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Background Red meat is a nutrient‐dense source of protein fundamental for older adults; however, red meat is also high in detrimental components, including saturated fat. It is unclear whether habitual red meat consumption is associated with risk of frailty. This study aimed to examine the prospective association between the consumption of total, unprocessed, and processed red meat and the risk of frailty in older adults. Methods We analysed data from 85 871 women aged ≥60 participating in the Nurses' Health Study. Consumption of total, unprocessed, and processed red meat was obtained from repeated food frequency questionnaires administered between 1980 and 2010. Frailty was defined as having at least three of the following five criteria from the FRAIL scale: fatigue, low strength, reduced aerobic capacity, having ≥5 chronic illnesses, and unintentional weight loss ≥5%. The occurrence of frailty was assessed every four years from 1992 to 2014. Results During 22 years of follow‐up (median follow‐up 14 years), we identified 13 279 incident cases of frailty. Women with a higher intake of red meat showed an increased risk of frailty after adjustment for lifestyle factors, medication use, and dietary factors. The relative risk (95% confidence interval) for one serving/day increment in consumption was 1.13 (1.08, 1.18) for total red meat, 1.08 (1.02, 1.15) for unprocessed red meat, and 1.26 (1.15, 1.39) for processed red meat. When each component of the frailty syndrome was individually examined, each of them was positively associated with total red meat consumption, except for the weight loss criterion. Replacing one serving/day of unprocessed red meat with other protein sources was associated with significantly lower risk of frailty; the risk reduction estimates were 22% for fish and 14% for nuts, while for replacement of processed red meat, the percentages were 33% for fish, 26% for nuts, 13% for legumes, and 16% for low‐fat dairy. Conclusions Habitual consumption of unprocessed and processed red meat was associated with a higher risk of frailty. Replacement of red meat by other protein sources might reduce the risk of frailty. These findings are in line with dietary guidelines promoting diets that emphasize plant‐based sources of protein.

Background Diet is one of the modifiable risk factors for cognitive decline. However, studies on dietary protein intake and cognitive decline have remained limited and inconclusive. Objectives In this study, we aimed to investigate the associations between long-term dietary protein intake and subsequent subjective cognitive decline (SCD). Methods We included 49,493 women from the Nurses' Health Study (NHS) (1984-2006) and 27,842 men from the Health Professionals Follow-up Study (HPFS) (1986-2002). For the NHS, average dietary intake was calculated from 7 repeated semi-quantitative FFQs (SFFQs), and SCD was assessed in 2012 and 2014. For the HPFS, average dietary intake was calculated from 5 repeated SFFQs, and SCD was assessed in 2008 and 2012. Poisson regression was used to examine the associations between dietary protein, amino acids, and various protein food sources with subsequent SCD. Results Higher protein intake compared with total carbohydrates was associated with lower odds of SCD. When substituting 5% energy from protein for the equivalent percentage of energy from total carbohydrates, the pooled multivariable-adjusted ORs (95% CIs) were 0.89 (0.85, 0.94) for total protein, 0.89 (0.84, 0.94) for animal protein, and 0.74 (0.62, 0.88) for plant protein. When substituting 5% of energy from animal protein with plant protein, the OR was 0.84 (95% CI: 0.72, 0.97). For protein food sources, higher intakes of beans/legumes, fish, and lean poultry were significantly associated with lower odds of SCD, but higher intake of hotdogs was associated with higher odds of SCD. Conclusions Higher protein intake was associated with lower odds of SCD when compared isocalorically with carbohydrate. Plant protein sources were also associated with lower odds when compared with animal protein sources. Our findings suggest that adequate protein intake, and choices of protein sources could play a role in the maintenance of cognition and should be studied further.

Global atmospheric carbon dioxide concentrations will continue increasing throughout the next century, with profound impacts on agriculture. The literature concerning the effects of climate change on viticulture has largely focused on the isolated impacts of variables such as temperature and soil water deficit. Likewise, the research on the effects of elevated atmospheric CO2 on grapevines is stunted at the categorical level, chiefly because of the difficulty of experimentally controlling the gaseous environment in situ for the years necessary to replicate the vineyard system in a future climate condition. Despite numerous studies on the short-term influence of environmental and cultural factors on grapevine development at elevated carbon dioxide, the long-term impacts remain poorly understood. The lack of field based elevated CO2 experiments in the United States is an added challenge to predicting viticultural changes, particularly in California. This review focuses on the systemic impact of atmospheric CO2 on Vitis vinifera, synthesizing physiological, phenological, and plant-pest interactions. Major findings from this synthesis inform of a predicted increase in pest pressure, advanced phenological timing, transient increase in water use efficiency for grapevine, and changes in grape berry chemistry. While water use efficiency is highly desirable, the prediction for current winegrape growing regions is a transient increase in water use efficiency subsequently limited by a lack of available soil water. Grapevine is influenced by the negative synergistic effects of heat, drought, and elevated CO2, which will alter cultural practices including harvest and pest/disease control, with downstream effects on winemaking. Several options for adaptation are discussed including leaf removal, planting alternative varieties and selective breeding of new varieties.

Diet is one of the modifiable risk factors for cognitive decline. However, human studies on total energy intake and cognitive function have remained limited and studies on fat intake and cognitive decline have been inconclusive. We aimed to examine prospectively the associations between long-term intakes of total energy and fat with subsequent subjective cognitive decline (SCD). A total of 49,493 women from the Nurses’ Health Study (NHS) and 27,842 men from the Health Professionals Follow-up Study (HPFS) were followed for over 20 years. Average dietary intake was calculated based on repeated food frequency questionnaires (SFFQs), and Poisson regression was used to evaluate associations. Higher total energy intake was significantly associated with greater odds of SCD in both cohorts. Comparing the highest with lowest quintiles of total energy intake, the pooled multivariable-adjusted ORs (95% CIs) for a 3-unit increment in SCD, corresponding to poor versus normal SCD, was 2.77 (2.53, 2.94). Each 500 kcal/day greater intake of total energy was associated with 48% higher odds of SCD. Intakes of both total fat and total carbohydrate appeared to contribute to the positive association with total energy intake although for the same percent of energy, the association was stronger for total fat. In conclusion, higher intakes of total energy, total fat, and total carbohydrate were adversely associated with SCD. Whether these associations are causal is unclear and deserves further investigation.

Summary Background & aims Unrestrained eating behavior has been thought to be a proxy for diet frequency, timing, and caloric intake. We investigated the association of unrestrained eating with mortality risk in the Nurses’ Health Study prospectively. Methods During follow-up (1994–2016), 21,953 deaths were documented among 63,999 eligible participants in analyses of eating anything at any time, 22,120 deaths were documented among 65,839 participants in analyses of no concern with figure change. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Results Eating anything at any time was associated with an increased mortality from cancer (overall HR, 95%CI: 1.07, 1.00–1.13; driven by gastrointestinal tract cancer: 1.30, 1.10–1.54) and respiratory disease (1.16, 1.05–1.29), and decreased cardiovascular disease-specific mortality (0.92, 0.86–0.99), compared to those without this behavior; however, no association was observed between this behavior and all-cause mortality (1.02, 0.99–1.05). Women who reported having no concern with figure change experienced higher risk of mortality from all-cause (1.08, 1.05–1.11), cancer (1.08, 1.02–1.14), and respiratory disease (1.18, 1.08–1.30), compared to those not reporting this behavior. Their combined effect was associated with a higher all-cause (1.09, 1.04–1.14), cancer-specific (overall: 1.18, 1.09–1.28; gastrointestinal tract cancer: 1.36, 1.08–1.71; lung cancer: 1.09; 1.04–1.14), and respiratory disease-specific (1.30, 1.13–1.50) mortality, and was inversely associated with cardiovascular disease-specific mortality (0.88, 0.80–0.98), compared to those exhibiting the opposite. Conclusions Unrestrained eating was associated with increased risk of all-cause, cancer-specific (particularly for gastrointestinal tract cancer and lung cancer), and respiratory disease-specific mortality, and decreased risk of cardiovascular disease-specific mortality.

Background Unrestrained eating behavior, as a potential proxy for diet frequency, timing, and caloric intake, has been questioned as a plausible risk factor for digestive system cancers, but epidemiological evidence remains sparse. Objectives We investigated prospectively the associations between unrestrained eating behavior and digestive system cancer risk. Methods Participants in the Nurses' Health Study who were free of cancer and reported dietary information in 1994 were followed for ≤18 y. Cox models were used to estimate HRs and 95% CIs for unrestrained eating (eating anything at any time, no concern with figure change, or both) and risk of digestive system cancers. Results During follow-up, 2064 digestive system cancer cases were documented among 70,450 eligible participants in analyses of eating anything at any time, In total, 2081 digestive system cancer cases were documented among 72,468 eligible participants in analyses of no concern with figure change. In fully adjusted analyses, women with the behavior of eating anything at any time had a higher risk of overall digestive system cancer (HR: 1.22; 95% CI: 1.10, 1.35), overall gastrointestinal tract cancer ((HR: 1.33; 95% CI: 1.18, 1.50), buccal cavity and pharynx cancer (HR: 1.50; 95% CI: 1.02, 2.21), esophageal cancer (HR: 1.62; 95% CI: 1.01, 2.62), small intestine cancer (HR: 1.92; 95% CI: 1.02,3. 59), and colorectal cancer (HR: 1.20; 95% CI: 1.04, 1.38), and a non-statistically significant increased risk of stomach cancer (HR: 1.54; 95% CI: 0.96,2.48), compared with women without this behavior. No statistically significant association was observed for pancreatic cancer and liver and gallbladder cancer. The combined effect of eating anything at any time and having no concern with figure change was associated with a significantly increased risk of overall digestive system cancer (HR: 1.27; 95% CI: 1.10, 1.46), overall gastrointestinal tract cancer (HR: 1.45; 95% CI: 1.23, 1.71), and colorectal cancer (HR: 1.34; 95% CI: 1.11, 1.63), compared with women exhibiting the opposite. Conclusions Unrestrained eating behavior was independently associated with increased risk of gastrointestinal tract cancers. The potential importance of unrestrained eating behavior modification in preventing gastrointestinal tract cancers should be noted.

Background We have developed a simple and globally applicable tool, the Global Diet Quality Score (GDQS), to measure diet quality. Objectives To test the utility of the GDQS, we examined the associations of the GDQS with weight change and risk of obesity in US women. Methods Health, lifestyle, and diet information were collected from women (n = 68,336) in the Nurses’ Health Study II (aged 27–44 y in 1991) through repeated questionnaires (1991–2015). The GDQS has 25 food groups (maximum = 49 points) and scoring higher points reflects a healthier diet. The association between GDQS change in 4-y intervals and concurrent weight change was computed with linear models adjusted for confounders. Results Mean ± SD weight gain across 4-y periods was 1.68 ± 6.26 kg. A >5-point improvement in GDQS was associated with −1.13 kg (95% CI: −1.19, −0.77 kg) weight gain compared with a score change of 5-point score decrease was associated with 1.13 kg (95% CI: 1.04, 1.22 kg) more weight gain in women aged 5-point increase and 1.32 (95% CI: 1.26, 1.37) for a >5-point decrease. Risk of obesity did not differ by age. Compared with other diet quality scores, the Alternate Healthy Eating Index-2010 had somewhat stronger associations than the GDQS (P

Background The prevalence of type 2 diabetes has increased substantially in India over the past 3 decades. Undiagnosed diabetes presents a public health challenge, especially in rural areas, where access to laboratory testing for diagnosis may not be readily available. Objectives The present work explores the use of several machine learning and statistical methods in the development of a predictive tool to screen for prediabetes using survey data from an FFQ to compute the Global Diet Quality Score (GDQS). Methods The outcome variable prediabetes status (yes/no) used throughout this study was determined based upon a fasting blood glucose measurement ≥100 mg/dL. The algorithms utilized included the generalized linear model (GLM), random forest, least absolute shrinkage and selection operator (LASSO), elastic net (EN), and generalized linear mixed model (GLMM) with family unit as a (cluster) random (intercept) effect to account for intrafamily correlation. Model performance was assessed on held-out test data, and comparisons made with respect to area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Results The GLMM, GLM, LASSO, and random forest modeling techniques each performed quite well (AUCs >0.70) and included the GDQS food groups and age, among other predictors. The fully adjusted GLMM, which included a random intercept for family unit, achieved slightly superior results (AUC of 0.72) in classifying the prediabetes outcome in these cluster-correlated data. Conclusions The models presented in the current work show promise in identifying individuals at risk of developing diabetes, although further studies are necessary to assess other potentially impactful predictors, as well as the consistency and generalizability of model performance. In addition, future studies to examine the utility of the GDQS in screening for other noncommunicable diseases are recommended.

Background Key nutrient deficits remain widespread throughout sub-Saharan Africa (SSA) whereas noncommunicable diseases (NCDs) now cause one-third of deaths. Easy-to-use metrics are needed to track contributions of diet quality to this double burden. Objectives We evaluated comparative performance of a novel food-based Global Diet Quality Score (GDQS) against other diet metrics in capturing nutrient adequacy and undernutrition in rural SSA adults. Methods We scored the GDQS, Minimum Dietary Diversity–Women (MDD-W), and Alternative Healthy Eating Index–2010 (AHEI-2010) using FFQ data from rural men and nonpregnant, nonlactating women of reproductive age (15–49 y) in 10 SSA countries. We evaluated Spearman correlations between metrics and energy-adjusted nutrient intakes, and age-adjusted associations with BMI, midupper arm circumference (MUAC), and hemoglobin in regression models. Results Correlations between the GDQS and an energy-adjusted aggregate measure of dietary protein, fiber, calcium, iron, zinc, vitamin A, folate, and vitamin B-12 adequacy were 0.34 (95% CI: 0.30, 0.38) in men and 0.37 (95% CI: 0.32, 0.41) in women. The GDQS was associated (P

Background The double burdens of under- and overnutrition are changing the health of individuals and the economic and disease burdens in China. Poor diet plays an important role; however, a valid and easily operationalized metric that could capture the full range of characteristics of the diet that are relevant to both under- and overnutrition is lacking in China. Objectives We aimed to examine the application of the Global Diet Quality Score (GDQS) to evaluate nutrient inadequacy and metabolic syndrome in different demographic groups of Chinese adults. Methods A total of 35,146 individuals (men 14,978, women 20,168) aged >18 y from the 2010–2012 China National Nutrition and Health Survey were included. We scored the GDQS using average intakes of 25 food groups from 3 d of 24-h dietary recalls. Double burden was defined as coexisting metabolic syndrome and nutrient inadequacy. Results Diet quality assessed by GDQS was significantly higher in urban than in rural residents (20.8 compared with 18.7), and increased with both educational level and household income (P-trends < 0.0001). A higher GDQS score was inversely associated with metabolic syndrome and nutrient inadequacy, or both (P-trends < 0.0001): multivariate adjusted ORs comparing extreme quintiles of GDQS were 0.79 (95% CI: 0.69, 0.91) for metabolic syndrome, 0.17 (95% CI: 0.14, 0.20) for nutrient inadequacy, and 0.59 (95% CI: 0.50, 0.69) for the double burden. These associations were consistent across different household income levels (P-interaction = 0.26), suggestively stronger in younger (

Background Evidence on concurrent changes in overall diet quality and weight and waist circumference in women of reproductive age from low- and middle-income countries is limited. Objectives We examined the associations of changes in the Global Diet Quality Score (GDQS) and each GDQS food group with concurrent weight and waist circumference change in Mexican women. Methods We followed prospectively 8967 nonpregnant nonlactating women aged 25–49 y in the Mexican Teachers’ Cohort between 2006 and 2008. We assessed diet using an FFQ of the previous year and anthropometric measures were self-reported. Regression models were used to examine 2-y changes in the GDQS and each food group (servings/d) with weight and waist circumference changes within the same period, adjusting for demographic and lifestyle factors. Results Compared with those with little change in the GDQS (−2 to 2 points), women with the largest increase in the GDQS (>5 points) had less weight (β: −0.81 kg/2 y; 95% CI: −1.11, −0.51 kg/2 y) and waist circumference gain (β: −1.05 cm/2 y; 95% CI: −1.62, −0.48 cm/2 y); likewise, women with the largest decrease in the GDQS (

Background We have developed a diet quality metric intended for global use. To assess its utility in high-income settings, an evaluation of its ability to predict chronic disease is needed. Objectives We aimed to prospectively examine the ability of the Global Diet Quality Score (GDQS) to predict the risk of type 2 diabetes in the United States, examine potential differences of association by age, and compare the GDQS with other diet quality scores. Methods Health, lifestyle, and diet information was collected from women (n = 88,520) in the Nurses’ Health Study II aged 27–44 y at baseline through repeated questionnaires between 1991 and 2017. The overall GDQS consists of 25 food groups. Points are awarded for higher intake of healthy groups and lower intake of unhealthy groups (maximum of 49 points). Multivariable HRs were computed for confirmed type 2 diabetes using proportional hazards models. We also compared the GDQS with the Minimum Diet Diversity score for Women (MDD-W) and the Alternate Healthy Eating Index-2010 (AHEI-2010). Results We ascertained 6305 incident cases of type 2 diabetes during follow-up. We observed a lower risk of diabetes with higher GDQS; the multivariable HR comparing extreme quintiles of the GDQS was 0.83 (95% CI: 0.76, 0.91; P-trend

Background Poor diet quality is a major driver of both classical malnutrition and noncommunicable disease (NCD) and was responsible for 22% of adult deaths in 2017. Most countries face dual burdens of undernutrition and NCDs, yet no simple global standard metric exists for monitoring diet quality in populations and population subgroups. Objectives We aimed to develop an easy-to-use metric for nutrient adequacy and diet related NCD risk in diverse settings. Methods Using cross-sectional and cohort data from nonpregnant, nonlactating women of reproductive age in 10 African countries as well as China, India, Mexico, and the United States, we undertook secondary analyses to develop novel metrics of diet quality and to evaluate associations between metrics and nutrient intakes and adequacy, anthropometry, biomarkers, type 2 diabetes, and iteratively modified metric design to improve performance and to compare novel metric performance to that of existing metrics. Results We developed the Global Diet Quality Score (GDQS), a food-based metric incorporating a more comprehensive list of food groups than most existing diet metrics, and a simple means of scoring consumed amounts. In secondary analyses, the GDQS performed comparably with the Minimum Dietary Diversity - Women indicator in predicting an energy-adjusted aggregate measure of dietary protein, fiber, calcium, iron, zinc, vitamin A, folate, and vitamin B12 adequacy and with anthropometric and biochemical indicators of undernutrition (including underweight, anemia, and serum folate deficiency), and the GDQS also performed comparably or better than the Alternative Healthy Eating Index - 2010 in capturing NCD-related outcomes (including metabolic syndrome, change in weight and waist circumference, and incident type 2 diabetes). Conclusions The simplicity of the GDQS and its ability to capture both nutrient adequacy and diet-related NCD risk render it a promising candidate for global monitoring platforms. Research is warranted to validate methods to operationalize GDQS assessment in population surveys, including a novel application–based 24-h recall system developed as part of this project.

Elevated first metatarsal, Metatarsus primus elevatus (MPE), has been a topic of controversy. Recent studies have supported a significantly elevated first metatarsal in hallux rigidus on weight-bearing radiographs (WBR). However, conventional radiographs have limitations for accurate measurement. Our objective was to comparatively assess MPE and other variables which can affect the spatial relationship of the forefoot in the HR group compared to controls using weight-bearing CT (WBCT). In this single-center, retrospective, case–control study, 25 patients (30 feet) with symptomatic HR and 30 controls were selected. WBCT parameters were measured by two independent investigators. Inter-observer reliabilities were assessed using intra-class correlation coefficients (ICCs). MPE was evaluated by measuring the direct distance between 1st and 2nd metatarsals. Independent t tests were performed to compare the two groups. A threshold of MPE to diagnose HR was calculated using the Receiver Operating Characteristic (ROC) curve. HR groups had increased hallux valgus angle (HVA) (8.52° in control vs 11.98° in HR) and MPE (2.92 vs 5.09 mm), decreased 1st metatarsal declination angle (21.09° vs 19.07°) 1st/2nd metatarsal declination ratio (87.45 vs 79.71) indicating elevated first metatarsal compared to controls. Dorsal translation of the first metatarsal at the first tarsometatarsal joint was observed in 21 (70%) patients of the HR group when defined as a step-off or discontinuation of the curvature along the first TMT joint. The threshold of MPE for diagnosis of HR was 4.19 mm with 77% sensitivity and 77% specificity. Our results confirmed a significantly elevated first metatarsal in the HR group compared to controls on WBCT. A MPE greater than 4.19 mm was found to be diagnostic for symptomatic HR. Significant number of patients in the HR group (70%) had dorsal translation of the first metatarsal at the first TMT joint which can contribute to increased MPE. The present study demonstrated significantly increased MPE in HR on WBCT and MPE greater than 4.19 mm on WBCT can be used as a diagnostic threshold for HR.

BACKGROUND Earlier evidence on the association between dietary polyunsaturated fatty acids and risk of diabetes has been conflicting. PURPOSE To quantitatively summarize previous studies on the association between dietary LA intake, its biomarkers, and the risk of type 2 diabetes mellitus (T2DM) in the general population. DATA SOURCES Our data sources included PubMed/MEDLINE, Scopus, and ISI Web of Science until 24 October 2020; reference lists of all related articles; and key journals. STUDY SELECTION We included prospective cohort studies that examined the associations of linoleic acid (LA) with the risk of T2DM in adults. DATA SYNTHESIS The inverse variance method was applied to calculate summary relative risk (RR) of LA intake and its biomarkers, and dose-response associations were modeled using restricted cubic splines. Twenty-three publications, covering a total of 31 prospective cohorts, were included; these studies included 297,685 participants (22,639 incident diabetes cases) with dietary intake assessment and 84,171 participants (18,458 incident diabetes cases) with biomarker measurements. High intake of LA was associated with a 6% lower risk of T2DM (summary relative risk [RR] 0.94, 95% CI 0.90, 0.99; I2 = 48.5%). In the dose-response analysis, each 5% increment in energy from LA intake was associated with a 10% lower risk of T2DM. There was also evidence of a linear association between LA intake and diabetes, with the lowest risk at highest intakes. The summary RR for diabetes per SD increment in LA concentrations in adipose tissue/blood compartments was 0.85 (95% CI 0.80, 0.90; I2 = 66.2%). The certainty of the evidence was assessed as moderate. LIMITATIONS A limitation of our work was the observational design of studies included in the analyses. CONCLUSIONS We found that a high intake of dietary LA and elevated concentrations of LA in the body were both significantly associated with a lower risk of T2DM. These findings support dietary recommendations to consume dietary LA.

The Mediterranean diet (MedDiet), one of the most studied and well-known dietary patterns worldwide, has been associated with a wide range of benefits for health. In the present narrative review, we aimed to provide a comprehensive overview of the current knowledge on the relation of the MedDiet to important health outcomes, considering both observational and intervention studies with both risk factors and clinical diseases as outcomes. In addition, we considered the clinical and public health impacts of the MedDiet on both human and planetary health. Earlier research confirmed by recent studies has provided strong evidence for the benefits of the MedDiet on cardiovascular health, including reduction in the incidence of cardiovascular outcomes as well as risk factors including obesity, hypertension, metabolic syndrome, and dyslipidaemia. There is also evidence that MedDiet is associated with lower rates of incident diabetes, and better glycaemic control in diabetic patients compared to control diets. In prospective studies, adherence to the MedDiet reduced mortality, especially cardiovascular mortality, hence increased longevity. In addition, it has been associated with less age-related cognitive dysfunction and lower incidence of neurodegenerative disorders, particularly Alzheimer's disease. Furthermore, the relatively low environmental impacts (water, nitrogen and carbon footprint) of the MedDiet is an additional positive aspect of the Mediterranean dietary model. It is likely that the combination of a healthy diet with social behaviours and the way of life of Mediterranean regions makes the MedDiet a sustainable lifestyle model that could likely be followed in other regions with country-specific and culturally appropriate variations.

OBJECTIVE Knowledge remains scarce regarding diet and systemic lupus erythematosus (SLE) risk. Our objective was to investigate 4 dietary quality scores and SLE risk overall and by anti-double-stranded DNA (anti-dsDNA) positive versus negative subtypes. METHODS We studied 79,568 women in the Nurses' Health Study (1984-2014) and 93,554 in the Nurses' Health Study II (1991-2013). Using validated food frequency questionnaires, we calculated 4 dietary scores: the 2010 Alternative Healthy Eating Index (AHEI-2010), the Alternative Mediterranean Diet Score (aMed), the Dietary Approach to Stop Hypertension (DASH), and the Empirical Dietary Inflammatory Pattern (EDIP). Incident SLE was confirmed by medical record review. Time-varying Cox regression models estimated pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) of SLE risk, overall and by anti-dsDNA, for cumulative average dietary quality score tertiles and individual AHEI-2010 components. RESULTS We identified 194 incident SLE cases. SLE risk was similar in women with the highest (versus lowest) dietary scores (AHEI-2010 HR 0.78 [95% CI 0.54-1.14], aMed HR 0.82 [95% CI 0.56-1.18], DASH HR 1.16 [95% CI 0.81-1.66], EDIP HR 0.83 [95% CI 0.57-1.21]). No association was demonstrated for anti-dsDNA+ or anti-dsDNA- SLE risk. Women in the highest (versus lowest) AHEI-2010 tertile of nut/legume intake had a decreased SLE risk (HR 0.59 [95% CI 0.40-0.87]). No association was demonstrated for other AHEI-2010 components and SLE risk. CONCLUSION We observed no association between long-term adherence to the AHEI-2010, aMed, DASH, or EDIP scores with SLE risk, suggesting a large effect of dietary quality on SLE risk is unlikely. However, potential reduction in overall SLE risk with high nut/legume intake warrants further investigation.

BACKGROUND: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes. OBJECTIVE: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status. METHOD: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8–20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models. RESULTS: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with

Background: Plant-based diets have been associated with lower risk of various diseases, including type 2 diabetes, cardiovascular disease, and other cardiometabolic risk factors. However, the association between plant-based diet quality and breast cancer remains unclear. Methods: We prospectively followed 76,690 women from the Nurses' Health Study (NHS, 1984–2016) and 93,295 women from the NHSII (1991–2017). Adherence to an overall plant-based diet index (PDI), a healthful PDI (hPDI), and an unhealthful PDI (uPDI) was assessed using previously developed indices. Cox proportional hazards models were used to estimate HR and 95% confidence intervals (CI) for incident invasive breast cancer. Results: Over 4,841,083 person-years of follow-up, we documented 12,482 incident invasive breast cancer cases. Women with greater adherence to PDI and hPDI were at modestly lower risk of breast cancer [(HRQ5 vs. Q1, 0.89; 95% CI, 0.84–0.95); (HRQ5 vs. Q1, 0.89; 95% CI, 0.83–0.94)]. We observed significant heterogeneity by estrogen receptor (ER) status, with the strongest inverse association between hPDI and breast cancer observed with ER-negative tumors [HRQ5 vs. Q1, 0.77; 95% CI, 0.65–0.90; Ptrend < 0.01]. We also found an inverse association between extreme quintiles of healthy plant foods and ER-negative breast cancer [HR, 0.74; 95% CI, 0.61–0.88; Ptrend < 0.01]. Conclusions: This study provides evidence that adherence to a healthful plant-based diet may reduce the risk of breast cancer, especially those that are more likely to be aggressive tumors. Impact: This is the first prospective study investigating the relation between healthful and unhealthful plant-based dietary indices and risk of total and subtype-specific breast cancer.

Background Folate may play a preventive role in the early stages of colorectal carcinogenesis, but long latencies may be needed to observe a reduction in colorectal cancer (CRC) incidence. In addition, concerns have been raised about the potential for cancer promotion with excessive folate intake, especially after the mandatory folic acid fortification in the United States in 1998. Objective We aimed to examine the association between folate intake in different chemical forms and CRC risk, especially in the postfortification era in the United States. Design We prospectively followed 86,320 women from the Nurses' Health Study (1980-2016). Folate intake was collected by validated food frequency questionnaires. CRC was self reported and confirmed by review of medical records. The association between the folate intake and CRC risk was assessed using Cox proportional hazards regression. Results We documented 1988 incident CRC cases during follow-up. Analyzing folate intake as a continuous variable, greater total folate intake 12-24 y before diagnosis was associated with lower risk of CRC (per increment of 400 dietary folate equivalents (DFE)/d, HR: 0.93, 95% CI: 0.85, 1.01 for 12-16 y; HR: 0.83, 95% CI: 0.75, 0.92 for 16-20 y; and HR: 0.87, 95% CI: 0.77, 0.99 for 20-24 y); and greater synthetic folic acid intake 16-24 y before diagnosis was also associated with a lower CRC risk (per increment of 400 DFE/d, HR: 0.91, 95% CI: 0.84, 0.99 for 16-20 y and HR: 0.91, 95% CI: 0.83-1.01 for 20-24 y). In the postfortification period (1998-2016), intake of total or specific forms of folate was not associated with CRC risk, even among multivitamin users. Conclusions Folate intake, both total and from synthetic forms, was associated with a lower risk of overall CRC after long latency periods. There was no evidence that high folate intake in the postfortification period was related to increased CRC risk in this US female population.

Type II diabetes is associated with poor breast cancer prognosis. To study the association between a diabetes risk reduction diet (DRRD) and survival following breast cancer, we followed 8,482 women with breast cancer from two large cohort studies. Information on diet and other factors was repeatedly measured in validated questionnaires every two to four years. The DRRD includes 9 components: higher intakes of cereal fiber, coffee, nuts, whole fruits and polyunsaturated/saturated fat ratio; and lower glycemic index, trans fat, sugar-sweetened beverages, and red meat. Cumulative average DRRD score was calculated using repeated measures of postdiagnostic diet. Deaths were assessed by family members or via National Death Index. Multivariable-adjusted HRs and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. During a median of 14 years of follow-up since diagnosis, 2,600 deaths occurred among participants, 1,042 of which were due to breast cancer. Women with higher postdiagnostic DRRD score had a 20% lower risk of breast cancer–specific mortality (top vs. bottom quintile HR = 0.80; 95% CI = 0.65–0.97; Ptrend = 0.02) and 34% lower risk of all-cause mortality (HR = 0.66; 95% CI = 0.58–0.76; Ptrend < 0.0001). Compared with women who consistently had lower score (≤median) before and after diagnosis, those whose score improved from low to high had a lower risk of breast cancer–specific mortality (HR = 0.77; 95% CI = 0.62–0.95) and overall mortality (HR = 0.85; 95% CI = 0.74–0.97). These findings demonstrate that greater adherence to DRRD was associated with better survival, suggesting postdiagnosis dietary modification consistent with type II diabetes prevention may be important for breast cancer survivors. Significance: This study suggests that greater adherence to the diabetes risk reduction diet after diagnosis associates with improved survival outcomes among a large number of breast cancer survivors.

Background Although colorectal cancer (CRC) incidence in the USA is declining overall, its incidence is increasing among those younger than 50 years of age. The reasons underlying the increasing trend are largely unknown, although behavioral changes, such as unhealthy diet and lifestyle factors, may be partially responsible. Design A prospective cohort study included 94 217 women aged 26-45 years at baseline. Validated anthropometric measures and lifestyle information were self-reported biennially. Exposures were four recommendation-based dietary indices—the prime diet quality score and three plant-based dietary indices; and two mechanism-based indices—the empirical dietary and lifestyle index for hyperinsulinemia (EDIH and ELIH). We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall CRC and for early-onset (before age 50) and after age 50 CRC separately. Results We documented 332 cases of CRC during 24 years of follow-up (2 113 655 person-years), with an average age of 52 ± 7 years at diagnosis. Hyperinsulinemic dietary and lifestyle patterns were associated with a higher risk of CRC. Multivariable-adjusted HRs (95% CIs) comparing participants in the highest versus lowest quartile were: 1.67 for EDIH (95% CI: 1.15-2.44, P-trend = 0.01) and 1.51 for ELIH (95% CI: 1.10-2.08, P-trend = 0.01). Moreover, per 75% increment in rank, ELIH appeared to be a stronger risk factor for early-onset CRC (HR = 1.86, 95% CI: 1.12-3.07) than after age 50 CRC (HR = 1.20, 95% CI: 0.83-1.73, P-heterogeneity = 0.16). The four recommendation-based indices were not significantly associated with overall, early-onset, or after age 50 CRC risk (per 75% increment in rank, HRs ranged from 0.75 to 1.28). Conclusion Dietary and lifestyle patterns contributing to hyperinsulinemia were associated with greater CRC risk in younger women. Moreover, the hyperinsulinemic lifestyle showed a suggestively stronger positive association with early-onset CRC risk, compared with after age 50 CRC. Our findings suggest that dietary and lifestyle interventions to reduce insulinemic potential may be effective for CRC prevention among younger women.

Background Virtual reality (VR) allows for presurgical planning. Intraoperatively, augmented reality (AR) enables integration of segmented anatomic information with neuronavigation into the microsurgical scene to provide guidance without workflow disruption. Combining VR and AR solutions may help guide microsurgical technique to improve safety, efficiency, and ergonomics. Objective To describe a VR/AR platform that provides VR planning and intraoperative guidance via microscope ocular injection of a comprehensive AR overlay of patient-specific 360°/3D anatomic model aligned and synchronized with neuronavigation. Methods Custom 360° models from preoperative imaging of 49 patients were utilized for preoperative planning using a VR-based surgical rehearsal platform. Each model was imported to SyncAR, the platform's intraoperative counterpart, which was coregistered with Medtronic StealthStation S8 and Zeiss or Leica microscope. The model was injected into the microscope oculars and referenced throughout by adjusting overlay opacity. For anatomic shifts or misalignment, the overlay was reregistered via manual realignment with known landmarks. Results No SyncAR-related complications occurred. SyncAR contributed positively to the 3D understanding of patient-specific anatomy and ability to operate. Preoperative planning and intraoperative AR with 360° models allowed for more precise craniotomy planning and execution. SyncAR was useful for guiding dissection, identifying critical structures including hidden anatomy, understanding regional anatomy, and facilitating resection. Manual realignment was performed in 48/49 surgeries. Gross total resection was achieved in 34/40 surgeries. All aneurysm clipping and microvascular decompression procedures were completed without complications. Conclusion SyncAR combined with VR planning has potential to enhance surgical performance by providing critical information in a user-friendly, continuously available, heads-up display format.

Background The activation of insulin pathways is hypothesized to promote tumor growth and worsen breast cancer survival. Sugar-sweetened beverages (SSBs) can lead to a higher risk of insulin resistance and may affect survival. The authors prospectively evaluated the relation of postdiagnostic SSB and artificially sweetened beverage (ASB) consumption with mortality among women with breast cancer. Methods In total, 8863 women with stage I through III breast cancer were identified during follow-up of the Nurses' Health Study (NHS; 1980-2010) and Nurses' Health Study II (NHSII; 1991-2011). Women completed a validated food frequency questionnaire every 4 years after diagnosis and were followed until death or the end of follow-up (2014 for the NHS and 2015 for the NHSII). Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer-specific and all-cause mortality after adjusting for measures of adiposity and other potential predictors of cancer survival. Results With a median follow-up of 11.5 years, 2482 deaths were prospectively documented, including 1050 deaths from breast cancer. Compared with women who had no consumption, women who had SSB consumption after diagnosis had higher breast cancer-specific mortality (>1 to 3 servings per week: HR, 1.31 [95% CI, 1.09-1.58]; >3 servings per week: HR, 1.35 [95% CI, 1.12-1.62]; Ptrend = .001) and all-cause mortality (>1 to 3 servings per week: HR, 1.21 [95% CI, 1.07-1.37]; >3 servings per week: HR, 1.28 [95% CI, 1.13-1.45]; Ptrend = .0001). In contrast, ASB consumption was not associated with higher breast cancer-specific or all-cause mortality. Furthermore, replacing 1 serving per day of SSB consumption with 1 serving per day of ASB consumption was not associated with a lower risk of mortality. Conclusions Higher postdiagnostic SSB consumption among breast cancer survivors was associated with higher breast cancer-specific mortality and death from all causes.

A lack of prospective studies has been a major barrier for assessing the role of the microbiome in human health and disease on a population-wide scale. To address this significant knowledge gap, we have launched a large-scale collection targeting fecal and oral microbiome specimens from 20,000 women within the Nurses’ Health Study II cohort (the Microbiome Among Nurses study, or Micro-N). Leveraging the rich epidemiologic data that have been repeatedly collected from this cohort since 1989; the established biorepository of archived blood, urine, buccal cell, and tumor tissue specimens; the available genetic and biomarker data; the cohort’s ongoing follow-up; and the BIOM-Mass microbiome research platform, Micro-N furnishes unparalleled resources for future prospective studies to interrogate the interplay between host, environmental factors, and the microbiome in human health. These prospectively collected materials will provide much-needed evidence to infer causality in microbiome-associated outcomes, paving the way toward development of microbiota-targeted modulators, preventives, diagnostics and therapeutics. Here, we describe a generalizable, scalable and cost-effective platform used for stool and oral microbiome specimen and metadata collection in the Micro-N study as an example of how prospective studies of the microbiome may be carried out. This Perspective from the Harvard Chan Microbiome in Public Health Center describes a generalizable and scalable approach to stool and oral microbiome and metadata collection in the Micro-N (Microbiome Among Nurses) study, to show how to carry out prospective studies of the microbiome.

OBJECTIVE To determine which attributes of residency applicants were most commonly assessed by large and small animal American College of Veterinary Surgeons diplomates and to determine which evaluation methods were perceived to assess those attributes. STUDY DESIGN Online survey. SAMPLE POPULATION American College of Veterinary Surgeons board-certified surgeons as of March 2019. METHODS An online survey was sent to eligible individuals. Respondents rated the importance of 23 attributes assessed by the Veterinary Internship and Residency Matching Program (VIRMP) application as well the usefulness of interviews, conversations with people knowledgeable with the applicants, and review of the VIRMP packet for evaluating each of these attributes. Responses were compared between large and small animal practitioners and between individuals involved in residency selection (supervisors) and individuals not involved in residency selection (nonsupervisors). RESULTS Surveys were completed by 221 individuals (14.6% response rate). Seventeen of the 23 attributes were considered important by most respondents. Grade point average (GPA) and class rank were used as screening tools by 73% and 65% of supervisors, respectively. Letters of reference (LOR) were ranked as the most important part of the VIRMP packet. Conversations with people knowledgeable with the applicant was the only method judged by most respondents to be appropriate to evaluate all 23 attributes. Responses were similar between large and small animal supervisors and nonsupervisors. CONCLUSION Respondents considered conversations with people knowledgeable with the applicant to be the most useful methods for assessing a resident applicant, but LOR, GPA, and class rank were also important. IMPACT Resident applicants and mentors can use this information to strengthen applications.

Heavy alcohol consumption in mid-adulthood is an established risk factor of colorectal cancer (CRC). Alcohol use in early adulthood is common, but its association with subsequent CRC risk remains largely unknown. We prospectively investigated the association of average alcohol intake in early adulthood (age 18-22) with CRC risk later in life among 191,543 participants of the Nurses’ Health Study ([NHS], 1988-2014), NHSII (1989-2015) and Health Professionals Follow-Up Study (1988-2014). Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs), which were pooled using random effects models. We documented 2,624 CRC cases. High alcohol consumption in early adulthood (≥15 g/day) was associated with a higher CRC risk (multivariable HR 1.28, 95% CI 0.99 to 1.66, P(trend)=0.02; P(heterogeneity)=0.44), after adjusting for potential confounding factors in early adulthood. Among never/light smokers in early adulthood, the risk associated with high alcohol consumption in early adulthood was elevated (HR 1.53, 95% CI 1.04 to 2.24), compared with those who had

Importance: Type 2 diabetes (T2D) is associated with poor breast cancer prognosis. Adherence to a dietary pattern associated with lower T2D risk may improve breast cancer outcomes. Objective: To evaluate the association between adherence to a diabetes risk reduction diet (DRRD) after diagnosis and survival outcomes following breast cancer. Method: We followed 8,320 women diagnosed with stage I-III breast cancer from two large prospective cohort studies, the Nurses’ Health Study (NHS; 1980-2014) and the NHSII (1991-2015). Information on diet and other covariates was repeatedly measured in validated follow-up questionnaires every two to four years. The DRRD adherence score includes 9 dietary components: higher intakes of cereal fiber, coffee, nuts, whole fruits and polyunsaturated:saturated fat ratio; and lower glycemic index of diet, lower intakes of trans fat, sugar-sweetened beverages/fruit juices, and red meat. Cumulative average DRRD score was calculated using repeated measures of diet after breast cancer diagnosis. Deaths were reported by family members or via the search of National Death Index, and cause of death was assigned by reviewing death certificates/medical records. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between DRRD score and breast cancer-specific and all-cause mortality were estimated using Cox proportional hazards models. Results: During a median of 16 years of follow-up after diagnosis, we ascertained 2,146 deaths, of which 948 were due to breast cancer. In the multivariable-adjusted models, women with higher post-diagnostic DRRD scores had a 17% lower risk of breast cancer-specific mortality (top vs. bottom quintile HR =0.83; 95%CI=0.67-1.02; p-trend=0.03) and 33% lower risk of all-cause mortality (HR =0.67; 95%CI=0.58-0.78; p-trend Conclusion: We found that greater adherence to the DRRD after breast cancer diagnosis was associated with better survival, suggesting dietary modification after diagnosis consistent with T2D prevention may be important to breast cancer survivors. Table 1. Multivariable HRs and 95% CIs for the association between post-diagnostic diabetes risk reduction diet score and mortality among breast cancer survivors using pooled data from NHS abd NHSII (N=8,320)Quintile 1Quintile 2Quintile 3Quintile 4Quintile 5p-trendMedian (IQR)20 (18-21)24 (23-25)27 (26-28)30 (29-31)34 (33-37)Breast cancer-specific mortalityNo. of events (n=948), 589,953 py207205184176176Model 11 (referent)0.97 (0.80-1.18)0.80 (0.65-0.97)0.79 (0.64-0.96)0.75 (0.61-0.92)0.0008Model 21 (referent)0.88 (0.72-1.07)0.76 (0.62-0.93)0.77 (0.63-0.95)0.83 (0.67-1.02)0.03Model 31 (referent)0.99 (0.81-1.20)0.82 (0.67-1.00)0.85 (0.69-1.04)0.86 (0.70-1.07)0.06All-cause mortalityNo. of events (n=2,146), 589,953 py506447476383334Model 11 (referent)0.83 (0.73-0.94)0.80 (0.71-0.91)0.67 (0.59-0.76)0.57 (0.50-0.65) Table 2. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between changes of diabetes risk reduction diet score before or after diagnosis and mortality among breast cancer survivors using pooled data from NHS abd NHSII (N=8,320)CharacteristicsHR (95% CI)Breast cancer-specific mortalityCross classified changesNo. of events (n=948), 589,953 pyLow to Low1 (referent)Low to High0.81 (0.65-1.00)High to Low0.97 (0.79-1.19)High to High0.87 (0.74-1.02)All-cause mortalityCross classified changesNo. of events (n=2,306), 589,953 pyLow to Low1 (referent)Low to High0.88 (0.76-1.02)High to Low0.99 (0.87-1.12)High to High0.80 (0.72-0.89) Citation Format: Tengteng Wang, Maryam Farvid, Jae Hee Kang, Michelle Holmes, Bernard Rosner, Rulla Tamimi, Walter Willett, A. Heather Eliassen. Diabetes risk reduction diet and survival following breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS2-09.

To address how the microbiome might modify the interaction between diet and cardiometabolic health, we analyzed longitudinal microbiome data from 307 male participants in the Health Professionals Follow-Up Study, together with long-term dietary information and measurements of biomarkers of glucose homeostasis, lipid metabolism and inflammation from blood samples. Here, we demonstrate that a healthy Mediterranean-style dietary pattern is associated with specific functional and taxonomic components of the gut microbiome, and that its protective associations with cardiometabolic health vary depending on microbial composition. In particular, the protective association between adherence to the Mediterranean diet and cardiometabolic disease risk was significantly stronger among participants with decreased abundance of Prevotella copri. Our findings advance the concept of precision nutrition and have the potential to inform more effective and precise dietary approaches for the prevention of cardiometabolic disease mediated through alterations in the gut microbiome. The beneficial effects of a Mediterranean diet on cardiometabolic health are associated with specific changes in the gut microbiome, suggesting a personalized approach towards cardiometabolic disease prevention.

Background: We investigated the associations of postdiagnostic dietary glycemic index (GI), glycemic load (GL), insulin index (II), and insulin load (IL) with breast cancer–specific and all-cause mortality. Methods: Among 8,932 women with stage I–III breast cancer identified in the Nurses' Health Study (NHS; 1980–2010) and NHSII (1991–2011), we prospectively evaluated the associations between postdiagnostic GI, GL, II, and IL, and breast cancer–specific and all-cause mortality. Participants completed a validated food frequency questionnaire every 4 years after diagnosis. Results: During follow-up by 2014 in the NHS and 2015 in the NHSII, 2,523 deaths, including 1,071 from breast cancer, were documented. Higher postdiagnostic GL was associated with higher risk of both breast cancer–specific mortality [HRQ5vsQ1 = 1.33; 95% confidence interval (CI) = 1.09–1.63; Ptrend = 0.008] and all-cause mortality (HRQ5vsQ1 = 1.26; 95% CI = 1.10–1.45; Ptrend = 0.0006). Higher all-cause mortality was also observed with higher postdiagnostic GI (HRQ5vsQ1 = 1.23; 95% CI = 1.08–1.40; Ptrend = 0.001), II (HRQ5vsQ1 = 1.20; 95% CI = 1.04–1.38; Ptrend = 0.005), and IL (HRQ5vsQ1 = 1.23; 95% CI = 1.07–1.42; Ptrend = 0.0003). The associations were not modified by insulin receptor or estrogen receptor status of the tumor, or body mass index. Conclusions: We found that higher dietary GL, reflecting postprandial glucose response, after a breast cancer diagnosis was associated with higher risk of breast cancer–specific mortality. Higher dietary GI, GL, II, and IL after a breast cancer diagnosis were associated with higher risk of death from any cause. Impact: These results suggest that carbohydrate quantity and quality may be important in breast cancer prognosis. See related commentary by McTiernan, p. 252

Associations between anthropometric factors and breast cancer (BC) risk have varied inconsistently by estrogen and/or progesterone receptor (ER/PR) status. Associations between prediagnostic anthropometric factors and risk of premenopausal and postmenopausal BC overall and ER/PR status subtypes were investigated in a pooled analysis of 20 prospective cohorts, including 36,297 BC cases among 1,061,915 women, using multivariable Cox regression analyses, controlling for reproductive factors, diet and other risk factors. We estimated dose–response relationships and tested for nonlinear associations using restricted cubic splines. Height showed positive, linear associations for premenopausal and postmenopausal BC risk (6–7% RR increase per 5 cm increment), with stronger associations for receptor-positive subtypes. Body mass index (BMI) at cohort baseline was strongly inversely associated with premenopausal BC risk, and strongly positively—and nonlinearly—associated with postmenopausal BC (especially among women who never used hormone replacement therapy). This was primarily observed for receptor-positive subtypes. Early adult BMI (at 18–20 years) showed inverse, linear associations for premenopausal and postmenopausal BC risk (21% and 11% RR decrease per 5 kg/m2, respectively) with stronger associations for receptor-negative subtypes. Adult weight gain since 18–20 years was positively associated with postmenopausal BC risk, stronger for receptor-positive subtypes, and among women who were leaner in early adulthood. Women heavier in early adulthood generally had reduced premenopausal BC risk, independent of later weight gain. Positive associations between height, baseline (adult) BMI, adult weight gain and postmenopausal BC risk were substantially stronger for hormone receptor-positive versus negative subtypes. Premenopausal BC risk was positively associated with height, but inversely with baseline BMI and weight gain (mostly in receptor-positive subtypes). Inverse associations with early adult BMI seemed stronger in receptor-negative subtypes of premenopausal and postmenopausal BC. Electronic supplementary material The online version of this article (10.1007/s10654-020-00688-3) contains supplementary material, which is available to authorized users.

PURPOSE Labia majora, the embryologic homologs of the scrotum, are ideal donor tissue for transgender scrotoplasty. The technique is detailed, and surgical outcomes are assessed for scrotoplasty using labia majora rotational advancement flaps. METHODS We retrospectively reviewed the outcomes of phalloplasty patients who underwent either primary or secondary labia majora flap scrotoplasty and perineal reconstruction from October 1, 2017, to December 1, 2019. Bilateral elevation and rotational flap advancement from the posterior to anterior position formed a pouch-like scrotum. Perineal reconstruction involved multilayered closure with apposition of the inner thigh skin. RESULTS The mean follow-up was 12.5 months (0.5-26 months). One hundred forty-seven scrotoplasties were performed. Of the 147 total scrotoplasty patients, 133 had labia majora flap scrotoplasty and perineal reconstruction with single-stage phalloplasty. Distal flap necrosis occurred in 6 patients (4.1%); 5 were ipsilateral to the groin dissection required for phalloplasty. Large (>1 cm diameter) perineoscrotal junction dehiscence occurred in 7 patients (4.7%). All wounds were managed conservatively except for 3 patients who developed urethrocutaneous fistulas at the perineoscrotal junction. All 3 patients required fistula repair. Two (1.4%) scrotal hematomas and 3 (2.0%) perineal hematomas were seen; all required operative intervention. CONCLUSIONS Labia majora flap scrotoplasty via the bilateral rotational advancement technique and perineal reconstruction can be safely performed during phalloplasty. Minor wound complications are common and frequently heal with conservative management. Wounds that do not heal may be associated with urethral complications. Hematomas are rare but usually require operative intervention.

An abnormal clinical Allen's test is not a definitive exclusion criterion for free radial forearm flap use. A surgical Allen's test may be useful to determine whether flap harvest is feasible in patients with an abnormal clinical Allen's test.

Purpose: DLYE5953A is an antibody–drug conjugate consisting of an anti-LY6E antibody covalently linked to the cytotoxic agent monomethyl auristatin E. This study characterized the safety, pharmacokinetics, immunogenicity, potential biomarkers, and antitumor activity of DLYE5953A in patients with metastatic solid tumors. Patients and Methods: This was a phase I, open-label, 3+3 dose-escalation, and dose-expansion study of DLYE5953A administered intravenously every 21 days (Q3W) in patients with locally advanced or metastatic solid malignancies. Results: Sixty-eight patients received DLYE5953A (median, four cycles; range, 1–27). No dose-limiting toxicities were identified during dose escalation (0.2–2.4 mg/kg; n = 20). The recommended phase II dose (RP2D) of 2.4 mg/kg Q3W was based on overall safety and tolerability. Dose-expansion cohorts for HER2-negative metastatic breast cancer (HER2-negative MBC; n = 23) and non–small cell lung cancer (NSCLC; n = 25) patients were enrolled at the RP2D. Among patients receiving DLYE5953A 2.4 mg/kg (n = 55), the most common (≥30%) related adverse events (AEs) included alopecia, fatigue, nausea, and peripheral neuropathy. Grade ≥3 related AEs occurred in 14 of 55 (26%) patients, with neutropenia being the most common (13%). DLYE5953A demonstrated linear total antibody pharmacokinetics at doses of ≥0.8 mg/kg with low unconjugated monomethyl auristatin E levels in blood. Partial response was confirmed in eight of 68 (12%) patients, including three of 29 patients with MBC (10%) and five of 25 patients with NSCLC (20%) at the RP2D. Stable disease was the best response for 37 of 68 (54%) patients. Conclusions: DLYE5953A administered at 2.4 mg/kg has acceptable safety. Preliminary evidence of antitumor activity in patients with HER2-negative MBC and NSCLC supports further investigation of LY6E as a therapeutic target.

Sustainable development of India’s food system must ensure a growing population is fed while minimizing both widespread malnutrition and the environmental impacts of food production. After assessing current adequacy of nutrient supplies at the national level, associated natural resource use (land, fresh water) and greenhouse gas (GHG) emissions, we apply an integrated subnational environmental and nutritional optimization approach to explore resource constraints that might limit the achievement of national food self-sufficiency goals. We find that India currently has the capacity to produce sufficient amounts of nutritious foods, supplying vitamins and minerals that would mostly exceed requirements. Regional cropland use could be reduced by up to 50%, water demand by up to 65% and combined resource inputs by up to 40% while still supporting adequate nutrition. Associated GHG emissions would decline by 26–34% and could possibly be sequestered in agroforestry systems. Such dietary shifts could lower the number of diet-related premature deaths by 14–30%. Achieving these potential gains, however, would require a major transition from current production and consumption patterns, particularly of refined cereals, to free-up resources for more traditional and nutritious foods. An integrated subnational environmental and nutritional optimization approach indicates that, with a transition from current production and consumption patterns, India has the capacity to achieve national food self-sufficiency goals while reducing regional cropland use, water demand and GHG emissions.

States and institutions increasingly rely on articulation agreements to streamline vertical transfer, although the effectiveness of those policies on transfer student outcomes remains unclear. To better understand this effectiveness, we explored a partnership between the College of Engineering at a mid-Atlantic research university and two community colleges located within the same state. We interviewed engineering faculty and academic advisors (i.e., the street-level bureaucrats who implement policy) to explore how an articulation agreement influences processes and policies related to coursework transfer. Our results revealed complexities in the implementation of the articulation policy as it collides with an enrollment management university policy that differs in purpose. Their collision has challenging implications for transfer students and for the faculty and advisors responsible for interfacing with those students.

Summary We report findings from a new survey of US public attitudes toward human-animal chimeric embryo (HACE) research, designed to compare with recently reported Japanese survey data. We find that 59% of the US public can personally accept the process of injecting human induced pluripotent stem cells into genetically modified swine embryos and having human tissues produced in a pig's body transplanted into a human. This is greater acceptance than in Japan, and there is even strong acceptance among those with strong religious affiliations and who self-identify as conservatives. We argue that strong public support for HACE research, as well as the emerging literature suggesting that humanization of research animals is very unlikely, should compel the NIH to lift its current moratorium on HACE research., Highlights • 430 US participants in a national survey on human-animal chimeric embryo research • 83% of respondents can personally accept research on human-animal chimeric embryos • Self-identified political conservatives accept human-animal chimera research • Individuals opposed to animal research also accept human-animal chimera research, In this report, Crane and colleagues report findings on US public attitudes toward human-animal chimeric embryo research. A majority of survey respondents personally accept the process of injecting human stem cells into genetically modified swine embryos and transplanting human tissues produced in a pig's body. Strong public support should compel the NIH to lift the moratorium on human-animal chimeric embryo research.

Background To compare the prevalence of healthy aging among adults age 70 and older from 5 European countries recruited for the DO-HEALTH clinical trial. Participants were selected for absence of prior major health events. Methods Cross-sectional analysis of DO-HEALTH baseline data. All 2,157 participants (mean age 74.9, SD 4.4; 61.7% women) were included and 2,123 had data for all domains of the healthy aging status (HA) definition. HA was assessed based on the Nurses` Health Study (NHS) definition requiring four domains: no major chronic diseases, no disabilities, no cognitive impairment (Montreal Cognitive Assessment, MoCA ≥25), no mental health limitation (GDS-5 Results Overall, 41.8% of DO-HEALTH participants were healthy agers with significant variability by country: Austria (Innsbruck) 58.3%, Switzerland (Zurich, Basel, Geneva) 51.2%, Germany (Berlin) 37.6%, France (Toulouse) 36.7% and Portugal (Coimbra) 8.8% (p Conclusions Despite the same inclusion and exclusion criteria preselecting relatively healthy adults age 70 years and older, HA prevalence in DO-HEALTH varied significantly between countries and was highest in participants from Austria and Switzerland, lowest in participants from Portugal. Independent of country, younger age, female gender, lower BMI and better physical function were associated with HA. Trial registration DO-HEALTH was registered under the protocol NCT01745263 at the International Trials Registry (clinicaltrials.gov), and under the protocol number 2012–001249-41 at the Registration at the European Community Clinical Trial System (EudraCT).

Background The relation between sodium intake and cardiovascular disease remains controversial, owing in part to inaccurate assessment of sodium intake. Assessing 24-hour urinary excretion over a period of multiple days is considered to be an accurate method. Methods We included individual-participant data from six prospective cohorts of generally healthy adults; sodium and potassium excretion was assessed with the use of at least two 24-hour urine samples per participant. The primary outcome was a cardiovascular event (coronary revascularization or fatal or nonfatal myocardial infarction or stroke). We analyzed each cohort using consistent methods and combined the results using a random-effects meta-analysis. Results Among 10,709 participants, who had a mean (±SD) age of 51.5±12.6 years and of whom 54.2% were women, 571 cardiovascular events were ascertained during a median study follow-up of 8.8 years (incidence rate, 5.9 per 1000 person-years). The median 24-hour urinary sodium excretion was 3270 mg (10th to 90th percentile, 2099 to 4899). Higher sodium excretion, lower potassium excretion, and a higher sodium-to-potassium ratio were all associated with a higher cardiovascular risk in analyses that were controlled for confounding factors (P≤0.005 for all comparisons). In analyses that compared quartile 4 of the urinary biomarker (highest) with quartile 1 (lowest), the hazard ratios were 1.60 (95% confidence interval [CI], 1.19 to 2.14) for sodium excretion, 0.69 (95% CI, 0.51 to 0.91) for potassium excretion, and 1.62 (95% CI, 1.25 to 2.10) for the sodium-to-potassium ratio. Each daily increment of 1000 mg in sodium excretion was associated with an 18% increase in cardiovascular risk (hazard ratio, 1.18; 95% CI, 1.08 to 1.29), and each daily increment of 1000 mg in potassium excretion was associated with an 18% decrease in risk (hazard ratio, 0.82; 95% CI, 0.72 to 0.94). Conclusions Higher sodium and lower potassium intakes, as measured in multiple 24-hour urine samples, were associated in a dose-response manner with a higher cardiovascular risk. These findings may support reducing sodium intake and increasing potassium intake from current levels. (Funded by the American Heart Association and the National Institutes of Health.).

Indoor navigation systems offer many application possibilities for people who need information about the scenery and the possible fixed and mobile obstacles placed along the paths. In these systems, the main factors considered for their construction and evaluation are the level of accuracy and the delivery time of the information. However, it is necessary to notice obstacles placed above the user&rsquo, s waistline to avoid accidents and collisions. In this paper, different methodologies are associated to define a hybrid navigation model called iterative pedestrian dead reckoning (i-PDR). i-PDR combines the PDR algorithm with a Kalman linear filter to correct the location, reducing the system&rsquo, s margin of error iteratively. Obstacle perception was addressed through the use of stereo vision combined with a musical sounding scheme and spoken instructions that covered an angle of 120 degrees in front of the user. The results obtained in the margin of error and the maximum processing time are 0.70 m and 0.09 s, respectively, with obstacles at ground level and suspended with an accuracy equivalent to 90%.

Background Evidence regarding the role of diet quality, especially its change, in subjective cognitive decline (SCD) is scarce. Objectives To examine associations of long-term diet qualities, including Alternate Mediterranean Diet (AMED), Dietary Approaches to Stop Hypertension (DASH), and Alternate Healthy Eating Index 2010 (AHEI-2010) with SCD in the Nurses' Health Study. Methods We followed 49,493 female registered nurses averaged 48 years from 1984 to 2014. Diet scores were derived from seven repeated food frequency questionnaires in 1984, 1986, and every four years afterward until 2006. Self-reported SCD was assessed in 2012 and 2014 by a 7-item questionnaire on memory and cognition changes. Categorical SCD score was classified as "none" (0 points, 40.8%), "moderate" (0.5-2.5 points, 46.9%), and "severe" (3-7 points, 12.3%). Results Multinomial and linear regression models were adjusted for total calorie, demographic characteristics, major lifestyle, and clinical factors. Comparing top vs. bottom quintiles of AMED, DASH, and AHEI-2010, multivariable-adjusted odds ratios (ORs) (95% confidence intervals, CIs) for severe vs. none SCD were 0.57 (0.51, 0.64), 0.61 (0.55, 0.68), and 0.81 (0.73, 0.90), respectively. Similar associations remained for three diet indices evaluated 28 years before SCD assessment. Compared to participants with lowest diet quality tertiles in both remote and recent years, the lowest odds of severe SCD was observed among those who maintained highest diet quality tertiles over time, with a 40%, 32%, and 20% lower odds of severe SCD for AMED, DASH, and AHEI-2010, respectively. Moreover, the odds of severe SCD was lower among those with improved diets over time; for each standard deviation higher in diet quality change, reduced risks were 11% for AMED, 5% for DASH, and 3% for AHEI-2010, respectively. Conclusion Our findings support beneficial roles of long-term adherence to, and improvement in healthy dietary patterns for maintenance of subjective cognition in women.

Background: Debate exists on the optimum fixation construct for large avulsion fractures of the fifth metatarsal base. We compared the biomechanical strength of 2 headless compression screws vs a hook plate for fixation of these fractures. Methods: Large avulsion fractures were simulated on 10 matched pairs of fresh-frozen cadaveric specimens. Specimens were assigned to receive two 2.5-mm headless compression screws or an anatomic fifth metatarsal hook plate, then cyclically loaded through the plantar fascia and metatarsal base. Specimens underwent 100 cycles at 50%, 75%, and 100% physiological load for a total of 300 cycles. Results: The hook plate group demonstrated a significantly higher number of cycles to failure compared with the screw group (270.7 ± 66.0 [range 100-300] cycles vs 178.6 ± 95.7 [range 24-300] cycles, respectively; P = .039). Seven of 10 hook plate specimens remained intact at the maximum 300 cycles compared with 2 of 10 screw specimens. Nine of 10 plate specimens survived at least 1 cycle at 100% physiologic load compared with 5 of 10 screw specimens. Conclusion: A hook plate construct was biomechanically superior to a headless compression screw construct for fixation of large avulsion fractures of the fifth metatarsal base. Clinical Relevance: Whether using hook plates or headless compression screws, surgeons should consider protecting patient weight-bearing after fixation of fifth metatarsal base large avulsion fracture until bony union has occurred.

Background Whether egg consumption is associated with the risk of type 2 diabetes (T2D) remains unsettled. Objectives We evaluated the association between egg consumption and T2D risk in 3 large US prospective cohorts, and performed a systematic review and meta-analysis of prospective cohort studies. Methods We followed 82,750 women from the Nurses' Health Study (NHS; 1980-2012), 89,636 women from the NHS II (1991-2017), and 41,412 men from the Health Professionals Follow-up Study (HPFS; 1986-2016) who were free of T2D, cardiovascular disease, and cancer at baseline. Egg consumption was assessed every 2-4 y using a validated FFQ. We used Cox proportional hazard models to estimate HRs and 95% CIs. Results During a total of 5,529,959 person-years of follow-up, we documented 20,514 incident cases of T2D in the NHS, NHS II, and HPFS. In the pooled multivariable model adjusted for updated BMI, lifestyle, and dietary confounders, a 1-egg/d increase was associated with a 14% (95% CI: 7%, 20%) higher T2D risk. In random-effects meta-analysis of 16 prospective cohort studies (589,559 participants; 41,248 incident T2D cases), for each 1 egg/d, the pooled RR of T2D was 1.07 (95% CI: 0.99, 1.15; I2 = 69.8%). There were, however, significant differences by geographic region (P for interaction = 0.01). Each 1 egg/d was associated with higher T2D risk among US studies (RR: 1.18; 95% CI: 1.10, 1.27; I2 = 51.3%), but not among European (RR: 0.99; 95% CI: 0.85, 1.15; I2 = 73.5%) or Asian (RR: 0.82; 95% CI: 0.62, 1.09; I2 = 59.1%) studies. Conclusions Results from the updated meta-analysis show no overall association between moderate egg consumption and risk of T2D. Whether the heterogeneity of the associations among US, European, and Asian cohorts reflects differences in egg consumption habits warrants further investigation.This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42019127860.

Background Observational studies report higher blood pressure (BP) among individuals with lower 25-hydroxyvitamin D concentration. Whether dosage of vitamin D supplementation has a differential effect on BP control remains unclear. Objective The study aimed to determine if daily vitamin D supplementation with 2000 IU is more effective than 800 IU for BP control among older adults. Methods This randomized, double-blind, ancillary trial of the Zurich Multiple Endpoint Vitamin D Trial in Knee Osteoarthritis enrolled adults aged ≥60 y who underwent elective surgery due to severe knee osteoarthritis. Participants were randomly assigned to receive high dose (2000 IU) or standard dose (800 IU) daily vitamin D3 for 24 mo. Outcomes included daytime and 24-h mean systolic BP. BP variability and serum 25-hydroxyvitamin D concentration were examined in a post hoc and observational analysis. Results Of the 273 participants randomly assigned, 250 participants completed a follow-up 24-h ambulatory BP monitoring (mean age: 70.4 ± 6.4 y; 47.2% men). The difference in daytime mean systolic BP reduction between the 2000 IU (n = 123) and 800 IU (n = 127) groups was not statistically significant (-2.75 mm Hg vs. -3.94 mm Hg; difference: 1.18 mm Hg; 95% CI: -0.68, 3.05; P = 0.21), consistent with 24-h mean systolic BP. However, systolic BP variability was significantly reduced with 2000 IU (average real variability: -0.37 mm Hg) compared to 800 IU vitamin D3 (0.11 mm Hg; difference: -0.48 mm Hg; 95% CI: -0.94, -0.01; P = 0.045). Independent of group allocation, maximal reductions in mean BP were observed at 28.7 ng/mL of achieved serum 25-hydroxyvitamin D concentrations. Conclusions While daily 2000 IU and 800 IU vitamin D3 reduced mean systolic BP over 2 y to a small and similar extent, 2000 IU reduced mean systolic BP variability significantly more compared with 800 IU. However, without a placebo control group we cannot ascertain whether vitamin D supplementation effectively reduces BP.This trial was registered at www.clinicaltrials.gov as NCT00599807.