Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (P-Bonferroni <1.06 x 10(-7)). In additional analyses in 7,278 participants,Peer reviewe

Benchmark numerical simulations of rarefied non-reacting gas flows using an open-source DSMC code

Validation and verification represent an important element in the development of a computational code. The aim is establish both confidence in the algorithm and its suitability for the intended purpose. In this paper, a direct simulation Monte Carlo solver, called dsmcFoam, is carefully investigated for its ability to solve low and high speed non-reacting gas flows in simple and complex geometries. The test cases are: flow over sharp and truncated flat plates, the Mars Pathfinder probe, a micro-channel with heated internal steps, and a simple micro-channel. For all the cases investigated, dsmcFoam demonstrates very good agreement with experimental and numerical data available in the literature

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Precarious Goals: A Biopsychological Model of Adaptive Strivings Articulates How Harsh Social Worlds Erode Physical Health

Environments erode health by shaping biologically based goal systems, or adaptive strivings, that help a brain regulate bodily energy resources. Adaptive strivings let predictive brain processes anticipate and meet even modest shifts in impending metabolic demands. Adaptive strivings serve growth, social potency, and safety. Striving for personal and social growth (transcendence striving) improves energy regulation and promotes health. But adverse environments can foster precarious strivings that cause organic damage even in the absence of fight-flight responses or distressing emotions: Agonistic striving (persistently seeking to influence others) and dissipated striving (disengaging to be safe) impair regulation and foster illness by generating perpetual power contests or perceptions of self-inefficacy. Threats to social power or status endanger health by inducing precarious strivings that amplify adversities. Emotional transcendence striving, however, may dampen harsh health impacts. Research has replicated the three strivings across differences of race, sex, and age and indicates that agonistic striving contributes to hypertension, somatic symptoms, and alcohol use disorders. Harmful health effects of agonistic striving are moderated by emotional transcendence striving indexed by the ability to modulate anger or physical pain. Agonistic striving mediates the association between exposure to neighborhood disorder and hypertension after controlling for negative emotions and disease-prone traits

Application of the Social Action Theory to Understand Factors Associated with Risky Sexual Behavior Among Individuals in Residential Substance Abuse Treatment

Risky sexual behavior (RSB) is a leading cause of HIV/AIDS, particularly among urban substance users. Using the social action theory, an integrative systems model of sociocognitive, motivational, and environmental influences, as a guiding framework, the current study examined (1) environmental influences, (2) psychopathology and affect, (3) HIV-related attitudes and knowledge, and (4) self-regulatory skills/deficits as factors associated with event-level condom use (CU) among a sample of 156 substance users residing at a residential substance abuse treatment center (M age = 41.85; SD = 8.59; 75% male). RSB was assessed using event-level measurement of CU given its advantages for improved accuracy of recall and ability for an examination of situational variables. A logistic regression predicting event-level CU indicated the significant contribution of partner type (environmental influences), less favorable attitudes towards condoms (HIV-related attitudes and knowledge), and higher levels of risk-taking propensity (self-regulatory skills/deficits) in predicting greater likelihood of not having used a condom at one\u27s most recent sexual encounter. This study contributes to the literature examining HIV risk behaviors among substance users within a theory-driven model of risk