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

A configurational approach to innovation performance: The role of creativity

In this study, we analyze new ways of conceptualizing improvements in firms’ innovation by implementing the “right-factors configuration,” illustrated through an analog of a recipe and its ingredients. Specifically, we research the multiple combinations of three ingredients (creativity, innovation networks, and resources) required to accomplish the innovation recipe. Using a sample of firms from a Spanish science and technology park, we apply qualitative comparative analysis (QCA)—specifically, fuzzy-set QCA (fsQCA)—to test the importance of each component in technological and non-technological innovation. First, the results suggest a map of combinations of innovative ingredients with eight possible patterns. Second, they show that the only ingredient needed is the combination of a creative climate and creative intensity. Finally, the methods of obtaining technological and non-technological innovations differ. The implications for management and policymakers are discussed, and directions for future research are highlighted

Role of diet in type 2 diabetes incidence: umbrella review of meta-analyses of prospective observational studies

OBJECTIVE: To summarise the evidence of associations between dietary factors and incidence of type 2 diabetes and to evaluate the strength and validity of these associations. DESIGN: Umbrella review of systematic reviews with meta-analyses of prospective observational studies. DATA SOURCES: PubMed, Web of Science, and Embase, searched up to August 2018. ELIGIBILITY CRITERIA: Systematic reviews with meta-analyses reporting summary risk estimates for the associations between incidence of type 2 diabetes and dietary behaviours or diet quality indices, food groups, foods, beverages, alcoholic beverages, macronutrients, and micronutrients. RESULTS: 53 publications were included, with 153 adjusted summary hazard ratios on dietary behaviours or diet quality indices (n=12), food groups and foods (n=56), beverages (n=10), alcoholic beverages (n=12), macronutrients (n=32), and micronutrients (n=31), regarding incidence of type 2 diabetes. Methodological quality was high for 75% (n=115) of meta-analyses, moderate for 23% (n=35), and low for 2% (n=3). Quality of evidence was rated high for an inverse association for type 2 diabetes incidence with increased intake of whole grains (for an increment of 30 g/day, adjusted summary hazard ratio 0.87 (95% confidence interval 0.82 to 0.93)) and cereal fibre (for an increment of 10 g/day, 0.75 (0.65 to 0.86)), as well as for moderate intake of total alcohol (for an intake of 12-24 g/day v no consumption, 0.75 (0.67 to 0.83)). Quality of evidence was also high for the association for increased incidence of type 2 diabetes with higher intake of red meat (for an increment of 100 g/day, 1.17 (1.08 to 1.26)), processed meat (for an increment of 50 g/day, 1.37 (1.22 to 1.54)), bacon (per two slices/day, 2.07 (1.40 to 3.05)), and sugar sweetened beverages (for an increase of one serving/day, 1.26 (1.11 to 1.43)). CONCLUSIONS: Overall, the association between dietary factors and type 2 diabetes has been extensively studied, but few of the associations were graded as high quality of evidence. Further factors are likely to be important in type 2 diabetes prevention; thus, more well conducted research, with more detailed assessment of diet, is needed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018088106

Dietary fibre, whole grains, and risk of colorectal cancer: systematic review and dose-response meta-analysis of prospective studies

Objective To investigate the association between intake of dietary fibre and whole grains and risk of colorectal cancer

Body size and obesity during adulthood, and risk of lympho-haematopoietic cancers: an update of the WCRF-AICR systematic review of published prospective studies.

BACKGROUND: To summarise the evidence on the associations between body mass index (BMI) and BMI in early adulthood, height, waist circumference (WC) and waist-to-hip ratio (WHR), and risk of lympho-haematopoietic cancers. METHOD: We conducted a meta-analysis of prospective studies and identified relevant studies published up to December 2017 by searching PubMed. A random-effects model was used to calculate dose-response summary relative risks (RRs). RESULTS: Our findings showed BMI, and BMI in early adulthood (aged 18-21 years) is associated with the risk of Hodgkin's and non-Hodgkin's lymphoma (HL and NHL), diffuse large beta-cell lymphoma (DLBCL), Leukaemia including acute and chronic myeloid lymphoma (AML and CML), and chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM). The summary RR per 5 kg/m2 increase in BMI were 1.12 [95% confidence interval (CI): 1.05-1.20] for HL, 1.05 (95% CI: 1.03-1.08) for NHL, 1.11 (95% CI: 1.05-1.16) for DLBCL, 1.06 (95% CI: 1.03-1.09) for ML, 1.09 (95% CI: 1.03-1.15) for leukaemia, 1.13 (95% CI: 1.04-1.24) for AML, 1.13 (95% CI: 1.05-1.22) for CML and 1.04 (95% CI: 1.00-1.09) for CLL, and were1.12 (95% CI: 1.05-1.19) for NHL, 1.22 (95% CI: 1.09-1.37) for DLBCL, and 1.19 (95% CI: 1.03-1.38) for FL for BMI in early adulthood analysis. Results on mortality showed a 15%, 16% and 17% increased risk of NHL, MM and leukaemia, respectively. Greater height increased the risk of NHL by 7%, DLBCL by 10%, FL by 9%, MM by 5% and Leukaemia by 7%. WHR was associated with increased risk of DLBCL by 12%. No association was found between higher WC and risk of MM. CONCLUSION: Our results revealed that general adiposity in adulthood and early adulthood, and greater height may increase the risk of almost all types of lympho-haematopoietic cancers and this adds to a growing body of evidence linking body fatness to several types of cancers.This work was funded by the World Cancer Research Fund Network (grant number 2007/SP01) as part of the Continuous Update Project (http://www.wcrf-uk.org/)

Effects of outer hair cell loss on the frequency selectivity of the patas monkey auditory system

This report describes a study that took advantage of the unique reactivity of the patas monkey (Erythrocebus patas) to dihydrostreptomycin-sulfate (DHSM) to investigate the effects of selective outer hair cell (OHC) lesions on psychophysical tuning curves (PTC). Four patas monkeys were trained using operant reinforcement techniques to perform forward masking PTCs at frequencies of 500 Hz, 2, 4, and 8 kHz, at 10 dB SL. Steady and pulsed-tone thresholds were also measured from 63 Hz to 40 kHz in half-octave steps. The animals were given daily i.m. injections of DHSM at 20 mg/kg per day until shifts in absolute threshold at 16 kHz exceeded 10 dB, at which time the drug was discontinued. Initial changes in PTC shape included elevations in the tip region associated with the increase in threshold and no elevation or a hypersensitivity of the low-frequency tail region. In general, threshold and therefore PTC tip elevations of at least 40 dB were required before any increase in the low-frequency tail became evident. Following completion of psychophysical testing, animals were sacrificed and cytochochleograms were determined. At frequencies corresponding to regions of complete OHC loss and complete IHC retention a lack of selectivity was evident and PTCs closely resemble low-pass filters. This residual low-pass tuning is similar to that seen in VIIIth nerve fibers in ears devoid of OHCs and in basilar membrane transfer functions from traumatized ears. PTCs taken at frequencies corresponding to areas with no loss of receptors showed no systematic changes in sensitivity or selectivity. Because toss of normal OHC function results in greater than a 50-dB toss in sensitivity, as well as a detuned PTC, these findings strongly support the suggestion that the role of the OHC system is to increase the sensitivity and selectivity of the auditory system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26889/1/0000455.pd

Surgical Video Motion Magnification with Suppression of Instrument Artefacts

Video motion magnification could directly highlight subsurface blood vessels in endoscopic video in order to prevent inadvertent damage and bleeding. Applying motion filters to the full surgical image is however sensitive to residual motion from the surgical instruments and can impede practical application due to aberration motion artefacts. By storing the temporal filter response from local spatial frequency information for a single cardiovascular cycle prior to tool introduction to the scene, a filter can be used to determine if motion magnification should be active for a spatial region of the surgical image. In this paper, we propose a strategy to reduce aberration due to non-physiological motion for surgical video motion magnification. We present promising results on endoscopic transnasal transsphenoidal pituitary surgery with a quantitative comparison to recent methods using Structural Similarity (SSIM), as well as qualitative analysis by comparing spatio-temporal cross sections of the videos and individual frames.Comment: Early accept to the Internation Conference on Medical Imaging Computing and Computer Assisted Intervention (MICCAI) 2020 Presentation available here: https://www.youtube.com/watch?v=kKI_Ygny76Q Supplementary video available here: https://www.youtube.com/watch?v=8DUkcHI149

World Cancer Research Fund International: Continuous Update Project—systematic literature review and meta-analysis of observational cohort studies on physical activity, sedentary behavior, adiposity, and weight change and breast cancer risk

Purpose: The purpose of the present study was to systematically review the complex associations between energy balance-related factors and breast cancer risk, for which previous evidence has suggested different associations in the life course of women and by hormone receptor (HR) status of the tumor. Methods: Relevant publications on adulthood physical activity, sedentary behavior, body mass index (BMI), waist and hip circumferences, waist-to-hip ratio, and weight change and pre- and postmenopausal breast cancer risk were identified in PubMed up to 30 April 2017. Random-effects meta-analyses were conducted to summarize the relative risks across studies. Results: One hundred and twenty-six observational cohort studies comprising over 22,900 premenopausal and 103,000 postmenopausal breast cancer cases were meta-analyzed. Higher physical activity was inversely associated with both pre- and postmenopausal breast cancers, whereas increased sitting time was positively associated with postmenopausal breast cancer. Although higher early adult BMI (ages 18–30 years) was inversely associated with pre- and postmenopausal breast cancers, adult weight gain and greater body adiposity increased breast cancer risk in postmenopausal women, and the increased risk was evident for HR+ but not HR− breast cancers, and among never but not current users of postmenopausal hormones. The evidence was less consistent in premenopausal women. There were no associations with adult weight gain, inverse associations with adult BMI (study baseline) and hip circumference, and non-significant associations with waist circumference and waist-to-hip ratio that were reverted to positive associations on average in studies accounting for BMI. No significant associations were observed for HR-defined premenopausal breast cancers. Conclusion: Better understanding on the impact of these factors on pre- and postmenopausal breast cancers and their subtypes along the life course is needed

Cholesterol and breast cancer risk: a systematic review and meta-analysis of prospective studies

The objective of the present study was to conduct the first systematic review and meta-analysis of prospective studies investigating the associations between total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels and the risk of breast cancer. Relevant studies were identified in PubMed (up to January 2014). Inclusion criteria were original peer-reviewed publications with a prospective design. Random-effects models were used to estimate summary hazard ratios (HR) and 95 % CI. Distinction was made between studies that did or did not exclude cancer cases diagnosed during the first years of follow-up, thereby eliminating potential preclinical bias. Overall, the summary HR for the association between TC and breast cancer risk was 0·97 (95 % CI 0·94, 1·00; dose–response per 1 mmol/l increment, thirteen studies), and that between HDL-C and breast cancer risk was 0·86 (95 % CI 0·69, 1·09; dose–response per 1 mmol/l increment, six studies), with high heterogeneity (I 2= 67 and 47 %, respectively). For studies that eliminated preclinical bias, an inverse association was observed between the risk of breast cancer and TC (dose–response HR 0·94 (95 % CI 0·89, 0·99), seven studies, I 2= 78 %; highest v. lowest HR 0·82 (95 % CI 0·66, 1·02), nine studies, I 2= 81 %) and HDL-C (dose–response HR 0·81 (95 % CI 0·65, 1·02), five studies, I 2= 30 %; highest v. lowest HR 0·82 (95 % CI 0·69, 0·98), five studies, I 2= 0 %). There was no association observed between LDL-C and the risk of breast cancer (four studies). The present meta-analysis confirms the evidence of a modest but statistically significant inverse association between TC and more specifically HDL-C and the risk of breast cancer, supported by mechanistic plausibility from experimental studies. Further large prospective studies that adequately control for preclinical bias are needed to confirm the results on the role of cholesterol level and its fractions in the aetiology of breast cancer