Non-linear behavior of unbraced two-bay reinforced concrete frames

In this investigation, the primary objective was to study the nonlinear behavior of unbraced two-bay concrete frames and to determine the extent to which ultimate load theory or limit design can be applied to these structures. The frame behavior was investigated analytically by two methods. In the first method the frame stability equation was derived assuming that members of the frame possess an elasto-plastic moment-curvature relationship. This stability analysis was also carried out by another model consisting of a column attached to a linear spring and carrying the total frame load. The second method was through a computer program which took material and geometric nonlinearities of concrete frames into account. A model concrete frame, with a scale factor of approximately one-third was considered. Variable parameters were loading condition, column reinforcement ratio, and beam to column load ratio. For each frame, the gravity loads were increased proportionally until 75% of the frame ultimate capacity under gravity loads was reached. Then; while these gravity loads were held constant, lateral load was applied and increased to failure. The overall geometry, 21-in high columns and 84-in long beam, were kept the same for all of model frames investigated. The computer study and the stability model analysis indicated that all frames remained stable until four plastic hinges (two in each bay) formed, thus producing a combined sway mechanism. Based on the scope of this study, it appears that limit design may be employed for unbraced reinforced concrete structures

Dietary Manganese, Plasma Markers of Inflammation, and the Development of Type 2 Diabetes in Postmenopausal Women: Findings From the Womens Health Initiative.

OBJECTIVE: To examine the association between manganese intake and the risk of type 2 diabetes in postmenopausal women and determine whether this association is mediated by circulating markers of inflammation. RESEARCH DESIGN AND METHODS: We included 84,285 postmenopausal women without a history of diabetes from the national Womens Health Initiative Observational Study (WHI-OS). Replication analysis was then conducted among 62,338 women who participated in the WHI-Clinical Trial (WHI-CT). Additionally, data from a case-control study of 3,749 women nested in the WHI-OS with information on biomarkers of inflammation and endothelial dysfunction were examined using mediation analysis to determine the relative contributions of these known biomarkers by which manganese affects type 2 diabetes risk. RESULTS: Compared with the lowest quintile of energy-adjusted dietary manganese, WHI-OS participants in the highest quintile had a 30% lower risk of type 2 diabetes (hazard ratio [HR] 0.70 [95% CI 0.65, 0.76]). A consistent association was also confirmed in the WHI-CT (HR 0.79 [95% CI 0.73, 0.85]). In the nested case-control study, higher energy-adjusted dietary manganese was associated with lower circulating levels of inflammatory biomarkers that significantly mediated the association between dietary manganese and type 2 diabetes risk. Specifically, 19% and 12% of type 2 diabetes risk due to manganese were mediated through interleukin 6 and hs-CRP, respectively. CONCLUSIONS: Higher intake of manganese was directly associated with a lower type 2 diabetes risk independent of known risk factors. This association may be partially mediated by inflammatory biomarkers

Associations between birthweight and preterm birth and the ages at menarche and menopause.

BACKGROUND: Women who reach menarche and menopause at earlier ages have been shown to be at increased risk for numerous conditions including cardiovascular disease, cancer, depression, and obesity; however, risk factors for earlier ages of menarche and menopause are not fully understood. Therefore, we aimed to perform a retrospective investigation of the associations between a personal birthweight and/or being born preterm and the age of and menarche and menopause and related events in the Womens Health Initiative, a large, racially and ethnically diverse cohort of postmenopausal women. METHODS: At study entry, women reported their birthweight by category (< 6 lbs., 6-7 lbs. 15 oz, 8-9 lbs. 15 oz, or ≥ 10 lbs.) and preterm birth status (4 or more weeks premature). Ages at events related to menarche and menopause were also self-reported. Linear regression and logistic regression models were used to estimate unadjusted and adjusted effect estimates (β) and odds ratios (OR), respectively (n ≤ 86,857). Individuals born preterm were excluded from all birthweight analyses. RESULTS: After adjustments, individuals born weighing < 6lbs. were more likely to reach natural menopause at an earlier age (adjusted β=-0.361, SE = 0.09, P = < 0.001) and have a shorter reproductive window (adjusted β = -0.287, SE = 0.10, p < 0.004) compared to individuals weighing 6-7 lbs. 15 oz. Individuals born preterm were also more likely to reach natural menopause at an earlier age (adjusted β=-0.506, SE = 0.16, P = 0.001) and have a shorter reproductive window (adjusted β = -0.418, SE = 0.17, p < 0.006). CONCLUSIONS: These findings raise concerns that, as more preterm and low birthweight individuals survive to adulthood, the prevalence of earlier-onset menarche and menopause may increase. Clinical counseling and interventions aimed at reducing the incidence of preterm and low birthweight births, as well as intensification of lifestyle modifications to reduce CVD risk among women with these early-life risk factors, should be prioritized

Pharmacoepidemiology evaluation of bumetanide as a potential candidate for drug repurposing for Alzheimers disease.

INTRODUCTION: Bumetanide, a loop diuretic, was identified as a candidate drug for repurposing for Alzheimers disease (AD) based on its effects on transcriptomic apolipoprotein E signatures. Cross-sectional analyses of electronic health records suggest that bumetanide is associated with decreased prevalence of AD; however, temporality between bumetanide exposure and AD development has not been established. METHODS: We evaluated Medicare claims data using Cox proportional hazards regression to evaluate the association between time-dependent use of bumetanide and time to first AD diagnosis while controlling for patient characteristics. Multiple sensitivity analyses were conducted to test the robustness of the findings. RESULTS: We sampled 833,561 Medicare beneficiaries, 60.8% female, with mean (standard deviation) age of 70.4 (12). Bumetanide use was not significantly associated with AD risk (hazard ratio 1.05; 95% confidence interval, 0.99-1.10). DISCUSSION: Using a nationwide dataset and a retrospective cohort study design, we were not able to identify a time-dependent effect of bumetanide lowering AD risk. HIGHLIGHTS: Bumetanide was identified as a candidate for repurposing for Alzheimers disease (AD). We evaluated the association between bumetanide use and risk of AD. We used Medicare data and accounted for duration of bumetanide use. Bumetanide use was not significantly associated with risk of AD

Relationships Between APOE, Type 2 Diabetes, and Cardiovascular Disease in Postmenopausal Women.

BACKGROUND: The apolipoprotein E (APOE) ε4 allele, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD) are well-established risk factors for dementia. Relationships between APOE and incidence of T2DM and CVD are not fully understood but may shed light on the mechanisms underlying dementia pathogenesis. METHODS: Postmenopausal women (N = 6 795) from the Womens Health Initiative hormone therapy clinical trial with APOE genotyping and no prior diagnosis of T2DM or CVD were included. We examined associations of APOE status (APOE2+ [ε2/ε2, ε2/ε3], APOE3 [ε3/ε3], and APOE4+ [ε4/ε4, ε3/ε4] carriers) with incidence of T2DM, coronary heart disease, stroke, and total CVD events using Cox regression. CVD outcomes were examined in baseline non-statin users and adjusted for statin initiation over follow-up to account for possible confounding by statins. RESULTS: Among all participants (mean age 66.7 ± 6.5 years, 100% non-Hispanic White), 451 (6.6%) were using statins at baseline. Over the follow-up (mean 14.9 and 16.0 years for T2DM and CVD, respectively), 1 564 participants developed T2DM and 1 578 developed CVD. T2DM incidence did not differ significantly by APOE status (ps ≥ .09). Among non-statin users, APOE4+ had higher incidence of total CVD (hazard ratio [95% confidence interval] = 1.18 [1.02-1.38], p = .03) compared with APOE3 carriers, but risks for coronary heart disease (1.09 [0.87-1.36], p = .47) and stroke (1.14 [0.91-1.44], p = .27) were not significantly elevated when examined individually. CVD outcomes did not differ between APOE2+ and APOE3 carriers (ps ≥ 0.11). CONCLUSIONS: T2DM risk did not differ by APOE status among postmenopausal women, but APOE4+ carriers not using statins had an increased risk of total CVD events

Energy-Adjusted Dietary Inflammatory Index and Diabetes Risk in Postmenopausal Hispanic Women.

BACKGROUND: Type 2 diabetes is a major public health concern in the United States and worldwide. The dietary inflammatory index (DII) and the energy-adjusted DII (E-DII) are tools that assess dietary inflammation. Previous evidence suggests that obesity can modify the association between inflammation and disease. OBJECTIVE: The aim of this study was to evaluate the association between the DII/E-DII and incident diabetes in self-identified Hispanic women from the Womens Health Initiative (WHI). The secondary aim was to evaluate whether obesity modifies the association between the DII/E-DII scores and incident diabetes. DESIGN: Participants were from the WHI Observational Study and the Clinical Trial Components (except women from the treatment arm in the Dietary Modification Trial) conducted among postmenopausal women in the United States. DII/E-DII scores were calculated from a self-administered food frequency questionnaire at baseline that included 122 food items, of which 12 are representative of Hispanic eating patterns. PARTICIPANTS/SETTINGS: Participants included 3,849 postmenopausal women who self-identified as Hispanic that were recruited for the WHI from 1993 to 1998 at 40 US clinical centers. MAIN OUTCOME MEASURES: The outcome was incident diabetes. STATISTICAL ANALYSIS PERFORMED: Cox regression models were used to assess the association between DII/E-DII and incident diabetes. Models were adjusted for age at baseline, lifestyle-related risk factors, known type 2 diabetes mellitus (T2DM) risk factors, and neighborhood socioeconomic status. Interaction was tested between the DII/E-DII scores and obesity. RESULTS: The incidence of diabetes was 13.1% after a median follow-up of 13 years. Higher E-DII scores were associated with a higher risk of incident diabetes (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.04-1.14). There was no interaction between E-DII scores and obesity (P = 0.73). CONCLUSIONS: Pro-inflammatory diets, as measured by higher E-DII scores, were associated with a higher risk of incident diabetes. Future research is needed for understanding how the inflammatory potential of diets can be decreased

Comparison of the Ketogenic Ratio of Macronutrients With the Low-Carbohydrate Diet Score and Their Association With Risk of Type 2 Diabetes in Postmenopausal Women: A Secondary Analysis of the Womens Health Initiative.

BACKGROUND: Previous attempts to identify low-carbohydrate diets (LCDs) in epidemiological studies relied on the LCD Score, which is unable to identify ketogenic dieters. Ketogenic ratios of macronutrients are clinical equations proposed to predict ketogenic diets; however, their utility in epidemiological studies is unknown. OBJECTIVE: To determine the number of participants consuming a ketogenic diet, compare ketogenic ratios to the LCD Score, and evaluate their association with type 2 diabetes mellitus (T2DM). DESIGN: Secondary analysis of the Womens Health Initiative with 17.9 ± 6.03 years of follow-up. Baseline food frequency questionnaires were used to calculate the ketogenic ratio as follows: (0.9 × grams fat + 0.46 × grams protein) / (0.1 × grams fat + 0.58 × grams protein + grams net carbohydrate), a value ≥1.5 is the minimum threshold for a ketogenic diet. PARTICIPANTS/SETTING: One hundred twenty-five nine hundred eighty-two postmenopausal women without diabetes (aged 50 to 79 years) enrolled in the multicenter Womens Health Initiative observational study and clinical trials were included. MAIN OUTCOME MEASURES: Risk of self-reported incident T2DM. STATISTICAL ANALYSES PERFORMED: Cox proportional hazards models, adjusted for age, race, ethnicity, education, income, health insurance, relationship status, geographic region, Womens Health Initiative study component, female hormone use, smoking status, alcohol use, recreational physical activity, total energy intake, diet quality, body mass index, hyperlipidemia, and hypertension, were used to compare hazard ratios and 95% CIs for T2DM among quintiles of the ketogenic ratio. RESULTS: A total of 18,775 incident cases of T2DM occurred. The median ketogenic ratio was 0.35 (interquartile range 0.28 to 0.42) and 15 individuals (0.01%) exceeded the threshold for a ketogenic diet. Higher ketogenic ratio quintiles were associated with increased risk of T2DM in a dose-dependent manner. Comparing extreme quintiles of the ketogenic ratio, the hazard ratio for diabetes was 1.24 (95% CI 1.18 to 1.31; Ptrend < 0.001) in fully adjusted models. Similarly, comparing extreme quintiles, the hazard ratio for diabetes was 1.36 (95% CI 1.29 to 1.43; Ptrend < 0.001) for the LCD Score and 1.13 (95% CI 1.07 to 1.19; Ptrend < 0.001) for the simplified ketogenic ratio in fully adjusted models. CONCLUSIONS: Increasing ketogenic ratio values are associated with increased risk of T2DM and align well with LCD Scores; however, too few participants consumed a ketogenic diet to determine its association with T2DM

Biomarkers of glucose homeostasis as mediators of the relationship of body mass index and waist circumference with COVID-19 outcomes among postmenopausal women: The Womens Health Initiative.

BACKGROUND & AIMS: Systematic reviews, meta-analyses and Mendelian randomization studies suggest that cardiometabolic diseases may be associated with COVID-19 risk and prognosis, with evidence implicating insulin resistance (IR) as a common biological mechanism. As driving factors for IR, we examined body mass index (BMI) and waist circumference (WC) among postmenopausal women in association with COVID-19 outcomes (positivity and hospitalization), and the role of glucose homeostasis as a mediator of this relationship. METHODS: Associations of BMI and WC at baseline (1993-1998) with COVID-19 outcomes collected at Survey 1 (June-December, 2020) and/or Survey 2 (September-December, 2021) were evaluated among 42,770 Womens Health Initiative (WHI) participants (baseline age: 59.36 years) of whom 16,526 self-reported having taken ≥1 COVID-19 test, with 1242 reporting ≥1 positive COVID-19 test and 362 reporting ≥1 COVID-19 hospitalization. We applied logistic regression and causal mediation analyses to sub-samples with available fasting biomarkers of glucose homeostasis (glucose, insulin, Homeostatic Model Assessment for Insulin Resistance, Homeostasis Model Assessment for β-cell function, Quantitative Insulin-sensitivity Check Index, Triglyceride-Glucose index (TyG)) at baseline, whereby 57 of 759 reported COVID-19 test positivity and 23 of 1896 reported COVID-19 hospitalization. RESULTS: In fully adjusted models, higher BMI, WC and TyG were associated with COVID-19 test positivity and hospitalization. Glucose concentrations mediated associations of BMI and WC with COVID-19 positivity, whereas TyG mediated BMI and WCs associations with COVID-19 hospitalization. CONCLUSIONS: Obesity and central obesity markers collected an average of 24 years prior were associated with COVID-19 outcomes among postmenopausal women. Glucose concentration and TyG partly mediated these associations

Cocoa Extract Supplementation and Risk of Type 2 Diabetes: The Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) Randomized Clinical Trial.

OBJECTIVE: Observational studies have indicated that cocoa flavanol supplementation may be a promising strategy for type 2 diabetes (T2D) prevention. We aimed to directly evaluate its clinical efficacy in a large randomized clinical trial (RCT). RESEARCH DESIGN AND METHOD: The Cocoa Supplement and Multivitamin Outcomes Study (COMSOS) was a 2 × 2 factorial RCT performed from June 2015 to December 2020 that tested cocoa extract and a multivitamin for the prevention of cardiovascular disease (CVD) and cancer. A total of 21,442 U.S. adults free of CVD and recent cancer, including 12,666 women aged ≥65 years and 8,776 men aged ≥60 years, were randomly assigned to receive cocoa extract [500 mg/day cocoa flavanols, including 80 mg (-)-epicatechin] or placebo. In this study, we included 18,381 participants without diabetes at enrollment and examined the effect of cocoa extract supplementation on incident self-reported T2D in intention-to-treat analyses. RESULTS: During a median follow-up of 3.5 years, 801 incident T2D cases were reported. Compared with placebo, taking a cocoa extract supplement did not reduce T2D (adjusted hazard ratio 1.04, 95% CI 0.91-1.20, P = 0.58). Stratification analyses showed that the effect of cocoa extract supplementation was not significantly modified by sex, race, BMI, smoking, physical activity, dietary quality, flavanol status at baseline, or randomized multivitamin assignment. CONCLUSIONS: Middle-aged and older adults taking a cocoa extract supplement for a median of 3.5 years did not reduce their risk of incident T2D. Further studies of cocoa extract supplementation beginning earlier in adulthood and in populations with different background diets are warranted

Identifying the relation between food groups and biological ageing: a data-driven approach.

BACKGROUND: Heterogeneity in ageing rates drives the need for research into lifestyle secrets of successful agers. Biological age, predicted by epigenetic clocks, has been shown to be a more reliable measure of ageing than chronological age. Dietary habits are known to affect the ageing process. However, much remains to be learnt about specific dietary habits that may directly affect the biological process of ageing. OBJECTIVE: To identify food groups that are directly related to biological ageing, using Copula Graphical Models. METHODS: We performed a preregistered analysis of 3,990 postmenopausal women from the Womens Health Initiative, based in North America. Biological age acceleration was calculated by the epigenetic clock PhenoAge using whole-blood DNA methylation. Copula Graphical Modelling, a powerful data-driven exploratory tool, was used to examine relations between food groups and biological ageing whilst adjusting for an extensive amount of confounders. Two food group-age acceleration networks were established: one based on the MyPyramid food grouping system and another based on item-level food group data. RESULTS: Intake of eggs, organ meat, sausages, cheese, legumes, starchy vegetables, added sugar and lunch meat was associated with biological age acceleration, whereas intake of peaches/nectarines/plums, poultry, nuts, discretionary oil and solid fat was associated with decelerated ageing. CONCLUSION: We identified several associations between specific food groups and biological ageing. These findings pave the way for subsequent studies to ascertain causality and magnitude of these relationships, thereby improving the understanding of biological mechanisms underlying the interplay between food groups and biological ageing