Technical note: Determination of binary gas-phase diffusion coefficients of unstable and adsorbing atmospheric trace gases at low temperature – arrested flow and twin tube method

Gas-phase diffusion is the first step for all heterogeneous reactions under atmospheric conditions. Knowledge of binary diffusion coefficients is important for the interpretation of laboratory studies regarding heterogeneous trace gas uptake and reactions. Only for stable, nonreactive and nonpolar gases do well-established models for the estimation of diffusion coefficients from viscosity data exist. Therefore, we have used two complementary methods for the measurement of binary diffusion coefficients in the temperature range of 200 to 300 K: the arrested flow method is best suited for unstable gases, and the twin tube method is best suited for stable but adsorbing trace gases. Both methods were validated by the measurement of the diffusion coefficients of methane and ethane in helium and air as well as nitric oxide in helium. Using the arrested flow method the diffusion coefficients of ozone in air, dinitrogen pentoxide and chlorine nitrate in helium, and nitrogen were measured. The twin tube method was used for the measurement of the diffusion coefficient of nitrogen dioxide and dinitrogen tetroxide in helium and nitrogen

Amount of Social Contact and Hip Fracture Mortality: SOCIAL CONTACT AND MORTALITY AFTER HIP FRACTURE

To study the association between amount of social contact and mortality after hip fracture in elderly participants

Advanced electron cyclotron heating and current drive experiments on the stellarator Wendelstein 7-X

During the first operational phase (OP 1.1) of Wendelstein 7-X (W7-X) electron cyclotron resonance heating (ECRH) was the exclusive heating method and provided plasma start-up, wall conditioning, heating and current drive. Six gyrotrons were commissioned for OP1.1 and used in parallel for plasma operation with a power of up to 4.3 MW. During standard X2-heating the spatially localized power deposition with high power density allowed controlling the radial profiles of the electron temperature and the rotational transform. Even though W7-X was not fully equipped with first wall tiles and operated with a graphite limiter instead of a divertor, electron densities of n e > 3·1019 m-3 could be achieved at electron temperatures of several keV and ion temperatures above 2 keV. These plasma parameters allowed the first demonstration of a multipath O2-heating scenario, which is envisaged for safe operation near the X-cutoff-density of 1.2·1020 m-3 after full commissioning of the ECRH system in the next operation phase OP1.2

Epigenome-Wide Association Study of Incident Type 2 Diabetes in a British Population: EPIC-Norfolk Study.

Epigenetic changes may contribute substantially to risks of diseases of aging. Previous studies reported seven methylation variable positions (MVPs) robustly associated with incident type 2 diabetes mellitus (T2DM). However, their causal roles in T2DM are unclear. In an incident T2DM case-cohort study nested within the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort, we used whole blood DNA collected at baseline, up to 11 years before T2DM onset, to investigate the role of methylation in the etiology of T2DM. We identified 15 novel MVPs with robust associations with incident T2DM and robustly confirmed three MVPs identified previously (near to TXNIP, ABCG1, and SREBF1). All 18 MVPs showed directionally consistent associations with incident and prevalent T2DM in independent studies. Further conditional analyses suggested that the identified epigenetic signals appear related to T2DM via glucose and obesity-related pathways acting before the collection of baseline samples. We integrated genome-wide genetic data to identify methylation-associated quantitative trait loci robustly associated with 16 of the 18 MVPs and found one MVP, cg00574958 at CPT1A, with a possible direct causal role in T2DM. None of the implicated genes were previously highlighted by genetic association studies, suggesting that DNA methylation studies may reveal novel biological mechanisms involved in tissue responses to glycemia

An atlas of genetic scores to predict multi-omic traits

The use of omic modalities to dissect the molecular underpinnings of common diseases and traits is becoming increasingly common. But multi-omic traits can be genetically predicted, which enables highly cost-effective and powerful analyses for studies that do not have multi-omics. Here we examine a large cohort (the INTERVAL study; n = 50,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, n = 3,175; Olink, n = 4,822), plasma metabolomics (Metabolon HD4, n = 8,153), serum metabolomics (Nightingale, n = 37,359) and whole-blood Illumina RNA sequencing (n = 4,136), and use machine learning to train genetic scores for 17,227 molecular traits, including 10,521 that reach Bonferroni-adjusted significance. We evaluate the performance of genetic scores through external validation across cohorts of individuals of European, Asian and African American ancestries. In addition, we show the utility of these multi-omic genetic scores by quantifying the genetic control of biological pathways and by generating a synthetic multi-omic dataset of the UK Biobank to identify disease associations using a phenome-wide scan. We highlight a series of biological insights with regard to genetic mechanisms in metabolism and canonical pathway associations with disease; for example, JAK-STAT signalling and coronary atherosclerosis. Finally, we develop a portal ( https://www.omicspred.org/ ) to facilitate public access to all genetic scores and validation results, as well as to serve as a platform for future extensions and enhancements of multi-omic genetic scores

Variants associated withHHIP expression have sex-differential effects on lung function

Publisher Copyright: © 2020 Fawcett KA et al.Background: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium. Results: Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P<5x10 -8) interactions with sex on lung function, and 21 showed suggestive interactions (P<1x10 -6). The strongest signal, from rs7697189 (chr4:145436894) on forced expiratory volume in 1 second (FEV 1) (P=3.15x10 -15), was replicated (P=0.016) in SpiroMeta. The C allele increased FEV 1 more in males (untransformed FEV 1 β=0.028 [SE 0.0022] litres) than females (β=0.009 [SE 0.0014] litres), and this effect was not accounted for by differential effects on height, smoking or pubertal age. rs7697189 resides upstream of the hedgehog-interacting protein ( HHIP) gene and was previously associated with lung function and HHIP lung expression. We found HHIP expression was significantly different between the sexes (P=6.90x10 -6), but we could not detect sex differential effects of rs7697189 on expression. Conclusions: We identified a novel genotype-by-sex interaction at a putative enhancer region upstream of the HHIP gene. Establishing the mechanism by which HHIP SNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases in both sexes.Peer reviewe

Risk thresholds for alcohol consumption : combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies

Background Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease. Methods We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose-response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12.5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5.6 years [5th-95th percentile 1.04-13.5]) from 71 011 participants from 37 studies. Findings In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5.4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1.14, 95% CI, 1.10-1.17), coronary disease excluding myocardial infarction (1.06, 1.00-1.11), heart failure (1.09, 1.03-1.15), fatal hypertensive disease (1.24, 1.15-1.33); and fatal aortic aneurysm (1.15, 1.03-1.28). By contrast, increased alcohol consumption was loglinearly associated with a lower risk of myocardial infarction (HR 0.94, 0.91-0.97). In comparison to those who reported drinking >0-100-200-350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1-2 years, or 4-5 years, respectively. Interpretation In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines. Copyright (C) The Author(s). Published by Elsevier Ltd.Peer reviewe

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Variants associated with HHIP expression have sexdifferential effects on lung function

Background: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females.Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium.Results: Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P-8) interactions with sex on lung function, and 21 showed suggestive interactions (P-6). The strongest signal, from rs7697189 (chr4:145436894) on forced expiratory volume in 1 second (FEV1) (P=3.15x10-15), was replicated (P=0.016) in SpiroMeta. The C allele increased FEV1 more in males (untransformed FEV1 β=0.028 [SE 0.0022] litres) than females (β=0.009 [SE 0.0014] litres), and this effect was not accounted for by differential effects on height, smoking or pubertal age. rs7697189 resides upstream of the hedgehog-interacting protein (HHIP) gene and was previously associated with lung function and HHIP lung expression. We found HHIP expression was significantly different between the sexes (P=6.90x10-6), but we could not detect sex differential effects of rs7697189 on expression.Conclusions: We identified a novel genotype-by-sex interaction at a putative enhancer region upstream of the HHIP gene. Establishing the mechanism by which HHIP SNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases in both sexes.</p