Research Triangle Park

About: Research Triangle Park is a nonprofit organization based out in Durham, North Carolina, United States. It is known for research contribution in the topics: Population & Environmental exposure. The organization has 24961 authors who have published 35800 publications receiving 1684504 citations. The organization is also known as: RTP.

Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability

Abstract: The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case–control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD—for both European- and African-American individuals—and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.

One-to-many propensity score matching in cohort studies

Abstract: Background Among the large number of cohort studies that employ propensity score matching, most match patients 1:1. Increasing the matching ratio is thought to improve precision but may come with a trade-off with respect to bias. Objective To evaluate several methods of propensity score matching in cohort studies through simulation and empirical analyses. Methods We simulated cohorts of 20 000 patients with exposure prevalence of 10%–50%. We simulated five dichotomous and five continuous confounders. We estimated propensity scores and matched using digit-based greedy (“greedy”), pairwise nearest neighbor within a caliper (“nearest neighbor”), and a nearest neighbor approach that sought to balance the scores of the comparison patient above and below that of the treated patient (“balanced nearest neighbor”). We matched at both fixed and variable matching ratios and also evaluated sequential and parallel schemes for the order of formation of 1:n match groups. We then applied this same approach to two cohorts of patients drawn from administrative claims data. Results Increasing the match ratio beyond 1:1 generally resulted in somewhat higher bias. It also resulted in lower variance with variable ratio matching but higher variance with fixed. The parallel approach generally resulted in higher mean squared error but lower bias than the sequential approach. Variable ratio, parallel, balanced nearest neighbor matching generally yielded the lowest bias and mean squared error. Conclusions 1:n matching can be used to increase precision in cohort studies. We recommend a variable ratio, parallel, balanced 1:n, nearest neighbor approach that increases precision over 1:1 matching at a small cost in bias. Copyright © 2012 John Wiley & Sons, Ltd.

The intracellular degradation of poly(ε-caprolactone)

Abstract: Poly(epsilon-caprolactone) [PEC], a biodegradable aliphatic polyester, undergoes a two-stage degradation process: The first lengthy phase involves nonenzymatic hydrolytic cleavage of ester groups, the second phase beginning when the polymer is more highly crystalline, and of low molecular weight. The cellular events of the second phase were examined by implanting gelatin capsules containing 25 mg of low molecular weight (Mn 3000) PEC powders, 106 to 500 micron, in rats. PEC fragments ultimately were degraded in phagosomes of macrophages and giant cells, the process requiring less than 13 days for completion at some sites. PEC was also identified within fibroblasts. These studies support the intracellular degradation of PEC as the principal pathway of degradation once the molecular weight of the aged polymer is reduced to 3000 or less.