BMI and all cause mortality: systematic review and non-linear dose-response meta-analysis of 230 cohort studies with 3.74 million deaths among 30.3 million participants

 To conduct a systematic review and meta-analysis of cohort studies of body mass index (BMI) and the risk of all cause mortality, and to clarify the shape and the nadir of the dose-response curve, and the influence on the results of confounding from smoking, weight loss associated with disease, and preclinical disease. PubMed and Embase databases searched up to 23 September 2015. Cohort studies that reported adjusted risk estimates for at least three categories of BMI in relation to all cause mortality. Summary relative risks were calculated with random effects models. Non-linear associations were explored with fractional polynomial models. 230 cohort studies (207 publications) were included. The analysis of never smokers included 53 cohort studies (44 risk estimates) with >738 144 deaths and >9 976 077 participants. The analysis of all participants included 228 cohort studies (198 risk estimates) with >3 744 722 deaths among 30 233 329 participants. The summary relative risk for a 5 unit increment in BMI was 1.18 (95% confidence interval 1.15 to 1.21; I(2)=95%, n=44) among never smokers, 1.21 (1.18 to 1.25; I(2)=93%, n=25) among healthy never smokers, 1.27 (1.21 to 1.33; I(2)=89%, n=11) among healthy never smokers with exclusion of early follow-up, and 1.05 (1.04 to 1.07; I(2)=97%, n=198) among all participants. There was a J shaped dose-response relation in never smokers (Pnon-linearity <0.001), and the lowest risk was observed at BMI 23-24 in never smokers, 22-23 in healthy never smokers, and 20-22 in studies of never smokers with ≥20 years follow-up. In contrast there was a U shaped association between BMI and mortality in analyses with a greater potential for bias including all participants, current, former, or ever smokers, and in studies with a short duration of follow-up (<5 years or <10 years), or with moderate study quality scores. Overweight and obesity is associated with increased risk of all cause mortality and the nadir of the curve was observed at BMI 23-24 among never smokers, 22-23 among healthy never smokers, and 20-22 with longer durations of follow-up. The increased risk of mortality observed in underweight people could at least partly be caused by residual confounding from prediagnostic disease. Lack of exclusion of ever smokers, people with prevalent and preclinical disease, and early follow-up could bias the results towards a more U shaped association

Epigenetic activation and silencing of the gene that encodes IFN-γ

Transcriptional activation and repression of genes that are developmentally regulated or exhibit cell-type specific expression patterns is largely achieved by modifying the chromatin template at a gene locus. Complex formation of stable epigenetic histone marks, loss or gain of DNA methylation, alterations in chromosome conformation, and specific utilization of both proximal and distal transcriptional enhancers and repressors all contribute to this process. In addition, long noncoding RNAs are a new species of regulatory RNAs that either positively or negatively regulate transcription of target gene loci. IFN-γ is a pro-inflammatory cytokine with critical functions in both innate and adaptive arms of the immune. This review focuses on our current understanding of how the chromatin template is modified at the IFNG locus during developmental processes leading to its transcriptional activation and silencing

Body mass index, abdominal fatness, fat mass and the risk of atrial fibrillation: a systematic review and dose–response meta-analysis of prospective studies

Different adiposity measures have been associ- ated with increased risk of atrial fibrillation, however, results have previously only been summarized for BMI. We therefore conducted a systematic review and meta- analysis of prospective studies to clarify the association between different adiposity measures and risk of atrial fibrillation. PubMed and Embase databases were searched up to October 24th 2016. Summary relative risks (RRs) were calculated using random effects models. Twenty-nine unique prospective studies (32 publications) were included. Twenty-five studies (83,006 cases, 2,405,381 participants) were included in the analysis of BMI and atrial fibrillation. The summary RR was 1.28 (95% confidence interval: 1.20–1.38, I 2 = 97%) per 5 unit increment in BMI, 1.18 (95% CI: 1.12–1.25, I 2 = 73%, n = 5) and 1.32 (95% CI: 1.16–1.51, I 2 = 91%, n = 3) per 10 cm increase in waist and hip circumference, respectively, 1.09 (95% CI: 1.02–1.16, I 2 = 44%, n = 4) per 0.1 unit increase in waist- to-hip ratio, 1.09 (95% CI: 1.02–1.16, I 2 = 94%, n = 4) per 5 kg increase in fat mass, 1.10 (95% CI: 0.92–1.33, I 2 = 90%, n = 3) per 10% increase in fat percentage, 1.10 (95% CI: 1.08–1.13, I 2 = 74%, n = 10) per 5 kg increase in weight, and 1.08 (95% CI: 0.97–1.19, I 2 = 86%, n = 2) per 5% increase in weight gain. The association between BMI and atrial fibrillation was non- linear, p nonlinearity \ 0.0001, with a stronger association at higher BMI levels, however, increased risk was observed even at a BMI of 22–24 compared to 20. In conclusion, general and abdominal adiposity and higher body fat mass increase the risk of atrial fibrillation

Is attending a mental process?

The nature of attention has been the topic of a lively research programme in psychology for over a century. But there is widespread agreement that none of the theories on offer manage to fully capture the nature of attention. Recently, philosophers have become interested in the debate again after a prolonged period of neglect. This paper contributes to the project of explaining the nature of attention. It starts off by critically examining Christopher Mole’s prominent “adverbial” account of attention, which traces the failure of extant psychological theories to their assumption that attending is a kind of process. It then defends an alternative, process-based view of the metaphysics of attention, on which attention is understood as an activity and not, as psychologists seem to implicitly assume, an accomplishment. The entrenched distinction between accomplishments and activities is shown to shed new light on the metaphysics of attention. It also provides a novel diagnosis of the empirical state of play

Dietary fibre intake and the risk of diverticular disease: a systematic review and meta-analysis of prospective studies

BACKGROUND: A high intake of dietary fibre has been associated with a reduced risk of diverticular disease in several studies; however, the dose-response relationship between fibre intake and diverticular disease risk has varied, and the available studies have not been summarised in a meta-analysis. We conducted a systematic review and meta-analysis of prospective cohort studies to clarify the association between dietary fibre intake, fibre subtypes, and the risk of diverticular disease. METHODS: PubMed and Embase databases were searched up to August 9th 2018. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model and nonlinear associations were modelled using fractional polynomial models. RESULTS: Five prospective cohort studies with 19,282 cases and 865,829 participants were included in the analysis of dietary fibre and diverticular disease risk. The summary RR was 0.74 (95% CI 0.71-0.78, I2 = 0%) per 10 g/day. There was no evidence of a nonlinear association between dietary fibre intake and diverticular disease risk, pnonlinearity = 0.35, and there was a 23%, 41% and 58% reduction in risk for an intake of 20, 30, and 40 g/day, respectively, compared to 7.5 g/day. There was no evidence of publication bias with Egger's test, p = 0.58 and the association persisted in subgroup and sensitivity analyses. The summary RR per 10 g/day was 0.74 (95% CI 0.67-0.81, I2 = 60%, n = 4) for cereal fibre, 0.56 (95% CI 0.37-0.84, I2 = 73%, n = 2) for fruit fibre, and 0.80 (95% CI 0.45-1.44, I2 = 87%, n = 2) for vegetable fibre. CONCLUSIONS: These results suggest that a high fibre intake may reduce the risk of diverticular disease and individuals consuming 30 g of fibre per day have a 41% reduction in risk compared to persons with a low fibre intake. Further studies are needed on fibre types and risk of diverticular disease and diverticulitis

Performance of the Micromegas detector in the CAST experiment

The gaseous Micromegas detector designed for the CERN Axion search experiment CAST, operated smoothly during Phase-I, which included the 2003 and 2004 running periods. It exhibited linear response in the energy range of interest (1-10keV), good spatial sensitivity and energy resolution (15-19% FWHM at 5.9keV)as well as remarkable stability. The detector's upgrade for the 2004 run, supported by the development of advanced offline analysis tools, improved the background rejection capability, leading to an average rate 5x10^-5 counts/sec/cm^2/keV with 94% cut efficiency. Also, the origin of the detected background was studied with a Monte Carlo simulation, using the GEANT4 package.Comment: Prepared for PSD7: The Seventh International Conference on Position Sensitive Detectors, Liverpool, United Kingdom, 12-16 Sep. 200

Physical activity and the risk of gestational diabetes mellitus: a systematic review and dose-response meta-analysis of epidemiological studies

Physical activity has been inconsistently associated with risk of gestational diabetes mellitus in epidemiological studies, and questions remain about the strength and shape of the dose-response relationship between the two. We therefore conducted a systematic review and meta-analysis of cohort studies and randomized trials on physical activity and gestational diabetes mellitus. PubMed, Embase and Ovid databases were searched for cohort studies, and randomized controlled trials of physical activity and risk of gestational diabetes mellitus, up to August 5th 2015. Summary relative risks (RRs) were estimated using a random effects model. Twenty-five studies (26 publications) were included. For total physical activity the summary RR for high versus low activity was 0.62 (95 % CI 0.41-0.94, I(2) = 0 %, n = 4) before pregnancy, and 0.66 (95 % CI 0.36-1.21, I(2) = 0 %, n = 3) during pregnancy. For leisure-time physical activity the respective summary RRs for high versus low activity was 0.78 (95 % CI 0.61-1.00, I(2) = 47 %, n = 8) before pregnancy, and it was 0.80 (95 % CI 0.64-1.00, I(2) = 17 %, n = 17) during pregnancy. The summary RR for pre-pregnancy activity was 0.70 (95 % CI 0.49-1.01, I(2) = 72.6 %, n = 3) per increment of 5 h/week and for activity during pregnancy was 0.98 (95 % CI 0.87-1.09, I(2) = 0 %, n = 3) per 5 h/week. There was evidence of a nonlinear association between physical activity before pregnancy and the risk of gestational diabetes mellitus, pnonlinearity = 0.005, with a slightly steeper association at lower levels of activity although further reductions in risk were observed up to 10 h/week. There was also evidence of nonlinearity for physical activity in early pregnancy, pnonlinearity = 0.008, with no further reduction in risk above 8 h/week. There was some indication of inverse associations between walking (before and during pregnancy) and vigorous activity (before pregnancy) and the risk of gestational diabetes mellitus. This meta-analysis suggests that there is a significant inverse association between physical activity before pregnancy and in early pregnancy and the risk of gestational diabetes mellitus. Further studies are needed to clarify the association between specific types and intensities of activity and gestational diabetes mellitus

Laboratory-based and office-based Globorisk scores to predict 10-year risk of cardiovascular diseases among Iranians: results from the Fasa PERSIAN cohort.

BACKGROUND: Globorisk is a novel risk prediction model for predicting cardiovascular disease (CVD). Globorisk is a country-specific risk prediction model that determines CVD risk for all countries. This model has two versions; laboratory-based and office-based. This study aimed to determine the agreement between laboratory-based and office-based models in a large sample of the general population. METHODS: Baseline data from the Fasa cohort study was used for the current study. In total, 6810 participants ≥ 40 years without any history of cardiovascular disease or stroke were included in the study. To determine the laboratory-based risk model, factors include age, sex, current smoking status, history of diabetes, systolic blood pressure (SBP), and total cholesterol. To estimate the office-based risk model, factors were age, sex, current smoking status, SBP, and body mass index (BMI). Kappa statistics was used to distinguish the agreement between grouped scores in these two models. Additionally, correlation coefficients and scatter plots were used to determine the linear correlation between the two models. RESULTS: In this study 46.53% of the participants were men. The mean age (SD) of participants was 51.08 (7.88) years. Agreements between the two models were moderate and substantial in all women and all men, respectively. The agreement between the two CVD risk groups was 90.15% (kappa = 0.717) in all men, 92.94% (kappa = 0.571) among men aged  60 years (r = 0.94). Among all women, there was a very strong positive correlation (r = 0.87), and the strong positive correlation remained among  60 years old (r = 0.76). CONCLUSION: The Globorisk office-based model which is easier to use as it does not require blood testing can determine the risk groups in this population. The Globorisk office-based model may be used for CVD risk screening in low-middle income countries where resources are limited

Vitamin D status and risk of rheumatoid arthritis: systematic review and meta-analysis

Background Vitamin D is important for immunomodulation and may play a role in autoimmune diseases. Studies have reported a high prevalence of vitamin D deficiency in rheumatoid arthritis (RA) patients, and vitamin D status, assessed by circulating 25-hydroxyvitamin D [25(OH)D] concentration, is inversely associated with RA disease activity. However, it is unclear whether vitamin D deficiency increases the risk of later developing RA. We conducted a systematic review and meta-analysis of pre-diagnostic 25(OH)D concentrations and risk of RA. Methods Medline and Embase databases were searched in December 2021 using various keywords for ‘vitamin D’, ‘rheumatoid arthritis’, and ‘prospective study’. Publications identified from the search were screened for eligibility, studies were excluded if vitamin D status was measured at or after RA diagnosis, and data were extracted from relevant articles. Bayesian meta-analysis was used to estimate the summary relative risk (RR) and 95% credible interval (CrI) for risk of RA in relation to circulating 25(OH)D concentrations, as well as the between-study heterogeneity. Results The search strategy yielded 908 records, of which 4 publications reporting on 7 studies, involving a total of 15,604 participants and 1049 incident RA cases, were included in the meta-analysis. There was no suggestion of an association between 25(OH)D concentration and subsequent risk of RA. The pooled RR per 25 nmol/L increment in 25(OH)D was 0.96 (95% CrI 0.82–1.13; I2 = 52%). No associations were evident in men (RR = 1.02, 95% CrI 0.65–1.61; I2 = 77%, 2 studies) or women (RR = 0.94, 95% CrI 0.73–1.22; I2 = 71%, 4 studies). Conclusions This systematic review and meta-analysis did not identify evidence of an association between 25(OH)D and RA risk, but there was notable between-study heterogeneity and a lack of precision. Investigations in large-scale prospective studies with long follow-up or suitably designed Mendelian randomisation studies with consideration of potential non-linear relationships are needed to determine whether vitamin D is involved in RA aetiology