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

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

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

Progress on a spherical TPC for low energy neutrino detection

The new concept of the spherical TPC aims at relatively large target masses with low threshold and background, keeping an extremely simple and robust operation. Such a device would open the way to detect the neutrino-nucleus interaction, which, although a standard process, remains undetected due to the low energy of the neutrino-induced nuclear recoils. The progress in the development of the fist 1 m$^3$ prototype at Saclay is presented. Other physics goals of such a device could include supernova detection, low energy neutrino oscillations and study of non-standard properties of the neutrino, among others.Comment: 3 pages, talk given at the 9th Workshop on Topics in Astroparticle and Underground Physics, Zaragoza, September 10-1

Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies

Background Although neutrophils have been linked to the progression of cancer, uncertainty exists around their association with cancer outcomes, depending on the site, outcome and treatments considered. We aimed to evaluate the strength and validity of evidence on the association between either the neutrophil to lymphocyte ratio (NLR) or tumour-associated neutrophils (TAN) and cancer prognosis. Methods We searched MEDLINE, Embase and Cochrane Database of Systematic Reviews from inception to 29 May 2020 for systematic reviews and meta-analyses of observational studies on neutrophil counts (here NLR or TAN) and specific cancer outcomes related to disease progression or survival. The available evidence was graded as strong, highly suggestive, suggestive, weak or uncertain through the application of pre-set GRADE criteria. Results A total of 204 meta-analyses from 86 studies investigating the association between either NLR or TAN and cancer outcomes met the criteria for inclusion. All but one meta-analyses found a hazard ratio (HR) which increased risk (HR > 1). We did not find sufficient meta-analyses to evaluate TAN and cancer outcomes (N = 9). When assessed for magnitude of effect, significance and bias related to heterogeneity and small study effects, 18 (9%) associations between NLR and outcomes in composite cancer endpoints (combined analysis), cancers treated with immunotherapy and some site specific cancers (urinary, nasopharyngeal, gastric, breast, endometrial, soft tissue sarcoma and hepatocellular cancers) were supported by strong evidence. Conclusion In total, 60 (29%) meta-analyses presented strong or highly suggestive evidence. Although the NLR and TAN hold clinical promise in their association with poor cancer prognosis, further research is required to provide robust evidence, assess causality and test clinical utility

Blood pressure, hypertension and the risk of atrial fibrillation: a systematic review and meta-analysis of cohort studies

Elevated blood pressure and hypertension have been associated with increased risk of atrial fibrillation in a number of epidemiological studies, however, the strength of the association has differed between studies. We conducted a systematic review and meta-analysis of the association between blood pressure and hypertension and atrial fibrillation. PubMed and Embase databases were searched for studies of hypertension and blood pressure and atrial fibrillation up to June 6th 2022. Cohort studies reporting adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) of atrial fibrillation associated with hypertension or blood pressure were included. A random effects model was used to estimate summary RRs. Sixty eight cohort studies were included in the meta-analysis. The summary RR was 1.50 (95% CI: 1.42-1.58, I2 = 98.1%, n = 56 studies) for people with hypertension compared to those without hypertension (1,080,611 cases, 30,539,230 participants), 1.18 (95% CI: 1.16-1.21, I2 = 65.9%, n = 37 studies) per 20 mmHg increase in systolic blood pressure (346,471 cases, 14,569,396 participants), and 1.07 (95% CI: 1.03-1.11, I2 = 91.5%, n = 22 studies) per 10 mmHg increase in diastolic blood pressure (332,867 cases, 14,354,980 participants). There was evidence of a nonlinear association between diastolic blood pressure and atrial fibrillation with a steeper increase in risk at lower levels of diastolic blood pressure, but for systolic blood pressure the association appeared to be linear. For both systolic and diastolic blood pressure, the risk increased even within the normal range of blood pressure and persons at the high end of systolic and diastolic blood pressure around 180/110 mmHg had a 1.8-2.3 fold higher risk of atrial fibrillation compared to those with a blood pressure of 90/60 mmHg. These results suggest that elevated blood pressure and hypertension increases the risk of atrial fibrillation and there is some increase in risk even within the normal range of systolic and diastolic blood pressure

Metformin Decreases the Incidence of Pancreatic Ductal Adenocarcinoma Promoted by Diet-induced Obesity in the Conditional KrasG12D Mouse Model.

Pancreatic ductal adenocarcinoma (PDAC) is a particularly deadly disease. Chronic conditions, including obesity and type-2 diabetes are risk factors, thus making PDAC amenable to preventive strategies. We aimed to characterize the chemo-preventive effects of metformin, a widely used anti-diabetic drug, on PDAC development using the KrasG12D mouse model subjected to a diet high in fats and calories (HFCD). LSL-KrasG12D/+;p48-Cre (KC) mice were given control diet (CD), HFCD, or HFCD with 5 mg/ml metformin in drinking water for 3 or 9 months. After 3 months, metformin prevented HFCD-induced weight gain, hepatic steatosis, depletion of intact acini, formation of advanced PanIN lesions, and stimulation of ERK and mTORC1 in pancreas. In addition to reversing hepatic and pancreatic histopathology, metformin normalized HFCD-induced hyperinsulinemia and hyperleptinemia among the 9-month cohort. Importantly, the HFCD-increased PDAC incidence was completely abrogated by metformin (p &lt; 0.01). The obesogenic diet also induced a marked increase in the expression of TAZ in pancreas, an effect abrogated by metformin. In conclusion, administration of metformin improved the metabolic profile and eliminated the promoting effects of diet-induced obesity on PDAC formation in KC mice. Given the established safety profile of metformin, our findings have a strong translational potential for novel chemo-preventive strategies for PDAC

Lowering the background level and the energy threshold of Micromegas x-ray detectors for axion searches

Axion helioscopes search for solar axions by their conversion in x-rays in the presence of high magnetic fields. The use of low background x-ray detectors is an essential component contributing to the sensitivity of these searches. In this work, we review the recent advances on Micromegas detectors used in the CERN Axion Solar Telescope (CAST) and proposed for the future International Axion Observatory (IAXO). The actual setup in CAST has achieved background levels below 10$^{-6}$ keV$^{-1}$ cm$^{-2}$ s$^{-1}$, a factor 100 lower than the first generation of Micromegas detectors. This reduction is based on active and passive shielding techniques, the selection of radiopure materials, offline discrimination techniques and the high granularity of the readout. We describe in detail the background model of the detector, based on its operation at CAST site and at the Canfranc Underground Laboratory (LSC), as well as on Geant4 simulations. The best levels currently achieved at LSC are low than 10$^{-7}$ keV$^{-1}$ cm$^{-2}$ s$^{-1}$ and show good prospects for the application of this technology in IAXO. Finally, we present some ideas and results for reducing the energy threshold of these detectors below 1 keV, using high-transparent windows, autotrigger electronics and studying the cluster shape at different energies. As a high flux of axion-like-particles is expected in this energy range, a sub-keV threshold detector could enlarge the physics case of axion helioscopes.Comment: Proceedings of 3rd International Conference on Technology and Instrumentation in Particle Physics (TIPP 2014

Micromegas in a Bulk

In this paper we present a novel way to manufacture the bulk Micromegas detector. A simple process based on the PCB (Printed Circuit Board) technology is employed to produce the entire sensitive detector. Such fabrication process could be extended to very large area detectors made by the industry. The low cost fabrication together with the robustness of the electrode materials will make it extremely attractive for several applications ranging from particle physics and astrophysics to medicineComment: 6 pages, 4 figure

Influence of tooth loss on mandibular morphology : a cone-beam computed tomography study

Tooth loss adversely affects patients? health and psychosocial wellbeing. In addition, it changes mandibular morphology. Objective: To evaluate the effect of tooth loss, age, and gender on mandibular morphology. Cone-beam computed tomographic (CBCT) scans of 101 patients were examined to measure the gonial angle (GA), ramus height (RH) and condylar height (CH). Patients? age, gender, and dental status were recorded. Repeated measures analysis of variance (ANOVA) was used to assess the impact of gender, age, and tooth loss on the GA, RH and CH. The mean measurements of the GA, RH and CH were compared between dentate/edentulous patients after splitting by gender. The GA was larger in edentulous patients compared to dentate ones, in females than in males, and in older than in younger. RH on the right side was significantly longer than on the left side (P< 0.0001), and also longer in males and younger patients. CH was shorter in younger than in older patients and in dentate than in edentulous patients. Tooth loss is associated with changes in mandibular morphology and its prevention would avoid these irreversible changes