A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers. | Office of Cancer Genomics

Cancer.gov

We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks.

Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2

PubMed Central

Wright, Fred A.; Strug, Lisa J.; Doshi, Vishal K.; Commander, Clayton W.; Blackman, Scott M.; Sun, Lei; Berthiaume, Yves; Cutler, David; Cojocaru, Andreea; Collaco, J. Michael; Corey, Mary; Dorfman, Ruslan; Goddard, Katrina; Green, Deanna; Kent, Jack W.; Lange, Ethan M.; Lee, Seunggeun; Li, Weili; Luo, Jingchun; Mayhew, Gregory M.; Naughton, Kathleen M.; Pace, Rhonda G.; Paré, Peter; Rommens, Johanna M.; Sandford, Andrew; Stonebraker, Jaclyn R.; Sun, Wei; Taylor, Chelsea; Vanscoy, Lori L.; Zou, Fei; Blangero, John; Zielenski, Julian; O’Neal, Wanda K.; Drumm, Mitchell L.; Durie, Peter R.; Knowles, Michael R.; Cutting, Garry R.

2012-01-01

A combined genome-wide association and linkage study was used to identify loci causing variation in CF lung disease severity. A significant association (P=3. 34 × 10-8) near EHF and APIP (chr11p13) was identified in F508del homozygotes (n=1,978). The association replicated in F508del homozygotes (P=0.006) from a separate family-based study (n=557), with P=1.49 × 10-9 for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family-based study identified a significant QTL on chromosome 20q13.2 (LOD=5.03). Our findings provide insight into the causes of variation in lung disease severity in CF and suggest new therapeutic targets for this life-limiting disorder. PMID:21602797

Males Perform Better in Identifying Voices During Menstruation Than Females: A Pilot Study.

PubMed

Wang, Xue; Xu, Xin; Liu, Yangyang

2016-10-01

The objective of the present study is to investigate gender differences in the ability to identify females' voice during menstruation. In Study 1, 55 male participants (M age = 19.6 years, SD = 1.0) were asked to listen to vocal samples from women during both ovulation and menstruation and to identify which recordings featured menstruating women. The results showed that the accuracy of men's responses (M = 56.73%, SD = 0.21) was significantly higher than 50%. In Study 2, 118 female students (M age = 19.4 years, SD = 1.6) completed the same task. The results indicated that the accuracy of women's performance was nearly 50%. These preliminary findings suggest that men are better able to identify women's voices during menstruation than women. Future work could consider several significant variables for the purpose of validating the results. © The Author(s) 2016.

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.

Association of genetic and non-genetic risk factors with the development of prostate cancer in Malaysian men.

PubMed

Munretnam, Khamsigan; Alex, Livy; Ramzi, Nurul Hanis; Chahil, Jagdish Kaur; Kavitha, I S; Hashim, Nikman Adli Nor; Lye, Say Hean; Velapasamy, Sharmila; Ler, Lian Wee

2014-01-01

There is growing global interest to stratify men into different levels of risk to developing prostate cancer, thus it is important to identify common genetic variants that confer the risk. Although many studies have identified more than a dozen common genetic variants which are highly associated with prostate cancer, none have been done in Malaysian population. To determine the association of such variants in Malaysian men with prostate cancer, we evaluated a panel of 768 SNPs found previously associated with various cancers which also included the prostate specific SNPs in a population based case control study (51 case subjects with prostate cancer and 51 control subjects) in Malaysian men of Malay, Chinese and Indian ethnicity. We identified 21 SNPs significantly associated with prostate cancer. Among these, 12 SNPs were strongly associated with increased risk of prostate cancer while remaining nine SNPs were associated with reduced risk. However, data analysis based on ethnic stratification led to only five SNPs in Malays and 3 SNPs in Chinese which remained significant. This could be due to small sample size in each ethnic group. Significant non-genetic risk factors were also identified for their association with prostate cancer. Our study is the first to investigate the involvement of multiple variants towards susceptibility for PC in Malaysian men using genotyping approach. Identified SNPs and non-genetic risk factors have a significant association with prostate cancer.

A Penalized Robust Method for Identifying Gene-Environment Interactions

PubMed Central

Shi, Xingjie; Liu, Jin; Huang, Jian; Zhou, Yong; Xie, Yang; Ma, Shuangge

2015-01-01

In high-throughput studies, an important objective is to identify gene-environment interactions associated with disease outcomes and phenotypes. Many commonly adopted methods assume specific parametric or semiparametric models, which may be subject to model mis-specification. In addition, they usually use significance level as the criterion for selecting important interactions. In this study, we adopt the rank-based estimation, which is much less sensitive to model specification than some of the existing methods and includes several commonly encountered data and models as special cases. Penalization is adopted for the identification of gene-environment interactions. It achieves simultaneous estimation and identification and does not rely on significance level. For computation feasibility, a smoothed rank estimation is further proposed. Simulation shows that under certain scenarios, for example with contaminated or heavy-tailed data, the proposed method can significantly outperform the existing alternatives with more accurate identification. We analyze a lung cancer prognosis study with gene expression measurements under the AFT (accelerated failure time) model. The proposed method identifies interactions different from those using the alternatives. Some of the identified genes have important implications. PMID:24616063

Genome-association analysis of Korean Holstein milk traits using genomic estimated breeding value.

PubMed

Shin, Donghyun; Lee, Chul; Park, Kyoung-Do; Kim, Heebal; Cho, Kwang-Hyeon

2017-03-01

Holsteins are known as the world's highest-milk producing dairy cattle. The purpose of this study was to identify genetic regions strongly associated with milk traits (milk production, fat, and protein) using Korean Holstein data. This study was performed using single nucleotide polymorphism (SNP) chip data (Illumina BovineSNP50 Beadchip) of 911 Korean Holstein individuals. We inferred each genomic estimated breeding values based on best linear unbiased prediction (BLUP) and ridge regression using BLUPF90 and R. We then performed a genome-wide association study and identified genetic regions related to milk traits. We identified 9, 6, and 17 significant genetic regions related to milk production, fat and protein, respectively. These genes are newly reported in the genetic association with milk traits of Holstein. This study complements a recent Holstein genome-wide association studies that identified other SNPs and genes as the most significant variants. These results will help to expand the knowledge of the polygenic nature of milk production in Holsteins.

Genome-association analysis of Korean Holstein milk traits using genomic estimated breeding value

PubMed Central

Shin, Donghyun; Lee, Chul; Park, Kyoung-Do; Kim, Heebal; Cho, Kwang-hyeon

2017-01-01

Objective Holsteins are known as the world’s highest-milk producing dairy cattle. The purpose of this study was to identify genetic regions strongly associated with milk traits (milk production, fat, and protein) using Korean Holstein data. Methods This study was performed using single nucleotide polymorphism (SNP) chip data (Illumina BovineSNP50 Beadchip) of 911 Korean Holstein individuals. We inferred each genomic estimated breeding values based on best linear unbiased prediction (BLUP) and ridge regression using BLUPF90 and R. We then performed a genome-wide association study and identified genetic regions related to milk traits. Results We identified 9, 6, and 17 significant genetic regions related to milk production, fat and protein, respectively. These genes are newly reported in the genetic association with milk traits of Holstein. Conclusion This study complements a recent Holstein genome-wide association studies that identified other SNPs and genes as the most significant variants. These results will help to expand the knowledge of the polygenic nature of milk production in Holsteins. PMID:26954162

Exome sequencing of a large family identifies potential candidate genes contributing risk to bipolar disorder.

PubMed

Zhang, Tianxiao; Hou, Liping; Chen, David T; McMahon, Francis J; Wang, Jen-Chyong; Rice, John P

2018-03-01

Bipolar disorder is a mental illness with lifetime prevalence of about 1%. Previous genetic studies have identified multiple chromosomal linkage regions and candidate genes that might be associated with bipolar disorder. The present study aimed to identify potential susceptibility variants for bipolar disorder using 6 related case samples from a four-generation family. A combination of exome sequencing and linkage analysis was performed to identify potential susceptibility variants for bipolar disorder. Our study identified a list of five potential candidate genes for bipolar disorder. Among these five genes, GRID1(Glutamate Receptor Delta-1 Subunit), which was previously reported to be associated with several psychiatric disorders and brain related traits, is particularly interesting. Variants with functional significance in this gene were identified from two cousins in our bipolar disorder pedigree. Our findings suggest a potential role for these genes and the related rare variants in the onset and development of bipolar disorder in this one family. Additional research is needed to replicate these findings and evaluate their patho-biological significance. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

The risk of placental abruption and placenta previa in pregnant women with chronic hepatitis B viral infection: a systematic review and meta-analysis.

PubMed

Huang, Q T; Chen, J H; Zhong, M; Xu, Y Y; Cai, C X; Wei, S S; Hang, L L; Liu, Q; Yu, Y H

2014-08-01

Several epidemiological studies have found a positive association between chronic hepatitis B virus (CHB) infection and the risk of placental abruption and placenta previa, but various studies have reported conflicting findings. The objective was to systematically review the literature to determine a possible association between CHB infection and these two placental complications. We conducted a computerized search in electronic database through March 1, 2014, supplemented with a manual search of reference lists, to identify original published research on placental abruption and placenta previa rates in women with CHB infection. Data were independently extracted, and relative risks were calculated. The meta-analysis was performed using Stata version 10.0 software. Five studies involving 9088 placenta previa cases were identified. No significant association between CHB infection and placenta previa was identified (OR = 0.98, 95% CI = 0.60-1.62). Five studies involving 15571 placental abruption cases were identified. No significant association between CHB infection and placental abruption was identified (OR = 1.42, 95% CI, 0.93-2.15). The immune response against the virus represents a key factor in determining infection outcomes. No observation of significant increased risk of the placental complications could be partially explained by the complex immune response during CHB infection. Our meta-analysis found no evidence of significant associations between CHB infection and increased risk of placental abruption as well as placenta previa. Further well-designed studies were warranted to assess any potential association between CHB infection and increased risk of placental abruption as well as placenta previa. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preoperative vitamin D level as predictor of post-thyroidectomy hypocalcemia in patients sustaining transient parathyroid injury.

PubMed

Danan, Deepa; Shonka, David C

2017-07-01

Several studies have sought to identify predictors of postoperative hypocalcemia after total thyroidectomy; however, there have been conflicting results regarding the impact of preoperative vitamin D deficiency. The medical records of patients undergoing total thyroidectomy were retrospectively reviewed. The number of parathyroid glands identified or reimplanted at the time of surgery was used as a marker of transient parathyroid gland damage. Sixty-seven patients were included in the study. Vitamin D deficiency was a significant predictor of hypocalcemia in patients in whom ≥3 parathyroid glands were identified, but not in patients in whom 0-2 parathyroid glands were identified intraoperatively (odds ratio [OR] 5.8; P = .036). Vitamin D deficiency is a significant predictor of postoperative hypocalcemia in patients in whom ≥3 parathyroid glands are identified intraoperatively, but not in patients who sustain minimal transient damage to the parathyroid glands. © 2017 Wiley Periodicals, Inc.

An Exploratory Study of the Five-Factor Personality Traits Model as Predictors among Women in Science, Technology, Engineering, and Mathematics Fields at Indiana State University

NASA Astrophysics Data System (ADS)

Challa, Sowmya

The purpose of this study is to identify any trends in personality traits of students at a mid-western university along with the influence of gender, choice of STEM or non-STEM academic major, and level of education on personality traits. The chosen mid-western university is Indiana State University (ISU) located in Terre Haute, Indiana. This study investigated the personality traits of student's through administering Goldberg's (1999) International Personality Item Pool of the Big Five Broad Domains of Personality. The personality profiles of students at ISU who have taken the questionnare are summarized. The personality profiles of female students were analyzed further with special focus to identify the role of level of education and choice of major among female students. Based on the responses of the study's subjects, there are significant relationships found between gender and all of the big five personality traits. Level of education, graduate or undergraduate, had significant impact on extraversion, agreeability, concientiousness, and emotional stability. Choice of STEM and non-STEM major impacted emotional stability for subjects in general but its influence is not significant among female subjects. Choice of STEM or non-STEM major had a significant influence on the intelligence/imagination trait for both male and female subjects. Level of education did not have any significant influence on intellegence/imagination. Overall, this study found a few significant relationships between Big-Five personality traits and identified categorizations.

Genome-Wide Association Study for Identification and Validation of Novel SNP Markers for Sr6 Stem Rust Resistance Gene in Bread Wheat.

PubMed

Mourad, Amira M I; Sallam, Ahmed; Belamkar, Vikas; Wegulo, Stephen; Bowden, Robert; Jin, Yue; Mahdy, Ezzat; Bakheit, Bahy; El-Wafaa, Atif A; Poland, Jesse; Baenziger, Peter S

2018-01-01

Stem rust (caused by Puccinia graminis f. sp. tritici Erikss. & E. Henn.), is a major disease in wheat ( Triticum aestivium L.). However, in recent years it occurs rarely in Nebraska due to weather and the effective selection and gene pyramiding of resistance genes. To understand the genetic basis of stem rust resistance in Nebraska winter wheat, we applied genome-wide association study (GWAS) on a set of 270 winter wheat genotypes (A-set). Genotyping was carried out using genotyping-by-sequencing and ∼35,000 high-quality SNPs were identified. The tested genotypes were evaluated for their resistance to the common stem rust race in Nebraska (QFCSC) in two replications. Marker-trait association identified 32 SNP markers, which were significantly (Bonferroni corrected P < 0.05) associated with the resistance on chromosome 2D. The chromosomal location of the significant SNPs (chromosome 2D) matched the location of Sr6 gene which was expected in these genotypes based on pedigree information. A highly significant linkage disequilibrium (LD, r 2 ) was found between the significant SNPs and the specific SSR marker for the Sr6 gene ( Xcfd43 ). This suggests the significant SNP markers are tagging Sr6 gene. Out of the 32 significant SNPs, eight SNPs were in six genes that are annotated as being linked to disease resistance in the IWGSC RefSeq v1.0. The 32 significant SNP markers were located in nine haplotype blocks. All the 32 significant SNPs were validated in a set of 60 different genotypes (V-set) using single marker analysis. SNP markers identified in this study can be used in marker-assisted selection, genomic selection, and to develop KASP (Kompetitive Allele Specific PCR) marker for the Sr6 gene. Novel SNPs for Sr6 gene, an important stem rust resistant gene, were identified and validated in this study. These SNPs can be used to improve stem rust resistance in wheat.

Disparities in Beef Tapeworm Identification Rates in the Abattoirs of Gauteng Province, South Africa: A Descriptive Epidemiologic Study.

PubMed

Qekwana, Daniel Nenene; Oguttu, James Wabwire; Venter, Dries; Odoi, Agricola

2016-01-01

Bovine Taenia saginata cysticercus infections (also called bovine cysticercosis or beef measles) is usually diagnosed in cattle only during post-mortem meat inspection. The aim of this study was to investigate the identification rates of these infections in and to identify predictors/determinants of variations in the identification rates in abattoirs in Gauteng province, South Africa. Retrospective data for over 1.4 million cattle carcasses inspected in 26 abattoirs between January 2010 and December 2013 were used for the study. The identification rates (proportion of bovine Taenia saginata cysticercus positive carcasses) were computed and generalized estimating equations used to identify predictors/determinants of identification rates. The overall identification rate was 0.70% (95% CI: 0.45, 0.95). Significantly (p< 0.05) lower rates were reported during summer (0.55%) than other seasons. Some geographic areas reported significantly (p<0.05) higher rates than others. The identification rates in high throughput abattoirs was significantly (p<0.05) higher (RR: 9.4; 95% CI: 4.7-19.1) than in low throughput abattoirs. Similarly, the identification rates among animals from feedlots were significantly (p<0.05) higher (RR: 1.6; 95% CI: 1.7-3.5) than those from non-feedlot sources. No significant (p>0.05) association was identified between identification rates and either the number of meat inspectors per abattoir or the provider of inspection services. Although no significant association was found between identification rates and provider of inspection services, follow-up studies will need to be done to specifically investigate the potential conflict of interest arising from the fact that abattoir owners hire meat inspection services directly. Capture of abattoir surveillance data needs to include farm address and for each case to be reported separately. Finally, information on the type of identified cysts (alive or calcified) need to be collected to help better estimate risk to consumers. This study provides useful baseline data to guide future studies, surveillance and control efforts.

Use of electronic data and existing screening tools to identify clinically significant obstructive sleep apnea.

PubMed

Severson, Carl A; Pendharkar, Sachin R; Ronksley, Paul E; Tsai, Willis H

2015-01-01

To assess the ability of electronic health data and existing screening tools to identify clinically significant obstructive sleep apnea (OSA), as defined by symptomatic or severe OSA. The present retrospective cohort study of 1041 patients referred for sleep diagnostic testing was undertaken at a tertiary sleep centre in Calgary, Alberta. A diagnosis of clinically significant OSA or an alternative sleep diagnosis was assigned to each patient through blinded independent chart review by two sleep physicians. Predictive variables were identified from online questionnaire data, and diagnostic algorithms were developed. The performance of electronically derived algorithms for identifying patients with clinically significant OSA was determined. Diagnostic performance of these algorithms was compared with versions of the STOP-Bang questionnaire and adjusted neck circumference score (ANC) derived from electronic data. Electronic questionnaire data were highly sensitive (>95%) at identifying clinically significant OSA, but not specific. Sleep diagnostic testing-determined respiratory disturbance index was very specific (specificity ≥95%) for clinically relevant disease, but not sensitive (<35%). Derived algorithms had similar accuracy to the STOP-Bang or ANC, but required fewer questions and calculations. These data suggest that a two-step process using a small number of clinical variables (maximizing sensitivity) and objective diagnostic testing (maximizing specificity) is required to identify clinically significant OSA. When used in an online setting, simple algorithms can identify clinically relevant OSA with similar performance to existing decision rules such as the STOP-Bang or ANC.

Can CT imaging of the chest, abdomen, and pelvis identify all vertebral injuries of the thoracolumbar spine without dedicated reformatting?

PubMed

Imran, Jonathan B; Madni, Tarik D; Pruitt, Jeffrey H; Cornelius, Canon; Subramanian, Madhu; Clark, Audra T; Mokdad, Ali A; Rizk, Paul; Minei, Joseph P; Cripps, Michael W; Eastman, Alexander L

2018-07-01

The main objective of this study was to compare detection rates of clinically significant thoracolumbar spine (TLS) fracture between computed tomography (CT) imaging of the chest, abdomen, and spine (CT CAP) and CT for the thoracolumbar spine (CT TL). We retrospectively identified patients at our institution with a TLS fracture over a two-year period that had both CT CAP and reformatted CT TL imaging. The sensitivity of CT CAP to identify fracture was calculated for each fracture type. A total of 516 TLS fractures were identified in 125 patients using reformatted CT TL spine imaging. Overall, 69 of 512 fractures (13%) were missed on CT CAP that were identified on CT TL. Of those, there were no clinically significant missed fractures. CT CAP could potentially be used as a screening tool for clinically significant TLS injuries. Copyright © 2017 Elsevier Inc. All rights reserved.

Genome-wide Association Study Identifies African-Specific Susceptibility Loci in African Americans with Inflammatory Bowel Disease

PubMed Central

Brant, Steven R.; Okou, David T.; Simpson, Claire L.; Cutler, David J.; Haritunians, Talin; Bradfield, Jonathan P.; Chopra, Pankaj; Prince, Jarod; Begum, Ferdouse; Kumar, Archana; Huang, Chengrui; Venkateswaran, Suresh; Datta, Lisa W.; Wei, Zhi; Thomas, Kelly; Herrinton, Lisa J.; Klapproth, Jan-Micheal A.; Quiros, Antonio J.; Seminerio, Jenifer; Liu, Zhenqiu; Alexander, Jonathan S.; Baldassano, Robert N.; Dudley-Brown, Sharon; Cross, Raymond K.; Dassopoulos, Themistocles; Denson, Lee A.; Dhere, Tanvi A.; Dryden, Gerald W.; Hanson, John S.; Hou, Jason K.; Hussain, Sunny Z.; Hyams, Jeffrey S.; Isaacs, Kim L.; Kader, Howard; Kappelman, Michael D.; Katz, Jeffry; Kellermayer, Richard; Kirschner, Barbara S.; Kuemmerle, John F.; Kwon, John H.; Lazarev, Mark; Li, Ellen; Mack, David; Mannon, Peter; Moulton, Dedrick E.; Newberry, Rodney D.; Osuntokun, Bankole O.; Patel, Ashish S.; Saeed, Shehzad A.; Targan, Stephan R.; Valentine, John F.; Wang, Ming-Hsi; Zonca, Martin; Rioux, John D.; Duerr, Richard H.; Silverberg, Mark S.; Cho, Judy H.; Hakonarson, Hakon; Zwick, Michael E.; McGovern, Dermot P.B.; Kugathasan, Subra

2016-01-01

Background & Aims The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn’s disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. Methods We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified [IBD-U]) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P<5.0×10−8 in meta-analysis with a nominal evidence (P<.05) in each scan were considered to have genome-wide significance. Results We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance associations for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P<1.6×10−6): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on conditioning), IL12B, PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20 (in strong linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC. Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated with IBD at the HLA locus, contained SNPs with unique association patterns with African-specific alleles. Conclusions We performed a genome-wide association study of African Americans with IBD and identified loci associated with CD and UC in only this population; we also replicated loci identified in European populations. The detection of variants associated with IBD risk in only people of African descent demonstrates the importance of studying the genetics of IBD and other complex diseases in populations beyond those of European ancestry. PMID:27693347

Identification of potential transcriptomic markers in developing pediatric sepsis: a weighted gene co-expression network analysis and a case-control validation study.

PubMed

Li, Yiping; Li, Yanhong; Bai, Zhenjiang; Pan, Jian; Wang, Jian; Fang, Fang

2017-12-13

Sepsis represents a complex disease with the dysregulated inflammatory response and high mortality rate. The goal of this study was to identify potential transcriptomic markers in developing pediatric sepsis by a co-expression module analysis of the transcriptomic dataset. Using the R software and Bioconductor packages, we performed a weighted gene co-expression network analysis to identify co-expression modules significantly associated with pediatric sepsis. Functional interpretation (gene ontology and pathway analysis) and enrichment analysis with known transcription factors and microRNAs of the identified candidate modules were then performed. In modules significantly associated with sepsis, the intramodular analysis was further performed and "hub genes" were identified and validated by quantitative real-time PCR (qPCR) in this study. 15 co-expression modules in total were detected, and four modules ("midnight blue", "cyan", "brown", and "tan") were most significantly associated with pediatric sepsis and suggested as potential sepsis-associated modules. Gene ontology analysis and pathway analysis revealed that these four modules strongly associated with immune response. Three of the four sepsis-associated modules were also enriched with known transcription factors (false discovery rate-adjusted P < 0.05). Hub genes were identified in each of the four modules. Four of the identified hub genes (MYB proto-oncogene like 1, killer cell lectin like receptor G1, stomatin, and membrane spanning 4-domains A4A) were further validated to be differentially expressed between septic children and controls by qPCR. Four pediatric sepsis-associated co-expression modules were identified in this study. qPCR results suggest that hub genes in these modules are potential transcriptomic markers for pediatric sepsis diagnosis. These results provide novel insights into the pathogenesis of pediatric sepsis and promote the generation of diagnostic gene sets.

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.

Load Handling and Repetitive Movements Are Associated with Chronic Low Back Pain among Jute Mill Workers in India

PubMed Central

Goswami, S.; Dasgupta, S.; Samanta, A.; Talukdar, G.; Chanda, A.; Ray Karmakar, P.; Bhattacharya, D.

2016-01-01

Introduction. WHO recognizes low back pain as one of the most important ergonomic stressors. Therefore, the present study was designed to find out the magnitude of the problem among jute mill workers in India and identify possible associations. Methodology. This cross-sectional workplace based study was conducted among eight (8) selected jute mills of India. Subjects with self-reported back pain for at least last 12 weeks were included and n = 717 male jute mill workers actively engaged in work entered the study and completed all assessments. Results. Among all participants 55% (n = 392) had current chronic low back pain. Age was an important association with subjects in the age group of 40–59 years more likely to have pain (p = 0.02, OR 1.44). Regarding ergonomic risk factors lifting of load of more than 20 kg (p = 0.04, OR 1.42) and repetitive movements of limbs (p = 0.03, OR 0.67) were significant associations of chronic low back pain. Conclusion. This study identified a significant prevalence of current chronic low back pain among jute mill workers. Regarding ergonomic risk factors the present study has identified two significant associations: lifting of load above 20 kg and repetitive movements of limbs. Therefore, this study has identified need for workplace interventions in this occupational group employing approximately 3,50,000 workers in India. PMID:27563463

Ultrasound and computed tomography of the iliosacral lymphatic centre in dogs with anal sac gland carcinoma.

PubMed

Pollard, R E; Fuller, M C; Steffey, M A

2017-06-01

In this prospective study, we hypothesized that computed tomography (CT) would identify more normal and abnormal iliosacral lymph nodes (LNs) than abdominal ultrasound in dogs with anal sac gland carcinoma (ASGC). Twelve client-owned dogs with ASGC but without distant metastasis were enrolled. Abdominal ultrasound and contrast-enhanced CT scans of the abdomen were obtained. Iliosacral LNs were counted and assessed for location, laterality and size. Significantly (P < 0.00001) more iliosacral LNs were identified with CT (61) than ultrasound (30), including significantly (P = 0.00012) more medial iliac LNs with CT (33) than ultrasound (19). There was no difference in number of internal iliac LNs identified with CT versus ultrasound. Significantly (P = 0.000061) more sacral LNs were identified with CT (15) than ultrasound (0). Ultrasound identified slightly more (7) abnormal iliosacral LNs than CT (5). Contrast CT was able to identify more normal but not more abnormal LNs than ultrasound. © 2015 John Wiley & Sons Ltd.

Joint source based morphometry identifies linked gray and white matter group differences.

PubMed

Xu, Lai; Pearlson, Godfrey; Calhoun, Vince D

2009-02-01

We present a multivariate approach called joint source based morphometry (jSBM), to identify linked gray and white matter regions which differ between groups. In jSBM, joint independent component analysis (jICA) is used to decompose preprocessed gray and white matter images into joint sources and statistical analysis is used to determine the significant joint sources showing group differences and their relationship to other variables of interest (e.g. age or sex). The identified joint sources are groupings of linked gray and white matter regions with common covariation among subjects. In this study, we first provide a simulation to validate the jSBM approach. To illustrate our method on real data, jSBM is then applied to structural magnetic resonance imaging (sMRI) data obtained from 120 chronic schizophrenia patients and 120 healthy controls to identify group differences. JSBM identified four joint sources as significantly associated with schizophrenia. Linked gray-white matter regions identified in each of the joint sources included: 1) temporal--corpus callosum, 2) occipital/frontal--inferior fronto-occipital fasciculus, 3) frontal/parietal/occipital/temporal--superior longitudinal fasciculus and 4) parietal/frontal--thalamus. Age effects on all four joint sources were significant, but sex effects were significant only for the third joint source. Our findings demonstrate that jSBM can exploit the natural linkage between gray and white matter by incorporating them into a unified framework. This approach is applicable to a wide variety of problems to study linked gray and white matter group differences.

Spatial analysis of gastroschisis in Massachusetts and Texas

PubMed Central

Yazdy, Mahsa M.; Werler, Martha M.; Anderka, Marlene; Langlois, Peter H.; Vieira, Veronica M.

2014-01-01

Purpose Previous research has suggested gastroschisis, a congenital malformation, may be linked to environmental or infectious factors and cases can occur in clusters. The objective of this study was to identify geographic areas of elevated gastroschisis risk. Methods Cases of gastroschisis were identified from birth defect registries in Massachusetts and Texas. Random samples of live births were selected as controls. Generalized additive models were used to create a continuous map surface of odds ratios (OR) by smoothing over latitude and longitude. Maternal age, race/ethnicity, education, cigarette smoking, and insurance status (MA only) were assessed for confounding. We used permutation tests to identify statistically significant areas of increased risk. Results An area of increased risk was identified in north-central Massachusetts, but was not significant after adjustment (p-value=0.07; OR=2.0). In Texas, two statistically significant areas of increased risk were identified after adjustment (p-value=0.02; OR=1.3 and 1.2). Texas had sufficient data to assess the combination of space and time, which identified an increased risk in 2003 and 2004. Conclusion This study suggests there were areas of elevated gastroschisis risk in Massachusetts and Texas that cannot be explained by the risk factors we assessed. Additional exploration of underlying artifactual, environmental, infectious, or behavioral factors may further our understanding of gastroschisis. PMID:25454289

Peer support of complex health behaviors in prevention and disease management with special reference to diabetes: systematic reviews.

PubMed

Fisher, Edwin B; Boothroyd, Renée I; Elstad, Emily A; Hays, Laura; Henes, Amy; Maslow, Gary R; Velicer, Clayton

2017-01-01

Examine Peer Support (PS) for complex, sustained health behaviors in prevention or disease management with emphasis on diabetes prevention and management. PS was defined as emotional, motivational and practical assistance provided by nonprofessionals for complex health behaviors. Initial review examined 65 studies drawn from 1442 abstracts identified through PubMed, published 1/1/2000-7/15/2011. From this search, 24 reviews were also identified. Extension of the search in diabetes identified 30 studies published 1/1/2000-12/31/2015. In initial review, 54 of all 65 studies (83.1%) reported significant impacts of PS, 40 (61.5%) reporting between-group differences and another 14 (21.5%) reporting significant within-group changes. Across 19 of 24 reviews providing quantifiable findings, a median of 64.5% of studies reviewed reported significant effects of PS. In extended review of diabetes, 26 of all 30 studies (86.7%) reported significant impacts of PS, 17 (56.7%) reporting between-group differences and another nine (30.0%) reporting significant within-group changes. Among 19 of these 30 reporting HbA1c data, average reduction was 0.76 points. Studies that did not find effects of PS included other sources of support, implementation or methodological problems, lack of acceptance of interventions, poor fit to recipient needs, and possible harm of unmoderated PS. Across diverse settings, including under-resourced countries and health care systems, PS is effective in improving complex health behaviors in disease prevention and management including in diabetes.

Gene-set analysis based on the pharmacological profiles of drugs to identify repurposing opportunities in schizophrenia.

PubMed

de Jong, Simone; Vidler, Lewis R; Mokrab, Younes; Collier, David A; Breen, Gerome

2016-08-01

Genome-wide association studies (GWAS) have identified thousands of novel genetic associations for complex genetic disorders, leading to the identification of potential pharmacological targets for novel drug development. In schizophrenia, 108 conservatively defined loci that meet genome-wide significance have been identified and hundreds of additional sub-threshold associations harbour information on the genetic aetiology of the disorder. In the present study, we used gene-set analysis based on the known binding targets of chemical compounds to identify the 'drug pathways' most strongly associated with schizophrenia-associated genes, with the aim of identifying potential drug repositioning opportunities and clues for novel treatment paradigms, especially in multi-target drug development. We compiled 9389 gene sets (2496 with unique gene content) and interrogated gene-based p-values from the PGC2-SCZ analysis. Although no single drug exceeded experiment wide significance (corrected p<0.05), highly ranked gene-sets reaching suggestive significance including the dopamine receptor antagonists metoclopramide and trifluoperazine and the tyrosine kinase inhibitor neratinib. This is a proof of principle analysis showing the potential utility of GWAS data of schizophrenia for the direct identification of candidate drugs and molecules that show polypharmacy. © The Author(s) 2016.

Is case-chaos methodology an appropriate alternative to conventional case-control studies for investigating outbreaks?

PubMed

Edelstein, Michael; Wallensten, Anders; Kühlmann-Berenzon, Sharon

2014-08-15

Case-chaos methodology is a proposed alternative to case-control studies that simulates controls by randomly reshuffling the exposures of cases. We evaluated the method using data on outbreaks in Sweden. We identified 5 case-control studies from foodborne illness outbreaks that occurred between 2005 and 2012. Using case-chaos methodology, we calculated odds ratios 1,000 times for each exposure. We used the median as the point estimate and the 2.5th and 97.5th percentiles as the confidence interval. We compared case-chaos matched odds ratios with their respective case-control odds ratios in terms of statistical significance. Using Spearman's correlation, we estimated the correlation between matched odds ratios and the proportion of cases exposed to each exposure and quantified the relationship between the 2 using a normal linear mixed model. Each case-control study identified an outbreak vehicle (odds ratios = 4.9-45). Case-chaos methodology identified the outbreak vehicle 3 out of 5 times. It identified significant associations in 22 of 113 exposures that were not associated with outcome and 5 of 18 exposures that were significantly associated with outcome. Log matched odds ratios correlated with their respective proportion of cases exposed (Spearman ρ = 0.91) and increased significantly with the proportion of cases exposed (b = 0.054). Case-chaos methodology missed the outbreak source 2 of 5 times and identified spurious associations between a number of exposures and outcome. Measures of association correlated with the proportion of cases exposed. We recommended against using case-chaos analysis during outbreak investigations. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Admixture Mapping of African-American Women in the AMBER Consortium Identifies New Loci for Breast Cancer and Estrogen-Receptor Subtypes.

PubMed

Ruiz-Narváez, Edward A; Sucheston-Campbell, Lara; Bensen, Jeannette T; Yao, Song; Haddad, Stephen; Haiman, Christopher A; Bandera, Elisa V; John, Esther M; Bernstein, Leslie; Hu, Jennifer J; Ziegler, Regina G; Deming, Sandra L; Olshan, Andrew F; Ambrosone, Christine B; Palmer, Julie R; Lunetta, Kathryn L

2016-01-01

Recent genetic admixture coupled with striking differences in incidence of estrogen receptor (ER) breast cancer subtypes, as well as severity, between women of African and European ancestry, provides an excellent rationale for performing admixture mapping in African American women with breast cancer risk. We performed the largest breast cancer admixture mapping study with in African American women to identify novel genomic regions associated with the disease. We conducted a genome-wide admixture scan using 2,624 autosomal ancestry informative markers (AIMs) in 3,629 breast cancer cases (including 1,968 ER-positive, 1093 ER-negative, and 601 triple-negative) and 4,658 controls from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium, a collaborative study of four large geographically different epidemiological studies of breast cancer in African American women. We used an independent case-control study to test for SNP association in regions with genome-wide significant admixture signals. We found two novel genome-wide significant regions of excess African ancestry, 4p16.1 and 17q25.1, associated with ER-positive breast cancer. Two regions known to harbor breast cancer variants, 10q26 and 11q13, were also identified with excess of African ancestry. Fine-mapping of the identified genome-wide significant regions suggests the presence of significant genetic associations with ER-positive breast cancer in 4p16.1 and 11q13. In summary, we identified three novel genomic regions associated with breast cancer risk by ER status, suggesting that additional previously unidentified variants may contribute to the racial differences in breast cancer risk in the African American population.

Risk factors for renal dysfunction after total knee joint replacement.

PubMed

Hassan, Basim K; Sahlström, Arne; Dessau, Ram B

2015-12-01

Renal injury and dysfunction are serious complications after major surgery, which may lead to increased morbidity and mortality. The objective of our study was to identify the possible risk factors for renal dysfunction after total knee joint replacement. A retrospective study was conducted among 702 consecutive primary knee joint replacements performed between January 2009 and December 2012 in our department. Increased postoperative serum creatinine was considered indicative of postoperative renal injury according to RIFLE criteria. Sixty three patients (9.7%) had significant moderate or severe postoperative renal dysfunction in which 8 patients (1.2%) ended with severe and permanent renal impairment. Advanced age, low intraoperative blood pressure, hypertension, general anaesthesia, and prophylactic dicloxacillin were identified as significant risk factors. Male gender and BMI were independent risk factors for postoperative increase in serum creatinine. Smoking, female gender, diabetes mellitus and duration of surgery were not identified as significant risk factors.

Pooled Genome-Wide Analysis to Identify Novel Risk Loci for Pediatric Allergic Asthma

PubMed Central

Ricci, Giampaolo; Astolfi, Annalisa; Remondini, Daniel; Cipriani, Francesca; Formica, Serena; Dondi, Arianna; Pession, Andrea

2011-01-01

Background Genome-wide association studies of pooled DNA samples were shown to be a valuable tool to identify candidate SNPs associated to a phenotype. No such study was up to now applied to childhood allergic asthma, even if the very high complexity of asthma genetics is an appropriate field to explore the potential of pooled GWAS approach. Methodology/Principal Findings We performed a pooled GWAS and individual genotyping in 269 children with allergic respiratory diseases comparing allergic children with and without asthma. We used a modular approach to identify the most significant loci associated with asthma by combining silhouette statistics and physical distance method with cluster-adapted thresholding. We found 97% concordance between pooled GWAS and individual genotyping, with 36 out of 37 top-scoring SNPs significant at individual genotyping level. The most significant SNP is located inside the coding sequence of C5, an already identified asthma susceptibility gene, while the other loci regulate functions that are relevant to bronchial physiopathology, as immune- or inflammation-mediated mechanisms and airway smooth muscle contraction. Integration with gene expression data showed that almost half of the putative susceptibility genes are differentially expressed in experimental asthma mouse models. Conclusion/Significance Combined silhouette statistics and cluster-adapted physical distance threshold analysis of pooled GWAS data is an efficient method to identify candidate SNP associated to asthma development in an allergic pediatric population. PMID:21359210

Microarray-based DNA methylation study of Ewing's sarcoma of the bone.

PubMed

Park, Hye-Rim; Jung, Woon-Won; Kim, Hyun-Sook; Park, Yong-Koo

2014-10-01

Alterations in DNA methylation patterns are a hallmark of malignancy. However, the majority of epigenetic studies of Ewing's sarcoma have focused on the analysis of only a few candidate genes. Comprehensive studies are thus lacking and are required. The aim of the present study was to identify novel methylation markers in Ewing's sarcoma using microarray analysis. The current study reports the microarray-based DNA methylation study of 1,505 CpG sites of 807 cancer-related genes from 69 Ewing's sarcoma samples. The Illumina GoldenGate Methylation Cancer Panel I microarray was used, and with the appropriate controls (n=14), a total of 92 hypermethylated genes were identified in the Ewing's sarcoma samples. The majority of the hypermethylated genes were associated with cell adhesion, cell regulation, development and signal transduction. The overall methylation mean values were compared between patients who survived and those that did not. The overall methylation mean was significantly higher in the patients who did not survive (0.25±0.03) than in those who did (0.22±0.05) (P=0.0322). However, the overall methylation mean was not found to significantly correlate with age, gender or tumor location. GDF10 , OSM , APC and HOXA11 were the most significant differentially-methylated genes, however, their methylation levels were not found to significantly correlate with the survival rate. The DNA methylation profile of Ewing's sarcoma was characterized and 92 genes that were significantly hypermethylated were detected. A trend towards a more aggressive behavior was identified in the methylated group. The results of this study indicated that methylation may be significant in the development of Ewing's sarcoma.

Microarray-based DNA methylation study of Ewing’s sarcoma of the bone

PubMed Central

PARK, HYE-RIM; JUNG, WOON-WON; KIM, HYUN-SOOK; PARK, YONG-KOO

2014-01-01

Alterations in DNA methylation patterns are a hallmark of malignancy. However, the majority of epigenetic studies of Ewing’s sarcoma have focused on the analysis of only a few candidate genes. Comprehensive studies are thus lacking and are required. The aim of the present study was to identify novel methylation markers in Ewing’s sarcoma using microarray analysis. The current study reports the microarray-based DNA methylation study of 1,505 CpG sites of 807 cancer-related genes from 69 Ewing’s sarcoma samples. The Illumina GoldenGate Methylation Cancer Panel I microarray was used, and with the appropriate controls (n=14), a total of 92 hypermethylated genes were identified in the Ewing’s sarcoma samples. The majority of the hypermethylated genes were associated with cell adhesion, cell regulation, development and signal transduction. The overall methylation mean values were compared between patients who survived and those that did not. The overall methylation mean was significantly higher in the patients who did not survive (0.25±0.03) than in those who did (0.22±0.05) (P=0.0322). However, the overall methylation mean was not found to significantly correlate with age, gender or tumor location. GDF10, OSM, APC and HOXA11 were the most significant differentially-methylated genes, however, their methylation levels were not found to significantly correlate with the survival rate. The DNA methylation profile of Ewing’s sarcoma was characterized and 92 genes that were significantly hypermethylated were detected. A trend towards a more aggressive behavior was identified in the methylated group. The results of this study indicated that methylation may be significant in the development of Ewing’s sarcoma. PMID:25202378

Routine versus selective contrast imaging to identify the need for early re-intervention following laparoscopic fundoplication: A retrospective cohort study.

PubMed

Shahzad, Khalid; Menon, Ashok; Turner, Paul; Ward, Jeremy; Pursnani, Kishore; Alkhaffaf, Bilal

2015-08-01

The prompt recognition of complications is essential in reducing morbidity following anti-reflux surgery. Consequently, many centres employ a policy of routine post-operative contrast studies. The study aimed to examine whether routine contrast studies more effectively recognised early post-operative complications following anti-reflux surgery compared with selective use. This was a retrospective analysis of 240 adults who had undergone primary anti-reflux surgery. Selective use of water-soluble contrast swallows was employed for 115 patients (Group 1) while 125 patients (Group 2) had routine studies. 10 (0.9%) patients from Group 1 underwent contrast studies, four (40%) of which were abnormal. Routine studies in Group 2 identified thirty-two abnormalities (27%) however the inter-group difference was not significant (p = 0.32). Only one case from group 2 required immediate re-intervention. This was not statistically significant (p = 0.78). Multivariate analysis found no significant association between selective or routine imaging and re-intervention rates. One patient from group 2 presented three days following discharge with wrap migration requiring reoperation despite a normal post-operative study. Routine use of contrast imaging following anti-reflux and hiatus hernia surgery is not necessary. It does not identify a significantly greater number of post-operative complications in comparison to selective use. Additionally, routine use of contrast studies does not ensure the diagnosis of all complications in the post-operative period. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Genome-wide association study for rotator cuff tears identifies two significant single-nucleotide polymorphisms.

PubMed

Tashjian, Robert Z; Granger, Erin K; Farnham, James M; Cannon-Albright, Lisa A; Teerlink, Craig C

2016-02-01

The precise etiology of rotator cuff disease is unknown, but prior evidence suggests a role for genetic factors. Limited data exist identifying specific genes associated with rotator cuff tearing. The purpose of this study was to identify specific genes or genetic variants associated with rotator cuff tearing by a genome-wide association study with an independent set of rotator cuff tear cases. A set of 311 full-thickness rotator cuff tear cases genotyped on the Illumina 5M single-nucleotide polymorphism (SNP) platform were used in a genome-wide association study with 2641 genetically matched white population controls available from the Illumina iControls database. Tests of association were performed with GEMMA software at 257,558 SNPs that compose the intersection of Illumina SNP platforms and that passed general quality control metrics. SNPs were considered significant if P < 1.94 × 10(-7) (Bonferroni correction: 0.05/257,558). Tests of association revealed 2 significantly associated SNPs, one occurring in SAP30BP (rs820218; P = 3.8E-9) on chromosome 17q25 and another occurring in SASH1 (rs12527089; P = 1.9E-7) on chromosome 6q24. This study represents the first attempt to identify genetic factors influencing rotator cuff tearing by a genome-wide association study using a dense/complete set of SNPs. Two SNPs were significantly associated with rotator cuff tearing, residing in SAP30BP on chromosome 17 and SASH1 on chromosome 6. Both genes are associated with the cellular process of apoptosis. Identification of potential genes or genetic variants associated with rotator cuff tearing may help in identifying individuals at risk for the development of rotator cuff tearing. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

A review of interventions to reduce inter-observer variability in volume delineation in radiation oncology.

PubMed

Vinod, Shalini K; Min, Myo; Jameson, Michael G; Holloway, Lois C

2016-06-01

Inter-observer variability (IOV) in target volume and organ-at-risk (OAR) delineation is a source of potential error in radiation therapy treatment. The aims of this study were to identify interventions shown to reduce IOV in volume delineation. Medline and Pubmed databases were queried for relevant articles using various keywords to identify articles which evaluated IOV in target or OAR delineation for multiple (>2) observers. The search was limited to English language articles and to those published from 1 January 2000 to 31 December 2014. Reference lists of identified articles were scrutinised to identify relevant studies. Studies were included if they reported IOV in contouring before and after an intervention including the use of additional or alternative imaging. Fifty-six studies were identified. These were grouped into evaluation of guidelines (n = 9), teaching (n = 9), provision of an autocontour (n = 7) and the impact of imaging (n = 31) on IOV. Guidelines significantly reduced IOV in 7/9 studies. Teaching interventions reduced IOV in 8/9 studies, statistically significant in 4. The provision of an autocontour improved consistency of contouring in 6/7 studies, statistically significant in 5. The effect of additional imaging on IOV was variable. Pre-operative CT was useful in reducing IOV in contouring breast and liver cancers, PET scans in lung cancer, rectal cancer and lymphoma and MRI scans in OARs in head and neck cancers. Inter-observer variability in volume delineation can be reduced with the use of guidelines, provision of autocontours and teaching. The use of multimodality imaging is useful in certain tumour sites. © 2016 The Royal Australian and New Zealand College of Radiologists.

Is valve choice a significant determinant of paravalular leak post-transcatheter aortic valve implantation? A systematic review and meta-analysis.

PubMed

O'Sullivan, Katie E; Gough, Aideen; Segurado, Ricardo; Barry, Mitchel; Sugrue, Declan; Hurley, John

2014-05-01

Paravalvular regurgitation (PVR) following transcatheter aortic valve implantation (TAVI) is associated with poor survival. The two main valve delivery systems used to date differ significantly in both structure and deployment technique. The primary objective of this study was to perform a systematic review and meta-analysis of studies identifying PVR in patients post-TAVI using Medtronic CoreValve (MCV) and Edward Sapien (ES) valves in order to identify whether a significant difference exists between valve types. The secondary objective was to identify additional factors predisposing to PVR to provide an overview of the other associated considerations. A systematic review and meta-analysis of the current literature to identify PVR rate in patients with MCV and ES valves was performed. We also sought to examine other factors predisposing to PVR. A total of 5910 patients were identified from 9 studies. PVR rates for MCV and ES were analysed. MCV was associated with a higher PVR rate of 15.75% [95% confidence interval (CI) 12.48-19.32] compared with ES 3.93% [95% CI 1.05-8.38]. We separately reviewed predisposing factors associated with PVR. A formal comparison of the MCV and ES valve leakage rates by mixed-effects meta-regression with a fixed-effect moderator variable for valve type (MCV or ES) suggested a statistically significant difference in leakage rate between the two valve types (P = 0.0002). Unfavourable anatomical and pathological factors as well as valve choice have an impact on rates of PVR. Additionally, certain anatomical features dictate valve choice. A direct comparison of all the predisposing factors at this time is not possible and will require prospective multivariate analysis. There is, however, a significant difference in the PVR rates between valves based on the published observational data available to date. The ES valve associated with a lower incidence of PVR overall; therefore, we conclude that valve choice is indeed a significant determinant of PVR post-TAVI.

Prediagnostic Serum Biomarkers as Early Detection Tools for Pancreatic Cancer in a Large Prospective Cohort Study

PubMed Central

Nolen, Brian M.; Brand, Randall E.; Prosser, Denise; Velikokhatnaya, Liudmila; Allen, Peter J.; Zeh, Herbert J.; Grizzle, William E.; Lomakin, Aleksey; Lokshin, Anna E.

2014-01-01

Background The clinical management of pancreatic cancer is severely hampered by the absence of effective screening tools. Methods Sixty-seven biomarkers were evaluated in prediagnostic sera obtained from cases of pancreatic cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Results The panel of CA 19-9, OPN, and OPG, identified in a prior retrospective study, was not effective. CA 19-9, CEA, NSE, bHCG, CEACAM1 and PRL were significantly altered in sera obtained from cases greater than 1 year prior to diagnosis. Levels of CA 19-9, CA 125, CEA, PRL, and IL-8 were negatively associated with time to diagnosis. A training/validation study using alternate halves of the PLCO set failed to identify a biomarker panel with significantly improved performance over CA 19-9 alone. When the entire PLCO set was used for training at a specificity (SP) of 95%, a panel of CA 19-9, CEA, and Cyfra 21-1 provided significantly elevated sensitivity (SN) levels of 32.4% and 29.7% in samples collected <1 and >1 year prior to diagnosis, respectively, compared to SN levels of 25.7% and 17.2% for CA 19-9 alone. Conclusions Most biomarkers identified in previously conducted case/control studies are ineffective in prediagnostic samples, however several biomarkers were identified as significantly altered up to 35 months prior to diagnosis. Two newly derived biomarker combinations offered advantage over CA 19-9 alone in terms of SN, particularly in samples collected >1 year prior to diagnosis. However, the efficacy of biomarker-based tools remains limited at present. Several biomarkers demonstrated significant velocity related to time to diagnosis, an observation which may offer considerable potential for enhancements in early detection. PMID:24747429

Food Insecurity among Veterans: Findings from the Health and Retirement Study.

PubMed

Brostow, D P; Gunzburger, E; Thomas, K S

2017-01-01

We examined the prevalence of food insecurity in an older population, specifically assessing factors associated with food insecurity among U.S. military Veterans. Data from the 2012 wave of the Health and Retirement Study and the 2013 Health Care and Nutrition Mail Survey of 2560 male participants (1254 Veterans) were used to estimate the prevalence of food insecurity and to identify significant predictors of food insecurity among male Veterans. Among male Veterans, 6.4% reported food insecurity, compared to 11.9% of male non-veterans (p < 0.01). Younger age, difficulty with daily activities and depression were significantly associated with increased odds of food insecurity among male Veterans aged 50 to 64. In male Veterans age 65 years and older, current smoking, a psychiatric diagnosis and depression were significantly associated with increased odds of food insecurity. This study identified significant factors that may be used to target interventions to improve nutritional status among older male Veterans.

Historical Significance from Turkish Students' Perspective

ERIC Educational Resources Information Center

Avarogullari, Muhammet; Kolcu, Nurten

2016-01-01

The purpose of this study is to determine how students in a south-western province of Turkey employ historical significance which is one of the second order concepts of historical thinking. 44 11th and 12th grade students participated in the study. They were asked to identify the most significant 10 persons in the history and provide their reasons…

The Role of Difficulty in Identifying and Describing Feelings in Non-Suicidal Self-Injury Behavior (NSSI): Associations With Perceived Attachment Quality, Stressful Life Events, and Suicidal Ideation.

PubMed

Cerutti, Rita; Zuffianò, Antonio; Spensieri, Valentina

2018-01-01

Objective: Core alexithymic features, such as the difficulty in identifying and describing feelings, are associated with poor attachment styles and emotional trauma, which influence the capacity to regulate affect. Additionally, emotional regulation has been found to be the most commonly identified function associated with non-suicidal self-injury behavior (NSSI) in adolescents as they attempt to modulate strong emotions. However, few studies have examined the link between difficulty in identifying and describing feelings (core components of alexithymia), NSSI behaviors, quality of attachment, life stressors and suicidal ideation in healthy early adolescents. Consequently, this study aims to investigate these constructs and the relationship among them in a large non-clinical sample of adolescents. Methods: Seven hundred and nine middle school students (50.4% males), aged 10-15 years ( M = 12.6; SD = 1.06) were involved in this study. In order to investigate the variables considered in the study, the following measures were administered: the Deliberate Self-Harm Inventory exploring non-suicidal self-injurious behaviors; the Alexithymia Questionnaire for Children examining difficulty in identifying and describing feelings; the Inventory of Parent and Peer Attachment assessing the quality of parental and peer attachment; the Life Stressor Checklist-Revised outlining stressful/traumatic events and the Children's Depression Inventory evaluating suicidal ideation. Results: We found significantly positive relationships among difficulty in identifying and describing feelings, NSSI behaviors, stressful events, and suicidal ideation. Data indicated a significant negative association of difficulty in identifying and describing feelings with quality of attachment to parents and peers. Further findings highlighted that difficulty in identifying and describing feelings significantly mediated the effect of quality of attachment (parent and peer) on NSSI and suicidal ideation. Conclusion: The ability to identify and describing feelings is important to managing emotional expression and understanding the feelings of others, both crucial in attaining successful interpersonal relationships. Our data revealed that, while controlling for stressful life events, low levels of attachment may increase adolescents' difficulty in identifying and describing their own feelings, which in turn may increase the risk of both NSSI and suicidal ideation.

Amniotic fluid RNA gene expression profiling provides insights into the phenotype of Turner syndrome.

PubMed

Massingham, Lauren J; Johnson, Kirby L; Scholl, Thomas M; Slonim, Donna K; Wick, Heather C; Bianchi, Diana W

2014-09-01

Turner syndrome is a sex chromosome aneuploidy with characteristic malformations. Amniotic fluid, a complex biological material, could contribute to the understanding of Turner syndrome pathogenesis. In this pilot study, global gene expression analysis of cell-free RNA in amniotic fluid supernatant was utilized to identify specific genes/organ systems that may play a role in Turner syndrome pathophysiology. Cell-free RNA from amniotic fluid of five mid-trimester Turner syndrome fetuses and five euploid female fetuses matched for gestational age was extracted, amplified, and hybridized onto Affymetrix(®) U133 Plus 2.0 arrays. Significantly differentially regulated genes were identified using paired t tests. Biological interpretation was performed using Ingenuity Pathway Analysis and BioGPS gene expression atlas. There were 470 statistically significantly differentially expressed genes identified. They were widely distributed across the genome. XIST was significantly down-regulated (p < 0.0001); SHOX was not differentially expressed. One of the most highly represented organ systems was the hematologic/immune system, distinguishing the Turner syndrome transcriptome from other aneuploidies we previously studied. Manual curation of the differentially expressed gene list identified genes of possible pathologic significance, including NFATC3, IGFBP5, and LDLR. Transcriptomic differences in the amniotic fluid of Turner syndrome fetuses are due to genome-wide dysregulation. The hematologic/immune system differences may play a role in early-onset autoimmune dysfunction. Other genes identified with possible pathologic significance are associated with cardiac and skeletal systems, which are known to be affected in females with Turner syndrome. The discovery-driven approach described here may be useful in elucidating novel mechanisms of disease in Turner syndrome.

An ecological systems approach to bullying behaviors among middle school students in the United States.

PubMed

Lee, Chang-Hun

2011-05-01

The aim of this study is to identify an ecological prediction model of bullying behaviors. Based on an ecological systems theory, this study identifies significant factors influencing bullying behaviors at different levels of middle and high school. These levels include the microsystem, mesosystem, exosystem, and macrosystem. More specifically, the ecological factors investigated in this multilevel analysis are individual traits, family experiences, parental involvement, school climate, and community characteristics. Using data collected in 2008 from 485 randomly selected students in a school district, this study identifies a best-fitting structural model of bullying behavior. Findings suggest that the ecological model accounted for a high portion of variance in bullying behaviors. All of the ecological systems as well as individual traits were found to be significant influences on bullying behaviors either directly or indirectly.

Expression quantitative trait loci (eQTL) mapping in Puerto Rican children.

PubMed

Chen, Wei; Brehm, John M; Lin, Jerome; Wang, Ting; Forno, Erick; Acosta-Pérez, Edna; Boutaoui, Nadia; Canino, Glorisa; Celedón, Juan C

2015-01-01

Expression quantitative trait loci (eQTL) have been identified using tissue or cell samples from diverse human populations, thus enhancing our understanding of regulation of gene expression. However, few studies have attempted to identify eQTL in racially admixed populations such as Hispanics. We performed a systematic eQTL study to identify regulatory variants of gene expression in whole blood from 121 Puerto Rican children with (n = 63) and without (n = 58) asthma. Genome-wide genotyping was conducted using the Illumina Omni2.5M Bead Chip, and gene expression was assessed using the Illumina HT-12 microarray. After completing quality control, we performed a pair-wise genome analysis of ~15 K transcripts and ~1.3 M SNPs for both local and distal effects. This analysis was conducted under a regression framework adjusting for age, gender and principal components derived from both genotypic and mRNA data. We used a false discovery rate (FDR) approach to identify significant eQTL signals, which were next compared to top eQTL signals from existing eQTL databases. We then performed a pathway analysis for our top genes. We identified 36,720 local pairs in 3,391 unique genes and 1,851 distal pairs in 446 unique genes at FDR <0.05, corresponding to unadjusted P values lower than 1.5x10-4 and 4.5x10-9, respectively. A significant proportion of genes identified in our study overlapped with those identified in previous studies. We also found an enrichment of disease-related genes in our eQTL list. We present results from the first eQTL study in Puerto Rican children, who are members of a unique Hispanic cohort disproportionately affected with asthma, prematurity, obesity and other common diseases. Our study confirmed eQTL signals identified in other ethnic groups, while also detecting additional eQTLs unique to our study population. The identified eQTLs will help prioritize findings from future genome-wide association studies in Puerto Ricans.

Correlations between Developmental Kindergarten Screenings and Early Reading Indicators One Year Later

ERIC Educational Resources Information Center

Coughlan-Mainard, Kelly A.

2012-01-01

School districts in the U.S. are mandated to identify young children with disabilities. Developmental screeners are typically used to screen for such skill deficits. Academic tests are used in older students. A significant challenge is identifying children with potential learning disabilities early in their school career. This study identifies a…

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.

Joint source based morphometry identifies linked gray and white matter group differences

PubMed Central

Xu, Lai; Pearlson, Godfrey; Calhoun, Vince D.

2009-01-01

We present a multivariate approach called joint source based morphometry (jSBM), to identify linked gray and white matter regions which differ between groups. In jSBM, joint independent component analysis (jICA) is used to decompose preprocessed gray and white matter images into joint sources and statistical analysis is used to determine the significant joint sources showing group differences and their relationship to other variables of interest (e.g. age or sex). The identified joint sources are groupings of linked gray and white matter regions with common covariation among subjects. In this study, we first provide a simulation to validate the jSBM approach. To illustrate our method on real data, jSBM is then applied to structural magnetic resonance imaging (sMRI) data obtained from 120 chronic schizophrenia patients and 120 healthy controls to identify group differences. JSBM identified four joint sources as significantly associated with schizophrenia. Linked gray–white matter regions identified in each of the joint sources included: 1) temporal — corpus callosum, 2) occipital/frontal — inferior fronto-occipital fasciculus, 3) frontal/parietal/occipital/temporal —superior longitudinal fasciculus and 4) parietal/frontal — thalamus. Age effects on all four joint sources were significant, but sex effects were significant only for the third joint source. Our findings demonstrate that jSBM can exploit the natural linkage between gray and white matter by incorporating them into a unified framework. This approach is applicable to a wide variety of problems to study linked gray and white matter group differences. PMID:18992825

How to Improve Academic Optimism? an Inquiry from the Perspective of School Resource and Investment

ERIC Educational Resources Information Center

Wu, Jason Hsinchieh; Sheu, Tian-Ming

2015-01-01

Previous studies have identified many school variables which can have significant effect on academic optimism. However, most of these identified variables are leadership or psychological constructs; thus, it is often too abstract for school administrators to translate into real practice. Therefore, this study adopted the perspective of school…

Genome-wide association studies identify 25 genetic loci associated with resistance to Bacterial Cold Water Disease in rainbow trout

USDA-ARS?s Scientific Manuscript database

Bacterial cold water disease (BCWD) causes significant mortality and economic losses in salmonids aquaculture. In previous studies we have identified moderate-large effect QTL for BCWD resistance in rainbow trout (Oncorhynchus mykiss). However, the recent availability of a high density SNP array and...

Identifying Aspects of Parental Involvement that Affect the Academic Achievement of High School Students

ERIC Educational Resources Information Center

Roulette-McIntyre, Ovella; Bagaka's, Joshua G.; Drake, Daniel D.

2005-01-01

This study identified parental practices that relate positively to high school students' academic performance. Parents of 643 high school students participated in the study. Data analysis, using a multiple linear regression model, shows parent-school connection, student gender, and race are significant predictors of student academic performance.…

Gene expression of Caenorhabditis elegans neurons carries information on their synaptic connectivity.

PubMed

Kaufman, Alon; Dror, Gideon; Meilijson, Isaac; Ruppin, Eytan

2006-12-08

The claim that genetic properties of neurons significantly influence their synaptic network structure is a common notion in neuroscience. The nematode Caenorhabditis elegans provides an exciting opportunity to approach this question in a large-scale quantitative manner. Its synaptic connectivity network has been identified, and, combined with cellular studies, we currently have characteristic connectivity and gene expression signatures for most of its neurons. By using two complementary analysis assays we show that the expression signature of a neuron carries significant information about its synaptic connectivity signature, and identify a list of putative genes predicting neural connectivity. The current study rigorously quantifies the relation between gene expression and synaptic connectivity signatures in the C. elegans nervous system and identifies subsets of neurons where this relation is highly marked. The results presented and the genes identified provide a promising starting point for further, more detailed computational and experimental investigations.

Trans-Ethnic Meta-Analysis Identifies Common and Rare Variants Associated with Hepatocyte Growth Factor Levels in the Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Larson, Nicholas B.; Berardi, Cecilia; Decker, Paul A.; Wassel, Christina L.; Kirsch, Phillip S.; Pankow, James S.; Sale, Michele M.; de Andrade, Mariza; Sicotte, Hugues; Tang, Weihong; Hanson, Naomi Q.; Tsai, Michael Y.; Taylor, Kent D.; Bielinski, Suzette J.

2015-01-01

Summary Hepatocyte growth factor (HGF) is a mesenchyme-derived pleiotropic factor that regulates cell growth, motility, mitogenesis, and morphogenesis in a variety of cells, and increased serum levels of HGF have been linked to a number of clinical and subclinical cardiovascular disease phenotypes. However, little is currently known regarding what genetic factors influence HGF levels, despite evidence of substantial genetic contributions to HGF variation. Based upon ethnicity-stratified single-variant association analysis and trans-ethnic meta-analysis of 6201 participants of the Multi-Ethnic Study of Atherosclerosis (MESA), we discovered five statistically significant common and low-frequency variants: HGF missense polymorphism rs5745687 (p.E299K) as well as four variants (rs16844364, rs4690098, rs114303452, rs3748034) within or in proximity to HGFAC. We also identified two significant ethnicity-specific gene-level associations (A1BG in African Americans; FASN in Chinese Americans) based upon low-frequency/rare variants, while meta-analysis of gene-level results identified a significant association for HGFAC. However, identified single-variant associations explained modest proportions of the total trait variation and were not significantly associated with coronary artery calcium or coronary heart disease. Our findings indicate genetic factors influencing circulating HGF levels may be complex and ethnically diverse. PMID:25998175

Meta-Analysis of Genome-Wide Association Studies of Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Neale, Benjamin M.; Medland, Sarah E.; Ripke, Stephan; Asherson, Philip; Franke, Barbara; Lesch, Klaus-Peter; Faraone, Stephen V.; Nguyen, Thuy Trang; Schafer, Helmut; Holmans, Peter; Daly, Mark; Steinhausen, Hans-Christoph; Freitag, Christine; Reif, Andreas; Renner, Tobias J.; Romanos, Marcel; Romanos, Jasmin; Walitza, Susanne; Warnke, Andreas; Meyer, Jobst; Palmason, Haukur; Buitelaar, Jan; Vasquez, Alejandro Arias; Lambregts-Rommelse, Nanda; Gill, Michael; Anney, Richard J. L.; Langely, Kate; O'Donovan, Michael; Williams, Nigel; Owen, Michael; Thapar, Anita; Kent, Lindsey; Sergeant, Joseph; Roeyers, Herbert; Mick, Eric; Biederman, Joseph; Doyle, Alysa; Smalley, Susan; Loo, Sandra; Hakonarson, Hakon; Elia, Josephine; Todorov, Alexandre; Miranda, Ana; Mulas, Fernando; Ebstein, Richard P.; Rothenberger, Aribert; Banaschewski, Tobias; Oades, Robert D.; Sonuga-Barke, Edmund; McGough, James; Nisenbaum, Laura; Middleton, Frank; Hu, Xiaolan; Nelson, Stan

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. As prior genome-wide association studies (GWAS) have not yielded significant results, we conducted a meta-analysis of…

Meta-analysis identifies gene-by-environment interactions as demonstrated in a study of 4,965 mice.

PubMed

Kang, Eun Yong; Han, Buhm; Furlotte, Nicholas; Joo, Jong Wha J; Shih, Diana; Davis, Richard C; Lusis, Aldons J; Eskin, Eleazar

2014-01-01

Identifying environmentally-specific genetic effects is a key challenge in understanding the structure of complex traits. Model organisms play a crucial role in the identification of such gene-by-environment interactions, as a result of the unique ability to observe genetically similar individuals across multiple distinct environments. Many model organism studies examine the same traits but under varying environmental conditions. For example, knock-out or diet-controlled studies are often used to examine cholesterol in mice. These studies, when examined in aggregate, provide an opportunity to identify genomic loci exhibiting environmentally-dependent effects. However, the straightforward application of traditional methodologies to aggregate separate studies suffers from several problems. First, environmental conditions are often variable and do not fit the standard univariate model for interactions. Additionally, applying a multivariate model results in increased degrees of freedom and low statistical power. In this paper, we jointly analyze multiple studies with varying environmental conditions using a meta-analytic approach based on a random effects model to identify loci involved in gene-by-environment interactions. Our approach is motivated by the observation that methods for discovering gene-by-environment interactions are closely related to random effects models for meta-analysis. We show that interactions can be interpreted as heterogeneity and can be detected without utilizing the traditional uni- or multi-variate approaches for discovery of gene-by-environment interactions. We apply our new method to combine 17 mouse studies containing in aggregate 4,965 distinct animals. We identify 26 significant loci involved in High-density lipoprotein (HDL) cholesterol, many of which are consistent with previous findings. Several of these loci show significant evidence of involvement in gene-by-environment interactions. An additional advantage of our meta-analysis approach is that our combined study has significantly higher power and improved resolution compared to any single study thus explaining the large number of loci discovered in the combined study.

Meta-Analysis Identifies Gene-by-Environment Interactions as Demonstrated in a Study of 4,965 Mice

PubMed Central

Joo, Jong Wha J.; Shih, Diana; Davis, Richard C.; Lusis, Aldons J.; Eskin, Eleazar

2014-01-01

Identifying environmentally-specific genetic effects is a key challenge in understanding the structure of complex traits. Model organisms play a crucial role in the identification of such gene-by-environment interactions, as a result of the unique ability to observe genetically similar individuals across multiple distinct environments. Many model organism studies examine the same traits but under varying environmental conditions. For example, knock-out or diet-controlled studies are often used to examine cholesterol in mice. These studies, when examined in aggregate, provide an opportunity to identify genomic loci exhibiting environmentally-dependent effects. However, the straightforward application of traditional methodologies to aggregate separate studies suffers from several problems. First, environmental conditions are often variable and do not fit the standard univariate model for interactions. Additionally, applying a multivariate model results in increased degrees of freedom and low statistical power. In this paper, we jointly analyze multiple studies with varying environmental conditions using a meta-analytic approach based on a random effects model to identify loci involved in gene-by-environment interactions. Our approach is motivated by the observation that methods for discovering gene-by-environment interactions are closely related to random effects models for meta-analysis. We show that interactions can be interpreted as heterogeneity and can be detected without utilizing the traditional uni- or multi-variate approaches for discovery of gene-by-environment interactions. We apply our new method to combine 17 mouse studies containing in aggregate 4,965 distinct animals. We identify 26 significant loci involved in High-density lipoprotein (HDL) cholesterol, many of which are consistent with previous findings. Several of these loci show significant evidence of involvement in gene-by-environment interactions. An additional advantage of our meta-analysis approach is that our combined study has significantly higher power and improved resolution compared to any single study thus explaining the large number of loci discovered in the combined study. PMID:24415945

Biomarkers for early detection of pancreatic cancer — EDRN Public Portal

Cancer.gov

Background: The clinical management of pancreatic cancer is severely hampered by the absence of effective screening tools. Methods: Sixty-seven biomarkers were evaluated in prediagnostic sera obtained from cases of pancreatic cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Results: The panel of CA 19-9, OPN, and OPG, identified in a prior retrospective study, was not effective. CA 19-9, CEA, NSE, bHCG, CEACAM1 and PRL were significantly altered in sera obtained from cases greater than 1 year prior to diagnosis. Levels of CA 19-9, CA 125, CEA, PRL, and IL-8 were negatively correlated with time to diagnosis. A training/validation study using alternate halves of the PLCO set failed to identify a biomarker panel with significantly improved performance over CA 19-9 alone. When the entire PLCO set was used for training at a specificity (SP) of 95%, a panel of CA 19-9, CEA, and Cyfra 21-1 provided significantly elevated sensitivity (SN) levels of 32.4% and 29.7% in samples collected 1 year prior to diagnosis, respectively, compared to SN levels of 25.7% and 17.2% for CA 19-9 alone. Conclusions: Most biomarkers identified in previously conducted case/control studies are ineffective in prediagnostic samples, however several biomarkers were identified as significantly altered up to 35 months prior to diagnosis. Two newly derived biomarker combination offered some advantage of CA 19-9 alone in terms of SN, particularly in samples collected >1 year prior to diagnosis, however further study will be needed to fully define the implications of these findings.

The challenges, advantages and future of phenome-wide association studies.

PubMed

Hebbring, Scott J

2014-02-01

Over the last decade, significant technological breakthroughs have revolutionized human genomic research in the form of genome-wide association studies (GWASs). GWASs have identified thousands of statistically significant genetic variants associated with hundreds of human conditions including many with immunological aetiologies (e.g. multiple sclerosis, ankylosing spondylitis and rheumatoid arthritis). Unfortunately, most GWASs fail to identify clinically significant associations. Identifying biologically significant variants by GWAS also presents a challenge. The GWAS is a phenotype-to-genotype approach. As a complementary/alternative approach to the GWAS, investigators have begun to exploit extensive electronic medical record systems to conduct a genotype-to-phenotype approach when studying human disease - specifically, the phenome-wide association study (PheWAS). Although the PheWAS approach is in its infancy, this method has already demonstrated its capacity to rediscover important genetic associations related to immunological diseases/conditions. Furthermore, PheWAS has the advantage of identifying genetic variants with pleiotropic properties. This is particularly relevant for HLA variants. For example, PheWAS results have demonstrated that the HLA-DRB1 variant associated with multiple sclerosis may also be associated with erythematous conditions including rosacea. Likewise, PheWAS has demonstrated that the HLA-B genotype is not only associated with spondylopathies, uveitis, and variability in platelet count, but may also play an important role in other conditions, such as mastoiditis. This review will discuss and compare general PheWAS methodologies, describe both the challenges and advantages of the PheWAS, and provide insight into the potential directions in which PheWAS may lead. © 2013 The Authors. Immunology Published by John Wiley & Sons Ltd.

Significant events in psychotherapy: An update of research findings.

PubMed

Timulak, Ladislav

2010-11-01

Significant events research represents a specific approach to studying client-identified important moments in the therapy process. The current study provides an overview of the significant events research conducted, the methodology used together with findings and implications. PsychInfo database was searched with keywords such as significant events, important events, significant moments, important moments, and counselling or psychotherapy. The references of the selected studies were also searched. This process led to the identification of 41 primary studies that used client-identified significant event(s) as a main or secondary focus of the study. These were consequently reviewed with regard to their methodology and findings. The findings are presented according to type of study conducted. The impacts of helpful events reported by clients are focused on contributions to therapeutic relationship and to in-session outcomes. Hindering events focus on some client disappointment with the therapist or therapy. The group therapy modality highlighted additional helpful impacts (like learning from others). Perspectives on what is significant in therapy differ between clients and therapists. The intensive qualitative studies reviewed confirm that the processes involved in significant events are complex and ambiguous. Studies show that the helpful events may also contain many hindering elements and that specific events are deeply contextually embedded in the preceding events of therapy. Some studies suggest that helpful significant events are therapeutically productive although this may need to be established further. Specific intensive studies show that the clients' perceptions in therapy may differ dramatically from that of the therapist. Furthermore, the relational and emotional aspects of significant moments may be more important for the clients than the cognitive aspects of therapy which are frequently stressed by therapists. 2010 The British Psychological Society.

A systems biology strategy to identify molecular mechanisms of action and protein indicators of traumatic brain injury.

PubMed

Yu, Chenggang; Boutté, Angela; Yu, Xueping; Dutta, Bhaskar; Feala, Jacob D; Schmid, Kara; Dave, Jitendra; Tawa, Gregory J; Wallqvist, Anders; Reifman, Jaques

2015-02-01

The multifactorial nature of traumatic brain injury (TBI), especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior, has confounded attempts to elucidate the pathology underlying the progression of TBI. Here, systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury. To this end, we performed a meta-analysis of four distinct high-throughput gene expression studies involving different animal models of TBI. By using canonical pathways and a large human protein-interaction network as a scaffold, we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies. At 24 hr after injury, the significantly activated molecular signatures were nonspecific to TBI, whereas the significantly suppressed molecular signatures were specific to the nervous system. In particular, we identified a suppressed subnetwork consisting of 58 highly interacting, coregulated proteins associated with synaptic function. We selected three proteins from this subnetwork, postsynaptic density protein 95, nitric oxide synthase 1, and disrupted in schizophrenia 1, and hypothesized that their abundance would be significantly reduced after TBI. In a penetrating ballistic-like brain injury rat model of severe TBI, Western blot analysis confirmed our hypothesis. In addition, our analysis recovered 12 previously identified protein biomarkers of TBI. The results suggest that systems biology may provide an efficient, high-yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI. © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease.

PubMed

Brant, Steven R; Okou, David T; Simpson, Claire L; Cutler, David J; Haritunians, Talin; Bradfield, Jonathan P; Chopra, Pankaj; Prince, Jarod; Begum, Ferdouse; Kumar, Archana; Huang, Chengrui; Venkateswaran, Suresh; Datta, Lisa W; Wei, Zhi; Thomas, Kelly; Herrinton, Lisa J; Klapproth, Jan-Micheal A; Quiros, Antonio J; Seminerio, Jenifer; Liu, Zhenqiu; Alexander, Jonathan S; Baldassano, Robert N; Dudley-Brown, Sharon; Cross, Raymond K; Dassopoulos, Themistocles; Denson, Lee A; Dhere, Tanvi A; Dryden, Gerald W; Hanson, John S; Hou, Jason K; Hussain, Sunny Z; Hyams, Jeffrey S; Isaacs, Kim L; Kader, Howard; Kappelman, Michael D; Katz, Jeffry; Kellermayer, Richard; Kirschner, Barbara S; Kuemmerle, John F; Kwon, John H; Lazarev, Mark; Li, Ellen; Mack, David; Mannon, Peter; Moulton, Dedrick E; Newberry, Rodney D; Osuntokun, Bankole O; Patel, Ashish S; Saeed, Shehzad A; Targan, Stephan R; Valentine, John F; Wang, Ming-Hsi; Zonca, Martin; Rioux, John D; Duerr, Richard H; Silverberg, Mark S; Cho, Judy H; Hakonarson, Hakon; Zwick, Michael E; McGovern, Dermot P B; Kugathasan, Subra

2017-01-01

The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn's disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P < 5.0 × 10 -8 in meta-analysis with a nominal evidence (P < .05) in each scan were considered to have genome-wide significance. We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P < 1.6 × 10 -6 ): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on conditioning), IL12B,PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20 (in strong linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC. Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated with IBD at the HLA locus, contained SNPs with unique association patterns with African-specific alleles. We performed a genome-wide association study of African Americans with IBD and identified loci associated with UC in only this population; we also replicated IBD, CD, and UC loci identified in European populations. The detection of variants associated with IBD risk in only people of African descent demonstrates the importance of studying the genetics of IBD and other complex diseases in populations beyond those of European ancestry. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa

PubMed Central

Huckins, L M; Hatzikotoulas, K; Southam, L; Thornton, L M; Steinberg, J; Aguilera-McKay, F; Treasure, J; Schmidt, U; Gunasinghe, C; Romero, A; Curtis, C; Rhodes, D; Moens, J; Kalsi, G; Dempster, D; Leung, R; Keohane, A; Burghardt, R; Ehrlich, S; Hebebrand, J; Hinney, A; Ludolph, A; Walton, E; Deloukas, P; Hofman, A; Palotie, A; Palta, P; van Rooij, F J A; Stirrups, K; Adan, R; Boni, C; Cone, R; Dedoussis, G; van Furth, E; Gonidakis, F; Gorwood, P; Hudson, J; Kaprio, J; Kas, M; Keski-Rahonen, A; Kiezebrink, K; Knudsen, G-P; Slof-Op 't Landt, M C T; Maj, M; Monteleone, A M; Monteleone, P; Raevuori, A H; Reichborn-Kjennerud, T; Tozzi, F; Tsitsika, A; van Elburg, A; Adan, R A H; Alfredsson, L; Ando, T; Andreassen, O A; Aschauer, H; Baker, J H; Barrett, J C; Bencko, V; Bergen, A W; Berrettini, W H; Birgegard, A; Boni, C; Boraska Perica, V; Brandt, H; Breen, G; Bulik, C M; Carlberg, L; Cassina, M; Cichon, S; Clementi, M; Cohen-Woods, S; Coleman, J; Cone, R D; Courtet, P; Crawford, S; Crow, S; Crowley, J; Danner, U N; Davis, O S P; de Zwaan, M; Dedoussis, G; Degortes, D; DeSocio, J E; Dick, D M; Dikeos, D; Dina, C; Ding, B; Dmitrzak-Weglarz, M; Docampo, E; Duncan, L; Egberts, K; Ehrlich, S; Escaramís, G; Esko, T; Espeseth, T; Estivill, X; Favaro, A; Fernández-Aranda, F; Fichter, M M; Finan, C; Fischer, K; Floyd, J A B; Foretova, L; Forzan, M; Franklin, C S; Gallinger, S; Gambaro, G; Gaspar, H A; Giegling, I; Gonidakis, F; Gorwood, P; Gratacos, M; Guillaume, S; Guo, Y; Hakonarson, H; Halmi, K A; Hatzikotoulas, K; Hauser, J; Hebebrand, J; Helder, S; Herms, S; Herpertz-Dahlmann, B; Herzog, W; Hilliard, C E; Hinney, A; Hübel, C; Huckins, L M; Hudson, J I; Huemer, J; Inoko, H; Janout, V; Jiménez-Murcia, S; Johnson, C; Julià, A; Juréus, A; Kalsi, G; Kaminska, D; Kaplan, A S; Kaprio, J; Karhunen, L; Karwautz, A; Kas, M J H; Kaye, W; Kennedy, J L; Keski-Rahkonen, A; Kiezebrink, K; Klareskog, L; Klump, K L; Knudsen, G P S; Koeleman, B P C; Koubek, D; La Via, M C; Landén, M; Le Hellard, S; Levitan, R D; Li, D; Lichtenstein, P; Lilenfeld, L; Lissowska, J; Lundervold, A; Magistretti, P; Maj, M; Mannik, K; Marsal, S; Martin, N; Mattingsdal, M; McDevitt, S; McGuffin, P; Merl, E; Metspalu, A; Meulenbelt, I; Micali, N; Mitchell, J; Mitchell, K; Monteleone, P; Monteleone, A M; Mortensen, P; Munn-Chernoff, M A; Navratilova, M; Nilsson, I; Norring, C; Ntalla, I; Ophoff, R A; O'Toole, J K; Palotie, A; Pante, J; Papezova, H; Pinto, D; Rabionet, R; Raevuori, A; Rajewski, A; Ramoz, N; Rayner, N W; Reichborn-Kjennerud, T; Ripatti, S; Roberts, M; Rotondo, A; Rujescu, D; Rybakowski, F; Santonastaso, P; Scherag, A; Scherer, S W; Schmidt, U; Schork, N J; Schosser, A; Slachtova, L; Sladek, R; Slagboom, P E; Slof-Op 't Landt, M C T; Slopien, A; Soranzo, N; Southam, L; Steen, V M; Strengman, E; Strober, M; Sullivan, P F; Szatkiewicz, J P; Szeszenia-Dabrowska, N; Tachmazidou, I; Tenconi, E; Thornton, L M; Tortorella, A; Tozzi, F; Treasure, J; Tsitsika, A; Tziouvas, K; van Elburg, A A; van Furth, E F; Wagner, G; Walton, E; Watson, H; Wichmann, H-E; Widen, E; Woodside, D B; Yanovski, J; Yao, S; Yilmaz, Z; Zeggini, E; Zerwas, S; Zipfel, S; Collier, D A; Sullivan, P F; Breen, G; Bulik, C M; Zeggini, E

2018-01-01

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10−6), and rs7700147, an intergenic variant (P=2.93 × 10−5). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes. PMID:29155802

Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa.

PubMed

Huckins, L M; Hatzikotoulas, K; Southam, L; Thornton, L M; Steinberg, J; Aguilera-McKay, F; Treasure, J; Schmidt, U; Gunasinghe, C; Romero, A; Curtis, C; Rhodes, D; Moens, J; Kalsi, G; Dempster, D; Leung, R; Keohane, A; Burghardt, R; Ehrlich, S; Hebebrand, J; Hinney, A; Ludolph, A; Walton, E; Deloukas, P; Hofman, A; Palotie, A; Palta, P; van Rooij, F J A; Stirrups, K; Adan, R; Boni, C; Cone, R; Dedoussis, G; van Furth, E; Gonidakis, F; Gorwood, P; Hudson, J; Kaprio, J; Kas, M; Keski-Rahonen, A; Kiezebrink, K; Knudsen, G-P; Slof-Op 't Landt, M C T; Maj, M; Monteleone, A M; Monteleone, P; Raevuori, A H; Reichborn-Kjennerud, T; Tozzi, F; Tsitsika, A; van Elburg, A; Collier, D A; Sullivan, P F; Breen, G; Bulik, C M; Zeggini, E

2018-05-01

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10 -6 ), and rs7700147, an intergenic variant (P=2.93 × 10 -5 ). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes.

Genome-wide association study in Asia-adapted tropical maize reveals novel and explored genomic regions for sorghum downy mildew resistance.

PubMed

Rashid, Zerka; Singh, Pradeep Kumar; Vemuri, Hindu; Zaidi, Pervez Haider; Prasanna, Boddupalli Maruthi; Nair, Sudha Krishnan

2018-01-10

Globally, downy mildews are among the important foliar diseases of maize that cause significant yield losses. We conducted a genome-wide association study for sorghum downy mildew (SDM; Peronosclerospora sorghi) resistance in a panel of 368 inbred lines adapted to the Asian tropics. High density SNPs from Genotyping-by-sequencing were used in GWAS after controlling for population structure and kinship in the panel using a single locus mixed model. The study identified a set of 26 SNPs that were significantly associated with SDM resistance, with Bonferroni corrected P values ≤ 0.05. Among all the identified SNPs, the minor alleles were found to be favorable to SDM resistance in the mapping panel. Trend regression analysis with 16 independent genetic variants including 12 SNPs and four haplotype blocks identified SNP S2_6154311 on chromosome 2 with P value 2.61E-24 and contributing 26.7% of the phenotypic variation. Six of the SNPs/haplotypes were within the same chromosomal bins as the QTLs for SDM resistance mapped in previous studies. Apart from this, eight novel genomic regions for SDM resistance were identified in this study; they need further validation before being applied in the breeding pipeline. Ten SNPs identified in this study were co-located in reported mildew resistance genes.

Predicting Intentional Communication in Preverbal Preschoolers with Autism Spectrum Disorder.

PubMed

Sandbank, Micheal; Woynaroski, Tiffany; Watson, Linda R; Gardner, Elizabeth; Keçeli Kaysili, Bahar; Yoder, Paul

2017-06-01

Intentional communication has previously been identified as a value-added predictor of expressive language in preverbal preschoolers with autism spectrum disorder. In the present study, we sought to identify value-added predictors of intentional communication. Of five theoretically-motivated putative predictors of intentional communication measured early in the study (at study entry and 4 months after), three had significant zero-order correlations with later intentional communication (12 months after study entry) and were thus added to a linear model that predicted later intentional communication scores controlling for initial intentional communication scores at study entry. After controlling for initial intentional communication, early motor imitation was the only predictor that accounted for a significant amount of variance in children's later intentional communication.

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.

Genetic effects of PDGFRB and MARCH1 identified in GWAS revealing strong associations with semen production traits in Chinese Holstein bulls.

PubMed

Liu, Shuli; Yin, Hongwei; Li, Cong; Qin, Chunhua; Cai, Wentao; Cao, Mingyue; Zhang, Shengli

2017-07-03

Using a genome-wide association study strategy, our previous study discovered 19 significant single-nucleotide polymorphisms (SNPs) related to semen production traits in Chinese Holstein bulls. Among them, three SNPs were within or close to the phosphodiesterase 3A (PDE3A), membrane associated ring-CH-type finger 1 (MARCH1) and platelet derived growth factor receptor beta (PDGFRB) genes. The present study was designed with the objectives of identifying genetic polymorphism of the PDE3A, PDGFRB and MARCH1 genes and their effects on semen production traits in a Holstein bull population. A total of 20 SNPs were detected and genotyped in 730 bulls. Association analyses using de-regressed estimated breeding values of each semen production trait revealed four statistically significant SNPs for one or more semen production traits (P < 0.05): one SNP was located downstream of PDGFRB and three SNPs were located in the promoter of MARCH1. Interestingly, for MARCH1, haplotype-based analysis revealed significant associations of haplotypes with semen volume per ejaculate. Furthermore, high expression of the MARCH1 gene was observed in sperm cells. One SNP (rs43445726) in the regulatory region of MARCH1 had a significant effect on gene expression. Our study demonstrated the significant associations of genetic variants of the PDGFRB and MARCH1 genes with semen production traits. The identified SNPs may serve as genetic markers to optimize breeding programs for semen production traits in Holstein bull populations.

Assessing mental stress from the photoplethysmogram: a numerical study

PubMed Central

Charlton, Peter H; Celka, Patrick; Farukh, Bushra; Chowienczyk, Phil; Alastruey, Jordi

2018-01-01

Abstract Objective: Mental stress is detrimental to cardiovascular health, being a risk factor for coronary heart disease and a trigger for cardiac events. However, it is not currently routinely assessed. The aim of this study was to identify features of the photoplethysmogram (PPG) pulse wave which are indicative of mental stress. Approach: A numerical model of pulse wave propagation was used to simulate blood pressure signals, from which simulated PPG pulse waves were estimated using a transfer function. Pulse waves were simulated at six levels of stress by changing the model input parameters both simultaneously and individually, in accordance with haemodynamic changes associated with stress. Thirty-two feature measurements were extracted from pulse waves at three measurement sites: the brachial, radial and temporal arteries. Features which changed significantly with stress were identified using the Mann–Kendall monotonic trend test. Main results: Seventeen features exhibited significant trends with stress in measurements from at least one site. Three features showed significant trends at all three sites: the time from pulse onset to peak, the time from the dicrotic notch to pulse end, and the pulse rate. More features showed significant trends at the radial artery (15) than the brachial (8) or temporal (7) arteries. Most features were influenced by multiple input parameters. Significance: The features identified in this study could be used to monitor stress in healthcare and consumer devices. Measurements at the radial artery may provide superior performance than the brachial or temporal arteries. In vivo studies are required to confirm these observations. PMID:29658894

Integrating genome-wide association study and expression quantitative trait loci data identifies multiple genes and gene set associated with neuroticism.

PubMed

Fan, Qianrui; Wang, Wenyu; Hao, Jingcan; He, Awen; Wen, Yan; Guo, Xiong; Wu, Cuiyan; Ning, Yujie; Wang, Xi; Wang, Sen; Zhang, Feng

2017-08-01

Neuroticism is a fundamental personality trait with significant genetic determinant. To identify novel susceptibility genes for neuroticism, we conducted an integrative analysis of genomic and transcriptomic data of genome wide association study (GWAS) and expression quantitative trait locus (eQTL) study. GWAS summary data was driven from published studies of neuroticism, totally involving 170,906 subjects. eQTL dataset containing 927,753 eQTLs were obtained from an eQTL meta-analysis of 5311 samples. Integrative analysis of GWAS and eQTL data was conducted by summary data-based Mendelian randomization (SMR) analysis software. To identify neuroticism associated gene sets, the SMR analysis results were further subjected to gene set enrichment analysis (GSEA). The gene set annotation dataset (containing 13,311 annotated gene sets) of GSEA Molecular Signatures Database was used. SMR single gene analysis identified 6 significant genes for neuroticism, including MSRA (p value=2.27×10 -10 ), MGC57346 (p value=6.92×10 -7 ), BLK (p value=1.01×10 -6 ), XKR6 (p value=1.11×10 -6 ), C17ORF69 (p value=1.12×10 -6 ) and KIAA1267 (p value=4.00×10 -6 ). Gene set enrichment analysis observed significant association for Chr8p23 gene set (false discovery rate=0.033). Our results provide novel clues for the genetic mechanism studies of neuroticism. Copyright © 2017. Published by Elsevier Inc.

An Ecological Systems Approach to Bullying Behaviors among Middle School Students in the United States

ERIC Educational Resources Information Center

Lee, Chang-Hun

2011-01-01

The aim of this study is to identify an ecological prediction model of bullying behaviors. Based on an ecological systems theory, this study identifies significant factors influencing bullying behaviors at different levels of middle and high school. These levels include the microsystem, mesosystem, exosystem, and macrosystem. More specifically,…

Transcriptome Analysis of Three Sheep Intestinal Regions reveals Key Pathways and Hub Regulatory Genes of Large Intestinal Lipid Metabolism.

PubMed

Chao, Tianle; Wang, Guizhi; Ji, Zhibin; Liu, Zhaohua; Hou, Lei; Wang, Jin; Wang, Jianmin

2017-07-13

The large intestine, also known as the hindgut, is an important part of the animal digestive system. Recent studies on digestive system development in ruminants have focused on the rumen and the small intestine, but the molecular mechanisms underlying sheep large intestine metabolism remain poorly understood. To identify genes related to intestinal metabolism and to reveal molecular regulation mechanisms, we sequenced and compared the transcriptomes of mucosal epithelial tissues among the cecum, proximal colon and duodenum. A total of 4,221 transcripts from 3,254 genes were identified as differentially expressed transcripts. Between the large intestine and duodenum, differentially expressed transcripts were found to be significantly enriched in 6 metabolism-related pathways, among which PPAR signaling was identified as a key pathway. Three genes, CPT1A, LPL and PCK1, were identified as higher expression hub genes in the large intestine. Between the cecum and colon, differentially expressed transcripts were significantly enriched in 5 lipid metabolism related pathways, and CEPT1 and MBOAT1 were identified as hub genes. This study provides important information regarding the molecular mechanisms of intestinal metabolism in sheep and may provide a basis for further study.

Early gene expression during natural spinal cord regeneration in the salamander Ambystoma mexicanum.

PubMed

Monaghan, James R; Walker, John A; Page, Robert B; Putta, Srikrishna; Beachy, Christopher K; Voss, S Randal

2007-04-01

In contrast to mammals, salamanders have a remarkable ability to regenerate their spinal cord and recover full movement and function after tail amputation. To identify genes that may be associated with this greater regenerative ability, we designed an oligonucleotide microarray and profiled early gene expression during natural spinal cord regeneration in Ambystoma mexicanum. We sampled tissue at five early time points after tail amputation and identified genes that registered significant changes in mRNA abundance during the first 7 days of regeneration. A list of 1036 statistically significant genes was identified. Additional statistical and fold change criteria were applied to identify a smaller list of 360 genes that were used to describe predominant expression patterns and gene functions. Our results show that a diverse injury response is activated in concert with extracellular matrix remodeling mechanisms during the early acute phase of natural spinal cord regeneration. We also report gene expression similarities and differences between our study and studies that have profiled gene expression after spinal cord injury in rat. Our study illustrates the utility of a salamander model for identifying genes and gene functions that may enhance regenerative ability in mammals.

Meta-analysis identifies common variants associated with body mass index in East Asians

PubMed Central

Wen, Wanqing; Cho, Yoon Shin; Zheng, Wei; Dorajoo, Rajkumar; Kato, Norihiro; Qi, Lu; Chen, Chien-Hsiun; Delahanty, Ryan J.; Okada, Yukinori; Tabara, Yasuharu; Gu, Dongfeng; Zhu, Dingliang; Haiman, Christopher A.; Mo, Zengnan; Gao, Yu-Tang; Saw, Seang Mei; Go, Min Jin; Takeuchi, Fumihiko; Chang, Li-Ching; Kokubo, Yoshihiro; Liang, Jun; Hao, Mei; Marchand, Loic Le; Zhang, Yi; Hu, Yanling; Wong, Tien Yin; Long, Jirong; Han, Bok-Ghee; Kubo, Michiaki; Yamamoto, Ken; Su, Mei-Hsin; Miki, Tetsuro; Henderson, Brian E.; Song, Huaidong; Tan, Aihua; He, Jiang; Ng, Daniel P.-K.; Cai, Qiuyin; Tsunoda, Tatsuhiko; Tsai, Fuu-Jen; Iwai, Naoharu; Chen, Gary K.; Shi, Jiajun; Xu, Jianfeng; Sim, Xueling; Xiang, Yong-Bing; Maeda, Shiro; Ong, Rick T.H.; Li, Chun; Nakamura, Yusuke; Aung, Tin; Kamatani, Naoyuki; Liu, Jian Jun; Lu, Wei; Yokota, Mitsuhiro; Seielstad, Mark; Fann, Cathy S.J.; Wu, Jer-Yuarn; Lee, Jong-Young; Hu, Frank B.; Tanaka, Toshihiro; Tai, E. Shyong; Shu, Xiao Ou

2012-01-01

Multiple genetic loci associated with obesity or body mass index (BMI) have been identified through genome-wide association studies conducted predominantly in populations of European ancestry. We conducted a meta-analysis of associations between BMI and approximately 2.4 million SNPs in 27,715 East Asians, followed by in silico and de novo replication in 37,691 and 17,642 additional East Asians, respectively. We identified ten BMI-associated loci at the genome-wide significance level (P<5.0×10−8), including seven previously identified loci (FTO, SEC16B, MC4R, GIPR/QPCTL, ADCY3/RBJ, BDNF, and MAP2K5) and three novel loci in or near the CDKAL1,PCSK1, and GP2 genes. Three additional loci nearly reached the genome-wide significance threshold, including two previously identified loci in the GNPDA2 and TFAP2B genes and a new locus near PAX6, which all had P<5.0×10−7. Findings from this study may shed light on new pathways involved in obesity and demonstrate the value of conducting genetic studies in non-European populations. PMID:22344219

High-resolution copy number variation analysis of schizophrenia in Japan.

PubMed

Kushima, I; Aleksic, B; Nakatochi, M; Shimamura, T; Shiino, T; Yoshimi, A; Kimura, H; Takasaki, Y; Wang, C; Xing, J; Ishizuka, K; Oya-Ito, T; Nakamura, Y; Arioka, Y; Maeda, T; Yamamoto, M; Yoshida, M; Noma, H; Hamada, S; Morikawa, M; Uno, Y; Okada, T; Iidaka, T; Iritani, S; Yamamoto, T; Miyashita, M; Kobori, A; Arai, M; Itokawa, M; Cheng, M-C; Chuang, Y-A; Chen, C-H; Suzuki, M; Takahashi, T; Hashimoto, R; Yamamori, H; Yasuda, Y; Watanabe, Y; Nunokawa, A; Someya, T; Ikeda, M; Toyota, T; Yoshikawa, T; Numata, S; Ohmori, T; Kunimoto, S; Mori, D; Iwata, N; Ozaki, N

2017-03-01

Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (<100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio=3.04, P=9.3 × 10 -9 , 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novo CNVs (e.g., MBD5 deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novo CNVs and variable expressivity of CNVs.

Genome-wide association study meta-analysis identifies five new loci for systemic lupus erythematosus.

PubMed

Julià, Antonio; López-Longo, Francisco Javier; Pérez Venegas, José J; Bonàs-Guarch, Silvia; Olivé, Àlex; Andreu, José Luís; Aguirre-Zamorano, Mª Ángeles; Vela, Paloma; Nolla, Joan M; de la Fuente, José Luís Marenco; Zea, Antonio; Pego-Reigosa, José María; Freire, Mercedes; Díez, Elvira; Rodríguez-Almaraz, Esther; Carreira, Patricia; Blanco, Ricardo; Taboada, Víctor Martínez; López-Lasanta, María; Corbeto, Mireia López; Mercader, Josep M; Torrents, David; Absher, Devin; Marsal, Sara; Fernández-Nebro, Antonio

2018-05-30

Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with a complex genetic inheritance. Genome-wide association studies (GWAS) have significantly increased the number of significant loci associated with SLE risk. To date, however, established loci account for less than 30% of the disease heritability and additional risk variants have yet to be identified. Here we performed a GWAS followed by a meta-analysis to identify new genome-wide significant loci for SLE. We genotyped a cohort of 907 patients with SLE (cases) and 1524 healthy controls from Spain and performed imputation using the 1000 Genomes reference data. We tested for association using logistic regression with correction for the principal components of variation. Meta-analysis of the association results was subsequently performed on 7,110,321 variants using genetic data from a large cohort of 4036 patients with SLE and 6959 controls of Northern European ancestry. Genetic association was also tested at the pathway level after removing the effect of known risk loci using PASCAL software. We identified five new loci associated with SLE at the genome-wide level of significance (p < 5 × 10 - 8 ): GRB2, SMYD3, ST8SIA4, LAT2 and ARHGAP27. Pathway analysis revealed several biological processes significantly associated with SLE risk: B cell receptor signaling (p = 5.28 × 10 - 6 ), CTLA4 co-stimulation during T cell activation (p = 3.06 × 10 - 5 ), interleukin-4 signaling (p = 3.97 × 10 - 5 ) and cell surface interactions at the vascular wall (p = 4.63 × 10 - 5 ). Our results identify five novel loci for SLE susceptibility, and biologic pathways associated via multiple low-effect-size loci.

Genome-wide association study meta-analysis of European and Asian-ancestry samples identifies three novel loci associated with bipolar disorder.

PubMed

Chen, D T; Jiang, X; Akula, N; Shugart, Y Y; Wendland, J R; Steele, C J M; Kassem, L; Park, J-H; Chatterjee, N; Jamain, S; Cheng, A; Leboyer, M; Muglia, P; Schulze, T G; Cichon, S; Nöthen, M M; Rietschel, M; McMahon, F J; Farmer, A; McGuffin, P; Craig, I; Lewis, C; Hosang, G; Cohen-Woods, S; Vincent, J B; Kennedy, J L; Strauss, J

2013-02-01

Meta-analyses of bipolar disorder (BD) genome-wide association studies (GWAS) have identified several genome-wide significant signals in European-ancestry samples, but so far account for little of the inherited risk. We performed a meta-analysis of ∼750,000 high-quality genetic markers on a combined sample of ∼14,000 subjects of European and Asian-ancestry (phase I). The most significant findings were further tested in an extended sample of ∼17,700 cases and controls (phase II). The results suggest novel association findings near the genes TRANK1 (LBA1), LMAN2L and PTGFR. In phase I, the most significant single nucleotide polymorphism (SNP), rs9834970 near TRANK1, was significant at the P=2.4 × 10(-11) level, with no heterogeneity. Supportive evidence for prior association findings near ANK3 and a locus on chromosome 3p21.1 was also observed. The phase II results were similar, although the heterogeneity test became significant for several SNPs. On the basis of these results and other established risk loci, we used the method developed by Park et al. to estimate the number, and the effect size distribution, of BD risk loci that could still be found by GWAS methods. We estimate that >63,000 case-control samples would be needed to identify the ∼105 BD risk loci discoverable by GWAS, and that these will together explain <6% of the inherited risk. These results support previous GWAS findings and identify three new candidate genes for BD. Further studies are needed to replicate these findings and may potentially lead to identification of functional variants. Sample size will remain a limiting factor in the discovery of common alleles associated with BD.

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.

Quantifying second generation ethanol inhibition: Design of Experiments approach and kinetic model development.

PubMed

Schneiderman, Steven J; Johnson, Roger W; Menkhaus, Todd J; Gilcrease, Patrick C

2015-03-01

While softwoods represent a potential feedstock for second generation ethanol production, compounds present in their hydrolysates can inhibit fermentation. In this study, a novel Design of Experiments (DoE) approach was used to identify significant inhibitory effects on Saccharomyces cerevisiae D5A for the purpose of guiding kinetic model development. Although acetic acid, furfural and 5-hydroxymethyl furfural (HMF) were present at potentially inhibitory levels, initial factorial experiments only identified ethanol as a significant rate inhibitor. It was hypothesized that high ethanol levels masked the effects of other inhibitors, and a subsequent factorial design without ethanol found significant effects for all other compounds. When these non-ethanol effects were accounted for in the kinetic model, R¯(2) was significantly improved over an ethanol-inhibition only model (R¯(2)=0.80 vs. 0.76). In conclusion, when ethanol masking effects are removed, DoE is a valuable tool to identify significant non-ethanol inhibitors and guide kinetic model development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fundamental frequency and voice perturbation measures in smokers and non-smokers: An acoustic and perceptual study

NASA Astrophysics Data System (ADS)

Freeman, Allison

This research examined the fundamental frequency and perturbation (jitter % and shimmer %) measures in young adult (20-30 year-old) and middle-aged adult (40-55 year-old) smokers and non-smokers; there were 36 smokers and 36 non-smokers. Acoustic analysis was carried out utilizing one task: production of sustained /a/. These voice samples were analyzed utilizing Multi-Dimensional Voice Program (MDVP) software, which provided values for fundamental frequency, jitter %, and shimmer %.These values were analyzed for trends regarding smoking status, age, and gender. Statistical significance was found regarding the fundamental frequency, jitter %, and shimmer % for smokers as compared to non-smokers; smokers were found to have significantly lower fundamental frequency values, and significantly higher jitter % and shimmer % values. Statistical significance was not found regarding fundamental frequency, jitter %, and shimmer % for age group comparisons. With regard to gender, statistical significance was found regarding fundamental frequency; females were found to have statistically higher fundamental frequencies as compared to males. However, the relationships between gender and jitter % and shimmer % lacked statistical significance. These results indicate that smoking negatively affects voice quality. This study also examined the ability of untrained listeners to identify smokers and non-smokers based on their voices. Results of this voice perception task suggest that listeners are not accurately able to identify smokers and non-smokers, as statistical significance was not reached. However, despite a lack of significance, trends in data suggest that listeners are able to utilize voice quality to identify smokers and non-smokers.

Consumer factors predicting level of treatment response to illness management and recovery.

PubMed

White, Dominique A; McGuire, Alan B; Luther, Lauren; Anderson, Adrienne I; Phalen, Peter; McGrew, John H

2017-12-01

This study aims to identify consumer-level predictors of level of treatment response to illness management and recovery (IMR) to target the appropriate consumers and aid psychiatric rehabilitation settings in developing intervention adaptations. Secondary analyses from a multisite study of IMR were conducted. Self-report data from consumer participants of the parent study (n = 236) were analyzed for the current study. Consumers completed prepost surveys assessing illness management, coping, goal-related hope, social support, medication adherence, and working alliance. Correlations and multiple regression analyses were run to identify self-report variables that predicted level of treatment response to IMR. Analyses revealed that goal-related hope significantly predicted level of improved illness self-management, F(1, 164) = 10.93, p < .001, R2 = .248, R2 change = .05. Additionally, we found that higher levels of maladaptive coping at baseline were predictive of higher levels of adaptive coping at follow-up, F(2, 180) = 5.29, p < .02, R2 = .38, R2 change = .02. Evidence did not support additional predictors. Previously, consumer-level predictors of level of treatment response have not been explored for IMR. Although 2 significant predictors were identified, study findings suggest more work is needed. Future research is needed to identify additional consumer-level factors predictive of IMR treatment response in order to identify who would benefit most from this treatment program. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Age and Other Risk Factors Influencing Long-Term Mortality in Patients With Traumatic Cervical Spine Fracture.

PubMed

Bank, Matthew; Gibbs, Katie; Sison, Cristina; Kutub, Nawshin; Paptheodorou, Angelos; Lee, Samuel; Stein, Adam; Bloom, Ona

2018-01-01

To identify clinical or demographic variables that influence long-term mortality, as well as in-hospital mortality, with a particular focus on the effects of age. Cervical spine fractures with or without spinal cord injury (SCI) disproportionately impact the elderly who constitute an increasing percentage of the US population. We analyzed data collected for 10 years at a state-designated level I trauma center to identify variables that influenced in-hospital and long-term mortality among elderly patients with traumatic cervical spine fracture with or without SCI. Acute in-hospital mortality was determined from hospital records and long-term mortality within the study period (2003-2013) was determined from the National Death Index. Univariate and multivariate regression analyses were used to identify factors influencing survival. Data from patients (N = 632) with cervical spine fractures were analyzed, the majority (66%) of whom were geriatric (older than age 64). Most patients (62%) had a mild/moderate injury severity score (ISS; median, interquartile range: 6, 5). Patients with SCI had significantly longer lengths of stay (14.1 days), days on a ventilator (3.5 days), and higher ISS (14.9) than patients without SCI ( P < .0001 for all). Falls were the leading mechanism of injury for patients older than age 64. Univariate analysis identified that long-term survival decreased significantly for all patients older than age 65 (hazard ratio [HR]: 1.07; P < .0001). Multivariate analysis demonstrated age (HR: 1.08; P < .0001), gender (HR: 1.60; P < .0007), and SCI status (HR: 1.45, P < .02) significantly influenced survival during the study period. This study identified age, gender, and SCI status as significant variables for this study population influencing long-term survival among patients with cervical spine fractures. Our results support the growing notion that cervical spine injuries in geriatric patients with trauma may warrant additional research.

Age and Other Risk Factors Influencing Long-Term Mortality in Patients With Traumatic Cervical Spine Fracture

PubMed Central

Bank, Matthew; Gibbs, Katie; Sison, Cristina; Kutub, Nawshin; Paptheodorou, Angelos; Lee, Samuel; Stein, Adam; Bloom, Ona

2018-01-01

Objective: To identify clinical or demographic variables that influence long-term mortality, as well as in-hospital mortality, with a particular focus on the effects of age. Summary and Background Data: Cervical spine fractures with or without spinal cord injury (SCI) disproportionately impact the elderly who constitute an increasing percentage of the US population. Methods: We analyzed data collected for 10 years at a state-designated level I trauma center to identify variables that influenced in-hospital and long-term mortality among elderly patients with traumatic cervical spine fracture with or without SCI. Acute in-hospital mortality was determined from hospital records and long-term mortality within the study period (2003-2013) was determined from the National Death Index. Univariate and multivariate regression analyses were used to identify factors influencing survival. Results: Data from patients (N = 632) with cervical spine fractures were analyzed, the majority (66%) of whom were geriatric (older than age 64). Most patients (62%) had a mild/moderate injury severity score (ISS; median, interquartile range: 6, 5). Patients with SCI had significantly longer lengths of stay (14.1 days), days on a ventilator (3.5 days), and higher ISS (14.9) than patients without SCI (P < .0001 for all). Falls were the leading mechanism of injury for patients older than age 64. Univariate analysis identified that long-term survival decreased significantly for all patients older than age 65 (hazard ratio [HR]: 1.07; P < .0001). Multivariate analysis demonstrated age (HR: 1.08; P < .0001), gender (HR: 1.60; P < .0007), and SCI status (HR: 1.45, P < .02) significantly influenced survival during the study period. Conclusion: This study identified age, gender, and SCI status as significant variables for this study population influencing long-term survival among patients with cervical spine fractures. Our results support the growing notion that cervical spine injuries in geriatric patients with trauma may warrant additional research. PMID:29760965

A Genome-Wide Association Study of Chronic Obstructive Pulmonary Disease in Hispanics

PubMed Central

Chen, Wei; Brehm, John M.; Manichaikul, Ani; Cho, Michael H.; Boutaoui, Nadia; Yan, Qi; Burkart, Kristin M.; Enright, Paul L.; Rotter, Jerome I.; Petersen, Hans; Leng, Shuguang; Obeidat, Ma’en; Bossé, Yohan; Brandsma, Corry-Anke; Hao, Ke; Rich, Stephen S.; Powell, Rhea; Avila, Lydiana; Soto-Quiros, Manuel; Silverman, Edwin K.; Tesfaigzi, Yohannes; Barr, R. Graham

2015-01-01

Rationale: Genome-wide association studies (GWAS) of chronic obstructive pulmonary disease (COPD) have identified disease-susceptibility loci, mostly in subjects of European descent. Objectives: We hypothesized that by studying Hispanic populations we would be able to identify unique loci that contribute to COPD pathogenesis in Hispanics but remain undetected in GWAS of non-Hispanic populations. Methods: We conducted a metaanalysis of two GWAS of COPD in independent cohorts of Hispanics in Costa Rica and the United States (Multi-Ethnic Study of Atherosclerosis [MESA]). We performed a replication study of the top single-nucleotide polymorphisms in an independent Hispanic cohort in New Mexico (the Lovelace Smokers Cohort). We also attempted to replicate prior findings from genome-wide studies in non-Hispanic populations in Hispanic cohorts. Measurements and Main Results: We found no genome-wide significant association with COPD in our metaanalysis of Costa Rica and MESA. After combining the top results from this metaanalysis with those from our replication study in the Lovelace Smokers Cohort, we identified two single-nucleotide polymorphisms approaching genome-wide significance for an association with COPD. The first (rs858249, combined P value = 6.1 × 10−8) is near the genes KLHL7 and NUPL2 on chromosome 7. The second (rs286499, combined P value = 8.4 × 10−8) is located in an intron of DLG2. The two most significant single-nucleotide polymorphisms in FAM13A from a previous genome-wide study in non-Hispanics were associated with COPD in Hispanics. Conclusions: We have identified two novel loci (in or near the genes KLHL7/NUPL2 and DLG2) that may play a role in COPD pathogenesis in Hispanic populations. PMID:25584925

A genome-wide association study of chronic obstructive pulmonary disease in Hispanics.

PubMed

Chen, Wei; Brehm, John M; Manichaikul, Ani; Cho, Michael H; Boutaoui, Nadia; Yan, Qi; Burkart, Kristin M; Enright, Paul L; Rotter, Jerome I; Petersen, Hans; Leng, Shuguang; Obeidat, Ma'en; Bossé, Yohan; Brandsma, Corry-Anke; Hao, Ke; Rich, Stephen S; Powell, Rhea; Avila, Lydiana; Soto-Quiros, Manuel; Silverman, Edwin K; Tesfaigzi, Yohannes; Barr, R Graham; Celedón, Juan C

2015-03-01

Genome-wide association studies (GWAS) of chronic obstructive pulmonary disease (COPD) have identified disease-susceptibility loci, mostly in subjects of European descent. We hypothesized that by studying Hispanic populations we would be able to identify unique loci that contribute to COPD pathogenesis in Hispanics but remain undetected in GWAS of non-Hispanic populations. We conducted a metaanalysis of two GWAS of COPD in independent cohorts of Hispanics in Costa Rica and the United States (Multi-Ethnic Study of Atherosclerosis [MESA]). We performed a replication study of the top single-nucleotide polymorphisms in an independent Hispanic cohort in New Mexico (the Lovelace Smokers Cohort). We also attempted to replicate prior findings from genome-wide studies in non-Hispanic populations in Hispanic cohorts. We found no genome-wide significant association with COPD in our metaanalysis of Costa Rica and MESA. After combining the top results from this metaanalysis with those from our replication study in the Lovelace Smokers Cohort, we identified two single-nucleotide polymorphisms approaching genome-wide significance for an association with COPD. The first (rs858249, combined P value = 6.1 × 10(-8)) is near the genes KLHL7 and NUPL2 on chromosome 7. The second (rs286499, combined P value = 8.4 × 10(-8)) is located in an intron of DLG2. The two most significant single-nucleotide polymorphisms in FAM13A from a previous genome-wide study in non-Hispanics were associated with COPD in Hispanics. We have identified two novel loci (in or near the genes KLHL7/NUPL2 and DLG2) that may play a role in COPD pathogenesis in Hispanic populations.

Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia.

PubMed

Ruderfer, Douglas M; Fanous, Ayman H; Ripke, Stephan; McQuillin, Andrew; Amdur, Richard L; Gejman, Pablo V; O'Donovan, Michael C; Andreassen, Ole A; Djurovic, Srdjan; Hultman, Christina M; Kelsoe, John R; Jamain, Stephane; Landén, Mikael; Leboyer, Marion; Nimgaonkar, Vishwajit; Nurnberger, John; Smoller, Jordan W; Craddock, Nick; Corvin, Aiden; Sullivan, Patrick F; Holmans, Peter; Sklar, Pamela; Kendler, Kenneth S

2014-09-01

Bipolar disorder and schizophrenia are two often severe disorders with high heritabilities. Recent studies have demonstrated a large overlap of genetic risk loci between these disorders but diagnostic and molecular distinctions still remain. Here, we perform a combined genome-wide association study (GWAS) of 19 779 bipolar disorder (BP) and schizophrenia (SCZ) cases versus 19 423 controls, in addition to a direct comparison GWAS of 7129 SCZ cases versus 9252 BP cases. In our case-control analysis, we identify five previously identified regions reaching genome-wide significance (CACNA1C, IFI44L, MHC, TRANK1 and MAD1L1) and a novel locus near PIK3C2A. We create a polygenic risk score that is significantly different between BP and SCZ and show a significant correlation between a BP polygenic risk score and the clinical dimension of mania in SCZ patients. Our results indicate that first, combining diseases with similar genetic risk profiles improves power to detect shared risk loci and second, that future direct comparisons of BP and SCZ are likely to identify loci with significant differential effects. Identifying these loci should aid in the fundamental understanding of how these diseases differ biologically. These findings also indicate that combining clinical symptom dimensions and polygenic signatures could provide additional information that may someday be used clinically.

Development and testing of new candidate psoriatic arthritis screening questionnaires combining optimal questions from existing tools.

PubMed

Coates, Laura C; Walsh, Jessica; Haroon, Muhammad; FitzGerald, Oliver; Aslam, Tariq; Al Balushi, Farida; Burden, A D; Burden-Teh, Esther; Caperon, Anna R; Cerio, Rino; Chattopadhyay, Chandrabhusan; Chinoy, Hector; Goodfield, Mark J D; Kay, Lesley; Kelly, Stephen; Kirkham, Bruce W; Lovell, Christopher R; Marzo-Ortega, Helena; McHugh, Neil; Murphy, Ruth; Reynolds, Nick J; Smith, Catherine H; Stewart, Elizabeth J C; Warren, Richard B; Waxman, Robin; Wilson, Hilary E; Helliwell, Philip S

2014-09-01

Several questionnaires have been developed to screen for psoriatic arthritis (PsA), but head-to-head studies have found limitations. This study aimed to develop new questionnaires encompassing the most discriminative questions from existing instruments. Data from the CONTEST study, a head-to-head comparison of 3 existing questionnaires, were used to identify items with a Youden index score of ≥0.1. These were combined using 4 approaches: CONTEST (simple additions of questions), CONTESTw (weighting using logistic regression), CONTESTjt (addition of a joint manikin), and CONTESTtree (additional questions identified by classification and regression tree [CART] analysis). These candidate questionnaires were tested in independent data sets. Twelve individual questions with a Youden index score of ≥0.1 were identified, but 4 of these were excluded due to duplication and redundancy. Weighting for 2 of these questions was included in CONTESTw. Receiver operating characteristic (ROC) curve analysis showed that involvement in 6 joint areas on the manikin was predictive of PsA for inclusion in CONTESTjt. CART analysis identified a further 5 questions for inclusion in CONTESTtree. CONTESTtree was not significant on ROC curve analysis and discarded. The other 3 questionnaires were significant in all data sets, although CONTESTw was slightly inferior to the others in the validation data sets. Potential cut points for referral were also discussed. Of 4 candidate questionnaires combining existing discriminatory items to identify PsA in people with psoriasis, 3 were found to be significant on ROC curve analysis. Testing in independent data sets identified 2 questionnaires (CONTEST and CONTESTjt) that should be pursued for further prospective testing. Copyright © 2014 by the American College of Rheumatology.

Intervention Practices in the Retention of Competitive Employment among Individuals Who Are Blind or Visually Impaired.

ERIC Educational Resources Information Center

Sikka, Anjoo; Stephens, Barry C.

This report discusses the results of a national study of 89 rehabilitation counselors that investigated the methods by which an individual could retain competitive employment after the onset of a significant vision loss. The purpose of the study was to identify and describe strategies that contribute to successful job retention and identify best…

A Comparative Needs Analysis of Supportive Services for Non-Handicapped and Handicapped Persons Seeking Post-Secondary Education from the Community College System.

ERIC Educational Resources Information Center

Graham, Gary L.; And Others

This study was concerned with identifying the specific information needs and personal needs of handicapped students and comparing the selected needs with needs of general students. The study hypothesis was that there is no significant difference between identified needs of handicapped students and those of general students. The significance…

Validation of Genome-Wide Prostate Cancer Associations in Men of African Descent

PubMed Central

Chang, Bao-Li; Spangler, Elaine; Gallagher, Stephen; Haiman, Christopher A.; Henderson, Brian; Isaacs, William; Benford, Marnita L.; Kidd, LaCreis R.; Cooney, Kathleen; Strom, Sara; Ann Ingles, Sue; Stern, Mariana C.; Corral, Roman; Joshi, Amit D.; Xu, Jianfeng; Giri, Veda N.; Rybicki, Benjamin; Neslund-Dudas, Christine; Kibel, Adam S.; Thompson, Ian M.; Leach, Robin J.; Ostrander, Elaine A.; Stanford, Janet L.; Witte, John; Casey, Graham; Eeles, Rosalind; Hsing, Ann W.; Chanock, Stephen; Hu, Jennifer J.; John, Esther M.; Park, Jong; Stefflova, Klara; Zeigler-Johnson, Charnita; Rebbeck, Timothy R.

2010-01-01

Background Genome-wide association studies (GWAS) have identified numerous prostate cancer susceptibility alleles, but these loci have been identified primarily in men of European descent. There is limited information about the role of these loci in men of African descent. Methods We identified 7,788 prostate cancer cases and controls with genotype data for 47 GWAS-identified loci. Results We identified significant associations for SNP rs10486567 at JAZF1, rs10993994 at MSMB, rs12418451 and rs7931342 at 11q13, and rs5945572 and rs5945619 at NUDT10/11. These associations were in the same direction and of similar magnitude as those reported in men of European descent. Significance was attained at all report prostate cancer susceptibility regions at chromosome 8q24, including associations reaching genome-wide significance in region 2. Conclusion We have validated in men of African descent the associations at some, but not all, prostate cancer susceptibility loci originally identified in European descent populations. This may be due to heterogeneity in genetic etiology or in the pattern of genetic variation across populations. Impact The genetic etiology of prostate cancer in men of African descent differs from that of men of European descent. PMID:21071540

Nuclear power systems for lunar and Mars exploration

NASA Technical Reports Server (NTRS)

Sovie, R. J.; Bozek, J. M.

1990-01-01

Initial studies of a variety of mission scenarios for the new Space Exploration Initiative, and the technologies necessary to enable or significantly enhance them, have identified the development of advanced space power systems whether solar, chemical or nuclear to be of prime importance. Lightweight, compact, reliable power systems for planetary rovers and a variety of surface vehicles, utility surface power, and power for advanced propulsion systems have been identified as critical needs for these missions. These mission scenarios, the concomitant power system requirements, and power system options considered are discussed. The significant potential benefits of nuclear power are identified for meeting the power needs of the above applications.

Revisiting profile of deliberate self-harm at a tertiary care hospital after an interval of 10 years.

PubMed

Singh, Paramjeet; Shah, Raghav; Midha, Purav; Soni, Ajitabh; Bagotia, Sunil; Gaur, Kusum Lata

2016-01-01

Sociocultural factors complement psychopathological factors that result in deliberate self-harm (DSH). A study of change in these factors over time is essential for preventive action. To identify factors influencing DSH, which have shown significant variation over a period of 10 years. Two hospital-based cross-sectional analytic types of observational studies were performed at two different times at an interval of 10 years. Sociodemographic profile, factors related to DSH, stressful life events, and psychiatric disorders were assessed in two groups of patients drawn from the same tertiary care hospital, 100 consecutive patients in 2002 and 117 in 2012. The observations were compared to identify factors that have undergone significant change. Descriptive statistics along with Chi-square test was used in this study. A significant decrease in the overall number of married subjects (60% vs. 43%) and an increase in the number of unmarried females (34% vs. 61%) were seen. A significant increase in the overall number of rural subjects (17% vs. 34%) and especially in a number of rural females (7% vs. 23%) was also seen. An increase in subjects from middle socioeconomic class (15% vs. 29%) and education up to secondary school (9% vs. 25%) was also seen. A significantly higher number of subjects had a psychiatric disorder (50% vs. 81%) with a significant increase in diagnoses of depression (36% vs. 67%). Family and social issues remain the most common antecedent stressful events. Chemical methods are still the most preferred means, but a higher number (8% vs. 18%) report a history of self-harm. Variations in factors responsible for DSH identified in this comparative study have preventive implications.

DNA methylation Landscape of body size variation in sheep.

PubMed

Cao, Jiaxue; Wei, Caihong; Liu, Dongming; Wang, Huihua; Wu, Mingming; Xie, Zhiyuan; Capellini, Terence D; Zhang, Li; Zhao, Fuping; Li, Li; Zhong, Tao; Wang, Linjie; Lu, Jian; Liu, Ruizao; Zhang, Shifang; Du, Yongfei; Zhang, Hongping; Du, Lixin

2015-10-16

Sub-populations of Chinese Mongolian sheep exhibit significant variance in body mass. In the present study, we sequenced the whole genome DNA methylation in these breeds to detect whether DNA methylation plays a role in determining the body mass of sheep by Methylated DNA immunoprecipitation - sequencing method. A high quality methylation map of Chinese Mongolian sheep was obtained in this study. We identified 399 different methylated regions located in 93 human orthologs, which were previously reported as body size related genes in human genome-wide association studies. We tested three regions in LTBP1, and DNA methylation of two CpG sites showed significant correlation with its RNA expression. Additionally, a particular set of differentially methylated windows enriched in the "development process" (GO: 0032502) was identified as potential candidates for association with body mass variation. Next, we validated small part of these windows in 5 genes; DNA methylation of SMAD1, TSC1 and AKT1 showed significant difference across breeds, and six CpG were significantly correlated with RNA expression. Interestingly, two CpG sites showed significant correlation with TSC1 protein expression. This study provides a thorough understanding of body size variation in sheep from an epigenetic perspective.

The Relationship between Students' Motivation and Perceptions of the Learning Environment

ERIC Educational Resources Information Center

Chouinard, Ashley

2017-01-01

The purpose of this quantitative study was to identify if there was a significant relationship between dental hygiene students' perceptions of the learning environment and their motivational orientation. The study was also designed to determine if there was a significant difference in satisfaction with the learning environment between first-year,…

Emotional Intelligence Profiles and Learning Strategies in Secondary School Students

ERIC Educational Resources Information Center

Inglés, Cándido J.; Martínez-Monteagudo, María C.; Pérez Fuentes, Maria C.; García-Fernández, José M.; Molero, María del Mar; Suriá-Martinez, Raquel; Gázquez, José J.

2017-01-01

The aim of this study was to analyse the relationship among emotional intelligence (EI) and learning strategies, identifying different emotional intelligence profiles and determining possible statistically significant differences in learning strategies through the identified profiles. Thousand and seventy-one Spaniards secondary school students…

Job Satisfaction/Dissatisfaction of Nonpublic School Administrators

ERIC Educational Resources Information Center

Houpt, Jessica Jean

2009-01-01

Purpose. The purpose of this study was to (a) identify sources of job satisfaction/dissatisfaction in selected nonpublic schools that serve exceptional special education students in California; (b) identify the sources of dissatisfaction; (c) ascertain any significant difference between male and female perceptions of the…

Diagnosing pyogenic, brucella and tuberculous spondylitis using histopathology and MRI: A retrospective study.

PubMed

Li, Tao; Liu, Tao; Jiang, Zhensong; Cui, Xingang; Sun, Jianmin

2016-10-01

The present study examined the histopathological and magnetic resonance imaging (MRI) features of pyogenic, brucella and tuberculous spondylitis (PS, BS and TS, respectively). A total of 22 PS, 20 BS and 20 TS patients were included in the study. Histopathological examination was used to assess the lesion structure and composition, and the MRI observation identified the lesion location and signal features. The following histopathological and MRI features were identified significantly more in patients with PS than in patients with BS and TS: Predominant neutrophil infiltration, abnormal intervertebral disk signal, lesions on the ventral and lateral sides of the vertebral bodies, and thick and irregular abscess walls. The following histopathological and MRI features were identified significantly more in patients with BS than in patients with PS and TS: Predominant lymphocyte infiltration, new bone formation, epithelioid granuloma, lesions on the ventral sides of the vertebral bodies, no, or very mild, vertebral body deformation, no abnormal paraspinal soft tissue signal, no intraosseous or paraspinal abscesses, and thin and irregular abscess walls. The following histopathological and MRI features were identified significantly more in patients with TS than in patients with BS and PS: Sequestrum, Langerhans giant cells, caseous necrosis, lesions primarily in the thoracic region and on the lateral sides of the vertebral bodies, no obvious intervertebral disk damage, obvious vertebral body deformation, abnormal paraspinal soft tissue signal, intraosseous or paraspinal abscesses, and thin and smooth abscess walls. In conclusion, it can be suggested that these significant differences in histopathological and MRI features between the three different types of spondylitis may contribute towards the differential diagnosis of the diseases.

Serum bone alkaline phosphatase and calcaneus bone density predict fractures: a prospective study.

PubMed

Ross, P D; Kress, B C; Parson, R E; Wasnich, R D; Armour, K A; Mizrahi, I A

2000-01-01

The aim of this study was to assess the ability of serum bone-specific alkaline phosphatase (bone ALP), creatinine-corrected urinary collagen crosslinks (CTx) and calcaneus bone mineral density (BMD) to identify postmenopausal women who have an increased risk of osteoporotic fractures. Calcaneus BMD and biochemical markers of bone turnover (serum bone ALP and urinary CTx) were measured in 512 community-dwelling postmenopausal women (mean age at baseline 69 years) participating in the Hawaii Osteoporosis Study. New spine and nonspine fractures subsequent to the BMD and biochemical bone markers measurements were recorded over an average of 2.7 years. Lateral spinal radiographs were used to identify spine fractures. Nonspine fractures were identified by self-report at the time of each examination. During the 2.7-year follow-up, at least one osteoporotic fracture occurred in 55 (10.7%) of the 512 women. Mean baseline serum bone ALP and urinary CTx were significantly higher among women who experienced an osteoporotic fracture compared with those women who did not fracture. In separate age-adjusted logistic regression models, serum bone ALP, urinary CTx and calcaneus BMD were each significantly associated with new fractures (odds ratios of 1.53, 1.54 and 1.61 per SD, respectively). Multiple variable logistic regression analysis identified BMD and serum bone ALP as significant predictors of fracture (p = 0.002 and 0.017, respectively). The results from this investigation indicate that increased bone turnover is significantly associated with an increased risk of osteoporotic fracture in postmenopausal women. This association is similar in magnitude and independent of that observed for BMD.

A genome-wide scan study identifies a single nucleotide substitution in ASIP associated with white versus non-white coat-colour variation in sheep (Ovis aries)

PubMed Central

Li, M-H; Tiirikka, T; Kantanen, J

2014-01-01

In sheep, coat colour (and pattern) is one of the important traits of great biological, economic and social importance. However, the genetics of sheep coat colour has not yet been fully clarified. We conducted a genome-wide association study of sheep coat colours by genotyping 47 303 single-nucleotide polymorphisms (SNPs) in the Finnsheep population in Finland. We identified 35 SNPs associated with all the coat colours studied, which cover genomic regions encompassing three known pigmentation genes (TYRP1, ASIP and MITF) in sheep. Eighteen of these associations were confirmed in further tests between white versus non-white individuals, but none of the 35 associations were significant in the analysis of only non-white colours. Across the tests, the s66432.1 in ASIP showed significant association (P=4.2 × 10−11 for all the colours; P=2.3 × 10−11 for white versus non-white colours) with the variation in coat colours and strong linkage disequilibrium with other significant variants surrounding the ASIP gene. The signals detected around the ASIP gene were explained by differences in white versus non-white alleles. Further, a genome scan for selection for white coat pigmentation identified a strong and striking selection signal spanning ASIP. Our study identified the main candidate gene for the coat colour variation between white and non-white as ASIP, an autosomal gene that has been directly implicated in the pathway regulating melanogenesis. Together with ASIP, the two other newly identified genes (TYRP1 and MITF) in the Finnsheep, bordering associated SNPs, represent a new resource for enriching sheep coat-colour genetics and breeding. PMID:24022497

Proteome Analysis for Understanding Abiotic Stress (Salinity and Drought) Tolerance in Date Palm (Phoenix dactylifera L.).

PubMed

El Rabey, Haddad A; Al-Malki, Abdulrahman L; Abulnaja, Khalid O; Rohde, Wolfgang

2015-01-01

This study was carried out to study the proteome of date palm under salinity and drought stress conditions to possibly identify proteins involved in stress tolerance. For this purpose, three-month-old seedlings of date palm cultivar "Sagie" were subjected to drought (27.5 g/L polyethylene glycol 6000) and salinity stress conditions (16 g/L NaCl) for one month. DIGE analysis of protein extracts identified 47 differentially expressed proteins in leaves of salt- and drought-treated palm seedlings. Mass spectrometric analysis identified 12 proteins; three out of them were significantly changed under both salt and drought stress, while the other nine were significantly changed only in salt-stressed plants. The levels of ATP synthase alpha and beta subunits, an unknown protein and some of RubisCO fragments were significantly changed under both salt and drought stress conditions. Changes in abundance of superoxide dismutase, chlorophyll A-B binding protein, light-harvesting complex1 protein Lhca1, RubisCO activase, phosphoglycerate kinase, chloroplast light-harvesting chlorophyll a/b-binding protein, phosphoribulokinase, transketolase, RubisCO, and some of RubisCO fragments were significant only for salt stress.

Genome-wide association study and accuracy of genomic prediction for teat number in Duroc pigs using genotyping-by-sequencing.

PubMed

Tan, Cheng; Wu, Zhenfang; Ren, Jiangli; Huang, Zhuolin; Liu, Dewu; He, Xiaoyan; Prakapenka, Dzianis; Zhang, Ran; Li, Ning; Da, Yang; Hu, Xiaoxiang

2017-03-29

The number of teats in pigs is related to a sow's ability to rear piglets to weaning age. Several studies have identified genes and genomic regions that affect teat number in swine but few common results were reported. The objective of this study was to identify genetic factors that affect teat number in pigs, evaluate the accuracy of genomic prediction, and evaluate the contribution of significant genes and genomic regions to genomic broad-sense heritability and prediction accuracy using 41,108 autosomal single nucleotide polymorphisms (SNPs) from genotyping-by-sequencing on 2936 Duroc boars. Narrow-sense heritability and dominance heritability of teat number estimated by genomic restricted maximum likelihood were 0.365 ± 0.030 and 0.035 ± 0.019, respectively. The accuracy of genomic predictions, calculated as the average correlation between the genomic best linear unbiased prediction and phenotype in a tenfold validation study, was 0.437 ± 0.064 for the model with additive and dominance effects and 0.435 ± 0.064 for the model with additive effects only. Genome-wide association studies (GWAS) using three methods of analysis identified 85 significant SNP effects for teat number on chromosomes 1, 6, 7, 10, 11, 12 and 14. The region between 102.9 and 106.0 Mb on chromosome 7, which was reported in several studies, had the most significant SNP effects in or near the PTGR2, FAM161B, LIN52, VRTN, FCF1, AREL1 and LRRC74A genes. This region accounted for 10.0% of the genomic additive heritability and 8.0% of the accuracy of prediction. The second most significant chromosome region not reported by previous GWAS was the region between 77.7 and 79.7 Mb on chromosome 11, where SNPs in the FGF14 gene had the most significant effect and accounted for 5.1% of the genomic additive heritability and 5.2% of the accuracy of prediction. The 85 significant SNPs accounted for 28.5 to 28.8% of the genomic additive heritability and 35.8 to 36.8% of the accuracy of prediction. The three methods used for the GWAS identified 85 significant SNPs with additive effects on teat number, including SNPs in a previously reported chromosomal region and SNPs in novel chromosomal regions. Most significant SNPs with larger estimated effects also had larger contributions to the total genomic heritability and accuracy of prediction than other SNPs.

Gene-based rare allele analysis identified a risk gene of Alzheimer's disease.

PubMed

Kim, Jong Hun; Song, Pamela; Lim, Hyunsun; Lee, Jae-Hyung; Lee, Jun Hong; Park, Sun Ah

2014-01-01

Alzheimer's disease (AD) has a strong propensity to run in families. However, the known risk genes excluding APOE are not clinically useful. In various complex diseases, gene studies have targeted rare alleles for unsolved heritability. Our study aims to elucidate previously unknown risk genes for AD by targeting rare alleles. We used data from five publicly available genetic studies from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the database of Genotypes and Phenotypes (dbGaP). A total of 4,171 cases and 9,358 controls were included. The genotype information of rare alleles was imputed using 1,000 genomes. We performed gene-based analysis of rare alleles (minor allele frequency≤3%). The genome-wide significance level was defined as meta P<1.8×10(-6) (0.05/number of genes in human genome = 0.05/28,517). ZNF628, which is located at chromosome 19q13.42, showed a genome-wide significant association with AD. The association of ZNF628 with AD was not dependent on APOE ε4. APOE and TREM2 were also significantly associated with AD, although not at genome-wide significance levels. Other genes identified by targeting common alleles could not be replicated in our gene-based rare allele analysis. We identified that rare variants in ZNF628 are associated with AD. The protein encoded by ZNF628 is known as a transcription factor. Furthermore, the associations of APOE and TREM2 with AD were highly significant, even in gene-based rare allele analysis, which implies that further deep sequencing of these genes is required in AD heritability studies.

Examination of association to autism of common genetic variationin genes related to dopamine.

PubMed

Anderson, B M; Schnetz-Boutaud, N; Bartlett, J; Wright, H H; Abramson, R K; Cuccaro, M L; Gilbert, J R; Pericak-Vance, M A; Haines, J L

2008-12-01

Autism is a severe neurodevelopmental disorder characterized by a triad of complications. Autistic individuals display significant disturbances in language and reciprocal social interactions, combined with repetitive and stereotypic behaviors. Prevalence studies suggest that autism is more common than originally believed, with recent estimates citing a rate of one in 150. Although multiple genetic linkage and association studies have yielded multiple suggestive genes or chromosomal regions, a specific risk locus has yet to be identified and widely confirmed. Because many etiologies have been suggested for this complex syndrome, we hypothesize that one of the difficulties in identifying autism genes is that multiple genetic variants may be required to significantly increase the risk of developing autism. Thus, we took the alternative approach of examining 14 prominent dopamine pathway candidate genes for detailed study by genotyping 28 single nucleotide polymorphisms. Although we did observe a nominally significant association for rs2239535 (P=0.008) on chromosome 20, single-locus analysis did not reveal any results as significant after correction for multiple comparisons. No significant interaction was identified when Multifactor Dimensionality Reduction was employed to test specifically for multilocus effects. Although genome-wide linkage scans in autism have provided support for linkage to various loci along the dopamine pathway, our study does not provide strong evidence of linkage or association to any specific gene or combination of genes within the pathway. These results demonstrate that common genetic variation within the tested genes located within this pathway at most play a minor to moderate role in overall autism pathogenesis.

Characterizing the successful student in general chemistry and physical science classes in terms of Jung's personality types as identified by the Myers-Briggs Type Indicator

NASA Astrophysics Data System (ADS)

Riley, Wayne David

1998-11-01

A student's success in a science class can depend upon previous experiences, motivation, and the level of interest in the subject. Since psychological type is intrinsic to a person's whole being, it can be influential upon the student's motivation and interests. Thus, a study of student psychological types versus the level of success in a class, as measured by a percentage, has potential to uncover certain personality characteristics which may be helpful to or which may hinder a student's learning environment. This study was initiated, using the Myers-Briggs Type Indicator, to evaluate any correlation between a student's personality type and his/her performance in a science class. A total of 1041 students from three classes: Chemistry 121/122, Chemistry 112, Physical Science 100, volunteered for the study. An analysis of variance (ANOVA) was used to determine the levels of significance among sixteen personality types' averages. The results reveal that for the Chemistry 1121/122 course, the average score of the INTJ personality type was 5.1 to 12.6 points higher than every other personality type. The ANOVA identifies 3 personality types with averages significantly below the INTJ at the p < 0.05 significance level. The ANOVA analysis for the Chemistry 112 course identified significances between student scores at p = 0.08. The significance level for the differences among scores for the Physical Science 100 course was determined at a level of p = 0.02. Significance levels for p < 0.05 and <0.01 were identified between several groups in this course. The data suggest, that although personality type may not predict a particular student's success in a science class, students with certain personality traits may be favored in a chemistry class due the structure of the instruction and the presentation of the subject matter.

Quantitative trait locus analysis of plasma cholesterol levels and body weight by controlling the effects of the Apoa2 allele in mice.

PubMed

Suto, Jun-ichi

2007-04-01

Colleagues and I previously performed quantitative trait locus (QTL) analysis on plasma total-cholesterol (T-CHO) levels in C57BL/6J (B6) x RR F2 mice. We identified only one significant QTL (Cq6) on chromosome 1 in a region containing the Apoa2 gene locus, a convincing candidate gene for Cq6. Because Cq6 was a highly significant QTL, we considered that the detection of other potential QTLs might be hindered. In the present study, QTL analysis was performed in B6.KK-Apoa2b N(8) x RR F2 mice [B6.KK-Apoa2b N(8) is a partial congenic strain carrying the Apoa2b allele from the KK strain, and RR also has the Apoa2b allele] by controlling of the effects of the Apoa2 allele, for identifying additional QTLs. Although no significant QTLs were identified, 2 suggestive QTLs were found on chromosomes 2 and 3 in place of the effects of the Apoa2 allele. A significant body weight QTL was identified on chromosome 3 (Bwq7, peak LOD score 5.2); its effect on body weight was not significant in previously analyzed B6 x RR F2 mice. Suggestive body weight QTL that had been identified in B6 x RR F2 mice on chromosome 4 (LOD score 3.8) was not identified in B6.KK-Apoa2b N(8) x RR F2 mice. Thus, contrary to expectation, the genetic control of body weight was also altered significantly by controlling of the effects of the Apoa2 allele. The QTL mapping strategy by controlling of the effects of a major QTL facilitated the identification of additional QTLs.

Pattern and predictors of alcohol use disorders in a family practice in Nigeria.

PubMed

Obadeji, Adetunji; Oluwole, Lateef O; Dada, Mobolaji U; Ajiboye, Adedotun S

2015-01-01

Primary care has been identified as a key setting for the reduction of alcohol-related harm, while general practitioners are expected to play a significant role. The study aimed at identifying pattern of, and factors that are associated with alcohol use disorders (AUDs) among patients attending Family Medicine unit of State University Teaching Hospital. Sample was selected through a random sampling from a population of patients, aged 18-65 years, attending the general medical out-patients unit of the hospital from January to April 2013. A pretested, semi-structured questionnaire was administered, incorporating sociodemographics and the diagnoses made by the attending Physician. The participants also completed the alcohol use disorders identification test (AUDIT) questionnaire and the patient health questionnaire-9. The prevalence of AUDs among the population of general out-patients was 9.7%. The AUDIT scores of the participants range from 0 to 29 with a mean of 1.3 (standard deviation = 4.08). AUDs were significantly associated with gender, level of education, occupational class, and the presence of significant depressive symptoms (P < 0.05). There was no statistically significant association found for age, employment status, marital status, and religion. The prevalence of AUDs among population studied was lower compared with a similar study in similar setting, but however, significant. AUDs were predicted by gender, lower education level, occupational group, and the presence of significant depressive symptoms mostly in the mild to moderate form. Identifying the group at risk in clinical setting may go a long way in reducing the adverse effect of AUDs in our society.

Genetic associations with viral respiratory illnesses and asthma control in children

PubMed Central

Loisel, Dagan A; Du, Gaixin; Ahluwalia, Tarunveer Singh; Tisler, Christopher J.; Evans, Michael D.; Myers, Rachel A.; Gangnon, Ronald E.; Kreiner-Møller, Eskil; Bønnelykke, Klaus; Bisgaard, Hans; Jackson, Daniel J.; Lemanske, Robert F.; Nicolae, Dan L.; Gern, James E.; Ober, Carole

2015-01-01

Background Viral respiratory infections can cause acute wheezing illnesses in children and exacerbations of asthma. Objective We sought to identify variation in genes with known antiviral and pro-inflammatory functions to identify specific associations with more severe viral respiratory illnesses and the risk of virus-induced exacerbations during the peak fall season. Methods The associations between genetic variation at 326 SNPs in 63 candidate genes and 10 phenotypes related to viral respiratory infection and asthma control were examined in 226 children enrolled in the RhinoGen study. Replication of asthma control phenotypes was performed in 2,128 children in the Copenhagen Prospective Study on Asthma in Childhood (COPSAC). Significant associations in RhinoGen were further validated using virus-induced wheezing illness and asthma phenotypes in an independent sample of 122 children enrolled in the Childhood Origins of Asthma birth cohort study (COAST). Results A significant excess of P values smaller than 0.05 was observed in the analysis of the 10 RhinoGen phenotypes. Polymorphisms in 12 genes were significantly associated with variation in the four phenotypes showing a significant enrichment of small P values. Six of those genes (STAT4, JAK2, MX1, VDR, DDX58, and EIF2AK2) also showed significant associations with asthma exacerbations in the COPSAC study or with asthma or virus-induced wheezing phenotypes in the COAST study. Conclusions We identified genetic factors contributing to individual differences in childhood viral respiratory illnesses and virus-induced exacerbations of asthma. Defining mechanisms of these associations may provide insight into the pathogenesis of viral respiratory infections and virus-induced exacerbations of asthma. PMID:26399222

Identifying treatment responders and predictors of improvement after cognitive-behavioral therapy for juvenile fibromyalgia.

PubMed

Sil, Soumitri; Arnold, Lesley M; Lynch-Jordan, Anne; Ting, Tracy V; Peugh, James; Cunningham, Natoshia; Powers, Scott W; Lovell, Daniel J; Hashkes, Philip J; Passo, Murray; Schikler, Kenneth N; Kashikar-Zuck, Susmita

2014-07-01

The primary objective of this study was to estimate a clinically significant and quantifiable change in functional disability to identify treatment responders in a clinical trial of cognitive-behavioral therapy (CBT) for youth with juvenile fibromyalgia (JFM). The second objective was to examine whether baseline functional disability (Functional Disability Inventory), pain intensity, depressive symptoms (Children's Depression Inventory), coping self-efficacy (Pain Coping Questionnaire), and parental pain history predicted treatment response in disability at 6-month follow-up. Participants were 100 adolescents (11-18 years of age) with JFM enrolled in a recently published clinical trial comparing CBT to a fibromyalgia education (FE) intervention. Patients were identified as achieving a clinically significant change in disability (i.e., were considered treatment responders) if they achieved both a reliable magnitude of change (estimated as a > or = 7.8-point reduction on the FDI) using the Reliable Change Index, and a reduction in FDI disability grade based on established clinical reference points. Using this rigorous standard, 40% of patients who received CBT (20 of 50) were identified as treatment responders, compared to 28% who received FE (14 of 50). For CBT, patients with greater initial disability and higher coping efficacy were significantly more likely to achieve a clinically significant improvement in functioning. Pain intensity, depressive symptoms, and parent pain history did not significantly predict treatment response. Estimating clinically significant change for outcome measures in behavioral trials sets a high bar but is a potentially valuable approach to improve the quality of clinical trials, to enhance interpretability of treatment effects, and to challenge researchers to develop more potent and tailored interventions. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Examination of Association to Autism of Common Genetic Variation in Genes Related to Dopamine

PubMed Central

Anderson, B.M.; Schnetz-Boutaud, N.; Bartlett, J.; Wright, H.H.; Abramson, R.K.; Cuccaro, M.L.; Gilbert, J.R.; Pericak-Vance, M.A.; Haines, J.L.

2010-01-01

Autism is a severe neurodevelopmental disorder characterized by a triad of complications. Autistic individuals display significant disturbances in language and reciprocal social interactions, combined with repetitive and stereotypic behaviors. Prevalence studies suggest that autism is more common than originally believed, with recent estimates citing a rate of one in 150. Although this genomic approach has yielded multiple suggestive regions, a specific risk locus has yet to be identified and widely confirmed. Because many etiologies have been suggested for this complex syndrome, we hypothesize that one of the difficulties in identifying autism genes is that multiple genetic variants may be required to significantly increase the risk of developing autism. Thus we took the alternative approach of examining 14 prominent dopamine pathway candidate genes for detailed study by genotyping 28 SNPs. Although we did observe a nominally significant association for rs2239535 (p=.008) on chromosome 20, single locus analysis did not reveal any results as significant after correction for multiple comparisons. No significant interaction was identified when Multifactor Dimensionality Reduction (MDR) was employed to test specifically for multilocus effects. Although genome-wide linkage scans in autism have provided support for linkage to various loci along the dopamine pathway, our study does not provide strong evidence of linkage or association to any specific gene or combination of genes within the pathway. These results demonstrate that common genetic variation within the tested genes located within this pathway at most play a minor to moderate role in overall autism pathogenesis. PMID:19360691

Identifying ADHD children using hemodynamic responses during a working memory task measured by functional near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Gu, Yue; Miao, Shuo; Han, Junxia; Liang, Zhenhu; Ouyang, Gaoxiang; Yang, Jian; Li, Xiaoli

2018-06-01

Objective. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting children and adults. Previous studies found that functional near-infrared spectroscopy (fNIRS) can reveal significant group differences in several brain regions between ADHD children and healthy controls during working memory tasks. This study aimed to use fNIRS activation patterns to identify ADHD children from healthy controls. Approach. FNIRS signals from 25 ADHD children and 25 healthy controls performing the n-back task were recorded; then, multivariate pattern analysis was used to discriminate ADHD individuals from healthy controls, and classification performance was evaluated for significance by the permutation test. Main results. The results showed that 86.0% (p<0.001 ) of participants can be correctly classified in leave-one-out cross-validation. The most discriminative brain regions included the bilateral dorsolateral prefrontal cortex, inferior medial prefrontal cortex, right posterior prefrontal cortex, and right temporal cortex. Significance. This study demonstrated that, in a small sample, multivariate pattern analysis can effectively identify ADHD children from healthy controls based on fNIRS signals, which argues for the potential utility of fNIRS in future assessments.

Systemic Metabolomic Changes in Blood Samples of Lung Cancer Patients Identified by Gas Chromatography Time-of-Flight Mass Spectrometry

PubMed Central

Miyamoto, Suzanne; Taylor, Sandra L.; Barupal, Dinesh K.; Taguchi, Ayumu; Wohlgemuth, Gert; Wikoff, William R.; Yoneda, Ken Y.; Gandara, David R.; Hanash, Samir M.; Kim, Kyoungmi; Fiehn, Oliver

2015-01-01

Lung cancer is a leading cause of cancer deaths worldwide. Metabolic alterations in tumor cells coupled with systemic indicators of the host response to tumor development have the potential to yield blood profiles with clinical utility for diagnosis and monitoring of treatment. We report results from two separate studies using gas chromatography time-of-flight mass spectrometry (GC-TOF MS) to profile metabolites in human blood samples that significantly differ from non-small cell lung cancer (NSCLC) adenocarcinoma and other lung cancer cases. Metabolomic analysis of blood samples from the two studies yielded a total of 437 metabolites, of which 148 were identified as known compounds and 289 identified as unknown compounds. Differential analysis identified 15 known metabolites in one study and 18 in a second study that were statistically different (p-values <0.05). Levels of maltose, palmitic acid, glycerol, ethanolamine, glutamic acid, and lactic acid were increased in cancer samples while amino acids tryptophan, lysine and histidine decreased. Many of the metabolites were found to be significantly different in both studies, suggesting that metabolomics appears to be robust enough to find systemic changes from lung cancer, thus showing the potential of this type of analysis for lung cancer detection. PMID:25859693

Potential Reporting Bias in Neuroimaging Studies of Sex Differences.

PubMed

David, Sean P; Naudet, Florian; Laude, Jennifer; Radua, Joaquim; Fusar-Poli, Paolo; Chu, Isabella; Stefanick, Marcia L; Ioannidis, John P A

2018-04-17

Numerous functional magnetic resonance imaging (fMRI) studies have reported sex differences. To empirically evaluate for evidence of excessive significance bias in this literature, we searched for published fMRI studies of human brain to evaluate sex differences, regardless of the topic investigated, in Medline and Scopus over 10 years. We analyzed the prevalence of conclusions in favor of sex differences and the correlation between study sample sizes and number of significant foci identified. In the absence of bias, larger studies (better powered) should identify a larger number of significant foci. Across 179 papers, median sample size was n = 32 (interquartile range 23-47.5). A median of 5 foci related to sex differences were reported (interquartile range, 2-9.5). Few articles (n = 2) had titles focused on no differences or on similarities (n = 3) between sexes. Overall, 158 papers (88%) reached "positive" conclusions in their abstract and presented some foci related to sex differences. There was no statistically significant relationship between sample size and the number of foci (-0.048% increase for every 10 participants, p = 0.63). The extremely high prevalence of "positive" results and the lack of the expected relationship between sample size and the number of discovered foci reflect probable reporting bias and excess significance bias in this literature.

Assessment of life stress in gay and bisexual men with the gay affect and life events scale.

PubMed

Malcolm, James P

2002-01-01

The Gay Affect and Life Events Scale (GALES) was administered to a sample of gay-identified and non-gay-identified behaviourally bisexual married men (n = 186) and a comparative sample of never-married gay-identified men (n = 33). All participants in the study reported moderate levels of life stress in the preceding six months. No significant differences were found between the ever-married and never-married groups on the Overall Stress Value Score (OSV) of the GALES. Among the ever-married, those who identified as gay/homosexual reported significantly higher life stress than those who identified as bisexual. No differences were found within the ever-married between those who remained with their heterosexual partner and those who had separated. Difficulties in the use of the Nott and Vedhara (1995) version of the GALES with both gay men and populations of behaviourally bisexual men are reported.

A pilot study identifying a potential plasma biomarker for determining EGFR mutations in exons 19 or 21 in lung cancer patients

PubMed Central

Pamungkas, Aryo D.; Medriano, Carl A.; Sim, Eunjung; Lee, Sungyong; Park, Youngja H.

2017-01-01

The most common type of lung cancer is non-small cell lung cancer (NSCLC), which is frequently characterized by a mutation in the epidermal growth factor receptor (EGFR). Determining the presence of an EGFR mutation in lung cancer is important, as it determines the type of treatment that a patients will receive. Therefore, the aim of the present study was to apply high-resolution metabolomics (HRM) using liquid chromatography-mass spectrometry to identify significant compounds in human plasma samples obtained from South Korean NSCLC patients, as potential biomarkers for providing early detection and diagnosis of minimally-invasive NSCLC. The metabolic differences between lung cancer patients without EGFR mutations were compared with patients harboring EGFR mutations. Univariate analysis was performed, with a false discovery rate of q=0.05, in order to identify significant metabolites between the two groups. In addition, hierarchical clustering analysis was performed to discriminate between the metabolic profiles of the two groups. Furthermore, the significant metabolites were identified and mapped using Mummichog software, in order to generate a potential metabolic network model. Using metabolome-wide association studies, metabolic alterations were identified. Linoleic acid [303.23 m/z, (M+Na)+], 5-methyl tetrahydrofolate [231.10 m/z, (M+2H)+] and N-succinyl-L-glutamate-5 semialdehyde [254.06 m/z, (M+Na)+], were observed to be elevated in patients harboring EGFR mutations, whereas tetradecanoyl carnitine [394.29 m/z, (M+Na)+] was observed to be reduced. This suggests that these compounds may be affected by the EGFR mutation. In conclusion, the present study identified four potential biomarkers in patients with EGFR mutations, using HRM combined with pathway analysis. These results may facilitate the development of novel diagnostic tools for EGFR mutation detection in patients with lung cancer. PMID:28487968

Genome-wide association study identifies Loci and candidate genes for body composition and meat quality traits in Beijing-You chickens.

PubMed

Liu, Ranran; Sun, Yanfa; Zhao, Guiping; Wang, Fangjie; Wu, Dan; Zheng, Maiqing; Chen, Jilan; Zhang, Lei; Hu, Yaodong; Wen, Jie

2013-01-01

Body composition and meat quality traits are important economic traits of chickens. The development of high-throughput genotyping platforms and relevant statistical methods have enabled genome-wide association studies in chickens. In order to identify molecular markers and candidate genes associated with body composition and meat quality traits, genome-wide association studies were conducted using the Illumina 60 K SNP Beadchip to genotype 724 Beijing-You chickens. For each bird, a total of 16 traits were measured, including carcass weight (CW), eviscerated weight (EW), dressing percentage, breast muscle weight (BrW) and percentage (BrP), thigh muscle weight and percentage, abdominal fat weight and percentage, dry matter and intramuscular fat contents of breast and thigh muscle, ultimate pH, and shear force of the pectoralis major muscle at 100 d of age. The SNPs that were significantly associated with the phenotypic traits were identified using both simple (GLM) and compressed mixed linear (MLM) models. For nine of ten body composition traits studied, SNPs showing genome wide significance (P<2.59E-6) have been identified. A consistent region on chicken (Gallus gallus) chromosome 4 (GGA4), including seven significant SNPs and four candidate genes (LCORL, LAP3, LDB2, TAPT1), were found to be associated with CW and EW. Another 0.65 Mb region on GGA3 for BrW and BrP was identified. After measuring the mRNA content in beast muscle for five genes located in this region, the changes in GJA1 expression were found to be consistent with that of breast muscle weight across development. It is highly possible that GJA1 is a functional gene for breast muscle development in chickens. For meat quality traits, several SNPs reaching suggestive association were identified and possible candidate genes with their functions were discussed.

Herbal medicine for hand-foot syndrome induced by fluoropyrimidines: A systematic review and meta-analysis.

PubMed

Deng, Bo; Sun, Wei

2018-04-16

The aims of this study were to evaluate the efficacy of herbal medicine for the prevention and management of hand-foot syndrome (HFS) induced by fluoropyrimidines and to identify herbs associated with HFS alleviation for further research. The PubMed, Cochrane, Springer, China National Knowledge Infrastructure, and Wanfang databases were searched up to May 2017 for randomized controlled trials (RCTs) that evaluated herbal medicine for relieving HFS in patients undergoing fluoropyrimidine-based chemotherapy. Study evaluation and synthesis methods were in accordance with the Cochrane Handbook, and data were analyzed using RevMan 5.3. In total, 35 RCTs (2,668 participants) were included. Meta-analysis showed that the addition of herbal medicine significantly reduced the incidences of all-grade and high-grade HFS. The total effective rate and complete remission rate of HFS patients increased significantly with herbal medicine arm. Further sensitivity analysis identified Paeoniae Radix Alba, Carthami Flos, Cinnamomi Ramulus, and Glycyrrhizae Radix et Rhizoma as being consistently associated with significant reductions in HFS incidence without important heterogeneity. However, the lack of blinding in most studies may have led to overestimation of these effects. More high-quality RCTs and experimental research are needed to confirm and investigate the efficacy of the herbs identified in this study. Copyright © 2018 John Wiley & Sons, Ltd.

Risk management in inpatient units in the Czech Republic from the point of view of nurses in leadership positions.

PubMed

Prokešová, Radka; Brabcová, Iva; Pokojová, Radka; Bártlová, Sylva

2016-12-01

The goal of this study was to assess specific features of risk management from the point of view of nurses in leadership positions in inpatient units in Czech hospitals. The study was performed using a quantitative research strategy, i.e., a questionnaire. The data sample was analyzed using SPSS v. 23.0. Pearson's chi-square and analysis of adjusted residues were used for identifying the existence associations of nominal and/or ordinal quantities. 315 nurses in leadership positions working in inpatient units of Czech hospitals were included in the sample. The sample was created using random selection by means of quotas. Based on the study results, statistically significant relations between the respondents' education and the utilization of methods to identify risks were identified. Furthermore, statistically significant relationships were found between a nurse's functional role within the system and regular analysis and evaluation of risks and between the type of the healthcare facility and the degree of patient involvement in risk management. The study found statistically significant correlations that can be used to increase the effectiveness of risk management in inpatient units of Czech hospitals. From this perspective, the fact that patient involvement in risk management was only reported by 37.8% of respondents seems to be the most notable problem.

Molecular docking and NMR binding studies to identify novel inhibitors of human phosphomevalonate kinase

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

Boonsri, Pornthip; Department of Chemistry, NANOTEC Center of Nanotechnology, National Nanotechnology Center, Faculty of Science, Kasetsart University, Bangkok 10900; Neumann, Terrence S.

2013-01-04

Highlights: Black-Right-Pointing-Pointer Natural and synthetic inhibitors of human phosphomevalonate kinase identified. Black-Right-Pointing-Pointer Virtual screening yielded a hit rate of 15%, with inhibitor K{sub d}'s of 10-60 {mu}M. Black-Right-Pointing-Pointer NMR studies indicate significant protein conformational changes upon binding. -- Abstract: Phosphomevalonate kinase (PMK) phosphorylates mevalonate-5-phosphate (M5P) in the mevalonate pathway, which is the sole source of isoprenoids and steroids in humans. We have identified new PMK inhibitors with virtual screening, using autodock. Promising hits were verified and their affinity measured using NMR-based {sup 1}H-{sup 15}N heteronuclear single quantum coherence (HSQC) chemical shift perturbation and fluorescence titrations. Chemical shift changes were monitored,more » plotted, and fitted to obtain dissociation constants (K{sub d}). Tight binding compounds with K{sub d}'s ranging from 6-60 {mu}M were identified. These compounds tended to have significant polarity and negative charge, similar to the natural substrates (M5P and ATP). HSQC cross peak changes suggest that binding induces a global conformational change, such as domain closure. Compounds identified in this study serve as chemical genetic probes of human PMK, to explore pharmacology of the mevalonate pathway, as well as starting points for further drug development.« less

In vivo and in vitro evaluation of sterols from Gymnema sylvestrte R. Br.

PubMed

Vats, Sharad; Kamal, Raka

2013-12-01

Gymnema sylvestre R. Br. is an important medicinal plant known for its antidiabetic potential. In the present study, phytosterols from G. sylvestre was identified and quantified in vivo and in vitro. Maximum callus induction was observed in MS medium supplemented with 0.5 mg L(-1) of 2, 4-D. The protein content was significantly high both in aerial plant parts and callus tissue. Phytosterols were identified using chromatographic and spectral studies. beta-sitosterol, campesterol and stigmasterol were identified both in vivo and in vitro. Lanosterol was identified only in callus culture. Phytosterols have reported for the first time in callus culture of G. sylvestre.

Non-Targeted Metabolomics Analysis of Golden Retriever Muscular Dystrophy-Affected Muscles Reveals Alterations in Arginine and Proline Metabolism, and Elevations in Glutamic and Oleic Acid In Vivo.

PubMed

Abdullah, Muhammad; Kornegay, Joe N; Honcoop, Aubree; Parry, Traci L; Balog-Alvarez, Cynthia J; O'Neal, Sara K; Bain, James R; Muehlbauer, Michael J; Newgard, Christopher B; Patterson, Cam; Willis, Monte S

2017-07-29

Like Duchenne muscular dystrophy (DMD), the Golden Retriever Muscular Dystrophy (GRMD) dog model of DMD is characterized by muscle necrosis, progressive paralysis, and pseudohypertrophy in specific skeletal muscles. This severe GRMD phenotype includes moderate atrophy of the biceps femoris (BF) as compared to unaffected normal dogs, while the long digital extensor (LDE), which functions to flex the tibiotarsal joint and serves as a digital extensor, undergoes the most pronounced atrophy. A recent microarray analysis of GRMD identified alterations in genes associated with lipid metabolism and energy production. We, therefore, undertook a non-targeted metabolomics analysis of the milder/earlier stage disease GRMD BF muscle versus the more severe/chronic LDE using GC-MS to identify underlying metabolic defects specific for affected GRMD skeletal muscle. Untargeted metabolomics analysis of moderately-affected GRMD muscle (BF) identified eight significantly altered metabolites, including significantly decreased stearamide (0.23-fold of controls, p = 2.89 × 10 -3 ), carnosine (0.40-fold of controls, p = 1.88 × 10 -2 ), fumaric acid (0.40-fold of controls, p = 7.40 × 10 -4 ), lactamide (0.33-fold of controls, p = 4.84 × 10 -2 ), myoinositol-2-phosphate (0.45-fold of controls, p = 3.66 × 10 -2 ), and significantly increased oleic acid (1.77-fold of controls, p = 9.27 × 10 -2 ), glutamic acid (2.48-fold of controls, p = 2.63 × 10 -2 ), and proline (1.73-fold of controls, p = 3.01 × 10 -2 ). Pathway enrichment analysis identified significant enrichment for arginine/proline metabolism (p = 5.88 × 10 -4 , FDR 4.7 × 10 -2 ), where alterations in L-glutamic acid, proline, and carnosine were found. Additionally, multiple Krebs cycle intermediates were significantly decreased (e.g., malic acid, fumaric acid, citric/isocitric acid, and succinic acid), suggesting that altered energy metabolism may be underlying the observed GRMD BF muscle dysfunction. In contrast, two pathways, inosine-5'-monophosphate (VIP Score 3.91) and 3-phosphoglyceric acid (VIP Score 3.08) mainly contributed to the LDE signature, with two metabolites (phosphoglyceric acid and inosine-5'-monophosphate) being significantly decreased. When the BF and LDE were compared, the most significant metabolite was phosphoric acid, which was significantly less in the GRMD BF compared to control and GRMD LDE groups. The identification of elevated BF oleic acid (a long-chain fatty acid) is consistent with recent microarray studies identifying altered lipid metabolism genes, while alterations in arginine and proline metabolism are consistent with recent studies identifying elevated L-arginine in DMD patient sera as a biomarker of disease. Together, these studies demonstrate muscle-specific alterations in GRMD-affected muscle, which illustrate previously unidentified metabolic changes.

First-Line Matched Related Donor Hematopoietic Stem Cell Transplantation Compared to Immunosuppressive Therapy in Acquired Severe Aplastic Anemia

PubMed Central

Peinemann, Frank; Grouven, Ulrich; Kröger, Nicolaus; Bartel, Carmen; Pittler, Max H.; Lange, Stefan

2011-01-01

Introduction Acquired severe aplastic anemia (SAA) is a rare and progressive disease characterized by an immune-mediated functional impairment of hematopoietic stem cells. Transplantation of these cells is a first-line treatment option if HLA-matched related donors are available. First-line immunosuppressive therapy may be offered as alternative. The aim was to compare the outcome of these patients in controlled trials. Methods A systematic search was performed in the bibliographic databases MEDLINE, EMBASE, and The Cochrane Library. To show an overview of various outcomes by treatment group we conducted a meta-analysis on overall survival. We evaluated whether studies reported statistically significant factors for improved survival. Results 26 non-randomized controlled trials (7,955 patients enrolled from 1970 to 2001) were identified. We did not identify any RCTs. Risk of bias was high except in 4 studies. Young age and recent year of treatment were identified as factors for improved survival in the HSCT group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the IST group. In 19 studies (4,855 patients), summary statistics were sufficient to be included in meta-analysis. Considerable heterogeneity did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies. Conclusions Young age and recent year of treatment were identified as factors for improved survival in the transplant group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the immunosuppressive group. Considerable heterogeneity of non-randomized controlled studies did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies. PMID:21541024

Genome–wide association study of carcass weight in commercial Hanwoo cattle

PubMed Central

Edea, Zewdu; Jeoung, Yeong Ho; Shin, Sung-Sub; Ku, Jaeul; Seo, Sungbo; Kim, Il-Hoi; Kim, Sang-Wook

2018-01-01

Objective The objective of the present study was to validate genes and genomic regions associated with carcass weight using a low-density single nucleotide polymorphism (SNP) Chip in Hanwoo cattle breed. Methods Commercial Hanwoo steers (n = 220) were genotyped with 20K GeneSeek genomic profiler BeadChip. After applying the quality control of criteria of a call rate ≥90% and minor allele frequency (MAF) ≥0.01, a total of 15,235 autosomal SNPs were left for genome-wide association (GWA) analysis. The GWA tests were performed using single-locus mixed linear model. Age at slaughter was fitted as fixed effect and sire included as a covariate. The level of genome-wide significance was set at 3.28×10−6 (0.05/15,235), corresponding to Bonferroni correction for 15,235 multiple independent tests. Results By employing EMMAX approach which is based on a mixed linear model and accounts for population stratification and relatedness, we identified 17 and 16 loci significantly (p<0.001) associated with carcass weight for the additive and dominant models, respectively. The second most significant (p = 0.000049) SNP (ARS-BFGL-NGS-28234) on bovine chromosome 4 (BTA4) at 21 Mb had an allele substitution effect of 43.45 kg. Some of the identified regions on BTA2, 6, 14, 22, and 24 were previously reported to be associated with quantitative trait loci for carcass weight in several beef cattle breeds. Conclusion This is the first genome-wide association study using SNP chips on commercial Hanwoo steers, and some of the loci newly identified in this study may help to better DNA markers that determine increased beef production in commercial Hanwoo cattle. Further studies using a larger sample size will allow confirmation of the candidates identified in this study. PMID:29103288

Dysmobility syndrome: current perspectives.

PubMed

Hill, Keith D; Farrier, Kaela; Russell, Melissa; Burton, Elissa

2017-01-01

A new term, dysmobility syndrome, has recently been described as a new approach to identify older people at risk of poor health outcomes. The aim was to undertake a systematic review of the existing research literature on dysmobility syndrome. All articles reporting dysmobility syndrome were identified in a systematic review of Medline (Proquest), CINAHL, PubMed, PsycInfo, EMBASE, and Scopus databases. Key characteristics of identified studies were extracted and summarized. The systematic review identified five papers (three cross-sectional, one case control, and one longitudinal study). No intervention studies were identified. Prevalence of dysmobility syndrome varied between studies (22%-34% in three of the studies). Dysmobility syndrome was shown to be associated with reduced function, increased falls and fractures, and a longitudinal study showed its significant association with mortality. Early research on dysmobility syndrome indicates that it may be a useful classification approach to identify older people at risk of adverse health outcomes and to target for early interventions. Future research needs to standardize the optimal mix of measures and cut points, and investigate whether balance performance may be a more useful factor than history of falls for dysmobility syndrome.

Sleep in patients with remitted bipolar disorders: a meta-analysis of actigraphy studies.

PubMed

Geoffroy, P A; Scott, J; Boudebesse, C; Lajnef, M; Henry, C; Leboyer, M; Bellivier, F; Etain, B

2015-02-01

Sleep dysregulation is highly prevalent in bipolar disorders (BDs), with previous actigraphic studies demonstrating sleep abnormalities during depressive, manic, and interepisode periods. We undertook a meta-analysis of published actigraphy studies to identify whether any abnormalities in the reported sleep profiles of remitted BD cases differ from controls. A systematic review identified independent studies that were eligible for inclusion in a random effects meta-analysis. Effect sizes for actigraphy parameters were expressed as standardized mean differences (SMD) with 95% confidence intervals (95% CI). Nine of 248 identified studies met eligibility criteria. Compared with controls (N=210), remitted BD cases (N=202) showed significant differences in SMD for sleep latency (0.51 [0.28-0.73]), sleep duration (0.57 [0.30-0.84]), wake after sleep onset (WASO) (0.28 [0.06-0.50]) and sleep efficiency (-0.38 [-0.70-0.07]). Moderate heterogeneity was identified for sleep duration (I2=44%) and sleep efficiency (I2=44%). Post hoc meta-regression analyses demonstrated that larger SMD for sleep duration were identified for studies with a greater age difference between BD cases and controls (β=0.22; P=0.03) and non-significantly lower levels of residual depressive symptoms in BD cases (β=-0.13; P=0.07). This meta-analysis of sleep in remitted bipolar disorder highlights disturbances in several sleep parameters. Future actigraphy studies should pay attention to age matching and levels of residual depressive symptoms. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Association of ALOX5AP with ischemic stroke: a population-based case-control study.

PubMed

Kaushal, Ritesh; Pal, Prodipto; Alwell, Kathleen; Haverbusch, Mary; Flaherty, Matthew; Moomaw, Charles; Sekar, Padmini; Kissela, Brett; Kleindorfer, Dawn; Chakraborty, Ranajit; Broderick, Joseph; Deka, Ranjan; Woo, Daniel

2007-06-01

Arachidonate 5-lipoxygenase activating protein (ALOX5AP) has been reported to demonstrate linkage and association with ischemic stroke and myocardial infarction. However, replication studies have been conflicting and to date, a significant proportion of blacks have not been studied. We prospectively recruited cases of ischemic stroke from all 16 hospitals in the Greater Cincinnati/Northern Kentucky region and demographically matched them to stroke-free population-based controls. Single nucleotide polymorphisms (SNPs) were selected based on association with ischemic stroke in prior studies. Allelic, genotypic and haplotypic association testing was performed using HAPLOVIEW. Multiple logistic regression was used to control for the presence of traditional risk factors including hypertension, diabetes, hypercholesterolemia and smoking. A total of 357 cases and 482 controls were genotyped. The SNPs, rs9579646 and rs4769874 were found to be significantly associated at both allelic (P=0.019 and P<10(-4), respectively) and genotypic level with ischemic stroke among whites after correction for multiple testing. Haplotype association was identified with ischemic stroke as well as ischemic stroke subtypes among whites. Although an overall haplotype association with ischemic stroke was identified among blacks no evidence of association among individual haplotypes, alleles or genotypes were observed. Allele frequencies for the SNPs examined were markedly different among whites and blacks. In conclusion, we report significant association of variants of ALOX5AP with ischemic stroke and ischemic stroke subtypes among whites. No significant association was identified among blacks.

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.

Identification of Quantitative Trait Loci That Determine Plasma Total-Cholesterol and Triglyceride Concentrations in DDD/Sgn and C57BL/6J Inbred Mice.

PubMed

Suto, Jun-Ichi; Kojima, Misaki

2017-01-01

DDD/Sgn mice have significantly higher plasma lipid concentrations than C57BL/6J mice. In the present study, we performed quantitative trait loci (QTL) mapping for plasma total-cholesterol (CHO) and triglyceride (TG) concentrations in reciprocal F 2 male intercross populations between the two strains. By single-QTL scans, we identified four significant QTL on chromosomes (Chrs) 1, 5, 17, and 19 for CHO and two significant QTL on Chrs 1 and 12 for TG. By including cross direction as an interactive covariate, we identified separate significant QTL on Chr 17 for CHO but none for TG. When the large phenotypic effect of QTL on Chr 1 was controlled by composite interval mapping, we identified three additional significant QTL on Chrs 3, 4, and 9 for CHO but none for TG. QTL on Chr 19 was a novel QTL for CHO and the allelic effect of this QTL significantly differed between males and females. Whole-exome sequence analysis in DDD/Sgn mice suggested that Apoa2 and Acads were the plausible candidate genes underlying CHO QTL on Chrs 1 and 5, respectively. Thus, we identified a multifactorial basis for plasma lipid concentrations in male mice. These findings will provide insight into the genetic mechanisms of plasma lipid metabolism.

Identification of Quantitative Trait Loci That Determine Plasma Total-Cholesterol and Triglyceride Concentrations in DDD/Sgn and C57BL/6J Inbred Mice

PubMed Central

Kojima, Misaki

2017-01-01

DDD/Sgn mice have significantly higher plasma lipid concentrations than C57BL/6J mice. In the present study, we performed quantitative trait loci (QTL) mapping for plasma total-cholesterol (CHO) and triglyceride (TG) concentrations in reciprocal F2 male intercross populations between the two strains. By single-QTL scans, we identified four significant QTL on chromosomes (Chrs) 1, 5, 17, and 19 for CHO and two significant QTL on Chrs 1 and 12 for TG. By including cross direction as an interactive covariate, we identified separate significant QTL on Chr 17 for CHO but none for TG. When the large phenotypic effect of QTL on Chr 1 was controlled by composite interval mapping, we identified three additional significant QTL on Chrs 3, 4, and 9 for CHO but none for TG. QTL on Chr 19 was a novel QTL for CHO and the allelic effect of this QTL significantly differed between males and females. Whole-exome sequence analysis in DDD/Sgn mice suggested that Apoa2 and Acads were the plausible candidate genes underlying CHO QTL on Chrs 1 and 5, respectively. Thus, we identified a multifactorial basis for plasma lipid concentrations in male mice. These findings will provide insight into the genetic mechanisms of plasma lipid metabolism. PMID:28642824

Clinical Features and Risk Factors of Skeletal-Related Events in Genitourinary Cancer Patients with Bone Metastasis: A Retrospective Analysis of Prostate Cancer, Renal Cell Carcinoma, and Urothelial Carcinoma.

PubMed

Owari, Takuya; Miyake, Makito; Nakai, Yasushi; Morizawa, Yosuke; Itami, Yoshitaka; Hori, Shunta; Anai, Satoshi; Tanaka, Nobumichi; Fujimoto, Kiyohide

2018-06-06

The objective of the present study was to report the incidence of skeletal-related events (SREs) and identify risk factors for SREs in patients with genitourinary cancer with newly diagnosed bone metastasis. This retrospective study included 180 patients with bone metastasis from prostate cancer (PCa; n = 111), renal cell carcinoma (RCC; n = 43), and urothelial carcinoma (UC; n = 26). Clinical factors at the time of diagnosis of bone metastasis were evaluated with Cox proportional hazards regression analysis to identify independent risk factors for SREs. During follow-up, 29 (26%) patients with PCa, 30 (70%) with RCC, and 15 (58%) with UC developed SREs. Treatment with bone-modifying agents (BMAs) before the development of SREs and within 6 months from the diagnosis of bone metastasis significantly delayed the time to first SRE as compared to nonuse of BMAs. Multivariate analysis identified type of primary cancer (PCa vs. RCC, PCa vs. UC), performance status, and bone pain as significant independent predictive risk factors for SREs. Treatment with BMAs significantly delayed the development of first SREs. The identified predictors of SREs might be useful to select patients who would benefit most from early treatment with BMAs. © 2018 S. Karger AG, Basel.

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.

Relationships between Self-Concept and Resilience Profiles in Young People with Disabilities

ERIC Educational Resources Information Center

Suriá Martínez, Raquel

2016-01-01

Introduction: The present study aims to identify different profiles in self-concept and resilience. In addition, statistically significant differences in self-concept domains among the profiles previously identified are analyzed. Method: The AF5 Self-Concept Questionnaire ("Cuestionario de Autoconcepto AF5") and the Resilience Scale were…

Children's Identification of Stress Related Factors and Coping Strategies.

ERIC Educational Resources Information Center

Paterno, JoAnna; And Others

Although many educators believe that children are under stress, formally testing children for stress and coping is very difficult. This study compiled and analyzed the significant mean differences of the frequency of identified stressors and coping strategy responses between school groups to identify stressors and coping strategies as perceived by…

The Effects of Needs, Organizational Factors and Teacher's Characteristics on Job Satisfaction in Kindergarten Teachers.

ERIC Educational Resources Information Center

Avi-Itzhak, Tamara E.

The purpose of this study is to: (1) identify and assess perceived professional needs of kindergarten teachers; (2) identify perceived professional needs, organizational factors and teachers' characteristics which significantly discriminate between "satisfied teachers" vs. "dissatisfied teachers"; and (3) assess their relative…

Identifying Outpatients with Entrenched Suicidal Ideation Following Hospitalization

ERIC Educational Resources Information Center

O'Connor, Stephen S.; Jobes, David A.; Comtois, Katherine Anne; Atkins, David C.; Janis, Karin; Chessen, Chloe E.; Landes, Sara J.

2012-01-01

The purpose of this study was to identify outpatients who experience entrenched suicidal ideation following inpatient psychiatric hospitalization. Our findings suggest that the use of a suicidal ambivalence index score was helpful at discriminating those who reported significantly greater ratings of suicidal ideation across a 1-year period of…

A phenomenological study of millennial students and traditional pedagogies.

PubMed

Toothaker, Rebecca; Taliaferro, Donna

The Millennial generation comprises the majority of learners in the traditional university setting. Nurse educators identify problems developing teaching strategies in education that undergraduate Millennial nursing students find engaging and meaningful. The purpose of this study was to identify the perception of Millennial students participating in traditional pedagogies and its significant implications for nursing education. This interpretive phenomenological study recorded the lived experiences of Millennial nursing students' experiences in traditional classrooms. One on one interviews with 13 Millennial students were conducted. Data collection and analysis aligned with van Manen's method. There are five themes that emerged from the data: physically present, mentally dislocated; unspoken peer pressure; wanting more from the professors; surface learning; and lack of trust. The essence focuses around the central theme of belonging, while students identified the most significant challenge in a classroom was disengaging professors. Recommendations for faculty to engage nursing students through a method of shared responsibility of educational approach are given. Blended teaching pedagogies that offer traditional and active methods are recommended. Published by Elsevier Inc.

Types of pelvic floor dysfunctions in nulliparous, vaginal delivery, and cesarean section female patients with obstructed defecation syndrome identified by echodefecography.

PubMed

Murad-Regadas, Sthela M; Regadas, Francisco Sérgio P; Rodrigues, Lusmar V; Oliveira, Leticia; Barreto, Rosilma G L; de Souza, Marcellus H L P; Silva, Flavio Roberto S

2009-10-01

This study aims to show pelvic floor dysfunctions in women with obstructed defecation syndrome (ODS), comparing nulliparous to those with vaginal delivery or cesarean section using the echodefecography (ECD). Three hundred seventy female patients with ODS were reviewed retrospectively and were divided in Group I-105 nulliparous, Group II-165 had at least one vaginal delivery, and Group III-comprised of 100 patients delivered only by cesarean section. All patients had been submitted to ECD to identify pelvic floor dysfunctions. No statistical significance was found between the groups with regard to anorectocele grade. Intussusception was identified in 40% from G I, 55.0% from G II, and 30.0% from G III, with statistical significance between Groups I and II. Intussusception was associated with significant anorectocele in 24.8%, 36.3%, and 18% patients from G I, II, and III, respectively. Anismus was identified in 39.0% from G I, 28.5% from G II, and 60% from G III, with statistical significance between Groups I and III. Anismus was associated with significant anorectocele in 22.8%, 15.7%, and 24% patients from G I, II, and III, respectively. Sigmoidocele/enterocele was identified in 7.6% from G I, 10.9% G II, and was associated with significant rectocele in 3.8% and 7.3% patients from G I and II, respectively. The distribution of pelvic floor dysfunctions showed no specific pattern across the groups, suggesting the absence of a correlation between these dysfunctions and vaginal delivery.

Soy intake and breast cancer risk: A meta-analysis of epidemiological studies

NASA Astrophysics Data System (ADS)

Bahrom, Suhaila; Idris, Nik Ruzni Nik

2016-06-01

The impact of soy intake on breast cancer risk has been investigated extensively. However, these studies reported conflicting results. The objective of this study is to perform comprehensive review and updated meta-analysis on the association between soy intake and breast cancer risk and to identify significant factors which may contribute to the inconsistencies of results of the individual studies. Based on reviews of existing meta-analysis, we identified four main factors which contributed to the inconsistencies of results of individual studies on the association of soy intake and breast cancer risk namely; region, menopausal status of the patients, soy type and study design. Accordingly, we performed an updated meta-analysis of 57 studies grouped by the identified factors. Pooled ORs of studies carried out in Asian countries suggested that soy isoflavones consumption was inversely associated with the risk of breast cancer among both pre and postmenopausal women (OR=0.63, 95% CI: 0.54-0.74 for premenopausal women; OR=0.63, 95% CI: 0.52-0.75 for postmenopausal women). However, pooled OR of studies carried out in Western countries shows that there is no statistically significant association between soy intake and breast cancer risk (OR=0.98, 95% CI: 0.93-1.03). Our study suggests that soy food intake is associated with significantly reduced risk of breast cancer for women in Asian but not in Western countries. Further epidemiological studies need to be conducted with more comprehensive information about the dietary intake and relative exposure among the women in these two different regions.

The Canadian Pharmacogenomics Network for Drug Safety: a model for safety pharmacology.

PubMed

Ross, Colin J D; Visscher, Henk; Sistonen, Johanna; Brunham, Liam R; Pussegoda, Kusala; Loo, Tenneille T; Rieder, Michael J; Koren, Gideon; Carleton, Bruce C; Hayden, Michael R

2010-07-01

Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death in the developed world, and the direct medical costs of ADRs exceed $100 billion annually in the United States alone. Pharmacogenomics research seeks to identify genetic factors that are responsible for individual differences in drug efficacy and susceptibility to ADRs. This has led to several genetic tests that are currently being used to provide clinical recommendations. The Canadian Pharmacogenomics Network for Drug Safety is a nation-wide effort established in Canada to identify novel predictive genomic markers of severe ADRs in children and adults. A surveillance network has been established in 17 of Canada's major hospitals to identify patients experiencing specific ADRs and to collect biological samples and relevant clinical history for genetic association studies. To identify ADR-associated genetic markers that could be incorporated into predictive tests that will reduce the occurrence of serious ADRs, high-throughput genomic analyses are conducted with samples from patients that have suffered serious ADRs and matched control patients. ADRs represent a significant unmet medical problem with significant morbidity and mortality, and Canadian Pharmacogenomics Network for Drug Safety is a nation-wide network in Canada that seeks to identify genetic factors responsible for interindividual differences in susceptibility to serious ADRs. Active ADR surveillance is necessary to identify and recruit patients who suffer from serious ADRs. National and international collaborations are required to recruit sufficient patients for these studies. Several pharmacogenomics tests are currently in clinical use to provide dosing recommendations, and the number of pharmacogenomics tests is expected to significantly increase in the future.

Acute Effects of Exercise Mode on Arterial Stiffness and Wave Reflection in Healthy Young Adults: A Systematic Review and Meta-Analysis

PubMed Central

Pierce, Doris R.; Doma, Kenji; Leicht, Anthony S.

2018-01-01

Background: This systematic review and meta-analysis quantified the effect of acute exercise mode on arterial stiffness and wave reflection measures including carotid-femoral pulse wave velocity (cf-PWV), augmentation index (AIx), and heart rate corrected AIx (AIx75). Methods: Using standardized terms, database searches from inception until 2017 identified 45 studies. Eligible studies included acute aerobic and/or resistance exercise in healthy adults, pre- and post-intervention measurements or change values, and described their study design. Data from included studies were analyzed and reported in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA guidelines. Meta-analytical data were reported via forest plots using absolute differences with 95% confidence intervals with the random effects model accounting for between-study heterogeneity. Reporting bias was assessed via funnel plots and, individual studies were evaluated for bias using the Cochrane Collaboration's tool for assessing risk of bias. A modified PEDro Scale was applied to appraise methodological concerns inherent to included studies. Results: Acute aerobic exercise failed to change cf-PWV (mean difference: 0.00 ms−1 [95% confidence interval: −0.11, 0.11], p = 0.96), significantly reduced AIx (−4.54% [−7.05, −2.04], p = 0.0004) and significantly increased AIx75 (3.58% [0.56, 6.61], p = 0.02). Contrastingly, acute resistance exercise significantly increased cf-PWV (0.42 ms−1 [0.17, 0.66], p = 0.0008), did not change AIx (1.63% [−3.83, 7.09], p = 0.56), and significantly increased AIx75 (15.02% [8.71, 21.33], p < 0.00001). Significant heterogeneity was evident within all comparisons except cf-PWV following resistance exercise, and several methodological concerns including low applicability of exercise protocols and lack of control intervention were identified. Conclusions: Distinct arterial stiffness and wave reflection responses were identified following acute exercise with overall increases in both cf-PWV and AIx75 following resistance exercise potentially arising fromcardiovascular and non-cardiovascular factors that likely differ from those following aerobic exercise. Future studies should address identified methodological limitations to enhance interpretation and applicability of arterial stiffness and wave reflection indices to exercise and health. PMID:29487535

Does gratitude enhance prosociality?: A meta-analytic review.

PubMed

Ma, Lawrence K; Tunney, Richard J; Ferguson, Eamonn

2017-06-01

Theoretical models suggest that gratitude is linked to increased prosociality. To date, however, there is a lack of a comprehensive quantitative synthesis of results to support this claim. In this review we aimed to (a) examine the overall strength of the association between gratitude and prosociality, and (b) identify the theoretical and methodological variables that moderate this link. We identified 252 effect sizes from 91 studies across 65 papers-(Total N = 18,342 participants). The present meta-analysis revealed a statistically significant, and moderate positive correlation between gratitude and prosociality (r = .374). This association was significantly larger among studies that assessed reciprocal outcomes relative to nonreciprocal outcomes, and in particular among studies that examined direct -compared with indirect -reciprocity. Studies that examined gratitude as an affective state reported significantly larger effect size studies assessing gratitude as a trait . Studies that examined benefit-triggered gratitude (in response to other's kindness) had a stronger effect that generalized gratitude that focuses on the appreciation of what is valued and cherished in life. Finally, studies that manipulated gratitude in vivo (e.g., economic games) had larger effect sizes compared with those based on recalled incidents when the person felt grateful. We describe the theoretical and practical significance of the results. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Polymorphisms in the Tlr4 and Tlr5 Gene Are Significantly Associated with Inflammatory Bowel Disease in German Shepherd Dogs

PubMed Central

Kathrani, Aarti; House, Arthur; Catchpole, Brian; Murphy, Angela; German, Alex; Werling, Dirk; Allenspach, Karin

2010-01-01

Inflammatory bowel disease (IBD) is considered to be the most common cause of vomiting and diarrhoea in dogs, and the German shepherd dog (GSD) is particularly susceptible. The exact aetiology of IBD is unknown, however associations have been identified between specific single-nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) and human IBD. However, to date, no genetic studies have been undertaken in canine IBD. The aim of this study was to investigate whether polymorphisms in canine TLR 2, 4 and 5 genes are associated with IBD in GSDs. Mutational analysis of TLR2, TLR4 and TLR5 was performed in 10 unrelated GSDs with IBD. Four non-synonymous SNPs (T23C, G1039A, A1571T and G1807A) were identified in the TLR4 gene, and three non-synonymous SNPs (G22A, C100T and T1844C) were identified in the TLR5 gene. The non-synonymous SNPs identified in TLR4 and TLR5 were evaluated further in a case-control study using a SNaPSHOT multiplex reaction. Sequencing information from 55 unrelated GSDs with IBD were compared to a control group consisting of 61 unrelated GSDs. The G22A SNP in TLR5 was significantly associated with IBD in GSDs, whereas the remaining two SNPs were found to be significantly protective for IBD. Furthermore, the two SNPs in TLR4 (A1571T and G1807A) were in complete linkage disequilibrium, and were also significantly associated with IBD. The TLR5 risk haplotype (ACC) without the two associated TLR4 SNP alleles was significantly associated with IBD, however the presence of the two TLR4 SNP risk alleles without the TLR5 risk haplotype was not statistically associated with IBD. Our study suggests that the three TLR5 SNPs and two TLR4 SNPs; A1571T and G1807A could play a role in the pathogenesis of IBD in GSDs. Further studies are required to confirm the functional importance of these polymorphisms in the pathogenesis of this disease. PMID:21203467

Polymorphisms in the TLR4 and TLR5 gene are significantly associated with inflammatory bowel disease in German shepherd dogs.

PubMed

Kathrani, Aarti; House, Arthur; Catchpole, Brian; Murphy, Angela; German, Alex; Werling, Dirk; Allenspach, Karin

2010-12-23

Inflammatory bowel disease (IBD) is considered to be the most common cause of vomiting and diarrhoea in dogs, and the German shepherd dog (GSD) is particularly susceptible. The exact aetiology of IBD is unknown, however associations have been identified between specific single-nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) and human IBD. However, to date, no genetic studies have been undertaken in canine IBD. The aim of this study was to investigate whether polymorphisms in canine TLR 2, 4 and 5 genes are associated with IBD in GSDs. Mutational analysis of TLR2, TLR4 and TLR5 was performed in 10 unrelated GSDs with IBD. Four non-synonymous SNPs (T23C, G1039A, A1571T and G1807A) were identified in the TLR4 gene, and three non-synonymous SNPs (G22A, C100T and T1844C) were identified in the TLR5 gene. The non-synonymous SNPs identified in TLR4 and TLR5 were evaluated further in a case-control study using a SNaPSHOT multiplex reaction. Sequencing information from 55 unrelated GSDs with IBD were compared to a control group consisting of 61 unrelated GSDs. The G22A SNP in TLR5 was significantly associated with IBD in GSDs, whereas the remaining two SNPs were found to be significantly protective for IBD. Furthermore, the two SNPs in TLR4 (A1571T and G1807A) were in complete linkage disequilibrium, and were also significantly associated with IBD. The TLR5 risk haplotype (ACC) without the two associated TLR4 SNP alleles was significantly associated with IBD, however the presence of the two TLR4 SNP risk alleles without the TLR5 risk haplotype was not statistically associated with IBD. Our study suggests that the three TLR5 SNPs and two TLR4 SNPs; A1571T and G1807A could play a role in the pathogenesis of IBD in GSDs. Further studies are required to confirm the functional importance of these polymorphisms in the pathogenesis of this disease.

Can the height of fall predict long bone fracture in children under 24 months?

PubMed

Hansoti, Bhakti; Beattie, Tom

2005-12-01

It can be difficult to determine the exact mechanism of injury in infants and babies aged 24 months and under. Falls are the most common mechanism of injury in children. The purpose of this study is to identify the relationship between reported height of fall and long bone fracture. All children aged under 24 months who sustained a fracture (in the year 2003) were identified prospectively on the departmental fracture database. These children were matched for age and sex with children identified as having fallen but not having sustained a fracture. Sixty-three children aged 24 months and under were studied. The median height of fall in this group was 48 cm and that in the control group was 20 cm, P<0.001. A significant correlation was observed between the height of fall (cm) and severity of injury (Pearson's correlation coefficient=0.255). Receiver operating characteristic analysis indicates that the likelihood of significant fracture requiring admission and/or manipulation under anaesthesia occurs with a fall from a height of 56 cm [sensitivity 80% (confidence interval 29-97%), specificity 79% (confidence interval 70-86%)]. It was not possible to identify a height at which the risk of any fracture injury became significantly more likely. Height of fall is only one factor that must be considered in dealing with fracture injury in children aged 24 months or under. However, significant injury presenting with falls from less than 50 cm should be critically evaluated.

Perception of emotionally loaded vocal expressions and its connection to responses to music. A cross-cultural investigation: Estonia, Finland, Sweden, Russia, and the USA

PubMed Central

Waaramaa, Teija; Leisiö, Timo

2013-01-01

The present study focused on voice quality and the perception of the basic emotions from speech samples in cross-cultural conditions. It was examined whether voice quality, cultural, or language background, age, or gender were related to the identification of the emotions. Professional actors (n2) and actresses (n2) produced non-sense sentences (n32) and protracted vowels (n8) expressing the six basic emotions, interest, and a neutral emotional state. The impact of musical interests on the ability to distinguish between emotions or valence (on an axis positivity – neutrality – negativity) from voice samples was studied. Listening tests were conducted on location in five countries: Estonia, Finland, Russia, Sweden, and the USA with 50 randomly chosen participants (25 males and 25 females) in each country. The participants (total N = 250) completed a questionnaire eliciting their background information and musical interests. The responses in the listening test and the questionnaires were statistically analyzed. Voice quality parameters and the share of the emotions and valence identified correlated significantly with each other for both genders. The percentage of emotions and valence identified was clearly above the chance level in each of the five countries studied, however, the countries differed significantly from each other for the identified emotions and the gender of the speaker. The samples produced by females were identified significantly better than those produced by males. Listener's age was a significant variable. Only minor gender differences were found for the identification. Perceptual confusion in the listening test between emotions seemed to be dependent on their similar voice production types. Musical interests tended to have a positive effect on the identification of the emotions. The results also suggest that identifying emotions from speech samples may be easier for those listeners who share a similar language or cultural background with the speaker. PMID:23801972

Spatio-temporal pattern analysis for evaluation of the spread of human infections with avian influenza A(H7N9) virus in China, 2013-2014.

PubMed

Dong, Wen; Yang, Kun; Xu, Quanli; Liu, Lin; Chen, Juan

2017-10-24

A large number (n = 460) of A(H7N9) human infections have been reported in China from March 2013 through December 2014, and H7N9 outbreaks in humans became an emerging issue for China health, which have caused numerous disease outbreaks in domestic poultry and wild bird populations, and threatened human health severely. The aims of this study were to investigate the directional trend of the epidemic and to identify the significant presence of spatial-temporal clustering of influenza A(H7N9) human cases between March 2013 and December 2014. Three distinct epidemic phases of A(H7N9) human infections were identified in this study. In each phase, standard deviational ellipse analysis was conducted to examine the directional trend of disease spreading, and retrospective space-time permutation scan statistic was then used to identify the spatio-temporal cluster patterns of H7N9 outbreaks in humans. The ever-changing location and the increasing size of the three identified standard deviational ellipses showed that the epidemic moved from east to southeast coast, and hence to some central regions, with a future epidemiological trend of continue dispersing to more central regions of China, and a few new human cases might also appear in parts of the western China. Furthermore, A(H7N9) human infections were clustering in space and time in the first two phases with five significant spatio-temporal clusters (p < 0.05), but there was no significant cluster identified in phase III. There was a new epidemiologic pattern that the decrease in significant spatio-temporal cluster of A(H7N9) human infections was accompanied with an obvious spatial expansion of the outbreaks during the study period, and identification of the spatio-temporal patterns of the epidemic can provide valuable insights for better understanding the spreading dynamics of the disease in China.

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.

Novel Loci for Metabolic Networks and Multi-Tissue Expression Studies Reveal Genes for Atherosclerosis

PubMed Central

Inouye, Michael; Ripatti, Samuli; Kettunen, Johannes; Lyytikäinen, Leo-Pekka; Oksala, Niku; Laurila, Pirkka-Pekka; Kangas, Antti J.; Soininen, Pasi; Savolainen, Markku J.; Viikari, Jorma; Kähönen, Mika; Perola, Markus; Salomaa, Veikko; Raitakari, Olli; Lehtimäki, Terho; Taskinen, Marja-Riitta; Järvelin, Marjo-Riitta; Ala-Korpela, Mika; Palotie, Aarno; de Bakker, Paul I. W.

2012-01-01

Association testing of multiple correlated phenotypes offers better power than univariate analysis of single traits. We analyzed 6,600 individuals from two population-based cohorts with both genome-wide SNP data and serum metabolomic profiles. From the observed correlation structure of 130 metabolites measured by nuclear magnetic resonance, we identified 11 metabolic networks and performed a multivariate genome-wide association analysis. We identified 34 genomic loci at genome-wide significance, of which 7 are novel. In comparison to univariate tests, multivariate association analysis identified nearly twice as many significant associations in total. Multi-tissue gene expression studies identified variants in our top loci, SERPINA1 and AQP9, as eQTLs and showed that SERPINA1 and AQP9 expression in human blood was associated with metabolites from their corresponding metabolic networks. Finally, liver expression of AQP9 was associated with atherosclerotic lesion area in mice, and in human arterial tissue both SERPINA1 and AQP9 were shown to be upregulated (6.3-fold and 4.6-fold, respectively) in atherosclerotic plaques. Our study illustrates the power of multi-phenotype GWAS and highlights candidate genes for atherosclerosis. PMID:22916037

Identifying community thresholds for lotic benthic diatoms in response to human disturbance.

PubMed

Tang, Tao; Tang, Ting; Tan, Lu; Gu, Yuan; Jiang, Wanxiang; Cai, Qinghua

2017-06-23

Although human disturbance indirectly influences lotic assemblages through modifying physical and chemical conditions, identifying thresholds of human disturbance would provide direct evidence for preventing anthropogenic degradation of biological conditions. In the present study, we used data obtained from tributaries of the Three Gorges Reservoir in China to detect effects of human disturbance on streams and to identify disturbance thresholds for benthic diatoms. Diatom species composition was significantly affected by three in-stream stressors including TP, TN and pH. Diatoms were also influenced by watershed % farmland and natural environmental variables. Considering three in-stream stressors, TP was positively influenced by % farmland and % impervious surface area (ISA). In contrast, TN and pH were principally affected by natural environmental variables. Among measured natural environmental variables, average annual air temperature, average annual precipitation, and topsoil % CaCO 3 , % gravel, and total exchangeable bases had significant effects on study streams. When effects of natural variables were accounted for, substantial compositional changes in diatoms occurred when farmland or ISA land use exceeded 25% or 0.3%, respectively. Our study demonstrated the rationale for identifying thresholds of human disturbance for lotic assemblages and addressed the importance of accounting for effects of natural factors for accurate disturbance thresholds.

Evaluation of APRI and FIB-4 for noninvasive assessment of significant fibrosis and cirrhosis in HBeAg-negative CHB patients with ALT ≤ 2 ULN: A retrospective cohort study.

PubMed

Li, Qiang; Ren, Xiaojing; Lu, Chuan; Li, Weixia; Huang, Yuxian; Chen, Liang

2017-03-01

To evaluate the performance of aspartate transaminase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) to predict significant fibrosis and cirrhosis in hepatitis B virus e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with alanine transaminase (ALT) ≤ twice the upper limit of normal (2 ULN).Histologic and laboratory data of 236 HBeAg-negative CHB patients with ALT ≤ 2 ULN were analyzed. Predicted fibrosis stage, based on established scales and cut-offs for APRI and FIB-4, was compared with METAVIR scores obtained from liver biopsy.In this study, the areas under the receiver operating characteristic curves (AUROCs) of APRI were lower than that of FIB-4 (0.62 vs 0.69; P = 0.019) for diagnosing significant fibrosis; however APRI and FIB-4 were comparable for diagnosing cirrhosis (0.77 vs 0.81; P = 0.374). When the cut-off proposed by WHO HBV guideline for APRI (>2.0) was used, no cirrhotic patients were correctly predicted. For FIB-4, the WHO proposed cut-off of 3.25 correctly identified significant fibrosis 83% of the time; but for APRI, the WHO proposed cut-off of 1.5 identified significant fibrosis 56%. In ruling out significant fibrosis, the WHO proposed APRI cut-off of 0.5 had a predictive value of 39%, and the FIB-4 cut-off of 1.45 correctly identified lack of significant fibrosis in 47% of the patients. In this study, based on ROC analysis, the optimal cut-offs were 0.46 and 0.65 for APRI, and 1.05 and 1.29 for FIB-4, for diagnosing significant fibrosis and cirrhosis, respectively. When the new cut-off of APRI (>0.65) was used, 82% of the cirrhotic patients were correctly predicted. In ruling out significant fibrosis, the new APRI cut-off (<0.46) had a predictive value of 80%, and new FIB-4 cut-off (<1.05) correctly identified lack of significant fibrosis in 84% of the patients.The WHO guidelines proposed cut-offs might be higher for HBeAg-negative CHB patients with ALT ≤2 ULN, and might underestimate the proportion of significant fibrosis and cirrhosis. A new set of cut-offs should be used to predict significant fibrosis and cirrhosis in this specific population.

Drug-Induced Dental Caries: A Disproportionality Analysis Using Data from VigiBase.

PubMed

de Campaigno, Emilie Patras; Kebir, Inès; Montastruc, Jean-Louis; Rueter, Manuela; Maret, Delphine; Lapeyre-Mestre, Maryse; Sallerin, Brigitte; Despas, Fabien

2017-12-01

Dental caries is defined as a pathological breakdown of the tooth. It is an infectious phenomenon involving a multifactorial aetiology. The impact of drugs on cariogenic risk has been poorly investigated. In this study, we identified drugs suspected to induce dental caries as adverse drug reactions (ADRs) and then studied a possible pathogenic mechanism for each drug that had a statistically significant disproportionality. We extracted individual case safety reports of dental caries associated with drugs from VigiBase ® (the World Health Organization global individual case safety report database). We calculated disproportionality for each drug with a reporting odds ratio (ROR) and 99% confidence interval. We analysed the pharmacodynamics of each drug that had a statistically significant disproportionality. In VigiBase ® , 5229 safety reports for dental caries concerning 733 drugs were identified. Among these drugs, 88 had a significant ROR, and for 65 of them (73.9%), no information about dental caries was found in the summaries of the product characteristics, the Micromedex ® DRUGDEX, or the Martindale databases. Regarding the pharmacological classes of drugs involved in dental caries, we identified bisphosphonates, atropinic drugs, antidepressants, corticoids, immunomodulating drugs, antipsychotics, antiepileptics, opioids and β 2 -adrenoreceptor agonist drugs. Regarding possible pathogenic mechanisms for these drugs, we identified changes in salivary flow/composition for 54 drugs (61.4%), bone metabolism changes for 31 drugs (35.2%), hyperglycaemia for 32 drugs (36.4%) and/or immunosuppression for 23 drugs (26.1%). For nine drugs (10.2%), the mechanism was unclear. We identified 88 drugs with a significant positive disproportionality for dental caries. Special attention has to be paid to bisphosphonates, atropinic drugs, immunosuppressants and drugs causing hyperglycaemia.

Genome-Wide Association Study in African Americans with Acute Respiratory Distress Syndrome Identifies the Selectin P Ligand Gene as a Risk Factor.

PubMed

Bime, Christian; Pouladi, Nima; Sammani, Saad; Batai, Ken; Casanova, Nancy; Zhou, Tong; Kempf, Carrie L; Sun, Xiaoguang; Camp, Sara M; Wang, Ting; Kittles, Rick A; Lussier, Yves A; Jones, Tiffanie K; Reilly, John P; Meyer, Nuala J; Christie, Jason D; Karnes, Jason H; Gonzalez-Garay, Manuel; Christiani, David C; Yates, Charles R; Wurfel, Mark M; Meduri, Gianfranco U; Garcia, Joe G N

2018-06-01

Genetic factors are involved in acute respiratory distress syndrome (ARDS) susceptibility. Identification of novel candidate genes associated with increased risk and severity will improve our understanding of ARDS pathophysiology and enhance efforts to develop novel preventive and therapeutic approaches. To identify genetic susceptibility targets for ARDS. A genome-wide association study was performed on 232 African American patients with ARDS and 162 at-risk control subjects. The Identify Candidate Causal SNPs and Pathways platform was used to infer the association of known gene sets with the top prioritized intragenic SNPs. Preclinical validation of SELPLG (selectin P ligand gene) was performed using mouse models of LPS- and ventilator-induced lung injury. Exonic variation within SELPLG distinguishing patients with ARDS from sepsis control subjects was confirmed in an independent cohort. Pathway prioritization analysis identified a nonsynonymous coding SNP (rs2228315) within SELPLG, encoding P-selectin glycoprotein ligand 1, to be associated with increased susceptibility. In an independent cohort, two exonic SELPLG SNPs were significantly associated with ARDS susceptibility. Additional support for SELPLG as an ARDS candidate gene was derived from preclinical ARDS models where SELPLG gene expression in lung tissues was significantly increased in both ventilator-induced (twofold increase) and LPS-induced (5.7-fold increase) murine lung injury models compared with controls. Furthermore, Selplg -/- mice exhibited significantly reduced LPS-induced inflammatory lung injury compared with wild-type C57/B6 mice. Finally, an antibody that neutralizes P-selectin glycoprotein ligand 1 significantly attenuated LPS-induced lung inflammation. These findings identify SELPLG as a novel ARDS susceptibility gene among individuals of European and African descent.

System-based Identification of Toxicity Pathways Associated With Multi-Walled Carbon Nanotube-Induced Pathological Responses

PubMed Central

Snyder-Talkington, Brandi N.; Dymacek, Julian; Porter, Dale W.; Wolfarth, Michael G.; Mercer, Robert R.; Pacurari, Maricica; Denvir, James; Castranova, Vincent; Qian, Yong; Guo, Nancy L.

2014-01-01

The fibrous shape and biopersistence of multi-walled carbon nanotubes (MWCNT) have raised concern over their potential toxicity after pulmonary exposure. As in vivo exposure to MWCNT produced a transient inflammatory and progressive fibrotic response, this study sought to identify significant biological processes associated with lung inflammation and fibrosis pathology data, based upon whole genome mRNA expression, bronchoaveolar lavage scores, and morphometric analysis from C57BL/6J mice exposed by pharyngeal aspiration to 0, 10, 20, 40, or 80 µg MWCNT at 1, 7, 28, or 56 days post-exposure. Using a novel computational model employing non-negative matrix factorization and Monte Carlo Markov Chain simulation, significant biological processes with expression similar to MWCNT-induced lung inflammation and fibrosis pathology data in mice were identified. A subset of genes in these processes was determined to be functionally related to either fibrosis or inflammation by Ingenuity Pathway Analysis and were used to determine potential significant signaling cascades. Two genes determined to be functionally related to inflammation and fibrosis, vascular endothelial growth factor A (vegfa) and C-C motif chemokine 2 (ccl2), were confirmed by in vitro studies of mRNA and protein expression in small airway epithelial cells exposed to MWCNT as concordant with in vivo expression. This study identified that the novel computational model was sufficient to determine biological processes strongly associated with the pathology of lung inflammation and fibrosis and could identify potential toxicity signaling pathways and mechanisms of MWCNT exposure which could be used for future animal studies to support human risk assessment and intervention efforts. PMID:23845593

Identification of a New Susceptibility Locus for Systemic Lupus Erythematosus on Chromosome 12 in Individuals of European Ancestry

PubMed Central

Demirci, F. Yesim; Wang, Xingbin; Kelly, Jennifer A.; Morris, David L.; Barmada, M. Michael; Feingold, Eleanor; Kao, Amy H.; Sivils, Kathy L.; Bernatsky, Sasha; Pineau, Christian; Clarke, Ann; Ramsey-Goldman, Rosalind; Vyse, Timothy J.; Gaffney, Patrick M.; Manzi, Susan; Kamboh, M. Ilyas

2016-01-01

Objective Genome-wide association studies (GWASs) in individuals of European ancestry identified a number of systemic lupus erythematosus (SLE) susceptibility loci using earlier versions of high-density genotyping platforms. Follow-up studies on suggestive GWAS regions using larger samples and more markers identified additional SLE loci in European-descent subjects. Here we report the results of a multi-stage study that we performed to identify novel SLE loci. Methods In Stage 1, we conducted a new GWAS of SLE in a North American case-control sample of European ancestry (n=1,166) genotyped on Affymetrix Genome-Wide Human SNP Array 6.0. In Stage 2, we further investigated top new suggestive GWAS hits by in silico evaluation and meta-analysis using an additional dataset of European-descent subjects (>2,500 individuals), followed by replication of top meta-analysis findings in another dataset of European-descent subjects (>10,000 individuals) in Stage 3. Results As expected, our GWAS revealed most significant associations at the major histocompatibility complex locus (6p21), which easily surpassed genome-wide significance threshold (P<5×10−8). Several other SLE signals/loci previously implicated in Caucasians and/or Asians were also supported in Stage 1 discovery sample and strongest signals were observed at 2q32/STAT4 (P=3.6×10−7) and at 8p23/BLK (P=8.1×10−6). Stage 2 meta-analyses identified a new genome-wide significant SLE locus at 12q12 (meta P=3.1×10−8), which was replicated in Stage 3. Conclusion Our multi-stage study identified and replicated a new SLE locus that warrants further follow-up in additional studies. Publicly available databases suggest that this new SLE signal falls within a functionally relevant genomic region and near biologically important genes. PMID:26316170

[Effects of tai chi in postmenopausal women with osteoporosis: a systematic review].

PubMed

Chang, Ting-Jung; Ting, Yu-Ting; Sheu, Shei-Lan; Chang, Hsiao-Yun

2014-10-01

Tai chi has been increasingly applied in osteoporosis patients. However, systematic reviews of the efficacy of this practice have been few and of limited scope. This study reviews previous experimental research work using tai chi as an intervention in postmenopausal women with osteoporosis and to appraise the reported research designs used, tai chi methods used, and outcomes. A systematic review method was used to search 14 databases for articles published between January 1980 and July 2013. Searched keywords included: "tai chi," "osteoporosis," and "postmenopausal women". The 2,458 articles initially identified were reduced to 4 valid articles based on considerations of criteria and repeatability. The 4 valid articles used either a randomized clinical trial (RCT) or a controlled clinical trial (CCT). They were further analyzed and synthesized in terms of common variables such as balance, muscle strength, and quality of life. Three of the 4 studies identified significant pretest / posttest differences in physiological aspects of quality of life in participants but did not obtain consistent results in terms of the psychological aspects. While reports identified a significant and positive tai chi effect on balance, they all used different measurements to do so. Only one of the four studies identified significant improvement in muscle strength. Therefore, this review could not identify clear support for the effectiveness of tai chi on balance or muscle strength. This review did not definitively support the positive effects of tai chi on balance, muscle strength, and quality of life in postmenopausal women with osteoporosis. The designs used in the tai chi interventions may be referenced for future studies. We suggest that future studies use data triangulation rather than a single-item tool to validate the research in order to cross-verify the same information. This may strengthen the research and increase the credibility and the validity of related findings.

Convergent Genetic and Expression Datasets Highlight TREM2 in Parkinson's Disease Susceptibility.

PubMed

Liu, Guiyou; Liu, Yongquan; Jiang, Qinghua; Jiang, Yongshuai; Feng, Rennan; Zhang, Liangcai; Chen, Zugen; Li, Keshen; Liu, Jiafeng

2016-09-01

A rare TREM2 missense mutation (rs75932628-T) was reported to confer a significant Alzheimer's disease (AD) risk. A recent study indicated no evidence of the involvement of this variant in Parkinson's disease (PD). Here, we used the genetic and expression data to reinvestigate the potential association between TREM2 and PD susceptibility. In stage 1, using 10 independent studies (N = 89,157; 8787 cases and 80,370 controls), we conducted a subgroup meta-analysis. We identified a significant association between rs75932628 and PD (P = 3.10E-03, odds ratio (OR) = 3.88, 95 % confidence interval (CI) 1.58-9.54) in No-Northern Europe subgroup, and significantly increased PD risks (P = 0.01 for Mann-Whitney test) in No-Northern Europe subgroup than in Northern Europe subgroup. In stage 2, we used the summary results from a large-scale PD genome-wide association study (GWAS; N = 108,990; 13,708 cases and 95,282 controls) to search for other TREM2 variants contributing to PD susceptibility. We identified 14 single-nucleotide polymorphisms (SNPs) associated with PD within 50-kb upstream and downstream range of TREM2. In stage 3, using two brain expression GWAS datasets (N = 773), we identified 6 of the 14 SNPs regulating increased expression of TREM2. In stage 4, using the whole human genome microarray data (N = 50), we further identified significantly increased expression of TREM2 in PD cases compared with controls in human prefrontal cortex. In summary, convergent genetic and expression datasets demonstrate that TREM2 is a potent risk factor for PD and may be a therapeutic target in PD and other neurodegenerative diseases.

MiR-422a as a Potential Cellular MicroRNA Biomarker for Postmenopausal Osteoporosis

PubMed Central

Cao, Zheng; Moore, Benjamin T.; Wang, Yang; Peng, Xian-Hao; Lappe, Joan M.; Recker, Robert R.; Xiao, Peng

2014-01-01

Background MicroRNAs (miRNAs) are a class of short non-coding RNA molecules that regulate gene expression by targeting mRNAs. Recently, miRNAs have been shown to play important roles in the etiology of various diseases. However, little is known about their roles in the development of osteoporosis. Circulating monocytes are osteoclast precursors that also produce various factors important for osteoclastogenesis. Previously, we have identified a potential biomarker miR-133a in circulating monocytes for postmenopausal osteoporosis. In this study, we aimed to further identify significant miRNA biomarkers in human circulating monocytes underlying postmenopausal osteoporosis. Methodology/Principal Findings We used ABI TaqMan miRNA array followed by qRT-PCR validation in human circulating monocytes from 10 high BMD and 10 low BMD postmenopausal Caucasian women to identify miRNA biomarkers. MiR-422a was up-regulated with marginal significance (P = 0.065) in the low compared with the high BMD group in the array analysis. However, a significant up-regulation of miR-422a was identified in the low BMD group by qRT-PCR analysis (P = 0.029). We also performed bioinformatic target gene analysis and found several potential target genes of miR-422a which are involved in osteoclastogenesis. Further qRT-PCR analyses of the target genes in the same study subjects showed that the expression of five of these genes (CBL, CD226, IGF1, PAG1, and TOB2) correlated negatively with miR-422a expression. Conclusions/Significance Our study suggests that miR-422a in human circulating monocytes (osteoclast precursors) is a potential miRNA biomarker underlying postmenopausal osteoporosis. PMID:24820117

Genome-wide association study identifies multiple loci associated with bladder cancer risk

PubMed Central

Figueroa, Jonine D.; Ye, Yuanqing; Siddiq, Afshan; Garcia-Closas, Montserrat; Chatterjee, Nilanjan; Prokunina-Olsson, Ludmila; Cortessis, Victoria K.; Kooperberg, Charles; Cussenot, Olivier; Benhamou, Simone; Prescott, Jennifer; Porru, Stefano; Dinney, Colin P.; Malats, Núria; Baris, Dalsu; Purdue, Mark; Jacobs, Eric J.; Albanes, Demetrius; Wang, Zhaoming; Deng, Xiang; Chung, Charles C.; Tang, Wei; Bas Bueno-de-Mesquita, H.; Trichopoulos, Dimitrios; Ljungberg, Börje; Clavel-Chapelon, Françoise; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth; Tjønneland, Anne; Brenan, Paul; Chang-Claude, Jenny; Riboli, Elio; Conti, David; Gago-Dominguez, Manuela; Stern, Mariana C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Hohensee, Chancellor; Rodabough, Rebecca; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Chen, Constance; De Vivo, Immaculata; Giovannucci, Edward; Hunter, David J.; Kraft, Peter; Lindstrom, Sara; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Kamat, Ashish M.; Lerner, Seth P.; Barton Grossman, H.; Lin, Jie; Gu, Jian; Pu, Xia; Hutchinson, Amy; Burdette, Laurie; Wheeler, William; Kogevinas, Manolis; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Schwenn, Molly; Karagas, Margaret R.; Johnson, Alison; Schned, Alan; Armenti, Karla R.; Hosain, G.M.; Andriole, Gerald; Grubb, Robert; Black, Amanda; Ryan Diver, W.; Gapstur, Susan M.; Weinstein, Stephanie J.; Virtamo, Jarmo; Haiman, Chris A.; Landi, Maria T.; Caporaso, Neil; Fraumeni, Joseph F.; Vineis, Paolo; Wu, Xifeng; Silverman, Debra T.; Chanock, Stephen; Rothman, Nathaniel

2014-01-01

Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10−5 was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10−9) and rs907611 on 11p15.5 (P = 4.11 × 10−8). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10−7) and rs4510656 on 6p22.3 (P = 6.98 × 10−7); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis. PMID:24163127

Meta-analysis of incidence of early lung toxicity in 3-dimensional conformal irradiation of breast carcinomas

PubMed Central

2013-01-01

Background This meta-analysis aims to ascertain the significance of early lung toxicity with 3-Dimensional (3D) conformal irradiation for breast carcinomas and identify the sub-groups of patients with increased risk. Methods Electronic databases, reference sections of major oncological textbooks and identified studies were searched for synonyms of breast radiotherapy and radiation pneumonitis (RP). Major studies in thoracic irradiation were reviewed to identify factors frequently associated with RP. Meta-analysis for RP incidence estimation and odds ratio calculation were carried out. Results The overall incidence of Clinical and Radiological RP is 14% and 42% respectively. Ten studies were identified. Dose-volume Histogram (DVH) related dosimetric factors (Volume of lung receiving certain dose, Vdose and Mean lung Dose, MLD), supraclavicular fossa (SCF) irradiation and age are significantly associated with RP, but not sequential chemotherapy and concomitant use of Tamoxifen. A poorly powered study in IMN group contributed to the negative finding. Smoking has a trend towards protective effect against RP. Conclusion Use of other modalities may be considered when Ipsilateral lung V20Gy > 30% or MLD > 15 Gy. Extra caution is needed in SCF and IMN irradiation as they are likely to influence these dosimetric parameters. PMID:24229418

Tibiofemoral Osteoarthritis and Varus-Valgus Laxity

PubMed Central

Freisinger, Gregory M.; Schmitt, Laura C.; Wanamaker, Andrea B.; Siston, Robert A.; Chaudhari, Ajit M. W.

2017-01-01

The purpose of this study was to systematically review and synthesize the literature measuring varus-valgus laxity in individuals with tibiofemoral osteoarthritis (OA). Specifically, we aimed to identify varus-valgus laxity differences between persons with OA and controls, by radiographic disease severity, by frontal plane knee alignment, and by sex. We also aimed to identify if there was a relationship between varus-valgus laxity and clinical performance and self-reported function. We systematically searched for peer-reviewed original research articles in PubMed, Scopus, and CINAHL to identify all existing literature regarding knee OA and objective measurement of varus-valgus laxity in vivo. Forty articles were identified that met the inclusion criteria and data were extracted. Varus-valgus laxity was significantly greater in individuals with OA compared with controls in a majority of studies, while no study found laxity to be significantly greater in controls. Varus-valgus laxity of the knee was reported in persons with OA and varying degrees of frontal plane alignment, disease severity, clinical performance, and self-reported function but no consensus finding could be identified. Females with knee OA appear to have more varus-valgus laxity than males. Meta-analysis was not possible due to the heterogeneity of the subject populations and differences in laxity measurement devices, applied loading, and laxity definitions. Increased varus-valgus laxity is a characteristic of knee joints with OA. Large variances exist in reported varus-valgus laxity and may be due to differences in measurement devices. Prospective studies on joint laxity are needed to identify if increased varus-valgus laxity is a causative factor in OA incidence and progression. PMID:27680888

A correlational and predictive study of creativity and personality of college students.

PubMed

Sanz de Acedo Baquedano, María Teresa; Sanz de Acedo Lizarraga, María Luisa

2012-11-01

The goals of this study were to examine the relationship between creativity and personality, to identify what personality variables better predict creativity, and to determine whether significant differences exist among them in relation to gender. The research was conducted with a sample of 87 students at the Universidad Pública de Navarra, Spain. We administered the Creative Intelligence Test (CREA), which provides a cognitive measure for creativity and the Situational Personality Questionnaire (SPQ), which is composed of 15 personality features. Positive and significant correlations between creativity and independence, cognitive control, and tolerance personality scales were found. Negative and significant correlations between creativity and anxious, dominant, and aggressive personalities were also found. Moreover, four personality variables that positively predicted creativity (efficacy, independence, cognitive control, and integrity-honesty) and another four that negatively predicted creativity (emotional stability, anxiety, dominance, and leadership) were identified. The results did not show significant differences in creativity and personality in relation to gender, except in self-concept and in social adjustment. In conclusion, the results from this study can potentially be used to expand the types of features that support creative personalities.

Paternal exposure to medical-related radiation associated with low birthweight infants

PubMed Central

Chen, Shi; Yang, Yingying; QV, Yimin; Zou, Yun; ZHU, Huijuan; Gong, Fengying; Zou, Yongwei; Yang, Hongbo; WANG, Linjie; Lian, Bill Q.; Liu, Cynthia; Jiang, Yu; Yan, Chengsheng; LI, Jianqiang; Wang, Qing; Pan, Hui

2018-01-01

Abstract Low birthweight (LBW) is closely associated with fetal and perinatal mortality and morbidity. We identified the risk factors of LBW and geographical differences in LBW incidence in 30 Chinese provinces in the present study. This study was a population-based, retrospective cohort study performed in 30 Chinese provinces. We used data from the free National Pre-pregnancy Checkups Project, which is a countrywide population-based retrospective cohort study. To identify regional differences in LBW incidence, we used the Qinling-Huaihe climate line to divide China into northern and southern sections and the Heihe-Tengchong economic line to divide it into eastern and western sections. Multivariate unconditional logistic regression analysis with SAS 9.4 was used for data analysis. P < .05 was considered statistically significant. LBW incidence was 4.54% in rural China. Southern China had a significantly higher incidence (4.65%) than northern China (4.28%). Our main risk factor for LBW is paternal exposure to radiation (odds ratio = 1.537), which has never been studied before. This study identifies multiple risk factors of couples giving birth to LBW babies including paternal risk factors. PMID:29480847

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.

Identification of Candidate Genes Underlying an Iron Efficiency Quantitative Trait Locus in Soybean1

PubMed Central

Peiffer, Gregory A.; King, Keith E.; Severin, Andrew J.; May, Gregory D.; Cianzio, Silvia R.; Lin, Shun Fu; Lauter, Nicholas C.; Shoemaker, Randy C.

2012-01-01

Prevalent on calcareous soils in the United States and abroad, iron deficiency is among the most common and severe nutritional stresses in plants. In soybean (Glycine max) commercial plantings, the identification and use of iron-efficient genotypes has proven to be the best form of managing this soil-related plant stress. Previous studies conducted in soybean identified a significant iron efficiency quantitative trait locus (QTL) explaining more than 70% of the phenotypic variation for the trait. In this research, we identified candidate genes underlying this QTL through molecular breeding, mapping, and transcriptome sequencing. Introgression mapping was performed using two related near-isogenic lines in which a region located on soybean chromosome 3 required for iron efficiency was identified. The region corresponds to the previously reported iron efficiency QTL. The location was further confirmed through QTL mapping conducted in this study. Transcriptome sequencing and quantitative real-time-polymerase chain reaction identified two genes encoding transcription factors within the region that were significantly induced in soybean roots under iron stress. The two induced transcription factors were identified as homologs of the subgroup lb basic helix-loop-helix (bHLH) genes that are known to regulate the strategy I response in Arabidopsis (Arabidopsis thaliana). Resequencing of these differentially expressed genes unveiled a significant deletion within a predicted dimerization domain. We hypothesize that this deletion disrupts the Fe-DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (FIT)/bHLH heterodimer that has been shown to induce known iron acquisition genes. PMID:22319075

[Clinical observation of modified Da Chaihu decoction in treating essential hypertension with anxiety].

PubMed

Zhang, Xiang-Dong; Cheng, Wang-Qiang; Wang, Yong-Gang; Zhang, Zheng

2017-06-01

To observe the clinical efficacy of modified Da Chaihu decoction in treating essential hypertension with anxiety, the randomized, controlled, clinical trial was performed in this study. One hundred and twenty-six hypertensive patients with anxiety meeting the inclusive criteria were randomized into the treatment group and the control group. All of the included patients in the above 2 groups were treated by amlodipine besylate tablets. Patients in the treatment group were given Chinese herbal medicine modified Da Chaihu decoction every day. And patients in the control group were given flupentixol and melitracen tablets. The treatment course was 4 weeks. Blood pressure, the score of traditional Chinese medicine syndrome, blood lipids, C reactive protein, the Hamilton anxiety scale score and adverse effects were observed. It has been identified that, both systolic and diastolic blood pressure were significantly reduced (P<0.05). However, no significant difference between the treatment group and the control group was identified. For traditional Chinese medicine syndrome, it was significantly improved in the treatment group (P<0.05). For blood lipids, TC, TG, HDL-C, and LDL-C were significantly improved in the treatment group (P<0.05). After treatment, only TC was significantly reduced in the treatment group when compared to the control group (P<0.05). For C reactive protein, it was significantly reduced in the treatment group after treatment (P<0.05). For anxiety, no significant difference between the treatment group and the control group on the Hamilton anxiety scale score was identified. For adverse effect, no severe adverse effect was identified in this study. The modified Da Chaihu decoction maybe effective in the treatment of essential hypertension with anxiety. In addition to a certain role in lowering blood pressure, the modified Da Chaihu decoction was also effective in improving traditional Chinese medicine syndrome and blood lipids, reducing the level of C reactive protein, relieving anxiety with little adverse effect. Copyright© by the Chinese Pharmaceutical Association.

Vaginal birth after cesarean: new insights on maternal and neonatal outcomes.

PubMed

Guise, Jeanne-Marie; Denman, Mary Anna; Emeis, Cathy; Marshall, Nicole; Walker, Miranda; Fu, Rongwei; Janik, Rosalind; Nygren, Peggy; Eden, Karen B; McDonagh, Marian

2010-06-01

To systematically review the evidence about maternal and neonatal outcomes relating to vaginal birth after cesarean (VBAC). Relevant studies were identified from multiple searches of MEDLINE, DARE, and the Cochrane databases (1980 to September 2009) and from recent systematic reviews, reference lists, reviews, editorials, Web sites, and experts. Inclusion criteria limited studies to the English-language and human studies conducted in the United States and developed countries specifically evaluating birth after previous cesarean delivery. Studies focusing on high-risk maternal or neonatal conditions, including breech vaginal delivery, or fewer than 10 patients were excluded. Poor-quality studies were not included in analyses. We identified 3,134 citations and reviewed 963 articles for inclusion; 203 articles met the inclusion criteria and were quality rated. Overall rates of maternal harms were low for both trial of labor and elective repeat cesarean delivery. Although rare in both elective repeat cesarean delivery and trial of labor, maternal mortality was significantly increased for elective repeat cesarean delivery at 0.013% compared with 0.004% for trial of labor. The rates of maternal hysterectomy, hemorrhage, and transfusions did not differ significantly between trial of labor and elective repeat cesarean delivery. The rate of uterine rupture for all women with prior cesarean was 0.30%, and the risk was significantly increased for trial of labor (0.47% compared with 0.03% for elective repeat cesarean delivery). Perinatal mortality was also significantly increased for trial of labor (0.13% compared with 0.05% for elective repeat cesarean delivery). Overall the best evidence suggests that VBAC is a reasonable choice for the majority of women. Adverse outcomes were rare for both elective repeat cesarean delivery and trial of labor. Definitive studies are lacking to identify patients who are at greatest risk for adverse outcomes.

Soybean Resistance to White Mold: Evaluation of Soybean Germplasm Under Different Conditions and Validation of QTL

PubMed Central

Kandel, Ramkrishna; Chen, Charles Y.; Grau, Craig R.; Dorrance, Ann E.; Liu, Jean Q.; Wang, Yang; Wang, Dechun

2018-01-01

Soybean (Glycine max L. Merr.) white mold (SWM), caused by Sclerotinia sclerotiorum (Lib) de Barry), is a devastating fungal disease in the Upper Midwest of the United States and southern Canada. Various methods exist to evaluate for SWM resistance and many quantitative trait loci (QTL) with minor effect governing SWM resistance have been identified in prior studies. This study aimed to predict field resistance to SWM using low-cost and efficient greenhouse inoculation methods and to confirm the QTL reported in previous studies. Three related but independent studies were conducted in the field, greenhouse, and laboratory to evaluate for SWM resistance. The first study evaluated 66 soybean plant introductions (PIs) with known field resistance to SWM using the greenhouse drop-mycelium inoculation method. These 66 PIs were significantly (P < 0.043) different for resistance to SWM. However, year was highly significant (P < 0.00001), while PI x year interaction was not significant (P < 0.623). The second study compared plant mortality (PM) of 35 soybean breeding lines or varieties in greenhouse inoculation methods with disease severity index (DSI) in field evaluations. Moderate correlation (r) between PM under drop-mycelium method and DSI in field trials (r = 0.65, p < 0.0001) was obtained. The PM under spray-mycelium was also correlated significantly with DSI from field trials (r = 0.51, p < 0.0018). Likewise, significant correlation (r = 0.62, p < 0.0001) was obtained between PM across greenhouse inoculation methods and DSI across field trials. These findings suggest that greenhouse inoculation methods could predict the field resistance to SWM. The third study attempted to validate 33 QTL reported in prior studies using seven populations that comprised a total of 392 F4 : 6 lines derived from crosses involving a partially resistant cultivar “Skylla,” five partially resistant PIs, and a known susceptible cultivar “E00290.” The estimates of broad-sense heritability (h2) ranged from 0.39 to 0.66 in the populations. Of the seven populations, four had h2 estimates that were significantly different from zero (p < 0.05). Single marker analysis across populations and inoculation methods identified 11 significant SSRs (p < 0.05) corresponding to 10 QTL identified by prior studies. Thus, these five new PIs could be used as new sources of resistant alleles to develop SWM resistant commercial cultivars. PMID:29731761

A Multi-Ethnic Meta-Analysis of Genome-Wide Association Studies in Over 100,000 Subjects Identifies 23 Fibrinogen-Associated Loci but no Strong Evidence of a Causal Association between Circulating Fibrinogen and Cardiovascular Disease

PubMed Central

Sabater-Lleal, Maria; Huang, Jie; Chasman, Daniel; Naitza, Silvia; Dehghan, Abbas; Johnson, Andrew D; Teumer, Alexander; Reiner, Alex P; Folkersen, Lasse; Basu, Saonli; Rudnicka, Alicja R; Trompet, Stella; Mälarstig, Anders; Baumert, Jens; Bis, Joshua C.; Guo, Xiuqing; Hottenga, Jouke J; Shin, So-Youn; Lopez, Lorna M; Lahti, Jari; Tanaka, Toshiko; Yanek, Lisa R; Oudot-Mellakh, Tiphaine; Wilson, James F; Navarro, Pau; Huffman, Jennifer E; Zemunik, Tatijana; Redline, Susan; Mehra, Reena; Pulanic, Drazen; Rudan, Igor; Wright, Alan F; Kolcic, Ivana; Polasek, Ozren; Wild, Sarah H; Campbell, Harry; Curb, J David; Wallace, Robert; Liu, Simin; Eaton, Charles B.; Becker, Diane M.; Becker, Lewis C.; Bandinelli, Stefania; Räikkönen, Katri; Widen, Elisabeth; Palotie, Aarno; Fornage, Myriam; Green, David; Gross, Myron; Davies, Gail; Harris, Sarah E; Liewald, David C; Starr, John M; Williams, Frances M.K.; Grant, P.J.; Spector, Timothy D.; Strawbridge, Rona J; Silveira, Angela; Sennblad, Bengt; Rivadeneira, Fernando; Uitterlinden, Andre G; Franco, Oscar H; Hofman, Albert; van Dongen, Jenny; Willemsen, G; Boomsma, Dorret I; Yao, Jie; Jenny, Nancy Swords; Haritunians, Talin; McKnight, Barbara; Lumley, Thomas; Taylor, Kent D; Rotter, Jerome I; Psaty, Bruce M; Peters, Annette; Gieger, Christian; Illig, Thomas; Grotevendt, Anne; Homuth, Georg; Völzke, Henry; Kocher, Thomas; Goel, Anuj; Franzosi, Maria Grazia; Seedorf, Udo; Clarke, Robert; Steri, Maristella; Tarasov, Kirill V; Sanna, Serena; Schlessinger, David; Stott, David J; Sattar, Naveed; Buckley, Brendan M; Rumley, Ann; Lowe, Gordon D; McArdle, Wendy L; Chen, Ming-Huei; Tofler, Geoffrey H; Song, Jaejoon; Boerwinkle, Eric; Folsom, Aaron R.; Rose, Lynda M.; Franco-Cereceda, Anders; Teichert, Martina; Ikram, M Arfan; Mosley, Thomas H; Bevan, Steve; Dichgans, Martin; Rothwell, Peter M.; Sudlow, Cathie L M; Hopewell, Jemma C.; Chambers, John C.; Saleheen, Danish; Kooner, Jaspal S.; Danesh, John; Nelson, Christopher P; Erdmann, Jeanette; Reilly, Muredach P.; Kathiresan, Sekar; Schunkert, Heribert; Morange, Pierre-Emmanuel; Ferrucci, Luigi; Eriksson, Johan G; Jacobs, David; Deary, Ian J; Soranzo, Nicole; Witteman, Jacqueline CM; de Geus, Eco JC; Tracy, Russell P.; Hayward, Caroline; Koenig, Wolfgang; Cucca, Francesco; Jukema, J Wouter; Eriksson, Per; Seshadri, Sudha; Markus, Hugh S.; Watkins, Hugh; Samani, Nilesh J; Wallaschofski, Henri; Smith, Nicholas L.; Tregouet, David; Ridker, Paul M.; Tang, Weihong; Strachan, David P.; Hamsten, Anders; O’Donnell, Christopher J.

2013-01-01

Background Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease (CVD), range from 34 to 50%. Genetic variants so far identified by genome-wide association (GWA) studies only explain a small proportion (< 2%) of its variation. Methods and Results We conducted a meta-analysis of 28 GWA studies, including more than 90,000 subjects of European ancestry, the first GWA meta-analysis of fibrinogen levels in 7 African Americans studies totaling 8,289 samples, and a GWA study in Hispanic-Americans totaling 1,366 samples. Evaluation for association of SNPs with clinical outcomes included a total of 40,695 cases and 85,582 controls for coronary artery disease (CAD), 4,752 cases and 24,030 controls for stroke, and 3,208 cases and 46,167 controls for venous thromboembolism (VTE). Overall, we identified 24 genome-wide significant (P<5×10−8) independent signals in 23 loci, including 15 novel associations, together accounting for 3.7% of plasma fibrinogen variation. Gene-set enrichment analysis highlighted key roles in fibrinogen regulation for the three structural fibrinogen genes and pathways related to inflammation, adipocytokines and thyrotrophin-releasing hormone signaling. Whereas lead SNPs in a few loci were significantly associated with CAD, the combined effect of all 24 fibrinogen-associated lead SNPs was not significant for CAD, stroke or VTE. Conclusion We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and CAD, stroke or VTE. PMID:23969696

Risk factors for antenatal depression, postnatal depression and parenting stress.

PubMed

Leigh, Bronwyn; Milgrom, Jeannette

2008-04-16

Given that the prevalence of antenatal and postnatal depression is high, with estimates around 13%, and the consequences serious, efforts have been made to identify risk factors to assist in prevention, identification and treatment. Most risk factors associated with postnatal depression have been well researched, whereas predictors of antenatal depression have been less researched. Risk factors associated with early parenting stress have not been widely researched, despite the strong link with depression. The aim of this study was to further elucidate which of some previously identified risk factors are most predictive of three outcome measures: antenatal depression, postnatal depression and parenting stress and to examine the relationship between them. Primipara and multiparae women were recruited antenatally from two major hoitals as part of the beyondblue National Postnatal Depression Program 1. In this subsidiary study, 367 women completed an additional large battery of validated questionnaires to identify risk factors in the antenatal period at 26-32 weeks gestation. A subsample of these women (N = 161) also completed questionnaires at 10-12 weeks postnatally. Depression level was measured by the Beck Depression Inventory (BDI). Regression analyses identified significant risk factors for the three outcome measures. (1). Significant predictors for antenatal depression: low self-esteem, antenatal anxiety, low social support, negative cognitive style, major life events, low income and history of abuse. (2). Significant predictors for postnatal depression: antenatal depression and a history of depression while also controlling for concurrent parenting stress, which was a significant variable. Antenatal depression was identified as a mediator between seven of the risk factors and postnatal depression. (3). Postnatal depression was the only significant predictor for parenting stress and also acted as a mediator for other risk factors. Risk factor profiles for antenatal depression, postnatal depression and parenting stress differ but are interrelated. Antenatal depression was the strongest predictor of postnatal depression, and in turn postnatal depression was the strongest predictor for parenting stress. These results provide clinical direction suggesting that early identification and treatment of perinatal depression is important.

Opposing roles of PGD2 in GBM.

PubMed

Ferreira, Matthew Thomas; Gomes, Renata Nascimento; Panagopoulos, Alexandros Theodoros; de Almeida, Fernando Gonçalves; Veiga, José Carlos Esteves; Colquhoun, Alison

2018-01-01

The World Health Organization classifies glioblastoma (GBM) as a grade IV astrocytoma. Despite the advances in chemotherapy, surgery, and radiation treatments that improve a patient's length of survival, the overall trajectory of the disease remains unchanged. GBM cells produce significant levels of various types of bioactive lipids. Prostaglandin D 2 (PGD 2 ) influences both pro- and anti-tumorigenic activities in the cell; however, its role in GBM is unclear. Therefore, this study aimed to identify the impact of PGD 2 on GBM cell activities in vitro. First we looked to identify the presence of the PGD 2 synthesis pathway through RT-PCR, immunohistochemistry, and HPLC-MS/MS in three GBM cell lines. Then, to observe PGD 2 's effects on cell count and apoptosis/mitosis (Hoechst 33342 stain), and migration (Transwell Assay), the cells were treated in vitro with physiological (<1μM) and/or supraphysiological (>1μM) concentrations of PGD 2 over 72h. HPLC-MS/MS was used to identify the lipid composition of patients with either Grade II/III gliomas or GBM. We identified the presence of endogenous PGD 2 with its corresponding enzymes and receptors. Exogenous PGD 2 both increased cell count (<1μM) and decreased cell count (10μM) in a concentration-dependent manner. There were no significant effects on apoptosis. A significant decrease in mitotic activity was seen only in U251MG, and a significant increase was seen in migration with 5μM PGD 2 treatments. A very significant increase of PGD 2 was seen from Grade II/III gliomas to GBM. Our study demonstrates that prostaglandin D 2 possesses a dynamic, concentration-dependent effect in GBM cell activities. The increase of PGD 2 production in GBM patients suggests a pro-tumorigenic role of PGD 2 in glioma growth and invasion. Therefore, prostaglandin signaling in GBM requires further investigation to identify new targets for more effective therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

Validation of genetic polymorphisms on BTA14 associated with carcass trait in a commercial Hanwoo population.

PubMed

Sharma, A; Dang, C G; Kim, K S; Kim, J J; Lee, H K; Kim, H C; Yeon, S H; Kang, H S; Lee, S H

2014-12-01

The objective of this study was to validate the association of significant SNPs identified from a previous genome-wide association study with carcass weight (CWT) in a commercial Hanwoo population. We genotyped 13 SNPs located on BTA14 in 867 steers from Korea Hanwoo feedlot bulls. Of these 13 SNPs, five SNPs, namely rs29021868, rs110061498, rs109546980, rs42404006 and rs42303720, were found to be significantly associated (P < 0.001) with CWT. These five significant markers spanned the 24.3 to 29.4 Mb region of BTA14. The most significant marker (rs29021868) for CWT in this study had a 13.07 kg allele substitution effect and accounted for 2.4% of the additive genetic variance in the commercial Hanwoo population. The SNP marker rs109546980 was found to be significantly associated with both CWT (P < 0.001) and eye muscle area (P < 0.001) and could potentially be exploited for marker-assisted selection in Hanwoo cattle. We also genotyped the ss319607402 variation, which maps to intron2 of PLAG1 gene and which is already reported to be associated with height, to identify any significant association with carcass weight; however, no such association was observed in this Hanwoo commercial population. © 2014 Stichting International Foundation for Animal Genetics.

A systematic review on the effectiveness of titratable over nontitratable mandibular advancement appliances for sleep apnea.

PubMed

Sivaramakrishnan, Gowri; Sridharan, Kannan

2017-01-01

Mandibular advancement appliances are being tested for use in patients with obstructive sleep apnea (OSA). However, the effectiveness of titration of these appliances does not have conclusive evidence. Systematic reviews help us to compile all available clinical evidence using statistical principles. Hence, the aim of this systematic review is to identify the effectiveness of titratable over nontitratable mandibular advancement appliances in patients with mild to moderate OSA. This review objective is to identify if titration of these appliances produce significant benefits over fixed appliances. Electronic databases were searched to identify eligible studies based on set inclusion criteria. Data extraction form was created and the data were extracted. The participants were mild to moderate OSA patients who received mandibular advancement appliances. Studies included a comparison between titratable and nontitratable mandibular advancement appliance. Of the five included studies, three were observational and two were a randomized trial. All these studies were conducted in adults. The outcome attributes were polysomnographic readings and apnea-hypopnea index (AHI). A significant heterogeneity was seen between the eligible studies and hence a meta-analysis could not be performed. The results from this systematic review did not show significant advantages of titratable appliances, although titratable appliances performed better from individual studies as regards to reduction in AHI and polysomnography. The reason is the lack of sufficient clinical trials on the same. More high quality randomized controlled trials comparing titratable and fixed appliances have to be initiated to get to conclusive evidence.

Association of genetic variants of GRIN2B with autism.

PubMed

Pan, Yongcheng; Chen, Jingjing; Guo, Hui; Ou, Jianjun; Peng, Yu; Liu, Qiong; Shen, Yidong; Shi, Lijuan; Liu, Yalan; Xiong, Zhimin; Zhu, Tengfei; Luo, Sanchuan; Hu, Zhengmao; Zhao, Jingping; Xia, Kun

2015-02-06

Autism (MIM 209850) is a complex neurodevelopmental disorder characterized by social communication impairments and restricted repetitive behaviors. It has a high heritability, although much remains unclear. To evaluate genetic variants of GRIN2B in autism etiology, we performed a system association study of common and rare variants of GRIN2B and autism in cohorts from a Chinese population, involving a total sample of 1,945 subjects. Meta-analysis of a triad family cohort and a case-control cohort identified significant associations of multiple common variants and autism risk (Pmin = 1.73 × 10(-4)). Significantly, the haplotype involved with the top common variants also showed significant association (P = 1.78 × 10(-6)). Sanger sequencing of 275 probands from a triad cohort identified several variants in coding regions, including four common variants and seven rare variants. Two of the common coding variants were located in the autism-related linkage disequilibrium (LD) block, and both were significantly associated with autism (P < 9 × 10(-3)) using an independent control cohort. Burden analysis and case-only analysis of rare coding variants identified by Sanger sequencing did not find this association. Our study for the first time reveals that common variants and related haplotypes of GRIN2B are associated with autism risk.

Significance of genetic variants in DLC1 and their association with hepatocellular carcinoma

PubMed Central

XIE, CHENG-RONG; SUN, HONG-GUANG; SUN, YU; ZHAO, WEN-XIU; ZHANG, SHENG; WANG, XIAO-MIN; YIN, ZHEN-YU

2015-01-01

DLC1 has been shown to be downregulated or absent in hepatocellular carcinoma (HCC) and is associated with tumorigenesis and development. However, only a small number of studies have focused on genetic variations of DLC1. The present study performed exon sequencing for the DLC1 gene in HCC tissue samples from 105 patients to identify functional genetic variation of DLC1 and its association with HCC susceptibility, clinicopathological features and prognosis. A novel missense mutation and four non-synonymous single nucleotide polymorphisms (SNPs; rs3816748, rs11203495, rs3816747 and rs532841) were identified. A significant correlation of rs3816747 polymorphisms with HCC susceptibility was identified. Compared to individuals with the GG genotype of rs3816747, those with the GA (odds ratio (OR)=0.486; P=0.037) or GA+AA genotype (OR=0.51; P=0.039) were associated with a significantly decreased HCC risk. Furthermore, patients with the GC+CC genotype of rs3816748, the TC+CC genotype of rs11203495 or the GA+AA genotype of rs3816747 had small-sized tumors compared with those carrying the wild-type genotype. No significant association of DLC1 SNPs with the patients' prognosis was found. These results indicated that genetic variations in the DLC1 gene may confer a risk for HCC. PMID:26095787

The prevalence and clinical significance of maxillary sinus mucous retention cysts in a general clinic population.

PubMed

Rhodus, N L

1990-02-01

Previous studies have documented the occurrence and potential clinical significance of MSMR cysts. Studies also have alluded to a relationship between the MSMR cyst and certain signs or symptoms of disease. We determined the prevalence of MSMR cysts in a general clinic population and identified some important correlations with clinical signs and symptoms.

Effectiveness of trauma team on medical resource utilization and quality of care for patients with major trauma.

PubMed

Wang, Chih-Jung; Yen, Shu-Ting; Huang, Shih-Fang; Hsu, Su-Chen; Ying, Jeremy C; Shan, Yan-Shen

2017-07-24

Trauma is one of the leading causes of death in Taiwan, and its medical expenditure escalated drastically. This study aimed to explore the effectiveness of trauma team, which was established in September 2010, on medical resource utilization and quality of care among major trauma patients. This was a retrospective study, using trauma registry data bank and inpatient medical service charge databases. Study subjects were major trauma patients admitted to a medical center in Tainan during 2009 and 2013, and was divided into case group (from January, 2011 to August, 2013) and comparison group (from January, 2009 to August, 2010). Significant reductions in several items of medical resource utilization were identified after the establishment of trauma team. In the sub-group of patients who survived to discharge, examination, radiology and operation charges declined significantly. The radiation and examination charges reduced significantly in the subcategories of ISS = 16 ~ 24 and ISS > 24 respectively. However, no significant effectiveness on quality of care was identified. The establishment of trauma team is effective in containing medical resource utilization. In order to verify the effectiveness on quality of care, extended time frame and extra study subjects are needed.

Institutional prescreening for detection and eradication of methicillin-resistant Staphylococcus aureus in patients undergoing elective orthopaedic surgery.

PubMed

Kim, David H; Spencer, Maureen; Davidson, Susan M; Li, Ling; Shaw, Jeremy D; Gulczynski, Diane; Hunter, David J; Martha, Juli F; Miley, Gerald B; Parazin, Stephen J; Dejoie, Pamela; Richmond, John C

2010-08-04

Surgical site infection has been identified as one of the most important preventable sources of morbidity and mortality associated with medical treatment. The purpose of the present study was to evaluate the feasibility and efficacy of an institutional prescreening program for the preoperative detection and eradication of both methicillin-resistant and methicillin-sensitive Staphylococcus aureus in patients undergoing elective orthopaedic surgery. Data were collected prospectively during a single-center study. A universal prescreening program, employing rapid polymerase chain reaction analysis of nasal swabs followed by an eradication protocol of intranasal mupirocin and chlorhexidine showers for identified carriers, was implemented. Surgical site infection rates were calculated and compared with a historical control period immediately preceding the start of the screening program. During the study period, 7019 of 7338 patients underwent preoperative screening before elective surgery, for a successful screening rate of 95.7%. One thousand five hundred and eighty-eight (22.6%) of the patients were identified as Staphylococcus aureus carriers, and 309 (4.4%) were identified as methicillin-resistant Staphylococcus aureus carriers. A significantly higher rate of surgical site infection was observed among methicillin-resistant Staphylococcus aureus carriers (0.97%; three of 309) compared with noncarriers (0.14%; seven of 5122) (p = 0.0162). Although a higher rate of surgical site infection was also observed among methicillin-sensitive Staphylococcus aureus carriers (0.19%; three of 1588) compared with noncarriers, this difference did not achieve significance (p = 0.709). Overall, thirteen cases of surgical site infection were identified during the study period, for an institutional infection rate of 0.19%. This rate was significantly lower than that observed during the control period (0.45%; twenty-four cases of surgical site infection among 5293 patients) (p = 0.0093). Implementation of an institution-wide prescreening program for the identification and eradication of methicillin-resistant and methicillin-sensitive Staphylococcus aureus carrier status among patients undergoing elective orthopaedic surgery is feasible and can lead to significant reductions in postoperative rates of surgical site infection. Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.

A study of the early detection of insect infestations and density/distribution of host plants. [Rio Grande

NASA Technical Reports Server (NTRS)

Hart, W. G. (Principal Investigator); Ingle, S. J.; Davis, M. R.

1975-01-01

The author has identified the following significant results. With comparative observations of film types and seasonal influences on reflectance characteristics, many crop varieties can be identified. This study shows that citrus, sugar cane, brush, some winter vegetables, and grain crops could be identified. Vegetative patterns in border areas can be detected. This information can be useful in detecting avenues of entry of pest species and areas of stress that require vigilance in stopping the spread of destructive species. Influence of some environmental factors on crops that may be confused with pest injury, or related factors, can be detected and identified with Skylab data (S-190B).

Effect of polymorphisms in the CSN3 (κ-casein) gene on milk production traits in Chinese Holstein Cattle.

PubMed

Alim, M A; Dong, T; Xie, Y; Wu, X P; Zhang, Yi; Zhang, Shengli; Sun, D X

2014-11-01

This study was designed to evaluate significant associations between single nucleotide polymorphisms (SNPs) and milk composition and milk production traits in Chinese Holstein cows. Six SNPs were identified in the κ-casein gene using pooled DNA sequencing. The identified SNPs were genotyped by Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) methods from 507 individuals. Out of six, we identified three non-synonymous SNPs (g.10888T>C, g.10924C>A and g.10944A>G) that changed in the protein product. SIFT (Sorting_Intolerant_From_Tolerant) prediction score (0.01) demonstrated that protein changed Isoleucine > Threonine (g.10888T>C) will affect the phenotypes. Significant associations between identified SNPs and three yield traits (milk, protein and fat) and two composition traits (fat and protein percentages) were found whereas it did not reach significance for fat percentage in haplotypes association. Importantly, the significant SNPs in our results showed a large proportion of the phenotypic variation of milk protein yield and concentration. Our results suggest that CSN3 is an important candidate gene that influences milk production traits, and identified polymorphisms and haplotypes could be used as a genetic marker in programs of marker-assisted selection for the genetic improvement of milk production traits in dairy cattle.

Integrating Multiple Data Sources for Combinatorial Marker Discovery: A Study in Tumorigenesis.

PubMed

Bandyopadhyay, Sanghamitra; Mallik, Saurav

2018-01-01

Identification of combinatorial markers from multiple data sources is a challenging task in bioinformatics. Here, we propose a novel computational framework for identifying significant combinatorial markers ( s) using both gene expression and methylation data. The gene expression and methylation data are integrated into a single continuous data as well as a (post-discretized) boolean data based on their intrinsic (i.e., inverse) relationship. A novel combined score of methylation and expression data (viz., ) is introduced which is computed on the integrated continuous data for identifying initial non-redundant set of genes. Thereafter, (maximal) frequent closed homogeneous genesets are identified using a well-known biclustering algorithm applied on the integrated boolean data of the determined non-redundant set of genes. A novel sample-based weighted support ( ) is then proposed that is consecutively calculated on the integrated boolean data of the determined non-redundant set of genes in order to identify the non-redundant significant genesets. The top few resulting genesets are identified as potential s. Since our proposed method generates a smaller number of significant non-redundant genesets than those by other popular methods, the method is much faster than the others. Application of the proposed technique on an expression and a methylation data for Uterine tumor or Prostate Carcinoma produces a set of significant combination of markers. We expect that such a combination of markers will produce lower false positives than individual markers.

A comparison of traditional plant knowledge between students and herders in northern Kenya.

PubMed

Bruyere, Brett L; Trimarco, Jonathan; Lemungesi, Saruni

2016-10-13

The Samburu region of northern Kenya is undergoing significant change, driven by factors including greater value on formal education, improvements in infrastructure and development, a shift from community to private ownership of land, increased sedentary lifestyles and global climate change. One outcome of these changes are an increasingly greater likelihood for adolescent boys to be enrolled in school rather than herding livestock on behalf of the family in a landscape shared with numerous native vegetation and wildlife species. This study compared identification and knowledge of native plant species between boys enrolled in school with boys of similar age but primary responsibility as herders, called moran. Study participants walked an approximately 100 m path with 10 flagged points in which they were asked to identify any plant species at that point and associated facts of each species, within a 1 m radius. On average, moran identified 38 species compared to 20 for students, including nearly 13 (of a possible 15) species considered to have high cultural significance. Students identified an average of 8.6 culturally-significant plants. Further, moran shared nearly 18 correct facts about the plants, compared with ten for students. In addition, herding frequency was the only significant predictor of plant identification in a linear regression. The results demonstrate that while formal education undoubtedly provides benefits to students, attendance in school in lieu of the traditional role of herders has consequences on young men in Samburu related to ability to identify native and culturally-significant plants. This further shows the importance for communities like those in Samburu undergoing change need to develop alternative options to transmit local traditional knowledge to its younger generations.

Differences in Error Detection Skills by Band and Choral Preservice Teachers

ERIC Educational Resources Information Center

Stambaugh, Laura A.

2016-01-01

Band and choral preservice teachers (N = 44) studied band and choral scores, listened to recordings of school ensembles, and identified errors in the recordings. Results indicated that preservice teachers identified significantly more errors when listening to recordings of their primary area (band majors listening to band, p = 0.045; choral majors…

Canadian and Australian Pre-Service Teachers' Use, Confidence and Success in Various Behaviour Management Strategies

ERIC Educational Resources Information Center

Reupert, Andrea; Woodcock, Stuart

2011-01-01

The purpose of this study was twofold; first, to identify Australian and Canadian pre-service teachers' use, confidence and success in various behaviour management strategies, and second, to identify significant differences between the two cohorts. Pooled data indicated that pre-service teachers most frequently employ low level corrective…

Advanced Computer Image Generation Techniques Exploiting Perceptual Characteristics. Final Report.

ERIC Educational Resources Information Center

Stenger, Anthony J.; And Others

This study suggests and identifies computer image generation (CIG) algorithms for visual simulation that improve the training effectiveness of CIG simulators and identifies areas of basic research in visual perception that are significant for improving CIG technology. The first phase of the project entailed observing three existing CIG simulators.…

Study of application of ERTS-1 imagery to fracture-related mine safety hazards in the coal mining industry

NASA Technical Reports Server (NTRS)

Wier, C. E. (Principal Investigator); Wobber, F. J. (Principal Investigator); Russell, O. R.; Amato, R. V.

1972-01-01

The author has identified the following significant results. Numerous fractures are identifiable on the 1:120,000 color infrared photography. Some of these fractures are in the proximity of operating open pit mines and should provide opportunities for field checking and confirmation.

Residents-as-teachers programs in psychiatry: a systematic review.

PubMed

Dewey, Charlene M; Coverdale, John H; Ismail, Nadia J; Culberson, John W; Thompson, Britta M; Patton, Cynthia S; Friedland, Joan A

2008-02-01

Because psychiatry residents have important roles as teachers and significant opportunities to contribute to medical student education, we set out to: identify all randomized control trials (RCT) for residents' teaching skills programs in psychiatry and to identify the efficacy of those interventions for improving teaching skills; identify the strengths and weaknesses of the available studies across medical disciplines; and identify currently available methods for enhancing residents' teaching skills for residents training in psychiatry. The published English-language literature was searched using PubMed, Social Sciences Index, and PsycINFO databases, with key search words including: residents, teaching skills, residents as teachers, psychiatry, and assessments. Both RCT and controlled, nonrandomized trials of residents' teaching programs directed to enhance residents' teaching skills were selected and critically appraised. Of 13 trials identified and reviewed, most included residents in internal medicine. Only one included psychiatry residents and assessed their ability to teach interviewing skills to medical students. Along with other studies, this study demonstrated improvement in residents' teaching skills. Overall, interventions and outcome measures were heterogeneous while the quality of methodologies varied. Five studies were of higher quality, representing examples of quality educational research. Several described group differences, blinding, good follow-up, and use of valid, reliable tools. Only one trial exists that incorporated psychiatry residents. Significant opportunity to advance educational research in this field exists. Psychiatry residency program directors should incorporate high-quality methodologies and can benefit from the findings of trials in other disciplines.

Spatial analysis of precipitation time series over the Upper Indus Basin

NASA Astrophysics Data System (ADS)

Latif, Yasir; Yaoming, Ma; Yaseen, Muhammad

2018-01-01

The upper Indus basin (UIB) holds one of the most substantial river systems in the world, contributing roughly half of the available surface water in Pakistan. This water provides necessary support for agriculture, domestic consumption, and hydropower generation; all critical for a stable economy in Pakistan. This study has identified trends, analyzed variability, and assessed changes in both annual and seasonal precipitation during four time series, identified herein as: (first) 1961-2013, (second) 1971-2013, (third) 1981-2013, and (fourth) 1991-2013, over the UIB. This study investigated spatial characteristics of the precipitation time series over 15 weather stations and provides strong evidence of annual precipitation by determining significant trends at 6 stations (Astore, Chilas, Dir, Drosh, Gupis, and Kakul) out of the 15 studied stations, revealing a significant negative trend during the fourth time series. Our study also showed significantly increased precipitation at Bunji, Chitral, and Skardu, whereas such trends at the rest of the stations appear insignificant. Moreover, our study found that seasonal precipitation decreased at some locations (at a high level of significance), as well as periods of scarce precipitation during all four seasons. The observed decreases in precipitation appear stronger and more significant in autumn; having 10 stations exhibiting decreasing precipitation during the fourth time series, with respect to time and space. Furthermore, the observed decreases in precipitation appear robust and more significant for regions at high elevation (>1300 m). This analysis concludes that decreasing precipitation dominated the UIB, both temporally and spatially including in the higher areas.

The Frequency of AVN Following Reconstructive Hip Surgery in Children With Cerebral Palsy: A Systematic Review.

PubMed

Hesketh, Kim; Leveille, Lise; Mulpuri, Kishore

2016-03-01

Children with cerebral palsy (CP) undergoing reconstructive hip surgery are at risk for developing avascular necrosis (AVN). The purpose of this systematic review was to investigate the reported frequency of AVN, the amount and quality of literature available, and possibly identity risk factors for developing AVN following reconstructive surgery for hip displacement in children with CP. We performed a review of the literature using EMBASE and MEDLINE databases. Studies investigating the outcome of reconstructive hip surgery in patients with CP that identified the presence or absence of AVN were included. Study quality was assessed using the Methodological Index for Non-Randomized Studies and the Oxford Centre for Evidence-Based Medicine scale. Three hundred and ninety-nine articles were identified using our search strategy. Twenty-nine studies were included for data extraction after full-text review. The frequency of AVN ranged from 0% to 46% with an overall rate across studies of 7.5%. Presence of AVN was the primary outcome in 2 studies. The frequency of AVN in these studies was significantly higher than other studies at 37% and 46%. No statistically significant associations were found between age at surgery, severity of hip subluxation, length of follow-up, or type of surgery (combined varus derotation osteotomy and pelvic osteotomy vs. varus derotation osteotomy alone), and the rate of AVN. The majority of studies did not comment on methods used for determining diagnosis or severity of AVN and clinical significance was not well documented. Children with CP undergoing reconstructive hip surgery are at risk of developing AVN. Frequency and severity of this complication is poorly documented in the literature. On the basis of current evidence no significant risk factors were identified; however, it is not possible to draw firm conclusions about them. Incidence of AVN was higher in studies in which AVN was a primary outcome suggesting that the true frequency of AVN may be higher than is currently understood.

Drug-induced sedation endoscopy (DISE) classification systems: a systematic review and meta-analysis.

PubMed

Dijemeni, Esuabom; D'Amone, Gabriele; Gbati, Israel

2017-12-01

Drug-induced sedation endoscopy (DISE) classification systems have been used to assess anatomical findings on upper airway obstruction, and decide and plan surgical treatments and act as a predictor for surgical treatment outcome for obstructive sleep apnoea management. The first objective is to identify if there is a universally accepted DISE grading and classification system for analysing DISE findings. The second objective is to identify if there is one DISE grading and classification treatment planning framework for deciding appropriate surgical treatment for obstructive sleep apnoea (OSA). The third objective is to identify if there is one DISE grading and classification treatment outcome framework for determining the likelihood of success for a given OSA surgical intervention. A systematic review was performed to identify new and significantly modified DISE classification systems: concept, advantages and disadvantages. Fourteen studies proposing a new DISE classification system and three studies proposing a significantly modified DISE classification were identified. None of the studies were based on randomised control trials. DISE is an objective method for visualising upper airway obstruction. The classification and assessment of clinical findings based on DISE is highly subjective due to the increasing number of DISE classification systems. Hence, this creates a growing divergence in surgical treatment planning and treatment outcome. Further research on a universally accepted objective DISE assessment is critically needed.

Risk Factors Associated with Preterm Delivery after Fetoscopic Laser Surgery for Twin Twin Transfusion Syndrome

PubMed Central

PAPANNA, Ramesha; BLOCK-ABRAHAM, Dana; Mann, Lovepreet K; BUHIMSCHI, Irina A.; BEBBINGTON, Michael; GARCIA, Elisa; KAHLEK, Nahla; HARMAN, Christopher; JOHNSON, Anthony; BASCHAT, Ahmet; MOISE, Kenneth J.

2014-01-01

OBJECTIVE Despite improved perinatal survival following fetoscopic laser surgery (FLS) for twin twin transfusion syndrome (TTTS), prematurity remains an important contributor to perinatal mortality and morbidity. The objective of the study was to identify risk factors for complicated preterm delivery after FLS. STUDY DESIGN Retrospective cohort study of prospectively collected data on maternal/fetal demographics and pre-operative, operative and post-operative variables of 459 patients treated in 3 U.S. fetal centers. Multivariate linear regression was performed to identify significant risk factors associated with preterm delivery, which was cross-validated using K-fold method. Multivariate logistic regression was performed to identify risk factors for early vs. late preterm delivery based on median gestational age at delivery of 32 weeks. RESULTS There were significant differences in case selection and outcomes between the centers. After controlling for the center of surgery, a multivariate analysis indicated a lower maternal age at procedure, history of previous prematurity, shortened cervical length, use of amnioinfusion, 12 Fr cannula diameter, lack of a collagen plug placement and iatrogenic preterm premature rupture of membranes (iPPROM) were significantly associated with a lower gestational age at delivery. CONCLUSION Specific fetal/maternal and operative variables are associated with preterm delivery after FLS for the treatment of TTTS. Further studies to modify some of these variables may decrease the perinatal morbidity after laser therapy. PMID:24013922

Efficiently Identifying Significant Associations in Genome-wide Association Studies

PubMed Central

Eskin, Eleazar

2013-01-01

Abstract Over the past several years, genome-wide association studies (GWAS) have implicated hundreds of genes in common disease. More recently, the GWAS approach has been utilized to identify regions of the genome that harbor variation affecting gene expression or expression quantitative trait loci (eQTLs). Unlike GWAS applied to clinical traits, where only a handful of phenotypes are analyzed per study, in eQTL studies, tens of thousands of gene expression levels are measured, and the GWAS approach is applied to each gene expression level. This leads to computing billions of statistical tests and requires substantial computational resources, particularly when applying novel statistical methods such as mixed models. We introduce a novel two-stage testing procedure that identifies all of the significant associations more efficiently than testing all the single nucleotide polymorphisms (SNPs). In the first stage, a small number of informative SNPs, or proxies, across the genome are tested. Based on their observed associations, our approach locates the regions that may contain significant SNPs and only tests additional SNPs from those regions. We show through simulations and analysis of real GWAS datasets that the proposed two-stage procedure increases the computational speed by a factor of 10. Additionally, efficient implementation of our software increases the computational speed relative to the state-of-the-art testing approaches by a factor of 75. PMID:24033261

Identification of AaCASPS7, an effector caspase in Aedes albopictus.

PubMed

Feng, Lingyan; Liu, Hao; Li, Xiaomei; Qiao, Jialu; Wang, Shengya; Guo, Deyin; Liu, Qingzhen

2016-11-15

Aedes albopictus mosquito is a vector of various arboviruses and is becoming a significant threat to public health due to its rapid global expansion. Several reports suggest that apoptosis could be a factor limiting arbovirus infection in mosquitoes. Thus, it is significant to identify apoptosis pathway and study the correlation between apoptosis and virus infection in mosquitoes. Apoptosis is a type of programmed cell death that plays a vital role in immunity, development, and tissue homeostasis. Caspases are a family of conserved proteases playing important roles in apoptosis. In this study, we identified Aedes albopictus AaCASPS7, a caspase shared high identity with dipteran insect drICE orthologs. Phylogenetic analysis showed the closest relative of AaCASPS7 was Aedes aegypti AeCASPS7. AaCASPS7 displayed several features that were typical of an effector caspase and showed significant activity to effector caspase substrates. Aacasps7 transcripts were expressed ubiquitously in developmental and adult stages in Aedes albopictus mosquitoes. Transient expression of AaCASPS7 induced caspase-dependent apoptosis in C6/36 cells. Taken together the above data, this study identified a novel caspase, AaCASPS7, which might function as an apoptotic caspase. Further study the function of AaCASPS7 would facilitate better understanding the apoptotic mechanism in Aedes albopictus mosquito. Copyright © 2016 Elsevier B.V. All rights reserved.

Fall Hazards Within Senior Independent Living: A Case-Control Study.

PubMed

Kim, Daejin; Portillo, Margaret

2018-01-01

The main purpose of this research was to identify significant relationships between environmental hazards and older adults' falling. Falls can present a major health risk to older persons. Identifying potential environmental hazards that increase fall risks can be effective for developing fall prevention strategies that can create safer residential environments for older adults. The research included a retrospective analysis of 449 fall incident reports in two case-control buildings. In the homes of 88 older adults residing in independent living, an observational study was conducted to identify environmental hazards using two assessment tools including Westmead Home Safety Assessment (WeHSA) and resident interviews. A fall history analysis indicated that falls occurred in the bathroom were significantly associated with hospitalization. The observational study revealed that the bathroom was the most common place for environmental hazards. The research showed, with increasing age and use of mobility assistive aids, there was a corresponding increase in the total number of environmental hazards. Home hazards were significantly and independently associated with the incidence rate of falls. In other words, the high fall rate building included more environmental hazards compared to the low fall rate building while controlling for residents' age and mobility. The current study provides empirical evidence of the link between environmental hazards and older adults' falling, which is useful for developing effective fall intervention design strategies.

Comparing identified and statistically significant lipids and polar metabolites in 15-year old serum and dried blood spot samples for longitudinal studies: Comparing lipids and metabolites in serum and DBS samples

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

Kyle, Jennifer E.; Casey, Cameron P.; Stratton, Kelly G.

The use of dried blood spots (DBS) has many advantages over traditional plasma and serum samples such as smaller blood volume required, storage at room temperature, and ability for sampling in remote locations. However, understanding the robustness of different analytes in DBS samples is essential, especially in older samples collected for longitudinal studies. Here we analyzed DBS samples collected in 2000-2001 and stored at room temperature and compared them to matched serum samples stored at -80°C to determine if they could be effectively used as specific time points in a longitudinal study following metabolic disease. Four hundred small molecules weremore » identified in both the serum and DBS samples using gas chromatograph-mass spectrometry (GC-MS), liquid chromatography-MS (LC-MS) and LC-ion mobility spectrometry-MS (LC-IMS-MS). The identified polar metabolites overlapped well between the sample types, though only one statistically significant polar metabolite in a case-control study was conserved, indicating degradation occurs in the DBS samples affecting quantitation. Differences in the lipid identifications indicated that some oxidation occurs in the DBS samples. However, thirty-six statistically significant lipids correlated in both sample types indicating that lipid quantitation was more stable across the sample types.« less

Response to Instruction in Preschool: Results of Two Randomized Studies with Children At Significant Risk of Reading Difficulties

PubMed Central

Lonigan, Christopher J.; Phillips, Beth M.

2015-01-01

Although response-to-instruction (RTI) approaches have received increased attention, few studies have evaluated the potential impacts of RTI approaches with preschool populations. This manuscript presents results of two studies examining impacts of Tier II instruction with preschool children. Participating children were identified as substantially delayed in the acquisition of early literacy skills despite exposure to high-quality, evidence-based classroom instruction. Study 1 included 93 children (M age = 58.2 months; SD = 3.62) attending 12 Title I preschools. Study 2 included 184 children (M age = 58.2 months; SD = 3.38) attending 19 Title I preschools. The majority of children were Black/African American, and about 60% were male. In both studies, eligible children were randomized to receive either 11 weeks of need-aligned, small-group instruction or just Tier I. Tier II instruction in Study 1 included variations of activities for code- and language-focused domains with prior evidence of efficacy in non-RTI contexts. Tier II instruction in Study 2 included instructional activities narrower in scope, more intensive, and delivered to smaller groups of children. Impacts of Tier II instruction in Study 1 were minimal; however, there were significant and moderate-to-large impacts in Study 2. These results identify effective Tier II instruction but indicate that the context in which children are identified may alter the nature of Tier II instruction that is required. Children identified as eligible for Tier II in an RTI framework likely require more intensive and more narrowly focused instruction than do children at general risk of later academic difficulties. PMID:26869730

Hip fracture risk in relation to vitamin D supplementation and serum 25-hydroxyvitamin D levels: a systematic review and meta-analysis of randomised controlled trials and observational studies

PubMed Central

2010-01-01

Background Vitamin D supplementation for fracture prevention is widespread despite conflicting interpretation of relevant randomised controlled trial (RCT) evidence. This study summarises quantitatively the current evidence from RCTs and observational studies regarding vitamin D, parathyroid hormone (PTH) and hip fracture risk. Methods We undertook separate meta-analyses of RCTs examining vitamin D supplementation and hip fracture, and observational studies of serum vitamin D status (25-hydroxyvitamin D (25(OH)D) level), PTH and hip fracture. Results from RCTs were combined using the reported hazard ratios/relative risks (RR). Results from case-control studies were combined using the ratio of 25(OH)D and PTH measurements of hip fracture cases compared with controls. Original published studies of vitamin D, PTH and hip fracture were identified through PubMed and Web of Science databases, searches of reference lists and forward citations of key papers. Results The seven eligible RCTs identified showed no significant difference in hip fracture risk in those randomised to cholecalciferol or ergocalciferol supplementation versus placebo/control (RR = 1.13[95%CI 0.98-1.29]; 801 cases), with no significant difference between trials of <800 IU/day and ≥800 IU/day. The 17 identified case-control studies found 33% lower serum 25(OH)D levels in cases compared to controls, based on 1903 cases. This difference was significantly greater in studies with population-based compared to hospital-based controls (χ21 (heterogeneity) = 51.02, p < 0.001) and significant heterogeneity was present overall (χ216 (heterogeneity) = 137.9, p < 0.001). Serum PTH levels in hip fracture cases did not differ significantly from controls, based on ten case-control studies with 905 cases (χ29 (heterogeneity) = 149.68, p < 0.001). Conclusions Neither higher nor lower dose vitamin D supplementation prevented hip fracture. Randomised and observational data on vitamin D and hip fracture appear to differ. The reason for this is unclear; one possible explanation is uncontrolled confounding in observational studies. Post-fracture PTH levels are unrelated to hip fracture risk. PMID:20540727

Gliomatosis cerebri: Prognosis based on current molecular markers.

PubMed

Maharaj, Monish M; Phan, Kevin; Xu, Joshua; Fairhall, Jacob; Reddy, Rajesh; Rao, Prashanth J V

2017-09-01

This study aims to review the literature and identify key molecular markers affecting the prognosis of Gliomatosis cerebri (2) to evaluate the level of evidence and identify outstanding markers requiring further study. A literature search was conducted across 5 major databases using the key terms: "Molecular markers" AND "Gliomatosis cerebri" OR "diffuse astrocytoma." Critical appraisal and data presentation was performed inline with the PRISMA guidelines. Following search strategy implementation, 11 studies were included in the final review process. Our data demonstrates significant prognostic value associated with IDH1 132H mutation and variable evidence surrounding the role of INA expression, MGMT promoter methylation and other factors. However, there are significant limitations in the level of evidence obtained. As the genetic basis for the pathogenesis of Gliomatosis cerebri continues to widen, there is little data on markers aside from IDH1 mutation available. IDH1 132H mutation has been demonstrated to have significant effect on survival, particularly in patients with Gliomatosis cerebri type 2. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Predictors of success of external cephalic version: Bi-center study].

PubMed

Dochez, V; Delbos, L; Esbelin, J; Volteau, C; Winer, N; Sentilhes, L

2016-05-01

In the literature, success rate of external cephalic version (ECV) is 39 to 65%. This study aims to identify potential predictors of a successful ECV. Retrospective bi-center study performed from January 2011 through December 2012 at Angers University Hospital and Nantes University Hospital from January 2011 through December 2011. Were identified the demographic and ultrasonography characteristics of patients and the data of the process. One hundred and seventy-eight patients were included, 88 in Angers and 90 in Nantes; 16.3% of ECV were successful. Multiparity (OR 28.45; P<0.01) and transverse position (OR 0.63; P<0.01) are the two significant predictors. There is no significant difference found for center, operator, position of the placenta, amniotic fluid or presence of a uterine scar. The success rate in our two French university centers is much lower than that reported in the literature. Parity and transverse position are the only 2 significant predictors of ECV success. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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.

Proton pump inhibitors alter the composition of the gut microbiota.

PubMed

Jackson, Matthew A; Goodrich, Julia K; Maxan, Maria-Emanuela; Freedberg, Daniel E; Abrams, Julian A; Poole, Angela C; Sutter, Jessica L; Welter, Daphne; Ley, Ruth E; Bell, Jordana T; Spector, Tim D; Steves, Claire J

2016-05-01

Proton pump inhibitors (PPIs) are drugs used to suppress gastric acid production and treat GI disorders such as peptic ulcers and gastro-oesophageal reflux. They have been considered low risk, have been widely adopted, and are often over-prescribed. Recent studies have identified an increased risk of enteric and other infections with their use. Small studies have identified possible associations between PPI use and GI microbiota, but this has yet to be carried out on a large population-based cohort. We investigated the association between PPI usage and the gut microbiome using 16S ribosomal RNA amplification from faecal samples of 1827 healthy twins, replicating results within unpublished data from an interventional study. We identified a significantly lower abundance in gut commensals and lower microbial diversity in PPI users, with an associated significant increase in the abundance of oral and upper GI tract commensals. In particular, significant increases were observed in Streptococcaceae. These associations were replicated in an independent interventional study and in a paired analysis between 70 monozygotic twin pairs who were discordant for PPI use. We propose that the observed changes result from the removal of the low pH barrier between upper GI tract bacteria and the lower gut. Our findings describe a significant impact of PPIs on the gut microbiome and should caution over-use of PPIs, and warrant further investigation into the mechanisms and their clinical consequences. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Identifying patients with hypertension: a case for auditing electronic health record data.

PubMed

Baus, Adam; Hendryx, Michael; Pollard, Cecil

2012-01-01

Problems in the structure, consistency, and completeness of electronic health record data are barriers to outcomes research, quality improvement, and practice redesign. This nonexperimental retrospective study examines the utility of importing de-identified electronic health record data into an external system to identify patients with and at risk for essential hypertension. We find a statistically significant increase in cases based on combined use of diagnostic and free-text coding (mean = 1,256.1, 95% CI 1,232.3-1,279.7) compared to diagnostic coding alone (mean = 1,174.5, 95% CI 1,150.5-1,198.3). While it is not surprising that significantly more patients are identified when broadening search criteria, the implications are critical for quality of care, the movement toward the National Committee for Quality Assurance's Patient-Centered Medical Home program, and meaningful use of electronic health records. Further, we find a statistically significant increase in potential cases based on the last two or more blood pressure readings greater than or equal to 140/90 mm Hg (mean = 1,353.9, 95% CI 1,329.9-1,377.9).

A SYSTEMATIC REVIEW OF INTERVENTIONS TARGETING PATERNAL MENTAL HEALTH IN THE PERINATAL PERIOD.

PubMed

Rominov, Holly; Pilkington, Pamela D; Giallo, Rebecca; Whelan, Thomas A

2016-05-01

Interventions targeting parents' mental health in the perinatal period are critical due to potential consequences of perinatal mental illness for the parent, the infant, and their family. To date, most programs have targeted mothers. This systematic review explores the current status and evidence for intervention programs aiming to prevent or treat paternal mental illness in the perinatal period. Electronic databases were systematically searched to identify peer-reviewed studies that described an intervention targeting fathers' mental health in the perinatal period. Mental health outcomes included depression, anxiety, and stress as well as more general measures of psychological functioning. Eleven studies were identified. Three of five psychosocial interventions and three massage-technique interventions reported significant effects. None of the couple-based interventions reported significant effects. A number of methodological limitations were identified, including inadequate reporting of study designs, and issues with the timing of interventions. The variability in outcomes measures across the studies made it difficult to evaluate the overall effectiveness of the interventions. Father-focused interventions aimed at preventing perinatal mood problems will be improved if future studies utilize more rigorous research strategies. © 2016 Michigan Association for Infant Mental Health.

HYPE: a WFD tool for the identification of significant and sustained upward trends in groundwater time series

NASA Astrophysics Data System (ADS)

Lopez, Benjamin; Croiset, Nolwenn; Laurence, Gourcy

2014-05-01

The Water Framework Directive 2006/11/CE (WFD) on the protection of groundwater against pollution and deterioration asks Member States to identify significant and sustained upward trends in all bodies or groups of bodies of groundwater that are characterised as being at risk in accordance with Annex II to Directive 2000/60/EC. The Directive indicates that the procedure for the identification of significant and sustained upward trends must be based on a statistical method. Moreover, for significant increases of concentrations of pollutants, trend reversals are identified as being necessary. This means to be able to identify significant trend reversals. A specific tool, named HYPE, has been developed in order to help stakeholders working on groundwater trend assessment. The R encoded tool HYPE provides statistical analysis of groundwater time series. It follows several studies on the relevancy of the use of statistical tests on groundwater data series (Lopez et al., 2011) and other case studies on the thematic (Bourgine et al., 2012). It integrates the most powerful and robust statistical tests for hydrogeological applications. HYPE is linked to the French national database on groundwater data (ADES). So monitoring data gathered by the Water Agencies can be directly processed. HYPE has two main modules: - a characterisation module, which allows to visualize time series. HYPE calculates the main statistical characteristics and provides graphical representations; - a trend module, which identifies significant breaks, trends and trend reversals in time series, providing result table and graphical representation (cf figure). Additional modules are also implemented to identify regional and seasonal trends and to sample time series in a relevant way. HYPE has been used successfully in 2012 by the French Water Agencies to satisfy requirements of the WFD, concerning characterization of groundwater bodies' qualitative status and evaluation of the risk of non-achievement of good status. Bourgine B. et al. 2012, Ninth International Geostatistics Congress, Oslo, Norway June 11 - 15. Lopez B. et al. 2011, Final Report BRGM/RP-59515-FR. 166p.

Generalization and dilution of association results from European GWAS in populations of non-European ancestry: the PAGE study.

PubMed

Carlson, Christopher S; Matise, Tara C; North, Kari E; Haiman, Christopher A; Fesinmeyer, Megan D; Buyske, Steven; Schumacher, Fredrick R; Peters, Ulrike; Franceschini, Nora; Ritchie, Marylyn D; Duggan, David J; Spencer, Kylee L; Dumitrescu, Logan; Eaton, Charles B; Thomas, Fridtjof; Young, Alicia; Carty, Cara; Heiss, Gerardo; Le Marchand, Loic; Crawford, Dana C; Hindorff, Lucia A; Kooperberg, Charles L

2013-09-01

The vast majority of genome-wide association study (GWAS) findings reported to date are from populations with European Ancestry (EA), and it is not yet clear how broadly the genetic associations described will generalize to populations of diverse ancestry. The Population Architecture Using Genomics and Epidemiology (PAGE) study is a consortium of multi-ancestry, population-based studies formed with the objective of refining our understanding of the genetic architecture of common traits emerging from GWAS. In the present analysis of five common diseases and traits, including body mass index, type 2 diabetes, and lipid levels, we compare direction and magnitude of effects for GWAS-identified variants in multiple non-EA populations against EA findings. We demonstrate that, in all populations analyzed, a significant majority of GWAS-identified variants have allelic associations in the same direction as in EA, with none showing a statistically significant effect in the opposite direction, after adjustment for multiple testing. However, 25% of tagSNPs identified in EA GWAS have significantly different effect sizes in at least one non-EA population, and these differential effects were most frequent in African Americans where all differential effects were diluted toward the null. We demonstrate that differential LD between tagSNPs and functional variants within populations contributes significantly to dilute effect sizes in this population. Although most variants identified from GWAS in EA populations generalize to all non-EA populations assessed, genetic models derived from GWAS findings in EA may generate spurious results in non-EA populations due to differential effect sizes. Regardless of the origin of the differential effects, caution should be exercised in applying any genetic risk prediction model based on tagSNPs outside of the ancestry group in which it was derived. Models based directly on functional variation may generalize more robustly, but the identification of functional variants remains challenging.

Generalization and Dilution of Association Results from European GWAS in Populations of Non-European Ancestry: The PAGE Study

PubMed Central

Carlson, Christopher S.; Matise, Tara C.; North, Kari E.; Haiman, Christopher A.; Fesinmeyer, Megan D.; Buyske, Steven; Schumacher, Fredrick R.; Peters, Ulrike; Franceschini, Nora; Ritchie, Marylyn D.; Duggan, David J.; Spencer, Kylee L.; Dumitrescu, Logan; Eaton, Charles B.; Thomas, Fridtjof; Young, Alicia; Carty, Cara; Heiss, Gerardo; Le Marchand, Loic; Crawford, Dana C.; Hindorff, Lucia A.; Kooperberg, Charles L.

2013-01-01

The vast majority of genome-wide association study (GWAS) findings reported to date are from populations with European Ancestry (EA), and it is not yet clear how broadly the genetic associations described will generalize to populations of diverse ancestry. The Population Architecture Using Genomics and Epidemiology (PAGE) study is a consortium of multi-ancestry, population-based studies formed with the objective of refining our understanding of the genetic architecture of common traits emerging from GWAS. In the present analysis of five common diseases and traits, including body mass index, type 2 diabetes, and lipid levels, we compare direction and magnitude of effects for GWAS-identified variants in multiple non-EA populations against EA findings. We demonstrate that, in all populations analyzed, a significant majority of GWAS-identified variants have allelic associations in the same direction as in EA, with none showing a statistically significant effect in the opposite direction, after adjustment for multiple testing. However, 25% of tagSNPs identified in EA GWAS have significantly different effect sizes in at least one non-EA population, and these differential effects were most frequent in African Americans where all differential effects were diluted toward the null. We demonstrate that differential LD between tagSNPs and functional variants within populations contributes significantly to dilute effect sizes in this population. Although most variants identified from GWAS in EA populations generalize to all non-EA populations assessed, genetic models derived from GWAS findings in EA may generate spurious results in non-EA populations due to differential effect sizes. Regardless of the origin of the differential effects, caution should be exercised in applying any genetic risk prediction model based on tagSNPs outside of the ancestry group in which it was derived. Models based directly on functional variation may generalize more robustly, but the identification of functional variants remains challenging. PMID:24068893

Compendium of meteorology scientific issues of 1950 still outstanding

NASA Technical Reports Server (NTRS)

Vaughan, W. W.

1986-01-01

The Compendium of Meteorology was published in 1951 by the American Meteorological Society. A review was made of the Compendium of Meteorology to identify the studies and future needs which the authors expressed in their papers. The needs as seen by the authors are organized into sections and papers following the format of the Compendium of Meteorology. In some cases the needs they identified are as valid today as they were in 1951. In other cases one will easily be able to identify examples where significant progress has been made. It is left to the individual scientists and scientific program managers to assess whether significant progress has been made over the past thirty-five years on these outstanding scientific issues.

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

PubMed

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; Guggenheim, Jeremy A; Bailey-Wilson, Joan E

2018-01-01

To identify genes and genetic markers associated with corneal astigmatism. 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. 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 ). 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.

Systems genetics of intravenous cocaine self-administration in the BXD recombinant inbred mouse panel

PubMed Central

Dickson, Price E.; Miller, Mellessa M.; Calton, Michele A.; Bubier, Jason A.; Cook, Melloni N.; Goldowitz, Daniel; Chesler, Elissa J.; Mittleman, Guy

2015-01-01

Rationale Cocaine addiction is a major public health problem with a substantial genetic basis for which the biological mechanisms remain largely unknown. Systems genetics is a powerful method for discovering novel mechanisms underlying complex traits, and intravenous drug self-administration (IVSA) is the gold standard for assessing volitional drug use in preclinical studies. We have integrated these approaches to identify novel genes and networks underling cocaine use in mice. Methods Mice from 39 BXD strains acquired cocaine IVSA (0.56 mg/kg/infusion). Mice from 29 BXD strains completed a full dose-response curve (0.032 – 1.8 mg/kg/infusion). Results We identified independent genetic correlations between cocaine IVSA and measures of environmental exploration and cocaine sensitization. We identified genome-wide significant QTL on chromosomes 7 and 11 associated with shifts in the dose-response curve and on chromosome 16 associated with sessions to acquire cocaine IVSA. Using publicly available gene expression data from the nucleus accumbens, midbrain, and prefrontal cortex of drug-naïve mice, we identified Aplp1 and Cyfip2 as positional candidates underlying the behavioral QTL on chromosomes 7 and 11, respectively. A genome-wide significant trans-eQTL linking Fam53b (a GWAS candidate for human cocaine dependence) on chromosome 7 to the cocaine IVSA behavioral QTL on chromosome 11 was identified in the midbrain; Fam53b and Cyfip2 were co-expressed genome-wide significantly in the midbrain. This finding indicates that cocaine IVSA studies using mice can identify genes involved in human cocaine use. Conclusions These data provide novel candidate genes underlying cocaine IVSA in mice, and suggest mechanisms driving human cocaine use. PMID:26581503

Haplotype-based identification of a microsomal transfer protein marker associated with the human lifespan

PubMed Central

Geesaman, Bard J.; Benson, Erica; Brewster, Stephanie J.; Kunkel, Louis M.; Blanché, Hélène; Thomas, Gilles; Perls, Thomas T.; Daly, Mark J.; Puca, Annibale A.

2003-01-01

We previously reported a genomewide linkage study for human longevity using 308 long-lived individuals (LLI) (centenarians or near-centenarians) in 137 sibships and identified statistically significant linkage within chromosome 4 near microsatellite D4S1564. This interval spans 12 million bp and contains ≈50 putative genes. To identify the specific gene and gene variants impacting lifespan, we performed a haplotype-based fine-mapping study of the interval. The resulting genetic association study identified a haplotype marker within microsomal transfer protein as a modifier of human lifespan. This same variant was tested in a second cohort of LLI from France, and although the association was not replicated, there was evidence for statistical distortion in the form of Hardy–Weinberg disequilibrium. Microsomal transfer protein has been identified as the rate-limiting step in lipoprotein synthesis and may affect longevity by subtly modulating this pathway. This study provides proof of concept for the feasibility of using the genomes of LLI to identify genes impacting longevity. PMID:14615589

Association of Phosphodiesterase 4D with ischemic stroke: a population-based case-control study.

PubMed

Woo, Daniel; Kaushal, Ritesh; Kissela, Brett; Sekar, Padmini; Wolujewicz, Michael; Pal, Prodipto; Alwell, Kathleen; Haverbusch, Mary; Ewing, Irene; Miller, Rosie; Kleindorfer, Dawn; Flaherty, Matthew; Chakraborty, Ranajit; Deka, Ranjan; Broderick, Joseph

2006-02-01

The Phosphodiesterase 4D (PDE4D) gene was reported recently to be associated with ischemic stroke in an Icelandic population. The association was found predominately with large vessel and cardioembolic stroke. However, 2 recent reports were unable to confirm this association, although a trend toward association with cardioembolic stroke was reported. None of the reports included significant proportions of blacks. We tested for genotype and haplotype association of polymorphisms of the PDE4D gene with ischemic stroke in a population-based, biracial, case-control study. A total of 357 cases of ischemic stroke and 482 stroke-free controls from the same community were examined. Single nucleotide polymorphisms (SNPs) were chosen based on significant associations reported previously. Linkage disequilibrium (LD), SNP, and haplotype association analysis was performed using PHASE 2.0 and Haploview 3.2. Although several univariate associations were identified, only 1 SNP (rs2910829) was found to be significantly associated with cardioembolic stroke among both whites and blacks. The rs152312 SNP was associated with cardioembolic stroke among whites after multiple comparison corrections. The same SNP was not associated with cardioembolic stroke among blacks. However, significant haplotype association was identified for both whites and blacks for all ischemic stroke, cardioembolic stroke, and stroke of unknown origin. Haplotype association was identified for small vessel stroke among whites. PDE4D is a risk factor for ischemic stroke and, in particular, for cardioembolic stroke, among whites and blacks. Further study of this gene is warranted.

Identification of FGF7 as a novel susceptibility locus for chronic obstructive pulmonary disease.

PubMed

Brehm, John M; Hagiwara, Koichi; Tesfaigzi, Yohannes; Bruse, Shannon; Mariani, Thomas J; Bhattacharya, Soumyaroop; Boutaoui, Nadia; Ziniti, John P; Soto-Quiros, Manuel E; Avila, Lydiana; Cho, Michael H; Himes, Blanca; Litonjua, Augusto A; Jacobson, Francine; Bakke, Per; Gulsvik, Amund; Anderson, Wayne H; Lomas, David A; Forno, Erick; Datta, Soma; Silverman, Edwin K; Celedón, Juan C

2011-12-01

Traditional genome-wide association studies (GWASs) of large cohorts of subjects with chronic obstructive pulmonary disease (COPD) have successfully identified novel candidate genes, but several other plausible loci do not meet strict criteria for genome-wide significance after correction for multiple testing. The authors hypothesise that by applying unbiased weights derived from unique populations we can identify additional COPD susceptibility loci. Methods The authors performed a homozygosity haplotype analysis on a group of subjects with and without COPD to identify regions of conserved homozygosity haplotype (RCHHs). Weights were constructed based on the frequency of these RCHHs in case versus controls, and used to adjust the p values from a large collaborative GWAS of COPD. The authors identified 2318 RCHHs, of which 576 were significantly (p<0.05) over-represented in cases. After applying the weights constructed from these regions to a collaborative GWAS of COPD, the authors identified two single nucleotide polymorphisms (SNPs) in a novel gene (fibroblast growth factor-7 (FGF7)) that gained genome-wide significance by the false discovery rate method. In a follow-up analysis, both SNPs (rs12591300 and rs4480740) were significantly associated with COPD in an independent population (combined p values of 7.9E-7 and 2.8E-6, respectively). In another independent population, increased lung tissue FGF7 expression was associated with worse measures of lung function. Weights constructed from a homozygosity haplotype analysis of an isolated population successfully identify novel genetic associations from a GWAS on a separate population. This method can be used to identify promising candidate genes that fail to meet strict correction for multiple testing.

Non-Targeted Metabolomics Analysis of Golden Retriever Muscular Dystrophy-Affected Muscles Reveals Alterations in Arginine and Proline Metabolism, and Elevations in Glutamic and Oleic Acid In Vivo

PubMed Central

Abdullah, Muhammad; Kornegay, Joe N.; Honcoop, Aubree; Parry, Traci L.; Balog-Alvarez, Cynthia J.; Muehlbauer, Michael J.; Newgard, Christopher B.; Patterson, Cam

2017-01-01

Background: Like Duchenne muscular dystrophy (DMD), the Golden Retriever Muscular Dystrophy (GRMD) dog model of DMD is characterized by muscle necrosis, progressive paralysis, and pseudohypertrophy in specific skeletal muscles. This severe GRMD phenotype includes moderate atrophy of the biceps femoris (BF) as compared to unaffected normal dogs, while the long digital extensor (LDE), which functions to flex the tibiotarsal joint and serves as a digital extensor, undergoes the most pronounced atrophy. A recent microarray analysis of GRMD identified alterations in genes associated with lipid metabolism and energy production. Methods: We, therefore, undertook a non-targeted metabolomics analysis of the milder/earlier stage disease GRMD BF muscle versus the more severe/chronic LDE using GC-MS to identify underlying metabolic defects specific for affected GRMD skeletal muscle. Results: Untargeted metabolomics analysis of moderately-affected GRMD muscle (BF) identified eight significantly altered metabolites, including significantly decreased stearamide (0.23-fold of controls, p = 2.89 × 10−3), carnosine (0.40-fold of controls, p = 1.88 × 10−2), fumaric acid (0.40-fold of controls, p = 7.40 × 10−4), lactamide (0.33-fold of controls, p = 4.84 × 10−2), myoinositol-2-phosphate (0.45-fold of controls, p = 3.66 × 10−2), and significantly increased oleic acid (1.77-fold of controls, p = 9.27 × 10−2), glutamic acid (2.48-fold of controls, p = 2.63 × 10−2), and proline (1.73-fold of controls, p = 3.01 × 10−2). Pathway enrichment analysis identified significant enrichment for arginine/proline metabolism (p = 5.88 × 10−4, FDR 4.7 × 10−2), where alterations in L-glutamic acid, proline, and carnosine were found. Additionally, multiple Krebs cycle intermediates were significantly decreased (e.g., malic acid, fumaric acid, citric/isocitric acid, and succinic acid), suggesting that altered energy metabolism may be underlying the observed GRMD BF muscle dysfunction. In contrast, two pathways, inosine-5′-monophosphate (VIP Score 3.91) and 3-phosphoglyceric acid (VIP Score 3.08) mainly contributed to the LDE signature, with two metabolites (phosphoglyceric acid and inosine-5′-monophosphate) being significantly decreased. When the BF and LDE were compared, the most significant metabolite was phosphoric acid, which was significantly less in the GRMD BF compared to control and GRMD LDE groups. Conclusions: The identification of elevated BF oleic acid (a long-chain fatty acid) is consistent with recent microarray studies identifying altered lipid metabolism genes, while alterations in arginine and proline metabolism are consistent with recent studies identifying elevated L-arginine in DMD patient sera as a biomarker of disease. Together, these studies demonstrate muscle-specific alterations in GRMD-affected muscle, which illustrate previously unidentified metabolic changes. PMID:28758940

Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study.

PubMed

de Vries, Paul S; Sabater-Lleal, Maria; Chasman, Daniel I; Trompet, Stella; Ahluwalia, Tarunveer S; Teumer, Alexander; Kleber, Marcus E; Chen, Ming-Huei; Wang, Jie Jin; Attia, John R; Marioni, Riccardo E; Steri, Maristella; Weng, Lu-Chen; Pool, Rene; Grossmann, Vera; Brody, Jennifer A; Venturini, Cristina; Tanaka, Toshiko; Rose, Lynda M; Oldmeadow, Christopher; Mazur, Johanna; Basu, Saonli; Frånberg, Mattias; Yang, Qiong; Ligthart, Symen; Hottenga, Jouke J; Rumley, Ann; Mulas, Antonella; de Craen, Anton J M; Grotevendt, Anne; Taylor, Kent D; Delgado, Graciela E; Kifley, Annette; Lopez, Lorna M; Berentzen, Tina L; Mangino, Massimo; Bandinelli, Stefania; Morrison, Alanna C; Hamsten, Anders; Tofler, Geoffrey; de Maat, Moniek P M; Draisma, Harmen H M; Lowe, Gordon D; Zoledziewska, Magdalena; Sattar, Naveed; Lackner, Karl J; Völker, Uwe; McKnight, Barbara; Huang, Jie; Holliday, Elizabeth G; McEvoy, Mark A; Starr, John M; Hysi, Pirro G; Hernandez, Dena G; Guan, Weihua; Rivadeneira, Fernando; McArdle, Wendy L; Slagboom, P Eline; Zeller, Tanja; Psaty, Bruce M; Uitterlinden, André G; de Geus, Eco J C; Stott, David J; Binder, Harald; Hofman, Albert; Franco, Oscar H; Rotter, Jerome I; Ferrucci, Luigi; Spector, Tim D; Deary, Ian J; März, Winfried; Greinacher, Andreas; Wild, Philipp S; Cucca, Francesco; Boomsma, Dorret I; Watkins, Hugh; Tang, Weihong; Ridker, Paul M; Jukema, Jan W; Scott, Rodney J; Mitchell, Paul; Hansen, Torben; O'Donnell, Christopher J; Smith, Nicholas L; Strachan, David P; Dehghan, Abbas

2017-01-01

An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap imputation in identifying associated loci, we compared the results of GWA studies of circulating fibrinogen based on the two reference panels. Using both HapMap and 1000G imputation we performed a meta-analysis of 22 studies comprising the same 91,953 individuals. We identified six additional signals using 1000G imputation, while 29 loci were associated using both HapMap and 1000G imputation. One locus identified using HapMap imputation was not significant using 1000G imputation. The genome-wide significance threshold of 5×10-8 is based on the number of independent statistical tests using HapMap imputation, and 1000G imputation may lead to further independent tests that should be corrected for. When using a stricter Bonferroni correction for the 1000G GWA study (P-value < 2.5×10-8), the number of loci significant only using HapMap imputation increased to 4 while the number of loci significant only using 1000G decreased to 5. In conclusion, 1000G imputation enabled the identification of 20% more loci than HapMap imputation, although the advantage of 1000G imputation became less clear when a stricter Bonferroni correction was used. More generally, our results provide insights that are applicable to the implementation of other dense reference panels that are under development.

Commercial truck crash injury severity analysis using gradient boosting data mining model.

PubMed

Zheng, Zijian; Lu, Pan; Lantz, Brenda

2018-06-01

Truck crashes contribute to a large number of injuries and fatalities. This study seeks to identify the contributing factors affecting truck crash severity using 2010 to 2016 North Dakota and Colorado crash data provided by the Federal Motor Carrier Safety Administration. To fulfill a gap of previous studies, broad considerations of company and driver characteristics, such as company size and driver's license class, along with vehicle types and crash characteristics are researched. Gradient boosting, a data mining technique, is applied to comprehensively analyze the relationship between crash severities and a set of heterogeneous risk factors. Twenty five variables were tested and 22 of them are identified as significant variables contributing to injury severities, however, top 11 variables account for more than 80% of injury forecasting. The relative variable importance analysis is conducted and furthermore marginal effects of all contributing factors are also illustrated in this research. Several factors such as trucking company attributes (e.g., company size), safety inspection values, trucking company commerce status (e.g., interstate or intrastate), time of day, driver's age, first harmful events, and registration condition are found to be significantly associated with crash injury severity. Even though most of the identified contributing factors are significant for all four levels of crash severity, their relative importance and marginal effect are all different. For the first time, trucking company and driver characteristics are proved to have significant impact on truck crash injury severity. Some of the results in this study reinforce previous studies' conclusions. Findings in this study can be helpful for transportation agencies to reduce injury severity, and develop efficient strategies to improve safety. Copyright © 2018 National Safety Council and Elsevier Ltd. All rights reserved.

Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study

PubMed Central

de Vries, Paul S.; Sabater-Lleal, Maria; Chasman, Daniel I.; Trompet, Stella; Kleber, Marcus E.; Chen, Ming-Huei; Wang, Jie Jin; Attia, John R.; Marioni, Riccardo E.; Weng, Lu-Chen; Grossmann, Vera; Brody, Jennifer A.; Venturini, Cristina; Tanaka, Toshiko; Rose, Lynda M.; Oldmeadow, Christopher; Mazur, Johanna; Basu, Saonli; Yang, Qiong; Ligthart, Symen; Hottenga, Jouke J.; Rumley, Ann; Mulas, Antonella; de Craen, Anton J. M.; Grotevendt, Anne; Taylor, Kent D.; Delgado, Graciela E.; Kifley, Annette; Lopez, Lorna M.; Berentzen, Tina L.; Mangino, Massimo; Bandinelli, Stefania; Morrison, Alanna C.; Hamsten, Anders; Tofler, Geoffrey; de Maat, Moniek P. M.; Draisma, Harmen H. M.; Lowe, Gordon D.; Zoledziewska, Magdalena; Sattar, Naveed; Lackner, Karl J.; Völker, Uwe; McKnight, Barbara; Huang, Jie; Holliday, Elizabeth G.; McEvoy, Mark A.; Starr, John M.; Hysi, Pirro G.; Hernandez, Dena G.; Guan, Weihua; Rivadeneira, Fernando; McArdle, Wendy L.; Slagboom, P. Eline; Zeller, Tanja; Psaty, Bruce M.; Uitterlinden, André G.; de Geus, Eco J. C.; Stott, David J.; Binder, Harald; Hofman, Albert; Franco, Oscar H.; Rotter, Jerome I.; Ferrucci, Luigi; Spector, Tim D.; Deary, Ian J.; März, Winfried; Greinacher, Andreas; Wild, Philipp S.; Cucca, Francesco; Boomsma, Dorret I.; Watkins, Hugh; Tang, Weihong; Ridker, Paul M.; Jukema, Jan W.; Scott, Rodney J.; Mitchell, Paul; Hansen, Torben; O'Donnell, Christopher J.; Smith, Nicholas L.; Strachan, David P.

2017-01-01

An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap imputation in identifying associated loci, we compared the results of GWA studies of circulating fibrinogen based on the two reference panels. Using both HapMap and 1000G imputation we performed a meta-analysis of 22 studies comprising the same 91,953 individuals. We identified six additional signals using 1000G imputation, while 29 loci were associated using both HapMap and 1000G imputation. One locus identified using HapMap imputation was not significant using 1000G imputation. The genome-wide significance threshold of 5×10−8 is based on the number of independent statistical tests using HapMap imputation, and 1000G imputation may lead to further independent tests that should be corrected for. When using a stricter Bonferroni correction for the 1000G GWA study (P-value < 2.5×10−8), the number of loci significant only using HapMap imputation increased to 4 while the number of loci significant only using 1000G decreased to 5. In conclusion, 1000G imputation enabled the identification of 20% more loci than HapMap imputation, although the advantage of 1000G imputation became less clear when a stricter Bonferroni correction was used. More generally, our results provide insights that are applicable to the implementation of other dense reference panels that are under development. PMID:28107422

The Impact of Spiritual Intelligence, Gender and Educational Background on Mental Health Among College Students.

PubMed

Pant, Naveen; Srivastava, S K

2017-11-30

The present study is conducted on 300 PG-level college students in Haridwar, Uttarakhand (India). The aim of the present study is to examine the level of spiritual intelligence and mental health, to observe relationship between these two variables and also to identify the difference in spiritual intelligence and mental health across gender and educational background (arts and science). The purposive sampling technique is used to select 300 college students of both disciplines of arts and science from the four different government degree colleges/campuses in Haridwar. Integrated Spiritual Intelligence Scale and Mithila Mental Health Status Inventory are used to observe the level of these variables among college students. In the present study, correlational design is employed. All the statistical analyses are done with the help of computer software SPSS. To observe relationship Pearson correlation and to identify the difference t test are used. Findings of the study revealed that spiritual intelligence and mental health relate significantly among arts students, and male and female arts students separately have significant relationship between spiritual intelligence and mental health. Spiritual intelligence and mental health relate significantly among science students, and male and female science students separately have significant relationship between spiritual intelligence and mental health. No significant difference is found between male and female students in terms of spiritual intelligence. No significant difference is found between arts and science students in terms of spiritual intelligence. No significant difference is found between male and female students in terms of mental health. No significant difference is found between arts and science students in terms of mental health.

Patient satisfaction constructs.

PubMed

Rahman, Muhammad Sabbir; Osmangani, Aahad M

2015-01-01

The purpose of this paper is to examine the five-factor structure of patients' satisfaction constructs toward private healthcare service providers. This research is a cross-sectional study. A questionnaire-based survey was conducted with previous and current Bangladeshi patients. Exploratory factor analysis was employed to extract the underlying constructs. Five underlying dimensions that play a significant role in structuring the satisfaction perceived by Bangladeshi private healthcare patients are identified in this study. Practical implications - The main contribution of this study is identifying the dimensions of satisfaction perceived by Bangladeshi patients regarding private healthcare service providers. Healthcare managers adopt the five identified underlying construct items in their business practices to improve their respective healthcare efficiency while ensuring overall customer satisfaction.

A meta-analysis of public microarray data identifies biological regulatory networks in Parkinson's disease.

PubMed

Su, Lining; Wang, Chunjie; Zheng, Chenqing; Wei, Huiping; Song, Xiaoqing

2018-04-13

Parkinson's disease (PD) is a long-term degenerative disease that is caused by environmental and genetic factors. The networks of genes and their regulators that control the progression and development of PD require further elucidation. We examine common differentially expressed genes (DEGs) from several PD blood and substantia nigra (SN) microarray datasets by meta-analysis. Further we screen the PD-specific genes from common DEGs using GCBI. Next, we used a series of bioinformatics software to analyze the miRNAs, lncRNAs and SNPs associated with the common PD-specific genes, and then identify the mTF-miRNA-gene-gTF network. Our results identified 36 common DEGs in PD blood studies and 17 common DEGs in PD SN studies, and five of the genes were previously known to be associated with PD. Further study of the regulatory miRNAs associated with the common PD-specific genes revealed 14 PD-specific miRNAs in our study. Analysis of the mTF-miRNA-gene-gTF network about PD-specific genes revealed two feed-forward loops: one involving the SPRK2 gene, hsa-miR-19a-3p and SPI1, and the second involving the SPRK2 gene, hsa-miR-17-3p and SPI. The long non-coding RNA (lncRNA)-mediated regulatory network identified lncRNAs associated with PD-specific genes and PD-specific miRNAs. Moreover, single nucleotide polymorphism (SNP) analysis of the PD-specific genes identified two significant SNPs, and SNP analysis of the neurodegenerative disease-specific genes identified seven significant SNPs. Most of these SNPs are present in the 3'-untranslated region of genes and are controlled by several miRNAs. Our study identified a total of 53 common DEGs in PD patients compared with healthy controls in blood and brain datasets and five of these genes were previously linked with PD. Regulatory network analysis identified PD-specific miRNAs, associated long non-coding RNA and feed-forward loops, which contribute to our understanding of the mechanisms underlying PD. The SNPs identified in our study can determine whether a genetic variant is associated with PD. Overall, these findings will help guide our study of the complex molecular mechanism of PD.

A genome-wide association study reveals candidate genes for the supernumerary nipple phenotype in sheep (Ovis aries).

PubMed

Peng, W-F; Xu, S-S; Ren, X; Lv, F-H; Xie, X-L; Zhao, Y-X; Zhang, M; Shen, Z-Q; Ren, Y-L; Gao, L; Shen, M; Kantanen, J; Li, M-H

2017-10-01

Genome-wide association studies (GWASs) have been widely applied in livestock to identify genes associated with traits of economic interest. Here, we conducted the first GWAS of the supernumerary nipple phenotype in Wadi sheep, a native Chinese sheep breed, based on Ovine Infinium HD SNP BeadChip genotypes in a total of 144 ewes (75 cases with four teats, including two normal and two supernumerary teats, and 69 control cases with two teats). We detected 63 significant SNPs at the chromosome-wise threshold. Additionally, one candidate region (chr1: 170.723-170.734 Mb) was identified by haplotype-based association tests, with one SNP (rs413490006) surrounding functional genes BBX and CD47 on chromosome 1 being commonly identified as significant by the two mentioned analyses. Moreover, Gene Ontology enrichment for the significant SNPs identified by the GWAS analysis was functionally clustered into the categories of receptor activity and synaptic membrane. In addition, pathway mapping revealed four promising pathways (Wnt, oxytocin, MAPK and axon guidance) involved in the development of the supernumerary nipple phenotype. Our results provide novel and important insights into the genetic mechanisms underlying the phenotype of supernumerary nipples in mammals, including humans. These findings may be useful for future breeding and genetics in sheep and other livestock. © 2017 Stichting International Foundation for Animal Genetics.

Telomerase expression in the mammalian heart

PubMed Central

Richardson, Gavin D.; Breault, David; Horrocks, Grace; Cormack, Suzanne; Hole, Nicholas; Owens, W. Andrew

2012-01-01

While the mammalian heart has low, but functionally significant, levels of telomerase expression, the cellular population responsible remains incompletely characterized. This study aimed to identify the cell types responsible for cardiac telomerase activity in neonatal, adult, and cryoinjured adult hearts using transgenic mice expressing green fluorescent protein (GFP), driven by the promoter for murine telomerase reverse transcriptase (mTert), which is a necessary and rate-limiting component of telomerase. A rare population of mTert-GFP-expressing cells was identified that possessed all detectable cardiac telomerase RNA and telomerase activity. It was heterogeneous and included cells coexpressing markers of cardiomyocytic, endothelial, and mesenchymal lineages, putative cardiac stem cell markers, and, interestingly, cardiomyocytes with a differentiated phenotype. Quantification using both flow cytometry and immunofluorescence identified a significant decline in mTert-GFP cells in adult animals compared to neonates (∼9- and ∼20-fold, respectively). Cardiac injury resulted in a ∼6.45-fold expansion of this population (P<0.005) compared with sham-operated controls. This study identifies the cells responsible for cardiac telomerase activity, demonstrates a significant diminution with age but a marked response to injury, and, given the relationship between telomerase activity and stem cell populations, suggests that they represent a potential target for further investigation of cardiac regenerative potential.—Richardson, G. D., Breault, D., Horrocks, G., Cormack, S., Hole, N., Owens, W. A. Telomerase expression in the mammalian heart. PMID:22919071

To be or not to be associated: power study of four statistical modeling approaches to identify parasite associations in cross-sectional studies

PubMed Central

Vaumourin, Elise; Vourc'h, Gwenaël; Telfer, Sandra; Lambin, Xavier; Salih, Diaeldin; Seitzer, Ulrike; Morand, Serge; Charbonnel, Nathalie; Vayssier-Taussat, Muriel; Gasqui, Patrick

2014-01-01

A growing number of studies are reporting simultaneous infections by parasites in many different hosts. The detection of whether these parasites are significantly associated is important in medicine and epidemiology. Numerous approaches to detect associations are available, but only a few provide statistical tests. Furthermore, they generally test for an overall detection of association and do not identify which parasite is associated with which other one. Here, we developed a new approach, the association screening approach, to detect the overall and the detail of multi-parasite associations. We studied the power of this new approach and of three other known ones (i.e., the generalized chi-square, the network and the multinomial GLM approaches) to identify parasite associations either due to parasite interactions or to confounding factors. We applied these four approaches to detect associations within two populations of multi-infected hosts: (1) rodents infected with Bartonella sp., Babesia microti and Anaplasma phagocytophilum and (2) bovine population infected with Theileria sp. and Babesia sp. We found that the best power is obtained with the screening model and the generalized chi-square test. The differentiation between associations, which are due to confounding factors and parasite interactions was not possible. The screening approach significantly identified associations between Bartonella doshiae and B. microti, and between T. parva, T. mutans, and T. velifera. Thus, the screening approach was relevant to test the overall presence of parasite associations and identify the parasite combinations that are significantly over- or under-represented. Unraveling whether the associations are due to real biological interactions or confounding factors should be further investigated. Nevertheless, in the age of genomics and the advent of new technologies, it is a considerable asset to speed up researches focusing on the mechanisms driving interactions between parasites. PMID:24860791

Barriers of Influenza Vaccination Intention and Behavior – A Systematic Review of Influenza Vaccine Hesitancy, 2005 – 2016

PubMed Central

Schmid, Philipp; Rauber, Dorothee; Betsch, Cornelia; Lidolt, Gianni; Denker, Marie-Luisa

2017-01-01

Background Influenza vaccine hesitancy is a significant threat to global efforts to reduce the burden of seasonal and pandemic influenza. Potential barriers of influenza vaccination need to be identified to inform interventions to raise awareness, influenza vaccine acceptance and uptake. Objective This review aims to (1) identify relevant studies and extract individual barriers of seasonal and pandemic influenza vaccination for risk groups and the general public; and (2) map knowledge gaps in understanding influenza vaccine hesitancy to derive directions for further research and inform interventions in this area. Methods Thirteen databases covering the areas of Medicine, Bioscience, Psychology, Sociology and Public Health were searched for peer-reviewed articles published between the years 2005 and 2016. Following the PRISMA approach, 470 articles were selected and analyzed for significant barriers to influenza vaccine uptake or intention. The barriers for different risk groups and flu types were clustered according to a conceptual framework based on the Theory of Planned Behavior and discussed using the 4C model of reasons for non-vaccination. Results Most studies were conducted in the American and European region. Health care personnel (HCP) and the general public were the most studied populations, while parental decisions for children at high risk were under-represented. This study also identifies understudied concepts. A lack of confidence, inconvenience, calculation and complacency were identified to different extents as barriers to influenza vaccine uptake in risk groups. Conclusion Many different psychological, contextual, sociodemographic and physical barriers that are specific to certain risk groups were identified. While most sociodemographic and physical variables may be significantly related to influenza vaccine hesitancy, they cannot be used to explain its emergence or intensity. Psychological determinants were meaningfully related to uptake and should therefore be measured in a valid and comparable way. A compendium of measurements for future use is suggested as supporting information. PMID:28125629

System-based identification of toxicity pathways associated with multi-walled carbon nanotube-induced pathological responses

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

Snyder-Talkington, Brandi N.; Dymacek, Julian; Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506-9300

2013-10-15

The fibrous shape and biopersistence of multi-walled carbon nanotubes (MWCNT) have raised concern over their potential toxicity after pulmonary exposure. As in vivo exposure to MWCNT produced a transient inflammatory and progressive fibrotic response, this study sought to identify significant biological processes associated with lung inflammation and fibrosis pathology data, based upon whole genome mRNA expression, bronchoaveolar lavage scores, and morphometric analysis from C57BL/6J mice exposed by pharyngeal aspiration to 0, 10, 20, 40, or 80 μg MWCNT at 1, 7, 28, or 56 days post-exposure. Using a novel computational model employing non-negative matrix factorization and Monte Carlo Markov Chainmore » simulation, significant biological processes with expression similar to MWCNT-induced lung inflammation and fibrosis pathology data in mice were identified. A subset of genes in these processes was determined to be functionally related to either fibrosis or inflammation by Ingenuity Pathway Analysis and was used to determine potential significant signaling cascades. Two genes determined to be functionally related to inflammation and fibrosis, vascular endothelial growth factor A (vegfa) and C-C motif chemokine 2 (ccl2), were confirmed by in vitro studies of mRNA and protein expression in small airway epithelial cells exposed to MWCNT as concordant with in vivo expression. This study identified that the novel computational model was sufficient to determine biological processes strongly associated with the pathology of lung inflammation and fibrosis and could identify potential toxicity signaling pathways and mechanisms of MWCNT exposure which could be used for future animal studies to support human risk assessment and intervention efforts. - Highlights: • A novel computational model identified toxicity pathways matching in vivo pathology. • Systematic identification of MWCNT-induced biological processes in mouse lungs • MWCNT-induced functional networks of lung inflammation and fibrosis were revealed. • Two functional, representative genes, ccl2 and vegfa, were validated in vitro.« less

Perceptions of Preparedness of NIU Students for On-Campus Interviewing and the Factors Identified as Significant in Their Preparation. An Evaluative Research Study.

ERIC Educational Resources Information Center

Mosser, John W.

Preparation for employment beyond the academic training colleges provide is an area of essential skills most students need to develop. This study sought to determine student perceptions of the factors that were significant in their preparation for on-campus interviews and of the helpfulness of the Northern Illinois University's Career Planning and…

The effectiveness and cost-effectiveness of first aid interventions for burns given to caregivers of children: A systematic review.

PubMed

Nurmatov, Ulugbek B; Mullen, Stephen; Quinn-Scoggins, Harriet; Mann, Mala; Kemp, Alison

2018-05-01

the effectiveness and cost-effectiveness of burns first-aid educational interventions given to caregivers of children. Systematic review of eligible studies from seven databases, international journals, trials repositories and contacted international experts. Of 985 potential studies, four met the inclusion criteria. All had high risk of bias and weak global rating. Two studies identified a statistically significant increase in knowledge after of a media campaign. King et al. (41.7% vs 63.2%, p<0.0001), Skinner et al. (59% vs 40%, p=0.004). Skinner et al. also identified fewer admissions (64.4% vs 35.8%, p<0.001) and surgical procedures (25.6% vs 11.4%, p<0.001). Kua et al. identified a significant improvement in caregiver's knowledge (22.9% vs 78.3%, 95% CI 49.2, 61.4) after face-to-face education intervention. Ozyazicioglu et al. evaluated the effect of a first-aid training program and showed a reduction in use of harmful traditional methods for burns in children (29% vs 16.1%, p<0.001). No data on cost-effectiveness was identified. There is a paucity of high quality research in this field and considerable heterogeneity across the included studies. Delivery and content of interventions varied. However, studies showed a positive effect on knowledge. No study evaluated the direct effect of the intervention on first aid administration. High quality clinical trials are needed. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

Faith-adapted psychological therapies for depression and anxiety: Systematic review and meta-analysis.

PubMed

Anderson, Naomi; Heywood-Everett, Suzanne; Siddiqi, Najma; Wright, Judy; Meredith, Jodi; McMillan, Dean

2015-05-01

Incorporating faith (religious or spiritual) perspectives into psychological treatments has attracted significant interest in recent years. However, previous suggestion that good psychiatric care should include spiritual components has provoked controversy. To try to address ongoing uncertainty in this field we present a systematic review and meta-analysis to assess the efficacy of faith-based adaptations of bona fide psychological therapies for depression or anxiety. A systematic review and meta-analysis of randomised controlled trials were performed. The literature search yielded 2274 citations of which 16 studies were eligible for inclusion. All studies used cognitive or cognitive behavioural models as the basis for their faith-adapted treatment (F-CBT). We identified statistically significant benefits of using F-CBT. However, quality assessment using the Cochrane risk of bias tool revealed methodological limitations that reduce the apparent strength of these findings. Whilst the effect sizes identified here were statistically significant, there were relatively a few relevant RCTs available, and those included were typically small and susceptible to significant biases. Biases associated with researcher or therapist allegiance were identified as a particular concern. Despite some suggestion that faith-adapted CBT may out-perform both standard CBT and control conditions (waiting list or "treatment as usual"), the effect sizes identified in this meta-analysis must be considered in the light of the substantial methodological limitations that affect the primary research data. Before firm recommendations about the value of faith-adapted treatments can be made, further large-scale, rigorously performed trials are required. Copyright © 2015 Elsevier B.V. All rights reserved.

Epidemiology of clinical feline herpesvirus infection in zoo-housed cheetahs (Acinonyx jubatus).

PubMed

Witte, Carmel L; Lamberski, Nadine; Rideout, Bruce A; Vaida, Florin; Citino, Scott B; Barrie, Michael T; Haefele, Holly J; Junge, Randall E; Murray, Suzan; Hungerford, Laura L

2017-10-15

OBJECTIVE To determine the incidence of and risk factors for clinical feline herpesvirus (FHV) infection in zoo-housed cheetahs and determine whether dam infection was associated with offspring infection. DESIGN Retrospective cohort study. ANIMALS 144 cheetah cubs born in 6 zoos from 1988 through 2007. PROCEDURES Data were extracted from the health records of cheetahs and their dams to identify incident cases of clinical FHV infection and estimate incidence from birth to 18 months of age. Univariate and multivariable Cox proportional hazards models, controlling for correlations among cheetahs with the same dam, were used to identify risk factors for incident FHV infection. RESULTS Cumulative incidence of FHV infection in cheetah cubs was 35% (50/144). No significant association between dam and offspring infection was identified in any model. Factors identified as significant through multivariable analysis varied by age group. For cheetahs up to 3 months of age, the most important predictor of FHV infection was having a dam that had received a preparturition FHV vaccine regimen that included a modified-live virus vaccine versus a dam that had received no preparturition vaccine. Other risk factors included being from a small litter, being born to a primiparous dam, and male sex. CONCLUSIONS AND CLINICAL RELEVANCE This study provided the first population-level characterization of the incidence of and risk factors for FHV infection in cheetahs, and findings confirmed the importance of this disease. Recognition that clinical FHV infection in the dam was not a significant predictor of disease in cubs and identification of other significant factors have implications for disease management.

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.

Evaluating the utility of companion animal tick surveillance practices for monitoring spread and occurrence of human Lyme disease in West Virginia, 2014-2016.

PubMed

Hendricks, Brian; Mark-Carew, Miguella; Conley, Jamison

2017-11-13

Domestic dogs and cats are potentially effective sentinel populations for monitoring occurrence and spread of Lyme disease. Few studies have evaluated the public health utility of sentinel programmes using geo-analytic approaches. Confirmed Lyme disease cases diagnosed by physicians and ticks submitted by veterinarians to the West Virginia State Health Department were obtained for 2014-2016. Ticks were identified to species, and only Ixodes scapularis were incorporated in the analysis. Separate ordinary least squares (OLS) and spatial lag regression models were conducted to estimate the association between average numbers of Ix. scapularis collected on pets and human Lyme disease incidence. Regression residuals were visualised using Local Moran's I as a diagnostic tool to identify spatial dependence. Statistically significant associations were identified between average numbers of Ix. scapularis collected from dogs and human Lyme disease in the OLS (β=20.7, P<0.001) and spatial lag (β=12.0, P=0.002) regression. No significant associations were identified for cats in either regression model. Statistically significant (P≤0.05) spatial dependence was identified in all regression models. Local Moran's I maps produced for spatial lag regression residuals indicated a decrease in model over- and under-estimation, but identified a higher number of statistically significant outliers than OLS regression. Results support previous conclusions that dogs are effective sentinel populations for monitoring risk of human exposure to Lyme disease. Findings reinforce the utility of spatial analysis of surveillance data, and highlight West Virginia's unique position within the eastern United States in regards to Lyme disease occurrence.

Multivariate analysis of variance of designed chromatographic data. A case study involving fermentation of rooibos tea.

PubMed

Marini, Federico; de Beer, Dalene; Walters, Nico A; de Villiers, André; Joubert, Elizabeth; Walczak, Beata

2017-03-17

An ultimate goal of investigations of rooibos plant material subjected to different stages of fermentation is to identify the chemical changes taking place in the phenolic composition, using an untargeted approach and chromatographic fingerprints. Realization of this goal requires, among others, identification of the main components of the plant material involved in chemical reactions during the fermentation process. Quantitative chromatographic data for the compounds for extracts of green, semi-fermented and fermented rooibos form the basis of preliminary study following a targeted approach. The aim is to estimate whether treatment has a significant effect based on all quantified compounds and to identify the compounds, which contribute significantly to it. Analysis of variance is performed using modern multivariate methods such as ANOVA-Simultaneous Component Analysis, ANOVA - Target Projection and regularized MANOVA. This study is the first one in which all three approaches are compared and evaluated. For the data studied, all tree methods reveal the same significance of the fermentation effect on the extract compositions, but they lead to its different interpretation. Copyright © 2017 Elsevier B.V. All rights reserved.

Association between foot type and lower extremity injuries: systematic literature review with meta-analysis.

PubMed

Tong, Jasper W K; Kong, Pui W

2013-10-01

Systematic literature review with meta-analysis. To investigate the association between nonneutral foot types (high arch and flatfoot) and lower extremity and low back injuries, and to identify the most appropriate methods to use for foot classification. A search of 5 electronic databases (PubMed, Embase, CINAHL, SPORTDiscus, and ProQuest Dissertations and Theses), Google Scholar, and the reference lists of included studies was conducted to identify relevant articles. The review included comparative cross-sectional, case-control, and prospective studies that reported qualitative/quantitative associations between foot types and lower extremity and back injuries. Quality of the selected studies was evaluated, and data synthesis for the level of association between foot types and injuries was conducted. A random-effects model was used to pool odds ratio (OR) and standardized mean difference (SMD) results for meta-analysis. Twenty-nine studies were included for meta-analysis. A significant association between nonneutral foot types and lower extremity injuries was determined (OR = 1.23; 95% confidence interval [CI]: 1.11, 1.37; P<.001). Foot posture index (OR = 2.58; 95% CI: 1.33, 5.02; P<.01) and visual/physical examination (OR = 1.17; 95% CI: 1.06, 1.28; P<.01) were 2 assessment methods using distinct foot-type categories that showed a significant association with lower extremity injuries. For foot-assessment methods using a continuous scale, measurements of lateral calcaneal pitch angle (SMD, 1.92; 95% CI: 1.44, 2.39; P<.00001), lateral talocalcaneal angle (SMD, 1.36; 95% CI: 0.93, 1.80; P<.00001), and navicular height (SMD, 0.34; 95% CI: 0.16, 0.52; P<.001) showed significant effect sizes in identifying high-arch foot, whereas the navicular drop test (SMD, 0.45; 95% CI: 0.03, 0.87; P<.05) and relaxed calcaneal stance position (SMD, 0.49; 95% CI: 0.01, 0.97; P<.05) displayed significant effect sizes in identifying flatfoot. Subgroup analyses revealed no significant associations for children with flatfoot, cross-sectional studies, or prospective studies on high arch. High-arch and flatfoot foot types are associated with lower extremity injuries, but the strength of this relationship is low. Although the foot posture index and visual/physical examination showed significance, they are qualitative measures. Radiographic and navicular height measurements can delineate high-arch foot effectively, with only anthropometric measures accurately classifying flatfoot. Prognosis, level 2a.

Cost-benefit value of microscopic examination of intervertebral discs.

PubMed

Grzybicki, D M; Callaghan, E J; Raab, S S

1998-09-01

Given the virtual absence of histologically detected, clinically unsuspected disease in intervertebral disc specimens, some authors have advocated that histological examination be discontinued. However, the examination of intervertebral disc specimens remains common practice in most pathology laboratories. No cost-benefit analysis of this practice has been made; therefore, the authors' goal in this study was perform such an analysis. Using the University of Iowa surgical pathology database, 1109 patients who had undergone a laminectomy were identified retrospectively. These cases were classified into four categories based on the patients' preoperative clinical diagnosis and final histopathological diagnosis: insignificant clinical diagnosis/insignificant pathological diagnosis (ICIP), significant clinical diagnosis/insignificant pathological diagnosis (SCIP), significant clinical diagnosis/significant pathological diagnosis (SCSP), and insignificant clinical diagnosis/significant pathological diagnosis (ICSP). A significant clinical diagnosis was defined as one other than a benign, noninfectious indication for laminectomy. A significant pathological diagnosis was a diagnosis other than degenerative changes. The cost-benefit value of performing a histological examination in cases with significant or insignificant clinical diagnoses was examined. The cases were classified as: 1068 ICIP, 17 SCIP, 21 SCSP, and three ICSP. On chart review, in all three cases of ICSP an epidural abscess was identified perioperatively and the subsequent histological diagnosis did not affect patient care. The costs per case of identifying a significant pathological diagnosis with a significant and an insignificant clinical diagnosis were $44.79 and $8811, respectively. Histological examination of intervertebral disc specimens is cost beneficial only if there is a significant preoperative clinical diagnosis.

Spatial variation in mortality risk for haematological malignancies near a petrochemical refinery: a population-based case-control study

PubMed Central

Di Salvo, Francesca; Meneghini, Elisabetta; Vieira, Veronica; Baili, Paolo; Mariottini, Mauro; Baldini, Marco; Micheli, Andrea; Sant, Milena

2015-01-01

Introduction The study investigated the geographic variation of mortality risk for hematological malignancies (HMs) in order to identify potential high-risk areas near an Italian petrochemical refinery. Material and methods A population-based case-control study was conducted and residential histories for 171 cases and 338 sex- and age-matched controls were collected. Confounding factors were obtained from interviews with consenting relatives for 109 HM deaths and 267 controls. To produce risk mortality maps, two different approaches were applied. We mapped (1) adptive kernel density relative risk estimation (KDE) for case-control studies which estimates a spatial relative risk function using the ratio between cases and controls’ densities, and (2) estimated odds ratios for case-control study data using generalized additive models (GAMs) to smooth the effect of location, a proxy for exposure, while adjusting for confounding variables. Results No high-risk areas for HM mortality were identified among all subjects (men and women combined), by applying both approaches. Using the adaptive KDE approach, we found a significant increase in death risk only among women in a large area 2–6 km southeast of the refinery and the application of GAMs also identified a similarly-located significant high-risk area among women only (global p-value<0.025). Potential confounding risk factors we considered in the GAM did not alter the results. Conclusion Both approaches identified a high-risk area close to the refinery among women only. Those spatial methods are useful tools for public policy management to determine priority areas for intervention. Our findings suggest several directions for further research in order to identify other potential environmental exposures that may be assessed in forthcoming studies based on detailed exposure modeling. PMID:26073202

Pharmacists' interventions on clinical asthma outcomes: a systematic review.

PubMed

Garcia-Cardenas, Victoria; Armour, Carol; Benrimoj, Shalom I; Martinez-Martinez, Fernando; Rotta, Inajara; Fernandez-Llimos, Fernando

2016-04-01

The objective of this systematic review was to evaluate the impact of pharmacists' interventions on clinical asthma outcomes on adult patients and to identify the outcome indicators used.PubMed, Scopus, Web of Science and Scielo were searched. Studies addressing pharmacists' interventions on adult asthma patients reporting clinical asthma outcomes were incorporated.11 clinical outcomes were identified in 21 studies. 10 studies measured the impact of the intervention on asthma control. Randomised controlled trials (RCT) and non-RCTs found positive results in percentages of controlled patients and Asthma Control Questionnaire (ACQ) scores. Discordant results were found for Asthma Control Test results. Asthma severity was assessed in four studies. One RCT found a significant decrease in the percentage of severe patients; two non-RCTs found significant improvements in severity scores. 11 studies reported pulmonary function indicators, showing inconsistent results. Eight studies measured asthma symptoms; three RCTs and four non-RCTs showed significant improvements.RCTs and non-RCTs generated similar results for most outcomes. Based on the evidence generated by RCTs, pharmacists' have a positive impact on the percentage of controlled patients, ACQ scores, severity and symptoms. Future research should report using the core outcome set of indicators established for asthma (PROSPERO CRD42014007019). Copyright ©ERS 2016.

Genome-wide association study of sex hormones, gonadotropins and sex hormone-binding protein in Chinese men.

PubMed

Chen, Zhuo; Tao, Sha; Gao, Yong; Zhang, Ju; Hu, Yanling; Mo, Linjian; Kim, Seong-Tae; Yang, Xiaobo; Tan, Aihua; Zhang, Haiying; Qin, Xue; Li, Li; Wu, Yongming; Zhang, Shijun; Zheng, S Lilly; Xu, Jianfeng; Mo, Zengnan; Sun, Jielin

2013-12-01

Sex hormones and gonadotropins exert a wide variety of effects in physiological and pathological processes. Accumulated evidence shows a strong heritable component of circulating concentrations of these hormones. Recently, several genome-wide association studies (GWASs) conducted in Caucasians have identified multiple loci that influence serum levels of sex hormones. However, the genetic determinants remain unknown in Chinese populations. In this study, we aimed to identify genetic variants associated with major sex hormones, gonadotropins, including testosterone, oestradiol, follicle-stimulating hormone (FSH), luteinising hormone (LH) and sex hormone binding globulin (SHBG) in a Chinese population. A two-stage GWAS was conducted in a total of 3495 healthy Chinese men (1999 subjects in the GWAS discovery stage and 1496 in the confirmation stage). We identified a novel genetic region at 15q21.2 (rs2414095 in CYP19A1), which was significantly associated with oestradiol and FSH in the Chinese population at a genome-wide significant level (p=6.54×10(-31) and 1.59×10(-16), respectively). Another single nucleotide polymorphism in CYP19A1 gene was significantly associated with oestradiol level (rs2445762, p=7.75×10(-28)). In addition, we confirmed the previous GWAS-identified locus at 17p13.1 for testosterone (rs2075230, p=1.13×10(-8)) and SHBG level (rs2075230, p=4.75×10(-19)) in the Chinese population. This study is the first GWAS investigation of genetic determinants of FSH and LH. The identification of novel susceptibility loci may provide more biological implications for the synthesis and metabolism of these hormones. More importantly, the confirmation of the genetic loci for testosterone and SHBG suggests common genetic components shared among different ethnicities.

Genome-wide study of resistant hypertension identified from electronic health records.

PubMed

Dumitrescu, Logan; Ritchie, Marylyn D; Denny, Joshua C; El Rouby, Nihal M; McDonough, Caitrin W; Bradford, Yuki; Ramirez, Andrea H; Bielinski, Suzette J; Basford, Melissa A; Chai, High Seng; Peissig, Peggy; Carrell, David; Pathak, Jyotishman; Rasmussen, Luke V; Wang, Xiaoming; Pacheco, Jennifer A; Kho, Abel N; Hayes, M Geoffrey; Matsumoto, Martha; Smith, Maureen E; Li, Rongling; Cooper-DeHoff, Rhonda M; Kullo, Iftikhar J; Chute, Christopher G; Chisholm, Rex L; Jarvik, Gail P; Larson, Eric B; Carey, David; McCarty, Catherine A; Williams, Marc S; Roden, Dan M; Bottinger, Erwin; Johnson, Julie A; de Andrade, Mariza; Crawford, Dana C

2017-01-01

Resistant hypertension is defined as high blood pressure that remains above treatment goals in spite of the concurrent use of three antihypertensive agents from different classes. Despite the important health consequences of resistant hypertension, few studies of resistant hypertension have been conducted. To perform a genome-wide association study for resistant hypertension, we defined and identified cases of resistant hypertension and hypertensives with treated, controlled hypertension among >47,500 adults residing in the US linked to electronic health records (EHRs) and genotyped as part of the electronic MEdical Records & GEnomics (eMERGE) Network. Electronic selection logic using billing codes, laboratory values, text queries, and medication records was used to identify resistant hypertension cases and controls at each site, and a total of 3,006 cases of resistant hypertension and 876 controlled hypertensives were identified among eMERGE Phase I and II sites. After imputation and quality control, a total of 2,530,150 SNPs were tested for an association among 2,830 multi-ethnic cases of resistant hypertension and 876 controlled hypertensives. No test of association was genome-wide significant in the full dataset or in the dataset limited to European American cases (n = 1,719) and controls (n = 708). The most significant finding was CLNK rs13144136 at p = 1.00x10-6 (odds ratio = 0.68; 95% CI = 0.58-0.80) in the full dataset with similar results in the European American only dataset. We also examined whether SNPs known to influence blood pressure or hypertension also influenced resistant hypertension. None was significant after correction for multiple testing. These data highlight both the difficulties and the potential utility of EHR-linked genomic data to study clinically-relevant traits such as resistant hypertension.

Potential link between body dysmorphic disorder symptoms and alexithymia in an eating-disordered treatment-seeking sample.

PubMed

Fenwick, Andrea Siân; Sullivan, Karen Anne

2011-09-30

This study aimed to explore the manifestation of body dysmorphic disorder symptoms in a sample of people with eating disorders and to investigate possible associations between body dysmorphia and alexithymia. Forty patients currently seeking treatment for an eating disorder completed a battery of six measures assessing alexithymia, mood, eating behaviours, weight-related body image, body dysmorphia and non-weight related body image. Significant moderate positive correlations (Pearson's r) between selected variables were found, suggesting that participants with high levels of dysmorphic concern (imagined ugliness) have more difficulty with the affective elements of alexithymia, that is, identifying and describing feelings. When depression, eating attitudes, and weight-related body image concerns were controlled for, significant moderate positive correlations between this alexithymia factor and dysmorphic concerns remained present. An independent-samples t-test between eating-disordered participants with and without symptoms of body dysmorphic disorder (BDD) revealed significant group differences in difficulties identifying feelings. This pattern of results was replicated when the groups were identified on the basis of dysmorphic concerns, as opposed to BDD symptoms. This study highlights the associations between alexithymia and body dysmorphia that have not previously been demonstrated. Copyright © 2011 Elsevier Ltd. All rights reserved.

Proteomic analysis reveals diverse proline hydroxylation-mediated oxygen-sensing cellular pathways in cancer cells

PubMed Central

Liu, Bing; Gao, Yankun; Ruan, Hai-Bin; Chen, Yue

2016-01-01

Proline hydroxylation is a critical cellular mechanism regulating oxygen-response pathways in tumor initiation and progression. Yet, its substrate diversity and functions remain largely unknown. Here, we report a system-wide analysis to characterize proline hydroxylation substrates in cancer cells using an immunoaffinity-purification assisted proteomics strategy. We identified 562 sites from 272 proteins in HeLa cells. Bioinformatic analysis revealed that proline hydroxylation substrates are significantly enriched with mRNA processing and stress-response cellular pathways with canonical and diverse flanking sequence motifs. Structural analysis indicates a significant enrichment of proline hydroxylation participating in the secondary structure of substrate proteins. Our study identified and validated Brd4, a key transcription factor, as a novel proline hydroxylation substrate. Functional analysis showed that the inhibition of proline hydroxylation pathway significantly reduced the proline hydroxylation abundance on Brd4 and affected Brd4-mediated transcriptional activity as well as cell proliferation in AML leukemia cells. Taken together, our study identified a broad regulatory role of proline hydroxylation in cellular oxygen-sensing pathways and revealed potentially new targets that dynamically respond to hypoxia microenvironment in tumor cells. PMID:27764789

Predicting Future Suicide Attempts among Depressed Suicide Ideators: A 10-year Longitudinal Study

PubMed Central

May, Alexis M.; Klonsky, E. David; Klein, Daniel N.

2012-01-01

Suicidal ideation and attempts are a major public health problem. Research has identified many risk factors for suicidality; however, most fail to identify which suicide ideators are at greatest risk of progressing to a suicide attempt. Thus, the present study identified predictors of future suicide attempts in a sample of psychiatric patients reporting suicidal ideation. The sample comprised 49 individuals who met full DSM-IV criteria for major depressive disorder and/or dysthymic disorder and reported suicidal ideation at baseline. Participants were followed for 10 years. Demographic, psychological, personality, and psychosocial risk factors were assessed using validated questionnaires and structured interviews. Phi coefficients and point-biserial correlations were used to identify prospective predictors of attempts, and logistic regressions were used to identify which variables predicted future attempts over and above past suicide attempts. Six significant predictors of future suicide attempts were identified – cluster A personality disorder, cluster B personality disorder, lifetime substance abuse, baseline anxiety disorder, poor maternal relationship, and poor social adjustment. Finally, exploratory logistic regressions were used to examine the unique contribution of each significant predictor controlling for the others. Co-morbid cluster B personality disorder emerged as the only robust, unique predictor of future suicide attempts among depressed suicide ideators. Future research should continue to identify variables that predict transition from suicidal thoughts to suicide attempts, as such work will enhance clinical assessment of suicide risk as well as theoretical models of suicide. PMID:22575331

Using a Brief Preschool Early Numeracy Skills Screener to Identify Young Children with Mathematics Difficulties

ERIC Educational Resources Information Center

Purpura, David J.; Reid, Erin E.; Eiland, Michael D.; Baroody, Arthur J.

2015-01-01

A critical component in enhancing academic success is identifying children at risk of later academic difficulties. Although significant efforts have been devoted to design effective assessment processes in elementary school, fewer efforts (particularly for mathematics) have been made for preschool. The focus of this study was to design and…

Identifying the Factors Affecting Science and Mathematics Achievement Using Data Mining Methods

ERIC Educational Resources Information Center

Kiray, S. Ahmet; Gok, Bilge; Bozkir, A. Selman

2015-01-01

The purpose of this article is to identify the order of significance of the variables that affect science and mathematics achievement in middle school students. For this aim, the study deals with the relationship between science and math in terms of different angles using the perspectives of multiple causes-single effect and of multiple…

The Role of School Principals in the Governorate of Ma'an in Promoting Intellectual Security among Students

ERIC Educational Resources Information Center

Waswas, Dima; Gasaymeh, Al-Mothana M.

2017-01-01

This study aims at identifying the role played by school principals in the Governorate of Ma'an to strengthen intellectual security of the school students; and identifying whether there are statistically significant differences in the roles of principals attributed to the variables: gender, academic level, and years of experience in…

A Comparison of Multiple Facets of Self-Concept in Gifted vs. Non-Identified Israeli Students

ERIC Educational Resources Information Center

Zeidner, Moshe; Shani-Zinovich, Inbal

2015-01-01

This study compares facets of self-concept in gifted and non-identified Israeli adolescent students. The self-concept mean score profile of gifted vs. non-selected Israeli students was significantly different, with gifted students reporting higher mean levels of academic self-concept, but lower mean levels of social, personal, and physical…

Anticipating cascading change in forests: Seeking a deeper understanding of the future

Treesearch

David N. Bengston; Mike Dockry; Stephen R. Shifley

2017-01-01

This study used a participatory group brainstorming process called the Futures Wheel to identify and evaluate the direct and higher-order implications of this trend: Central Hardwood forests lack age-class diversity and will uniformly grow old. Five 1st-order consequences of this trend were identified: continued significant decrease in early-successional forest,...

Identifying Victims of Abuse Using the Personality Inventory for Children: I. Applications for Adolescent Runaways.

ERIC Educational Resources Information Center

Rohr, Michael E.; And Others

The physical and sexual abuse of children and adolescents has been gaining attention as a national problem of social and clinical significance. In this study a model was developed in order to identify abuse (victimization) in an adolescent population (n=52). Four scales (Adjustment, Delinquency, Family Relations, and Anxiety) of the Personality…

Test Anxiety & Its Relation to Perceived Academic Self-Efficacy among Al Hussein Bin Talal University Students

ERIC Educational Resources Information Center

sa'ad alzboon, Habis

2016-01-01

This study aimed to identify the degree of perceived academic self-efficacy and the relationship nature between test anxiety and perceived academic self-efficacy among students of Al Hussein Bin Talal University (AHU). Moreover, to identify the degree of available statistical significance differences that are attributed to gender, college and…

Survey of Poetry Reading Strategy as the Modern Tool to Identify Poetry Reading Strategies

ERIC Educational Resources Information Center

Ebrahimi, Shirin Shafiei; Zainal, Zaidah

2016-01-01

This study examines common strategies that English as a Foreign language (EFL) students employ when reading English poetry. To identify the strategies, a survey was designed for data collection from TESL students. The result shows that students significantly tend to use the strategies that require their creativity to construct new ideas in the…

Gender Differences in the Vocational Interests of Youth Considering High Job Growth and Green Energy Occupations

ERIC Educational Resources Information Center

Robinson, Becky S.

2012-01-01

For more than 100 years, vocational psychologists and educational researchers have sought to identify the significant influences shaping occupational interests. This descriptive study used a series of vocational card sort exercises with 139 rural high school youth to identify gender differences in occupational interests toward working in 60 of the…

Perceptions of District Technology Coordinators regarding Factors that Influence Technology Integration in Teacher Practice

ERIC Educational Resources Information Center

Paszkowski, Diane M.

2008-01-01

Severe reductions in funding coupled with the imperative to measure and report teachers' ability to integrate technology into their practice pose a significant problem for school districts in New Jersey. This study was designed to identify factors that influence teacher use of technology. A review of the literature identified four areas of…

Caucasian Families Exhibit Significant Linkage of Myopia to Chromosome 11p.

PubMed

Musolf, Anthony M; Simpson, Claire L; Moiz, Bilal A; Long, Kyle A; Portas, Laura; Murgia, Federico; Ciner, Elise B; Stambolian, Dwight; Bailey-Wilson, Joan E

2017-07-01

Myopia is a common visual disorder caused by eye overgrowth, resulting in blurry vision. It affects one in four Americans, and its prevalence is increasing. The genetic mechanisms that underpin myopia are not completely understood. Here, we use genotype data and linkage analyses to identify high-risk genetic loci that are significantly linked to myopia. Individuals from 56 Caucasian families with a history of myopia were genotyped on an exome-based array, and the single nucleotide polymorphism (SNP) data were merged with microsatellite genotype data. Refractive error measures on the samples were converted into binary phenotypes consisting of affected, unaffected, or unknown myopia status. Parametric linkage analyses assuming an autosomal dominant model with 90% penetrance and 10% phenocopy rate were performed. Single variant two-point analyses yielded three significantly linked SNPs at 11p14.1 and 11p11.2; a further 45 SNPs at 11p were found to be suggestive. No other chromosome had any significant SNPs or more than seven suggestive linkages. Two of the significant SNPs were located in BBOX1-AS1 and one in the intergenic region between ORA47 and TRIM49B. Collapsed haplotype pattern two-point analysis and multipoint analyses also yielded multiple suggestively linked genes at 11p. Multipoint analysis also identified suggestive evidence of linkage on 20q13. We identified three genome-wide significant linked variants on 11p for myopia in Caucasians. Although the novel specific signals still need to be replicated, 11p is a promising region that has been identified by other linkage studies with a number of potentially interesting candidate genes. We hope that the identification of these regions on 11p as potential causal regions for myopia will lead to more focus on these regions and maybe possible replication of our specific linkage peaks in other studies. We further plan targeted sequencing on 11p for our most highly linked families to more clearly understand the source of the linkage in this region.

Deep Resequencing of GWAS Loci Identifies Rare Variants in CARD9, IL23R and RNF186 That Are Associated with Ulcerative Colitis

PubMed Central

Boucher, Gabrielle; Lo, Ken Sin; Rivas, Manuel A.; Stevens, Christine; Alikashani, Azadeh; Ladouceur, Martin; Ellinghaus, David; Törkvist, Leif; Goel, Gautam; Lagacé, Caroline; Annese, Vito; Bitton, Alain; Begun, Jakob; Brant, Steve R.; Bresso, Francesca; Cho, Judy H.; Duerr, Richard H.; Halfvarson, Jonas; McGovern, Dermot P. B.; Radford-Smith, Graham; Schreiber, Stefan; Schumm, Philip L.; Sharma, Yashoda; Silverberg, Mark S.; Weersma, Rinse K.; D'Amato, Mauro; Vermeire, Severine; Franke, Andre; Lettre, Guillaume; Xavier, Ramnik J.; Daly, Mark J.; Rioux, John D.

2013-01-01

Genome-wide association studies and follow-up meta-analyses in Crohn's disease (CD) and ulcerative colitis (UC) have recently identified 163 disease-associated loci that meet genome-wide significance for these two inflammatory bowel diseases (IBD). These discoveries have already had a tremendous impact on our understanding of the genetic architecture of these diseases and have directed functional studies that have revealed some of the biological functions that are important to IBD (e.g. autophagy). Nonetheless, these loci can only explain a small proportion of disease variance (∼14% in CD and 7.5% in UC), suggesting that not only are additional loci to be found but that the known loci may contain high effect rare risk variants that have gone undetected by GWAS. To test this, we have used a targeted sequencing approach in 200 UC cases and 150 healthy controls (HC), all of French Canadian descent, to study 55 genes in regions associated with UC. We performed follow-up genotyping of 42 rare non-synonymous variants in independent case-control cohorts (totaling 14,435 UC cases and 20,204 HC). Our results confirmed significant association to rare non-synonymous coding variants in both IL23R and CARD9, previously identified from sequencing of CD loci, as well as identified a novel association in RNF186. With the exception of CARD9 (OR = 0.39), the rare non-synonymous variants identified were of moderate effect (OR = 1.49 for RNF186 and OR = 0.79 for IL23R). RNF186 encodes a protein with a RING domain having predicted E3 ubiquitin-protein ligase activity and two transmembrane domains. Importantly, the disease-coding variant is located in the ubiquitin ligase domain. Finally, our results suggest that rare variants in genes identified by genome-wide association in UC are unlikely to contribute significantly to the overall variance for the disease. Rather, these are expected to help focus functional studies of the corresponding disease loci. PMID:24068945

Genome-Wide Association Study to Identify Single Nucleotide Polymorphisms (SNPs) Associated With the Development of Erectile Dysfunction in African-American Men After Radiotherapy for Prostate Cancer

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

Kerns, Sarah L.; Ostrer, Harry; Stock, Richard

2010-12-01

Purpose: To identify single nucleotide polymorphisms (SNPs) associated with erectile dysfunction (ED) among African-American prostate cancer patients treated with external beam radiation therapy. Methods and Materials: A cohort of African-American prostate cancer patients treated with external beam radiation therapy was observed for the development of ED by use of the five-item Sexual Health Inventory for Men (SHIM) questionnaire. Final analysis included 27 cases (post-treatment SHIM score {<=}7) and 52 control subjects (post-treatment SHIM score {>=}16). A genome-wide association study was performed using approximately 909,000 SNPs genotyped on Affymetrix 6.0 arrays (Affymetrix, Santa Clara, CA). Results: We identified SNP rs2268363, locatedmore » in the follicle-stimulating hormone receptor (FSHR) gene, as significantly associated with ED after correcting for multiple comparisons (unadjusted p = 5.46 x 10{sup -8}, Bonferroni p = 0.028). We identified four additional SNPs that tended toward a significant association with an unadjusted p value < 10{sup -6}. Inference of population substructure showed that cases had a higher proportion of African ancestry than control subjects (77% vs. 60%, p = 0.005). A multivariate logistic regression model that incorporated estimated ancestry and four of the top-ranked SNPs was a more accurate classifier of ED than a model that included only clinical variables. Conclusions: To our knowledge, this is the first genome-wide association study to identify SNPs associated with adverse effects resulting from radiotherapy. It is important to note that the SNP that proved to be significantly associated with ED is located within a gene whose encoded product plays a role in male gonad development and function. Another key finding of this project is that the four SNPs most strongly associated with ED were specific to persons of African ancestry and would therefore not have been identified had a cohort of European ancestry been screened. This study demonstrates the feasibility of a genome-wide approach to investigate genetic predisposition to radiation injury.« less

Stratifying risk in chronic kidney disease: an observational study of UK guidelines for measuring total proteinuria and albuminuria.

PubMed

Methven, S; Traynor, J P; Hair, M D; St J O'Reilly, D; Deighan, C J; MacGregor, M S

2011-08-01

Proteinuria predicts poor renal and cardiovascular outcomes. Some guidelines recommend measuring proteinuria using albumin:creatinine ratio (ACR), while others recommend total protein:creatinine ratio (TPCR). To compare renal outcomes and mortality in the populations identified by these different recommendations. Retrospective longitudinal cohort study. Baseline ACR and TPCR measurements were obtained from 5586 patients with chronic kidney disease (CKD) attending a Scottish hospital nephrology clinic. The cohort was divided into three groups with concordant results by ACR and TPCR (no proteinuria; low proteinuria; significant proteinuria) and one group with discordant results (significant proteinuria with TPCR, but not ACR). Outcomes were assessed using Kaplan-Meier plots and Cox proportional hazards models. Median follow-up was 3.5 years [interquartile range (IQR) 2.1-6.0]; 844 (15%) died at 3.0 years (IQR 1.8-4.7) and 468 (8%) started renal replacement therapy (RRT) at 1.7 years (IQR 0.6-3.4). Proteinuria was associated with a substantially increased risk of RRT and death. Patients with significant proteinuria by TPCR, but not ACR (n = 231) had high renal risk, and the highest all-cause mortality (log-rank P < 0.001). With multivariate analysis the risk fell below those with significant proteinuria with concordant results by ACR and TPCR but remained considerably higher than those without significant proteinuria. Proteinuria screening with TPCR identifies an additional 16% of patients with significant proteinuria, not identified using ACR. This subgroup has high renal risk, and high risk of all-cause mortality and therefore warrant identification. Guideline recommendations on proteinuria screening in CKD should be reconsidered.

Relationship between Teacher Views on Levels of Organizational Support--Organizational Identification and Climate of Initiative

ERIC Educational Resources Information Center

Nartgün, Senay Sezgin; Taskin, Sevgi

2017-01-01

This study aimed to identify secondary school teachers' views on levels of organizational support, organizational identification and climate of initiative and to determine whether there were any significant differences between these views based on teachers' demographic characteristics and whether there were significant differences between…

Religiosity and Authoritarianism as Predictors of Attitude toward the Disabled: A Regression Analysis.

ERIC Educational Resources Information Center

Tunick, Roy H.; And Others

1979-01-01

This study identifies predictors and correlates of attitudes toward the disabled. Authoritarianism, church attendance, religious orthodoxy, age, and education were significantly related to these attitudes of people in a Rocky Mountain Community. Significant predictors of the criterion were authoritarianism, religiosity, and age. Recommendations…

Agricultural Issues of Significance to Iowa Crop Producers and Their Educational Implications

ERIC Educational Resources Information Center

Licht, Melea A. R.; Martin, Robert A.

2007-01-01

The purpose of this study was to determine the agricultural information preferences of crop producers in Iowa and the implications for agricultural extension education. The objective was to identify agricultural information issues producers perceive as significant to their businesses. The results will help agricultural extension educators and…

Inclusion of Students with Significant Disabilities in SWPBS Evaluation Tools

ERIC Educational Resources Information Center

Kurth, Jennifer A.; Zagona, Alison; Hagiwara, Mayumi; Enyart, Matt

2017-01-01

Students with significant disabilities (intellectual and developmental disabilities) are predominantly educated in separate settings, and tend to have little access to schoolwide positive behavior supports (SWPBS). In this study, we first identified the most commonly cited SWPBS evaluation tools in the literature between 2010 and 2016. The SET,…

Legends of the field: influential scholars in multicultural counseling.

PubMed

Ponterotto, Joseph G; Fingerhut, Esther C; McGuinness, Ryan

2012-10-01

This study identified the most frequently cited scholars across 28 leading multicultural textbooks used in the training of counselors and counseling psychologists. Four spheres or clusters of multicultural scholars were identified and were characterized, respectively, as having either a profound, highly significant, significant, or important impact on the academic multicultural training of counseling graduate students. The top-cited scholars across the textbooks were also examined in relation to their scholarly productivity (number of publications) and their impact (number of citations) in peer-reviewed journals. Specifically, multicultural scholars were assessed on the delta-beta coefficient, Scopus and PsycINFO publications count, Scopus citations, and the increasingly popular h-index of scientific impact. Limitations of the study and implications of the findings for counseling training were highlighted.

Study motives, career choices and interest in paediatric dentistry among final year dental students in Nigeria

PubMed Central

2014-01-01

Background Students’ motives for studying Dentistry have been a subject of interest for years because of the potential for understanding the psychological makeup and subsequent job satisfaction for the dentist. It is also useful in identifying expectations of the profession. This study therefore tried to identify study motives and career preferences of dental students especially with respect to the practice of paediatric dentistry. Methods This was a cross-sectional study using a self-administered questionnaire. The final year students in six dental schools in Nigeria were required to fill the questionnaire. Students were asked to rank their motives and career preferences on a Likert like scale with points ranging from 0–5 where 0 represented a factor that had no influence on their decision and 5 represented a very influential factor. The underlying dimensions for study motives, career preference, impression about and motive for interest in the practice of paediatric dentistry were identified using factor analysis. Results One hundred and seventy nine of 223 students (80.3%) participated in this study. Motives for the practice of dentistry included characteristics of the profession, altruism and intellectual challenges, existence of artistic theme in dentistry and parent’s recommendation. Overall, 67.1% of respondents indicated interest in postgraduate studies and 50.8% were interested in paediatric dentistry practice. The main motives for showing interest in the practice of paediatric dentistry were ‘personal interest, professional interest and interest of significant others in children’, and ‘family influence’. Significantly more males than females were interested in the practice of paediatric dentistry though the motives for interest in the practice of paediatric dentistry did not differ significantly by sex or age. Conclusion The non-significant sex difference in the motives for interest in the practice of paediatric dentistry is a possible reflection of changes in strong cultural themes in the motives for career choices in Nigeria. PMID:24989055

Plasma metabonomics study of the patients with acute anterior uveitis based on ultra-performance liquid chromatography-mass spectrometry.

PubMed

Guo, Junguo; Yan, Tingqin; Bi, Hongsheng; Xie, Xiaofeng; Wang, Xingrong; Guo, Dadong; Jiang, Haiqiang

2014-06-01

The identification of the biomarkers of patients with acute anterior uveitis (AAU) may allow for a less invasive and more accurate diagnosis, as well as serving as a predictor in AAU progression and treatment response. The aim of this study was to identify the potential biomarkers and the metabolic pathways from plasma in patients with AAU. Both plasma metabolic biomarkers and metabolic pathways in the AAU patients versus healthy volunteers were investigated using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and a metabonomics approach. The principal component analysis (PCA) was used to separate AAU patients from healthy volunteers as well as to identify the different biomarkers between the two groups. Metabolic compounds were matched to the KEGG, METLIN, and HMDB databases, and metabolic pathways associated with AAU were identified. The PCA for UPLC-MS data shows that the metabolites in AAU patients were significantly different from those of healthy volunteers. Of the 4,396 total features detected by UPLC-MS, 102 features were significantly different between AAU patients and healthy volunteers according to the variable importance plot (VIP) values (greater than two) of partial least squares discriminate analysis (PLS-DA). Thirty-three metabolic compounds were identified and were considered as potential biomarkers. Meanwhile, ten metabolic pathways were found that were related to the AAU according to the identified biomarkers. These data suggest that metabolomics study can identify potential metabolites that differ between AAU patients and healthy volunteers. Based on the PCA, PLS-DA, several potential metabolic biomarkers and pathways in AAU patients were found and identified. In addition, the UPLC-MS technique combined with metabonomics could be a suitable systematic biology tool in research in clinical problems in ophthalmology, and can provide further insight into the pathophysiology of AAU.

Factors associated with parental reasons for "no-intent" to vaccinate female adolescents with human papillomavirus vaccine: National Immunization Survey - Teen 2008-2012.

PubMed

Cheruvu, Vinay K; Bhatta, Madhav P; Drinkard, Lauren N

2017-02-13

1) To identify socio-demographic factors associated with parental "no-intent" for their 13-17 year old unvaccinated daughter to receive the human papillomavirus (HPV) vaccine series within the next twelve months, 2) to describe patterns in "no-intent" by socio-demographic factors, and 3) to identify socio-demographic factors associated with parental reasons for "no-intent". Data from 2008-2012 National Immunization Survey - Teen (NIS - Teen) were examined in this study. Parents with "no-intent" to vaccinate their daughters were asked to identify reasons for their decision. All responses were categorized into five domains identified as barriers to receive the HPV vaccine series: 1) Safety and Effectiveness Concerns; 2) Systemic Barriers; 3) Vaccine Misinformation; 4) Lack of Knowledge about the Vaccine; and 5) Socio-cultural Barriers. Multivariable logistic regression models were performed to address the study objectives. Number of people in the household, household income, mother's age, education, health insurance, recommendation of a health care provider, and the survey year were significantly associated with parental "no-intent". Race/ethnicity, mother's education, marital status, recommendation of a health care provider, household income, age of the unvaccinated daughter, and the survey year, were significantly associated with one or more domains identified as barriers to receive the HPV vaccine. This study identified sub-groups of parents across different socio-demographic factors with "no-intent" for their adolescent daughters to receive the HPV vaccine. Developing strategies that target educational tools towards the identified sub-groups of parents about the purpose, safety, and efficacy of the HPV vaccine, and HPV infection, may help increase HPV vaccine acceptance, initiation and completion rates.

Evaluation of service quality of hospital outpatient department services.

PubMed

Chakravarty, Abhijit

2011-07-01

It has become essential for hospital managers to understand and measure consumer perspectives and service quality gaps, so that any perceived gap in delivery of service is identified and suitably addressed. A study was conducted at a peripheral service hospital to ascertain any service gap between consumer expectations and perceptions in respect of the hospital outpatient department (OPD) services. A cross-sectional study was conducted using SERVQUAL as the survey instrument, the instrument being validated for use in the hospital environment. Consumer ratings across 22 items of the survey instrument were collected in paired expectation and perception scores and then service quality gaps were identified and statistically analysed. Service quality gaps were identified to exist across all the five dimensions of the survey instrument, with statistically significant gaps across the dimensions of 'tangibles' and 'responsiveness.' The quality gaps were further validated by a total unweighted SERVQUAL score of (-) 1.63. The study concludes that significant service quality gaps existed in the delivery of the hospital OPD services, which need to be addressed by focused improvement efforts by the hospital management.

Latina Adolescents Health Risk Behaviors and Suicidal Ideation and Suicide Attempts: Results from the National Youth Risk Behavior Survey 2001-2013.

PubMed

Price, James H; Khubchandani, Jagdish

2017-06-01

Suicidal ideation and suicide attempts are more common in Latina adolescents than White or African-American adolescents. Several health risk behaviors have been identified as being associated with Latina adolescent suicides. However, to date, no study has identified the consistency and stability of these risk behaviors over time. This study utilized the national Youth Risk Behaviors Survey from 2001 to 2013 to estimate the prevalence of suicidal ideation, suicide attempts, and health risk behaviors associated with suicidal behaviors in Latina adolescents. Our analysis found the prevalence of suicidal ideation and suicide attempts varied significantly over the 13-year study span, decreasing from 2001 to 2009 and increased from 2011 to 2013. The analyses found 11 health risk behaviors that were significantly associated with both suicidal ideation and suicide attempts that did not vary over time. The stability of these 11 health risk behaviors associated with suicidal behaviors could be useful to school personnel to identify early at risk Latina adolescents who may benefit from school and community mental health resources.

Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice

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

Mao, Jian -Hua; Langley, Sasha A.; Huang, Yurong

Evidence has emerged that suggests a link between motor deficits, obesity and many neurological disorders. However, the contributing genetic risk factors are poorly understood. Here we used the Collaborative Cross (CC), a large panel of newly inbred mice that captures 90% of the known variation among laboratory mice, to identify the genetic loci controlling rotarod performance and its relationship with body weight in a cohort of 365 mice across 16 CC strains. Body weight and rotarod performance varied widely across CC strains and were significantly negatively correlated. Genetic linkage analysis identified 14 loci that were associated with body weight. However,more » 45 loci affected rotarod performance, seven of which were also associated with body weight, suggesting a strong link at the genetic level. As a result, we show that genes identified in this study overlap significantly with those related to neurological disorders and obesity found in human GWA studies. In conclusion, our results provide a genetic framework for studies of the connection between body weight, the central nervous system and behavior.« less

Predictors of attitude and intention to use knowledge management system among Korean nurses.

PubMed

Yun, Eun Kyoung

2013-12-01

Knowledge sharing using Knowledge Management (KM) systems helps nurses to understand and acquire appropriate knowledge that influences the quality of healthcare service. The purpose of this study was to identify organizational and individual factors influencing attitude and intention to use KM systems among Korean nurses. A cross-sectional survey design was used to study a sample of 245 nurses employed at five hospitals in Seoul. A multiple hierarchical regression was used to examine predictors of nurses' attitude and intention to use. From an individual perspective, nurse's informatics competency was identified as a significant factor influencing attitudes toward knowledge management usage within adhocracy and clan cultures. However, from an organizational perspective, level of hospital information system was identified as a significant factor influencing KM system usage within adhocracy cultures. The findings of this study will be helpful in better understanding and assessing the impact of the factors affecting the implementation of nursing knowledge management systems and in further developing successful managerial strategies using knowledge resources in healthcare settings. Copyright © 2013 Elsevier Ltd. All rights reserved.

Does clinical presentation predict response to a nonsurgical chronic disease management program for endstage hip and knee osteoarthritis?

PubMed

Eyles, Jillian P; Lucas, Barbara R; Patterson, Jillian A; Williams, Matthew J; Weeks, Kate; Fransen, Marlene; Hunter, David J

2014-11-01

To identify baseline characteristics of participants who will respond favorably following 6 months of participation in a chronic disease management program for hip and knee osteoarthritis (OA). This prospective cohort study assessed 559 participants at baseline and following 6 months of participation in the Osteoarthritis Chronic Care Program. Response was defined as the minimal clinically important difference of an 18% and 9-point absolute improvement in the Western Ontario and McMaster Universities Arthritis Index global score. Multivariate logistic regression modeling was used to identify predictors of response. Complete data were available for 308 participants. Those who withdrew within the study period were imputed as nonresponders. Three variables were independently associated with response: signal joint (knee vs hip), sex, and high level of comorbidity. Index joint and sex were significant in the multivariate model, but the model was not a sensitive predictor of response. Strong predictors of response to a chronic disease management program for hip and knee OA were not identified. The significant predictors that were found should be considered in future studies.

Identifying ADHD children using hemodynamic responses during a working memory task measured by functional near-infrared spectroscopy.

PubMed

Gu, Yue; Miao, Shuo; Han, Junxia; Liang, Zhenhu; Ouyang, Gaoxiang; Yang, Jian; Li, Xiaoli

2018-06-01

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting children and adults. Previous studies found that functional near-infrared spectroscopy (fNIRS) can reveal significant group differences in several brain regions between ADHD children and healthy controls during working memory tasks. This study aimed to use fNIRS activation patterns to identify ADHD children from healthy controls. FNIRS signals from 25 ADHD children and 25 healthy controls performing the n-back task were recorded; then, multivariate pattern analysis was used to discriminate ADHD individuals from healthy controls, and classification performance was evaluated for significance by the permutation test. The results showed that 86.0% ([Formula: see text]) of participants can be correctly classified in leave-one-out cross-validation. The most discriminative brain regions included the bilateral dorsolateral prefrontal cortex, inferior medial prefrontal cortex, right posterior prefrontal cortex, and right temporal cortex. This study demonstrated that, in a small sample, multivariate pattern analysis can effectively identify ADHD children from healthy controls based on fNIRS signals, which argues for the potential utility of fNIRS in future assessments.

Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice

DOE PAGES

Mao, Jian -Hua; Langley, Sasha A.; Huang, Yurong; ...

2015-11-09

Evidence has emerged that suggests a link between motor deficits, obesity and many neurological disorders. However, the contributing genetic risk factors are poorly understood. Here we used the Collaborative Cross (CC), a large panel of newly inbred mice that captures 90% of the known variation among laboratory mice, to identify the genetic loci controlling rotarod performance and its relationship with body weight in a cohort of 365 mice across 16 CC strains. Body weight and rotarod performance varied widely across CC strains and were significantly negatively correlated. Genetic linkage analysis identified 14 loci that were associated with body weight. However,more » 45 loci affected rotarod performance, seven of which were also associated with body weight, suggesting a strong link at the genetic level. As a result, we show that genes identified in this study overlap significantly with those related to neurological disorders and obesity found in human GWA studies. In conclusion, our results provide a genetic framework for studies of the connection between body weight, the central nervous system and behavior.« less

The role of body-related self-conscious emotions in motivating women's physical activity.

PubMed

Sabiston, Catherine M; Brunet, Jennifer; Kowalski, Kent C; Wilson, Philip M; Mack, Diane E; Crocker, Peter R E

2010-08-01

The purpose of this study was to test a model where body-related self-conscious emotions of shame, guilt, and pride were associated with physical activity regulations and behavior. Adult women (N = 389; M age = 29.82, SD = 15.20 years) completed a questionnaire assessing body-related pride, shame, and guilt, motivational regulations, and leisure-time physical activity. The hypothesized measurement and structural models were deemed adequate, as was a revised model examining shame-free guilt and guilt-free shame. In the revised structural model, body-related pride was positively significantly related to identified and intrinsic regulations. Body-related shame-free guilt was significantly associated with external, introjected, and identified regulations. Body-related guilt-free shame was significantly positively related to external and introjected regulation, and negatively associated with intrinsic regulation. Identified and intrinsic regulations were significantly positively related to physical activity (R2 = .62). These findings highlight the importance of targeting and understanding the realm of body-related self-conscious emotions and the associated links to regulations and physical activity behavior.

Private prayer associations with depression, anxiety and other health conditions: an analytical review of clinical studies.

PubMed

Anderson, James W; Nunnelley, Paige A

2016-09-01

To critically analyze appropriate clinical studies to assess the relationship between health conditions and the frequency of private prayer. Private prayer is defined as individuals praying for themselves. Using PubMed and other search engines, we identified over 300 articles reporting relationships between prayer and health conditions. We identified 41 observational clinical studies that evaluated the relationship between private prayer and health conditions. Prayer scores of 5 to 1 were assigned to studies, with 5 being private prayer for health and 1 being prayer in combination with meditation or Bible study. Frequency scores ranged from 3 to 1 with 3 being twice daily or more and 0 when frequency was not assessed. Studies were ranked from 8 to 1 based on the sum of Prayer and Frequency Scores. Twenty-one studies had Prayer-Frequency scores of 5 to 8, indicating that they evaluated private prayer (praying for one's own health) of suitable frequency in association with health conditions. Nine of 11 studies indicated that private prayer was associated with a significantly lower prevalence of depression (P value, <0.01). Optimism as well as coping were significantly improved by prayer in four studies (P value, P < 0.01). In 10 studies of mental health conditions-including anxiety and confusion-there was a significant benefit associated with prayer (P < 0.01), In the reviewed studies, prayer did not have a significant effect on physical health or blood pressure. The reported observational studies suggest that frequent private prayer is associated with a significant benefit for depression, optimism, coping, and other mental health conditions such as anxiety. Controlled clinical trials are required to critically assess the associations of private prayer and health conditions.

EB1 protein alteration characterizes sporadic but not ulcerative colitis associated colorectal cancer.

PubMed

Gemoll, Timo; Kollbeck, Sophie L; Karstens, Karl F; Hò, Gia G; Hartwig, Sonja; Strohkamp, Sarah; Schillo, Katharina; Thorns, Christoph; Oberländer, Martina; Kalies, Kathrin; Lehr, Stefan; Habermann, Jens K

2017-08-15

While carcinogenesis in Sporadic Colorectal Cancer (SCC) has been thoroughly studied, less is known about Ulcerative Colitis associated Colorectal Cancer (UCC). This study aimed to identify and validate differentially expressed proteins between clinical samples of SCC and UCC to elucidate new insights of UCC/SCC carcinogenesis and progression. Multiplex-fluorescence two-dimensional gel electrophoresis (2-D DIGE) and mass spectrometry identified 67 proteoforms representing 43 distinct proteins. After analysis by Ingenuity Pathway Analysis ® (IPA), subsequent Western blot validation proofed the differential expression of Heat shock 27 kDA protein 1 (HSPB1) and Microtubule-associated protein R/EB family, member 1 (EB1) while the latter one showed also expression differences by immunohistochemistry. Fresh frozen tissue of UCC ( n = 10) matched with SCC ( n = 10) was investigated. Proteins of cancerous intestinal mucosal cells were obtained by Laser Capture Microdissection (LCM) and compared by 2-D DIGE. Significant spots were identified by mass spectrometry. After IPA, three proteins [EB1, HSPB1, and Annexin 5 (ANXA5)] were chosen for further validation by Western blotting and tissue microarray-based immunohistochemistry. This study identified significant differences in protein expression of colorectal carcinoma cells from UCC patients compared to patients with SCC. Particularly, EB1 was validated in an independent clinical cohort.

Characteristics predicting laparoscopic skill in medical students: nine years' experience in a single center.

PubMed

Nomura, Tsutomu; Matsutani, Takeshi; Hagiwara, Nobutoshi; Fujita, Itsuo; Nakamura, Yoshiharu; Kanazawa, Yoshikazu; Makino, Hiroshi; Mamada, Yasuhiro; Fujikura, Terumichi; Miyashita, Masao; Uchida, Eiji

2018-01-01

We introduced laparoscopic simulator training for medical students in 2007. This study was designed to identify factors that predict the laparoscopic skill of medical students, to identify intergenerational differences in abilities, and to estimate the variability of results in each training group. Our ultimate goal was to determine the optimal educational program for teaching laparoscopic surgery to medical students. Between 2007 and 2015, a total of 270 fifth-year medical students were enrolled in this observational study. Before training, the participants were asked questions about their interest in laparoscopic surgery, experience with playing video games, confidence about driving, and manual dexterity. After the training, aspects of their competence (execution time, instrument path length, and economy of instrument movement) were assessed. Multiple regression analysis identified significant effects of manual dexterity, gender, and confidence about driving on the results of the training. The training results have significantly improved over recent years. The variability among the results in each training group was relatively small. We identified the characteristics of medical students with excellent laparoscopic skills. We observed educational benefits from interactions between medical students within each training group. Our study suggests that selection and grouping are important to the success of modern programs designed to train medical students in laparoscopic surgery.

Genome-wide association analysis of seedling root development in maize (Zea mays L.).

PubMed

Pace, Jordon; Gardner, Candice; Romay, Cinta; Ganapathysubramanian, Baskar; Lübberstedt, Thomas

2015-02-05

Plants rely on the root system for anchorage to the ground and the acquisition and absorption of nutrients critical to sustaining productivity. A genome wide association analysis enables one to analyze allelic diversity of complex traits and identify superior alleles. 384 inbred lines from the Ames panel were genotyped with 681,257 single nucleotide polymorphism markers using Genotyping-by-Sequencing technology and 22 seedling root architecture traits were phenotyped. Utilizing both a general linear model and mixed linear model, a GWAS study was conducted identifying 268 marker trait associations (p ≤ 5.3×10(-7)). Analysis of significant SNP markers for multiple traits showed that several were located within gene models with some SNP markers localized within regions of previously identified root quantitative trait loci. Gene model GRMZM2G153722 located on chromosome 4 contained nine significant markers. This predicted gene is expressed in roots and shoots. This study identifies putatively associated SNP markers associated with root traits at the seedling stage. Some SNPs were located within or near (<1 kb) gene models. These gene models identify possible candidate genes involved in root development at the seedling stage. These and respective linked or functional markers could be targets for breeders for marker assisted selection of seedling root traits.

Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations

PubMed Central

Chen, Brian H.; Hivert, Marie-France; Peters, Marjolein J.; Pilling, Luke C.; Hogan, John D.; Pham, Lisa M.; Harries, Lorna W.; Fox, Caroline S.; Bandinelli, Stefania; Dehghan, Abbas; Hernandez, Dena G.; Hofman, Albert; Hong, Jaeyoung; Joehanes, Roby; Johnson, Andrew D.; Munson, Peter J.; Rybin, Denis V.; Singleton, Andrew B.; Uitterlinden, André G.; Ying, Saixia; Melzer, David; Levy, Daniel; van Meurs, Joyce B.J.; Ferrucci, Luigi; Florez, Jose C.; Dupuis, Josée

2016-01-01

Genome-wide association studies (GWAS) have successfully identified genetic loci associated with glycemic traits. However, characterizing the functional significance of these loci has proven challenging. We sought to gain insights into the regulation of fasting insulin and fasting glucose through the use of gene expression microarray data from peripheral blood samples of participants without diabetes in the Framingham Heart Study (FHS) (n = 5,056), the Rotterdam Study (RS) (n = 723), and the InCHIANTI Study (Invecchiare in Chianti) (n = 595). Using a false discovery rate q <0.05, we identified three transcripts associated with fasting glucose and 433 transcripts associated with fasting insulin levels after adjusting for age, sex, technical covariates, and complete blood cell counts. Among the findings, circulating IGF2BP2 transcript levels were positively associated with fasting insulin in both the FHS and RS. Using 1000 Genomes–imputed genotype data, we identified 47,587 cis-expression quantitative trait loci (eQTL) and 6,695 trans-eQTL associated with the 433 significant insulin-associated transcripts. Of note, we identified a trans-eQTL (rs592423), where the A allele was associated with higher IGF2BP2 levels and with fasting insulin in an independent genetic meta-analysis comprised of 50,823 individuals. We conclude that integration of genomic and transcriptomic data implicate circulating IGF2BP2 mRNA levels associated with glucose and insulin homeostasis. PMID:27625022

The Impact of Time Perspective Latent Profiles on College Drinking: A Multidimensional Approach

PubMed Central

Braitman, Abby L.; Henson, James M.

2015-01-01

Background Zimbardo and Boyd’s1 time perspective, or the temporal framework individuals use to process information, has been shown to predict health behaviors such as alcohol use. Previous studies supported the predictive validity of individual dimensions of time perspective, with some dimensions acting as protective factors and others as risk factors. However, some studies produced findings contrary to the general body of literature. In addition, time perspective is a multidimensional construct, and the combination of perspectives may be more predictive than individual dimensions in isolation; consequently, multidimensional profiles are a more accurate measure of individual differences and more appropriate for predicting health behaviors. Objectives The current study identified naturally occurring profiles of time perspective and examined their association with risky alcohol use. Methods Data were collected from a college student sample (n = 431, mean age = 20.41 years) using an online survey. Time perspective profiles were identified using latent profile analysis. Results Bootstrapped regression models identified a protective class that engaged in significantly less overall drinking (β = −0.254) as well as engaging in significantly less episodic high risk drinking (β = −0.274). There was also emerging evidence of a high risk time perspective profile that was linked to more overall drinking (β = 0.198) and engaging in more high risk drinking (β = 0.245), though these differences were not significant. Conclusions/Importance These findings support examining time perspective in a multidimensional framework rather than individual dimensions in isolation. Implications include identifying students most in need of interventions, and tailoring interventions to target temporal framing in decision-making. PMID:25607806

The impact of time perspective latent profiles on college drinking: a multidimensional approach.

PubMed

Braitman, Abby L; Henson, James M

2015-04-01

Zimbardo and Boyd's(1) time perspective, or the temporal framework individuals use to process information, has been shown to predict health behaviors such as alcohol use. Previous studies supported the predictive validity of individual dimensions of time perspective, with some dimensions acting as protective factors and others as risk factors. However, some studies produced findings contrary to the general body of literature. In addition, time perspective is a multidimensional construct, and the combination of perspectives may be more predictive than individual dimensions in isolation; consequently, multidimensional profiles are a more accurate measure of individual differences and more appropriate for predicting health behaviors. The current study identified naturally occurring profiles of time perspective and examined their association with risky alcohol use. Data were collected from a college student sample (n = 431, mean age = 20.41 years) using an online survey. Time perspective profiles were identified using latent profile analysis. Bootstrapped regression models identified a protective class that engaged in significantly less overall drinking (β = -0.254) as well as engaging in significantly less episodic high risk drinking (β = -0.274). There was also emerging evidence of a high risk time perspective profile that was linked to more overall drinking (β = 0.198) and engaging in more high risk drinking (β = 0.245), though these differences were not significant. CONCLUSIONS/IMPORTANCE: These findings support examining time perspective in a multidimensional framework rather than individual dimensions in isolation. Implications include identifying students most in need of interventions, and tailoring interventions to target temporal framing in decision-making.

Integrative Analysis of GWASs, Human Protein Interaction, and Gene Expression Identified Gene Modules Associated With BMDs

PubMed Central

He, Hao; Zhang, Lei; Li, Jian; Wang, Yu-Ping; Zhang, Ji-Gang; Shen, Jie; Guo, Yan-Fang

2014-01-01

Context: To date, few systems genetics studies in the bone field have been performed. We designed our study from a systems-level perspective by integrating genome-wide association studies (GWASs), human protein-protein interaction (PPI) network, and gene expression to identify gene modules contributing to osteoporosis risk. Methods: First we searched for modules significantly enriched with bone mineral density (BMD)-associated genes in human PPI network by using 2 large meta-analysis GWAS datasets through a dense module search algorithm. One included 7 individual GWAS samples (Meta7). The other was from the Genetic Factors for Osteoporosis Consortium (GEFOS2). One was assigned as a discovery dataset and the other as an evaluation dataset, and vice versa. Results: In total, 42 modules and 129 modules were identified significantly in both Meta7 and GEFOS2 datasets for femoral neck and spine BMD, respectively. There were 3340 modules identified for hip BMD only in Meta7. As candidate modules, they were assessed for the biological relevance to BMD by gene set enrichment analysis in 2 expression profiles generated from circulating monocytes in subjects with low versus high BMD values. Interestingly, there were 2 modules significantly enriched in monocytes from the low BMD group in both gene expression datasets (nominal P value <.05). Two modules had 16 nonredundant genes. Functional enrichment analysis revealed that both modules were enriched for genes involved in Wnt receptor signaling and osteoblast differentiation. Conclusion: We highlighted 2 modules and novel genes playing important roles in the regulation of bone mass, providing important clues for therapeutic approaches for osteoporosis. PMID:25119315

Molecular subgroups of adult medulloblastoma: a long-term single-institution study.

PubMed

Zhao, Fu; Ohgaki, Hiroko; Xu, Lei; Giangaspero, Felice; Li, Chunde; Li, Peng; Yang, Zhijun; Wang, Bo; Wang, Xingchao; Wang, Zhenmin; Ai, Lin; Zhang, Jing; Luo, Lin; Liu, Pinan

2016-07-01

Recent transcriptomic approaches have demonstrated that there are at least 4 distinct subgroups in medulloblastoma (MB); however, survival studies of molecular subgroups in adult MB have been inconclusive because of small sample sizes. The aim of this study is to investigate the molecular subgroups in adult MB and identify their clinical and prognostic implications in a large, single-institution cohort. We determined gene expression profiles for 13 primary adult MBs. Bioinformatics tools were used to establish distinct molecular subgroups based on the most informative genes in the dataset. Immunohistochemistry with subgroup-specific antibodies was then used for validation within an independent cohort of 201 formalin-fixed MB tumors, in conjunction with a systematic analysis of clinical and histological characteristics. Three distinct molecular variants of adult MB were identified: the SHH, WNT, and group 4 subgroups. Validation of these subgroups in the 201-tumor cohort by immunohistochemistry identified significant differences in subgroup-specific demographics, histology, and metastatic status. The SHH subgroup accounted for the majority of the tumors (62%), followed by the group 4 subgroup (28%) and the WNT subgroup (10%). Group 4 tumors had significantly worse progression-free and overall survival compared with tumors of the other molecular subtypes. We have identified 3 subgroups of adult MB, characterized by distinct expression profiles, clinical features, pathological features, and prognosis. Clinical variables incorporated with molecular subgroup are more significantly informative for predicting adult patient outcome. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Land use mapping in Erie County, Pennsylvania: A pilot study

NASA Technical Reports Server (NTRS)

Mcmurtry, G. J.; Petersen, G. W. (Principal Investigator); May, G. A.

1974-01-01

The author has identified the following significant results. A pilot study was conducted to determine the feasibility of mapping land use in the Great Lakes Basin area utilizing ERTS-1 data. Small streams were clearly defined by the presence of trees along their length in predominantly agricultural country. Field patterns were easily differentiated from forested areas; dairy and beef farms were differentiated from other farmlands, but no attempt was made to identify crops. Large railroad lines and major highway systems were identified. The city of Erie and several smaller towns were identified, as well as residential areas between these towns, and docks along the shoreline in Erie. Marshes, forests, and beaches within Presque Isle State Park were correctly identified, using the DCLUS program. Bay water was differentiated from lake water, with a small amount of misclassification.

Role of genetic & environment risk factors in the aetiology of colorectal cancer in Malaysia.

PubMed

Ramzi, Nurul Hanis; Chahil, Jagdish Kaur; Lye, Say Hean; Munretnam, Khamsigan; Sahadevappa, Kavitha Itagi; Velapasamy, Sharmila; Hashim, Nikman Adli Nor; Cheah, Soon Keat; Lim, Gerard Chin Chye; Hussein, Heselynn; Haron, Mohd Roslan; Alex, Livy; Ler, Lian Wee

2014-06-01

Colorectal cancer (CRC) is second only to breast cancer as the leading cause of cancer-related deaths in Malaysia. In the Asia-Pacific area, it is the highest emerging gastrointestinal cancer. The aim of this study was to identify single nucleotide polymorphisms (SNPs) and environmental factors associated with CRC risk in Malaysia from a panel of cancer associated SNPs. In this case-control study, 160 Malaysian subjects were recruited, including both with CRC and controls. A total of 768 SNPs were genotyped and analyzed to distinguish risk and protective alleles. Genotyping was carried out using Illumina's BeadArray platform. Information on blood group, occupation, medical history, family history of cancer, intake of red meat and vegetables, exposure to radiation, smoking and drinking habits, etc was collected. Odds ratio (OR), 95% confidence interval (CI) were calculated. A panel of 23 SNPs significantly associated with colorectal cancer risk was identified (P<0.01). Of these, 12 SNPs increased the risk of CRC and 11 reduced the risk. Among the environmental risk factors investigated, high intake of red meat (more than 50% daily proportion) was found to be significantly associated with increased risk of CRC (OR=6.52, 95% CI :1.93-2.04, P=0.003). Two SNPs including rs2069521 and rs10046 in genes of cytochrome P450 (CYP) superfamily were found significantly associated with CRC risk. For gene-environment analysis, the A allele of rs2069521 showed a significant association with CRC risk when stratified by red meat intake. In this preliminary study, a panel of SNPs found to be significantly associated with CRC in Malaysian population, was identified. Also, red meat consumption and lack of physical exercise were risk factors for CRC, while consumption of fruits and vegetables served as protective factor.

Habitat and Vegetation Variables Are Not Enough When Predicting Tick Populations in the Southeastern United States

PubMed Central

Trout Fryxell, R. T.; Moore, J. E.; Collins, M. D.; Kwon, Y.; Jean-Philippe, S. R.; Schaeffer, S. M.; Odoi, A.; Kennedy, M.; Houston, A. E.

2015-01-01

Two tick-borne diseases with expanding case and vector distributions are ehrlichiosis (transmitted by Amblyomma americanum) and rickettiosis (transmitted by A. maculatum and Dermacentor variabilis). There is a critical need to identify the specific habitats where each of these species is likely to be encountered to classify and pinpoint risk areas. Consequently, an in-depth tick prevalence study was conducted on the dominant ticks in the southeast. Vegetation, soil, and remote sensing data were used to test the hypothesis that habitat and vegetation variables can predict tick abundances. No variables were significant predictors of A. americanum adult and nymph tick abundance, and no clustering was evident because this species was found throughout the study area. For A. maculatum adult tick abundance was predicted by NDVI and by the interaction between habitat type and plant diversity; two significant population clusters were identified in a heterogeneous area suitable for quail habitat. For D. variabilis no environmental variables were significant predictors of adult abundance; however, D. variabilis collections clustered in three significant areas best described as agriculture areas with defined edges. This study identified few landscape and vegetation variables associated with tick presence. While some variables were significantly associated with tick populations, the amount of explained variation was not useful for predicting reliably where ticks occur; consequently, additional research that includes multiple sampling seasons and locations throughout the southeast are warranted. This low amount of explained variation may also be due to the use of hosts for dispersal, and potentially to other abiotic and biotic variables. Host species play a large role in the establishment, maintenance, and dispersal of a tick species, as well as the maintenance of disease cycles, dispersal to new areas, and identification of risk areas. PMID:26656122

Environmental contaminant exposures and preterm birth: A comprehensive review

PubMed Central

Ferguson, Kelly K.; O’Neill, Marie S.; Meeker, John D.

2013-01-01

Preterm birth is a significant public health concern, as it is associated with high risk of infant mortality, various morbidities in both the neonatal period and later in life, and a significant societal economic burden. As many cases are of unknown etiology, identification of the contribution of environmental contaminant exposures is a priority in the study of preterm birth. This is a comprehensive review of all known studies published from 1992 through August 2012 linking maternal exposure to environmental chemicals during pregnancy with preterm birth. Using PubMed searches studies were identified that examined associations between preterm birth and exposure to 5 categories of environmental toxicants, including persistent organic pollutants, drinking water contaminants, atmospheric pollutants, metals and metalloids, and other environmental contaminants. Individual studies were summarized and specific suggestions made for future work in regard to exposure and outcome assessment methods as well as study design, with the recommendation of focusing on potential mediating toxicological mechanisms. In conclusion, no consistent evidence was found for positive associations between individual chemical exposures and preterm birth. By identifying limitations and addressing the gaps that may have impeded the ability to identify true associations thus far, this review can guide future epidemiologic studies of environmental exposures and preterm birth. PMID:23682677

Develop a land use-peak runoff classification system for highway engineering purposes

NASA Technical Reports Server (NTRS)

Stoeckeler, E. G. (Principal Investigator); Farrell, R. S.; Woodman, R. G.

1974-01-01

The author has identified the following significant results. Based on the detail study of the Sunkhaze Stream Watershed, it is believed that good detailed drainage studies can be derived from repetitive ERTS imagery. Land use maps tailored to hydrologic study can be prepared from ERTS imagery. Significant changes in the Sunkhaze Stream and Otter Stream Watersheds at spring flood conditions have given important information on the causes for flooding in the town of Bradley.

Spatio-temporal surveillance of water based infectious disease (malaria) in Rawalpindi, Pakistan using geostatistical modeling techniques.

PubMed

Ahmad, Sheikh Saeed; Aziz, Neelam; Butt, Amna; Shabbir, Rabia; Erum, Summra

2015-09-01

One of the features of medical geography that has made it so useful in health research is statistical spatial analysis, which enables the quantification and qualification of health events. The main objective of this research was to study the spatial distribution patterns of malaria in Rawalpindi district using spatial statistical techniques to identify the hot spots and the possible risk factor. Spatial statistical analyses were done in ArcGIS, and satellite images for land use classification were processed in ERDAS Imagine. Four hundred and fifty water samples were also collected from the study area to identify the presence or absence of any microbial contamination. The results of this study indicated that malaria incidence varied according to geographical location, with eco-climatic condition and showing significant positive spatial autocorrelation. Hotspots or location of clusters were identified using Getis-Ord Gi* statistic. Significant clustering of malaria incidence occurred in rural central part of the study area including Gujar Khan, Kaller Syedan, and some part of Kahuta and Rawalpindi Tehsil. Ordinary least square (OLS) regression analysis was conducted to analyze the relationship of risk factors with the disease cases. Relationship of different land cover with the disease cases indicated that malaria was more related with agriculture, low vegetation, and water class. Temporal variation of malaria cases showed significant positive association with the meteorological variables including average monthly rainfall and temperature. The results of the study further suggested that water supply and sewage system and solid waste collection system needs a serious attention to prevent any outbreak in the study area.

CR1 rs3818361 Polymorphism Contributes to Alzheimer's Disease Susceptibility in Chinese Population.

PubMed

Li, Yongning; Song, Dongjing; Jiang, Yongshuai; Wang, Jingwei; Feng, Rennan; Zhang, Liangcai; Wang, Guangyu; Chen, Zugen; Wang, Renzhi; Jiang, Qinghua; Liu, Guiyou

2016-08-01

Recent genome-wide association studies (GWAS) reported CR1 rs3818361 polymorphism to be an Alzheimer's disease (AD) susceptibility variant in European ancestry. Three independent studies investigated this association in Chinese population. However, these studies reported weak or no significant association. Here, we reinvestigated the association using all the samples from three independent studies in Chinese population (N = 4047, 1244 AD cases and 2803 controls). We also selected three independent studies in European ancestry population (N = 11787, 3939 AD cases and 7848 controls) to evaluate the effect of rs3818361 polymorphism on AD risk in different ethnic backgrounds. In Chinese population, we did not identified significant heterogeneity using additive, recessive, and dominant genetic models. Meta-analysis showed significant association between rs3818361 and AD with P = 6.00E-03 and P = 5.00E-03. We further identified no heterogeneity of rs3818361 polymorphism between Chinese and European populations. We found that rs3818361 polymorphism contributed to AD with similar genetic risk in Chinese and European populations. In summary, this is the first study to show significant association between rs3818361 polymorphism and AD in Chinese population by a meta-analysis method. Our findings indicate that the effect of CR1 rs3818361 polymorphism on AD risk in Chinese cohorts is consistent with the increased risk observed in European AD cohorts.

Genetic analysis of atherosclerosis identifies a major susceptibility locus in the major histocompatibility complex of mice.

PubMed

Grainger, Andrew T; Jones, Michael B; Li, Jing; Chen, Mei-Hua; Manichaikul, Ani; Shi, Weibin

2016-11-01

Recent genome-wide association studies (GWAS) have identified over 50 significant loci containing common variants associated with coronary artery disease. However, these variants explain only 26% of the genetic heritability of the disease, suggesting that many more variants remain to be discovered. Here, we examined the genetic basis underlying the marked difference between SM/J-Apoe -/- and BALB/cJ-Apoe -/- mice in atherosclerotic lesion formation. 206 female F 2 mice generated from an intercross between the two Apoe -/- strains were fed 12 weeks of western diet. Atherosclerotic lesion sizes in the aortic root were measured and 149 genetic markers genotyped across the entire genome. A significant locus, named Ath49 (LOD score: 4.18), for atherosclerosis was mapped to the H2 complex [mouse major histocompatibility complex (MHC)] on chromosome 17. Bioinformatic analysis identified 12 probable candidate genes, including Tnfrsf21, Adgrf1, Adgrf5, Mep1a, and Pla2g7. Corresponding human genomic regions of Ath49 showed significant association with coronary heart disease. Five suggestive loci on chromosomes 1, 4, 5, and 8 for atherosclerosis were also identified. Atherosclerotic lesion sizes were significantly correlated with HDL but not with non-HDL cholesterol, triglyceride or glucose levels in the F 2 cohort. We have identified the MHC as a major genetic determinant of atherosclerosis, highlighting the importance of inflammation in atherogenesis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The impact of polygamy on women's mental health: a systematic review.

PubMed

Shepard, L D

2013-03-01

Aims. The purpose of this systematic review is to identify and appraise the present state of prevalence research on the mental health of polygynous women, or plural wives, and to summarize its implications for future research and social work practice. Methods. PsycInfo (1967 to November 2011) and Medline (1985 to November 2011) databases, systematic bibliography hand-searches, personal communication with a leading expert, and gray literature searching were applied in a systematic literature search of the prevalence of mental-health issues in polygynous women compared to monogamous women. Twenty-two studies meeting eligibility criteria were identified. Study characteristics, methods and findings were systematically extracted and appraised for quality. Results. The identified studies are of mixed methodological quality, but generally suggest a more significant prevalence of mental-health issues in polygynous women compared to monogamous women. Individual studies report a higher prevalence of somatization, depression, anxiety, hostility, psychoticism and psychiatric disorder in polygynous wives as well as reduced life and marital satisfaction, problematic family functioning and low self-esteem. Conclusions. The current state of the research reveals with moderate confidence, a more significant prevalence of mental-health issues in polygynous women as compared to monogamous women. Implications for practice and research are indicated.

Household Air Pollution and Acute Lower Respiratory Infections in Adults: A Systematic Review.

PubMed

Jary, Hannah; Simpson, Hope; Havens, Deborah; Manda, Geoffrey; Pope, Daniel; Bruce, Nigel; Mortimer, Kevin

2016-01-01

Household air pollution from solid fuel burning kills over 4 million people every year including half a million children from acute lower respiratory infections. Although biologically plausible, it is not clear whether household air pollution is also associated with acute lower respiratory infections in adults. We systematically reviewed the literature on household air pollution and acute lower respiratory infection in adults to identify knowledge gaps and research opportunities. Ten bibliographic databases were searched to identify studies of household air pollution and adult acute lower respiratory infection. Data were extracted from eligible studies using standardised forms. From 4617 titles, 513 abstracts and 72 full-text articles were reviewed. Eight studies met the inclusion criteria of which 2 found a significant adjusted increased risk of acute lower respiratory infection, 2 identified a univariate association whilst 4 found no significant association. Study quality was generally limited. Heterogeneity in methods and findings precluded meta-analysis. A systematic review of the literature found limited evidence for an association between household air pollution and risk of acute lower respiratory infection in adults. Additional research, with carefully defined exposure and outcome measures, is required to complete the risk profile caused by household air pollution in adults. CRD42015028042.

Heterogeneity within compulsive buyers: a Q-sort study.

PubMed

Thornhill, Kate; Kellett, Stephen; Davies, Jason

2012-06-01

This study investigated how compulsive buyers make sense of their excessive shopping behaviour to explore possible sources of heterogeneity between compulsive buyers. Twenty female participants met 'caseness' for compulsive buying (CB) on the CB Scale (CBS), prior to completing a Q-sort specifically related to their experiences of shopping. Participants provided details of occupation, income, and debt levels and completed two psychometric scales: the Hospital Anxiety and Depression Scale (HADS) and Yale Brown Obsessive Compulsive Scale-Shopping Version (YBOCS-SV). Principle component analysis (PCA) identified two groups within the compulsive buyers (labelled positive reinforcement and emotional distress) that explained 44% of the study variance. Ten women defined the positive reinforcement factor and tended to identify with pleasurable aspects of buying. Six women characterized the emotional distress factor and endorsed varied financial, emotional, and interpersonal difficulties associated with their CB. The emotional distress group carried significantly greater current debt levels and had significantly more severe CB. The study illustrates that compulsive buyers can relate to their 'symptoms' in dissimilar ways. The clinical implications of such heterogeneity are discussed, methodological shortcomings identified, and areas for future research indicated. ©2011 The British Psychological Society.

Nursing leadership style and psychosocial work environment.

PubMed

Malloy, Terry; Penprase, Barbara

2010-09-01

This study examines the relationship between leadership style and the psychosocial work environment of registered nurses. Research consistently supports the positive relationship between transformational leadership style and job satisfaction. There is less evidence, which identifies the relationship between leadership style and psychosocial work environment. The Multifactor Leadership Questionnaire 5× was used to identify the leadership style. The Copenhagen Psychosocial Questionnaire was used to measure psychosocial work environment dimensions. Statistical analysis included Pearson's r correlation between leadership style and psychosocial work environment and anova to analyse group means. There is a significant correlation between leadership style and 22 out of the 37 dimensions of the psychosocial work environment. This correlation was significant ranging from r = 0.88, P < 0.01 to r = 0.18, P < 0.05. Nurses divided into groups based on transformational leadership scores of the immediate supervisor report significant differences in their psychosocial work environment. This study supports the significant correlation between leadership style and psychosocial work environment for registered nurses. The results of this study suggest that there would be an improvement in the nursing psychosocial work environment by implementation of transformational and contingent reward leadership behaviours. © 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.

Comparative Genome-Wide-Association Mapping Identifies Common Loci Controlling Root System Architecture and Resistance to Aphanomyces euteiches in Pea.

PubMed

Desgroux, Aurore; Baudais, Valentin N; Aubert, Véronique; Le Roy, Gwenola; de Larambergue, Henri; Miteul, Henri; Aubert, Grégoire; Boutet, Gilles; Duc, Gérard; Baranger, Alain; Burstin, Judith; Manzanares-Dauleux, Maria; Pilet-Nayel, Marie-Laure; Bourion, Virginie

2017-01-01

Combining plant genetic resistance with architectural traits that are unfavorable to disease development is a promising strategy for reducing epidemics. However, few studies have identified root system architecture (RSA) traits with the potential to limit root disease development. Pea is a major cultivated legume worldwide and has a wide level of natural genetic variability for plant architecture. The root pathogen Aphanomyces euteiches is a major limiting factor of pea crop yield. This study aimed to increase the knowledge on the diversity of loci and candidate genes controlling RSA traits in pea and identify RSA genetic loci associated with resistance to A. euteiches which could be combined with resistance QTL in breeding. A comparative genome wide association (GWA) study of plant architecture and resistance to A. euteiches was conducted at the young plant stage in a collection of 266 pea lines contrasted for both traits. The collection was genotyped using 14,157 SNP markers from recent pea genomic resources. It was phenotyped for ten root, shoot and overall plant architecture traits, as well as three disease resistance traits in controlled conditions, using image analysis. We identified a total of 75 short-size genomic intervals significantly associated with plant architecture and overlapping with 46 previously detected QTL. The major consistent intervals included plant shoot architecture or flowering genes ( PsLE, PsTFL1 ) with putative pleiotropic effects on root architecture. A total of 11 genomic intervals were significantly associated with resistance to A. euteiches confirming several consistent previously identified major QTL. One significant SNP, mapped to the major QTL Ae-Ps7.6 , was associated with both resistance and RSA traits. At this marker, the resistance-enhancing allele was associated with an increased total root projected area, in accordance with the correlation observed between resistance and larger root systems in the collection. Seven additional intervals associated with plant architecture overlapped with GWA intervals previously identified for resistance to A. euteiches . This study provides innovative results about genetic interdependency of root disease resistance and RSA inheritance. It identifies pea lines, QTL, closely-linked markers and candidate genes for marker-assisted-selection of RSA loci to reduce Aphanomyces root rot severity in future pea varieties.

Comparative Genome-Wide-Association Mapping Identifies Common Loci Controlling Root System Architecture and Resistance to Aphanomyces euteiches in Pea

PubMed Central

Desgroux, Aurore; Baudais, Valentin N.; Aubert, Véronique; Le Roy, Gwenola; de Larambergue, Henri; Miteul, Henri; Aubert, Grégoire; Boutet, Gilles; Duc, Gérard; Baranger, Alain; Burstin, Judith; Manzanares-Dauleux, Maria; Pilet-Nayel, Marie-Laure; Bourion, Virginie

2018-01-01

Combining plant genetic resistance with architectural traits that are unfavorable to disease development is a promising strategy for reducing epidemics. However, few studies have identified root system architecture (RSA) traits with the potential to limit root disease development. Pea is a major cultivated legume worldwide and has a wide level of natural genetic variability for plant architecture. The root pathogen Aphanomyces euteiches is a major limiting factor of pea crop yield. This study aimed to increase the knowledge on the diversity of loci and candidate genes controlling RSA traits in pea and identify RSA genetic loci associated with resistance to A. euteiches which could be combined with resistance QTL in breeding. A comparative genome wide association (GWA) study of plant architecture and resistance to A. euteiches was conducted at the young plant stage in a collection of 266 pea lines contrasted for both traits. The collection was genotyped using 14,157 SNP markers from recent pea genomic resources. It was phenotyped for ten root, shoot and overall plant architecture traits, as well as three disease resistance traits in controlled conditions, using image analysis. We identified a total of 75 short-size genomic intervals significantly associated with plant architecture and overlapping with 46 previously detected QTL. The major consistent intervals included plant shoot architecture or flowering genes (PsLE, PsTFL1) with putative pleiotropic effects on root architecture. A total of 11 genomic intervals were significantly associated with resistance to A. euteiches confirming several consistent previously identified major QTL. One significant SNP, mapped to the major QTL Ae-Ps7.6, was associated with both resistance and RSA traits. At this marker, the resistance-enhancing allele was associated with an increased total root projected area, in accordance with the correlation observed between resistance and larger root systems in the collection. Seven additional intervals associated with plant architecture overlapped with GWA intervals previously identified for resistance to A. euteiches. This study provides innovative results about genetic interdependency of root disease resistance and RSA inheritance. It identifies pea lines, QTL, closely-linked markers and candidate genes for marker-assisted-selection of RSA loci to reduce Aphanomyces root rot severity in future pea varieties. PMID:29354146

Refining Susceptibility Loci of Chronic Obstructive Pulmonary Disease with Lung eqtls

PubMed Central

Lamontagne, Maxime; Couture, Christian; Postma, Dirkje S.; Timens, Wim; Sin, Don D.; Paré, Peter D.; Hogg, James C.; Nickle, David; Laviolette, Michel; Bossé, Yohan

2013-01-01

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of mortality worldwide. Recent genome-wide association studies (GWAS) have identified robust susceptibility loci associated with COPD. However, the mechanisms mediating the risk conferred by these loci remain to be found. The goal of this study was to identify causal genes/variants within susceptibility loci associated with COPD. In the discovery cohort, genome-wide gene expression profiles of 500 non-tumor lung specimens were obtained from patients undergoing lung surgery. Blood-DNA from the same patients were genotyped for 1,2 million SNPs. Following genotyping and gene expression quality control filters, 409 samples were analyzed. Lung expression quantitative trait loci (eQTLs) were identified and overlaid onto three COPD susceptibility loci derived from GWAS; 4q31 (HHIP), 4q22 (FAM13A), and 19q13 (RAB4B, EGLN2, MIA, CYP2A6). Significant eQTLs were replicated in two independent datasets (n = 363 and 339). SNPs previously associated with COPD and lung function on 4q31 (rs1828591, rs13118928) were associated with the mRNA expression of HHIP. An association between mRNA expression level of FAM13A and SNP rs2045517 was detected at 4q22, but did not reach statistical significance. At 19q13, significant eQTLs were detected with EGLN2. In summary, this study supports HHIP, FAM13A, and EGLN2 as the most likely causal COPD genes on 4q31, 4q22, and 19q13, respectively. Strong lung eQTL SNPs identified in this study will need to be tested for association with COPD in case-control studies. Further functional studies will also be needed to understand the role of genes regulated by disease-related variants in COPD. PMID:23936167

Dynamic transcriptional signatures and network responses for clinical symptoms in influenza-infected human subjects using systems biology approaches.

PubMed

Linel, Patrice; Wu, Shuang; Deng, Nan; Wu, Hulin

2014-10-01

Recent studies demonstrate that human blood transcriptional signatures may be used to support diagnosis and clinical decisions for acute respiratory viral infections such as influenza. In this article, we propose to use a newly developed systems biology approach for time course gene expression data to identify significant dynamically response genes and dynamic gene network responses to viral infection. We illustrate the methodological pipeline by reanalyzing the time course gene expression data from a study with healthy human subjects challenged by live influenza virus. We observed clear differences in the number of significant dynamic response genes (DRGs) between the symptomatic and asymptomatic subjects and also identified DRG signatures for symptomatic subjects with influenza infection. The 505 common DRGs shared by the symptomatic subjects have high consistency with the signature genes for predicting viral infection identified in previous works. The temporal response patterns and network response features were carefully analyzed and investigated.

Transcriptional profiling of Medicago truncatula meristematic root cells

PubMed Central

Holmes, Peta; Goffard, Nicolas; Weiller, Georg F; Rolfe, Barry G; Imin, Nijat

2008-01-01

Background The root apical meristem of crop and model legume Medicago truncatula is a significantly different stem cell system to that of the widely studied model plant species Arabidopsis thaliana. In this study we used the Affymetrix Medicago GeneChip® to compare the transcriptomes of meristem and non-meristematic root to identify root meristem specific candidate genes. Results Using mRNA from root meristem and non-meristem we were able to identify 324 and 363 transcripts differentially expressed from the two regions. With bioinformatics tools developed to functionally annotate the Medicago genome array we could identify significant changes in metabolism, signalling and the differentially expression of 55 transcription factors in meristematic and non-meristematic roots. Conclusion This is the first comprehensive analysis of M. truncatula root meristem cells using this genome array. This data will facilitate the mapping of regulatory and metabolic networks involved in the open root meristem of M. truncatula and provides candidates for functional analysis. PMID:18302802

Integrative approaches for large-scale transcriptome-wide association studies

PubMed Central

Gusev, Alexander; Ko, Arthur; Shi, Huwenbo; Bhatia, Gaurav; Chung, Wonil; Penninx, Brenda W J H; Jansen, Rick; de Geus, Eco JC; Boomsma, Dorret I; Wright, Fred A; Sullivan, Patrick F; Nikkola, Elina; Alvarez, Marcus; Civelek, Mete; Lusis, Aldons J.; Lehtimäki, Terho; Raitoharju, Emma; Kähönen, Mika; Seppälä, Ilkka; Raitakari, Olli T.; Kuusisto, Johanna; Laakso, Markku; Price, Alkes L.; Pajukanta, Päivi; Pasaniuc, Bogdan

2016-01-01

Many genetic variants influence complex traits by modulating gene expression, thus altering the abundance levels of one or multiple proteins. Here, we introduce a powerful strategy that integrates gene expression measurements with summary association statistics from large-scale genome-wide association studies (GWAS) to identify genes whose cis-regulated expression is associated to complex traits. We leverage expression imputation to perform a transcriptome wide association scan (TWAS) to identify significant expression-trait associations. We applied our approaches to expression data from blood and adipose tissue measured in ~3,000 individuals overall. We imputed gene expression into GWAS data from over 900,000 phenotype measurements to identify 69 novel genes significantly associated to obesity-related traits (BMI, lipids, and height). Many of the novel genes are associated with relevant phenotypes in the Hybrid Mouse Diversity Panel. Our results showcase the power of integrating genotype, gene expression and phenotype to gain insights into the genetic basis of complex traits. PMID:26854917

Genome-wide association analysis identifies 30 new susceptibility loci for schizophrenia.

PubMed

Li, Zhiqiang; Chen, Jianhua; Yu, Hao; He, Lin; Xu, Yifeng; Zhang, Dai; Yi, Qizhong; Li, Changgui; Li, Xingwang; Shen, Jiawei; Song, Zhijian; Ji, Weidong; Wang, Meng; Zhou, Juan; Chen, Boyu; Liu, Yahui; Wang, Jiqiang; Wang, Peng; Yang, Ping; Wang, Qingzhong; Feng, Guoyin; Liu, Benxiu; Sun, Wensheng; Li, Baojie; He, Guang; Li, Weidong; Wan, Chunling; Xu, Qi; Li, Wenjin; Wen, Zujia; Liu, Ke; Huang, Fang; Ji, Jue; Ripke, Stephan; Yue, Weihua; Sullivan, Patrick F; O'Donovan, Michael C; Shi, Yongyong

2017-11-01

We conducted a genome-wide association study (GWAS) with replication in 36,180 Chinese individuals and performed further transancestry meta-analyses with data from the Psychiatry Genomics Consortium (PGC2). Approximately 95% of the genome-wide significant (GWS) index alleles (or their proxies) from the PGC2 study were overrepresented in Chinese schizophrenia cases, including ∼50% that achieved nominal significance and ∼75% that continued to be GWS in the transancestry analysis. The Chinese-only analysis identified seven GWS loci; three of these also were GWS in the transancestry analyses, which identified 109 GWS loci, thus yielding a total of 113 GWS loci (30 novel) in at least one of these analyses. We observed improvements in the fine-mapping resolution at many susceptibility loci. Our results provide several lines of evidence supporting candidate genes at many loci and highlight some pathways for further research. Together, our findings provide novel insight into the genetic architecture and biological etiology of schizophrenia.

Acute myeloid leukemia risk by industry and occupation.

PubMed

Tsai, Rebecca J; Luckhaupt, Sara E; Schumacher, Pam; Cress, Rosemary D; Deapen, Dennis M; Calvert, Geoffrey M

2014-11-01

Acute myeloid leukemia (AML) is the most common type of leukemia found in adults. Identifying jobs that pose a risk for AML may be useful for identifying new risk factors. A matched case-control analysis was conducted using California Cancer Registry data from 1988 to 2007. This study included 8999 cases of AML and 24 822 controls. Industries with a statistically significant increased AML risk were construction (matched odds ratio [mOR] = 1.13); crop production (mOR = 1.41); support activities for agriculture and forestry (mOR = 2.05); and animal slaughtering and processing (mOR = 2.09). Among occupations with a statistically significant increased AML risk were miscellaneous agricultural workers (mOR = 1.76); fishers and related fishing workers (mOR = 2.02); nursing, psychiatric and home health aides (mOR = 1.65); and janitors and building cleaners (mOR = 1.54). Further investigation is needed to confirm study findings and to identify specific exposures responsible for the increased risks.

Excess Metabolic Syndrome Risks Among Women Health Workers Compared With Men.

PubMed

Adeoye, Abiodun M; Adewoye, Ifeoluwa A; Dairo, David M; Adebiyi, Adewole; Lackland, Daniel T; Ogedegbe, Gbenga; Tayo, Bamidele O

2015-11-01

Metabolic syndrome is associated with higher rates of cardiovascular morbidity and mortality. Although significant disparities in the risks of metabolic syndrome by occupation type and sex are well documented, the factors associated with metabolic syndrome in low- to middle-income countries remain unclear. These gaps in evidence identify the need for patterns of metabolic syndrome among hospital personnel of both sexes in Nigeria. A total of 256 hospital workers comprising 32.8% men were studied. The mean age of the participants was 42.03 ± 9.4 years. Using International Diabetic Federation criteria, the prevalence of metabolic syndrome was 24.2%. Women were substantially and significantly more likely to be identified with metabolic syndrome compared with men (34.9% vs 2.4%, respectively; P=.0001). This study identified metabolic syndrome among health workers with over one third of women with metabolic syndrome compared with <10% of men. These results support the implementation of lifestyle modification programs for management of metabolic syndrome in the health care workplace. © 2015 Wiley Periodicals, Inc.

Acute myeloid leukemia risk by industry and occupation

PubMed Central

Tsai, Rebecca J.; Luckhaupt, Sara E.; Schumacher, Pam; Cress, Rosemary D.; Deapen, Dennis M.; Calvert, Geoffrey M.

2015-01-01

Acute myeloid leukemia (AML) is the most common type of leukemia found in adults. Identifying jobs that pose a risk for AML may be useful for identifying new risk factors. A matched case–control analysis was conducted using California Cancer Registry data from 1988 to 2007. This study included 8999 cases of AML and 24 822 controls. Industries with a statistically significant increased AML risk were construction (matched odds ratio [mOR] = 1.13); crop production (mOR = 1.41); support activities for agriculture and forestry (mOR = 2.05); and animal slaughtering and processing (mOR = 2.09). Among occupations with a statistically significant increased AML risk were miscellaneous agricultural workers (mOR = 1.76); fishers and related fishing workers (mOR = 2.02); nursing, psychiatric and home health aides (mOR = 1.65); and janitors and building cleaners (mOR = 1.54). Further investigation is needed to confirm study findings and to identify specific exposures responsible for the increased risks. PMID:24547710

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.

Factors of Significant Impact on Proficiency Levels of Adult ESL Learners within Post-Secondary Education in Puerto Rico

ERIC Educational Resources Information Center

Perez, Ramon

2011-01-01

This qualitative case study seeks to identify factors that have a significant impact on the second language proficiency levels of adult English as a Second Language (ESL) learners at a four-year university in Puerto Rico. Current data indicate that a significant percentage of adult ESL learners encounter major difficulties within the process of…

Toward the identification of causal genes in complex diseases: a gene-centric joint test of significance combining genomic and transcriptomic data.

PubMed

Charlesworth, Jac C; Peralta, Juan M; Drigalenko, Eugene; Göring, Harald Hh; Almasy, Laura; Dyer, Thomas D; Blangero, John

2009-12-15

Gene identification using linkage, association, or genome-wide expression is often underpowered. We propose that formal combination of information from multiple gene-identification approaches may lead to the identification of novel loci that are missed when only one form of information is available. Firstly, we analyze the Genetic Analysis Workshop 16 Framingham Heart Study Problem 2 genome-wide association data for HDL-cholesterol using a "gene-centric" approach. Then we formally combine the association test results with genome-wide transcriptional profiling data for high-density lipoprotein cholesterol (HDL-C), from the San Antonio Family Heart Study, using a Z-transform test (Stouffer's method). We identified 39 genes by the joint test at a conservative 1% false-discovery rate, including 9 from the significant gene-based association test and 23 whose expression was significantly correlated with HDL-C. Seven genes identified as significant in the joint test were not independently identified by either the association or expression tests. This combined approach has increased power and leads to the direct nomination of novel candidate genes likely to be involved in the determination of HDL-C levels. Such information can then be used as justification for a more exhaustive search for functional sequence variation within the nominated genes. We anticipate that this type of analysis will improve our speed of identification of regulatory genes causally involved in disease risk.

Detecting signatures of selection in nine distinct lines of broiler chickens.

PubMed

Stainton, John J; Haley, Chris S; Charlesworth, Brain; Kranis, Andreas; Watson, Kellie; Wiener, Pamela

2015-02-01

Modern commercial chickens have been bred for one of two specific purposes: meat production (broilers) or egg production (layers). This has led to large phenotypic changes, so that the genomic signatures of selection may be detectable using statistical techniques. Genetic differentiation between nine distinct broiler lines was calculated using Weir and Cockerham's pairwise FST estimator for 11 003 genome-wide markers to identify regions showing evidence of differential selection across lines. Differentiation measures were averaged into overlapping sliding windows for each line, and a permutation approach was used to determine the significance of each window. A total of 51 regions were found to show significant differentiation between the lines. Several lines were consistently found to share significant regions, suggesting that the pattern of line divergence is related to selection for broiler traits. The majority of the 51 regions contain QTL relating to broiler traits, but only five of them were found to be significantly enriched for broiler QTL, including a region on chromosome 27 containing 39 broiler QTL and 114 genes. Additionally, a number of these regions have been identified by other selection mapping studies. This study has identified a large number of potential selection signatures, and further tests with higher-density marker data may narrow these regions down to individual genes. © 2014 Stichting International Foundation for Animal Genetics.

Identifying high risk medications causing potential drug-drug interactions in outpatients: A prescription database study based on an online surveillance system.

PubMed

Toivo, T M; Mikkola, J A V; Laine, K; Airaksinen, M

2016-01-01

Drug-drug interactions (DDIs) are a significant cause for adverse drug events (ADEs). DDIs are often predictable and preventable, but their prevention and management require systematic service development. Most DDI studies focus on interaction rates in hospitalized patients. Less is known of DDIs in outpatients, particularly how community pharmacists could contribute to DDI management by applying their surveillance systems for identifying high-risk medications. The study was related to the implementation of the first online DDI surveillance system in Finnish community pharmacies. The goal was to demonstrate how community pharmacies can utilize their prospective surveillance system 1) for identifying high risk medications causing potential DDIs in outpatients, 2) for collaborative service development with local physicians, and 3) for academic risk management research purposes. All DDI alerts given by the online surveillance system were collected during a one-month period in 16 out of 17 University Pharmacy outlets in Finland, covering approximately 10% of the national outpatient prescription volume. The surveillance system was based on the FASS database, which categorizes DDIs into four classes (A-D) according to their clinical significance. Potential drug-drug DDIs were analyzed for 276,891 dispensed community pharmacy prescriptions. Potential DDIs were associated with 10.8%, or 31,110 of these prescriptions. Clinically significant interaction alerts categorized as FASS classes D (most severe, should be avoided) and C (clinically significant but controllable) were associated with 0.5% and 7.0% of the prescriptions, respectively. Methotrexate and warfarin had the highest risk of causing potentially serious (class D) interactions. These interaction alerts were most frequently between methotrexate and NSAIDs and warfarin and NSAIDs. In general, NSAIDs were the most commonly interacting drugs in this study. This study demonstrates that community pharmacies can actively contribute to DDI risk management and systematically use their surveillance systems for identifying patients having clinically significant DDIs. The findings also indicate that the majority of potentially serious interactions in outpatients involve a limited number of drugs, particularly NSAIDs, warfarin and methotrexate. Further research should focus on community pharmacists' involvement in DDI risk management in collaboration with local health care providers. Copyright © 2015 Elsevier Inc. All rights reserved.

Psychological Adaptation to Alteration of Body Image among Stoma Patients: A Descriptive Study.

PubMed

Jayarajah, Umesh; Samarasekera, Dharmabandhu Nandadeva

2017-01-01

Creation of an ostomy leads to significant change in the body image of the patient. However, adaptation to this alteration of body image is necessary for rehabilitation following surgery. The objective of this study was to identify the factors that influence adaptation to altered body image. An analytical cross-sectional study was conducted among 41 ostomy patients who were treated at a single tertiary care unit. Body image disturbance questionnaire (BIDQ) was used to assess the perception of body image. Data were analyzed using independent samples t -test (unpaired), Chi-square test, and Spearman's correlation. In our study, the mean BIDQ score was 2.22 (standard deviation ± 0.88). The body image disturbance was significantly associated with younger age ( P < 0.05). The prevalence of body image disturbance was significantly higher among overweight patients ( P < 0.05). Males had a higher BIDQ score than females. Those who had temporary stoma had significantly higher BIDQ score ( P < 0.05). Those who felt depressed or had thoughts of self-harm soon after surgery had significantly high body image disturbance score ( P < 0.05). There was a significant negative correlation with the perception of self-efficacy and body image disturbance ( P < 0.01). There was no significant association between body image disturbance and the diagnosis, type of surgery, or time duration after surgery. Poor adaptation to alteration of body image was associated with younger age, overweight, and temporary stoma. Individuals at risk of poor adaptation should be identified before surgery and counseled before surgery, after surgery, and during follow-up visits.

Orbital transfer vehicle launch operations study. Volume 2: Detailed summary

NASA Technical Reports Server (NTRS)

1986-01-01

A series of Operational Design Drivers were identified. Several of these could have significant impact(s) on program costs. These recommendations, for example, include such items as: complete factory assembly and checkout prior to shipment to the ground launch site to make significant reductions in time required at the launch site as well as overall manpower required to do this work; minimize use of nonstandard equipment when orbiter provided equipment is available; and require commonality (or interchangeability) of subsystem equipment elements that are common to the space station, Orbit Maneuvering Vehicles, and/or Orbit Transfer Vehicles. Several additional items were identified that will require a significant amount of management attention (and direction) to resolve. Key elements of the space based processing plans are discussed.

Factors influencing a problem-based learning implementation: A case study of IT courses

NASA Astrophysics Data System (ADS)

Darus, Norida Muhd; Mohd, Haslina; Baharom, Fauziah; Saip, Mohamed Ali; Puteh, Nurnasran; Marzuki @ Matt, Zaharin; Husain, Mohd Zabidin; Yasin, Azman

2016-08-01

IT students must be trained to work efficiently as teamwork. One of the techniques that can be used to train them is through Problem-Based Learning (PBL) approach. The PBL implementation can be influenced by various factors depending on the ultimate goal of the study. This study is focusing on the IT students' perception of the PBL implementation. The student's perception is important to ensure the successfulness of the PBL implementation. Therefore, it is important to identify the factors that might influence the implementation of PBL of IT courses. This study aims to identify some catalyst factors that may influence the PBL implementation of IT courses. The study involved three (3) main phases: identifying PBL implementation factors, constructing a PBL model, and PBL model validation using statistical analysis. Four main factors are identified: PBL Characteristics, PBL Course Assessment, PBL Practices, and PBL Perception. Based on these four factors, a PBL model is constructed. Then, based on the proposed PBL model, four hypotheses are formulated and analyzed to validate the model. All hypotheses are significantly acceptable. The result shows that the PBL Characteristics and PBL Course Assessment factors are significantly influenced the PBL Practices and indirectly influenced the Students' Perception of the PBL Implementation for IT courses. This PBL model can assist decision makers in enhancing the PBL teaching and learning strategy for IT courses. It is also can be tested to other courses in the future.

Nursing Faculty Professional Development: A Study Using the National League for Nursing (NLN) Core Competencies for Nurse Educators for Development of Novice to Expert Nurse Educators

ERIC Educational Resources Information Center

Luoma, Kari L.

2013-01-01

The purpose of this quantitative research study was to identify core competencies that are most significant for nursing faculty to develop as they transition from novice to expert faculty. Professional development in a systematic approach may guide faculty to learn what is significant as they progress in the nurse faculty role. A quantitative…

Pre-admission criteria and pre-clinical achievement: Can they predict medical students performance in the clinical phase?

PubMed

Salem, Raneem O; Al-Mously, Najwa; AlFadil, Sara; Baalash, Amal

2016-01-01

Various factors affect medical students' performance during clinical phase. Identifying these factors would help in mentoring weak students and help in selection process for residency programmes. Our study objective is to evaluate the impact of pre-admission criteria, and pre-clinical grade point average (GPA) on undergraduate medical students' performance during clinical phase. This study has a cross-sectional design that includes fifth- and sixth-year female medical students (71). Data of clinical and pre-clinical GPA in medical school and pre-admission to medical school tests scores were collected. A significant correlation between clinical GPA with the pre-clinical GPA was observed (p < 0.05). Such significant correlation was not seen with other variables under study. A regression analysis was performed, and the only significant predictor of students clinical performance was the pre-clinical GPA (p < 0.001). However, no significant difference between students' clinical and pre-clinical GPA for both cohorts was observed (p > 0.05). Pre-clinical GPA is strongly correlated with and can predict medical students' performance during clinical years. Our study highlighted the importance of evaluating the academic performances of students in pre-clinical years before they move into clinical years in order to identify weak students to mentor them and monitor their progress.

Determinants of lower extremity amputations: an institutional experience.

PubMed

Soomro, Nabila; Khan, Mahjabeen; Ahmed, Syed Imran; Minhas, Muhammad Ali

2013-07-01

To determine the determinants of lower extremity amputations in diabetics and non-diabetics in a tertiary care institute. Cross-sectional, analytical study. Outpatients Department of the Institute of Physical Medicine and Rehabilitation, Dow University of Health Sciences, Karachi, from January 2007 to December 2010. All patients with amputations reporting at the study centre for prosthesis fitting were included in the study. Patient`s age, level of amputation, stump complications and associated risk factors of amputation were recorded on a structured proforma. Prosthesis and orthotic assessment were carried out. The frequency and determinants were collected to compare diabetic and non-diabetic amputees. The data was analyzed in SPSS windows version 16. A total of 1091 subjects were provided prosthesis, including 847 males (77.6%). Mean age in diabetic and nondiabetics being 49.6 ± 15.2 and 26.6 ± 17.9 years respectively which is significant at (p < 0.001). Socioeconomic status and educational levels were significantly associated with diabetic status (p < 0.001). Amputation was more common in non-diabetic 858 (78.6%) compared to diabetics 233 (21.4%). This study has identified that most common and significant predictors were gender, low social status and educational levels. Other significant predictors of amputation identified were type of lesion, (infections and ischaemia), initial diagnosis acute/chronic arterial insufficiency and diabetic foot.

Consumption of garlic and risk of colorectal cancer: An updated meta-analysis of prospective studies

PubMed Central

Hu, Ji-Yi; Hu, Yi-Wang; Zhou, Jiao-Jiao; Zhang, Meng-Wen; Li, Dan; Zheng, Shu

2014-01-01

AIM: To conduct an updated meta-analysis of prospective studies addressing the association between garlic consumption and colorectal cancer. METHODS: Eligible cohort studies were identified by searching MEDLINE (PubMed) and screening the references of related articles published up to October 2013. Meta-analyses were conducted for colorectal cancer in relation to consumption of raw and cooked (RC) garlic and garlic supplements, separately. The summary relative risks (RR) with 95%CI were calculated using fixed-effects or random-effects model depending on the heterogeneity among studies. RESULTS: A total of 5 prospective cohort studies were identified. In contrast to the previous meta-analysis, no significant associations were found between consumption of RC garlic (RR: 1.06; 95%CI: 0.95-1.19) or garlic supplements (RR: 1.12; 95%CI: 0.96-1.31) and risk of colorectal cancer. A non-significant protective effect of garlic supplement intake against colorectal cancer was observed in females (RR: 0.84; 95%CI: 0.64-1.11), but the opposite was the case in males (RR: 1.24; 95%CI: 0.96-1.59). CONCLUSION: Consumption of RC garlic or garlic supplements is not significantly associated with reduced colorectal cancer risk. PMID:25386091

Consumption of garlic and risk of colorectal cancer: an updated meta-analysis of prospective studies.

PubMed

Hu, Ji-Yi; Hu, Yi-Wang; Zhou, Jiao-Jiao; Zhang, Meng-Wen; Li, Dan; Zheng, Shu

2014-11-07

To conduct an updated meta-analysis of prospective studies addressing the association between garlic consumption and colorectal cancer. Eligible cohort studies were identified by searching MEDLINE (PubMed) and screening the references of related articles published up to October 2013. Meta-analyses were conducted for colorectal cancer in relation to consumption of raw and cooked (RC) garlic and garlic supplements, separately. The summary relative risks (RR) with 95%CI were calculated using fixed-effects or random-effects model depending on the heterogeneity among studies. A total of 5 prospective cohort studies were identified. In contrast to the previous meta-analysis, no significant associations were found between consumption of RC garlic (RR: 1.06; 95%CI: 0.95-1.19) or garlic supplements (RR: 1.12; 95%CI: 0.96-1.31) and risk of colorectal cancer. A non-significant protective effect of garlic supplement intake against colorectal cancer was observed in females (RR: 0.84; 95%CI: 0.64-1.11), but the opposite was the case in males (RR: 1.24; 95%CI: 0.96-1.59). Consumption of RC garlic or garlic supplements is not significantly associated with reduced colorectal cancer risk.

A genome-wide association study identifies candidate loci associated to syringomyelia secondary to Chiari-like malformation in Cavalier King Charles Spaniels.

PubMed

Ancot, Frédéric; Lemay, Philippe; Knowler, Susan P; Kennedy, Karen; Griffiths, Sandra; Cherubini, Giunio Bruto; Sykes, Jane; Mandigers, Paul J J; Rouleau, Guy A; Rusbridge, Clare; Kibar, Zoha

2018-03-22

Syringomyelia (SM) is a common condition affecting brachycephalic toy breed dogs and is characterized by the development of fluid-filled cavities within the spinal cord. It is often concurrent with a complex developmental malformation of the skull and craniocervical vertebrae called Chiari-like malformation (CM) characterized by a conformational change and overcrowding of the brain and cervical spinal cord particularly at the craniocervical junction. CM and SM have a polygenic mode of inheritance with variable penetrance. We identified six cranial T1-weighted sagittal MRI measurements that were associated to maximum transverse diameter of the syrinx cavity. Increased syrinx transverse diameter has been correlated previously with increased likelihood of behavioral signs of pain. We next conducted a whole genome association study of these traits in 65 Cavalier King Charles Spaniel (CKCS) dogs (33 controls, 32 with extreme phenotypes). Two loci on CFA22 and CFA26 were found to be significantly associated to two traits associated with a reduced volume and altered orientation of the caudal cranial fossa. Their reconstructed haplotypes defined two associated regions that harbor only two genes: PCDH17 on CFA22 and ZWINT on CFA26. PCDH17 codes for a cell adhesion molecule expressed specifically in the brain and spinal cord. ZWINT plays a role in chromosome segregation and its expression is increased with the onset of neuropathic pain. Targeted genomic sequencing of these regions identified respectively 37 and 339 SNPs with significantly associated P values. Genotyping of tagSNPs selected from these 2 candidate loci in an extended cohort of 461 CKCS (187 unaffected, 274 SM affected) identified 2 SNPs on CFA22 that were significantly associated to SM strengthening the candidacy of this locus in SM development. We identified 2 loci on CFA22 and CFA26 that contained only 2 genes, PCDH17 and ZWINT, significantly associated to two traits associated with syrinx transverse diameter. The locus on CFA22 was significantly associated to SM secondary to CM in the CKCS dog breed strengthening its candidacy for this disease. This study will provide an entry point for identification of the genetic factors predisposing to this condition and its underlying pathogenic mechanisms.

An in-depth analysis identifies two new independent signals in 11q23.3 associated with vitiligo in the Chinese Han population.

PubMed

Zhao, Suli; Fang, Fang; Tang, Xianfa; Dou, Jinfa; Wang, Wenjun; Zheng, Xiaodong; Sun, Liangdan; Zhang, Anping

2017-10-01

Vitiligo is an autoimmune disease, characterized by progressive loss of skin pigmentation, which is caused by the interactions of multiple factors, such as heredity, immunity and environment. Recently, a single nucleotide polymorphism (SNP) rs638893 at 11q23.3 region was identified as a risk factor for vitiligo in genome-wide association studies and multiple SNPs in this region have been associated with other autoimmune diseases. This study aims to identify additional susceptibility variants associated with vitiligo at 11q23.3 in the Chinese Han population. We selected and genotyped 26 SNPs at 11q23.3 in an independent cohort including 2924 cases and 4048 controls using the Sequenom MassArray iPLEX ® system. Bonferroni adjustment was used for multiple comparisons and P value <1.92×10 -3 (0.05/26) was considered statistically significant. The A allele of rs613791 and G allele of rs523604 located in CXCR5 were observed to be significantly associated with vitiligo (OR=1.21, 95% CI: 1.11-1.31, P=1.20×10 -5 ; OR=1.14, 95% CI: 1.07-1.23, P=1.90×10 -4 , respectively). The C allele of rs638893 (a previously reported one) located upstream of DDX6 was also significantly associated with vitiligo (OR=1.25, 95% CI: 1.12-1.38, P=3.04×10 -5 ). The genotypes distribution of 3 SNPs also showed significant differences between case and control (rs613791: P=7.00×10 -6 , rs523604: P=4.00×10 -3 , rs638893: P=1.20×10 -5 , respectively). The two newly identified SNPs (rs613791 and rs523604) showed independent associations with vitiligo by linkage disequilibrium analysis and conditional logistic regression. The study identified two new independent signals in the associated locus 11q23.3 for vitiligo. The presence of multiple independent variants emphasizes an important role of this region in disease susceptibility. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension

PubMed Central

Lu, Xiangfeng; Wang, Laiyuan; Lin, Xu; Huang, Jianfeng; Charles Gu, C.; He, Meian; Shen, Hongbing; He, Jiang; Zhu, Jingwen; Li, Huaixing; Hixson, James E.; Wu, Tangchun; Dai, Juncheng; Lu, Ling; Shen, Chong; Chen, Shufeng; He, Lin; Mo, Zengnan; Hao, Yongchen; Mo, Xingbo; Yang, Xueli; Li, Jianxin; Cao, Jie; Chen, Jichun; Fan, Zhongjie; Li, Ying; Zhao, Liancheng; Li, Hongfan; Lu, Fanghong; Yao, Cailiang; Yu, Lin; Xu, Lihua; Mu, Jianjun; Wu, Xianping; Deng, Ying; Hu, Dongsheng; Zhang, Weidong; Ji, Xu; Guo, Dongshuang; Guo, Zhirong; Zhou, Zhengyuan; Yang, Zili; Wang, Renping; Yang, Jun; Zhou, Xiaoyang; Yan, Weili; Sun, Ningling; Gao, Pingjin; Gu, Dongfeng

2015-01-01

Hypertension is a common disorder and the leading risk factor for cardiovascular disease and premature deaths worldwide. Genome-wide association studies (GWASs) in the European population have identified multiple chromosomal regions associated with blood pressure, and the identified loci altogether explain only a small fraction of the variance for blood pressure. The differences in environmental exposures and genetic background between Chinese and European populations might suggest potential different pathways of blood pressure regulation. To identify novel genetic variants affecting blood pressure variation, we conducted a meta-analysis of GWASs of blood pressure and hypertension in 11 816 subjects followed by replication studies including 69 146 additional individuals. We identified genome-wide significant (P < 5.0 × 10−8) associations with blood pressure, which included variants at three new loci (CACNA1D, CYP21A2, and MED13L) and a newly discovered variant near SLC4A7. We also replicated 14 previously reported loci, 8 (CASZ1, MOV10, FGF5, CYP17A1, SOX6, ATP2B1, ALDH2, and JAG1) at genome-wide significance, and 6 (FIGN, ULK4, GUCY1A3, HFE, TBX3-TBX5, and TBX3) at a suggestive level of P = 1.81 × 10−3 to 5.16 × 10−8. These findings provide new mechanistic insights into the regulation of blood pressure and potential targets for treatments. PMID:25249183

Systematic review of depression, anxiety, and other indicators of psychological distress among U.S. and Canadian medical students.

PubMed

Dyrbye, Liselotte N; Thomas, Matthew R; Shanafelt, Tait D

2006-04-01

To systematically review articles reporting on depression, anxiety, and burnout among U.S. and Canadian medical students. Medline and PubMed were searched to identify peer-reviewed English-language studies published between January 1980 and May 2005 reporting on depression, anxiety, and burnout among U.S. and Canadian medical students. Searches used combinations of the Medical Subject Heading terms medical student and depression, depressive disorder major, depressive disorder, professional burnout, mental health, depersonalization, distress, anxiety, or emotional exhaustion. Reference lists of retrieved articles were inspected to identify relevant additional articles. Demographic information, instruments used, prevalence data on student distress, and statistically significant associations were abstracted. The search identified 40 articles on medical student psychological distress (i.e., depression, anxiety, burnout, and related mental health problems) that met the authors' criteria. No studies of burnout among medical students were identified. The studies suggest a high prevalence of depression and anxiety among medical students, with levels of overall psychological distress consistently higher than in the general population and age-matched peers by the later years of training. Overall, the studies suggest psychological distress may be higher among female students. Limited data were available regarding the causes of student distress and its impact on academic performance, dropout rates, and professional development. Medical school is a time of significant psychological distress for physicians-in-training. Currently available information is insufficient to draw firm conclusions on the causes and consequences of student distress. Large, prospective, multicenter studies are needed to identify personal and training-related features that influence depression, anxiety, and burnout among students and explore relationships between distress and competency.

Stress and coping strategies among Arab medical students: towards a research agenda.

PubMed

Elzubeir, M A; Elzubeir, K E; Magzoub, M E

2010-04-01

Research conducted in the past ten years in the area of stress and coping among Arab medical students has identified some important issues, but other significant aspects have not yet been explored. To provide a systematic review of studies reporting on stress, anxiety and coping among Arab medical students and to identify implications for future research. PubMed was searched to identify peer-reviewed English-language studies published between January 1998 and October 2009 reporting on stress and coping among undergraduate Arab medical students. Search strategy used combinations of the terms: Arab medical student, stress, PBL, psychological distress, depression, anxiety and coping strategies. Demographic information on respondents, instruments used, prevalence data and statistically significant associations were abstracted. The search identified 8 articles that met the specified inclusion criteria. Within the limited range of Arab medical students studied, studies suggest these students have a high prevalence of perceived stress, depression and anxiety, with levels of perceived psychological stress as high as those reported in the international literature for medical students of other regions of the world. Limited data were available regarding coping strategies, the impact of stress on academic performance and attrition among Arab students. No data were available regarding the impact of problem-based learning on stress and coping. The existing literature confirms that stress, depression and anxiety are common among Arab medical students, as for students elsewhere. Little is known about the contribution of different curricula approaches to perceived stress and what coping strategies institutions and students apply to help alleviate stress. Large, prospective, multicentre, multi-method studies are needed to identify personal and curricula features that influence stress, depression, anxiety and coping strategies among Arab students.

A genome-wide association and gene-environment interaction study for serum triglycerides levels in a healthy Chinese male population.

PubMed

Tan, Aihua; Sun, Jielin; Xia, Ning; Qin, Xue; Hu, Yanling; Zhang, Shijun; Tao, Sha; Gao, Yong; Yang, Xiaobo; Zhang, Haiying; Kim, Seong-Tae; Peng, Tao; Lin, Xiaoling; Li, Li; Mo, Linjian; Liang, Zhengjia; Shi, Deyi; Huang, Zhang; Huang, Xianghua; Liu, Ming; Ding, Qiang; Trent, Jeffrey M; Zheng, S Lilly; Mo, Zengnan; Xu, Jianfeng

2012-04-01

Triglyceride (TG) is a complex phenotype influenced by both genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified genes or loci affecting lipid levels; however, such studies in Chinese populations are limited. A two-stage GWAS were conducted to identify genetic variants that were associated with TG in a Chinese population of 3495 men. Gene-environment interactions on serum TG levels were further investigated for the seven single nucleotide polymorphisms (SNPs) that were studied in both stages. Two previously reported SNPs (rs651821 in APOA5, rs328 in LPL) were replicated in the second stage, and the combined P-values were 9.19 × 10(-26) and 1.41 × 10(-9) for rs651821 and rs328, respectively. More importantly, a significant interaction between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol consumption on serum TG levels were observed (P = 3.34 × 10(-5)). Rs671 was significantly associated with serum TG levels in drinkers (P = 1.90 × 10(-10)), while no association was observed in non-drinkers (P > 0.05). For drinkers, men carrying the AA/AG genotype have significantly lower serum TG levels, compared with men carrying the GG genotype. For men with the GG genotype, the serum TG levels increased with the quantity of alcohol intake (P = 1.28 × 10(-8) for trend test). We identified a novel, significant interaction effect between alcohol consumption and the ALDH2 rs671 polymorphism on TG levels, which suggests that the effect of alcohol intake on TG occurs in a two-faceted manner. Just one drink can increase TG level in susceptible individuals who carry the GG genotype, while individuals carrying AA/AG genotypes may actually benefit from moderate drinking.

Eating for the better: a social marketing review (2000-2012).

PubMed

Carins, Julia E; Rundle-Thiele, Sharyn R

2014-07-01

The present study sought to identify both the ingredients for success and the potential impediments to social marketing effectiveness for healthy eating behaviour, focusing on studies conducted over the last 10 years. A comprehensive literature review was undertaken examining seventeen databases to identify studies reporting the use of social marketing to address healthy eating. Thirty-four empirical studies were analysed to examine the effectiveness of social marketing interventions to improve healthy eating behaviour using Andreasen's (2002) social marketing benchmark criteria. Statistical analysis was undertaken to quantitatively evaluate whether effectiveness varied between study categories (subsets). Healthy eating empirical studies published from 2000 onwards. Empirical studies that self-identified as social marketing. Sixteen social marketing studies (subset 1) were identified in the review. These were systematic studies which sought to change behaviour through tailored solutions (e.g. use of marketing tools beyond communication was clearly evident) that delivered value to the target audience. For these sixteen studies, the mean number of criteria identified was five. Six studies met all six criteria. Positive change to healthy eating behaviour was found in fourteen of sixteen studies. The sixteen studies that met the definition of social marketing used significantly more of Andreasen's (2002) criteria and were more effective in achieving behavioural change than the eighteen studies in subset 2. Social marketing is an involved process and it is important that studies identifying as social marketing adopt social marketing benchmark criteria. Social marketing when employed to its full extent offers the potential to change healthy eating.

Feasibility and demonstration of a cloud-based RIID analysis system

NASA Astrophysics Data System (ADS)

Wright, Michael C.; Hertz, Kristin L.; Johnson, William C.; Sword, Eric D.; Younkin, James R.; Sadler, Lorraine E.

2015-06-01

A significant limitation in the operational utility of handheld and backpack radioisotope identifiers (RIIDs) is the inability of their onboard algorithms to accurately and reliably identify the isotopic sources of the measured gamma-ray energy spectrum. A possible solution is to move the spectral analysis computations to an external device, the cloud, where significantly greater capabilities are available. The implementation and demonstration of a prototype cloud-based RIID analysis system have shown this type of system to be feasible with currently available communication and computational technology. A system study has shown that the potential user community could derive significant benefits from an appropriately implemented cloud-based analysis system and has identified the design and operational characteristics required by the users and stakeholders for such a system. A general description of the hardware and software necessary to implement reliable cloud-based analysis, the value of the cloud expressed by the user community, and the aspects of the cloud implemented in the demonstrations are discussed.

A genome-wide scan identifies variants in NFIB associated with metastasis in patients with osteosarcoma

PubMed Central

Mirabello, Lisa; Koster, Roelof; Moriarity, Branden S.; Spector, Logan G.; Meltzer, Paul S.; Gary, Joy; Machiela, Mitchell J.; Pankratz, Nathan; Panagiotou, Orestis A.; Largaespada, David; Wang, Zhaoming; Gastier-Foster, Julie M.; Gorlick, Richard; Khanna, Chand; de Toledo, Silvia Regina Caminada; Petrilli, Antonio S.; Patiño-Garcia, Ana; Sierrasesúmaga, Luis; Lecanda, Fernando; Andrulis, Irene L.; Wunder, Jay S.; Gokgoz, Nalan; Serra, Massimo; Hattinger, Claudia; Picci, Piero; Scotlandi, Katia; Flanagan, Adrienne M.; Tirabosco, Roberto; Amary, Maria Fernanda; Halai, Dina; Ballinger, Mandy L.; Thomas, David M.; Davis, Sean; Barkauskas, Donald A.; Marina, Neyssa; Helman, Lee; Otto, George M.; Becklin, Kelsie L.; Wolf, Natalie K.; Weg, Madison T.; Tucker, Margaret; Wacholder, Sholom; Fraumeni, Joseph F.; Caporaso, Neil E.; Boland, Joseph F.; Hicks, Belynda D.; Vogt, Aurelie; Burdett, Laurie; Yeager, Meredith; Hoover, Robert N.; Chanock, Stephen J.; Savage, Sharon A.

2015-01-01

Metastasis is the leading cause of death in osteosarcoma patients, the most common pediatric bone malignancy. We conducted a multi-stage genome-wide association study of osteosarcoma metastasis at diagnosis in 935 osteosarcoma patients to determine whether germline genetic variation contributes to risk of metastasis. We identified a SNP, rs7034162, in NFIB significantly associated with metastasis in European osteosarcoma cases, as well as in cases of African and Brazilian ancestry (meta-analysis of all cases: P=1.2×10−9, OR 2.43, 95% CI 1.83–3.24). The risk allele was significantly associated with lowered NFIB expression, which led to increased osteosarcoma cell migration, proliferation, and colony formation. Additionally, a transposon screen in mice identified a significant proportion of osteosarcomas harboring inactivating insertions in Nfib, and had lowered Nfib expression. These data suggest that germline genetic variation at rs7034162 is important in osteosarcoma metastasis, and that NFIB is an osteosarcoma metastasis susceptibility gene. PMID:26084801

Identifying the Role of National Digital Cadastral Database (ndcdb) in Malaysia and for Land-Based Analysis

NASA Astrophysics Data System (ADS)

Halim, N. Z. A.; Sulaiman, S. A.; Talib, K.; Yusof, O. M.; Wazir, M. A. M.; Adimin, M. K.

2017-10-01

This paper explains the process carried out in identifying the significant role of NDCDB in Malaysia specifically in the land-based analysis. The research was initially a part of a larger research exercise to identify the significance of NDCDB from the legal, technical, role and land-based analysis perspectives. The research methodology of applying the Delphi technique is substantially discussed in this paper. A heterogeneous panel of 14 experts was created to determine the importance of NDCDB from the role standpoint. Seven statements pertaining the significant role of NDCDB in Malaysia and land-based analysis were established after three rounds of consensus building. The agreed statements provided a clear definition to describe the important role of NDCDB in Malaysia and for land-based analysis, which was limitedly studied that lead to unclear perception to the general public and even the geospatial community. The connection of the statements with disaster management is discussed concisely at the end of the research.

Genome-Wide and Gene-Based Meta-Analyses Identify Novel Loci Influencing Blood Pressure Response to Hydrochlorothiazide.

PubMed

Salvi, Erika; Wang, Zhiying; Rizzi, Federica; Gong, Yan; McDonough, Caitrin W; Padmanabhan, Sandosh; Hiltunen, Timo P; Lanzani, Chiara; Zaninello, Roberta; Chittani, Martina; Bailey, Kent R; Sarin, Antti-Pekka; Barcella, Matteo; Melander, Olle; Chapman, Arlene B; Manunta, Paolo; Kontula, Kimmo K; Glorioso, Nicola; Cusi, Daniele; Dominiczak, Anna F; Johnson, Julie A; Barlassina, Cristina; Boerwinkle, Eric; Cooper-DeHoff, Rhonda M; Turner, Stephen T

2017-01-01

This study aimed to identify novel loci influencing the antihypertensive response to hydrochlorothiazide monotherapy. A genome-wide meta-analysis of blood pressure (BP) response to hydrochlorothiazide was performed in 1739 white hypertensives from 6 clinical trials within the International Consortium for Antihypertensive Pharmacogenomics Studies, making it the largest study to date of its kind. No signals reached genome-wide significance (P<5×10 - 8 ), and the suggestive regions (P<10 -5 ) were cross-validated in 2 black cohorts treated with hydrochlorothiazide. In addition, a gene-based analysis was performed on candidate genes with previous evidence of involvement in diuretic response, in BP regulation, or in hypertension susceptibility. Using the genome-wide meta-analysis approach, with validation in blacks, we identified 2 suggestive regulatory regions linked to gap junction protein α1 gene (GJA1) and forkhead box A1 gene (FOXA1), relevant for cardiovascular and kidney function. With the gene-based approach, we identified hydroxy-delta-5-steroid dehydrogenase, 3 β- and steroid δ-isomerase 1 gene (HSD3B1) as significantly associated with BP response (P<2.28×10 - 4 ). HSD3B1 encodes the 3β-hydroxysteroid dehydrogenase enzyme and plays a crucial role in the biosynthesis of aldosterone and endogenous ouabain. By amassing all of the available pharmacogenomic studies of BP response to hydrochlorothiazide, and using 2 different analytic approaches, we identified 3 novel loci influencing BP response to hydrochlorothiazide. The gene-based analysis, never before applied to pharmacogenomics of antihypertensive drugs to our knowledge, provided a powerful strategy to identify a locus of interest, which was not identified in the genome-wide meta-analysis because of high allelic heterogeneity. These data pave the way for future investigations on new pathways and drug targets to enhance the current understanding of personalized antihypertensive treatment. © 2016 American Heart Association, Inc.

The hURAT1 rs559946 polymorphism and the incidence of gout in Han Chinese men.

PubMed

Li, C; Yu, Q; Han, L; Wang, C; Chu, N; Liu, S

2014-01-01

Our previous study identified rs559946, a human urate transporter 1 (hURAT1) single nucleotide polymorphism (SNP), as being significantly associated with risk of primary hyperuricaemia (HUA) in a Han Chinese population. In the current study we aimed to identify the genetic effects of rs559946 on gout susceptibility in Han Chinese men. A total of 335 patients with gout and 376 healthy controls were recruited for a case-control association study. To examine the functional effect of rs559946, we performed luciferase reporter assays and an electrophoretic mobility shift assay (EMSA). rs559946 was found to be significantly associated with gout susceptibility (p = 0.004), with T-allele carriers showing a decreased risk of gout [odds ratio (OR) 0.70, 95% confidence interval (CI) 0.55-0.89]. Multiple linear regression analysis identified a significant association between rs559946 genotypes and tophi. Luciferase reporter assays show increased transcriptional activity of the hURAT1 promoter with the C allele of rs559946. EMSA detected binding of nuclear proteins to both the T and C alleles, although increased binding was observed with the T allele. Cold competition assays suggest that rs559946 may bind within a glucocorticoid receptor (GR) binding motif. Our study suggests that the rs559946 polymorphism is associated with increased HUA risk and may also contribute to gout development in Han Chinese men. The T to C substitution within rs559946 increased the transcriptional activity, and potentially increases gout susceptibility.

Measuring Severity of Anxiety and Depression in Patients with Inflammatory Bowel Disease: Low Concordance Between Patients and Male Gastroenterologists.

PubMed

Janmohamed, Neha; Steinhart, A Hillary

2017-07-01

Studies have indicated that anxiety and depression are significant contributors to reporting of increased disease activity in patients with inflammatory bowel disease (IBD). Thus, for the appropriate clinical management of these patients, it is important that gastroenterologists are able to recognize these conditions. This study aimed to examine the level of agreement between gastroenterologists and patients with IBD for the presence of clinically significant anxiety and depression. Before consultation, patients completed the Hospital Anxiety and Depression Survey. After the consultation, the gastroenterologist recorded whether they believed the patient was anxious and depressed and if so, whether any further action had been taken. Seventy-five patients participated in this study, with a response rate of 88%. Self-reported questionnaires indicated that 31% and 11% of patients were identified as probable for having anxiety and depression, respectively. The level of agreement between the patient and gastroenterologist as to the presence of anxiety or depression was fair to moderate (kappa statistic 0.32 and 0.41, respectively). In only 50% of cases was further action taken by gastroenterologists during consultation for distressed patients, mostly in the form of a patient discussion. Agreement between gastroenterologists and IBD patients regarding the presence of clinically significant anxiety or depression was low, with no further action taken after consultation for 50% of patients who were identified by gastroenterologists as being anxious or depressed. This study highlights the need for educating gastroenterologists to improve their ability to identify IBD patient distress.

Risk of cancer in patients with scleroderma: a population based cohort study

PubMed Central

Hill, C; Nguyen, A; Roder, D; Roberts-Thomson, P

2003-01-01

Background: Previous studies have suggested an increased risk of cancer among patients with scleroderma. Objective: To study a population based cohort of patients with scleroderma in South Australia. Methods: Subjects with scleroderma were identified from the South Australian Scleroderma Registry established in 1993. All subjects on the scleroderma registry were linked to the South Australian Cancer Registry to identify all cases of cancer until 31 December 2000. Standardised incidence ratios (SIRs) for cancer for subjects with scleroderma were determined using the age- and sex-specific rates for South Australia. Results: In 441 patients with scleroderma, 90 cases of cancer were identified, 47 of which developed after inclusion on the scleroderma registry. The SIRs for all cancers among these patients were significantly increased (SIR=1.99; 95% confidence interval (95% CI) 1.46 to 2.65) compared with the cancer incidence rates for South Australia. The SIRs for lung cancer (SIR=5.9; 95% CI 3.05 to 10.31) were also significantly increased. The SIRs for all cancers among the subgroups with diffuse scleroderma (SIR=2.73; 95% CI 1.31 to 5.02) and limited scleroderma (SIR=1.85; 95% CI 1.23 to 2.68) were significantly increased. Conclusions: This population based cohort study provides evidence that scleroderma is associated with cancer, and in particular, lung cancer. In addition, both diffuse and limited forms of scleroderma are associated with a similarly increased risk of cancer. PMID:12860727

Identifying the Behavior Patterns That Influence on Students' Achievement in Psychological Foundations of Learning and Development: A Case of Mekelle University, Ethiopia

ERIC Educational Resources Information Center

Sekar, J. Master Arul; Eyasu, Mengesha

2018-01-01

Generally, the behavior patterns concerns a social significance of values. This paper highlights the various behavior patterns like planner behavior, solution oriented behavior, and prescriptive behavior patterns. The main objective of the present study is to identify the behavior patterns that influence on students' achievement in psychological…

Tricks, Lies and Mistakes: Identifying Theory of Mind Concepts within Storybooks Shared with Deaf Children

ERIC Educational Resources Information Center

Chilton, Helen

2017-01-01

Recent years have seen a significant interest in Theory of Mind (ToM), the specific groups in which it may be restricted and the opportunities which might enhance or suppress development. Previous studies have identified gaps in the literature concerning ideas for intervention and strategies which may augment the development of ToM skills.…

Using the 3-Sigma Limit to Identify Significantly Long Pauses during Composing.

ERIC Educational Resources Information Center

Kelly, Leonard P.; Nolan, Thomas W.

Ten deaf college freshmen and a comparison group of five hearing students participated in a study of a method to identify long pauses in written composition that have important statistical properties. Subjects first wrote two initial drafts of short stories they had viewed on video tape. Later, they revised and recopied their two originals and one…

The Level of Awareness of Safety Measures Practiced in School Laboratories among Pre-Service Science Teachers at Najran University

ERIC Educational Resources Information Center

Fagihi, Yahea Ali

2018-01-01

This study is an attempt to identify the level of awareness of safety measures practiced in school laboratories among pre-service Science teachers at Najran University. It also aims to identify the sources of safety measures awareness and the statistically significant differences among the sample responses due to specialization and grade…

The contribution of psychological factors to recovery after mild traumatic brain injury: is cluster analysis a useful approach?

PubMed

Snell, Deborah L; Surgenor, Lois J; Hay-Smith, E Jean C; Williman, Jonathan; Siegert, Richard J

2015-01-01

Outcomes after mild traumatic brain injury (MTBI) vary, with slow or incomplete recovery for a significant minority. This study examines whether groups of cases with shared psychological factors but with different injury outcomes could be identified using cluster analysis. This is a prospective observational study following 147 adults presenting to a hospital-based emergency department or concussion services in Christchurch, New Zealand. This study examined associations between baseline demographic, clinical, psychological variables (distress, injury beliefs and symptom burden) and outcome 6 months later. A two-step approach to cluster analysis was applied (Ward's method to identify clusters, K-means to refine results). Three meaningful clusters emerged (high-adapters, medium-adapters, low-adapters). Baseline cluster-group membership was significantly associated with outcomes over time. High-adapters appeared recovered by 6-weeks and medium-adapters revealed improvements by 6-months. The low-adapters continued to endorse many symptoms, negative recovery expectations and distress, being significantly at risk for poor outcome more than 6-months after injury (OR (good outcome) = 0.12; CI = 0.03-0.53; p < 0.01). Cluster analysis supported the notion that groups could be identified early post-injury based on psychological factors, with group membership associated with differing outcomes over time. Implications for clinical care providers regarding therapy targets and cases that may benefit from different intensities of intervention are discussed.

Multiple New Loci Associated with Kidney Function and Chronic Kidney Disease: The CKDGen consortium

PubMed Central

Köttgen, Anna; Pattaro, Cristian; Böger, Carsten A.; Fuchsberger, Christian; Olden, Matthias; Glazer, Nicole L.; Parsa, Afshin; Gao, Xiaoyi; Yang, Qiong; Smith, Albert V.; O’Connell, Jeffrey R.; Li, Man; Schmidt, Helena; Tanaka, Toshiko; Isaacs, Aaron; Ketkar, Shamika; Hwang, Shih-Jen; Johnson, Andrew D.; Dehghan, Abbas; Teumer, Alexander; Paré, Guillaume; Atkinson, Elizabeth J.; Zeller, Tanja; Lohman, Kurt; Cornelis, Marilyn C.; Probst-Hensch, Nicole M.; Kronenberg, Florian; Tönjes, Anke; Hayward, Caroline; Aspelund, Thor; Eiriksdottir, Gudny; Launer, Lenore; Harris, Tamara B.; Rapmersaud, Evadnie; Mitchell, Braxton D.; Boerwinkle, Eric; Struchalin, Maksim; Cavalieri, Margherita; Singleton, Andrew; Giallauria, Francesco; Metter, Jeffery; de Boer, Ian; Haritunians, Talin; Lumley, Thomas; Siscovick, David; Psaty, Bruce M.; Zillikens, M. Carola; Oostra, Ben A.; Feitosa, Mary; Province, Michael; Levy, Daniel; de Andrade, Mariza; Turner, Stephen T.; Schillert, Arne; Ziegler, Andreas; Wild, Philipp S.; Schnabel, Renate B.; Wilde, Sandra; Muenzel, Thomas F.; Leak, Tennille S; Illig, Thomas; Klopp, Norman; Meisinger, Christa; Wichmann, H.-Erich; Koenig, Wolfgang; Zgaga, Lina; Zemunik, Tatijana; Kolcic, Ivana; Minelli, Cosetta; Hu, Frank B.; Johansson, Åsa; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Schreiber, Stefan; Aulchenko, Yurii S; Rivadeneira, Fernando; Uitterlinden, Andre G; Hofman, Albert; Imboden, Medea; Nitsch, Dorothea; Brandstätter, Anita; Kollerits, Barbara; Kedenko, Lyudmyla; Mägi, Reedik; Stumvoll, Michael; Kovacs, Peter; Boban, Mladen; Campbell, Susan; Endlich, Karlhans; Völzke, Henry; Kroemer, Heyo K.; Nauck, Matthias; Völker, Uwe; Polasek, Ozren; Vitart, Veronique; Badola, Sunita; Parker, Alexander N.; Ridker, Paul M.; Kardia, Sharon L. R.; Blankenberg, Stefan; Liu, Yongmei; Curhan, Gary C.; Franke, Andre; Rochat, Thierry; Paulweber, Bernhard; Prokopenko, Inga; Wang, Wei; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Shlipak, Michael G.; van Duijn, Cornelia M.; Borecki, Ingrid; Krämer, Bernhard K.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Witteman, Jacqueline C.; Pramstaller, Peter P.; Rettig, Rainer; Hastie, Nick; Chasman, Daniel I.; Kao, W. H.; Heid, Iris M.; Fox, Caroline S.

2010-01-01

Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 Caucasian individuals from 20 population-based studies to identify new susceptibility loci for reduced renal function, estimated by serum creatinine (eGFRcrea), cystatin C (eGFRcys), and CKD (eGFRcrea <60 ml/min/1.73m2; n = 5,807 CKD cases). Follow-up of the 23 genome-wide significant loci (p<5×10−8) in 22,982 replication samples identified 13 novel loci for renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2, and SLC7A9) and 7 creatinine production and secretion loci (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72, BCAS3). These results further our understanding of biologic mechanisms of kidney function by identifying loci potentially influencing nephrogenesis, podocyte function, angiogenesis, solute transport, and metabolic functions of the kidney. PMID:20383146

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

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.

Students' Perceptions and Faculty Measured Competencies in Higher Education

ERIC Educational Resources Information Center

Malechwanzi, J. Muthiani; Lei, Hongde; Wang, Lu

2016-01-01

This study aims to investigate whether there is significant relationship between students' perceived faculty competencies and faculty evaluated competencies. The study identified four main dimensions for measuring faculty competencies namely: teaching, research, additional services and advising. This study adopted a mixed method design. The study…

Perceived Parenting Styles and Goal Orientations: A Study of Teacher Education Students in Hong Kong

ERIC Educational Resources Information Center

Chan, Kwok-wai; Chan, Siu-mui

2005-01-01

Two achievement goals and three perceived parenting styles were identified in a sample of Hong Kong teacher education students. Significant correlations exist within the perceived parenting styles and the achievement goals. Parental authoritativeness was significantly and positively related to learning goal, and parental authoritarianism was…

Stress and anxiety among nursing students: A review of intervention strategies in literature between 2009 and 2015.

PubMed

Turner, Katrina; McCarthy, Valerie Lander

2017-01-01

Undergraduate nursing students experience significant stress and anxiety, inhibiting learning and increasing attrition. Twenty-six intervention studies were identified and evaluated, updating a previous systematic review which categorized interventions targeting: (1) stressors, (2) coping, or (3) appraisal. The majority of interventions in this review aimed to reduce numbers or intensity of stressors through curriculum development (12) or to improve students' coping skills (8). Two studies reported interventions using only cognitive reappraisal while three interventions combined reappraisal with other approaches. Strength of evidence was limited by choice of study design, sample size, and lack of methodological rigor. Some statistically significant support was found for interventions focused on reducing stressors through curriculum development or improving students' coping skills. No statistically significant studies using reappraisal, either alone or in combination with other approaches, were identified, although qualitative findings suggested the potential benefits of this approach do merit further study. Progress was noted since 2008 in the increased number of studies and greater use of validated outcome measures but the review concluded further methodologically sound, adequately powered studies, especially randomized controlled trials, are needed to determine which interventions are effective to address the issue of excessive stress and anxiety among undergraduate nursing students. Copyright © 2016 Elsevier Ltd. All rights reserved.

Systematic review and meta-analysis of dropout rates in individual psychotherapy for generalized anxiety disorder.

PubMed

Gersh, Elon; Hallford, David J; Rice, Simon M; Kazantzis, Nikolaos; Gersh, Hannah; Gersh, Benji; McCarty, Carolyn A

2017-12-01

Despite being a relatively prevalent and debilitating disorder, Generalized Anxiety Disorder (GAD) is the second least studied anxiety disorder and among the most difficult to treat. Dropout from psychotherapy is concerning as it is associated with poorer outcomes, leads to service inefficiencies and can disproportionately affect disadvantaged populations. No study to date has calculated a weighted mean dropout rate for GAD and explored associated correlates. A systematic review was conducted using PsycINFO, Medline and Embase databases, identifying studies investigating individual psychotherapies for adults with GAD. Forty-five studies, involving 2224 participants, were identified for meta-analysis. The weighted mean dropout rate was 16.99% (95% confidence interval 14.42%-19.91%). The Q-statistic indicated significant heterogeneity among studies. Moderator analysis and meta-regressions indicated no statistically significant effect of client age, sex, symptom severity, comorbidity, treatment type, study type (randomized trial or not), study quality, number of sessions or therapist experience. In research investigating psychotherapy for GAD, approximately one in six clients can be expected to drop out of treatment. Dropout rate was not significantly moderated by the client, therapist or treatment variables investigated. Future research should specify the definition of dropout, reasons for dropout and associated correlates to assist the field's progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Predictors of Recurrent Hospital Admission for Patients Presenting With Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State.

PubMed

Bradford, Annabel L; Crider, Courtney Champagne; Xu, Xizheng; Naqvi, Syed Hasan

2017-01-01

Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are two serious, preventable complications of diabetes mellitus. Analysis of variables associated with recurrent DKA and HHS admission has the potential to improve patient outcomes by identifying possible areas for intervention. The aim of this study was to evaluate potential predictors of recurrent DKA or HHS admission. This was a retrospective case-control study of 367 patients presenting during a 5-year period with DKA or HHS at a US tertiary academic medical center. Six potential readmission risk factors identified via literature review were coded as "1" if present and "0" if absent. Readmission odds ratios (ORs) for each risk factor and for the combined score of significant risk factors were calculated by logistic regression. Readmission odds were significantly increased for patients with age < 35, history of depression or substance/alcohol abuse, and self-pay/publicly funded insurance. HbA1C > 10.6% on admission and ethnic minority status did not significantly increase readmission odds, with inadequate study power for these variables. A total "ABCD" score, based on Age (< 35 years), Behavioral health (depression), insurance Coverage (self-pay/publicly funded insurance), and Drug/alcohol abuse, also had a significant effect on readmission odds. Consideration of individual risk factors and the use of a scoring system based on objective predictors of recurrent DKA and HHS admission could be of value in helping identify patients with high readmission risk, allowing interventions to be targeted most effectively to reduce readmission rates, associated morbidity, and mortality.

Gene-environment interaction in atopic diseases: a population-based twin study of early-life exposures.

PubMed

Kahr, Niklas; Naeser, Vibeke; Stensballe, Lone Graff; Kyvik, Kirsten Ohm; Skytthe, Axel; Backer, Vibeke; Bønnelykke, Klaus; Thomsen, Simon Francis

2015-01-01

The development of atopic diseases early in life suggests an important role of perinatal risk factors. To study whether early-life exposures modify the genetic influence on atopic diseases in a twin population. Questionnaire data on atopic diseases from 850 monozygotic and 2279 like-sex dizygotic twin pairs, 3-9 years of age, from the Danish Twin Registry were cross-linked with data on prematurity, Cesarean section, maternal age at birth, parental cohabitation, season of birth and maternal smoking during pregnancy, from the Danish National Birth Registry. Significant predictors of atopic diseases were identified with logistic regression and subsequently tested for genetic effect modification using variance components analysis. After multivariable adjustment, prematurity (gestational age below 32 weeks) [odds ratio (OR) = 1.93, confidence interval (CI) = 1.45-2.56], Cesarean section (OR = 1.25, CI = 1.05-1.49) and maternal smoking during pregnancy (OR = 1.70, CI = 1.42-2.04) significantly influenced the risk of asthma, whereas none of the factors were significantly associated with atopic dermatitis and hay fever. Variance components analysis stratified by exposure status showed no significant change in the heritability of asthma according to the identified risk factors. In this population-based study of children, there was no evidence of genetic effect modification of atopic diseases by several identified early-life risk factors. The causal relationship between these risk factors and atopic diseases may therefore be mediated via mechanisms different from gene-environment interaction. © 2014 John Wiley & Sons Ltd.

Use of selected ambulatory dental services in Taiwan before and after global budgeting: a longitudinal study to identify trends in hospital and clinic-based services.

PubMed

Lin, Chienhung; Chao, Hailun

2012-09-25

The Taiwan government adopted National Health Insurance (NHI) in 1995, providing universal health care to all citizens. It was financed by mandatory premium contributions made by employers, employees, and the government. Since then, the government has faced increasing challenges to control NHI expenditures. The aim of this study was to determine trends in the provision of dental services in Taiwan after the implementation of global budgeting in 1998 and to identify areas of possible concern. This longitudinal before/after study was based on data from the National Health Insurance Research Database from 1996 to 2001. These data were subjected to logistic regression analysis. Linear regression analysis was used to examine changes in delivery of specific services after global budgeting implementation. Utilization of hospital and clinic services was compared. Reimbursement for dental services increased significantly while the number of visits per patient remained steady in both hospitals and clinics. In hospitals, visits for root canal procedures, ionomer restoration, tooth extraction and tooth scaling increased significantly. In dental clinics, visits for amalgam restoration decreased significantly while those for ionomer restoration, tooth extraction, and tooth scaling increased significantly. After the adoption of global budgeting, expenditures for dental services increased dramatically while the number of visits per patient did not, indicating a possible shift in patients to hospital facilities that received additional National Health Insurance funding. The identified trends indicate increased utilization of dental services and uneven distribution of care and dentists. These trends may be compromising the quality of dental care delivered in Taiwan.

Prognostic role of CD133 expression in colorectal cancer: a meta-analysis.

PubMed

Wang, Ke; Xu, Jianjun; Zhang, Junshu; Huang, Jian

2012-12-05

CD133 has been identified as a putative cancer stem cell marker in colorectal cancer (CRC). However, the clinical and prognostic significance of CD133 in CRC remains controversial. Publications were identified which assessed the clinical or prognostic significance of CD133 in CRC up to October 2012. A meta-analysis was performed to clarify the association between CD133 expression and clinical outcomes. A total of 12 studies met the inclusion criteria, and comprised 3652 cases. Analysis of these data showed that CD133 was not significantly associated with the depth of CRC invasion (odds ratio [OR] = 1.44, 95% confidence interval [CI]: 0.77-2.68, Z = 1.15, P = 0.252) or tumor differentiation (OR = 0.63, 95% CI: 0.28-1.46, Z = -1.06, P = 0.286). Also, there was no statistically significant association of CD133 with lymph node metastasis (OR = 1.16, 95% CI: 0.87-1.54, Z = 1.05, P = 0.315) or lymphatic invasion (OR = 1.08, 95% CI: 0.81-1.43, Z = 0.53, P = 0.594). However, in identified studies, overexpression of CD133 was highly correlated with reduced overall survival (relative risk [RR] = 2.14, 95% CI: 1.45-3.17, Z = 3.81, P = 0.0001). CD133 may play an important role in the progression of CRC, and overexpression of CD133 is closely related with poorer patient survival. If these findings are confirmed by well-designed prospective studies, CD133 may be a useful maker for clinical applications.

Evaluation of dietary patterns among Norwegian postmenopausal women using plasma carotenoids as biomarkers.

PubMed

Markussen, Marianne S; Veierød, Marit B; Sakhi, Amrit K; Ellingjord-Dale, Merete; Blomhoff, Rune; Ursin, Giske; Andersen, Lene F

2015-02-28

A number of studies have examined dietary patterns in various populations. However, to study to what extent such patterns capture meaningful differences in consumption of foods is of interest. In the present study, we identified important dietary patterns in Norwegian postmenopausal women (age 50-69 years, n 361), and evaluated these patterns by examining their associations with plasma carotenoids. Diet was assessed by a 253-item FFQ. These 253 food items were categorised into forty-six food groups, and dietary patterns were identified using principal component analysis. We used the partial correlation coefficient (r(adj)) and multiple linear regression analysis to examine the associations between the dietary patterns and the plasma carotenoids α-carotene, β-carotene, β-cryptoxanthin, lutein, lycopene and zeaxanthin. Overall, four dietary patterns were identified: the 'Western'; 'Vegetarian'; 'Continental'; 'High-protein'. The 'Western' dietary pattern scores were significantly inversely correlated with plasma lutein, zeaxanthin, lycopene and total carotenoids (-0·25 ≤ r(adj) ≤ -0·13). The 'Vegetarian' dietary pattern scores were significantly positively correlated with all the plasma carotenoids (0·15 ≤ r(adj) ≤ 0·24). The 'Continental' dietary pattern scores were significantly inversely correlated with plasma lutein and α-carotene (r(adj) = -0·13). No significant association between the 'High-protein' dietary pattern scores and the plasma carotenoids was found. In conclusion, the healthy dietary pattern, the 'Vegetarian' pattern, is associated with a more favourable profile of the plasma carotenoids than our unhealthy dietary patterns, the 'Western' and 'Continental' patterns.

Identification of a protein associated with the activity of cytokine-induced killer cells

PubMed Central

Cao, Jingsong; Chen, Cong; Gao, Yongqiang; Hu, Li; Liang, Yu; Xiao, Jianhua

2017-01-01

Cytokine-induced killer cells (CIKs) adoptive immunotherapy for efficient antitumor ability is used clinically, but details regarding the proteins associated with CIK activity remain unclear. In the current study, the cytotoxicity of CIKs on hepatoma was identified to be significantly downregulated by 1.61-fold following gentamincin treatment. Further research revealed that a differentially expressed protein (P43) was significantly downregulated by 1.22-fold using one-dimensional gel electrophoresis analysis. Of these, the P43 was identified as human haptoglobin using liquid chromatography-mass spectrometry. Western blotting demonstrated that the haptoglobin specifically reacted with rabbit anti-human-haptoglobin. Furthermore, western blotting results verified that the haptoglobin was significantly downregulated by 1.17-fold compared with the control group. In addition, the expression of haptoglobin mRNA was significantly downregulated by 1.73-fold following gentamincin treatment. Taken together, the results of the present study demonstrated that the expression of haptoglobin protein was associated with the activity of CIKs, and the results will be beneficial to the further investigation of CIK activity-enhancement mechanism. PMID:29163711

Complexity of intracranial pressure correlates with outcome after traumatic brain injury

PubMed Central

Lu, Cheng-Wei; Czosnyka, Marek; Shieh, Jiann-Shing; Smielewska, Anna; Pickard, John D.

2012-01-01

This study applied multiscale entropy analysis to investigate the correlation between the complexity of intracranial pressure waveform and outcome after traumatic brain injury. Intracranial pressure and arterial blood pressure waveforms were low-pass filtered to remove the respiratory and pulse components and then processed using a multiscale entropy algorithm to produce a complexity index. We identified significant differences across groups classified by the Glasgow Outcome Scale in intracranial pressure, pressure-reactivity index and complexity index of intracranial pressure (P < 0.0001; P = 0.001; P < 0.0001, respectively). Outcome was dichotomized as survival/death and also as favourable/unfavourable. The complexity index of intracranial pressure achieved the strongest statistical significance (F = 28.7; P < 0.0001 and F = 17.21; P < 0.0001, respectively) and was identified as a significant independent predictor of mortality and favourable outcome in a multivariable logistic regression model (P < 0.0001). The results of this study suggest that complexity of intracranial pressure assessed by multiscale entropy was significantly associated with outcome in patients with brain injury. PMID:22734128

Convergent evidence from systematic analysis of GWAS revealed genetic basis of esophageal cancer.

PubMed

Gao, Xue-Xin; Gao, Lei; Wang, Jiu-Qiang; Qu, Su-Su; Qu, Yue; Sun, Hong-Lei; Liu, Si-Dang; Shang, Ying-Li

2016-07-12

Recent genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with risk of esophageal cancer (EC). However, investigation of genetic basis from the perspective of systematic biology and integrative genomics remains scarce.In this study, we explored genetic basis of EC based on GWAS data and implemented a series of bioinformatics methods including functional annotation, expression quantitative trait loci (eQTL) analysis, pathway enrichment analysis and pathway grouped network analysis.Two hundred and thirteen risk SNPs were identified, in which 44 SNPs were found to have significantly differential gene expression in esophageal tissues by eQTL analysis. By pathway enrichment analysis, 170 risk genes mapped by risk SNPs were enriched into 38 significant GO terms and 17 significant KEGG pathways, which were significantly grouped into 9 sub-networks by pathway grouped network analysis. The 9 groups of interconnected pathways were mainly involved with muscle cell proliferation, cellular response to interleukin-6, cell adhesion molecules, and ethanol oxidation, which might participate in the development of EC.Our findings provide genetic evidence and new insight for exploring the molecular mechanisms of EC.

Protein arginine methyltransferase 7 promotes breast cancer cell invasion through the induction of MMP9 expression

PubMed Central

Baldwin, R. Mitchell; Haghandish, Nasim; Daneshmand, Manijeh; Amin, Shahrier; Paris, Geneviève; Falls, Theresa J.; Bell, John C.; Islam, Shahidul; Côté, Jocelyn

2015-01-01

Recent evidence points to the protein arginine methyltransferase (PRMT) family of enzymes playing critical roles in cancer. PRMT7 has been identified in several gene expression studies to be associated with increased metastasis and decreased survival in breast cancer patients. However, this has not been extensively studied. Here we report that PRMT7 expression is significantly upregulated in both primary breast tumour tissues and in breast cancer lymph node metastases. We have demonstrated that reducing PRMT7 levels in invasive breast cancer cells using RNA interference significantly decreased cell invasion in vitro and metastasis in vivo. Conversely, overexpression of PRMT7 in non-aggressive MCF7 cells enhanced their invasiveness. Furthermore, we show that PRMT7 induces the expression of matrix metalloproteinase 9 (MMP9), a well-known mediator of breast cancer metastasis. Importantly, we significantly rescued invasion of aggressive breast cancer cells depleted of PRMT7 by the exogenous expression of MMP9. Our results demonstrate that upregulation of PRMT7 in breast cancer may have a significant role in promoting cell invasion through the regulation of MMP9. This identifies PRMT7 as a novel and potentially significant biomarker and therapeutic target for breast cancer. PMID:25605249

Protein arginine methyltransferase 7 promotes breast cancer cell invasion through the induction of MMP9 expression.

PubMed

Baldwin, R Mitchell; Haghandish, Nasim; Daneshmand, Manijeh; Amin, Shahrier; Paris, Geneviève; Falls, Theresa J; Bell, John C; Islam, Shahidul; Côté, Jocelyn

2015-02-20

Recent evidence points to the protein arginine methyltransferase (PRMT) family of enzymes playing critical roles in cancer. PRMT7 has been identified in several gene expression studies to be associated with increased metastasis and decreased survival in breast cancer patients. However, this has not been extensively studied. Here we report that PRMT7 expression is significantly upregulated in both primary breast tumour tissues and in breast cancer lymph node metastases. We have demonstrated that reducing PRMT7 levels in invasive breast cancer cells using RNA interference significantly decreased cell invasion in vitro and metastasis in vivo. Conversely, overexpression of PRMT7 in non-aggressive MCF7 cells enhanced their invasiveness. Furthermore, we show that PRMT7 induces the expression of matrix metalloproteinase 9 (MMP9), a well-known mediator of breast cancer metastasis. Importantly, we significantly rescued invasion of aggressive breast cancer cells depleted of PRMT7 by the exogenous expression of MMP9. Our results demonstrate that upregulation of PRMT7 in breast cancer may have a significant role in promoting cell invasion through the regulation of MMP9. This identifies PRMT7 as a novel and potentially significant biomarker and therapeutic target for breast cancer.

Can Australians identify snakes?

PubMed

Morrison, J J; Pearn, J H; Covacevich, J; Nixon, J

1983-07-23

A study of the ability of Australians to identify snakes was undertaken, in which 558 volunteers (primary and secondary schoolchildren, doctors and university science and medical students) took part. Over all, subjects correctly identified an average of 19% of snakes; 28% of subjects could identify a taipan, 59% could identify a death adder, 18% a tiger snake, 23% an eastern (or common) brown snake, and 0.5% a rough-scaled snake. Eighty-six per cent of subjects who grew up in rural areas could identify a death adder; only 4% of those who grew up in an Australian capital city could identify a nonvenomous python. Male subjects identified snakes more accurately than did female subjects. Doctors and medical students correctly identified an average of 25% of snakes. The ability to identify medically significant Australian snakes was classified according to the observer's background, education, sex, and according to the individual snake species. Australians need to be better educated about snakes indigenous to this country.

Using Hospitalization and Mortality Data to Identify Areas at Risk for Adolescent Suicide.

PubMed

Chen, Kun; Aseltine, Robert H

2017-08-01

The purpose of this study is to use statewide data on inpatient hospitalizations for suicide attempts and suicide mortality to identify communities and school districts at risk for adolescent suicide. Five years of data (2010-2014) from the Office of the Connecticut Medical Examiner and the Connecticut Hospital Inpatient Discharge Database were analyzed. A mixed-effects Poisson regression model was used to assess whether suicide attempt/mortality rates in the state's 119 school districts were significantly better or worse than expected after adjusting for 10 community-level characteristics. Ten districts were at significantly higher risk for suicidal behavior, with suicide mortality/hospitalization rates ranging from 154% to 241% of their expected rates, after accounting for their community characteristics. Four districts were identified as having significantly lower risk for suicide attempts than expected after accounting for community-level advantages and disadvantages. Data capturing hospitalization for suicide attempts and suicide deaths can inform prevention activities by identifying high-risk areas to which resources should be allocated, as well as low-risk areas that may provide insight into the best practices in suicide prevention. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Mapping Late Leaf Spot Resistance in Peanut (Arachis hypogaea) Using QTL-seq Reveals Markers for Marker-Assisted Selection.

PubMed

Clevenger, Josh; Chu, Ye; Chavarro, Carolina; Botton, Stephanie; Culbreath, Albert; Isleib, Thomas G; Holbrook, C C; Ozias-Akins, Peggy

2018-01-01

Late leaf spot (LLS; Cercosporidium personatum ) is a major fungal disease of cultivated peanut ( Arachis hypogaea ). A recombinant inbred line population segregating for quantitative field resistance was used to identify quantitative trait loci (QTL) using QTL-seq. High rates of false positive SNP calls using established methods in this allotetraploid crop obscured significant QTLs. To resolve this problem, robust parental SNPs were first identified using polyploid-specific SNP identification pipelines, leading to discovery of significant QTLs for LLS resistance. These QTLs were confirmed over 4 years of field data. Selection with markers linked to these QTLs resulted in a significant increase in resistance, showing that these markers can be immediately applied in breeding programs. This study demonstrates that QTL-seq can be used to rapidly identify QTLs controlling highly quantitative traits in polyploid crops with complex genomes. Markers identified can then be deployed in breeding programs, increasing the efficiency of selection using molecular tools. Key Message: Field resistance to late leaf spot is a quantitative trait controlled by many QTLs. Using polyploid-specific methods, QTL-seq is faster and more cost effective than QTL mapping.

Mapping Late Leaf Spot Resistance in Peanut (Arachis hypogaea) Using QTL-seq Reveals Markers for Marker-Assisted Selection

PubMed Central

Clevenger, Josh; Chu, Ye; Chavarro, Carolina; Botton, Stephanie; Culbreath, Albert; Isleib, Thomas G.; Holbrook, C. C.; Ozias-Akins, Peggy

2018-01-01

Late leaf spot (LLS; Cercosporidium personatum) is a major fungal disease of cultivated peanut (Arachis hypogaea). A recombinant inbred line population segregating for quantitative field resistance was used to identify quantitative trait loci (QTL) using QTL-seq. High rates of false positive SNP calls using established methods in this allotetraploid crop obscured significant QTLs. To resolve this problem, robust parental SNPs were first identified using polyploid-specific SNP identification pipelines, leading to discovery of significant QTLs for LLS resistance. These QTLs were confirmed over 4 years of field data. Selection with markers linked to these QTLs resulted in a significant increase in resistance, showing that these markers can be immediately applied in breeding programs. This study demonstrates that QTL-seq can be used to rapidly identify QTLs controlling highly quantitative traits in polyploid crops with complex genomes. Markers identified can then be deployed in breeding programs, increasing the efficiency of selection using molecular tools. Key Message: Field resistance to late leaf spot is a quantitative trait controlled by many QTLs. Using polyploid-specific methods, QTL-seq is faster and more cost effective than QTL mapping. PMID:29459876

Comparative proteomic analysis using samples obtained with laser microdissection and saturation dye labelling.

PubMed

Wilson, Kate E; Marouga, Rita; Prime, John E; Pashby, D Paul; Orange, Paul R; Crosier, Steven; Keith, Alexander B; Lathe, Richard; Mullins, John; Estibeiro, Peter; Bergling, Helene; Hawkins, Edward; Morris, Christopher M

2005-10-01

Comparative proteomic methods are rapidly being applied to many different biological systems including complex tissues. One pitfall of these methods is that in some cases, such as oncology and neuroscience, tissue complexity requires isolation of specific cell types and sample is limited. Laser microdissection (LMD) is commonly used for obtaining such samples for proteomic studies. We have combined LMD with sensitive thiol-reactive saturation dye labelling of protein samples and 2-D DIGE to identify protein changes in a test system, the isolated CA1 pyramidal neurone layer of a transgenic (Tg) rat carrying a human amyloid precursor protein transgene. Saturation dye labelling proved to be extremely sensitive with a spot map of over 5,000 proteins being readily produced from 5 mug total protein, with over 100 proteins being significantly altered at p < 0.0005. Of the proteins identified, all showed coherent changes associated with transgene expression. It was, however, difficult to identify significantly different proteins using PMF and MALDI-TOF on gels containing less than 500 mug total protein. The use of saturation dye labelling of limiting samples will therefore require the use of highly sensitive MS techniques to identify the significantly altered proteins isolated using methods such as LMD.

Identifying Patients with Hypertension: A Case for Auditing Electronic Health Record Data

PubMed Central

Baus, Adam; Hendryx, Michael; Pollard, Cecil

2012-01-01

Problems in the structure, consistency, and completeness of electronic health record data are barriers to outcomes research, quality improvement, and practice redesign. This nonexperimental retrospective study examines the utility of importing de-identified electronic health record data into an external system to identify patients with and at risk for essential hypertension. We find a statistically significant increase in cases based on combined use of diagnostic and free-text coding (mean = 1,256.1, 95% CI 1,232.3–1,279.7) compared to diagnostic coding alone (mean = 1,174.5, 95% CI 1,150.5—1,198.3). While it is not surprising that significantly more patients are identified when broadening search criteria, the implications are critical for quality of care, the movement toward the National Committee for Quality Assurance's Patient-Centered Medical Home program, and meaningful use of electronic health records. Further, we find a statistically significant increase in potential cases based on the last two or more blood pressure readings greater than or equal to 140/90 mm Hg (mean = 1,353.9, 95% CI 1,329.9—1,377.9). PMID:22737097

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.

Self-confidence of anglers in identification of freshwater sport fish

USGS Publications Warehouse

Chizinski, C.J.; Martin, D. R.; Pope, Kevin L.

2014-01-01

Although several studies have focused on how well anglers identify species using replicas and pictures, there has been no study assessing the confidence that can be placed in angler's ability to identify recreationally important fish. Understanding factors associated with low self-confidence will be useful in tailoring education programmes to improve self-confidence in identifying common species. The purposes of this assessment were to quantify the confidence of recreational anglers to identify 13 commonly encountered warm water fish species and to relate self-confidence to species availability and angler experience. Significant variation was observed in anglers self-confidence among species and levels of self-declared skill, with greater confidence associated with greater skill and with greater exposure. This study of angler self-confidence strongly highlights the need for educational programmes that target lower skilled anglers and the importance of teaching all anglers about less common species, regardless of skill level.

Risk factors for antenatal depression, postnatal depression and parenting stress

PubMed Central

Leigh, Bronwyn; Milgrom, Jeannette

2008-01-01

Background Given that the prevalence of antenatal and postnatal depression is high, with estimates around 13%, and the consequences serious, efforts have been made to identify risk factors to assist in prevention, identification and treatment. Most risk factors associated with postnatal depression have been well researched, whereas predictors of antenatal depression have been less researched. Risk factors associated with early parenting stress have not been widely researched, despite the strong link with depression. The aim of this study was to further elucidate which of some previously identified risk factors are most predictive of three outcome measures: antenatal depression, postnatal depression and parenting stress and to examine the relationship between them. Methods Primipara and multiparae women were recruited antenatally from two major hoitals as part of the beyondblue National Postnatal Depression Program [1]. In this subsidiary study, 367 women completed an additional large battery of validated questionnaires to identify risk factors in the antenatal period at 26–32 weeks gestation. A subsample of these women (N = 161) also completed questionnaires at 10–12 weeks postnatally. Depression level was measured by the Beck Depression Inventory (BDI). Results Regression analyses identified significant risk factors for the three outcome measures. (1). Significant predictors for antenatal depression: low self-esteem, antenatal anxiety, low social support, negative cognitive style, major life events, low income and history of abuse. (2). Significant predictors for postnatal depression: antenatal depression and a history of depression while also controlling for concurrent parenting stress, which was a significant variable. Antenatal depression was identified as a mediator between seven of the risk factors and postnatal depression. (3). Postnatal depression was the only significant predictor for parenting stress and also acted as a mediator for other risk factors. Conclusion Risk factor profiles for antenatal depression, postnatal depression and parenting stress differ but are interrelated. Antenatal depression was the strongest predictor of postnatal depression, and in turn postnatal depression was the strongest predictor for parenting stress. These results provide clinical direction suggesting that early identification and treatment of perinatal depression is important. PMID:18412979

Liquid Water Transport in the Reactant Channels of Proton Exchange Membrane Fuel Cells

NASA Astrophysics Data System (ADS)

Banerjee, Rupak

Water management has been identified as a critical issue in the development of PEM fuel cells for automotive applications. Water is present inside the PEM fuel cell in three phases, i.e. liquid phase, vapor phase and mist phase. Liquid water in the reactant channels causes flooding of the cell and blocks the transport of reactants to the reaction sites at the catalyst layer. Understanding the behavior of liquid water in the reactant channels would allow us to devise improved strategies for removing liquid water from the reactant channels. In situ fuel cell tests have been performed to identify and diagnose operating conditions which result in the flooding of the fuel cell. A relationship has been identified between the liquid water present in the reactant channels and the cell performance. A novel diagnostic technique has been established which utilizes the pressure drop multiplier in the reactant channels to predict the flooding of the cell or the drying-out of the membrane. An ex-situ study has been undertaken to quantify the liquid water present in the reactant channels. A new parameter, the Area Coverage Ratio (ACR), has been defined to identify the interfacial area of the reactant channel which is blocked for reactant transport by the presence of liquid water. A parametric study has been conducted to study the effect of changing temperature and the inlet relative humidity on the ACR. The ACR decreases with increase in current density as the gas flow rates increase, removing water more efficiently. With increase in temperature, the ACR decreases rapidly, such that by 60°C, there is no significant ACR to be reported. Inlet relative humidity of the gases does change the saturation of the gases in the channel, but did not show any significant effect on the ACR. Automotive powertrains, which is the target for this work, are continuously faced with transient changes. Water management under transient operating conditions is significantly more challenging and has not been investigated in detail. This study begins to investigate the effects of changing operating conditions on liquid water transport through the reactant channels. It has been identified that rapidly increasing temperature leads to the dry-out of the membrane and rapidly cooling the cell below 55°C results in the start of cell flooding. In changing the operating load of the PEMFC, overshoot in the pressure drop in the reactant channel has been identified for the first time as part of this investigation. A parametric study has been conducted to identify the factors which influence this overshoot behavior.

Identifying the association between interleukin-6 and lichen planus: A meta-analysis.

PubMed

Yin, Meng; Li, Guifeng; Song, Hui; Lin, Song

2017-05-01

Numerous studies have examined the association between interleukin-6 and the pathogenesis of lichen planus (LP)/oral LP (OLP) in various populations; however, there is a lack of systematic analysis. The aim of the present study was to assess this association more precisely, thus a meta-analysis was performed. Case-control studies, which were published up to December 2015, were obtained from PubMed, Embase and the China National Knowledge Infrastructure databases. Data were extracted and pooled mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Ultimately, eight studies were included, comprising 299 LP/OLP cases and 231 control subjects. Overall, the pooled MD for IL-6 was 16.24 (95% CI, 9.84-22.64; I 2 =99% for heterogeneity). In the subgroup analysis by ethnicity, a significant increase of the IL-6 expression level was identified among Asian individuals, but not in Caucasian individuals. Thus, IL-6 may be significant in the pathogenesis of LP. However, further studies are required to validate these associations.

Identifying the association between interleukin-6 and lichen planus: A meta-analysis

PubMed Central

Yin, Meng; Li, Guifeng; Song, Hui; Lin, Song

2017-01-01

Numerous studies have examined the association between interleukin-6 and the pathogenesis of lichen planus (LP)/oral LP (OLP) in various populations; however, there is a lack of systematic analysis. The aim of the present study was to assess this association more precisely, thus a meta-analysis was performed. Case-control studies, which were published up to December 2015, were obtained from PubMed, Embase and the China National Knowledge Infrastructure databases. Data were extracted and pooled mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Ultimately, eight studies were included, comprising 299 LP/OLP cases and 231 control subjects. Overall, the pooled MD for IL-6 was 16.24 (95% CI, 9.84–22.64; I2=99% for heterogeneity). In the subgroup analysis by ethnicity, a significant increase of the IL-6 expression level was identified among Asian individuals, but not in Caucasian individuals. Thus, IL-6 may be significant in the pathogenesis of LP. However, further studies are required to validate these associations. PMID:28529737

Effects of Dexamethasone and Placebo on Symptom Clusters in Advanced Cancer Patients: A Preliminary Report.

PubMed

Yennurajalingam, Sriram; Williams, Janet L; Chisholm, Gary; Bruera, Eduardo

2016-03-01

Advanced cancer patients frequently experience debilitating symptoms that occur in clusters, but few pharmacological studies have targeted symptom clusters. Our objective was to examine the effects of dexamethasone on symptom clusters in patients with advanced cancer. We reviewed the data from a previous randomized clinical trial to determine the effects of dexamethasone on cancer symptoms. Symptom clusters were identified according to baseline symptoms by using principal component analysis. Correlations and change in the severity of symptom clusters were analyzed after study treatment. A total of 114 participants were included in this study. Three clusters were identified: fatigue/anorexia-cachexia/depression (FAD), sleep/anxiety/drowsiness (SAD), and pain/dyspnea (PD). Changes in severity of FAD and PD significantly correlated over time (at baseline, day 8, and day 15). The FAD cluster was associated with significant improvement in severity at day 8 and day 15, whereas no significant change was observed with the SAD cluster or PD cluster after dexamethasone treatment. The results of this preliminary study suggest significant correlation over time and improvement in the FAD cluster at day 8 and day 15 after treatment with dexamethasone. These findings suggest that fatigue, anorexia-cachexia, and depression may share a common pathophysiologic basis. Further studies are needed to investigate this cluster and target anti-inflammatory therapies. ©AlphaMed Press.

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans.

PubMed

Amin Al Olama, Ali; Dadaev, Tokhir; Hazelett, Dennis J; Li, Qiuyan; Leongamornlert, Daniel; Saunders, Edward J; Stephens, Sarah; Cieza-Borrella, Clara; Whitmore, Ian; Benlloch Garcia, Sara; Giles, Graham G; Southey, Melissa C; Fitzgerald, Liesel; Gronberg, Henrik; Wiklund, Fredrik; Aly, Markus; Henderson, Brian E; Schumacher, Fredrick; Haiman, Christopher A; Schleutker, Johanna; Wahlfors, Tiina; Tammela, Teuvo L; Nordestgaard, Børge G; Key, Tim J; Travis, Ruth C; Neal, David E; Donovan, Jenny L; Hamdy, Freddie C; Pharoah, Paul; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Thibodeau, Stephen N; Mcdonnell, Shannon K; Schaid, Daniel J; Maier, Christiane; Vogel, Walther; Luedeke, Manuel; Herkommer, Kathleen; Kibel, Adam S; Cybulski, Cezary; Wokołorczyk, Dominika; Kluzniak, Wojciech; Cannon-Albright, Lisa; Brenner, Hermann; Butterbach, Katja; Arndt, Volker; Park, Jong Y; Sellers, Thomas; Lin, Hui-Yi; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Batra, Jyotsna; Clements, Judith A; Spurdle, Amanda; Teixeira, Manuel R; Paulo, Paula; Maia, Sofia; Pandha, Hardev; Michael, Agnieszka; Kierzek, Andrzej; Govindasami, Koveela; Guy, Michelle; Lophatonanon, Artitaya; Muir, Kenneth; Viñuela, Ana; Brown, Andrew A; Freedman, Mathew; Conti, David V; Easton, Douglas; Coetzee, Gerhard A; Eeles, Rosalind A; Kote-Jarai, Zsofia

2015-10-01

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same region. © The Author 2015. Published by Oxford University Press.

Managing the deteriorating patient in a simulated environment: nursing students' knowledge, skill and situation awareness.

PubMed

Cooper, Simon; Kinsman, Leigh; Buykx, Penny; McConnell-Henry, Tracy; Endacott, Ruth; Scholes, Julie

2010-08-01

To examine, in a simulated environment, the ability of final-year nursing students to assess, identify and respond to patients either deteriorating or at risk of deterioration. The early identification and management of patient deterioration has a major impact on patient outcomes. 'Failure to rescue' is of international concern, with significant concerns over nurses' ability to detect deterioration, the reasons for which are unknown. Mixed methods incorporating quantitative measures of performance (knowledge, skill and situation awareness) and, to be reported at a later date, a qualitative reflective review of decision processes. Fifty-one final-year, final-semester student nurses attended a simulation laboratory. Students completed a knowledge questionnaire and two video-recorded simulated scenarios (mannequin based) to assess skill performance. The scenarios simulated deteriorating patients with hypovolaemic and septic shock. Situation awareness was measured by randomly stopping each scenario and asking a series of questions relating to the situation. The mean knowledge score was 74% (range 46-100%) and the mean skill performance score across both scenarios was 60% (range 30-78%). Skill performance improved significantly (p < 0.01) by the second scenario. However, skill performance declined significantly in both scenarios as the patient's condition deteriorated (hypovolaemia scenario: p = 0.012, septic scenario: p = 0.000). The mean situation awareness score across both scenarios was 59% (range 38-82%). Participants tended to identify physiological indicators of deterioration (77%) but had low comprehension scores (44%). Knowledge scores suggest, on average, a satisfactory academic preparation, but this study identified significant deficits in students' ability to manage patient deterioration. This study suggests that student nurses, at the point of qualification, may be inadequately prepared to identify and manage deteriorating patients in the clinical setting.

Associations of A-FABP and H-FABP markers with the content of intramuscular fat in Beijing-You chicken.

PubMed

Ye, M H; Chen, J L; Zhao, G P; Zheng, M Q; Wen, J

2010-01-01

This study has assessed the association of single nucleotide polymorphisms (SNP) identified in the adipocyte fatty acid binding protein (A-FABP) and heart-type fatty acid binding protein (H-FABP) genes with the content of intramuscular fat (IMF) in a population of male Beijing-You chickens. A previously described SNP in the chicken A-FABP gene had a significant (P < 0.05) effect on IMF content. Chickens inheriting the homozygous BB genotype at A-FABP had a significantly higher content of IMF in thigh muscles and breast muscles than did those inheriting the AA and AB genotypes. A novel SNP, identified here, in the H-FABP gene was also significantly (P < 0.05) associated with IMF content in thigh and breast muscle. Chickens inheriting the genotypes of DD and CD had much higher content of IMF than those inheriting the homozygous genotype of CC. Markers at the A-FABP and H-FABP genes were associated with IMF content in the studied population. Chickens inheriting the BB genotype at A-FABP, along with the CD genotype at H-FABP, produced muscles with a much higher content of IMF when compared with all other genotypes. A weak interaction between A-FABP and H-FABP was detected (P < 0.09) for IMF content in the tested population. The statistical significance of interaction is tentative because of the limited number of observations for some genotypic combinations. Markers identified within the A-FABP and H-FABP genes are suitable for future use in identifying chickens with the genetic potential to produce more desirable muscle with higher IMF content, at least in the population of Beijing-You male chickens.

Single nucleotide polymorphism and haplotype effects associated with somatic cell score in German Holstein cattle

PubMed Central

2014-01-01

Background To better understand the genetic determination of udder health, we performed a genome-wide association study (GWAS) on a population of 2354 German Holstein bulls for which daughter yield deviations (DYD) for somatic cell score (SCS) were available. For this study, we used genetic information of 44 576 informative single nucleotide polymorphisms (SNPs) and 11 725 inferred haplotype blocks. Results When accounting for the sub-structure of the analyzed population, 16 SNPs and 10 haplotypes in six genomic regions were significant at the Bonferroni threshold of P ≤ 1.14 × 10-6. The size of the identified regions ranged from 0.05 to 5.62 Mb. Genomic regions on chromosomes 5, 6, 18 and 19 coincided with known QTL affecting SCS, while additional genomic regions were found on chromosomes 13 and X. Of particular interest is the region on chromosome 6 between 85 and 88 Mb, where QTL for mastitis traits and significant SNPs for SCS in different Holstein populations coincide with our results. In all identified regions, except for the region on chromosome X, significant SNPs were present in significant haplotypes. The minor alleles of identified SNPs on chromosomes 18 and 19, and the major alleles of SNPs on chromosomes 6 and X were favorable for a lower SCS. Differences in somatic cell count (SCC) between alternative SNP alleles reached 14 000 cells/mL. Conclusions The results support the polygenic nature of the genetic determination of SCS, confirm the importance of previously reported QTL, and provide evidence for the segregation of additional QTL for SCS in Holstein cattle. The small size of the regions identified here will facilitate the search for causal genetic variations that affect gene functions. PMID:24898131

Evaluation of APRI and FIB-4 for noninvasive assessment of significant fibrosis and cirrhosis in HBeAg-negative CHB patients with ALT ≤ 2 ULN

PubMed Central

Li, Qiang; Ren, Xiaojing; Lu, Chuan; Li, Weixia; Huang, Yuxian; Chen, Liang

2017-01-01

Abstract To evaluate the performance of aspartate transaminase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) to predict significant fibrosis and cirrhosis in hepatitis B virus e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with alanine transaminase (ALT) ≤ twice the upper limit of normal (2 ULN). Histologic and laboratory data of 236 HBeAg-negative CHB patients with ALT ≤ 2 ULN were analyzed. Predicted fibrosis stage, based on established scales and cut-offs for APRI and FIB-4, was compared with METAVIR scores obtained from liver biopsy. In this study, the areas under the receiver operating characteristic curves (AUROCs) of APRI were lower than that of FIB-4 (0.62 vs 0.69; P = 0.019) for diagnosing significant fibrosis; however APRI and FIB-4 were comparable for diagnosing cirrhosis (0.77 vs 0.81; P = 0.374). When the cut-off proposed by WHO HBV guideline for APRI (>2.0) was used, no cirrhotic patients were correctly predicted. For FIB-4, the WHO proposed cut-off of 3.25 correctly identified significant fibrosis 83% of the time; but for APRI, the WHO proposed cut-off of 1.5 identified significant fibrosis 56%. In ruling out significant fibrosis, the WHO proposed APRI cut-off of 0.5 had a predictive value of 39%, and the FIB-4 cut-off of 1.45 correctly identified lack of significant fibrosis in 47% of the patients. In this study, based on ROC analysis, the optimal cut-offs were 0.46 and 0.65 for APRI, and 1.05 and 1.29 for FIB-4, for diagnosing significant fibrosis and cirrhosis, respectively. When the new cut-off of APRI (>0.65) was used, 82% of the cirrhotic patients were correctly predicted. In ruling out significant fibrosis, the new APRI cut-off (<0.46) had a predictive value of 80%, and new FIB-4 cut-off (<1.05) correctly identified lack of significant fibrosis in 84% of the patients. The WHO guidelines proposed cut-offs might be higher for HBeAg-negative CHB patients with ALT ≤2 ULN, and might underestimate the proportion of significant fibrosis and cirrhosis. A new set of cut-offs should be used to predict significant fibrosis and cirrhosis in this specific population. PMID:28328813

Risk factors for death from canine parvoviral-related disease in Australia.

PubMed

Ling, Monika; Norris, Jacqueline M; Kelman, Mark; Ward, Michael P

2012-08-17

Canine parvovirus (CPV) is a highly contagious cause of serious and often fatal disease in dogs worldwide despite the availability of safe and efficacious vaccines. Although a number of studies have focussed on identifying risk factors in disease development, risk factors associated with death from CPV are largely unknown. In this study we analysed a total of 1451 CPV cases reported from an Australian surveillance system - using univariate and multivariate techniques - to determine significant risk factors associated with death and euthanasia. A crude case fatality rate of 42.3% was estimated - higher than has been reported previously. We found that 3.3% of CPV cases had a history of vaccination in the previous 12 months, despite having completed the primary puppy vaccination course. The majority (89.5%) of these cases occurred in dogs <12 months of age, indicating failure of the primary vaccination course to provide protective immunity (most likely due to interference of the vaccine antigen with maternal antibodies but other reasons are discussed). Extending the age at which the final puppy vaccination is administered might be one of several strategies to consider. The final multivariate model showed that in non-litter CPV cases, risk of death was significantly associated with season of diagnosis (summer) and pedigree type (hounds and non-sporting dogs). Euthanasia in non-litter CPV cases was significantly associated with season of diagnosis (summer), state of residence (Northern Territory/South Australia/Tasmania combined), age (

Computational genomic analysis of PARK7 interactome reveals high BBS1 gene expression as a prognostic factor favoring survival in malignant pleural mesothelioma.

PubMed

Vavougios, Georgios D; Solenov, Evgeniy I; Hatzoglou, Chrissi; Baturina, Galina S; Katkova, Liubov E; Molyvdas, Paschalis Adam; Gourgoulianis, Konstantinos I; Zarogiannis, Sotirios G

2015-10-01

The aim of our study was to assess the differential gene expression of Parkinson protein 7 (PARK7) interactome in malignant pleural mesothelioma (MPM) using data mining techniques to identify novel candidate genes that may play a role in the pathogenicity of MPM. We constructed the PARK7 interactome using the ConsensusPathDB database. We then interrogated the Oncomine Cancer Microarray database using the Gordon Mesothelioma Study, for differential gene expression of the PARK7 interactome. In ConsensusPathDB, 38 protein interactors of PARK7 were identified. In the Gordon Mesothelioma Study, 34 of them were assessed out of which SUMO1, UBC3, KIAA0101, HDAC2, DAXX, RBBP4, BBS1, NONO, RBBP7, HTRA2, and STUB1 were significantly overexpressed whereas TRAF6 and MTA2 were significantly underexpressed in MPM patients (network 2). Furthermore, Kaplan-Meier analysis revealed that MPM patients with high BBS1 expression had a median overall survival of 16.5 vs. 8.7 mo of those that had low expression. For validation purposes, we performed a meta-analysis in Oncomine database in five sarcoma datasets. Eight network 2 genes (KIAA0101, HDAC2, SUMO1, RBBP4, NONO, RBBP7, HTRA2, and MTA2) were significantly differentially expressed in an array of 18 different sarcoma types. Finally, Gene Ontology annotation enrichment analysis revealed significant roles of the PARK7 interactome in NuRD, CHD, and SWI/SNF protein complexes. In conclusion, we identified 13 novel genes differentially expressed in MPM, never reported before. Among them, BBS1 emerged as a novel predictor of overall survival in MPM. Finally, we identified that PARK7 interactome is involved in novel pathways pertinent in MPM disease. Copyright © 2015 the American Physiological Society.

A Genome Wide Association Study Identifies Common Variants Associated with Lipid Levels in the Chinese Population

PubMed Central

Wu, Chen; Yang, Handong; Yu, Dianke; Yang, Xiaobo; Zhang, Xiaomin; Wang, Yiqin; Sun, Jielin; Gao, Yong; Tan, Aihua; He, Yunfeng; Zhang, Haiying; Qin, Xue; Zhu, Jingwen; Li, Huaixing; Lin, Xu; Zhu, Jiang; Min, Xinwen; Lang, Mingjian; Li, Dongfeng; Zhai, Kan; Chang, Jiang; Tan, Wen; Yuan, Jing; Chen, Weihong; Wang, Youjie; Wei, Sheng; Miao, Xiaoping; Wang, Feng; Fang, Weimin; Liang, Yuan; Deng, Qifei; Dai, Xiayun; Lin, Dafeng; Huang, Suli; Guo, Huan; Lilly Zheng, S.; Xu, Jianfeng; Lin, Dongxin; Hu, Frank B.; Wu, Tangchun

2013-01-01

Plasma lipid levels are important risk factors for cardiovascular disease and are influenced by genetic and environmental factors. Recent genome wide association studies (GWAS) have identified several lipid-associated loci, but these loci have been identified primarily in European populations. In order to identify genetic markers for lipid levels in a Chinese population and analyze the heterogeneity between Europeans and Asians, especially Chinese, we performed a meta-analysis of two genome wide association studies on four common lipid traits including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) in a Han Chinese population totaling 3,451 healthy subjects. Replication was performed in an additional 8,830 subjects of Han Chinese ethnicity. We replicated eight loci associated with lipid levels previously reported in a European population. The loci genome wide significantly associated with TC were near DOCK7, HMGCR and ABO; those genome wide significantly associated with TG were near APOA1/C3/A4/A5 and LPL; those genome wide significantly associated with LDL were near HMGCR, ABO and TOMM40; and those genome wide significantly associated with HDL were near LPL, LIPC and CETP. In addition, an additive genotype score of eight SNPs representing the eight loci that were found to be associated with lipid levels was associated with higher TC, TG and LDL levels (P = 5.52×10-16, 1.38×10-6 and 5.59×10-9, respectively). These findings suggest the cumulative effects of multiple genetic loci on plasma lipid levels. Comparisons with previous GWAS of lipids highlight heterogeneity in allele frequency and in effect size for some loci between Chinese and European populations. The results from our GWAS provided comprehensive and convincing evidence of the genetic determinants of plasma lipid levels in a Chinese population. PMID:24386095

Dietary patterns, insulin sensitivity and adiposity in the multi-ethnic Insulin Resistance Atherosclerosis Study population.

PubMed

Liese, Angela D; Schulz, Mandy; Moore, Charity G; Mayer-Davis, Elizabeth J

2004-12-01

Epidemiological investigations increasingly employ dietary-pattern techniques to fully integrate dietary data. The present study evaluated the relationship of dietary patterns identified by cluster analysis with measures of insulin sensitivity (SI) and adiposity in the multi-ethnic, multi-centre Insulin Resistance Atherosclerosis Study (IRAS, 1992-94). Cross-sectional data from 980 middle-aged adults, of whom 67 % had normal and 33 % had impaired glucose tolerance, were analysed. Usual dietary intake was obtained by an interviewer-administered, validated food-frequency questionnaire. Outcomes included SI, fasting insulin (FI), BMI and waist circumference. The relationship of dietary patterns to log(SI+1), log(FI), BMI and waist circumference was modelled with multivariable linear regressions. Cluster analysis identified six distinct diet patterns--'dark bread', 'wine', 'fruits', 'low-frequency eaters', 'fries' and 'white bread'. The 'white bread' and the 'fries' patterns over-represented the Hispanic IRAS population predominantly from two centres, while the 'wine' and 'dark bread' groups were dominated by non-Hispanic whites. The dietary patterns were associated significantly with each of the outcomes first at the crude, clinical level (P<0.001). Furthermore, they were significantly associated with FI, BMI and waist circumference independent of age, sex, race or ethnicity, clinic, family history of diabetes, smoking and activity (P<0.004), whereas significance was lost for SI. Studying the total dietary behaviour via a pattern approach allowed us to focus both on the qualitative and quantitative dimensions of diet. The present study identified highly consistent associations of distinct dietary patterns with measures of insulin resistance and adiposity, which are risk factors for diabetes and heart disease.

The Impact on Staff of Working with Personality Disordered Offenders: A Systematic Review

PubMed Central

Freestone, Mark C.; Wilson, Kim; Jones, Rose; Mikton, Chris; Milsom, Sophia; Sonigra, Ketan; Taylor, Celia; Campbell, Colin

2015-01-01

Background Personality disordered offenders (PDOs) are generally considered difficult to manage and to have a negative impact on staff working with them. Aims This study aimed to provide an overview of studies examining the impact on staff of working with PDOs, identify impact areas associated with working with PDOs, identify gaps in existing research,and direct future research efforts. Methods The authors conducted a systematic review of the English-language literature from 1964–2014 across 20 databases in the medical and social sciences. Results 27 papers were included in the review. Studies identified negative impacts upon staff including: negative attitudes, burnout, stress, negative counter-transferential experiences; two studies found positive impacts of job excitement and satisfaction, and the evidence related to perceived risk of violence from PDOs was equivocal. Studies demonstrated considerable heterogeneity and meta-analysis was not possible. The overall level of identified evidence was low: 23 studies (85%) were descriptive only, and only one adequately powered cohort study was found. Conclusions The review identified a significant amount of descriptive literature, but only one cohort study and no trials or previous systematic reviews of literatures. Clinicians and managers working with PDOs should be aware of the potential impacts identified, but there is an urgent need for further research focusing on the robust evaluation of interventions to minimise harm to staff working with offenders who suffer from personality disorder. PMID:26305891

Transcriptome Analysis of CD4+ T Cells in Coeliac Disease Reveals Imprint of BACH2 and IFNγ Regulation

PubMed Central

Molloy, Ben; Dominguez Castro, Patricia; Cormican, Paul; Trimble, Valerie; Mahmud, Nasir; McManus, Ross

2015-01-01

Genetic studies have to date identified 43 genome wide significant coeliac disease susceptibility (CD) loci comprising over 70 candidate genes. However, how altered regulation of such disease associated genes contributes to CD pathogenesis remains to be elucidated. Recently there has been considerable emphasis on characterising cell type specific and stimulus dependent genetic variants. Therefore in this study we used RNA sequencing to profile over 70 transcriptomes of CD4+ T cells, a cell type crucial for CD pathogenesis, in both stimulated and resting samples from individuals with CD and unaffected controls. We identified extensive transcriptional changes across all conditions, with the previously established CD gene IFNy the most strongly up-regulated gene (log2 fold change 4.6; Padjusted = 2.40x10-11) in CD4+ T cells from CD patients compared to controls. We show a significant correlation of differentially expressed genes with genetic studies of the disease to date (Padjusted = 0.002), and 21 CD candidate susceptibility genes are differentially expressed under one or more of the conditions used in this study. Pathway analysis revealed significant enrichment of immune related processes. Co-expression network analysis identified several modules of coordinately expressed CD genes. Two modules were particularly highly enriched for differentially expressed genes (P<2.2x10-16) and highlighted IFNy and the genetically associated transcription factor BACH2 which showed significantly reduced expression in coeliac samples (log2FC -1.75; Padjusted = 3.6x10-3) as key regulatory genes in CD. Genes regulated by BACH2 were very significantly over-represented among our differentially expressed genes (P<2.2x10-16) indicating that reduced expression of this master regulator of T cell differentiation promotes a pro-inflammatory response and strongly corroborates genetic evidence that BACH2 plays an important role in CD pathogenesis. PMID:26444573

Increase in virulence of Sporothrix brasiliensis over five years in a patient with chronic disseminated sporotrichosis.

PubMed

Freitas, Dayvison F S; Santos, Suelen S; Almeida-Paes, Rodrigo; de Oliveira, Manoel M E; do Valle, Antonio C F; Gutierrez-Galhardo, Maria Clara; Zancopé-Oliveira, Rosely M; Nosanchuk, Joshua D

2015-01-01

The metropolitan region of Rio de Janeiro is hyperendemic for cat-associated sporotrichosis. This study aimed to assess the virulence of serial Sporothrix isolates from a 61-year-old male patient with chronic, destructive disseminated sporotrichosis. Five Sporothrix isolates were cultured from skin exudates and bone samples over a 5-year period, and all were molecularly identified as Sporothrix brasiliensis. The final isolate was significantly more virulent in Galleria mellonella larvae compared to earlier isolates. We conclude that S. brasiliensis has the capacity to increase in virulence in vivo. This finding is significant to clinicians caring for individuals with S. brasiliensis disease and it suggests that further studies are needed to identify the mechanisms underlying pathogenicity enhancement during chronic disease.

Increase in virulence of Sporothrix brasiliensis over five years in a patient with chronic disseminated sporotrichosis

PubMed Central

Freitas, Dayvison FS; Santos, Suelen S; Almeida-Paes, Rodrigo; de Oliveira, Manoel ME; do Valle, Antonio CF; Gutierrez-Galhardo, Maria Clara; Zancopé-Oliveira, Rosely M; Nosanchuk, Joshua d

2015-01-01

Abstract The metropolitan region of Rio de Janeiro is hyperendemic for cat-associated sporotrichosis. This study aimed to assess the virulence of serial Sporothrix isolates from a 61-year-old male patient with chronic, destructive disseminated sporotrichosis. Five Sporothrix isolates were cultured from skin exudates and bone samples over a 5-year period, and all were molecularly identified as Sporothrix brasiliensis. The final isolate was significantly more virulent in Galleria mellonella larvae compared to earlier isolates. We conclude that S. brasiliensis has the capacity to increase in virulence in vivo. This finding is significant to clinicians caring for individuals with S. brasiliensis disease and it suggests that further studies are needed to identify the mechanisms underlying pathogenicity enhancement during chronic disease. PMID:25668479

Children with bilateral cochlear implants identify emotion in speech and music.

PubMed

Volkova, Anna; Trehub, Sandra E; Schellenberg, E Glenn; Papsin, Blake C; Gordon, Karen A

2013-03-01

This study examined the ability of prelingually deaf children with bilateral implants to identify emotion (i.e. happiness or sadness) in speech and music. Participants in Experiment 1 were 14 prelingually deaf children from 5-7 years of age who had bilateral implants and 18 normally hearing children from 4-6 years of age. They judged whether linguistically neutral utterances produced by a man and woman sounded happy or sad. Participants in Experiment 2 were 14 bilateral implant users from 4-6 years of age and the same normally hearing children as in Experiment 1. They judged whether synthesized piano excerpts sounded happy or sad. Child implant users' accuracy of identifying happiness and sadness in speech was well above chance levels but significantly below the accuracy achieved by children with normal hearing. Similarly, their accuracy of identifying happiness and sadness in music was well above chance levels but significantly below that of children with normal hearing, who performed at ceiling. For the 12 implant users who participated in both experiments, performance on the speech task correlated significantly with performance on the music task and implant experience was correlated with performance on both tasks. Child implant users' accurate identification of emotion in speech exceeded performance in previous studies, which may be attributable to fewer response alternatives and the use of child-directed speech. Moreover, child implant users' successful identification of emotion in music indicates that the relevant cues are accessible at a relatively young age.

High-heeled shoes and musculoskeletal injuries: a narrative systematic review

PubMed Central

Barnish, Maxwell S; Barnish, Jean

2016-01-01

Objectives To conduct the first systematic review from an epidemiological perspective regarding the association between high-heeled shoe wear and hallux valgus, musculoskeletal pain, osteoarthritis (OA) and both first-party and second-party injury in human participants without prior musculoskeletal conditions. Setting A systematic review of international peer-reviewed scientific literature across seven major languages. Data sources Searches were conducted on seven major bibliographic databases in July 2015 to initially identify all scholarly articles on high-heeled shoes. Supplementary manual searches were conducted. Titles, abstracts and full-text articles were sequentially screened to identify all articles assessing epidemiological evidence regarding the association between high-heeled shoe wear and hallux valgus, musculoskeletal pain, OA and both first-party and second-party injury in human participants without prior musculoskeletal conditions. Standardised data extraction and quality assessment (Threats to Validity tool) were conducted. Primary and secondary outcome measures Musculoskeletal pain or OA as assessed by clinical diagnosis or clinical assessment tool. First-party or second-party injury. Results 644 unique records were identified, 56 full-text articles were screened and 18 studies included in the review. Four studies assessed the relationship with hallux valgus and three found a significant association. Two studies assessed the association with OA and neither found a significant association. Five studies assessed the association with musculoskeletal pain and three found a significant association. Eight studies assessed first-party injury and seven found evidence of a significant injury toll associated with high-heeled shoes. One study provided data on second-party injury and the injury toll was low. Conclusions High-heeled shoes were shown to be associated with hallux valgus, musculoskeletal pain and first-party injury. No conclusive evidence regarding OA and second-party injury was found. Societal and clinical relevance of these findings is discussed. Concern is expressed about the expectation to wear high-heeled shoes in some work and social situations and access by children. PMID:26769789

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.

Association of Genome-Wide Variation with Highly Sensitive Cardiac Troponin-T (hs-cTnT) Levels in European- and African-Americans: A Meta-Analysis from the Atherosclerosis Risk in Communities and the Cardiovascular Health Studies

PubMed Central

Yu, Bing; Barbalic, Maja; Brautbar, Ariel; Nambi, Vijay; Hoogeveen, Ron C.; Tang, Weihong; Mosley, Thomas H.; Rotter, Jerome I.; deFilippi, Christopher R.; O’Donnell, Christopher J.; Kathiresan, Sekar; Rice, Ken; Heckbert, Susan R.; Ballantyne, Christie M.; Psaty, Bruce M.; Boerwinkle, Eric

2013-01-01

Background High levels of cardiac troponin T measured by a highly sensitive assay (hs-cTnT) are strongly associated with incident coronary heart disease (CHD) and heart failure (HF). No large-scale genome-wide association study (GWAS) of hs-cTnT has been reported to date. We sought to identify novel genetic variants that are associated with hs-cTnT levels. Methods and Results We performed a GWAS in 9,491 European-Americans and 2,053 African-Americans free of CHD and HF from 2 prospective cohorts: the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS). GWASs were conducted in each study and race stratum. Fixed-effect meta-analyses combined the results of linear regression from 2 cohorts within each race stratum, and then across race strata to produce overall estimates and p-values. The meta-analysis identified a significant association at chromosome 8q13 (rs10091374, p = 9.06 × 10−9) near the nuclear receptor coactivator 2 (NCOA2) gene. Over-expression of NCOA2 can be detected in myoblasts An additional analysis using logistic regression and the clinically motivated 99th percentile cut-point detected a significant association at 1q32 (rs10091374, p = 9.06 × 10−8) in the gene TNNT2, which encodes the cardiac troponin T protein itself. The hs-cTnT-associated SNPs were not associated with CHD in a large case-control study, but rs12564445 was significantly associated with incident HF in ARIC European-Americans (HR = 1.16, p-value = 0.004). Conclusions We identified 2 loci, near NCOA2 and in the TNNT2 gene, at which variation was significantly associated with hs-cTnT levels. Further use of the new assay should enable replication of these results. PMID:23247143

Physician satisfaction with a critical care clinical information system using a multimethod evaluation of usability.

PubMed

Hudson, Darren; Kushniruk, Andre; Borycki, Elizabeth; Zuege, Danny J

2018-04-01

Physician satisfaction with electronic medical records has often been poor. Usability has frequently been identified as a source for decreased satisfaction. While surveys can identify many issues, and are logistically easier to administer, they may miss issues identified using other methods This study sought to understand the level of physician satisfaction and usability issues associated with a critical care clinical information system (eCritical Alberta) implemented throughout the province of Alberta, Canada. All critical care attending physicians using the system were invited to participate in an online survey. Questions included components of the User Acceptance of Information Technology and Usability Questionnaire as well as free text feedback on system components. Physicians were also invited to participate in a think aloud test using simulated scenarios. The transcribed think aloud text and questionnaire were subjected to textual analysis. 82% of all eligible physicians completed the on-line survey (n = 61). Eight physicians were invited and seven completed the think aloud test. Overall satisfaction with the system was moderate. Usability was identified as a significant factor contributing to satisfaction. The major usability factors identified were system response time and layout. The think aloud component identified additional factors beyond those identified in the on-line survey. This study found a modestly high level of physician satisfaction with a province-wide clinical critical care information system. Usability continues to be a significant factor in physician satisfaction. Using multiple methods of evaluation can capture the benefits of a large sample size and deeper understanding of the issues. Copyright © 2018 Elsevier B.V. All rights reserved.

Adaptation problems with nursing home application for elderly persons: an application of the Roy adaptation nursing model.

PubMed

Farkas, L

1981-09-01

This study sought to identify adaptation problems on the part of elderly persons and significant others that were associated with nursing home applications for elderly persons. Within the framework of the Roy Adaptation Nursing Model, an ex post facto research design was utilized to identify these adaptation problems. The four adaptive modes in this model are: physiological, self-concept, role function, and interdependence. The study group (n = 22) and a control group of elderly persons living in Calgary, as well as their significant others, were administered a structured questionnaire. Five hypotheses relating to overall adaptation problems, powerlessness, role reversal, guilt, and knowledge and utilization of services were formulated and tested. Only the hypothesis indicating role reversal on the part of the significant others was accepted. Adaptation problems encountered by the elderly which were associated with nursing home applications occurred in the self-concept and interdependence adaptive modes. The adaptation problems perceived by the significant others, which were associated with nursing home applications for their elderly, occurred in the self-concept, role function, and interdependence modes. Adaptation problems from the significant others' perception rather than from the elderly persons' perception appear to be more significantly associated with nursing home applications.

Clinical significance of In vivo Cytarabine Induced Gene Expression Signature in AML

PubMed Central

Lamba, Jatinder K.; Pounds, Stanley; Cao, Xueyuan; Crews, Kristine R.; Cogle, Christopher R.; Bhise, Neha; Raimondi, Susana C.; Downing, James R.; Baker, Sharyn D.; Ribeiro, Raul C.; Rubnitz, Jeffrey E.

2016-01-01

Despite initial remission, approximately 60-70% of adult and 30% of pediatric patients experience relapse or refractory AML. Studies so far have identified base line gene expression profiles of pathogenic and prognostic significance in AML, however extent of change in gene expression post-initiation of treatment has not been investigated. Exposure of leukemic cells to chemotherapeutic agents such as cytarabine, a mainstay of AML chemotherapy can trigger adaptive response by influencing leukemic cell transcriptome and hence development of resistance or refractory disease. It is however challenging to perform such a study due to lack of availability of specimens post-drug treatment. In this study our primary objective was to identify in vivo cytarabine induced changes in leukemia cell transcriptome and to evaluate their impact on clinical outcome. Our results highlight genes relevant to cytarabine resistance and support the concept of targeting cytarabine-induced genes as a means of improving response. PMID:26366682

Clinical significance of in vivo cytarabine-induced gene expression signature in AML.

PubMed

Lamba, Jatinder K; Pounds, Stanley; Cao, Xueyuan; Crews, Kristine R; Cogle, Christopher R; Bhise, Neha; Raimondi, Susana C; Downing, James R; Baker, Sharyn D; Ribeiro, Raul C; Rubnitz, Jeffrey E

2016-01-01

Despite initial remission, ∼60-70% of adult and 30% of pediatric patients experience relapse or refractory AML. Studies so far have identified base line gene expression profiles of pathogenic and prognostic significance in AML; however, the extent of change in gene expression post-initiation of treatment has not been investigated. Exposure of leukemic cells to chemotherapeutic agents such as cytarabine, a mainstay of AML chemotherapy, can trigger adaptive response by influencing leukemic cell transcriptome and, hence, development of resistance or refractory disease. It is, however, challenging to perform such a study due to lack of availability of specimens post-drug treatment. The primary objective of this study was to identify in vivo cytarabine-induced changes in leukemia cell transcriptome and to evaluate their impact on clinical outcome. The results highlight genes relevant to cytarabine resistance and support the concept of targeting cytarabine-induced genes as a means of improving response.

Vulnerabilities and caregiving in an ethnically diverse HIV-infected population.

PubMed

Moody, Anissa L; Morgello, Susan; Gerits, Pieter; Byrd, Desiree

2009-04-01

The current study aimed to identify the primary informal caregivers of a group of urban HIV+ adults (n = 250) and to determine relationships between demographic, medical, and substance use characteristics and caregivers types. Reported caregiver types included 36.8% familial, 22.4% significant other, and 22.8% institutional or other caregiver relationships. The remaining 18% of the sample reported having no individual that rendered informal care. Factors associated with the absence of an informal caregiver included African American race and low education. Hispanic participants reported the highest frequency of family caregivers while participants with a history of substance disorder were less likely to identify a significant other as a caregiver. This study demonstrates the evolving nature of informal caregiving in HIV, race- and education-related disparities in the absence of primary caregivers, and the importance of sociocultural and demographic factors in the study of HIV caregiving.

Zero-Inflated Poisson Modeling of Fall Risk Factors in Community-Dwelling Older Adults.

PubMed

Jung, Dukyoo; Kang, Younhee; Kim, Mi Young; Ma, Rye-Won; Bhandari, Pratibha

2016-02-01

The aim of this study was to identify risk factors for falls among community-dwelling older adults. The study used a cross-sectional descriptive design. Self-report questionnaires were used to collect data from 658 community-dwelling older adults and were analyzed using logistic and zero-inflated Poisson (ZIP) regression. Perceived health status was a significant factor in the count model, and fall efficacy emerged as a significant predictor in the logistic models. The findings suggest that fall efficacy is important for predicting not only faller and nonfaller status but also fall counts in older adults who may or may not have experienced a previous fall. The fall predictors identified in this study--perceived health status and fall efficacy--indicate the need for fall-prevention programs tailored to address both the physical and psychological issues unique to older adults. © The Author(s) 2014.

Nurses' perceptions of involvement in Thunder Project. American Association of Critical-Care Nurses Thunder Project task force.

PubMed

1995-03-01

The American Association of Critical-Care Nurse's (AACN) Thunder Project was conceptualized and developed to provide critical-care nurses with a research protocol ready for institutional review and implementation. Project goals included providing a research package (protocol, educational, and data collection materials) and a topic of clinical significance to critical-care nurses. Site coordinators and research associates were identified at participating institutions to coordinate and implement all study activities. In this article, an evaluation study undertaken to recount perceptions of site coordinators and research associates in relation to project goals and research experience is described. Data demonstrated that study goals were achieved, and research experience was considered professionally enhancing. Written comments described barriers to project implementation at participating sites. Obtaining informed consent and physician approval and/or cooperation were identified as significant barriers to implementation at some sites.

Identification of Metabolic Modifiers That Underlie Phenotypic Variations in Energy-Balance Regulation

PubMed Central

Chang, Chia Lin; Cai, James J.; Cheng, Po Jen; Chueh, Ho Yen; Hsu, Sheau Yu Teddy

2011-01-01

OBJECTIVE Although recent studies have shown that human genomes contain hundreds of loci that exhibit signatures of positive selection, variants that are associated with adaptation in energy-balance regulation remain elusive. We reasoned that the difficulty in identifying such variants could be due to heterogeneity in selection pressure and that an integrative approach that incorporated experiment-based evidence and population genetics-based statistical judgments would be needed to reveal important metabolic modifiers in humans. RESEARCH DESIGN AND METHODS To identify common metabolic modifiers that underlie phenotypic variation in diabetes-associated or obesity-associated traits in humans, or both, we screened 207 candidate loci for regulatory single nucleotide polymorphisms (SNPs) that exhibited evidence of gene–environmental interactions. RESULTS Three SNPs (rs3895874, rs3848460, and rs937301) at the 5′ gene region of human GIP were identified as prime metabolic-modifier candidates at the enteroinsular axis. Functional studies have shown that GIP promoter reporters carrying derived alleles of these three SNPs (haplotype GIP−1920A) have significantly lower transcriptional activities than those with ancestral alleles at corresponding positions (haplotype GIP−1920G). Consistently, studies of pregnant women who have undergone a screening test for gestational diabetes have shown that patients with a homozygous GIP−1920A/A genotype have significantly lower serum concentrations of glucose-dependent insulinotropic polypeptide (GIP) than those carrying an ancestral GIP−1920G haplotype. After controlling for a GIPR variation, we showed that serum glucose concentrations of patients carrying GIP−1920A/A homozygotes are significantly higher than that of those carrying an ancestral GIP−1920G haplotype (odds ratio 3.53). CONCLUSIONS Our proof-of-concept study indicates that common regulatory GIP variants impart a difference in GIP and glucose metabolism. The study also provides a rare example that identified the common variant-common phenotypic variation pattern based on evidence of moderate gene–environmental interactions. PMID:21300845

Supplementary search methods were more effective and offered better value than bibliographic database searching: A case study from public health and environmental enhancement.

PubMed

Cooper, Chris; Lovell, Rebecca; Husk, Kerryn; Booth, Andrew; Garside, Ruth

2018-06-01

We undertook a systematic review to evaluate the health benefits of environmental enhancement and conservation activities. We were concerned that a conventional process of study identification, focusing on exhaustive searches of bibliographic databases as the primary search method, would be ineffective, offering limited value. The focus of this study is comparing study identification methods. We compare (1) an approach led by searches of bibliographic databases with (2) an approach led by supplementary search methods. We retrospectively assessed the effectiveness and value of both approaches. Effectiveness was determined by comparing (1) the total number of studies identified and screened and (2) the number of includable studies uniquely identified by each approach. Value was determined by comparing included study quality and by using qualitative sensitivity analysis to explore the contribution of studies to the synthesis. The bibliographic databases approach identified 21 409 studies to screen and 2 included qualitative studies were uniquely identified. Study quality was moderate, and contribution to the synthesis was minimal. The supplementary search approach identified 453 studies to screen and 9 included studies were uniquely identified. Four quantitative studies were poor quality but made a substantive contribution to the synthesis; 5 studies were qualitative: 3 studies were good quality, one was moderate quality, and 1 study was excluded from the synthesis due to poor quality. All 4 included qualitative studies made significant contributions to the synthesis. This case study found value in aligning primary methods of study identification to maximise location of relevant evidence. Copyright © 2017 John Wiley & Sons, Ltd.

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

Network-based Analysis of Genome Wide Association Data Provides Novel Candidate Genes for Lipid and Lipoprotein Traits*

PubMed Central

Sharma, Amitabh; Gulbahce, Natali; Pevzner, Samuel J.; Menche, Jörg; Ladenvall, Claes; Folkersen, Lasse; Eriksson, Per; Orho-Melander, Marju; Barabási, Albert-László

2013-01-01

Genome wide association studies (GWAS) identify susceptibility loci for complex traits, but do not identify particular genes of interest. Integration of functional and network information may help in overcoming this limitation and identifying new susceptibility loci. Using GWAS and comorbidity data, we present a network-based approach to predict candidate genes for lipid and lipoprotein traits. We apply a prediction pipeline incorporating interactome, co-expression, and comorbidity data to Global Lipids Genetics Consortium (GLGC) GWAS for four traits of interest, identifying phenotypically coherent modules. These modules provide insights regarding gene involvement in complex phenotypes with multiple susceptibility alleles and low effect sizes. To experimentally test our predictions, we selected four candidate genes and genotyped representative SNPs in the Malmö Diet and Cancer Cardiovascular Cohort. We found significant associations with LDL-C and total-cholesterol levels for a synonymous SNP (rs234706) in the cystathionine beta-synthase (CBS) gene (p = 1 × 10−5 and adjusted-p = 0.013, respectively). Further, liver samples taken from 206 patients revealed that patients with the minor allele of rs234706 had significant dysregulation of CBS (p = 0.04). Despite the known biological role of CBS in lipid metabolism, SNPs within the locus have not yet been identified in GWAS of lipoprotein traits. Thus, the GWAS-based Comorbidity Module (GCM) approach identifies candidate genes missed by GWAS studies, serving as a broadly applicable tool for the investigation of other complex disease phenotypes. PMID:23882023

Evidence for prospective associations among depression and obesity in population-based studies.

PubMed

Faith, M S; Butryn, M; Wadden, T A; Fabricatore, A; Nguyen, A M; Heymsfield, S B

2011-05-01

Obesity may lead to depression or be one of its consequences. We reviewed population-based studies in order to, first, identify the most commonly used research methods, and, second, to evaluate the strength of evidence for prospective associations among obesity and depression. We examined 25 studies, of which 10 tested 'obesity-to-depression' pathways, and 15 tested 'depression-to-obesity' pathways. Descriptive statistics summarized the frequency with which various measurements, designs and data analytic strategies were used. We tallied the number of studies that reported any vs. no statistically significant associations, and report on effect sizes, identified moderating variables within reports, and sought common findings across studies. Results indicated considerable methodological heterogeneity in the literature. Depression was assessed by clinical interview in 44% of studies, weight and height were directly measured in 32%, and only 12% used both. In total, 80% of the studies reported significant obesity-to-depression associations, with odds ratios generally in the range of 1.0 to 2.0, while only 53% of the studies reported significant depression-to-obesity associations. Sex was a common moderating variable. Thus, there was good evidence that obesity is prospectively associated with increased depression, with less consistent evidence that depression leads to obesity. Recommendations for future research regarding study samples, measurement and data analysis are provided. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.

Tulane University School of Continuing Studies: Case Study in Online Quality Improvement

ERIC Educational Resources Information Center

McLennan, Kay L.

2011-01-01

Online asynchronous courses constitute a significant portion of Tulane University's School of Continuing Studies (SCS) curriculum. Online instruction is sufficiently important to the School of Continuing Studies that it merited special attention in the form of a two-year review to ensure its quality. The review identified and implemented different…

Assessment without action; a randomised evaluation of the interRAI home care compared to a national assessment tool on identification of needs and service provision for older people in New Zealand.

PubMed

Parsons, Matthew; Senior, Hugh; Mei-Hu Chen, Xenia; Jacobs, Stephen; Parsons, John; Sheridan, Nicolette; Kenealy, Timothy

2013-09-01

Comprehensive geriatric assessment (CGA) is considered the cornerstone of good practice, as it identifies need across multiple domains such as social, physical and psychological. The interRAI home care (interRAI-HC), probably the most well-researched and supported community-based CGA has been implemented globally, often at considerable expense. Policy-makers, managers and clinicians anticipate significant gains in health outcomes following such investment; however, the implementation of CGA is often undertaken in the absence of community service development. This study sought to compare the interRAI-HC with an existing CGA [the Support Needs Assessment (SNA)] in community-dwelling older people. A randomised controlled trial was undertaken from January 2006 to January 2007 comparing the interRAI-HC and the SNA in 316 people (65+) referred for assessment of needs with follow-up at 1 and 4 months. Outcomes included health-related quality of life, physical function, social support, cognitive status, mood and health service usage as well as identified need. The study found that significantly more support needs were identified using the interRAI-HC compared to the SNA. More social and carer support were recommended by SNA and more rehabilitation and preventive health screens were recommended by interRAI-HC. Despite these differences, the mean healthcare use was similar at 4 months, although interRAI-HC participants had more Emergency Department presentations and hospital admissions. No statistically significant differences between groups were reported in terms of outcomes. In conclusion, the interRAI-HC was found to identify more unmet support needs than the SNA though resulted in no favourable outcomes for the older person or their carer. The study highlights the need to invest attention around the service context to maximise outcomes based on identified needs. © 2013 John Wiley & Sons Ltd.

Distributed lags time series analysis versus linear correlation analysis (Pearson's r) in identifying the relationship between antipseudomonal antibiotic consumption and the susceptibility of Pseudomonas aeruginosa isolates in a single Intensive Care Unit of a tertiary hospital.

PubMed

Erdeljić, Viktorija; Francetić, Igor; Bošnjak, Zrinka; Budimir, Ana; Kalenić, Smilja; Bielen, Luka; Makar-Aušperger, Ksenija; Likić, Robert

2011-05-01

The relationship between antibiotic consumption and selection of resistant strains has been studied mainly by employing conventional statistical methods. A time delay in effect must be anticipated and this has rarely been taken into account in previous studies. Therefore, distributed lags time series analysis and simple linear correlation were compared in their ability to evaluate this relationship. Data on monthly antibiotic consumption for ciprofloxacin, piperacillin/tazobactam, carbapenems and cefepime as well as Pseudomonas aeruginosa susceptibility were retrospectively collected for the period April 2006 to July 2007. Using distributed lags analysis, a significant temporal relationship was identified between ciprofloxacin, meropenem and cefepime consumption and the resistance rates of P. aeruginosa isolates to these antibiotics. This effect was lagged for ciprofloxacin and cefepime [1 month (R=0.827, P=0.039) and 2 months (R=0.962, P=0.001), respectively] and was simultaneous for meropenem (lag 0, R=0.876, P=0.002). Furthermore, a significant concomitant effect of meropenem consumption on the appearance of multidrug-resistant P. aeruginosa strains (resistant to three or more representatives of classes of antibiotics) was identified (lag 0, R=0.992, P<0.001). This effect was not delayed and it was therefore identified both by distributed lags analysis and the Pearson's correlation coefficient. Correlation coefficient analysis was not able to identify relationships between antibiotic consumption and bacterial resistance when the effect was delayed. These results indicate that the use of diverse statistical methods can yield significantly different results, thus leading to the introduction of possibly inappropriate infection control measures. Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Predictive factors for complications in children with esophageal atresia and tracheoesophageal fistula.

PubMed

Shah, R; Varjavandi, V; Krishnan, U

2015-04-01

The objective of this study was to describe the incidence of complications in children with esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) at a tertiary pediatric hospital and to identify predictive factors for their occurrence. A retrospective chart review of 110 patients born in or transferred to Sydney Children's Hospital with EA/TEF between January 1999 and December 2010 was done. Univariate and multivariate regression analyses were performed to identify predictive factors for the occurrence of complications in these children. From univariate analysis, early esophageal stricture formation was more likely in children with 'long-gap' EA (odds ratio [OR] = 16.32). Patients with early strictures were more likely to develop chest infections (OR = 3.33). Patients with severe tracheomalacia were more likely to experience 'cyanotic/dying' (OR = 180) and undergo aortopexy (OR = 549). Patients who had gastroesophageal reflux disease were significantly more likely to require fundoplication (OR = 10.83) and undergo aortopexy (OR = 6.417). From multivariate analysis, 'long-gap' EA was a significant predictive factor for late esophageal stricture formation (P = 0.007) and for gastrostomy insertion (P = 0.001). Reflux was a significant predictive factor for requiring fundoplication (P = 0.007) and gastrostomy (P = 0.002). Gastrostomy insertion (P = 0.000) was a significant predictive factor for undergoing fundoplication. Having a prior fundoplication (P = 0.001) was a significant predictive factor for undergoing a subsequent aortopexy. Predictive factors for the occurrence of complications post EA/TEF repair were identified in this large single centre pediatric study. © 2014 International Society for Diseases of the Esophagus.

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)

Impact of civil war on emotion recognition: the denial of sadness in Sierra Leone.

PubMed

Umiltà, Maria Allessandra; Wood, Rachel; Loffredo, Francesca; Ravera, Roberto; Gallese, Vittorio

2013-01-01

Studies of children with atypical emotional experience demonstrate that childhood exposure to high levels of hostility and threat biases emotion perception. This study investigates emotion processing, in former child soldiers and non-combatant civilians. All participants have experienced prolonged violence exposure during childhood. The study, carried out in Sierra Leone, aimed to examine the effects of exposure to and forced participation in acts of extreme violence on the emotion processing of young adults war survivors. A total of 76 young, male adults (38 former child soldier survivors and 38 civilian survivors) were tested in order to assess participants' ability to identify four different facial emotion expressions from photographs and movies. Both groups were able to recognize facial expressions of emotion. However, despite their general ability to correctly identify facial emotions, participants showed a significant response bias in their recognition of sadness. Both former soldiers and civilians made more errors in identifying expressions of sadness than in the other three emotions and when mislabeling sadness participants most often described it as anger. Conversely, when making erroneous identifications of other emotions, participants were most likely to label the expressed emotion as sadness. In addition, while for three of the four emotions participants were better able to make a correct identification the greater the intensity of the expression, this pattern was not observed for sadness. During movies presentation the recognition of sadness was significantly worse for soldiers. While both former child soldiers and civilians were found to be able to identify facial emotions, a significant response bias in their attribution of negative emotions was observed. Such bias was particularly pronounced in former child soldiers. These findings point to a pervasive long-lasting effect of childhood exposure to violence on emotion processing in later life.

Impact of civil war on emotion recognition: the denial of sadness in Sierra Leone

PubMed Central

Umiltà, Maria Allessandra; Wood, Rachel; Loffredo, Francesca; Ravera, Roberto; Gallese, Vittorio

2013-01-01

Studies of children with atypical emotional experience demonstrate that childhood exposure to high levels of hostility and threat biases emotion perception. This study investigates emotion processing, in former child soldiers and non-combatant civilians. All participants have experienced prolonged violence exposure during childhood. The study, carried out in Sierra Leone, aimed to examine the effects of exposure to and forced participation in acts of extreme violence on the emotion processing of young adults war survivors. A total of 76 young, male adults (38 former child soldier survivors and 38 civilian survivors) were tested in order to assess participants' ability to identify four different facial emotion expressions from photographs and movies. Both groups were able to recognize facial expressions of emotion. However, despite their general ability to correctly identify facial emotions, participants showed a significant response bias in their recognition of sadness. Both former soldiers and civilians made more errors in identifying expressions of sadness than in the other three emotions and when mislabeling sadness participants most often described it as anger. Conversely, when making erroneous identifications of other emotions, participants were most likely to label the expressed emotion as sadness. In addition, while for three of the four emotions participants were better able to make a correct identification the greater the intensity of the expression, this pattern was not observed for sadness. During movies presentation the recognition of sadness was significantly worse for soldiers. While both former child soldiers and civilians were found to be able to identify facial emotions, a significant response bias in their attribution of negative emotions was observed. Such bias was particularly pronounced in former child soldiers. These findings point to a pervasive long-lasting effect of childhood exposure to violence on emotion processing in later life. PMID:24027541

Bone Mineral Density Variation in Men is influenced by Sex-Specific and Non Sex-Specific Quantitative Trait Loci

PubMed Central

Peacock, Munro; Koller, Daniel L.; Lai, Dongbing; Hui, Siu; Foroud, Tatiana; Econs, Michael J.

2009-01-01

Introduction A major predictor of age-related osteoporotic fracture is peak areal bone mineral density (aBMD) which is a highly heritable trait. However, few linkage and association studies have been performed in men to identify the genes contributing to normal variation in aBMD. The aim of this study was to perform a genome wide scan in healthy men to identify quantitative trait loci (QTL) that were significantly linked to aBMD and to test whether any of these might be sex-specific. Methods aBMD at the spine and hip were measured in 515 pairs of brothers, aged 18-61 (405 white pairs, 110 black pairs). Linkage analysis in the brother sample was compared with results in a previously published sample of 774 sister pairs to identify sex-specific quantitative trait loci (QTL). Results A genome wide scan identified significant QTL (LOD>3.6) for aBMD on chromosomes 4q21 (hip), 7q34 (spine), 14q32 (hip), 19p13 (hip), 21q21 (hip), and 22q13 (hip). Analysis suggested that the QTL on chromosome 7q34, 14q32, and 21q21 were male-specific whereas the others were not sex-specific. Conclusions This study demonstrates that six QTL were significantly linked with aBMD in men. One was linked to spine and five were linked to hip. When compared to published data in women from the same geographical region, the QTL on chromosomes 7, 14 and 21 were male-specific. The occurrence of sex-specific genes in humans for aBMD has important implications for the pathogenesis and treatment of osteoporosis. PMID:19427925

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.

MiR-422a as a potential cellular microRNA biomarker for postmenopausal osteoporosis.

PubMed

Cao, Zheng; Moore, Benjamin T; Wang, Yang; Peng, Xian-Hao; Lappe, Joan M; Recker, Robert R; Xiao, Peng

2014-01-01

MicroRNAs (miRNAs) are a class of short non-coding RNA molecules that regulate gene expression by targeting mRNAs. Recently, miRNAs have been shown to play important roles in the etiology of various diseases. However, little is known about their roles in the development of osteoporosis. Circulating monocytes are osteoclast precursors that also produce various factors important for osteoclastogenesis. Previously, we have identified a potential biomarker miR-133a in circulating monocytes for postmenopausal osteoporosis. In this study, we aimed to further identify significant miRNA biomarkers in human circulating monocytes underlying postmenopausal osteoporosis. We used ABI TaqMan miRNA array followed by qRT-PCR validation in human circulating monocytes from 10 high BMD and 10 low BMD postmenopausal Caucasian women to identify miRNA biomarkers. MiR-422a was up-regulated with marginal significance (P = 0.065) in the low compared with the high BMD group in the array analysis. However, a significant up-regulation of miR-422a was identified in the low BMD group by qRT-PCR analysis (P = 0.029). We also performed bioinformatic target gene analysis and found several potential target genes of miR-422a which are involved in osteoclastogenesis. Further qRT-PCR analyses of the target genes in the same study subjects showed that the expression of five of these genes (CBL, CD226, IGF1, PAG1, and TOB2) correlated negatively with miR-422a expression. Our study suggests that miR-422a in human circulating monocytes (osteoclast precursors) is a potential miRNA biomarker underlying postmenopausal osteoporosis.

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.

[Investigation of color vision in acute unilateral optic neuritis using a web-based color vision test].

PubMed

Kuchenbecker, J; Blum, M; Paul, F

2016-03-01

In acute unilateral optic neuritis (ON) color vision defects combined with a decrease in visual acuity and contrast sensitivity frequently occur. This study investigated whether a web-based color vision test is a reliable detector of acquired color vision defects in ON and, if so, which charts are particularly suitable. In 12 patients with acute unilateral ON, a web-based color vision test ( www.farbsehtest.de ) with 25 color plates (16 Velhagen/Broschmann and 9 Ishihara color plates) was performed. For each patient the affected eye was tested first and then the unaffected eye. The mean best-corrected distance visual acuity (BCDVA) in the ON eye was 0.36 ± 0.20 and 1.0 ± 0.1 in the contralateral eye. The number of incorrectly read plates correlated with the visual acuity. For the ON eye a total of 134 plates were correctly identified and 166 plates were incorrectly identified, while for the disease-free fellow eye, 276 plates were correctly identified and 24 plates were incorrectly identified. Both of the blue/yellow plates were identified correctly 14 times and incorrectly 10 times using the ON eye and exclusively correctly (24 times) using the fellow eye. The Velhagen/Broschmann plates were incorrectly identified significantly more frequently in comparison with the Ishihara plates. In 4 out of 16 Velhagen/Broschmann plates and 5 out of 9 Ishihara plates, no statistically significant differences between the ON eye and the fellow eye could be detected. The number of incorrectly identified plates correlated with a decrease in visual acuity. Red/green and blue/yellow plates were incorrectly identified significantly more frequently with the ON eye, while the Velhagen/Broschmann color plates were incorrectly identified significantly more frequently than the Ishihara color plates. Thus, under defined test conditions the web-based color vision test can also be used to detect acquired color vision defects, such as those caused by ON. Optimization of the test by altering the combination of plates may be a useful next step.

Identification of the most significant electrode positions in electromyographic evaluation of swallowing-related movements in humans.

PubMed

Zaretsky, E; Pluschinski, P; Sader, R; Birkholz, P; Neuschaefer-Rube, C; Hey, Christiane

2017-02-01

Surface electromyography (sEMG) is a well-established procedure for recording swallowing-related muscle activities. Because the use of a large number of sEMG channels is time consuming and technically sophisticated, the aim of this study was to identify the most significant electrode positions associated with oropharyngeal swallowing activities. Healthy subjects (N = 16) were tested with a total of 42 channels placed in M. masseter, M. orbicularis oris, submental and paralaryngeal regions. Each test subject swallowed 10 ml of water five times. After having identified 16 optimal electrode positions, that is, positions with the strongest signals quantified by the highest integral values, differences to 26 other ones were determined by a Mann-Whitney U test. Kruskal-Wallis H test was utilized for the analysis of differences between single subjects, subject subgroups, and single electrode positions. Factors associated with sEMG signals were examined in a linear regression. Sixteen electrode positions were chosen by a simple ranking of integral values. These positions delivered significantly higher signals than the other 26 positions. Differences between single electrode positions and between test subjects were also significant. Sixteen most significant positions were identified which represent swallowing-related muscle potentials in healthy subjects.

Use of high-resolution 3.0-T magnetic resonance imaging to characterize atherosclerotic plaques in patients with cerebral infarction

PubMed Central

XU, PENG; LV, LULU; LI, SHAODONG; GE, HAITAO; RONG, YUTAO; HU, CHUNFENG; XU, KAI

2015-01-01

The present study aimed to evaluate the utility of high-resolution magnetic resonance imaging (MRI) in the characterization of atherosclerotic plaques in patients with acute and non-acute cerebral infarction. High-resolution MRI of unilateral stenotic middle cerebral arteries was performed to evaluate the degree of stenosis, the wall and plaque areas, plaque enhancement patterns and lumen remodeling features in 15 and 17 patients with acute and non-acute cerebral infarction, respectively. No significant difference was identified in the vascular stenosis rate between acute and non-acute patients. Overall, plaque eccentricity was observed in 29 patients, including 13 acute and 16 non-acute cases, with no significant difference identified between these groups. The wall area of stenotic arteries and the number of cases with plaque enhancement were significantly greater in the acute patients, but no significant difference in plaque or lumen area was identified between the 2 patient groups. Lumen remodeling patterns of stenotic arteries significantly differed between the acute and non-acute patients; the former predominantly demonstrated positive remodeling, and the latter group demonstrated evidence of negative remodeling. In conclusion, patients with acute and non-acute cerebral infarction exhibit specific characteristics in stenotic arteries and plaques, which can be effectively evaluated by high-resolution MRI. PMID:26668651

Gene-by-Psychosocial Factor Interactions Influence Diastolic Blood Pressure in European and African Ancestry Populations: Meta-Analysis of Four Cohort Studies.

PubMed

Smith, Jennifer A; Zhao, Wei; Yasutake, Kalyn; August, Carmella; Ratliff, Scott M; Faul, Jessica D; Boerwinkle, Eric; Chakravarti, Aravinda; Diez Roux, Ana V; Gao, Yan; Griswold, Michael E; Heiss, Gerardo; Kardia, Sharon L R; Morrison, Alanna C; Musani, Solomon K; Mwasongwe, Stanford; North, Kari E; Rose, Kathryn M; Sims, Mario; Sun, Yan V; Weir, David R; Needham, Belinda L

2017-12-18

Inter-individual variability in blood pressure (BP) is influenced by both genetic and non-genetic factors including socioeconomic and psychosocial stressors. A deeper understanding of the gene-by-socioeconomic/psychosocial factor interactions on BP may help to identify individuals that are genetically susceptible to high BP in specific social contexts. In this study, we used a genomic region-based method for longitudinal analysis, Longitudinal Gene-Environment-Wide Interaction Studies (LGEWIS), to evaluate the effects of interactions between known socioeconomic/psychosocial and genetic risk factors on systolic and diastolic BP in four large epidemiologic cohorts of European and/or African ancestry. After correction for multiple testing, two interactions were significantly associated with diastolic BP. In European ancestry participants, outward/trait anger score had a significant interaction with the C10orf107 genomic region ( p = 0.0019). In African ancestry participants, depressive symptom score had a significant interaction with the HFE genomic region ( p = 0.0048). This study provides a foundation for using genomic region-based longitudinal analysis to identify subgroups of the population that may be at greater risk of elevated BP due to the combined influence of genetic and socioeconomic/psychosocial risk factors.

Improving Understanding of Emotional Speech Acoustic Content

NASA Astrophysics Data System (ADS)

Tinnemore, Anna

Children with cochlear implants show deficits in identifying emotional intent of utterances without facial or body language cues. A known limitation to cochlear implants is the inability to accurately portray the fundamental frequency contour of speech which carries the majority of information needed to identify emotional intent. Without reliable access to the fundamental frequency, other methods of identifying vocal emotion, if identifiable, could be used to guide therapies for training children with cochlear implants to better identify vocal emotion. The current study analyzed recordings of adults speaking neutral sentences with a set array of emotions in a child-directed and adult-directed manner. The goal was to identify acoustic cues that contribute to emotion identification that may be enhanced in child-directed speech, but are also present in adult-directed speech. Results of this study showed that there were significant differences in the variation of the fundamental frequency, the variation of intensity, and the rate of speech among emotions and between intended audiences.

Histopathologic Findings of Potential Kidney Donors With Asymptomatic Microscopic Hematuria: Impact on Donation.

PubMed

Hassan, E A; Ali, T Z; Abdulbaki, A; Ibrahim, I A; Almanae, H M; Aleid, H A

2017-10-01

Isolated microscopic hematuria (IMH) is not uncommon in potential kidney donors. The aim was to study the kidney biopsy findings of potential kidney donors with IMH and the impact of the histopathologic diagnoses on the decision to accept or decline such donors from kidney donation. In this retrospective study, all the potential kidney donors with IMH were identified from the medical records of patients who underwent kidney biopsies between January 2010 and December 2016. Forty-five such individuals were identified. The mean age of these potential donors was 32.6 years and 76% were male. All of them had normal blood pressure and no significant proteinuria. Seventeen (38%) biopsies showed histopathologic abnormalities; thin basement membrane disease (n = 13; 28%) was the most common cause followed by immunoglobulin (Ig)A nephropathy (n = 4; 9%). Donors with abnormal biopsy findings were excluded from donation. However, 62% of the potential donors had normal kidney biopsy findings and were accepted for kidney donation. IMH justifies extensive work-up including kidney biopsy to identify donors who may have underlying significant glomerular pathology excluding them from kidney donation. On the other hand, kidney biopsy also helps in accepting the donors if it does not show significant abnormality. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification and Characterization of Unique Subgroups of Chronic Pain Individuals with Dispositional Personality Traits.

PubMed

Mehta, S; Rice, D; McIntyre, A; Getty, H; Speechley, M; Sequeira, K; Shapiro, A P; Morley-Forster, P; Teasell, R W

2016-01-01

Objective. The current study attempted to identify and characterize distinct CP subgroups based on their level of dispositional personality traits. The secondary objective was to compare the difference among the subgroups in mood, coping, and disability. Methods. Individuals with chronic pain were assessed for demographic, psychosocial, and personality measures. A two-step cluster analysis was conducted in order to identify distinct subgroups of patients based on their level of personality traits. Differences in clinical outcomes were compared using the multivariate analysis of variance based on cluster membership. Results. In 229 participants, three clusters were formed. No significant difference was seen among the clusters on patient demographic factors including age, sex, relationship status, duration of pain, and pain intensity. Those with high levels of dispositional personality traits had greater levels of mood impairment compared to the other two groups (p < 0.05). Significant difference in disability was seen between the subgroups. Conclusions. The study identified a high risk group of CP individuals whose level of personality traits significantly correlated with impaired mood and coping. Use of pharmacological treatment alone may not be successful in improving clinical outcomes among these individuals. Instead, a more comprehensive treatment involving psychological treatments may be important in managing the personality traits that interfere with recovery.

Effectiveness of the Neonatal Discharge Program for Very Low-Birth-Weight Infants on Parental Efficacy and Psychological Distress.

PubMed

Shandra Bos, Lakshmi; Shorey, Shefaly; Kulantaipian, Tamill Salvee; Sng, Jane S P; Tam, Wilson W S; Koh, Serena S L

2018-05-17

This pilot study aimed to (i) evaluate the effectiveness of a neonatal discharge program, (ii) identify relationships between parent and infant factors and parental efficacy and psychological distress, and (iii) identify ways to improve the neonatal discharge program. A quasiexperimental 1-group pretest/posttest design was used. Through consecutive sampling, 42 participants were recruited. Data were collected using self-report questionnaires. Self-administering instruments gathered data on parental efficacy and psychological distress as well as feedback and recommendations on the intervention. A significant increase in parental efficacy and a reduction in psychological distress were observed from pre- to postdischarge intervention. Significant relationships were found between parental efficacy and infants' gestational age, birth weight, gender, and participants' level of education, and a significant relationship was found between psychological distress and number of children from previous pregnancies. Moreover, an Internet-based program, in addition to the face-to-face teaching, was identified as a preferred option to aid in information retention. It is important to evaluate and enhance the neonatal discharge program to suit the parents of today while providing them with informational and emotional support. Future studies should explore parental coping and the long-term effects of their infant's birth and the intervention.

Therapist effects and IAPT Psychological Wellbeing Practitioners (PWPs): a multilevel modelling and mixed methods analysis.

PubMed

Green, Helen; Barkham, Michael; Kellett, Stephen; Saxon, David

2014-12-01

The aim of this research was (a) to determine the extent of therapist effects in Psychological Wellbeing Practitioners (PWPs) delivering guided self-help in IAPT services and (b) to identify factors that defined effective PWP clinical practice. Using patient (N = 1122) anxiety and depression outcomes (PHQ-9 and GAD-7), the effectiveness of N = 21 PWPs across 6 service sites was examined using multi-level modelling. PWPs and their clinical supervisors were also interviewed and completed measures of ego strength, intuition and resilience. Therapist effects accounted for around 9 per cent of the variance in patient outcomes. One PWP had significantly better than average outcomes on both PHQ-9 and GAD-7 while 3 PWPs were significantly below average on the PHQ-9 and 2 were below average on the GAD-7. Computed PWP ranks identified quartile clusters of the most (N = 5) and least (N = 5) effective PWPs. More effective PWPs generated higher rates of reliable and clinically significant change and displayed greater resilience, organisational abilities, knowledge and confidence. Study weaknesses are identified and methodological considerations for future studies examining therapist effects in low intensity cognitive behaviour therapy are provided. Copyright © 2014 Elsevier Ltd. All rights reserved.

Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations.

PubMed

Chen, Brian H; Hivert, Marie-France; Peters, Marjolein J; Pilling, Luke C; Hogan, John D; Pham, Lisa M; Harries, Lorna W; Fox, Caroline S; Bandinelli, Stefania; Dehghan, Abbas; Hernandez, Dena G; Hofman, Albert; Hong, Jaeyoung; Joehanes, Roby; Johnson, Andrew D; Munson, Peter J; Rybin, Denis V; Singleton, Andrew B; Uitterlinden, André G; Ying, Saixia; Melzer, David; Levy, Daniel; van Meurs, Joyce B J; Ferrucci, Luigi; Florez, Jose C; Dupuis, Josée; Meigs, James B; Kolaczyk, Eric D

2016-12-01

Genome-wide association studies (GWAS) have successfully identified genetic loci associated with glycemic traits. However, characterizing the functional significance of these loci has proven challenging. We sought to gain insights into the regulation of fasting insulin and fasting glucose through the use of gene expression microarray data from peripheral blood samples of participants without diabetes in the Framingham Heart Study (FHS) (n = 5,056), the Rotterdam Study (RS) (n = 723), and the InCHIANTI Study (Invecchiare in Chianti) (n = 595). Using a false discovery rate q <0.05, we identified three transcripts associated with fasting glucose and 433 transcripts associated with fasting insulin levels after adjusting for age, sex, technical covariates, and complete blood cell counts. Among the findings, circulating IGF2BP2 transcript levels were positively associated with fasting insulin in both the FHS and RS. Using 1000 Genomes-imputed genotype data, we identified 47,587 cis-expression quantitative trait loci (eQTL) and 6,695 trans-eQTL associated with the 433 significant insulin-associated transcripts. Of note, we identified a trans-eQTL (rs592423), where the A allele was associated with higher IGF2BP2 levels and with fasting insulin in an independent genetic meta-analysis comprised of 50,823 individuals. We conclude that integration of genomic and transcriptomic data implicate circulating IGF2BP2 mRNA levels associated with glucose and insulin homeostasis. © 2016 by the American Diabetes Association.

Identifying Predictors, Moderators, and Mediators of Antidepressant Response in Major Depressive Disorder: Neuroimaging Approaches

PubMed Central

Phillips, Mary L.; Chase, Henry W.; Sheline, Yvette I.; Etkin, Amit; Almeida, Jorge R.C.; Deckersbach, Thilo; Trivedi, Madhukar H.

2015-01-01

Objective Despite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major depressive disorder. Method In this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes. Results The authors first highlight the most consistent findings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergically modulated reward neural circuitry, centered on the ventral striatum and medial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specific measures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression. Conclusions Limitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter- and longer-term clinical and functional outcomes. PMID:25640931

Investigation of 95 variants identified in a genome-wide study for association with mortality after acute coronary syndrome.

PubMed

Morgan, Thomas M; House, John A; Cresci, Sharon; Jones, Philip; Allayee, Hooman; Hazen, Stanley L; Patel, Yesha; Patel, Riyaz S; Eapen, Danny J; Waddy, Salina P; Quyyumi, Arshed A; Kleber, Marcus E; März, Winfried; Winkelmann, Bernhard R; Boehm, Bernhard O; Krumholz, Harlan M; Spertus, John A

2011-09-29

Genome-wide association studies (GWAS) have identified new candidate genes for the occurrence of acute coronary syndrome (ACS), but possible effects of such genes on survival following ACS have yet to be investigated. We examined 95 polymorphisms in 69 distinct gene regions identified in a GWAS for premature myocardial infarction for their association with post-ACS mortality among 811 whites recruited from university-affiliated hospitals in Kansas City, Missouri. We then sought replication of a positive genetic association in a large, racially diverse cohort of myocardial infarction patients (N = 2284) using Kaplan-Meier survival analyses and Cox regression to adjust for relevant covariates. Finally, we investigated the apparent association further in 6086 additional coronary artery disease patients. After Cox adjustment for other ACS risk factors, of 95 SNPs tested in 811 whites only the association with the rs6922269 in MTHFD1L was statistically significant, with a 2.6-fold mortality hazard (P = 0.007). The recessive A/A genotype was of borderline significance in an age- and race-adjusted analysis of the entire combined cohort (N = 3095; P = 0.052), but this finding was not confirmed in independent cohorts (N = 6086). We found no support for the hypothesis that the GWAS-identified variants in this study substantially alter the probability of post-ACS survival. Large-scale, collaborative, genome-wide studies may be required in order to detect genetic variants that are robustly associated with survival in patients with coronary artery disease.

Identification and function analysis of contrary genes in Dupuytren's contracture.

PubMed

Ji, Xianglu; Tian, Feng; Tian, Lijie

2015-07-01

The present study aimed to analyze the expression of genes involved in Dupuytren's contracture (DC), using bioinformatic methods. The profile of GSE21221 was downloaded from the gene expression ominibus, which included six samples, derived from fibroblasts and six healthy control samples, derived from carpal-tunnel fibroblasts. A Distributed Intrusion Detection System was used in order to identify differentially expressed genes. The term contrary genes is proposed. Contrary genes were the genes that exhibited opposite expression patterns in the positive and negative groups, and likely exhibited opposite functions. These were identified using Coexpress software. Gene ontology (GO) function analysis was conducted for the contrary genes. A network of GO terms was constructed using the reduce and visualize gene ontology database. Significantly expressed genes (801) and contrary genes (98) were screened. A significant association was observed between Chitinase-3-like protein 1 and ten genes in the positive gene set. Positive regulation of transcription and the activation of nuclear factor-κB (NF-κB)-inducing kinase activity exhibited the highest degree values in the network of GO terms. In the present study, the expression of genes involved in the development of DC was analyzed, and the concept of contrary genes proposed. The genes identified in the present study are involved in the positive regulation of transcription and activation of NF-κB-inducing kinase activity. The contrary genes and GO terms identified in the present study may potentially be used for DC diagnosis and treatment.

Factors in Patient Empowerment: A Survey of an Online Patient Research Network.

PubMed

Chiauzzi, Emil; DasMahapatra, Pronabesh; Cochin, Elisenda; Bunce, Mikele; Khoury, Raya; Dave, Purav

2016-12-01

Providers and healthcare organizations have begun recognizing the importance of patient empowerment as a driver of patient-centered care. Unfortunately, most studies have investigated empowerment with single diseases. Identifying factors of empowerment across conditions and populations would enable a greater understanding of this construct. The purpose of this study was to understand empowerment in relation to health information-seeking, interactions with providers and peers, and healthcare access in chronic disease patients. This study also sought to identify key empowerment factors and their association with patient characteristics. Participants were recruited through PatientsLikeMe, an online research platform where patients share their personal and medical history data. Patients completed an online survey that assessed self-reported health behavior (e.g. knowledge-seeking, experiences with healthcare providers, and peer interactions) and healthcare access. An exploratory factor analysis identified key empowerment domains. Domain level sum scores and sum of all domains (total score) were compared across patient characteristics and diseases. Overall, 3988 participants were included in the study, with the majority actively involved in their healthcare, but many cited difficulties with matching their treatment goals with those of their physician (34 %) and spending sufficient time with the physician (36 %). Factor analysis identified two domains-Positive Patient-Provider Interaction, and Knowledge and Personal Control-that explained >60 % of the overall variance in the observed variables. Mean total empowerment scores for patients with a primary complaint of Parkinson's disease (61.8) and multiple sclerosis (60.3) were significantly greater than fibromyalgia (55.3) and chronic fatigue syndrome (54.8). Patients who were older, male, more educated, and insured also reported significantly greater levels of empowerment. The two domains of empowerment identified in this study are consistent with previous studies, but the differences in empowerment levels across diseases suggest a need for further studies on disease-related attributes of empowerment. Future research should examine the pathways for empowerment, as well as the relationship between empowerment domains and clinical outcomes.

Beliefs and attitudes toward vegetarian lifestyle across generations.

PubMed

Pribis, Peter; Pencak, Rose C; Grajales, Tevni

2010-05-01

The objective of the study was to examine whether reasons to adopt vegetarian lifestyle differ significantly among generations. Using a Food Frequency Questionnaire (FFQ), we identified that 4% of the participants were vegans, 25% lacto-ovo-vegetarians, 4% pesco-vegetarians and 67% non-vegetarian. Younger people significantly agreed more with the moral reason and with the environmental reason. People ages 41-60 significantly agreed more with the health reason. There are significant differences across generations as to why people choose to live a vegetarian lifestyle.

The Illinois Best Practice School Study: 2003-2006. Research & Policy Report 1-2007

ERIC Educational Resources Information Center

Curry, Lynne; Pacha, Joseph; Baker, Paul J.

2007-01-01

The Illinois Best Practice School Study is part of a national research study to investigate successful practices in schools. This multi-year study (2003-2006) sought to identify and analyze the best practices of schools that are considered to be consistent high performers despite significant poverty levels. The Illinois study (underwritten by the…

Does Training Matter? Comparing the Behaviour Management Strategies of Pre-Service Teachers in a Four-Year Program and Those in a One-Year Program

ERIC Educational Resources Information Center

Woodcock, Stuart; Reupert, Andrea

2013-01-01

Survey-based research was conducted with Australian pre-service teachers to identify the classroom management strategies that they would employ, their confidence in employing them, and the effectiveness of the strategies. Furthermore, the study aimed to identify significant differences in these variables between pre-service teachers in the final…

COMPLEXO: identifying the missing heritability of breast cancer via next generation collaboration.

PubMed

Southey, Melissa C; Park, Daniel J; Nguyen-Dumont, Tu; Campbell, Ian; Thompson, Ella; Trainer, Alison H; Chenevix-Trench, Georgia; Simard, Jacques; Dumont, Martine; Soucy, Penny; Thomassen, Mads; Jønson, Lars; Pedersen, Inge S; Hansen, Thomas Vo; Nevanlinna, Heli; Khan, Sofia; Sinilnikova, Olga; Mazoyer, Sylvie; Lesueur, Fabienne; Damiola, Francesca; Schmutzler, Rita; Meindl, Alfons; Hahnen, Eric; Dufault, Michael R; Chris Chan, Tl; Kwong, Ava; Barkardóttir, Rosa; Radice, Paolo; Peterlongo, Paolo; Devilee, Peter; Hilbers, Florentine; Benitez, Javier; Kvist, Anders; Törngren, Therese; Easton, Douglas; Hunter, David; Lindstrom, Sara; Kraft, Peter; Zheng, Wei; Gao, Yu-Tang; Long, Jirong; Ramus, Susan; Feng, Bing-Jian; Weitzel, Jeffrey N; Nathanson, Katherine; Offit, Kenneth; Joseph, Vijai; Robson, Mark; Schrader, Kasmintan; Wang, San; Kim, Yeong C; Lynch, Henry; Snyder, Carrie; Tavtigian, Sean; Neuhausen, Susan; Couch, Fergus J; Goldgar, David E

2013-06-21

Linkage analysis, positional cloning, candidate gene mutation scanning and genome-wide association study approaches have all contributed significantly to our understanding of the underlying genetic architecture of breast cancer. Taken together, these approaches have identified genetic variation that explains approximately 30% of the overall familial risk of breast cancer, implying that more, and likely rarer, genetic susceptibility alleles remain to be discovered.

[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.

Whole genome association study identifies regions of the bovine genome and biological pathways involved in carcass trait performance in Holstein-Friesian cattle.

PubMed

Doran, Anthony G; Berry, Donagh P; Creevey, Christopher J

2014-10-01

Four traits related to carcass performance have been identified as economically important in beef production: carcass weight, carcass fat, carcass conformation of progeny and cull cow carcass weight. Although Holstein-Friesian cattle are primarily utilized for milk production, they are also an important source of meat for beef production and export. Because of this, there is great interest in understanding the underlying genomic structure influencing these traits. Several genome-wide association studies have identified regions of the bovine genome associated with growth or carcass traits, however, little is known about the mechanisms or underlying biological pathways involved. This study aims to detect regions of the bovine genome associated with carcass performance traits (employing a panel of 54,001 SNPs) using measures of genetic merit (as predicted transmitting abilities) for 5,705 Irish Holstein-Friesian animals. Candidate genes and biological pathways were then identified for each trait under investigation. Following adjustment for false discovery (q-value < 0.05), 479 quantitative trait loci (QTL) were associated with at least one of the four carcass traits using a single SNP regression approach. Using a Bayesian approach, 46 QTL were associated (posterior probability > 0.5) with at least one of the four traits. In total, 557 unique bovine genes, which mapped to 426 human orthologs, were within 500kbs of QTL found associated with a trait using the Bayesian approach. Using this information, 24 significantly over-represented pathways were identified across all traits. The most significantly over-represented biological pathway was the peroxisome proliferator-activated receptor (PPAR) signaling pathway. A large number of genomic regions putatively associated with bovine carcass traits were detected using two different statistical approaches. Notably, several significant associations were detected in close proximity to genes with a known role in animal growth such as glucagon and leptin. Several biological pathways, including PPAR signaling, were shown to be involved in various aspects of bovine carcass performance. These core genes and biological processes may form the foundation for further investigation to identify causative mutations involved in each trait. Results reported here support previous findings suggesting conservation of key biological processes involved in growth and metabolism.

GWAS-identified risk variants for major depressive disorder: Preliminary support for an association with late-life depressive symptoms and brain structural alterations.

PubMed

Ryan, Joanne; Artero, Sylvaine; Carrière, Isabelle; Maller, Jerome J; Meslin, Chantal; Ritchie, Karen; Ancelin, Marie-Laure

2016-01-01

A number of genome-wide association studies (GWAS) have investigated risk factors for major depressive disorder (MDD), however there has been little attempt to replicate these findings in population-based studies of depressive symptoms. Variants within three genes, BICC1, PCLO and GRM7 were selected for replication in our study based on the following criteria: they were identified in a prior MDD GWAS study; a subsequent study found evidence that they influenced depression risk; and there is a solid biological basis for a role in depression. We firstly investigated whether these variants were associated with depressive symptoms in our population-based cohort of 929 elderly (238 with clinical depressive symptoms and 691 controls), and secondly to investigate associations with structural brain alterations. A number of nominally significant associations were identified, but none reached Bonferroni-corrected significance levels. Common SNPs in BICC1 and PCLO were associated with a 50% and 30% decreased risk of depression, respectively. PCLO rs2522833 was also associated with the volume of grey matter (p=1.6×10(-3)), and to a lesser extent with hippocampal volume and white matter lesions. Among depressed individuals rs9870680 (GRM7) was associated with the volume of grey and white matter (p=10(-4) and 8.3×10(-3), respectively). Our results provide some support for the involvement of BICC1 and PCLO in late-life depressive disorders and preliminary evidence that these genetic variants may also influence brain structural volumes. However effect sizes remain modest and associations did not reach corrected significance levels. Further large imaging studies are needed to confirm our findings. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Coxiella burnetii in Humans and Ticks in Rural Senegal

PubMed Central

Mediannikov, Oleg; Fenollar, Florence; Socolovschi, Cristina; Diatta, Georges; Bassene, Hubert; Molez, Jean-François; Sokhna, Cheikh; Trape, Jean-François; Raoult, Didier

2010-01-01

Background Q fever is a worldwide zoonotic disease caused by Coxiella burnetii. Epidemiologically, animals are considered reservoirs and humans incidental hosts. Methodology/Principal Findings We investigated Q fever in rural Senegal. Human samples (e.g., sera, saliva, breast milk, feces) were screened in the generally healthy population of two villages of the Sine-Saloum region. Ticks were collected in four regions. Seroprevalence was studied by immunofluorescence, and all other samples were tested by two qPCR systems for detection of C. burnetii. Positive samples were genotyped (multispacer typing) by amplification and sequencing of three spacers. Strains were isolated by cell culture. We found that the seroprevalence may be as high as 24.5% (59 of 238 studied) in Dielmo village. We identified spontaneous excretion of C. burnetii by humans through faeces and milk. Hard and soft ticks (8 species) were infected in 0–37.6%. We identified three genotypes of C. burnetii. The previously identified genotype 6 was the most common in ticks in all studied regions and the only one found in human samples. Three strains of genotype 6 of C. burnetii were also recovered from soft tick Ornithodoros sonrai. Two other genotypes found in ticks, 35 and 36, were identified for the first time. Conclusions/Significance Q fever should be considered a significant public health threat in Senegal. Humans, similar to other mammals, may continuously excrete C. burnetii. PMID:20386603

Proposed shade guide for human facial skin and lip: a pilot study.

PubMed

Wee, Alvin G; Beatty, Mark W; Gozalo-Diaz, David J; Kim-Pusateri, Seungyee; Marx, David B

2013-08-01

Currently, no commercially available facial shade guide exists in the United States for the fabrication of facial prostheses. The purpose of this study was to measure facial skin and lip color in a human population sample stratified by age, gender, and race. Clustering analysis was used to determine optimal color coordinates for a proposed facial shade guide. Participants (n=119) were recruited from 4 racial/ethnic groups, 5 age groups, and both genders. Reflectance measurements of participants' noses and lower lips were made by using a spectroradiometer and xenon arc lamp with a 45/0 optical configuration. Repeated measures ANOVA (α=.05), to identify skin and lip color differences, resulting from race, age, gender, and location, and a hierarchical clustering analysis, to identify clusters of skin colors) were used. Significant contributors to L*a*b* facial color were race and facial location (P<.01). b* affected all factors (P<.05). Age affected only b* (P<.001), while gender affected only L* (P<.05) and b* (P<.05). Analyses identified 5 clusters of skin color. The study showed that skin color caused by age and gender primarily occurred within the yellow-blue axis. A significant lightness difference between gender groups was also found. Clustering analysis identified 5 distinct skin shade tabs. Copyright © 2013 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

Novel genetic risk factors for asthma in African American children: Precision Medicine and the SAGE II Study.

PubMed

White, Marquitta J; Risse-Adams, O; Goddard, P; Contreras, M G; Adams, J; Hu, D; Eng, C; Oh, S S; Davis, A; Meade, K; Brigino-Buenaventura, E; LeNoir, M A; Bibbins-Domingo, K; Pino-Yanes, M; Burchard, E G

2016-07-01

Asthma, an inflammatory disorder of the airways, is the most common chronic disease of children worldwide. There are significant racial/ethnic disparities in asthma prevalence, morbidity, and mortality among US children. This trend is mirrored in obesity, which may share genetic and environmental risk factors with asthma. The majority of asthma biomedical research has been performed in populations of European decent. We sought to identify genetic risk factors for asthma in African American children. We also assessed the generalizability of genetic variants associated with asthma in European and Asian populations to African American children. Our study population consisted of 1227 (812 asthma cases, 415 controls) African American children with genome-wide single nucleotide polymorphism (SNP) data. Logistic regression was used to identify associations between SNP genotype and asthma status. We identified a novel variant in the PTCHD3 gene that is significantly associated with asthma (rs660498, p = 2.2 × 10(-7)) independent of obesity status. Approximately 5 % of previously reported asthma genetic associations identified in European populations replicated in African Americans. Our identification of novel variants associated with asthma in African American children, coupled with our inability to replicate the majority of findings reported in European Americans, underscores the necessity for including diverse populations in biomedical studies of asthma.

Student paramedic experience of transition into the workforce: A scoping review.

PubMed

Kennedy, Sean; Kenny, Amanda; O'Meara, Peter

2015-10-01

In this article we present the findings from a scoping review that sought to identify what is known about the experiences of paramedic students transitioning into the workforce. Within the emergency healthcare sector, paramedics are primarily tasked with the assessment, treatment and safe transport of patients to hospital. New paramedics entering the workforce are exposed to the full extent of human emotion, injury and suffering as part of their everyday work. There is evidence from other healthcare disciplines that the transition to practice period can be difficult for new graduates. We utilised Arksey and O'Malley's five-stage scoping review framework to identify what is known about the transition of paramedicine graduates to the workplace. The framework involves identifying relevant studies; study selection; charting the data; and collating, summarizing and reporting results. We identified eleven articles that explored transition of newly qualified paramedics. Thematic content was identified and discussed into four separate categories. Each theme revealing the emotional, physical and social impacts new paramedics face as they strive to find acceptance in a new workplace and culture. Given the significant role that paramedics have in modern healthcare, the transition from student to practitioner is a period of significant stress to the new paramedic. Limited research in this field though inhibits a thorough understanding of these issues. Copyright © 2015. Published by Elsevier Ltd.

Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index

PubMed Central

Wen, Wanqing; Zheng, Wei; Okada, Yukinori; Takeuchi, Fumihiko; Tabara, Yasuharu; Hwang, Joo-Yeon; Dorajoo, Rajkumar; Li, Huaixing; Tsai, Fuu-Jen; Yang, Xiaobo; He, Jiang; Wu, Ying; He, Meian; Zhang, Yi; Liang, Jun; Guo, Xiuqing; Sheu, Wayne Huey-Herng; Delahanty, Ryan; Guo, Xingyi; Kubo, Michiaki; Yamamoto, Ken; Ohkubo, Takayoshi; Go, Min Jin; Liu, Jian Jun; Gan, Wei; Chen, Ching-Chu; Gao, Yong; Li, Shengxu; Lee, Nanette R.; Wu, Chen; Zhou, Xueya; Song, Huaidong; Yao, Jie; Lee, I-Te; Long, Jirong; Tsunoda, Tatsuhiko; Akiyama, Koichi; Takashima, Naoyuki; Cho, Yoon Shin; Ong, Rick TH; Lu, Ling; Chen, Chien-Hsiun; Tan, Aihua; Rice, Treva K; Adair, Linda S.; Gui, Lixuan; Allison, Matthew; Lee, Wen-Jane; Cai, Qiuyin; Isomura, Minoru; Umemura, Satoshi; Kim, Young Jin; Seielstad, Mark; Hixson, James; Xiang, Yong-Bing; Isono, Masato; Kim, Bong-Jo; Sim, Xueling; Lu, Wei; Nabika, Toru; Lee, Juyoung; Lim, Wei-Yen; Gao, Yu-Tang; Takayanagi, Ryoichi; Kang, Dae-Hee; Wong, Tien Yin; Hsiung, Chao Agnes; Wu, I-Chien; Juang, Jyh-Ming Jimmy; Shi, Jiajun; Choi, Bo Youl; Aung, Tin; Hu, Frank; Kim, Mi Kyung; Lim, Wei Yen; Wang, Tzung-Dao; Shin, Min-Ho; Lee, Jeannette; Ji, Bu-Tian; Lee, Young-Hoon; Young, Terri L.; Shin, Dong Hoon; Chun, Byung-Yeol; Cho, Myeong-Chan; Han, Bok-Ghee; Hwu, Chii-Min; Assimes, Themistocles L.; Absher, Devin; Yan, Xiaofei; Kim, Eric; Kuo, Jane Z.; Kwon, Soonil; Taylor, Kent D.; Chen, Yii-Der I.; Rotter, Jerome I.; Qi, Lu; Zhu, Dingliang; Wu, Tangchun; Mohlke, Karen L.; Gu, Dongfeng; Mo, Zengnan; Wu, Jer-Yuarn; Lin, Xu; Miki, Tetsuro; Tai, E. Shyong; Lee, Jong-Young; Kato, Norihiro; Shu, Xiao-Ou; Tanaka, Toshihiro

2014-01-01

Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488–47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10−13), ALDH2/MYL2 (rs671, P = 3.40 × 10−11; rs12229654, P = 4.56 × 10−9), ITIH4 (rs2535633, P = 1.77 × 10−10) and NT5C2 (rs11191580, P = 3.83 × 10−8) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10−8) and an additional 14 at P < 1.0 × 10−3 with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity. PMID:24861553

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.

Histopathological findings in farmed rainbow trout (Oncorhynchus mykiss) naturally infected with 3 different Aeromonas species

PubMed Central

Zepeda-Velázquez, Andrea Paloma; Vega-Sánchez, Vicente; Salgado-Miranda, Celene; Soriano-Vargas, Edgardo

2015-01-01

This study describes the macroscopic and microscopic lesions in farmed rainbow trout (Oncorhynchus mykiss) naturally infected with genetically identified Aeromonas salmonicida, A. hydrophila, and A. veronii species. The genus Aeromonas includes bacteria that naturally inhabit both waterways and organisms. At least 27 Aeromonas species have been identified to date, some of which can cause significant economic losses in aquaculture. As up to 68.8% of Aeromonas isolates may be misidentified in routine biochemical and phenotypic tests, however, reported cases of Aeromonas infection in fish may be wrongly identified. Our findings confirmed that the 3 Aeromonas species studied are associated with septicemia and dermal lesions in rainbow trout. PMID:26130859

An evaluation of voice stress analysis techniques in a simulated AWACS environment

NASA Astrophysics Data System (ADS)

Jones, William A., Jr.

1990-08-01

The purpose was to determine if voice analysis algorithms are an effective measure of stress resulting from high workload. Fundamental frequency, frequency jitter, and amplitude shimmer algorithms were employed to measure the effects of stress in crewmember communications data in simulated AWACS mission scenarios. Two independent workload measures were used to identify levels of stress: a predictor model developed by the simulation author based upon scenario generated stimulus events; and the duration of communication for each weapons director, representative of the individual's response to the induced stress. Between eight and eleven speech samples were analyzed for each of the sixteen Air Force officers who participated in the study. Results identified fundamental frequency and frequency jitter as statistically significant vocal indicators of stress, while amplitude shimmer showed no signs of any significant relationship with workload or stress. Consistent with previous research, the frequency algorithm was identified as the most reliable measure. However, the results did not reveal a sensitive discrimination measure between levels of stress, but rather, did distinguish between the presence or absence of stress. The results illustrate a significant relationship between fundamental frequency and the effects of stress and also a significant inverse relationship with jitter, though less dramatic.

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.

Is Health-Related Quality of Life after Radical Cystectomy Using Validated Questionnaires Really Better in Patients with Ileal Orthotopic Neobladder Compared to Ileal Conduit: A Meta-Analysis of Retrospective Comparative Studies.

PubMed

Cerruto, Maria A; D'Elia, Carolina; Siracusano, Salvatore; Porcaro, Antonio B; Cacciamani, Giovanni; De Marchi, Davide; Niero, Mauro; Lonardi, Cristina; Iafrate, Massimo; Bassi, Pierfrancesco; Belgrano, Emanuele; Imbimbo, Ciro; Racioppi, Marco; Talamini, Renato; Ciciliato, Stefano; Toffoli, Laura; Rizzo, Michele; Visalli, Francesco; Verze, Paolo; Artibani, Walter

2017-07-01

From the most recent systematic revision of the literature, an orthotopic neobladder would seem to show marginally better health related quality of life (HR-QoL) scores compared with an ileal conduit. The aim of this study was to review all relevant published studies about the comparison between ileal orthotopic neobladder (IONB) and ileal conduit using validated HR-QoL questionnaires. Studies were identified by searching multiple literature databases. Data were synthesized using meta-analytic methods conformed to the PRISMA statement. The literature search identified 10 papers; pooled effect sizes of combined quality of life outcomes for ileal conduit versus IONB showed a significantly better HR-QoL in patients with IONB (Hedges' g = 0.278; p = 0.000);. The present study has an important limitation due to the type of the analyzed comparative studies, all retrospective and not randomized. This meta-analysis of not-randomized, retrospective comparative studies on the impact of ileal conduit versus IONB on HR-QoL showed a significant advantage of IONB subgroups.

Identifying thresholds for relationships between impacts of rationing of nursing care and nurse- and patient-reported outcomes in Swiss hospitals: a correlational study.

PubMed

Schubert, Maria; Clarke, Sean P; Glass, Tracy R; Schaffert-Witvliet, Bianca; De Geest, Sabina

2009-07-01

In the Rationing of Nursing Care in Switzerland Study, implicit rationing of care was the only factor consistently significantly associated with all six studied patient outcomes. These results highlight the importance of rationing as a new system factor regarding patient safety and quality of care. Since at least some rationing of care appears inevitable, it is important to identify the thresholds of its influences in order to minimize its negative effects on patient outcomes. To describe the levels of implicit rationing of nursing care in a sample of Swiss acute care hospitals and to identify clinically meaningful thresholds of rationing. Descriptive cross-sectional multi-center study. Five Swiss-German and three Swiss-French acute care hospitals. 1338 nurses and 779 patients. Implicit rationing of nursing care was measured using the newly developed Basel Extent of Rationing of Nursing Care (BERNCA) instrument. Other variables were measured using survey items from the International Hospital Outcomes Study battery. Data were summarized using appropriate descriptive measures, and logistic regression models were used to define a clinically meaningful rationing threshold level. For the studied patient outcomes, identified rationing threshold levels varied from 0.5 (i.e., between 0 ('never') and 1 ('rarely') to 2 ('sometimes')). Three of the identified patient outcomes (nosocomial infections, pressure ulcers, and patient satisfaction) were particularly sensitive to rationing, showing negative consequences anywhere it was consistently reported (i.e., average BERNCA scores of 0.5 or above). In other cases, increases in negative outcomes were first observed from the level of 1 (average ratings of rarely). Rationing scores generated using the BERNCA instrument provide a clinically meaningful method for tracking the correlates of low resources or difficulties in resource allocation on patient outcomes. Thresholds identified here provide parameters for administrators to respond to whenever rationing reports exceed the determined level of '0.5' or '1'. Since even very low levels of rationing had negative consequences on three of the six studied outcomes, it is advisable to treat consistent evidence of any rationing as a significant threat to patient safety and quality of care.

Analysis of space systems study for the space disposal of nuclear waste study report. Volume 2: Technical report

NASA Technical Reports Server (NTRS)

1981-01-01

Reasonable space systems concepts were systematically identified and defined and a total system was evaluated for the space disposal of nuclear wastes. Areas studied include space destinations, space transportation options, launch site options payload protection approaches, and payload rescue techniques. Systems level cost and performance trades defined four alternative space systems which deliver payloads to the selected 0.85 AU heliocentric orbit destination at least as economically as the reference system without requiring removal of the protective radiation shield container. No concepts significantly less costly than the reference concept were identified.

A comparison between the clinical significance and growth mixture modelling early change methods at predicting negative outcomes.

PubMed

Flood, Nicola; Page, Andrew; Hooke, Geoff

2018-05-03

Routine outcome monitoring benefits treatment by identifying potential no change and deterioration. The present study compared two methods of identifying early change and their ability to predict negative outcomes on self-report symptom and wellbeing measures. 1467 voluntary day patients participated in a 10-day group Cognitive Behaviour Therapy (CBT) program and completed the symptom and wellbeing measures daily. Early change, as defined by (a) the clinical significance method and (b) longitudinal modelling, was compared on each measure. Early change, as defined by the simpler clinical significance method, was superior at predicting negative outcomes than longitudinal modelling. The longitudinal modelling method failed to detect a group of deteriorated patients, and agreement between the early change methods and the final unchanged outcome was higher for the clinical significance method. Therapists could use the clinical significance early change method during treatment to alert them of patients at risk for negative outcomes, which in turn could allow therapists to prevent those negative outcomes from occurring.

Spatial earthquake hazard assessment of Evansville, Indiana

USGS Publications Warehouse

Rockaway, T.D.; Frost, J.D.; Eggert, D.L.; Luna, R.

1997-01-01

The earthquake hazard has been evaluated for a 150-square-kilometer area around Evansville, Indiana. GIS-QUAKE, a system that combines liquefaction and ground motion analysis routines with site-specific geological, geotechnical, and seismological information, was used for the analysis. The hazard potential was determined by using 586 SPT borings, 27 CPT sounding, 39 shear-wave velocity profiles and synthesized acceleration records for body-wave magnitude 6.5 and 7.3 mid-continental earthquakes, occurring at distances of 50 km and 250 km, respectively. The results of the GIS-QUAKE hazard analyses for Evansville identify areas with a high hazard potential that had not previously been identified in earthquake zonation studies. The Pigeon Creek area specifically is identified as having significant potential for liquefaction-induced damage. Damage as a result of ground motion amplification is determined to be a moderate concern throughout the area. Differences in the findings of this zonation study and previous work are attributed to the size and range of the database, the hazard evaluation methodologies, and the geostatistical interpolation techniques used to estimate the hazard potential. Further, assumptions regarding the groundwater elevations made in previous studies are also considered to have had a significant effect on the results.

Are there associations between sleep bruxism, chronic stress, and sleep quality?

PubMed

Ohlmann, Brigitte; Bömicke, Wolfgang; Habibi, Yasamin; Rammelsberg, Peter; Schmitter, Marc

2018-07-01

The purpose of this study was to identify associations between definite sleep bruxism, as defined by the American academy of sleep medicine, and chronic stress and sleep quality. Sleep bruxism was determined by use of questionnaires, assessment of clinical symptoms, and recording of electromyographic and electrocardiographic data (recorded by the Bruxoff ® device). The study included 67 participants. Of these, 38 were identified as bruxers and 29 as non-bruxers. The 38 bruxers were further classified as 17 moderate and 21 intense bruxers. Self-reported stress and self-reported sleep quality were determined by use of the validated questionnaires "Trier Inventory for the Assessment of Chronic Stress" (TICS) and the "Pittsburgh Sleep Quality Index" (PSQI). No statistically significant association was found between sleep bruxism and self-reported stress or sleep quality. However, a significant association between specific items of chronic stress and poor sleep quality was identified. The results of this study indicate an association between subjective sleep quality and subjective chronic stress, irrespective of the presence or absence of sleep bruxism. Chronic stress and sleep quality do not seem to be associated with sleep bruxism. (clinical trial no. NCT03039985). Copyright © 2018 Elsevier Ltd. All rights reserved.

Social and Behavioral Outcomes following Childhood Traumatic Brain Injury: What Predicts Outcome at 12 Months Post-Insult?

PubMed

Catroppa, Cathy; Hearps, Stephen; Crossley, Louise; Yeates, Keith; Beauchamp, Miriam; Fusella, Jessica; Anderson, Vicki

2017-04-01

This study sought to investigate social and behavioral outcomes 12 months following childhood traumatic brain injury (TBI) and to identify predictors of these outcomes. The study also compared rates of impairment in social and behavioral outcomes at 12 months post-injury between children with TBI and a typically developing (TD) control group. The study comprised 114 children ages 5.5 to 16.0 years, 79 with mild, moderate, or severe TBI and 35 TD children, group-matched for age, sex and socio-economic status. Children with TBI were recruited via consecutive hospital admissions and TD children from the community. Social and behavioral outcomes were measured via parent-rated questionnaires. Analysis of covariance models identified a significant mean difference between the mild and moderate groups for social problems only, but the moderate and severe TBI groups showed a higher rate of impairment, particularly in externalizing problems. Pre-injury function, injury severity, parent mental health, and child self-esteem all contributed significantly to predicting social and behavioral outcomes. Both injury and non-injury factors should be considered when identifying children at risk for long-term difficulties in social and behavioral domains.

NCLEX-RN performance: predicting success on the computerized examination.

PubMed

Beeman, P B; Waterhouse, J K

2001-01-01

Since the adoption of the Computerized Adaptive Testing (CAT) format of the National Certification Licensure Examination for Registered Nurses (NCLEX-RN), no studies have been reported in the literature on predictors of successful performance by baccalaureate nursing graduates on the licensure examination. In this study, a discriminant analysis was used to identify which of 21 variables can be significant predictors of success on the CAT NCLEX-RN. The convenience sample consisted of 289 individuals who graduated from a baccalaureate nursing program between 1995 and 1998. Seven significant predictor variables were identified. The total number of C+ or lower grades earned in nursing theory courses was the best predictor, followed by grades in several individual nursing courses. More than 93 per cent of graduates were correctly classified. Ninety-four per cent of NCLEX "passes" were correctly classified, as were 92 per cent of NCLEX failures. This degree of accuracy in classifying CAT NCLEX-RN failures represents a marked improvement over results reported in previous studies of licensure examinations, and suggests the discriminant function will be helpful in identifying future students in danger of failure. J Prof Nurs 17:158-165, 2001. Copyright 2001 by W.B. Saunders Company

Genetic association of impulsivity in young adults: a multivariate study

PubMed Central

Khadka, S; Narayanan, B; Meda, S A; Gelernter, J; Han, S; Sawyer, B; Aslanzadeh, F; Stevens, M C; Hawkins, K A; Anticevic, A; Potenza, M N; Pearlson, G D

2014-01-01

Impulsivity is a heritable, multifaceted construct with clinically relevant links to multiple psychopathologies. We assessed impulsivity in young adult (N~2100) participants in a longitudinal study, using self-report questionnaires and computer-based behavioral tasks. Analysis was restricted to the subset (N=426) who underwent genotyping. Multivariate association between impulsivity measures and single-nucleotide polymorphism data was implemented using parallel independent component analysis (Para-ICA). Pathways associated with multiple genes in components that correlated significantly with impulsivity phenotypes were then identified using a pathway enrichment analysis. Para-ICA revealed two significantly correlated genotype–phenotype component pairs. One impulsivity component included the reward responsiveness subscale and behavioral inhibition scale of the Behavioral-Inhibition System/Behavioral-Activation System scale, and the second impulsivity component included the non-planning subscale of the Barratt Impulsiveness Scale and the Experiential Discounting Task. Pathway analysis identified processes related to neurogenesis, nervous system signal generation/amplification, neurotransmission and immune response. We identified various genes and gene regulatory pathways associated with empirically derived impulsivity components. Our study suggests that gene networks implicated previously in brain development, neurotransmission and immune response are related to impulsive tendencies and behaviors. PMID:25268255

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

Novel genes identified in a high-density genome wide association study for nicotine dependence.

PubMed

Bierut, Laura Jean; Madden, Pamela A F; Breslau, Naomi; Johnson, Eric O; Hatsukami, Dorothy; Pomerleau, Ovide F; Swan, Gary E; Rutter, Joni; Bertelsen, Sarah; Fox, Louis; Fugman, Douglas; Goate, Alison M; Hinrichs, Anthony L; Konvicka, Karel; Martin, Nicholas G; Montgomery, Grant W; Saccone, Nancy L; Saccone, Scott F; Wang, Jen C; Chase, Gary A; Rice, John P; Ballinger, Dennis G

2007-01-01

Tobacco use is a leading contributor to disability and death worldwide, and genetic factors contribute in part to the development of nicotine dependence. To identify novel genes for which natural variation contributes to the development of nicotine dependence, we performed a comprehensive genome wide association study using nicotine dependent smokers as cases and non-dependent smokers as controls. To allow the efficient, rapid, and cost effective screen of the genome, the study was carried out using a two-stage design. In the first stage, genotyping of over 2.4 million single nucleotide polymorphisms (SNPs) was completed in case and control pools. In the second stage, we selected SNPs for individual genotyping based on the most significant allele frequency differences between cases and controls from the pooled results. Individual genotyping was performed in 1050 cases and 879 controls using 31 960 selected SNPs. The primary analysis, a logistic regression model with covariates of age, gender, genotype and gender by genotype interaction, identified 35 SNPs with P-values less than 10(-4) (minimum P-value 1.53 x 10(-6)). Although none of the individual findings is statistically significant after correcting for multiple tests, additional statistical analyses support the existence of true findings in this group. Our study nominates several novel genes, such as Neurexin 1 (NRXN1), in the development of nicotine dependence while also identifying a known candidate gene, the beta3 nicotinic cholinergic receptor. This work anticipates the future directions of large-scale genome wide association studies with state-of-the-art methodological approaches and sharing of data with the scientific community.

Adenotonsillectomy for Obstructive Sleep Apnea and Quality of Life: Systematic Review and Meta-analysis.

PubMed

Todd, Cameron A; Bareiss, Anna K; McCoul, Edward D; Rodriguez, Kimsey H

2017-11-01

Objective To determine the impact of adenotonsillectomy on the quality of life of pediatric patients with obstructive sleep apnea (OSA) and to identify gaps in the current research. Data Sources The MEDLINE, EMBASE, and Cochrane databases were systematically searched via the Ovid portal on June 18, 2016, for English-language articles. Review Methods Full-text articles were selected that studied boys and girls <18 years of age who underwent adenotonsillectomy for OSA or sleep-disordered breathing and that recorded validated, quantitative quality-of-life outcomes. Studies that lacked such measures, performed adenotonsillectomy for indications other than OSA or sleep-disordered breathing, or grouped adenotonsillectomy with other procedures were excluded. Results Of the 328 articles initially identified, 37 were included for qualitative analysis. The level of evidence was generally low. All studies involving short-term follow-up (≤6 months) showed improvement in quality-of-life scores after adenotonsillectomy as compared with preoperative values. Studies involving long-term follow-up (>6 months) showed mixed results. Modifications to and concurrent procedures with conventional adenotonsillectomy were also identified that showed quality-of-life improvements. Three studies were identified for meta-analysis that compared pre- and postoperative Obstructive Sleep Apnea-18 scores. Short- and long-term follow-up versus preoperative scores showed significant improvement ( P < .001). Short- and long-term scores showed no significant difference. Conclusion This systematic review and meta-analysis demonstrate adenotonsillectomy's effectiveness in improving the quality of life of pediatric patients with OSA. This is well demonstrated in the short term and has strong indications in the long term.

Using natural language processing for identification of herpes zoster ophthalmicus cases to support population-based study.

PubMed

Zheng, Chengyi; Luo, Yi; Mercado, Cheryl; Sy, Lina; Jacobsen, Steven J; Ackerson, Brad; Lewin, Bruno; Tseng, Hung Fu

2018-06-19

Diagnosis codes are inadequate for accurately identifying herpes zoster ophthalmicus (HZO). There is significant lack of population-based studies on HZO due to the high expense of manual review of medical records. To assess whether HZO can be identified from the clinical notes using natural language processing (NLP). To investigate the epidemiology of HZO among HZ population based on the developed approach. A retrospective cohort analysis. A total of 49,914 southern California residents aged over 18 years, who had a new diagnosis of HZ. An NLP-based algorithm was developed and validated with the manually curated validation dataset (n=461). The algorithm was applied on over 1 million clinical notes associated with the study population. HZO versus non-HZO cases were compared by age, sex, race, and comorbidities. We measured the accuracy of NLP algorithm. NLP algorithm achieved 95.6% sensitivity and 99.3% specificity. Compared to the diagnosis codes, NLP identified significant more HZO cases among HZ population (13.9% versus 1.7%). Compared to the non-HZO group, the HZO group was older, had more males, had more Whites, and had more outpatient visits. We developed and validated an automatic method to identify HZO cases with high accuracy. As one of the largest studies on HZO, our finding emphasizes the importance of preventing HZ in the elderly population. This method can be a valuable tool to support population-based studies and clinical care of HZO in the era of big data. This article is protected by copyright. All rights reserved.

A Population-Based Study of the Incidence of Burning Mouth Syndrome

PubMed Central

Kohorst, John J.; Bruce, Alison J.; Torgerson, Rochelle R.; Schenck, Louis A.; Davis, Mark D. P.

2015-01-01

Objective To calculate the incidence of burning mouth syndrome (BMS) in Olmsted County, Minnesota, from 2000 to 2010. Patients and Methods Using the medical record linkage system of the Rochester Epidemiology Project, we identified newly diagnosed cases of BMS from January 1, 2000, through December 31, 2010. Diagnoses were confirmed through the presence of burning pain symptoms of the oral mucosa with normal oral examination findings and no associated clinical signs. Incidence was estimated using decennial census data for Olmsted County. Results In total, 169 incident cases were identified, representing an annual age- and sex-adjusted incidence of BMS of 11.4 per 100,000 person-years. Age-adjusted incidence was significantly higher in women than men (18.8 [95% CI, 16.4–22.9] vs 3.7 [95% CI, 2.6–5.7] per 100,000 person-years [P<.001]). Postmenopausal women aged 50 to 89 years had the highest disease incidence, with the maximal rate in women aged 70 to 79 years (70.3 per 100,000 person-years). After age 50 years, BMS incidence in men and women significantly increased across age-groups (P=.02). Olmsted County study participants were predominantly white, which is a study limitation. In addition, diagnostic criteria for identifying BMS in the present study may not apply for all situations because no diagnostic criteria are universally recognized for identifying BMS. Conclusion To our knowledge, this is the first population-based incidence study of BMS reported to date. The data show that BMS is an uncommon disease highly associated with female sex and advancing age. PMID:25176397

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.

Impact of Chronic Condition Status and Severity on the Time to First Dental Visit for Newly Medicaid-Enrolled Children in Iowa

PubMed Central

Chi, Donald L; Momany, Elizabeth T; Neff, John; Jones, Michael P; Warren, John J; Slayton, Rebecca L; Weber-Gasparoni, Karin; Damiano, Peter C

2011-01-01

Objective To assess the extent to which chronic condition (CC) status and severity affected how soon children had a dental visit after enrolling in Medicaid. Data Source Enrollment and claims data (2003–2008) for newly Medicaid-enrolled children ages 3–14 in Iowa. Study Design 3M Clinical Risk Grouping methods were used to identify CC status (no/yes) and CC severity (less severe/more severe). Survival analysis was used to identify the factors associated with earlier first dental visits after initially enrolling in Medicaid. Principal Findings Children with a CC were 17 percent more likely to have earlier first dental visits after enrolling in Medicaid (p<.0001). There was no significant difference by CC severity. Children who lived in a dental health professional shortage area and those who did not utilize primary medical care had significantly later first Medicaid dental visits, whereas these factors failed to reach statistical significance for children with a CC. Conclusion While newly Medicaid-enrolled children with a CC were significantly more likely to have earlier first dental visits, we failed to detect a relationship between CC severity and the time to first Medicaid dental visit. The determinants of first Medicaid dental visits were heterogeneous across subgroups of newly Medicaid-enrolled children. Future studies should identify the sociobehavioral factors associated with CCs that are potential barriers to earlier first Medicaid dental visits for newly Medicaid-enrolled children. PMID:20849559

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

Yield, Composition and Antioxidant Capacity of the Essential Oil of Sweet Basil and Holy Basil as Influenced by Distillation Methods.

PubMed

Shiwakoti, Santosh; Saleh, Osama; Poudyal, Shital; Barka, Abdulssamad; Qian, Yanping; Zheljazkov, Valtcho D

2017-04-01

The profile and bioactivity of essential oil (EO) depends on genetic, environmental, and other factors. We hypothesized that the basil EO may be influenced by the distillation methods. Hence, a study was conducted to evaluate the effect of steam distillation (SD) and hydrodistillation (HD) extraction method on the yield, composition, and bioactivity of EO of sweet basil (Ocimum basilicum) and holy basil (Ocimum tenuiflorum). In both basil species, the EO yield (content) was significantly higher from SD than from HD. There were significant differences in the compounds' concentrations of EO obtained from SD and HD as well, however, the same compounds were identified in the EO from HD and SD. In the EO of O. basilicum, the concentration of 74% of the identified compounds were higher in SD than HD, whereas in the EO of O. tenuiflorum, the concentration of 84% of identified compounds were higher in SD than in HD. However, the concentrations of two of the major compounds of O. basilicum EO (estragole and methyl cinnamate) and a major compound of O. tenuiflorum EO (methyl eugenol) were significantly higher in HD than in SD. The type of distillation did not affect the antioxidant capacity of basil EO within the species. This study demonstrated that the type of distillation may significantly affect oil yield and composition but not the antioxidant capacity of the EO from sweet and holy basil. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Determinants of practice nurses' intention to implement a new smoking cessation intervention: the importance of attitude and innovation characteristics.

PubMed

Smit, Eline Suzanne; de Vries, Hein; Hoving, Ciska

2013-12-01

To identify determinants of practice nurses' intention to implement a new smoking cessation intervention and to investigate the independent value of attitude and Rogers' innovation characteristics. While effective smoking cessation interventions exist, implementation is often suboptimal. No previous studies have disentangled the independent value of beliefs towards implementation and innovation characteristics in explaining implementation. A cross-sectional descriptive study. In 2010, 56 of 91 general practice nurses who participated in an intervention effectiveness trial completed an online questionnaire concerning demographics, patient population characteristics, attitude, innovation characteristics, self-efficacy, perceived social influence and intention to implement the intervention in the future. Recruitment success during the trial was defined as the number of patients participating. To detect differences between intending and non-intending practice nurses, independent sample t-tests and Chi-squared tests were conducted. Correlation coefficients were calculated to identify associations between potential determinants of intention. To identify significant determinants logistic hierarchical regression analyses were conducted. Innovation characteristics and attitude were both significantly associated with practice nurses' intention to implement. While recruitment success showed a significant positive association with intention, perceived patient support was only a significant determinant when including innovation characteristics or attitude. To increase new interventions' implementation rates, it is most important to convince health professionals of its beneficial characteristics, to generate a positive attitude towards the intervention, to aid practice nurses in recruiting smoking patients and to increase perceived patient support. © 2013 John Wiley & Sons Ltd.

Success in baccalaureate nursing programs: a matter of accommodation?

PubMed

Haislett, J; Hughes, R B; Atkinson, G; Williams, C L

1993-02-01

This article explores student learning styles as an important variable in four-year baccalaureate nursing programs. Student learning styles were assessed by Kolb's Learning Style Inventory-1985 (LSI-1985), which identifies the accommodator, diverger, assimilator, and converger learning styles. The authors examined the relationship between learning style and academic performance as measured by grade-point ratio (GPR) and studied behaviors and attitudes as measured by Brown and Holtzman's (1964) Survey of Study Habits and Attitudes. Analysis indicated that this sample (N = 100) included mainly assimilators and divergers, making reflective observation the most common mode of learning. Compared to the accommodator/converger group, the assimilator/diverger group earned a significantly higher GPR, significantly better scores on the study habits variable of Work Methods (WM), and moderately better scores on the study attitude variable of Educational Acceptance (EA). Accommodators were identified as the most at-risk learning style group, and specific interventions were suggested to assist accommodators in adapting to the academic rigors of a nursing curriculum.

Discovery and validation of sub-threshold genome-wide association study loci using epigenomic signatures

PubMed Central

Wang, Xinchen; Tucker, Nathan R; Rizki, Gizem; Mills, Robert; Krijger, Peter HL; de Wit, Elzo; Subramanian, Vidya; Bartell, Eric; Nguyen, Xinh-Xinh; Ye, Jiangchuan; Leyton-Mange, Jordan; Dolmatova, Elena V; van der Harst, Pim; de Laat, Wouter; Ellinor, Patrick T; Newton-Cheh, Christopher; Milan, David J; Kellis, Manolis; Boyer, Laurie A

2016-01-01

Genetic variants identified by genome-wide association studies explain only a modest proportion of heritability, suggesting that meaningful associations lie 'hidden' below current thresholds. Here, we integrate information from association studies with epigenomic maps to demonstrate that enhancers significantly overlap known loci associated with the cardiac QT interval and QRS duration. We apply functional criteria to identify loci associated with QT interval that do not meet genome-wide significance and are missed by existing studies. We demonstrate that these 'sub-threshold' signals represent novel loci, and that epigenomic maps are effective at discriminating true biological signals from noise. We experimentally validate the molecular, gene-regulatory, cellular and organismal phenotypes of these sub-threshold loci, demonstrating that most sub-threshold loci have regulatory consequences and that genetic perturbation of nearby genes causes cardiac phenotypes in mouse. Our work provides a general approach for improving the detection of novel loci associated with complex human traits. DOI: http://dx.doi.org/10.7554/eLife.10557.001 PMID:27162171

Identifying influential nodes in complex networks: A node information dimension approach

NASA Astrophysics Data System (ADS)

Bian, Tian; Deng, Yong

2018-04-01

In the field of complex networks, how to identify influential nodes is a significant issue in analyzing the structure of a network. In the existing method proposed to identify influential nodes based on the local dimension, the global structure information in complex networks is not taken into consideration. In this paper, a node information dimension is proposed by synthesizing the local dimensions at different topological distance scales. A case study of the Netscience network is used to illustrate the efficiency and practicability of the proposed method.

Methodological quality of teaching communication skills to undergraduate medical students: a mapping review.

PubMed

Sanson-Fisher, Rob; Hobden, Breanne; Waller, Amy; Dodd, Natalie; Boyd, Lucy

2018-06-27

Patient-clinician communication training is a core component of the undergraduate medical program. As with all areas of medicine, the best available evidence for teaching these skills should be incorporated into training programs. Examining the volume, type and design-quality of publications in this field can help to determine whether research is following a natural scientific progression to inform interactional skills training. This study aimed to review: (i) whether the proportion of publications examining teaching interactional skills to undergraduate medical students by study type, across three time-periods (2007-2008, 2011-2012, 2015-2016), changed over time (i.e. measurement, descriptive or interventions studies); and (ii) the proportion of intervention studies meeting Cochrane Effective Practice and Organisation of Care (EPOC) research design criteria. Medline, PubMed, PsycInfo and the Cochrane Database were searched for studies published in English from 2007 to 2016. Title and abstract reviews were performed for the included years. Articles were examined against the inclusion/exclusion criteria and those included were coded into descriptive, measurement or intervention categories. A total of 243 relevant publications were identified. Fifty-two were published from 2007 to 2008, 75 from 2011 to 2012 and 116 from 2015 to 2016. Most identified studies were descriptive (63%), followed by measurement studies (22%) and intervention studies (15%). The proportion of descriptive studies increased significantly over time. However, the proportion of intervention studies did not change and the proportion of measures studies significantly decreased. Of the 37 intervention studies identified within the three time-periods, only 16 (43%) met EPOC study design criteria. The largest proportion of identified studies were descriptive, however, descriptive research is not sufficient to ensure communication skills training can effectively improve interactions between clinicians and patients. A more rigorous approach to research in this area is needed to inform education strategies.

Positive concomitant test reactions to allergens in the standard patch test series.

PubMed

Landeck, Lilla; González, Ernesto; Baden, Lynn; Neumann, Konrad; Schalock, Peter

2010-05-01

Patch testing is performed to evaluate suspected allergic contact dermatitis. Common wisdom suggests that various allergens cross-react but only a few larger studies have published confirmations of this. The purpose of our study was to identify significant correlations between positive test reactions in a screening series. A total of 1235 patients undergoing patch testing to the Hermal standard series at the Massachusetts General Hospital, Contact Dermatitis Clinic between 1990 and 2006 were investigated. Two or more positive reactions were seen in 411 patients (33.3%). Sensitizations to eight pairs of allergens were found to have significant correlation (P

Does Quality of Radiotherapy Predict Outcomes of Multicentre Cooperative Group Trials? A Literature Review

PubMed Central

Fairchild, Alysa; Straube, William; Laurie, Fran; Followill, David

2013-01-01

Central review of radiotherapy (RT) delivery within multicentre clinical trials was initiated in the early 1970’s in the USA. Early quality assurance (QA) publications often focused on metrics related to process, logistics and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. Medline search was performed to identify multicentre studies which described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicentre studies (1980–2012) were identified, plus one Patterns of Care Study. Disease sites were hematologic, head and neck, lung, breast and pancreas. Between 0% and 97% of treatment plans received an overall grade of acceptable. In seven trials, failure rates were significantly higher after inadequate versus adequate RT. 5/9 and 2/5 trials reported significantly worse overall and progression-free survival after poor quality RT, respectively. One reported a significant correlation and two reported non-significant trends towards increased toxicity with non-compliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question. PMID:23683829

Genome-Wide Association Study Identifies Common Genetic Variants Associated with Salivary Gland Carcinoma and its Subtypes

PubMed Central

Xu, Li; Tang, Hongwei; Chen, Diane W.; El-Naggar, Adel K.; Wei, Peng; Sturgis, Erich M.

2015-01-01

BACKGROUND Salivary gland carcinomas (SGCs) are a rare malignancy with unknown etiology. We aimed to identify genetic variants modifying risk of SGC and its major subtypes, adenoid cystic carcinoma (ACCA) and mucoepidermoid carcinoma (MECA). METHODS We conducted a genome-wide association study in 309 well-defined SGC cases and 535 cancer-free controls. We performed a SNP-level discovery study in non-Hispanic whites followed by a replication study in Hispanics. A logistic regression was applied to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs). A meta-analysis was conducted of the results. RESULTS Genome-wide significant association with SGC in non-Hispanic whites was detected at coding SNPs in CHRNA2 (OR=8.55, 95%CI: 4.53–16.13, P = 3.6 × 10−11), OR4F15 (OR=5.26, 95%CI: 3.13–8.83, P = 3.5 × 10−10), ZNF343 (OR=3.28, 95%CI: 2.12–5.07, P = 9.1 × 10−8), and PARP4 (OR=2.00, 95%CI: 1.54–2.59, P = 1.7 × 10−7). Meta-analysis of the non-Hispanic white and Hispanic cohorts identified another genome-wide significant SNP in ELL2 (meta-OR=1.86, 95%CI: 1.48–2.34, P = 1.3 × 10−7). Risk alleles largely enriched in MECA, where the SNPs in CHRNA2, OR4F15, and ZNF343 had ORs of 15.71 (95%CI: 6.59–37.47, P = 5.2 × 10−10), 15.60 (95%CI: 6.50–37.41, P = 7.5 × 10−10), and 6.49 (95%CI: 3.36–12.52, P = 2.5 × 10−8), respectively. None of these SNPs retained significant association with ACCA. CONCLUSIONS These findings, for the first time, identify a panel of SNPs associated with SGC risk. Confirmation of these findings along with functional analysis of identified SNPs are needed. PMID:25823930

Genome-wide association study identifies common genetic variants associated with salivary gland carcinoma and its subtypes.

PubMed

Xu, Li; Tang, Hongwei; Chen, Diane W; El-Naggar, Adel K; Wei, Peng; Sturgis, Erich M

2015-07-15

Salivary gland carcinomas (SGCs) are a rare malignancy with unknown etiology. The objective of the current study was to identify genetic variants modifying the risk of SGC and its major subtypes: adenoid cystic carcinoma and mucoepidermoid carcinoma. The authors conducted a genome-wide association study in 309 well-defined SGC cases and 535 cancer-free controls. A single-nucleotide polymorphism (SNP)-level discovery study was performed in non-Hispanic white individuals followed by a replication study in Hispanic individuals. A logistic regression analysis was applied to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). A meta-analysis of the results was conducted. A genome-wide significant association with SGC in non-Hispanic white individuals was detected at coding SNPs in CHRNA2 (cholinergic receptor, nicotinic, alpha 2 [neuronal]) (OR, 8.55; 95% CI, 4.53-16.13 [P = 3.6 × 10(-11)]), OR4F15 (olfactory receptor, family 4, subfamily F, member 15) (OR, 5.26; 95% CI, 3.13-8.83 [P = 3.5 × 10(-10)]), ZNF343 (zinc finger protein 343) (OR, 3.28; 95% CI, 2.12-5.07 [P = 9.1 × 10(-8)]), and PARP4 (poly(ADP-ribose) polymerase family, member 4) (OR, 2.00; 95% CI, 1.54-2.59 [P = 1.7 × 10(-7)]). Meta-analysis of the non-Hispanic white and Hispanic cohorts identified another genome-wide significant SNP in ELL2 (meta-OR, 1.86; 95% CI, 1.48-2.34 [P = 1.3 × 10(-7)]). Risk alleles were largely enriched in mucoepidermoid carcinoma, in which the SNPs in CHRNA2, OR4F15, and ZNF343 had ORs of 15.71 (95% CI, 6.59-37.47 [P = 5.2 × 10(-10)]), 15.60 (95% CI, 6.50-37.41 [P = 7.5 × 10(-10)]), and 6.49 (95% CI, 3.36-12.52 [P = 2.5 × 10(-8)]), respectively. None of these SNPs retained a significant association with adenoid cystic carcinoma. To the best of the authors' knowledge, the current study is the first to identify a panel of SNPs associated with the risk of SGC. Confirmation of these findings along with functional analysis of identified SNPs are needed. © 2015 American Cancer Society.

Is It Feasible to Identify Natural Clusters of TSC-Associated Neuropsychiatric Disorders (TAND)?

PubMed

Leclezio, Loren; Gardner-Lubbe, Sugnet; de Vries, Petrus J

2018-04-01

Tuberous sclerosis complex (TSC) is a genetic disorder with multisystem involvement. The lifetime prevalence of TSC-Associated Neuropsychiatric Disorders (TAND) is in the region of 90% in an apparently unique, individual pattern. This "uniqueness" poses significant challenges for diagnosis, psycho-education, and intervention planning. To date, no studies have explored whether there may be natural clusters of TAND. The purpose of this feasibility study was (1) to investigate the practicability of identifying natural TAND clusters, and (2) to identify appropriate multivariate data analysis techniques for larger-scale studies. TAND Checklist data were collected from 56 individuals with a clinical diagnosis of TSC (n = 20 from South Africa; n = 36 from Australia). Using R, the open-source statistical platform, mean squared contingency coefficients were calculated to produce a correlation matrix, and various cluster analyses and exploratory factor analysis were examined. Ward's method rendered six TAND clusters with good face validity and significant convergence with a six-factor exploratory factor analysis solution. The "bottom-up" data-driven strategies identified a "scholastic" cluster of TAND manifestations, an "autism spectrum disorder-like" cluster, a "dysregulated behavior" cluster, a "neuropsychological" cluster, a "hyperactive/impulsive" cluster, and a "mixed/mood" cluster. These feasibility results suggest that a combination of cluster analysis and exploratory factor analysis methods may be able to identify clinically meaningful natural TAND clusters. Findings require replication and expansion in larger dataset, and could include quantification of cluster or factor scores at an individual level. Copyright © 2018 Elsevier Inc. All rights reserved.

Genotype-by-sequencing facilitates genetic mapping of a stem rust resistance locus in Aegilops umbellulata, a wild relative of cultivated wheat.

PubMed

Edae, Erena A; Olivera, Pablo D; Jin, Yue; Poland, Jesse A; Rouse, Matthew N

2016-12-15

Wild relatives of wheat play a significant role in wheat improvement as a source of genetic diversity. Stem rust disease of wheat causes significant yield losses at the global level and stem rust pathogen race TTKSK (Ug99) is virulent to most previously deployed resistance genes. Therefore, the objective of this study was to identify loci conferring resistance to stem rust pathogen races including Ug99 in an Aegilops umbelluata bi-parental mapping population using genotype-by-sequencing (GBS) SNP markers. A bi-parental F 2:3 population derived from a cross made between stem rust resistant accession PI 298905 and stem rust susceptible accession PI 542369 was used for this study. F 2 individuals were evaluated with stem rust race TTTTF followed by testing F 2:3 families with races TTTTF and TTKSK. The segregation pattern of resistance to both stem rust races suggested the presence of one resistance gene. A genetic linkage map, comprised 1,933 SNP markers, was created for all seven chromosomes of Ae. umbellulata using GBS. A major stem rust resistance QTL that explained 80% and 52% of the phenotypic variations for TTTTF and TTKSK, respectively, was detected on chromosome 2U of Ae. umbellulata. The novel resistance gene for stem rust identified in this study can be transferred to commercial wheat varieties assisted by the tightly linked markers identified here. These markers identified through our mapping approach can be a useful strategy to identify and track the resistance gene in marker-assisted breeding in wheat.

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

Functional outcomes of conservatively managed acute ruptures of the Achilles tendon.

PubMed

Lawrence, J E; Nasr, P; Fountain, D M; Berman, L; Robinson, A H N

2017-01-01

This prospective cohort study aims to determine if the size of the tendon gap following acute rupture of the Achilles tendon shows an association with the functional outcome following non-operative treatment. All patients presenting within two weeks of an acute unilateral rupture of the Achilles tendon between July 2012 and July 2015 were considered for the study. In total, 38 patients (nine female, 29 male, mean age 52 years; 29 to 78) completed the study. Dynamic ultrasound examination was performed to confirm the diagnosis and measure the gap between ruptured tendon ends. Outcome was assessed using dynamometric testing of plantarflexion and the Achilles tendon Total Rupture score (ATRS) six months after the completion of a rehabilitation programme. Patients with a gap ≥ 10 mm with the ankle in the neutral position had significantly greater peak torque deficit than those with gaps < 10 mm (mean 23.3%; 7% to 52% vs 14.3%; 0% to 47%, p = 0.023). However, there was no difference in ATRS between the two groups (mean score 87.2; 74 to 100 vs 87.4; 68 to 97, p = 0.467). There was no significant correlation between gap size and torque deficit (τ = 0.103), suggesting a non-linear relationship. There was also no significant correlation between ATRS and peak torque deficit (τ = -0.305). This is the first study to identify an association between tendon gap and functional outcome in acute rupture of the Achilles tendon. We have identified 10 mm as a gap size at which deficits in plantarflexion strength become significantly greater, however, the precise relationship between gap size and plantarflexion strength remains unclear. Large, multicentre studies will be needed to clarify this relationship and identify population subgroups in whom deficits in peak torque are reflected in patient-reported outcome measures. Cite this article: Bone Joint J 2017;99-B:87-93. ©2017 The British Editorial Society of Bone & Joint Surgery.

Feminist music therapy pedagogy: a survey of music therapy educators.

PubMed

Hahna, Nicole D; Schwantes, Melody

2011-01-01

This study surveyed 188 music therapy educators regarding their views and use of feminist pedagogy and feminist music therapy. The purpose of this study was two-fold: (a) to determine how many music therapy educators used feminist pedagogy and (b) to determine if there was a relationship between the use of feminist pedagogy and academic rank of the participants. Seventy-two participants responded to this study, with 69 participants included for data analysis. Stake and Hoffman's (2000) feminist pedagogy survey was adapted for this study, examining four subscales of feminist pedagogy: (a) participatory learning, (b) validation of personal experience/development of confidence, (c) political/ social activism, and (d) critical thinking/open-mindedness. The results revealed that 46% (n=32) of participants identified as feminist music therapists and 67% (n=46) of participants identified as using feminist pedagogy. Results of a mixed analysis of variance revealed a statistically significant difference within the four survey subscales (p<.0001), no significant difference (p=.32) for academic rank, and no significant interaction (p=.08) of academic rank and the four survey subscales. Tukey's post hoc analysis of the data indicated that the survey subscale measuring political activism (p<.0001) was significantly lower than the other three survey subscales. In addition, a qualitative analysis on open-ended responses is also included. Discussion of the results, limitations, and areas for future research are addressed.

Risk factors of significant pain syndrome 90 days after minor thoracic injury: trajectory analysis.

PubMed

Daoust, Raoul; Emond, Marcel; Bergeron, Eric; LeSage, Natalie; Camden, Stéphanie; Guimont, Chantal; Vanier, Laurent; Chauny, Jean-Marc

2013-11-01

The objective was to identify the risk factors of clinically significant pain at 90 days in patients with minor thoracic injury (MTI) discharged from the emergency department (ED). A prospective, multicenter, cohort study was conducted in four Canadian EDs from November 2006 to November 2010. All consecutive patients aged 16 years or older with MTI were eligible at discharge from EDs. They underwent standardized clinical and radiologic evaluations at 1 and 2 weeks, followed by standardized telephone interviews at 30 and 90 days. A pain trajectory model characterized groups of patients with different pain evolutions and ascertained specific risk factors in each group through multivariate analysis. In this cohort of 1,132 patients, 734 were eligible for study inclusion. The authors identified a pain trajectory that characterized 18.2% of the study population experiencing clinically significant pain (>3 of 10) at 90 days after a MTI. Multivariate modeling found two or more rib fractures, smoking, and initial oxygen saturation below 95% to be predictors of this group of patients. To the authors' knowledge, this is the first prospective study of trajectory modeling to detect risk factors associated with significant pain at 90 days after MTI. These factors may help in planning specific treatment strategies and should be validated in another prospective cohort. © 2013 by the Society for Academic Emergency Medicine.

The use of the temporal scan statistic to detect methicillin-resistant Staphylococcus aureus clusters in a community hospital.

PubMed

Faires, Meredith C; Pearl, David L; Ciccotelli, William A; Berke, Olaf; Reid-Smith, Richard J; Weese, J Scott

2014-07-08

In healthcare facilities, conventional surveillance techniques using rule-based guidelines may result in under- or over-reporting of methicillin-resistant Staphylococcus aureus (MRSA) outbreaks, as these guidelines are generally unvalidated. The objectives of this study were to investigate the utility of the temporal scan statistic for detecting MRSA clusters, validate clusters using molecular techniques and hospital records, and determine significant differences in the rate of MRSA cases using regression models. Patients admitted to a community hospital between August 2006 and February 2011, and identified with MRSA>48 hours following hospital admission, were included in this study. Between March 2010 and February 2011, MRSA specimens were obtained for spa typing. MRSA clusters were investigated using a retrospective temporal scan statistic. Tests were conducted on a monthly scale and significant clusters were compared to MRSA outbreaks identified by hospital personnel. Associations between the rate of MRSA cases and the variables year, month, and season were investigated using a negative binomial regression model. During the study period, 735 MRSA cases were identified and 167 MRSA isolates were spa typed. Nine different spa types were identified with spa type 2/t002 (88.6%) the most prevalent. The temporal scan statistic identified significant MRSA clusters at the hospital (n=2), service (n=16), and ward (n=10) levels (P ≤ 0.05). Seven clusters were concordant with nine MRSA outbreaks identified by hospital staff. For the remaining clusters, seven events may have been equivalent to true outbreaks and six clusters demonstrated possible transmission events. The regression analysis indicated years 2009-2011, compared to 2006, and months March and April, compared to January, were associated with an increase in the rate of MRSA cases (P ≤ 0.05). The application of the temporal scan statistic identified several MRSA clusters that were not detected by hospital personnel. The identification of specific years and months with increased MRSA rates may be attributable to several hospital level factors including the presence of other pathogens. Within hospitals, the incorporation of the temporal scan statistic to standard surveillance techniques is a valuable tool for healthcare workers to evaluate surveillance strategies and aid in the identification of MRSA clusters.

The impact of cognitive impairment, neurological soft signs and subdepressive symptoms on functional outcome in bipolar disorder.

PubMed

Baş, Tuba Öcek; Poyraz, Cana Aksoy; Baş, Alper; Poyraz, Burç Çağrı; Tosun, Musa

2015-03-15

Cognitive impairments and subsyndromal depressive symptoms are present during euthymic periods of bipolar disorder (BD). Most studies have determined that cognitive impairments and residual depressive symptoms have major impacts on psychosocial functioning. The aim of the present study was to identify the major factor responsible for low psychosocial functioning in a subgroup of patients with BD despite clinical recovery. Sixty patients with bipolar I disorder and 41 healthy subjects were enrolled in this study. Cognitive performance, neurological soft signs (NSSs), psychosocial functioning, residual mood symptoms and illness characteristics were assessed. Using the median value of the Functioning Assessment Short Test (FAST) as the cut-off point, the patients were divided into two groups, high- (n=29) or low-functioning (n=31), and they were compared based on total NSS, residual depressive symptoms, cognitive performance and clinical variables. Performances on the verbal memory tests and social functioning were significantly worse in the euthymic patients with BD. Increased rates of NSS were identified in the patients compared with the normal controls. The low-functioning patients performed significantly worse on verbal memory, and their NSS and residual depressive symptoms were significantly higher compared to high-functioning patients. In the regression analysis, subsyndromal depressive symptoms and verbal learning measures were identified as the best predictors of psychosocial functioning. The patients were artificially separated into two groups based on a FAST score cut-off. In this study, residual depressive symptoms and verbal memory impairments were the most prominent factors associated with the level of functioning. Copyright © 2014 Elsevier B.V. All rights reserved.

Comprehensive analysis of single- and multi-vehicle large truck at-fault crashes on rural and urban roadways in Alabama.

PubMed

Islam, Samantha; Jones, Steven L; Dye, Daniel

2014-06-01

The research described in this paper analyzed injury severities at a disaggregate level for single-vehicle (SV) and multi-vehicle (MV) large truck at-fault accidents for rural and urban locations in Alabama. Given the occurrence of a crash, four separate random parameter logit models of injury severity (with possible outcomes of major, minor, and possible or no injury) were estimated. The models identified different sets of factors that can lead to effective policy decisions aimed at reducing large truck-at-fault accidents for respective locations. The results of the study clearly indicated that there are differences between the influences of a variety of variables on the injury severities resulting from urban vs. rural SV and MV large truck at-fault accidents. The results showed that some variables were significant only in one type of accident model (SV or MV) but not in the other accident model. Again, some variables were found to be significant in one location (rural or urban) but not in other locations. The study also identified important factors that significantly impact the injury severity resulting from SV and MV large truck at-fault accidents in urban and rural locations based on the estimated values of average direct pseudo-elasticity. A careful study of the results of this study will help policy makers and transportation agencies identify location specific recommendations to increase safety awareness related to large truck involved accidents and to improve overall highway safety. Copyright © 2014 Elsevier Ltd. All rights reserved.

Reflex Cough and Disease Duration as Predictors of Swallowing Dysfunction in Parkinson's Disease.

PubMed

Troche, Michelle S; Schumann, Beate; Brandimore, Alexandra E; Okun, Michael S; Hegland, Karen W

2016-12-01

Patients with Parkinson's disease (PD) have progressive and pervasive disorders of airway protection. Recent work has highlighted the relationship between reflex and voluntary cough and swallowing safety. The goal of this study was to test the sensitivity and specificity of several airway protective and disease-specific factors for predicting swallowing safety outcomes in PD. Sixty-four participants (44 males) completed measures of voluntary and reflex cough, and swallowing safety. Clinical predictors included disease severity and duration, and cough airflow and sensitivity measures. ROC and Chi-square analyses identified predictors of swallowing safety (penetration-aspiration score) in PD. Disease duration significantly discriminated between patients with normal and abnormal swallowing safety (p = 0.027, sensitivity: 71 %, specificity: 55.4 %). Cough reflex sensitivity significantly discriminated between patients who penetrated above the level of the vocal folds and those with more severe penetration/aspiration (p = 0.021, sensitivity: 71.0 %, specificity 57.6 %). Urge-to-cough sensitivity (log-log linear slope) was the only variable which significantly discriminated between patients with penetration versus aspiration (p = 0.017, sensitivity: 85.7 %, specificity 73.2 %). It is important to identify the factors which influence airway protective outcomes in PD especially given that aspiration pneumonia is a leading cause of death. Results from this study highlight the ecological validity of reflex cough in the study of airway protection and this study further identifies important factors to consider in the screening of airway protective deficits in PD.

Genome-Wide Association Study for Susceptibility to and Recoverability From Mastitis in Danish Holstein Cows.

PubMed

Welderufael, B G; Løvendahl, Peter; de Koning, Dirk-Jan; Janss, Lucas L G; Fikse, W F

2018-01-01

Because mastitis is very frequent and unavoidable, adding recovery information into the analysis for genetic evaluation of mastitis is of great interest from economical and animal welfare point of view. Here we have performed genome-wide association studies (GWAS) to identify associated single nucleotide polymorphisms (SNPs) and investigate the genetic background not only for susceptibility to - but also for recoverability from mastitis. Somatic cell count records from 993 Danish Holstein cows genotyped for a total of 39378 autosomal SNP markers were used for the association analysis. Single SNP regression analysis was performed using the statistical software package DMU. Substitution effect of each SNP was tested with a t -test and a genome-wide significance level of P -value < 10 -4 was used to declare significant SNP-trait association. A number of significant SNP variants were identified for both traits. Many of the SNP variants associated either with susceptibility to - or recoverability from mastitis were located in or very near to genes that have been reported for their role in the immune system. Genes involved in lymphocyte developments (e.g., MAST3 and STAB2 ) and genes involved in macrophage recruitment and regulation of inflammations ( PDGFD and PTX3 ) were suggested as possible causal genes for susceptibility to - and recoverability from mastitis, respectively. However, this is the first GWAS study for recoverability from mastitis and our results need to be validated. The findings in the current study are, therefore, a starting point for further investigations in identifying causal genetic variants or chromosomal regions for both susceptibility to - and recoverability from mastitis.

Educational, employment, and social participation of young adult graduates from the paediatric Southern Cochlear Implant Programme, New Zealand.

PubMed

Goh, Terence; Bird, Philip; Pearson, John; Mustard, Jill

2016-01-01

The purpose of this study is to observe the education and vocational achievements and social participation of cochlear implant recipients as they graduate from a paediatric cochlear implant programme and identify any significant associations that might exist. This study identified 56 patients from the Southern Cochlear Implant Programme (SCIP) who received cochlear implants before the age of 19 (paediatric) and are now over the age of 19 (adult). A questionnaire investigated their education, employment, and identity with the hearing and deaf communities. Also included were the satisfaction with life scale and Hearing Participation Scale (HPS). Subjects ranged in age from 19 to 32. Twenty-six patients responded to the questionnaire, including one non-user. Twenty identified strongly or very strongly with the hearing community. There was weak evidence of a linear association between strong identity with the hearing community and a higher HPS score. No other statistically significant associations were detected. Interestingly, 12 out of 26 participants found employment through family. Positive outcome trends in education and employment were seen in this study although no statistical significance was achieved. There is a strong bias for those who use their cochlear implants regularly, and there are no data available for those who do not use their cochlear implants for comparison as only one non-user completed the survey, despite efforts to include this group. This study shows that there is perceived benefit in implantation for patients who use it regularly but further research is needed with a more diverse group of cochlear implant recipients.

Living and learning in a rural environment: a nursing student perspective.

PubMed

Pront, Leeanne; Kelton, Moira; Munt, Rebecca; Hutton, Alison

2013-03-01

This study investigates the influences on nursing student learning who live and learn in the same rural environment. A declining health workforce has been identified both globally and in Australia, the effects of which have become significantly apparent in the rural nursing sector. In support of rural educational programs the literature portrays rural clinical practice experiences as significant to student learning. However, there is little available research on what influences learning for the nursing student who studies in their own rural community. The aim of this study was to understand what influences student learning in the rural clinical environment. Through a multiple case study design five nursing students and two clinical preceptors from a rural clinical venue were interviewed. The interviews were transcribed and thematically analysed to identify factors that influenced student learning outcomes. The most significant influence on nursing student learning in the rural clinical environment was found to include the environment itself, the complex relationships unique to living and studying in a rural community along with the capacity to link theory to practice. The rural environment influences those in it, the demands placed on them, the relationships they form, the ability to promote learning and the time to teach and learn. Copyright © 2012. Published by Elsevier Ltd.

The experience of electroconvulsive therapy and its impact on associated stigma: A meta-analysis.

PubMed

Aoki, Yuta; Yamaguchi, Sosei; Ando, Shuntaro; Sasaki, Natsuki; Bernick, Peter J; Akiyama, Tsuyoshi

2016-12-01

Despite its efficacy and safety, electroconvulsive therapy (ECT) is underutilized, in part due to stigma associated with the treatment. The aim of this study was to test the hypothesis that experiencing ECT has an impact on associated stigma, as measured by patient and family knowledge of and attitudes toward ECT. A comprehensive literature search was conducted using MEDLINE, EMBASE and PsycINFO. Studies with cross-sectional and/or longitudinal designs were identified. Studies were further categorized into subcategories based on participant type (patients or patient family members) and outcome domain (knowledge or attitudes). Effect size (Cohen's d) was calculated for each study and then integrated into each subcategory (participant type by outcome domain) using a random effect model. Eight studies were identified as being eligible for analysis. Two studies were cross-sectional, five were longitudinal and one incorporated both designs. Analysis of the longitudinal studies indicated that experiencing ECT both increased knowledge of and improved attitudes toward ECT in patients; in family members of patients, analysis showed significant positive change in knowledge of ECT, but no significant change in attitudes toward ECT. Experience with ECT may have a positive impact on knowledge of and attitudes toward ECT. However, the quality of evidence of included studies was low; further research is required in order to clarify the relationship and to identify information of use to individuals considering ECT as a treatment option. © The Author(s) 2016.

Spatial Visualization Ability and Impact of Drafting Models: A Quasi Experimental Study

ERIC Educational Resources Information Center

Katsioloudis, Petros J.; Jovanovic, Vukica

2014-01-01

A quasi experimental study was done to determine significant positive effects among three different types of visual models and to identify whether any individual type or combination contributed towards a positive increase of spatial visualization ability for students in engineering technology courses. In particular, the study compared the use of…

Working People and Lifelong Learning. A Study of the Impact of an Employee Development Scheme.

ERIC Educational Resources Information Center

Beattie, Andy

A British study verified whether the educational participation of Ford Motor Company's manual workers significantly increased following introduction of the Employee Development and Assistance Program (EDAP) and identified the features that contributed to its success. Over the past 15 years, studies of working class adults' educational…

Lead with Passion: Effective Leadership Characteristics as Perceived by School Administrators and Teachers

ERIC Educational Resources Information Center

Manuel, La Tanya Antoinette

2017-01-01

The purpose of this mixed methods research study was to examine how educators lead with passion. The study identified key characteristics in school administrators and teachers who lead effective schools. This research study analyzed whether there were any significant differences in the leadership styles of administrators and teachers. Five…

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…

An Emerging Description of Successful Bilingual Instruction: Executive Summary of Part I of the SBIF Study.

ERIC Educational Resources Information Center

Tikunoff, William J.

The Significant Bilingual Instructional Features (SBIF) descriptive study identified, described, and verified important features of bilingual education for instuction of limited English proficient students. Part I involved the study of 58 classrooms and 232 students, grade K-12, at six diverse sites representing a variety of ethnolinguistic…

An Instrumental Case Study of Administrative Smart Practices for Fully Online Programs and Degrees

ERIC Educational Resources Information Center

Gregory, Charles V.

2017-01-01

The purpose of this instrumental case study was to explore administrators' responses to significant administrative challenges of fully online programs and degrees. The case was a single public community college located in the Integrated Postsecondary Education Data System Plains Region. In this study Bardach's (1994) method to identify and…

Response to Instruction in Preschool: Results of Two Randomized Studies with Children at Significant Risk of Reading Difficulties

ERIC Educational Resources Information Center

Lonigan, Christopher J.; Phillips, Beth M.

2016-01-01

Although response-to-instruction (RTI) approaches have received increased attention, few studies have evaluated the potential impacts of RTI approaches with preschool populations. This article presents results of 2 studies examining impacts of Tier II instruction with preschool children. Participating children were identified as substantially…

The Impact of Active Workstations on Workplace Productivity and Performance: A Systematic Review

PubMed Central

Ojo, Samson O.; Chater, Angel M.

2018-01-01

Active workstations have been recommended for reducing sedentary behavior in the workplace. It is important to understand if the use of these workstations has an impact on worker productivity. The aim of this systematic review was to examine the effect of active workstations on workplace productivity and performance. A total of 3303 articles were initially identified by a systematic search and seven articles met eligibility criteria for inclusion. A quality appraisal was conducted to assess risk of bias, confounding, internal and external validity, and reporting. Most of the studies reported cognitive performance as opposed to productivity. Five studies assessed cognitive performance during use of an active workstation, usually in a single session. Sit-stand desks had no detrimental effect on performance, however, some studies with treadmill and cycling workstations identified potential decreases in performance. Many of the studies lacked the power required to achieve statistical significance. Three studies assessed workplace productivity after prolonged use of an active workstation for between 12 and 52 weeks. These studies reported no significant effect on productivity. Active workstations do not appear to decrease workplace performance. PMID:29495542

The Impact of Active Workstations on Workplace Productivity and Performance: A Systematic Review.

PubMed

Ojo, Samson O; Bailey, Daniel P; Chater, Angel M; Hewson, David J

2018-02-27

Active workstations have been recommended for reducing sedentary behavior in the workplace. It is important to understand if the use of these workstations has an impact on worker productivity. The aim of this systematic review was to examine the effect of active workstations on workplace productivity and performance. A total of 3303 articles were initially identified by a systematic search and seven articles met eligibility criteria for inclusion. A quality appraisal was conducted to assess risk of bias, confounding, internal and external validity, and reporting. Most of the studies reported cognitive performance as opposed to productivity. Five studies assessed cognitive performance during use of an active workstation, usually in a single session. Sit-stand desks had no detrimental effect on performance, however, some studies with treadmill and cycling workstations identified potential decreases in performance. Many of the studies lacked the power required to achieve statistical significance. Three studies assessed workplace productivity after prolonged use of an active workstation for between 12 and 52 weeks. These studies reported no significant effect on productivity. Active workstations do not appear to decrease workplace performance.