Background: Many malnourished children in resource-poor settings fail to fulfill their developmental potential. Objective: The objectives of this analysis were to examine the nutritional, psychosocial, environmental, and household correlates of child development in Bihar, India, and identify mediators between dietary diversity and mental development. Methods: Using 2-stage cluster randomized sampling, we surveyed 4360 households with children 6-18 mo of age in the West Champaran district of Bihar. We measured motor and mental development with the use of the Developmental Milestones Checklist II. In a random subsample (n = 2838), we measured anthropometric characteristics and hemoglobin. Cluster-adjusted multiple linear regression analysis was used to examine the associations between nutrition indicators and development scores. Sobel's test was used to assess significant mediators in the association between diet diversity and development scores. Analyses were stratified by children 6-11 and 12-18 mo of age. Results: In all children, length-for-age z score (LAZ), dietary diversity, and psychosocial stimulation were significant (P < 0.05) correlates of motor development scores [(β coefficient ± SE) in children 6-11 mo: LAZ = 0.46 ± 0.08, dietary diversity = 0.43±0.09, and stimulation = 0.15±0.04; in children 12-18 mo: LAZ = 0.73±0.07, dietary diversity = 0.30±0.09, and stimulation = 0.316 0.05] and mental development scores [(b coefficient6 SE) in children 6-11 mo: LAZ = 0.576 0.10, dietary diversity = 0.84±0.13, and stimulation = 0.54±0.07; in children 12-18 mo: LAZ = 0.54±0.11, dietary diversity = 0.40±0.16, and stimulation = 0.62±0.09] . Stimulation, gross motor development, and fine motor development were significant mediators in the relation between dietary diversity and mental development. Conclusion: Strategies to improve dietary diversity and psychosocial stimulation could have important implications for child development of young North Indian children.

Background: Infection is associated with impaired nutritional status, especially for infants younger than 5 years. Objectives: We assessed the impact of infection indicated by both acute phase proteins (APP), C-reactive protein (CRP), and α-1-acid-glycoprotein (AGP), and as reported by maternal recall on the nutritional status of infants. Materials and methods: A total of 505 pregnant women were enrolled in a nested longitudinal cohort study of vitamin A (VA). Data from 385 children are reported here. The incidence and severity of respiratory infection and diarrhea (previous 14 days) were assessed by maternal recall; infant/child feeding practices were collected. Infant weight, recumbent length, and heel-prick capillary blood were taken at 9 months postpartum. Indicators of the VA status [retinol binding protein (RBP)], iron status (Hb, ferritin), and subclinical inflammation APP, CRP (>5 mg/L), and AGP (>1 g/L) were determined. Impacts of infection on the infant nutritional status were estimated using logistic regression models. Results: Infection prevalence, based on elevated CRP and AGP levels, was 36.7%. For diarrhea reported symptoms, 42.4% of infants at 9 months had no indication of infection as indicated by CRP and AGP; for acute respiratory reported symptoms, 42.6% had no indication of infection. There was a significant positive association with infection among VA-deficient (RBP < 0.83 μmol/L) infants based on maternal reported symptoms but not with iron deficiency (ferritin < 12 μg/L). The odds of having infection, based on increased CRP and AGP, in underweight infants was 3.7 times higher (OR: 3.7; 95% CI: 2.3, 4.5; P = 0.019). Infants with iron deficiency were less likely (OR: 0.40; 95% CI: 0.1, 0.7; P = 0.001) to have infection based on CRP and AGP, while infants with VA deficiency were five times more likely (OR: 5.06; 95% CI: 3.2, 7.1; P = 0.0001) to have infection. Conclusion: Acute phase proteins are more useful in defining infection in a population than reported symptoms of illness. Not controlling for inflammation in a population while assessing the nutritional status might result in inaccurate prevalence estimation.

Objective Dietary practices in Kenya often fail to provide adequate nutrition during the first 1000 days of life, from conception to 2 years of age. We developed and qualitatively assessed the acceptability of easy-to-use dietary tools consisting of a marked bowl, slotted spoon and illustrated counselling card to support appropriate dietary practices during pregnancy, exclusive breast-feeding and complementary feeding of children aged 6-24 months. Design We conducted qualitative research to assess community acceptability and obtain feedback on the design of the dietary tools. Setting This research took place in urban and rural communities in Western Kenya. Subjects We conducted twelve focus group discussions with community members (mothers, husbands, mothers-in-law, community leaders) and five interviews with government nutritionists to assess acceptability and obtain recommendations on design and delivery of the tools. We conducted 24-28 d of user testing with fourteen pregnant women, fourteen breast-feeding women and thirty-two mothers with infants aged 6-18 months. Results Tools were positively received by communities. Mothers perceived improvements in their own and their children's food intakes including quantity, frequency, consistency and diversity. Many attributed perceived own and child's weight gain and/or increased energy to tool use. A minority reported using the bowl for other activities (n 9) or not using the bowl due to food insecurity (n 5). Conclusions Results suggest that such tools have the potential to positively impact maternal and child dietary practices. Future work should quantitatively assess the impact on diet and nutrition outcomes and the underlying behavioural domains associated with changes.

Objective The contribution of subsidized food commodities to total food consumption is unknown. We estimated the proportion of individual energy intake from food commodities receiving the largest subsidies from 1995 to 2010 (corn, soyabeans, wheat, rice, sorghum, dairy and livestock). Design Integrating information from three federal databases (MyPyramid Equivalents, Food Intakes Converted to Retail Commodities, and What We Eat in America) with data from the 2001-2006 National Health and Nutrition Examination Surveys, we computed a Subsidy Score representing the percentage of total energy intake from subsidized commodities. We examined the score's distribution and the probability of having a 'high' (≥70th percentile) v. 'low' (≤30th percentile) score, across the population and subgroups, using multivariate logistic regression. Setting Community-dwelling adults in the USA. Subjects Participants (n 11 811) aged 18-64 years. Results Median Subsidy Score was 56·7 % (interquartile range 47·2-65·4 %). Younger, less educated, poorer, and Mexican Americans had higher scores. After controlling for covariates, age, education and income remained independently associated with the score: compared with individuals aged 55-64 years, individuals aged 18-24 years had a 50 % higher probability of having a high score (P<0·0001). Individuals reporting less than high-school education had 21 % higher probability of having a high score than individuals reporting college completion or higher (P=0·003); individuals in the lowest tertile of income had an 11 % higher probability of having a high score compared with individuals in the highest tertile (P=0·02). Conclusions Over 50 % of energy in US diets is derived from federally subsidized commodities.

Inconclusive evidence for how food environments affect health may result from an emphasis on residential neighborhood-based measures of exposure. We used an activity space approach to examine whether 1) measures of food access and 2) associations with diet and BMI differ between residential and activity space food environments among low-income African American women in Atlanta, Georgia (n = 199). Although residential and activity space environments differed across all dimensions of food access, being located farther away from ‘unhealthy’ outlets was associated with lower BMI in both environments. Future research should move beyond asking whether residential and activity space environments differ, toward examining if, how, and under what conditions these differences impact the estimation of health effects.

Background: Optimal patient selection for radiotherapy in pancreatic ductal adenocarcinoma (PDAC) is unestablished. Molecular profiling may select patients at high risk for locoregional recurrence (LRR) who would benefit from radiation. Methods: We included resectable pancreatic cancer (R-PDAC) patients, divided into training and validation cohorts, treated among three insti-tutions with surgery and adjuvant chemotherapy, and borderline resectable or locally advanced pancreatic cancer (BR/LA-PDAC) patients treated with chemotherapy with or without radiation at the primary study institution. We isolated RNA from R-PDAC surgical specimens. Using NanoS-tring, we identified miRNAs differentially expressed between normal and malignant pancreatic tissue. ElasticNet regression identified two miRNAs most predictive of LRR in the training co-hort, miR-181b/d and miR-575, which were used to generate a risk score (RS). We evaluated the association of the median-dichotomized RS with recurrence and overall survival (OS). Results: We identified 183 R-PDAC and 77 BR/LA-PDAC patients with median follow up of 37 months treated between 2001 and 2014. On multivariable analysis of the R-PDAC training cohort (n = 90), RS was associated with worse LRR (HR = 1.34; 95%CI 1.27–11.38; p = 0.017) and OS (HR = 2.89; 95%CI 1.10–4.76; p = 0.027). In the R-PDAC validation cohort, RS was associated with worse LRR (HR = 2.39; 95%CI 1.03–5.54; p = 0.042), but not OS (p = 0.087). For BR/LA-PDAC, RS was associated with worse LRR (HR = 2.71; 95%CI 1.14–6.48; p = 0.025), DR (HR = 1.93; 95%CI 1.10–3.38; p = 0.022), and OS (HR = 1.97; 95%CI 1.17–3.34; p = 0.011). Additionally, after stratifying by RS and receipt of radiation in BR/LA-PDAC patients, high RS patients who did not receive radiation had worse LRR (p = 0.018), DR (p = 0.006), and OS (p < 0.001) compared to patients with either low RS or patients who received radiation, irrespective of RS. Conclusions: RS predicted worse LRR and OS in R-PDAC and worse LRR, DR, and OS in BR/LA-PDAC. This may select patients who would benefit from radiation and should be validated prospectively.

BACKGROUND: Countries continue to debate the need for decontamination of cold-chain food packaging to reduce possible SARS-CoV-2 fomite transmission among workers. While laboratory-based studies demonstrate persistence of SARS-CoV-2 on surfaces, the likelihood of fomite-mediated transmission under real-life conditions is uncertain. METHODS: Using a quantitative risk assessment model, we simulated in a frozen food packaging facility 1) SARS-CoV-2 fomite-mediated infection risks following worker exposure to contaminated plastic packaging; and 2) reductions in these risks attributed to masking, handwashing, and vaccination. FINDINGS: In a representative facility with no specific interventions, SARS-CoV-2 infection risk to a susceptible worker from contact with contaminated packaging was 2·8 × 10 -3 per 1h-period (95%CI: 6·9 × 10 -6 , 2·4 × 10 -2 ). Implementation of standard infection control measures, handwashing and masks (9·4 × 10 -6 risk per 1h-period, 95%CI: 2·3 × 10 -8 , 8·1 × 10 -5 ), substantially reduced risk (99·7%). Vaccination of the susceptible worker (two doses Pfizer/Moderna, vaccine effectiveness: 86-99%) combined with handwashing and masking reduced risk to less than 1·0 × 10 -6 . Simulating increased infectiousness/transmissibility of new variants (2-, 10-fold viral shedding) among a fully vaccinated workforce, handwashing and masks continued to mitigate risk (2·0 × 10 -6 -1·1 × 10 -5 risk per 1h-period). Decontamination of packaging in addition to these interventions reduced infection risks to below the 1·0 × 10 -6 risk threshold. INTERPRETATION: Fomite-mediated SARS-CoV-2 infection risks were very low under cold-chain conditions. Handwashing and masking provide significant protection to workers, especially when paired with vaccination. FUNDING: U.S. Department of Agriculture.

Double fortified salt (DFS) has proven efficacy in addressing iron deficiency and anaemia, thus improving maternal and child nutrition outcomes. However, DFS delivery in large-scale settings is less understood, with limited documentation of its fidelity of implementation (FOI). We assessed the FOI of the DFS intervention in Uttar Pradesh, India, to improve the design and implementation of such programmes that aim to reduce the anaemia burden, especially in women of reproductive age (WRA). We conducted in-depth interviews with DFS programme staff (n = 25) and end-user WRAs (23), guided by a programme impact pathway. We transcribed and thematically analysed the interviews and used an adapted analytic framework to document FOI across four domains—objects of intervention, implementation staff, implementation context and target of implementation. DFS utilisation remained low due to a combination of factors including poor product quality, distribution challenges, ineffective promotion and low awareness amongst end-user WRAs. Motivation levels were higher amongst district-level staff compared to frontline staff, who lacked supervisory support and effective incentives to promote DFS. Three typologies of DFS users emerged—‘believers’, ‘thrifters’ and ‘naysayers’—who indicated differing reasons for DFS purchase and its use or nonuse. The implementation of the DFS programme varied significantly from its theorised programme impact pathway. The adapted analytic framework helped document FOI and assess the programme's readiness for impact assessments and subsequent scale-up. The programme needs product quality improvements, incentivised distribution and stronger promotion to effectively deliver and improve the realisation of its potential as an anaemia prevention strategy.

Severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) is a worldwide health concern, and new treatment strategies are needed. Targeting inflammatory innate immunity pathways holds therapeutic promise, but effective molecular targets remain elusive. Here, we show that human caspase-4 (CASP4) and its mouse homolog, caspase-11 (CASP11), are up-regulated in SARS–CoV-2 infections and that CASP4 expression correlates with severity of SARS–CoV-2 infection in humans. SARS–CoV-2–infected Casp112/2 mice were protected from severe weight loss and lung pathology, including blood vessel damage, compared to wild-type (WT) mice and mice lacking the caspase downstream effector gasdermin-D (Gsdmd2/2). Notably, viral titers were similar regardless of CASP11 knockout. Global transcriptomics of SARS–CoV-2–infected WT, Casp112/2, and Gsdmd2/2 lungs identified restrained expression of inflammatory molecules and altered neutrophil gene signatures in Casp112/2 mice. We confirmed that protein levels of inflammatory mediators interleukin (IL)-1β, IL-6, and CXCL1, as well as neutrophil functions, were reduced in Casp112/2 lungs. Additionally, Casp112/2 lungs accumulated less von Willebrand factor, a marker for endothelial damage, but expressed more Kruppel-Like Factor 2, a transcription factor that maintains vascular integrity. Overall, our results demonstrate that CASP4/11 promotes detrimental SARS–CoV-2–induced inflammation and coagulopathy, largely independently of GSDMD, identifying CASP4/11 as a promising drug target for treatment and prevention of severe COVID-19.

Background: Circular migration is the dominant pattern of movement in India and is a livelihood strategy used by many food insecure rural households. Repeated shifts in food environments have important implications on household food security and dietary patterns but have not been studied. Objective: To explore differences in the food environment, food security, and food availability between home and destination spaces. Methods: Mixed-methods research was conducted among circular migrant families working and residing on brick kilns in the state of Bihar. Utilizing stratified cluster sampling, 2 rounds of cross-sectional data were collected from 2564 families. Additionally, 25 in-depth interviews were conducted with circular migrant parents, kiln owners, and labor contractors. The Food Insecurity Experience Scale was validated for use in our study population. Bivariate analyses were conducted to estimate the association of food insecurity with sociodemographic variables. Qualitative data were analyzed using descriptive thematic methods. Results: Seventy percent of respondents utilized at least one nonmarket source of food at the origin; at the destination, sources of food were limited to the private market. Despite higher food prices at the destination, perceived food affordability was higher during periods of migration, resulting in improved food security. Tubers, rice, and wheat were typically available in the household daily, whereas fruits, eggs, and dairy were typically unavailable during the week. Conclusions: Circular migration can enable short-term food security by improving food affordability. Policy frameworks must address the root causes of chronic food insecurity, especially among rural-to-rural circular migrant families.