Association of BMI with overall and cause-specific mortality: a population-based cohort study of 3·6 million adults in the UK.

BACKGROUND: BMI is known to be strongly associated with all-cause mortality, but few studies have been large enough to reliably examine associations between BMI and a comprehensive range of cause-specific mortality outcomes. METHODS: In this population-based cohort study, we used UK primary care data from the Clinical Practice Research Datalink (CPRD) linked to national mortality registration data and fitted adjusted Cox regression models to examine associations between BMI and all-cause mortality, and between BMI and a comprehensive range of cause-specific mortality outcomes (recorded by International Classification of Diseases, 10th revision [ICD-10] codes). We included all individuals with BMI data collected at age 16 years and older and with subsequent follow-up time available. Follow-up began at whichever was the latest of: start of CPRD research-standard follow up, the 5-year anniversary of the first BMI record, or on Jan 1, 1998 (start date for death registration data); follow-up ended at death or on March 8, 2016. Fully adjusted models were stratified by sex and adjusted for baseline age, smoking, alcohol use, diabetes, index of multiple deprivation, and calendar period. Models were fitted in both never-smokers only and the full study population. We also did an extensive range of sensitivity analyses. The expected age of death for men and women aged 40 years at baseline, by BMI category, was estimated from a Poisson model including BMI, age, and sex. FINDINGS: 3 632 674 people were included in the full study population; the following results are from the analysis of never-smokers, which comprised 1 969 648 people and 188 057 deaths. BMI had a J-shaped association with overall mortality; the estimated hazard ratio per 5 kg/m2 increase in BMI was 0·81 (95% CI 0·80-0·82) below 25 kg/m2 and 1·21 (1·20-1·22) above this point. BMI was associated with all cause of death categories except for transport-related accidents, but the shape of the association varied. Most causes, including cancer, cardiovascular diseases, and respiratory diseases, had a J-shaped association with BMI, with lowest risk occurring in the range 21-25 kg/m2. For mental and behavioural, neurological, and accidental (non-transport-related) causes, BMI was inversely associated with mortality up to 24-27 kg/m2, with little association at higher BMIs; for deaths from self-harm or interpersonal violence, an inverse linear association was observed. Associations between BMI and mortality were stronger at younger ages than at older ages, and the BMI associated with lowest mortality risk was higher in older individuals than in younger individuals. Compared with individuals of healthy weight (BMI 18·5-24·9 kg/m2), life expectancy from age 40 years was 4·2 years shorter in obese (BMI ≥30·0 kg/m2) men and 3·5 years shorter in obese women, and 4·3 years shorter in underweight (BMI <18·5 kg/m2) men and 4·5 years shorter in underweight women. When smokers were included in analyses, results for most causes of death were broadly similar, although marginally stronger associations were seen among people with lower BMI, suggesting slight residual confounding by smoking. INTERPRETATION: BMI had J-shaped associations with overall mortality and most specific causes of death; for mental and behavioural, neurological, and external causes, lower BMI was associated with increased mortality risk. FUNDING: Wellcome Trust

Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults.

BACKGROUND: High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers. METHODS: With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects. FINDINGS: 5·24 million individuals were included; 166,955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m(2) increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56-1·69; p<0·0001), gallbladder (1·31, 1·12-1·52; p<0·0001), kidney (1·25, 1·17-1·33; p<0·0001), cervix (1·10, 1·03-1·17; p=0·00035), thyroid (1·09, 1·00-1·19; p=0·0088), and leukaemia (1·09, 1·05-1·13; p≤0·0001). BMI was positively associated with liver (1·19, 1·12-1·27), colon (1·10, 1·07-1·13), ovarian (1·09, 1.04-1.14), and postmenopausal breast cancers (1·05, 1·03-1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95-1·00; premenopausal breast cancer 0·89, 0·86-0·92) and in never-smokers (prostate 0·96, 0·93-0·99; premenopausal breast cancer 0·89, 0·85-0·94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93-1·05; oral cavity 1·07, 0·91-1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m(2) population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI. INTERPRETATION: BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups. FUNDING: National Institute for Health Research, Wellcome Trust, and Medical Research Council

Características espermáticas de caprinos Moxotó de acordo com a morfologia escrotal.

bitstream/item/36457/1/CT-06.pd

Scale invariant scalar metric fluctuations during inflation: non-perturbative formalism from a 5D vacuum

We extend to 5D an approach of a 4D non-perturbative formalism to study scalar metric fluctuations of a 5D Riemann-flat de Sitter background metric. In contrast with the results obtained in 4D, the spectrum of cosmological scalar metric fluctuations during inflation can be scale invariant and the background inflaton field can take sub-Planckian values.Comment: final version to be published in Eur. Phys. J.

The phase portrait of a matter bounce in Horava-Lifshitz cosmology

The occurrence of a bounce in FRW cosmology requires modifications of general relativity. An example of such a modification is the recently proposed Horava-Lifshitz theory of gravity, which includes a ``dark radiation'' term with a negative coefficient in the analog of the Friedmann equation. This paper describes a phase space analysis of models of this sort with the aim of determining to what extent bouncing solutions can occur. A simplification, valid in the relevant region, allows a reduction of the dimension of phase space so that visualization in three dimensions is possible. It is found that a bounce is possible, but not generic in models under consideration. Apart from previously known bouncing solutions some new ones are also described. Other interesting solutions found include ones which describe a novel sort of oscillating universes.Comment: 14 pages, 8 figure

Active gravitational mass and the invariant characterization of Reissner-Nordstrom spacetime

We analyse the concept of active gravitational mass for Reissner-Nordstrom spacetime in terms of scalar polynomial invariants and the Karlhede classification. We show that while the Kretschmann scalar does not produce the expected expression for the active gravitational mass, both scalar polynomial invariants formed from the Weyl tensor, and the Cartan scalars, do.Comment: 6 pages Latex, to appear in General Relativity and Gravitatio

Selection of a molecule that specifically targets the cell-surface Human Epidermal growth factor Receptor 2: in silico docking simulation

[Excerpt] Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% of the total cancer cases and 14% of the cancer deaths.1 Human Epidermal growth factor Receptor 2 (HER2) is a protein that is overexpressed in 25-30% of breast cancers and is involved in cell growth regulation, survival and differentiation.2 Aptamers generated from Systematic Evolution of Ligands by EXponential Enrichment (SELEX) emerged as a potential new tool for the development of targeted cancer therapies due to their three-dimensional structures that specifically recognize cell surface receptors, such as HER2.3 In this study, HER2-aptamers were screened and identified using SELEX. To design an approach for computational analysis of the isolated aptamers, their structures were modelled by mfold4, a web-based methodology for DNA structure prediction and hybridization software. The HER2 protein structure was obtained from Protein Data Bank (PDB) and using ZDOCK server5, the aptamer-target interactions were predicted through a combination of shape complementarity and statistical potential terms for scoring. [...]info:eu-repo/semantics/publishedVersio