Neuropilin 2 in osteoblasts regulates trabecular bone mass in male mice.

Introduction: Neuropilin 2 (NRP2) mediates the effects of class 3 semaphorins and vascular endothelial growth factor and is implicated in axonal guidance and angiogenesis. Moreover, NRP2 expression is suggested to be involved in the regulation of bone homeostasis. Indeed, osteoblasts and osteoclasts express NRP2 and male and female global Nrp2 knockout mice have a reduced bone mass accompanied by reduced osteoblast and increased osteoclast counts. Methods: We first examined the in vitro effect of the calciotropic hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on Nrp2 transcription in osteoblasts. We next generated mice with a conditional deletion of Nrp2 in the osteoblast cell lineage under control of the paired related homeobox 1 promoter and mice with a conditional Nrp2 knockdown in osteoclasts under control of the Lysozyme promoter. Mice were examined under basal conditions or after treatment with either the bone anabolic vitamin D3 analog WY 1048 or with 1,25(OH)2D3. Results and discussion: We show that Nrp2 expression is induced by 1,25(OH)2D3 in osteoblasts and is associated with enrichment of the vitamin D receptor in an intronic region of the Nrp2 gene. In male mice, conditional deletion of Nrp2 in osteoblast precursors and mature osteoblasts recapitulated the bone phenotype of global Nrp2 knockout mice, with a reduced cortical cross-sectional tissue area and lower trabecular bone content. However, female mice with reduced osteoblastic Nrp2 expression display a reduced cross-sectional tissue area but have a normal trabecular bone mass. Treatment with the vitamin D3 analog WY 1048 (0.4 µg/kg/d, 14 days, ip) resulted in a similar increase in bone mass in both genotypes and genders. Deleting Nrp2 from the osteoclast lineage did not result in a bone phenotype, even though in vitro osteoclastogenesis of hematopoietic cells derived from mutant mice was significantly increased. Moreover, treatment with a high dose of 1,25(OH)2D3 (0.5 µg/kg/d, 6 days, ip), to induce osteoclast-mediated bone resorption, resulted in a similar reduction in trabecular and cortical bone mass. In conclusion, osteoblastic Nrp2 expression is suggested to regulate bone homeostasis in a sex-specific manner.

Stylizing Ribbons: Computing Surface Contours With Temporally Coherent Orientations.

Line work is a core element for the stylization of computer animations used by recent shows. However, existing stylization techniques are limited to edge treatments based on brush strokes or textures applied solely on top of curves. In this work, we propose new stylization effects by offering artists direct control over the inside and outside of surface contours. To this end, we introduce a method that creates ribbons, geometry strips of possibly varying width, that extrude from each side of the surface contour with temporally coherent orientations. Our contributions include the generation of spatially and temporally consistent normal orientations along visible contours and a trimming routine that converts arrangements of offset curves into ribbons free of intersections. We demonstrate the expressiveness and versatility of stylized ribbons by applying various effects on both character and shadow edges from animation sequences.

Molecular insights into mineralotropic hormone inter-regulation.

The regulation of mineral homeostasis involves the three mineralotropic hormones PTH, FGF23 and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Early research efforts focused on PTH and 1,25(OH)2D3 and more recently on FGF23 have revealed that each of these hormones regulates the expression of the other two. Despite early suggestions of transcriptional processes, it has been only recently that research effort have begun to delineate the genomic mechanisms underpinning this regulation for 1,25(OH)2D3 and FGF23; the regulation of PTH by 1,25(OH)2D3, however, remains obscure. We review here our molecular understanding of how PTH induces Cyp27b1 expression, the gene encoding the enzyme responsible for the synthesis of 1,25(OH)2D3. FGF23 and 1,25(OH)2D3, on the other hand, function by suppressing production of 1,25(OH)2D3. PTH stimulates the PKA-induced recruitment of CREB and its coactivator CBP at CREB occupied sites within the kidney-specific regulatory regions of Cyp27b1. PKA activation also promotes the nuclear translocation of SIK bound coactivators such as CRTC2, where it similarly interacts with CREB occupied Cyp27b1 sites. The negative actions of both FGF23 and 1,25(OH)2D3 appear to suppress Cyp27b1 expression by opposing the recruitment of CREB coactivators at this gene. Reciprocal gene actions are seen at Cyp24a1, the gene encoding the enzyme that degrades 1,25(OH)2D3, thereby contributing to the overall regulation of blood levels of 1,25(OH)2D3. Relative to PTH regulation, we summarize what is known of how 1,25(OH)2D3 regulates PTH suppression. These studies suggest that it is not 1,25(OH)2D3 that controls PTH levels in healthy subjects, but rather calcium itself. Finally, we describe current progress using an in vivo approach that furthers our understanding of the regulation of Fgf23 expression by PTH and 1,25(OH)2D3 and provide the first evidence that P may act to induce Fgf23 expression via a complex transcriptional mechanism in bone. It is clear, however, that additional advances will need to be made to further our understanding of the inter-regulation of each of these hormonal genes.

Vitamin D receptor cross-talk with p63 signaling promotes epidermal cell fate.

The vitamin D receptor with its ligand 1,25 dihydroxy vitamin D3 (1,25D3) regulates epidermal stem cell fate, such that VDR removal from Krt14 expressing keratinocytes delays re-epithelialization of epidermis after wound injury in mice. In this study we deleted Vdr from Lrig1 expressing stem cells in the isthmus of the hair follicle then used lineage tracing to evaluate the impact on re-epithelialization following injury. We showed that Vdr deletion from these cells prevents their migration to and regeneration of the interfollicular epidermis without impairing their ability to repopulate the sebaceous gland. To pursue the molecular basis for these effects of VDR, we performed genome wide transcriptional analysis of keratinocytes from Vdr cKO and control littermate mice. Ingenuity Pathway analysis (IPA) pointed us to the TP53 family including p63 as a partner with VDR, a transcriptional factor that is essential for proliferation and differentiation of epidermal keratinocytes. Epigenetic studies on epidermal keratinocytes derived from interfollicular epidermis showed that VDR is colocalized with p63 within the specific regulatory region of MED1 containing super-enhancers of epidermal fate driven transcription factor genes such as Fos and Jun. Gene ontology analysis further implicated that Vdr and p63 associated genomic regions regulate genes involving stem cell fate and epidermal differentiation. To demonstrate the functional interaction between VDR and p63, we evaluated the response to 1,25(OH)2D3 of keratinocytes lacking p63 and noted a reduction in epidermal cell fate determining transcription factors such as Fos, Jun. We conclude that VDR is required for the epidermal stem cell fate orientation towards interfollicular epidermis. We propose that this role of VDR involves cross-talk with the epidermal master regulator p63 through super-enhancer mediated epigenetic dynamics.

Assessing the impact of regional laboratory networks in East and West Africa on national health security capacities.

National laboratories are a fundamental capacity for public health, contributing to disease surveillance and outbreak response. The establishment of regional laboratory networks has been posited as a means of improving health security across multiple countries. Our study objective was to assess whether membership in regional laboratory networks in Africa has an effect on national health security capacities and outbreak response. We conducted a literature review to select regional laboratory networks in the Eastern and Western African regions. We examined data from the World Health Organization Joint External Evaluation (JEE) mission reports, the 2018 WHO States Parties Annual Report (SPAR), and the 2019 Global Health Security Index (GHS). We compared the average scores of countries that are members of a regional laboratory network to those that are not. We also assessed country-level diagnostic and testing indicators during the COVID-19 pandemic. We found no significant differences in any of the selected health security metrics for member versus non-member countries of the either the East Africa Public Health Laboratory Networking Project (EAPHLNP) in the Eastern Africa region, nor for the West African Network of Clinical Laboratories (RESAOLAB) in the Western Africa region. No statistically significant differences were observed in COVID-19 testing rates in either region. Small sample sizes and the inherent heterogeneities in governance, health, and other factors between countries within and between regions limited all analyses. These results suggest potential benefit in setting baseline capacity for network inclusion and developing regional metrics for measuring network impact, but also beyond national health security capacities, other effects that may be required to justify continued support for regional laboratory networks.

Genome-wide analyses of gene expression profile identify key genes and pathways involved in skeletal response to phosphate and 1,25-dihydroxyvitamin D3 in vivo.

Phosphate (P) is an essential element involved in various biological actions, such as bone integrity, energy production, cell signaling and molecular component. P homeostasis is modulated by 4 main tissues; intestine, kidney, bone, and parathyroid gland, where 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), parathyroid hormone and fibroblast growth factor 23 (FGF23) are produced and/or have an influence. In bone, serum P level modulates the production of FGF23 which then controls not only P excretion but also vitamin D metabolism in kidney in an endocrine manner. The hormonally active form of vitamin D, 1,25(OH)2D3, also has a significant effect on skeletal cells via its receptor, the vitamin D receptor, to control gene expression which mediates bone metabolism as well as mineral homeostasis. In this study, we adopted RNA-seq analysis to understand genome-wide skeletal gene expression regulation in response to P and 1,25(OH)2D3. We examined lumbar 5 vertebrae from the mice that were fed P deficient diet for a week followed by an acute high P diet for 3, 6, and 24 h as well as mice treated with 1,25(OH)2D3 intraperitoneally for 6 h. Further identification and exploration of the genes regulated by P and 1,25(OH)2D3 showed that P dynamically modulates the expression of skeletal genes involved in various biological processes while 1,25(OH)2D3 regulates genes highly related to bone metabolism. Our in vivo data were then compared with in vitro data that we previously obtained, which suggests that the gene expression profiles presented in this report mainly represent those of osteocytes. Interestingly, it was found that even though the skeletal response to P is distinguished from that to 1,25(OH)2D3, both factors have an effect on Wnt signaling pathway to modulate bone homeostasis. Taken together, this report presents genome-wide data that provide a foundation to understand molecular mechanisms by which skeletal cells respond to P and 1,25(OH)2D3.

A parathyroid hormone/salt-inducible kinase signaling axis controls renal vitamin D activation and organismal calcium homeostasis.

The renal actions of parathyroid hormone (PTH) promote 1,25-vitamin D generation; however, the signaling mechanisms that control PTH-dependent vitamin D activation remain unknown. Here, we demonstrated that salt-inducible kinases (SIKs) orchestrated renal 1,25-vitamin D production downstream of PTH signaling. PTH inhibited SIK cellular activity by cAMP-dependent PKA phosphorylation. Whole-tissue and single-cell transcriptomics demonstrated that both PTH and pharmacologic SIK inhibitors regulated a vitamin D gene module in the proximal tubule. SIK inhibitors increased 1,25-vitamin D production and renal Cyp27b1 mRNA expression in mice and in human embryonic stem cell-derived kidney organoids. Global- and kidney-specific Sik2/Sik3 mutant mice showed Cyp27b1 upregulation, elevated serum 1,25-vitamin D, and PTH-independent hypercalcemia. The SIK substrate CRTC2 showed PTH and SIK inhibitor-inducible binding to key Cyp27b1 regulatory enhancers in the kidney, which were also required for SIK inhibitors to increase Cyp27b1 in vivo. Finally, in a podocyte injury model of chronic kidney disease-mineral bone disorder (CKD-MBD), SIK inhibitor treatment stimulated renal Cyp27b1 expression and 1,25-vitamin D production. Together, these results demonstrated a PTH/SIK/CRTC signaling axis in the kidney that controls Cyp27b1 expression and 1,25-vitamin D synthesis. These findings indicate that SIK inhibitors might be helpful for stimulation of 1,25-vitamin D production in CKD-MBD.

Impact of simulated flight conditions on supraventricular and ventricular ectopy.

Though billions of passengers and crew travel by air each year and are exposed to altitude equivalents of 7000-8000 feet, the health impact of cabin oxygenation levels has not been well studied. The hypoxic environment may produce ectopic heartbeats that may increase the risk of acute in-flight cardiac events. We enrolled forty older and at-risk participants under a block-randomized crossover design in a hypobaric chamber study to examine associations between flight oxygenation and both ventricular (VE) and supraventricular ectopy (SVE). We monitored participant VE and SVE every 5 min under both flight and control conditions to investigate the presence and rate of VE and SVE. While the presence of VE did not differ according to condition, the presence of SVE was higher during flight conditions (e.g. OR ratio = 1.77, 95% CI: 1.21, 2.59 for SVE couplets). Rates of VE and SVE were higher during flight conditions (e.g. RR ratio = 1.25, 95% CI: 1.03, 1.52 for VE couplets, RR ratio = 1.76, 95% CI: 1.39, 2.22 for SVE couplets). The observed higher presence and rate of ectopy tended to increase with duration of the flight condition. Further study of susceptible passengers and crew may elucidate the specific associations between intermittent or sustained ectopic heartbeats and hypoxic pathways.

Highlights from the 24th workshop on vitamin D in Austin, September 2022.

The 24th Workshop on Vitamin D was held September 7-9, 2022 in Austin, Texas and covered a wide diversity of research in the vitamin D field from across the globe. Here, we summarize the meeting, individual sessions, awards and presentations given.

The effect of interviewer-respondent age difference on the reporting of sexual activity in the Demographic and Health Surveys: Analysis of data from 21 countries.

Background: Interviewer effects can have consequential impacts on survey data, particularly for reporting sensitive attitudes and behaviours such as sexual activity and drug use, yet these effects remain understudied in low- and middle-income countries. The Demographic and Health Surveys (DHS) present a unique opportunity to study interviewer effects on the self-report of sensitive topics in low- and middle-income countries by including interviewer characteristics data. This paper aims to narrow the gap in research on interviewer effects by studying the effects that age difference between interviewer and respondent and interviewer survey experience have on the reporting of ever having sexual intercourse. Methods: We used DHS data from 91 066 women and 56 336 men in 21 countries where the standard DHS was implemented among all women of reproductive age, and interviewer characteristics were included in the data set. Using a Bayesian cross-classified model with random intercepts for interviewer and cluster, we assessed whether the effect of an age difference of 10 years or greater was associated with a difference in self-report of ever having sexual intercourse, adjusting for respondent demographics. Results: There was a meaningful association between an age difference of greater than ten years and reporting of ever having had sexual intercourse in most countries for both genders after adjusting for interviewer age and experience, rural or urban cluster, and individual-level characteristics. Among women, the marginal posterior probability of reporting ever having sexual intercourse if the interviewer was ten years or more years older was lower for 17 of 19 countries (countries ranged from -12.50 to 3.90 percentage points). Among men, the marginal posterior probability was lower for 16 of 20 countries, ranging from -18.30 to 17.10 percentage points. Conclusions: In most countries, women and men were less likely to report ever having sexual activity if the interviewer was ten or more years older than them, adjusting for potential confounders. These findings have important implications for interpreting numerous sexual health indicators, such as unmet family planning needs and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) risk. Survey administrators may consider more careful interviewer-respondent characteristic matching or novel approaches like Audio Computer Assisted Self Interview to minimize interviewer-induced variance.

Genomic mechanisms controlling renal vitamin D metabolism.

Vitamin D metabolism centers on regulation in the kidney of CYP27B1 induction by PTH, suppression by FGF23 and 1,25(OH)2D3, and reciprocal CYP24A1 suppression by PTH, and induction by FGF23 and 1,25(OH)2D3. This coordinated genomic regulation through enhancer modules results in the production and dynamic maintenance of circulating endocrine 1,25(OH)2D3 which, together with PTH and FGF23, controls mineral homeostasis. We discovered enhancers near Cyp27b1 in the mouse kidney located within intronic regions of Mettl1 and Mettl21b genes. These kidney-specific enhancers ("M1", "M21") control Cyp27b1. Through CRISPR/Cas deletion, we found that PTH activation of Cyp27b1 is lost with deletion of M1, whereas FGF23 suppression is lost with deletion of M21. The combination of both deletions (M1/M21-DIKO) eliminated the suppression by 1,25(OH)2D3. Cyp24a1 activation by 1,25(OH)2D3 is controlled by a promoter proximal pair of VDREs as well as a distal region - 35 to - 37 kb (DS2). We also found that FGF23 activation and PTH suppression of Cyp24a1 was located in a region - 21 to - 37 kb downstream (DS1). More recently, using in vivo ChIP-seq in mouse kidney, we demonstrate that PTH activation rapidly induces increased recruitment of pCREB and its coactivators, CBP and CRTC2, to the M1 and M21 enhancers near the Cyp27b1 gene. At distal enhancers of the Cyp24a1 gene, PTH suppression promotes dismisses CBP with only minor changes in pCREB and CRTC2 occupancy, all of which correlate with a suppression of basal histone acetylation across this locus and reduced transcripts. Surprisingly, we find that 1,25(OH)2D3 suppression increases the occupancy of CRTC2 in the M1 enhancer, a novel observation for CRTC2 and/or 1,25(OH)2D3 action. The suppressive actions of 1,25(OH)2D3 and FGF23 at the Cyp27b1 gene are associated with a reduction in CBP recruitment at these enhancers. Although FGF23-regulated transcription factors remain unknown, we hypothesize that VDR occupancy induced at the M1 and M21 enhancers by 1,25(OH)2D3 likely disrupts or competes with the active conformation of these CREB modules thereby preventing full induction by PTH. Our findings show coactivators such as CRTC2 and CBP contribute to Cyp27b1 and Cyp24a1 transcription and provide molecular insight into the coordinated mechanistic actions of PTH, FGF23, and 1,25(OH)2D3 in the kidney that regulate mineral homeostasis.

ORDINAL PROBIT FUNCTIONAL OUTCOME REGRESSION WITH APPLICATION TO COMPUTER-USE BEHAVIOR IN RHESUS MONKEYS.

Research in functional regression has made great strides in expanding to non-Gaussian functional outcomes, but exploration of ordinal functional outcomes remains limited. Motivated by a study of computer-use behavior in rhesus macaques (Macaca mulatta), we introduce the Ordinal Probit Functional Outcome Regression model (OPFOR). OPFOR models can be fit using one of several basis functions including penalized B-splines, wavelets, and O'Sullivan splines-the last of which typically performs best. Simulation using a variety of underlying covariance patterns shows that the model performs reasonably well in estimation under multiple basis functions with near nominal coverage for joint credible intervals. Finally, in application, we use Bayesian model selection criteria adapted to functional outcome regression to best characterize the relation between several demographic factors of interest and the monkeys' computer use over the course of a year. In comparison with a standard ordinal longitudinal analysis, OPFOR outperforms a cumulative-link mixed-effects model in simulation and provides additional and more nuanced information on the nature of the monkeys' computer-use behavior.

Rapid genomic changes by mineralotropic hormones and kinase SIK inhibition drive coordinated renal Cyp27b1 and Cyp24a1 expression via CREB modules.

Vitamin D metabolism centers on kidney regulation of Cyp27b1 by mineralotropic hormones, including induction by parathyroid hormone (PTH), suppression by fibroblast growth factor 23 (FGF23) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and reciprocal regulations for Cyp24a1. This coordinated genomic regulation results in production of endocrine 1,25(OH)2D3, which, together with PTH and FGF23, controls mineral homeostasis. However, how these events are coordinated is unclear. Here, using in vivo chromatin immunoprecipitation sequencing in mouse kidney, we demonstrate that PTH activation rapidly induces increased recruitment of phosphorylated (p-133) CREB (pCREB) and its coactivators, CBP (CREB-binding protein) and CRTC2 (CREB-regulated transcription coactivator 2), to previously defined kidney-specific M1 and M21 enhancers near the Cyp27b1 gene. At distal enhancers of the Cyp24a1 gene, PTH suppression dismisses CBP with only minor changes in pCREB and CRTC2 occupancy, all of which correlate with decreased genomic activity and reduced transcripts. Treatment of mice with salt-inducible kinase inhibitors (YKL-05-099 and SK-124) yields rapid genomic recruitment of CRTC2 to Cyp27b1, limited interaction of CBP, and a transcriptional response for both Cyp27b1 and Cyp24a1 that mirrors the actions of PTH. Surprisingly, we find that 1,25(OH)2D3 suppression increases the occupancy of CRTC2 in the M1 enhancer, a novel observation for CRTC2 and 1,25(OH)2D3 action. Suppressive actions of 1,25(OH)2D3 and FGF23 at the Cyp27b1 gene are associated with reduced CBP recruitment at these CREB-module enhancers that disrupts full PTH induction. Our findings show that CRTC2 contributes to transcription of both Cyp27b1 and Cyp24a1, demonstrate salt-inducible kinase inhibition as a key modulator of vitamin D metabolism, and provide molecular insight into the coordinated mechanistic actions of PTH, FGF23, and 1,25(OH)2D3 in the kidney that regulate mineral homeostasis.

The Impact of Virtual Interviewing During the COVID-19 Pandemic on the Residency Application Process: One Institution's Experience.

PURPOSE: To assess the impact of virtual interviewing during the COVID-19 pandemic on the residency application process and to compare applicant costs and time spent interviewing during the 2020-2021 application cycle with prior years. METHOD: Fourth-year medical students at the University of Kansas School of Medicine applying for first-year residency positions via the National Resident Matching Program Match completed an electronic 46-item survey after submitting their rank lists during each application cycle from 2015-2016 to 2020-2021. The authors used descriptive statistics and t tests to analyze and compare responses to demographics questions and questions regarding number of submitted applications, offered and completed interviews, ranked programs, costs, and time spent interviewing. They used thematic analysis to code respondents' narrative comments about the virtual interviewing experience. RESULTS: From 2015-2016 to 2020-2021, 994 (of 1,190; 83.5%) respondents completed the survey. From 2019-2020 to 2020-2021, the average total cost of applying to residency per applicant dropped by $3,566 (P < .001) and the average time spent interviewing dropped by 13.3 days (P < .001). At the same time, the average number of applications per applicant dropped by 3.4, and applicants completed the same number of interviews and ranked 2.3 fewer programs, none of which were statistically significant differences. Narrative comments from 113 (79%) respondents in 2020-2021 revealed 4 themes related to virtual interviewing: convenience of time and cost, positive aspects of the process, negative aspects of the process, and overall impressions of the program. CONCLUSIONS: Virtual interviewing during the 2020-2021 application cycle resulted in an approximately 80% reduction in cost for applicants and an approximately 50% decrease in time spent interviewing compared with previous years but was not associated with large increases in number of submitted applications, completed interviews, or ranked programs. Applicants generally perceived virtual interviewing as positive although they raised notable concerns.

Financial Assistance for Health Security: Effects of International Financial Assistance on Capacities for Preventing, Detecting, and Responding to Public Health Emergencies.

BACKGROUND: Health security funding is intended to improve capacities for preventing, detecting, and responding to public health emergencies. Recent years have witnessed substantial increases in the amounts of donor financial assistance to health security from countries, philanthropies, and other development partners. To date, no work has examined the effects of assistance on health security capacity development over time. This paper presents an analysis of the time-lagged effects of assistance for health security (AHS) on levels of capacity. METHODS: We collected publicly available health security assessment scores published between 2010 and 2019 and data relating to financial AHS. Using validated methods, we rescaled assessment scores on analogous scales to enable comparison and binned them in quartiles. We then used a distributed lag model (DLM) in a Bayesian ordinal regression framework to assess the effects of AHS on capacity development over time. RESULTS: Strong evidence exists for associations between financial assistance and select capacities on a variety of lagged time intervals. Financial assistance had positive effects on zoonotic disease capacities in the year it was disbursed, and positive effects on legislation, laboratory, workforce, and risk communication capacities one year after disbursal. Financial assistance had negative effects on laboratory and emergency response capacities two years after it was disbursed. Financial assistance did not have measurable effects on coordination, antimicrobial resistance (AMR), food safety, biosafety, surveillance, or response preparedness capacities over the timeframe considered. CONCLUSION: Financial AHS is associated with positive effects for several core health security capacities. However, for the majority of capacities, levels of funding were not significantly associated with capacity level, though we cannot fully exclude endogeneity. Future work should continue to investigate these relationships in different contexts and examine other factors that may contribute to capacity development.

Exploring behavioural factors affecting nutritional supplement use among children in Honduras.

OBJECTIVE: This study explored social and behavioural factors associated with a home fortification of complementary foods program among families of undernourished children in 14 rural communities in Honduras. DESIGN: We collected and analysed survey data from a convenience sample of 196 households participating in a nutritional program using home fortification of complementary foods in 2017. The program supplied families with a soy-based atole powder fortified with micronutrients. A research team completed a face-to-face survey exploring social and behavioural factors associated with nutritional supplement use. Anthropometric measurements for participating children were abstracted from health clinic records of previous quarterly appointments. SETTING: The study took place in San Jose del Negrito, Honduras. PARTICIPANTS: Participants were parents or guardians of children enrolled in the nutrition program. RESULTS: Nearly half of participant families shared the nutritional supplement with other family members besides the index child, while 10 % reported using the supplement as a meal replacement for the child. Low education level of mothers was associated with improper use of the supplement (P = 0·005). Poorer families were more likely to share the supplement (P = 0·013). CONCLUSIONS: These results highlight the challenges of programs using home fortification of complementary foods in the context of food scarcity. Findings highlight the importance of increasing rural children's overall caloric intake, perhaps by increasing access to locally available protein sources. Results also suggest transitioning nutritional programs to family-based interventions to increase overall intended compliance to nutrition programming.

Adjusting COVID-19 Seroprevalence Survey Results to Account for Test Sensitivity and Specificity.

Population-based seroprevalence surveys can provide useful estimates of the number of individuals previously infected with serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and still susceptible, as well as contribute to better estimates of the case-fatality rate and other measures of coronavirus disease 2019 (COVID-19) severity. No serological test is 100% accurate, however, and the standard correction that epidemiologists use to adjust estimates relies on estimates of the test sensitivity and specificity often based on small validation studies. We have developed a fully Bayesian approach to adjust observed prevalence estimates for sensitivity and specificity. Application to a seroprevalence survey conducted in New York State in 2020 demonstrates that this approach results in more realistic-and narrower-credible intervals than the standard sensitivity analysis using confidence interval endpoints. In addition, the model permits incorporating data on the geographical distribution of reported case counts to create informative priors on the cumulative incidence to produce estimates and credible intervals for smaller geographic areas than often can be precisely estimated with seroprevalence surveys.