Residual stresses in cold-formed steel members: review of measurement methods and numerical modelling

The determination of residual stress distributions in cold-formed members is revisited considering both experimental and numerical methodologies. Destructive, semi-destructive and non-destructive techniques are reviewed with special emphasis on sectioning, hole drilling and X-ray diffraction; the particularities of each procedure on cold-formed sections are addressed. Theory on metal strip deformation and roll design is exposed before analytical and incremental closed-formed expressions are presented and compared to experimental results for press-braked sections. Finally, the most important works on finite element simulations of roll forming are revisited, highlighting the computational limitations and the capability for predicting residual stresses.FASTCOLD project (FAtigue STrength of COLD-formed structural steel details; Ref. 745982–2017) funded by Research Fund for Coal and Steel (RFCS) of the European Commissio

Body composition and risk of vascular‐metabolic mortality risk in 113 000 Mexican men and women without prior chronic disease

Background: Body‐mass index is the sum of fat mass index (FMI) and lean mass index (LMI), which vary by age, sex, and impact on disease outcomes. We investigated the separate and joint relevance of FMI and LMI with vascular‐metabolic causes of death in Mexican adults. Methods and Results: A total of 113 025 adults aged 35 to 74 years and free from diabetes or other chronic diseases when recruited into the Mexico City Prospective Study were followed for 19 years. Cox models estimated sex‐specific death rate ratios from vascular‐metabolic causes after adjustment for confounders and exclusion of the first 5 years of follow‐up. To account for the strong correlation between FMI and LMI, additional models estimated rate ratios associated with “residual FMI” and “residual LMI” (ie, the residuals from linear regression analyses of FMI on LMI, or vice versa). In both sexes, higher FMI and LMI were associated with higher risks of vascular‐metabolic mortality. For a given (ie, fixed) level of LMI, the rate ratio (95% CI) for vascular‐metabolic mortality per 1 kg/m2 higher residual FMI strengthened and was higher in women (1.52 [1.38–1.68]) than in men (1.19 [1.13–1.25]). By contrast, for a given level of FMI, higher residual LMI was inversely associated with vascular‐metabolic mortality (rate ratio per 1 kg/m2 0.67 [0.56–0.80] in women and 0.94 [0.90–0.98] in men). Conclusions: In this study, higher residual FMI was more strongly associated with vascular‐metabolic mortality in women than in men. Conversely, higher residual LMI was inversely associated with vascular‐metabolic mortality, particularly in women

Adiposity and NMR-measured lipid and metabolic biomarkers among 30,000 Mexican adults

Background: Adiposity is a major cause of morbidity and mortality in part due to effects on blood lipids. Nuclear magnetic resonance (NMR) spectroscopy provides direct information on >130 biomarkers mostly related to blood lipid particles. Methods: Among 28,934 Mexican adults without chronic disease and not taking lipid-lowering therapy, we examine the cross-sectional relevance of body-mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), and hip circumference (HC) to NMR-measured metabolic biomarkers. Confounder-adjusted associations between each adiposity measure and NMR biomarkers are estimated before and after mutual adjustment for other adiposity measures. Results: Markers of general (ie, BMI), abdominal (ie, WC and WHR) and gluteo-femoral (ie, HC) adiposity all display similar and strong associations across the NMR-platform of biomarkers, particularly for biomarkers that increase cardiometabolic risk. Higher adiposity associates with higher levels of Apolipoprotein-B (about 0.35, 0.30, 0.35, and 0.25 SD higher Apolipoprotein-B per 2-SD higher BMI, WHR, WC, and HC, respectively), higher levels of very low-density lipoprotein particles (and the cholesterol, triglycerides, and phospholipids within these lipoproteins), higher levels of all fatty acids (particularly mono-unsaturated fatty acids) and multiple changes in other metabolic biomarkers including higher levels of branched-chain amino acids and the inflammation biomarker glycoprotein acetyls. Associations for general and abdominal adiposity are fairly independent of each other but, given general and abdominal adiposity, higher gluteo-femoral adiposity is associated with a strongly favourable cardiometabolic lipid profile. Conclusions: Our results provide insight to the lipidic and metabolomic signatures of different adiposity markers in a previously understudied population where adiposity is common but lipid-lowering therapy is not

Body Composition and Risk of Vascular‐Metabolic Mortality Risk in 113 000 Mexican Men and Women Without Prior Chronic Disease

Background Body‐mass index is the sum of fat mass index (FMI) and lean mass index (LMI), which vary by age, sex, and impact on disease outcomes. We investigated the separate and joint relevance of FMI and LMI with vascular‐metabolic causes of death in Mexican adults. Methods and Results A total of 113 025 adults aged 35 to 74 years and free from diabetes or other chronic diseases when recruited into the Mexico City Prospective Study were followed for 19 years. Cox models estimated sex‐specific death rate ratios from vascular‐metabolic causes after adjustment for confounders and exclusion of the first 5 years of follow‐up. To account for the strong correlation between FMI and LMI, additional models estimated rate ratios associated with “residual FMI” and “residual LMI” (ie, the residuals from linear regression analyses of FMI on LMI, or vice versa). In both sexes, higher FMI and LMI were associated with higher risks of vascular‐metabolic mortality. For a given (ie, fixed) level of LMI, the rate ratio (95% CI) for vascular‐metabolic mortality per 1 kg/m2 higher residual FMI strengthened and was higher in women (1.52 [1.38–1.68]) than in men (1.19 [1.13–1.25]). By contrast, for a given level of FMI, higher residual LMI was inversely associated with vascular‐metabolic mortality (rate ratio per 1 kg/m2 0.67 [0.56–0.80] in women and 0.94 [0.90–0.98] in men). Conclusions In this study, higher residual FMI was more strongly associated with vascular‐metabolic mortality in women than in men. Conversely, higher residual LMI was inversely associated with vascular‐metabolic mortality, particularly in women

Human genetics uncovers MAP3K15 as an obesity-independent therapeutic target for diabetes

We performed collapsing analyses on 454,796 UK Biobank (UKB) exomes to detect gene-level associations with diabetes. Recessive carriers of nonsynonymous variants in MAP3K15 were 30% less likely to develop diabetes (P = 5.7 × 10−10) and had lower glycosylated hemoglobin (β = −0.14 SD units, P = 1.1 × 10−24). These associations were independent of body mass index, suggesting protection against insulin resistance even in the setting of obesity. We replicated these findings in 96,811 Admixed Americans in the Mexico City Prospective Study (P < 0.05). Moreover, the protective effect of MAP3K15 variants was stronger in individuals who did not carry the Latino-enriched SLC16A11 risk haplotype (P = 6.0 × 10−4). Separately, we identified a Finnish-enriched MAP3K15 protein-truncating variant associated with decreased odds of both type 1 and type 2 diabetes (P < 0.05) in FinnGen. No adverse phenotypes were associated with protein-truncating MAP3K15 variants in the UKB, supporting this gene as a therapeutic target for diabetes

Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity

Large-scale human exome sequencing can identify rare protein-coding variants with a large impact on complex traits such as body adiposity. We sequenced the exomes of 645,626 individuals from the United Kingdom, the United States, and Mexico and estimated associations of rare coding variants with body mass index (BMI). We identified 16 genes with an exome-wide significant association with BMI, including those encoding five brain-expressed G protein-coupled receptors (CALCR, MC4R, GIPR, GPR151, and GPR75). Protein-truncating variants in GPR75 were observed in ∼4/10,000 sequenced individuals and were associated with 1.8 kilograms per square meter lower BMI and 54% lower odds of obesity in the heterozygous state. Knock out of Gpr75 in mice resulted in resistance to weight gain and improved glycemic control in a high-fat diet model. Inhibition of GPR75 may provide a therapeutic strategy for obesity

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)