Long working hours and risk of coronary heart disease and stroke: a systematic review and meta-analysis of published and unpublished data for 603 838 individuals

Background: Long working hours might increase the risk of cardiovascular disease, but prospective evidence is scarce, imprecise, and mostly limited to coronary heart disease. We aimed to assess long working hours as a risk factor for incident coronary heart disease and stroke. 

Methods We identified published studies through a systematic review of PubMed and Embase from inception to Aug 20, 2014. We obtained unpublished data for 20 cohort studies from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium and open-access data archives. We used cumulative random-effects meta-analysis to combine effect estimates from published and unpublished data. 

Findings We included 25 studies from 24 cohorts in Europe, the USA, and Australia. The meta-analysis of coronary heart disease comprised data for 603 838 men and women who were free from coronary heart disease at baseline; the meta-analysis of stroke comprised data for 528 908 men and women who were free from stroke at baseline. Follow-up for coronary heart disease was 5·1 million person-years (mean 8·5 years), in which 4768 events were recorded, and for stroke was 3·8 million person-years (mean 7·2 years), in which 1722 events were recorded. In cumulative meta-analysis adjusted for age, sex, and socioeconomic status, compared with standard hours (35-40 h per week), working long hours (≥55 h per week) was associated with an increase in risk of incident coronary heart disease (relative risk [RR] 1·13, 95% CI 1·02-1·26; p=0·02) and incident stroke (1·33, 1·11-1·61; p=0·002). The excess risk of stroke remained unchanged in analyses that addressed reverse causation, multivariable adjustments for other risk factors, and different methods of stroke ascertainment (range of RR estimates 1·30-1·42). We recorded a dose-response association for stroke, with RR estimates of 1·10 (95% CI 0·94-1·28; p=0·24) for 41-48 working hours, 1·27 (1·03-1·56; p=0·03) for 49-54 working hours, and 1·33 (1·11-1·61; p=0·002) for 55 working hours or more per week compared with standard working hours (p_trend<0·0001).

Interpretation Employees who work long hours have a higher risk of stroke than those working standard hours; the association with coronary heart disease is weaker. These findings suggest that more attention should be paid to the management of vascular risk factors in individuals who work long hours. 

Analysis of the early-time optical spectra of SN 2011fe in M101

The nearby Type Ia supernova SN 2011fe in M101 (cz=241 km s^-1) provides a unique opportunity to study the early evolution of a "normal" Type Ia supernova, its compositional structure, and its elusive progenitor system. We present 18 high signal-to-noise spectra of SN 2011fe during its first month beginning 1.2 days post-explosion and with an average cadence of 1.8 days. This gives a clear picture of how various line-forming species are distributed within the outer layers of the ejecta, including that of unburned material (C+O). We follow the evolution of C II absorption features until they diminish near maximum light, showing overlapping regions of burned and unburned material between ejection velocities of 10,000 and 16,000 km s^-1. This supports the notion that incomplete burning, in addition to progenitor scenarios, is a relevant source of spectroscopic diversity among SNe Ia. The observed evolution of the highly Doppler-shifted O I 7774 absorption features detected within five days post-explosion indicate the presence of O I with expansion velocities from 11,500 to 21,000 km s^-1. The fact that some O I is present above C II suggests that SN 2011fe may have had an appreciable amount of unburned oxygen within the outer layers of the ejecta.

Influence of trace substances on methanation catalysts used in dynamic biogas upgrading

The aim of this work was to study the possible deactivation effects of biogas trace ammonia concentrations on methanation catalysts. It was found that small amounts of ammonia led to a slight decrease in the catalyst activity. A decrease in the catalyst deactivation by carbon formation was also observed, with ammonia absorbed on the active catalyst sites. This was via a suppression of the carbon formation and deposition on the catalyst, since it requires a higher number of active sites than for the methanation of carbon oxides. From the paper findings, no special pretreatment for ammonia removal from the biogas fed to a methanation process is required.

Gene regulatory mechanisms underpinning prostate cancer susceptibility

Molecular characterization of genome-wide association study (GWAS) loci can uncover key genes and biological mechanisms underpinning complex traits and diseases. Here we present deep, high-throughput characterization of gene regulatory mechanisms underlying prostate cancer risk loci. Our methodology integrates data from 295 prostate cancer chromatin immunoprecipitation and sequencing experiments with genotype and gene expression data from 602 prostate tumor samples. The analysis identifies new gene regulatory mechanisms affected by risk locus SNPs, including widespread disruption of ternary androgen receptor (AR)-FOXA1 and AR-HOXB13 complexes and competitive binding mechanisms. We identify 57 expression quantitative trait loci at 35 risk loci, which we validate through analysis of allele-specific expression. We further validate predicted regulatory SNPs and target genes in prostate cancer cell line models. Finally, our integrated analysis can be accessed through an interactive visualization tool. This analysis elucidates how genome sequence variation affects disease predisposition via gene regulatory mechanisms and identifies relevant genes for downstream biomarker and drug development.