network pharmacology. All of the chemical ingredients of YCHD were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. Absorption, distribution, metabolism and excretion screening with oral bioavailability (OB) screening, drug-likeness (DL) and intestinal epithelial permeability (Caco-2) evaluation were applied to discover the bioactive compounds in YCHD. Following this, target prediction, pathway identification and network construction were employed to clarify the mechanism of action of YCHD. Following OB screening, and evaluation of DL and Caco-2, 34 compounds in YCHD were identified as potential active ingredients, of which 30 compounds were associated with 217 protein targets. A total of 31 significant pathways were obtained by performing enrichment analyses of 217 proteins using the JEPETTO 3.x plugin, and 16 classes of gene-associated diseases were revealed by performing enrichment analyses using Database for Annotation, Visualization and Integrated Discovery v6.7. The present study identified potential active compounds and significant pathways in YCHD. In addition, the mechanism of action of YCHD in the treatment of various diseases through multiple pathways was clarified. PMID:28791364

English soccer teams' aggressive behavior when playing away from home.

PubMed

Thomas, Sion; Reeves, Colin; Smith, Andrew

2006-04-01

Speculation about key factors affecting home advantage still exists. The present study investigated aggressive behavior amongst English Football Premiership (soccer) players and its relation to home advantage. The frequency of aggressive behaviour, identified by the award of a penalty or disciplinary card (yellow for caution or red for dismissal) was analysed over 2000-2003. Chi-square analyses assessed whether a greater frequency of aggressive behavior was performed by teams away from home. In decided matches, teams playing away received significantly more cautions (yellow cards) than home teams. A further analysis of tied matches indicated that away teams received significantly more cautions (yellow cards) than home teams. No significant differences between home and away teams were found for dismissals and penalties awarded. Reasons for these findings are considered.

Changes in the highest frequency of breath sounds without wheezing during methacholine inhalation challenge in children.

PubMed

Habukawa, Chizu; Murakami, Katsumi; Mochizuki, Hiroyuki; Takami, Satoru; Muramatsu, Reiko; Tadaki, Hiromi; Hagiwara, Satomi; Mizuno, Takahisa; Arakawa, Hirokazu; Nagasaka, Yukio

2010-04-01

It is difficult for clinicians to identify changes in breath sounds caused by bronchoconstriction when wheezing is not audible. A breath sound analyser can identify changes in the frequency of breath sounds caused by bronchoconstriction. The present study aimed to identify the changes in the frequency of breath sounds during bronchoconstriction and bronchodilatation using a breath sound analyser. Thirty-six children (8.2 +/- 3.7 years; males : females, 22 : 14) underwent spirometry, methacholine inhalation challenge and breath sound analysis. Methacholine inhalation challenge was performed and baseline respiratory resistance, minimum dose of methacholine (bronchial sensitivity) and speed of bronchoconstriction in response to methacholine (Sm: bronchial reactivity) were calculated. The highest frequency of inspiratory breath sounds (HFI), the highest frequency of expiratory breath sounds (HFE) and the percentage change in HFI and HFE were determined. The HFI and HFE were compared before methacholine inhalation (pre-HFI and pre-HFE), when respiratory resistance reached double the baseline value (max HFI and max HFE), and after bronchodilator inhalation (post-HFI and post-HFE). Breath sounds increased during methacholine-induced bronchoconstriction. Max HFI was significantly greater than pre-HFI (P < 0.001), and decreased to the basal level after bronchodilator inhalation. Post-HFI was significantly lower than max HFI (P < 0.001). HFI and HFE were also significantly changed (P < 0.001). The percentage change in HFI showed a significant correlation with the speed of bronchoconstriction in response to methacholine (P = 0.007). Methacholine-induced bronchoconstriction significantly increased HFI, and the increase in HFI was correlated with bronchial reactivity.

Construction accidents: identification of the main associations between causes, mechanisms and stages of the construction process.

PubMed

Carrillo-Castrillo, Jesús A; Trillo-Cabello, Antonio F; Rubio-Romero, Juan C

2017-06-01

To identify the most frequent causes of accidents in the construction sector in order to help safety practitioners in the task of prioritizing preventive actions depending on the stage of construction. Official accident investigation reports are analysed. A causation pattern is identified with the proportion of causes in each of the different possible groups of causes. Significant associations of the types of causes with accident mechanisms and construction stages have been identified. Significant differences have been found in accident causation depending on the mechanism of the accident and the construction stage ongoing. These results should be used to prioritize preventive actions to combat the most likely causes for each accident mechanism and construction stage.

Pathway Analysis in Attention Deficit Hyperactivity Disorder: An Ensemble Approach

PubMed Central

Mooney, Michael A.; McWeeney, Shannon K.; Faraone, Stephen V.; Hinney, Anke; Hebebrand, Johannes; Nigg, Joel T.; Wilmot, Beth

2016-01-01

Despite a wealth of evidence for the role of genetics in attention deficit hyperactivity disorder (ADHD), specific and definitive genetic mechanisms have not been identified. Pathway analyses, a subset of gene-set analyses, extend the knowledge gained from genome-wide association studies (GWAS) by providing functional context for genetic associations. However, there are numerous methods for association testing of gene sets and no real consensus regarding the best approach. The present study applied six pathway analysis methods to identify pathways associated with ADHD in two GWAS datasets from the Psychiatric Genomics Consortium. Methods that utilize genotypes to model pathway-level effects identified more replicable pathway associations than methods using summary statistics. In addition, pathways implicated by more than one method were significantly more likely to replicate. A number of brain-relevant pathways, such as RhoA signaling, glycosaminoglycan biosynthesis, fibroblast growth factor receptor activity, and pathways containing potassium channel genes, were nominally significant by multiple methods in both datasets. These results support previous hypotheses about the role of regulation of neurotransmitter release, neurite outgrowth and axon guidance in contributing to the ADHD phenotype and suggest the value of cross-method convergence in evaluating pathway analysis results. PMID:27004716

Procurement of a Nanoindenter for Structure-Function Analyses of Biologically Inspired High Performance Composite Materials

DTIC Science & Technology

2012-01-13

abalone shell (Figures 3, 4). Here, we can see that the damage is significantly mitigated in the nacreous regions while cracks formed in the Calcitic...properties. Page 5 / 11 Identifying the crack propagation mechanisms helps to identify new designs for impact resistant materials, so the...human tooth from dentin – dentin/ enamel junction – enamel . It is clear that higher resolution scans are necessary to interrogate local structure

Meta-Analysis in Genome-Wide Association Datasets: Strategies and Application in Parkinson Disease

PubMed Central

Evangelou, Evangelos; Maraganore, Demetrius M.; Ioannidis, John P.A.

2007-01-01

Background Genome-wide association studies hold substantial promise for identifying common genetic variants that regulate susceptibility to complex diseases. However, for the detection of small genetic effects, single studies may be underpowered. Power may be improved by combining genome-wide datasets with meta-analytic techniques. Methodology/Principal Findings Both single and two-stage genome-wide data may be combined and there are several possible strategies. In the two-stage framework, we considered the options of (1) enhancement of replication data and (2) enhancement of first-stage data, and then, we also considered (3) joint meta-analyses including all first-stage and second-stage data. These strategies were examined empirically using data from two genome-wide association studies (three datasets) on Parkinson disease. In the three strategies, we derived 12, 5, and 49 single nucleotide polymorphisms that show significant associations at conventional levels of statistical significance. None of these remained significant after conservative adjustment for the number of performed analyses in each strategy. However, some may warrant further consideration: 6 SNPs were identified with at least 2 of the 3 strategies and 3 SNPs [rs1000291 on chromosome 3, rs2241743 on chromosome 4 and rs3018626 on chromosome 11] were identified with all 3 strategies and had no or minimal between-dataset heterogeneity (I2 = 0, 0 and 15%, respectively). Analyses were primarily limited by the suboptimal overlap of tested polymorphisms across different datasets (e.g., only 31,192 shared polymorphisms between the two tier 1 datasets). Conclusions/Significance Meta-analysis may be used to improve the power and examine the between-dataset heterogeneity of genome-wide association studies. Prospective designs may be most efficient, if they try to maximize the overlap of genotyping platforms and anticipate the combination of data across many genome-wide association studies. PMID:17332845

Childhood cancer in small geographical areas and proximity to air-polluting industries.

PubMed

Ortega-García, Juan A; López-Hernández, Fernando A; Cárceles-Álvarez, Alberto; Fuster-Soler, José L; Sotomayor, Diana I; Ramis, Rebeca

2017-07-01

Pediatric cancer has been associated with exposure to certain environmental carcinogens. The purpose of this work is to analyse the relationship between environmental pollution and pediatric cancer risk. We analysed all incidences of pediatric cancer (<15) diagnosed in a Spanish region during the period 1998-2015. The place of residence of each patient and the exact geographical coordinates of main industrial facilities was codified in order to analyse the spatial distribution of cases of cancer in relation to industrial areas. Focal tests and focused Scan methodology were used for the identification of high-incidence-rate spatial clusters around the main industrial pollution foci. The crude rate for the period was 148.0 cases per 1,000,0000 children. The incidence of pediatric cancer increased significantly along the period of study. With respect to spatial distribution, results showed significant high incidence around some industrial pollution foci group and the Scan methodology identify spatial clustering. We observe a global major incidence of non Hodgkin lymphomas (NHL) considering all foci, and high incidence of Sympathetic Nervous System Tumour (SNST) around Energy and Electric and organic and inorganic chemical industries foci group. In the analysis foci to foci, the focused Scan test identifies several significant spatial clusters. Particularly, three significant clusters were identified: the first of SNST was around energy-generating chemical industries (2 cases versus the expected 0.26), another of NHL was around residue-valorisation plants (5 cases versus the expected 0.91) and finally one cluster of Hodgkin lymphoma around building materials (3 cases versus the expected 2.2) CONCLUSION: Results suggest a possible association between proximity to certain industries and pediatric cancer risk. More evidences are necessary before establishing the relationship between industrial pollution and pediatric cancer incidence. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Continuing difficulties in interpreting CNV data: lessons from a genome-wide CNV association study of Australian HNPCC/lynch syndrome patients.

PubMed

Talseth-Palmer, Bente A; Holliday, Elizabeth G; Evans, Tiffany-Jane; McEvoy, Mark; Attia, John; Grice, Desma M; Masson, Amy L; Meldrum, Cliff; Spigelman, Allan; Scott, Rodney J

2013-03-26

Hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome (LS) is a cancer syndrome characterised by early-onset epithelial cancers, especially colorectal cancer (CRC) and endometrial cancer. The aim of the current study was to use SNP-array technology to identify genomic aberrations which could contribute to the increased risk of cancer in HNPCC/LS patients. Individuals diagnosed with HNPCC/LS (100) and healthy controls (384) were genotyped using the Illumina Human610-Quad SNP-arrays. Copy number variation (CNV) calling and association analyses were performed using Nexus software, with significant results validated using QuantiSNP. TaqMan Copy-Number assays were used for verification of CNVs showing significant association with HNPCC/LS identified by both software programs. We detected copy number (CN) gains associated with HNPCC/LS status on chromosome 7q11.21 (28% cases and 0% controls, Nexus; p =3.60E-20 and QuantiSNP; p < 1.00E-16) and 16p11.2 (46% in cases, while a CN loss was observed in 23% of controls, Nexus; p = 4.93E-21 and QuantiSNP; p = 5.00E-06) via in silico analyses. TaqMan Copy-Number assay was used for validation of CNVs showing significant association with HNPCC/LS. In addition, CNV burden (total CNV length, average CNV length and number of observed CNV events) was significantly greater in cases compared to controls. A greater CNV burden was identified in HNPCC/LS cases compared to controls supporting the notion of higher genomic instability in these patients. One intergenic locus on chromosome 7q11.21 is possibly associated with HNPCC/LS and deserves further investigation. The results from this study highlight the complexities of fluorescent based CNV analyses. The inefficiency of both CNV detection methods to reproducibly detect observed CNVs demonstrates the need for sequence data to be considered alongside intensity data to avoid false positive results.

Genome-wide association mapping of frost tolerance in barley (Hordeum vulgare L.)

PubMed Central

2013-01-01

Background Frost tolerance is a key trait with economic and agronomic importance in barley because it is a major component of winter hardiness, and therefore limits the geographical distribution of the crop and the effective transfer of quality traits between spring and winter crop types. Three main frost tolerance QTL (Fr-H1, Fr-H2 and Fr-H3) have been identified from bi-parental genetic mapping but it can be argued that those mapping populations only capture a portion of the genetic diversity of the species. A genetically broad dataset consisting of 184 genotypes, representative of the barley gene pool cultivated in the Mediterranean basin over an extended time period, was genotyped with 1536 SNP markers. Frost tolerance phenotype scores were collected from two trial sites, Foradada (Spain) and Fiorenzuola (Italy) and combined with the genotypic data in genome wide association analyses (GWAS) using Eigenstrat and kinship approaches to account for population structure. Results GWAS analyses identified twelve and seven positive SNP associations at Foradada and Fiorenzuola, respectively, using Eigenstrat and six and four, respectively, using kinship. Linkage disequilibrium analyses of the significant SNP associations showed they are genetically independent. In the kinship analysis, two of the significant SNP associations were tightly linked to the Fr-H2 and HvBmy loci on chromosomes 5H and 4HL, respectively. The other significant kinship associations were located in genomic regions that have not previously been associated with cold stress. Conclusions Haplotype analysis revealed that most of the significant SNP loci are fixed in the winter or facultative types, while they are freely segregating within the un-adapted spring barley genepool. Although there is a major interest in detecting new variation to improve frost tolerance of available winter and facultative types, from a GWAS perspective, working within the un-adapted spring germplasm pool is an attractive alternative strategy which would minimize statistical issues, simplify the interpretation of the data and identify phenology independent genetic determinants of frost tolerance. PMID:23802597

Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS.

PubMed

Swerdlow, Neal R; Light, Gregory A; Sprock, Joyce; Calkins, Monica E; Green, Michael F; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Nuechterlein, Keith H; Radant, Allen D; Ray, Amrita; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Stone, William S; Sugar, Catherine A; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Braff, David L

2014-02-01

Startle inhibition by weak prepulses (PPI) is studied to understand the biology of information processing in schizophrenia patients and healthy comparison subjects (HCS). The Consortium on the Genetics of Schizophrenia (COGS) identified associations between PPI and single nucleotide polymorphisms in schizophrenia probands and unaffected relatives, and linkage analyses extended evidence for the genetics of PPI deficits in schizophrenia in the COGS-1 family study. These findings are being extended in a 5-site "COGS-2" study of 1800 patients and 1200 unrelated HCS to facilitate genetic analyses. We describe a planned interim analysis of COGS-2 PPI data. Eyeblink startle was measured in carefully screened HCS and schizophrenia patients (n=1402). Planned analyses of PPI (60 ms intervals) assessed effects of diagnosis, sex and test site, PPI-modifying effects of medications and smoking, and relationships between PPI and neurocognitive measures. 884 subjects met strict inclusion criteria. ANOVA of PPI revealed significant effects of diagnosis (p=0.0005) and sex (p<0.002), and a significant diagnosis×test site interaction. HCS>schizophrenia PPI differences were greatest among patients not taking 2nd generation antipsychotics, and were independent of smoking status. Modest but significant relationships were detected between PPI and performance in specific neurocognitive measures. The COGS-2 multi-site study detects schizophrenia-related PPI deficits reported in single-site studies, including patterns related to diagnosis, prepulse interval, sex, medication and other neurocognitive measures. Site differences were detected and explored. The target COGS-2 schizophrenia "endophenotype" of reduced PPI should prove valuable for identifying and confirming schizophrenia risk genes in future analyses. Copyright © 2013 Elsevier B.V. All rights reserved.

Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS

PubMed Central

Swerdlow, Neal R.; Light, Gregory A.; Sprock, Joyce; Calkins, Monica E.; Green, Michael F.; Greenwood, Tiffany A.; Gur, Raquel E.; Gur, Ruben C.; Lazzeroni, Laura C.; Nuechterlein, Keith H.; Radant, Allen D.; Ray, Amrita; Seidman, Larry J.; Siever, Larry J.; Silverman, Jeremy M.; Stone, William S.; Sugar, Catherine A.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Braff, David L.

2014-01-01

Background Startle inhibition by weak prepulses (PPI) is studied to understand the biology of information processing in schizophrenia patients and healthy comparison subjects (HCS). The Consortium on the Genetics of Schizophrenia (COGS) identified associations between PPI and single nucleotide polymorphisms in schizophrenia probands and unaffected relatives, and linkage analyses extended evidence for the genetics of PPI deficits in schizophrenia in the COGS-1 family study. These findings are being extended in a 5-site “COGS-2” study of 1800 patients and 1200 unrelated HCS to facilitate genetic analyses. We describe a planned interim analysis of COGS-2 PPI data. Methods Eyeblink startle was measured in carefully screened HCS and schizophrenia patients (n=1402). Planned analyses of PPI (60 ms intervals) assessed effects of diagnosis, sex and test site, PPI-modifying effects of medications and smoking, and relationships between PPI and neurocognitive measures. Results 884 subjects met strict inclusion criteria. ANOVA of PPI revealed significant effects of diagnosis (p=0.0005) and sex (p<0.002), and a significant diagnosis × test site interaction. HCS > schizophrenia PPI differences were greatest among patients not taking 2nd generation antipsychotics, and were independent of smoking status. Modest but significant relationships were detected between PPI and performance in specific neurocognitive measures. Discussion The COGS-2 multi-site study detects schizophrenia-related PPI deficits reported in single-site studies, including patterns related to diagnosis, prepulse interval, sex, medication and other neurocognitive measures. Site differences were detected and explored. The target COGS-2 schizophrenia “endophenotype” of reduced PPI should prove valuable for identifying and confirming schizophrenia risk genes in future analyses. PMID:24405980

Pre-clinical cognitive phenotypes for Alzheimer disease: a latent profile approach.

PubMed

Hayden, Kathleen M; Kuchibhatla, Maragatha; Romero, Heather R; Plassman, Brenda L; Burke, James R; Browndyke, Jeffrey N; Welsh-Bohmer, Kathleen A

2014-11-01

Cognitive profiles for pre-clinical Alzheimer disease (AD) can be used to identify groups of individuals at risk for disease and better characterize pre-clinical disease. Profiles or patterns of performance as pre-clinical phenotypes may be more useful than individual test scores or measures of global decline. To evaluate patterns of cognitive performance in cognitively normal individuals to derive latent profiles associated with later onset of disease using a combination of factor analysis and latent profile analysis. The National Alzheimer Coordinating Centers collect data, including a battery of neuropsychological tests, from participants at 29 National Institute on Aging-funded Alzheimer Disease Centers across the United States. Prior factor analyses of this battery demonstrated a four-factor structure comprising memory, attention, language, and executive function. Factor scores from these analyses were used in a latent profile approach to characterize cognition among a group of cognitively normal participants (N = 3,911). Associations between latent profiles and disease outcomes an average of 3 years later were evaluated with multinomial regression models. Similar analyses were used to determine predictors of profile membership. Four groups were identified; each with distinct characteristics and significantly associated with later disease outcomes. Two groups were significantly associated with development of cognitive impairment. In post hoc analyses, both the Trail Making Test Part B, and a contrast score (Delayed Recall - Trails B), significantly predicted group membership and later cognitive impairment. Latent profile analysis is a useful method to evaluate patterns of cognition in large samples for the identification of preclinical AD phenotypes; comparable results, however, can be achieved with very sensitive tests and contrast scores. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Using Co-authorship Networks to Map and Analyse Global Neglected Tropical Disease Research with an Affiliation to Germany

PubMed Central

Bender, Max Ernst; Edwards, Suzanne; von Philipsborn, Peter; Steinbeis, Fridolin; Keil, Thomas; Tinnemann, Peter

2015-01-01

Background Research on Neglected Tropical Diseases (NTDs) has increased in recent decades, and significant need-gaps in diagnostic and treatment tools remain. Analysing bibliometric data from published research is a powerful method for revealing research efforts, partnerships and expertise. We aim to identify and map NTD research networks in Germany and their partners abroad to enable an informed and transparent evaluation of German contributions to NTD research. Methodology/Principal Findings A SCOPUS database search for articles with German author affiliations that were published between 2002 and 2012 was conducted for kinetoplastid and helminth diseases. Open-access tools were used for data cleaning and scientometrics (OpenRefine), geocoding (OpenStreetMaps) and to create (Table2Net), visualise and analyse co-authorship networks (Gephi). From 26,833 publications from around the world that addressed 11 diseases, we identified 1,187 (4.4%) with at least one German author affiliation, and we processed 972 publications for the five most published-about diseases. Of those, we extracted 4,007 individual authors and 863 research institutions to construct co-author networks. The majority of co-authors outside Germany were from high-income countries and Brazil. Collaborations with partners on the African continent remain scattered. NTD research within Germany was distributed among 220 research institutions. We identified strong performers on an individual level by using classic parameters (number of publications, h-index) and social network analysis parameters (betweenness centrality). The research network characteristics varied strongly between diseases. Conclusions/Significance The share of NTD publications with German affiliations is approximately half of its share in other fields of medical research. This finding underlines the need to identify barriers and expand Germany’s otherwise strong research activities towards NTDs. A geospatial analysis of research collaborations with partners abroad can support decisions to strengthen research capacity, particularly in low- and middle-income countries, which were less involved in collaborations than high-income countries. Identifying knowledge hubs within individual researcher networks complements traditional scientometric indicators that are used to identify opportunities for collaboration. Using free tools to analyse research processes and output could facilitate data-driven health policies. Our findings contribute to the prioritisation of efforts in German NTD research at a time of impending local and global policy decisions. PMID:26719978

Functional genomics annotation of a statistical epistasis network associated with bladder cancer susceptibility.

PubMed

Hu, Ting; Pan, Qinxin; Andrew, Angeline S; Langer, Jillian M; Cole, Michael D; Tomlinson, Craig R; Karagas, Margaret R; Moore, Jason H

2014-04-11

Several different genetic and environmental factors have been identified as independent risk factors for bladder cancer in population-based studies. Recent studies have turned to understanding the role of gene-gene and gene-environment interactions in determining risk. We previously developed the bioinformatics framework of statistical epistasis networks (SEN) to characterize the global structure of interacting genetic factors associated with a particular disease or clinical outcome. By applying SEN to a population-based study of bladder cancer among Caucasians in New Hampshire, we were able to identify a set of connected genetic factors with strong and significant interaction effects on bladder cancer susceptibility. To support our statistical findings using networks, in the present study, we performed pathway enrichment analyses on the set of genes identified using SEN, and found that they are associated with the carcinogen benzo[a]pyrene, a component of tobacco smoke. We further carried out an mRNA expression microarray experiment to validate statistical genetic interactions, and to determine if the set of genes identified in the SEN were differentially expressed in a normal bladder cell line and a bladder cancer cell line in the presence or absence of benzo[a]pyrene. Significant nonrandom sets of genes from the SEN were found to be differentially expressed in response to benzo[a]pyrene in both the normal bladder cells and the bladder cancer cells. In addition, the patterns of gene expression were significantly different between these two cell types. The enrichment analyses and the gene expression microarray results support the idea that SEN analysis of bladder in population-based studies is able to identify biologically meaningful statistical patterns. These results bring us a step closer to a systems genetic approach to understanding cancer susceptibility that integrates population and laboratory-based studies.

Effective techniques for changing physical activity and healthy eating intentions and behaviour: A systematic review and meta-analysis.

PubMed

McDermott, Máirtín S; Oliver, Madalyn; Iverson, Don; Sharma, Rajeev

2016-11-01

The primary aim of this study was to review the evidence on the impact of a change in intention on behaviour and to identify (1) behaviour change techniques (BCTs) associated with changes in intention and (2) whether the same BCTs are also associated with changes in behaviour. A systematic review was conducted to identify interventions that produced a significant change in intention and assessed the impact of this change on behaviour at a subsequent time point. Each intervention was coded using a taxonomy of BCTs targeting healthy eating and physical activity. A series of meta-regression analyses were conducted to identify effective BCTs. In total, 25 reports were included. Interventions had a medium-to-large effect on intentions (d +  = 0.64) and a small-to-medium effect (d +  = 0.41) on behaviour. One BCT, 'provide information on the consequences of behaviour in general', was significantly associated with a positive change in intention. One BCT, 'relapse prevention/coping planning', was associated with a negative change in intention. No BCTs were found to have significant positive effects on behaviour. However, one BCT, 'provide feedback on performance', was found to have a significant negative effect. BCTs aligned with social cognitive theory were found to have significantly greater positive effects on intention (d +  = 0.83 vs. 0.56, p < .05), but not behaviour (d +  = 0.35 vs. 0.23, ns), than those aligned with the theory of planned behaviour. Although the included studies support the notion that a change in intention is associated with a change in behaviour, this review failed to produce evidence on how to facilitate behaviour change through a change in intention. Larger meta-analyses incorporating interventions targeting a broader range of behaviours may be warranted. Statement of contribution What is already known on this subject? Prior research on the causal relationship between intention and behaviour has produced mixed findings. Further experimental research to determine the precise nature of these variables is clearly warranted. However, precise guidance on how to change intention is still lacking. What does this study add? This study aimed to identify behaviour change techniques associated with changes in intention and behaviour. Techniques with positive effects on intention were identified; however, these did not have an impact on behaviour. Larger meta-analyses incorporating interventions targeting a broader range of behaviours may be warranted. © 2016 The British Psychological Society.

Using exploratory data analysis to identify and predict patterns of human Lyme disease case clustering within a multistate region, 2010-2014.

PubMed

Hendricks, Brian; Mark-Carew, Miguella

2017-02-01

Lyme disease is the most commonly reported vectorborne disease in the United States. The objective of our study was to identify patterns of Lyme disease reporting after multistate inclusion to mitigate potential border effects. County-level human Lyme disease surveillance data were obtained from Kentucky, Maryland, Ohio, Pennsylvania, Virginia, and West Virginia state health departments. Rate smoothing and Local Moran's I was performed to identify clusters of reporting activity and identify spatial outliers. A logistic generalized estimating equation was performed to identify significant associations in disease clustering over time. Resulting analyses identified statistically significant (P=0.05) clusters of high reporting activity and trends over time. High reporting activity aggregated near border counties in high incidence states, while low reporting aggregated near shared county borders in non-high incidence states. Findings highlight the need for exploratory surveillance approaches to describe the extent to which state level reporting affects accurate estimation of Lyme disease progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparative Proteomic Analysis of Carbonylated Proteins from the Striatum and Cortex of Pesticide-Treated Mice

PubMed Central

Coughlan, Christina; Walker, Douglas I.; Lohr, Kelly M.; Richardson, Jason R.; Saba, Laura M.; Caudle, W. Michael; Fritz, Kristofer S.; Roede, James R.

2015-01-01

Epidemiological studies indicate exposures to the herbicide paraquat (PQ) and fungicide maneb (MB) are associated with increased risk of Parkinson's disease (PD). Oxidative stress appears to be a premier mechanism that underlies damage to the nigrostriatal dopamine system in PD and pesticide exposure. Enhanced oxidative stress leads to lipid peroxidation and production of reactive aldehydes; therefore, we conducted proteomic analyses to identify carbonylated proteins in the striatum and cortex of pesticide-treated mice in order to elucidate possible mechanisms of toxicity. Male C57BL/6J mice were treated biweekly for 6 weeks with saline, PQ (10 mg/kg), MB (30 mg/kg), or the combination of PQ and MB (PQMB). Treatments resulted in significant behavioral alterations in all treated mice and depleted striatal dopamine in PQMB mice. Distinct differences in 4-hydroxynonenal-modified proteins were observed in the striatum and cortex. Proteomic analyses identified carbonylated proteins and peptides from the cortex and striatum, and pathway analyses revealed significant enrichment in a variety of KEGG pathways. Further analysis showed enrichment in proteins of the actin cytoskeleton in treated samples, but not in saline controls. These data indicate that treatment-related effects on cytoskeletal proteins could alter proper synaptic function, thereby resulting in impaired neuronal function and even neurodegeneration. PMID:26345149

The Influence of Metabolic Syndrome and Sex on the DNA Methylome in Schizophrenia

PubMed Central

Lines, Brittany N.

2018-01-01

Introduction The mechanism by which metabolic syndrome occurs in schizophrenia is not completely known; however, previous work suggests that changes in DNA methylation may be involved which is further influenced by sex. Within this study, the DNA methylome was profiled to identify altered methylation associated with metabolic syndrome in a schizophrenia population on atypical antipsychotics. Methods Peripheral blood from schizophrenia subjects was utilized for DNA methylation analyses. Discovery analyses (n = 96) were performed using an epigenome-wide analysis on the Illumina HumanMethylation450K BeadChip based on metabolic syndrome diagnosis. A secondary discovery analysis was conducted based on sex. The top hits from the discovery analyses were assessed in an additional validation set (n = 166) using site-specific methylation pyrosequencing. Results A significant increase in CDH22 gene methylation in subjects with metabolic syndrome was identified in the overall sample. Additionally, differential methylation was found within the MAP3K13 gene in females and the CCDC8 gene within males. Significant differences in methylation were again observed for the CDH22 and MAP3K13 genes, but not CCDC8, in the validation sample set. Conclusions This study provides preliminary evidence that DNA methylation may be associated with metabolic syndrome and sex in schizophrenia. PMID:29850476

Validation of PDE9A Gene Identified in GWAS Showing Strong Association with Milk Production Traits in Chinese Holstein.

PubMed

Yang, Shao-Hua; Bi, Xiao-Jun; Xie, Yan; Li, Cong; Zhang, Sheng-Li; Zhang, Qin; Sun, Dong-Xiao

2015-11-05

Phosphodiesterase9A (PDE9A) is a cyclic guanosine monophosphate (cGMP)-specific enzyme widely expressed among the tissues, which is important in activating cGMP-dependent signaling pathways. In our previous genome-wide association study, a single nucleotide polymorphism (SNP) (BTA-55340-no-rs(b)) located in the intron 14 of PDE9A, was found to be significantly associated with protein yield. In addition, we found that PDE9A was highly expressed in mammary gland by analyzing its mRNA expression in different tissues. The objectives of this study were to identify genetic polymorphisms of PDE9A and to determine the effects of these variants on milk production traits in dairy cattle. DNA sequencing identified 11 single nucleotide polymorphisms (SNPs) and six SNPs in 5' regulatory region were genotyped to test for the subsequent association analyses. After Bonferroni correction for multiple testing, all these identified SNPs were statistically significant for one or more milk production traits (p < 0.0001~0.0077). Interestingly, haplotype-based association analysis revealed similar effects on milk production traits (p < 0.01). In follow-up RNA expression analyses, two SNPs (c.-1376 G>A, c.-724 A>G) were involved in the regulation of gene expression. Consequently, our findings provide confirmatory evidences for associations of PDE9A variants with milk production traits and these identified SNPs may serve as genetic markers to accelerate Chinese Holstein breeding program.

Meaning profiles of dwellings, pathways, and metaphors in design: implications for education

NASA Astrophysics Data System (ADS)

Casakin, Hernan; Kreitler, Shulamith

2017-11-01

The study deals with the roles and interrelations of the meaning-based assessments of dwellings, pathways and metaphors in design performance. It is grounded in the Meaning Theory [Kreitler, S., and H. Kreitler. 1990. The Cognitive Foundations of Personality Traits. New York: Plenum], which enables identifying the cognitive contents and processes underlying cognitive performance in different domains, thus rendering them more accessible to educational training. The objectives were to identify the components of the meaning profiles of dwellings, pathways, and metaphors as perceived by design students; to analyse their interrelations; and to examine which of the identified components of these constructs serve as best predictors of design performance aided by the use of metaphors. Participants were administered a design task and questionnaires about the Dimensional Profiles of Dwellings, Pathways, and Metaphors, based on the meaning system. Factors based on the factor analyses of the responses to the three questionnaires were used in regression analyses as predictors of the performance score in a design task. The following three factors of the dimensional meaning profiles of metaphors were significant predictors of design performance: sensory, functional, and structural evaluations. Implications for design education are discussed, primarily concerning the important role of metaphor in design problem-solving.

Multilayer-omics analysis of renal cell carcinoma, including the whole exome, methylome and transcriptome.

PubMed

Arai, Eri; Sakamoto, Hiromi; Ichikawa, Hitoshi; Totsuka, Hirohiko; Chiku, Suenori; Gotoh, Masahiro; Mori, Taisuke; Nakatani, Tamao; Ohnami, Sumiko; Nakagawa, Tohru; Fujimoto, Hiroyuki; Wang, Linghua; Aburatani, Hiroyuki; Yoshida, Teruhiko; Kanai, Yae

2014-09-15

The aim of this study was to identify pathways that have a significant impact during renal carcinogenesis. Sixty-seven paired samples of both noncancerous renal cortex tissue and cancerous tissue from patients with clear cell renal cell carcinomas (RCCs) were subjected to whole-exome, methylome and transcriptome analyses using Agilent SureSelect All Exon capture followed by sequencing on an Illumina HiSeq 2000 platform, Illumina Infinium HumanMethylation27 BeadArray and Agilent SurePrint Human Gene Expression microarray, respectively. Sanger sequencing and quantitative reverse transcription-PCR were performed for technical verification. MetaCore software was used for pathway analysis. Somatic nonsynonymous single-nucleotide mutations, insertions/deletions and intragenic breaks of 2,153, 359 and 8 genes were detected, respectively. Mutations of GCN1L1, MED12 and CCNC, which are members of CDK8 mediator complex directly regulating β-catenin-driven transcription, were identified in 16% of the RCCs. Mutations of MACF1, which functions in the Wnt/β-catenin signaling pathway, were identified in 4% of the RCCs. A combination of methylome and transcriptome analyses further highlighted the significant role of the Wnt/β-catenin signaling pathway in renal carcinogenesis. Genetic aberrations and reduced expression of ERC2 and ABCA13 were frequent in RCCs, and MTOR mutations were identified as one of the major disrupters of cell signaling during renal carcinogenesis. Our results confirm that multilayer-omics analysis can be a powerful tool for revealing pathways that play a significant role in carcinogenesis. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

Multilayer-omics analysis of renal cell carcinoma, including the whole exome, methylome and transcriptome

PubMed Central

Arai, Eri; Sakamoto, Hiromi; Ichikawa, Hitoshi; Totsuka, Hirohiko; Chiku, Suenori; Gotoh, Masahiro; Mori, Taisuke; Nakatani, Tamao; Ohnami, Sumiko; Nakagawa, Tohru; Fujimoto, Hiroyuki; Wang, Linghua; Aburatani, Hiroyuki; Yoshida, Teruhiko; Kanai, Yae

2014-01-01

The aim of this study was to identify pathways that have a significant impact during renal carcinogenesis. Sixty-seven paired samples of both noncancerous renal cortex tissue and cancerous tissue from patients with clear cell renal cell carcinomas (RCCs) were subjected to whole-exome, methylome and transcriptome analyses using Agilent SureSelect All Exon capture followed by sequencing on an Illumina HiSeq 2000 platform, Illumina Infinium HumanMethylation27 BeadArray and Agilent SurePrint Human Gene Expression microarray, respectively. Sanger sequencing and quantitative reverse transcription-PCR were performed for technical verification. MetaCore software was used for pathway analysis. Somatic nonsynonymous single-nucleotide mutations, insertions/deletions and intragenic breaks of 2,153, 359 and 8 genes were detected, respectively. Mutations of GCN1L1, MED12 and CCNC, which are members of CDK8 mediator complex directly regulating β-catenin-driven transcription, were identified in 16% of the RCCs. Mutations of MACF1, which functions in the Wnt/β-catenin signaling pathway, were identified in 4% of the RCCs. A combination of methylome and transcriptome analyses further highlighted the significant role of the Wnt/β-catenin signaling pathway in renal carcinogenesis. Genetic aberrations and reduced expression of ERC2 and ABCA13 were frequent in RCCs, and MTOR mutations were identified as one of the major disrupters of cell signaling during renal carcinogenesis. Our results confirm that multilayer-omics analysis can be a powerful tool for revealing pathways that play a significant role in carcinogenesis. PMID:24504440

Holocaust exposure and subsequent suicide risk: a population-based study.

PubMed

Bursztein Lipsicas, Cendrine; Levav, Itzhak; Levine, Stephen Z

2017-03-01

To examine the association between the extent of genocide exposure and subsequent suicide risk among Holocaust survivors. Persons born in Holocaust-exposed European countries during the years 1922-1945 that immigrated to Israel by 1965 were identified in the Population Registry (N = 209,429), and followed up for suicide (1950-2014). They were divided into three groups based on likely exposure to Nazi persecution: those who immigrated before (indirect; n = 20,229; 10%), during (partial direct; n = 17,189; 8%), and after (full direct; n = 172,061; 82%) World War II. Groups were contrasted for suicide risk, accounting for the extent of genocide in their respective countries of origin, high (>70%) or lower levels (<50%). Cox model survival analyses were computed examining calendar year at suicide. Sensitivity analyses were recomputed for two additional suicide-associated variables (age and years since immigration) for each exposure group. All analyses were adjusted for confounders. Survival analysis showed that compared to the indirect exposure group, the partial direct exposure group from countries with high genocide level had a statistically significant (P < .05) increased suicide risk for the main outcome (calendar year: HR 1.78, 95% CI 1.09, 2.90). This effect significantly (P < .05) replicated in two sensitivity analyses for countries with higher relative levels of genocide (age: HR 1.77, 95% CI 1.09, 2.89; years since immigration: HR 1.85, 95% CI 1.14, 3.02). The full direct exposure group was not at significant suicide risk compared to the indirect exposure group. Suicide associations for groups from countries with relative lower level of genocide were not statistically significant. This study partly converges with findings identifying Holocaust survivors (full direct exposure) as a resilient group. A tentative mechanism for higher vulnerability to suicide risk of the partial direct exposure group from countries with higher genocide exposure includes protracted guilt feelings, having directly witnessed atrocities and escaped death.

Changes in Georgia restaurant and bar smoking policies from 2006 to 2012.

PubMed

Chandora, Rachna D; Whitney, Carrie F; Weaver, Scott R; Eriksen, Michael P

2015-05-14

The purpose of this study is to examine the change in smoking policy status among Georgia restaurants and bars from 2006 to 2012 and to identify restaurant and bar characteristics that are associated with allowing smoking. Data were obtained from similar cross-sectional indoor air surveys conducted in 2006 and 2012 in Georgia. Both surveys were designed to gather information about restaurant and bar smoking policies. Weighted χ(2) analyses were performed to identify changes in smoking policy status and other variables from 2006 to 2012. Weighted logistic regression analysis was used to test for significant associations between an establishment's smoking policy and other characteristics. The percentage of restaurants and bars in Georgia that allowed smoking nearly doubled, from 9.1% in 2006 to 17.6% in 2012. The analyses also showed a significant increase in the percentage of establishments that allow smoking when minors are present. Having a liquor license was a significant predictor of allowing smoking. The Smokefree Air Act was enacted in 2005 to protect the health and welfare of Georgia citizens, but study results suggest that policy makers should reevaluate the law and consider strengthening it to make restaurants and bars 100% smokefree without exemptions.

Data on xylem sap proteins from Mn- and Fe-deficient tomato plants obtained using shotgun proteomics.

PubMed

Ceballos-Laita, Laura; Gutierrez-Carbonell, Elain; Takahashi, Daisuke; Abadía, Anunciación; Uemura, Matsuo; Abadía, Javier; López-Millán, Ana Flor

2018-04-01

This article contains consolidated proteomic data obtained from xylem sap collected from tomato plants grown in Fe- and Mn-sufficient control, as well as Fe-deficient and Mn-deficient conditions. Data presented here cover proteins identified and quantified by shotgun proteomics and Progenesis LC-MS analyses: proteins identified with at least two peptides and showing changes statistically significant (ANOVA; p ≤ 0.05) and above a biologically relevant selected threshold (fold ≥ 2) between treatments are listed. The comparison between Fe-deficient, Mn-deficient and control xylem sap samples using a multivariate statistical data analysis (Principal Component Analysis, PCA) is also included. Data included in this article are discussed in depth in the research article entitled "Effects of Fe and Mn deficiencies on the protein profiles of tomato ( Solanum lycopersicum) xylem sap as revealed by shotgun analyses" [1]. This dataset is made available to support the cited study as well to extend analyses at a later stage.

Race and diurnal blood pressure patterns. A review and meta-analysis.

PubMed

Profant, J; Dimsdale, J E

1999-05-01

Investigators have reported variable findings regarding the role of race in diurnal blood pressure patterns. We performed a review and meta-analysis of this literature to identify the overall effect of race on circadian blood pressure patterns. Eighteen studies involving 2852 participants were reviewed. Meta-analyses were conducted using effect sizes calculated from the data provided directly in the study reports. Separate meta-analyses were conducted on effect sizes for differences between blacks and whites in daytime and nighttime systolic and diastolic blood pressure and nocturnal dip in systolic and diastolic blood pressure. To evaluate discrepancies in findings from studies involving American versus non-American blacks, overall meta-analyses as well as within-subset meta-analyses of black/white differences were conducted for comparisons involving American and non-American blacks. Results of overall meta-analyses indicate that blacks experience higher levels of systolic and diastolic blood pressure, both at night and during the day. These differences were significantly greater at night than during the day (P<0.05). Results of within-subset analyses involving American blacks mirrored those for all black/white comparisons, except that the effect of race on nocturnal dip, ie, that American blacks experienced less of a dip in both systolic and diastolic blood pressure at night, was significant (P<0.05). In contrast, the effect of race on nocturnal dip was not significant for comparisons involving non-American blacks. These results suggest a consistent difference in the chronobiology of blood pressure, particularly in American blacks.

Understanding the Impact of School Factors on School Counselor Burnout: A Mixed-Methods Study

ERIC Educational Resources Information Center

Bardhoshi, Gerta; Schweinle, Amy; Duncan, Kelly

2014-01-01

This mixed-methods study investigated the relationship between burnout and performing noncounseling duties among a national sample of professional school counselors, while identifying school factors that could attenuate this relationship. Results of regression analyses indicate that performing noncounseling duties significantly predicted burnout…

Structure and Content in Social Cognition: Conceptual and Empirical Analyses.

ERIC Educational Resources Information Center

Edelstein, Wolfgang; And Others

1984-01-01

Conceptual analysis of two perspective-taking tasks identified a number of subtasks calling for equivalent operations of social reasoning within tasks of different content. Subtasks hypothetically formed a logical and developmental sequence of abilities required for decentering. The developmental significance of the hierarchy was tested among 121…

Functional Analysis and Treatment of Multiply Controlled Inappropriate Mealtime Behavior

ERIC Educational Resources Information Center

Bachmeyer, Melanie H.; Piazza, Cathleen C.; Fredrick, Laura D.; Reed, Gregory K.; Rivas, Kristi D.; Kadey, Heather J.

2009-01-01

Functional analyses identified children whose inappropriate mealtime behavior was maintained by escape and adult attention. Function-based extinction procedures were tested individually and in combination. Attention extinction alone did not result in decreases in inappropriate mealtime behavior or a significant increase in acceptance. By contrast,…

Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii

PubMed Central

Mahamad Maifiah, Mohd Hafidz; Cheah, Soon-Ee; Johnson, Matthew D.; Han, Mei-Ling; Boyce, John D.; Thamlikitkul, Visanu; Forrest, Alan; Kaye, Keith S.; Hertzog, Paul; Purcell, Anthony W.; Song, Jiangning; Velkov, Tony; Creek, Darren J.; Li, Jian

2016-01-01

Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxin-susceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03–149.1 (polymyxin-susceptible) and 03–149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxin-resistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii. PMID:26924392

Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii.

PubMed

Maifiah, Mohd Hafidz Mahamad; Cheah, Soon-Ee; Johnson, Matthew D; Han, Mei-Ling; Boyce, John D; Thamlikitkul, Visanu; Forrest, Alan; Kaye, Keith S; Hertzog, Paul; Purcell, Anthony W; Song, Jiangning; Velkov, Tony; Creek, Darren J; Li, Jian

2016-02-29

Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxin-susceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03-149.1 (polymyxin-susceptible) and 03-149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxin-resistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii.

Peptidome analysis of amniotic fluid from pregnancies with preeclampsia.

PubMed

Qian, Yating; Zhang, Lei; Rui, Can; Ding, Hongjuan; Mao, Pengyuan; Ruan, Hongjie; Jia, Ruizhe

2017-11-01

Preeclampsia (PE), a life‑threatening, complicated pregnancy‑associated disease, has recently become a research focus in obstetrics. However, the peptidome of the amniotic fluid in PE patients has rarely been investigated. The present study used peptidomic profiling to perform a comparative analysis of human amniotic fluid between normal and PE pregnancies. Centrifugal ultrafiltration and liquid chromatography‑tandem mass spectrometry (LC‑MS/MS) was combined with isotopomeric dimethyl labels to gain a deeper understanding of the role of proteins and the peptidome in the onset of PE. Following ultrafiltration and LC‑MS/MS, 352 peptides were identified. Of these, 23 peptides were observed to be significantly differentially expressed (6 downregulated and 17 upregulated; P<0.05). Using Gene Ontology and Blastp analyses, the functions and biological activities of these 23 peptides were identified and revealed to include autophagy, signal transduction, receptor activity, enzymatic activity and nucleic acid binding. In addition, a bibliographic search revealed that some of the identified peptides, including Titin, are crucial to the pathogenesis underlying PE. The present study identified 23 peptides expressed at significantly different levels in the amniotic fluid of PE and normal pregnancies. A comprehensive peptidome analysis is more efficient than a simple biomarker analysis at revealing deficiencies and improving the detection rate in diseases. These analyses therefore provide a substantial advantage in applications aimed at the discovery of disease‑specific biomarkers.

Discovering genetic variants in Crohn's disease by exploring genomic regions enriched of weak association signals.

PubMed

D'Addabbo, Annarita; Palmieri, Orazio; Maglietta, Rosalia; Latiano, Anna; Mukherjee, Sayan; Annese, Vito; Ancona, Nicola

2011-08-01

A meta-analysis has re-analysed previous genome-wide association scanning definitively confirming eleven genes and further identifying 21 new loci. However, the identified genes/loci still explain only the minority of genetic predisposition of Crohn's disease. To identify genes weakly involved in disease predisposition by analysing chromosomal regions enriched of single nucleotide polymorphisms with modest statistical association. We utilized the WTCCC data set evaluating 1748 CD and 2938 controls. The identification of candidate genes/loci was performed by a two-step procedure: first of all chromosomal regions enriched of weak association signals were localized; subsequently, weak signals clustered in gene regions were identified. The statistical significance was assessed by non parametric permutation tests. The cytoband enrichment analysis highlighted 44 regions (P≤0.05) enriched with single nucleotide polymorphisms significantly associated with the trait including 23 out of 31 previously confirmed and replicated genes. Importantly, we highlight further 20 novel chromosomal regions carrying approximately one hundred genes/loci with modest association. Amongst these we find compelling functional candidate genes such as MAPT, GRB2 and CREM, LCT, and IL12RB2. Our study suggests a different statistical perspective to discover genes weakly associated with a given trait, although further confirmatory functional studies are needed. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. All rights reserved.

Genetic overlap between diagnostic subtypes of ischemic stroke.

PubMed

Holliday, Elizabeth G; Traylor, Matthew; Malik, Rainer; Bevan, Steve; Falcone, Guido; Hopewell, Jemma C; Cheng, Yu-Ching; Cotlarciuc, Ioana; Bis, Joshua C; Boerwinkle, Eric; Boncoraglio, Giorgio B; Clarke, Robert; Cole, John W; Fornage, Myriam; Furie, Karen L; Ikram, M Arfan; Jannes, Jim; Kittner, Steven J; Lincz, Lisa F; Maguire, Jane M; Meschia, James F; Mosley, Thomas H; Nalls, Mike A; Oldmeadow, Christopher; Parati, Eugenio A; Psaty, Bruce M; Rothwell, Peter M; Seshadri, Sudha; Scott, Rodney J; Sharma, Pankaj; Sudlow, Cathie; Wiggins, Kerri L; Worrall, Bradford B; Rosand, Jonathan; Mitchell, Braxton D; Dichgans, Martin; Markus, Hugh S; Levi, Christopher; Attia, John; Wray, Naomi R

2015-03-01

Despite moderate heritability, the phenotypic heterogeneity of ischemic stroke has hampered gene discovery, motivating analyses of diagnostic subtypes with reduced sample sizes. We assessed evidence for a shared genetic basis among the 3 major subtypes: large artery atherosclerosis (LAA), cardioembolism, and small vessel disease (SVD), to inform potential cross-subtype analyses. Analyses used genome-wide summary data for 12 389 ischemic stroke cases (including 2167 LAA, 2405 cardioembolism, and 1854 SVD) and 62 004 controls from the Metastroke consortium. For 4561 cases and 7094 controls, individual-level genotype data were also available. Genetic correlations between subtypes were estimated using linear mixed models and polygenic profile scores. Meta-analysis of a combined LAA-SVD phenotype (4021 cases and 51 976 controls) was performed to identify shared risk alleles. High genetic correlation was identified between LAA and SVD using linear mixed models (rg=0.96, SE=0.47, P=9×10(-4)) and profile scores (rg=0.72; 95% confidence interval, 0.52-0.93). Between LAA and cardioembolism and SVD and cardioembolism, correlation was moderate using linear mixed models but not significantly different from zero for profile scoring. Joint meta-analysis of LAA and SVD identified strong association (P=1×10(-7)) for single nucleotide polymorphisms near the opioid receptor μ1 (OPRM1) gene. Our results suggest that LAA and SVD, which have been hitherto treated as genetically distinct, may share a substantial genetic component. Combined analyses of LAA and SVD may increase power to identify small-effect alleles influencing shared pathophysiological processes. © 2015 American Heart Association, Inc.

An evidence-based review of pregabalin for the treatment of fibromyalgia.

PubMed

Arnold, Lesley M; Choy, Ernest; Clauw, Daniel J; Oka, Hiroshi; Whalen, Ed; Semel, David; Pauer, Lynne; Knapp, Lloyd

2018-04-16

Pregabalin, an α2-δ agonist, is approved for the treatment of fibromyalgia (FM) in the United States, Japan, and 37 other countries. The purpose of this article was to provide an in-depth, evidence-based summary of pregabalin for FM as demonstrated in randomized, placebo-controlled clinical studies, including open-label extensions, meta-analyses, combination studies and post-hoc analyses of clinical study data. PubMed was searched using the term "pregabalin AND fibromyalgia" and the Cochrane Library with the term "pregabalin". Both searches were conducted on 2 March 2017 with no other date limits set. Eleven randomized, double-blind, placebo-controlled clinical studies were identified including parallel group, two-way crossover and randomized withdrawal designs. One was a neuroimaging study. Five open-label extensions were also identified. Evidence of efficacy was demonstrated across the studies identified with significant and clinically relevant improvements in pain, sleep quality and patient status. The safety and tolerability profile of pregabalin is consistent across all the studies identified, including in adolescents, with dizziness and somnolence the most common adverse events reported. These efficacy and safety data are supported by meta-analyses (13 studies). Pregabalin in combination with other pharmacotherapies (7 studies) is also efficacious. Post-hoc analyses have demonstrated the onset of pregabalin efficacy as early as 1-2 days after starting treatment, examined the effect of pregabalin on other aspects of sleep beyond quality, and shown it is effective irrespective of the presence of a wide variety of patient demographic and clinical characteristics. Pregabalin is a treatment option for FM; its clinical utility has been comprehensively demonstrated.

An application of statistics to comparative metagenomics

PubMed Central

Rodriguez-Brito, Beltran; Rohwer, Forest; Edwards, Robert A

2006-01-01

Background Metagenomics, sequence analyses of genomic DNA isolated directly from the environments, can be used to identify organisms and model community dynamics of a particular ecosystem. Metagenomics also has the potential to identify significantly different metabolic potential in different environments. Results Here we use a statistical method to compare curated subsystems, to predict the physiology, metabolism, and ecology from metagenomes. This approach can be used to identify those subsystems that are significantly different between metagenome sequences. Subsystems that were overrepresented in the Sargasso Sea and Acid Mine Drainage metagenome when compared to non-redundant databases were identified. Conclusion The methodology described herein applies statistics to the comparisons of metabolic potential in metagenomes. This analysis reveals those subsystems that are more, or less, represented in the different environments that are compared. These differences in metabolic potential lead to several testable hypotheses about physiology and metabolism of microbes from these ecosystems. PMID:16549025

An application of statistics to comparative metagenomics.

PubMed

Rodriguez-Brito, Beltran; Rohwer, Forest; Edwards, Robert A

2006-03-20

Metagenomics, sequence analyses of genomic DNA isolated directly from the environments, can be used to identify organisms and model community dynamics of a particular ecosystem. Metagenomics also has the potential to identify significantly different metabolic potential in different environments. Here we use a statistical method to compare curated subsystems, to predict the physiology, metabolism, and ecology from metagenomes. This approach can be used to identify those subsystems that are significantly different between metagenome sequences. Subsystems that were overrepresented in the Sargasso Sea and Acid Mine Drainage metagenome when compared to non-redundant databases were identified. The methodology described herein applies statistics to the comparisons of metabolic potential in metagenomes. This analysis reveals those subsystems that are more, or less, represented in the different environments that are compared. These differences in metabolic potential lead to several testable hypotheses about physiology and metabolism of microbes from these ecosystems.

Assessing the estrogenic potency in a Portuguese wastewater treatment plant using an integrated approach.

PubMed

Diniz, Mário S; Maurício, Rita; Petrovic, Mira; López de Alda, Maria J; Amaral, Leonor; Peres, Isabel; Barceló, Damiá; Santana, Fernando

2010-01-01

The estrogenic potency of a wastewater treatment plant (WWTP) was evaluated using chemical and biological analyses, which showed that after the station treatment processes some of the selected endocrine disruptor compounds (EDCs) were still present in the treated effluent (e.g., bisphenol A, alkylphenols, estrone). Thus, the most common endocrine EDCs were identified and quantified and the overall estrogenicity of the treated effluent assessed by integrating the results. Male goldfish (Carassius auratus) were used as biological indicators in a 28-day experiment. Vitellogenin (Vtg), gonadosomatic and hepatosomatic indices, steroids (17beta-estradiol and 11-ketotestosterone) and histopathology were biomarkers used in fish to evaluate WWTP treated effluent estrogenicity, in combination with instrumental analyses. The results showed a significant increase (P < 0.01) in plasma and liver Vtg, which were significantly correlated (r = 0.66; P < 0.01). The gonadosmatic index was significantly (P < 0.01) reduced in exposed fish. The steroid analyses revealed significant elevations in 17beta-estradiol and depressed 11-ketotestosterone concentrations. The histological examinations show changes in exposed fish gonads, such as regressed testes and in some cases (43% to 75%) the development of ovo-testis in fish exposed to 50% and 100% treated effluent.

Identification of indicator congeners and evaluation of emission pattern of polychlorinated naphthalenes in industrial stack gas emissions by statistical analyses.

PubMed

Liu, Guorui; Cai, Zongwei; Zheng, Minghui; Jiang, Xiaoxu; Nie, Zhiqiang; Wang, Mei

2015-01-01

Identifying marker congeners of unintentionally produced polychlorinated naphthalenes (PCNs) from industrial thermal sources might be useful for predicting total PCN (∑2-8PCN) emissions by the determination of only indicator congeners. In this study, potential indicator congeners were identified based on the PCN data in 122 stack gas samples from over 60 plants involved in more than ten industrial thermal sources reported in our previous case studies. Linear regression analyses identified that the concentrations of CN27/30, CN52/60, and CN66/67 correlated significantly with ∑2-8PCN (R(2)=0.77, 0.80, and 0.58, respectively; n=122, p<0.05), which might be good candidates for indicator congeners. Equations describing relationships between indicators and ∑2-8PCN were established. The linear regression analyses involving 122 samples showed that the relationships between the indicator congeners and ∑2-8PCN were not significantly affected by factors such as industry types, raw materials used, or operating conditions. Hierarchical cluster analysis and similarity calculations for the 122 stack gas samples were adopted to group those samples and evaluating their similarity and difference based on the PCN homolog distributions from different industrial thermal sources. Generally, the fractions of less chlorinated homologs comprised of di-, tri-, and tetra-homologs were much higher than that of more chlorinated homologs for up to 111 stack gas samples contained in group 1 and 2, which indicating the dominance of lower chlorinated homologs in stack gas from industrial thermal sources. Copyright © 2014 Elsevier Ltd. All rights reserved.

Periodicity in marine extinction events

NASA Technical Reports Server (NTRS)

Sepkoski, J. John, Jr.; Raup, David M.

1986-01-01

The periodicity of extinction events is examined in detail. In particular, the temporal distribution of specific, identifiable extinction events is analyzed. The nature and limitations of the data base on the global fossil record is discussed in order to establish limits of resolution in statistical analyses. Peaks in extinction intensity which appear to differ significantly from background levels are considered, and new analyses of the temporal distribution of these peaks are presented. Finally, some possible causes of periodicity and of interdependence among extinction events over the last quarter billion years of earth history are examined.

Molecular biology of bladder cancer.

PubMed

Martin-Doyle, William; Kwiatkowski, David J

2015-04-01

Classic as well as more recent large-scale genomic analyses have uncovered multiple genes and pathways important for bladder cancer development. Genes involved in cell-cycle control, chromatin regulation, and receptor tyrosine and PI3 kinase-mammalian target of rapamycin signaling pathways are commonly mutated in muscle-invasive bladder cancer. Expression-based analyses have identified distinct types of bladder cancer that are similar to subsets of breast cancer, and have prognostic and therapeutic significance. These observations are leading to novel therapeutic approaches in bladder cancer, providing optimism for therapeutic progress. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of Interventions on Survival in Acute Respiratory Distress Syndrome: an Umbrella Review of 159 Published Randomized Trials and 29 Meta-analyses

PubMed Central

Tonelli, Adriano R.; Zein, Joe; Adams, Jacob; Ioannidis, John P.A.

2014-01-01

Purpose Multiple interventions have been tested in acute respiratory distress syndrome (ARDS). We examined the entire agenda of published randomized controlled trials (RCTs) in ARDS that reported on mortality and of respective meta-analyses. Methods We searched PubMed, the Cochrane Library and Web of Knowledge until July 2013. We included RCTs in ARDS published in English. We excluded trials of newborns and children; and those on short-term interventions, ARDS prevention or post-traumatic lung injury. We also reviewed all meta-analyses of RCTs in this field that addressed mortality. Treatment modalities were grouped in five categories: mechanical ventilation strategies and respiratory care, enteral or parenteral therapies, inhaled / intratracheal medications, nutritional support and hemodynamic monitoring. Results We identified 159 published RCTs of which 93 had overall mortality reported (n= 20,671 patients) - 44 trials (14,426 patients) reported mortality as a primary outcome. A statistically significant survival benefit was observed in 8 trials (7 interventions) and two trials reported an adverse effect on survival. Among RTCs with >50 deaths in at least 1 treatment arm (n=21), 2 showed a statistically significant mortality benefit of the intervention (lower tidal volumes and prone positioning), 1 showed a statistically significant mortality benefit only in adjusted analyses (cisatracurium) and 1 (high-frequency oscillatory ventilation) showed a significant detrimental effect. Across 29 meta-analyses, the most consistent evidence was seen for low tidal volumes and prone positioning in severe ARDS. Conclusions There is limited supportive evidence that specific interventions can decrease mortality in ARDS. While low tidal volumes and prone positioning in severe ARDS seem effective, most sporadic findings of interventions suggesting reduced mortality are not corroborated consistently in large-scale evidence including meta-analyses. PMID:24667919

Traffic crash involvement: experiential driving knowledge and stressful contextual antecedents.

PubMed

Legree, Peter J; Heffner, Tonia S; Psotka, Joseph; Martin, Daniel E; Medsker, Gina J

2003-02-01

Researchers have rarely examined stressful environments and psychological characteristics as predictors of driving behavior in the same study. The authors hypothesized that (a) safer drivers more accurately assess physical and emotional traffic hazards and (b) stress and emotional states elevate crash risk. The hypotheses were evaluated with procedural and declarative tacit driving knowledge tests requiring assessment of emotional and contextual hazards and with accident reports describing crash antecedents, including stressful events and environmental conditions. Analyses identified separate driving knowledge factors corresponding to emotional and contextual hazards that were significantly related to the crash criteria. Accident report analyses show that stress significantly elevates at-fault crash risk. The results demonstrate the importance of experiential knowledge acquired without instruction (procedural or tacit knowledge) and provide safety recommendations.

Deaf college students' mathematical skills relative to morphological knowledge, reading level, and language proficiency.

PubMed

Kelly, Ronald R; Gaustad, Martha G

2007-01-01

This study of deaf college students examined specific relationships between their mathematics performance and their assessed skills in reading, language, and English morphology. Simple regression analyses showed that deaf college students' language proficiency scores, reading grade level, and morphological knowledge regarding word segmentation and meaning were all significantly correlated with both the ACT Mathematics Subtest and National Technical Institute for the Deaf (NTID) Mathematics Placement Test scores. Multiple regression analyses identified the best combination from among these potential independent predictors of students' performance on both the ACT and NTID mathematics tests. Additionally, the participating deaf students' grades in their college mathematics courses were significantly and positively associated with their reading grade level and their knowledge of morphological components of words.

Identifying familiar strangers in human encounter networks

NASA Astrophysics Data System (ADS)

Liang, Di; Li, Xiang; Zhang, Yi-Qing

2016-10-01

Familiar strangers, pairs of individuals who encounter repeatedly but never know each other, have been discovered for four decades yet lack an effective method to identify. Here we propose a novel method called familiar stranger classifier (FSC) to identify familiar strangers from three empirical datasets, and classify human relationships into four types, i.e., familiar stranger (FS), in-role (IR), friend (F) and stranger (S). The analyses of the human encounter networks show that the average number of FS one may encounter is finite but larger than the Dunbar Number, and their encounters are structurally more stable and denser than those of S, indicating the encounters of FS are not limited by the social capacity, and more robust than the random scenario. Moreover, the temporal statistics of encounters between FS over the whole time span show strong periodicity, which are diverse from the bursts of encounters within one day, suggesting the significance of longitudinal patterns of human encounters. The proposed method to identify FS in this paper provides a valid framework to understand human encounter patterns and analyse complex human social behaviors.

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.

PubMed

Jin, Ying; Andersen, Genevieve; Yorgov, Daniel; Ferrara, Tracey M; Ben, Songtao; Brownson, Kelly M; Holland, Paulene J; Birlea, Stanca A; Siebert, Janet; Hartmann, Anke; Lienert, Anne; van Geel, Nanja; Lambert, Jo; Luiten, Rosalie M; Wolkerstorfer, Albert; Wietze van der Veen, J P; Bennett, Dorothy C; Taïeb, Alain; Ezzedine, Khaled; Kemp, E Helen; Gawkrodger, David J; Weetman, Anthony P; Kõks, Sulev; Prans, Ele; Kingo, Külli; Karelson, Maire; Wallace, Margaret R; McCormack, Wayne T; Overbeck, Andreas; Moretti, Silvia; Colucci, Roberta; Picardo, Mauro; Silverberg, Nanette B; Olsson, Mats; Valle, Yan; Korobko, Igor; Böhm, Markus; Lim, Henry W; Hamzavi, Iltefat; Zhou, Li; Mi, Qing-Sheng; Fain, Pamela R; Santorico, Stephanie A; Spritz, Richard A

2016-11-01

Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment.

Occurrence of mycotoxins and yeasts and moulds identification in corn silages in tropical climate.

PubMed

Carvalho, B F; Ávila, C L S; Krempser, P M; Batista, L R; Pereira, M N; Schwan, R F

2016-05-01

This study was aimed to identify yeasts and moulds as well as to detect mycotoxin in corn silages in southern Minas Gerais, Brazil. Corn silages from 36 farms were sampled to analyse dry matter, crude protein, ether extract, ash, neutral detergent fibre, nonfibre carbohydrates and mycotoxins contents, yeasts and moulds population, pH and temperature values. The mycotoxins found in high frequency were aflatoxin in 77·7% of analysed samples, ochratoxin (33·3%) and zearalenone (22·2%). There was no significant correlation between the mycotoxin concentration and the presence of moulds. The pH was negatively correlated with ochratoxin concentration. Aspergillus fumigatus was identified in all silages that presented growth of moulds. Ten different yeast species were identified using the culture-dependent method: Candida diversa, Candida ethanolica, Candida rugosa, Issatchenkia orientalis, Kluyveromyces marxianus, Pichia manshurica, Pichia membranifaciens, Saccharomyces cerevisiae, Trichosporon asahii and Trichosporon japonicum. Another six different yeast species were identified using the culture-independent method. A high mycotoxin contamination rate (91·6% of the analysed silages) was observed. The results indicated that conventional culturing and PCR-DGGE should be combined to optimally describe the microbiota associated with corn silage. This study provides information about the corn silage fermentation dynamics and our findings are relevant to optimization of this silage fermentation. © 2016 The Society for Applied Microbiology.

Ecological Patterns Among Bacteria and Microbial Eukaryotes Derived from Network Analyses in a Low-Salinity Lake.

PubMed

Jones, Adriane Clark; Hambright, K David; Caron, David A

2018-05-01

Microbial communities are comprised of complex assemblages of highly interactive taxa. We employed network analyses to identify and describe microbial interactions and co-occurrence patterns between microbial eukaryotes and bacteria at two locations within a low salinity (0.5-3.5 ppt) lake over an annual cycle. We previously documented that the microbial diversity and community composition within Lake Texoma, southwest USA, were significantly affected by both seasonal forces and a site-specific bloom of the harmful alga, Prymnesium parvum. We used network analyses to answer ecological questions involving both the bacterial and microbial eukaryotic datasets and to infer ecological relationships within the microbial communities. Patterns of connectivity at both locations reflected the seasonality of the lake including a large rain disturbance in May, while a comparison of the communities between locations revealed a localized response to the algal bloom. A network built from shared nodes (microbial operational taxonomic units and environmental variables) and correlations identified conserved associations at both locations within the lake. Using network analyses, we were able to detect disturbance events, characterize the ecological extent of a harmful algal bloom, and infer ecological relationships not apparent from diversity statistics alone.

HRCT findings of collagen vascular disease-related interstitial pneumonia (CVD-IP): a comparative study among individual underlying diseases.

PubMed

Tanaka, N; Kunihiro, Y; Kubo, M; Kawano, R; Oishi, K; Ueda, K; Gondo, T

2018-05-29

To identify characteristic high-resolution computed tomography (CT) findings for individual collagen vascular disease (CVD)-related interstitial pneumonias (IPs). The HRCT findings of 187 patients with CVD, including 55 patients with rheumatoid arthritis (RA), 50 with systemic sclerosis (SSc), 46 with polymyositis/dermatomyositis (PM/DM), 15 with mixed connective tissue disease, 11 with primary Sjögren's syndrome, and 10 with systemic lupus erythematosus, were evaluated. Lung parenchymal abnormalities were compared among CVDs using χ 2 test, Kruskal-Wallis test, and multiple logistic regression analysis. A CT-pathology correlation was performed in 23 patients. In RA-IP, honeycombing was identified as the significant indicator based on multiple logistic regression analyses. Traction bronchiectasis (81.8%) was further identified as the most frequent finding based on χ 2 test. In SSc IP, lymph node enlargement and oesophageal dilatation were identified as the indicators based on multiple logistic regression analyses, and ground-glass opacity (GGO) was the most extensive based on Kruskal-Wallis test, which reflects the higher frequency of the pathological nonspecific interstitial pneumonia (NSIP) pattern present in the CT-pathology correlation. In PM/DM IP, airspace consolidation and the absence of honeycombing were identified as the indicators based on multiple logistic regression analyses, and predominance of consolidation over GGO (32.6%) and predominant subpleural distribution of GGO/consolidation (41.3%) were further identified as the most frequent findings based on χ 2 test, which reflects the higher frequency of the pathological NSIP and/or the organising pneumonia patterns present in the CT-pathology correlation. Several characteristic high-resolution CT findings with utility for estimating underlying CVD were identified. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Genome Wide Association Study of Sepsis in Extremely Premature Infants

PubMed Central

Srinivasan, Lakshmi; Page, Grier; Kirpalani, Haresh; Murray, Jeffrey C.; Das, Abhik; Higgins, Rosemary D.; Carlo, Waldemar A.; Bell, Edward F.; Goldberg, Ronald N.; Schibler, Kurt; Sood, Beena G.; Stevenson, David K.; Stoll, Barbara J.; Van Meurs, Krisa P.; Johnson, Karen J.; Levy, Joshua; McDonald, Scott A.; Zaterka-Baxter, Kristin M.; Kennedy, Kathleen A.; Sánchez, Pablo J.; Duara, Shahnaz; Walsh, Michele C.; Shankaran, Seetha; Wynn, James L.; Cotten, C. Michael

2017-01-01

Objective To identify genetic variants associated with sepsis (early and late-onset) using a genome wide association (GWA) analysis in a cohort of extremely premature infants. Study Design Previously generated GWA data from the Neonatal Research Network’s anonymized genomic database biorepository of extremely premature infants were used for this study. Sepsis was defined as culture-positive early-onset or late-onset sepsis or culture-proven meningitis. Genomic and whole genome amplified DNA was genotyped for 1.2 million single nucleotide polymorphisms (SNPs); 91% of SNPs were successfully genotyped. We imputed 7.2 million additional SNPs. P values and false discovery rates were calculated from multivariate logistic regression analysis adjusting for gender, gestational age and ancestry. Target statistical value was p<10−5. Secondary analyses assessed associations of SNPs with pathogen type. Pathway analyses were also run on primary and secondary end points. Results Data from 757 extremely premature infants were included: 351 infants with sepsis and 406 infants without sepsis. No SNPs reached genome-wide significance levels (5×10−8); two SNPs in proximity to FOXC2 and FOXL1 genes achieved target levels of significance. In secondary analyses, SNPs for ELMO1, IRAK2 (Gram positive sepsis), RALA, IMMP2L (Gram negative sepsis) and PIEZO2 (fungal sepsis) met target significance levels. Pathways associated with sepsis and Gram negative sepsis included gap junctions, fibroblast growth factor receptors, regulators of cell division and Interleukin-1 associated receptor kinase 2 (p values<0.001 and FDR<20%). Conclusions No SNPs met genome-wide significance in this cohort of ELBW infants; however, areas of potential association and pathways meriting further study were identified. PMID:28283553

Account for Clinical Heterogeneity in Assessment of Catheter-based Renal Denervation among Resistant Hypertension Patients: Subgroup Meta-analysis

PubMed Central

Chen, Xiao-Han; Kim, Sehee; Zeng, Xiao-Xi; Chen, Zhi-Bing; Cui, Tian-Lei; Hu, Zhang-Xue; Li, Yi; Fu, Ping

2017-01-01

Background: Catheter-based renal denervation (RDN) is a novel treatment for resistant hypertension (RH). A recent meta-analysis reported that RDN did not significantly reduce blood pressure (BP) based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations. Methods: This was a meta-analysis of 9 randomized clinical trials (RCTs) among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure (SBP) level, antihypertensive medication change rates, and coronary heart disease (CHD). Results: In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-h SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP ≥155 mmHg (1 mmHg = 0.133 kPa) and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months (P = 0.100 and P = 0.009, respectively). Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months (P < 0.001). Conclusions: In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBP. PMID:28639575

Account for Clinical Heterogeneity in Assessment of Catheter-based Renal Denervation among Resistant Hypertension Patients: Subgroup Meta-analysis.

PubMed

Chen, Xiao-Han; Kim, Sehee; Zeng, Xiao-Xi; Chen, Zhi-Bing; Cui, Tian-Lei; Hu, Zhang-Xue; Li, Yi; Fu, Ping

2017-07-05

Catheter-based renal denervation (RDN) is a novel treatment for resistant hypertension (RH). A recent meta-analysis reported that RDN did not significantly reduce blood pressure (BP) based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations. This was a meta-analysis of 9 randomized clinical trials (RCTs) among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure (SBP) level, antihypertensive medication change rates, and coronary heart disease (CHD). In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-h SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP ≥155 mmHg (1 mmHg = 0.133 kPa) and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months (P = 0.100 and P= 0.009, respectively). Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months (P < 0.001). In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBP.

The acute effects of grape polyphenols supplementation on endothelial function in adults: meta-analyses of controlled trials.

PubMed

Li, Shao-Hua; Tian, Hong-Bo; Zhao, Hong-Jin; Chen, Liang-Hua; Cui, Lian-Qun

2013-01-01

The acute effects of grape polyphenols on endothelial function in adults are inconsistent. Here, we performed meta-analyses to determine these acute effects as measured by flow-mediated dilation (FMD). Trials were searched in PubMed, Embase and the Cochrane Library database. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the PROSPERO register and our registration number is CRD42013004157. Nine studies were included in the present meta-analyses. The results showed that the FMD level was significantly increased in the initial 120 min after intake of grape polyphenols as compared with controls. Meta-regression and subgroup analyses were performed and showed that a health status was the main effect modifier of the significant heterogeneity. Subgroups indicated that intake of grape polyphenols could significantly increase FMD in healthy subjects, and the increased FMD appeared to be more obviously in subjects with high cardiovascular risk factors. Moreover, the peak effect of grape polyphenols on FMD in healthy subjects was found 30 min after ingestion, which was different from the effect in subjects with high cardiovascular risk factors, in whom the peak effect was found 60 min after ingestion. Endothelial function can be significantly improved in healthy adults in the initial 2 h after intake of grape polyphenols. The acute effect of grape polyphenols on endothelial function may be more significant but the peak effect is delayed in subjects with a smoking history or coronary heart disease as compared with the healthy subjects.

The Acute Effects of Grape Polyphenols Supplementation on Endothelial Function in Adults: Meta-Analyses of Controlled Trials

PubMed Central

Li, Shao-Hua; Tian, Hong-Bo; Zhao, Hong-Jin; Chen, Liang-Hua; Cui, Lian-Qun

2013-01-01

Background The acute effects of grape polyphenols on endothelial function in adults are inconsistent. Here, we performed meta-analyses to determine these acute effects as measured by flow-mediated dilation (FMD). Methods Trials were searched in PubMed, Embase and the Cochrane Library database. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the PROSPERO register and our registration number is CRD42013004157. Results Nine studies were included in the present meta-analyses. The results showed that the FMD level was significantly increased in the initial 120 min after intake of grape polyphenols as compared with controls. Meta-regression and subgroup analyses were performed and showed that a health status was the main effect modifier of the significant heterogeneity. Subgroups indicated that intake of grape polyphenols could significantly increase FMD in healthy subjects, and the increased FMD appeared to be more obviously in subjects with high cardiovascular risk factors. Moreover, the peak effect of grape polyphenols on FMD in healthy subjects was found 30 min after ingestion, which was different from the effect in subjects with high cardiovascular risk factors, in whom the peak effect was found 60 min after ingestion. Conclusions Endothelial function can be significantly improved in healthy adults in the initial 2 h after intake of grape polyphenols. The acute effect of grape polyphenols on endothelial function may be more significant but the peak effect is delayed in subjects with a smoking history or coronary heart disease as compared with the healthy subjects. PMID:23894543

Impact of a pharmacy technician-centered medication reconciliation program on medication discrepancies and implementation of recommendations.

PubMed

Kraus, Sarah K; Sen, Sanchita; Murphy, Michelle; Pontiggia, Laura

2017-01-01

To evaluate the impact of a pharmacy-technician centered medication reconciliation (PTMR) program by identifying and quantifying medication discrepancies and outcomes of pharmacist medication reconciliation recommendations. A retrospective chart review was performed on two-hundred patients admitted to the internal medicine teaching services at Cooper University Hospital in Camden, NJ. Patients were selected using a stratified systematic sample approach and were included if they received a pharmacy technician medication history and a pharmacist medication reconciliation at any point during their hospital admission. Pharmacist identified medication discrepancies were analyzed using descriptive statistics, bivariate analyses. Potential risk factors were identified using multivariate analyses, such as logistic regression and CART. The priority level of significance was set at 0.05. Three-hundred and sixty-five medication discrepancies were identified out of the 200 included patients. The four most common discrepancies were omission (64.7%), non-formulary omission (16.2%), dose discrepancy (10.1%), and frequency discrepancy (4.1%). Twenty-two percent of pharmacist recommendations were implemented by the prescriber within 72 hours. A PTMR program with dedicated pharmacy technicians and pharmacists identifies many medication discrepancies at admission and provides opportunities for pharmacist reconciliation recommendations.

Impact of a pharmacy technician-centered medication reconciliation program on medication discrepancies and implementation of recommendations

PubMed Central

2016-01-01

Objectives: To evaluate the impact of a pharmacy-technician centered medication reconciliation (PTMR) program by identifying and quantifying medication discrepancies and outcomes of pharmacist medication reconciliation recommendations. Methods: A retrospective chart review was performed on two-hundred patients admitted to the internal medicine teaching services at Cooper University Hospital in Camden, NJ. Patients were selected using a stratified systematic sample approach and were included if they received a pharmacy technician medication history and a pharmacist medication reconciliation at any point during their hospital admission. Pharmacist identified medication discrepancies were analyzed using descriptive statistics, bivariate analyses. Potential risk factors were identified using multivariate analyses, such as logistic regression and CART. The priority level of significance was set at 0.05. Results: Three-hundred and sixty-five medication discrepancies were identified out of the 200 included patients. The four most common discrepancies were omission (64.7%), non-formulary omission (16.2%), dose discrepancy (10.1%), and frequency discrepancy (4.1%). Twenty-two percent of pharmacist recommendations were implemented by the prescriber within 72 hours. Conclusion: A PTMR program with dedicated pharmacy technicians and pharmacists identifies many medication discrepancies at admission and provides opportunities for pharmacist reconciliation recommendations. PMID:28690691

Microarray Analyses and Comparisons of Upper or Lower Flanks of Rice Shoot Base Preceding Gravitropic Bending

PubMed Central

Zang, Aiping; Chen, Haiying; Dou, Xianying; Jin, Jing; Cai, Weiming

2013-01-01

Gravitropism is a complex process involving a series of physiological pathways. Despite ongoing research, gravitropism sensing and response mechanisms are not well understood. To identify the key transcripts and corresponding pathways in gravitropism, a whole-genome microarray approach was used to analyze transcript abundance in the shoot base of rice (Oryza sativa sp. japonica) at 0.5 h and 6 h after gravistimulation by horizontal reorientation. Between upper and lower flanks of the shoot base, 167 transcripts at 0.5 h and 1202 transcripts at 6 h were discovered to be significantly different in abundance by 2-fold. Among these transcripts, 48 were found to be changed both at 0.5 h and 6 h, while 119 transcripts were only changed at 0.5 h and 1154 transcripts were changed at 6 h in association with gravitropism. MapMan and PageMan analyses were used to identify transcripts significantly changed in abundance. The asymmetric regulation of transcripts related to phytohormones, signaling, RNA transcription, metabolism and cell wall-related categories between upper and lower flanks were demonstrated. Potential roles of the identified transcripts in gravitropism are discussed. Our results suggest that the induction of asymmetrical transcription, likely as a consequence of gravitropic reorientation, precedes gravitropic bending in the rice shoot base. PMID:24040303

Garlic intake lowers fasting blood glucose: meta-analysis of randomized controlled trials.

PubMed

Hou, Li-qiong; Liu, Yun-hui; Zhang, Yi-yi

2015-01-01

Garlic is a common spicy flavouring agent also used for certain therapeutic purposes. Garlic's effects on blood glucose have been the subject of many clinical and animal studies, however, studies reporting hypoglycemic effects of garlic in humans are conflicting. A comprehensive literature search was conducted to identify relevant trials of garlic or garlic extracts on markers of glycemic control [fasting blood glucose (FBG), postprandial glucose (PPG), glycosylated haemoglobin (HbA1c)]. A meta-analysis of the effect of garlic intake on human was done to assess garlic's effectiveness in lowering glucose levels. Two reviewers extracted data from each of the identified studies. Seven eligible randomized controlled trials with 513 subjects were identified. Pooled analyses showed that garlic intake results in a statistically significant lowering in FBG [SMD=-1.67; 95% CI (-2.80, -0.55), p=0.004]. Our pooled analyses did not include PPG control and HbA1c outcomes. Because only 1 study included in the meta-analysis reported PPG variables and only 2 studies reported HbA1c variables. In conclusion, the current meta-analysis showed that the administration of garlic resulted in a significant reduction in FBG concentrations. More trials are needed to investigate the effectiveness of garlic on HbA1c and PPG.

Polyphenol composition and antioxidant activity of Kei-apple (Dovyalis caffra) juice.

PubMed

Loots, Du Toit; van der Westhuizen, Francois H; Jerling, Johann

2006-02-22

The polyphenolic and ascorbate (ASC) components as well as the antioxidant capacity of Kei-apple (Dovyalis caffra) juice were analyzed and compared to three other fruit juices. The Kei-apple juice had significantly the highest total polyphenolic concentrations (1013 mg gallic acid equivalent/L), and solid phase (C(18)) fractionation identified the majority of these polyphenols to be phenolic acids. The Kei-apple juice also had significantly the highest ASC concentrations (658 mg/L), which showed exceptional heat stability with very little conversion to dehydroascorbate (DHA). Antioxidant capacities of both the unfractionated fruit juices and their solid phase-extracted fractions, as determined by oxygen radical absorbance capacity and ferric reducing antioxidant power analyses, correlated well to the polyphenol concentrations. Gas chromatography-mass spectrometry analyses showed caffeic acid as the most abundant polyphenol present (128.7 mg/L) in the Kei-apple juice; it contributed to 63% of the total antioxidant capacity (of all of the individual compounds identified). Other notable polyphenols identified in higher concentrations included p-coumaric acid, p-hydroxyphenylacetic acid, and protocatechuic acid. Our results therefore support the putative high antioxidant value linked to this fruit and better define this potential in terms of the major antioxidants that exist in the Kei-apple.

Genetic Structure of Bluefin Tuna in the Mediterranean Sea Correlates with Environmental Variables

PubMed Central

Riccioni, Giulia; Stagioni, Marco; Landi, Monica; Ferrara, Giorgia; Barbujani, Guido; Tinti, Fausto

2013-01-01

Background Atlantic Bluefin Tuna (ABFT) shows complex demography and ecological variation in the Mediterranean Sea. Genetic surveys have detected significant, although weak, signals of population structuring; catch series analyses and tagging programs identified complex ABFT spatial dynamics and migration patterns. Here, we tested the hypothesis that the genetic structure of the ABFT in the Mediterranean is correlated with mean surface temperature and salinity. Methodology We used six samples collected from Western and Central Mediterranean integrated with a new sample collected from the recently identified easternmost reproductive area of Levantine Sea. To assess population structure in the Mediterranean we used a multidisciplinary framework combining classical population genetics, spatial and Bayesian clustering methods and a multivariate approach based on factor analysis. Conclusions FST analysis and Bayesian clustering methods detected several subpopulations in the Mediterranean, a result also supported by multivariate analyses. In addition, we identified significant correlations of genetic diversity with mean salinity and surface temperature values revealing that ABFT is genetically structured along two environmental gradients. These results suggest that a preference for some spawning habitat conditions could contribute to shape ABFT genetic structuring in the Mediterranean. However, further studies should be performed to assess to what extent ABFT spawning behaviour in the Mediterranean Sea can be affected by environmental variation. PMID:24260341

Deciphering deterioration mechanisms of complex diseases based on the construction of dynamic networks and systems analysis

NASA Astrophysics Data System (ADS)

Li, Yuanyuan; Jin, Suoqin; Lei, Lei; Pan, Zishu; Zou, Xiufen

2015-03-01

The early diagnosis and investigation of the pathogenic mechanisms of complex diseases are the most challenging problems in the fields of biology and medicine. Network-based systems biology is an important technique for the study of complex diseases. The present study constructed dynamic protein-protein interaction (PPI) networks to identify dynamical network biomarkers (DNBs) and analyze the underlying mechanisms of complex diseases from a systems level. We developed a model-based framework for the construction of a series of time-sequenced networks by integrating high-throughput gene expression data into PPI data. By combining the dynamic networks and molecular modules, we identified significant DNBs for four complex diseases, including influenza caused by either H3N2 or H1N1, acute lung injury and type 2 diabetes mellitus, which can serve as warning signals for disease deterioration. Function and pathway analyses revealed that the identified DNBs were significantly enriched during key events in early disease development. Correlation and information flow analyses revealed that DNBs effectively discriminated between different disease processes and that dysfunctional regulation and disproportional information flow may contribute to the increased disease severity. This study provides a general paradigm for revealing the deterioration mechanisms of complex diseases and offers new insights into their early diagnoses.

Using multivariate analyses and GIS to identify pollutants and their spatial patterns in urban soils in Galway, Ireland.

PubMed

Zhang, Chaosheng

2006-08-01

Galway is a small but rapidly growing tourism city in western Ireland. To evaluate its environmental quality, a total of 166 surface soil samples (0-10 cm depth) were collected from parks and grasslands at the density of 1 sample per 0.25 km2 at the end of 2004. All samples were analysed using ICP-AES for the near-total concentrations of 26 chemical elements. Multivariate statistics and GIS techniques were applied to classify the elements and to identify elements influenced by human activities. Cluster analysis (CA) and principal component analysis (PCA) classified the elements into two groups: the first group predominantly derived from natural sources, the second being influenced by human activities. GIS mapping is a powerful tool in identifying the possible sources of pollutants. Relatively high concentrations of Cu, Pb and Zn were found in the city centre, old residential areas, and along major traffic routes, showing significant effects of traffic pollution. The element As is enriched in soils of the old built-up areas, which can be attributed to coal and peat combustion for home heating. Such significant spatial patterns of pollutants displayed by urban soils may imply potential health threat to residents of the contaminated areas of the city.

An initial evaluation of the Social Communication Questionnaire for the assessment of autism spectrum disorders in children with Down syndrome.

PubMed

Magyar, Caroline I; Pandolfi, Vincent; Dill, Charles A

2012-02-01

This study investigated the psychometric properties of the Social Communication Questionnaire (SCQ) in a sample of children with Down syndrome (DS), many of whom had a co-occurring autism spectrum disorder (ASD). The SCQ is a widely used ASD screening measure; however, its measurement properties have not been comprehensively evaluated specifically in children with DS, a group that seems to be at higher risk for an ASD. Exploratory and confirmatory factor analyses, scale reliability, convergent and discriminant correlations, significance tests between groups of children with DS and DS + ASD, and diagnostic accuracy analyses were conducted. Factor analyses identified 2 reliable factors that we labeled Social-Communication and Stereotyped Behavior and Unusual Interests. Pearson correlations with Autism Diagnostic Interview-Revised subscales indicated support for the SCQ's convergent validity and some support for the discriminant validity of the factor-based scales. Significance tests and receiver operating characteristic analyses indicated that children with DS + ASD obtained significantly higher SCQ factor-based and total scores than children with DS alone, and that the SCQ Total Score evidenced good sensitivity and adequate specificity. Results indicated initial psychometric support for the SCQ as an ASD screening measure in children with DS. The SCQ should be considered as part of a multimethod evaluation when screening children with DS.

Multi-country health surveys: are the analyses misleading?

PubMed

Masood, Mohd; Reidpath, Daniel D

2014-05-01

The aim of this paper was to review the types of approaches currently utilized in the analysis of multi-country survey data, specifically focusing on design and modeling issues with a focus on analyses of significant multi-country surveys published in 2010. A systematic search strategy was used to identify the 10 multi-country surveys and the articles published from them in 2010. The surveys were selected to reflect diverse topics and foci; and provide an insight into analytic approaches across research themes. The search identified 159 articles appropriate for full text review and data extraction. The analyses adopted in the multi-country surveys can be broadly classified as: univariate/bivariate analyses, and multivariate/multivariable analyses. Multivariate/multivariable analyses may be further divided into design- and model-based analyses. Of the 159 articles reviewed, 129 articles used model-based analysis, 30 articles used design-based analyses. Similar patterns could be seen in all the individual surveys. While there is general agreement among survey statisticians that complex surveys are most appropriately analyzed using design-based analyses, most researchers continued to use the more common model-based approaches. Recent developments in design-based multi-level analysis may be one approach to include all the survey design characteristics. This is a relatively new area, however, and there remains statistical, as well as applied analytic research required. An important limitation of this study relates to the selection of the surveys used and the choice of year for the analysis, i.e., year 2010 only. There is, however, no strong reason to believe that analytic strategies have changed radically in the past few years, and 2010 provides a credible snapshot of current practice.

Genetic and epigenetic differences associated with environmental gradients in replicate populations of two salt marsh perennials.

PubMed

Foust, C M; Preite, V; Schrey, A W; Alvarez, M; Robertson, M H; Verhoeven, K J F; Richards, C L

2016-04-01

While traits and trait plasticity are partly genetically based, investigating epigenetic mechanisms may provide more nuanced understanding of the mechanisms underlying response to environment. Using AFLP and methylation-sensitive AFLP, we tested the hypothesis that differentiation to habitats along natural salt marsh environmental gradients occurs at epigenetic, but not genetic loci in two salt marsh perennials. We detected significant genetic and epigenetic structure among populations and among subpopulations, but we found multilocus patterns of differentiation to habitat type only in epigenetic variation for both species. In addition, more epigenetic than genetic loci were correlated with habitat in both species. When we analysed genetic and epigenetic variation simultaneously with partial Mantel, we found no correlation between genetic variation and habitat and a significant correlation between epigenetic variation and habitat in Spartina alterniflora. In Borrichia frutescens, we found significant correlations between epigenetic and/or genetic variation and habitat in four of five populations when populations were analysed individually, but there was no significant correlation between genetic or epigenetic variation and habitat when analysed jointly across the five populations. These analyses suggest that epigenetic mechanisms are involved in the response to salt marsh habitats, but also that the relationships among genetic and epigenetic variation and habitat vary by species. Site-specific conditions may also cloud our ability to detect response in replicate populations with similar environmental gradients. Future studies analysing sequence data and the correlation between genetic variation and DNA methylation will be powerful to identify the contributions of genetic and epigenetic response to environmental gradients. © 2016 John Wiley & Sons Ltd.

Analyses in support of risk-informed natural gas vehicle maintenance facility codes and standards :

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

Ekoto, Isaac W.; Blaylock, Myra L.; LaFleur, Angela Christine

2014-03-01

Safety standards development for maintenance facilities of liquid and compressed gas fueled large-scale vehicles is required to ensure proper facility design and operation envelopes. Standard development organizations are utilizing risk-informed concepts to develop natural gas vehicle (NGV) codes and standards so that maintenance facilities meet acceptable risk levels. The present report summarizes Phase I work for existing NGV repair facility code requirements and highlights inconsistencies that need quantitative analysis into their effectiveness. A Hazardous and Operability study was performed to identify key scenarios of interest. Finally, scenario analyses were performed using detailed simulations and modeling to estimate the overpressure hazardsmore » from HAZOP defined scenarios. The results from Phase I will be used to identify significant risk contributors at NGV maintenance facilities, and are expected to form the basis for follow-on quantitative risk analysis work to address specific code requirements and identify effective accident prevention and mitigation strategies.« less

Validation of the Readiness for Return-To-Work Scale in Outpatient Occupational Rehabilitation in Canada.

PubMed

Park, Joanne; Roberts, Mary Roduta; Esmail, Shaniff; Rayani, Fahreen; Norris, Colleen M; Gross, Douglas P

2018-06-01

Purpose To examine construct and concurrent validity of the Readiness for Return-To-Work (RRTW) Scale with injured workers participating in an outpatient occupational rehabilitation program. Methods Lost-time claimants (n = 389) with sub-acute or chronic musculoskeletal disorders completed the RRTW Scale on their first day of their occupational rehabilitation program. Statistical analysis included exploratory and confirmatory factor analyses of the readiness items, reliability analyses, and correlation with related scales and questionnaires. Results For claimants in the non-job attached/not working group (n = 165), three factors were found (1) Contemplation (2) Prepared for Action-Self-evaluative and (3) Prepared for Action-Behavioural. The precontemplation stage was not identified within this sample of injured workers. For claimants who were job attached/working group in some capacity (n = 224), two factors were identified (1) Uncertain Maintenance and (2) Proactive Maintenance. Expected relationships and statistically significant differences were found among the identified Return-To-Work (RTW) readiness factors and related constructs of pain, physical and mental health and RTW expectations. Conclusion Construct and concurrent validity of the RRTW Scale were supported in this study. The results of this study indicate the construct of readiness for RTW can vary by disability duration and occupational category. Physical health appears to be a significant barrier to RRTW for the job attached/working group while mental health significantly compromises RRTW with the non-job attached/not working group.

Common Trajectories of Regional Competitiveness in the Knowledge Economy: A European Investigation

ERIC Educational Resources Information Center

Brioschi, Maria Sole; Cassia, Lucio

2006-01-01

This paper analyses a number of European regions which, in the last two decades, have exhibited a significant shift towards knowledge-intensive industrial sectors coupled with a considerable increase in competitiveness and growth. The analysis identifies the main factors of territorial development behind each regional renewal process and captures…

Bem Sex Role Inventory Undifferentiated Score: A Comparison of Sexual Dysfunction Patients with Sexual Offenders.

ERIC Educational Resources Information Center

Dwyer, Margretta; And Others

1988-01-01

Examined Bem Sex Role undifferentiated scores on 93 male sex offenders as compared with 50 male sexually dysfunctional patients. Chi-square analyses revealed significant difference: offenders obtained undifferentiated scores more often than did sexual dysfunctional population. Concluded that Bem Sex Role Inventory is useful in identifying sexual…

Case-Control Genome-Wide Association Study of Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Neale, Benjamin M.; Medland, Sarah; Ripke, Stephan; Anney, Richard J. L.; Asherson, Philip; Buitelaar, Jan; Franke, Barbara; Gill, Michael; Kent, Lindsey; Holmans, Peter; Middleton, Frank; Thapar, Anita; Lesch, Klaus-Peter; Faraone, Stephen V.; Daly, Mark; Nguyen, Thuy Trang; Schafer, Helmut; Steinhausen, Hans-Christoph; Reif, Andreas; Renner, Tobias J.; Romanos, Marcel; Romanos, Jasmin; Warnke, Andreas; Walitza, Susanne; Freitag, Christine; Meyer, Jobst; Palmason, Haukur; Rothenberger, Aribert; Hawi, Ziarih; Sergeant, Joseph; Roeyers, Herbert; Mick, Eric; Biederman, Joseph

2010-01-01

Objective: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. Thus additional genome-wide association studies (GWAS) are needed. Method: We used case-control analyses of 896 cases…

The NASA Electric Propulsion Program

NASA Technical Reports Server (NTRS)

Byers, David C.; Wasel, Robert A.

1987-01-01

The NASA OAST Propulsion, Power and Energy Division supports electric propulsion for a broad class of missions. Concepts with potential to significantly benefit or enable space exploration and exploitation are identified and advanced toward applications in the near to far term. Recent program progress in mission/system analyses and in electrothermal, ion, and electromagnetic technologies are summarized.

Integrating evolutionary and functional approaches to infer adaptation at specific loci.

PubMed

Storz, Jay F; Wheat, Christopher W

2010-09-01

Inferences about adaptation at specific loci are often exclusively based on the static analysis of DNA sequence variation. Ideally,population-genetic evidence for positive selection serves as a stepping-off point for experimental studies to elucidate the functional significance of the putatively adaptive variation. We argue that inferences about adaptation at specific loci are best achieved by integrating the indirect, retrospective insights provided by population-genetic analyses with the more direct, mechanistic insights provided by functional experiments. Integrative studies of adaptive genetic variation may sometimes be motivated by experimental insights into molecular function, which then provide the impetus to perform population genetic tests to evaluate whether the functional variation is of adaptive significance. In other cases, studies may be initiated by genome scans of DNA variation to identify candidate loci for recent adaptation. Results of such analyses can then motivate experimental efforts to test whether the identified candidate loci do in fact contribute to functional variation in some fitness-related phenotype. Functional studies can provide corroborative evidence for positive selection at particular loci, and can potentially reveal specific molecular mechanisms of adaptation.

Identifying contextual influences of community reintegration among injured servicemembers.

PubMed

Hawkins, Brent L; McGuire, Francis A; Britt, Thomas W; Linder, Sandra M

2015-01-01

Research suggests that community reintegration (CR) after injury and rehabilitation is difficult for many injured servicemembers. However, little is known about the influence of the contextual factors, both personal and environmental, that influence CR. Framed within the International Classification of Functioning, Disability and Health and Social Cognitive Theory, the quantitative portion of a larger mixed-methods study of 51 injured, community-dwelling servicemembers compared the relative contribution of contextual factors between groups of servicemembers with different levels of CR. Cluster analysis indicated three groups of servicemembers showing low, moderate, and high levels of CR. Statistical analyses identified contextual factors (e.g., personal and environmental factors) that significantly discriminated between CR clusters. Multivariate analysis of variance and discriminant analysis indicated significant contributions of general self-efficacy, services and assistance barriers, physical and structural barriers, attitudes and support barriers, perceived level of disability and/or handicap, work and school barriers, and policy barriers on CR scores. Overall, analyses indicated that injured servicemembers with lower CR scores had lower general self-efficacy scores, reported more difficulty with environmental barriers, and reported their injuries as more disabling.

Exploring New Zealand prescription data using sequence symmetry analyses for predicting adverse drug reactions.

PubMed

Nishtala, P S; Chyou, T-Y

2017-04-01

Prescription sequence symmetry analyses (PSSA) is a ubiquitous tool employed in pharmacoepidemiological research to predict adverse drug reactions (ADRs). Several studies have reported the advantage of PSSA as a method that can be applied to a large prescription database with computational ease. The objective of this study was to validate New Zealand (NZ) prescription database as a potential source for identifying ADRs using the PSSA method. We analysed de-identified individual-level prescription data for people aged 65 years and above for the period 2005 to 2014 from the pharmaceutical collections supplied by the NZ Ministry of Health. We selected six positive controls that have been previously investigated and reported for causing ADRs. The six positive controls identified were amiodarone (repeated twice), frusemide, simvastatin, lithium and fluticasone. Amiodarone and lithium have been reported to induce thyroid dysfunction. Simvastatin reported to cause muscle cramps while fluticasone is well documented to cause oral candidiasis. Thyroxine was identified as a marker drug to treat hypothyroidism associated with amiodarone and lithium. Carbimazole was identified as a marker drug to treat hyperthyroidism associated with amiodarone use. Quinine sulphate was identified as a marker drug to treat muscle cramps associated with statins. In addition, we also analysed six negative controls that are unlikely to be associated with ADRs. The main outcome measure is to determine associations with ADRs using adjusted sequence ratios (ASR), and 95% confidence intervals RESULTS AND DISCUSSION: Our analyses confirmed a significant signal for all six positive controls. Significant positive associations were noted for amiodarone [ASR = 3·57, 95% CI (3·17-4·02)], and lithium chloride induced hypothyroidism [ASR = 3·43, 95% CI (2·55-4·70)]. Amiodarone was also strongly associated with hyperthyroidism [ASR = 8·81 95% CI (5·86-13·77)]. Simvastatin was associated with muscle cramps [ASR = 1·69, 95% CI (1·61-1·77)]. Fluticasone was positively associated with oral candidiasis [ASR = 2·34, 95% CI (2·19-2·50)]. Frusemide was associated with hypokalaemia [ASR = 2·94, 95% CI (2·83-3·05]). No strong associations were noted for the negative pairs. It is important to highlight that PSSA automatically controls for all confounding factors including unknown and unmeasured confounding variables, plus the effect of temporal trend in prescriptions, and hence allows a more robust ADR detection especially when confounding factors are difficult to determine or measure. New Zealand prescription database can be a potential source to identify ADRs engaging the PSSA method, and this could complement pharmacovigilance surveillance in NZ. The PSSA can be an important method for post-marketing surveillance and monitoring of ADRs which have relatively short latency. However, the predictive validity of PSSA will be compromised in certain scenarios, particularly when sample size is small, when new drugs are in the market and data are sparse. © 2016 John Wiley & Sons Ltd.

HbA2 levels in β-thalassaemia carriers with the Filipino β0-deletion: are the levels higher than what is found with non-deletional forms of β0-thalassaemia?

PubMed

George, E; Teh, Lai Kuan; Tan, Jama; Lai, Mei I; Wong, Lily

2013-01-01

Classical carriers of β-thalassaemia are identified by a raised HbA2 level. Earlier studies indicated that the Filipino β-deletion has high raised HbA2 levels. The introduction of automated high performance liquid chromatography (HPLC) for thalassaemia screening is an important advance in technology for haematology laboratories. The BioRad Variant II Hb analyser is a common instrument used to quantify HbA2 levels in thalassaemia screening. This study aimed to determine HbA2 levels in carriers of Filipino β-mutation using the BioRad Variant II Hb analyser. The Filipino β-deletion was identified using gap-polymerase chain reaction (PCR) in the parents of transfusion dependent β-thalassaemia patients who were homozygous for the Filipino β-deletion in the indigenous population of Sabah, Malaysia. Hb subtypes were quantified on the BioRad Variant II Hb analyser. Concurrent α-thalassaemia was identified by multiplex gap-PCR for deletions and amplification refractory mutation system (ARMS)-PCR for non-deletional mutations. The mean HbA2 level for Filipino β-thalassaemia trait was 5.9 ± 0.47 and with coinheritance of α-thalassaemia was 6.3 ± 0.44 (-α heterozygous) and 6.7 ± 0.36 (-α homozygous). The HbA2 levels were all >4% in keeping with the findings of classical β-thalassaemia trait and significantly higher than levels seen in non-deletional forms of β-thalassaemia. The HbA2 level measured on the BioRad Variant II Hb analyser was lower than the level in the first description of the Filipino β-thalassaemia. β-thalassaemia trait with coinheritance of α-thalassaemia (-α) is associated with significantly higher HbA2 level.

Factors associated with seasonal influenza vaccination in pregnant women.

PubMed

Henninger, Michelle L; Irving, Stephanie A; Thompson, Mark; Avalos, Lyndsay Ammon; Ball, Sarah W; Shifflett, Pat; Naleway, Allison L

2015-05-01

This observational study followed a cohort of pregnant women during the 2010-2011 influenza season to determine factors associated with vaccination. Participants were 1105 pregnant women who completed a survey assessing health beliefs related to vaccination upon enrollment and were then followed to determine vaccination status by the end of the 2010-2011 influenza season. We conducted univariate and multivariate analyses to explore factors associated with vaccination status and a factor analysis of survey items to identify health beliefs associated with vaccination. Sixty-three percent (n=701) of the participants were vaccinated. In the univariate analyses, multiple factors were associated with vaccination status, including maternal age, race, marital status, educational level, and gravidity. Factor analysis identified two health belief factors associated with vaccination: participant's positive views (factor 1) and negative views (factor 2) of influenza vaccination. In a multivariate logistic regression model, factor 1 was associated with increased likelihood of vaccination (adjusted odds ratio [aOR]=2.18; 95% confidence interval [CI]=1.72-2.78), whereas factor 2 was associated with decreased likelihood of vaccination (aOR=0.36; 95% CI=0.28-0.46). After controlling for the two health belief factors in multivariate analyses, demographic factors significant in univariate analyses were no longer significant. Women who received a provider recommendation were about three times more likely to be vaccinated (aOR=3.14; 95% CI=1.99-4.96). Pregnant women's health beliefs about vaccination appear to be more important than demographic and maternal factors previously associated with vaccination status. Provider recommendation remains one of the most critical factors influencing vaccination during pregnancy.

The sumLINK statistic for genetic linkage analysis in the presence of heterogeneity.

PubMed

Christensen, G B; Knight, S; Camp, N J

2009-11-01

We present the "sumLINK" statistic--the sum of multipoint LOD scores for the subset of pedigrees with nominally significant linkage evidence at a given locus--as an alternative to common methods to identify susceptibility loci in the presence of heterogeneity. We also suggest the "sumLOD" statistic (the sum of positive multipoint LOD scores) as a companion to the sumLINK. sumLINK analysis identifies genetic regions of extreme consistency across pedigrees without regard to negative evidence from unlinked or uninformative pedigrees. Significance is determined by an innovative permutation procedure based on genome shuffling that randomizes linkage information across pedigrees. This procedure for generating the empirical null distribution may be useful for other linkage-based statistics as well. Using 500 genome-wide analyses of simulated null data, we show that the genome shuffling procedure results in the correct type 1 error rates for both the sumLINK and sumLOD. The power of the statistics was tested using 100 sets of simulated genome-wide data from the alternative hypothesis from GAW13. Finally, we illustrate the statistics in an analysis of 190 aggressive prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics, where we identified a new susceptibility locus. We propose that the sumLINK and sumLOD are ideal for collaborative projects and meta-analyses, as they do not require any sharing of identifiable data between contributing institutions. Further, loci identified with the sumLINK have good potential for gene localization via statistical recombinant mapping, as, by definition, several linked pedigrees contribute to each peak.

Whole-Genome Sequencing of Pharmacogenetic Drug Response in Racially Diverse Children with Asthma.

PubMed

Mak, Angel C Y; White, Marquitta J; Eckalbar, Walter L; Szpiech, Zachary A; Oh, Sam S; Pino-Yanes, Maria; Hu, Donglei; Goddard, Pagé; Huntsman, Scott; Galanter, Joshua; Wu, Ann Chen; Himes, Blanca E; Germer, Soren; Vogel, Julia M; Bunting, Karen L; Eng, Celeste; Salazar, Sandra; Keys, Kevin L; Liberto, Jennifer; Nuckton, Thomas J; Nguyen, Thomas A; Torgerson, Dara G; Kwok, Pui-Yan; Levin, Albert M; Celedón, Juan C; Forno, Erick; Hakonarson, Hakon; Sleiman, Patrick M; Dahlin, Amber; Tantisira, Kelan G; Weiss, Scott T; Serebrisky, Denise; Brigino-Buenaventura, Emerita; Farber, Harold J; Meade, Kelley; Lenoir, Michael A; Avila, Pedro C; Sen, Saunak; Thyne, Shannon M; Rodriguez-Cintron, William; Winkler, Cheryl A; Moreno-Estrada, Andrés; Sandoval, Karla; Rodriguez-Santana, Jose R; Kumar, Rajesh; Williams, L Keoki; Ahituv, Nadav; Ziv, Elad; Seibold, Max A; Darnell, Robert B; Zaitlen, Noah; Hernandez, Ryan D; Burchard, Esteban G

2018-06-15

Albuterol, a bronchodilator medication, is the first-line therapy for asthma worldwide. There are significant racial/ethnic differences in albuterol drug response. To identify genetic variants important for bronchodilator drug response (BDR) in racially diverse children. We performed the first whole-genome sequencing pharmacogenetics study from 1,441 children with asthma from the tails of the BDR distribution to identify genetic association with BDR. We identified population-specific and shared genetic variants associated with BDR, including genome-wide significant (P < 3.53 × 10 -7 ) and suggestive (P < 7.06 × 10 -6 ) loci near genes previously associated with lung capacity (DNAH5), immunity (NFKB1 and PLCB1), and β-adrenergic signaling (ADAMTS3 and COX18). Functional analyses of the BDR-associated SNP in NFKB1 revealed potential regulatory function in bronchial smooth muscle cells. The SNP is also an expression quantitative trait locus for a neighboring gene, SLC39A8. The lack of other asthma study populations with BDR and whole-genome sequencing data on minority children makes it impossible to perform replication of our rare variant associations. Minority underrepresentation also poses significant challenges to identify age-matched and population-matched cohorts of sufficient sample size for replication of our common variant findings. The lack of minority data, despite a collaboration of eight universities and 13 individual laboratories, highlights the urgent need for a dedicated national effort to prioritize diversity in research. Our study expands the understanding of pharmacogenetic analyses in racially/ethnically diverse populations and advances the foundation for precision medicine in at-risk and understudied minority populations.

Comprehensive evaluation of disease- and trait-specific enrichment for eight functional elements among GWAS-identified variants.

PubMed

Markunas, Christina A; Johnson, Eric O; Hancock, Dana B

2017-07-01

Genome-wide association study (GWAS)-identified variants are enriched for functional elements. However, we have limited knowledge of how functional enrichment may differ by disease/trait and tissue type. We tested a broad set of eight functional elements for enrichment among GWAS-identified SNPs (p < 5×10 -8 ) from the NHGRI-EBI Catalog across seven disease/trait categories: cancer, cardiovascular disease, diabetes, autoimmune disease, psychiatric disease, neurological disease, and anthropometric traits. SNPs were annotated using HaploReg for the eight functional elements across any tissue: DNase sites, expression quantitative trait loci (eQTL), sequence conservation, enhancers, promoters, missense variants, sequence motifs, and protein binding sites. In addition, tissue-specific annotations were considered for brain vs. blood. Disease/trait SNPs were compared to a control set of 4809 SNPs matched to the GWAS SNPs (N = 1639) on allele frequency, gene density, distance to nearest gene, and linkage disequilibrium at ~3:1 ratio. Enrichment analyses were conducted using logistic regression, with Bonferroni correction. Overall, a significant enrichment was observed for all functional elements, except sequence motifs. Missense SNPs showed the strongest magnitude of enrichment. eQTLs were the only functional element significantly enriched across all diseases/traits. Magnitudes of enrichment were generally similar across diseases/traits, where enrichment was statistically significant. Blood vs. brain tissue effects on enrichment were dependent on disease/trait and functional element (e.g., cardiovascular disease: eQTLs P TissueDifference  = 1.28 × 10 -6 vs. enhancers P TissueDifference  = 0.94). Identifying disease/trait-relevant functional elements and tissue types could provide new insight into the underlying biology, by guiding a priori GWAS analyses (e.g., brain enhancer elements for psychiatric disease) or facilitating post hoc interpretation.

Pathway-driven gene stability selection of two rheumatoid arthritis GWAS identifies and validates new susceptibility genes in receptor mediated signalling pathways.

PubMed

Eleftherohorinou, Hariklia; Hoggart, Clive J; Wright, Victoria J; Levin, Michael; Coin, Lachlan J M

2011-09-01

Rheumatoid arthritis (RA) is the commonest chronic, systemic, inflammatory disorder affecting ∼1% of the world population. It has a strong genetic component and a growing number of associated genes have been discovered in genome-wide association studies (GWAS), which nevertheless only account for 23% of the total genetic risk. We aimed to identify additional susceptibility loci through the analysis of GWAS in the context of biological function. We bridge the gap between pathway and gene-oriented analyses of GWAS, by introducing a pathway-driven gene stability-selection methodology that identifies potential causal genes in the top-associated disease pathways that may be driving the pathway association signals. We analysed the WTCCC and the NARAC studies of ∼5000 and ∼2000 subjects, respectively. We examined 700 pathways comprising ∼8000 genes. Ranking pathways by significance revealed that the NARAC top-ranked ∼6% laid within the top 10% of WTCCC. Gene selection on those pathways identified 58 genes in WTCCC and 61 in NARAC; 21 of those were common (P(overlap)< 10(-21)), of which 16 were novel discoveries. Among the identified genes, we validated 10 known RA associations in WTCCC and 13 in NARAC, not discovered using single-SNP approaches on the same data. Gene ontology functional enrichment analysis on the identified genes showed significant over-representation of signalling activity (P< 10(-29)) in both studies. Our findings suggest a novel model of RA genetic predisposition, which involves cell-membrane receptors and genes in second messenger signalling systems, in addition to genes that regulate immune responses, which have been the focus of interest previously.

HPLC-MS and GC-MS analyses combined with orthogonal partial least squares to identify cytotoxic constituents from turmeric (Curcuma longa L.).

PubMed

Jiang, Jianlan; Zhang, Huan; Li, Zidan; Zhang, Xiaohang; Su, Xin; Li, Yan; Qiao, Bin; Yuan, Yingjin

2013-08-01

We investigated the fingerprints of 48 batches of turmeric total extracts (TTE) by HPLC-MS-MS and GC-MS analyses and 43 characteristic peaks (22 constituents from HPLC-MS-MS; 21 from GC-MS) were analyzed qualitatively and quantitatively. An MTT {3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide} assay was implemented to measure the cytotoxicity of the TTE against HeLa cells. Then we utilized orthogonal partial least squares analysis, which correlated the chemical composition of the TTE to its cytotoxic activity, to identify potential cytotoxic constituents from turmeric. The result showed that 19 constituents contributed significantly to the cytotoxicity. The obtained result was verified by canonical correlation analysis. Comparison with previous reports also indicated some interaction between the curcuminoids and sesquiterpenoids in turmeric.

Redefining diagnosis-related groups (DRGs) for palliative care - a cross-sectional study in two German centres.

PubMed

Vogl, Matthias; Schildmann, Eva; Leidl, Reiner; Hodiamont, Farina; Kalies, Helen; Maier, Bernd Oliver; Schlemmer, Marcus; Roller, Susanne; Bausewein, Claudia

2018-04-05

Hospital costs and cost drivers in palliative care are poorly analysed. It remains unknown whether current German Diagnosis-Related Groups, mainly relying on main diagnosis or procedure, reproduce costs adequately. The aim of this study was therefore to analyse costs and reimbursement for inpatient palliative care and to identify relevant cost drivers. Two-center, standardised micro-costing approach with patient-level cost calculations and analysis of the reimbursement situation for patients receiving palliative care at two German hospitals (7/2012-12/2013). Data were analysed for the total group receiving hospital care covering, but not exclusively, palliative care (group A) and the subgroup receiving palliative care only (group B). Patient and care characteristics predictive of inpatient costs of palliative care were derived by generalised linear models and investigated by classification and regression tree analysis. Between 7/2012 and 12/2013, 2151 patients received care in the two hospitals including, but not exclusively, on the PCUs (group A). In 2013, 784 patients received care on the two PCUs only (group B). Mean total costs per case were € 7392 (SD 7897) (group A) and € 5763 (SD 3664) (group B), mean total reimbursement per case € 5155 (SD 6347) (group A) and € 4278 (SD 2194) (group B). For group A/B on the ward, 58%/67% of the overall costs and 48%/53%, 65%/82% and 64%/72% of costs for nursing, physicians and infrastructure were reimbursed, respectively. Main diagnosis did not significantly influence costs. However, duration of palliative care and total length of stay were (related to the cost calculation method) identified as significant cost drivers. Related to the cost calculation method, total length of stay and duration of palliative care were identified as significant cost drivers. In contrast, main diagnosis did not reflect costs. In addition, results show that reimbursement within the German Diagnosis-Related Groups system does not reproduce the costs adequately, but causes a financing gap for inpatient palliative care.

Effects of green tea catechins with or without caffeine on glycemic control in adults: a meta-analysis of randomized controlled trials.

PubMed

Zheng, Xin-Xin; Xu, Yan-Lu; Li, Shao-Hua; Hui, Rutai; Wu, Yong-Jian; Huang, Xiao-Hong

2013-04-01

The effect of green tea catechins (GTCs) with or without caffeine on glycemic control is controversial. We aimed to identify and quantify the effects of GTCs or GTC-caffeine mixtures on glucose metabolism in adults. A comprehensive literature search was conducted to identify relevant trials of GTCs with or without caffeine on markers of glycemic control [fasting blood glucose (FBG), fasting blood insulin (FBI), glycated hemoglobin (Hb A1c), and homeostatic model assessment of insulin resistance (HOMA-IR)]. Weighted mean differences were calculated for net changes by using fixed-effects models. Prespecified subgroup analyses were performed to explore the influence of covariates on net changes in FBG and FBI concentrations. Twenty-two eligible randomized controlled trials with 1584 subjects were identified. Pooled analyses showed that FBG (-1.48 mg/dL; 95% CI: -2.57, -0.40 mg/dL) decreased significantly with GTCs with or without caffeine, whereas FBI (0.04 μU/mL; 95% CI: -0.36, 0.45 μU/mL), Hb A1c (-0.04%; 95% CI: -0.15, 0.08%), and HOMA-IR (-0.05; 95% CI: -0.37, 0.26) did not. Subgroup analyses indicated that the glucose-lowering effect was apparent when the duration of follow-up was over a median of 12 wk. Overall, no significant heterogeneity was detected for FBG, FBI, Hb A1c, or HOMA-IR. The meta-analysis showed that the administration of GTCs with or without caffeine resulted in a significant reduction in FBG. The limited data available on GTCs did not support a positive effect on FBI, Hb A1c, or HOMA-IR. Thus, more large and well-designed trials are needed in the future. This trial was registered at http://www.crd.york.ac.uk/prospero as CRD42012002139.

Morphological and functional abnormalities of salience network in the early-stage of paranoid schizophrenia.

PubMed

Pu, Weidan; Li, Li; Zhang, Huiran; Ouyang, Xuan; Liu, Haihong; Zhao, Jingping; Li, Lingjiang; Xue, Zhimin; Xu, Ke; Tang, Haibo; Shan, Baoci; Liu, Zhening; Wang, Fei

2012-10-01

A salience network (SN), mainly composed of the anterior insula (AI) and anterior cingulate cortex (ACC), has been suggested to play an important role in salience attribution which has been proposed as central to the pathology of paranoid schizophrenia. The role of this SN in the pathophysiology of paranoid schizophrenia, however, still remains unclear. In the present study, voxel-based morphometry and resting-state functional connectivity analyses were combined to identify morphological and functional abnormalities in the proposed SN in the early-stage of paranoid schizophrenia (ESPS). Voxel-based morphometry and resting-state functional connectivity analyses were applied to 90 ESPS patients and 90 age- and sex-matched healthy controls (HC). Correlation analyses were performed to examine the relationships between various clinical variables and both gray matter morphology and functional connectivity within the SN in ESPS. Compared to the HC group, the ESPS group showed significantly reduced gray matter volume (GMV) in both bilateral AI and ACC. Moreover, significantly reduced functional connectivity within the SN sub-networks was identified in the ESPS group. These convergent morphological and functional deficits in SN were significantly associated with hallucinations. Additionally, illness duration correlated with reduced GMV in the left AI in ESPS. In conclusion, these findings provide convergent evidence for the morphological and functional abnormalities of the SN in ESPS. Moreover, the association of illness duration with the reduced GMV in the left AI suggests that the SN and the AI, in particular, may manifest progressive morphological changes that are especially important in the emergence of ESPS. Copyright © 2012 Elsevier B.V. All rights reserved.

Serum chemerin levels are independently associated with quality of life in colorectal cancer survivors: A pilot study

PubMed Central

Lee, Jee-Yon; Lee, Mi-Kyung; Kim, Nam-Kyu; Chu, Sang-Hui; Lee, Duk-Chul; Lee, Hye-Sun

2017-01-01

Background Colorectal cancer (CRC) survivors are known to experience various symptoms that significantly affect their quality of life (QOL); therefore, it is important to identify clinical markers related with CRC survivor QOL. Here we investigated the relationship between serum chemerin levels, a newly identified proinflammatory adipokine, and QOL in CRC survivors. Methods A data of total of 110 CRC survivors were analysed in the study. Serum chemerin levels were measured with an enzyme immunoassay analyser. Functional Assessment of Cancer Therapy (FACT) scores were used as an indicator of QOL in CRC survivors. Results Weak but not negligible relationships were observed between serum chemerin levels and FACT-General (G) (r = -0.22, p<0.02), FACT-Colorectal cancer (C) (r = -0.23, p<0.02) and FACT-Fatigue (F) scores (r = -0.27, p<0.01) after adjusting for confounding factors. Both stepwise and enter method multiple linear regression analyses confirmed that serum chemerin levels were independently associated with FACT-G (stepwise: β = -0.15, p<0.01; enter: β = -0.12, p = 0.02), FACT-C (stepwise: β = -0.19, p<0.01; enter; β = -0.14, p = 0.02) and FACT-F scores (stepwise: β = -0.23, p<0.01; enter: β = -0.20, p<0.01). Conclusions Our results demonstrate a weak inverse relationship between serum chemerin and CRC survivor QOL. Although it is impossible to determine causality, our findings suggest that serum chemerin levels may have a significant association with CRC survivor QOL. Further prospective studies are required to confirm the clinical significance of our pilot study. PMID:28475614

Appointment length, psychiatrists' communication behaviors, and medication management appointment adherence.

PubMed

Cruz, Mario; Roter, Debra L; Cruz, Robyn F; Wieland, Melissa; Larson, Susan; Cooper, Lisa A; Pincus, Harold Alan

2013-09-01

The authors explored the relationship between critical elements of medication management appointments (appointment length, patient-centered talk, and positive nonverbal affect among providers) and patient appointment adherence. The authors used an exploratory, cross-sectional design employing quantitative analysis of 83 unique audio recordings of split treatment medication management appointments for 46 African-American and 37 white patients with 24 psychiatrists at four ambulatory mental health clinics. All patients had a diagnosis of depression. Data collected included demographic information; Patient Health Questionnaire-9 scores for depression severity; psychiatrist verbal and nonverbal communication behaviors during medication management appointments, identified by the Roter Interaction Analysis System during analysis of audio recordings; and appointment adherence. Bivariate analyses were employed to identify covariates that might influence appointment adherence. Generalized estimating equations (GEEs) were employed to assess the relationship between appointment length, psychiatrist patient-centered talk, and positive voice tone ratings and patient appointment adherence, while adjusting for covariates and the clustering of observations within psychiatrists. Wald chi square analyses were used to test whether all or some variables significantly influenced appointment adherence. GEE revealed a significant relationship between positive voice tone ratings and appointment adherence (p=.03). Chi square analyses confirmed the hypothesis of a positive and significant relationship between appointment adherence and positive voice tone ratings (p=.03) but not longer visit length and more patient-centered communication. The nonverbal conveyance of positive affect was associated with greater adherence to medication management appointments by depressed patients. These findings potentially have important implications for communication skills training and adherence research.

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.

[Pancreatic acinar neoplasms : Comparative molecular characterization].

PubMed

Bergmann, F

2016-11-01

Pancreatic acinar cell carcinomas are biologically aggressive neoplasms for which treatment options are very limited. The molecular mechanisms of tumor initiation and progression are largely not understood and precursor lesions have not yet been identified. In this study, pancreatic acinar cell carcinomas were cytogenetically characterized as well as by molecular and immunohistochemical analyses. Corresponding investigations were carried out on pancreatic ductal adenocarcinomas and pancreatic neuroendocrine neoplasms augmented by functional analyses. We show that pancreatic acinar cell carcinomas display a microsatellite stable, chromosomal unstable genotype, characterized by recurrent chromosomal imbalances that clearly discriminate them from pancreatic ductal adenocarcinomas and neuroendocrine neoplasms. Based on findings obtained from comparative genomic hybridization, candidate genes could be identified, such as deleted in colorectal cancer (DCC) and c-MYC. Furthermore, several therapeutic targets were identified in acinar cell carcinomas and other pancreatic neoplasms, including epidermal growth factor receptor (EGFR), L1 cell adhesion molecule (L1CAM) and heat shock protein 90 (HSP90). Moreover, L1CAM was shown to play a significant role in the tumorigenesis of pancreatic ductal adenocarcinoma. Functional analyses in cell lines derived from pancreatic neuroendocrine neoplasms revealed promising anti-tumorigenic effects using EGFR and HSP90 inhibitors affecting the cell cycle and in the case of HSP90, regulating several other oncogenes. Finally, based on mutational analyses of mitochondrial DNA, molecular evidence is provided that acinar cell cystadenomas (or better cystic acinar transformation) represent non-clonal lesions, suggesting an inflammatory reactive non-neoplastic nature.

Stress among mothers of children with intellectual disabilities in urban India: role of gender and maternal coping.

PubMed

John, Aesha

2012-07-01

The study assessed stress among mothers of young children with intellectual disabilities in urban India and examined the extent to which child functioning and maternal coping predict maternal stress. Through qualitative analyses, the study identified negative and positive dimensions of Indian mothers' caregiving experiences. Mothers completed Parenting Stress Index-Short Form, and children's teachers completed Vineland-II teacher rating form. Maternal responses to a semi-structured interview were rated to assess maternal coping and content analysed to derive qualitative themes. Three-fourths of the sample obtained a clinically significant stress score, and maternal coping emerged as a robust predictor of stress for mothers of boys with intellectual disabilities. Qualitative analyses indicated positive and negative maternal experiences related to self, child, family and community. The high level of stress has important clinical implications. Similarly, the significant role of maternal coping, moderating role of child gender and the multidimensional caregiving experiences have implications for future research and family interventions in India. © 2012 Blackwell Publishing Ltd.

Molecular markers of carcinogenesis for risk stratification of individuals with colorectal polyps: a case-control study.

PubMed

Gupta, Samir; Sun, Han; Yi, Sang; Storm, Joy; Xiao, Guanghua; Balasubramanian, Bijal A; Zhang, Song; Ashfaq, Raheela; Rockey, Don C

2014-10-01

Risk stratification using number, size, and histology of colorectal adenomas is currently suboptimal for identifying patients at increased risk for future colorectal cancer. We hypothesized that molecular markers of carcinogenesis in adenomas, measured via immunohistochemistry, may help identify high-risk patients. To test this hypothesis, we conducted a retrospective, 1:1 matched case-control study (n = 216; 46% female) in which cases were patients with colorectal cancer and synchronous adenoma and controls were patients with adenoma but no colorectal cancer at baseline or within 5 years of follow-up. In phase I of analyses, we compared expression of molecular markers of carcinogenesis in case and control adenomas, blind to case status. In phase II of analyses, patients were randomly divided into independent training and validation groups to develop a model for predicting case status. We found that seven markers [p53, p21, Cox-2, β-catenin (BCAT), DNA-dependent protein kinase (DNApkcs), survivin, and O6-methylguanine-DNA methyltransferase (MGMT)] were significantly associated with case status on unadjusted analyses, as well as analyses adjusted for age and advanced adenoma status (P < 0.01 for at least one marker component). When applied to the validation set, a predictive model using these seven markers showed substantial accuracy for identifying cases [area under the receiver operation characteristic curve (AUC), 0.83; 95% confidence interval (CI), 0.74-0.92]. A parsimonious model using three markers performed similarly to the seven-marker model (AUC, 0.84). In summary, we found that molecular markers of carcinogenesis distinguished adenomas from patients with and without colorectal cancer. Furthermore, we speculate that prospective studies using molecular markers to identify individuals with polyps at risk for future neoplasia are warranted. ©2014 American Association for Cancer Research.

Differences of Perceived Image Generated through the Web Site: Empirical Evidence Obtained in Spanish Destinations

PubMed Central

Blazquez-Resino, Juan J.; Muro-Rodriguez, Ana I.; Perez-Jimenez, Israel R.

2016-01-01

In this paper, a study of the perceived destination image created by promotional Web Pages is expounded in an attempt to identify their differences as generators of destination image in the consumers' mind. Specifically, it seeks to analyse whether the web sites of different Spanish regions improve the image that consumers have of the destination, identifying their main dimensions and analysing its effect on satisfaction and intentions of the future behavior of potential visitors. To achieve these objectives and verify the hypotheses, a laboratory experiment was performed, where it was determined what changes are produced in the tourist's previous image after browsing the tourist webs of three different regions. Moreover, it analyses the differences in the effect of the perceived image on satisfaction and potential visitors' future behavioral intentions. The results obtained enable us to identify differences in the composition of the perceived image according to the destination, while confirming the significant effect of different perceived image dimensions regarding satisfaction. The results allow managers to gain a better understanding of the effectiveness of their sites from a consumer perspective as well as suggestions to follow in order to achieve greater efficiency in their communication actions in order to improve the motivation of visitors to go to the destination. PMID:27933027

Differences of Perceived Image Generated through the Web Site: Empirical Evidence Obtained in Spanish Destinations.

PubMed

Blazquez-Resino, Juan J; Muro-Rodriguez, Ana I; Perez-Jimenez, Israel R

2016-01-01

In this paper, a study of the perceived destination image created by promotional Web Pages is expounded in an attempt to identify their differences as generators of destination image in the consumers' mind. Specifically, it seeks to analyse whether the web sites of different Spanish regions improve the image that consumers have of the destination, identifying their main dimensions and analysing its effect on satisfaction and intentions of the future behavior of potential visitors. To achieve these objectives and verify the hypotheses, a laboratory experiment was performed, where it was determined what changes are produced in the tourist's previous image after browsing the tourist webs of three different regions. Moreover, it analyses the differences in the effect of the perceived image on satisfaction and potential visitors' future behavioral intentions. The results obtained enable us to identify differences in the composition of the perceived image according to the destination, while confirming the significant effect of different perceived image dimensions regarding satisfaction. The results allow managers to gain a better understanding of the effectiveness of their sites from a consumer perspective as well as suggestions to follow in order to achieve greater efficiency in their communication actions in order to improve the motivation of visitors to go to the destination.

Using Cluster Analysis to Compartmentalize a Large Managed Wetland Based on Physical, Biological, and Climatic Geospatial Attributes.

PubMed

Hahus, Ian; Migliaccio, Kati; Douglas-Mankin, Kyle; Klarenberg, Geraldine; Muñoz-Carpena, Rafael

2018-04-27

Hierarchical and partitional cluster analyses were used to compartmentalize Water Conservation Area 1, a managed wetland within the Arthur R. Marshall Loxahatchee National Wildlife Refuge in southeast Florida, USA, based on physical, biological, and climatic geospatial attributes. Single, complete, average, and Ward's linkages were tested during the hierarchical cluster analyses, with average linkage providing the best results. In general, the partitional method, partitioning around medoids, found clusters that were more evenly sized and more spatially aggregated than those resulting from the hierarchical analyses. However, hierarchical analysis appeared to be better suited to identify outlier regions that were significantly different from other areas. The clusters identified by geospatial attributes were similar to clusters developed for the interior marsh in a separate study using water quality attributes, suggesting that similar factors have influenced variations in both the set of physical, biological, and climatic attributes selected in this study and water quality parameters. However, geospatial data allowed further subdivision of several interior marsh clusters identified from the water quality data, potentially indicating zones with important differences in function. Identification of these zones can be useful to managers and modelers by informing the distribution of monitoring equipment and personnel as well as delineating regions that may respond similarly to future changes in management or climate.

Analysis of the sleep quality of elderly people using biomedical signals.

PubMed

Moreno-Alsasua, L; Garcia-Zapirain, B; Mendez-Zorrilla, A

2015-01-01

This paper presents a technical solution that analyses sleep signals captured by biomedical sensors to find possible disorders during rest. Specifically, the method evaluates electrooculogram (EOG) signals, skin conductance (GSR), air flow (AS), and body temperature. Next, a quantitative sleep quality analysis determines significant changes in the biological signals, and any similarities between them in a given time period. Filtering techniques such as the Fourier transform method and IIR filters process the signal and identify significant variations. Once these changes have been identified, all significant data is compared and a quantitative and statistical analysis is carried out to determine the level of a person's rest. To evaluate the correlation and significant differences, a statistical analysis has been calculated showing correlation between EOG and AS signals (p=0,005), EOG, and GSR signals (p=0,037) and, finally, the EOG and Body temperature (p=0,04). Doctors could use this information to monitor changes within a patient.

Psychological Well-Being and the Human Conserved Transcriptional Response to Adversity

PubMed Central

Fredrickson, Barbara L.; Grewen, Karen M.; Algoe, Sara B.; Firestine, Ann M.; Arevalo, Jesusa M. G.; Ma, Jeffrey; Cole, Steve W.

2015-01-01

Research in human social genomics has identified a conserved transcriptional response to adversity (CTRA) characterized by up-regulated expression of pro-inflammatory genes and down-regulated expression of Type I interferon- and antibody-related genes. This report seeks to identify the specific aspects of positive psychological well-being that oppose such effects and predict reduced CTRA gene expression. In a new confirmation study of 122 healthy adults that replicated the approach of a previously reported discovery study, mixed effect linear model analyses identified a significant inverse association between expression of CTRA indicator genes and a summary measure of eudaimonic well-being from the Mental Health Continuum – Short Form. Analyses of a 2- representation of eudaimonia converged in finding correlated psychological and social subdomains of eudaimonic well-being to be the primary carriers of CTRA associations. Hedonic well-being showed no consistent CTRA association independent of eudaimonic well-being, and summary measures integrating hedonic and eudaimonic well-being showed less stable CTRA associations than did focal measures of eudaimonia (psychological and social well-being). Similar results emerged from analyses of pooled discovery and confirmation samples (n = 198). Similar results also emerged from analyses of a second new generalization study of 107 healthy adults that included the more detailed Ryff Scales of Psychological Well-being and found this more robust measure of eudaimonic well-being to also associate with reduced CTRA gene expression. Five of the 6 major sub-domains of psychological well-being predicted reduced CTRA gene expression when analyzed separately, and 3 remained distinctively prognostic in mutually adjusted analyses. All associations were independent of demographic characteristics, health-related confounders, and RNA indicators of leukocyte subset distribution. These results identify specific sub-dimensions of eudaimonic well-being as promising targets for future interventions to mitigate CTRA gene expression, and provide no support for any independent favorable contribution from hedonic well-being. PMID:25811656

Application of earth resources technology satellite data to urban and regional planning: Test site, County of Los Angeles

NASA Technical Reports Server (NTRS)

Raje, S.; Mcknight, J.; Willoughby, G.; Economy, R. (Principal Investigator)

1974-01-01

The author has identified the following significant results. The County of Los Angeles photointerpreted ERTS film products to define problems of interest, coordinated ground truth over the complex test site including interfaces with secondary users as well as participated in on-line analyses of the GE multispectral information extraction systems. Interactive machine analyses were carried out, developing techniques and procedures as well as evaluating the outputs for community and regional planning. Extensive aircraft underflight coverage was provided that was valuable both in inputs preparation and outputs evaluation of the machine-aided analyses. One of the nonstandard ERTS images led to the discovery of a major new fault lineament on the northern slope of the Santa Monica Mountains.

Continuing difficulties in interpreting CNV data: lessons from a genome-wide CNV association study of Australian HNPCC/lynch syndrome patients

PubMed Central

2013-01-01

Background Hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome (LS) is a cancer syndrome characterised by early-onset epithelial cancers, especially colorectal cancer (CRC) and endometrial cancer. The aim of the current study was to use SNP-array technology to identify genomic aberrations which could contribute to the increased risk of cancer in HNPCC/LS patients. Methods Individuals diagnosed with HNPCC/LS (100) and healthy controls (384) were genotyped using the Illumina Human610-Quad SNP-arrays. Copy number variation (CNV) calling and association analyses were performed using Nexus software, with significant results validated using QuantiSNP. TaqMan Copy-Number assays were used for verification of CNVs showing significant association with HNPCC/LS identified by both software programs. Results We detected copy number (CN) gains associated with HNPCC/LS status on chromosome 7q11.21 (28% cases and 0% controls, Nexus; p = 3.60E-20 and QuantiSNP; p < 1.00E-16) and 16p11.2 (46% in cases, while a CN loss was observed in 23% of controls, Nexus; p = 4.93E-21 and QuantiSNP; p = 5.00E-06) via in silico analyses. TaqMan Copy-Number assay was used for validation of CNVs showing significant association with HNPCC/LS. In addition, CNV burden (total CNV length, average CNV length and number of observed CNV events) was significantly greater in cases compared to controls. Conclusion A greater CNV burden was identified in HNPCC/LS cases compared to controls supporting the notion of higher genomic instability in these patients. One intergenic locus on chromosome 7q11.21 is possibly associated with HNPCC/LS and deserves further investigation. The results from this study highlight the complexities of fluorescent based CNV analyses. The inefficiency of both CNV detection methods to reproducibly detect observed CNVs demonstrates the need for sequence data to be considered alongside intensity data to avoid false positive results. PMID:23531357

Identification of Cost Indicators with Significant Economic Impact on the Total Treatment Costs of Chronic Heart Failure Patients - A Meta-Analysis.

PubMed

Hameed, Ahmed S; Modre-Osprian, Robert; Schreier, Günter

2017-01-01

Increasing treatment costs of HF patients affect the initiation of appropriate treatment method. Divergent approaches to measure the costs of treatment and the lack of common cost indicators impede the comparison of therapy settings. In the context of the present meta-analysis, key cost indicators from the perspective of healthcare providers are to be identified, described, analyzed and quantified. This review helps narrowing down the cost indicators, which have the most significant economic impact on the total treatment costs of HF patients. Telemedical services are to be compared to standard therapy methods. The identification process was based on several steps. For the quantitative synthesis, we used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. An additional set of criteria was defined for the following qualitative analysis. 5 key cost indicators were identified with significant economic impact on the treatment costs of HF patients. 95% of the reported treatment costs could be captured based on the identified cost indicators.

Relating genes to function: identifying enriched transcription factors using the ENCODE ChIP-Seq significance tool.

PubMed

Auerbach, Raymond K; Chen, Bin; Butte, Atul J

2013-08-01

Biological analysis has shifted from identifying genes and transcripts to mapping these genes and transcripts to biological functions. The ENCODE Project has generated hundreds of ChIP-Seq experiments spanning multiple transcription factors and cell lines for public use, but tools for a biomedical scientist to analyze these data are either non-existent or tailored to narrow biological questions. We present the ENCODE ChIP-Seq Significance Tool, a flexible web application leveraging public ENCODE data to identify enriched transcription factors in a gene or transcript list for comparative analyses. The ENCODE ChIP-Seq Significance Tool is written in JavaScript on the client side and has been tested on Google Chrome, Apple Safari and Mozilla Firefox browsers. Server-side scripts are written in PHP and leverage R and a MySQL database. The tool is available at http://encodeqt.stanford.edu. abutte@stanford.edu Supplementary material is available at Bioinformatics online.

Patterns of Gray Matter Abnormalities in Schizophrenia Based on an International Mega-analysis.

PubMed

Gupta, Cota Navin; Calhoun, Vince D; Rachakonda, Srinivas; Chen, Jiayu; Patel, Veena; Liu, Jingyu; Segall, Judith; Franke, Barbara; Zwiers, Marcel P; Arias-Vasquez, Alejandro; Buitelaar, Jan; Fisher, Simon E; Fernandez, Guillen; van Erp, Theo G M; Potkin, Steven; Ford, Judith; Mathalon, Daniel; McEwen, Sarah; Lee, Hyo Jong; Mueller, Bryon A; Greve, Douglas N; Andreassen, Ole; Agartz, Ingrid; Gollub, Randy L; Sponheim, Scott R; Ehrlich, Stefan; Wang, Lei; Pearlson, Godfrey; Glahn, David C; Sprooten, Emma; Mayer, Andrew R; Stephen, Julia; Jung, Rex E; Canive, Jose; Bustillo, Juan; Turner, Jessica A

2015-09-01

Analyses of gray matter concentration (GMC) deficits in patients with schizophrenia (Sz) have identified robust changes throughout the cortex. We assessed the relationships between diagnosis, overall symptom severity, and patterns of gray matter in the largest aggregated structural imaging dataset to date. We performed both source-based morphometry (SBM) and voxel-based morphometry (VBM) analyses on GMC images from 784 Sz and 936 controls (Ct) across 23 scanning sites in Europe and the United States. After correcting for age, gender, site, and diagnosis by site interactions, SBM analyses showed 9 patterns of diagnostic differences. They comprised separate cortical, subcortical, and cerebellar regions. Seven patterns showed greater GMC in Ct than Sz, while 2 (brainstem and cerebellum) showed greater GMC for Sz. The greatest GMC deficit was in a single pattern comprising regions in the superior temporal gyrus, inferior frontal gyrus, and medial frontal cortex, which replicated over analyses of data subsets. VBM analyses identified overall cortical GMC loss and one small cluster of increased GMC in Sz, which overlapped with the SBM brainstem component. We found no significant association between the component loadings and symptom severity in either analysis. This mega-analysis confirms that the commonly found GMC loss in Sz in the anterior temporal lobe, insula, and medial frontal lobe form a single, consistent spatial pattern even in such a diverse dataset. The separation of GMC loss into robust, repeatable spatial patterns across multiple datasets paves the way for the application of these methods to identify subtle genetic and clinical cohort effects. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Hospital level analysis to improve patient flow.

PubMed

Khanna, Sankalp; Boyle, Justin; Good, Norm; Bugden, Simon; Scott, Mark

2013-01-01

The complexity of hospital operations ensures that one-size-fits-all solutions seldom work. As hospitals turn to evidence based strategies to redesign flow, it is critical that they tailor the strategies to suit their individual service. This paper analyses the effect of hospital occupancy on inpatient and emergency department patient flow parameters at the Caboolture hospital in Queensland, Australia, and identifies critical levels, or choke points, that result in performance decline. The effect of weekdays and weekends on patient flow is also investigated. We compare these findings to a previous study that has analysed patient flow across Queensland hospitals grouped by size, and discover several differences in the interaction between rising occupancy and patient flow parameters including rates of patient flow, length of stay, and access block. We also identify significantly higher choke points for Caboolture hospital as compared to other similarly sized Queensland hospitals, which suggest that patient flow here can be redesigned to operate at higher levels of occupancy without degrading flow performance. The findings support arguments for hospitals to analyse patient flow at a service level to deliver optimum service improvement.

Efficient Exploitation of Separation Space in Two-Dimensional Liquid Chromatography System for Comprehensive and Efficient Proteomic Analyses.

PubMed

Lee, Hangyeore; Mun, Dong-Gi; So, Jeong Eun; Bae, Jingi; Kim, Hokeun; Masselon, Christophe; Lee, Sang-Won

2016-12-06

Proteomics aims to achieve complete profiling of the protein content and protein modifications in cells, tissues, and biofluids and to quantitatively determine changes in their abundances. This information serves to elucidate cellular processes and signaling pathways and to identify candidate protein biomarkers and/or therapeutic targets. Analyses must therefore be both comprehensive and efficient. Here, we present a novel online two-dimensional reverse-phase/reverse-phase liquid chromatography separation platform, which is based on a newly developed online noncontiguous fractionating and concatenating device (NCFC fractionator). In bottom-up proteomics analyses of a complex proteome, this system provided significantly improved exploitation of the separation space of the two RPs, considerably increasing the numbers of peptides identified compared to a contiguous 2D-RP/RPLC method. The fully automated online 2D-NCFC-RP/RPLC system bypassed a number of labor-intensive manual processes required with the previously described offline 2D-NCFC RP/RPLC method, and thus, it offers minimal sample loss in a context of highly reproducible 2D-RP/RPLC experiments.

VDR regulation of microRNA differs across prostate cell models suggesting extremely flexible control of transcription.

PubMed

Singh, Prashant K; Long, Mark D; Battaglia, Sebastiano; Hu, Qiang; Liu, Song; Sucheston-Campbell, Lara E; Campbell, Moray J

2015-01-01

The Vitamin D Receptor (VDR) is a member of the nuclear receptor superfamily and is of therapeutic interest in cancer and other settings. Regulation of microRNA (miRNA) by the VDR appears to be important to mediate its actions, for example, to control cell growth. To identify if and to what extent VDR-regulated miRNA patterns change in prostate cancer progression, we undertook miRNA microarray analyses in 7 cell models representing non-malignant and malignant prostate cells (RWPE-1, RWPE-2, HPr1, HPr1AR, LNCaP, LNCaP-C4-2, and PC-3). To focus on primary VDR regulatory events, we undertook expression analyses after 30 minutes treatment with 1α,25(OH)2D3. Across all models, 111 miRNAs were significantly modulated by 1α,25(OH)2D3 treatment. Of these, only 5 miRNAs were modulated in more than one cell model, and of these, only 3 miRNAs were modulated in the same direction. The patterns of miRNA regulation, and the networks they targeted, significantly distinguished the different cell types. Integration of 1α,25(OH)2D3-regulated miRNAs with published VDR ChIP-seq data showed significant enrichment of VDR peaks in flanking regions of miRNAs. Furthermore, mRNA and miRNA expression analyses in non-malignant RWPE-1 cells revealed patterns of miRNA and mRNA co-regulation; specifically, 13 significant reciprocal patterns were identified and these patterns were also observed in TCGA prostate cancer data. Lastly, motif search analysis revealed differential motif enrichment within VDR peaks flanking mRNA compared to miRNA genes. Together, this study revealed that miRNAs are rapidly regulated in a highly cell-type specific manner, and are significantly co-integrated with mRNA regulation.

Peer Victimization and Sexual Risk Differences Between Lesbian, Gay, Bisexual, Transgender, or Questioning and Nontransgender Heterosexual Youths in Grades 7–12

PubMed Central

Espelage, Dorothy L.

2013-01-01

Objectives. Before and after accounting for peer victimization, we estimated sexual risk disparities between students who self-identified as lesbian, gay, bisexual, transgender, or questioning (LGBTQ) and students who self-identified as nontransgender heterosexual. Methods. Students in grades 7 through 12 in Dane County, Wisconsin, were given the Web-administered Dane County Youth Assessment. One set of analyses was based on a sample that included 11 337 students. Subsequent analyses were based on a sample from which we screened out students who may not have been responding to survey items truthfully. Various multilevel-modeling and propensity-score-matching strategies ensured robustness of the results, examined disparities at lower and higher victimization rates, and explored heterogeneity among LGBTQ-identified youths. Finally, propensity-score-matching strategies estimated LGBTQ–heterosexual disparities in 2 matched samples: a sample that reported higher victimization and one that reported lower victimization. Results. Across 7 sexual risk outcomes, and in middle and high school, LGBTQ-identified youths reported engaging in riskier behavior than did heterosexual-identified youths after we accounted for peer victimization. Risk differentials were present in middle and high school. The LGBTQ group was heterogeneous, with lesbian/gay- and bisexual-identified youths generally appearing most risky, and questioning-identified youths least risky. In the matched sample with lower average victimization rates, LGBTQ-identified youths perceived a greater risk of sexually transmitted infections despite not engaging in sexually risky behavior at significantly higher rates; in the matched sample with higher average victimization rates, all outcomes were significantly different. Conclusions. Demonstrated LGBTQ–heterosexual risk differentials in grades 7 through 8 suggest that interventions need to be implemented during middle school. These interventions should also be differentiated to address the unique risk patterns among LGBTQ subgroups. Finally, models of sexual risk disparities must expand beyond peer victimization. PMID:23947999

MACROINVERTEBRATE INVENTORIES OF THE WHITE RIVER, COLORADO AND UTAH: SIGNIFICANCE OF ANNUAL, SEASONAL, AND SPATIAL VARIATION IN THE DESIGN OF BIOMONITORING NETWORKS FOR POLLUTION DETECTION

EPA Science Inventory

An aquatic macroinvertebrate monitoring program is suggested for 'early warning' detection of toxic discharges to streams in oil shale development areas. Changes in stream biota are used to signal need for increasing levels of chemical analyses to identify and quantify toxic poll...

Predictors of College Student Suicidal Ideation: Gender Differences

ERIC Educational Resources Information Center

Stephenson, Hugh; Pena-Shaff, Judith; Quirk, Priscilla

2006-01-01

There is a need to identify students at risk for suicide. Predictors of suicidality were examined separately for men and women in a college health survey of 630 students. Women reported higher levels of suicidal ideation than men in the previous year. Separate regression analyses for men and women accounted for significant amounts of the variance…

What Do We Know and How Well Do We Know It? Identifying Practice-Based Insights in Education

ERIC Educational Resources Information Center

Miller, Barbara; Pasley, Joan

2012-01-01

Knowledge derived from practice forms a significant portion of the knowledge base in the education field, yet is not accessible using existing empirical research methods. This paper describes a systematic, rigorous, grounded approach to collecting and analysing practice-based knowledge using the authors' research in teacher leadership as an…

ERTS-1 imagery interpretation techniques in the Tennessee Valley. [land use and soil mapping

NASA Technical Reports Server (NTRS)

Bodenheimer, R. E. (Principal Investigator)

1974-01-01

The author has identified the following significant results. The feasibility of delineating major soil associations and land uses through computerized analyses is discussed. Useful and potential applications in detecting landscape change and land use mapping are described. Recommendations for improving the data processing effort in a multidisciplinary program are presented.

29 CFR 37.54 - What are a Governor's obligations to develop and maintain a Methods of Administration?

Code of Federal Regulations, 2011 CFR

2011-07-01

... records and data kept by the recipient under § 37.37, including analyses by race/ethnicity, sex, age, and disability status; (B) An investigation of any significant differences identified in paragraph (A) of this... determine whether these differences appear to be caused by discrimination. This investigation must be...

Enhancing Force Concept Inventory Diagnostics to Identify Dominant Misconceptions in First-Year Engineering Physics

ERIC Educational Resources Information Center

Martin-Blas, Teresa; Seidel, Luis; Serrano-Fernandez, Ana

2010-01-01

This work presents the results of a study whose aim is to detect systematic errors about the concept of force among freshmen students. The researchers analysed the results of the Force Concept Inventory test, which was administered to two different groups of students. The results show that, although there were significant performance variations…

Dose-volume effects in pathologic lymph nodes in locally advanced cervical cancer.

PubMed

Bacorro, Warren; Dumas, Isabelle; Escande, Alexandre; Gouy, Sebastien; Bentivegna, Enrica; Morice, Philippe; Haie-Meder, Christine; Chargari, Cyrus

2018-03-01

In cervical cancer patients, dose-volume relationships have been demonstrated for tumor and organs-at-risk, but not for pathologic nodes. The nodal control probability (NCP) according to dose/volume parameters was investigated. Patients with node-positive cervical cancer treated curatively with external beam radiotherapy (EBRT) and image-guided brachytherapy (IGABT) were identified. Nodal doses during EBRT, IGABT and boost were converted to 2-Gy equivalent (α/β = 10 Gy) and summed. Pathologic nodes were followed individually from diagnosis to relapse. Statistical analyses comprised log-rank tests (univariate analyses), Cox proportional model (factors with p ≤ 0.1 in univariate) and Probit analyses. A total of 108 patients with 254 unresected pathological nodes were identified. The mean nodal volume at diagnosis was 3.4 ± 5.8 cm 3 . The mean total nodal EQD2 doses were 55.3 ± 5.6 Gy. Concurrent chemotherapy was given in 96%. With a median follow-up of 33.5 months, 20 patients (18.5%) experienced relapse in nodes considered pathologic at diagnosis. Overall nodal recurrence rate was 9.1% (23/254). On univariate analyses, nodal volume (threshold: 3 cm 3 , p < .0001) and lymph node dose (≥57.5 Gy α/β10 , p = .039) were significant for nodal control. The use of simultaneous boost was borderline for significance (p = .07). On multivariate analysis, volume (HR = 8.2, 4.0-16.6, p < .0001) and dose (HR = 2, 1.05-3.9, p = .034) remained independent factors. Probit analysis combining dose and volume showed significant relationships with NCP, with increasing gap between the curves with higher nodal volumes. A nodal dose-volume effect on NCP is demonstrated for the first time, with increasing NCP benefit of additional doses to higher-volume nodes. Copyright © 2018 Elsevier Inc. All rights reserved.

Does speed matter? The impact of operative time on outcome in laparoscopic surgery

PubMed Central

Jackson, Timothy D.; Wannares, Jeffrey J.; Lancaster, R. Todd; Rattner, David W.

2012-01-01

Introduction Controversy exists concerning the importance of operative time on patient outcomes. It is unclear whether faster is better or haste makes waste or similarly whether slower procedures represent a safe, meticulous approach or inexperienced dawdling. The objective of the present study was to determine the effect of operative time on 30-day outcomes in laparoscopic surgery. Methods Patients who underwent laparoscopic general surgery procedures (colectomy, cholecystectomy, Nissen fundoplication, inguinal hernia, and gastric bypass) from the ACS-NSQIP 2005–2008 participant use file were identified. Exclusion criteria were defined a priori to identify same-day admission, elective procedures. Operative time was divided into deciles and summary statistics were analyzed. Univariate analyses using a Cochran-Armitage test for trend were completed. The effect of operative time on 30-day morbidity was further analyzed for each procedure type using multivariate regression controlling for case complexity and additional patient factors. Patients within the highest deciles were excluded to reduce outlier effect. Results A total of 76,748 elective general surgical patients who underwent laparoscopic procedures were analyzed. Univariate analyses of deciles of operative time demonstrated a statistically significant trend (p \\ 0.0001) toward increasing odds of complications with increasing operative time for laparoscopic colectomy (n = 10,135), cholecystectomy (n = 37,407), Nissen fundoplication (n = 4,934), and gastric bypass (n = 17,842). The trend was not found to be significant for laparoscopic inguinal hernia repair (n = 6,430; p = 0.14). Multivariate modeling revealed the effect of operative time to remain significant after controlling for additional patient factors. Conclusion Increasing operative time was associated with increased odds of complications and, therefore, it appears that speed may matter in laparoscopic surgery. These analyses are limited in their inability to adjust for all patient factors, potential confounders, and case complexities. Additional hierarchical multivariate analyses at the surgeon level would be important to examine this relationship further. PMID:21298533

Does speed matter? The impact of operative time on outcome in laparoscopic surgery.

PubMed

Jackson, Timothy D; Wannares, Jeffrey J; Lancaster, R Todd; Rattner, David W; Hutter, Matthew M

2011-07-01

Controversy exists concerning the importance of operative time on patient outcomes. It is unclear whether faster is better or haste makes waste or similarly whether slower procedures represent a safe, meticulous approach or inexperienced dawdling. The objective of the present study was to determine the effect of operative time on 30-day outcomes in laparoscopic surgery. Patients who underwent laparoscopic general surgery procedures (colectomy, cholecystectomy, Nissen fundoplication, inguinal hernia, and gastric bypass) from the ACS-NSQIP 2005-2008 participant use file were identified. Exclusion criteria were defined a priori to identify same-day admission, elective procedures. Operative time was divided into deciles and summary statistics were analyzed. Univariate analyses using a Cochran-Armitage test for trend were completed. The effect of operative time on 30-day morbidity was further analyzed for each procedure type using multivariate regression controlling for case complexity and additional patient factors. Patients within the highest deciles were excluded to reduce outlier effect. A total of 76,748 elective general surgical patients who underwent laparoscopic procedures were analyzed. Univariate analyses of deciles of operative time demonstrated a statistically significant trend (p<0.0001) toward increasing odds of complications with increasing operative time for laparoscopic colectomy (n=10,135), cholecystectomy (n=37,407), Nissen fundoplication (n=4,934), and gastric bypass (n=17,842). The trend was not found to be significant for laparoscopic inguinal hernia repair (n=6,430; p=0.14). Multivariate modeling revealed the effect of operative time to remain significant after controlling for additional patient factors. Increasing operative time was associated with increased odds of complications and, therefore, it appears that speed may matter in laparoscopic surgery. These analyses are limited in their inability to adjust for all patient factors, potential confounders, and case complexities. Additional hierarchical multivariate analyses at the surgeon level would be important to examine this relationship further.

Surrogacy of progression free survival for overall survival in metastatic breast cancer studies: Meta-analyses of published studies.

PubMed

Kundu, Madan G; Acharyya, Suddhasatta

2017-02-01

PFS is often used as a surrogate endpoint for OS in metastatic breast cancer studies. We have evaluated the association of treatment effect on PFS with significant HR OS (and how this association is affected by other factors) in published prospective metastatic breast cancer studies. A systematic literature search in PubMed identified prospective metastatic breast cancer studies. Treatment effects on PFS were determined using hazard ratio (HR PFS ), increase in median PFS (ΔMED PFS ) and % increase in median PFS (%ΔMED PFS ). Diagnostic accuracy of PFS measures (HR PFS , ΔMED PFS and %ΔMED PFS ) in predicting significant HR OS was assessed using receiver operating characteristic (ROC) curves and classification tree approach (CART). Seventy-four cases (i.e., treatment to control comparisons) from 65 individual publications were identified for the analyses. Of these, 16 cases reported significant treatment effect on HR OS at 5% level of significance. Median number of deaths reported in these cases were 153. Area under the ROC curve (AUC) for diagnostic measures as HR PFS , ΔMED PFS and %ΔMED PFS were 0.69, 0.70 and 0.75, respectively. Classification tree results identified %ΔMED PFS and number of deaths as diagnostic measure for significant HR OS . Only 7.9% (3/39) cases with ΔMED PFS shorter than 48.27% reported significant HR OS . There were 7 cases with ΔMED PFS of 48.27% or more and number of deaths reported as 227 or more - of these 5 cases reported significant HR OS . %ΔMED PFS was found to be a better diagnostic measure for predicting significant HR OS . Our analysis results also suggest that consideration of total number of deaths may further improve its diagnostic performance. Based on our study results, the studies with 50% improvement in median PFS are more likely to produce significant HR OS if the total number of OS events at the time of analysis is 227 or more. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of commercial utility of ERTS-A imagery in structural reconnaissance for minerals and petroleum

NASA Technical Reports Server (NTRS)

Saunders, D. F. (Principal Investigator)

1973-01-01

The author has identified the following significant results. Initial analytical results in Area 3 have been very encouraging. Not only have new major lineaments been detected but many of the intersections of those lineaments correlate with the general location of known mineral deposits while others appear to outline petroleum-bearing basins and uplifts. If later analyses confirm these results the economic impact of ERTS type imagery could be very significant in worldwide mineral and petroleum reconnaissance.

Using Meta-analyses for Comparative Effectiveness Research

PubMed Central

Ruppar, Todd M.; Phillips, Lorraine J.; Chase, Jo-Ana D.

2012-01-01

Comparative effectiveness research seeks to identify the most effective interventions for particular patient populations. Meta-analysis is an especially valuable form of comparative effectiveness research because it emphasizes the magnitude of intervention effects rather than relying on tests of statistical significance among primary studies. Overall effects can be calculated for diverse clinical and patient-centered variables to determine the outcome patterns. Moderator analyses compare intervention characteristics among primary studies by determining if effect sizes vary among studies with different intervention characteristics. Intervention effectiveness can be linked to patient characteristics to provide evidence for patient-centered care. Moderator analyses often answer questions never posed by primary studies because neither multiple intervention characteristics nor populations are compared in single primary studies. Thus meta-analyses provide unique contributions to knowledge. Although meta-analysis is a powerful comparative effectiveness strategy, methodological challenges and limitations in primary research must be acknowledged to interpret findings. PMID:22789450

Intestinal stoma in patients with colorectal cancer from the perspective of 20-year period of clinical observation.

PubMed

Banaszkiewicz, Zbigniew; Woda, Łukasz P; Zwoliński, Tomasz; Tojek, Krzysztof; Jarmocik, Paweł; Jawień, Arkadiusz

2015-01-01

Intestinal stoma is a procedure most often performed in patients with colorectal cancer. To identify the percentage of patients with colorectal cancer in which the intestinal stoma was performed. We retrospectively analysed 443 patients treated during a 20-year period (1994-2013) due to colorectal cancer, in which the intestinal stoma was made during the first surgical intervention. In the second analysed decade, a significant decrease in the percentage of created stomas, definitive stomas in particular, was observed. Stomas were made significantly more often in patients with a tumour located in the rectum, the left half of the colon, and in patients undergoing urgent surgeries. An increased incidence of intestinal stomas was associated with a higher severity of illness and higher proportion of unresectable and non-radical procedures. The definitive stomas were significantly more often made in men and in patients with tumours located in the rectum, whereas temporary stomas were created significantly more often in patients undergoing urgent operations. In the last decade (2004-2013) the number of intestinal stomas in patients operated due to colorectal cancer was significantly reduced.

[Fine mapping of complex disease susceptibility loci].

PubMed

Song, Qingfeng; Zhang, Hongxing; Ma, Yilong; Zhou, Gangqiao

2014-01-01

Genome-wide association studies (GWAS) using single nucleotide polymorphism (SNP) markers have identified more than 3800 susceptibility loci for more than 660 diseases or traits. However, the most significantly associated variants or causative variants in these loci and their biological functions have remained to be clarified. These causative variants can help to elucidate the pathogenesis and discover new biomarkers of complex diseases. One of the main goals in the post-GWAS era is to identify the causative variants and susceptibility genes, and clarify their functional aspects by fine mapping. For common variants, imputation or re-sequencing based strategies were implemented to increase the number of analyzed variants and help to identify the most significantly associated variants. In addition, functional element, expression quantitative trait locus (eQTL) and haplotype analyses were performed to identify functional common variants and susceptibility genes. For rare variants, fine mapping was carried out by re-sequencing, rare haplotype analysis, family-based analysis, burden test, etc.This review summarizes the strategies and problems for fine mapping.

Temporal and spatial changes of rainfall and streamflow in the Upper Tekezē-Atbara river basin, Ethiopia

NASA Astrophysics Data System (ADS)

Gebremicael, Tesfay G.; Mohamed, Yasir A.; Zaag, Pieter v.; Hagos, Eyasu Y.

2017-04-01

The Upper Tekezē-Atbara river sub-basin, part of the Nile Basin, is characterized by high temporal and spatial variability of rainfall and streamflow. In spite of its importance for sustainable water use and food security, the changing patterns of streamflow and its association with climate change is not well understood. This study aims to improve the understanding of the linkages between rainfall and streamflow trends and identify possible drivers of streamflow variabilities in the basin. Trend analyses and change-point detections of rainfall and streamflow were analysed using Mann-Kendall and Pettitt tests, respectively, using data records for 21 rainfall and 9 streamflow stations. The nature of changes and linkages between rainfall and streamflow were carefully examined for monthly, seasonal and annual flows, as well as indicators of hydrologic alteration (IHA). The trend and change-point analyses found that 19 of the tested 21 rainfall stations did not show statistically significant changes. In contrast, trend analyses on the streamflow showed both significant increasing and decreasing patterns. A decreasing trend in the dry season (October to February), short season (March to May), main rainy season (June to September) and annual totals is dominant in six out of the nine stations. Only one out of nine gauging stations experienced significant increasing flow in the dry and short rainy seasons, attributed to the construction of Tekezē hydropower dam upstream this station in 2009. Overall, streamflow trends and change-point timings were found to be inconsistent among the stations. Changes in streamflow without significant change in rainfall suggests factors other than rainfall drive the change. Most likely the observed changes in streamflow regimes could be due to changes in catchment characteristics of the basin. Further studies are needed to verify and quantify the hydrological changes shown in statistical tests by identifying the physical mechanisms behind those changes. The findings from this study are useful as a prerequisite for studying the effects of catchment management dynamics on the hydrological variabilities in the basin.

Volatile compound in cut and un-cut flowers of tetraploid Freesia hybrida.

PubMed

Ao, Man; Liu, Baofeng; Wang, Li

2013-01-01

The flower volatile compounds (FVCs) of two tetraploid Freesia hybrida (pink-yellow and yellow) cultivars and their cut flowers were analysed by headspace solid-phase microextraction combined with gas chromatography-mass spectrometry. Twelve FVCs were identified in the pink-yellow cultivar, with linalool as the major compound; 30 FVCs were identified in the yellow cultivar, with linalool and terpineol as the two major compounds. The FVCs (>1%) of the two cut flower cultivars were very similar to that of the un-cut flowers, and no significant difference was observed.

Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium.

PubMed

Ng, Maggie C Y; Graff, Mariaelisa; Lu, Yingchang; Justice, Anne E; Mudgal, Poorva; Liu, Ching-Ti; Young, Kristin; Yanek, Lisa R; Feitosa, Mary F; Wojczynski, Mary K; Rand, Kristin; Brody, Jennifer A; Cade, Brian E; Dimitrov, Latchezar; Duan, Qing; Guo, Xiuqing; Lange, Leslie A; Nalls, Michael A; Okut, Hayrettin; Tajuddin, Salman M; Tayo, Bamidele O; Vedantam, Sailaja; Bradfield, Jonathan P; Chen, Guanjie; Chen, Wei-Min; Chesi, Alessandra; Irvin, Marguerite R; Padhukasahasram, Badri; Smith, Jennifer A; Zheng, Wei; Allison, Matthew A; Ambrosone, Christine B; Bandera, Elisa V; Bartz, Traci M; Berndt, Sonja I; Bernstein, Leslie; Blot, William J; Bottinger, Erwin P; Carpten, John; Chanock, Stephen J; Chen, Yii-Der Ida; Conti, David V; Cooper, Richard S; Fornage, Myriam; Freedman, Barry I; Garcia, Melissa; Goodman, Phyllis J; Hsu, Yu-Han H; Hu, Jennifer; Huff, Chad D; Ingles, Sue A; John, Esther M; Kittles, Rick; Klein, Eric; Li, Jin; McKnight, Barbara; Nayak, Uma; Nemesure, Barbara; Ogunniyi, Adesola; Olshan, Andrew; Press, Michael F; Rohde, Rebecca; Rybicki, Benjamin A; Salako, Babatunde; Sanderson, Maureen; Shao, Yaming; Siscovick, David S; Stanford, Janet L; Stevens, Victoria L; Stram, Alex; Strom, Sara S; Vaidya, Dhananjay; Witte, John S; Yao, Jie; Zhu, Xiaofeng; Ziegler, Regina G; Zonderman, Alan B; Adeyemo, Adebowale; Ambs, Stefan; Cushman, Mary; Faul, Jessica D; Hakonarson, Hakon; Levin, Albert M; Nathanson, Katherine L; Ware, Erin B; Weir, David R; Zhao, Wei; Zhi, Degui; Arnett, Donna K; Grant, Struan F A; Kardia, Sharon L R; Oloapde, Olufunmilayo I; Rao, D C; Rotimi, Charles N; Sale, Michele M; Williams, L Keoki; Zemel, Babette S; Becker, Diane M; Borecki, Ingrid B; Evans, Michele K; Harris, Tamara B; Hirschhorn, Joel N; Li, Yun; Patel, Sanjay R; Psaty, Bruce M; Rotter, Jerome I; Wilson, James G; Bowden, Donald W; Cupples, L Adrienne; Haiman, Christopher A; Loos, Ruth J F; North, Kari E

2017-04-01

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10-8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations.

Prognostic factors for return to work in patients with sciatica.

PubMed

Grøvle, Lars; Haugen, Anne J; Keller, Anne; Ntvig, Bård; Brox, Jens I; Grotle, Margreth

2013-12-01

Little is known about the prognostic factors for work-related outcomes of sciatica caused by disc herniation. To identify the prognostic factors for return to work (RTW) during a 2-year follow-up among sciatica patients referred to secondary care. Multicenter prospective cohort study including 466 patients. Administrative data from the National Sickness Benefit Register were accessed for 227 patients. Two samples were used. Sample A comprised patients who at the time of inclusion in the cohort reported being on partial sick leave or complete sick leave or were undergoing rehabilitation because of back pain/sciatica. Sample B comprised patients who, according to the sickness benefit register, at the time of inclusion received sickness benefits or rehabilitation allowances because of back pain/sciatica. In Sample A, the outcome was self-reported return to full-time work at the 2-year follow-up. In Sample B, the outcome was time to first sustained RTW, defined as the first period of more than 60 days without receiving benefits from the register. Significant baseline predictors of self-reported RTW at 2 years (Analysis A) were identified by multivariate logistic regression. Significant predictors of time to sustained RTW (Analysis B) were identified by multivariate Cox proportional hazard modeling. Both analyses included adjustment for age and sex. To assess the effect of surgery on the probability of RTW, analyses similar to A and B were performed, including the variable surgery (yes/no). One-fourth of the patients were still out of work at the 2-year follow-up. In Sample A (n=237), younger age, better general health, lower baseline sciatica bothersomeness, less fear-avoidance work, and a negative straight-leg-raising test result were significantly associated with a higher probability of RTW at the 2-year follow-up. Surgery was not significantly associated with the outcome. In Sample B (n=125), history of sciatica, duration of the current sciatica episode more than 3 months, greater sciatica bothersomeness, fear-avoidance work, and back pain were significantly associated with a longer time to sustained RTW. Surgery was significantly negatively associated with time to sustained RTW both in univariate (hazard ratio [HR] 0.60; 95% confidence interval [CI] 0.39, 0.93; p=.02) and in multivariate (HR 0.49; 95% CI 0.31, 0.79; p=.003) analyses. The baseline factors associated with RTW identified in multivariate analysis were age, general health, history of sciatica, duration of the current episode, baseline sciatica bothersomeness, fear-avoidance work, back pain, and the straight-leg-raising test result. Surgical treatment was associated with slower RTW, but surgical patients were more severely affected than patients treated without surgery; so, this finding should be interpreted with caution. Copyright © 2013 Elsevier Inc. All rights reserved.

Exploratory Temporal and Spatial Analysis of Myocardial Infarction Hospitalizations in Calgary, Canada

PubMed Central

Liu, Xiaoxiao; Bertazzon, Stefania

2017-01-01

Spatial and temporal analyses are critical to understand the pattern of myocardial infarction (MI) hospitalizations over space and time, and to identify their underlying determinants. In this paper, we analyze MI hospitalizations in Calgary from 2004 to 2013, stratified by age and gender. First, a seasonal trend decomposition analyzes the seasonality; then a linear regression models the trend component. Moran’s I and hot spot analyses explore the spatial pattern. Though exploratory, results show that most age and gender groups feature a statistically significant decline over the 10 years, consistent with previous studies in Canada. Decline rates vary across ages and genders, with the slowest decline observed for younger males. Each gender exhibits a seasonal pattern with peaks in both winter and summer. Spatially, MI hot spots are identified in older communities, and in socioeconomically and environmentally disadvantaged communities. In the older communities, higher MI rates appear to be more highly associated with demographics. Conversely, worse air quality appears to be locally associated with higher MI incidence in younger age groups. The study helps identify areas of concern, where MI hot spots are identified for younger age groups, suggesting the need for localized public health policies to target local risk factors. PMID:29232910

Risk factors for highly pathogenic avian influenza in commercial layer chicken farms in bangladesh during 2011.

PubMed

Osmani, M G; Thornton, R N; Dhand, N K; Hoque, M A; Milon, Sk M A; Kalam, M A; Hossain, M; Yamage, M

2014-12-01

A case-control study conducted during 2011 involved 90 randomly selected commercial layer farms infected with highly pathogenic avian influenza type A subtype H5N1 (HPAI) and 175 control farms randomly selected from within 5 km of infected farms. A questionnaire was designed to obtain information about potential risk factors for contracting HPAI and was administered to farm owners or managers. Logistic regression analyses were conducted to identify significant risk factors. A total of 20 of 43 risk factors for contracting HPAI were identified after univariable logistic regression analysis. A multivariable logistic regression model was derived by forward stepwise selection. Both unmatched and matched analyses were performed. The key risk factors identified were numbers of staff, frequency of veterinary visits, presence of village chickens roaming on the farm and staff trading birds. Aggregating these findings with those from other studies resulted in a list of 16 key risk factors identified in Bangladesh. Most of these related to biosecurity. It is considered feasible for Bangladesh to achieve a very low incidence of HPAI. Using the cumulative list of risk factors to enhance biosecurity pertaining to commercial farms would facilitate this objective. © 2013 Blackwell Verlag GmbH.

Psychological effects of disaster relief activities on Japan ground self-defense force personnel following the 2011 great east Japan earthquake.

PubMed

Dobashi, Kosuke; Nagamine, Masanori; Shigemura, Jun; Tsunoda, Tomoya; Shimizu, Kunio; Yoshino, Aihide; Nomura, Soichiro

2014-01-01

Disaster relief workers are potentially exposed to severe stressors on the job, resulting in a variety of psychological responses. This study aims to clarify the psychological effects of disaster relief activities on Japan Ground Self-Defense Force (JGSDF) personnel following the 2011 Great East Japan Earthquake. A self-report questionnaire was administered to 606 JGSDF personnel one month after completing the disaster relief mission. Posttraumatic stress responses and general psychological distress were assessed using the Impact of Event Scale-Revised (IES-R) and the K10 scales. Associations between outcome variables and independent variables (age, gender, military rank, length of deployment, and exposure to dead bodies) were measured with univariate analyses and subsequent multiple logistic regression analyses. The mean (± SD) IES-R score was 6.2 (± 8.1), and the mean K10 score was 12.8 (± 4.4). In the univariate analyses, exposure to dead bodies and age were identified as significant factors for IES-R and K10 scores, (p < 0.01). However, the multiple logistic regression analyses did not reveal any significant factors although body handlers' exposure approached significance for IES-R. The subjects reported very low psychological responses despite the severe nature of their disaster relief activities. Several factors may account for the low levels of psychological distress and posttraumatic symptoms observed in this study.

An Empirical Typology of Social Networks and Its Association With Physical and Mental Health: A Study With Older Korean Immigrants

PubMed Central

Jang, Yuri; Lee, Beom S.; Ko, Jung Eun; Haley, William E.; Chiriboga, David A.

2015-01-01

Objectives. In the context of social convoy theory, the purposes of the study were (a) to identify an empirical typology of the social networks evident in older Korean immigrants and (b) to examine its association with self-rated health and depressive symptoms. Method. The sample consisted of 1,092 community-dwelling older Korean immigrants in Florida and New York. Latent class analyses were conducted to identify the optimal social network typology based on 8 indicators of interpersonal relationships and activities. Bivariate and multivariate analyses were conducted to examine how the identified social network typology was associated with self-rating of health and depressive symptoms. Results. Results from the latent class analysis identified 6 clusters as being most optimal, and they were named diverse, unmarried/diverse, married/coresidence, family focused, unmarried/restricted, and restricted. Memberships in the clusters of diverse and married/coresidence were significantly associated with more favorable ratings of health and lower levels of depressive symptoms. Discussion. Notably, no distinct network solely composed of friends was identified in the present sample of older immigrants; this may reflect the disruptions in social convoys caused by immigration. The findings of this study promote our understanding of the unique patterns of social connectedness in older immigrants. PMID:23887929

Developmental trajectories in siblings of children with autism: cognition and language from 4 months to 7 years.

PubMed

Gamliel, Ifat; Yirmiya, Nurit; Jaffe, Dena H; Manor, Orly; Sigman, Marian

2009-08-01

We compared the cognitive and language development at 4, 14, 24, 36, 54 months, and 7 years of siblings of children with autism (SIBS-A) to that of siblings of children with typical development (SIBS-TD) using growth curve analyses. At 7 years, 40% of the SIBS-A, compared to 16% of SIBS-TD, were identified with cognitive, language and/or academic difficulties, identified using direct tests and/or parental reports. This sub-group was identified as SIBS-A-broad phenotype (BP). Results indicated that early language scores (14-54 months), but not cognitive scores of SIBS-A-BP and SIBS-A-nonBP were significantly lower compared to the language scores of SIBS-TD, and that the rate of development was also significantly different, thus pinpointing language as a major area of difficulty for SIBS-A during the preschool years.

Accuracy Rates of Ancestry Estimation by Forensic Anthropologists Using Identified Forensic Cases.

PubMed

Thomas, Richard M; Parks, Connie L; Richard, Adam H

2017-07-01

A common task in forensic anthropology involves the estimation of the ancestry of a decedent by comparing their skeletal morphology and measurements to skeletons of individuals from known geographic groups. However, the accuracy rates of ancestry estimation methods in actual forensic casework have rarely been studied. This article uses 99 forensic cases with identified skeletal remains to develop accuracy rates for ancestry estimations conducted by forensic anthropologists. The overall rate of correct ancestry estimation from these cases is 90.9%, which is comparable to most research-derived rates and those reported by individual practitioners. Statistical tests showed no significant difference in accuracy rates depending on examiner education level or on the estimated or identified ancestry. More recent cases showed a significantly higher accuracy rate. The incorporation of metric analyses into the ancestry estimate in these cases led to a higher accuracy rate. © 2017 American Academy of Forensic Sciences.

Is there a place for extended assessments in addressing child sexual abuse allegations? How sensitivity and specificity impact professional perspectives.

PubMed

Williams, Javonda; Nelson-Gardell, Debra; Coulborn Faller, Kathleen; Tishelman, Amy; Cordisco-Steele, Linda

2014-01-01

Using data from a survey of perceptions of 932 child welfare professionals about the utility of extended assessments, the researchers constructed a scale to measure respondents' views about sensitivity (ensuring sexually abused children are correctly identified) and specificity (ensuring nonabused children are correctly identified) in child sexual abuse evaluations. On average, respondents scored high (valuing sensitivity) on the sensitivity versus specificity scale. Next, the researchers undertook bivariate analyses to identify independent variables significantly associated with the sensitivity versus specificity scale. Then those variables were entered into a multiple regression. Four independent variables were significantly related to higher sensitivity scores: encountering cases requiring extended assessments, valuing extended assessments among scarce resources, less concern about proving cases in court, and viewing the goal of extended assessments as understanding needs of child and family (adjusted R2 = .34).

Some findings on the applications of ERTS and Skylab imagery for metropolitan land use analysis

NASA Technical Reports Server (NTRS)

Alexander, R. H. (Principal Investigator); Milazzo, V. A.

1974-01-01

The author has identified the following significant results. Work undertaken on a three-sensor land use data evaluation for a portion of the Phoenix area is reported. Analyses between land use data generated from 1970 high altitude photography and that detectable from ERTS and Skylab, especially in terms of changes in land use indicate that ERTS and Skylab imagery can be used effectively to detect and identify areas of post-1970 land use change, especially those documenting urban expansion at the rural-urban fringe. Significant preliminary findings on the utility of ERTS and Skylab data for metropolitan land use analysis, substantiated by evaluation with 1970 and 1972 ground control land use data are reported.

Identification of alcohol abuse and transition from long-term unemployment to disability pension.

PubMed

Nurmela, Kirsti; Heikkinen, Virpi; Hokkanen, Risto; Ylinen, Aarne; Uitti, Jukka; Mattila, Aino; Joukamaa, Matti; Virtanen, Pekka

2015-07-01

The aim of the study was to reveal potential gaps and inconsistencies in the identification of alcohol abuse in health care and in employment services and to analyse the granting of disability pensions with respect to the alcohol abuse identification pattern. The material consisted of documentary information on 505 long-term unemployed subjects with low employability sent to the development project entitled 'Eligibility for a Disability Pension' in 2001-2006 in Finland. The dichotomous variables 'Alcohol abuse identified in employment services' and 'Alcohol abuse identified in health care' were cross-tabulated to obtain a four-class variable 'Alcohol abuse identification pattern'. Logistic regression analyses were conducted to ascertain the association of alcohol abuse identification pattern with the granting of disability pensions. Alcohol abuse was detected by both health care and employment services in 47% of those identified as abusers (41% of examinees). Each service systems also identified cases that the other did not. When alcohol abuse was identified in health care only, the OR for a disability pension being granted was 2.8 (95% CI 1.5-5.2) compared with applicants without identified alcohol abuse. The result remained the same and statistically significant after adjusting for confounders. Alcohol abuse identified in health care was positively associated with the granting of a disability pension. Closer co-operation between employment services and health care could help to identify those long-term unemployed individuals with impaired work ability in need of thorough medical examination. © 2015 the Nordic Societies of Public Health.

Using the MMPI-2-RF to discriminate psychometrically identified schizotypic college students from a matched comparison sample.

PubMed

Hunter, Helen K; Bolinskey, P Kevin; Novi, Jonathan H; Hudak, Daniel V; James, Alison V; Myers, Kevin R; Schuder, Kelly M

2014-01-01

This study investigates the extent to which the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF) profiles of 52 individuals making up a psychometrically identified schizotypes (SZT) sample could be successfully discriminated from the protocols of 52 individuals in a matched comparison (MC) sample. Replication analyses were performed with an additional 53 pairs of SZT and MC participants. Results showed significant differences in mean T-score values between these 2 groups across a variety of MMPI-2-RF scales. Results from discriminant function analyses indicate that schizotypy can be predicted effectively using 4 MMPI-2-RF scales and that this method of classification held up on replication. Additional results demonstrated that these MMPI-2-RF scales nominally outperformed MMPI-2 scales suggested by previous research as being indicative of schizophrenia liability. Directions for future research with the MMPI-2-RF are suggested.

Caring for children with learning disabilities who present problem behaviours: a maternal perspective.

PubMed

Johnson, Robert F; O'Reilly, Michelle; Vostanis, Panos

2006-09-01

The theoretical cognitive model of stress and coping provides a structure to obtain and analyse maternal perceptions of caring for children with learning disabilities who present severe problem behaviours. The Family Fund database identified 18 families who met the sample criteria of children aged five years to 15 years with severe to moderate learning disability presenting severe problem behaviour. Physical aggression was reported to be the primary behavioural problem for 13 of the children. Interviews undertaken with the main carer of the child at their home were taped and transcribed. The data were analysed using grounded theory techniques which identified 'secondary stressors' for the parent. These were social isolation, conflict, limitation of lifestyle and self-blame. It is proposed that the amalgamated impact of these can weaken parents' coping resources and, therefore, may prove to be as significant to the negative association with maternal wellbeing as the problem behaviour.

Propulsion Investigation for Zero and Near-Zero Emissions Aircraft

NASA Technical Reports Server (NTRS)

Snyder, Christopher A.; Berton, Jeffrey J.; Brown, Gerald v.; Dolce, James L.; Dravid, Marayan V.; Eichenberg, Dennis J.; Freeh, Joshua E.; Gallo, Christopher A.; Jones, Scott M.; Kundu, Krishna P.;

Distinct effects of reminding mortality and physical pain on the default-mode activity and activity underlying self-reflection.

PubMed

Shi, Zhenhao; Han, Shihui

2018-06-01

Behavioral research suggests that reminding both mortality and negative affect influences self-related thoughts. Using functional magnetic resonance imaging (MRI), we tested the hypothesis that reminders of mortality and physical pain decrease brain activity underlying self-related thoughts. Three groups of adults underwent priming procedures during which they answered questions pertaining to mortality, physical pain, or leisure time, respectively. Before and after priming, participants performed personality trait judgments on oneself or a celebrity, identified the font of words, or passively viewed a fixation. The default-mode activity and neural activity underlying self-reflection were identified by contrasting viewing a fixation vs. font judgment and trait judgments on oneself vs. a celebrity, respectively. The analyses of the pre-priming functional MRI (fMRI) data identified the default-mode activity in the posterior cingulate cortex (PCC), ventral medial prefrontal cortex (MPFC), and parahippocampal gyrus, and the activity underlying instructed self-reflection in both the ventral and dorsal regions of the MPFC. The analyses of the post-priming fMRI data revealed that, relative to leisure time priming, reminding mortality significantly reduced the default-mode PCC activity, and reminding physical pain significantly decreased the dorsal MPFC activity during instructed self-reflection. Our findings suggest distinct neural underpinnings of the effect of reminding morality and aversive emotion on default-mode and instructed self-reflection.

Type D personality and health status in cardiovascular disease populations: a meta-analysis of prospective studies.

PubMed

Versteeg, Henneke; Spek, Viola; Pedersen, Susanne S; Denollet, Johan

2012-12-01

Knowledge of the factors associated with individual differences in patient-reported outcomes is essential to identify high-risk patients and improve secondary prevention. In this meta-analysis, we examined the association between Type D personality and the individual differences in patient-reported physical and mental health status among cardiovascular patients. A computerized search of the literature through PUBMED and PsychINFO (from 1995 to May 2011) was performed and prospective studies were selected that analysed the association between Type D personality and health status in cardiovascular patients. Two separate meta-analyses were performed for the association of Type D personality with physical and mental health status, respectively. Of all identified studies, ten studies met the selection criteria. The meta-analyses showed that Type D was associated with a two-fold increased odds for impaired physical health status (3035 patients, OR 1.94, 95% CI 1.49-2.52) and a 2.5-fold increased odds for impaired mental health status (2213 patients, OR 2.55, 95% CI 1.57-4.16). There was no significant heterogeneity between the studies on physical health status (Q = 12.78; p = 0.17; I(2 )= 29.59), but there was between those on mental health status (Q = 21.91; p = 0.003; I(2 )= 68.04). Subgroup analyses showed that the association between Type D and mental health status decreased yet remained significant when adjusting for baseline health status. Type D personality was shown to be an independent correlate of impaired patient-reported physical and mental health status in various cardiovascular patient groups. Clinicians should be aware of the association between chronic psychological distress and poor patient-reported outcomes.

Health disparities among common subcultural identities of young gay men: physical, mental, and sexual health.

PubMed

Lyons, Anthony; Hosking, Warwick

2014-11-01

Researchers, policymakers, and health agencies have tended to treat gay men as a relatively homogeneous population, with little attention given to its many subcultural identities. In this study, we focused on young gay men and investigated a range of health-related differences according to common subcultural identities, such as Bear, Cub, and Twink. In a nationwide cross-sectional online survey of 1,034 Australian gay men aged 18-39 years, 44% reported a subcultural identity, the two most common being Cub (9%) and Twink (20%). Logistic and linear regression analyses compared Cub- and Twink-identified men and those without a subcultural identity (Non-identified) on a range of health-related outcomes. After adjusting for differences in age and body mass index (BMI), Twink-identified men had the highest risk profile overall, including significantly higher rates of smoking tobacco and alcohol consumption. They were also significantly more likely to report engaging in receptive anal sex. In addition, Cub-identified men were significantly more likely to report being in an ongoing relationship while Non-identified men were significantly less likely to report experiences of discrimination in the past 12 months. Differences on measures of mental health between the three groups were no longer significant after adjusting for age and BMI. In summary, we found numerous health-related differences according to subcultural identity that warrant further investigation by researchers, health agencies, and others concerned with further understanding and addressing health-related challenges of gay men.

Distributed Neural Processing Predictors of Multi-dimensional Properties of Affect

PubMed Central

Bush, Keith A.; Inman, Cory S.; Hamann, Stephan; Kilts, Clinton D.; James, G. Andrew

2017-01-01

Recent evidence suggests that emotions have a distributed neural representation, which has significant implications for our understanding of the mechanisms underlying emotion regulation and dysregulation as well as the potential targets available for neuromodulation-based emotion therapeutics. This work adds to this evidence by testing the distribution of neural representations underlying the affective dimensions of valence and arousal using representational models that vary in both the degree and the nature of their distribution. We used multi-voxel pattern classification (MVPC) to identify whole-brain patterns of functional magnetic resonance imaging (fMRI)-derived neural activations that reliably predicted dimensional properties of affect (valence and arousal) for visual stimuli viewed by a normative sample (n = 32) of demographically diverse, healthy adults. Inter-subject leave-one-out cross-validation showed whole-brain MVPC significantly predicted (p < 0.001) binarized normative ratings of valence (positive vs. negative, 59% accuracy) and arousal (high vs. low, 56% accuracy). We also conducted group-level univariate general linear modeling (GLM) analyses to identify brain regions whose response significantly differed for the contrasts of positive versus negative valence or high versus low arousal. Multivoxel pattern classifiers using voxels drawn from all identified regions of interest (all-ROIs) exhibited mixed performance; arousal was predicted significantly better than chance but worse than the whole-brain classifier, whereas valence was not predicted significantly better than chance. Multivoxel classifiers derived using individual ROIs generally performed no better than chance. Although performance of the all-ROI classifier improved with larger ROIs (generated by relaxing the clustering threshold), performance was still poorer than the whole-brain classifier. These findings support a highly distributed model of neural processing for the affective dimensions of valence and arousal. Finally, joint error analyses of the MVPC hyperplanes encoding valence and arousal identified regions within the dimensional affect space where multivoxel classifiers exhibited the greatest difficulty encoding brain states – specifically, stimuli of moderate arousal and high or low valence. In conclusion, we highlight new directions for characterizing affective processing for mechanistic and therapeutic applications in affective neuroscience. PMID:28959198

Multi-variant study of obesity risk genes in African Americans: The Jackson Heart Study.

PubMed

Liu, Shijian; Wilson, James G; Jiang, Fan; Griswold, Michael; Correa, Adolfo; Mei, Hao

2016-11-30

Genome-wide association study (GWAS) has been successful in identifying obesity risk genes by single-variant association analysis. For this study, we designed steps of analysis strategy and aimed to identify multi-variant effects on obesity risk among candidate genes. Our analyses were focused on 2137 African American participants with body mass index measured in the Jackson Heart Study and 657 common single nucleotide polymorphisms (SNPs) genotyped at 8 GWAS-identified obesity risk genes. Single-variant association test showed that no SNPs reached significance after multiple testing adjustment. The following gene-gene interaction analysis, which was focused on SNPs with unadjusted p-value<0.10, identified 6 significant multi-variant associations. Logistic regression showed that SNPs in these associations did not have significant linear interactions; examination of genetic risk score evidenced that 4 multi-variant associations had significant additive effects of risk SNPs; and haplotype association test presented that all multi-variant associations contained one or several combinations of particular alleles or haplotypes, associated with increased obesity risk. Our study evidenced that obesity risk genes generated multi-variant effects, which can be additive or non-linear interactions, and multi-variant study is an important supplement to existing GWAS for understanding genetic effects of obesity risk genes. Copyright © 2016 Elsevier B.V. All rights reserved.

Significance of functional disease-causal/susceptible variants identified by whole-genome analyses for the understanding of human diseases.

PubMed

Hitomi, Yuki; Tokunaga, Katsushi

2017-01-01

Human genome variation may cause differences in traits and disease risks. Disease-causal/susceptible genes and variants for both common and rare diseases can be detected by comprehensive whole-genome analyses, such as whole-genome sequencing (WGS), using next-generation sequencing (NGS) technology and genome-wide association studies (GWAS). Here, in addition to the application of an NGS as a whole-genome analysis method, we summarize approaches for the identification of functional disease-causal/susceptible variants from abundant genetic variants in the human genome and methods for evaluating their functional effects in human diseases, using an NGS and in silico and in vitro functional analyses. We also discuss the clinical applications of the functional disease causal/susceptible variants to personalized medicine.

Effects on Task Performance and Psychophysiological Measures of Performance During Normobaric Hypoxia Exposure

NASA Technical Reports Server (NTRS)

Stephens, Chad; Kennedy, Kellie; Napoli, Nicholas; Demas, Matthew; Barnes, Laura; Crook, Brenda; Williams, Ralph; Last, Mary Carolyn; Schutte, Paul

2017-01-01

Human-autonomous systems have the potential to mitigate pilot cognitive impairment and improve aviation safety. A research team at NASA Langley conducted an experiment to study the impact of mild normobaric hypoxia induction on aircraft pilot performance and psychophysiological state. A within-subjects design involved non-hypoxic and hypoxic exposures while performing three 10-minute tasks. Results indicated the effect of 15,000 feet simulated altitude did not induce significant performance decrement but did produce increase in perceived workload. Analyses of psychophysiological responses evince the potential of biomarkers for hypoxia onset. This study represents on-going work at NASA intending to add to the current knowledge of psychophysiologically-based input to automation to increase aviation safety. Analyses involving coupling across physiological systems and wavelet transforms of cortical activity revealed patterns that can discern between the simulated altitude conditions. Specifically, multivariate entropy of ECG/Respiration components were found to be significant predictors (p< 0.02) of hypoxia. Furthermore, in EEG, there was a significant decrease in mid-level beta (15.19-18.37Hz) during the hypoxic condition in thirteen of sixteen sites across the scalp. Task performance was not appreciably impacted by the effect of 15,000 feet simulated altitude. Analyses of psychophysiological responses evince the potential of biomarkers for mild hypoxia onset.The potential for identifying shifts in underlying cortical and physiological systems could serve as a means to identify the onset of deteriorated cognitive state. Enabling such assessment in future flightdecks could permit increasingly autonomous systems-supported operations. Augmenting human operator through assessment of cognitive impairment has the potential to further improve operator performance and mitigate human error in safety critical contexts. This study represents ongoing work at NASA intending to add to the current knowledge of psychophysiologically-based input to automation to increase aviation safety.

Accuracy of medical subject heading indexing of dental survival analyses.

PubMed

Layton, Danielle M; Clarke, Michael

2014-01-01

To assess the Medical Subject Headings (MeSH) indexing of articles that employed time-to-event analyses to report outcomes of dental treatment in patients. Articles published in 2008 in 50 dental journals with the highest impact factors were hand searched to identify articles reporting dental treatment outcomes over time in human subjects with time-to-event statistics (included, n = 95), without time-to-event statistics (active controls, n = 91), and all other articles (passive controls, n = 6,769). The search was systematic (kappa 0.92 for screening, 0.86 for eligibility). Outcome-, statistic- and time-related MeSH were identified, and differences in allocation between groups were analyzed with chi-square and Fischer exact statistics. The most frequently allocated MeSH for included and active control articles were "dental restoration failure" (77% and 52%, respectively) and "treatment outcome" (54% and 48%, respectively). Outcome MeSH was similar between these groups (86% and 77%, respectively) and significantly greater than passive controls (10%, P < .001). Significantly more statistical MeSH were allocated to the included articles than to the active or passive controls (67%, 15%, and 1%, respectively, P < .001). Sixty-nine included articles specifically used Kaplan-Meier or life table analyses, but only 42% (n = 29) were indexed as such. Significantly more time-related MeSH were allocated to the included than the active controls (92% and 79%, respectively, P = .02), or to the passive controls (22%, P < .001). MeSH allocation within MEDLINE to time-to-event dental articles was inaccurate and inconsistent. Statistical MeSH were omitted from 30% of the included articles and incorrectly allocated to 15% of active controls. Such errors adversely impact search accuracy.

Broad DNA methylation changes of spermatogenesis, inflammation and immune response-related genes in a subgroup of sperm samples for assisted reproduction.

PubMed

Schütte, B; El Hajj, N; Kuhtz, J; Nanda, I; Gromoll, J; Hahn, T; Dittrich, M; Schorsch, M; Müller, T; Haaf, T

2013-11-01

Aberrant sperm DNA methylation patterns, mainly in imprinted genes, have been associated with male subfertility and oligospermia. Here, we performed a genome-wide methylation analysis in sperm samples representing a wide range of semen parameters. Sperm DNA samples of 38 males attending a fertility centre were analysed with Illumina HumanMethylation27 BeadChips, which quantify methylation of >27 000 CpG sites in cis-regulatory regions of almost 15 000 genes. In an unsupervised analysis of methylation of all analysed sites, the patient samples clustered into a major and a minor group. The major group clustered with samples from normozoospermic healthy volunteers and, thus, may more closely resemble the normal situation. When correlating the clusters with semen and clinical parameters, the sperm counts were significantly different between groups with the minor group exhibiting sperm counts in the low normal range. A linear model identified almost 3000 CpGs with significant methylation differences between groups. Functional analysis revealed a broad gain of methylation in spermatogenesis-related genes and a loss of methylation in inflammation- and immune response-related genes. Quantitative bisulfite pyrosequencing validated differential methylation in three of five significant candidate genes on the array. Collectively, we identified a subgroup of sperm samples for assisted reproduction with sperm counts in the low normal range and broad methylation changes (affecting approximately 10% of analysed CpG sites) in specific pathways, most importantly spermatogenesis-related genes. We propose that epigenetic analysis can supplement traditional semen parameters and has the potential to provide new insights into the aetiology of male subfertility. © 2013 American Society of Andrology and European Academy of Andrology.

The prevalence and characteristics of low back pain among sitting workers in a Japanese manufacturing company.

PubMed

Inoue, Gen; Miyagi, Masayuki; Uchida, Kentaro; Ishikawa, Tetsuhiro; Kamoda, Hiroto; Eguchi, Yawara; Orita, Sumihisa; Yamauchi, Kazuyo; Takaso, Masashi; Tsuchiya, Kei-Ichi; Takahashi, Kazuhisa; Ohtori, Seiji

2015-01-01

Low back pain (LBP) is a major public health problem and the most common cause of workers' disability, resulting in substantial economic burden in terms of workers' compensation and medical costs. Sitting is a recognized potential risk factor for developing LBP. Therefore, eliminating risk factors associated with working conditions and individual work capacity may be beneficial in preventing LBP in sitting workers. The purpose of this prospective cross-sectional study is to investigate the prevalence of LBP and examine risk factors that contribute to the development of LBP in sitting workers at an electronics manufacturing company. A cross-sectional survey was administered to all subjects to assess the prevalence of LBP persisting for at least 48 h during the recent week. Data on demographic characteristics and potential risk factors for LBP were collected at routine annual check-ups. Patients with LBP completed the Roland-Morris Disability Questionnaire (RDQ), which provided information on the attributes of LBP. Univariate and multivariate regression analyses examined the association between LBP and potential risk factors. Of the 1,329 sitting workers, 201 (15.1 %) acknowledged experiencing LBP during the recent week. In female workers, weight and body mass index were significantly correlated with the RDQ score. Univariate analyses identified male sex, prior history of LBP, height ≥170 cm, and weight ≥70 kg as significant risk factors of LBP. Multivariate logistic regression analyses identified prior history of LBP and past history of lumbar spine surgery as significant risk factors of LBP. This study characterized the prevalence and attributes of LBP in Japanese sitting workers and provided information about potential risk factors contributing to occurrence of LBP in the workplace.

Dramatic expansion of the black widow toxin arsenal uncovered by multi-tissue transcriptomics and venom proteomics.

PubMed

Haney, Robert A; Ayoub, Nadia A; Clarke, Thomas H; Hayashi, Cheryl Y; Garb, Jessica E

2014-06-11

Animal venoms attract enormous interest given their potential for pharmacological discovery and understanding the evolution of natural chemistries. Next-generation transcriptomics and proteomics provide unparalleled, but underexploited, capabilities for venom characterization. We combined multi-tissue RNA-Seq with mass spectrometry and bioinformatic analyses to determine venom gland specific transcripts and venom proteins from the Western black widow spider (Latrodectus hesperus) and investigated their evolution. We estimated expression of 97,217 L. hesperus transcripts in venom glands relative to silk and cephalothorax tissues. We identified 695 venom gland specific transcripts (VSTs), many of which BLAST and GO term analyses indicate may function as toxins or their delivery agents. ~38% of VSTs had BLAST hits, including latrotoxins, inhibitor cystine knot toxins, CRISPs, hyaluronidases, chitinase, and proteases, and 59% of VSTs had predicted protein domains. Latrotoxins are venom toxins that cause massive neurotransmitter release from vertebrate or invertebrate neurons. We discovered ≥ 20 divergent latrotoxin paralogs expressed in L. hesperus venom glands, significantly increasing this biomedically important family. Mass spectrometry of L. hesperus venom identified 49 proteins from VSTs, 24 of which BLAST to toxins. Phylogenetic analyses showed venom gland specific gene family expansions and shifts in tissue expression. Quantitative expression analyses comparing multiple tissues are necessary to identify venom gland specific transcripts. We present a black widow venom specific exome that uncovers a trove of diverse toxins and associated proteins, suggesting a dynamic evolutionary history. This justifies a reevaluation of the functional activities of black widow venom in light of its emerging complexity.

Does the inclusion of grey literature influence estimates of intervention effectiveness reported in meta-analyses?

PubMed

McAuley, L; Pham, B; Tugwell, P; Moher, D

2000-10-07

The inclusion of only a subset of all available evidence in a meta-analysis may introduce biases and threaten its validity; this is particularly likely if the subset of included studies differ from those not included, which may be the case for published and grey literature (unpublished studies, with limited distribution). We set out to examine whether exclusion of grey literature, compared with its inclusion in meta-analysis, provides different estimates of the effectiveness of interventions assessed in randomised trials. From a random sample of 135 meta-analyses, we identified and retrieved 33 publications that included both grey and published primary studies. The 33 publications contributed 41 separate meta-analyses from several disease areas. General characteristics of the meta-analyses and associated studies and outcome data at the trial level were collected. We explored the effects of the inclusion of grey literature on the quantitative results using logistic-regression analyses. 33% of the meta-analyses were found to include some form of grey literature. The grey literature, when included, accounts for between 4.5% and 75% of the studies in a meta-analysis. On average, published work, compared with grey literature, yielded significantly larger estimates of the intervention effect by 15% (ratio of odds ratios=1.15 [95% CI 1.04-1.28]). Excluding abstracts from the analysis further compounded the exaggeration (1.33 [1.10-1.60]). The exclusion of grey literature from meta-analyses can lead to exaggerated estimates of intervention effectiveness. In general, meta-analysts should attempt to identify, retrieve, and include all reports, grey and published, that meet predefined inclusion criteria.

Catchment scale controls the temporal connection of transpiration and diel fluctuations in streamflow

Treesearch

C.B. Graham; H.R. Barnard; K.L. Kavanagh; J.P. McNamara

2012-01-01

Diel fluctuations can comprise a significant portion of summer discharge in small to medium catchments. The source of these signals and the manner in which they are propagated to stream gauging sites is poorly understood. In this work, we analysed stream discharge from 15 subcatchments in Dry Creek, Idaho, Reynolds Creek, Idaho, and HJ Andrews, Oregon. We identified...

Exploration review

USGS Publications Warehouse

Wilburn, D.R.; Vasil, R.L.; Nolting, A.

2011-01-01

This summary of international mineral exploration activities for the year 2010 draws upon available information from industry sources, published literature and U.S. Geological Survey (USGS) specialists. The summary provides data on exploration budgets by region and mineral commodity, identifies significant mineral discoveries and areas of mineral exploration, discusses government programs affecting the mineral exploration industry and presents analyses of exploration activities performed by the mineral industry.

Use of LANDSAT imagery for wildlife habitat mapping in northeast and eastcentral Alaska

NASA Technical Reports Server (NTRS)

Laperriere, A. J. (Principal Investigator)

1976-01-01

The author has identified the following significant results. Indications are that Alaskan scenes dated later than about September 5th are unsuitable for vegetational analyses. Such fall data exhibit a limited dynamic range relative to summer scenes and the informational content of the data is reduced such that discrimination between many vegetation types is no longer possible.

Research-Based Teacher Education? Exploring the Meaning Potentials of Swedish Teacher Education

ERIC Educational Resources Information Center

Alvunger, Daniel; Wahlström, Ninni

2018-01-01

In this article, we explore the meaning potentials of teacher education in terms of the significance of a research-based approach and the different pedagogic identities that such an approach implies. The study's aim is to examine the important factors for education to be considered research-based and to identify and analyse the research base of…

Resin transfer molding for advanced composite primary wing and fuselage structures

NASA Technical Reports Server (NTRS)

Markus, Alan

1992-01-01

The stitching and resin transfer molding (RTM) processes developed at Douglas Aircraft Co. are successfully demonstrating significant cost reductions with good damage tolerance properties. These attributes were identified as critical to application of advanced composite materials to commercial aircraft primary structures. The RTM/stitching developments, cost analyses, and test results are discussed of the NASA Advanced Composites Technology program.

Modelling the Reasons for Training Choices: Technical Paper. Support Document

ERIC Educational Resources Information Center

Smith, Andrew; Oczkowski, Eddie; Hill, Mark

2009-01-01

This report provides the technical details on the modelling aspects of identifying significant drivers for the reasons for using certain types of training and for the choice of training types. The employed data is from the 2005 Survey of Employer Use and Views of the VET system (SEUV). The data has previously been analysed in NCVER (2006). This…

A Persian version of the parental bonding instrument: factor structure and psychometric properties.

PubMed

Behzadi, Behnaz; Parker, Gordon

2015-02-28

The Parental Bonding Instrument (PBI) is a widely used self-report measure for quantifying key parenting styles as perceived by the child during its first 16 years. While its development study identified two key parental dimensions, subsequent studies have variably confirmed those two or argued for one or more additional parental constructs. We developed a Persian translation of the PBI and administered it to a sample of 340 high school students. The construct validity of the Persian PBI was examined by Exploratory Factor Analysis while Confirmatory Factor Analysis was used to identify the most adequate model. Analyses of the Persian PBI favored a four-factor model for both parental forms. The Persian PBI has a factorial structure consistent with constructs identified in western cultures, as well as high internal consistency and test-retest reliability. Multivariate analyses indicated significant differences between boys and girls across some factors. The PBI appears an acceptable and appropriate measure for quantifying parent-child bonding in Iranian samples. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk.

PubMed

Day, Felix R; Thompson, Deborah J; Helgason, Hannes; Chasman, Daniel I; Finucane, Hilary; Sulem, Patrick; Ruth, Katherine S; Whalen, Sean; Sarkar, Abhishek K; Albrecht, Eva; Altmaier, Elisabeth; Amini, Marzyeh; Barbieri, Caterina M; Boutin, Thibaud; Campbell, Archie; Demerath, Ellen; Giri, Ayush; He, Chunyan; Hottenga, Jouke J; Karlsson, Robert; Kolcic, Ivana; Loh, Po-Ru; Lunetta, Kathryn L; Mangino, Massimo; Marco, Brumat; McMahon, George; Medland, Sarah E; Nolte, Ilja M; Noordam, Raymond; Nutile, Teresa; Paternoster, Lavinia; Perjakova, Natalia; Porcu, Eleonora; Rose, Lynda M; Schraut, Katharina E; Segrè, Ayellet V; Smith, Albert V; Stolk, Lisette; Teumer, Alexander; Andrulis, Irene L; Bandinelli, Stefania; Beckmann, Matthias W; Benitez, Javier; Bergmann, Sven; Bochud, Murielle; Boerwinkle, Eric; Bojesen, Stig E; Bolla, Manjeet K; Brand, Judith S; Brauch, Hiltrud; Brenner, Hermann; Broer, Linda; Brüning, Thomas; Buring, Julie E; Campbell, Harry; Catamo, Eulalia; Chanock, Stephen; Chenevix-Trench, Georgia; Corre, Tanguy; Couch, Fergus J; Cousminer, Diana L; Cox, Angela; Crisponi, Laura; Czene, Kamila; Davey Smith, George; de Geus, Eco J C N; de Mutsert, Renée; De Vivo, Immaculata; Dennis, Joe; Devilee, Peter; Dos-Santos-Silva, Isabel; Dunning, Alison M; Eriksson, Johan G; Fasching, Peter A; Fernández-Rhodes, Lindsay; Ferrucci, Luigi; Flesch-Janys, Dieter; Franke, Lude; Gabrielson, Marike; Gandin, Ilaria; Giles, Graham G; Grallert, Harald; Gudbjartsson, Daniel F; Guénel, Pascal; Hall, Per; Hallberg, Emily; Hamann, Ute; Harris, Tamara B; Hartman, Catharina A; Heiss, Gerardo; Hooning, Maartje J; Hopper, John L; Hu, Frank; Hunter, David J; Ikram, M Arfan; Im, Hae Kyung; Järvelin, Marjo-Riitta; Joshi, Peter K; Karasik, David; Kellis, Manolis; Kutalik, Zoltan; LaChance, Genevieve; Lambrechts, Diether; Langenberg, Claudia; Launer, Lenore J; Laven, Joop S E; Lenarduzzi, Stefania; Li, Jingmei; Lind, Penelope A; Lindstrom, Sara; Liu, YongMei; Luan, Jian'an; Mägi, Reedik; Mannermaa, Arto; Mbarek, Hamdi; McCarthy, Mark I; Meisinger, Christa; Meitinger, Thomas; Menni, Cristina; Metspalu, Andres; Michailidou, Kyriaki; Milani, Lili; Milne, Roger L; Montgomery, Grant W; Mulligan, Anna M; Nalls, Mike A; Navarro, Pau; Nevanlinna, Heli; Nyholt, Dale R; Oldehinkel, Albertine J; O'Mara, Tracy A; Padmanabhan, Sandosh; Palotie, Aarno; Pedersen, Nancy; Peters, Annette; Peto, Julian; Pharoah, Paul D P; Pouta, Anneli; Radice, Paolo; Rahman, Iffat; Ring, Susan M; Robino, Antonietta; Rosendaal, Frits R; Rudan, Igor; Rueedi, Rico; Ruggiero, Daniela; Sala, Cinzia F; Schmidt, Marjanka K; Scott, Robert A; Shah, Mitul; Sorice, Rossella; Southey, Melissa C; Sovio, Ulla; Stampfer, Meir; Steri, Maristella; Strauch, Konstantin; Tanaka, Toshiko; Tikkanen, Emmi; Timpson, Nicholas J; Traglia, Michela; Truong, Thérèse; Tyrer, Jonathan P; Uitterlinden, André G; Edwards, Digna R Velez; Vitart, Veronique; Völker, Uwe; Vollenweider, Peter; Wang, Qin; Widen, Elisabeth; van Dijk, Ko Willems; Willemsen, Gonneke; Winqvist, Robert; Wolffenbuttel, Bruce H R; Zhao, Jing Hua; Zoledziewska, Magdalena; Zygmunt, Marek; Alizadeh, Behrooz Z; Boomsma, Dorret I; Ciullo, Marina; Cucca, Francesco; Esko, Tõnu; Franceschini, Nora; Gieger, Christian; Gudnason, Vilmundur; Hayward, Caroline; Kraft, Peter; Lawlor, Debbie A; Magnusson, Patrik K E; Martin, Nicholas G; Mook-Kanamori, Dennis O; Nohr, Ellen A; Polasek, Ozren; Porteous, David; Price, Alkes L; Ridker, Paul M; Snieder, Harold; Spector, Tim D; Stöckl, Doris; Toniolo, Daniela; Ulivi, Sheila; Visser, Jenny A; Völzke, Henry; Wareham, Nicholas J; Wilson, James F; Spurdle, Amanda B; Thorsteindottir, Unnur; Pollard, Katherine S; Easton, Douglas F; Tung, Joyce Y; Chang-Claude, Jenny; Hinds, David; Murray, Anna; Murabito, Joanne M; Stefansson, Kari; Ong, Ken K; Perry, John R B

2017-06-01

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to ∼370,000 women, we identify 389 independent signals (P < 5 × 10 -8 ) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ∼7.4% of the population variance in age at menarche, corresponding to ∼25% of the estimated heritability. We implicate ∼250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility.

Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

PubMed Central

Day, Felix R; Thompson, Deborah J; Helgason, Hannes; Chasman, Daniel I; Finucane, Hilary; Sulem, Patrick; Ruth, Katherine S; Whalen, Sean; Sarkar, Abhishek K; Albrecht, Eva; Altmaier, Elisabeth; Amini, Marzyeh; Barbieri, Caterina M; Boutin, Thibaud; Campbell, Archie; Demerath, Ellen; Giri, Ayush; He, Chunyan; Hottenga, Jouke J; Karlsson, Robert; Kolcic, Ivana; Loh, Po-Ru; Lunetta, Kathryn L; Mangino, Massimo; Marco, Brumat; McMahon, George; Medland, Sarah E; Nolte, Ilja M; Noordam, Raymond; Nutile, Teresa; Paternoster, Lavinia; Perjakova, Natalia; Porcu, Eleonora; Rose, Lynda M; Schraut, Katharina E; Segrè, Ayellet V; Smith, Albert V; Stolk, Lisette; Teumer, Alexander; Andrulis, Irene L; Bandinelli, Stefania; Beckmann, Matthias W; Benitez, Javier; Bergmann, Sven; Bochud, Murielle; Boerwinkle, Eric; Bojesen, Stig E; Bolla, Manjeet K; Brand, Judith S; Brauch, Hiltrud; Brenner, Hermann; Broer, Linda; Brüning, Thomas; Buring, Julie E; Campbell, Harry; Catamo, Eulalia; Chanock, Stephen; Chenevix-Trench, Georgia; Corre, Tanguy; Couch, Fergus J; Cousminer, Diana L; Cox, Angela; Crisponi, Laura; Czene, Kamila; Smith, George Davey; de Geus, Eco JCN; de Mutsert, Renée; De Vivo, Immaculata; Dennis, Joe; Devilee, Peter; dos-Santos-Silva, Isabel; Dunning, Alison M; Eriksson, Johan G; Fasching, Peter A; Fernández-Rhodes, Lindsay; Ferrucci, Luigi; Flesch-Janys, Dieter; Franke, Lude; Gabrielson, Marike; Gandin, Ilaria; Giles, Graham G; Grallert, Harald; Gudbjartsson, Daniel F; Guénel, Pascal; Hall, Per; Hallberg, Emily; Hamann, Ute; Harris, Tamara B; Hartman, Catharina A; Heiss, Gerardo; Hooning, Maartje J; Hopper, John L; Hu, Frank; Hunter, David J; Ikram, M Arfan; Im, Hae Kyung; Järvelin, Marjo-Riitta; Joshi, Peter K; Karasik, David; Kellis, Manolis; Kutalik, Zoltan; LaChance, Genevieve; Lambrechts, Diether; Langenberg, Claudia; Launer, Lenore J; Laven, Joop S E; Lenarduzzi, Stefania; Li, Jingmei; Lind, Penelope A; Lindstrom, Sara; Liu, YongMei; Luan, Jian’an; Mägi, Reedik; Mannermaa, Arto; Mbarek, Hamdi; McCarthy, Mark I; Meisinger, Christa; Meitinger, Thomas; Menni, Cristina; Metspalu, Andres; Michailidou, Kyriaki; Milani, Lili; Milne, Roger L; Montgomery, Grant W; Mulligan, Anna M; Nalls, Mike A; Navarro, Pau; Nevanlinna, Heli; Nyholt, Dale R; Oldehinkel, Albertine J; O’Mara, Tracy A; Padmanabhan, Sandosh; Palotie, Aarno; Pedersen, Nancy; Peters, Annette; Peto, Julian; Pharoah, Paul D P; Pouta, Anneli; Radice, Paolo; Rahman, Iffat; Ring, Susan M; Robino, Antonietta; Rosendaal, Frits R; Rudan, Igor; Rueedi, Rico; Ruggiero, Daniela; Sala, Cinzia F; Schmidt, Marjanka K; Scott, Robert A; Shah, Mitul; Sorice, Rossella; Southey, Melissa C; Sovio, Ulla; Stampfer, Meir; Steri, Maristella; Strauch, Konstantin; Tanaka, Toshiko; Tikkanen, Emmi; Timpson, Nicholas J; Traglia, Michela; Truong, Thérèse; Tyrer, Jonathan P; Uitterlinden, André G; Velez Edwards, Digna R; Vitart, Veronique; Völker, Uwe; Vollenweider, Peter; Wang, Qin; Widen, Elisabeth; van Dijk, Ko Willems; Willemsen, Gonneke; Winqvist, Robert; Wolffenbuttel, Bruce H R; Zhao, Jing Hua; Zoledziewska, Magdalena; Zygmunt, Marek; Alizadeh, Behrooz Z; Boomsma, Dorret I; Ciullo, Marina; Cucca, Francesco; Esko, Tõnu; Franceschini, Nora; Gieger, Christian; Gudnason, Vilmundur; Hayward, Caroline; Kraft, Peter; Lawlor, Debbie A; Magnusson, Patrik K E; Martin, Nicholas G; Mook-Kanamori, Dennis O; Nohr, Ellen A; Polasek, Ozren; Porteous, David; Price, Alkes L; Ridker, Paul M; Snieder, Harold; Spector, Tim D; Stöckl, Doris; Toniolo, Daniela; Ulivi, Sheila; Visser, Jenny A; Völzke, Henry; Wareham, Nicholas J; Wilson, James F; Spurdle, Amanda B; Thorsteindottir, Unnur; Pollard, Katherine S; Easton, Douglas F; Tung, Joyce Y; Chang-Claude, Jenny; Hinds, David; Murray, Anna; Murabito, Joanne M; Stefansson, Kari; Ong, Ken K; Perry, John R B

2018-01-01

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project–imputed genotype data in up to ~370,000 women, we identify 389 independent signals (P < 5 × 10−8) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ~7.4% of the population variance in age at menarche, corresponding to ~25% of the estimated heritability. We implicate ~250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility. PMID:28436984

Integrated analysis of germline and somatic variants in ovarian cancer.

PubMed

Kanchi, Krishna L; Johnson, Kimberly J; Lu, Charles; McLellan, Michael D; Leiserson, Mark D M; Wendl, Michael C; Zhang, Qunyuan; Koboldt, Daniel C; Xie, Mingchao; Kandoth, Cyriac; McMichael, Joshua F; Wyczalkowski, Matthew A; Larson, David E; Schmidt, Heather K; Miller, Christopher A; Fulton, Robert S; Spellman, Paul T; Mardis, Elaine R; Druley, Todd E; Graubert, Timothy A; Goodfellow, Paul J; Raphael, Benjamin J; Wilson, Richard K; Ding, Li

2014-01-01

We report the first large-scale exome-wide analysis of the combined germline-somatic landscape in ovarian cancer. Here we analyse germline and somatic alterations in 429 ovarian carcinoma cases and 557 controls. We identify 3,635 high confidence, rare truncation and 22,953 missense variants with predicted functional impact. We find germline truncation variants and large deletions across Fanconi pathway genes in 20% of cases. Enrichment of rare truncations is shown in BRCA1, BRCA2 and PALB2. In addition, we observe germline truncation variants in genes not previously associated with ovarian cancer susceptibility (NF1, MAP3K4, CDKN2B and MLL3). Evidence for loss of heterozygosity was found in 100 and 76% of cases with germline BRCA1 and BRCA2 truncations, respectively. Germline-somatic interaction analysis combined with extensive bioinformatics annotation identifies 222 candidate functional germline truncation and missense variants, including two pathogenic BRCA1 and 1 TP53 deleterious variants. Finally, integrated analyses of germline and somatic variants identify significantly altered pathways, including the Fanconi, MAPK and MLL pathways.

The Effect of Executive Function on Science Achievement Among Normally Developing 10-Year Olds

NASA Astrophysics Data System (ADS)

Lederman, Sheri G.

Executive function (EF) is an umbrella term used to identify a set of discrete but interrelated cognitive abilities that enable individuals to engage in goal-directed, future-oriented action in response to a novel context. Developmental studies indicate that EF is predictive of reading and math achievement in middle childhood. The purpose of this study was to identify the association between EF and science achievement among normally developing 10 year olds. A sample of fifth grade students from a Northeastern suburban community participated in tests of EF, science, and intelligence. Consistent with adult models of EF, principal components analysis identified a three-factor model of EF organization in middle childhood, including cognitive flexibility, working memory, and inhibition. Multiple regression analyses revealed that executive function processes of cognitive flexibility, working memory, and inhibition were all predictive of science performance. Post hoc analyses revealed that high-performing science students differed significantly from low-performing students in both cognitive flexibility and working memory. These findings suggest that complex academic demands specific to science achievement rely on the emergence and maturation of EF components.

Looking Māori Predicts Decreased Rates of Home Ownership: Institutional Racism in Housing Based on Perceived Appearance

PubMed Central

2015-01-01

This study examined differences in rates of home ownership among Māori (the indigenous peoples of New Zealand). We identified systematic factors that predicted why some Māori were more likely to own their own home (partially or fully) relative to other Māori. Data were drawn from a large national postal sample of 561 self-identified Māori collected as part of the New Zealand Attitudes and Values Study. As predicted, our analyses indicated that self-reported appearance as Māori, or the extent to which people thought they personally displayed features which visibly identified them as Māori to others, significantly predicted decreased rates of home ownership. This association held when adjusting for numerous demographic covariates, such as education, level of deprivation of the immediate area, household income, age, relationship status, region of residence, and so forth. Our analyses suggest there is, or at least has been in the recent past, institutional racism against Māori in New Zealand’s home lending industry based on merely appearing more Māori. PMID:25738961

Looking Māori predicts decreased rates of home ownership: institutional racism in housing based on perceived appearance.

PubMed

Houkamau, Carla A; Sibley, Chris G

2015-01-01

This study examined differences in rates of home ownership among Māori (the indigenous peoples of New Zealand). We identified systematic factors that predicted why some Māori were more likely to own their own home (partially or fully) relative to other Māori. Data were drawn from a large national postal sample of 561 self-identified Māori collected as part of the New Zealand Attitudes and Values Study. As predicted, our analyses indicated that self-reported appearance as Māori, or the extent to which people thought they personally displayed features which visibly identified them as Māori to others, significantly predicted decreased rates of home ownership. This association held when adjusting for numerous demographic covariates, such as education, level of deprivation of the immediate area, household income, age, relationship status, region of residence, and so forth. Our analyses suggest there is, or at least has been in the recent past, institutional racism against Māori in New Zealand's home lending industry based on merely appearing more Māori.

Rare diseases in Italy: analysis of the costs and pharmacotherapy.

PubMed

Petrelli, Fabio; Grappasonni, Iolanda; Kračmarová, Lenka; Cioffi, Pasquale; Tayebati, Seyed Khosrow; Esposito, Lucia

2013-08-01

Purpose of this research was to analyse the rare diseases drug supply paths in the Italian region of Campania (Health District 47 of the Local Medical Company Naples 1), with a particular focus on current regulations in this field, and quantify the economic incidence of such pathologies in each quarter of 2007 and 2008. Rare, or orphan, diseases are especially serious and onerous from every point of view. Patients meet significant difficulties in obtaining information and in identifying the most appropriate treatment path within the health care system. Pharmaceutical prescriptions were analysed in order to identify the number of patients for each pathology in each quarter of the years 2007 and 2008, the drugs used, the quantity of each drug, and the costs for treatments. Data show a significant increase of costs during each quarter of the year 2008, as well as from 2007 to 2008. In the absence of specific guidelines for the Campania Region, the Local Medical Company of Naples 1 has established a procedure for patients affected by rare diseases that enables them to receive at no cost products that otherwise would not be distributed for free by the health care system.

Analysis of the 5 iron golf swing when hitting for maximum distance.

PubMed

Healy, Aoife; Moran, Kieran A; Dickson, Jane; Hurley, Cillian; Smeaton, Alan F; O'Connor, Noel E; Kelly, Philip; Haahr, Mads; Chockalingam, Nachiappan

2011-07-01

Most previous research on golf swing mechanics has focused on the driver club. The aim of this study was to identify the kinematic factors that contribute to greater hitting distance when using the 5 iron club. Three-dimensional marker coordinate data were collected (250 Hz) to calculate joint kinematics at eight key swing events, while a swing analyser measured club swing and ball launch characteristics. Thirty male participants were assigned to one of two groups, based on their ball launch speed (high: 52.9 ± 2.1 m · s(-1); low: 39.9 ± 5.2 m · s(-1)). Statistical analyses were used to identify variables that differed significantly between the two groups. Results showed significant differences were evident between the two groups for club face impact point and a number of joint angles and angular velocities, with greater shoulder flexion and less left shoulder internal rotation in the backswing, greater extension angular velocity in both shoulders at early downswing, greater left shoulder adduction angular velocity at ball contact, greater hip joint movement and X Factor angle during the downswing, and greater left elbow extension early in the downswing appearing to contribute to greater hitting distance with the 5 iron club.

A survey of variable selection methods in two Chinese epidemiology journals

PubMed Central

2010-01-01

Background Although much has been written on developing better procedures for variable selection, there is little research on how it is practiced in actual studies. This review surveys the variable selection methods reported in two high-ranking Chinese epidemiology journals. Methods Articles published in 2004, 2006, and 2008 in the Chinese Journal of Epidemiology and the Chinese Journal of Preventive Medicine were reviewed. Five categories of methods were identified whereby variables were selected using: A - bivariate analyses; B - multivariable analysis; e.g. stepwise or individual significance testing of model coefficients; C - first bivariate analyses, followed by multivariable analysis; D - bivariate analyses or multivariable analysis; and E - other criteria like prior knowledge or personal judgment. Results Among the 287 articles that reported using variable selection methods, 6%, 26%, 30%, 21%, and 17% were in categories A through E, respectively. One hundred sixty-three studies selected variables using bivariate analyses, 80% (130/163) via multiple significance testing at the 5% alpha-level. Of the 219 multivariable analyses, 97 (44%) used stepwise procedures, 89 (41%) tested individual regression coefficients, but 33 (15%) did not mention how variables were selected. Sixty percent (58/97) of the stepwise routines also did not specify the algorithm and/or significance levels. Conclusions The variable selection methods reported in the two journals were limited in variety, and details were often missing. Many studies still relied on problematic techniques like stepwise procedures and/or multiple testing of bivariate associations at the 0.05 alpha-level. These deficiencies should be rectified to safeguard the scientific validity of articles published in Chinese epidemiology journals. PMID:20920252

Gene Expression Analysis to Assess the Relevance of Rodent Models to Human Lung Injury.

PubMed

Sweeney, Timothy E; Lofgren, Shane; Khatri, Purvesh; Rogers, Angela J

2017-08-01

The relevance of animal models to human diseases is an area of intense scientific debate. The degree to which mouse models of lung injury recapitulate human lung injury has never been assessed. Integrating data from both human and animal expression studies allows for increased statistical power and identification of conserved differential gene expression across organisms and conditions. We sought comprehensive integration of gene expression data in experimental acute lung injury (ALI) in rodents compared with humans. We performed two separate gene expression multicohort analyses to determine differential gene expression in experimental animal and human lung injury. We used correlational and pathway analyses combined with external in vitro gene expression data to identify both potential drivers of underlying inflammation and therapeutic drug candidates. We identified 21 animal lung tissue datasets and three human lung injury bronchoalveolar lavage datasets. We show that the metasignatures of animal and human experimental ALI are significantly correlated despite these widely varying experimental conditions. The gene expression changes among mice and rats across diverse injury models (ozone, ventilator-induced lung injury, LPS) are significantly correlated with human models of lung injury (Pearson r = 0.33-0.45, P < 1E -16 ). Neutrophil signatures are enriched in both animal and human lung injury. Predicted therapeutic targets, peptide ligand signatures, and pathway analyses are also all highly overlapping. Gene expression changes are similar in animal and human experimental ALI, and provide several physiologic and therapeutic insights to the disease.

Improving external cephalic version for foetal breech presentation

PubMed Central

Zandstra, H.; Mertens, H.J.M.M.

2013-01-01

Objectives: If success rate of external cephalic version (ECV) increases, the rate of primary caesarean sections declines. The aims of this retrospective cohort study were to evaluate the ECV and to identify factors associated with the success rate of ECV for breech presentation at term. The second aim of this study was to analyse the outcome of labour of all patients with a foetus in breech near term. Methods: All women with a foetus in breech near or at term were included. Logistic regression analyses were performed to identify the association between patient characteristics and success rate of ECV. Results: The overall rate of successful ECV’s was 19%. Foetal and maternal complications after ECV were negligible. BMI, type of breech and amount of amniotic fluid were significantly correlated with a successful ECV. The rate of primary caesarean sections for the group of patients who underwent an ECV was lower than the rate in the group who did not (52.9% vs. 79.6%). The rate of spontaneous deliveries was increased after ECV (36% versus 12%). After successful ECV the rate of spontaneous deliveries was 75%; after unsuccessful ECV 26.8%. Conclusion: The overall rate of successful ECV was low (19%). BMI, type of breech and amount of amniotic fluid were significantly correlated with a successful ECV. The rate of primary caesarean sections was significantly lower in patients with ECV (52.9% versus 79.6%). The rate of spontaneous deliveries was significantly higher (36% versus 12%). PMID:24753933

Improving external cephalic version for foetal breech presentation.

PubMed

Zandstra, H; Mertens, H J M M

2013-01-01

If success rate of external cephalic version (ECV) increases, the rate of primary caesarean sections -declines. The aims of this retrospective cohort study were to evaluate the ECV and to identify factors associated with the success rate of ECV for breech presentation at term. The second aim of this study was to analyse the outcome of labour of all patients with a foetus in breech near term. All women with a foetus in breech near or at term were included. Logistic regression analyses were -performed to identify the association between patient characteristics and success rate of ECV. The overall rate of successful ECV's was 19%. Foetal and maternal complications after ECV were negligible. BMI, type of breech and amount of amniotic fluid were significantly correlated with a successful ECV. The rate of primary caesarean sections for the group of patients who underwent an ECV was lower than the rate in the group who did not (52.9% vs. 79.6%). The rate of spontaneous deliveries was increased after ECV (36% versus 12%). After successful ECV the rate of spontaneous deliveries was 75%; after unsuccessful ECV 26.8%. The overall rate of successful ECV was low (19%). BMI, type of breech and amount of amniotic fluid were significantly correlated with a successful ECV. The rate of primary caesarean sections was significantly lower in patients with ECV (52.9% versus 79.6%). The rate of spontaneous deliveries was significantly higher (36% -versus 12%).

Stool-based biomarkers of interstitial cystitis/bladder pain syndrome.

PubMed

Braundmeier-Fleming, A; Russell, Nathan T; Yang, Wenbin; Nas, Megan Y; Yaggie, Ryan E; Berry, Matthew; Bachrach, Laurie; Flury, Sarah C; Marko, Darlene S; Bushell, Colleen B; Welge, Michael E; White, Bryan A; Schaeffer, Anthony J; Klumpp, David J

2016-05-18

Interstitial cystitis/bladder pain syndrome (IC) is associated with significant morbidity, yet underlying mechanisms and diagnostic biomarkers remain unknown. Pelvic organs exhibit neural crosstalk by convergence of visceral sensory pathways, and rodent studies demonstrate distinct bacterial pain phenotypes, suggesting that the microbiome modulates pelvic pain in IC. Stool samples were obtained from female IC patients and healthy controls, and symptom severity was determined by questionnaire. Operational taxonomic units (OTUs) were identified by16S rDNA sequence analysis. Machine learning by Extended Random Forest (ERF) identified OTUs associated with symptom scores. Quantitative PCR of stool DNA with species-specific primer pairs demonstrated significantly reduced levels of E. sinensis, C. aerofaciens, F. prausnitzii, O. splanchnicus, and L. longoviformis in microbiota of IC patients. These species, deficient in IC pelvic pain (DIPP), were further evaluated by Receiver-operator characteristic (ROC) analyses, and DIPP species emerged as potential IC biomarkers. Stool metabolomic studies identified glyceraldehyde as significantly elevated in IC. Metabolomic pathway analysis identified lipid pathways, consistent with predicted metagenome functionality. Together, these findings suggest that DIPP species and metabolites may serve as candidates for novel IC biomarkers in stool. Functional changes in the IC microbiome may also serve as therapeutic targets for treating chronic pelvic pain.

Association of Genetic Loci with Sleep Apnea in European Americans and African-Americans: The Candidate Gene Association Resource (CARe)

PubMed Central

Patel, Sanjay R.; Goodloe, Robert; De, Gourab; Kowgier, Matthew; Weng, Jia; Buxbaum, Sarah G.; Cade, Brian; Fulop, Tibor; Gharib, Sina A.; Gottlieb, Daniel J.; Hillman, David; Larkin, Emma K.; Lauderdale, Diane S.; Li, Li; Mukherjee, Sutapa; Palmer, Lyle; Zee, Phyllis; Zhu, Xiaofeng; Redline, Susan

2012-01-01

Although obstructive sleep apnea (OSA) is known to have a strong familial basis, no genetic polymorphisms influencing apnea risk have been identified in cross-cohort analyses. We utilized the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe) to identify sleep apnea susceptibility loci. Using a panel of 46,449 polymorphisms from roughly 2,100 candidate genes on a customized Illumina iSelect chip, we tested for association with the apnea hypopnea index (AHI) as well as moderate to severe OSA (AHI≥15) in 3,551 participants of the Cleveland Family Study and two cohorts participating in the Sleep Heart Health Study. Among 647 African-Americans, rs11126184 in the pleckstrin (PLEK) gene was associated with OSA while rs7030789 in the lysophosphatidic acid receptor 1 (LPAR1) gene was associated with AHI using a chip-wide significance threshold of p-value<2×10−6. Among 2,904 individuals of European ancestry, rs1409986 in the prostaglandin E2 receptor (PTGER3) gene was significantly associated with OSA. Consistency of effects between rs7030789 and rs1409986 in LPAR1 and PTGER3 and apnea phenotypes were observed in independent clinic-based cohorts. Novel genetic loci for apnea phenotypes were identified through the use of customized gene chips and meta-analyses of cohort data with replication in clinic-based samples. The identified SNPs all lie in genes associated with inflammation suggesting inflammation may play a role in OSA pathogenesis. PMID:23155414

Metabolomic profiling in the prediction of gestational diabetes mellitus

PubMed Central

Huynh, Jennifer; Xiong, Grace; Lee, Hang; Wenger, Julia; Clish, Clary; Nathan, David; Thadhani, Ravi; Gerszten, Robert

2015-01-01

Aims/hypothesis Metabolomic profiling in populations with impaired glucose tolerance has revealed that branched chain and aromatic amino acids (BCAAs) are predictive of type 2 diabetes. Because gestational diabetes mellitus (GDM) shares pathophysiological similarities with type 2 diabetes, the metabolite profile predictive of type 2 diabetes could potentially identify women who will develop GDM. Methods We conducted a nested case–control study of 18- to 40-year-old women who participated in the Massachusetts General Hospital Obstetrical Maternal Study between 1998 and 2007. Participants were enrolled during their first trimester of a singleton pregnancy and fasting serum samples were collected. The women were followed throughout pregnancy and identified as having GDM or normal glucose tolerance (NGT) in the third trimester. Women with GDM (n=96) were matched to women with NGT (n=96) by age, BMI, gravidity and parity. Liquid chromatography–mass spectrometry was used to measure the levels of 91 metabolites. Results Data analyses revealed the following characteristics (mean±SD): age 32.8±4.4 years, BMI 28.3±5.6 kg/m2, gravidity 2±1 and parity 1±1. Six metabolites (anthranilic acid, alanine, glutamate, creatinine, allantoin and serine) were identified as having significantly different levels between the two groups in conditional logistic regression analyses (p<0.05). The levels of the BCAAs did not differ significantly between GDM and NGT. Conclusions/interpretation Metabolic markers identified as being predictive of type 2 diabetes may not have the same predictive power for GDM. However, further study in a racially/ethnically diverse population-based cohort is necessary. PMID:25748329

How is communication of vaccines in traditional media: a systematic review.

PubMed

Catalan-Matamoros, Daniel; Peñafiel-Saiz, Carmen

2018-06-01

Taking into account that a key determinant in public approval of vaccinations is how the media constructs and frames messages about vaccination programmes, our aim is to review communication studies exploring media coverage of vaccines within traditional media venues. Using a registered protocol (PROSPERO: 42017072849), a systematic review was conducted that searched in three international electronic databases (PubMed, Scopus, and the International Bibliography of Social Science) for articles published between 2007 and 2017 following content-analysis methods. The characteristics and outcomes were systematically identified and described. The search yielded 24 eligible studies that were further analysed in the review. Media coverage of vaccines has been largely studied during the last decade. Findings revealed that 62% ( n = 15) of studies analysed the human papillomavirus vaccine, 87% ( n = 21) examined newspapers, and 62% ( n = 15) examined North American media. In relation to media content analyses, 75% found negative messages on vaccines and 83% identified a lack of accurate information. This systematic review suggests an agenda for further research. There is a significant need to analyse other types of traditional media beyond newspapers. Future studies should focus on other geographical areas such as low-income countries and on analysing visual materials and digital media. We found that negative messages and inaccurate information are common in media coverage on vaccines; therefore, further research focusing on these topics is needed. Officials in public health organizations should develop a close collaboration with the media to improve public communication on vaccines.

Data-driven subtypes of major depressive disorder: a systematic review

PubMed Central

2012-01-01

Background According to current classification systems, patients with major depressive disorder (MDD) may have very different combinations of symptoms. This symptomatic diversity hinders the progress of research into the causal mechanisms and treatment allocation. Theoretically founded subtypes of depression such as atypical, psychotic, and melancholic depression have limited clinical applicability. Data-driven analyses of symptom dimensions or subtypes of depression are scarce. In this systematic review, we examine the evidence for the existence of data-driven symptomatic subtypes of depression. Methods We undertook a systematic literature search of MEDLINE, PsycINFO and Embase in May 2012. We included studies analyzing the depression criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) of adults with MDD in latent variable analyses. Results In total, 1176 articles were retrieved, of which 20 satisfied the inclusion criteria. These reports described a total of 34 latent variable analyses: 6 confirmatory factor analyses, 6 exploratory factor analyses, 12 principal component analyses, and 10 latent class analyses. The latent class techniques distinguished 2 to 5 classes, which mainly reflected subgroups with different overall severity: 62 of 71 significant differences on symptom level were congruent with a latent class solution reflecting severity. The latent class techniques did not consistently identify specific symptom clusters. Latent factor techniques mostly found a factor explaining the variance in the symptoms depressed mood and interest loss (11 of 13 analyses), often complemented by psychomotor retardation or fatigue (8 of 11 analyses). However, differences in found factors and classes were substantial. Conclusions The studies performed to date do not provide conclusive evidence for the existence of depressive symptom dimensions or symptomatic subtypes. The wide diversity of identified factors and classes might result either from the absence of patterns to be found, or from the theoretical and modeling choices preceding analysis. PMID:23210727

Genetic Determinants of Trabecular and Cortical Volumetric Bone Mineral Densities and Bone Microstructure

PubMed Central

Kähönen, Mika; Raitakari, Olli; Laaksonen, Marika; Sievänen, Harri; Viikari, Jorma; Lyytikäinen, Leo-Pekka; Mellström, Dan; Karlsson, Magnus; Ljunggren, Östen; Grundberg, Elin; Kemp, John P.; Sayers, Adrian; Nethander, Maria; Evans, David M.; Vandenput, Liesbeth; Tobias, Jon H.; Ohlsson, Claes

2013-01-01

Most previous genetic epidemiology studies within the field of osteoporosis have focused on the genetics of the complex trait areal bone mineral density (aBMD), not being able to differentiate genetic determinants of cortical volumetric BMD (vBMD), trabecular vBMD, and bone microstructural traits. The objective of this study was to separately identify genetic determinants of these bone traits as analysed by peripheral quantitative computed tomography (pQCT). Separate GWA meta-analyses for cortical and trabecular vBMDs were performed. The cortical vBMD GWA meta-analysis (n = 5,878) followed by replication (n = 1,052) identified genetic variants in four separate loci reaching genome-wide significance (RANKL, rs1021188, p = 3.6×10−14; LOC285735, rs271170, p = 2.7×10−12; OPG, rs7839059, p = 1.2×10−10; and ESR1/C6orf97, rs6909279, p = 1.1×10−9). The trabecular vBMD GWA meta-analysis (n = 2,500) followed by replication (n = 1,022) identified one locus reaching genome-wide significance (FMN2/GREM2, rs9287237, p = 1.9×10−9). High-resolution pQCT analyses, giving information about bone microstructure, were available in a subset of the GOOD cohort (n = 729). rs1021188 was significantly associated with cortical porosity while rs9287237 was significantly associated with trabecular bone fraction. The genetic variant in the FMN2/GREM2 locus was associated with fracture risk in the MrOS Sweden cohort (HR per extra T allele 0.75, 95% confidence interval 0.60–0.93) and GREM2 expression in human osteoblasts. In conclusion, five genetic loci associated with trabecular or cortical vBMD were identified. Two of these (FMN2/GREM2 and LOC285735) are novel bone-related loci, while the other three have previously been reported to be associated with aBMD. The genetic variants associated with cortical and trabecular bone parameters differed, underscoring the complexity of the genetics of bone parameters. We propose that a genetic variant in the RANKL locus influences cortical vBMD, at least partly, via effects on cortical porosity, and that a genetic variant in the FMN2/GREM2 locus influences GREM2 expression in osteoblasts and thereby trabecular number and thickness as well as fracture risk. PMID:23437003

Gene-Based Genome-Wide Association Analysis in European and Asian Populations Identified Novel Genes for Rheumatoid Arthritis.

PubMed

Zhu, Hong; Xia, Wei; Mo, Xing-Bo; Lin, Xiang; Qiu, Ying-Hua; Yi, Neng-Jun; Zhang, Yong-Hong; Deng, Fei-Yan; Lei, Shu-Feng

2016-01-01

Rheumatoid arthritis (RA) is a complex autoimmune disease. Using a gene-based association research strategy, the present study aims to detect unknown susceptibility to RA and to address the ethnic differences in genetic susceptibility to RA between European and Asian populations. Gene-based association analyses were performed with KGG 2.5 by using publicly available large RA datasets (14,361 RA cases and 43,923 controls of European subjects, 4,873 RA cases and 17,642 controls of Asian Subjects). For the newly identified RA-associated genes, gene set enrichment analyses and protein-protein interactions analyses were carried out with DAVID and STRING version 10.0, respectively. Differential expression verification was conducted using 4 GEO datasets. The expression levels of three selected 'highly verified' genes were measured by ELISA among our in-house RA cases and controls. A total of 221 RA-associated genes were newly identified by gene-based association study, including 71'overlapped', 76 'European-specific' and 74 'Asian-specific' genes. Among them, 105 genes had significant differential expressions between RA patients and health controls at least in one dataset, especially for 20 genes including 11 'overlapped' (ABCF1, FLOT1, HLA-F, IER3, TUBB, ZKSCAN4, BTN3A3, HSP90AB1, CUTA, BRD2, HLA-DMA), 5 'European-specific' (PHTF1, RPS18, BAK1, TNFRSF14, SUOX) and 4 'Asian-specific' (RNASET2, HFE, BTN2A2, MAPK13) genes whose differential expressions were significant at least in three datasets. The protein expressions of two selected genes FLOT1 (P value = 1.70E-02) and HLA-DMA (P value = 4.70E-02) in plasma were significantly different in our in-house samples. Our study identified 221 novel RA-associated genes and especially highlighted the importance of 20 candidate genes on RA. The results addressed ethnic genetic background differences for RA susceptibility between European and Asian populations and detected a long list of overlapped or ethnic specific RA genes. The study not only greatly increases our understanding of genetic susceptibility to RA, but also provides important insights into the ethno-genetic homogeneity and heterogeneity of RA in both ethnicities.

Genomics of the Effect of Spinal Cord Stimulation on an Animal Model of Neuropathic Pain.

PubMed

Vallejo, Ricardo; Tilley, Dana M; Cedeño, David L; Kelley, Courtney A; DeMaegd, Margaret; Benyamin, Ramsin

2016-08-01

Few studies have evaluated single-gene changes modulated by spinal cord stimulation (SCS), providing a narrow understanding of molecular changes. Genomics allows for a robust analysis of holistic gene changes in response to stimulation. Rats were randomized into six groups to determine the effect of continuous SCS in uninjured and spared-nerve injury (SNI) animals. After behavioral assessment, tissues from the dorsal quadrant of the spinal cord (SC) and dorsal root ganglion (DRG) underwent full-genome microarray analyses. Weighted Gene Correlation Network Analysis (WGCNA), and Gene Ontology (GO) analysis identified similar expression patterns, molecular functions and biological processes for significant genes. Microarray analyses reported 20,985 gene probes in SC and 19,104 in DRG. WGCNA sorted 7449 SC and 4275 DRG gene probes into 29 and 9 modules, respectively. WGCNA provided significant modules from paired comparisons of experimental groups. GO analyses reported significant biological processes influenced by injury, as well as the presence of an electric field. The genes Tlr2, Cxcl16, and Cd68 were used to further validate the microarray based on significant response to SCS in SNI animals. They were up-regulated in the SC while both Tlr2 and Cd68 were up-regulated in the DRG. The process described provides highly significant interconnected genes and pathways responsive to injury and/or electric field in the SC and DRG. Genes in the SC respond significantly to the SCS in both injured and uninjured animals, while those in the DRG significantly responded to injury, and SCS in injured animals. © 2016 International Neuromodulation Society.

Prediction of future risk of insulin resistance and metabolic syndrome based on Korean boy's metabolite profiling.

PubMed

Lee, AeJin; Jang, Han Byul; Ra, Moonjin; Choi, Youngshim; Lee, Hye-Ja; Park, Ju Yeon; Kang, Jae Heon; Park, Kyung-Hee; Park, Sang Ick; Song, Jihyun

2015-01-01

Childhood obesity is strongly related to future insulin resistance and metabolic syndrome. Thus, identifying early biomarkers of obesity-related diseases based on metabolic profiling is useful to control future metabolic disorders. We compared metabolic profiles between obese and normal-weight children and investigated specific biomarkers of future insulin resistance and metabolic syndrome. In all, 186 plasma metabolites were analysed at baseline and after 2 years in 109 Korean boys (age 10.5±0.4 years) from the Korean Child Obesity Cohort Study using the AbsoluteIDQ™ p180 Kit. We observed that levels of 41 metabolites at baseline and 40 metabolites at follow-up were significantly altered in obese children (p<0.05). Obese children showed significantly higher levels of branched-chain amino acids (BCAAs) and several acylcarnitines and lower levels of acyl-alkyl phosphatidylcholines. Also, baseline BCAAs were significantly positively correlated with both homeostasis model assessment for insulin resistance (HOMA-IR) and continuous metabolic risk score at the 2-year follow-up. In logistic regression analyses with adjustments for degree of obesity at baseline, baseline BCAA concentration, greater than the median value, was identified as a predictor of future risk of insulin resistance and metabolic syndrome. High BCAA concentration could be "early" biomarkers for predicting future metabolic diseases. Copyright © 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Predicting story goodness performance from cognitive measures following traumatic brain injury.

PubMed

Lê, Karen; Coelho, Carl; Mozeiko, Jennifer; Krueger, Frank; Grafman, Jordan

2012-05-01

This study examined the prediction of performance on measures of the Story Goodness Index (SGI; Lê, Coelho, Mozeiko, & Grafman, 2011) from executive function (EF) and memory measures following traumatic brain injury (TBI). It was hypothesized that EF and memory measures would significantly predict SGI outcomes. One hundred sixty-seven individuals with TBI participated in the study. Story retellings were analyzed using the SGI protocol. Three cognitive measures--Delis-Kaplan Executive Function System (D-KEFS; Delis, Kaplan, & Kramer, 2001) Sorting Test, Wechsler Memory Scale--Third Edition (WMS-III; Wechsler, 1997) Working Memory Primary Index (WMI), and WMS-III Immediate Memory Primary Index (IMI)--were entered into a multiple linear regression model for each discourse measure. Two sets of regression analyses were performed, the first with the Sorting Test as the first predictor and the second with it as the last. The first set of regression analyses identified the Sorting Test and IMI as the only significant predictors of performance on measures of the SGI. The second set identified all measures as significant predictors when evaluating each step of the regression function. The cognitive variables predicted performance on the SGI measures, although there were differences in the amount of explained variance. The results (a) suggest that storytelling ability draws on a number of underlying skills and (b) underscore the importance of using discrete cognitive tasks rather than broad cognitive indices to investigate the cognitive substrates of discourse.

A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure.

PubMed

Sung, Yun J; Winkler, Thomas W; de Las Fuentes, Lisa; Bentley, Amy R; Brown, Michael R; Kraja, Aldi T; Schwander, Karen; Ntalla, Ioanna; Guo, Xiuqing; Franceschini, Nora; Lu, Yingchang; Cheng, Ching-Yu; Sim, Xueling; Vojinovic, Dina; Marten, Jonathan; Musani, Solomon K; Li, Changwei; Feitosa, Mary F; Kilpeläinen, Tuomas O; Richard, Melissa A; Noordam, Raymond; Aslibekyan, Stella; Aschard, Hugues; Bartz, Traci M; Dorajoo, Rajkumar; Liu, Yongmei; Manning, Alisa K; Rankinen, Tuomo; Smith, Albert Vernon; Tajuddin, Salman M; Tayo, Bamidele O; Warren, Helen R; Zhao, Wei; Zhou, Yanhua; Matoba, Nana; Sofer, Tamar; Alver, Maris; Amini, Marzyeh; Boissel, Mathilde; Chai, Jin Fang; Chen, Xu; Divers, Jasmin; Gandin, Ilaria; Gao, Chuan; Giulianini, Franco; Goel, Anuj; Harris, Sarah E; Hartwig, Fernando Pires; Horimoto, Andrea R V R; Hsu, Fang-Chi; Jackson, Anne U; Kähönen, Mika; Kasturiratne, Anuradhani; Kühnel, Brigitte; Leander, Karin; Lee, Wen-Jane; Lin, Keng-Hung; 'an Luan, Jian; McKenzie, Colin A; Meian, He; Nelson, Christopher P; Rauramaa, Rainer; Schupf, Nicole; Scott, Robert A; Sheu, Wayne H H; Stančáková, Alena; Takeuchi, Fumihiko; van der Most, Peter J; Varga, Tibor V; Wang, Heming; Wang, Yajuan; Ware, Erin B; Weiss, Stefan; Wen, Wanqing; Yanek, Lisa R; Zhang, Weihua; Zhao, Jing Hua; Afaq, Saima; Alfred, Tamuno; Amin, Najaf; Arking, Dan; Aung, Tin; Barr, R Graham; Bielak, Lawrence F; Boerwinkle, Eric; Bottinger, Erwin P; Braund, Peter S; Brody, Jennifer A; Broeckel, Ulrich; Cabrera, Claudia P; Cade, Brian; Caizheng, Yu; Campbell, Archie; Canouil, Mickaël; Chakravarti, Aravinda; Chauhan, Ganesh; Christensen, Kaare; Cocca, Massimiliano; Collins, Francis S; Connell, John M; de Mutsert, Renée; de Silva, H Janaka; Debette, Stephanie; Dörr, Marcus; Duan, Qing; Eaton, Charles B; Ehret, Georg; Evangelou, Evangelos; Faul, Jessica D; Fisher, Virginia A; Forouhi, Nita G; Franco, Oscar H; Friedlander, Yechiel; Gao, He; Gigante, Bruna; Graff, Misa; Gu, C Charles; Gu, Dongfeng; Gupta, Preeti; Hagenaars, Saskia P; Harris, Tamara B; He, Jiang; Heikkinen, Sami; Heng, Chew-Kiat; Hirata, Makoto; Hofman, Albert; Howard, Barbara V; Hunt, Steven; Irvin, Marguerite R; Jia, Yucheng; Joehanes, Roby; Justice, Anne E; Katsuya, Tomohiro; Kaufman, Joel; Kerrison, Nicola D; Khor, Chiea Chuen; Koh, Woon-Puay; Koistinen, Heikki A; Komulainen, Pirjo; Kooperberg, Charles; Krieger, Jose E; Kubo, Michiaki; Kuusisto, Johanna; Langefeld, Carl D; Langenberg, Claudia; Launer, Lenore J; Lehne, Benjamin; Lewis, Cora E; Li, Yize; Lim, Sing Hui; Lin, Shiow; Liu, Ching-Ti; Liu, Jianjun; Liu, Jingmin; Liu, Kiang; Liu, Yeheng; Loh, Marie; Lohman, Kurt K; Long, Jirong; Louie, Tin; Mägi, Reedik; Mahajan, Anubha; Meitinger, Thomas; Metspalu, Andres; Milani, Lili; Momozawa, Yukihide; Morris, Andrew P; Mosley, Thomas H; Munson, Peter; Murray, Alison D; Nalls, Mike A; Nasri, Ubaydah; Norris, Jill M; North, Kari; Ogunniyi, Adesola; Padmanabhan, Sandosh; Palmas, Walter R; Palmer, Nicholette D; Pankow, James S; Pedersen, Nancy L; Peters, Annette; Peyser, Patricia A; Polasek, Ozren; Raitakari, Olli T; Renström, Frida; Rice, Treva K; Ridker, Paul M; Robino, Antonietta; Robinson, Jennifer G; Rose, Lynda M; Rudan, Igor; Sabanayagam, Charumathi; Salako, Babatunde L; Sandow, Kevin; Schmidt, Carsten O; Schreiner, Pamela J; Scott, William R; Seshadri, Sudha; Sever, Peter; Sitlani, Colleen M; Smith, Jennifer A; Snieder, Harold; Starr, John M; Strauch, Konstantin; Tang, Hua; Taylor, Kent D; Teo, Yik Ying; Tham, Yih Chung; Uitterlinden, André G; Waldenberger, Melanie; Wang, Lihua; Wang, Ya X; Wei, Wen Bin; Williams, Christine; Wilson, Gregory; Wojczynski, Mary K; Yao, Jie; Yuan, Jian-Min; Zonderman, Alan B; Becker, Diane M; Boehnke, Michael; Bowden, Donald W; Chambers, John C; Chen, Yii-Der Ida; de Faire, Ulf; Deary, Ian J; Esko, Tõnu; Farrall, Martin; Forrester, Terrence; Franks, Paul W; Freedman, Barry I; Froguel, Philippe; Gasparini, Paolo; Gieger, Christian; Horta, Bernardo Lessa; Hung, Yi-Jen; Jonas, Jost B; Kato, Norihiro; Kooner, Jaspal S; Laakso, Markku; Lehtimäki, Terho; Liang, Kae-Woei; Magnusson, Patrik K E; Newman, Anne B; Oldehinkel, Albertine J; Pereira, Alexandre C; Redline, Susan; Rettig, Rainer; Samani, Nilesh J; Scott, James; Shu, Xiao-Ou; van der Harst, Pim; Wagenknecht, Lynne E; Wareham, Nicholas J; Watkins, Hugh; Weir, David R; Wickremasinghe, Ananda R; Wu, Tangchun; Zheng, Wei; Kamatani, Yoichiro; Laurie, Cathy C; Bouchard, Claude; Cooper, Richard S; Evans, Michele K; Gudnason, Vilmundur; Kardia, Sharon L R; Kritchevsky, Stephen B; Levy, Daniel; O'Connell, Jeff R; Psaty, Bruce M; van Dam, Rob M; Sims, Mario; Arnett, Donna K; Mook-Kanamori, Dennis O; Kelly, Tanika N; Fox, Ervin R; Hayward, Caroline; Fornage, Myriam; Rotimi, Charles N; Province, Michael A; van Duijn, Cornelia M; Tai, E Shyong; Wong, Tien Yin; Loos, Ruth J F; Reiner, Alex P; Rotter, Jerome I; Zhu, Xiaofeng; Bierut, Laura J; Gauderman, W James; Caulfield, Mark J; Elliott, Paul; Rice, Kenneth; Munroe, Patricia B; Morrison, Alanna C; Cupples, L Adrienne; Rao, Dabeeru C; Chasman, Daniel I

2018-03-01

Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 × 10 -8 ) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 × 10 -8 ). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2). Copyright © 2018 American Society of Human Genetics. All rights reserved.

Meta-analyses of Adverse Effects Data Derived from Randomised Controlled Trials as Compared to Observational Studies: Methodological Overview

PubMed Central

Golder, Su; Loke, Yoon K.; Bland, Martin

2011-01-01

Background There is considerable debate as to the relative merits of using randomised controlled trial (RCT) data as opposed to observational data in systematic reviews of adverse effects. This meta-analysis of meta-analyses aimed to assess the level of agreement or disagreement in the estimates of harm derived from meta-analysis of RCTs as compared to meta-analysis of observational studies. Methods and Findings Searches were carried out in ten databases in addition to reference checking, contacting experts, citation searches, and hand-searching key journals, conference proceedings, and Web sites. Studies were included where a pooled relative measure of an adverse effect (odds ratio or risk ratio) from RCTs could be directly compared, using the ratio of odds ratios, with the pooled estimate for the same adverse effect arising from observational studies. Nineteen studies, yielding 58 meta-analyses, were identified for inclusion. The pooled ratio of odds ratios of RCTs compared to observational studies was estimated to be 1.03 (95% confidence interval 0.93–1.15). There was less discrepancy with larger studies. The symmetric funnel plot suggests that there is no consistent difference between risk estimates from meta-analysis of RCT data and those from meta-analysis of observational studies. In almost all instances, the estimates of harm from meta-analyses of the different study designs had 95% confidence intervals that overlapped (54/58, 93%). In terms of statistical significance, in nearly two-thirds (37/58, 64%), the results agreed (both studies showing a significant increase or significant decrease or both showing no significant difference). In only one meta-analysis about one adverse effect was there opposing statistical significance. Conclusions Empirical evidence from this overview indicates that there is no difference on average in the risk estimate of adverse effects of an intervention derived from meta-analyses of RCTs and meta-analyses of observational studies. This suggests that systematic reviews of adverse effects should not be restricted to specific study types. Please see later in the article for the Editors' Summary PMID:21559325

A HIV-1 heterosexual transmission chain in Guangzhou, China: a molecular epidemiological study.

PubMed

Han, Zhigang; Leung, Tommy W C; Zhao, Jinkou; Wang, Ming; Fan, Lirui; Li, Kai; Pang, Xinli; Liang, Zhenbo; Lim, Wilina W L; Xu, Huifang

2009-09-25

We conducted molecular analyses to confirm four clustering HIV-1 infections (Patient A, B, C & D) in Guangzhou, China. These cases were identified by epidemiological investigation and suspected to acquire the infection through a common heterosexual transmission chain. Env C2V3V4 region, gag p17/p24 junction and partial pol gene of HIV-1 genome from serum specimens of these infected cases were amplified by reverse transcription polymerase chain reaction (RT-PCR) and nucleotide sequenced. Phylogenetic analyses indicated that their viral nucleotide sequences were significantly clustered together (bootstrap value is 99%, 98% and 100% in env, gag and pol tree respectively). Evolutionary distance analysis indicated that their genetic diversities of env, gag and pol genes were significantly lower than non-clustered controls, as measured by unpaired t-test (env gene comparison: p < 0.005; gag gene comparison: p < 0.005; pol gene comparison: p < 0.005). Epidemiological results and molecular analyses consistently illustrated these four cases represented a transmission chain which dispersed in the locality through heterosexual contact involving commercial sex worker.

Centre of pressure patterns in the golf swing: individual-based analysis.

PubMed

Ball, Kevin; Best, Russell

2012-06-01

Weight transfer has been identified as important in group-based analyses. The aim of this study was to extend this work by examining the importance of weight transfer in the golf swing on an individual basis. Five professional and amateur golfers performed 50 swings with the driver, hitting a ball into a net. The golfer's centre of pressure position and velocity, parallel with the line of shot, were measured by two force plates at eight swing events that were identified from high-speed video. The relationships between these parameters and club head velocity at ball contact were examined using regression statistics. The results did support the use of group-based analysis, with all golfers returning significant relationships. However, results were also individual-specific, with golfers returning different combinations of significant factors. Furthermore, factors not identified in group-based analysis were significant on an individual basis. The most consistent relationship was a larger weight transfer range associated with a larger club head velocity (p < 0.05). All golfers also returned at least one significant relationship with rate of weight transfer at swing events (p < 0.01). Individual-based analysis should form part of performance-based biomechanical analysis of sporting skills.

How individual participant data meta-analyses have influenced trial design, conduct, and analysis.

PubMed

Tierney, Jayne F; Pignon, Jean-Pierre; Gueffyier, Francois; Clarke, Mike; Askie, Lisa; Vale, Claire L; Burdett, Sarah

2015-11-01

To demonstrate how individual participant data (IPD) meta-analyses have impacted directly on the design and conduct of trials and highlight other advantages IPD might offer. Potential examples of the impact of IPD meta-analyses on trials were identified at an international workshop, attended by individuals with experience in the conduct of IPD meta-analyses and knowledge of trials in their respective clinical areas. Experts in the field who did not attend were asked to provide any further examples. We then examined relevant trial protocols, publications, and Web sites to verify the impacts of the IPD meta-analyses. A subgroup of workshop attendees sought further examples and identified other aspects of trial design and conduct that may inform IPD meta-analyses. We identified 52 examples of IPD meta-analyses thought to have had a direct impact on the design or conduct of trials. After screening relevant trial protocols and publications, we identified 28 instances where IPD meta-analyses had clearly impacted on trials. They have influenced the selection of comparators and participants, sample size calculations, analysis and interpretation of subsequent trials, and the conduct and analysis of ongoing trials, sometimes in ways that would not possible with systematic reviews of aggregate data. We identified additional potential ways that IPD meta-analyses could be used to influence trials. IPD meta-analysis could be better used to inform the design, conduct, analysis, and interpretation of trials. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

How individual participant data meta-analyses have influenced trial design, conduct, and analysis

PubMed Central

Tierney, Jayne F.; Pignon, Jean-Pierre; Gueffyier, Francois; Clarke, Mike; Askie, Lisa; Vale, Claire L.; Burdett, Sarah; Alderson, P.; Askie, L.; Bennett, D.; Burdett, S.; Clarke, M.; Dias, S.; Emberson, J.; Gueyffier, F.; Iorio, A.; Macleod, M.; Mol, B.W.; Moons, C.; Parmar, M.; Perera, R.; Phillips, R.; Pignon, J.P.; Rees, J.; Reitsma, H.; Riley, R.; Rovers, M.; Rydzewska, L.; Schmid, C.; Shepperd, S.; Stenning, S.; Stewart, L.; Tierney, J.; Tudur Smith, C.; Vale, C.; Welge, J.; White, I.; Whiteley, W.

2015-01-01

Objectives To demonstrate how individual participant data (IPD) meta-analyses have impacted directly on the design and conduct of trials and highlight other advantages IPD might offer. Study Design and Setting Potential examples of the impact of IPD meta-analyses on trials were identified at an international workshop, attended by individuals with experience in the conduct of IPD meta-analyses and knowledge of trials in their respective clinical areas. Experts in the field who did not attend were asked to provide any further examples. We then examined relevant trial protocols, publications, and Web sites to verify the impacts of the IPD meta-analyses. A subgroup of workshop attendees sought further examples and identified other aspects of trial design and conduct that may inform IPD meta-analyses. Results We identified 52 examples of IPD meta-analyses thought to have had a direct impact on the design or conduct of trials. After screening relevant trial protocols and publications, we identified 28 instances where IPD meta-analyses had clearly impacted on trials. They have influenced the selection of comparators and participants, sample size calculations, analysis and interpretation of subsequent trials, and the conduct and analysis of ongoing trials, sometimes in ways that would not possible with systematic reviews of aggregate data. We identified additional potential ways that IPD meta-analyses could be used to influence trials. Conclusions IPD meta-analysis could be better used to inform the design, conduct, analysis, and interpretation of trials. PMID:26186982

Splenectomy Causes 10-Fold Increased Risk of Portal Venous System Thrombosis in Liver Cirrhosis Patients.

PubMed

Qi, Xingshun; Han, Guohong; Ye, Chun; Zhang, Yongguo; Dai, Junna; Peng, Ying; Deng, Han; Li, Jing; Hou, Feifei; Ning, Zheng; Zhao, Jiancheng; Zhang, Xintong; Wang, Ran; Guo, Xiaozhong

2016-07-19

BACKGROUND Portal venous system thrombosis (PVST) is a life-threatening complication of liver cirrhosis. We conducted a retrospective study to comprehensively analyze the prevalence and risk factors of PVST in liver cirrhosis. MATERIAL AND METHODS All cirrhotic patients without malignancy admitted between June 2012 and December 2013 were eligible if they underwent contrast-enhanced CT or MRI scans. Independent predictors of PVST in liver cirrhosis were calculated in multivariate analyses. Subgroup analyses were performed according to the severity of PVST (any PVST, main portal vein [MPV] thrombosis >50%, and clinically significant PVST) and splenectomy. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. RESULTS Overall, 113 cirrhotic patients were enrolled. The prevalence of PVST was 16.8% (19/113). Splenectomy (any PVST: OR=11.494, 95%CI=2.152-61.395; MPV thrombosis >50%: OR=29.987, 95%CI=3.247-276.949; clinically significant PVST: OR=40.415, 95%CI=3.895-419.295) and higher hemoglobin (any PVST: OR=0.974, 95%CI=0.953-0.996; MPV thrombosis >50%: OR=0.936, 95%CI=0.895-0.980; clinically significant PVST: OR=0.935, 95%CI=0.891-0.982) were the independent predictors of PVST. The prevalence of PVST was 13.3% (14/105) after excluding splenectomy. Higher hemoglobin was the only independent predictor of MPV thrombosis >50% (OR=0.952, 95%CI=0.909-0.997). No independent predictors of any PVST or clinically significant PVST were identified in multivariate analyses. Additionally, PVST patients who underwent splenectomy had a significantly higher proportion of clinically significant PVST but lower MELD score than those who did not undergo splenectomy. In all analyses, the in-hospital mortality was not significantly different between cirrhotic patient with and without PVST. CONCLUSIONS Splenectomy may increase by at least 10-fold the risk of PVST in liver cirrhosis independent of severity of liver dysfunction.

Splenectomy Causes 10-Fold Increased Risk of Portal Venous System Thrombosis in Liver Cirrhosis Patients

PubMed Central

Qi, Xingshun; Han, Guohong; Ye, Chun; Zhang, Yongguo; Dai, Junna; Peng, Ying; Deng, Han; Li, Jing; Hou, Feifei; Ning, Zheng; Zhao, Jiancheng; Zhang, Xintong; Wang, Ran; Guo, Xiaozhong

2016-01-01

Background Portal venous system thrombosis (PVST) is a life-threatening complication of liver cirrhosis. We conducted a retrospective study to comprehensively analyze the prevalence and risk factors of PVST in liver cirrhosis. Material/Methods All cirrhotic patients without malignancy admitted between June 2012 and December 2013 were eligible if they underwent contrast-enhanced CT or MRI scans. Independent predictors of PVST in liver cirrhosis were calculated in multivariate analyses. Subgroup analyses were performed according to the severity of PVST (any PVST, main portal vein [MPV] thrombosis >50%, and clinically significant PVST) and splenectomy. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. Results Overall, 113 cirrhotic patients were enrolled. The prevalence of PVST was 16.8% (19/113). Splenectomy (any PVST: OR=11.494, 95%CI=2.152–61.395; MPV thrombosis >50%: OR=29.987, 95%CI=3.247–276.949; clinically significant PVST: OR=40.415, 95%CI=3.895–419.295) and higher hemoglobin (any PVST: OR=0.974, 95%CI=0.953–0.996; MPV thrombosis >50%: OR=0.936, 95%CI=0.895–0.980; clinically significant PVST: OR=0.935, 95%CI=0.891–0.982) were the independent predictors of PVST. The prevalence of PVST was 13.3% (14/105) after excluding splenectomy. Higher hemoglobin was the only independent predictor of MPV thrombosis >50% (OR=0.952, 95%CI=0.909–0.997). No independent predictors of any PVST or clinically significant PVST were identified in multivariate analyses. Additionally, PVST patients who underwent splenectomy had a significantly higher proportion of clinically significant PVST but lower MELD score than those who did not undergo splenectomy. In all analyses, the in-hospital mortality was not significantly different between cirrhotic patient with and without PVST. Conclusions Splenectomy may increase by at least 10-fold the risk of PVST in liver cirrhosis independent of severity of liver dysfunction. PMID:27432511

Fluoropyrimidine and platinum toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses.

PubMed

Campbell, Jared M; Bateman, Emma; Peters, Micah Dj; Bowen, Joanne M; Keefe, Dorothy M; Stephenson, Matthew D

2016-03-01

Fluoropyrimidine (FU) and platinum-based chemotherapies are greatly complicated by their associated toxicities. This umbrella systematic review synthesized all systematic reviews that investigated associations between germline variations and toxicity, with the aim of informing personalized medicine. Systematic reviews are important in pharmacogenetics where false positives are common. Four systematic reviews were identified for FU-induced toxicity and three for platinum. Polymorphisms of DPYD and TYMS, but not MTHFR, were statistically significantly associated with FU-induced toxicity (although only DPYD had clinical significance). For platinum, GSTP1 was found to not be associated with toxicity. This umbrella systematic review has synthesized the best available evidence on the pharmacogenetics of FU and platinum toxicity. It provides a useful reference for clinicians and identifies important research gaps.

Analysis of audiometric notch as a noise-induced hearing loss phenotype in US youth: data from the National Health And Nutrition Examination Survey, 2005-2010.

PubMed

Bhatt, Ishan S; Guthrie, O'neil

2017-06-01

Bilateral audiometric notch (BN) at 4000-6000 Hz was identified as a noise-induced hearing loss (NIHL) phenotype for genetic association analysis in college-aged musicians. This study analysed BN in a sample of US youth. Prevalence of the BN within the study sample was determined and logistic-regression analyses were performed to identify audiologic and other demographic factors associated with BN. Computer-simulated "flat" audiograms were used to estimate potential influence of false-positive rates in estimating the prevalence of the BN. 2348 participants (12-19 years) following the inclusion criteria were selected from the National Health and Nutrition Examination Survey data (2005-2010). The prevalence of BN was 16.6%. Almost 55.6% of the participants showed notch in at least one ear. Noise exposure, gender, ethnicity and age showed significant relationship with the BN. Computer simulation revealed that 5.5% of simulated participants with "flat" audiograms showed BN. Association of noise exposure with BN suggests that it is a useful NIHL phenotype for genetic association analyses. However, further research is necessary to reduce false-positive rates in notch identification.

Arsenic levels in drinking water and mortality of liver cancer in Taiwan.

PubMed

Lin, Hung-Jung; Sung, Tzu-I; Chen, Chi-Yi; Guo, How-Ran

2013-11-15

The carcinogenic effect of arsenic is well documented, but epidemiologic data on liver cancer were limited. To evaluate the dose-response relationship between arsenic in drinking water and mortality of liver cancer, we conducted a study in 138 villages in the southwest coast area of Taiwan. We assessed arsenic levels in drinking water using data from a survey conducted by the government and reviewed death certificates from 1971 to 1990 to identify liver cancer cases. Using village as the unit, we conducted multi-variate regression analyses and then performed post hoc analyses to validate the findings. During the 20-year period, 802 male and 301 female mortality cases of liver cancer were identified. After adjusting for age, arsenic levels above 0.64 mg/L were associated with an increase in the liver cancer mortality in both genders, but no significant effect was observed for lower exposure categories. Post hoc analyses and a review of literature supported these findings. We concluded that exposures to high arsenic levels in drinking water are associated with the occurrence of liver cancer, but such an effect is not prominent at exposure levels lower than 0.64 mg/L. Copyright © 2013 Elsevier B.V. All rights reserved.

Using exceedance probabilities to detect anomalies in routinely recorded animal health data, with particular reference to foot-and-mouth disease in Viet Nam.

PubMed

Richards, K K; Hazelton, M L; Stevenson, M A; Lockhart, C Y; Pinto, J; Nguyen, L

2014-10-01

The widespread availability of computer hardware and software for recording and storing disease event information means that, in theory, we have the necessary information to carry out detailed analyses of factors influencing the spatial distribution of disease in animal populations. However, the reliability of such analyses depends on data quality, with anomalous records having the potential to introduce significant bias and lead to inappropriate decision making. In this paper we promote the use of exceedance probabilities as a tool for detecting anomalies when applying hierarchical spatio-temporal models to animal health data. We illustrate this methodology through a case study data on outbreaks of foot-and-mouth disease (FMD) in Viet Nam for the period 2006-2008. A flexible binomial logistic regression was employed to model the number of FMD infected communes within each province of the country. Standard analyses of the residuals from this model failed to identify problems, but exceedance probabilities identified provinces in which the number of reported FMD outbreaks was unexpectedly low. This finding is interesting given that these provinces are on major cattle movement pathways through Viet Nam. Copyright © 2014 Elsevier Ltd. All rights reserved.

Construct and Compare Gene Coexpression Networks with DAPfinder and DAPview.

PubMed

Skinner, Jeff; Kotliarov, Yuri; Varma, Sudhir; Mine, Karina L; Yambartsev, Anatoly; Simon, Richard; Huyen, Yentram; Morgun, Andrey

2011-07-14

DAPfinder and DAPview are novel BRB-ArrayTools plug-ins to construct gene coexpression networks and identify significant differences in pairwise gene-gene coexpression between two phenotypes. Each significant difference in gene-gene association represents a Differentially Associated Pair (DAP). Our tools include several choices of filtering methods, gene-gene association metrics, statistical testing methods and multiple comparison adjustments. Network results are easily displayed in Cytoscape. Analyses of glioma experiments and microarray simulations demonstrate the utility of these tools. DAPfinder is a new friendly-user tool for reconstruction and comparison of biological networks.

Lack of association between two key SNPs on chromosome 12p13 and ischemic stroke in Chinese Uyghur population.

PubMed

Tong, Yeqing; Zhan, Faxian; Han, Jinjun; Zhang, Yanwei; Yin, Xiaoxu; Geng, Yijie; Hou, Shuangyi; Ye, Jianjun; Guan, Xuhua; Han, Shenhong; Wang, Yunxia; Mason, Katherine A; Lu, Zuxun; Liu, Jiafa; Cheng, Jinquan

2012-12-15

Recent genome-wide association studies (GWAS) have identified two key SNPs (rs11833579 and rs12425791) on chromosome 12p13 that were significantly associated with stroke in Caucasians. However, the validity of the association has remained controversial. We performed genetic association analyses in a very unique population which has 60% European ancestry and 40% East Asian ancestry. No significant association between these two SNPs and ischemic stroke was detected in this Chinese Uyghur population. Copyright © 2012 Elsevier B.V. All rights reserved.

The impact of policy changes on consumer behaviour and alcohol consumption in Scania, Sweden 1999-2005.

PubMed

Stafström, Martin; Ostergren, Per-Ölof

2014-01-01

To analyse the hypothesis that a gradual deregulation of traveller allowances, starting in 2001 and ending in 2004, on alcoholic beverages changed consumer behaviours that ultimately led to an increase in alcohol consumption in southern Sweden between in 2005 compared with 1999. The data for this general population random sample prospective cohort study with repeated measurements were collected in 1999 (T1) and in 2005 (T2) in the county of Scania, analysing the answers from 8612 individuals, who at T1 were alcohol consumers and 18-80 years old. Aggregate age-adjusted general mean alcohol consumption did not change significantly between T1 and T2. Significant downward changes were found in a number of demographical and socioeconomic sub-groups. Generalized linear model analyses indicated that the uptake of buying alcohol from a private person was associated with significantly higher consumption (P < 0.001). No longer buying alcohol from a private person, consuming illicitly distilled spirits or buying alcohol abroad were significantly associated with lower consumption at follow-up. Interaction effects between changing consumer behaviours were also identified. The deregulation of the cross-border trade of alcohol into Sweden did not, within our sample, lead to an increase in consumption. There were, however, significant decreases in consumption levels within different socio-demographic sub-groups. In relation to changing consumer behaviours both upward and downward shifts in drinking trends were observed. © The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Is somatic comorbidity associated with more somatic symptoms, mental distress, or unhealthy lifestyle in elderly cancer survivors?

PubMed

Grov, Ellen Karine; Fosså, Sophie D; Dahl, Alv A

2009-06-01

The associations of lifestyle factors, somatic symptoms, mental distress, and somatic comorbidity in elderly cancer survivors have not been well studied. This study examines these associations among elderly cancer survivors (age >or=65 years) in a population-based sample. A cross-sectional comparative study of Norwegian elderly cancer survivors. Combining information from The Norwegian Cancer Registry, and by self-reporting, 972 elderly cancer survivors were identified, of whom 632 (65%) had somatic comorbidity and 340 did not. Elderly cancer survivors with somatic comorbidity had significantly higher BMI, more performed minimal physical activity, had more somatic symptoms, used more medication, and had more frequently seen a medical doctor than survivors without somatic comorbidity. In multivariable analyses, unhealthy lifestyle and higher somatic symptoms scores were significantly associated with cancer cases with somatic comorbidity. In univariate analyses those with somatic comorbidity were significantly older, had lower levels of education, higher proportions of BMI >or= 30, less physical activity, poorer self-rated health, higher somatic symptoms score, more mental distress, had more frequently seen a medical doctor last year, and more frequently used daily medication. Our outcome measures of lifestyle, somatic symptoms and mental distress were all significantly associated with somatic comorbidity in elderly cancer survivors, however only lifestyle and somatic symptoms were significant in multivariable analyses. In elderly cancer survivors not only cancer, but also somatic comorbidity, deserve attention. Such comorbidity is associated with unhealthy lifestyles, more somatic symptoms and mental distress which should be evaluated and eventually treated.

Genome-Wide Linkage and Positional Association Analyses Identify Associations of Novel AFF3 and NTM Genes with Triglycerides: The GenSalt Study

PubMed Central

Li, Changwei; Bazzano, Lydia A.L.; Rao, Dabeeru C.; Hixson, James E.; He, Jiang; Gu, Dongfeng; Gu, Charles C.; Shimmin, Lawrence C.; Jaquish, Cashell E.; Schwander, Karen; Liu, De-Pei; Huang, Jianfeng; Lu, Fanghong; Cao, Jie; Chong, Shen; Lu, Xiangfeng; Kelly, Tanika N.

2016-01-01

We conducted a genome-wide linkage scan and positional association study to identify genes and variants influencing blood lipid levels among participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. The GenSalt study was conducted among 1906 participants from 633 Han Chinese families. Lipids were measured from overnight fasting blood samples using standard methods. Multipoint quantitative trait genome-wide linkage scans were performed on the high-density lipoprotein, low-density lipoprotein, and log-transformed triglyceride phenotypes. Using dense panels of single nucleotide polymorphisms (SNPs), single-marker and gene-based association analyses were conducted to follow-up on promising linkage signals. Additive associations between each SNP and lipid phenotypes were tested using mixed linear regression models. Gene-based analyses were performed by combining P-values from single-marker analyses within each gene using the truncated product method (TPM). Significant associations were assessed for replication among 777 Asian participants of the Multi-ethnic Study of Atherosclerosis (MESA). Bonferroni correction was used to adjust for multiple testing. In the GenSalt study, suggestive linkage signals were identified at 2p11.2–2q12.1 [maximum multipoint LOD score (MML) = 2.18 at 2q11.2] and 11q24.3–11q25 (MML = 2.29 at 11q25) for the log-transformed triglyceride phenotype. Follow-up analyses of these two regions revealed gene-based associations of charged multivesicular body protein 3 (CHMP3), ring finger protein 103 (RNF103), AF4/FMR2 family, member 3 (AFF3), and neurotrimin (NTM ) with triglycerides (P = 4 × 10−4, 1.00 × 10−5, 2.00 × 10−5, and 1.00 × 10−7, respectively). Both the AFF3 and NTM triglyceride associations were replicated among MESA study participants (P = 1.00 × 10−7 and 8.00 × 10−5, respectively). Furthermore, NTM explained the linkage signal on chromosome 11. In conclusion, we identified novel genes associated with lipid phenotypes in linkage regions on chromosomes 2 and 11. PMID:25819087

Tailored interventions to overcome identified barriers to change: effects on professional practice and health care outcomes

PubMed Central

Baker, Richard; Camosso-Stefinovic, Janette; Gillies, Clare; Shaw, Elizabeth J; Cheater, Francine; Flottorp, Signe; Robertson, Noelle

2014-01-01

Background In the previous version of this review, the effectiveness of interventions tailored to barriers to change was found to be uncertain. Objectives To assess the effectiveness of interventions tailored to address identified barriers to change on professional practice or patient outcomes. Search methods For this update, in addition to the EPOC Register and pending files, we searched the following databases without language restrictions, from inception until August 2007: MEDLINE, EMBASE, CINAHL, BNI and HMIC. We searched the National Research Register to November 2007. We undertook further searches to October 2009 to identify potentially eligible published or ongoing trials. Selection criteria Randomised controlled trials (RCTs) of interventions tailored to address prospectively identified barriers to change that reported objectively measured professional practice or healthcare outcomes in which at least one group received an intervention designed to address prospectively identified barriers to change. Data collection and analysis Two reviewers independently assessed quality and extracted data. We undertook quantitative and qualitative analyses. The quantitative analyses had two elements. We carried out a meta-regression to compare interventions tailored to address identified barriers to change with either no interventions or an intervention(s) not tailored to the barriers.We carried out heterogeneity analyses to investigate sources of differences in the effectiveness of interventions. These included the effects of: risk of bias, concealment of allocation, rigour of barrier analysis, use of theory, complexity of interventions, and the reported presence of administrative constraints. Main results We included 26 studies comparing an intervention tailored to address identified barriers to change to no intervention or an intervention(s) not tailored to the barriers. The effect sizes of these studies varied both across and within studies. Twelve studies provided enough data to be included in the quantitative analysis. A meta-regression model was fitted adjusting for baseline odds by fitting it as a covariate, to obtain the pooled odds ratio of 1.54 (95% CI, 1.16 to 2.01) from Bayesian analysis and 1.52 (95% CI, 1.27 to 1.82, P < 0.001) from classical analysis. The heterogeneity analyses found that no study attributes investigated were significantly associated with effectiveness of the interventions. Authors’ conclusions Interventions tailored to prospectively identified barriers are more likely to improve professional practice than no intervention or dissemination of guidelines. However, the methods used to identify barriers and tailor interventions to address them need further development. Research is required to determine the effectiveness of tailored interventions in comparison with other interventions. PMID:20238340

Prison Radicalization: The New Extremist Training Grounds?

DTIC Science & Technology

2007-09-01

distributing and collecting survey data , and the data analysis. The analytical methodology includes descriptive and inferential statistical methods, in... statistical analysis of the responses to identify significant correlations and relationships. B. SURVEY DATA COLLECTION To effectively access a...Q18, Q19, Q20, and Q21. Due to the exploratory nature of this small survey, data analyses were confined mostly to descriptive statistics and

Alabama's Education Report Card, 2000: Significant Predictors of Student Achievement at the District and School Level. Research Brief.

ERIC Educational Resources Information Center

Miller-Whitehead, Marie

This paper examines Alabama's State Education Report Card for the year 2000. It identifies predictors for student academic achievement at both the district and school levels for 128 public school systems and 1,272 public schools. Separate analyses were conducted for 61 city and 67 county school systems. The variables included number of students,…

Targeting Mechanisms of Resistance to Taxane-Based Chemotherapy

DTIC Science & Technology

2008-09-01

12]. Another interesting gene ; monoamine oxidase A ( MAOA ) was upregulated in patients with PSA relapse (Figure 8A). Quantitative real-time PCR (qRT...from prostate. After excluding genes previously shown to be influenced by the radical prostatectomy procedure, we identified 51 genes with significant...analyses confirmed overexpression of GDF15 may confer resistance to chemotherapy in prostate cancer cells. Gene expression changes after

Biomass fuel use for household cooking in Swaziland: is there an association with anaemia and stunting in children aged 6-36 months?

PubMed

Machisa, Mercilene; Wichmann, Janine; Nyasulu, Peter S

2013-09-01

This study is the second to investigate the association between the use of biomass fuels (BMF) for household cooking and anaemia and stunting in children. Such fuels include coal, charcoal, wood, dung and crop residues. Data from the 2006-2007 Swaziland Demographic and Health Survey (a cross-sectional study design) were analysed. Childhood stunting was ascertained through age and height, and anaemia through haemoglobin measurement. The association between BMF use and health outcomes was determined in multinomial logistic regression analyses. Various confounders were considered in the analyses. A total of 1150 children aged 6-36 months were included in the statistical analyses, of these 596 (51.8%) and 317 (27.6%) were anaemic and stunted, respectively. BMF use was not significantly associated with childhood anaemia in univariate analysis. Independent risk factors for childhood anaemia were child's age, history of childhood diarrhoea and mother's anaemia status. No statistically significant association was observed between BMF use and childhood stunting, after adjusting for child's gender, age, birth weight and preceding birth interval. This study identified the need to prioritize childhood anaemia and stunting as health outcomes and the introduction of public health interventions in Swaziland. Further research is needed globally on the potential effects of BMF use on childhood anaemia and stunting.

What We Have Learned from the Recent Meta-analyses on Diagnostic Methods for Atherosclerotic Plaque Regression.

PubMed

Biondi-Zoccai, Giuseppe; Mastrangeli, Simona; Romagnoli, Enrico; Peruzzi, Mariangela; Frati, Giacomo; Roever, Leonardo; Giordano, Arturo

2018-01-17

Atherosclerosis has major morbidity and mortality implications globally. While it has often been considered an irreversible degenerative process, recent evidence provides compelling proof that atherosclerosis can be reversed. Plaque regression is however difficult to appraise and quantify, with competing diagnostic methods available. Given the potential of evidence synthesis to provide clinical guidance, we aimed to review recent meta-analyses on diagnostic methods for atherosclerotic plaque regression. We identified 8 meta-analyses published between 2015 and 2017, including 79 studies and 14,442 patients, followed for a median of 12 months. They reported on atherosclerotic plaque regression appraised with carotid duplex ultrasound, coronary computed tomography, carotid magnetic resonance, coronary intravascular ultrasound, and coronary optical coherence tomography. Overall, all meta-analyses showed significant atherosclerotic plaque regression with lipid-lowering therapy, with the most notable effects on echogenicity, lipid-rich necrotic core volume, wall/plaque volume, dense calcium volume, and fibrous cap thickness. Significant interactions were found with concomitant changes in low density lipoprotein cholesterol, high density lipoprotein cholesterol, and C-reactive protein levels, and with ethnicity. Atherosclerotic plaque regression and conversion to a stable phenotype is possible with intensive medical therapy and can be demonstrated in patients using a variety of non-invasive and invasive imaging modalities.

Cytotoxic analysis and chemical characterization of fractions of the hydroalcoholic extract of the Euterpe oleracea Mart. seed in the MCF-7 cell line.

PubMed

Freitas, Dayanne da S; Morgado-Díaz, José A; Gehren, Adriana S; Vidal, Flávia C B; Fernandes, Raquel Maria T; Romão, Wanderson; Tose, Lilian V; Frazão, Fabiola N S; Costa, Maria Célia P; Silva, Dulcelena F; Nascimento, Maria do Desterro S B

2017-06-01

To analyse the antineoplastic activity of fractions derived from the hydroalcoholic extract of Euterpe oleracea Mart. seed in the MCF-7 cell line and to identify the compounds responsible for the antineoplastic action. Cells were treated with 10, 20, 40 and 60 μg/ml with the hexane, chloroform and ethyl acetate fraction (EAF) of the hydroalcoholic extract of açaí seed, for 24 and 48 h. After treatment, cell viability was measured using MTT assay and cell death was assessed using the Annexin-Pi assay. The most cytotoxic fraction under study was analysed by mass spectrometry using an electrospray ionization source and a cyclotron analyser coupled to a Fourier transform. Data were analysed statistically by analysis of variance (ANOVA) or by Student's t-test, where appropriate. All fractions caused significant reduction in the cell viability, but the EAF was the most cytotoxic (P < 0.001). It was observed the absence of significant annexin staining but increase Pi staining (P < 0.001). The EAF is composed of epicatechin, proanthocyanidin A 2 and trimeric and tetrameric procyanidins. In this study, we demonstrated that EAF was the most effective fraction in reducing cell viability and causing necroptosis in the MCF-7 cell. © 2017 Royal Pharmaceutical Society.

Quantitative cancer risk assessment based on NIOSH and UCC epidemiological data for workers exposed to ethylene oxide.

PubMed

Valdez-Flores, Ciriaco; Sielken, Robert L; Teta, M Jane

2010-04-01

The most recent epidemiological data on individual workers in the NIOSH and updated UCC occupational studies have been used to characterize the potential excess cancer risks of environmental exposure to ethylene oxide (EO). In addition to refined analyses of the separate cohorts, power has been increased by analyzing the combined cohorts. In previous SMR analyses of the separate studies and the present analyses of the updated and pooled studies of over 19,000 workers, none of the SMRs for any combination of the 12 cancer endpoints and six sub-cohorts analyzed were statistically significantly greater than one including the ones of greatest previous interest: leukemia, lymphohematopoietic tissue, lymphoid tumors, NHL, and breast cancer. In our study, no evidence of a positive cumulative exposure-response relationship was found. Fitted Cox proportional hazards models with cumulative EO exposure do not have statistically significant positive slopes. The lack of increasing trends was corroborated by categorical analyses. Cox model estimates of the concentrations corresponding to a 1-in-a-million extra environmental cancer risk are all greater than approximately 1ppb and are more than 1500-fold greater than the 0.4ppt estimate in the 2006 EPA draft IRIS risk assessment. The reasons for this difference are identified and discussed. Copyright 2009 Elsevier Inc. All rights reserved.

Analytical performance of reciprocal isotope labeling of proteome digests for quantitative proteomics and its application for comparative studies of aerobic and anaerobic Escherichia coli proteomes.

PubMed

Lo, Andy; Weiner, Joel H; Li, Liang

2013-09-17

Due to limited sample amounts, instrument time considerations, and reagent costs, only a small number of replicate experiments are typically performed for quantitative proteome analyses. Generation of reproducible data that can be readily assessed for consistency within a small number of datasets is critical for accurate quantification. We report our investigation of a strategy using reciprocal isotope labeling of two comparative samples as a tool for determining proteome changes. Reciprocal labeling was evaluated to determine the internal consistency of quantified proteome changes from Escherichia coli grown under aerobic and anaerobic conditions. Qualitatively, the peptide overlap between replicate analyses of the same sample and reverse labeled samples were found to be within 8%. Quantitatively, reciprocal analyses showed only a slight increase in average overall inconsistency when compared with replicate analyses (1.29 vs. 1.24-fold difference). Most importantly, reverse labeling was successfully used to identify spurious values resulting from incorrect peptide identifications and poor peak fitting. After removal of 5% of the peptide data with low reproducibility, a total of 275 differentially expressed proteins (>1.50-fold difference) were consistently identified and were then subjected to bioinformatics analysis. General considerations and guidelines for reciprocal labeling experimental design and biological significance of obtained results are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

Profiling oil sands mixtures from industrial developments and natural groundwaters for source identification.

PubMed

Frank, Richard A; Roy, James W; Bickerton, Greg; Rowland, Steve J; Headley, John V; Scarlett, Alan G; West, Charles E; Peru, Kerry M; Parrott, Joanne L; Conly, F Malcolm; Hewitt, L Mark

2014-01-01

The objective of this study was to identify chemical components that could distinguish chemical mixtures in oil sands process-affected water (OSPW) that had potentially migrated to groundwater in the oil sands development area of northern Alberta, Canada. In the first part of the study, OSPW samples from two different tailings ponds and a broad range of natural groundwater samples were assessed with historically employed techniques as Level-1 analyses, including geochemistry, total concentrations of naphthenic acids (NAs) and synchronous fluorescence spectroscopy (SFS). While these analyses did not allow for reliable source differentiation, they did identify samples containing significant concentrations of oil sands acid-extractable organics (AEOs). In applying Level-2 profiling analyses using electrospray ionization high resolution mass spectrometry (ESI-HRMS) and comprehensive multidimensional gas chromatography time-of-flight mass spectrometry (GC × GC-TOF/MS) to samples containing appreciable AEO concentrations, differentiation of natural from OSPW sources was apparent through measurements of O2:O4 ion class ratios (ESI-HRMS) and diagnostic ions for two families of suspected monoaromatic acids (GC × GC-TOF/MS). The resemblance between the AEO profiles from OSPW and from 6 groundwater samples adjacent to two tailings ponds implies a common source, supporting the use of these complimentary analyses for source identification. These samples included two of upward flowing groundwater collected <1 m beneath the Athabasca River, suggesting OSPW-affected groundwater is reaching the river system.

The relationship between mineral contents, particle matter and bottom ash distribution during pellet combustion: molar balance and chemometric analysis.

PubMed

Jeguirim, Mejdi; Kraiem, Nesrine; Lajili, Marzouk; Guizani, Chamseddine; Zorpas, Antonis; Leva, Yann; Michelin, Laure; Josien, Ludovic; Limousy, Lionel

2017-04-01

This paper aims to identify the correlation between the mineral contents in agropellets and particle matter and bottom ash characteristics during combustion in domestic boilers. Four agrifood residues with higher mineral contents, namely grape marc (GM), tomato waste (TW), exhausted olive mill solid waste (EOMSW) and olive mill wastewater (OMWW), were selected. Then, seven different pellets were produced from pure residues or their mixture and blending with sawdust. The physico-chemical properties of the produced pellets were analysed using different analytical techniques, and a particular attention was paid to their mineral contents. Combustion tests were performed in 12-kW domestic boiler. The particle matter (PM) emission was characterised through the particle number and mass quantification for different particle size. The bottom ash composition and size distribution were also characterised. Molar balance and chemometric analyses were performed to identify the correlation between the mineral contents and PM and bottom ash characteristics. The performed analyses indicate that K, Na, S and Cl are released partially or completely during combustion tests. In contrast, Ca, Mg, Si, P, Al, Fe and Mn are retained in the bottom ash. The chemometric analyses indicate that, in addition to the operating conditions and the pellet ash contents, K and Si concentrations have a significant effect on the PM emissions as well as on the agglomeration of bottom ash.

Identifying predictors of resilience at inpatient and 3-month post-spinal cord injury.

PubMed

Driver, Simon; Warren, Ann Marie; Reynolds, Megan; Agtarap, Stephanie; Hamilton, Rita; Trost, Zina; Monden, Kimberly

2016-01-01

To identify (1) changes in psychosocial factors, (2) relationships between psychosocial factors, and (3) significant predictors of resilience in adults with spinal cord injury (SCI) during inpatient rehabilitation and at 3-month post-discharge. Cross sectional with convenience sample based on inclusion/exclusion criteria. Inpatient rehabilitation hospital and community-based follow-up. Individuals with a SCI. Not applicable. Demographic, resilience, self-efficacy for managing a chronic health issue, depression, social roles/activity limitations, and pain. The final sample consisted of 44 respondents (16 women and 28 men). Results of repeated measure analyses of variance indicated no significant changes in variables between inpatient and 3-month follow-up. Bivariate correlations revealed associations between resilience and self-efficacy at inpatient (r = 0.54, P < 0.001), and resilience and depression (r = -0.69, P < 0.001) and self-efficacy (r = 0.67, P < 0.001) at 3-month follow-up. Hierarchical regression analyses a significant model predicting resilience at inpatient stay (R = 0.61; adjusted R(2) = 0.24, P = 0.023), and at 3-month follow-up (R = 0.83; adjusted R(2) = 0.49, P = 0.022). Self-efficacy was the strongest predictor at inpatient stay (β = 0.46, P = 0.006) and depression was strongest at 3-month follow-up (β = -0.80, P = 0.007). Results suggest that although resilience appears to be stable from inpatient to 3-month follow-up, different factors are stronger predictors of resilience across time. Based on current results, an assessment of self-efficacy during inpatient rehabilitation and an identification of depression at 3-month follow-up may be important factors to help identify those at risk of health issues overtime.

Mouse and Human Genetic Analyses Associate Kalirin with Ventral Striatal Activation during Impulsivity and with Alcohol Misuse

PubMed Central

Peña-Oliver, Yolanda; Carvalho, Fabiana M.; Sanchez-Roige, Sandra; Quinlan, Erin B.; Jia, Tianye; Walker-Tilley, Tom; Rulten, Stuart L.; Pearl, Frances M. G.; Banaschewski, Tobias; Barker, Gareth J.; Bokde, Arun L. W.; Büchel, Christian; Conrod, Patricia J.; Flor, Herta; Gallinat, Jürgen; Garavan, Hugh; Heinz, Andreas; Gowland, Penny; Paillere Martinot, Marie-Laure; Paus, Tomáš; Rietschel, Marcella; Robbins, Trevor W.; Smolka, Michael N.; Schumann, Gunter; Stephens, David N.

2016-01-01

Impulsivity is associated with a spectrum of psychiatric disorders including drug addiction. To investigate genetic associations with impulsivity and initiation of drug taking, we took a two-step approach. First, we identified genes whose expression level in prefrontal cortex, striatum and accumbens were associated with impulsive behavior in the 5-choice serial reaction time task across 10 BXD recombinant inbred (BXD RI) mouse strains and their progenitor C57BL/6J and DBA2/J strains. Behavioral data were correlated with regional gene expression using GeneNetwork (www.genenetwork.org), to identify 44 genes whose probability of association with impulsivity exceeded a false discovery rate of < 0.05. We then interrogated the IMAGEN database of 1423 adolescents for potential associations of SNPs in human homologs of those genes identified in the mouse study, with brain activation during impulsive performance in the Monetary Incentive Delay task, and with novelty seeking scores from the Temperament and Character Inventory, as well as alcohol experience. There was a significant overall association between the human homologs of impulsivity-related genes and percentage of premature responses in the MID task and with fMRI BOLD-response in ventral striatum (VS) during reward anticipation. In contrast, no significant association was found between the polygenic scores and anterior cingulate cortex activation. Univariate association analyses revealed that the G allele (major) of the intronic SNP rs6438839 in the KALRN gene was significantly associated with increased VS activation. Additionally, the A-allele (minor) of KALRN intronic SNP rs4634050, belonging to the same haplotype block, was associated with increased frequency of binge drinking. PMID:27092175

Preoperative determinant of early postoperative renal function following radical cystectomy and intestinal urinary diversion.

PubMed

Gondo, Tatsuo; Ohno, Yoshio; Nakashima, Jun; Hashimoto, Takeshi; Nakagami, Yoshihiro; Tachibana, Masaaki

2017-02-01

To identify preoperative factors correlated with postoperative early renal function in patients who had undergone radical cystectomy (RC) and intestinal urinary diversion. We retrospectively identified 201 consecutive bladder cancer patients without distant metastasis who had undergone RC at our institution between 2003 and 2012. The estimated glomerular filtration rate (eGFR) was calculated using the modified Chronic Kidney Disease Epidemiology equation before RC and 3 months following RC. Univariate and stepwise multiple linear regression analyses were applied to estimate postoperative renal function and to identify significant preoperative predictors of postoperative renal function. Patients who had undergone intestinal urinary diversion and were available for the collection of follow-up data (n = 164) were eligible for the present study. Median preoperative and postoperative eGFRs were 69.7 (interquartile range [IQR] 56.3-78.0) and 70.7 (IQR 57.3-78.1), respectively. In univariate analyses, age, preoperative proteinuria, thickness of abdominal subcutaneous fat tissue (TSF), preoperative serum creatinine level, preoperative eGFR, and urinary diversion type were significantly associated with postoperative eGFR. In a stepwise multiple linear regression analysis, preoperative eGFR, age, and TSF were significant factors for predicting postoperative eGFR (p < 0.001, p = 0.02, and p = 0.046, respectively). The estimated postoperative eGFRs correlated well with the actual postoperative eGFRs (r = 0.65, p < 0.001). Preoperative eGFR, age, and TSF were independent preoperative factors for determining postoperative renal function in patients who had undergone RC and intestinal urinary diversion. These results may be used for patient counseling before surgery, including the planning of perioperative chemotherapy administration.

A Genome-Wide Association Analysis Reveals Epistatic Cancellation of Additive Genetic Variance for Root Length in Arabidopsis thaliana.

PubMed

Lachowiec, Jennifer; Shen, Xia; Queitsch, Christine; Carlborg, Örjan

2015-01-01

Efforts to identify loci underlying complex traits generally assume that most genetic variance is additive. Here, we examined the genetics of Arabidopsis thaliana root length and found that the genomic narrow-sense heritability for this trait in the examined population was statistically zero. The low amount of additive genetic variance that could be captured by the genome-wide genotypes likely explains why no associations to root length could be found using standard additive-model-based genome-wide association (GWA) approaches. However, as the broad-sense heritability for root length was significantly larger, and primarily due to epistasis, we also performed an epistatic GWA analysis to map loci contributing to the epistatic genetic variance. Four interacting pairs of loci were revealed, involving seven chromosomal loci that passed a standard multiple-testing corrected significance threshold. The genotype-phenotype maps for these pairs revealed epistasis that cancelled out the additive genetic variance, explaining why these loci were not detected in the additive GWA analysis. Small population sizes, such as in our experiment, increase the risk of identifying false epistatic interactions due to testing for associations with very large numbers of multi-marker genotypes in few phenotyped individuals. Therefore, we estimated the false-positive risk using a new statistical approach that suggested half of the associated pairs to be true positive associations. Our experimental evaluation of candidate genes within the seven associated loci suggests that this estimate is conservative; we identified functional candidate genes that affected root development in four loci that were part of three of the pairs. The statistical epistatic analyses were thus indispensable for confirming known, and identifying new, candidate genes for root length in this population of wild-collected A. thaliana accessions. We also illustrate how epistatic cancellation of the additive genetic variance explains the insignificant narrow-sense and significant broad-sense heritability by using a combination of careful statistical epistatic analyses and functional genetic experiments.

Applying machine learning to identify autistic adults using imitation: An exploratory study.

PubMed

Li, Baihua; Sharma, Arjun; Meng, James; Purushwalkam, Senthil; Gowen, Emma

2017-01-01

Autism spectrum condition (ASC) is primarily diagnosed by behavioural symptoms including social, sensory and motor aspects. Although stereotyped, repetitive motor movements are considered during diagnosis, quantitative measures that identify kinematic characteristics in the movement patterns of autistic individuals are poorly studied, preventing advances in understanding the aetiology of motor impairment, or whether a wider range of motor characteristics could be used for diagnosis. The aim of this study was to investigate whether data-driven machine learning based methods could be used to address some fundamental problems with regard to identifying discriminative test conditions and kinematic parameters to classify between ASC and neurotypical controls. Data was based on a previous task where 16 ASC participants and 14 age, IQ matched controls observed then imitated a series of hand movements. 40 kinematic parameters extracted from eight imitation conditions were analysed using machine learning based methods. Two optimal imitation conditions and nine most significant kinematic parameters were identified and compared with some standard attribute evaluators. To our knowledge, this is the first attempt to apply machine learning to kinematic movement parameters measured during imitation of hand movements to investigate the identification of ASC. Although based on a small sample, the work demonstrates the feasibility of applying machine learning methods to analyse high-dimensional data and suggest the potential of machine learning for identifying kinematic biomarkers that could contribute to the diagnostic classification of autism.

A Quantitative Assessment of the Reporting Quality of Herbal Medicine Research: The Road to Improvement.

PubMed

Naumann, Ken

2018-02-01

To quantify different aspects of the quality of reporting of herbal medicine clinical trials, to determine how that quality is affecting the conclusions of meta-analyses, and to target areas for improvement in future herbal medicine research reporting. The Electronic databases PubMed, Academic Search Premier, ScienceDirect, and Alt HealthWatch were searched for meta-analyses of herbal medicines in refereed journals and Cochrane Reviews in the years 2000-2004 and 2010-2014. The search was limited to meta-analyses of randomized controlled trials involving humans and published in English. Judgments and descriptions within the meta-analyses were used to report on risks of bias in the included clinical trials and the meta-analyses themselves. Out of 3264 citations, 9 journal-published meta-analyses were selected from 2000 to 2004, 116 from 2010 to 2014, and 44 Cochrane Reviews from 2010 to 2014. Across both time frames and categories of publication, <42% of the trials included in the meta-analyses described adequate randomization; <19% described concealment methods; <26% described double blinding; <29% described outcome assessment blinding, ≤53% discussed incomplete data, and <36% were nonselective in their reporting. Less than 54% of trials reported on adverse events and 64% of meta-analyses did not include a single trial with a low risk of bias. Taxonomic verification and chemical characterization of test products were infrequent in trials. Only 40% of meta-analyses considered publication bias and, of those that did, 90% found evidence for it. Cochrane Reviews were more likely than other sources to make negative conclusions of efficacy or to defer conclusions because of the absence of high quality trials. Meta-analyses of herbal medicines include a significant number of clinical trials that do not meet the recommended standards for clinical trial reporting. This quantitative assessment identified significant publication bias and other bias risks that may be due to inadequate trial design or incomplete reporting of outcomes. Suggested improvements to herbal medicine clinical trial reporting are discussed.

Spatial quantile regression using INLA with applications to childhood overweight in Malawi.

PubMed

Mtambo, Owen P L; Masangwi, Salule J; Kazembe, Lawrence N M

2015-04-01

Analyses of childhood overweight have mainly used mean regression. However, using quantile regression is more appropriate as it provides flexibility to analyse the determinants of overweight corresponding to quantiles of interest. The main objective of this study was to fit a Bayesian additive quantile regression model with structured spatial effects for childhood overweight in Malawi using the 2010 Malawi DHS data. Inference was fully Bayesian using R-INLA package. The significant determinants of childhood overweight ranged from socio-demographic factors such as type of residence to child and maternal factors such as child age and maternal BMI. We observed significant positive structured spatial effects on childhood overweight in some districts of Malawi. We recommended that the childhood malnutrition policy makers should consider timely interventions based on risk factors as identified in this paper including spatial targets of interventions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ruminal paramphistomosis in cattle from northeastern Algeria: prevalence, parasite burdens and species identification

PubMed Central

Titi, Amal; Mekroud, Abdeslam; Chibat, Mohamed el Hadi; Boucheikhchoukh, Mehdi; Zein-Eddine, Rima; Djuikwo-Teukeng, Félicité F.; Vignoles, Philippe; Rondelaud, Daniel; Dreyfuss, Gilles

2014-01-01

Slaughterhouse samples were analysed over a two-year period (September 2010–August 2012) in Jijel (northeastern Algeria) in order to determine seasonal variations in the prevalence and intensity of bovine paramphistomosis in a Mediterranean climate and identify paramphistome species using molecular biology. In spring and summer, significantly higher prevalences and lower parasite burdens were noted in bull calves, thus indicating an effect of season on these parameters. In contrast, the differences among seasonal prevalences or among seasonal parasite burdens were not significant in the case of old cows. Eleven adult worms from the slaughterhouses of Jijel and three neighbouring departments (Constantine, El Tarf and Setif) were analysed using molecular markers for species identification. Two different species, Calicophoron daubneyi and C. microbothrium, were found. The presence of these two paramphistomids raises the question of their respective frequency in the definitive host and local intermediate hosts. PMID:25279553

Childhood Victimization, Attachment, Coping, and Substance Use Among Victimized Women on Probation and Parole.

PubMed

Dishon-Brown, Amanda; Golder, Seana; Renn, Tanya; Winham, Katherine; Higgins, George E; Logan, T K

2017-06-01

Justice-involved women report high rates of victimization across their life span, and these experiences contribute to their involvement in the criminal justice (CJ) system. Within this population, research has identified an overlap among victimization and substance use, a high-risk coping mechanism. Furthermore, research indicates attachment style is related to coping and high-risk behaviors. Research is needed to understand the relationship among these mechanisms as they relate to intimate partner violence (IPV). To address this gap, this study investigated the relationship between attachment, coping, childhood victimization, substance use, and IPV among 406 victimized women on probation/parole. Results of 6 multivariate regression analyses were statistically significant, accounting for 8%-13% of the variance in IPV. Particularly, childhood sexual victimization and negative coping were significant in all analyses. Findings provide practitioners, administrators, and policymakers information about the specific needs of justice-involved women.

EGFR immunoexpression, RAS immunoexpression and their effects on survival in lung adenocarcinoma cases.

PubMed

Gundogdu, Ahmet Gokhan; Onder, Sevgen; Firat, Pinar; Dogan, Riza

2014-06-01

The impacts of epidermal growth factor receptor (EGFR) immunoexpression and RAS immunoexpression on the survival and prognosis of lung adenocarcinoma patients are debated in the literature. Twenty-six patients, who underwent pulmonary resections between 2002 and 2007 in our clinic, and whose pathologic examinations yielded adenocarcinoma, were included in the study. EGFR and RAS expression levels were examined by immunohistochemical methods. The results were compared with the survival, stage of the disease, nodal involvement, lymphovascular invasion, and pleural invasion. Nonparametric bivariate analyses were used for statistical analyses. A significant link between EGFR immunoexpression and survival has been identified while RAS immunoexpression and survival have been proven to be irrelevant. Neither EGFR, nor RAS has displayed a significant link with the stage of the disease, nodal involvement, lymphovascular invasion, or pleural invasion. Positive EGFR immunoexpression affects survival negatively, while RAS immunoexpression has no effect on survival in lung adenocarcinoma patients.

Evidence for localised HIV related micro-epidemics associated with the decentralised provision of antiretroviral treatment in rural South Africa: a spatio-temporal analysis of changing mortality patterns (2007-2010).

PubMed

Mee, Paul; Collinson, Mark A; Madhavan, Sangeetha; Root, Elisabeth Dowling; Tollman, Stephen M; Byass, Peter; Kahn, Kathleen

2014-06-01

In this study we analysed the spatial and temporal changes in patterns of mortality over a period when antiretroviral therapy (ART) was rolled out in a rural region of north-eastern South Africa. Previous studies have identified localised concentrated HIV related sub-epidemics and recommended that micro-level analyses be carried out in order to direct focused interventions. Data from an ongoing health and socio-demographic surveillance study was used in the analysis. The follow-up was divided into two periods, 2007-2008 and 2009-2010, representing the times immediately before and after the effects on mortality of the decentralised ART provision from a newly established local health centre would be expected to be evident. The study population at the start of the analysis was approximately 73 000 individuals. Data were aggregated by village and also using a 2 × 2 km grid. We identified villages, grid squares and regions in the site where mortality rates within each time period or rate ratios between the periods differed significantly from the overall trends. We used clustering techniques to identify cause-specific mortality hotspots. Comparing the two periods, there was a 30% decrease in age and gender standardised adult HIV-related and TB (HIV/TB) mortality with no change in mortality due to other causes. There was considerable spatial heterogeneity in the mortality patterns. Areas separated by 2 to 4 km with very different epidemic trajectories were identified. There was evidence that the impact of ART in reducing HIV/TB mortality was greatest in communities with higher mortality rates in the earlier period. This study shows the value of conducting high resolution spatial analyses in order to understand how local micro-epidemics contribute to changes seen over a wider area. Such analyses can support targeted interventions.

Intestinal stoma in patients with colorectal cancer from the perspective of 20-year period of clinical observation

PubMed Central

Banaszkiewicz, Zbigniew; Woda, Łukasz P.; Tojek, Krzysztof; Jarmocik, Paweł; Jawień, Arkadiusz

2015-01-01

Introduction Intestinal stoma is a procedure most often performed in patients with colorectal cancer. Aim To identify the percentage of patients with colorectal cancer in which the intestinal stoma was performed. Material and methods We retrospectively analysed 443 patients treated during a 20-year period (1994–2013) due to colorectal cancer, in which the intestinal stoma was made during the first surgical intervention. Results In the second analysed decade, a significant decrease in the percentage of created stomas, definitive stomas in particular, was observed. Stomas were made significantly more often in patients with a tumour located in the rectum, the left half of the colon, and in patients undergoing urgent surgeries. An increased incidence of intestinal stomas was associated with a higher severity of illness and higher proportion of unresectable and non-radical procedures. The definitive stomas were significantly more often made in men and in patients with tumours located in the rectum, whereas temporary stomas were created significantly more often in patients undergoing urgent operations. Conclusions In the last decade (2004–2013) the number of intestinal stomas in patients operated due to colorectal cancer was significantly reduced. PMID:25960811

Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci

PubMed Central

Glubb, Dylan M.; Johnatty, Sharon E.; Quinn, Michael C.J.; O’Mara, Tracy A.; Tyrer, Jonathan P.; Gao, Bo; Fasching, Peter A.; Beckmann, Matthias W.; Lambrechts, Diether; Vergote, Ignace; Velez Edwards, Digna R.; Beeghly-Fadiel, Alicia; Benitez, Javier; Garcia, Maria J.; Goodman, Marc T.; Thompson, Pamela J.; Dörk, Thilo; Dürst, Matthias; Modungo, Francesmary; Moysich, Kirsten; Heitz, Florian; du Bois, Andreas; Pfisterer, Jacobus; Hillemanns, Peter; Karlan, Beth Y.; Lester, Jenny; Goode, Ellen L.; Cunningham, Julie M.; Winham, Stacey J.; Larson, Melissa C.; McCauley, Bryan M.; Kjær, Susanne Krüger; Jensen, Allan; Schildkraut, Joellen M.; Berchuck, Andrew; Cramer, Daniel W.; Terry, Kathryn L.; Salvesen, Helga B.; Bjorge, Line; Webb, Penny M.; Grant, Peter; Pejovic, Tanja; Moffitt, Melissa; Hogdall, Claus K.; Hogdall, Estrid; Paul, James; Glasspool, Rosalind; Bernardini, Marcus; Tone, Alicia; Huntsman, David; Woo, Michelle; Group, AOCS; deFazio, Anna; Kennedy, Catherine J.; Pharoah, Paul D.P.; MacGregor, Stuart; Chenevix-Trench, Georgia

2017-01-01

We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that MEF2D and ZNF100 are targets of candidate outcome variants at 1q22 and 19p12, respectively. At 19p12, the chromatin interaction of a putative regulatory element with the ZNF100 promoter region correlated with candidate outcome variants. At 1q22, putative regulatory elements enhanced MEF2D promoter activity and haplotypes containing candidate outcome variants modulated these effects. In a public dataset, MEF2D and ZNF100 expression were both associated with ovarian cancer progression-free or overall survival time. In an extended set of 6,162 epithelial ovarian cancer patients, we found that functional candidates at the 1q22 and 19p12 loci, as well as other regional variants, were nominally associated with patient outcome; however, no associations reached our threshold for statistical significance (p<1×10-5). Larger patient numbers will be needed to convincingly identify any true associations at these loci. PMID:29029385

Discovery of Novel Antimicrobial Peptides from Varanus komodoensis (Komodo Dragon) by Large-Scale Analyses and De-Novo-Assisted Sequencing Using Electron-Transfer Dissociation Mass Spectrometry.

PubMed

Bishop, Barney M; Juba, Melanie L; Russo, Paul S; Devine, Megan; Barksdale, Stephanie M; Scott, Shaylyn; Settlage, Robert; Michalak, Pawel; Gupta, Kajal; Vliet, Kent; Schnur, Joel M; van Hoek, Monique L

2017-04-07

Komodo dragons are the largest living lizards and are the apex predators in their environs. They endure numerous strains of pathogenic bacteria in their saliva and recover from wounds inflicted by other dragons, reflecting the inherent robustness of their innate immune defense. We have employed a custom bioprospecting approach combining partial de novo peptide sequencing with transcriptome assembly to identify cationic antimicrobial peptides from Komodo dragon plasma. Through these analyses, we identified 48 novel potential cationic antimicrobial peptides. All but one of the identified peptides were derived from histone proteins. The antimicrobial effectiveness of eight of these peptides was evaluated against Pseudomonas aeruginosa (ATCC 9027) and Staphylococcus aureus (ATCC 25923), with seven peptides exhibiting antimicrobial activity against both microbes and one only showing significant potency against P. aeruginosa. This study demonstrates the power and promise of our bioprospecting approach to cationic antimicrobial peptide discovery, and it reveals the presence of a plethora of novel histone-derived antimicrobial peptides in the plasma of the Komodo dragon. These findings may have broader implications regarding the role that intact histones and histone-derived peptides play in defending the host from infection. Data are available via ProteomeXChange with identifier PXD005043.

Longitudinal Examination of Symptom Profiles among Breast Cancer Survivors

PubMed Central

Avis, Nancy E.; Levine, Beverly; Marshall, Sarah A.; Ip, Edward H.

2017-01-01

Context Identification of cancer patients with similar symptom profiles may facilitate targeted symptom management. Objectives To identify subgroups of breast cancer survivors based on differential experience of symptoms, examine change in subgroup membership over time, and identify relevant characteristics and quality of life (QOL) among subgroups. Methods Secondary analyses of data from 653 breast cancer survivors recruited within 8 months of diagnosis who completed questionnaires at five timepoints. Hidden Markov modeling was used to: 1) formulate symptom profiles based on prevalence and severity of eight symptoms commonly associated with breast cancer, and 2) estimate probabilities of changing subgroup membership over 18 months of follow-up. Ordinal repeated measures were used to: 3) identify patient characteristics related to subgroup membership, and 4) evaluate the relationship between symptom subgroup and QOL. Results A seven-subgroup model provided the best fit: 1) low symptom burden, 2) mild fatigue, 3) mild fatigue and mild pain, 4) moderate fatigue and moderate pain, 5) moderate fatigue and moderate psychological, 6) moderate fatigue, mild pain, mild psychological; and 7) high symptom burden. Seventy percent of survivors remained in the same subgroup over time. In multivariable analyses, chemotherapy and greater illness intrusiveness were significantly related to greater symptom burden, while not being married or partnered, no difficulty paying for basics, and greater social support were protective. Higher symptom burden was associated with lower QOL. Survivors who reported psychological symptoms had significantly lower QOL than did survivors with pain symptoms. Conclusion Cancer survivors can be differentiated by their symptom profiles. PMID:28042076

Genome-wide meta-analysis of SNP-by9-ACEI/ARB and SNP-by-thiazide diuretic and effect on serum potassium in cohorts of European and African ancestry.

PubMed

Irvin, Marguerite R; Sitlani, Colleen M; Noordam, Raymond; Avery, Christie L; Bis, Joshua C; Floyd, James S; Li, Jin; Limdi, Nita A; Srinivasasainagendra, Vinodh; Stewart, James; de Mutsert, Renée; Mook-Kanamori, Dennis O; Lipovich, Leonard; Kleinbrink, Erica L; Smith, Albert; Bartz, Traci M; Whitsel, Eric A; Uitterlinden, Andre G; Wiggins, Kerri L; Wilson, James G; Zhi, Degui; Stricker, Bruno H; Rotter, Jerome I; Arnett, Donna K; Psaty, Bruce M; Lange, Leslie A

2018-06-01

We evaluated interactions of SNP-by-ACE-I/ARB and SNP-by-TD on serum potassium (K+) among users of antihypertensive treatments (anti-HTN). Our study included seven European-ancestry (EA) (N = 4835) and four African-ancestry (AA) cohorts (N = 2016). We performed race-stratified, fixed-effect, inverse-variance-weighted meta-analyses of 2.5 million SNP-by-drug interaction estimates; race-combined meta-analysis; and trans-ethnic fine-mapping. Among EAs, we identified 11 significant SNPs (P < 5 × 10 -8 ) for SNP-ACE-I/ARB interactions on serum K+ that were located between NR2F1-AS1 and ARRDC3-AS1 on chromosome 5 (top SNP rs6878413 P = 1.7 × 10 -8 ; ratio of serum K+ in ACE-I/ARB exposed compared to unexposed is 1.0476, 1.0280, 1.0088 for the TT, AT, and AA genotypes, respectively). Trans-ethnic fine mapping identified the same group of SNPs on chromosome 5 as genome-wide significant for the ACE-I/ARB analysis. In conclusion, SNP-by-ACE-I /ARB interaction analyses uncovered loci that, if replicated, could have future implications for the prevention of arrhythmias due to anti-HTN treatment-related hyperkalemia. Before these loci can be identified as clinically relevant, future validation studies of equal or greater size in comparison to our discovery effort are needed.

Relationships Between the Way Students Are Assessed in Science Classrooms and Science Achievement Across Canada

NASA Astrophysics Data System (ADS)

Chu, Man-Wai; Fung, Karen

2018-04-01

Canadian students experience many different assessments throughout their schooling (O'Connor 2011). There are many benefits to using a variety of assessment types, item formats, and science-based performance tasks in the classroom to measure the many dimensions of science education. Although using a variety of assessments is beneficial, it is unclear exactly what types, format, and tasks are used in Canadian science classrooms. Additionally, since assessments are often administered to help improve student learning, this study identified assessments that may improve student learning as measured using achievement scores on a standardized test. Secondary analyses of the students' and teachers' responses to the questionnaire items asked in the Pan-Canadian Assessment Program were performed. The results of the hierarchical linear modeling analyses indicated that both students and teachers identified teacher-developed classroom tests or quizzes as the most common types of assessments used. Although this ranking was similar across the country, statistically significant differences in terms of the assessments that are used in science classrooms among the provinces were also identified. The investigation of which assessment best predicted student achievement scores indicated that minds-on science performance-based tasks significantly explained 4.21% of the variance in student scores. However, mixed results were observed between the student and teacher responses towards tasks that required students to choose their own investigation and design their own experience or investigation. Additionally, teachers that indicated that they conducted more demonstrations of an experiment or investigation resulted in students with lower scores.

Epigenomic Elements Analyses for Promoters Identify ESRRG as a New Susceptibility Gene for Obesity-related Traits

PubMed Central

Dong, Shan-Shan; Guo, Yan; Zhu, Dong-Li; Chen, Xiao-Feng; Wu, Xiao-Ming; Shen, Hui; Chen, Xiang-Ding; Tan, Li-Jun; Tian, Qing; Deng, Hong-Wen; Yang, Tie-Lin

2016-01-01

OBJECTIVES With ENCODE epigenomic data and results from published genome-wide association studies (GWASs), we aimed to find regulatory signatures of obesity genes and discover novel susceptibility genes. METHODS Obesity genes were obtained from public GWASs databases and their promoters were annotated based on the regulatory elements information. Significantly enriched or depleted epigenomic elements in the promoters of obesity genes were evaluated and all human genes were then prioritized according to the existence of the selected elements to predict new candidate genes. Top ranked genes were subsequently applied to validate their associations with obesity-related traits in three independent in-house GWASs samples. RESULTS We identified RAD21 and EZH2 as over-represented, STAT2 and IRF3 as depleted transcription factors. Histone modification of H3K9me3 and chromatin state segmentation of “poised promoter” and “repressed” were overrepresented. All genes were prioritized and we selected the top five genes for validation at population level. Combined results from the three GWASs samples, rs7522101 in ESRRG remained significantly associated with BMI after multiple testing corrections (P = 7.25 × 10−5). It was also associated with β-cell function (P = 1.99 × 10−3) and fasting glucose level (P < 0.05) in the meta-analyses of glucose and insulin-related traits consortium (MAGIC) dataset. CONCLUSIONS In summary, we identified epigenomic characteristics for obesity genes and suggested ESRRG as a novel obesity susceptibility gene. PMID:27113491

Integrated analyses for genetic markers of polycystic ovary syndrome with 9 case-control studies of gene expression profiles.

PubMed

Lu, Chenqi; Liu, Xiaoqin; Wang, Lin; Jiang, Ning; Yu, Jun; Zhao, Xiaobo; Hu, Hairong; Zheng, Saihua; Li, Xuelian; Wang, Guiying

2017-01-10

Due to genetic heterogeneity and variable diagnostic criteria, genetic studies of polycystic ovary syndrome are particularly challenging. Furthermore, lack of sufficiently large cohorts limits the identification of susceptibility genes contributing to polycystic ovary syndrome. Here, we carried out a systematic search of studies deposited in the Gene Expression Omnibus database through August 31, 2016. The present analyses included studies with: 1) patients with polycystic ovary syndrome and normal controls, 2) gene expression profiling of messenger RNA, and 3) sufficient data for our analysis. Ultimately, a total of 9 studies with 13 datasets met the inclusion criteria and were performed for the subsequent integrated analyses. Through comprehensive analyses, there were 13 genetic factors overlapped in all datasets and identified as significant specific genes for polycystic ovary syndrome. After quality control assessment, there were six datasets remained. Further gene ontology enrichment and pathway analyses suggested that differentially expressed genes mainly enriched in oocyte pathways. These findings provide potential molecular markers for diagnosis and prognosis of polycystic ovary syndrome, and need in-depth studies on the exact function and mechanism in polycystic ovary syndrome.

AMP kinase-related kinase NUAK2 affects tumor growth, migration, and clinical outcome of human melanoma.

PubMed

Namiki, Takeshi; Tanemura, Atsushi; Valencia, Julio C; Coelho, Sergio G; Passeron, Thierry; Kawaguchi, Masakazu; Vieira, Wilfred D; Ishikawa, Masashi; Nishijima, Wataru; Izumo, Toshiyuki; Kaneko, Yasuhiko; Katayama, Ichiro; Yamaguchi, Yuji; Yin, Lanlan; Polley, Eric C; Liu, Hongfang; Kawakami, Yutaka; Eishi, Yoshinobu; Takahashi, Eishi; Yokozeki, Hiroo; Hearing, Vincent J

2011-04-19

The identification of genes that participate in melanomagenesis should suggest strategies for developing therapeutic modalities. We used a public array comparative genomic hybridization (CGH) database and real-time quantitative PCR (qPCR) analyses to identify the AMP kinase (AMPK)-related kinase NUAK2 as a candidate gene for melanomagenesis, and we analyzed its functions in melanoma cells. Our analyses had identified a locus at 1q32 where genomic gain is strongly associated with tumor thickness, and we used real-time qPCR analyses and regression analyses to identify NUAK2 as a candidate gene at that locus. Associations of relapse-free survival and overall survival of 92 primary melanoma patients with NUAK2 expression measured using immunohistochemistry were investigated using Kaplan-Meier curves, log rank tests, and Cox regression models. Knockdown of NUAK2 induces senescence and reduces S-phase, decreases migration, and down-regulates expression of mammalian target of rapamycin (mTOR). In vivo analysis demonstrated that knockdown of NUAK2 suppresses melanoma tumor growth in mice. Survival analysis showed that the risk of relapse is greater in acral melanoma patients with high levels of NUAK2 expression than in acral melanoma patients with low levels of NUAK2 expression (hazard ratio = 3.88; 95% confidence interval = 1.44-10.50; P = 0.0075). These data demonstrate that NUAK2 expression is significantly associated with the oncogenic features of melanoma cells and with the survival of acral melanoma patients. NUAK2 may provide a drug target to suppress melanoma progression. This study further supports the importance of NUAK2 in cancer development and tumor progression, while AMPK has antioncogenic properties.

Can Preoperative Psychological Assessment Predict Outcomes After Temporomandibular Joint Arthroscopy?

PubMed

Bouloux, Gary F; Zerweck, Ashley G; Celano, Marianne; Dai, Tian; Easley, Kirk A

2015-11-01

Psychological assessment has been used successfully to predict patient outcomes after cardiothoracic and bariatric surgery. The purpose of this study was to determine whether preoperative psychological assessment could be used to predict patient outcomes after temporomandibular joint arthroscopy. Consecutive patients with temporomandibular dysfunction (TMD) who could benefit from arthroscopy were enrolled in a prospective cohort study. All patients completed the Millon Behavior Medicine Diagnostic survey before surgery. The primary predictor variable was the preoperative psychological scores. The primary outcome variable was the difference in pain between the pre- and postoperative periods. The Spearman rank correlation coefficient and the Pearson product-moment correlation were used to determine the association between psychological factors and change in pain. Univariable and multivariable analyses were performed using a mixed-effects linear model and multiple linear regression. A P value of .05 was considered significant. Eighty-six patients were enrolled in the study. Seventy-five patients completed the study and were included in the final analyses. The mean change in visual analog scale (VAS) pain score 1 month after arthroscopy was -15.4 points (95% confidence interval, -6.0 to -24.7; P < .001). Jaw function also improved after surgery (P < .001). No association between change in VAS pain score and each of the 5 preoperative psychological factors was identified with univariable correlation analyses. Multivariable analyses identified that a greater pain decrease was associated with a longer duration of preoperative symptoms (P = .054) and lower chronic anxiety (P = .064). This study has identified a weak association between chronic anxiety and the magnitude of pain decrease after arthroscopy for TMD. Further studies are needed to clarify the role of chronic anxiety in the outcome after surgical procedures for the treatment of TMD. Copyright © 2015. Published by Elsevier Inc.

Systematic review of publications on economic evaluations of caries prevention programs.

PubMed

Mariño, R J; Khan, A R; Morgan, M

2013-01-01

The aim of this study was to perform a systematic review of economic evaluations (EEs) of dental caries prevention programs to objectively retrieve, synthesize and describe available information on the field. Several strategies were combined to search for literature published between January 1975 and April 2012. MEDLINE, EconoLit and ISI formed the basis of the literature search. The study selection was done using predefined inclusion and exclusion criteria. Bibliographic listings of all retrieved articles were hand-searched. The search identified 206 references. An evaluative framework was developed based on the Centre for Reviews and Dissemination's 'Guidance for undertaking reviews in health care' (York University, 2009). Background information included publication vehicle, year of publication, geographic focus, type of preventive program and type of economic analysis. 63 studies were included in the review. The most common preventive strategies evaluated were dental sealants (n = 13), water fluoridation (n = 12) and mixed interventions (n = 12). By type of EE undertaken, 30 were cost-effectiveness analyses, 22 were cost-benefit analyses, and 5 presented both cost-effectiveness and cost-benefit analyses. Few studies were cost-utility analyses (n = 5) or cost minimization analyses (n = 2). By year of publication, most were published after 2003. The review revealed that, although the number of publications reporting EEs has increased significantly in recent years, the quality of the reporting needs to be improved. The main methodological problems identified in the review were the limited information provided on adjustments for discounting in addition to inadequate sensitivity analyses. Attention also needs to be given to the analysis and interpretation of the results of the EEs. Copyright © 2013 S. Karger AG, Basel.

Genome-wide significant localization for working and spatial memory: Identifying genes for psychosis using models of cognition.

PubMed

Knowles, Emma E M; Carless, Melanie A; de Almeida, Marcio A A; Curran, Joanne E; McKay, D Reese; Sprooten, Emma; Dyer, Thomas D; Göring, Harald H; Olvera, Rene; Fox, Peter; Almasy, Laura; Duggirala, Ravi; Kent, Jack W; Blangero, John; Glahn, David C

2014-01-01

It is well established that risk for developing psychosis is largely mediated by the influence of genes, but identifying precisely which genes underlie that risk has been problematic. Focusing on endophenotypes, rather than illness risk, is one solution to this problem. Impaired cognition is a well-established endophenotype of psychosis. Here we aimed to characterize the genetic architecture of cognition using phenotypically detailed models as opposed to relying on general IQ or individual neuropsychological measures. In so doing we hoped to identify genes that mediate cognitive ability, which might also contribute to psychosis risk. Hierarchical factor models of genetically clustered cognitive traits were subjected to linkage analysis followed by QTL region-specific association analyses in a sample of 1,269 Mexican American individuals from extended pedigrees. We identified four genome wide significant QTLs, two for working and two for spatial memory, and a number of plausible and interesting candidate genes. The creation of detailed models of cognition seemingly enhanced the power to detect genetic effects on cognition and provided a number of possible candidate genes for psychosis. © 2013 Wiley Periodicals, Inc.

Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium

PubMed Central

Lu, Yingchang; Justice, Anne E.; Mudgal, Poorva; Liu, Ching-Ti; Young, Kristin; Feitosa, Mary F.; Rand, Kristin; Dimitrov, Latchezar; Duan, Qing; Guo, Xiuqing; Lange, Leslie A.; Nalls, Michael A.; Okut, Hayrettin; Tayo, Bamidele O.; Vedantam, Sailaja; Bradfield, Jonathan P.; Chen, Guanjie; Chesi, Alessandra; Irvin, Marguerite R.; Padhukasahasram, Badri; Zheng, Wei; Allison, Matthew A.; Ambrosone, Christine B.; Bandera, Elisa V.; Berndt, Sonja I.; Blot, William J.; Bottinger, Erwin P.; Carpten, John; Chanock, Stephen J.; Chen, Yii-Der Ida; Conti, David V.; Cooper, Richard S.; Fornage, Myriam; Freedman, Barry I.; Garcia, Melissa; Goodman, Phyllis J.; Hsu, Yu-Han H.; Hu, Jennifer; Huff, Chad D.; Ingles, Sue A.; John, Esther M.; Kittles, Rick; Klein, Eric; Li, Jin; McKnight, Barbara; Nayak, Uma; Nemesure, Barbara; Olshan, Andrew; Salako, Babatunde; Sanderson, Maureen; Shao, Yaming; Siscovick, David S.; Stanford, Janet L.; Strom, Sara S.; Witte, John S.; Yao, Jie; Zhu, Xiaofeng; Ziegler, Regina G.; Zonderman, Alan B.; Ambs, Stefan; Cushman, Mary; Faul, Jessica D.; Hakonarson, Hakon; Levin, Albert M.; Nathanson, Katherine L.; Weir, David R.; Zhi, Degui; Arnett, Donna K.; Kardia, Sharon L. R.; Oloapde, Olufunmilayo I.; Rao, D. C.; Williams, L. Keoki; Becker, Diane M.; Borecki, Ingrid B.; Evans, Michele K.; Harris, Tamara B.; Hirschhorn, Joel N.; Psaty, Bruce M.; Wilson, James G.; Bowden, Donald W.; Cupples, L. Adrienne; Haiman, Christopher A.; Loos, Ruth J. F.; North, Kari E.

2017-01-01

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10−8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations. PMID:28430825

Cancer-related identity and positive affect in survivors of prostate cancer.

PubMed

Bellizzi, Keith M; Blank, Thomas O

2007-03-01

Despite a shift in the cancer culture and language used to describe individuals diagnosed with this disease, the extent to which individuals with cancer adopt a particular cancer-related identity and the impact of these identities in relation to their well-being is virtually unknown. Using a cross-sectional study design and a metropolitan tumor registry, a mail questionnaire to examine post-treatment quality of life was sent to prostate cancer (PCa) survivors. The sample consisted of 490 PCa survivors, ranging in age from 49-88 (M = 69.7; SD = 7.8), one to eight years after diagnosis. The outcome measure used in these analyses was the PANAS to assess positive and negative affect. The most frequently reported cancer-related identity was "someone who has had PCa" (57%). The least reported self view was "victim" (1%). Twenty-six percent of men self-identified as "survivors" while 6% thought of themselves as "cancer conquerors." Only 9% self-identified as a "patient." Multivariate analyses, adjusted for potential confounders, show respondents who identified themselves as "survivors" or "cancer conquerors" reported significantly higher scores on positive affect than men who self-identified as "patients" (p < .001). Although the majority of respondents identified themselves as "someone who has had cancer," identifying as a "survivor" or "someone who has conquered cancer" appears to have adaptive value for positive mood. Those who perceive themselves as survivors of prostate cancer may derive some benefit in well-being associated with this self assessment.

Maintenance: organizational modes, activities and health and safety. Use of a French national survey and in-situ analyses.

PubMed

Grusenmeyer, Corinne

2014-12-01

Maintenance activities are identified as critical both to operator safety and to systems safety and reliability. However, it is still difficult to identify maintenance workers in French occupational accident and disease statistics. Moreover, few analyses of these activities and of organizational changes in this field have been conducted. This paper presents two different approaches to this same issue. Analyses were aimed firstly at identifying the occupational exposures of these operators and at comparing them with occupational exposures of production staff and, secondly at developing understanding of normal real maintenance activities, i.e. maintenance activities that are normally actually carried out, while taking into account the socio-technical system and maintenance organization within which they lie. The use of the French SUMER 2003 survey shows that occupational exposures of maintenance staff to various constraints are more frequent than occupational exposures of their production colleagues. However, maintenance staff appear to have greater independence. Analyses were also conducted in a subcontracting urban public transport company, who outsources some maintenance work. Those analyses highlight a complex network of companies involved in maintenance activities, a substantial number of work interruptions and a significant fragmentation of the internal technicians' activities that can be cognitively costly, reduce anticipation possibilities and lead to incidents or accidents. Above all they underline internal technicians' contributions to the completion of outsourced interventions and interdependent relationships between the activities of the internal and the external technicians. Outsourcing maintenance interventions thus raises the question of risks associated with the interdependence of actual work activities undertaken by the different types of staff, since they contribute to the same maintenance intervention. This study therefore pinpoints the need to integrate inter-organizational interactions in order to understand the variability of maintenance activities and its relationships with reliability and safety. In this respect, some suggestions are provided with a prevention aim. Copyright © 2014 Elsevier Ltd. All rights reserved.

PCR Primers for Metazoan Nuclear 18S and 28S Ribosomal DNA Sequences

PubMed Central

Machida, Ryuji J.; Knowlton, Nancy

2012-01-01

Background Metagenetic analyses, which amplify and sequence target marker DNA regions from environmental samples, are increasingly employed to assess the biodiversity of communities of small organisms. Using this approach, our understanding of microbial diversity has expanded greatly. In contrast, only a few studies using this approach to characterize metazoan diversity have been reported, despite the fact that many metazoan species are small and difficult to identify or are undescribed. One of the reasons for this discrepancy is the availability of universal primers for the target taxa. In microbial studies, analysis of the 16S ribosomal DNA is standard. In contrast, the best gene for metazoan metagenetics is less clear. In the present study, we have designed primers that amplify the nuclear 18S and 28S ribosomal DNA sequences of most metazoan species with the goal of providing effective approaches for metagenetic analyses of metazoan diversity in environmental samples, with a particular emphasis on marine biodiversity. Methodology/Principal Findings Conserved regions suitable for designing PCR primers were identified using 14,503 and 1,072 metazoan sequences of the nuclear 18S and 28S rDNA regions, respectively. The sequence similarity of both these newly designed and the previously reported primers to the target regions of these primers were compared for each phylum to determine the expected amplification efficacy. The nucleotide diversity of the flanking regions of the primers was also estimated for genera or higher taxonomic groups of 11 phyla to determine the variable regions within the genes. Conclusions/Significance The identified nuclear ribosomal DNA primers (five primer pairs for 18S and eleven for 28S) and the results of the nucleotide diversity analyses provide options for primer combinations for metazoan metagenetic analyses. Additionally, advantages and disadvantages of not only the 18S and 28S ribosomal DNA, but also other marker regions as targets for metazoan metagenetic analyses, are discussed. PMID:23049971

Predictors of persistent pain after total knee arthroplasty: a systematic review and meta-analysis.

PubMed

Lewis, G N; Rice, D A; McNair, P J; Kluger, M

2015-04-01

Several studies have identified clinical, psychosocial, patient characteristic, and perioperative variables that are associated with persistent postsurgical pain; however, the relative effect of these variables has yet to be quantified. The aim of the study was to provide a systematic review and meta-analysis of predictor variables associated with persistent pain after total knee arthroplasty (TKA). Included studies were required to measure predictor variables prior to or at the time of surgery, include a pain outcome measure at least 3 months post-TKA, and include a statistical analysis of the effect of the predictor variable(s) on the outcome measure. Counts were undertaken of the number of times each predictor was analysed and the number of times it was found to have a significant relationship with persistent pain. Separate meta-analyses were performed to determine the effect size of each predictor on persistent pain. Outcomes from studies implementing uni- and multivariable statistical models were analysed separately. Thirty-two studies involving almost 30 000 patients were included in the review. Preoperative pain was the predictor that most commonly demonstrated a significant relationship with persistent pain across uni- and multivariable analyses. In the meta-analyses of data from univariate models, the largest effect sizes were found for: other pain sites, catastrophizing, and depression. For data from multivariate models, significant effects were evident for: catastrophizing, preoperative pain, mental health, and comorbidities. Catastrophizing, mental health, preoperative knee pain, and pain at other sites are the strongest independent predictors of persistent pain after TKA. © The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Perturbation analyses of intermolecular interactions

NASA Astrophysics Data System (ADS)

Koyama, Yohei M.; Kobayashi, Tetsuya J.; Ueda, Hiroki R.

2011-08-01

Conformational fluctuations of a protein molecule are important to its function, and it is known that environmental molecules, such as water molecules, ions, and ligand molecules, significantly affect the function by changing the conformational fluctuations. However, it is difficult to systematically understand the role of environmental molecules because intermolecular interactions related to the conformational fluctuations are complicated. To identify important intermolecular interactions with regard to the conformational fluctuations, we develop herein (i) distance-independent and (ii) distance-dependent perturbation analyses of the intermolecular interactions. We show that these perturbation analyses can be realized by performing (i) a principal component analysis using conditional expectations of truncated and shifted intermolecular potential energy terms and (ii) a functional principal component analysis using products of intermolecular forces and conditional cumulative densities. We refer to these analyses as intermolecular perturbation analysis (IPA) and distance-dependent intermolecular perturbation analysis (DIPA), respectively. For comparison of the IPA and the DIPA, we apply them to the alanine dipeptide isomerization in explicit water. Although the first IPA principal components discriminate two states (the α state and PPII (polyproline II) + β states) for larger cutoff length, the separation between the PPII state and the β state is unclear in the second IPA principal components. On the other hand, in the large cutoff value, DIPA eigenvalues converge faster than that for IPA and the top two DIPA principal components clearly identify the three states. By using the DIPA biplot, the contributions of the dipeptide-water interactions to each state are analyzed systematically. Since the DIPA improves the state identification and the convergence rate with retaining distance information, we conclude that the DIPA is a more practical method compared with the IPA. To test the feasibility of the DIPA for larger molecules, we apply the DIPA to the ten-residue chignolin folding in explicit water. The top three principal components identify the four states (native state, two misfolded states, and unfolded state) and their corresponding eigenfunctions identify important chignolin-water interactions to each state. Thus, the DIPA provides the practical method to identify conformational states and their corresponding important intermolecular interactions with distance information.

Perturbation analyses of intermolecular interactions.

PubMed

Koyama, Yohei M; Kobayashi, Tetsuya J; Ueda, Hiroki R

2011-08-01

Conformational fluctuations of a protein molecule are important to its function, and it is known that environmental molecules, such as water molecules, ions, and ligand molecules, significantly affect the function by changing the conformational fluctuations. However, it is difficult to systematically understand the role of environmental molecules because intermolecular interactions related to the conformational fluctuations are complicated. To identify important intermolecular interactions with regard to the conformational fluctuations, we develop herein (i) distance-independent and (ii) distance-dependent perturbation analyses of the intermolecular interactions. We show that these perturbation analyses can be realized by performing (i) a principal component analysis using conditional expectations of truncated and shifted intermolecular potential energy terms and (ii) a functional principal component analysis using products of intermolecular forces and conditional cumulative densities. We refer to these analyses as intermolecular perturbation analysis (IPA) and distance-dependent intermolecular perturbation analysis (DIPA), respectively. For comparison of the IPA and the DIPA, we apply them to the alanine dipeptide isomerization in explicit water. Although the first IPA principal components discriminate two states (the α state and PPII (polyproline II) + β states) for larger cutoff length, the separation between the PPII state and the β state is unclear in the second IPA principal components. On the other hand, in the large cutoff value, DIPA eigenvalues converge faster than that for IPA and the top two DIPA principal components clearly identify the three states. By using the DIPA biplot, the contributions of the dipeptide-water interactions to each state are analyzed systematically. Since the DIPA improves the state identification and the convergence rate with retaining distance information, we conclude that the DIPA is a more practical method compared with the IPA. To test the feasibility of the DIPA for larger molecules, we apply the DIPA to the ten-residue chignolin folding in explicit water. The top three principal components identify the four states (native state, two misfolded states, and unfolded state) and their corresponding eigenfunctions identify important chignolin-water interactions to each state. Thus, the DIPA provides the practical method to identify conformational states and their corresponding important intermolecular interactions with distance information.

Genetic analyses reveal unusually high diversity of infectious haematopoietic necrosis virus in rainbow trout aquaculture

USGS Publications Warehouse

Troyer, Ryan M.; LaPatra, Scott E.; Kurath, Gael

2000-01-01

Infectious haematopoietic necrosis virus (IHNV) is the most significant virus pathogen of salmon and trout in North America. Previous studies have shown relatively low genetic diversity of IHNV within large geographical regions. In this study, the genetic heterogeneity of 84 IHNV isolates sampled from rainbow trout (Oncorhynchus mykiss) over a 20 year period at four aquaculture facilities within a 12 mile stretch of the Snake River in Idaho, USA was investigated. The virus isolates were characterized using an RNase protection assay (RPA) and nucleotide sequence analyses. Among the 84 isolates analysed, 46 RPA haplotypes were found and analyses revealed a high level of genetic heterogeneity relative to that detected in other regions. Sequence analyses revealed up to 7·6% nucleotide divergence, which is the highest level of diversity reported for IHNV to date. Phylogenetic analyses identified four distinct monophyletic clades representing four virus lineages. These lineages were distributed across facilities, and individual facilities contained multiple lineages. These results suggest that co-circulating IHNV lineages of relatively high genetic diversity are present in the IHNV populations in this rainbow trout culture study site. Three of the four lineages exhibited temporal trends consistent with rapid evolution.

Measuring the youth bullying experience: a systematic review of the psychometric properties of available instruments.

PubMed

Vessey, Judith; Strout, Tania D; DiFazio, Rachel L; Walker, Allison

2014-12-01

Bullying is a significant problem in schools and measuring this concept remains problematic. The purposes of this study were to (1) identify the published self-report measures developed to assess youth bullying; (2) evaluate their psychometric properties and instrument characteristics; and (3) evaluate the quality of identified psychometric papers evaluating youth bullying measures. A systematic review of the literature was conducted using 4 electronic databases. Data extraction and appraisal of identified instruments were completed using a standardized method and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Thirty-one articles describing 27 self-report instruments were evaluated in our analysis. Quality assessments ranged from 18% to 91%, with 6 papers reaching or exceeding a quality score of 75%. Limited evidence supporting the reliability, validity, and responsiveness of existing youth bullying measures was identified. Evidence supporting the psychometric soundness of the instruments identified was limited. Many measures were in early development and additional evaluation is necessary to validate their psychometric properties. A pool of instruments possesses acceptable initial psychometric dependability for selected assessment purposes. These findings have significant implications for assessing youth bullying and designing and evaluating school-based interventions. © 2014, American School Health Association.

Personalized genomic analyses for cancer mutation discovery and interpretation

PubMed Central

Jones, Siân; Anagnostou, Valsamo; Lytle, Karli; Parpart-Li, Sonya; Nesselbush, Monica; Riley, David R.; Shukla, Manish; Chesnick, Bryan; Kadan, Maura; Papp, Eniko; Galens, Kevin G.; Murphy, Derek; Zhang, Theresa; Kann, Lisa; Sausen, Mark; Angiuoli, Samuel V.; Diaz, Luis A.; Velculescu, Victor E.

2015-01-01

Massively parallel sequencing approaches are beginning to be used clinically to characterize individual patient tumors and to select therapies based on the identified mutations. A major question in these analyses is the extent to which these methods identify clinically actionable alterations and whether the examination of the tumor tissue alone is sufficient or whether matched normal DNA should also be analyzed to accurately identify tumor-specific (somatic) alterations. To address these issues, we comprehensively evaluated 815 tumor-normal paired samples from patients of 15 tumor types. We identified genomic alterations using next-generation sequencing of whole exomes or 111 targeted genes that were validated with sensitivities >95% and >99%, respectively, and specificities >99.99%. These analyses revealed an average of 140 and 4.3 somatic mutations per exome and targeted analysis, respectively. More than 75% of cases had somatic alterations in genes associated with known therapies or current clinical trials. Analyses of matched normal DNA identified germline alterations in cancer-predisposing genes in 3% of patients with apparently sporadic cancers. In contrast, a tumor-only sequencing approach could not definitively identify germline changes in cancer-predisposing genes and led to additional false-positive findings comprising 31% and 65% of alterations identified in targeted and exome analyses, respectively, including in potentially actionable genes. These data suggest that matched tumor-normal sequencing analyses are essential for precise identification and interpretation of somatic and germline alterations and have important implications for the diagnostic and therapeutic management of cancer patients. PMID:25877891

Frontotemporal dementia and its subtypes: a genome-wide association study.

PubMed

Ferrari, Raffaele; Hernandez, Dena G; Nalls, Michael A; Rohrer, Jonathan D; Ramasamy, Adaikalavan; Kwok, John B J; Dobson-Stone, Carol; Brooks, William S; Schofield, Peter R; Halliday, Glenda M; Hodges, John R; Piguet, Olivier; Bartley, Lauren; Thompson, Elizabeth; Haan, Eric; Hernández, Isabel; Ruiz, Agustín; Boada, Mercè; Borroni, Barbara; Padovani, Alessandro; Cruchaga, Carlos; Cairns, Nigel J; Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta; Forloni, Gianluigi; Galimberti, Daniela; Fenoglio, Chiara; Serpente, Maria; Scarpini, Elio; Clarimón, Jordi; Lleó, Alberto; Blesa, Rafael; Waldö, Maria Landqvist; Nilsson, Karin; Nilsson, Christer; Mackenzie, Ian R A; Hsiung, Ging-Yuek R; Mann, David M A; Grafman, Jordan; Morris, Christopher M; Attems, Johannes; Griffiths, Timothy D; McKeith, Ian G; Thomas, Alan J; Pietrini, P; Huey, Edward D; Wassermann, Eric M; Baborie, Atik; Jaros, Evelyn; Tierney, Michael C; Pastor, Pau; Razquin, Cristina; Ortega-Cubero, Sara; Alonso, Elena; Perneczky, Robert; Diehl-Schmid, Janine; Alexopoulos, Panagiotis; Kurz, Alexander; Rainero, Innocenzo; Rubino, Elisa; Pinessi, Lorenzo; Rogaeva, Ekaterina; St George-Hyslop, Peter; Rossi, Giacomina; Tagliavini, Fabrizio; Giaccone, Giorgio; Rowe, James B; Schlachetzki, Johannes C M; Uphill, James; Collinge, John; Mead, Simon; Danek, Adrian; Van Deerlin, Vivianna M; Grossman, Murray; Trojanowski, John Q; van der Zee, Julie; Deschamps, William; Van Langenhove, Tim; Cruts, Marc; Van Broeckhoven, Christine; Cappa, Stefano F; Le Ber, Isabelle; Hannequin, Didier; Golfier, Véronique; Vercelletto, Martine; Brice, Alexis; Nacmias, Benedetta; Sorbi, Sandro; Bagnoli, Silvia; Piaceri, Irene; Nielsen, Jørgen E; Hjermind, Lena E; Riemenschneider, Matthias; Mayhaus, Manuel; Ibach, Bernd; Gasparoni, Gilles; Pichler, Sabrina; Gu, Wei; Rossor, Martin N; Fox, Nick C; Warren, Jason D; Spillantini, Maria Grazia; Morris, Huw R; Rizzu, Patrizia; Heutink, Peter; Snowden, Julie S; Rollinson, Sara; Richardson, Anna; Gerhard, Alexander; Bruni, Amalia C; Maletta, Raffaele; Frangipane, Francesca; Cupidi, Chiara; Bernardi, Livia; Anfossi, Maria; Gallo, Maura; Conidi, Maria Elena; Smirne, Nicoletta; Rademakers, Rosa; Baker, Matt; Dickson, Dennis W; Graff-Radford, Neill R; Petersen, Ronald C; Knopman, David; Josephs, Keith A; Boeve, Bradley F; Parisi, Joseph E; Seeley, William W; Miller, Bruce L; Karydas, Anna M; Rosen, Howard; van Swieten, John C; Dopper, Elise G P; Seelaar, Harro; Pijnenburg, Yolande A L; Scheltens, Philip; Logroscino, Giancarlo; Capozzo, Rosa; Novelli, Valeria; Puca, Annibale A; Franceschi, Massimo; Postiglione, Alfredo; Milan, Graziella; Sorrentino, Paolo; Kristiansen, Mark; Chiang, Huei-Hsin; Graff, Caroline; Pasquier, Florence; Rollin, Adeline; Deramecourt, Vincent; Lebert, Florence; Kapogiannis, Dimitrios; Ferrucci, Luigi; Pickering-Brown, Stuart; Singleton, Andrew B; Hardy, John; Momeni, Parastoo

2014-07-01

Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72--have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10(-8)) single-nucleotide polymorphisms. We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10(-8)). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, HLA locus (immune system), for rs9268877 (p=1·05 × 10(-8); odds ratio=1·204 [95% CI 1·11-1·30]), rs9268856 (p=5·51 × 10(-9); 0·809 [0·76-0·86]) and rs1980493 (p value=1·57 × 10(-8), 0·775 [0·69-0·86]) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural FTD subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10(-7); 0·814 [0·71-0·92]). Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation in cis. Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and to shed light on the pathomechanisms contributing to FTD. The National Institute of Neurological Disorders and Stroke and National Institute on Aging, the Wellcome/MRC Centre on Parkinson's disease, Alzheimer's Research UK, and Texas Tech University Health Sciences Center. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genome-Wide Associations between Genetic and Epigenetic Variation Influence mRNA Expression and Insulin Secretion in Human Pancreatic Islets

PubMed Central

Olsson, Anders H.; Volkov, Petr; Bacos, Karl; Dayeh, Tasnim; Hall, Elin; Nilsson, Emma A.; Ladenvall, Claes; Rönn, Tina; Ling, Charlotte

2014-01-01

Genetic and epigenetic mechanisms may interact and together affect biological processes and disease development. However, most previous studies have investigated genetic and epigenetic mechanisms independently, and studies examining their interactions throughout the human genome are lacking. To identify genetic loci that interact with the epigenome, we performed the first genome-wide DNA methylation quantitative trait locus (mQTL) analysis in human pancreatic islets. We related 574,553 single nucleotide polymorphisms (SNPs) with genome-wide DNA methylation data of 468,787 CpG sites targeting 99% of RefSeq genes in islets from 89 donors. We identified 67,438 SNP-CpG pairs in cis, corresponding to 36,783 SNPs (6.4% of tested SNPs) and 11,735 CpG sites (2.5% of tested CpGs), and 2,562 significant SNP-CpG pairs in trans, corresponding to 1,465 SNPs (0.3% of tested SNPs) and 383 CpG sites (0.08% of tested CpGs), showing significant associations after correction for multiple testing. These include reported diabetes loci, e.g. ADCY5, KCNJ11, HLA-DQA1, INS, PDX1 and GRB10. CpGs of significant cis-mQTLs were overrepresented in the gene body and outside of CpG islands. Follow-up analyses further identified mQTLs associated with gene expression and insulin secretion in human islets. Causal inference test (CIT) identified SNP-CpG pairs where DNA methylation in human islets is the potential mediator of the genetic association with gene expression or insulin secretion. Functional analyses further demonstrated that identified candidate genes (GPX7, GSTT1 and SNX19) directly affect key biological processes such as proliferation and apoptosis in pancreatic β-cells. Finally, we found direct correlations between DNA methylation of 22,773 (4.9%) CpGs with mRNA expression of 4,876 genes, where 90% of the correlations were negative when CpGs were located in the region surrounding transcription start site. Our study demonstrates for the first time how genome-wide genetic and epigenetic variation interacts to influence gene expression, islet function and potential diabetes risk in humans. PMID:25375650

What Makes Sports Fans Interactive? Identifying Factors Affecting Chat Interactions in Online Sports Viewing

PubMed Central

Yeo, Jaeryong; Lee, Juyeong

2016-01-01

Sports fans are able to watch games from many locations using TV services while interacting with other fans online. In this paper, we identify the factors that affect sports viewers’ online interactions. Using a large-scale dataset of more than 25 million chat messages from a popular social TV site for baseball, we extract various game-related factors, and investigate the relationships between these factors and fans’ interactions using a series of multiple regression analyses. As a result, we identify several factors that are significantly related to viewer interactions. In addition, we determine that the influence of these factors varies according to the user group; i.e., active vs. less active users, and loyal vs. non-loyal users. PMID:26849568

Gender differences in depression severity and symptoms across depressive sub-types.

PubMed

Parker, Gordon; Fletcher, Kathryn; Paterson, Amelia; Anderson, Josephine; Hong, Michael

2014-01-01

Lifetime rates of depression are distinctly higher in women reflecting both real and artefactual influences. Most prevalence studies quantifying a female preponderance have examined severity-based diagnostic groups such as major depression or dysthymia. We examined gender differences across three depressive sub-type conditions using four differing measures to determine whether any gender differences emerge more from severity or symptom prevalence, reflect nuances of the particular measure, or whether depressive sub-type is influential. A large clinical sample was recruited. Patients completed two severity-weighted depression measures: the Depression in the Medically Ill 10 (DMI-10) and Quick Inventory of Depressive Symptoms-Self-Report (QIDS-SR) and two measures weighting symptoms and illness correlates of melancholic and non-melancholic depressive disorders - the Severity of Depressive Symptoms (SDS) and Sydney Melancholia Prototype Index (SMPI). Analyses were undertaken of three diagnostic groups comprising those with unipolar melancholic, unipolar non-melancholic and bipolar depressive conditions. Women in the two unipolar groups scored only marginally (and non-significantly) higher than men on the depression severity measures. Women in the bipolar depression group, did however, score significantly higher than men on depression severity. On measures weighted to assessing melancholic and non-melancholic symptoms, there were relatively few gender differences identified in the melancholic and non-melancholic sub-sets, while more gender differences were quantified in the bipolar sub-set. The symptoms most commonly and consistently differentiating by gender were those assessing appetite/weight change and psychomotor disturbance. Our analyses of several measures and the minimal differentiation of depressive symptoms and symptom severity argues against any female preponderance in unipolar depression being contributed to distinctly by these depression rating measures. Our analyses indicated that gender had minimal if any impact on depression severity estimates. Gender differences in depressive symptoms and severity were more distinctive in bipolar patients, a finding seemingly not previously identified or reported. The study had considerable power reflecting large sample sizes and thus risks assigning significant differences where none truly exist, although we repeated analyses after controlling for the type I error rate. Copyright © 2014 Elsevier B.V. All rights reserved.

Robust and Comprehensive Analysis of 20 Osteoporosis Candidate Genes by Very High-Density Single-Nucleotide Polymorphism Screen Among 405 White Nuclear Families Identified Significant Association and Gene–Gene Interaction

PubMed Central

Xiong, Dong-Hai; Shen, Hui; Zhao, Lan-Juan; Xiao, Peng; Yang, Tie-Lin; Guo, Yan; Wang, Wei; Guo, Yan-Fang; Liu, Yong-Jun; Recker, Robert R; Deng, Hong-Wen

2007-01-01

Many “novel” osteoporosis candidate genes have been proposed in recent years. To advance our knowledge of their roles in osteoporosis, we screened 20 such genes using a set of high-density SNPs in a large family-based study. Our efforts led to the prioritization of those osteoporosis genes and the detection of gene–gene interactions. Introduction We performed large-scale family-based association analyses of 20 novel osteoporosis candidate genes using 277 single nucleotide polymorphisms (SNPs) for the quantitative trait BMD variation and the qualitative trait osteoporosis (OP) at three clinically important skeletal sites: spine, hip, and ultradistal radius (UD). Materials and Methods One thousand eight hundred seventy-three subjects from 405 white nuclear families were genotyped and analyzed with an average density of one SNP per 4 kb across the 20 genes. We conducted association analyses by SNP- and haplotype-based family-based association test (FBAT) and performed gene–gene interaction analyses using multianalytic approaches such as multifactor-dimensionality reduction (MDR) and conditional logistic regression. Results and Conclusions We detected four genes (DBP, LRP5, CYP17, and RANK) that showed highly suggestive associations (10,000-permutation derived empirical global p ≤ 0.01) with spine BMD/OP; four genes (CYP19, RANK, RANKL, and CYP17) highly suggestive for hip BMD/OP; and four genes (CYP19, BMP2, RANK, and TNFR2) highly suggestive for UD BMD/OP. The associations between BMP2 with UD BMD and those between RANK with OP at the spine, hip, and UD also met the experiment-wide stringent criterion (empirical global p ≤ 0.0007). Sex-stratified analyses further showed that some of the significant associations in the total sample were driven by either male or female subjects. In addition, we identified and validated a two-locus gene–gene interaction model involving GCR and ESR2, for which prior biological evidence exists. Our results suggested the prioritization of osteoporosis candidate genes from among the many proposed in recent years and revealed the significant gene–gene interaction effects influencing osteoporosis risk. PMID:17002564

Expression of thymidylate synthase (TS) and its prognostic significance in patients with cutaneous angiosarcoma.

PubMed

Shimizu, A; Kaira, K; Okubo, Y; Utsumi, D; Bolag, A; Yasuda, M; Takahashi, K; Ishikawa, O

2017-01-01

Cutaneous angiosarcoma (CA) is extremely rare, and little is known about the biological significance of possible biomarkers for chemotherapeutic agents. Thymidylate synthase (TS) is an attractive target for cancer treatment in various human neoplasms. It remains unclear whether the expression of TS is associated with the clinicopathological features of CA patients. The aim of this study was to elucidate the relationship between TS expression and the clinicopathological significance in CA patients. Fifty-one patients with CA were included in this study. TS expression and Ki-67 labeling index were examined using immunohistochemical analysis. TS was positively expressed in 39% (20/51) of CA patients. No statistically significant prognostic factor was identified as a predictor of overall survival (OS) for all patients by univariate analysis, whereas a significant prognostic variable for progression free survival (PFS) was found to be the clinical stage. In addition, both univariate and multivariate analyses confirmed that positive expression of TS was a significant predictor of worse PFS in CA patients of clinical stage 1. Positive TS expression in CA was identified as a significant predictor of worse outcome in patients of clinical stage 1.

Diagnosis isn't enough: Understanding the connections between high health care utilization, chronic conditions and disabilities among U.S. working age adults.

PubMed

Reichard, Amanda; Gulley, Stephen P; Rasch, Elizabeth K; Chan, Leighton

2015-10-01

Under the ACA, new programs are being developed to enhance care coordination and reduce health care costs among people with chronic conditions, disabilities, and high utilization of health care. However, the relationships between these groups are not well understood. Our aims were to (1) identify high utilizers of health care in the U.S. working age (18-64) population, (2) examine the overlap between this group and people with chronic conditions and/or disabilities, (3) identify predictors of high service use or cost among these subpopulations, and (4) recommend approaches for stratification of individuals with high health care utilization. Using pooled national data from the Medical Expenditure Panel Survey (2006-2008), we created indices to identify elevated or high utilization and cost groups. We performed descriptive analyses, bivariate comparisons and multivariate analyses to examine the relations between these populations and individuals with chronic conditions and/or disabilities. While the large majority of persons with high use/cost had chronic conditions, the minority of persons with chronic conditions had high health care utilization. However, among persons with chronic conditions, disability was a significant predictor of high utilization. Annual expenditures were significantly elevated among people with disabilities, particularly when activities of daily living were limited. We conclude that medical diagnosis alone is insufficient for the development of eligibility criteria for, or the evaluation of, programs intended to better the delivery or coordination of services for high utilizers of health care services. New approaches are needed to assess functional limitations and identify ongoing needs for services and supports. Published by Elsevier Inc.

Development and validation of PRISM: a survey tool to identify diabetes self-management barriers.

PubMed

Cox, Elizabeth D; Fritz, Katie A; Hansen, Kristofer W; Brown, Roger L; Rajamanickam, Victoria; Wiles, Kaelyn E; Fate, Bryan H; Young, Henry N; Moreno, Megan A

2014-04-01

Although most children with type 1 diabetes do not achieve optimal glycemic control, no systematic method exists to identify and address self-management barriers. This study develops and validates PRISM (Problem Recognition in Illness Self-Management), a survey-based tool for efficiently identifying self-management barriers experienced by children/adolescents with diabetes and their parents. Adolescents 13 years and older and parents of children 8 years and older visiting for routine diabetes management (n=425) were surveyed about self-management barriers. HbA1c was abstracted from the electronic health record. To develop PRISM, exploratory and confirmatory factor analyses were used. To assess validity, the association of PRISM scores with HbA1c was examined using linear regression. Factor analyses of adolescent and parent data yielded well-fitting models of self-management barriers, reflecting the following domains: (1) Understanding and Organizing Care, (2) Regimen Pain and Bother, (3) Denial of Disease and Consequences, and (4) Healthcare Team, (5) Family, or (6) Peer Interactions. All models exhibited good fit, with χ(2) ratios<2.21, root mean square errors of approximation<0.09, Confirmatory Fit Indices and Tucker-Lewis Indices both >0.92, and weighted root mean square residuals<1.71. Greater PRISM barrier scores were significantly associated with higher HbA1cs. Our findings suggest at least six different domains exist within self-management barriers, nearly all of which are significantly related to HbA1c. PRISM could be used in clinical practice to identify each child and family's unique self-management barriers, allowing existing self-management resources to be tailored to the family's barriers, ultimately improving effectiveness of such services. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Development and Validation of PRISM: A Survey Tool to Identify Diabetes Self-Management Barriers

PubMed Central

Cox, Elizabeth D.; Fritz, Katie A.; Hansen, Kristofer W.; Brown, Roger L.; Rajamanickam, Victoria; Wiles, Kaelyn E.; Fate, Bryan H.; Young, Henry N.; Moreno, Megan A.

2014-01-01

Aims Although most children with type 1 diabetes don’t achieve optimal glycemic control, no systematic method exists to identify and address self-management barriers. This study develops and validates PRISM (Problem Recognition in Illness Self-Management), a survey-based tool for efficiently identifying self-management barriers experienced by children/adolescents with diabetes and their parents. Methods Adolescents 13 years and older and parents of children 8 years and older visiting for routine diabetes management (n=425) were surveyed about self-management barriers. HbA1c was abstracted from the electronic health record. To develop PRISM, exploratory and confirmatory factor analyses were used. To assess validity, the association of PRISM scores with HbA1c was examined using linear regression. Results Factor analyses of adolescent and parent data yielded well-fitting models of self-management barriers, reflecting the following domains: 1) Understanding and Organizing Care, 2) Regimen Pain and Bother, 3) Denial of Disease and Consequences, and 4) Healthcare Team, 5) Family, or 6) Peer Interactions. All models exhibited good fit, with X2 ratios<2.21, root mean square errors of approximation<0.09, Confirmatory Fit Indices and Tucker-Lewis Indices both >0.92, and weighted root mean square residuals<1.71. Greater PRISM barrier scores were significantly associated with higher HbA1cs. Conclusions Our findings suggest at least six different domains exist within self-management barriers, nearly all of which are significantly related to HbA1c. PRISM could be used in clinical practice to identify each child and family’s unique self-management barriers, allowing existing self-management resources to be tailored to the family’s barriers, ultimately improving effectiveness of such services. PMID:24552680

Prevalence of posttraumatic stress disorder among road traffic accident survivors: A PRISMA-compliant meta-analysis.

PubMed

Lin, Wanli; Gong, Lina; Xia, Miaojuan; Dai, Wenjie

2018-01-01

Involvement in road traffic accidents (RTAs) may put individuals at increased risk for a wide range of psychiatric disorders, among which posttraumatic stress disorder (PTSD) presents a public health issue. However, a great disparity was observed among studies exploring the prevalence of PTSD among RTA survivors. This meta-analysis aimed to explore the pooled prevalence of PTSD among RTA survivors. Electronic databases of PubMed, Embase, Web of Science, PsycARTICLES, PsycINFO, and CINAHL were searched to identify relevant studies. Study selection and data extraction were conducted independently by 2 investigators, and a meta-analysis was performed to synthesize the data. Heterogeneity among studies was evaluated using the Cochran Q test and quantified using the I statistic. Subgroup analyses were performed to identify the source of the heterogeneity. The possibility of publication bias was assessed using Egger linear test. Fifteen eligible studies containing 6804 RTA survivors were identified in this meta-analysis, of which 1489 were identified with PTSD. The pooled prevalence of PTSD among RTA survivors was 22.25% (95% confidence interval: 16.71%-28.33%). A high degree of heterogeneity was observed across studies (I = 97.1%, P < .001), with reported PTSD prevalence ranging from 6.3% to 58.3%. Subgroup analyses found that the prevalence of PTSD among RTA survivors varied significantly across studies in relation to the instrument used to assess PTSD, country, race, gender, and education level (P < .05). The high pooled prevalence of PTSD among RTA survivors found in this study significantly underscores the need for providing timely and effective intervention strategies for RTA survivors. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Prevalence of posttraumatic stress disorder among road traffic accident survivors

PubMed Central

Lin, Wanli; Gong, Lina; Xia, Miaojuan; Dai, Wenjie

2018-01-01

Abstract Background: Involvement in road traffic accidents (RTAs) may put individuals at increased risk for a wide range of psychiatric disorders, among which posttraumatic stress disorder (PTSD) presents a public health issue. However, a great disparity was observed among studies exploring the prevalence of PTSD among RTA survivors. This meta-analysis aimed to explore the pooled prevalence of PTSD among RTA survivors. Methods: Electronic databases of PubMed, Embase, Web of Science, PsycARTICLES, PsycINFO, and CINAHL were searched to identify relevant studies. Study selection and data extraction were conducted independently by 2 investigators, and a meta-analysis was performed to synthesize the data. Heterogeneity among studies was evaluated using the Cochran Q test and quantified using the I2 statistic. Subgroup analyses were performed to identify the source of the heterogeneity. The possibility of publication bias was assessed using Egger linear test. Results: Fifteen eligible studies containing 6804 RTA survivors were identified in this meta-analysis, of which 1489 were identified with PTSD. The pooled prevalence of PTSD among RTA survivors was 22.25% (95% confidence interval: 16.71%–28.33%). A high degree of heterogeneity was observed across studies (I2 = 97.1%, P < .001), with reported PTSD prevalence ranging from 6.3% to 58.3%. Subgroup analyses found that the prevalence of PTSD among RTA survivors varied significantly across studies in relation to the instrument used to assess PTSD, country, race, gender, and education level (P < .05). Conclusion: The high pooled prevalence of PTSD among RTA survivors found in this study significantly underscores the need for providing timely and effective intervention strategies for RTA survivors. PMID:29505023

Metabolomic profiling in the prediction of gestational diabetes mellitus.

PubMed

Bentley-Lewis, Rhonda; Huynh, Jennifer; Xiong, Grace; Lee, Hang; Wenger, Julia; Clish, Clary; Nathan, David; Thadhani, Ravi; Gerszten, Robert

2015-06-01

Metabolomic profiling in populations with impaired glucose tolerance has revealed that branched chain and aromatic amino acids (BCAAs) are predictive of type 2 diabetes. Because gestational diabetes mellitus (GDM) shares pathophysiological similarities with type 2 diabetes, the metabolite profile predictive of type 2 diabetes could potentially identify women who will develop GDM. We conducted a nested case-control study of 18- to 40-year-old women who participated in the Massachusetts General Hospital Obstetrical Maternal Study between 1998 and 2007. Participants were enrolled during their first trimester of a singleton pregnancy and fasting serum samples were collected. The women were followed throughout pregnancy and identified as having GDM or normal glucose tolerance (NGT) in the third trimester. Women with GDM (n = 96) were matched to women with NGT (n = 96) by age, BMI, gravidity and parity. Liquid chromatography-mass spectrometry was used to measure the levels of 91 metabolites. Data analyses revealed the following characteristics (mean ± SD): age 32.8 ± 4.4 years, BMI 28.3 ± 5.6 kg/m(2), gravidity 2 ± 1 and parity 1 ± 1. Six metabolites (anthranilic acid, alanine, glutamate, creatinine, allantoin and serine) were identified as having significantly different levels between the two groups in conditional logistic regression analyses (p < 0.05). The levels of the BCAAs did not differ significantly between GDM and NGT. Metabolic markers identified as being predictive of type 2 diabetes may not have the same predictive power for GDM. However, further study in a racially/ethnically diverse population-based cohort is necessary.

Integrated Analyses of Gene Expression Profiles Digs out Common Markers for Rheumatic Diseases

PubMed Central

Wang, Lan; Wu, Long-Fei; Lu, Xin; Mo, Xing-Bo; Tang, Zai-Xiang; Lei, Shu-Feng; Deng, Fei-Yan

2015-01-01

Objective Rheumatic diseases have some common symptoms. Extensive gene expression studies, accumulated thus far, have successfully identified signature molecules for each rheumatic disease, individually. However, whether there exist shared factors across rheumatic diseases has yet to be tested. Methods We collected and utilized 6 public microarray datasets covering 4 types of representative rheumatic diseases including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and osteoarthritis. Then we detected overlaps of differentially expressed genes across datasets and performed a meta-analysis aiming at identifying common differentially expressed genes that discriminate between pathological cases and normal controls. To further gain insights into the functions of the identified common differentially expressed genes, we conducted gene ontology enrichment analysis and protein-protein interaction analysis. Results We identified a total of eight differentially expressed genes (TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, PRF1), each associated with at least 3 of the 4 studied rheumatic diseases. Meta-analysis warranted the significance of the eight genes and highlighted the general significance of four genes (CX3CR1, LY96, TLR5, and PRF1). Protein-protein interaction and gene ontology enrichment analyses indicated that the eight genes interact with each other to exert functions related to immune response and immune regulation. Conclusion The findings support that there exist common factors underlying rheumatic diseases. For rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and osteoarthritis diseases, those common factors include TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, and PRF1. In-depth studies on these common factors may provide keys to understanding the pathogenesis and developing intervention strategies for rheumatic diseases. PMID:26352601

Dysfunctional attitudes and poor problem solving skills predict hopelessness in major depression.

PubMed

Cannon, B; Mulroy, R; Otto, M W; Rosenbaum, J F; Fava, M; Nierenberg, A A

1999-09-01

Hopelessness is a significant predictor of suicidality, but not all depressed patients feel hopeless. If clinicians can predict hopelessness, they may be able to identify those patients at risk of suicide and focus interventions on factors associated with hopelessness. In this study, we examined potential predictors of hopelessness in a sample of depressed outpatients. In this study, we examined potential demographic, diagnostic, and symptom predictors of hopelessness in a sample of 138 medication-free outpatients (73 women and 65 men) with a primary diagnosis of major depression. The significance of predictors was evaluated in both simple and multiple regression analyses. Consistent with previous studies, we found no significant associations between demographic and diagnostic variables and greater hopelessness. Hopelessness was significantly associated with greater depression severity, poor problem solving abilities as assessed by the Problem Solving Inventory, and each of two measures of dysfunctional cognitions (the Dysfunctional Attitudes Scale and the Cognitions Questionnaire). In a stepwise multiple regression equation, however, only dysfunctional cognitions and poor problem solving offered non-redundant prediction of hopelessness scores, and accounted for 20% of the variance in these scores. This study is based on depressed patients entering into an outpatient treatment protocol. All analyses were correlational in nature, and no causal links can be concluded. Our findings, identifying clinical correlates of hopelessness, provide clinicians with potential additional targets for assessment and treatment of suicidal risk. In particular, clinical attention to dysfunctional attitudes and problem solving skills may be important for further reduction of hopelessness and perhaps suicidal risk.

Radiation-Induced Cytogenetic Damage as a Predictor of Cancer Risk for Protons and Fe Ions

NASA Technical Reports Server (NTRS)

Williams, Jerry R.

1999-01-01

We have successfully completed the series of experiments planned for year 1 and the first part of year 2 measuring the induction of chromosome aberrations induced in multiple cell types by three model space radiations: Fe-ions, protons and photons. Most of these data have now been compiled and a significant part subjected to detailed data analyses, although continuing data analysis is an important part of our current and future efforts. These analyses are directed toward defining the patterns of chromosomal damage induction by the three radiations and the extent to which such patterns are dependent on the type of cell irradiated. Our studies show significant differences, both quantitatively and qualitatively, between response of different cell types to these radiations however there is an overall pattern that characterizes each type of radiation in most cell lines. Thus our data identifies general dose-response patterns for each radiation for induction of multiple types of chromosomal aberrations but also identifies significant differences in response between some cell types. Specifically, we observe significant resistance for induction of aberrations in rat mammary epithelial cells when they are irradiated in vivo and assayed in vitro. Further, we have observed some remarkable differences in susceptibility to certain radiation-induced aberrations in cells whose genome has been modulated for two cancer- relevant genes, TP53 and CDKNIA. This data, if confirmed, may represent the first evidence of gene-specific differences in cellular metabolism of damage induced by densely-ionizing radiation that confers substantial sensitivity to protons compared to photons.

Using permutation tests to enhance causal inference in interrupted time series analysis.

PubMed

Linden, Ariel

2018-06-01

Interrupted time series analysis (ITSA) is an evaluation methodology in which a single treatment unit's outcome is studied serially over time and the intervention is expected to "interrupt" the level and/or trend of that outcome. The internal validity is strengthened considerably when the treated unit is contrasted with a comparable control group. In this paper, we introduce a robustness check based on permutation tests to further improve causal inference. We evaluate the effect of California's Proposition 99 for reducing cigarette sales by iteratively casting each nontreated state into the role of "treated," creating a comparable control group using the ITSAMATCH package in Stata, and then evaluating treatment effects using ITSA regression. If statistically significant "treatment effects" are estimated for pseudotreated states, then any significant changes in the outcome of the actual treatment unit (California) cannot be attributed to the intervention. We perform these analyses setting the cutpoint significance level to P > .40 for identifying balanced matches (the highest threshold possible for which controls could still be found for California) and use the difference in differences of trends as the treatment effect estimator. Only California attained a statistically significant treatment effect, strengthening confidence in the conclusion that Proposition 99 reduced cigarette sales. The proposed permutation testing framework provides an additional robustness check to either support or refute a treatment effect identified in for the true treated unit in ITSA. Given its value and ease of implementation, this framework should be considered as a standard robustness test in all multiple group interrupted time series analyses. © 2018 John Wiley & Sons, Ltd.

Telangiectatic Matting is Associated with Hypersensitivity and a Bleeding Tendency.

PubMed

Kadam, Pooja; Lim, Jerrick; Paver, Ian; Connor, David E; Parsi, Kurosh

2018-04-01

The aim was to investigate the pathogenesis of telangiectatic matting (TM) and identify possible risk factors. This study had two parts. The clinical records of consecutive patients were retrospectively analysed to identify risk factors for TM. In the second part, the haemostatic and coagulation profile of the subset of patients with TM were analysed and compared with controls using standard coagulation tests, platelet function and a global assay of coagulation (rotational thromboelastometry, ROTEM). In 352 consecutive patients presenting to a phlebology practice, 25 patients had TM (7.1%). All 25 patients were female with the median age of 45 (27-57) years. A comprehensive medical history was taken. Among 27 possible risk factors assessed, statistically significant associations included recurrent epistaxis, easy bruising, hypersensitivity (eczema, hives, hay fever, and rhinitis), previous treatment with sclerotherapy or endovenous laser for lower limb veins, and a family history of telangiectasias. Variables not associated with TM included oral contraceptive intake, hormone replacement therapy, and age. The haemostatic and coagulation profile of 12 patients (6 male and 6 female) with TM did not differ significantly from those without TM. TM is associated with both hypersensitivity and a bleeding tendency. This study revealed no significant increase in the incidence of haemostatic abnormalities in patients with TM compared with the control group. Given the significant association with hypersensitivity disorders, the underlying mast cell hyper-reactivity may contribute to both hypersensitivity and a bleeding tendency and predispose patients to TM. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Overweight, but not obesity, paradox on mortality following coronary artery bypass grafting.

PubMed

Takagi, Hisato; Umemoto, Takuya

2016-09-01

To determine whether an "obesity paradox" on post-coronary artery bypass grafting (CABG) mortality exists, we abstracted exclusively adjusted odds ratios (ORs) and/or hazard ratios (HRs) for mortality from each study, and then combined them in a meta-analysis. MEDLINE and EMBASE were searched through April 2015 using PubMed and OVID, to identify comparative studies, of overweight or obese versus normal weight patients undergoing CABG, reporting adjusted relative risk estimates for short-term (30-day or in-hospital) and/or mid-to-long-term all-cause mortality. Our search identified 14 eligible studies. In total our meta-analysis included data on 79,140 patients undergoing CABG. Pooled analyses in short-term mortality demonstrated that overweight was associated with a statistically significant 15% reduction relative to normal weight (OR, 0.85; 95% confidence interval [CI], 0.74-0.98; p=0.03) and no statistically significant differences between mild obesity, moderate/severe obesity, or overall obesity and normal weight. Pooled analyses in mid-to-long-term mortality demonstrated that overweight was associated with a statistically significant 10% reduction relative to normal weight (HR, 0.90; 95% CI, 0.84 to 0.96; p=0.001); and no statistically significant differences between mild obesity, moderate/severe obesity, or overall obesity and normal weight. Overweight, but not obesity, may be associated with better short-term and mid-to-long-term post-CABG survival relative to normal weight. An overweight, but not obesity, paradox on post-CABG mortality appears to exist. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Predicting academic performance and clinical competency for international dental students: seeking the most efficient and effective measures.

PubMed

Stacey, D Graham; Whittaker, John M

2005-02-01

Measures used in the selection of international dental students to a U.S. D.D.S. program were examined to identify the grouping that most effectively and efficiently predicted academic performance and clinical competency. Archival records from the International Dental Program (IDP) at Loma Linda University provided data on 171 students who had trained in countries outside the United States. The students sought admission to the D.D.S. degree program, successful completion of which qualified them to sit for U.S. licensure. As with most dental schools, competition is high for admission to the D.D.S. program. The study's goal was to identify what measures contributed to a fair and accurate selection process for dental school applicants from other nations. Multiple regression analyses identified National Board Part II and dexterity measures as significant predictors of academic performance and clinical competency. National Board Part I, TOEFL, and faculty interviews added no significant additional help in predicting eventual academic performance and clinical competency.

Key team physical and technical performance indicators indicative of team quality in the soccer Chinese super league.

PubMed

Yang, Gai; Leicht, Anthony S; Lago, Carlos; Gómez, Miguel-Ángel

2018-01-01

The aim of this study was to identify the key physical and technical performance variables related to team quality in the Chinese Super League (CSL). Teams' performance variables were collected from 240 matches and analysed via analysis of variance between end-of-season-ranked groups and multinomial logistic regression. Significant physical performance differences between groups were identified for sprinting (top-ranked group vs. upper-middle-ranked group) and total distance covered without possession (upper and upper-middle-ranked groups and lower-ranked group). For technical performance, teams in the top-ranked group exhibited a significantly greater amount of possession in opponent's half, number of entry passes in the final 1/3 of the field and the Penalty Area, and 50-50 challenges than lower-ranked teams. Finally, time of possession increased the probability of a win compared with a draw. The current study identified key performance indicators that differentiated end-season team quality within the CSL.

Lymph node status as a prognostic factor after palliative resection of primary tumor for patients with metastatic colorectal cancer.

PubMed

Li, Qingguo; Wang, Changjian; Li, Yaqi; Li, Xinxiang; Xu, Ye; Cai, Guoxiang; Lian, Peng; Cai, Sanjun

2017-07-18

Lymph node (LN) status is one of the most important predictors for M0 colorectal cancer patients. However, its clinical impact on stage IV colorectal cancer remains unclear. The study aimed to explore the prognostic value of LN status after palliative resection of primary tumor for patients with metastatic colorectal cancer (mCRC). We combined analyses of mCRC patients in Surveillance, Epidemiology and End Results (SEER) database and Fudan University Shanghai Cancer Center (FUSCC).A total of 17,553 patients with mCRC were identified in SEER database. X-tile program was adopted to identify 2 and 10 as optimal cutoff values for negative lymph node (NLN) count to divide patients into 3 subgroups of high, middle and low risk of cancer related death. N stage and NLN count were verified as independent prognostic factors in multivariate analyses of patients in whole cohort and in subgroup analyses of each N stage (P<0.05). Validation of FUSCC cohort of patients demonstrated that metastatic tumor burden (P = 0.042), NLN count (P = 0.039) and sequential chemotherapy (P = 0.040) were significant predictors of poorer CSS. Specifically, the prognosis of patients at stage N0 was significantly more favorable than that of patients at stage N2 (P = 0.038). In conclusion, primary tumor LN status was a strong predictor of CSS after palliative resection of metastatic colorectal cancer. Advanced N stage and small number of NLN were correlated with high risk of cancer related death after palliative resection of primary tumor.

Bad nights or bad bars? Multi-level analysis of environmental predictors of aggression in late-night large-capacity bars and clubs.

PubMed

Graham, Kathryn; Bernards, Sharon; Osgood, D Wayne; Wells, Samantha

2006-11-01

To clarify environmental predictors of bar-room aggression by differentiating relationships due to nightly variations versus across bar variations, frequency versus severity of aggression and patron versus staff aggression. Male-female pairs of researcher-observers conducted 1334 observations in 118 large capacity (> 300) bars and clubs in Toronto, Canada. Observers independently rated aspects of the environment (e.g. crowding) at every visit and wrote detailed narratives of each incident of aggression that occurred. Measures of severity of aggression for the visit were calculated by aggregating ratings for each person in aggressive incidents. Although bivariate analyses confirmed the significance of most environmental predictors of aggression identified in previous research, multivariate analyses identified the following key visit-level predictors (controlling for bar-level relationships): rowdiness/permissive environment and people hanging around after closing predicted both frequency and severity of aggression; sexual activity, contact and competition and people with two or more drinks at closing predicted frequency but not severity of aggression; lack of staff monitoring predicted more severe patron aggression, while having more and better coordinated staff predicted more severe staff aggression. Intoxication of patrons was significantly associated with more frequent and severe patron aggression at the bar level (but not at the visit level) in the multivariate analyses and negatively associated with severity of staff aggression at the visit level. The results demonstrate clearly the importance of the immediate environment (not just the type of bar or characteristics of usual patrons) and the importance of specific environmental factors, including staff behaviour, in predicting both frequency and severity of aggression.

Aberrant Calreticulin Expression in Articular Cartilage of Dio2 Deficient Mice

PubMed Central

Bomer, Nils; Cornelis, Frederique M. F.; Ramos, Yolande F. M.; den Hollander, Wouter; Lakenberg, Nico; van der Breggen, Ruud; Storms, Lies; Slagboom, P. Eline; Lories, Rik J. U.; Meulenbelt, Ingrid

2016-01-01

Objective To identify intrinsic differences in cartilage gene expression profiles between wild-type- and Dio2-/--mice, as a mechanism to investigate factors that contribute to prolonged healthy tissue homeostasis. Methods Previously generated microarray-data (Illumina MouseWG-6 v2) of knee cartilage of wild-type and Dio2 -/- -mice were re-analyzed to identify differential expressed genes independent of mechanical loading conditions by forced treadmill-running. RT-qPCR and western blot analyses of overexpression and knockdown of Calr in mouse chondro-progenitor cells (ATDC5) were applied to assess the direct effect of differential Calr expression on cartilage deposition. Results Differential expression analyses of articular cartilage of Dio2-/- (N = 9) and wild-type-mice (N = 11) while applying a cutoff threshold (P < 0.05 (FDR) and FC > |1,5|) resulted in 1 probe located in Calreticulin (Calr) that was found significantly downregulated in Dio2-/- mice (FC = -1.731; P = 0.044). Furthermore, overexpression of Calr during early chondrogenesis in ATDC5 cells leads to decreased proteoglycan deposition and corresponding lower Aggrecan expression, whereas knocking down Calr expression does not lead to histological differences of matrix composition. Conclusion We here demonstrate that the beneficial homeostatic state of articular cartilage in Dio2-/- mice is accompanied with significant lower expression of Calr. Functional analyses further showed that upregulation of Calr expression could act as an initiator of cartilage destruction. The consistent association between Calr and Dio2 expression suggests that enhanced expression of these genes facilitate detrimental effects on cartilage integrity. PMID:27163789

Biomarker analyses in REGARD gastric/GEJ carcinoma patients treated with VEGFR2-targeted antibody ramucirumab.

PubMed

Fuchs, Charles S; Tabernero, Josep; Tomášek, Jiří; Chau, Ian; Melichar, Bohuslav; Safran, Howard; Tehfe, Mustapha A; Filip, Dumitru; Topuzov, Eldar; Schlittler, Luis; Udrea, Anghel Adrian; Campbell, William; Brincat, Stephen; Emig, Michael; Melemed, Symantha A; Hozak, Rebecca R; Ferry, David; Caldwell, C William; Ajani, Jaffer A

2016-10-11

Angiogenesis inhibition is an important strategy for cancer treatment. Ramucirumab, a human IgG1 monoclonal antibody that targets VEGF receptor 2 (VEGFR2), inhibits VEGF-A, -C, -D binding and endothelial cell proliferation. To attempt to identify prognostic and predictive biomarkers, retrospective analyses were used to assess tumour (HER2, VEGFR2) and serum (VEGF-C and -D, and soluble (s) VEGFR1 and 3) biomarkers in phase 3 REGARD patients with metastatic gastric/gastroesophageal junction carcinoma. A total of 152 out of 355 (43%) patients randomised to ramucirumab or placebo had ⩾1 evaluable biomarker result using VEGFR2 immunohistochemistry or HER2, immunohistochemistry or FISH, of blinded baseline tumour tissue samples. Serum samples (32 patients, 9%) were assayed for VEGF-C and -D, and sVEGFR1 and 3. None of the biomarkers tested were associated with ramucirumab efficacy at a level of statistical significance. High VEGFR2 endothelial expression was associated with a non-significant prognostic trend toward shorter progression-free survival (high vs low HR=1.65, 95% CI=0.84,3.23). Treatment with ramucirumab was associated with a trend toward improved survival in both high (HR=0.69, 95% CI=0.38, 1.22) and low (HR=0.73, 95% CI=0.42, 1.26) VEGFR2 subgroups. The benefit associated with ramucirumab did not appear to differ by tumoural HER2 expression. REGARD exploratory analyses did not identify a strong potentially predictive biomarker of ramucirumab efficacy; however, statistical power was limited.

Systematic Review of Health Economic Analyses of Measles and Rubella Immunization Interventions.

PubMed

Thompson, Kimberly M; Odahowski, Cassie L

2016-07-01

Economic analyses for vaccine-preventable diseases provide important insights about the value of prevention. We reviewed the literature to identify all of the peer-reviewed, published economic analyses of interventions related to measles and rubella immunization options to assess the different types of analyses performed and characterize key insights. We searched PubMed, the Science Citation Index, and references from relevant articles for studies in English and found 67 analyses that reported primary data and quantitative estimates of benefit-cost or cost-effectiveness analyses for measles and/or rubella immunization interventions. We removed studies that we characterized as cost-minimization analyses from this sample because they generally provide insights that focused on more optimal strategies to achieve the same health outcome. The 67 analyses we included demonstrate the large economic benefits associated with preventing measles and rubella infections using vaccines and the benefit of combining measles and rubella antigens into a formulation that saves the costs associated with injecting the vaccines separately. Despite the importance of population immunity and dynamic viral transmission, most of the analyses used static models to estimate cases prevented and characterize benefits, although the use of dynamic models continues to increase. Many of the analyses focused on characterizing the most significant adverse outcomes (e.g., mortality for measles, congenital rubella syndrome for rubella) and/or only direct costs, and the most complete analyses present data from high-income countries. © 2014 Society for Risk Analysis.

Altered plasma levels of cytokines, soluble adhesion molecules and matrix metalloproteases in venous thrombosis.

PubMed

Mosevoll, Knut Anders; Lindås, Roald; Tvedt, Tor Henrik Anderson; Bruserud, Øystein; Reikvam, Håkon

2015-07-01

Recent studies have emphasized the importance of the inflammatory response mediated by monocyte and neutrophil activation in deep venous thrombosis (DVT); we therefore investigated whether this response was reflected in the plasma profile of inflammatory mediators in patients with suspected DVT. We included a group of 169 consecutive patients admitted to hospital from the primary health care service with suspected lower limb DVT. Plasma levels of 43 mediators were examined for a cohort of 89 consecutive patients and 20 healthy controls by Luminex multiplex analyses, i.e. 13 interleukins, 3 immunomodulatory cytokines, 8 chemokines, 8 growth factors, 3 adhesion molecules and 8 matrix metalloproteases. Selected mediators were analyzed for a second cohort of 80 consecutive patients. Thirty-five of 169 (21%) of referred patients were diagnosed with DVT. Only P-selectin (p<0.0001), vascular cell adhesion protein 1 (VCAM-1, p=0.0009), matrix metalloprotease 8 (MMP-8, p=0.0151) and hepatocyte growth factor (HGF, p=0.0415) differed significantly when comparing patients with and without DVT. When comparing DVT patients with healthy controls we observed significant differences for several mediators, where P-selectin (p=0.0009), VCAM-1 (p<0.0001), all the MMPs (all p<0.0014) and HGF (p<0.0001) showed the strongest significant differences. Unsupervised hierarchical clustering analyses based on biomarkers showing differences between patients with and without DVT could be used to identify patient subsets that differed significantly in DVT frequency. Plasma biomarker profiling of selected soluble mediators can be used to identify subsets among patients with suspected lower limb thrombosis that differ significantly in their frequencies of DVT. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Cross Sectional Study of Public Knowledge and Attitude towards Antibiotics in Putrajaya, Malaysia.

PubMed

Lim, Ka Keat; Teh, Chew Charn

2012-12-01

The objective of the study was to assess public knowledge and attitudes regarding antibiotic utilization in Putrajaya, Malaysia. A self-administered questionnaire survey was conducted among public attending a local hospital. The four-part questionnaire collected responses on demographic characteristics, recent use of antibiotics, knowledge and attitude statements. Cronbach's alpha for knowledge and attitude statements were 0.68 and 0.74 respectively. Only questionnaires with complete responses were analysed. General linear modelling was used to identify demographic characteristics which contributed significantly to knowledge and attitude. Multiple logistic regression was used to determine the adjusted odds ratios of obtaining an inappropriate response for each knowledge and attitude statement. The relationship between antibiotic knowledge and attitude was examined using Pearson's correlation and correlation between related statements was performed using the Chi-square test. In all statistical analyses, a p-value of < 0.05 was considered statistically significant. There was positive correlation (p<0.001) between mean knowledge (6.07±2.52) and attitude scores (5.59±1.67). Highest education level (p<0.001) and healthcare-related occupation (p=0.001) contributed significantly to knowledge. Gender (p=0.010), race (p=0.005), highest education level (p<0.001), employment status (p=0.016) and healthcare-related occupation (p=0.005) contributed significantly to attitude. The differences in score between demographic groups were small. Misconceptions that antibiotics would work on both bacterial and viral infections were reported. Approximately three quarters of respondents expected antibiotics for treatment of coughs and colds. Close to two thirds (60%) believed that taking antibiotics would improve recovery. Several demographic groups were identified as 'high risk' with respect to gaps in knowledge and attitude. This study has identified important knowledge and attitude gaps as well as people 'at risk'. These findings would be useful in strategizing targeted antibiotic awareness campaigns and patient counselling.

A Cross Sectional Study of Public Knowledge and Attitude towards Antibiotics in Putrajaya, Malaysia

PubMed Central

Lim, Ka Keat; Teh, Chew Charn

2012-01-01

Objective: The objective of the study was to assess public knowledge and attitudes regarding antibiotic utilization in Putrajaya, Malaysia. Methods: A self-administered questionnaire survey was conducted among public attending a local hospital. The four-part questionnaire collected responses on demographic characteristics, recent use of antibiotics, knowledge and attitude statements. Cronbach’s alpha for knowledge and attitude statements were 0.68 and 0.74 respectively. Only questionnaires with complete responses were analysed. General linear modelling was used to identify demographic characteristics which contributed significantly to knowledge and attitude. Multiple logistic regression was used to determine the adjusted odds ratios of obtaining an inappropriate response for each knowledge and attitude statement. The relationship between antibiotic knowledge and attitude was examined using Pearson’s correlation and correlation between related statements was performed using the Chi-square test. In all statistical analyses, a p-value of < 0.05 was considered statistically significant. Results: There was positive correlation (p<0.001) between mean knowledge (6.07±2.52) and attitude scores (5.59±1.67). Highest education level (p<0.001) and healthcare-related occupation (p=0.001) contributed significantly to knowledge. Gender (p=0.010), race (p=0.005), highest education level (p<0.001), employment status (p=0.016) and healthcare-related occupation (p=0.005) contributed significantly to attitude. The differences in score between demographic groups were small. Misconceptions that antibiotics would work on both bacterial and viral infections were reported. Approximately three quarters of respondents expected antibiotics for treatment of coughs and colds. Close to two thirds (60%) believed that taking antibiotics would improve recovery. Several demographic groups were identified as ‘high risk’ with respect to gaps in knowledge and attitude. Conclusions: This study has identified important knowledge and attitude gaps as well as people ‘at risk’. These findings would be useful in strategizing targeted antibiotic awareness campaigns and patient counselling. PMID:23532680

Nonsyndromic cleft palate: An association study at GWAS candidate loci in a multiethnic sample.

PubMed

Ishorst, Nina; Francheschelli, Paola; Böhmer, Anne C; Khan, Mohammad Faisal J; Heilmann-Heimbach, Stefanie; Fricker, Nadine; Little, Julian; Steegers-Theunissen, Regine P M; Peterlin, Borut; Nowak, Stefanie; Martini, Markus; Kruse, Teresa; Dunsche, Anton; Kreusch, Thomas; Gölz, Lina; Aldhorae, Khalid; Halboub, Esam; Reutter, Heiko; Mossey, Peter; Nöthen, Markus M; Rubini, Michele; Ludwig, Kerstin U; Knapp, Michael; Mangold, Elisabeth

2018-06-01

Nonsyndromic cleft palate only (nsCPO) is a common and multifactorial form of orofacial clefting. In contrast to successes achieved for the other common form of orofacial clefting, that is, nonsyndromic cleft lip with/without cleft palate (nsCL/P), genome wide association studies (GWAS) of nsCPO have identified only one genome wide significant locus. Aim of the present study was to investigate whether common variants contribute to nsCPO and, if so, to identify novel risk loci. We genotyped 33 SNPs at 27 candidate loci from 2 previously published nsCPO GWAS in an independent multiethnic sample. It included: (i) a family-based sample of European ancestry (n = 212); and (ii) two case/control samples of Central European (n = 94/339) and Arabian ancestry (n = 38/231), respectively. A separate association analysis was performed for each genotyped dataset, and meta-analyses were performed. After association analysis and meta-analyses, none of the 33 SNPs showed genome-wide significance. Two variants showed nominally significant association in the imputed GWAS dataset and exhibited a further decrease in p-value in a European and an overall meta-analysis including imputed GWAS data, respectively (rs395572: P MetaEU  = 3.16 × 10 -4 ; rs6809420: P MetaAll  = 2.80 × 10 -4 ). Our findings suggest that there is a limited contribution of common variants to nsCPO. However, the individual effect sizes might be too small for detection of further associations in the present sample sizes. Rare variants may play a more substantial role in nsCPO than in nsCL/P, for which GWAS of smaller sample sizes have identified genome-wide significant loci. Whole-exome/genome sequencing studies of nsCPO are now warranted. © 2018 Wiley Periodicals, Inc.

Association of genome-wide variation with the risk of incident heart failure in adults of European and African ancestry: a prospective meta-analysis from the cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium.

PubMed

Smith, Nicholas L; Felix, Janine F; Morrison, Alanna C; Demissie, Serkalem; Glazer, Nicole L; Loehr, Laura R; Cupples, L Adrienne; Dehghan, Abbas; Lumley, Thomas; Rosamond, Wayne D; Lieb, Wolfgang; Rivadeneira, Fernando; Bis, Joshua C; Folsom, Aaron R; Benjamin, Emelia; Aulchenko, Yurii S; Haritunians, Talin; Couper, David; Murabito, Joanne; Wang, Ying A; Stricker, Bruno H; Gottdiener, John S; Chang, Patricia P; Wang, Thomas J; Rice, Kenneth M; Hofman, Albert; Heckbert, Susan R; Fox, Ervin R; O'Donnell, Christopher J; Uitterlinden, Andre G; Rotter, Jerome I; Willerson, James T; Levy, Daniel; van Duijn, Cornelia M; Psaty, Bruce M; Witteman, Jacqueline C M; Boerwinkle, Eric; Vasan, Ramachandran S

2010-06-01

Although genetic factors contribute to the onset of heart failure (HF), no large-scale genome-wide investigation of HF risk has been published to date. We have investigated the association of 2,478,304 single-nucleotide polymorphisms with incident HF by meta-analyzing data from 4 community-based prospective cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study. Eligible participants for these analyses were of European or African ancestry and free of clinical HF at baseline. Each study independently conducted genome-wide scans and imputed data to the approximately 2.5 million single-nucleotide polymorphisms in HapMap. Within each study, Cox proportional hazards regression models provided age- and sex-adjusted estimates of the association between each variant and time to incident HF. Fixed-effect meta-analyses combined results for each single-nucleotide polymorphism from the 4 cohorts to produce an overall association estimate and P value. A genome-wide significance P value threshold was set a priori at 5.0x10(-7). During a mean follow-up of 11.5 years, 2526 incident HF events (12%) occurred in 20 926 European-ancestry participants. The meta-analysis identified a genome-wide significant locus at chromosomal position 15q22 (1.4x10(-8)), which was 58.8 kb from USP3. Among 2895 African-ancestry participants, 466 incident HF events (16%) occurred during a mean follow-up of 13.7 years. One genome-wide significant locus was identified at 12q14 (6.7x10(-8)), which was 6.3 kb from LRIG3. We identified 2 loci that were associated with incident HF and exceeded genome-wide significance. The findings merit replication in other community-based settings of incident HF.

A critical review of low-carbohydrate diets in people with Type 2 diabetes.

PubMed

van Wyk, H J; Davis, R E; Davies, J S

2016-02-01

The efficacy of low-carbohydrate diets (LCD) in people with Type 2 diabetes has divided the nutrition community. This review seeks to re-examine the available data to clarify understanding. A comprehensive search of databases was used to identify meta-analyses of LCD in Type 2 diabetes. To improve the quality of the studies analysed, the following inclusion criteria were applied: randomized control trials ≥ 4 weeks in people aged > 18 years with Type 2 diabetes; a carbohydrate intake ≤ 45% of total energy intake per day; and a dietary intake assessment at the end of the study. The resulting studies were subjected to a thematic analysis. Nine meta-analyses were identified containing 153 studies. Twelve studies met our amended inclusion criteria. There were no significant differences in metabolic markers, including glycaemic control, between the two diets, although weight loss with a LCD was greater in one study. Carbohydrate intake at 1 year in very LCD (< 50 g of carbohydrates) ranged from 132 to 162 g. In some studies, the difference between diets was as little as 8 g/day of carbohydrates. Total energy intake remains the dietary predictor of body weight. A LCD appears no different from a high-carbohydrate diet in terms of metabolic markers and glycaemic control. Very LCDs may not be sustainable over a medium to longer term as carbohydrate intake in diets within studies often converged toward a more moderate level. The variable quality of studies included in earlier meta-analyses likely explains the previous inconsistent findings between meta-analyses. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

Nonpharmacological interventions for ADHD: systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatments.

PubMed

Sonuga-Barke, Edmund J S; Brandeis, Daniel; Cortese, Samuele; Daley, David; Ferrin, Maite; Holtmann, Martin; Stevenson, Jim; Danckaerts, Marina; van der Oord, Saskia; Döpfner, Manfred; Dittmann, Ralf W; Simonoff, Emily; Zuddas, Alessandro; Banaschewski, Tobias; Buitelaar, Jan; Coghill, David; Hollis, Chris; Konofal, Eric; Lecendreux, Michel; Wong, Ian C K; Sergeant, Joseph

2013-03-01

Nonpharmacological treatments are available for attention deficit hyperactivity disorder (ADHD), although their efficacy remains uncertain. The authors undertook meta-analyses of the efficacy of dietary (restricted elimination diets, artificial food color exclusions, and free fatty acid supplementation) and psychological (cognitive training, neurofeedback, and behavioral interventions) ADHD treatments. Using a common systematic search and a rigorous coding and data extraction strategy across domains, the authors searched electronic databases to identify published randomized controlled trials that involved individuals who were diagnosed with ADHD (or who met a validated cutoff on a recognized rating scale) and that included an ADHD outcome. Fifty-four of the 2,904 nonduplicate screened records were included in the analyses. Two different analyses were performed. When the outcome measure was based on ADHD assessments by raters closest to the therapeutic setting, all dietary (standardized mean differences=0.21-0.48) and psychological (standardized mean differences=0.40-0.64) treatments produced statistically significant effects. However, when the best probably blinded assessment was employed, effects remained significant for free fatty acid supplementation (standardized mean difference=0.16) and artificial food color exclusion (standardized mean difference=0.42) but were substantially attenuated to nonsignificant levels for other treatments. Free fatty acid supplementation produced small but significant reductions in ADHD symptoms even with probably blinded assessments, although the clinical significance of these effects remains to be determined. Artificial food color exclusion produced larger effects but often in individuals selected for food sensitivities. Better evidence for efficacy from blinded assessments is required for behavioral interventions, neurofeedback, cognitive training, and restricted elimination diets before they can be supported as treatments for core ADHD symptoms.

Evaluating rehabilitation goals of visually impaired children in multidisciplinary care according to ICF-CY guidelines.

PubMed

Rainey, Linda; van Nispen, Ruth; van Rens, Ger

2014-11-01

To gain qualitative insight into the rehabilitation goals of visually impaired children and how these goals relate to the structure of the International Classification of Functioning, Disability and Health (ICF) and patient characteristics. A patient record study was conducted, analysing rehabilitation goals and characteristics of children with a suspected visual impairment in the Netherlands (<18 years) who applied for multidisciplinary services in 2012 (N = 289). Chi-square analyses for trend in rehabilitation content across age bands and additional analyses were performed. The three most common diagnoses were nystagmus (21.2%), cerebral visual impairment (16.2%) and albinism (6.1%). Rehabilitation goals for children aged <7 years were mostly aimed at 'physical (visual) functioning' (36.7%) and 'environmental factors' (36.7%). For children ≥7 years, significantly more goals were identified on activity and participation (A&P) domains (52.2%). Three A and P domains presented a significant linear trend on the number of rehabilitation goals across age bands: (1) 'Learning and applying knowledge' (13.042, p < 0.001), (4) 'Mobility' (31.340, p < 0.001) and (8) 'Major life areas' (5.925, p = 0.015). Regression analysis showed that both age and visual acuity significantly contributed to the number of A and P goals. Although analyses were based on a selection of patient records, the number and nature of rehabilitation goals differ significantly with age. Many A and P goals seem underrepresented at the intake procedure, for example: communication, peer interaction and participating in leisure activities. A systematic, standardized procedure is required to catalogue all existing goals and to be able to evaluate progress and potential new or other important goals. © 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

The moderating effect of ANKK1 on the association of family environment with longitudinal executive function following traumatic brain injury in early childhood: A preliminary study.

PubMed

Smith-Paine, Julia; Wade, Shari L; Treble-Barna, Amery; Zhang, Nanhua; Zang, Huaiyu; Martin, Lisa J; Yeates, Keith Owen; Taylor, H Gerry; Kurowski, Brad G

2018-05-02

This study examined whether the ankyrin repeat and kinase domain containing 1 gene (ANKK1) C/T single-nucleotide polymorphism (SNP) rs1800497 moderated the association of family environment with long-term executive function (EF) following traumatic injury in early childhood. Caregivers of children with traumatic brain injury (TBI) and children with orthopedic injury (OI) completed the Behavior Rating Inventory of Executive Function (BRIEF) at post injury visits. DNA was collected to identify the rs1800497 genotype in the ANKK1 gene. General linear models examined gene-environment interactions as moderators of the effects of TBI on EF at two times post injury (12 months and 7 years). At 12 months post injury, analyses revealed a significant 3-way interaction of genotype with level of permissive parenting and injury type. Post-hoc analyses showed genetic effects were more pronounced for children with TBI from more positive family environments, such that children with TBI who were carriers of the risk allele (T-allele) had significantly poorer EF compared to non-carriers only when they were from more advantaged environments. At 7 years post injury, analyses revealed a significant 2-way interaction of genotype with level of authoritarian parenting. Post-hoc analyses found that carriers of the risk allele had significantly poorer EF compared to non-carriers only when they were from more advantaged environments. These results suggest a gene-environment interaction involving the ANKK1 gene as a predictor of EF in a pediatric injury population. The findings highlight the importance of considering environmental influences in future genetic studies on recovery following TBI and other traumatic injuries in childhood.

ILDgenDB: integrated genetic knowledge resource for interstitial lung diseases (ILDs).

PubMed

Mishra, Smriti; Shah, Mohammad I; Sarkar, Malay; Asati, Nimisha; Rout, Chittaranjan

2018-01-01

Interstitial lung diseases (ILDs) are a diverse group of ∼200 acute and chronic pulmonary disorders that are characterized by variable amounts of inflammation, fibrosis and architectural distortion with substantial morbidity and mortality. Inaccurate and delayed diagnoses increase the risk, especially in developing countries. Studies have indicated the significant roles of genetic elements in ILDs pathogenesis. Therefore, the first genetic knowledge resource, ILDgenDB, has been developed with an objective to provide ILDs genetic data and their integrated analyses for the better understanding of disease pathogenesis and identification of diagnostics-based biomarkers. This resource contains literature-curated disease candidate genes (DCGs) enriched with various regulatory elements that have been generated using an integrated bioinformatics workflow of databases searches, literature-mining and DCGs-microRNA (miRNAs)-single nucleotide polymorphisms (SNPs) association analyses. To provide statistical significance to disease-gene association, ILD-specificity index and hypergeomatric test scores were also incorporated. Association analyses of miRNAs, SNPs and pathways responsible for the pathogenesis of different sub-classes of ILDs were also incorporated. Manually verified 299 DCGs and their significant associations with 1932 SNPs, 2966 miRNAs and 9170 miR-polymorphisms were also provided. Furthermore, 216 literature-mined and proposed biomarkers were identified. The ILDgenDB resource provides user-friendly browsing and extensive query-based information retrieval systems. Additionally, this resource also facilitates graphical view of predicted DCGs-SNPs/miRNAs and literature associated DCGs-ILDs interactions for each ILD to facilitate efficient data interpretation. Outcomes of analyses suggested the significant involvement of immune system and defense mechanisms in ILDs pathogenesis. This resource may potentially facilitate genetic-based disease monitoring and diagnosis.Database URL: http://14.139.240.55/ildgendb/index.php.

Whole exome sequencing identifies novel candidate genes that modify chronic obstructive pulmonary disease susceptibility.

PubMed

Bruse, Shannon; Moreau, Michael; Bromberg, Yana; Jang, Jun-Ho; Wang, Nan; Ha, Hongseok; Picchi, Maria; Lin, Yong; Langley, Raymond J; Qualls, Clifford; Klensney-Tait, Julia; Zabner, Joseph; Leng, Shuguang; Mao, Jenny; Belinsky, Steven A; Xing, Jinchuan; Nyunoya, Toru

2016-01-07

Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible airflow limitation in response to inhalation of noxious stimuli, such as cigarette smoke. However, only 15-20 % smokers manifest COPD, suggesting a role for genetic predisposition. Although genome-wide association studies have identified common genetic variants that are associated with susceptibility to COPD, effect sizes of the identified variants are modest, as is the total heritability accounted for by these variants. In this study, an extreme phenotype exome sequencing study was combined with in vitro modeling to identify COPD candidate genes. We performed whole exome sequencing of 62 highly susceptible smokers and 30 exceptionally resistant smokers to identify rare variants that may contribute to disease risk or resistance to COPD. This was a cross-sectional case-control study without therapeutic intervention or longitudinal follow-up information. We identified candidate genes based on rare variant analyses and evaluated exonic variants to pinpoint individual genes whose function was computationally established to be significantly different between susceptible and resistant smokers. Top scoring candidate genes from these analyses were further filtered by requiring that each gene be expressed in human bronchial epithelial cells (HBECs). A total of 81 candidate genes were thus selected for in vitro functional testing in cigarette smoke extract (CSE)-exposed HBECs. Using small interfering RNA (siRNA)-mediated gene silencing experiments, we showed that silencing of several candidate genes augmented CSE-induced cytotoxicity in vitro. Our integrative analysis through both genetic and functional approaches identified two candidate genes (TACC2 and MYO1E) that augment cigarette smoke (CS)-induced cytotoxicity and, potentially, COPD susceptibility.

Effects of storage temperature on airway exosome integrity for diagnostic and functional analyses

PubMed Central

Maroto, Rosario; Zhao, Yingxin; Jamaluddin, Mohammad; Popov, Vsevolod L.; Wang, Hongwang; Kalubowilage, Madumali; Zhang, Yueqing; Luisi, Jonathan; Sun, Hong; Culbertson, Christopher T.; Bossmann, Stefan H.; Motamedi, Massoud; Brasier, Allan R.

2017-01-01

ABSTRACT Background: Extracellular vesicles contain biological molecules specified by cell-type of origin and modified by microenvironmental changes. To conduct reproducible studies on exosome content and function, storage conditions need to have minimal impact on airway exosome integrity. Aim: We compared surface properties and protein content of airway exosomes that had been freshly isolated vs. those that had been treated with cold storage or freezing. Methods: Mouse bronchoalveolar lavage fluid (BALF) exosomes purified by differential ultracentrifugation were analysed immediately or stored at +4°C or −80°C. Exosomal structure was assessed by dynamic light scattering (DLS), transmission electron microscopy (TEM) and charge density (zeta potential, ζ). Exosomal protein content, including leaking/dissociating proteins, were identified by label-free LC-MS/MS. Results: Freshly isolated BALF exosomes exhibited a mean diameter of 95 nm and characteristic morphology. Storage had significant impact on BALF exosome size and content. Compared to fresh, exosomes stored at +4°C had a 10% increase in diameter, redistribution to polydisperse aggregates and reduced ζ. Storage at −80°C produced an even greater effect, resulting in a 25% increase in diameter, significantly reducing the ζ, resulting in multilamellar structure formation. In fresh exosomes, we identified 1140 high-confidence proteins enriched in 19 genome ontology biological processes. After storage at room temperature, 848 proteins were identified. In preparations stored at +4°C, 224 proteins appeared in the supernatant fraction compared to the wash fractions from freshly prepared exosomes; these proteins represent exosome leakage or dissociation of loosely bound “peri-exosomal” proteins. In preparations stored at −80°C, 194 proteins appeared in the supernatant fraction, suggesting that distinct protein groups leak from exosomes at different storage temperatures. Conclusions: Storage destabilizes the surface characteristics, morphological features and protein content of BALF exosomes. For preservation of the exosome protein content and representative functional analysis, airway exosomes should be analysed immediately after isolation. PMID:28819550

Effects of storage temperature on airway exosome integrity for diagnostic and functional analyses.

PubMed

Maroto, Rosario; Zhao, Yingxin; Jamaluddin, Mohammad; Popov, Vsevolod L; Wang, Hongwang; Kalubowilage, Madumali; Zhang, Yueqing; Luisi, Jonathan; Sun, Hong; Culbertson, Christopher T; Bossmann, Stefan H; Motamedi, Massoud; Brasier, Allan R

2017-01-01

Background : Extracellular vesicles contain biological molecules specified by cell-type of origin and modified by microenvironmental changes. To conduct reproducible studies on exosome content and function, storage conditions need to have minimal impact on airway exosome integrity. Aim : We compared surface properties and protein content of airway exosomes that had been freshly isolated vs. those that had been treated with cold storage or freezing. Methods : Mouse bronchoalveolar lavage fluid (BALF) exosomes purified by differential ultracentrifugation were analysed immediately or stored at +4°C or -80°C. Exosomal structure was assessed by dynamic light scattering (DLS), transmission electron microscopy (TEM) and charge density (zeta potential, ζ). Exosomal protein content, including leaking/dissociating proteins, were identified by label-free LC-MS/MS. Results : Freshly isolated BALF exosomes exhibited a mean diameter of 95 nm and characteristic morphology. Storage had significant impact on BALF exosome size and content. Compared to fresh, exosomes stored at +4°C had a 10% increase in diameter, redistribution to polydisperse aggregates and reduced ζ. Storage at -80°C produced an even greater effect, resulting in a 25% increase in diameter, significantly reducing the ζ, resulting in multilamellar structure formation. In fresh exosomes, we identified 1140 high-confidence proteins enriched in 19 genome ontology biological processes. After storage at room temperature, 848 proteins were identified. In preparations stored at +4°C, 224 proteins appeared in the supernatant fraction compared to the wash fractions from freshly prepared exosomes; these proteins represent exosome leakage or dissociation of loosely bound "peri-exosomal" proteins. In preparations stored at -80°C, 194 proteins appeared in the supernatant fraction, suggesting that distinct protein groups leak from exosomes at different storage temperatures. Conclusions : Storage destabilizes the surface characteristics, morphological features and protein content of BALF exosomes. For preservation of the exosome protein content and representative functional analysis, airway exosomes should be analysed immediately after isolation.

The importance and pitfalls of correlational science in palliative care research.

PubMed

Klepstad, Pål; Kaasa, Stein

2012-12-01

Correlational science discovers associations between patient characteristics, symptoms and biomarkers. Correlational science using data from cross-sectional studies is the most frequently applied study design in palliative care research. The purpose of this review is to address the importance and potential pitfalls in correlational science. Associations observed in correlational science studies can be the basis for generating hypotheses that can be tested in experimental studies and are the basic data needed to develop classification systems that can predict patient outcomes. Major pitfalls in correlational science are that associations do not equate with causality and that statistical significance does not necessarily equal a correlation that is of clinical interest. Researchers should be aware of the end-points that are clinically relevant, that end-points should be defined before the start of the analyses, and that studies with several end-points should account for multiplicity. Correlational science in palliative care research can identify related clinical factors and biomarkers. Interpretation of identified associations should be done with careful consideration of the limitations underlying correlational analyses.

New genetic loci link adipose and insulin biology to body fat distribution.

PubMed

Shungin, Dmitry; Winkler, Thomas W; Croteau-Chonka, Damien C; Ferreira, Teresa; Locke, Adam E; Mägi, Reedik; Strawbridge, Rona J; Pers, Tune H; Fischer, Krista; Justice, Anne E; Workalemahu, Tsegaselassie; Wu, Joseph M W; Buchkovich, Martin L; Heard-Costa, Nancy L; Roman, Tamara S; Drong, Alexander W; Song, Ci; Gustafsson, Stefan; Day, Felix R; Esko, Tonu; Fall, Tove; Kutalik, Zoltán; Luan, Jian'an; Randall, Joshua C; Scherag, André; Vedantam, Sailaja; Wood, Andrew R; Chen, Jin; Fehrmann, Rudolf; Karjalainen, Juha; Kahali, Bratati; Liu, Ching-Ti; Schmidt, Ellen M; Absher, Devin; Amin, Najaf; Anderson, Denise; Beekman, Marian; Bragg-Gresham, Jennifer L; Buyske, Steven; Demirkan, Ayse; Ehret, Georg B; Feitosa, Mary F; Goel, Anuj; Jackson, Anne U; Johnson, Toby; Kleber, Marcus E; Kristiansson, Kati; Mangino, Massimo; Leach, Irene Mateo; Medina-Gomez, Carolina; Palmer, Cameron D; Pasko, Dorota; Pechlivanis, Sonali; Peters, Marjolein J; Prokopenko, Inga; Stančáková, Alena; Sung, Yun Ju; Tanaka, Toshiko; Teumer, Alexander; Van Vliet-Ostaptchouk, Jana V; Yengo, Loïc; Zhang, Weihua; Albrecht, Eva; Ärnlöv, Johan; Arscott, Gillian M; Bandinelli, Stefania; Barrett, Amy; Bellis, Claire; Bennett, Amanda J; Berne, Christian; Blüher, Matthias; Böhringer, Stefan; Bonnet, Fabrice; Böttcher, Yvonne; Bruinenberg, Marcel; Carba, Delia B; Caspersen, Ida H; Clarke, Robert; Daw, E Warwick; Deelen, Joris; Deelman, Ewa; Delgado, Graciela; Doney, Alex Sf; Eklund, Niina; Erdos, Michael R; Estrada, Karol; Eury, Elodie; Friedrich, Nele; Garcia, Melissa E; Giedraitis, Vilmantas; Gigante, Bruna; Go, Alan S; Golay, Alain; Grallert, Harald; Grammer, Tanja B; Gräßler, Jürgen; Grewal, Jagvir; Groves, Christopher J; Haller, Toomas; Hallmans, Goran; Hartman, Catharina A; Hassinen, Maija; Hayward, Caroline; Heikkilä, Kauko; Herzig, Karl-Heinz; Helmer, Quinta; Hillege, Hans L; Holmen, Oddgeir; Hunt, Steven C; Isaacs, Aaron; Ittermann, Till; James, Alan L; Johansson, Ingegerd; Juliusdottir, Thorhildur; Kalafati, Ioanna-Panagiota; Kinnunen, Leena; Koenig, Wolfgang; Kooner, Ishminder K; Kratzer, Wolfgang; Lamina, Claudia; Leander, Karin; Lee, Nanette R; Lichtner, Peter; Lind, Lars; Lindström, Jaana; Lobbens, Stéphane; Lorentzon, Mattias; Mach, François; Magnusson, Patrik Ke; Mahajan, Anubha; McArdle, Wendy L; Menni, Cristina; Merger, Sigrun; Mihailov, Evelin; Milani, Lili; Mills, Rebecca; Moayyeri, Alireza; Monda, Keri L; Mooijaart, Simon P; Mühleisen, Thomas W; Mulas, Antonella; Müller, Gabriele; Müller-Nurasyid, Martina; Nagaraja, Ramaiah; Nalls, Michael A; Narisu, Narisu; Glorioso, Nicola; Nolte, Ilja M; Olden, Matthias; Rayner, Nigel W; Renstrom, Frida; Ried, Janina S; Robertson, Neil R; Rose, Lynda M; Sanna, Serena; Scharnagl, Hubert; Scholtens, Salome; Sennblad, Bengt; Seufferlein, Thomas; Sitlani, Colleen M; Smith, Albert Vernon; Stirrups, Kathleen; Stringham, Heather M; Sundström, Johan; Swertz, Morris A; Swift, Amy J; Syvänen, Ann-Christine; Tayo, Bamidele O; Thorand, Barbara; Thorleifsson, Gudmar; Tomaschitz, Andreas; Troffa, Chiara; van Oort, Floor Va; Verweij, Niek; Vonk, Judith M; Waite, Lindsay L; Wennauer, Roman; Wilsgaard, Tom; Wojczynski, Mary K; Wong, Andrew; Zhang, Qunyuan; Zhao, Jing Hua; Brennan, Eoin P; Choi, Murim; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Gharavi, Ali G; Hedman, Åsa K; Hivert, Marie-France; Huang, Jinyan; Kanoni, Stavroula; Karpe, Fredrik; Keildson, Sarah; Kiryluk, Krzysztof; Liang, Liming; Lifton, Richard P; Ma, Baoshan; McKnight, Amy J; McPherson, Ruth; Metspalu, Andres; Min, Josine L; Moffatt, Miriam F; Montgomery, Grant W; Murabito, Joanne M; Nicholson, George; Nyholt, Dale R; Olsson, Christian; Perry, John Rb; Reinmaa, Eva; Salem, Rany M; Sandholm, Niina; Schadt, Eric E; Scott, Robert A; Stolk, Lisette; Vallejo, Edgar E; Westra, Harm-Jan; Zondervan, Krina T; Amouyel, Philippe; Arveiler, Dominique; Bakker, Stephan Jl; Beilby, John; Bergman, Richard N; Blangero, John; Brown, Morris J; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chines, Peter S; Claudi-Boehm, Simone; Collins, Francis S; Crawford, Dana C; Danesh, John; de Faire, Ulf; de Geus, Eco Jc; Dörr, Marcus; Erbel, Raimund; Eriksson, Johan G; Farrall, Martin; Ferrannini, Ele; Ferrières, Jean; Forouhi, Nita G; Forrester, Terrence; Franco, Oscar H; Gansevoort, Ron T; Gieger, Christian; Gudnason, Vilmundur; Haiman, Christopher A; Harris, Tamara B; Hattersley, Andrew T; Heliövaara, Markku; Hicks, Andrew A; Hingorani, Aroon D; Hoffmann, Wolfgang; Hofman, Albert; Homuth, Georg; Humphries, Steve E; Hyppönen, Elina; Illig, Thomas; Jarvelin, Marjo-Riitta; Johansen, Berit; Jousilahti, Pekka; Jula, Antti M; Kaprio, Jaakko; Kee, Frank; Keinanen-Kiukaanniemi, Sirkka M; Kooner, Jaspal S; Kooperberg, Charles; Kovacs, Peter; Kraja, Aldi T; Kumari, Meena; Kuulasmaa, Kari; Kuusisto, Johanna; Lakka, Timo A; Langenberg, Claudia; Le Marchand, Loic; Lehtimäki, Terho; Lyssenko, Valeriya; Männistö, Satu; Marette, André; Matise, Tara C; McKenzie, Colin A; McKnight, Barbara; Musk, Arthur W; Möhlenkamp, Stefan; Morris, Andrew D; Nelis, Mari; Ohlsson, Claes; Oldehinkel, Albertine J; Ong, Ken K; Palmer, Lyle J; Penninx, Brenda W; Peters, Annette; Pramstaller, Peter P; Raitakari, Olli T; Rankinen, Tuomo; Rao, D C; Rice, Treva K; Ridker, Paul M; Ritchie, Marylyn D; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J; Saramies, Jouko; Sarzynski, Mark A; Schwarz, Peter Eh; Shuldiner, Alan R; Staessen, Jan A; Steinthorsdottir, Valgerdur; Stolk, Ronald P; Strauch, Konstantin; Tönjes, Anke; Tremblay, Angelo; Tremoli, Elena; Vohl, Marie-Claude; Völker, Uwe; Vollenweider, Peter; Wilson, James F; Witteman, Jacqueline C; Adair, Linda S; Bochud, Murielle; Boehm, Bernhard O; Bornstein, Stefan R; Bouchard, Claude; Cauchi, Stéphane; Caulfield, Mark J; Chambers, John C; Chasman, Daniel I; Cooper, Richard S; Dedoussis, George; Ferrucci, Luigi; Froguel, Philippe; Grabe, Hans-Jörgen; Hamsten, Anders; Hui, Jennie; Hveem, Kristian; Jöckel, Karl-Heinz; Kivimaki, Mika; Kuh, Diana; Laakso, Markku; Liu, Yongmei; März, Winfried; Munroe, Patricia B; Njølstad, Inger; Oostra, Ben A; Palmer, Colin Na; Pedersen, Nancy L; Perola, Markus; Pérusse, Louis; Peters, Ulrike; Power, Chris; Quertermous, Thomas; Rauramaa, Rainer; Rivadeneira, Fernando; Saaristo, Timo E; Saleheen, Danish; Sinisalo, Juha; Slagboom, P Eline; Snieder, Harold; Spector, Tim D; Stefansson, Kari; Stumvoll, Michael; Tuomilehto, Jaakko; Uitterlinden, André G; Uusitupa, Matti; van der Harst, Pim; Veronesi, Giovanni; Walker, Mark; Wareham, Nicholas J; Watkins, Hugh; Wichmann, H-Erich; Abecasis, Goncalo R; Assimes, Themistocles L; Berndt, Sonja I; Boehnke, Michael; Borecki, Ingrid B; Deloukas, Panos; Franke, Lude; Frayling, Timothy M; Groop, Leif C; Hunter, David J; Kaplan, Robert C; O'Connell, Jeffrey R; Qi, Lu; Schlessinger, David; Strachan, David P; Thorsteinsdottir, Unnur; van Duijn, Cornelia M; Willer, Cristen J; Visscher, Peter M; Yang, Jian; Hirschhorn, Joel N; Zillikens, M Carola; McCarthy, Mark I; Speliotes, Elizabeth K; North, Kari E; Fox, Caroline S; Barroso, Inês; Franks, Paul W; Ingelsson, Erik; Heid, Iris M; Loos, Ruth Jf; Cupples, L Adrienne; Morris, Andrew P; Lindgren, Cecilia M; Mohlke, Karen L

2015-02-12

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Relevant genetic differentiation among Brazilian populations of Anastrepha fraterculus (Diptera, Tephritidae)

PubMed Central

Manni, Mosè; Lima, Kátia Manuela; Guglielmino, Carmela Rosalba; Lanzavecchia, Silvia Beatriz; Juri, Marianela; Vera, Teresa; Cladera, Jorge; Scolari, Francesca; Gomulski, Ludvik; Bonizzoni, Mariangela; Gasperi, Giuliano; Silva, Janisete Gomes; Malacrida, Anna Rodolfa

2015-01-01

Abstract We used a population genetic approach to detect the presence of genetic diversity among six populations of Anastrepha fraterculus across Brazil. To this aim, we used Simple Sequence Repeat (SSR) markers, which may capture the presence of differentiative processes across the genome in distinct populations. Spatial analyses of molecular variance were used to identify groups of populations that are both genetically and geographically homogeneous while also being maximally differentiated from each other. The spatial analysis of genetic diversity indicates that the levels of diversity among the six populations vary significantly on an eco-geographical basis. Particularly, altitude seems to represent a differentiating adaptation, as the main genetic differentiation is detected between the two populations present at higher altitudes and the other four populations at sea level. The data, together with the outcomes from different cluster analyses, identify a genetic diversity pattern that overlaps with the distribution of the known morphotypes in the Brazilian area. PMID:26798258

Iron-absorption band analysis for the discrimination of iron-rich zones

NASA Technical Reports Server (NTRS)

Rowan, L. C. (Principal Investigator)

1973-01-01

The author has identified the following significant results. Study has concentrated on the two primary aspects of the project, structural analysis through evaluation of lineaments and circular features and spectral analyses through digital computer-processing techniques. Several previously unrecognized lineaments are mapped which may be the surface manifestations of major fault or fracture zones. Two of these, the Walker Lane and the Midas Trench lineament system, transect the predominantly NNE-NNW-trending moutain ranges for more than 500 km. Correlation of major lineaments with productive mining districts implies a genetic relationship, the 50 circular or elliptical features delineated suggest a related role for Tertiary volcanism. Color-ratio composites have been used to identify limonitic zones and to discriminate mafic and felsic rock by combing diazo color transparencies of three different ratios. EROS Data Center scene identification number for color composite in this report is ER 1 CC 500. Refinement of enhancement procedures for the ratio images is progressing. Fieldwork in coordination with both spectral and structural analyses is underway.

New genetic loci link adipose and insulin biology to body fat distribution

PubMed Central

Strawbridge, Rona J; Pers, Tune H; Fischer, Krista; Justice, Anne E; Workalemahu, Tsegaselassie; Wu, Joseph M.W.; Buchkovich, Martin L; Heard-Costa, Nancy L; Roman, Tamara S; Drong, Alexander W; Song, Ci; Gustafsson, Stefan; Day, Felix R; Esko, Tonu; Fall, Tove; Kutalik, Zoltán; Luan, Jian’an; Randall, Joshua C; Scherag, André; Vedantam, Sailaja; Wood, Andrew R; Chen, Jin; Fehrmann, Rudolf; Karjalainen, Juha; Kahali, Bratati; Liu, Ching-Ti; Schmidt, Ellen M; Absher, Devin; Amin, Najaf; Anderson, Denise; Beekman, Marian; Bragg-Gresham, Jennifer L; Buyske, Steven; Demirkan, Ayse; Ehret, Georg B; Feitosa, Mary F; Goel, Anuj; Jackson, Anne U; Johnson, Toby; Kleber, Marcus E; Kristiansson, Kati; Mangino, Massimo; Leach, Irene Mateo; Medina-Gomez, Carolina; Palmer, Cameron D; Pasko, Dorota; Pechlivanis, Sonali; Peters, Marjolein J; Prokopenko, Inga; Stančáková, Alena; Sung, Yun Ju; Tanaka, Toshiko; Teumer, Alexander; Van Vliet-Ostaptchouk, Jana V; Yengo, Loïc; Zhang, Weihua; Albrecht, Eva; Ärnlöv, Johan; Arscott, Gillian M; Bandinelli, Stefania; Barrett, Amy; Bellis, Claire; Bennett, Amanda J; Berne, Christian; Blüher, Matthias; Böhringer, Stefan; Bonnet, Fabrice; Böttcher, Yvonne; Bruinenberg, Marcel; Carba, Delia B; Caspersen, Ida H; Clarke, Robert; Daw, E Warwick; Deelen, Joris; Deelman, Ewa; Delgado, Graciela; Doney, Alex SF; Eklund, Niina; Erdos, Michael R; Estrada, Karol; Eury, Elodie; Friedrich, Nele; Garcia, Melissa E; Giedraitis, Vilmantas; Gigante, Bruna; Go, Alan S; Golay, Alain; Grallert, Harald; Grammer, Tanja B; Gräßler, Jürgen; Grewal, Jagvir; Groves, Christopher J; Haller, Toomas; Hallmans, Goran; Hartman, Catharina A; Hassinen, Maija; Hayward, Caroline; Heikkilä, Kauko; Herzig, Karl-Heinz; Helmer, Quinta; Hillege, Hans L; Holmen, Oddgeir; Hunt, Steven C; Isaacs, Aaron; Ittermann, Till; James, Alan L; Johansson, Ingegerd; Juliusdottir, Thorhildur; Kalafati, Ioanna-Panagiota; Kinnunen, Leena; Koenig, Wolfgang; Kooner, Ishminder K; Kratzer, Wolfgang; Lamina, Claudia; Leander, Karin; Lee, Nanette R; Lichtner, Peter; Lind, Lars; Lindström, Jaana; Lobbens, Stéphane; Lorentzon, Mattias; Mach, François; Magnusson, Patrik KE; Mahajan, Anubha; McArdle, Wendy L; Menni, Cristina; Merger, Sigrun; Mihailov, Evelin; Milani, Lili; Mills, Rebecca; Moayyeri, Alireza; Monda, Keri L; Mooijaart, Simon P; Mühleisen, Thomas W; Mulas, Antonella; Müller, Gabriele; Müller-Nurasyid, Martina; Nagaraja, Ramaiah; Nalls, Michael A; Narisu, Narisu; Glorioso, Nicola; Nolte, Ilja M; Olden, Matthias; Rayner, Nigel W; Renstrom, Frida; Ried, Janina S; Robertson, Neil R; Rose, Lynda M; Sanna, Serena; Scharnagl, Hubert; Scholtens, Salome; Sennblad, Bengt; Seufferlein, Thomas; Sitlani, Colleen M; Smith, Albert Vernon; Stirrups, Kathleen; Stringham, Heather M; Sundström, Johan; Swertz, Morris A; Swift, Amy J; Syvänen, Ann-Christine; Tayo, Bamidele O; Thorand, Barbara; Thorleifsson, Gudmar; Tomaschitz, Andreas; Troffa, Chiara; van Oort, Floor VA; Verweij, Niek; Vonk, Judith M; Waite, Lindsay L; Wennauer, Roman; Wilsgaard, Tom; Wojczynski, Mary K; Wong, Andrew; Zhang, Qunyuan; Zhao, Jing Hua; Brennan, Eoin P.; Choi, Murim; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Gharavi, Ali G; Hedman, Åsa K; Hivert, Marie-France; Huang, Jinyan; Kanoni, Stavroula; Karpe, Fredrik; Keildson, Sarah; Kiryluk, Krzysztof; Liang, Liming; Lifton, Richard P; Ma, Baoshan; McKnight, Amy J; McPherson, Ruth; Metspalu, Andres; Min, Josine L; Moffatt, Miriam F; Montgomery, Grant W; Murabito, Joanne M; Nicholson, George; Nyholt, Dale R; Olsson, Christian; Perry, John RB; Reinmaa, Eva; Salem, Rany M; Sandholm, Niina; Schadt, Eric E; Scott, Robert A; Stolk, Lisette; Vallejo, Edgar E.; Westra, Harm-Jan; Zondervan, Krina T; Amouyel, Philippe; Arveiler, Dominique; Bakker, Stephan JL; Beilby, John; Bergman, Richard N; Blangero, John; Brown, Morris J; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chines, Peter S; Claudi-Boehm, Simone; Collins, Francis S; Crawford, Dana C; Danesh, John; de Faire, Ulf; de Geus, Eco JC; Dörr, Marcus; Erbel, Raimund; Eriksson, Johan G; Farrall, Martin; Ferrannini, Ele; Ferrières, Jean; Forouhi, Nita G; Forrester, Terrence; Franco, Oscar H; Gansevoort, Ron T; Gieger, Christian; Gudnason, Vilmundur; Haiman, Christopher A; Harris, Tamara B; Hattersley, Andrew T; Heliövaara, Markku; Hicks, Andrew A; Hingorani, Aroon D; Hoffmann, Wolfgang; Hofman, Albert; Homuth, Georg; Humphries, Steve E; Hyppönen, Elina; Illig, Thomas; Jarvelin, Marjo-Riitta; Johansen, Berit; Jousilahti, Pekka; Jula, Antti M; Kaprio, Jaakko; Kee, Frank; Keinanen-Kiukaanniemi, Sirkka M; Kooner, Jaspal S; Kooperberg, Charles; Kovacs, Peter; Kraja, Aldi T; Kumari, Meena; Kuulasmaa, Kari; Kuusisto, Johanna; Lakka, Timo A; Langenberg, Claudia; Le Marchand, Loic; Lehtimäki, Terho; Lyssenko, Valeriya; Männistö, Satu; Marette, André; Matise, Tara C; McKenzie, Colin A; McKnight, Barbara; Musk, Arthur W; Möhlenkamp, Stefan; Morris, Andrew D; Nelis, Mari; Ohlsson, Claes; Oldehinkel, Albertine J; Ong, Ken K; Palmer, Lyle J; Penninx, Brenda W; Peters, Annette; Pramstaller, Peter P; Raitakari, Olli T; Rankinen, Tuomo; Rao, DC; Rice, Treva K; Ridker, Paul M; Ritchie, Marylyn D.; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J; Saramies, Jouko; Sarzynski, Mark A; Schwarz, Peter EH; Shuldiner, Alan R; Staessen, Jan A; Steinthorsdottir, Valgerdur; Stolk, Ronald P; Strauch, Konstantin; Tönjes, Anke; Tremblay, Angelo; Tremoli, Elena; Vohl, Marie-Claude; Völker, Uwe; Vollenweider, Peter; Wilson, James F; Witteman, Jacqueline C; Adair, Linda S; Bochud, Murielle; Boehm, Bernhard O; Bornstein, Stefan R; Bouchard, Claude; Cauchi, Stéphane; Caulfield, Mark J; Chambers, John C; Chasman, Daniel I; Cooper, Richard S; Dedoussis, George; Ferrucci, Luigi; Froguel, Philippe; Grabe, Hans-Jörgen; Hamsten, Anders; Hui, Jennie; Hveem, Kristian; Jöckel, Karl-Heinz; Kivimaki, Mika; Kuh, Diana; Laakso, Markku; Liu, Yongmei; März, Winfried; Munroe, Patricia B; Njølstad, Inger; Oostra, Ben A; Palmer, Colin NA; Pedersen, Nancy L; Perola, Markus; Pérusse, Louis; Peters, Ulrike; Power, Chris; Quertermous, Thomas; Rauramaa, Rainer; Rivadeneira, Fernando; Saaristo, Timo E; Saleheen, Danish; Sinisalo, Juha; Slagboom, P Eline; Snieder, Harold; Spector, Tim D; Stefansson, Kari; Stumvoll, Michael; Tuomilehto, Jaakko; Uitterlinden, André G; Uusitupa, Matti; van der Harst, Pim; Veronesi, Giovanni; Walker, Mark; Wareham, Nicholas J; Watkins, Hugh; Wichmann, H-Erich; Abecasis, Goncalo R; Assimes, Themistocles L; Berndt, Sonja I; Boehnke, Michael; Borecki, Ingrid B; Deloukas, Panos; Franke, Lude; Frayling, Timothy M; Groop, Leif C; Hunter, David J.; Kaplan, Robert C; O’Connell, Jeffrey R; Qi, Lu; Schlessinger, David; Strachan, David P; Thorsteinsdottir, Unnur; van Duijn, Cornelia M; Willer, Cristen J; Visscher, Peter M; Yang, Jian; Hirschhorn, Joel N; Zillikens, M Carola; McCarthy, Mark I; Speliotes, Elizabeth K; North, Kari E; Fox, Caroline S; Barroso, Inês; Franks, Paul W; Ingelsson, Erik; Heid, Iris M; Loos, Ruth JF; Cupples, L Adrienne; Morris, Andrew P; Lindgren, Cecilia M; Mohlke, Karen L

2014-01-01

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10−8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms. PMID:25673412

An Analysis of the "Classic" Papers in Aesthetic Surgery.

PubMed

Joyce, Cormac W; Joyce, K M; Kelly, John C; Kelly, Jack L; Carroll, Sean M; Sugrue, Conor

2015-02-01

Over the past 50 years, there has been a significant increase in published articles in the medical literature. The aesthetic surgery literature is vast, consisting of a plethora of diverse articles written by a myriad of illustrious authors. Despite this considerable archive of published material, it remains nebulous as to which precise papers have had the greatest impact on our specialty. The aim of our study was to identify and analyse the characteristics of the top 50 papers in the field of aesthetic surgery in the published literature. The 50 most cited papers were identified in several surgical journals through the Web of Science. The articles were ranked in order of the number of citations received. These classic 50 papers were analysed for article type, their journal distribution, level of evidence as well as geographic and institutional origin. Six journals contributed to the top 50 papers in aesthetic surgery with Plastic and Reconstructive Surgery contributing the most with 31 papers.

Factors which motivate the use of social networks by students.

PubMed

González Sanmamed, Mercedes; Muñoz Carril, Pablo C; Dans Álvarez de Sotomayor, Isabel

2017-05-01

The aim of this research was to identify those factors which motivate the use of social networks by 4th year students in Secondary Education between the ages of 15 and 18. 1,144 students from 29 public and private schools took part. The data were analysed using Partial Least Squares Structural Equation Modelling technique. Versatility was confirmed to be the variable which most influences the motivation of students in their use of social networks. The positive relationship between versatility in the use of social networks and educational uses was also significant. The characteristics of social networks are analysed according to their versatility and how this aspect makes them attractive to students. The positive effects of social networks are discussed in terms of educational uses and their contribution to school learning. There is also a warning about the risks associated with misuse of social networks, and finally, the characteristics and conditions for the development of good educational practice through social networks are identified.

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

PubMed Central

Christophersen, Ingrid E.; Rienstra, Michiel; Roselli, Carolina; Yin, Xiaoyan; Geelhoed, Bastiaan; Barnard, John; Lin, Honghuang; Arking, Dan E.; Smith, Albert V.; Albert, Christine M.; Chaffin, Mark; Tucker, Nathan R.; Li, Molong; Klarin, Derek; Bihlmeyer, Nathan A; Low, Siew-Kee; Weeke, Peter E.; Müller-Nurasyid, Martina; Smith, J. Gustav; Brody, Jennifer A.; Niemeijer, Maartje N.; Dörr, Marcus; Trompet, Stella; Huffman, Jennifer; Gustafsson, Stefan; Schurman, Claudia; Kleber, Marcus E.; Lyytikäinen, Leo-Pekka; Seppälä, Ilkka; Malik, Rainer; Horimoto, Andrea R. V. R.; Perez, Marco; Sinisalo, Juha; Aeschbacher, Stefanie; Thériault, Sébastien; Yao, Jie; Radmanesh, Farid; Weiss, Stefan; Teumer, Alexander; Choi, Seung Hoan; Weng, Lu-Chen; Clauss, Sebastian; Deo, Rajat; Rader, Daniel J.; Shah, Svati; Sun, Albert; Hopewell, Jemma C.; Debette, Stephanie; Chauhan, Ganesh; Yang, Qiong; Worrall, Bradford B.; Paré, Guillaume; Kamatani, Yoichiro; Hagemeijer, Yanick P.; Verweij, Niek; Siland, Joylene E.; Kubo, Michiaki; Smith, Jonathan D.; Van Wagoner, David R.; Bis, Joshua C.; Perz, Siegfried; Psaty, Bruce M.; Ridker, Paul M.; Magnani, Jared W.; Harris, Tamara B.; Launer, Lenore J.; Shoemaker, M. Benjamin; Padmanabhan, Sandosh; Haessler, Jeffrey; Bartz, Traci M.; Waldenberger, Melanie; Lichtner, Peter; Arendt, Marina; Krieger, Jose E.; Kähönen, Mika; Risch, Lorenz; Mansur, Alfredo J.; Peters, Annette; Smith, Blair H.; Lind, Lars; Scott, Stuart A.; Lu, Yingchang; Bottinger, Erwin B.; Hernesniemi, Jussi; Lindgren, Cecilia M.; Wong, Jorge; Huang, Jie; Eskola, Markku; Morris, Andrew P.; Ford, Ian; Reiner, Alex P.; Delgado, Graciela; Chen, Lin Y.; Chen, Yii-Der Ida; Sandhu, Roopinder K.; Li, Man; Boerwinkle, Eric; Eisele, Lewin; Lannfelt, Lars; Rost, Natalia; Anderson, Christopher D.; Taylor, Kent D.; Campbell, Archie; Magnusson, Patrik K.; Porteous, David; Hocking, Lynne J.; Vlachopoulou, Efthymia; Pedersen, Nancy L.; Nikus, Kjell; Orho-Melander, Marju; Hamsten, Anders; Heeringa, Jan; Denny, Joshua C.; Kriebel, Jennifer; Darbar, Dawood; Newton-Cheh, Christopher; Shaffer, Christian; Macfarlane, Peter W.; Heilmann, Stefanie; Almgren, Peter; Huang, Paul L.; Sotoodehnia, Nona; Soliman, Elsayed Z.; Uitterlinden, Andre G.; Hofman, Albert; Franco, Oscar H.; Völker, Uwe; Jöckel, Karl-Heinz; Sinner, Moritz F.; Lin, Henry J.; Guo, Xiuqing; Dichgans, Martin; Ingelsson, Erik; Kooperberg, Charles; Melander, Olle; Loos, Ruth J. F.; Laurikka, Jari; Conen, David; Rosand, Jonathan; van der Harst, Pim; Lokki, Marja-Liisa; Kathiresan, Sekar; Pereira, Alexandre; Jukema, J. Wouter; Hayward, Caroline; Rotter, Jerome I.; März, Winfried; Lehtimäki, Terho; Stricker, Bruno H.; Chung, Mina K.; Felix, Stephan B.; Gudnason, Vilmundur; Alonso, Alvaro; Roden, Dan M.; Kääb, Stefan; Chasman, Daniel I.; Heckbert, Susan R.; Benjamin, Emelia J.; Tanaka, Toshihiro; Lunetta, Kathryn L.; Lubitz, Steven A.; Ellinor, Patrick T.

2017-01-01

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death.1,2 Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups.3–7 To further define the genetic basis of atrial fibrillation, we performed large-scale, multi-racial meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 18,398 individuals with atrial fibrillation and 91,536 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,806 cases and 132,612 referents. We identified 12 novel genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate new potential targets for drug discovery.8 PMID:28416818

An effective approach for annotation of protein families with low sequence similarity and conserved motifs: identifying GDSL hydrolases across the plant kingdom.

PubMed

Vujaklija, Ivan; Bielen, Ana; Paradžik, Tina; Biđin, Siniša; Goldstein, Pavle; Vujaklija, Dušica

2016-02-18

The massive accumulation of protein sequences arising from the rapid development of high-throughput sequencing, coupled with automatic annotation, results in high levels of incorrect annotations. In this study, we describe an approach to decrease annotation errors of protein families characterized by low overall sequence similarity. The GDSL lipolytic family comprises proteins with multifunctional properties and high potential for pharmaceutical and industrial applications. The number of proteins assigned to this family has increased rapidly over the last few years. In particular, the natural abundance of GDSL enzymes reported recently in plants indicates that they could be a good source of novel GDSL enzymes. We noticed that a significant proportion of annotated sequences lack specific GDSL motif(s) or catalytic residue(s). Here, we applied motif-based sequence analyses to identify enzymes possessing conserved GDSL motifs in selected proteomes across the plant kingdom. Motif-based HMM scanning (Viterbi decoding-VD and posterior decoding-PD) and the here described PD/VD protocol were successfully applied on 12 selected plant proteomes to identify sequences with GDSL motifs. A significant number of identified GDSL sequences were novel. Moreover, our scanning approach successfully detected protein sequences lacking at least one of the essential motifs (171/820) annotated by Pfam profile search (PfamA) as GDSL. Based on these analyses we provide a curated list of GDSL enzymes from the selected plants. CLANS clustering and phylogenetic analysis helped us to gain a better insight into the evolutionary relationship of all identified GDSL sequences. Three novel GDSL subfamilies as well as unreported variations in GDSL motifs were discovered in this study. In addition, analyses of selected proteomes showed a remarkable expansion of GDSL enzymes in the lycophyte, Selaginella moellendorffii. Finally, we provide a general motif-HMM scanner which is easily accessible through the graphical user interface ( http://compbio.math.hr/ ). Our results show that scanning with a carefully parameterized motif-HMM is an effective approach for annotation of protein families with low sequence similarity and conserved motifs. The results of this study expand current knowledge and provide new insights into the evolution of the large GDSL-lipase family in land plants.

Search for Bs0 oscillations using inclusive lepton events

NASA Astrophysics Data System (ADS)

ALEPH Collaboration; Barate, R.; et al.

1999-03-01

A search for Bs0 oscillations is performed using a sample of semileptonic b-hadron decays collected by the ALEPH experiment during 1991-95. Compared to previous inclusive lepton analyses, the proper time resolution and b-flavour mistag rate are significantly improved. Additional sensitivity to Bs0 mixing is obtained by identifying subsamples of events having a Bs0 purity which is higher than the average for the whole data sample. Unbinned maximum likelihood amplitude fits are performed to derive a lower limit of Δ m s > 9.5 ps-1 at the 95% confidence limit (95% CL). Combining with the ALEPH Ds--based analyses yields Δ m s > 9.6 ps-1 at 95% CL.

Convergence tests on tax burden and economic growth among China, Taiwan and the OECD countries

NASA Astrophysics Data System (ADS)

Wang, David Han-Min

2007-07-01

The unfolding globalization has profound impact on a wide range of nations’ policies including tax and economy policies. This study adopts the time series and cluster analyses to examine the convergence property of tax burden and per capita gross domestic product among Taiwan, China and the OECD countries. The empirical results show that there is no significant relationship between the integration process and fiscal convergence among countries. However, the cluster analyses identify that the group of China, Taiwan, and Korea was stably moving toward one model during the 1970s, 1980s and 1990s. And, the convergence of tax burden is found in the group, but no pairwise convergence exists.

Emerging patterns of somatic mutations in cancer

PubMed Central

Watson, Ian R.; Takahashi, Koichi; Futreal, P. Andrew; Chin, Lynda

2014-01-01

The advance in technological tools for massively parallel, high-throughput sequencing of DNA has enabled the comprehensive characterization of somatic mutations in large number of tumor samples. Here, we review recent cancer genomic studies that have assembled emerging views of the landscapes of somatic mutations through deep sequencing analyses of the coding exomes and whole genomes in various cancer types. We discuss the comparative genomics of different cancers, including mutation rates, spectrums, and roles of environmental insults that influence these processes. We highlight the developing statistical approaches used to identify significantly mutated genes, and discuss the emerging biological and clinical insights from such analyses as well as the challenges ahead translating these genomic data into clinical impacts. PMID:24022702

Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry

PubMed Central

Benjamin, Emelia J.; Rice, Kenneth M.; Arking, Dan E.; Pfeufer, Arne; van Noord, Charlotte; Smith, Albert V.; Schnabel, Renate B.; Bis, Joshua C.; Boerwinkle, Eric; Sinner, Moritz F.; Dehghan, Abbas; Lubitz, Steven A.; D’Agostino, Ralph B.; Lumley, Thomas; Ehret, Georg B.; Heeringa, Jan; Aspelund, Thor; Newton-Cheh, Christopher; Larson, Martin G.; Marciante, Kristin D.; Soliman, Elsayed Z.; Rivadeneira, Fernando; Wang, Thomas J.; Eiriksdottir, Gudny; Levy, Daniel; Psaty, Bruce M.; Li, Man; Chamberlain, Alanna M.; Hofman, Albert; Vasan, Ramachandran S.; Harris, Tamara B.; Rotter, Jerome I.; Kao, W.H. Linda; Agarwal, Sunil K.; Ch. Stricker, Bruno H.; Wang, Ke; Launer, Lenore J.; Smith, Nicholas L.; Chakravarti, Aravinda; Uitterlinden, Andre G.; Wolf, Philip A; Sotoodehnia, Nona; Kottgen, Anna; van Duijn, Cornelia M.; Lunetta, Kathryn L.; Heckbert, Susan R.; Gudnason, Vilmundur; Alonso, Alvaro; Kaab, Stefan; Ellinor, Patrick T.; Witteman, Jacqueline C.

2009-01-01

We conducted meta-analyses of genome-wide association studies (GWAS) for atrial fibrillation (AF) in participants from five community-based cohorts. Meta-analyses of 896 prevalent (15,768 referents) and 2,517 incident (21,337 referents) AF cases identified a novel locus for AF (ZFHX3, rs2106261, risk ratio [RR]=1.19; P=2.3×10−7), an association that was replicated in the German AF Network (odds ratio=1.44; P=1.6×10−11). Combining the discovery and replication results, rs2106261 was significantly associated with AF (RR=1.25; P=1.8×10−15). PMID:19597492

Power, effects, confidence, and significance: an investigation of statistical practices in nursing research.

PubMed

Gaskin, Cadeyrn J; Happell, Brenda

2014-05-01

To (a) assess the statistical power of nursing research to detect small, medium, and large effect sizes; (b) estimate the experiment-wise Type I error rate in these studies; and (c) assess the extent to which (i) a priori power analyses, (ii) effect sizes (and interpretations thereof), and (iii) confidence intervals were reported. Statistical review. Papers published in the 2011 volumes of the 10 highest ranked nursing journals, based on their 5-year impact factors. Papers were assessed for statistical power, control of experiment-wise Type I error, reporting of a priori power analyses, reporting and interpretation of effect sizes, and reporting of confidence intervals. The analyses were based on 333 papers, from which 10,337 inferential statistics were identified. The median power to detect small, medium, and large effect sizes was .40 (interquartile range [IQR]=.24-.71), .98 (IQR=.85-1.00), and 1.00 (IQR=1.00-1.00), respectively. The median experiment-wise Type I error rate was .54 (IQR=.26-.80). A priori power analyses were reported in 28% of papers. Effect sizes were routinely reported for Spearman's rank correlations (100% of papers in which this test was used), Poisson regressions (100%), odds ratios (100%), Kendall's tau correlations (100%), Pearson's correlations (99%), logistic regressions (98%), structural equation modelling/confirmatory factor analyses/path analyses (97%), and linear regressions (83%), but were reported less often for two-proportion z tests (50%), analyses of variance/analyses of covariance/multivariate analyses of variance (18%), t tests (8%), Wilcoxon's tests (8%), Chi-squared tests (8%), and Fisher's exact tests (7%), and not reported for sign tests, Friedman's tests, McNemar's tests, multi-level models, and Kruskal-Wallis tests. Effect sizes were infrequently interpreted. Confidence intervals were reported in 28% of papers. The use, reporting, and interpretation of inferential statistics in nursing research need substantial improvement. Most importantly, researchers should abandon the misleading practice of interpreting the results from inferential tests based solely on whether they are statistically significant (or not) and, instead, focus on reporting and interpreting effect sizes, confidence intervals, and significance levels. Nursing researchers also need to conduct and report a priori power analyses, and to address the issue of Type I experiment-wise error inflation in their studies. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Gene expression patterns combined with network analysis identify hub genes associated with bladder cancer.

PubMed

Bi, Dongbin; Ning, Hao; Liu, Shuai; Que, Xinxiang; Ding, Kejia

2015-06-01

To explore molecular mechanisms of bladder cancer (BC), network strategy was used to find biomarkers for early detection and diagnosis. The differentially expressed genes (DEGs) between bladder carcinoma patients and normal subjects were screened using empirical Bayes method of the linear models for microarray data package. Co-expression networks were constructed by differentially co-expressed genes and links. Regulatory impact factors (RIF) metric was used to identify critical transcription factors (TFs). The protein-protein interaction (PPI) networks were constructed by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and clusters were obtained through molecular complex detection (MCODE) algorithm. Centralities analyses for complex networks were performed based on degree, stress and betweenness. Enrichment analyses were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Co-expression networks and TFs (based on expression data of global DEGs and DEGs in different stages and grades) were identified. Hub genes of complex networks, such as UBE2C, ACTA2, FABP4, CKS2, FN1 and TOP2A, were also obtained according to analysis of degree. In gene enrichment analyses of global DEGs, cell adhesion, proteinaceous extracellular matrix and extracellular matrix structural constituent were top three GO terms. ECM-receptor interaction, focal adhesion, and cell cycle were significant pathways. Our results provide some potential underlying biomarkers of BC. However, further validation is required and deep studies are needed to elucidate the pathogenesis of BC. Copyright © 2015 Elsevier Ltd. All rights reserved.

Event-related fMRI studies of false memory: An Activation Likelihood Estimation meta-analysis.

PubMed

Kurkela, Kyle A; Dennis, Nancy A

2016-01-29

Over the last two decades, a wealth of research in the domain of episodic memory has focused on understanding the neural correlates mediating false memories, or memories for events that never happened. While several recent qualitative reviews have attempted to synthesize this literature, methodological differences amongst the empirical studies and a focus on only a sub-set of the findings has limited broader conclusions regarding the neural mechanisms underlying false memories. The current study performed a voxel-wise quantitative meta-analysis using activation likelihood estimation to investigate commonalities within the functional magnetic resonance imaging (fMRI) literature studying false memory. The results were broken down by memory phase (encoding, retrieval), as well as sub-analyses looking at differences in baseline (hit, correct rejection), memoranda (verbal, semantic), and experimental paradigm (e.g., semantic relatedness and perceptual relatedness) within retrieval. Concordance maps identified significant overlap across studies for each analysis. Several regions were identified in the general false retrieval analysis as well as multiple sub-analyses, indicating their ubiquitous, yet critical role in false retrieval (medial superior frontal gyrus, left precentral gyrus, left inferior parietal cortex). Additionally, several regions showed baseline- and paradigm-specific effects (hit/perceptual relatedness: inferior and middle occipital gyrus; CRs: bilateral inferior parietal cortex, precuneus, left caudate). With respect to encoding, analyses showed common activity in the left middle temporal gyrus and anterior cingulate cortex. No analysis identified a common cluster of activation in the medial temporal lobe. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rare copy number variants in patients with congenital conotruncal heart defects.

PubMed

Xie, Hongbo M; Werner, Petra; Stambolian, Dwight; Bailey-Wilson, Joan E; Hakonarson, Hakon; White, Peter S; Taylor, Deanne M; Goldmuntz, Elizabeth

2017-03-01

Previous studies using different cardiac phenotypes, technologies and designs suggest a burden of large, rare or de novo copy number variants (CNVs) in subjects with congenital heart defects. We sought to identify disease-related CNVs, candidate genes, and functional pathways in a large number of cases with conotruncal and related defects that carried no known genetic syndrome. Cases and control samples were divided into two cohorts and genotyped to assess each subject's CNV content. Analyses were performed to ascertain differences in overall CNV prevalence and to identify enrichment of specific genes and functional pathways in conotruncal cases relative to healthy controls. Only findings present in both cohorts are presented. From 973 total conotruncal cases, a burden of rare CNVs was detected in both cohorts. Candidate genes from rare CNVs found in both cohorts were identified based on their association with cardiac development or disease, and/or their reported disruption in published studies. Functional and pathway analyses revealed significant enrichment of terms involved in either heart or early embryonic development. Our study tested one of the largest cohorts specifically with cardiac conotruncal and related defects. These results confirm and extend previous findings that CNVs contribute to disease risk for congenital heart defects in general and conotruncal defects in particular. As disease heterogeneity renders identification of single recurrent genes or loci difficult, functional pathway and gene regulation network analyses appear to be more informative. Birth Defects Research 109:271-295, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

MVisAGe Identifies Concordant and Discordant Genomic Alterations of Driver Genes in Squamous Tumors.

PubMed

Walter, Vonn; Du, Ying; Danilova, Ludmila; Hayward, Michele C; Hayes, D Neil

2018-06-15

Integrated analyses of multiple genomic datatypes are now common in cancer profiling studies. Such data present opportunities for numerous computational experiments, yet analytic pipelines are limited. Tools such as the cBioPortal and Regulome Explorer, although useful, are not easy to access programmatically or to implement locally. Here, we introduce the MVisAGe R package, which allows users to quantify gene-level associations between two genomic datatypes to investigate the effect of genomic alterations (e.g., DNA copy number changes on gene expression). Visualizing Pearson/Spearman correlation coefficients according to the genomic positions of the underlying genes provides a powerful yet novel tool for conducting exploratory analyses. We demonstrate its utility by analyzing three publicly available cancer datasets. Our approach highlights canonical oncogenes in chr11q13 that displayed the strongest associations between expression and copy number, including CCND1 and CTTN , genes not identified by copy number analysis in the primary reports. We demonstrate highly concordant usage of shared oncogenes on chr3q, yet strikingly diverse oncogene usage on chr11q as a function of HPV infection status. Regions of chr19 that display remarkable associations between methylation and gene expression were identified, as were previously unreported miRNA-gene expression associations that may contribute to the epithelial-to-mesenchymal transition. Significance: This study presents an important bioinformatics tool that will enable integrated analyses of multiple genomic datatypes. Cancer Res; 78(12); 3375-85. ©2018 AACR . ©2018 American Association for Cancer Research.

Transcriptome analyses provide insights into the difference of alkaloids biosynthesis in the Chinese goldthread (Coptis chinensis Franch.) from different biotopes.

PubMed

Chen, Hanting; Deng, Cao; Nie, Hu; Fan, Gang; He, Yang

2017-01-01

Coptis chinensis Franch., the Chinese goldthread ('Weilian' in Chinese), one of the most important medicinal plants from the family Ranunculaceae, and its rhizome has been widely used in Traditional Chinese Medicine for centuries. Here, we analyzed the chemical components and the transcriptome of the Chinese goldthread from three biotopes, including Zhenping, Zunyi and Shizhu. We built comprehensive, high-quality de novo transcriptome assemblies of the Chinese goldthread from short-read RNA-Sequencing data, obtaining 155,710 transcripts and 56,071 unigenes. More than 98.39% and 95.97% of core eukaryotic genes were found in the transcripts and unigenes respectively, indicating that this unigene set capture the majority of the coding genes. A total of 520,462, 493,718, and 507,247 heterozygous SNPs were identified in the three accessions from Zhenping, Zunyi, and Shizhu respectively, indicating high polymorphism in coding regions of the Chinese goldthread (∼1%). Chemical analyses of the rhizome identified six major components, including berberine, palmatine, coptisine, epiberberine, columbamine, and jatrorrhizine. Berberine has the highest concentrations, followed by coptisine, palmatine, and epiberberine sequentially for all the three accessions. The drug quality of the accession from Shizhu may be the highest among these accessions. Differential analyses of the transcriptome identified four pivotal candidate enzymes, including aspartate aminotransferaseprotein, polyphenol oxidase, primary-amine oxidase, and tyrosine decarboxylase, were significantly differentially expressed and may be responsible for the difference of alkaloids contents in the accessions from different biotopes.

Subgroup analyses in confirmatory clinical trials: time to be specific about their purposes.

PubMed

Tanniou, Julien; van der Tweel, Ingeborg; Teerenstra, Steven; Roes, Kit C B

2016-02-18

It is well recognized that treatment effects may not be homogeneous across the study population. Subgroup analyses constitute a fundamental step in the assessment of evidence from confirmatory (Phase III) clinical trials, where conclusions for the overall study population might not hold. Subgroup analyses can have different and distinct purposes, requiring specific design and analysis solutions. It is relevant to evaluate methodological developments in subgroup analyses against these purposes to guide health care professionals and regulators as well as to identify gaps in current methodology. We defined four purposes for subgroup analyses: (1) Investigate the consistency of treatment effects across subgroups of clinical importance, (2) Explore the treatment effect across different subgroups within an overall non-significant trial, (3) Evaluate safety profiles limited to one or a few subgroup(s), (4) Establish efficacy in the targeted subgroup when included in a confirmatory testing strategy of a single trial. We reviewed the methodology in line with this "purpose-based" framework. The review covered papers published between January 2005 and April 2015 and aimed to classify them in none, one or more of the aforementioned purposes. In total 1857 potentially eligible papers were identified. Forty-eight papers were selected and 20 additional relevant papers were identified from their references, leading to 68 papers in total. Nineteen were dedicated to purpose 1, 16 to purpose 4, one to purpose 2 and none to purpose 3. Seven papers were dedicated to more than one purpose, the 25 remaining could not be classified unambiguously. Purposes of the methods were often not specifically indicated, methods for subgroup analysis for safety purposes were almost absent and a multitude of diverse methods were developed for purpose (1). It is important that researchers developing methodology for subgroup analysis explicitly clarify the objectives of their methods in terms that can be understood from a patient's, health care provider's and/or regulator's perspective. A clear operational definition for consistency of treatment effects across subgroups is lacking, but is needed to improve the usability of subgroup analyses in this setting. Finally, methods to particularly explore benefit-risk systematically across subgroups need more research.

Chronic Exposure to Methamphetamine Disrupts Reinforcement-Based Decision Making in Rats.

PubMed

Groman, Stephanie M; Rich, Katherine M; Smith, Nathaniel J; Lee, Daeyeol; Taylor, Jane R

2018-03-01

The persistent use of psychostimulant drugs, despite the detrimental outcomes associated with continued drug use, may be because of disruptions in reinforcement-learning processes that enable behavior to remain flexible and goal directed in dynamic environments. To identify the reinforcement-learning processes that are affected by chronic exposure to the psychostimulant methamphetamine (MA), the current study sought to use computational and biochemical analyses to characterize decision-making processes, assessed by probabilistic reversal learning, in rats before and after they were exposed to an escalating dose regimen of MA (or saline control). The ability of rats to use flexible and adaptive decision-making strategies following changes in stimulus-reward contingencies was significantly impaired following exposure to MA. Computational analyses of parameters that track choice and outcome behavior indicated that exposure to MA significantly impaired the ability of rats to use negative outcomes effectively. These MA-induced changes in decision making were similar to those observed in rats following administration of a dopamine D2/3 receptor antagonist. These data use computational models to provide insight into drug-induced maladaptive decision making that may ultimately identify novel targets for the treatment of psychostimulant addiction. We suggest that the disruption in utilization of negative outcomes to adaptively guide dynamic decision making is a new behavioral mechanism by which MA rigidly biases choice behavior.

Spatial and temporal patterns in preterm birth in the United States.

PubMed

Byrnes, John; Mahoney, Richard; Quaintance, Cele; Gould, Jeffrey B; Carmichael, Suzan; Shaw, Gary M; Showen, Amy; Phibbs, Ciaran; Stevenson, David K; Wise, Paul H

2015-06-01

Despite years of research, the etiologies of preterm birth remain unclear. In order to help generate new research hypotheses, this study explored spatial and temporal patterns of preterm birth in a large, total-population dataset. Data on 145 million US births in 3,000 counties from the Natality Files of the National Center for Health Statistics for 1971-2011 were examined. State trends in early (<34 wk) and late (34-36 wk) preterm birth rates were compared. K-means cluster analyses were conducted to identify gestational age distribution patterns for all US counties over time. A weak association was observed between state trends in <34 wk birth rates and the initial absolute <34 wk birth rate. Significant associations were observed between trends in <34 wk and 34-36 wk birth rates and between white and African American <34 wk births. Periodicity was observed in county-level trends in <34 wk birth rates. Cluster analyses identified periods of significant heterogeneity and homogeneity in gestational age distributional trends for US counties. The observed geographic and temporal patterns suggest periodicity and complex, shared influences among preterm birth rates in the United States. These patterns could provide insight into promising hypotheses for further research.

Integrative Genomic Analyses Yields Cell Cycle Regulatory Programs with Prognostic Value

PubMed Central

Cheng, Chao; Lou, Shaoke; Andrews, Erik H.; Ung, Matthew H.; Varn, Frederick S.

2016-01-01

Liposarcoma is the second most common form of sarcoma, which has been categorized into four molecular subtypes, which are associated with differential prognosis of patients. However, the transcriptional regulatory programs associated with distinct histological and molecular subtypes of liposarcoma have not been investigated. This study uses integrative analyses to systematically define the transcriptional regulatory programs associated with liposarcoma. Likewise, computational methods are used to identify regulatory programs associated with different liposarcoma subtypes as well as programs that are predictive of prognosis. Further analysis of curated gene sets was used to identify prognostic gene signatures. The integration of data from a variety sources including gene expression profiles, transcription factor (TF) binding data from ChIP-seq experiments, curated gene sets, and clinical information of patients indicated discrete regulatory programs (e.g., controlled by E2F1 and E2F4) with significantly different regulatory activity in one or multiple subtypes of liposarcoma with respect to normal adipose tissue. These programs were also shown to be prognostic, wherein liposarcoma patients with higher E2F4 or E2F1 activity associated with unfavorable prognosis. A total of 259 gene sets were significantly associated with patient survival in liposarcoma, among which >50% are involved in cell cycle and proliferation. PMID:26856934

Risk factors for urinary tract infection in children with urinary urgency.

PubMed

Gondim, Rhaiana; Azevedo, Roberta; Braga, Ana Aparecida Nascimento Martinelli; Veiga, Maria Luiza; Barroso, Ubirajara

2018-01-01

To identify which independent variable would be strong predictor of febrile urinary tract infection (UTI) in children and adolescents with overactive bladder. A search was made of the institute's database for all patients diagnosed with overactive bladder over the preceding four years. Children and adolescents under 18 years of age with overactive bladder and no neurological or anatomical alterations of the lower urinary tract were included in the study. The independent variables were: sex, age, ethnicity (Brazilians of African descendence/others), the presence of urinary urgency, daytime incontinence, enuresis, frequent urination, infrequent voiding (≤3 voids/day), nocturia, holding maneuvers, straining to void, intermittent urinary flow, constipation and encopresis. An analysis was conducted to identify patients with febrile UTI and subsequently determine predictors of this condition. Univariate and multivariate analyses were performed. Overall, 326 patients (214 girls/112 boys) were evaluated. The mean age of the patients was 7.7±3.19 years (± standard deviation). The incidence of febrile UTI was 39.2%. Being female and infrequent voiding were factors significantly associated with febrile UTI, both in the univariate and multivariate analyses. These results show that being female and infrequent voiding constituted significant risk factors for a diagnosis of febrile UTI in these children. Copyright® by the International Brazilian Journal of Urology.

Multigene assays and molecular markers in breast cancer: systematic review of health economic analyses.

PubMed

Rouzier, Roman; Pronzato, Paolo; Chéreau, Elisabeth; Carlson, Josh; Hunt, Barnaby; Valentine, William J

2013-06-01

Breast cancer is the most common female cancer and is associated with a significant clinical and economic burden. Multigene assays and molecular markers represent an opportunity to direct chemotherapy only to patients likely to have significant benefit. This systematic review examines published health economic analyses to assess the support for adjuvant therapy decision making. Literature searches of PubMed, the Cochrane Library, and congress databases were carried out to identify economic evaluations of multigene assays and molecular markers published between 2002 and 2012. After screening and data extraction, study quality was assessed using the Quality of Health Economic Studies instrument. The review identified 29 publications that reported evaluations of two assays: Oncotype DX(®) and MammaPrint. Studies of both tests provided evidence that their routine use was cost saving or cost-effective versus conventional approaches. Benefits were driven by optimal allocation of adjuvant chemotherapy and reduction in chemotherapy utilization. Findings were sensitive to variation in the frequency of chemotherapy prescription, chemotherapy costs, and patients' risk profiles. Evidence suggests that multigene assays are likely cost saving or cost-effective relative to current approaches to adjuvant therapy. They should benefit decision making in early-stage breast cancer in a variety of settings worldwide.

Causal chain mapping: a novel method to analyse treatment compliance decisions relating to lymphatic filariasis elimination in Alor, Indonesia.

PubMed

Krentel, Alison; Aunger, Robert

2012-08-01

Many public health programmes require individuals to comply with particular behaviours that are novel to them, for example, acquiring new eating habits, accepting immunizations or taking a new medication. In particular, mass drug administration programmes only work to reduce the prevalence of a disease if significant proportions of the target population take the drug in question. In such cases, knowledge of the factors most likely to lead to high levels of compliance is crucial to the programme's success. Existing models of compliance tend to either address interpersonal, organizational or psychological causes independently. Here, the authors present a formal method for analysing relevant factors in the situational context of the compliant behaviour, identifying how these factors may interact within the individual. This method was developed from semantic network analysis, augmented to include environmental and demographic variables to show causal linkages-hence the name 'causal chain mapping'. The ability of this method to provide significant insight into the actual behaviour of individuals is demonstrated with examples from a mass drug administration for lymphatic filariasis in Alor District, Indonesia. The use of this method is likely to help identify key components influencing compliance, and thus make any public health programme reliant on the adoption of novel behaviours more effective.

Does the Use of Platelet-Rich Plasma at the Time of Surgery Improve Clinical Outcomes in Arthroscopic Rotator Cuff Repair When Compared With Control Cohorts? A Systematic Review of Meta-analyses.

PubMed

Saltzman, Bryan M; Jain, Akshay; Campbell, Kirk A; Mascarenhas, Randy; Romeo, Anthony A; Verma, Nikhil N; Cole, Brian J

2016-05-01

The aims of the study were as follows: (1) to perform a systematic review of meta-analyses evaluating platelet-rich plasma (PRP) use at the time of arthroscopic rotator cuff repair surgery and to determine its effect on retear rates and clinical outcomes; (2) to provide a framework for the analysis and interpretation of the best currently available evidence; and (3) to identify gaps within the literature where suggestions for continued investigational efforts would be valid. Literature searches were performed to identify meta-analyses examining arthroscopic rotator cuff repairs augmented with PRP versus control (no PRP). Clinical data were extracted and meta-analysis quality was assessed using the Quality of Reporting of Meta-analyses and Oxman-Guyatt scales. Seven meta-analyses met inclusion and exclusion criteria. All were considered as being of similar quality with Quality of Reporting of Meta-analyses scores >15 and Oxman scores of 7. A total of 3,193 overlapping patients treated were included with mean follow-up from 12 to 31 months. When compared with control patients, use of PRP at the time of rotator cuff repair did not result in significantly lower overall retear rates or improved clinical outcome scores. The following postoperative functional scores comparing PRP versus control were reported: Constant (no significant difference demonstrated with PRP use in 5 of 6 reporting meta-analyses), University of California - Los Angeles (no difference, 6 of 6), American Shoulder and Elbow Society (no difference, 4 of 4), and Simple Shoulder Test (no difference, 3 of 5). Subgroup analysis performed by 3 meta-analyses showed evidence of improved outcomes with solid PRP matrix versus liquid, small- and/or medium-sized versus large and/or massive tears, PRP application at the tendon-bone interface versus over tendon, and in the setting of double-row versus single-row rotator cuff. The current highest level of evidence suggests that PRP use at the time of arthroscopic rotator cuff repair does not universally improve retear rates or affect clinical outcome scores. However, the effects of PRP use on retear rates trend toward beneficial outcomes if evaluated in the context of the following specific variables: use of a solid PRP matrix; application of PRP at the tendon-bone interface; in double-row repairs; and with small- and/or medium-sized rotator cuff tears. Level III, systematic review of Level II and III studies. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Verification and characterization of chromosome duplication in haploid maize.

PubMed

de Oliveira Couto, E G; Resende Von Pinho, E V; Von Pinho, R G; Veiga, A D; de Carvalho, M R; de Oliveira Bustamante, F; Nascimento, M S

2015-06-26

Doubled haploid technology has been used by various private companies. However, information regarding chromosome duplication methodologies, particularly those concerning techniques used to identify duplication in cells, is limited. Thus, we analyzed and characterized artificially doubled haploids using microsatellites molecular markers, pollen viability, and flow cytometry techniques. Evaluated material was obtained using two different chromosome duplication protocols in maize seeds considered haploids, resulting from the cross between the haploid inducer line KEMS and 4 hybrids (GNS 3225, GNS 3032, GNS 3264, and DKB 393). Fourteen days after duplication, plant samples were collected and assessed by flow cytometry. Further, the plants were transplanted to a field, and samples were collected for DNA analyses using microsatellite markers. The tassels were collected during anthesis for pollen viability analyses. Haploid, diploid, and mixoploid individuals were detected using flow cytometry, demonstrating that this technique was efficient for identifying doubled haploids. The microsatellites markers were also efficient for confirming the ploidies preselected by flow cytometry and for identifying homozygous individuals. Pollen viability showed a significant difference between the evaluated ploidies when the Alexander and propionic-carmin stains were used. The viability rates between the plodies analyzed show potential for fertilization.

Using the Integrative Model of Behavioral Prediction to Understand College Students' STI Testing Beliefs, Intentions, and Behaviors.

PubMed

Wombacher, Kevin; Dai, Minhao; Matig, Jacob J; Harrington, Nancy Grant

2018-03-22

To identify salient behavioral determinants related to STI testing among college students by testing a model based on the integrative model of behavioral (IMBP) prediction. 265 undergraduate students from a large university in the Southeastern US. Formative and survey research to test an IMBP-based model that explores the relationships between determinants and STI testing intention and behavior. Results of path analyses supported a model in which attitudinal beliefs predicted intention and intention predicted behavior. Normative beliefs and behavioral control beliefs were not significant in the model; however, select individual normative and control beliefs were significantly correlated with intention and behavior. Attitudinal beliefs are the strongest predictor of STI testing intention and behavior. Future efforts to increase STI testing rates should identify and target salient attitudinal beliefs.

Predictors of Membership in Alcoholics Anonymous in a Sample of Successfully Remitted Alcoholics

PubMed Central

Krentzman, Amy R.; Robinson, Elizabeth A. R.; Perron, Brian E.; Cranford, James A.

2012-01-01

This study identifies factors associated with Alcoholics Anonymous (AA) membership in a sample of 81 persons who have achieved at least one year of total abstinence from drugs and alcohol. Forty-four were AA members, 37 were not. Logistic regression was used to test the cross-sectional associations of baseline demographic, substance-related, spiritual and religious, and personality variables with AA membership. Significant variables from the bivariate analyses were included in a multivariate model controlling for previous AA involvement. Having more positive views of God and more negative consequences of drinking were significantly associated with AA membership. This information can be used by clinicians to identify clients for whom AA might be a good fit, and can help others overcome obstacles to AA or explore alternative forms of abstinence support. PMID:21615004

A comparative study of Northern Ireland's estuaries based on the results of beam trawl fish surveys

NASA Astrophysics Data System (ADS)

Harrison, Trevor D.; Armour, Neil D.; McNeill, Michael T.; Moorehead, Peter W.

2017-11-01

The fish communities of Northern Ireland's estuaries were described and compared using data collected with a modified beam trawl over a six year period from 2009 to 2014. Multivariate analyses identified four estuary groups based on variations in their physico-chemical attributes. These groups broadly corresponded with the distribution and variation of estuary geomorphic types identified around the Irish coast. The dominant fish species captured were also among the main species reported in other North East Atlantic estuaries. A significant link between the estuary types and their fish communities was found; each estuary group contained a somewhat distinctive fish community. The fish communities also showed a significant relationship with the physico-chemical characteristics of the estuaries. Differences in fish species composition are attributed to habitat and environmental preferences of key estuary-associated species.

Developmental trajectories of paediatric headache - sex-specific analyses and predictors.

PubMed

Isensee, Corinna; Fernandez Castelao, Carolin; Kröner-Herwig, Birgit

2016-01-01

Headache is the most common pain disorder in children and adolescents and is associated with diverse dysfunctions and psychological symptoms. Several studies evidenced sex-specific differences in headache frequency. Until now no study exists that examined sex-specific patterns of change in paediatric headache across time and included pain-related somatic and (socio-)psychological predictors. Latent Class Growth Analysis (LCGA) was used in order to identify different trajectory classes of headache across four annual time points in a population-based sample (n = 3 227; mean age 11.34 years; 51.2 % girls). In multinomial logistic regression analyses the influence of several predictors on the class membership was examined. For girls, a four-class model was identified as the best fitting model. While the majority of girls reported no (30.5 %) or moderate headache frequencies (32.5 %) across time, one class with a high level of headache days (20.8 %) and a class with an increasing headache frequency across time (16.2 %) were identified. For boys a two class model with a 'no headache class' (48.6 %) and 'moderate headache class' (51.4 %) showed the best model fit. Regarding logistic regression analyses, migraine and parental headache proved to be stable predictors across sexes. Depression/anxiety was a significant predictor for all pain classes in girls. Life events, dysfunctional stress coping and school burden were also able to differentiate at least between some classes in both sexes. The identified trajectories reflect sex-specific differences in paediatric headache, as seen in the number and type of classes extracted. The documented risk factors can deliver ideas for preventive actions and considerations for treatment programmes.

Drivers of wetland conversion: a global meta-analysis.

PubMed

van Asselen, Sanneke; Verburg, Peter H; Vermaat, Jan E; Janse, Jan H

2013-01-01

Meta-analysis of case studies has become an important tool for synthesizing case study findings in land change. Meta-analyses of deforestation, urbanization, desertification and change in shifting cultivation systems have been published. This present study adds to this literature, with an analysis of the proximate causes and underlying forces of wetland conversion at a global scale using two complementary approaches of systematic review. Firstly, a meta-analysis of 105 case-study papers describing wetland conversion was performed, showing that different combinations of multiple-factor proximate causes, and underlying forces, drive wetland conversion. Agricultural development has been the main proximate cause of wetland conversion, and economic growth and population density are the most frequently identified underlying forces. Secondly, to add a more quantitative component to the study, a logistic meta-regression analysis was performed to estimate the likelihood of wetland conversion worldwide, using globally-consistent biophysical and socioeconomic location factor maps. Significant factors explaining wetland conversion, in order of importance, are market influence, total wetland area (lower conversion probability), mean annual temperature and cropland or built-up area. The regression analyses results support the outcomes of the meta-analysis of the processes of conversion mentioned in the individual case studies. In other meta-analyses of land change, similar factors (e.g., agricultural development, population growth, market/economic factors) are also identified as important causes of various types of land change (e.g., deforestation, desertification). Meta-analysis helps to identify commonalities across the various local case studies and identify which variables may lead to individual cases to behave differently. The meta-regression provides maps indicating the likelihood of wetland conversion worldwide based on the location factors that have determined historic conversions.

Drivers of Wetland Conversion: a Global Meta-Analysis

PubMed Central

van Asselen, Sanneke; Verburg, Peter H.; Vermaat, Jan E.; Janse, Jan H.

2013-01-01

Meta-analysis of case studies has become an important tool for synthesizing case study findings in land change. Meta-analyses of deforestation, urbanization, desertification and change in shifting cultivation systems have been published. This present study adds to this literature, with an analysis of the proximate causes and underlying forces of wetland conversion at a global scale using two complementary approaches of systematic review. Firstly, a meta-analysis of 105 case-study papers describing wetland conversion was performed, showing that different combinations of multiple-factor proximate causes, and underlying forces, drive wetland conversion. Agricultural development has been the main proximate cause of wetland conversion, and economic growth and population density are the most frequently identified underlying forces. Secondly, to add a more quantitative component to the study, a logistic meta-regression analysis was performed to estimate the likelihood of wetland conversion worldwide, using globally-consistent biophysical and socioeconomic location factor maps. Significant factors explaining wetland conversion, in order of importance, are market influence, total wetland area (lower conversion probability), mean annual temperature and cropland or built-up area. The regression analyses results support the outcomes of the meta-analysis of the processes of conversion mentioned in the individual case studies. In other meta-analyses of land change, similar factors (e.g., agricultural development, population growth, market/economic factors) are also identified as important causes of various types of land change (e.g., deforestation, desertification). Meta-analysis helps to identify commonalities across the various local case studies and identify which variables may lead to individual cases to behave differently. The meta-regression provides maps indicating the likelihood of wetland conversion worldwide based on the location factors that have determined historic conversions. PMID:24282580

Rapid Identification of Cell-Specific, Internalizing RNA Aptamers with Bioinformatics Analyses of a Cell-Based Aptamer Selection

PubMed Central

Thiel, William H.; Bair, Thomas; Peek, Andrew S.; Liu, Xiuying; Dassie, Justin; Stockdale, Katie R.; Behlke, Mark A.; Miller, Francis J.; Giangrande, Paloma H.

2012-01-01

Background The broad applicability of RNA aptamers as cell-specific delivery tools for therapeutic reagents depends on the ability to identify aptamer sequences that selectively access the cytoplasm of distinct cell types. Towards this end, we have developed a novel approach that combines a cell-based selection method (cell-internalization SELEX) with high-throughput sequencing (HTS) and bioinformatics analyses to rapidly identify cell-specific, internalization-competent RNA aptamers. Methodology/Principal Findings We demonstrate the utility of this approach by enriching for RNA aptamers capable of selective internalization into vascular smooth muscle cells (VSMCs). Several rounds of positive (VSMCs) and negative (endothelial cells; ECs) selection were performed to enrich for aptamer sequences that preferentially internalize into VSMCs. To identify candidate RNA aptamer sequences, HTS data from each round of selection were analyzed using bioinformatics methods: (1) metrics of selection enrichment; and (2) pairwise comparisons of sequence and structural similarity, termed edit and tree distance, respectively. Correlation analyses of experimentally validated aptamers or rounds revealed that the best cell-specific, internalizing aptamers are enriched as a result of the negative selection step performed against ECs. Conclusions and Significance We describe a novel approach that combines cell-internalization SELEX with HTS and bioinformatics analysis to identify cell-specific, cell-internalizing RNA aptamers. Our data highlight the importance of performing a pre-clear step against a non-target cell in order to select for cell-specific aptamers. We expect the extended use of this approach to enable the identification of aptamers to a multitude of different cell types, thereby facilitating the broad development of targeted cell therapies. PMID:22962591

Effects of a Randomized Reading Intervention Study Aimed at 9-Year-Olds: A 5-Year Follow-up.

PubMed

Wolff, Ulrika

2016-05-01

The present paper reports on a 5-year follow-up of a randomized reading intervention in grade 3 in Sweden. An intervention group (n = 57) received daily training for 12 weeks in phoneme/grapheme mapping, reading comprehension and reading speed, whereas a control group (n = 55) participated in ordinary classroom activities. The main aim was to investigate if there were remaining effects of the intervention on reading-related skills. Previous analyses showed that the intervention group performed significantly better than the control group on spelling, reading speed, reading comprehension and phoneme awareness at the immediate post-test with sustained effects 1 year later. Results from the 5-year follow-up show that the only significant difference between the intervention (n = 47) and the control group (n = 37) was on word decoding. There was also a significant interaction effect of group assignment and initial word decoding, in the way that the lowest-performing students benefitted the most from the intervention. Another aim was to examine if the children identified in a screening (n = 2212) as poor readers in grade 2 still performed worse than typical readers. The analyses showed that the typically developing students (n = 66) outperformed the students identified as poor readers in grade 2 on working memory, spelling, reading comprehension and word decoding. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Hyperthyroidism stimulates mitochondrial proton leak and ATP turnover in rat hepatocytes but does not change the overall kinetics of substrate oxidation reactions.

PubMed

Harper, M E; Brand, M D

1994-08-01

Thyroid hormones have well-known effects on oxidative phosphorylation, but there is little quantitative information on their important sites of action. We have used top-down elasticity analysis, an extension of metabolic control analysis, to identify the sites of action of thyroid hormones on oxidative phosphorylation in rat hepatocytes. We divided the oxidative phosphorylation system into three blocks of reactions: the substrate oxidation subsystem, the phosphorylating subsystem, and the mitochondrial proton leak subsystem and have identified those blocks of reactions whose kinetics are significantly changed by hyperthyroidism. Our results show significant effects on the kinetics of the proton leak and the phosphorylating subsystems. Quantitative analyses revealed that 43% of the increase in resting respiration rate in hyperthyroid hepatocytes compared with euthyroid hepatocytes was due to differences in the proton leak and 59% was due to differences in the activity of the phosphorylating subsystem. There were no significant effects on the substrate oxidation subsystem. Changes in nonmitochondrial oxygen consumption accounted for -2% of the change in respiration rate. Top-down control analysis revealed that the distribution of control over the rates of mitochondrial oxygen consumption, ATP synthesis and consumption, and proton leak and over mitochondrial membrane potential (delta psi m) was similar in hepatocytes from hyperthyroid and littermate-paired euthyroid controls. The results of this study include the first complete top-down elasticity and control analyses of oxidative phosphorylation in hepatocytes from hyperthyroid rats.

Beliefs about meditating among university students, faculty, and staff: a theory-based salient belief elicitation.

PubMed

Lederer, Alyssa M; Middlestadt, Susan E

2014-01-01

Stress impacts college students, faculty, and staff alike. Although meditation has been found to decrease stress, it is an underutilized strategy. This study used the Reasoned Action Approach (RAA) to identify beliefs underlying university constituents' decision to meditate. N=96 students, faculty, and staff at a large midwestern university during spring 2012. A survey measured the RAA global constructs and elicited the beliefs underlying intention to meditate. Thematic and frequency analyses and multiple regression were performed. Quantitative analyses showed that intention to meditate was significantly predicted (R2=.632) by attitude, perceived norm, and perceived behavioral control. Qualitative analyses revealed advantages (eg, reduced stress; feeling calmer), disadvantages (eg, takes time; will not work), and facilitating circumstances (eg, having more time; having quiet space) of meditating. Results of this theory-based research suggest how college health professionals can encourage meditation practice through individual, interpersonal, and environmental interventions.

A Measure of Team Resilience: Developing the Resilience at Work Team Scale.

PubMed

McEwen, Kathryn; Boyd, Carolyn M

2018-03-01

This study develops, and initial evaluates, a new measure of team-based resilience for use in research and practice. We conducted preliminary analyses, based on a cross-sectional sample of 344 employees nested within 31 teams. Seven dimensions were identified through exploratory and confirmatory factor analyses. The measure had high reliability and significant discrimination to indicate the presence of a unique team-based aspect of resilience that contributed to higher work engagement and higher self-rated team performance, over and above the effects of individual resilience. Multilevel analyses showed that team, but not individual, resilience predicted self-rated team performance. Practice implications include a need to focus on collective as well as individual behaviors in resilience-building. The measure provides a diagnostic instrument for teams and a scale to evaluate organizational interventions and research the relationship of resilience to other constructs.

Polymorphisms and allele frequencies of the ABO blood group gene among the Jomon, Epi-Jomon and Okhotsk people in Hokkaido, northern Japan, revealed by ancient DNA analysis.

PubMed

Sato, Takehiro; Kazuta, Hisako; Amano, Tetsuya; Ono, Hiroko; Ishida, Hajime; Kodera, Haruto; Matsumura, Hirofumi; Yoneda, Minoru; Dodo, Yukio; Masuda, Ryuichi

2010-10-01

To investigate the genetic characteristics of the ancient populations of Hokkaido, northern Japan, polymorphisms of the ABO blood group gene were analyzed for 17 Jomon/Epi-Jomon specimens and 15 Okhotsk specimens using amplified product-length polymorphism and restriction fragment length polymorphism analyses. Five ABO alleles were identified from the Jomon/ Epi-Jomon and Okhotsk people. Allele frequencies of the Jomon/Epi-Jomon and Okhotsk people were compared with those of the modern Asian, European and Oceanic populations. The genetic relationships inferred from principal component analyses indicated that both Jomon/Epi-Jomon and Okhotsk people are included in the same group as modern Asian populations. However, the genetic characteristics of these ancient populations in Hokkaido were significantly different from each other, which is in agreement with the conclusions from mitochondrial DNA and ABCC11 gene analyses that were previously reported.

50 years of rational‐emotive and cognitive‐behavioral therapy: A systematic review and meta‐analysis

PubMed Central

Cotet, Carmen; Matu, Silviu; Mogoase, Cristina; Stefan, Simona

2017-01-01

Objective Rational emotive behavior therapy (REBT), introduced by Albert Ellis in the late 1950s, is one of the main pillars of cognitive‐behavioral therapy. Existing reviews on REBT are overdue by 10 years or more. We aimed to summarize the effectiveness and efficacy of REBT since its beginnings and investigate the alleged mechanisms of change. Method Systematic search identified 84 articles, out of which 68 provided data for between‐group analyses and 39 for within‐group analyses. Results We found a medium effect size of REBT compared to other interventions on outcomes (d = 0.58) and on irrational beliefs (d = 0.70), at posttest. For the within‐group analyses, we obtained medium effects for both outcomes (d = 0.56) and irrational beliefs (d = 0.61). Several significant moderators emerged. Conclusion REBT is a sound psychological intervention. Directions for future studies are outlined, stemming from the limitations of existing ones. PMID:28898411

The response of numerical weather prediction analysis systems to FGGE 2b data

NASA Technical Reports Server (NTRS)

Hollingsworth, A.; Lorenc, A.; Tracton, S.; Arpe, K.; Cats, G.; Uppala, S.; Kallberg, P.

1985-01-01

An intercomparison of analyses of the main PGGE Level IIb data set is presented with three advanced analysis systems. The aims of the work are to estimate the extent and magnitude of the differences between the analyses, to identify the reasons for the differences, and finally to estimate the significance of the differences. Extratropical analyses only are considered. Objective evaluations of analysis quality, such as fit to observations, statistics of analysis differences, and mean fields are discussed. In addition, substantial emphasis is placed on subjective evaluation of a series of case studies that were selected to illustrate the importance of different aspects of the analysis procedures, such as quality control, data selection, resolution, dynamical balance, and the role of the assimilating forecast model. In some cases, the forecast models are used as selective amplifiers of analysis differences to assist in deciding which analysis was more nearly correct in the treatment of particular data.

The moral economy of austerity: analysing UK welfare reform.

PubMed

Morris, Lydia

2016-03-01

This paper notes the contemporary emergence of 'morality' in both sociological argument and political rhetoric, and analyses its significance in relation to ongoing UK welfare reforms. It revisits the idea of 'moral economy' and identifies two strands in its contemporary application; that all economies depend on an internal moral schema, and that some external moral evaluation is desirable. UK welfare reform is analysed as an example of the former, with reference to three distinct orientations advanced in the work of Freeden (1996), Laclau (2014), and Lockwood (1996). In this light, the paper then considers challenges to the reform agenda, drawn from third sector and other public sources. It outlines the forms of argument present in these challenges, based respectively on rationality, legality, and morality, which together provide a basis for evaluation of the welfare reforms and for an alternative 'moral economy'. © London School of Economics and Political Science 2016.

[Analysis of the technical efficiency of hospitals in the Spanish National Health Service].

PubMed

Pérez-Romero, Carmen; Ortega-Díaz, M Isabel; Ocaña-Riola, Ricardo; Martín-Martín, José Jesús

To analyse the technical efficiency and productivity of general hospitals in the Spanish National Health Service (NHS) (2010-2012) and identify explanatory hospital and regional variables. 230 NHS hospitals were analysed by data envelopment analysis for overall, technical and scale efficiency, and Malmquist index. The robustness of the analysis is contrasted with alternative input-output models. A fixed effects multilevel cross-sectional linear model was used to analyse the explanatory efficiency variables. The average rate of overall technical efficiency (OTE) was 0.736 in 2012; there was considerable variability by region. Malmquist index (2010-2012) is 1.013. A 23% variability in OTE is attributable to the region in question. Statistically significant exogenous variables (residents per 100 physicians, aging index, average annual income per household, essential public service expenditure and public health expenditure per capita) explain 42% of the OTE variability between hospitals and 64% between regions. The number of residents showed a statistically significant relationship. As regards regions, there is a statistically significant direct linear association between OTE and annual income per capita and essential public service expenditure, and an indirect association with the aging index and annual public health expenditure per capita. The significant room for improvement in the efficiency of hospitals is conditioned by region-specific characteristics, specifically aging, wealth and the public expenditure policies of each one. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Quantitative genetic analysis of the body composition and blood pressure association in two ethnically diverse populations.

PubMed

Ghosh, Sudipta; Dosaev, Tasbulat; Prakash, Jai; Livshits, Gregory

2017-04-01

The major aim of this study was to conduct comparative quantitative-genetic analysis of the body composition (BCP) and somatotype (STP) variation, as well as their correlations with blood pressure (BP) in two ethnically, culturally and geographically different populations: Santhal, indigenous ethnic group from India and Chuvash, indigenous population from Russia. Correspondently two pedigree-based samples were collected from 1,262 Santhal and1,558 Chuvash individuals, respectively. At the first stage of the study, descriptive statistics and a series of univariate regression analyses were calculated. Finally, multiple and multivariate regression (MMR) analyses, with BP measurements as dependent variables and age, sex, BCP and STP as independent variables were carried out in each sample separately. The significant and independent covariates of BP were identified and used for re-examination in pedigree-based variance decomposition analysis. Despite clear and significant differences between the populations in BCP/STP, both Santhal and Chuvash were found to be predominantly mesomorphic irrespective of their sex. According to MMR analyses variation of BP significantly depended on age and mesomorphic component in both samples, and in addition on sex, ectomorphy and fat mass index in Santhal and on fat free mass index in Chuvash samples, respectively. Additive genetic component contributes to a substantial proportion of blood pressure and body composition variance. Variance component analysis in addition to above mentioned results suggests that additive genetic factors influence BP and BCP/STP associations significantly. © 2017 Wiley Periodicals, Inc.

CpG island methylator phenotype identifies high risk patients among microsatellite stable BRAF mutated colorectal cancers

PubMed Central

Vedeld, Hege Marie; Merok, Marianne; Jeanmougin, Marine; Danielsen, Stine A.; Honne, Hilde; Presthus, Gro Kummeneje; Svindland, Aud; Sjo, Ole H.; Hektoen, Merete; Eknæs, Mette; Nesbakken, Arild; Lothe, Ragnhild A.

2017-01-01

The prognostic value of CpG island methylator phenotype (CIMP) in colorectal cancer remains unsettled. We aimed to assess the prognostic value of this phenotype analyzing a total of 1126 tumor samples obtained from two Norwegian consecutive colorectal cancer series. CIMP status was determined by analyzing the 5‐markers CAGNA1G, IGF2, NEUROG1, RUNX3 and SOCS1 by quantitative methylation specific PCR (qMSP). The effect of CIMP on time to recurrence (TTR) and overall survival (OS) were determined by uni‐ and multivariate analyses. Subgroup analyses were conducted according to MSI and BRAF mutation status, disease stage, and also age at time of diagnosis (<60, 60‐74, ≥75 years). Patients with CIMP positive tumors demonstrated significantly shorter TTR and worse OS compared to those with CIMP negative tumors (multivariate hazard ratio [95% CI] 1.86 [1.31‐2.63] and 1.89 [1.34‐2.65], respectively). In stratified analyses, CIMP tumors showed significantly worse outcome among patients with microsatellite stable (MSS, P < 0.001), and MSS BRAF mutated tumors (P < 0.001), a finding that persisted in patients with stage II, III or IV disease, and that remained significant in multivariate analysis (P < 0.01). Consistent results were found for all three age groups. To conclude, CIMP is significantly associated with inferior outcome for colorectal cancer patients, and can stratify the poor prognostic patients with MSS BRAF mutated tumors. PMID:28542846

Exploring longitudinal course and treatment-baseline severity interactions in secondary outcomes of smoking cessation treatment in individuals with attention-deficit hyperactivity disorder.

PubMed

Luo, Sean X; Wall, Melanie; Covey, Lirio; Hu, Mei-Chen; Scodes, Jennifer M; Levin, Frances R; Nunes, Edward V; Winhusen, Theresa

2018-01-25

A double blind, placebo-controlled randomized trial (NCT00253747) evaluating osmotic-release oral system methylphenidate (OROS-MPH) for smoking-cessation revealed a significant interaction effect in which participants with higher baseline ADHD severity had better abstinence outcomes with OROS-MPH while participants with lower baseline ADHD severity had worse outcomes. This current report examines secondary outcomes that might bear on the mechanism for this differential treatment effect. Longitudinal analyses were conducted to evaluate the effect of OROS-MPH on three secondary outcomes (ADHD symptom severity, nicotine craving, and withdrawal) in the total sample (N = 255, 56% Male), and in the high (N = 134) and low (N = 121) baseline ADHD severity groups. OROS-MPH significantly improved ADHD symptoms and nicotine withdrawal symptoms in the total sample, and exploratory analyses showed that in both higher and lower baseline severity groups, OROS-MPH statistically significantly improved these two outcomes. No effect on craving overall was detected, though exploratory analyses showed statistically significantly decreased craving in the high ADHD severity participants on OROS-MPH. No treatment by ADHD baseline severity interaction was detected for the outcomes. Methylphenidate improved secondary outcomes during smoking cessation independent of baseline ADHD severity, with no evident treatment-baseline severity interaction. Our results suggest divergent responses to smoking cessation treatment in the higher and lower severity groups cannot be explained by concordant divergence in craving, withdrawal and ADHD symptom severity, and alternative hypotheses may need to be identified.

Descriptive and Experimental Analyses of Potential Precursors to Problem Behavior

PubMed Central

Borrero, Carrie S.W; Borrero, John C

2008-01-01

We conducted descriptive observations of severe problem behavior for 2 individuals with autism to identify precursors to problem behavior. Several comparative probability analyses were conducted in addition to lag-sequential analyses using the descriptive data. Results of the descriptive analyses showed that the probability of the potential precursor was greater given problem behavior compared to the unconditional probability of the potential precursor. Results of the lag-sequential analyses showed a marked increase in the probability of a potential precursor in the 1-s intervals immediately preceding an instance of problem behavior, and that the probability of problem behavior was highest in the 1-s intervals immediately following an instance of the precursor. We then conducted separate functional analyses of problem behavior and the precursor to identify respective operant functions. Results of the functional analyses showed that both problem behavior and the precursor served the same operant functions. These results replicate prior experimental analyses on the relation between problem behavior and precursors and extend prior research by illustrating a quantitative method to identify precursors to more severe problem behavior. PMID:18468281

Investigation of cancer mortality inequalities between rural and urban areas in South Korea.

PubMed

Choi, Kyung-Mee

2016-02-01

Little is known about rural-urban cancer disparities, particularly in South Korea, and this study is to identify cancer-specific mortality inequalities between the rural and urban areas of the country. For 11 specific cancer sites, age-standardised mortality rates were analysed for the rural and urban administrative districts of South Korea during 2006-2011. The Poisson log linear regression models were employed to estimate cancer-specific mortality rates, and Bonferroni comparison method was used to identify rural-urban disparities. There were significant rural-urban disparities observed for all cancer sites except prostate, pancreas and leukaemia. The mortality rates of lung, liver and stomach cancers, the three most common cancers in the country, were observed to be significantly higher in rural areas than in metropolitan areas. In contrast, the reverse relationship was observed for the reproductive system (breast and uterus) and colon cancers. Central nervous system cancer mortality was observed to be significantly higher in rural areas than in non-metro urban areas. For the first time ever, significant rural-urban disparity patterns in cancer mortality rates in South Korea have been identified in this paper. Future investigations on cancer risk factors for the country should address these disparity patterns. © 2015 National Rural Health Alliance Inc.

High school science enrollment of black students

NASA Astrophysics Data System (ADS)

Goggins, Ellen O.; Lindbeck, Joy S.

How can the high school science enrollment of black students be increased? School and home counseling and classroom procedures could benefit from variables identified as predictors of science enrollment. The problem in this study was to identify a set of variables which characterize science course enrollment by black secondary students. The population consisted of a subsample of 3963 black high school seniors from The High School and Beyond 1980 Base-Year Survey. Using multiple linear regression, backward regression, and correlation analyses, the US Census regions and grades mostly As and Bs in English were found to be significant predictors of the number of science courses scheduled by black seniors.

Tamoxifen-Dependent Induction of AGR2 Is Associated with Increased Aggressiveness of Endometrial Cancer Cells.

PubMed

Hrstka, Roman; Podhorec, Jan; Nenutil, Rudolf; Sommerova, Lucia; Obacz, Joanna; Durech, Michal; Faktor, Jakub; Bouchal, Pavel; Skoupilova, Hana; Vojtesek, Borivoj

2017-05-28

Tamoxifen treatment in breast cancer patients is associated with increased risk of endometrial malignancies. Significantly, higher AGR2 expression was found in endometrial cancers that developed in women previously treated with tamoxifen compared to those who had not been exposed to tamoxifen. An association of elevated AGR2 level with myometrial invasion occurrence and invasion depth was also found. In vitro analyses identified a stimulatory effect of AGR2 on cellular proliferation. Although adverse tamoxifen effects on endometrial cells remain elusive, our work identifies elevated AGR2 as a candidate tamoxifen-dependent mechanism of action responsible for increased incidence of endometrial cancer.

Study of quiet turbofan STOL aircraft for short-haul transportation. Volume 2: Aircraft

NASA Technical Reports Server (NTRS)

1973-01-01

A study of the quiet turbofan STOL aircraft for short haul transportation was conducted. The objectives of the study were as follows: (1) to determine the relationships between STOL characteristics and economic and social viability of short haul air transportation, (2) to identify critical technology problems involving introduction of STOL short haul systems, (3) to define representative aircraft configurations, characteristics, and costs, and (4) to identify high payoff technology areas to improve STOL systems. The analyses of the aircraft designs which were generated to fulfill the objectives are summarized. The baseline aircraft characteristics are documented and significant trade studies are presented.

2010 drug packaging review: identifying problems to prevent errors.

PubMed

2011-06-01

Prescrire's analyses showed that the quality of drug packaging in 2010 still left much to be desired. Potentially dangerous packaging remains a significant problem: unclear labelling is source of medication errors; dosing devices for some psychotropic drugs create a risk of overdose; child-proof caps are often lacking; and too many patient information leaflets are misleading or difficult to understand. Everything that is needed for safe drug packaging is available; it is now up to regulatory agencies and drug companies to act responsibly. In the meantime, health professionals can help their patients by learning to identify the pitfalls of drug packaging and providing safe information to help prevent medication errors.

Comparative Profiling of Primary Colorectal Carcinomas and Liver Metastases Identifies LEF1 as a Prognostic Biomarker

PubMed Central

Lin, Albert Y.; Chua, Mei-Sze; Choi, Yoon-La; Yeh, William; Kim, Young H.; Azzi, Raymond; Adams, Gregg A.; Sainani, Kristin; van de Rijn, Matt; So, Samuel K.; Pollack, Jonathan R.

2011-01-01

Purpose We sought to identify genes of clinical significance to predict survival and the risk for colorectal liver metastasis (CLM), the most common site of metastasis from colorectal cancer (CRC). Patients and Methods We profiled gene expression in 31 specimens from primary CRC and 32 unmatched specimens of CLM, and performed Significance Analysis of Microarrays (SAM) to identify genes differentially expressed between these two groups. To characterize the clinical relevance of two highly-ranked differentially-expressed genes, we analyzed the expression of secreted phosphoprotein 1 (SPP1 or osteopontin) and lymphoid enhancer factor-1 (LEF1) by immunohistochemistry using a tissue microarray (TMA) representing an independent set of 154 patients with primary CRC. Results Supervised analysis using SAM identified 963 genes with significantly higher expression in CLM compared to primary CRC, with a false discovery rate of <0.5%. TMA analysis showed SPP1 and LEF1 protein overexpression in 60% and 44% of CRC cases, respectively. Subsequent occurrence of CLM was significantly correlated with the overexpression of LEF1 (chi-square p = 0.042), but not SPP1 (p = 0.14). Kaplan Meier analysis revealed significantly worse survival in patients with overexpression of LEF1 (p<0.01), but not SPP1 (p = 0.11). Both univariate and multivariate analyses identified stage (p<0.0001) and LEF1 overexpression (p<0.05) as important prognostic markers, but not tumor grade or SPP1. Conclusion Among genes differentially expressed between CLM and primary CRC, we demonstrate overexpression of LEF1 in primary CRC to be a prognostic factor for poor survival and increased risk for liver metastasis. PMID:21383983

Targeted sequencing identifies genetic polymorphisms of flavin-containing monooxygenase genes contributing to susceptibility of nicotine dependence in European American and African American.

PubMed

Zhang, Tian-Xiao; Saccone, Nancy L; Bierut, Laura J; Rice, John P

2017-04-01

Smoking is a leading cause of preventable death. Early studies based on samples of twins have linked the lifetime smoking practices to genetic predisposition. The flavin-containing monooxygenase (FMO) protein family consists of a group of enzymes that metabolize drugs and xenobiotics. Both FMO1 and FMO3 were potentially susceptible genes for nicotine metabolism process. In this study, we investigated the potential of FMO genes to confer risk of nicotine dependence via deep targeted sequencing in 2,820 study subjects comprising 1,583 nicotine dependents and 1,237 controls from European American and African American. Specifically, we focused on the two genomic segments including FMO1 , FMO3 , and pseudo gene FMO6P , and aimed to investigate the potential association between FMO genes and nicotine dependence. Both common and low-frequency/rare variants were analyzed using different algorithms. The potential functional significance of SNPs with association signal was investigated with relevant bioinformatics tools. We identified different clusters of significant common variants in European (with most significant SNP rs6674596, p  =   .0004, OR = 0.67, MAF_EA = 0.14, FMO1 ) and African Americans (with the most significant SNP rs6608453, p  =   .001, OR = 0.64, MAF_AA = 0.1, FMO6P ). No significant signals were identified through haplotype-based analyses. Gene network investigation indicated that both FMO1 and FMO3 have a strong relation with a variety of genes belonging to CYP gene families (with combined score greater than 0.9). Most of the significant variants identified were SNPs located within intron regions or with unknown functional significance, indicating a need for future work to understand the underlying functional significance of these signals. Our findings indicated significant association between FMO genes and nicotine dependence. Replications of our findings in other ethnic groups were needed in the future. Most of the significant variants identified were SNPs located within intronic regions or with unknown functional significance, indicating a need for future work to understand the underlying functional significance of these signals.

Mental health and American Indian women's multiple roles.

PubMed

Napholz, L

1995-01-01

The author's purpose in conducting this study was to identify the relationship of sex role orientation to indices of psychological well-being among 148 American Indian working women from the Midwest. Analyses revealed that the sex-typed group had significantly higher depression scores, higher role conflict scores, lower self-esteem scores and lower life satisfaction scores when compared with the cross-typed and androgynous groups. The undifferentiated group had significantly lower self-esteem scores when compared with the androgynous group. Further research is needed to understand how different sex role orientations support different roles that American Indian women occupy.

Land use change detection with LANDSAT-2 data for monitoring and predicting regional water quality degradation. [Arkansas

NASA Technical Reports Server (NTRS)

Macdonald, H.; Steele, K. (Principal Investigator); Waite, W.; Rice, R.; Shinn, M.; Dillard, T.; Petersen, C.

1977-01-01

The author has identified the following significant results. Comparison between LANDSAT 1 and 2 imagery of Arkansas provided evidence of significant land use changes during the 1972-75 time period. Analysis of Arkansas historical water quality information has shown conclusively that whereas point source pollution generally can be detected by use of water quality data collected by state and federal agencies, sampling methodologies for nonpoint source contamination attributable to surface runoff are totally inadequate. The expensive undertaking of monitoring all nonpoint sources for numerous watersheds can be lessened by implementing LANDSAT change detection analyses.

Systematic review and meta-analysis of candidate gene association studies of lower urinary tract symptoms in men.

PubMed

Cartwright, Rufus; Mangera, Altaf; Tikkinen, Kari A O; Rajan, Prabhakar; Pesonen, Jori; Kirby, Anna C; Thiagamoorthy, Ganesh; Ambrose, Chris; Gonzalez-Maffe, Juan; Bennett, Phillip R; Palmer, Tom; Walley, Andrew; Järvelin, Marjo-Riitta; Khullar, Vik; Chapple, Chris

2014-10-01

Although family studies have shown that male lower urinary tract symptoms (LUTS) are highly heritable, no systematic review exists of genetic polymorphisms tested for association with LUTS. To systematically review and meta-analyze studies assessing candidate polymorphisms/genes tested for an association with LUTS, and to assess the strength, consistency, and potential for bias among pooled associations. A systematic search of the PubMed and HuGE databases as well as abstracts of major urologic meetings was performed through to January 2013. Case-control studies reporting genetic associations in men with LUTS were included. Reviewers independently and in duplicate screened titles, abstracts, and full texts to determine eligibility, abstracted data, and assessed the credibility of pooled associations according to the interim Venice criteria. Authors were contacted for clarifications if needed. Meta-analyses were performed for variants assessed in more than two studies. We identified 74 eligible studies containing data on 70 different genes. A total of 35 meta-analyses were performed with statistical significance in five (ACE, ELAC2, GSTM1, TERT, and VDR). The heterogeneity was high in three of these meta-analyses. The rs731236 variant of the vitamin D receptor had a protective effect for LUTS (odds ratio: 0.64; 95% confidence interval, 0.49-0.83) with moderate heterogeneity (I(2)=27.2%). No evidence for publication bias was identified. Limitations include wide-ranging phenotype definitions for LUTS and limited power in most meta-analyses to detect smaller effect sizes. Few putative genetic risk variants have been reliably replicated across populations. We found consistent evidence of a reduced risk of LUTS associated with the common rs731236 variant of the vitamin D receptor gene in our meta-analyses. Combining the results from all previous studies of genetic variants that may cause urinary symptoms in men, we found significant variants in five genes. Only one, a variant of the vitamin D receptor, was consistently protective across different populations. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Plasma Glucose Level Is Predictive of Serum Ammonia Level After Retrograde Occlusion of Portosystemic Shunts.

PubMed

Ishikawa, Tsuyoshi; Aibe, Yuki; Matsuda, Takashi; Iwamoto, Takuya; Takami, Taro; Sakaida, Isao

2017-09-01

The purpose of this study was to evaluate predictors of reduction in ammonia levels by occlusion of portosystemic shunts (PSS) in patients with cirrhosis. Forty-eight patients with cirrhosis (21 women, 27 men; mean age, 67.8 years) with PSS underwent balloon-occluded retrograde transvenous obliteration (BRTO) at one institution between February 2008 and June 2014. The causes of cirrhosis were hepatitis B in one case, hepatitis C in 20 cases, alcohol in 15 cases, nonalcoholic steatohepatitis in eight cases, and other conditions in four cases. The Child-Pugh classes were A in 24 cases, B in 23 cases, and C in one case. The indication for BRTO was gastric varices in 40 cases and hepatic encephalopathy in eight cases. Testing was conducted before and 1 month after the procedure. Statistical analyses were performed to identify predictors of a clinically significant decline in ammonia levels after BRTO. Occlusion of PSS resulted in a clinically significant decrease in ammonia levels accompanied by increased portal venous flow and improved Child-Pugh score. Univariate analyses showed that a reduction in ammonia levels due to BRTO was significantly related to lower plasma glucose levels, higher RBC counts, and higher hemoglobin concentration before the treatment. Furthermore, multivariate logistic regression identified preoperative plasma glucose level as the strongest independent predictor of a significant ammonia reduction in response to BRTO. In addition, although BRTO resulted in significantly declined ammonia levels in patients with normal glucose tolerance before the procedure, ammonia levels were not significantly decreased after shunt occlusion in patients with diabetes mellitus or impaired glucose tolerance before BRTO, according to 75-g oral glucose tolerance test results. Preoperative plasma glucose level is a useful predictor of clinically significant ammonia reduction resulting from occlusion of PSS in patients with cirrhosis. Even if PSS are present, control of blood ammonia levels by BRTO alone may be difficult in patients with glucose intolerance.

77 FR 39959 - Draft Guidance To Implement Requirements for the Treatment of Air Quality Monitoring Data...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-06

... of the revised draft High Winds Guidance document, the EPA identifies example technical analyses that... identified analyses and any additional technical analyses that air agencies could use to demonstrate that the... Web site at http://www.epa.gov/ttn/analysis/exevents.htm for additional details on the draft non...

Spirituality as a Scientific Construct: Testing Its Universality across Cultures and Languages

PubMed Central

MacDonald, Douglas A.; Friedman, Harris L.; Brewczynski, Jacek; Holland, Daniel; Salagame, Kiran Kumar K.; Mohan, K. Krishna; Gubrij, Zuzana Ondriasova; Cheong, Hye Wook

2015-01-01

Using data obtained from 4004 participants across eight countries (Canada, India, Japan, Korea, Poland, Slovakia, Uganda, and the U.S.), the factorial reliability, validity and structural/measurement invariance of a 30-item version of Expressions of Spirituality Inventory (ESI-R) was evaluated. The ESI-R measures a five factor model of spirituality developed through the conjoint factor analysis of several extant measures of spiritual constructs. Exploratory factor analyses of pooled data provided evidence that the five ESI-R factors are reliable. Confirmatory analyses comparing four and five factor models revealed that the five dimensional model demonstrates superior goodness-of-fit with all cultural samples and suggest that the ESI-R may be viewed as structurally invariant. Measurement invariance, however, was not supported as manifested in significant differences in item and dimension scores and in significantly poorer fit when factor loadings were constrained to equality across all samples. Exploratory analyses with a second adjective measure of spirituality using American, Indian, and Ugandan samples identified three replicable factors which correlated with ESI-R dimensions in a manner supportive of convergent validity. The paper concludes with a discussion of the meaning of the findings and directions needed for future research. PMID:25734921

Development and validation of prognostic models in metastatic breast cancer: a GOCS study.

PubMed

Rabinovich, M; Vallejo, C; Bianco, A; Perez, J; Machiavelli, M; Leone, B; Romero, A; Rodriguez, R; Cuevas, M; Dansky, C

1992-01-01

The significance of several prognostic factors and the magnitude of their influence on response rate and survival were assessed by means of uni- and multivariate analyses in 362 patients with stage IV (UICC) breast carcinoma receiving combination chemotherapy as first systemic treatment over an 8-year period. Univariate analyses identified performance status and prior adjuvant radiotherapy as predictors of objective regression (OR), whereas the performance status, prior chemotherapy and radiotherapy (adjuvants), white blood cells count, SGOT and SGPT levels, and metastatic pattern were significantly correlated to survival. In multivariate analyses favorable characteristics associated to OR were prior adjuvant radiotherapy, no prior chemotherapy and postmenopausal status. Regarding survival, the performance status and visceral involvement were selected by the Cox model. The predictive accuracy of the logistic and the proportional hazards models was retrospectively tested in the training sample, and prospectively in a new population of 126 patients also receiving combined chemotherapy as first treatment for metastatic breast cancer. A certain overfitting to data in the training sample was observed with the regression model for response. However, the discriminative ability of the Cox model for survival was clearly confirmed.

The normal electrocardiogram of four species of conscious raptors.

PubMed

Talavera, J; Guzmán, M J; del Palacio, M J Fernández; Albert, A P; Bayón, A

2008-02-01

The aim of this study was to describe normal ECG patterns and values in four species of conscious raptors (Eurasian kestrel, Griffon vulture, Little owl, and Eurasian Eagle owl). Electrocardiograms were carried out in 75 conscious birds belonging to four species of raptors. Lead II waveforms were analysed to determine amplitudes and durations of waves and intervals. Morphologic patterns of P-QRS-T deflections were analysed in the six limb leads. Rhythm, heart rate, mean electrical axis, presence of Ta wave, ST slurring, and P-on-T phenomenon were also studied. The influence of species, body weight and heart rate in electrocardiographic variables were statistically analysed (P < 0.05). Sinus rhythm was present in all tracings, showing sinus arrhythmia in four cases. Ta wave was present in six tracings and P-on-T phenomenon in four. ST segment could be identified in all tracings, being mainly high above baseline. Significant differences between species were found for all the electrocardiographic parameters. The heart rate and body weight were also found to be a significant influence in most parameters. This study provides electrocardiographic data for four species of raptors that can be used to establish comparisons for clinical purposes.

FARVATX: FAmily-based Rare Variant Association Test for X-linked genes

PubMed Central

Choi, Sungkyoung; Lee, Sungyoung; Qiao, Dandi; Hardin, Megan; Cho, Michael H.; Silverman, Edwin K; Park, Taesung; Won, Sungho

2016-01-01

Although the X chromosome has many genes that are functionally related to human diseases, the complicated biological properties of the X chromosome have prevented efficient genetic association analyses, and only a few significantly associated X-linked variants have been reported for complex traits. For instance, dosage compensation of X-linked genes is often achieved via the inactivation of one allele in each X-linked variant in females; however, some X-linked variants can escape this X chromosome inactivation. Efficient genetic analyses cannot be conducted without prior knowledge about the gene expression process of X-linked variants, and misspecified information can lead to power loss. In this report, we propose new statistical methods for rare X-linked variant genetic association analysis of dichotomous phenotypes with family-based samples. The proposed methods are computationally efficient and can complete X-linked analyses within a few hours. Simulation studies demonstrate the statistical efficiency of the proposed methods, which were then applied to rare-variant association analysis of the X chromosome in chronic obstructive pulmonary disease (COPD). Some promising significant X-linked genes were identified, illustrating the practical importance of the proposed methods. PMID:27325607

FARVATX: Family-Based Rare Variant Association Test for X-Linked Genes.

PubMed

Choi, Sungkyoung; Lee, Sungyoung; Qiao, Dandi; Hardin, Megan; Cho, Michael H; Silverman, Edwin K; Park, Taesung; Won, Sungho

2016-09-01

Although the X chromosome has many genes that are functionally related to human diseases, the complicated biological properties of the X chromosome have prevented efficient genetic association analyses, and only a few significantly associated X-linked variants have been reported for complex traits. For instance, dosage compensation of X-linked genes is often achieved via the inactivation of one allele in each X-linked variant in females; however, some X-linked variants can escape this X chromosome inactivation. Efficient genetic analyses cannot be conducted without prior knowledge about the gene expression process of X-linked variants, and misspecified information can lead to power loss. In this report, we propose new statistical methods for rare X-linked variant genetic association analysis of dichotomous phenotypes with family-based samples. The proposed methods are computationally efficient and can complete X-linked analyses within a few hours. Simulation studies demonstrate the statistical efficiency of the proposed methods, which were then applied to rare-variant association analysis of the X chromosome in chronic obstructive pulmonary disease. Some promising significant X-linked genes were identified, illustrating the practical importance of the proposed methods. © 2016 WILEY PERIODICALS, INC.

Gene Expression Profiling of Histiocytic Sarcomas in a Canine Model: The Predisposed Flatcoated Retriever Dog

PubMed Central

Boerkamp, Kim M.; van Wolferen, Monique E.; Groot Koerkamp, Marian J. A.; van Leenen, Dik; Grinwis, Guy C. M.; Penning, Louis C.; Wiemer, Erik A. C.; Rutteman, Gerard R.

2013-01-01

Background The determination of altered expression of genes in specific tumor types and their effect upon cellular processes may create insight in tumorigenesis and help to design better treatments. The Flatcoated retriever is a dog breed with an exceptionally high incidence of histiocytic sarcomas. The breed develops two distinct entities of histiocytic neoplasia, a soft tissue form and a visceral form. Gene expression studies of these tumors have value for comparable human diseases such as histiocytic/dendritic cell sarcoma for which knowledge is difficult to accrue due to their rare occurrence. In addition, such studies may help in the search for genetic aberrations underlying the genetic predisposition in this dog breed. Methods Microarray analysis and pathway analyses were performed on fresh-frozen tissues obtained from Flatcoated retrievers with localized, soft tissue histiocytic sarcomas (STHS) and disseminated, visceral histiocytic sarcomas (VHS) and on normal canine spleens from various breeds. Expression differences of nine genes were validated with quantitative real-time PCR (qPCR) analyses. Results QPCR analyses identified the significantly altered expression of nine genes; PPBP, SpiC, VCAM1, ENPEP, ITGAD (down-regulated), and GTSF1, Col3a1, CD90 and LUM (up-regulated) in the comparison of both the soft tissue and the visceral form with healthy spleen. DAVID pathway analyses revealed 24 pathways that were significantly involved in the development of HS in general, most of which were involved in the DNA repair and replication process. Conclusions This study identified altered expression of nine genes not yet implicated in histiocytic sarcoma manifestations in the dog nor in comparable human histiocytic/dendritic sarcomas. Exploration of the downside effect of canine inbreeding strategies for the study of similar sarcomas in humans might also lead to the identification of genes related to these rare malignancies in the human. PMID:23936488

Landscape Patterns in Rainforest Phylogenetic Signal: Isolated Islands of Refugia or Structured Continental Distributions?

PubMed Central

Kooyman, Robert M.; Rossetto, Maurizio; Sauquet, Hervé; Laffan, Shawn W.

2013-01-01

Objectives Identify patterns of change in species distributions, diversity, concentrations of evolutionary history, and assembly of Australian rainforests. Methods We used the distribution records of all known rainforest woody species in Australia across their full continental extent. These were analysed using measures of species richness, phylogenetic diversity (PD), phylogenetic endemism (PE) and phylogenetic structure (net relatedness index; NRI). Phylogenetic structure was assessed using both continental and regional species pools. To test the influence of growth-form, freestanding and climbing plants were analysed independently, and in combination. Results Species richness decreased along two generally orthogonal continental axes, corresponding with wet to seasonally dry and tropical to temperate habitats. The PE analyses identified four main areas of substantially restricted phylogenetic diversity, including parts of Cape York, Wet Tropics, Border Ranges, and Tasmania. The continental pool NRI results showed evenness (species less related than expected by chance) in groups of grid cells in coastally aligned areas of species rich tropical and sub-tropical rainforest, and in low diversity moist forest areas in the south-east of the Great Dividing Range and in Tasmania. Monsoon and drier vine forests, and moist forests inland from upland refugia showed phylogenetic clustering, reflecting lower diversity and more relatedness. Signals for evenness in Tasmania and clustering in northern monsoon forests weakened in analyses using regional species pools. For climbing plants, values for NRI by grid cell showed strong spatial structuring, with high diversity and PE concentrated in moist tropical and subtropical regions. Conclusions/Significance Concentrations of rainforest evolutionary history (phylo-diversity) were patchily distributed within a continuum of species distributions. Contrasting with previous concepts of rainforest community distribution, our findings of continuous distributions and continental connectivity have significant implications for interpreting rainforest evolutionary history and current day ecological processes, and for managing rainforest diversity in changing circumstances. PMID:24312493

Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: A meta-analysis.

PubMed

Mazza, Mario Gennaro; Lucchi, Sara; Tringali, Agnese Grazia Maria; Rossetti, Aurora; Botti, Eugenia Rossana; Clerici, Massimo

2018-06-08

The immune and inflammatory system is involved in the etiology of mood disorders. Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) are inexpensive and reproducible biomarkers of inflammation. This is the first meta-analysis exploring the role of NLR and PLR in mood disorder. We identified 11 studies according to our inclusion criteria from the main Electronic Databases. Meta-analyses were carried out generating pooled standardized mean differences (SMDs) between index and healthy controls (HC). Heterogeneity was estimated. Relevant sensitivity and meta-regression analyses were conducted. Subjects with bipolar disorder (BD) had higher NLR and PLR as compared with HC (respectively SMD = 0.672; p < 0.001; I 2  = 82.4% and SMD = 0.425; p = 0.048; I 2  = 86.53%). Heterogeneity-based sensitivity analyses confirmed these findings. Subgroup analysis evidenced an influence of bipolar phase on the overall estimate whit studies including subjects in manic and any bipolar phase showing a significantly higher NLR and PLR as compared with HC whereas the effect was not significant among studies including only euthymic bipolar subjects. Meta-regression showed that age and sex influenced the relationship between BD and NLR but not the relationship between BD and PLR. Meta-analysis was not carried out for MLR because our search identified only one study when comparing BD to HC, and only one study when comparing MDD to HC. Subjects with major depressive disorder (MDD) had higher NLR as compared with HC (SMD = 0.670; p = 0.028; I 2  = 89.931%). Heterogeneity-based sensitivity analyses and meta-regression confirmed these findings. Our meta-analysis supports the hypothesis that an inflammatory activation occurs in mood disorders and NLR and PLR may be useful to detect this activation. More researches including comparison of NLR, PLR and MLR between different bipolar phases and between BD and MDD are needed. Copyright © 2018 Elsevier Inc. All rights reserved.

Freshwater reservoir offsets and food crusts: Isotope, AMS, and lipid analyses of experimental cooking residues

PubMed Central

Taché, Karine; Lovis, William A.

2018-01-01

Freshwater reservoir offsets (FROs) occur when AMS dates on charred, encrusted food residues on pottery predate a pot’s chronological context because of the presence of ancient carbon from aquatic resources such as fish. Research over the past two decades has demonstrated that FROs vary widely within and between water bodies and between fish in those water bodies. Lipid analyses have identified aquatic biomarkers that can be extracted from cooking residues as potential evidence for FROs. However, lacking has been efforts to determine empirically how much fish with FROs needs to be cooked in a pot with other resources to result in significant FRO on encrusted cooking residue and what percentage of fish C in a residue is needed to result in the recovery of aquatic biomarkers. Here we provide preliminary assessments of both issues. Our results indicate that in historically-contingent, high alkalinity environments <20% C from fish may result in a statistically significant FRO, but that biomarkers for aquatic resources may be present in the absence of a significant FRO. PMID:29694436

Managing Complexity in Evidence Analysis: A Worked Example in Pediatric Weight Management.

PubMed

Parrott, James Scott; Henry, Beverly; Thompson, Kyle L; Ziegler, Jane; Handu, Deepa

2018-05-02

Nutrition interventions are often complex and multicomponent. Typical approaches to meta-analyses that focus on individual causal relationships to provide guideline recommendations are not sufficient to capture this complexity. The objective of this study is to describe the method of meta-analysis used for the Pediatric Weight Management (PWM) Guidelines update and provide a worked example that can be applied in other areas of dietetics practice. The effects of PWM interventions were examined for body mass index (BMI), body mass index z-score (BMIZ), and waist circumference at four different time periods. For intervention-level effects, intervention types were identified empirically using multiple correspondence analysis paired with cluster analysis. Pooled effects of identified types were examined using random effects meta-analysis models. Differences in effects among types were examined using meta-regression. Context-level effects are examined using qualitative comparative analysis. Three distinct types (or families) of PWM interventions were identified: medical nutrition, behavioral, and missing components. Medical nutrition and behavioral types showed statistically significant improvements in BMIZ across all time points. Results were less consistent for BMI and waist circumference, although four distinct patterns of weight status change were identified. These varied by intervention type as well as outcome measure. Meta-regression indicated statistically significant differences between the medical nutrition and behavioral types vs the missing component type for both BMIZ and BMI, although the pattern varied by time period and intervention type. Qualitative comparative analysis identified distinct configurations of context characteristics at each time point that were consistent with positive outcomes among the intervention types. Although analysis of individual causal relationships is invaluable, this approach is inadequate to capture the complexity of dietetics practice. An alternative approach that integrates intervention-level with context-level meta-analyses may provide deeper understanding in the development of practice guidelines. Copyright © 2018 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

NMR Spectroscopy Identifies Metabolites Translocated from Powdery Mildew Resistant Rootstocks to Susceptible Watermelon Scions.

PubMed

Mahmud, Iqbal; Kousik, Chandrasekar; Hassell, Richard; Chowdhury, Kamal; Boroujerdi, Arezue F

2015-09-16

Powdery mildew (PM) disease causes significant loss in watermelon. Due to the unavailability of a commercial watermelon variety that is resistant to PM, grafting susceptible cultivars on wild resistant rootstocks is being explored as a short-term management strategy to combat this disease. Nuclear magnetic resonance-based metabolic profiles of susceptible and resistant rootstocks of watermelon and their corresponding susceptible scions (Mickey Lee) were compared to screen for potential metabolites related to PM resistance using multivariate principal component analysis. Significant score plot differences between the susceptible and resistant groups were revealed through Mahalanobis distance analysis. Significantly different spectral buckets and their corresponding metabolites (including choline, fumarate, 5-hydroxyindole-3-acetate, and melatonin) have been identified quantitatively using multivariate loading plots and verified by volcano plot analyses. The data suggest that these metabolites were translocated from the powdery mildew resistant rootstocks to their corresponding powdery mildew susceptible scions and can be related to PM disease resistance.

Men and women show similar survival outcome in stage IV breast cancer.

PubMed

Wu, San-Gang; Zhang, Wen-Wen; Liao, Xu-Lin; Sun, Jia-Yuan; Li, Feng-Yan; Su, Jing-Jun; He, Zhen-Yu

2017-08-01

To evaluate the clinicopathological features, patterns of distant metastases, and survival outcome between stage IV male breast cancer (MBC) and female breast cancer (FBC). Patients diagnosed with stage IV MBC and FBC between 2010 and 2013 were included using the Surveillance, Epidemiology, and End Results program. Univariate and multivariate Cox regression analyses were used to analyze risk factors for overall survival (OS). A total of 4997 patients were identified, including 60 MBC and 4937 FBC. Compared with FBC, patients with MBC were associated with a significantly higher rate of estrogen receptor-positive, progesterone receptor-positive, unmarried, lung metastases, and a lower frequency of liver metastases. Univariate and multivariate analyses showed no significant difference in OS between MBC and FBC. In the propensity score-matched population, there was also no difference in survival between MBC and FBC. Multivariate analysis of MBC showed that OS was longer for patients aged 50-69 years and with estrogen receptor-positive disease. There was no significant difference in survival outcome between stage IV MBC and FBC, but significant differences in clinicopathological features and patterns of metastases between the genders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Do ethnicity and gender matter when using the theory of planned behavior to understand fruit and vegetable consumption?

PubMed

Blanchard, Chris M; Kupperman, Janet; Sparling, Phillip B; Nehl, Eric; Rhodes, Ryan E; Courneya, Kerry S; Baker, Frank

2009-02-01

A majority of Americans do not meet the recommendation to eat five servings of fruits and vegetables per day (5-A-Day). The purpose of the present study was to examine the utility of the theory of planned behavior (TPB) for understanding 5-A-Day intentions and behavior and to determine whether any of the TPB relationships were moderated by ethnicity or gender. A total of 413 participants completed a baseline TPB questionnaire and a fruit and vegetable consumption measure 2 weeks later. Path analyses showed that affective attitude and perceived behavioral control significantly predicted intention for blacks, whites, males and females (R(2) ranged from .32 to .40), whereas subjective norm was a significant predictor for blacks, males, and females only. Intention significantly predicted 5-A-Day (R(2) ranged from .17 to .22) for all groups. Follow-up invariance analyses showed that the subjective norm/intention relationship was significantly stronger for black compared to white students. Finally, several key beliefs were identified for all four demographic groups. Therefore, the current results suggest that the TPB may be a useful framework to utilize when developing 5-A-Day interventions.

Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.

PubMed

Gormley, Padhraig; Anttila, Verneri; Winsvold, Bendik S; Palta, Priit; Esko, Tonu; Pers, Tune H; Farh, Kai-How; Cuenca-Leon, Ester; Muona, Mikko; Furlotte, Nicholas A; Kurth, Tobias; Ingason, Andres; McMahon, George; Ligthart, Lannie; Terwindt, Gisela M; Kallela, Mikko; Freilinger, Tobias M; Ran, Caroline; Gordon, Scott G; Stam, Anine H; Steinberg, Stacy; Borck, Guntram; Koiranen, Markku; Quaye, Lydia; Adams, Hieab H H; Lehtimäki, Terho; Sarin, Antti-Pekka; Wedenoja, Juho; Hinds, David A; Buring, Julie E; Schürks, Markus; Ridker, Paul M; Hrafnsdottir, Maria Gudlaug; Stefansson, Hreinn; Ring, Susan M; Hottenga, Jouke-Jan; Penninx, Brenda W J H; Färkkilä, Markus; Artto, Ville; Kaunisto, Mari; Vepsäläinen, Salli; Malik, Rainer; Heath, Andrew C; Madden, Pamela A F; Martin, Nicholas G; Montgomery, Grant W; Kurki, Mitja I; Kals, Mart; Mägi, Reedik; Pärn, Kalle; Hämäläinen, Eija; Huang, Hailiang; Byrnes, Andrea E; Franke, Lude; Huang, Jie; Stergiakouli, Evie; Lee, Phil H; Sandor, Cynthia; Webber, Caleb; Cader, Zameel; Muller-Myhsok, Bertram; Schreiber, Stefan; Meitinger, Thomas; Eriksson, Johan G; Salomaa, Veikko; Heikkilä, Kauko; Loehrer, Elizabeth; Uitterlinden, Andre G; Hofman, Albert; van Duijn, Cornelia M; Cherkas, Lynn; Pedersen, Linda M; Stubhaug, Audun; Nielsen, Christopher S; Männikkö, Minna; Mihailov, Evelin; Milani, Lili; Göbel, Hartmut; Esserlind, Ann-Louise; Christensen, Anne Francke; Hansen, Thomas Folkmann; Werge, Thomas; Kaprio, Jaakko; Aromaa, Arpo J; Raitakari, Olli; Ikram, M Arfan; Spector, Tim; Järvelin, Marjo-Riitta; Metspalu, Andres; Kubisch, Christian; Strachan, David P; Ferrari, Michel D; Belin, Andrea C; Dichgans, Martin; Wessman, Maija; van den Maagdenberg, Arn M J M; Zwart, John-Anker; Boomsma, Dorret I; Smith, George Davey; Stefansson, Kari; Eriksson, Nicholas; Daly, Mark J; Neale, Benjamin M; Olesen, Jes; Chasman, Daniel I; Nyholt, Dale R; Palotie, Aarno

2016-08-01

Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 × 10(-8)) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.

Associations between variants of the HAL gene and milk production traits in Chinese Holstein cows.

PubMed

Wang, Haifei; Jiang, Li; Wang, Wenwen; Zhang, Shengli; Yin, Zongjun; Zhang, Qin; Liu, Jian-Feng

2014-11-25

The histidine ammonia-lyse gene (HAL) encodes the histidine ammonia-lyase, which catalyzes the first reaction of histidine catabolism. In our previous genome-wide association study in Chinese Holstein cows to identify genetic variants affecting milk production traits, a SNP (rs41647754) located 357 bp upstream of HAL, was found to be significantly associated with milk yield and milk protein yield. In addition, the HAL gene resides within the reported QTLs for milk production traits. The aims of this study were to identify genetic variants in HAL and to test the association between these variants and milk production traits. Fifteen SNPs were identified within the regions under study of the HAL gene, including three coding mutations, seven intronic mutations, one promoter region mutation, and four 3'UTR mutations. Nine of these identified SNPs were chosen for subsequent genotyping and association analyses. Our results showed that five SNP markers (ss974768522, ss974768525, ss974768531, ss974768533 and ss974768534) were significantly associated with one or more milk production traits. Haplotype analysis showed that two haplotype blocks were significantly associated with milk yield and milk protein yield, providing additional support for the association between HAL variants and milk production traits in dairy cows (P < 0.05). Our study shows evidence of significant associations between SNPs within the HAL gene and milk production traits in Chinese Holstein cows, indicating the potential role of HAL variants in these traits. These identified SNPs may serve as genetic markers used in genomic selection schemes to accelerate the genetic gains of milk production traits in dairy cattle.

Genomic and molecular analysis of phage CMP1 from Clavibacter michiganensis subspecies michiganensis

PubMed Central

Wittmann, Johannes; Gartemann, Karl-Heinz; Eichenlaub, Rudolf

2011-01-01

Bacteriophage CMP1 is a member of the Siphoviridae family that infects specifically the plant-pathogen Clavibacter michiganensis subsp. michiganensis. The linear double- stranded DNA is terminally redundant and not circularly permuted. The complete nucleotide sequence of the bacteriophage CMP1 genome consists of 58,652 bp including the terminal redundant ends of 791 bp. The G+C content of the phage (57%) is significantly lower than that of its host (72.66%). 74 potential open reading frames were identified and annotated by different bioinformatic tools. Two large clusters which encode the early and the late functions could be identified which are divergently transcribed. There are only a few hypothetical gene products with conserved domains and significant similarity to sequences from the databases. Functional analyses confirmed the activity of four gene products, an endonuclease, an exonuclease, a single-stranded DNA binding protein and a thymidylate synthase. Partial genomic sequences of CN77, a phage of Clavibacter michiganensis subsp. nebraskensis, revealed a similar genome structure and significant similarities on the level of deduced amino acid sequences. An endolysin with peptidase activity has been identified for both phages, which may be good tools for disease control of tomato plants against Clavibacter infections. PMID:21687530

Genomic and molecular analysis of phage CMP1 from Clavibacter michiganensis subspecies michiganensis.

PubMed

Wittmann, Johannes; Gartemann, Karl-Heinz; Eichenlaub, Rudolf; Dreiseikelmann, Brigitte

2011-01-01

Bacteriophage CMP1 is a member of the Siphoviridae family that infects specifically the plant-pathogen Clavibacter michiganensis subsp. michiganensis. The linear double- stranded DNA is terminally redundant and not circularly permuted. The complete nucleotide sequence of the bacteriophage CMP1 genome consists of 58,652 bp including the terminal redundant ends of 791 bp. The G+C content of the phage (57%) is significantly lower than that of its host (72.66%). 74 potential open reading frames were identified and annotated by different bioinformatic tools. Two large clusters which encode the early and the late functions could be identified which are divergently transcribed. There are only a few hypothetical gene products with conserved domains and significant similarity to sequences from the databases. Functional analyses confirmed the activity of four gene products, an endonuclease, an exonuclease, a single-stranded DNA binding protein and a thymidylate synthase. Partial genomic sequences of CN77, a phage of Clavibacter michiganensis subsp. nebraskensis, revealed a similar genome structure and significant similarities on the level of deduced amino acid sequences. An endolysin with peptidase activity has been identified for both phages, which may be good tools for disease control of tomato plants against Clavibacter infections.

The role of general and specific stressors in the health and well-being of call centre operators.

PubMed

Mellor, David; Moore, Kathleen A; Siong, Zhong Ming Benjamin

2015-01-01

The call centre industry has developed a reputation for generating a highly stressful work environment with high absenteeism and turnover rates. Research has identified role ambiguity, role conflict, role overload, and work-family conflict as common stressors in other settings. Call centre research has additionally identified performance monitoring, job design and job opportunities as call centre specific stressors. This study investigated the impact of the identified stressors on burnout, somatic symptomology, and turnover intent among 126 call centre representatives (CCRs) from 11 call centres in metropolitan Melbourne, Australia. Hierarchical multiple regression analyses found that the common organizational stressors significantly explained between 10% and 53% of the variance in somatic symptomology, burnout (all 3 dimensions) and turnover intent. An additional amount of variance, between 6% and 22% in each of these dependent measures was significantly accounted for by the grouped call centre specific stressors. Overall, common organizational stressors and call centre specific stressors both significantly and independently contributed to burnout, somatic symptomology and turnover intent. These findings are discussed in relation to previous research, and suggestions for improved practice within call centres to safeguard the well-being of workers and for future research are provided.

SLUDGE TREATMENT PROJECT KOP CONCEPTUAL DESIGN CONTROL DECISION REPORT

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

CARRO CA

2010-03-09

This control decision addresses the Knock-Out Pot (KOP) Disposition KOP Processing System (KPS) conceptual design. The KPS functions to (1) retrieve KOP material from canisters, (2) remove particles less than 600 {micro}m in size and low density materials from the KOP material, (3) load the KOP material into Multi-Canister Overpack (MCO) baskets, and (4) stage the MCO baskets for subsequent loading into MCOs. Hazard and accident analyses of the KPS conceptual design have been performed to incorporate safety into the design process. The hazard analysis is documented in PRC-STP-00098, Knock-Out Pot Disposition Project Conceptual Design Hazard Analysis. The accident analysismore » is documented in PRC-STP-CN-N-00167, Knock-Out Pot Disposition Sub-Project Canister Over Lift Accident Analysis. Based on the results of these analyses, and analyses performed in support of MCO transportation and MCO processing and storage activities at the Cold Vacuum Drying Facility (CVDF) and Canister Storage Building (CSB), control decision meetings were held to determine the controls required to protect onsite and offsite receptors and facility workers. At the conceptual design stage, these controls are primarily defined by their safety functions. Safety significant structures, systems, and components (SSCs) that could provide the identified safety functions have been selected for the conceptual design. It is anticipated that some safety SSCs identified herein will be reclassified based on hazard and accident analyses performed in support of preliminary and detailed design.« less

Comprehensive high-resolution genomic profiling and cytogenetics of human chondrocyte cultures by GTG-banding, locus-specific FISH, SKY and SNP array.

PubMed

Wallenborn, M; Petters, O; Rudolf, D; Hantmann, H; Richter, M; Ahnert, P; Rohani, L; Smink, J J; Bulwin, G C; Krupp, W; Schulz, R M; Holland, H

2018-04-23

In the development of cell-based medicinal products, it is crucial to guarantee that the application of such an advanced therapy medicinal product (ATMP) is safe for the patients. The consensus of the European regulatory authorities is: "In conclusion, on the basis of the state of art, conventional karyotyping can be considered a valuable and useful technique to analyse chromosomal stability during preclinical studies". 408 chondrocyte samples (84 monolayers and 324 spheroids) from six patients were analysed using trypsin-Giemsa staining, spectral karyotyping and fluorescence in situ hybridisation, to evaluate the genetic stability of chondrocyte samples from non-clinical studies. Single nucleotide polymorphism (SNP) array analysis was performed on chondrocyte spheroids from five of the six donors. Applying this combination of techniques, the genetic analyses performed revealed no significant genetic instability until passage 3 in monolayer cells and interphase cells from spheroid cultures at different time points. Clonal occurrence of polyploid metaphases and endoreduplications were identified associated with prolonged cultivation time. Also, gonosomal losses were observed in chondrocyte spheroids, with increasing passage and duration of the differentiation phase. Interestingly, in one of the donors, chromosomal aberrations that are also described in extraskeletal myxoid chondrosarcoma were identified. The SNP array analysis exhibited chromosomal aberrations in two donors and copy neutral losses of heterozygosity regions in four donors. This study showed the necessity of combined genetic analyses at defined cultivation time points in quality studies within the field of cell therapy.

Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions.

PubMed

Balhana, Ricardo J C; Singla, Ashima; Sikder, Mahmudul Hasan; Withers, Mike; Kendall, Sharon L

2015-06-27

Mycobacteria inhabit diverse niches and display high metabolic versatility. They can colonise both humans and animals and are also able to survive in the environment. In order to succeed, response to environmental cues via transcriptional regulation is required. In this study we focused on the TetR family of transcriptional regulators (TFTRs) in mycobacteria. We used InterPro to classify the entire complement of transcriptional regulators in 10 mycobacterial species and these analyses showed that TFTRs are the most abundant family of regulators in all species. We identified those TFTRs that are conserved across all species analysed and those that are unique to the pathogens included in the analysis. We examined genomic contexts of 663 of the conserved TFTRs and observed that the majority of TFTRs are separated by 200 bp or less from divergently oriented genes. Analyses of divergent genes indicated that the TFTRs control diverse biochemical functions not limited to efflux pumps. TFTRs typically bind to palindromic motifs and we identified 11 highly significant novel motifs in the upstream regions of divergently oriented TFTRs. The C-terminal ligand binding domain from the TFTR complement in M. tuberculosis showed great diversity in amino acid sequence but with an overall architecture common to other TFTRs. This study suggests that mycobacteria depend on TFTRs for the transcriptional control of a number of metabolic functions yet the physiological role of the majority of these regulators remain unknown.

Phylogenetic Analyses of Shigella and Enteroinvasive Escherichia coli for the Identification of Molecular Epidemiological Markers: Whole-Genome Comparative Analysis Does Not Support Distinct Genera Designation

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

Pettengill, Emily A.; Pettengill, James B.; Binet, Rachel

As a leading cause of bacterial dysentery, Shigella represents a significant threat to public health and food safety. Related, but often overlooked, enteroinvasive Escherichia coli (EIEC) can also cause dysentery. Current typing methods have limited ability to identify and differentiate between these pathogens despite the need for rapid and accurate identification of pathogens for clinical treatment and outbreak response. We present a comprehensive phylogeny of Shigella and EIEC using whole genome sequencing of 169 samples, constituting unparalleled strain diversity, and observe a lack of monophyly between Shigella and EIEC and among Shigella taxonomic groups. The evolutionary relationships in the phylogenymore » are supported by analyses of population structure and hierarchical clustering patterns of translated gene homolog abundance. Lastly, we identified a panel of 404 single nucleotide polymorphism (SNP) markers specific to each phylogenetic cluster for more accurate identification of Shigella and EIEC. Our findings show that Shigella and EIEC are not distinct evolutionary groups within the E. coli genus and, thus, EIEC as a group is not the ancestor to Shigella. The multiple analyses presented provide evidence for reconsidering the taxonomic placement of Shigella. The SNP markers offer more discriminatory power to molecular epidemiological typing methods involving these bacterial pathogens.« less

Phylogenetic Analyses of Shigella and Enteroinvasive Escherichia coli for the Identification of Molecular Epidemiological Markers: Whole-Genome Comparative Analysis Does Not Support Distinct Genera Designation

DOE PAGES

Pettengill, Emily A.; Pettengill, James B.; Binet, Rachel

2016-01-19

As a leading cause of bacterial dysentery, Shigella represents a significant threat to public health and food safety. Related, but often overlooked, enteroinvasive Escherichia coli (EIEC) can also cause dysentery. Current typing methods have limited ability to identify and differentiate between these pathogens despite the need for rapid and accurate identification of pathogens for clinical treatment and outbreak response. We present a comprehensive phylogeny of Shigella and EIEC using whole genome sequencing of 169 samples, constituting unparalleled strain diversity, and observe a lack of monophyly between Shigella and EIEC and among Shigella taxonomic groups. The evolutionary relationships in the phylogenymore » are supported by analyses of population structure and hierarchical clustering patterns of translated gene homolog abundance. Lastly, we identified a panel of 404 single nucleotide polymorphism (SNP) markers specific to each phylogenetic cluster for more accurate identification of Shigella and EIEC. Our findings show that Shigella and EIEC are not distinct evolutionary groups within the E. coli genus and, thus, EIEC as a group is not the ancestor to Shigella. The multiple analyses presented provide evidence for reconsidering the taxonomic placement of Shigella. The SNP markers offer more discriminatory power to molecular epidemiological typing methods involving these bacterial pathogens.« less

Linkage analyses of cannabis dependence, craving, and withdrawal in the San Francisco family study.

PubMed

Ehlers, Cindy L; Gizer, Ian R; Vieten, Cassandra; Wilhelmsen, Kirk C

2010-04-05

Cannabis is the most widely used illicit drug in the United States. There is ample evidence that cannabis use has a heritable component, yet the genes underlying cannabis use disorders are yet to be completely identified. This study's aims were to map susceptibility loci for cannabis use and dependence and two narrower cannabis-related phenotypes of "craving" and "withdrawal" using a family study design. Participants were 2,524 adults participating in the University of California San Francisco (UCSF) Family Alcoholism Study. DSM-IV diagnoses of cannabis dependence, as well as indices of cannabis craving and withdrawal, were obtained using a modified version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). Genotypes were determined for a panel of 791 microsatellite polymorphisms. Multipoint variance component LOD scores were obtained using SOLAR. Genome-wide significance for linkage (LOD > 3.0) was not found for the DSM-IV cannabis dependence diagnosis; however, linkage analyses of cannabis "craving" and the cannabis withdrawal symptom of "nervous, tense, restless, or irritable" revealed five sites with LOD scores over 3.0 on chromosomes 1, 3, 6, 7, and 9. These results identify new regions of the genome associated with cannabis use phenotypes as well as corroborate the importance of several chromosome regions highlighted in previous linkage analyses for other substance dependence phenotypes.

The utility of estimating population-level trajectories of terminal wellbeing decline within a growth mixture modelling framework.

PubMed

Burns, R A; Byles, J; Magliano, D J; Mitchell, P; Anstey, K J

2015-03-01

Mortality-related decline has been identified across multiple domains of human functioning, including mental health and wellbeing. The current study utilised a growth mixture modelling framework to establish whether a single population-level trajectory best describes mortality-related changes in both wellbeing and mental health, or whether subpopulations report quite different mortality-related changes. Participants were older-aged (M = 69.59 years; SD = 8.08 years) deceased females (N = 1,862) from the dynamic analyses to optimise ageing (DYNOPTA) project. Growth mixture models analysed participants' responses on measures of mental health and wellbeing for up to 16 years from death. Multi-level models confirmed overall terminal decline and terminal drop in both mental health and wellbeing. However, modelling data from the same participants within a latent class growth mixture framework indicated that most participants reported stability in mental health (90.3 %) and wellbeing (89.0 %) in the years preceding death. Whilst confirming other population-level analyses which support terminal decline and drop hypotheses in both mental health and wellbeing, we subsequently identified that most of this effect is driven by a small, but significant minority of the population. Instead, most individuals report stable levels of mental health and wellbeing in the years preceding death.

Cells Comprising the Prostate Cancer Microenvironment Lack Recurrent Clonal Somatic Genomic Aberrations

PubMed Central

Bianchi-Frias, Daniella; Basom, Ryan; Delrow, Jeffrey J; Coleman, Ilsa M; Dakhova, Olga; Qu, Xiaoyu; Fang, Min; Franco, Omar E.; Ericson, Nolan G.; Bielas, Jason H.; Hayward, Simon W.; True, Lawrence; Morrissey, Colm; Brown, Lisha; Bhowmick, Neil A.; Rowley, David; Ittmann, Michael; Nelson, Peter S.

2017-01-01

Prostate cancer-associated stroma (CAS) plays an active role in malignant transformation, tumor progression, and metastasis. Molecular analyses of CAS have demonstrated significant changes in gene expression; however, conflicting evidence exists on whether genomic alterations in benign cells comprising the tumor microenvironment (TME) underlie gene expression changes and oncogenic phenotypes. This study evaluates the nuclear and mitochondrial DNA integrity of prostate carcinoma cells, CAS, matched benign epithelium and benign epithelium-associated stroma by whole genome copy number analyses, targeted sequencing of TP53, and fluorescence in situ hybridization. Comparative genomic hybridization (aCGH) of CAS revealed a copy-neutral diploid genome with only rare and small somatic copy number aberrations (SCNAs). In contrast, several expected recurrent SCNAs were evident in the adjacent prostate carcinoma cells, including gains at 3q, 7p, and 8q, and losses at 8p and 10q. No somatic TP53 mutations were observed in CAS. Mitochondrial DNA (mtDNA) extracted from carcinoma cells and stroma identified 23 somatic mtDNA mutations in neoplastic epithelial cells but only one mutation in stroma. Finally, genomic analyses identified no SCNAs, no loss of heterozygosity (LOH) or copy-neutral LOH in cultured cancer-associated fibroblasts (CAFs), which are known to promote prostate cancer progression in vivo. PMID:26753621

Genetic homogeneity of the invasive lionfish across the Northwestern Atlantic and the Gulf of Mexico based on Single Nucleotide Polymorphisms.

PubMed

Pérez-Portela, R; Bumford, A; Coffman, B; Wedelich, S; Davenport, M; Fogg, A; Swenarton, M K; Coleman, F; Johnston, M A; Crawford, D L; Oleksiak, M F

2018-03-22

Despite the devastating impact of the lionfish (Pterois volitans) invasion on NW Atlantic ecosystems, little genetic information about the invasion process is available. We applied Genotyping by Sequencing techniques to identify 1,220 single nucleotide polymorphic sites (SNPs) from 162 lionfish samples collected between 2013 and 2015 from two areas chronologically identified as the first and last invaded areas in US waters: the east coast of Florida and the Gulf of Mexico. We used population genomic analyses, including phylogenetic reconstruction, Bayesian clustering, genetic distances, Discriminant Analyses of Principal Components, and coalescence simulations for detection of outlier SNPs, to understand genetic trends relevant to the lionfish's long-term persistence. We found no significant differences in genetic structure or diversity between the two areas (F ST p-values > 0.01, and t-test p-values > 0.05). In fact, our genomic analyses showed genetic homogeneity, with enough gene flow between the east coast of Florida and Gulf of Mexico to erase previous signals of genetic divergence detected between these areas, secondary spreading, and bottlenecks in the Gulf of Mexico. These findings suggest rapid genetic changes over space and time during the invasion, resulting in one panmictic population with no signs of divergence between areas due to local adaptation.

Exploring the Interaction Natures in Plutonyl (VI) Complexes with Topological Analyses of Electron Density

PubMed Central

Du, Jiguang; Sun, Xiyuan; Jiang, Gang

2016-01-01

The interaction natures between Pu and different ligands in several plutonyl (VI) complexes are investigated by performing topological analyses of electron density. The geometrical structures in both gaseous and aqueous phases are obtained with B3LYP functional, and are generally in agreement with available theoretical and experimental results when combined with all-electron segmented all-electron relativistic contracted (SARC) basis set. The Pu–Oyl bond orders show significant linear dependence on bond length and the charge of oxygen atoms in plutonyl moiety. The closed-shell interactions were identified for Pu-Ligand bonds in most complexes with quantum theory of atoms in molecules (QTAIM) analyses. Meanwhile, we found that some Pu–Ligand bonds, like Pu–OH−, show weak covalent. The interactive nature of Pu–ligand bonds were revealed based on the interaction quantum atom (IQA) energy decomposition approach, and our results indicate that all Pu–Ligand interactions is dominated by the electrostatic attraction interaction as expected. Meanwhile it is also important to note that the quantum mechanical exchange-correlation contributions can not be ignored. By means of the non-covalent interaction (NCI) approach it has been found that some weak and repulsion interactions existed in plutonyl(VI) complexes, which can not be distinguished by QTAIM, can be successfully identified. PMID:27077844

Abnormally high expression of POLD1, MCM2, and PLK4 promotes relapse of acute lymphoblastic leukemia.

PubMed

Li, Sheng; Wang, Chengzhong; Wang, Weikai; Liu, Weidong; Zhang, Guiqin

2018-05-01

This study aimed to explore the underlying mechanism of relapsed acute lymphoblastic leukemia (ALL).Datasets of GSE28460 and GSE18497 were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between diagnostic and relapsed ALL samples were identified using Limma package in R, and a Venn diagram was drawn. Next, functional enrichment analyses of co-regulated DEGs were performed. Based on the String database, protein-protein interaction network and module analyses were also conducted. Moreover, transcription factors and miRNAs targeting co-regulated DEGs were predicted using the WebGestalt online tool.A total of 71 co-regulated DEGs were identified, including 56 co-upregulated genes and 15 co-downregulated genes. Functional enrichment analyses showed that upregulated DEGs were significantly enriched in the cell cycle, and DNA replication, and repair related pathways. POLD1, MCM2, and PLK4 were hub proteins in both protein-protein interaction network and module, and might be potential targets of E2F. Additionally, POLD1 and MCM2 were found to be regulated by miR-520H via E2F1.High expression of POLD1, MCM2, and PLK4 might play positive roles in the recurrence of ALL, and could serve as potential therapeutic targets for the treatment of relapsed ALL.

University Students' Knowledge Structures and Informal Reasoning on the Use of Genetically Modified Foods: Multidimensional Analyses

NASA Astrophysics Data System (ADS)

Wu, Ying-Tien

2013-10-01

This study aims to provide insights into the role of learners' knowledge structures about a socio-scientific issue (SSI) in their informal reasoning on the issue. A total of 42 non-science major university students' knowledge structures and informal reasoning were assessed with multidimensional analyses. With both qualitative and quantitative analyses, this study revealed that those students with more extended and better-organized knowledge structures, as well as those who more frequently used higher-order information processing modes, were more oriented towards achieving a higher-level informal reasoning quality. The regression analyses further showed that the "richness" of the students' knowledge structures explained 25 % of the variation in their rebuttal construction, an important indicator of reasoning quality, indicating the significance of the role of students' sophisticated knowledge structure in SSI reasoning. Besides, this study also provides some initial evidence for the significant role of the "core" concept within one's knowledge structure in one's SSI reasoning. The findings in this study suggest that, in SSI-based instruction, science instructors should try to identify students' core concepts within their prior knowledge regarding the SSI, and then they should try to guide students to construct and structure relevant concepts or ideas regarding the SSI based on their core concepts. Thus, students could obtain extended and well-organized knowledge structures, which would then help them achieve better learning transfer in dealing with SSIs.

An empirical typology of social networks and its association with physical and mental health: a study with older Korean immigrants.

PubMed

Park, Nan Sook; Jang, Yuri; Lee, Beom S; Ko, Jung Eun; Haley, William E; Chiriboga, David A

2015-01-01

In the context of social convoy theory, the purposes of the study were (a) to identify an empirical typology of the social networks evident in older Korean immigrants and (b) to examine its association with self-rated health and depressive symptoms. The sample consisted of 1,092 community-dwelling older Korean immigrants in Florida and New York. Latent class analyses were conducted to identify the optimal social network typology based on 8 indicators of interpersonal relationships and activities. Bivariate and multivariate analyses were conducted to examine how the identified social network typology was associated with self-rating of health and depressive symptoms. Results from the latent class analysis identified 6 clusters as being most optimal, and they were named diverse, unmarried/diverse, married/coresidence, family focused, unmarried/restricted, and restricted. Memberships in the clusters of diverse and married/coresidence were significantly associated with more favorable ratings of health and lower levels of depressive symptoms. Notably, no distinct network solely composed of friends was identified in the present sample of older immigrants; this may reflect the disruptions in social convoys caused by immigration. The findings of this study promote our understanding of the unique patterns of social connectedness in older immigrants. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117)

PubMed Central

Clarke, T-K; Adams, M J; Davies, G; Howard, D M; Hall, L S; Padmanabhan, S; Murray, A D; Smith, B H; Campbell, A; Hayward, C; Porteous, D J; Deary, I J; McIntosh, A M

2017-01-01

Alcohol consumption has been linked to over 200 diseases and is responsible for over 5% of the global disease burden. Well-known genetic variants in alcohol metabolizing genes, for example, ALDH2 and ADH1B, are strongly associated with alcohol consumption but have limited impact in European populations where they are found at low frequency. We performed a genome-wide association study (GWAS) of self-reported alcohol consumption in 112 117 individuals in the UK Biobank (UKB) sample of white British individuals. We report significant genome-wide associations at 14 loci. These include single-nucleotide polymorphisms (SNPs) in alcohol metabolizing genes (ADH1B/ADH1C/ADH5) and two loci in KLB, a gene recently associated with alcohol consumption. We also identify SNPs at novel loci including GCKR, CADM2 and FAM69C. Gene-based analyses found significant associations with genes implicated in the neurobiology of substance use (DRD2, PDE4B). GCTA analyses found a significant SNP-based heritability of self-reported alcohol consumption of 13% (se=0.01). Sex-specific analyses found largely overlapping GWAS loci and the genetic correlation (rG) between male and female alcohol consumption was 0.90 (s.e.=0.09, P-value=7.16 × 10−23). Using LD score regression, genetic overlap was found between alcohol consumption and years of schooling (rG=0.18, s.e.=0.03), high-density lipoprotein cholesterol (rG=0.28, s.e.=0.05), smoking (rG=0.40, s.e.=0.06) and various anthropometric traits (for example, overweight, rG=−0.19, s.e.=0.05). This study replicates the association between alcohol consumption and alcohol metabolizing genes and KLB, and identifies novel gene associations that should be the focus of future studies investigating the neurobiology of alcohol consumption. PMID:28937693

Pacific Ocean-wide profile of CYP1A1 expression, stable carbon and nitrogen isotope ratios, and organic contaminant burden in sperm whale skin biopsies.

PubMed

Godard-Codding, Céline A J; Clark, Rebecca; Fossi, Maria Cristina; Marsili, Letizia; Maltese, Silvia; West, Adam G; Valenzuela, Luciano; Rowntree, Victoria; Polyak, Ildiko; Cannon, John C; Pinkerton, Kim; Rubio-Cisneros, Nadia; Mesnick, Sarah L; Cox, Stephen B; Kerr, Iain; Payne, Roger; Stegeman, John J

2011-03-01

Ocean pollution affects marine organisms and ecosystems as well as humans. The International Oceanographic Commission recommends ocean health monitoring programs to investigate the presence of marine contaminants and the health of threatened species and the use of multiple and early-warning biomarker approaches. We explored the hypothesis that biomarker and contaminant analyses in skin biopsies of the threatened sperm whale (Physeter macrocephalus) could reveal geographical trends in exposure on an oceanwide scale. We analyzed cytochrome P450 1A1 (CYP1A1) expression (by immunohistochemistry), stable nitrogen and carbon isotope ratios (as general indicators of trophic position and latitude, respectively), and contaminant burdens in skin biopsies to explore regional trends in the Pacific Ocean. Biomarker analyses revealed significant regional differences within the Pacific Ocean. CYP1A1 expression was highest in whales from the Galapagos, a United Nations Educational, Scientific, and Cultural Organization World Heritage marine reserve, and was lowest in the sampling sites farthest away from continents. We examined the possible influence of the whales' sex, diet, or range and other parameters on regional variation in CYP1A1 expression, but data were inconclusive. In general, CYP1A1 expression was not significantly correlated with contaminant burdens in blubber. However, small sample sizes precluded detailed chemical analyses, and power to detect significant associations was limited. Our large-scale monitoring study was successful at identifying regional differences in CYP1A1 expression, providing a baseline for this known biomarker of exposure to aryl hydrocarbon receptor agonists. However, we could not identify factors that explained this variation. Future oceanwide CYP1A1 expression profiles in cetacean skin biopsies are warranted and could reveal whether globally distributed chemicals occur at biochemically relevant concentrations on a global basis, which may provide a measure of ocean integrity.

Pacific Ocean–Wide Profile of CYP1A1 Expression, Stable Carbon and Nitrogen Isotope Ratios, and Organic Contaminant Burden in Sperm Whale Skin Biopsies

PubMed Central

Godard-Codding, Céline A.J.; Clark, Rebecca; Fossi, Maria Cristina; Marsili, Letizia; Maltese, Silvia; West, Adam G.; Valenzuela, Luciano; Rowntree, Victoria; Polyak, Ildiko; Cannon, John C.; Pinkerton, Kim; Rubio-Cisneros, Nadia; Mesnick, Sarah L.; Cox, Stephen B.; Kerr, Iain; Payne, Roger; Stegeman, John J.

2011-01-01

Background Ocean pollution affects marine organisms and ecosystems as well as humans. The International Oceanographic Commission recommends ocean health monitoring programs to investigate the presence of marine contaminants and the health of threatened species and the use of multiple and early-warning biomarker approaches. Objective We explored the hypothesis that biomarker and contaminant analyses in skin biopsies of the threatened sperm whale (Physeter macrocephalus) could reveal geographical trends in exposure on an oceanwide scale. Methods We analyzed cytochrome P450 1A1 (CYP1A1) expression (by immunohistochemistry), stable nitrogen and carbon isotope ratios (as general indicators of trophic position and latitude, respectively), and contaminant burdens in skin biopsies to explore regional trends in the Pacific Ocean. Results Biomarker analyses revealed significant regional differences within the Pacific Ocean. CYP1A1 expression was highest in whales from the Galapagos, a United Nations Educational, Scientific, and Cultural Organization World Heritage marine reserve, and was lowest in the sampling sites farthest away from continents. We examined the possible influence of the whales’ sex, diet, or range and other parameters on regional variation in CYP1A1 expression, but data were inconclusive. In general, CYP1A1 expression was not significantly correlated with contaminant burdens in blubber. However, small sample sizes precluded detailed chemical analyses, and power to detect significant associations was limited. Conclusions Our large-scale monitoring study was successful at identifying regional differences in CYP1A1 expression, providing a baseline for this known biomarker of exposure to aryl hydrocarbon receptor agonists. However, we could not identify factors that explained this variation. Future oceanwide CYP1A1 expression profiles in cetacean skin biopsies are warranted and could reveal whether globally distributed chemicals occur at biochemically relevant concentrations on a global basis, which may provide a measure of ocean integrity. PMID:21134820

SOX9 Is a Progressive Factor in Prostate Cancer

DTIC Science & Technology

2013-09-01

immunohis- tochemical analyses of BCa xenografts or mouse mammary tis- sues are detailed in the supplemental data. Meta- analysis of Gene Expression—SOX9mRNA...accession no. GSE5460) using dChip software (29). The analysis of variance function in dChip identified gene probes with significant correlation to...tumor grade groups (right panel). The p values of the difference analysis (Fisher’s Exact Test) are indicated. SOX9 Controlled Wnt/-catenin Activity

Mechanisms of aquatic species invasions across the SALCC - an update

USGS Publications Warehouse

Benson, Amy J.

2014-01-01

Our project represents the first attempt to utilize the NAS Database within the context of a Landscape Conservation Cooperative conservation blueprint. A significant amount of effort during the past year was dedicated to determining the most appropriate use of these data for the purposes of identifying the mechanisms and patterns of aquatic species invasions. Descriptive analyses were first undertaken to characterize the spatial and temporal characteristics of the SALCC subset of NAS data.

Adaptation of the contraceptive self-efficacy scale for heterosexual Mexican men and women of reproductive age.

PubMed

Arias, María Luisa Flores; Champion, Jane Dimmitt; Soto, Norma Elva Sáenz

2017-08-01

Development of a Spanish Version Contraceptive Self-efficacy Scale for use among heterosexual Mexican populations of reproductive age inclusive of 18-35years. Methods of family planning have decreased in Mexico which may lead to an increase in unintended pregnancies. Contraceptive self-efficacy is considered a predictor and precursor for use of family planning methods. Cross-sectional, descriptive study design was used to assess contraceptive self-efficacy among a heterosexual Mexican population (N=160) of reproductive age (18-35years). Adaptation of a Spanish Version Contraceptive Self-efficacy scale was conducted prior to instrument administration. Exploratory and confirmatory factorial analyses identified seven factors with a variance of 72.812%. The adapted scale had a Cronbach alpha of 0.771. A significant correlation between the Spanish Version Contraceptive Self-efficacy Scale and the use of family planning methods was identified. The Spanish Version Contraceptive Self-efficacy scale has an acceptable Cronbach alpha. Exploratory factor analysis identified 7 components. A positive correlation between self-reported contraceptive self-efficacy and family planning method use was identified. This scale may be used among heterosexual Mexican men and women of reproductive age. The factor analysis (7 factors versus 4 factors for the original scale) identified a discrepancy for interpretation of the Spanish versus English language versions. Interpretation of findings obtained via the Spanish versión among heterosexual Mexican men and women of reproductive age require interpretation based upon these differences identified in these analyses. Copyright © 2017 Elsevier Inc. All rights reserved.

Screening for important unwarranted variation in clinical practice: a triple-test of processes of care, costs and patient outcomes.

PubMed

Partington, Andrew; Chew, Derek P; Ben-Tovim, David; Horsfall, Matthew; Hakendorf, Paul; Karnon, Jonathan

2017-03-01

Objective Unwarranted variation in clinical practice is a target for quality improvement in health care, but there is no consensus on how to identify such variation or to assess the potential value of initiatives to improve quality in these areas. This study illustrates the use of a triple test, namely the comparative analysis of processes of care, costs and outcomes, to identify and assess the burden of unwarranted variation in clinical practice. Methods Routinely collected hospital and mortality data were linked for patients presenting with symptoms suggestive of acute coronary syndromes at the emergency departments of four public hospitals in South Australia. Multiple regression models analysed variation in re-admissions and mortality at 30 days and 12 months, patient costs and multiple process indicators. Results After casemix adjustment, an outlier hospital with statistically significantly poorer outcomes and higher costs was identified. Key process indicators included admission patterns, use of invasive diagnostic procedures and length of stay. Performance varied according to patients' presenting characteristics and time of presentation. Conclusions The joint analysis of processes, outcomes and costs as alternative measures of performance inform the importance of reducing variation in clinical practice, as well as identifying specific targets for quality improvement along clinical pathways. Such analyses could be undertaken across a wide range of clinical areas to inform the potential value and prioritisation of quality improvement initiatives. What is known about the topic? Variation in clinical practice is a long-standing issue that has been analysed from many different perspectives. It is neither possible nor desirable to address all forms of variation in clinical practice: the focus should be on identifying important unwarranted variation to inform actions to reduce variation and improve quality. What does this paper add? This paper proposes the comparative analysis of processes of care, costs and outcomes for patients with similar diagnoses presenting at alternative hospitals, using linked, routinely collected data. This triple test of performance indicators extracts maximum value from routine data to identify priority areas for quality improvement to reduce important and unwarranted variations in clinical practice. What are the implications for practitioners? The proposed analyses need to be applied to other clinical areas to demonstrate the general application of the methods. The outputs can then be validated through the application of quality improvement initiatives in clinical areas with identified important and unwarranted variation. Validated frameworks for the comparative analysis of clinical practice provide an efficient approach to valuing and prioritising actions to improve health service quality.

Accident Analyses in Support of the Sludge Water System Safety Analysis

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

FINFROCK, S.H.

This document quantifies the potential health effects of the unmitigated hazards identified Hey (2002) for retrieval of sludge from the KE basin. It also identifies potential controls and any supporting mitigative analyses.

The contribution of online content to the promotion and normalisation of female genital cosmetic surgery: a systematic review of the literature.

PubMed

Mowat, Hayley; McDonald, Karalyn; Dobson, Amy Shields; Fisher, Jane; Kirkman, Maggie

2015-11-25

Women considering female genital cosmetic surgery (FGCS) are likely to use the internet as a key source of information during the decision-making process. The aim of this systematic review was to determine what is known about the role of the internet in the promotion and normalisation of female genital cosmetic surgery and to identify areas for future research. Eight social science, medical, and communication databases and Google Scholar were searched for peer-reviewed papers published in English. Results from all papers were analysed to identify recurring and unique themes. Five papers met inclusion criteria. Three of the papers reported investigations of website content of FGCS providers, a fourth compared motivations for labiaplasty publicised on provider websites with those disclosed by women in online communities, and the fifth analysed visual depictions of female genitalia in online pornography. Analysis yielded five significant and interrelated patterns of representation, each functioning to promote and normalise the practice of FGCS: pathologisation of genital diversity; female genital appearance as important to wellbeing; characteristics of women's genitals are important for sex life; female body as degenerative and improvable through surgery; and FGCS as safe, easy, and effective. A significant gap was identified in the literature: the ways in which user-generated content might function to perpetuate, challenge, or subvert the normative discourses prevalent in online pornography and surgical websites. Further research is needed to contribute to knowledge of the role played by the internet in the promotion and normalisation of female genital cosmetic surgery.

Longitudinal Examination of Symptom Profiles Among Breast Cancer Survivors.

PubMed

Avis, Nancy E; Levine, Beverly; Marshall, Sarah A; Ip, Edward H

2017-04-01

Identification of cancer patients with similar symptom profiles may facilitate targeted symptom management. To identify subgroups of breast cancer survivors based on differential experience of symptoms, examine change in subgroup membership over time, and identify relevant characteristics and quality of life (QOL) among subgroups. Secondary analyses of data from 653 breast cancer survivors recruited within eight months of diagnosis who completed questionnaires at five time points. Hidden Markov modeling was used to 1) formulate symptom profiles based on prevalence and severity of eight symptoms commonly associated with breast cancer and 2) estimate probabilities of changing subgroup membership over 18 months of follow-up. Ordinal repeated measures were used to 3) identify patient characteristics related to subgroup membership and 4) evaluate the relationship between symptom subgroup and QOL. A seven-subgroup model provided the best fit: 1) low symptom burden, 2) mild fatigue, 3) mild fatigue and mild pain, 4) moderate fatigue and moderate pain, 5) moderate fatigue and moderate psychological, 6) moderate fatigue, mild pain, mild psychological, and 7) high symptom burden. Seventy percent of survivors remained in the same subgroup over time. In multivariable analyses, chemotherapy and greater illness intrusiveness were significantly related to greater symptom burden, while not being married or partnered, no difficulty paying for basics, and greater social support were protective. Higher symptom burden was associated with lower QOL. Survivors who reported psychological symptoms had significantly lower QOL than did survivors with pain symptoms. Cancer survivors can be differentiated by their symptom profiles. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Outcomes Associated with Adolescent Marijuana and Alcohol Use Among Urban Young Adults: A Prospective Study

PubMed Central

Green, Kerry M.; Musci, Rashelle J.; Johnson, Renee M.; Matson, Pamela A.; Reboussin, Beth A.; Ialongo, Nicholas S.

2015-01-01

Objective This study identifies and compares outcomes in young adulthood associated with longitudinal patterns of alcohol and marijuana use during adolescence among urban youth. Method Data come from a cohort of 678 urban, predominantly Black children followed from ages 6–25 (1993–2012). Analyses are based on the 608 children who participated over time (53.6% male). Longitudinal patterning of alcohol and marijuana use were based on annual frequency reports from grades 8–12 and estimated through latent profile analysis. Results We identified four classes of alcohol and marijuana use including Non-Use (47%), Moderate Alcohol Use (28%), Moderate Alcohol/Increasing Marijuana Use (12%) and High Dual Use (13%). A marijuana only class was not identified. Analyses show negative outcomes in adulthood associated with all three adolescent substance use classes. Compared to the non-use class, all use classes had statistically significantly higher rates of substance dependence. Those in the ‘High Dual Use’ class had the lowest rate of high school graduation. Comparing classes with similar alcohol but different marijuana patterns, the ‘Moderate Alcohol/Increasing Marijuana Use’ class had a statistically significant increased risk of having a criminal justice record and developing substance use dependence in adulthood. Conclusion Among urban youth, heterogeneous patterns of alcohol and marijuana use across adolescence are evident, and these patterns are associated with distinct outcomes in adulthood. These findings suggest a need for targeted education and intervention efforts to address the needs of youth using both marijuana and alcohol, as well as the importance of universal early preventive intervention efforts. PMID:26517712

Growth and stress response mechanisms underlying post-feeding regenerative organ growth in the Burmese python.

PubMed

Andrew, Audra L; Perry, Blair W; Card, Daren C; Schield, Drew R; Ruggiero, Robert P; McGaugh, Suzanne E; Choudhary, Amit; Secor, Stephen M; Castoe, Todd A

2017-05-02

Previous studies examining post-feeding organ regeneration in the Burmese python (Python molurus bivittatus) have identified thousands of genes that are significantly differentially regulated during this process. However, substantial gaps remain in our understanding of coherent mechanisms and specific growth pathways that underlie these rapid and extensive shifts in organ form and function. Here we addressed these gaps by comparing gene expression in the Burmese python heart, liver, kidney, and small intestine across pre- and post-feeding time points (fasted, one day post-feeding, and four days post-feeding), and by conducting detailed analyses of molecular pathways and predictions of upstream regulatory molecules across these organ systems. Identified enriched canonical pathways and upstream regulators indicate that while downstream transcriptional responses are fairly tissue specific, a suite of core pathways and upstream regulator molecules are shared among responsive tissues. Pathways such as mTOR signaling, PPAR/LXR/RXR signaling, and NRF2-mediated oxidative stress response are significantly differentially regulated in multiple tissues, indicative of cell growth and proliferation along with coordinated cell-protective stress responses. Upstream regulatory molecule analyses identify multiple growth factors, kinase receptors, and transmembrane receptors, both within individual organs and across separate tissues. Downstream transcription factors MYC and SREBF are induced in all tissues. These results suggest that largely divergent patterns of post-feeding gene regulation across tissues are mediated by a core set of higher-level signaling molecules. Consistent enrichment of the NRF2-mediated oxidative stress response indicates this pathway may be particularly important in mediating cellular stress during such extreme regenerative growth.

Comparisons of Latinos, African Americans, and Caucasians with multiple sclerosis.

PubMed

Buchanan, Robert J; Zuniga, Miguel A; Carrillo-Zuniga, Genny; Chakravorty, Bonnie J; Tyry, Tuula; Moreau, Rachel L; Huang, Chunfeng; Vollmer, Timothy

2010-01-01

Identify racial/ethnic differences among people with multiple sclerosis (MS) in demographics, MS disease characteristics, and health services received. We analyzed enrollment data from the Registry of the North American Research Committee on Multiple Sclerosis (NARCOMS) Project to compare 26,967 Caucasians, 715 Latinos, and 1,313 African Americans with MS. Racial/ethnic analyses of NARCOMS data focused on descriptive characteristics, using ANOVA and chi-square tests to identify significant differences in means and frequencies among Caucasians, Latinos, and African Americans. We identified significant racial/ethnic differences in demographics, MS disease characteristics, and treatments. Caucasians were older when first MS symptoms were experienced (30.1 years) and at MS diagnosis (37.4 years) than Latinos (28.6 years and 34.5 years) or African Americans (29.8 years and 35.8 years). Larger proportions of Latinos reported normal function for mobility and bladder/bowel function compared to Caucasians. Larger proportions of Latinos (44.2 percent) and African Americans (45.8 percent) reported at least mild depression compared to only 38.7 percent of Caucasians. Larger proportions of Latinos never received mental health care or care from rehabilitation specialists than Caucasians or African Americans. A larger proportion of African Americans had never been treated by a neurologist specializing in MS and a smaller proportion of African Americans received care at a MS clinic than Caucasians or Latinos. Our findings highlight the need for future analyses to determine if age, disease duration, MS symptoms, and disability levels provide additional insights into racial/ethic differences in the use of MS-related providers.

Variable uptake of recommended interventions to reduce mother-to-child transmission of HIV in Australia, 1982-2005.

PubMed

Giles, Michelle L; McDonald, Ann M; Elliott, Elizabeth J; Ziegler, John B; Hellard, Margaret E; Lewin, Sharon R; Kaldor, John M

2008-08-04

To analyse the uptake of interventions known to reduce the risk of perinatal HIV transmission among Australian women with HIV infection (who knew their HIV status before delivery), and identify predictors of uptake. Retrospective analysis of perinatal HIV surveillance data in Australia. Women reported as having HIV infection and having given birth to a child (1982-2005) were identified through three mechanisms: an informal network of clinicians (1982-1993); an active surveillance program through paediatricians (since 1993); and state health department reports of children born to women newly diagnosed with HIV (since 1995). Uptake of interventions - avoidance of breastfeeding (after 1985), use of zidovudine during pregnancy (after 1994), and elective caesarean section (after 1999). Factors associated with uptake of these interventions were identified by univariate and multivariate analyses. 367 live births were reported in 291 women with HIV infection. Among the subgroup diagnosed with HIV infection before delivery, 4/255 (1.6%) elected to breastfeed (post 1985), 44/185 (24%) did not receive zidovudine (after 1994), and 41/118 (35%) did not have an elective caesarean section (after 1999). In multivariate analysis, there were significant differences in uptake of zidovudine and elective caesarean section according to year of birth and state in which the birth took place. In Australia between 1982 and 2005, uptake of interventions to reduce mother-to-child transmission of HIV was high. There were significant differences associated with use of zidovudine and mode of delivery according to location of delivery and year of birth.

Beryllium disease among construction trade workers at Department of Energy nuclear sites.

PubMed

Welch, Laura S; Ringen, Knut; Dement, John; Bingham, Eula; Quinn, Patricia; Shorter, Janet; Fisher, Miles

2013-10-01

A medical surveillance program was developed to identify current and former construction workers at significant risk for beryllium related disease from work at the DOE nuclear weapons facilities, and to improve surveillance among beryllium exposed workers. Medical examinations included a medical history and a beryllium blood lymphocyte proliferation test (BeLPT). Stratified and multivariate logistic regression analyses were used to explore the risk of disease by age, race, trade, and reported work in buildings where beryllium was used. After adjusting for covariates, the risk of BeS was significantly higher among boilermakers, roofers, and sheet metal workers, as suggested in the stratified analyses. Workers identified as sensitized to beryllium were interviewed to determine whether they had been subsequently diagnosed with chronic beryllium disease. Between 1998 and December 31, 2010 13,810 workers received a BeLPT through the BTMed program; 189 (1.4%) were sensitized to beryllium, and 28 reported that they had had a compensation claim accepted for CBD. These data on former construction workers gives us additional information about the predictive value of the blood BeLPT test for detection of CBD in populations with lower total lifetime exposures and more remote exposures than that experienced by current workers in beryllium machining operations. Through this surveillance program we have identified routes of exposures to beryllium and worked with DOE site personnel to identity and mitigate those exposures which still exist, as well as helping to focus attention on the risk for beryllium exposure among current demolition workers at these facilities. Copyright © 2013 Wiley Periodicals, Inc.

Epigenomic elements analyses for promoters identify ESRRG as a new susceptibility gene for obesity-related traits.

PubMed

Dong, S-S; Guo, Y; Zhu, D-L; Chen, X-F; Wu, X-M; Shen, H; Chen, X-D; Tan, L-J; Tian, Q; Deng, H-W; Yang, T-L

2016-07-01

With ENCODE epigenomic data and results from published genome-wide association studies (GWASs), we aimed to find regulatory signatures of obesity genes and discover novel susceptibility genes. Obesity genes were obtained from public GWAS databases and their promoters were annotated based on the regulatory element information. Significantly enriched or depleted epigenomic elements in the promoters of obesity genes were evaluated and all human genes were then prioritized according to the existence of the selected elements to predict new candidate genes. Top-ranked genes were subsequently applied to validate their associations with obesity-related traits in three independent in-house GWAS samples. We identified RAD21 and EZH2 as over-represented, and STAT2 (signal transducer and activator of transcription 2) and IRF3 (interferon regulatory transcription factor 3) as depleted transcription factors. Histone modification of H3K9me3 and chromatin state segmentation of 'poised promoter' and 'repressed' were over-represented. All genes were prioritized and we selected the top five genes for validation at the population level. Combining results from the three GWAS samples, rs7522101 in ESRRG (estrogen-related receptor-γ) remained significantly associated with body mass index after multiple testing corrections (P=7.25 × 10(-5)). It was also associated with β-cell function (P=1.99 × 10(-3)) and fasting glucose level (P<0.05) in the meta-analyses of glucose and insulin-related traits consortium (MAGIC) data set.Cnoclusions:In summary, we identified epigenomic characteristics for obesity genes and suggested ESRRG as a novel obesity-susceptibility gene.

Neighborhood Immigrant Acculturation and Diet among Hispanic Female Residents of NYC

PubMed Central

Park, Yoosun; Neckerman, Kathryn; Quinn, James; Weiss, Christopher; Jacobson, Judith; Rundle, Andrew

2013-01-01

Objective To identify predominant dietary patterns among Hispanic women and to determine whether adherence to dietary patterns is predicted by neighborhood level factors: linguistic isolation, poverty rate and the retail food environment. Design Cross-sectional analyses of predictors of adherence to dietary patterns identified from principle component analyses of data collected using the Study of Women’s Health Across the Nation (SWAN) food frequency questionnaire. Census data were used to measure poverty rates and the percent of Spanish speaking families in the neighborhood in which no one ≥ 14 years old spoke English very well (linguistic isolation) and the retail food environment was measured using business listings data. Setting New York City. Subjects 345 Hispanic women. Results Two major dietary patterns were identified: a healthy diet pattern loading high for vegetable, legumes, potato, fish, and other seafood which explained 17% of the variance in the FFQ data and an energy dense diet pattern loading high for red meat, poultry, pizza, french fries, and high energy drink, which explained 9% of the variance in the FFQ data. Adherence to the healthy diet pattern was positively associated with neighborhood linguistic isolation and negatively associated with neighborhood poverty. More fast food restaurants per Km2 in the neighborhood was significantly associated with lower adherence to the healthy diet. Adherence to the energy dense diet pattern was inversely, but not significantly, associated with neighborhood linguistic isolation. Conclusions These results are consistent with the hypothesis that living in immigrant enclaves is associated with healthy diet patterns among Hispanics. PMID:21414245

Next-generation DNA sequencing identifies novel gene variants and pathways involved in specific language impairment.

PubMed

Chen, Xiaowei Sylvia; Reader, Rose H; Hoischen, Alexander; Veltman, Joris A; Simpson, Nuala H; Francks, Clyde; Newbury, Dianne F; Fisher, Simon E

2017-04-25

A significant proportion of children have unexplained problems acquiring proficient linguistic skills despite adequate intelligence and opportunity. Developmental language disorders are highly heritable with substantial societal impact. Molecular studies have begun to identify candidate loci, but much of the underlying genetic architecture remains undetermined. We performed whole-exome sequencing of 43 unrelated probands affected by severe specific language impairment, followed by independent validations with Sanger sequencing, and analyses of segregation patterns in parents and siblings, to shed new light on aetiology. By first focusing on a pre-defined set of known candidates from the literature, we identified potentially pathogenic variants in genes already implicated in diverse language-related syndromes, including ERC1, GRIN2A, and SRPX2. Complementary analyses suggested novel putative candidates carrying validated variants which were predicted to have functional effects, such as OXR1, SCN9A and KMT2D. We also searched for potential "multiple-hit" cases; one proband carried a rare AUTS2 variant in combination with a rare inherited haplotype affecting STARD9, while another carried a novel nonsynonymous variant in SEMA6D together with a rare stop-gain in SYNPR. On broadening scope to all rare and novel variants throughout the exomes, we identified biological themes that were enriched for such variants, including microtubule transport and cytoskeletal regulation.

Next-generation DNA sequencing identifies novel gene variants and pathways involved in specific language impairment

PubMed Central

Chen, Xiaowei Sylvia; Reader, Rose H.; Hoischen, Alexander; Veltman, Joris A.; Simpson, Nuala H.; Francks, Clyde; Newbury, Dianne F.; Fisher, Simon E.

2017-01-01

A significant proportion of children have unexplained problems acquiring proficient linguistic skills despite adequate intelligence and opportunity. Developmental language disorders are highly heritable with substantial societal impact. Molecular studies have begun to identify candidate loci, but much of the underlying genetic architecture remains undetermined. We performed whole-exome sequencing of 43 unrelated probands affected by severe specific language impairment, followed by independent validations with Sanger sequencing, and analyses of segregation patterns in parents and siblings, to shed new light on aetiology. By first focusing on a pre-defined set of known candidates from the literature, we identified potentially pathogenic variants in genes already implicated in diverse language-related syndromes, including ERC1, GRIN2A, and SRPX2. Complementary analyses suggested novel putative candidates carrying validated variants which were predicted to have functional effects, such as OXR1, SCN9A and KMT2D. We also searched for potential “multiple-hit” cases; one proband carried a rare AUTS2 variant in combination with a rare inherited haplotype affecting STARD9, while another carried a novel nonsynonymous variant in SEMA6D together with a rare stop-gain in SYNPR. On broadening scope to all rare and novel variants throughout the exomes, we identified biological themes that were enriched for such variants, including microtubule transport and cytoskeletal regulation. PMID:28440294

Large-scale transcriptome sequencing and gene analyses in the crab-eating macaque (Macaca fascicularis) for biomedical research

PubMed Central

2012-01-01

Background As a human replacement, the crab-eating macaque (Macaca fascicularis) is an invaluable non-human primate model for biomedical research, but the lack of genetic information on this primate has represented a significant obstacle for its broader use. Results Here, we sequenced the transcriptome of 16 tissues originated from two individuals of crab-eating macaque (male and female), and identified genes to resolve the main obstacles for understanding the biological response of the crab-eating macaque. From 4 million reads with 1.4 billion base sequences, 31,786 isotigs containing genes similar to those of humans, 12,672 novel isotigs, and 348,160 singletons were identified using the GS FLX sequencing method. Approximately 86% of human genes were represented among the genes sequenced in this study. Additionally, 175 tissue-specific transcripts were identified, 81 of which were experimentally validated. In total, 4,314 alternative splicing (AS) events were identified and analyzed. Intriguingly, 10.4% of AS events were associated with transposable element (TE) insertions. Finally, investigation of TE exonization events and evolutionary analysis were conducted, revealing interesting phenomena of human-specific amplified trends in TE exonization events. Conclusions This report represents the first large-scale transcriptome sequencing and genetic analyses of M. fascicularis and could contribute to its utility for biomedical research and basic biology. PMID:22554259

Identifying profiles of actual and perceived motor competence among adolescents: associations with motivation, physical activity, and sports participation.

PubMed

De Meester, An; Maes, Jolien; Stodden, David; Cardon, Greet; Goodway, Jacqueline; Lenoir, Matthieu; Haerens, Leen

2016-11-01

The present study identified adolescents' motor competence (MC)-based profiles (e.g., high actual and low perceived MC), and accordingly investigated differences in motivation for physical education (PE), physical activity (PA) levels, and sports participation between profiles by using regression analyses. Actual MC was measured with the Körperkoordinationstest für Kinder. Adolescents (n = 215; 66.0% boys; mean age = 13.64 ± .58 years) completed validated questionnaires to assess perceived MC, motivation for PE, PA-levels, and sports participation. Actual and perceived MC were only moderately correlated and cluster analyses identified four groups. Two groups of overestimators (low - overestimation, average - overestimation) were identified (51%), who particularly displayed better motivation for PE when compared to their peers who accurately estimated themselves (low - accurate, average - accurate). Moreover, adolescents with low actual MC, but high perceived MC were significantly more active than adolescents with low actual MC who accurately estimated themselves. Results pointed in the same direction for organised sports participation. Underestimators were not found in the current sample, which is positive as underestimation might negatively influence adolescents' motivation to achieve and persist in PA and sports. In conclusion, results emphasise that developing perceived MC, especially among adolescents with low levels of actual MC, seems crucial to stimulate motivation for PE, and engagement in PA and sports.

Identifying Useful Auxiliary Variables for Incomplete Data Analyses: A Note on a Group Difference Examination Approach

ERIC Educational Resources Information Center

Raykov, Tenko; Marcoulides, George A.

2014-01-01

This research note contributes to the discussion of methods that can be used to identify useful auxiliary variables for analyses of incomplete data sets. A latent variable approach is discussed, which is helpful in finding auxiliary variables with the property that if included in subsequent maximum likelihood analyses they may enhance considerably…

Optimizing chronic disease management mega-analysis: economic evaluation.

PubMed

2013-01-01

As Ontario's population ages, chronic diseases are becoming increasingly common. There is growing interest in services and care models designed to optimize the management of chronic disease. To evaluate the cost-effectiveness and expected budget impact of interventions in chronic disease cohorts evaluated as part of the Optimizing Chronic Disease Management mega-analysis. Sector-specific costs, disease incidence, and mortality were calculated for each condition using administrative databases from the Institute for Clinical Evaluative Sciences. Intervention outcomes were based on literature identified in the evidence-based analyses. Quality-of-life and disease prevalence data were obtained from the literature. Analyses were restricted to interventions that showed significant benefit for resource use or mortality from the evidence-based analyses. An Ontario cohort of patients with each chronic disease was constructed and followed over 5 years (2006-2011). A phase-based approach was used to estimate costs across all sectors of the health care system. Utility values identified in the literature and effect estimates for resource use and mortality obtained from the evidence-based analyses were applied to calculate incremental costs and quality-adjusted life-years (QALYs). Given uncertainty about how many patients would benefit from each intervention, a system-wide budget impact was not determined. Instead, the difference in lifetime cost between an individual-administered intervention and no intervention was presented. Of 70 potential cost-effectiveness analyses, 8 met our inclusion criteria. All were found to result in QALY gains and cost savings compared with usual care. The models were robust to the majority of sensitivity analyses undertaken, but due to structural limitations and time constraints, few sensitivity analyses were conducted. Incremental cost savings per patient who received intervention ranged between $15 per diabetic patient with specialized nursing to $10,665 per patient wth congestive heart failure receiving in-home care. Evidence used to inform estimates of effect was often limited to a single trial with limited generalizability across populations, interventions, and health care systems. Because of the low clinical fidelity of health administrative data sets, intermediate clinical outcomes could not be included. Cohort costs included an average of all health care costs and were not restricted to costs associated with the disease. Intervention costs were based on resource use specified in clinical trials. Applying estimates of effect from the evidence-based analyses to real-world resource use resulted in cost savings for all interventions. On the basis of quality-of-life data identified in the literature, all interventions were found to result in a greater QALY gain than usual care would. Implementation of all interventions could offer significant cost reductions. However, this analysis was subject to important limitations. Chronic diseases are the leading cause of death and disability in Ontario. They account for a third of direct health care costs across the province. This study aims to evaluate the cost-effectiveness of health care interventions that might improve the management of chronic diseases. The evaluated interventions led to lower costs and better quality of life than usual care. Offering these options could reduce costs per patient. However, the studies used in this analysis were of medium to very low quality, and the methods had many limitations.

Whole exome sequence-based association analyses of plasma amyloid-β in African and European Americans; the Atherosclerosis Risk in Communities-Neurocognitive Study.

PubMed

Simino, Jeannette; Wang, Zhiying; Bressler, Jan; Chouraki, Vincent; Yang, Qiong; Younkin, Steven G; Seshadri, Sudha; Fornage, Myriam; Boerwinkle, Eric; Mosley, Thomas H

2017-01-01

We performed single-variant and gene-based association analyses of plasma amyloid-β (aβ) concentrations using whole exome sequence from 1,414 African and European Americans. Our goal was to identify genes that influence plasma aβ42 concentrations and aβ42:aβ40 ratios in late middle age (mean = 59 years), old age (mean = 77 years), or change over time (mean = 18 years). Plasma aβ measures were linearly regressed onto age, gender, APOE ε4 carrier status, and time elapsed between visits (fold-changes only) separately by race. Following inverse normal transformation of the residuals, seqMeta was used to conduct race-specific single-variant and gene-based association tests while adjusting for population structure. Linear regression models were fit on autosomal variants with minor allele frequencies (MAF)≥1%. T5 burden and Sequence Kernel Association (SKAT) gene-based tests assessed functional variants with MAF≤5%. Cross-race fixed effects meta-analyses were Bonferroni-corrected for the number of variants or genes tested. Seven genes were associated with aβ in late middle age or change over time; no associations were identified in old age. Single variants in KLKB1 (rs3733402; p = 4.33x10-10) and F12 (rs1801020; p = 3.89x10-8) were significantly associated with midlife aβ42 levels through cross-race meta-analysis; the KLKB1 variant replicated internally using 1,014 additional participants with exome chip. ITPRIP, PLIN2, and TSPAN18 were associated with the midlife aβ42:aβ40 ratio via the T5 test; TSPAN18 was significant via the cross-race meta-analysis, whereas ITPRIP and PLIN2 were European American-specific. NCOA1 and NT5C3B were associated with the midlife aβ42:aβ40 ratio and the fold-change in aβ42, respectively, via SKAT in African Americans. No associations replicated externally (N = 725). We discovered age-dependent genetic effects, established associations between vascular-related genes (KLKB1, F12, PLIN2) and midlife plasma aβ levels, and identified a plausible Alzheimer's Disease candidate gene (ITPRIP) influencing cell death. Plasma aβ concentrations may have dynamic biological determinants across the lifespan; plasma aβ study designs or analyses must consider age.

Genome-wide association and pathway analysis of feed efficiency in pigs reveal candidate genes and pathways for residual feed intake

PubMed Central

Do, Duy N.; Strathe, Anders B.; Ostersen, Tage; Pant, Sameer D.; Kadarmideen, Haja N.

2014-01-01

Residual feed intake (RFI) is a complex trait that is economically important for livestock production; however, the genetic and biological mechanisms regulating RFI are largely unknown in pigs. Therefore, the study aimed to identify single nucleotide polymorphisms (SNPs), candidate genes and biological pathways involved in regulating RFI using Genome-wide association (GWA) and pathway analyses. A total of 596 Yorkshire boars with phenotypes for two different measures of RFI (RFI1 and 2) and 60k genotypic data was used. GWA analysis was performed using a univariate mixed model and 12 and 7 SNPs were found to be significantly associated with RFI1 and RFI2, respectively. Several genes such as xin actin-binding repeat-containing protein 2 (XIRP2),tetratricopeptide repeat domain 29 (TTC29),suppressor of glucose, autophagy associated 1 (SOGA1),MAS1,G-protein-coupled receptor (GPCR) kinase 5 (GRK5),prospero-homeobox protein 1 (PROX1),GPCR 155 (GPR155), and FYVE domain containing the 26 (ZFYVE26) were identified as putative candidates for RFI based on their genomic location in the vicinity of these SNPs. Genes located within 50 kbp of SNPs significantly associated with RFI and RFI2 (q-value ≤ 0.2) were subsequently used for pathway analyses. These analyses were performed by assigning genes to biological pathways and then testing the association of individual pathways with RFI using a Fisher’s exact test. Metabolic pathway was significantly associated with both RFIs. Other biological pathways regulating phagosome, tight junctions, olfactory transduction, and insulin secretion were significantly associated with both RFI traits when relaxed threshold for cut-off p-value was used (p ≤ 0.05). These results implied porcine RFI is regulated by multiple biological mechanisms, although the metabolic processes might be the most important. Olfactory transduction pathway controlling the perception of feed via smell, insulin pathway controlling food intake might be important pathways for RFI. Furthermore, our study revealed key genes and genetic variants that control feed efficiency that could potentially be useful for genetic selection of more feed efficient pigs. PMID:25250046

Extramural vascular invasion and response to neoadjuvant chemoradiotherapy in rectal cancer: Influence of the CpG island methylator phenotype

PubMed Central

Williamson, Jeremy Stuart; Jones, Huw Geraint; Williams, Namor; Griffiths, Anthony Paul; Jenkins, Gareth; Beynon, John; Harris, Dean Anthony

2017-01-01

AIM To identify whether CpG island methylator phenotype (CIMP) is predictive of response to neoadjuvant chemoradiotherapy (NACRT) and outcomes in rectal cancer. METHODS Patients undergoing NACRT and surgical resection for rectal cancer in a tertiary referral centre between 2002-2011 were identified. Pre-treatment tumour biopsies were analysed for CIMP status (high, intermediate or low) using methylation specific PCR. KRAS and BRAF status were also determined using pyrosequencing analysis. Clinical information was extracted from case records and cancer services databases. Response to radiotherapy was measured by tumour regression scores determined upon histological examination of the resected specimen. The relationship between these molecular features, response to NACRT and oncological outcomes were analysed. RESULTS There were 160 patients analysed with a median follow-up time of 46.4 mo. Twenty-one (13%) patients demonstrated high levels of CIMP methylation (CIMP-H) and this was significantly associated with increased risk of extramural vascular invasion (EMVI) compared with CIMP-L [8/21 (38%) vs 15/99 (15%), P = 0.028]. CIMP status was not related to tumour regression after radiotherapy or survival, however EMVI was significantly associated with adverse survival (P < 0.001). Intermediate CIMP status was significantly associated with KRAS mutation (P = 0.01). There were 14 (9%) patients with a pathological complete response (pCR) compared to 116 (73%) patients having no or minimal regression after neoadjuvant chemoradiotherapy. Those patients with pCR had median survival of 106 mo compared to 65.8 mo with minimal regression, although this was not statistically significant (P = 0.26). Binary logistic regression analysis of the relationship between EMVI and other prognostic features revealed, EMVI positivity was associated with poor overall survival, advanced “T” stage and CIMP-H but not nodal status, age, sex, KRAS mutation status and presence of local or systemic recurrence. CONCLUSION We report a novel association of pre-treatment characterisation of CIMP-H with EMVI status which has prognostic implications and is not readily detectable on pre-treatment histological examination. PMID:28567185

Extramural vascular invasion and response to neoadjuvant chemoradiotherapy in rectal cancer: Influence of the CpG island methylator phenotype.

PubMed

Williamson, Jeremy Stuart; Jones, Huw Geraint; Williams, Namor; Griffiths, Anthony Paul; Jenkins, Gareth; Beynon, John; Harris, Dean Anthony

2017-05-15

To identify whether CpG island methylator phenotype (CIMP) is predictive of response to neoadjuvant chemoradiotherapy (NACRT) and outcomes in rectal cancer. Patients undergoing NACRT and surgical resection for rectal cancer in a tertiary referral centre between 2002-2011 were identified. Pre-treatment tumour biopsies were analysed for CIMP status (high, intermediate or low) using methylation specific PCR. KRAS and BRAF status were also determined using pyrosequencing analysis. Clinical information was extracted from case records and cancer services databases. Response to radiotherapy was measured by tumour regression scores determined upon histological examination of the resected specimen. The relationship between these molecular features, response to NACRT and oncological outcomes were analysed. There were 160 patients analysed with a median follow-up time of 46.4 mo. Twenty-one (13%) patients demonstrated high levels of CIMP methylation (CIMP-H) and this was significantly associated with increased risk of extramural vascular invasion (EMVI) compared with CIMP-L [8/21 (38%) vs 15/99 (15%), P = 0.028]. CIMP status was not related to tumour regression after radiotherapy or survival, however EMVI was significantly associated with adverse survival ( P < 0.001). Intermediate CIMP status was significantly associated with KRAS mutation ( P = 0.01). There were 14 (9%) patients with a pathological complete response (pCR) compared to 116 (73%) patients having no or minimal regression after neoadjuvant chemoradiotherapy. Those patients with pCR had median survival of 106 mo compared to 65.8 mo with minimal regression, although this was not statistically significant ( P = 0.26). Binary logistic regression analysis of the relationship between EMVI and other prognostic features revealed, EMVI positivity was associated with poor overall survival, advanced "T" stage and CIMP-H but not nodal status, age, sex, KRAS mutation status and presence of local or systemic recurrence. We report a novel association of pre-treatment characterisation of CIMP-H with EMVI status which has prognostic implications and is not readily detectable on pre-treatment histological examination.

Meta-Analyses and Orthodontic Evidence-Based Clinical Practice in the 21st Century

PubMed Central

Papadopoulos, Moschos A.

2010-01-01

Introduction: Aim of this systematic review was to assess the orthodontic related issues which currently provide the best evidence as documented by meta-analyses, by critically evaluating and discussing the methodology used in these studies. Material and Methods: Several electronic databases were searched and handsearching was also performed in order to identify the corresponding meta-analyses investigating orthodontic related subjects. In total, 197 studies were retrieved initially. After applying specific inclusion and exclusion criteria, 27 articles were identified as meta-analyses treating orthodontic-related subjects. Results: Many of these 27 papers presented sufficient quality and followed appropriate meta-analytic approaches to quantitatively synthesize data and presented adequately supported evidence. However, the methodology used in some of them presented weaknesses, limitations or deficiencies. Consequently, the topics in orthodontics which currently provide the best evidence, include some issues related to Class II or Class III treatment, treatment of transverse problems, external apical root resorption, dental anomalies, such as congenital missing teeth and tooth transposition, frequency of severe occlusal problems, nickel hypersensitivity, obstructive sleep apnea syndrome, and computer-assisted learning in orthodontic education. Conclusions: Only a few orthodontic related issues have been so far investigated by means of MAs. In addition, for some of these issues investigated in the corresponding MAs no definite conclusions could be drawn, due to significant methodological deficiencies of these studies. According to this investigation, it can be concluded that at the begin of the 21st century there is evidence for only a few orthodontic related issues as documented by meta-analyses, and more well-conducted high quality research studies are needed to produce strong evidence in order to support evidence-based clinical practice in orthodontics. PMID:21673839

Condition assessment of a highly porous limestone fortress: damage categories and structural integrity

NASA Astrophysics Data System (ADS)

Török, Ákos; Czinder, Balázs; Farkas, Orsolya; Görög, Péter; Kopecskó, Katalin; Lógó, János; Rozgonyi-Boissinot, Nikoletta; Vásárhelyi, Balázs

2016-04-01

An emblematic monument the Citadella fortress of Budapest has been studied in details to assess the condition of stone structure. The fortress is a large stone structure of 220 m in length and 60 m in width. The height of the porous limestone walls are in between 12-16 metres. The fortress was completed in 1854 but has been partly rebuilt due to changes in function and war related structural damages. The present paper provides an overview of the lithology, weathering forms and structural condition of the fortress related to a forthcoming restoration-reconstruction project. To assess the condition of stone both on site and laboratory analyses were performed. Lithological varieties were documented. Major identified lithotypes are porous oolitic limestone, less porous bioclastic limestone and fine grained highly porous limestone. To identify wet zones portable moisture meter was applied. Surface strength and weathering grade were also assessed using Schmidt hammer and Duroscop. Decay features were diagnosed and mapped. The most common forms are white weathering crusts, scaling and blistering of crusts as well as granular disintegration. Black weathering crusts were also recognized. Laboratory tests were focused on mechanical properties of stones and on mineralogical and chemical compositional analyses. Small samples of stone were collected and tested by optical microscopy, SEM-EDX, XRD and Thermogravimetric analyses. Laboratory analyses proved that the major salt responsible for the damage of external walls is gypsum, although significant amount of halite and hygroscopic salts were found both on the external walls and in the interior parts of the fortress. During structural analyses displacement of walls, tilting and major amount of cracks were recognized. Loss of material and subsidence also caused problems and at some places unstable wall sections were recognized.

Integrative analysis of micro-RNA, gene expression, and survival of glioblastoma multiforme.

PubMed

Huang, Yen-Tsung; Hsu, Thomas; Kelsey, Karl T; Lin, Chien-Ling

2015-02-01

Glioblastoma multiforme (GBM), the most common type of malignant brain tumor, is highly fatal. Limited understanding of its rapid progression necessitates additional approaches that integrate what is known about the genomics of this cancer. Using a discovery set (n = 348) and a validation set (n = 174) of GBM patients, we performed genome-wide analyses that integrated mRNA and micro-RNA expression data from GBM as well as associated survival information, assessing coordinated variability in each as this reflects their known mechanistic functions. Cox proportional hazards models were used for the survival analyses, and nonparametric permutation tests were performed for the micro-RNAs to investigate the association between the number of associated genes and its prognostication. We also utilized mediation analyses for micro-RNA-gene pairs to identify their mediation effects. Genome-wide analyses revealed a novel pattern: micro-RNAs related to more gene expressions are more likely to be associated with GBM survival (P = 4.8 × 10(-5)). Genome-wide mediation analyses for the 32,660 micro-RNA-gene pairs with strong association (false discovery rate [FDR] < 0.01%) identified 51 validated pairs with significant mediation effect. Of the 51 pairs, miR-223 had 16 mediation genes. These 16 mediation genes of miR-223 were also highly associated with various other micro-RNAs and mediated their prognostic effects as well. We further constructed a gene signature using the 16 genes, which was highly associated with GBM survival in both the discovery and validation sets (P = 9.8 × 10(-6)). This comprehensive study discovered mediation effects of micro-RNA to gene expression and GBM survival and provided a new analytic framework for integrative genomics. © 2014 WILEY PERIODICALS, INC.

Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review

PubMed Central

Kirksey, Meghan A.; Haskins, Stephen C.; Cheng, Jennifer; Liu, Spencer S.

2015-01-01

Background The use of peripheral nerve blocks for anesthesia and postoperative analgesia has increased significantly in recent years. Adjuvants are frequently added to local anesthetics to prolong analgesia following peripheral nerve blockade. Numerous randomized controlled trials and meta-analyses have examined the pros and cons of the use of various individual adjuvants. Objectives To systematically review adjuvant-related randomized controlled trials and meta-analyses and provide clinical recommendations for the use of adjuvants in peripheral nerve blocks. Methods Randomized controlled trials and meta-analyses that were published between 1990 and 2014 were included in the initial bibliographic search, which was conducted using Medline/PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Only studies that were published in English and listed block analgesic duration as an outcome were included. Trials that had already been published in the identified meta-analyses and included adjuvants not in widespread use and published without an Investigational New Drug application or equivalent status were excluded. Results Sixty one novel clinical trials and meta-analyses were identified and included in this review. The clinical trials reported analgesic duration data for the following adjuvants: buprenorphine (6), morphine (6), fentanyl (10), epinephrine (3), clonidine (7), dexmedetomidine (7), dexamethasone (7), tramadol (8), and magnesium (4). Studies of perineural buprenorphine, clonidine, dexamethasone, dexmedetomidine, and magnesium most consistently demonstrated prolongation of peripheral nerve blocks. Conclusions Buprenorphine, clonidine, dexamethasone, magnesium, and dexmedetomidine are promising agents for use in prolongation of local anesthetic peripheral nerve blocks, and further studies of safety and efficacy are merited. However, caution is recommended with use of any perineural adjuvant, as none have Food and Drug Administration approval, and concerns for side effects and potential toxicity persist. PMID:26355598

The displaced aggression questionnaire.

PubMed

Denson, Thomas F; Pedersen, William C; Miller, Norman

2006-06-01

Previous measures of aggressive personality have focused on direct aggression (i.e., retaliation toward the provoking agent). An original self-report measure of trait displaced aggression is presented. Exploratory and confirmatory factor analyses provided support for a 3-factor conceptualization of the construct. These analyses identified an affective dimension (angry rumination), a cognitive dimension (revenge planning), and a behavioral dimension (general tendency to engage in displaced aggression). The trait measure demonstrated good internal consistency and test-retest reliability as well as convergent and discriminant construct validity. Unlike other related personality measures, trait displaced aggression significantly predicted indirect indicators of real-world displaced aggression (i.e., self-reported domestic abuse and road rage) as well as laboratory displaced aggression in 2 experiments. Copyright 2006 APA, all rights reserved.

Maximizing the significance in Higgs boson pair analyses [Mad-Maximized Higgs Pair Analyses

DOE PAGES

Kling, Felix; Plehn, Tilman; Schichtel, Peter

2017-02-22

Here, we study Higgs pair production with a subsequent decay to a pair of photons and a pair of bottoms at the LHC. We use the log-likelihood ratio to identify the kinematic regions which either allow us to separate the di-Higgs signal from backgrounds or to determine the Higgs self-coupling. We find that both regions are separate enough to ensure that details of the background modeling will not affect the determination of the self-coupling. Assuming dominant statistical uncertainties we determine the best precision with which the Higgs self-coupling can be probed in this channel. We finally comment on the samemore » questions at a future 100 TeV collider.« less

Maximizing the significance in Higgs boson pair analyses [Mad-Maximized Higgs Pair Analyses

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

Kling, Felix; Plehn, Tilman; Schichtel, Peter

Here, we study Higgs pair production with a subsequent decay to a pair of photons and a pair of bottoms at the LHC. We use the log-likelihood ratio to identify the kinematic regions which either allow us to separate the di-Higgs signal from backgrounds or to determine the Higgs self-coupling. We find that both regions are separate enough to ensure that details of the background modeling will not affect the determination of the self-coupling. Assuming dominant statistical uncertainties we determine the best precision with which the Higgs self-coupling can be probed in this channel. We finally comment on the samemore » questions at a future 100 TeV collider.« less

The relationship between biomechanical variables and driving performance during the golf swing.

PubMed

Chu, Yungchien; Sell, Timothy C; Lephart, Scott M

2010-09-01

Swing kinematic and ground reaction force data from 308 golfers were analysed to identify the variables important to driving ball velocity. Regression models were applied at four selected events in the swing. The models accounted for 44-74% of variance in ball velocity. Based on the regression analyses, upper torso-pelvis separation (the X-Factor), delayed release (i.e. the initiation of movement) of the arms and wrists, trunk forward and lateral tilting, and weight-shifting during the swing were significantly related to ball velocity. Our results also verify several general coaching ideas that were considered important to increased ball velocity. The results of this study may serve as both skill and strength training guidelines for golfers.

Descriptive epidemiology of typhoid fever during an epidemic in Harare, Zimbabwe, 2012.

PubMed

Polonsky, Jonathan A; Martínez-Pino, Isabel; Nackers, Fabienne; Chonzi, Prosper; Manangazira, Portia; Van Herp, Michel; Maes, Peter; Porten, Klaudia; Luquero, Francisco J

2014-01-01

Typhoid fever remains a significant public health problem in developing countries. In October 2011, a typhoid fever epidemic was declared in Harare, Zimbabwe - the fourth enteric infection epidemic since 2008. To orient control activities, we described the epidemiology and spatiotemporal clustering of the epidemic in Dzivaresekwa and Kuwadzana, the two most affected suburbs of Harare. A typhoid fever case-patient register was analysed to describe the epidemic. To explore clustering, we constructed a dataset comprising GPS coordinates of case-patient residences and randomly sampled residential locations (spatial controls). The scale and significance of clustering was explored with Ripley K functions. Cluster locations were determined by a random labelling technique and confirmed using Kulldorff's spatial scan statistic. We analysed data from 2570 confirmed and suspected case-patients, and found significant spatiotemporal clustering of typhoid fever in two non-overlapping areas, which appeared to be linked to environmental sources. Peak relative risk was more than six times greater than in areas lying outside the cluster ranges. Clusters were identified in similar geographical ranges by both random labelling and Kulldorff's spatial scan statistic. The spatial scale at which typhoid fever clustered was highly localised, with significant clustering at distances up to 4.5 km and peak levels at approximately 3.5 km. The epicentre of infection transmission shifted from one cluster to the other during the course of the epidemic. This study demonstrated highly localised clustering of typhoid fever during an epidemic in an urban African setting, and highlights the importance of spatiotemporal analysis for making timely decisions about targetting prevention and control activities and reinforcing treatment during epidemics. This approach should be integrated into existing surveillance systems to facilitate early detection of epidemics and identify their spatial range.

Quality of life in patients receiving telemedicine enhanced chronic heart failure disease management: A meta-analysis.

PubMed

Knox, Liam; Rahman, Rachel J; Beedie, Chris

2017-08-01

Background Previous reviews have investigated the effectiveness of telemedicine in the treatment of heart failure (HF). Dependent variables have included hospitalisations, mortality rates, disease knowledge and health costs. Few reviews, however, have examined the variable of health-related quality of life (QoL). Methods Randomised controlled trials comparing the delivery methods of any form of telemedicine with usual care for the provision of HF disease-management were identified via searches of all relevant databases and reference lists. Studies had to report a quantitative measure for mental, physical or overall QoL in order to be included. Results A total of 33 studies were identified. However, poor reporting of data resulted in the exclusion of seven, leaving 26 studies with 7066 participants. Three separate, random effects meta-analyses were conducted for mental, physical and overall QoL. Telemedicine was not significantly more effective than usual care on mental and physical QoL (standardised mean difference (SMD) 0.03, (95% confidence interval (CI) -0.05-0.12), p = 0.45 and SMD 0.24, (95% CI -0.08-0.56), p = 0.14, respectively). However, when compared to usual care, telemedicine was associated with a small significant increase in overall QoL (SMD 0.23, (95% CI 0.09-0.37), p = 0.001). Moderator analyses indicated that telemedicine delivered over a long-duration (≥52 weeks) and via telemonitoring was most beneficial. Conclusion Compared to usual care, telemedicine significantly increases overall QoL in patients receiving HF disease management. Statistically non-significant but nonetheless positive trends were also observed for physical QoL. These findings provide preliminary support for the use of telemedicine in the management of heart failure without jeopardising patient well-being.

Descriptive Epidemiology of Typhoid Fever during an Epidemic in Harare, Zimbabwe, 2012

PubMed Central

Polonsky, Jonathan A.; Martínez-Pino, Isabel; Nackers, Fabienne; Chonzi, Prosper; Manangazira, Portia; Van Herp, Michel; Maes, Peter; Porten, Klaudia; Luquero, Francisco J.

2014-01-01

Background Typhoid fever remains a significant public health problem in developing countries. In October 2011, a typhoid fever epidemic was declared in Harare, Zimbabwe - the fourth enteric infection epidemic since 2008. To orient control activities, we described the epidemiology and spatiotemporal clustering of the epidemic in Dzivaresekwa and Kuwadzana, the two most affected suburbs of Harare. Methods A typhoid fever case-patient register was analysed to describe the epidemic. To explore clustering, we constructed a dataset comprising GPS coordinates of case-patient residences and randomly sampled residential locations (spatial controls). The scale and significance of clustering was explored with Ripley K functions. Cluster locations were determined by a random labelling technique and confirmed using Kulldorff's spatial scan statistic. Principal Findings We analysed data from 2570 confirmed and suspected case-patients, and found significant spatiotemporal clustering of typhoid fever in two non-overlapping areas, which appeared to be linked to environmental sources. Peak relative risk was more than six times greater than in areas lying outside the cluster ranges. Clusters were identified in similar geographical ranges by both random labelling and Kulldorff's spatial scan statistic. The spatial scale at which typhoid fever clustered was highly localised, with significant clustering at distances up to 4.5 km and peak levels at approximately 3.5 km. The epicentre of infection transmission shifted from one cluster to the other during the course of the epidemic. Conclusions This study demonstrated highly localised clustering of typhoid fever during an epidemic in an urban African setting, and highlights the importance of spatiotemporal analysis for making timely decisions about targetting prevention and control activities and reinforcing treatment during epidemics. This approach should be integrated into existing surveillance systems to facilitate early detection of epidemics and identify their spatial range. PMID:25486292

Alignment of practice guidelines with targeted-therapy drug funding policies in Ontario.

PubMed

Ramjeesingh, R; Meyer, R M; Brouwers, M; Chen, B E; Booth, C M

2013-02-01

We evaluated clinical practice guideline (cpg) recommendations from Cancer Care Ontario's Program in Evidence-Based Care (pebc) for molecularly targeted systemic treatments (tts) and subsequent funding decisions from the Ontario Ministry of Health and Long-Term Care. We identified pebc cpgs on tt published before June 1, 2010, and extracted information regarding the key evidence cited in support of cpg recommendations and the effect size associated with each tt. Those variables were compared with mohltc funding decisions as of June 2011. From 23 guidelines related to 17 tts, we identified 43 recommendations, among which 38 (88%) endorsed tt use. Among all the recommendations, 38 (88%) were based on published key evidence, with 82% (31 of 38) being supported by meta-analyses or phase iii trials. For the 38 recommendations endorsing tts, funding was approved in 28 (74%; odds ratio related to cpg recommendation: 29.9; p = 0.003). We were unable to demonstrate that recommendations associated with statistically significant improvements in overall survival [os: 14 of 16 (88%) vs. 8 of 14 (57%); p = 0.10] or disease- (dfs) or progression-free survival [pfs: 16 of 21 (76%) vs. 3 of 5 (60%); p = 0.59] were more likely to be funded than those with no significant difference. Moreover, we did not observe significant associations between funding approvals and absolute improvements of 3 months or more in os [6 of 6 (100%) vs. 3 of 6 (50%), p = 0.18] or pfs [6 of 8 (75%) vs. 10 of 12 (83%), p = 1.00]. For use of tts, most recommendations in pebc cpgs are based on meta-analyses or phase iii data, and funding decisions were strongly associated with those recommendations. Our data suggest a trend toward increased rates of funding for therapies with statistically significant improvements in os.

Quality of life in Chronic Pancreatitis is determined by constant pain, disability/unemployment, current smoking and associated co-morbidities

PubMed Central

Machicado, Jorge D.; Amann, Stephen T; Anderson, Michelle A.; Abberbock, Judah; Sherman, Stuart; Conwell, Darwin; Cote, Gregory A.; Singh, Vikesh K.; Lewis, Michele; Alkaade, Samer; Sandhu, Bimaljit S.; Guda, Nalini M.; Muniraj, Thiruvengadam; Tang, Gong; Baillie, John; Brand, Randall; Gardner, Timothy B.; Gelrud, Andres; Forsmark, Christopher E.; Banks, Peter A.; Slivka, Adam; Wilcox, C. Mel; Whitcomb, David C.; Yadav, Dhiraj

2018-01-01

Background Chronic pancreatitis (CP) has a profound independent effect on quality of life (QOL). Our aim was to identify factors that impact the QOL in CP patients. Methods We used data on 1,024 CP patients enrolled in the three NAPS2 studies. Information on demographics, risk factors, co-morbidities, disease phenotype and treatments was obtained from responses to structured questionnaires. Physical (PCS) and mental (MCS) component summary scores generated using responses to the Short Form-12 (SF-12) survey were used to assess QOL at enrollment. Multivariable linear regression models determined independent predictors of QOL. Results Mean PCS and MCS scores were 36.7±11.7 and 42.4±12.2, respectively. Significant (p<0.05) negative impact on PCS scores in multivariable analyses was noted due to constant mild-moderate pain with episodes of severe pain or constant severe pain (10 points), constant mild-moderate pain (5.2), pain-related disability/unemployment (5.1), current smoking (2.9 points) and medical co-morbidities. Significant (p<0.05) negative impact on MCS scores was related to constant pain irrespective of severity (6.8-6.9 points), current smoking (3.9 points) and pain-related disability/unemployment (2.4 points). In women, disability/unemployment resulted in an additional reduction 3.7 point reduction in MCS score. Final multivariable models explained 27% and 18% of the variance in PCS and MCS scores, respectively. Etiology, disease duration, pancreatic morphology, diabetes, exocrine insufficiency and prior endotherapy/pancreatic surgery had no significant independent effect on QOL. Conclusion Constant pain, pain-related disability/unemployment, current smoking, and concurrent co-morbidities significantly affect the QOL in CP. Further research is needed to identify factors impacting QOL not explained by our analyses. PMID:28244497

Quality of Life in Chronic Pancreatitis is Determined by Constant Pain, Disability/Unemployment, Current Smoking, and Associated Co-Morbidities.

PubMed

Machicado, Jorge D; Amann, Stephen T; Anderson, Michelle A; Abberbock, Judah; Sherman, Stuart; Conwell, Darwin L; Cote, Gregory A; Singh, Vikesh K; Lewis, Michele D; Alkaade, Samer; Sandhu, Bimaljit S; Guda, Nalini M; Muniraj, Thiruvengadam; Tang, Gong; Baillie, John; Brand, Randall E; Gardner, Timothy B; Gelrud, Andres; Forsmark, Christopher E; Banks, Peter A; Slivka, Adam; Wilcox, C Mel; Whitcomb, David C; Yadav, Dhiraj

2017-04-01

Chronic pancreatitis (CP) has a profound independent effect on quality of life (QOL). Our aim was to identify factors that impact the QOL in CP patients. We used data on 1,024 CP patients enrolled in the three NAPS2 studies. Information on demographics, risk factors, co-morbidities, disease phenotype, and treatments was obtained from responses to structured questionnaires. Physical and mental component summary (PCS and MCS, respectively) scores generated using responses to the Short Form-12 (SF-12) survey were used to assess QOL at enrollment. Multivariable linear regression models determined independent predictors of QOL. Mean PCS and MCS scores were 36.7±11.7 and 42.4±12.2, respectively. Significant (P<0.05) negative impact on PCS scores in multivariable analyses was noted owing to constant mild-moderate pain with episodes of severe pain or constant severe pain (10 points), constant mild-moderate pain (5.2), pain-related disability/unemployment (5.1), current smoking (2.9 points), and medical co-morbidities. Significant (P<0.05) negative impact on MCS scores was related to constant pain irrespective of severity (6.8-6.9 points), current smoking (3.9 points), and pain-related disability/unemployment (2.4 points). In women, disability/unemployment resulted in an additional 3.7 point reduction in MCS score. Final multivariable models explained 27% and 18% of the variance in PCS and MCS scores, respectively. Etiology, disease duration, pancreatic morphology, diabetes, exocrine insufficiency, and prior endotherapy/pancreatic surgery had no significant independent effect on QOL. Constant pain, pain-related disability/unemployment, current smoking, and concurrent co-morbidities significantly affect the QOL in CP. Further research is needed to identify factors impacting QOL not explained by our analyses.

Microarray analysis of gene expression profiles in ripening pineapple fruits.

PubMed

Koia, Jonni H; Moyle, Richard L; Botella, Jose R

2012-12-18

Pineapple (Ananas comosus) is a tropical fruit crop of significant commercial importance. Although the physiological changes that occur during pineapple fruit development have been well characterized, little is known about the molecular events that occur during the fruit ripening process. Understanding the molecular basis of pineapple fruit ripening will aid the development of new varieties via molecular breeding or genetic modification. In this study we developed a 9277 element pineapple microarray and used it to profile gene expression changes that occur during pineapple fruit ripening. Microarray analyses identified 271 unique cDNAs differentially expressed at least 1.5-fold between the mature green and mature yellow stages of pineapple fruit ripening. Among these 271 sequences, 184 share significant homology with genes encoding proteins of known function, 53 share homology with genes encoding proteins of unknown function and 34 share no significant homology with any database accession. Of the 237 pineapple sequences with homologs, 160 were up-regulated and 77 were down-regulated during pineapple fruit ripening. DAVID Functional Annotation Cluster (FAC) analysis of all 237 sequences with homologs revealed confident enrichment scores for redox activity, organic acid metabolism, metalloenzyme activity, glycolysis, vitamin C biosynthesis, antioxidant activity and cysteine peptidase activity, indicating the functional significance and importance of these processes and pathways during pineapple fruit development. Quantitative real-time PCR analysis validated the microarray expression results for nine out of ten genes tested. This is the first report of a microarray based gene expression study undertaken in pineapple. Our bioinformatic analyses of the transcript profiles have identified a number of genes, processes and pathways with putative involvement in the pineapple fruit ripening process. This study extends our knowledge of the molecular basis of pineapple fruit ripening and non-climacteric fruit ripening in general.

Microarray analysis of gene expression profiles in ripening pineapple fruits

PubMed Central

2012-01-01

Background Pineapple (Ananas comosus) is a tropical fruit crop of significant commercial importance. Although the physiological changes that occur during pineapple fruit development have been well characterized, little is known about the molecular events that occur during the fruit ripening process. Understanding the molecular basis of pineapple fruit ripening will aid the development of new varieties via molecular breeding or genetic modification. In this study we developed a 9277 element pineapple microarray and used it to profile gene expression changes that occur during pineapple fruit ripening. Results Microarray analyses identified 271 unique cDNAs differentially expressed at least 1.5-fold between the mature green and mature yellow stages of pineapple fruit ripening. Among these 271 sequences, 184 share significant homology with genes encoding proteins of known function, 53 share homology with genes encoding proteins of unknown function and 34 share no significant homology with any database accession. Of the 237 pineapple sequences with homologs, 160 were up-regulated and 77 were down-regulated during pineapple fruit ripening. DAVID Functional Annotation Cluster (FAC) analysis of all 237 sequences with homologs revealed confident enrichment scores for redox activity, organic acid metabolism, metalloenzyme activity, glycolysis, vitamin C biosynthesis, antioxidant activity and cysteine peptidase activity, indicating the functional significance and importance of these processes and pathways during pineapple fruit development. Quantitative real-time PCR analysis validated the microarray expression results for nine out of ten genes tested. Conclusions This is the first report of a microarray based gene expression study undertaken in pineapple. Our bioinformatic analyses of the transcript profiles have identified a number of genes, processes and pathways with putative involvement in the pineapple fruit ripening process. This study extends our knowledge of the molecular basis of pineapple fruit ripening and non-climacteric fruit ripening in general. PMID:23245313

Finding needles in a haystack: a methodology for identifying and sampling community-based youth smoking cessation programs.

PubMed

Emery, Sherry; Lee, Jungwha; Curry, Susan J; Johnson, Tim; Sporer, Amy K; Mermelstein, Robin; Flay, Brian; Warnecke, Richard

2010-02-01

Surveys of community-based programs are difficult to conduct when there is virtually no information about the number or locations of the programs of interest. This article describes the methodology used by the Helping Young Smokers Quit (HYSQ) initiative to identify and profile community-based youth smoking cessation programs in the absence of a defined sample frame. We developed a two-stage sampling design, with counties as the first-stage probability sampling units. The second stage used snowball sampling to saturation, to identify individuals who administered youth smoking cessation programs across three economic sectors in each county. Multivariate analyses modeled the relationship between program screening, eligibility, and response rates and economic sector and stratification criteria. Cumulative logit models analyzed the relationship between the number of contacts in a county and the number of programs screened, eligible, or profiled in a county. The snowball process yielded 9,983 unique and traceable contacts. Urban and high-income counties yielded significantly more screened program administrators; urban counties produced significantly more eligible programs, but there was no significant association between the county characteristics and program response rate. There is a positive relationship between the number of informants initially located and the number of programs screened, eligible, and profiled in a county. Our strategy to identify youth tobacco cessation programs could be used to create a sample frame for other nonprofit organizations that are difficult to identify due to a lack of existing directories, lists, or other traditional sample frames.

Monitoring so2 emission at the Soufriere Hills volcano: Implications for changes in eruptive conditions

USGS Publications Warehouse

Young, S.R.; Francis, P.W.; Barclay, J.; Casadevall, T.J.; Gardner, C.A.; Darroux, B.; Davies, M.A.; Delmelle, P.; Norton, G.E.; Maciejewski, A.J.H.; Oppenheimer, C.M.M.; Stix, J.; Watson, I.M.

1998-01-01

Correlation spectrometer measurements of sulfur dioxide (SO2) emission rates during the current eruption of the Soufriere Hills volcano, Montserrat, have contributed towards identifying different phases of volcanic activity. SO2 emission rate has increased from 550 td-1 (>6.4 kgs-1) after July 1996, with the uncertainty associated with any individual measurement ca. 30%. Significantly enhanced SO2 emission rates have been identified in association with early phreatic eruptions (800 td-1 (9.3 kgs-1)) and episodes of vigorous dome collapse and pyroclastic flow generation (900 to 1500 td-1 (10.4 to 17.4 kgs-1)). SO2 emission rate has proved a useful proxy measurement for magma production rate. Observed SO2 emission rates are significantly higher than those inferred from analyses of glass inclusions in phenocrysts, implying the existence of a S-rich magmatic vapour phase.

Effect of cinnamon on glucose control and lipid parameters.

PubMed

Baker, William L; Gutierrez-Williams, Gabriela; White, C Michael; Kluger, Jeffrey; Coleman, Craig I

2008-01-01

To perform a meta-analysis of randomized controlled trials of cinnamon to better characterize its impact on glucose and plasma lipids. A systematic literature search through July 2007 was conducted to identify randomized placebo-controlled trials of cinnamon that reported data on A1C, fasting blood glucose (FBG), or lipid parameters. The mean change in each study end point from baseline was treated as a continuous variable, and the weighted mean difference was calculated as the difference between the mean value in the treatment and control groups. A random-effects model was used. Five prospective randomized controlled trials (n = 282) were identified. Upon meta-analysis, the use of cinnamon did not significantly alter A1C, FBG, or lipid parameters. Subgroup and sensitivity analyses did not significantly change the results. Cinnamon does not appear to improve A1C, FBG, or lipid parameters in patients with type 1 or type 2 diabetes.

Health Literacy and Education as Mediators of Racial Disparities in Patient Activation Within an Elderly Patient Cohort.

PubMed

Eneanya, Nwamaka D; Winter, Michael; Cabral, Howard; Waite, Katherine; Henault, Lori; Bickmore, Timothy; Hanchate, Amresh; Wolf, Michael; Paasche-Orlow, Michael K

2016-01-01

The Patient Activation Measure (PAM) assesses facets of patient engagement to identify proactive health behaviors and is an important predictor of health outcomes. Health literacy and education are also important for patient participation and successful navigation of the health care system. Because health literacy, education, and patient activation are associated with racial disparities, we sought to investigate whether health literacy and education would mediate racial differences in patient activation. Participants were 265 older adults who participated in a computer-based exercise interventional study. Health literacy was assessed using the Test of Functional Health Literacy in Adults (TOFHLA). Of 210 eligible participants, 72% self-identified as Black and 28% as White. In adjusted analyses, education and health literacy each significantly reduced racial differences in patient activation. These findings are especially important when considering emerging data on the significance of patient activation and new strategies to increase patient engagement.

Euclidean distance can identify the mannitol level that produces the most remarkable integral effect on sugarcane micropropagation in temporary immersion bioreactors.

PubMed

Gómez, Daviel; Hernández, L Ázaro; Yabor, Lourdes; Beemster, Gerrit T S; Tebbe, Christoph C; Papenbrock, Jutta; Lorenzo, José Carlos

2018-03-15

Plant scientists usually record several indicators in their abiotic factor experiments. The common statistical management involves univariate analyses. Such analyses generally create a split picture of the effects of experimental treatments since each indicator is addressed independently. The Euclidean distance combined with the information of the control treatment could have potential as an integrating indicator. The Euclidean distance has demonstrated its usefulness in many scientific fields but, as far as we know, it has not yet been employed for plant experimental analyses. To exemplify the use of the Euclidean distance in this field, we performed an experiment focused on the effects of mannitol on sugarcane micropropagation in temporary immersion bioreactors. Five mannitol concentrations were compared: 0, 50, 100, 150 and 200 mM. As dependent variables we recorded shoot multiplication rate, fresh weight, and levels of aldehydes, chlorophylls, carotenoids and phenolics. The statistical protocol which we then carried out integrated all dependent variables to easily identify the mannitol concentration that produced the most remarkable integral effect. Results provided by the Euclidean distance demonstrate a gradually increasing distance from the control in function of increasing mannitol concentrations. 200 mM mannitol caused the most significant alteration of sugarcane biochemistry and physiology under the experimental conditions described here. This treatment showed the longest statistically significant Euclidean distance to the control treatment (2.38). In contrast, 50 and 100 mM mannitol showed the lowest Euclidean distances (0.61 and 0.84, respectively) and thus poor integrated effects of mannitol. The analysis shown here indicates that the use of the Euclidean distance can contribute to establishing a more integrated evaluation of the contrasting mannitol treatments.

Combining Genome Wide Association Study and lung eQTL analysis provides evidence for novel genes associated with asthma

PubMed Central

Nieuwenhuis, Maartje A.; Siedlinski, Matteusz; van den Berge, Maarten; Granell, Raquel; Li, Xingnan; Niens, Marijke; van der Vlies, Pieter; Altmüller, Janine; Nürnberg, Peter; Kerkhof, Marjan; van Schayck, Onno C.; Riemersma, Ronald A.; van der Molen, Thys; de Monchy, Jan G.; Bossé, Yohan; Sandford, Andrew; Bruijnzeel-Koomen, Carla A.; van Wijk, Roy G.; ten Hacken, Nick H.; Timens, Wim; Boezen, H. Marike; Henderson, John; Kabesch, Michael; Vonk, Judith M.; Postma, Dirkje S.; Koppelman, Gerard H.

2016-01-01

Background Genome wide association studies (GWAS) of asthma have identified single nucleotide polymorphisms (SNPs) that modestly increase the risk for asthma. This could be due to phenotypic heterogeneity of asthma. Bronchial hyperresponsiveness (BHR) is a phenotypic hallmark of asthma. We aim to identify susceptibility genes for asthma combined with BHR and analyse the presence of cis-eQTLs among replicated SNPs. Secondly, we compare the genetic association of SNPs previously associated with (doctor diagnosed) asthma to our GWAS of asthma with BHR. Methods A GWAS was performed in 920 asthmatics with BHR and 980 controls. Top SNPs of our GWAS were analysed in four replication cohorts and lung cis-eQTL analysis was performed on replicated SNPs. We investigated association of SNPs previously associated with asthma in our data. Results 368 SNPs were followed up for replication. Six SNPs in genes encoding ABI3BP, NAF1, MICA and the 17q21 locus replicated in one or more cohorts, with one locus (17q21) achieving genome wide significance after meta-analysis. Five out of 6 replicated SNPs regulated 35 gene transcripts in whole lung. Eight of 20 asthma associated SNPs from previous GWAS were significantly associated with asthma and BHR. Three SNPs, in IL-33 and GSDMB, showed larger effect sizes in our data compared to published literature. Conclusions Combining GWAS with subsequent lung eQTL analysis revealed disease associated SNPs regulating lung mRNA expression levels of potential new asthma genes. Adding BHR to the asthma definition does not lead to an overall larger genetic effect size than analysing (doctor’s diagnosed) asthma. PMID:27439200

Investigation of exomic variants associated with overall survival in ovarian cancer

PubMed Central

Ann Chen, Yian; Larson, Melissa C; Fogarty, Zachary C; Earp, Madalene A; Anton-Culver, Hoda; Bandera, Elisa V; Cramer, Daniel; Doherty, Jennifer A; Goodman, Marc T; Gronwald, Jacek; Karlan, Beth Y; Kjaer, Susanne K; Levine, Douglas A; Menon, Usha; Ness, Roberta B; Pearce, Celeste L; Pejovic, Tanja; Rossing, Mary Anne; Wentzensen, Nicolas; Bean, Yukie T; Bisogna, Maria; Brinton, Louise A; Carney, Michael E; Cunningham, Julie M; Cybulski, Cezary; deFazio, Anna; Dicks, Ed M; Edwards, Robert P; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Gore, Martin; Iversen, Edwin S; Jensen, Allan; Johnatty, Sharon E; Lester, Jenny; Lin, Hui-Yi; Lissowska, Jolanta; Lubinski, Jan; Menkiszak, Janusz; Modugno, Francesmary; Moysich, Kirsten B; Orlow, Irene; Pike, Malcolm C; Ramus, Susan J; Song, Honglin; Terry, Kathryn L; Thompson, Pamela J; Tyrer, Jonathan P; van den Berg, David J; Vierkant, Robert A; Vitonis, Allison F; Walsh, Christine; Wilkens, Lynne R; Wu, Anna H; Yang, Hannah; Ziogas, Argyrios; Berchuck, Andrew; Chenevix-Trench, Georgia; Schildkraut, Joellen M; Permuth-Wey, Jennifer; Phelan, Catherine M; Pharoah, Paul D P; Fridley, Brooke L

2016-01-01

Background While numerous susceptibility loci for epithelial ovarian cancer (EOC) have been identified, few associations have been reported with overall survival. In the absence of common prognostic genetic markers, we hypothesize that rare coding variants may be associated with overall EOC survival and assessed their contribution in two exome-based genotyping projects of the Ovarian Cancer Association Consortium (OCAC). Methods The primary patient set (Set 1) included 14 independent EOC studies (4293 patients) and 227,892 variants, and a secondary patient set (Set 2) included six additional EOC studies (1744 patients) and 114,620 variants. Because power to detect rare variants individually is reduced, gene-level tests were conducted. Sets were analyzed separately at individual variants and by gene, and then combined with meta-analyses (73,203 variants and 13,163 genes overlapped). Results No individual variant reached genome-wide statistical significance. A SNP previously implicated to be associated with EOC risk and, to a lesser extent, survival, rs8170, showed the strongest evidence of association with survival and similar effect size estimates across sets (Pmeta=1.1E-6, HRSet1=1.17, HRSet2=1.14). Rare variants in ATG2B, an autophagy gene important for apoptosis, were significantly associated with survival after multiple testing correction (Pmeta=1.1E-6; Pcorrected=0.01). Conclusions Common variant rs8170 and rare variants in ATG2B may be associated with EOC overall survival, although further study is needed. Impact This study represents the first exome-wide association study of EOC survival to include rare variant analyses, and suggests that complementary single variant and gene-level analyses in large studies are needed to identify rare variants that warrant follow-up study. PMID:26747452

Eosinophil-mediated signalling attenuates inflammatory responses in experimental colitis

PubMed Central

Masterson, Joanne C; McNamee, Eóin N; Fillon, Sophie A; Hosford, Lindsay; Harris, Rachel; Fernando, Shahan D; Jedlicka, Paul; Iwamoto, Ryo; Jacobsen, Elizabeth; Protheroe, Cheryl; Eltzschig, Holger K; Colgan, Sean P; Arita, Makoto; Lee, James J; Furuta, Glenn T

2015-01-01

Objective Eosinophils reside in the colonic mucosa and increase significantly during disease. Although a number of studies have suggested that eosinophils contribute to the pathogenesis of GI inflammation, the expanding scope of eosinophil-mediated activities indicate that they also regulate local immune responses and modulate tissue inflammation. We sought to define the impact of eosinophils that respond to acute phases of colitis in mice. Design Acute colitis was induced in mice by administration of dextran sulfate sodium, 2,4,6-trinitrobenzenesulfonic acid or oxazolone to C57BL/6J (control) or eosinophil deficient (PHIL) mice. Eosinophils were also depleted from mice using antibodies against interleukin (IL)-5 or by grafting bone marrow from PHIL mice into control mice. Colon tissues were collected and analysed by immunohistochemistry, flow cytometry and reverse transcription PCR; lipids were analysed by mass spectroscopy. Results Eosinophil-deficient mice developed significantly more severe colitis, and their colon tissues contained a greater number of neutrophils, than controls. This compensatory increase in neutrophils was accompanied by increased levels of the chemokines CXCL1 and CXCL2, which attract neutrophils. Lipidomic analyses of colonic tissue from eosinophil-deficient mice identified a deficiency in the docosahexaenoic acid-derived anti-inflammatory mediator 10, 17- dihydroxydocosahexaenoic acid (diHDoHE), namely protectin D1 (PD1). Administration of an exogenous PD1-isomer (10S, 17S-DiHDoHE) reduced the severity of colitis in eosinophil-deficient mice. The PD1-isomer also attenuated neutrophil infiltration and reduced levels of tumour necrosis factor-α, IL-1β, IL-6 and inducible NO-synthase in colons of mice. Finally, in vitro assays identified a direct inhibitory effect of PD1-isomer on neutrophil transepithelial migration. Conclusions Eosinophils exert a protective effect in acute mouse colitis, via production of anti-inflammatory lipid mediators. PMID:25209655

Cytokines in relation to autoantibodies before onset of symptoms for systemic lupus erythematosus.

PubMed

Eriksson, C; Rantapää-Dahlqvist, S

2014-06-01

A number of cytokines and chemokines were analysed and related to autoantibodies in blood samples pre-dating the onset of symptoms of systemic lupus erythematosus. Thirty-five patients with systemic lupus erythematosus (American College of Rheumatology criteria) were identified as having donated blood samples, prior to symptom onset, to the Biobank of northern Sweden. Altogether, 140 age- and sex-matched controls were also identified. The concentrations of interferon-α, interleukin-4, interleukin-9, interleukin-10, interferon inducible protein-10 and monocyte chemotactic protein-1 were analysed using multiplex technology and related to autoantibodies (ANA, ENA, anti-dsDNA and anti-histone antibodies) analysed from the same blood sample. The interferon-γ inducible protein-10 levels were higher in the pre-symptomatic individuals than in controls (p < 0.05) and correlated with interferon-α (p < 0.01). The interferon-γ inducible protein-10 and interferon-α concentrations were significantly increased in individuals positive for autoantibodies: interferon-γ inducible protein-10 for ANA; anti-SSA/Ro and anti-Jo-1 antibodies; interferon-α with anti-SSB/La antibodies. The levels of interleukin-10, interferon-γ inducible protein-10 and monocyte chemotactic protein-1 increased significantly from the pre-symptomatic individuals to after onset of systemic lupus erythematosus. An increased concentration of interferon-γ inducible protein-10 pre-dated the onset of systemic lupus erythematosus and was related to autoantibodies before the onset of disease. The levels of interferon-γ inducible protein-10 and interferon-α were correlated. These findings support the proposal that the interferon system is important early in the pathogenesis of systemic lupus erythematosus and autoantibody formation. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Identification of Immune Traits Correlated with Dairy Cow Health, Reproduction and Productivity

PubMed Central

Banos, Georgios; Wall, Eileen; Coffey, Michael P.; Bagnall, Ainsley; Gillespie, Sandra; Russell, George C.; McNeilly, Tom N.

2013-01-01

Detailed biological analyses (e.g. epidemiological, genetic) of animal health and fitness in the field are limited by the lack of large-scale recording of individual animals. An alternative approach is to identify immune traits that are associated with these important functions and can be subsequently used in more detailed studies. We have used an experimental dairy herd with uniquely dense phenotypic data to identify a range of potentially useful immune traits correlated with enhanced (or depressed) health and fitness. Blood samples from 248 dairy cows were collected at two-monthly intervals over a 10-month period and analysed for a number of immune traits, including levels of serum proteins associated with the innate immune response and circulating leukocyte populations. Immune measures were matched to individual cow records related to productivity, fertility and disease. Correlations between traits were calculated using bivariate analyses based on animal repeatability and random regression models with a Bonferroni correction to account for multiple testing. A number of significant correlations were found between immune traits and other recorded traits including: CD4+:CD8+ T lymphocyte ratio and subclinical mastitis; % CD8+ lymphocytes and fertility; % CD335+ natural killer cells and lameness episodes; and serum haptoglobin levels and clinical mastitis. Importantly these traits were not associated with reduced productivity and, in the case of cellular immune traits, were highly repeatable. Moreover these immune traits displayed significant between-animal variation suggesting that they may be altered by genetic selection. This study represents the largest simultaneous analysis of multiple immune traits in dairy cattle to-date and demonstrates that a number of immune traits are associated with health events. These traits represent useful selection markers for future programmes aimed at improving animal health and fitness. PMID:23776543

Genetic analyses of bolting in bulb onion (Allium cepa L.).

PubMed

Baldwin, Samantha; Revanna, Roopashree; Pither-Joyce, Meeghan; Shaw, Martin; Wright, Kathryn; Thomson, Susan; Moya, Leire; Lee, Robyn; Macknight, Richard; McCallum, John

2014-03-01

We present the first evidence for a QTL conditioning an adaptive trait in bulb onion, and the first linkage and population genetics analyses of candidate genes involved in photoperiod and vernalization physiology. Economic production of bulb onion (Allium cepa L.) requires adaptation to photoperiod and temperature such that a bulb is formed in the first year and a flowering umbel in the second. 'Bolting', or premature flowering before bulb maturation, is an undesirable trait strongly selected against by breeders during adaptation of germplasm. To identify genome regions associated with adaptive traits we conducted linkage mapping and population genetic analyses of candidate genes, and QTL analysis of bolting using a low-density linkage map. We performed tagged amplicon sequencing of ten candidate genes, including the FT-like gene family, in eight diverse populations to identify polymorphisms and seek evidence of differentiation. Low nucleotide diversity and negative estimates of Tajima's D were observed for most genes, consistent with purifying selection. Significant population differentiation was observed only in AcFT2 and AcSOC1. Selective genotyping in a large 'Nasik Red × CUDH2150' F2 family revealed genome regions on chromosomes 1, 3 and 6 associated (LOD > 3) with bolting. Validation genotyping of two F2 families grown in two environments confirmed that a QTL on chromosome 1, which we designate AcBlt1, consistently conditions bolting susceptibility in this cross. The chromosome 3 region, which coincides with a functionally characterised acid invertase, was not associated with bolting in other environments, but showed significant association with bulb sucrose content in this and other mapping pedigrees. These putative QTL and candidate genes were placed on the onion map, enabling future comparative studies of adaptive traits.

A Guide to the Natural History of Freshwater Lake Bacteria†

PubMed Central

Newton, Ryan J.; Jones, Stuart E.; Eiler, Alexander; McMahon, Katherine D.; Bertilsson, Stefan

2011-01-01

Summary: Freshwater bacteria are at the hub of biogeochemical cycles and control water quality in lakes. Despite this, little is known about the identity and ecology of functionally significant lake bacteria. Molecular studies have identified many abundant lake bacteria, but there is a large variation in the taxonomic or phylogenetic breadths among the methods used for this exploration. Because of this, an inconsistent and overlapping naming structure has developed for freshwater bacteria, creating a significant obstacle to identifying coherent ecological traits among these groups. A discourse that unites the field is sorely needed. Here we present a new freshwater lake phylogeny constructed from all published 16S rRNA gene sequences from lake epilimnia and propose a unifying vocabulary to discuss freshwater taxa. With this new vocabulary in place, we review the current information on the ecology, ecophysiology, and distribution of lake bacteria and highlight newly identified phylotypes. In the second part of our review, we conduct meta-analyses on the compiled data, identifying distribution patterns for bacterial phylotypes among biomes and across environmental gradients in lakes. We conclude by emphasizing the role that this review can play in providing a coherent framework for future studies. PMID:21372319

Evaluation of the personal dental services (wave 1) for Lambeth, Southwark and Lewisham primary care trusts--Part 2: Retrospective analyses of treatment and other dental record data.

PubMed

Best, Helen; Newton, Tim

2005-06-01

The purpose of the study was to undertake analyses of treatment data for the Personal Dental Services (PDS) of Lambeth, Southwark and Lewisham Primary Care Trusts and relate the analyses to the PDS goals of supporting practitioners deliver appropriate quality dental care and ensuring that appropriate quality safety net services are available for all residents. Analyses of treatment data provided by the Dental Practice Board were undertaken for the post-PDS period (February 1999-March 2003, based on data availability). Analyses of the clinic notes for 1500 patients were also undertaken for the 1 year pre-PDS period (October 1997-September 1998) and post-introduction of the PDS (October 1998-June 2003). Two sets of analyses were undertaken to evaluate trends in treatment claims for the Dental Practice Board data, absolute numbers of each type of treatment claimed each month and change in numbers of types of treatments claimed over time. The clinic notes were used to undertake post-PDS, pre-PDS comparisons of the number of treatment items and grouped treatment item categories undertaken and the number of courses and percentages of private treatment items provided. The following sociodemographic characteristics of the patients were also analysed, age, gender, exemption status and attendance status. Overall it was identified that the percentage reduction in the number of treatment items undertaken was 13% (95% CI -19%, -7%), post- as compared to the pre-PDS introduction period. On an annual basis it was identified that the percentage reduction in the number of treatment items undertaken per year per patient post-PDS was 4% (95% CI -6%, -2%). There were significant variations in the impact of the PDS on the number of treatment items undertaken for different types of patients. A limited number of treatment types changed significantly post- as compared to pre-PDS. The proportion of exempt patients treated did not increase post-PDS. It is possible that a less invasive style of dental treatment was provided during the course of the PDS, however, there was only limited evidence to indicate that dentists practice style changed based on types of treatment categories provided. The PDS provided a limited safety net service for local residents. In setting program goals the nature of quality dental practice requires definition and evaluation should be undertaken on a prospective basis.