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Lund Kold posted an update 2 days, 12 hours ago
Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta = -0.0264, p value = 3.5 × 10-8) in the discovery panel and was replicated in replication panel (beta = -0.07, p value = 0.005). This CpG is located at chr581649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value = 1.4 × 10-13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.Smoking has been associated with opposing risks of ulcerative colitis and Crohn’s disease. Whether these observational associations reflect actual causal associations, confounding, or reverse causation is unclear. Using a Mendelian randomization approach, we tested the hypothesis that smoking protects against ulcerative colitis and is a cause of Crohn’s disease. We included 118,683 white Danes aged ≥ 20 from the Copenhagen General Population Study (2003-2015) and the Copenhagen City Heart Study (1991-94 and 2001-03). During follow-up until 2018, we investigated the association of smoking and CHRNA3 rs1051730, where the T-allele is strongly associated with nicotine dependence, with risk of ulcerative colitis and Crohn’s disease. We identified 1312 cases of ulcerative colitis and 671 cases of Crohn’s disease. Compared to never-smokers, multivariable adjusted hazard ratios (HRs) for ulcerative colitis were 1.69(95% confidence interval [CI] 1.32-2.15) in former smokers and 2.27(1.74-2.96) in current smokers. Corresponding HRs for Crohn’s disease were 1.31(0.93-1.84) and 1.93(1.34-2.78), respectively. Among ever-smokers when compared to non-carriers of the CHRNA3 rs1051730 T-allele, age and sex adjusted HRs for risk of ulcerative colitis were 1.03(95%CI 0.89-1.18) in heterozygotes and 0.91(0.72-1.16) in homozygotes. Corresponding HRs for Crohn’s disease were 1.05(0.87-1.28) and 1.02(0.74-1.41), respectively. In a meta-analysis combined with UK Biobank, there was no evidence that CHRNA3 rs1051730 was associated with risk of ulcerative colitis or Crohn’s disease. In conclusion, current versus never-smoking was associated with unexpected 2.3-fold risk of ulcerative colitis and expected 1.9-fold risk of Crohn’s disease in prospective analyses; however, genetic evidence of lifelong increased smoking intensity did not support causal relationships.Clinical trials require participation of numerous patients, enormous research resources and substantial public funding. Time-consuming trials lead to delayed implementation of beneficial interventions and to reduced benefit to patients. This manuscript discusses two methods for the allocation of research resources and reviews a framework for prioritisation and design of clinical trials. The traditional error-driven approach of clinical trial design controls for type I and II errors. However, controlling for those statistical errors has limited relevance to policy makers. Therefore, this error-driven approach can be inefficient, waste research resources and lead to research with limited impact on daily practice. The novel value-driven approach assesses the currently available evidence and focuses on designing clinical trials that directly inform policy and treatment decisions. Estimating the net value of collecting further information, prior to undertaking a trial, informs a decision maker whether a clinical or health policy decision can be made with current information or if collection of extra evidence is justified. Additionally, estimating the net value of new information guides study design, data collection choices, and sample size estimation. The value-driven approach ensures the efficient use of research resources, reduces unnecessary burden to trial participants, and accelerates implementation of beneficial healthcare interventions.The objective of this study was to investigate the effect of seasonal variation on the frequency of post-farrowing dysgalactia syndrome (PFDS), sow body condition score (BCS), piglet survival, and weaning to estrus interval under intensive management systems. In addition, the effects of PFDS on litter characteristics and serum biochemistry, oxidative stress indices, thyroid, and cortisol profile were examined in order to identify potential biomarkers in the pre-farrowing stage. The study was conducted in summer and winter seasons in Nagaland, India, on 50 sows from 30 days before farrowing until weaning at 45 days. Sows were classified retrospectively into PFDS and non-PFDS. AD80 molecular weight Although statistically, no significant difference was noted in the occurrence of PFDS between the seasons, the proportion of PFDS development was substantially higher in winter than summer (37.5 vs. 26.9%). In winter, the incidence of piglet stillbirth and sow weaning to estrus period was significantly higher (p less then 0.05) and the sows to identify the critical values of serum T3 concentration in the immediate pre-farrowing period for prediction of sows developing PFDS after farrowing.Detection and mapping of landslides is one of the most important techniques used for reducing the impact of natural disasters especially in the Himalaya, owing to its high amount of tectonic deformation, seismicity, and unfavorable climatic conditions. Moreover, the northeastern part of the Himalaya, severely affected by landslides every monsoon, is poorly studied. The information on the inventories is inhomogeneous and lacking. In this context, satellite-based earth observation data, which has significantly advanced in the last decade and often serves as a potential source for data collection, monitoring, and damage assessment for disasters in a short time span, has been implemented. Keeping in mind the above framework, this study aims to exploit the potentials of Sentinel-1 synthetic aperture radar (SAR) and Sentinel-2 optical imagery for identifying new landslides in vegetated and hilly areas of the northeastern part of India. In order to assess the potentials of our data and methodology, a landslide event which occurred on 13 August 2016 1330 h (IST) in North Sikkim, India, triggered due to rainfall has been explored in detail.