Relationship of socio-demographics, comorbidities, symptoms and healthcare access with early COVID-19 presentation and disease severity.

BACKGROUND: COVID-19 studies are primarily from the inpatient setting, skewing towards severe disease. Race and comorbidities predict hospitalization, however, ambulatory presentation of milder COVID-19 disease and characteristics associated with progression to severe disease is not well-understood. METHODS: We conducted a retrospective chart review including all COVID-19 positive cases from Stanford Health Care (SHC) in March 2020 to assess demographics, comorbidities and symptoms in relationship to: 1) their access point of testing (outpatient, inpatient, and emergency room (ER)) and 2) development of severe disease. RESULTS: Two hundred fifty-seven patients tested positive: 127 (49%), 96 (37%), and 34 (13%) at outpatient, ER and inpatient, respectively. Overall, 61% were age < 55; age > 75 was rarer in outpatient setting (11%) than ER (14%) or inpatient (24%). Most patients presented with cough (86%), fever/chills (76%), or fatigue (63%). 65% of inpatients reported shortness of breath compared to 30-32% of outpatients and ER patients. Ethnic/minority patients had a significantly higher risk of developing severe disease (Asian OR = 4.8 [1.6-14.2], Hispanic OR = 3.6 [1.1-11.9]). Medicare-insured patients were marginally more likely (OR = 4.0 [0.9-17.8]). Other factors associated with developing severe disease included kidney disease (OR = 6.1 [1.0-38.1]), cardiovascular disease (OR = 4.7 [1.0-22.1], shortness of breath (OR = 5.4 [2.3-12.6]) and GI symptoms (OR = 3.3 [1.4-7.7]; hypertension without concomitant CVD or kidney disease was marginally significant (OR = 2.3 [0.8-6.5]). CONCLUSIONS: Early widespread symptomatic testing for COVID-19 in Silicon Valley included many less severely ill patients. Thorough manual review of symptomatology reconfirms the heterogeneity of COVID-19 symptoms, and challenges in using clinical characteristics to predict decline. We re-demonstrate that socio-demographics are consistently associated with severity.

Global Progress and Challenges in Implementing New Medications for Treating Multidrug-Resistant Tuberculosis.

Two new drugs-bedaquiline and delamanid-have recently been approved by stringent regulatory authorities to treat multidrug-resistant tuberculosis (TB) and recommended by the World Health Organization for use under defined programmatic conditions. Introducing the medications in TB programs worldwide has not kept pace with the need for these drugs. In response, the DR-TB STAT (Drug-Resistant TB Scale-up Treatment Action Team) task force was formed in April 2015 to monitor progress and help overcome challenges. Information was collected from multiple sources and assessed monthly. Some progress has been made in introducing bedaquiline: as of October 2015, a total of 1,258 persons were on the medication under programmatic conditions. For delamanid, >100 patients, but few under programmatic conditions, have received the medication. Coordinated global action might help assist making these medications accessible for persons who need them most.

Proximity to high streets, social isolation and social support in British adolescents: A longitudinal analysis of sociospatial influences on social connectedness using geospatial data.

High streets have been shown to be central to socio-economic activity, given their diverse residential, leisure, and commercial activities. This study explores the link between adolescent social isolation and proximity to, and land use mix in, high streets. Hypothesising that greater distance from high streets might increase social isolation, measured via social activities, friend contact frequency, and social support, we used multilevel modelling with data from the Millennium Cohort Study. We did not observe a relationship between proximity to high streets and these social isolation indicators, suggesting that high streets may either not significantly influence adolescent social engagement or that young people are willing to travel greater distances.

Genetic variation in NCAM1 contributes to left ventricular wall thickness in hypertensive families.

RATIONALE: Left ventricular (LV) mass and related phenotypes are heritable, important predictors of cardiovascular disease, particularly in hypertensive individuals. OBJECTIVE: Identify genetic predictors of echocardiographic phenotypes in hypertensive families. METHODS AND RESULTS: A multistage genome-wide association study (GWAS) was conducted in hypertensive-ascertained black families (HyperGEN, stage I; GENOA, stage II); findings were replicated in HyperGEN white families (stage III). Echocardiograms were collected using a common protocol, and participants were genotyped with the Affymetrix Genome-Wide Human SNP 6.0 Array. The following were analyzed using mixed models adjusted for ancestry: in stages I and II, 1258 and 989 blacks, respectively; and in stage III, 1316 whites. Phenotypes included LV mass, LV internal dimension (LVID), wall thicknesses (posterior [PWT] and intraventricular septum [IVST]), and relative wall thickness (RWT). In stage I, 5 single nucleotide polymorphisms (SNPs) had P≤10(-6). In stage II, 1 SNP (rs1436109; NCAM1 intron 1) replicated with the same phenotype (PWT, P=0.025) in addition to RWT (P=0.032). In stage III, rs1436109 was associated with RWT (P=5.47×10(-4)) and LVID (P=1.86×10(-4)). Fisher combined probability value for all stages was RWT=3.80×10(-9), PWT=3.12×10(-7), IVST=8.69×10(-7), LV mass=2.52×10(-3), and LVID=4.80×10(-4). CONCLUSIONS: This GWAS conducted in hypertensive families identified a variant in NCAM1 associated with LV wall thickness and RWT. NCAM is upregulated during the remodeling period of hypertrophy to heart failure in Dahl salt-sensitive rats. Our initial screening in hypertensive blacks may have provided the context for this novel locus.

Evidence for novel genetic loci associated with metabolic traits in Yup'ik people.

OBJECTIVES: To identify genomic regions associated with fasting plasma lipid profiles, insulin, glucose, and glycosylated hemoglobin in a Yup'ik study population, and to evaluate whether the observed associations between genetic factors and metabolic traits were modified by dietary intake of marine derived omega-3 polyunsaturated acids (n-3 PUFA). METHODS: A genome-wide linkage scan was conducted among 982 participants of the Center for Alaska Native Health Research study. n-3 PUFA intake was estimated using the nitrogen stable isotope ratio (δ(15) N) of erythrocytes. All genotyped SNPs located within genomic regions with LOD scores > 2 were subsequently tested for individual SNP associations with metabolic traits using linear models that account for familial correlation as well as age, sex, community group, and n-3 PUFA intake. Separate linear models were fit to evaluate interactions between the genotype of interest and n-3 PUFA intake. RESULTS: We identified several chromosomal regions linked to serum apolipoprotein A2, high density lipoprotein-, low density lipoprotein-, and total cholesterol, insulin, and glycosylated hemoglobin. Genetic variants found to be associated with total cholesterol mapped to a region containing previously validated lipid loci on chromosome 19, and additional novel peaks of biological interest were identified at 11q12.2-11q13.2. We did not observe any significant interactions between n-3 PUFA intake, genotypes, and metabolic traits. CONCLUSIONS: We have completed a whole genome linkage scan for metabolic traits in Native Alaskans, confirming previously identified loci, and offering preliminary evidence of novel loci implicated in chronic disease pathogenesis in this population.

Gene expression patterns in peripheral blood cells associated with radiographic severity in African Americans with early rheumatoid arthritis.

Gene expression profiling may be used to stratify patients by disease severity to test the hypothesis that variable disease outcome has a genetic component. In order to define unique expression signatures in African American rheumatoid arthritis (RA) patients with severe erosive disease, we undertook a gene expression study using samples of RNA from peripheral blood mononuclear cells (PBMCs). RNA from baseline PBMC samples of 96 African American RA patients with early RA (<2 years disease duration) was hybridized to cDNA probes of the Illumina Human HT-V3 expression array. Expression analyses were performed using the ca. 25,000 cDNA probes, and then expression levels were compared to the total number of erosions in radiographs of the hands and feet at baseline and 36 months. Using a false discovery rate cutoff of Q = 0.30, 1,138 genes at baseline and 680 genes at 36 months significantly correlated with total erosions. No evidence of a signal differentiating disease progression, or change in erosion scores between baseline and 36 months, was found. Further analyses demonstrated that the differential gene expression signature was localized to the patients with the most erosive disease (>10 erosions). Ingenuity Pathway Analysis demonstrated that genes with fold change greater than 1.5 implicated immune pathways such as CTLA signaling in cytotoxic T lymphocytes. These results demonstrate that CLEAR patients with early RA having the most severe erosive disease, as compared to more mild cases (<10 erosions), may be characterized by a set of differentially expressed genes that represent biological pathways with relevance to autoimmune disease.

Subjective and objective indicators of neighbourhood safety and physical activity among UK adolescents.

BACKGROUND: The health benefits of regular physical activity in adolescence are well-documented and many health-related behaviours are established in adolescence. The neighbourhood environment is a key setting for physical activity for adolescents and feeling unsafe in their neighbourhood may be a potential barrier to physical activity. AIM: This study aimed to examine associations between neighbourhood safety and physical activity using objective and subjective measures for both. METHODS: Participants (n = 10,913) came from the Millennium Cohort Study, a nationally representative UK longitudinal birth cohort. Linear regression and Zero Inflated Poisson models were used to examine associations between subjective and objective indicators of safety (self-reported safety, Index of Multiple Deprivation crime, Reported Crime Incidence) and physical activity (self-reported weekly and device-measured physical activity). RESULTS: Adolescents who feel unsafe in their neighbourhood, or who live in areas with high IMD crime or violent crime rates report 0.29 (95% CI -0.49, -0.09) 0.32 (95% CI -0.47, -0.16) and 0.20 (95% CI -0.39, -0.20) fewer days of physical activity, respectively. No associations were found between Reported Crime Incidence and either objective or subjective measures of physical activity. CONCLUSIONS: This study demonstrates varying associations between subjective safety and objective crime with physical activity levels in adolescence, highlighting the complexities around subjective and objective measurements and their associations with health outcomes.

Linking the Urban Environment and Health: An Innovative Methodology for Measuring Individual-Level Environmental Exposures.

Environmental exposures (EE) are increasingly recognised as important determinants of health and well-being. Understanding the influences of EE on health is critical for effective policymaking, but better-quality spatial data is needed. This article outlines the theoretical and technical foundations used for the construction of individual-level environmental exposure measurements for the population of a northern English city, Bradford. The work supports 'Connected Bradford', an entire population database linking health, education, social care, environmental and other local government data over a period of forty years. We argue that our current understanding of environmental effects on health outcomes is limited both by methodological shortcomings in the quantification of the environment and by a lack of consistency in the measurement of built environment features. To address these shortcomings, we measure the environmental exposure for a series of different domains including air quality, greenspace and greenness, public transport, walkability, traffic, buildings and the built form, street centrality, land-use intensity, and food environments as well as indoor dwelling qualities. We utilise general practitioners' historical patient information to identify the precise geolocation and duration of a person's residence. We model a person's local neighbourhood, and the probable routes to key urban functions aggregated across the city. We outline the specific geospatial procedure used to quantify the environmental exposure for each domain and use the example of exposure to fast-food outlets to illustrate the methodological challenges in the creation of city and nationwide environmental exposure databases. The proposed EE measures will enable critical research into the relationship and causal links between the built environment and health, informing planning and policy-making.

Shaping Pathways to Child Health: A Systematic Review of Street-Scale Interventions in City Streets.

Street-level built environment factors, for example, walking infrastructure, building density, availability of public transport, and proliferation of fast-food outlets can impact on health by influencing our ability to engage in healthy behaviour. Unhealthy environments are often clustered in deprived areas, thus interventions to improve the built environments may improve health and reduce inequalities. The aim of this review was to identify whether street-level built environment interventions can improve children's health in high income countries. A secondary aim was to describe key built environment elements targeted in interventions and research gaps. A systematic review of published literature was conducted by a multi-disciplinary team. Ten intervention papers were included. Physical activity or play was the only health outcome assessed. Most interventions described temporary changes including closure of streets to traffic (N = 6), which were mainly located in deprived neighbourhoods, or the addition of technology to 'gamify' active travel to school (N = 2). Two studies reported permanent changes to street design. There was limited evidence that closing streets to traffic was associated with increases in activity or play and inconclusive evidence with changes to street design and using technology to gamify active travel. Our ability to draw conclusions was hampered by inadequate study designs. Description of interventions was poor. Rigorous evaluation of built environment interventions remains challenging. We recommend a multi-disciplinary approach to evaluation, explicit reporting of built environment indicators targeted in interventions and offer solutions to others working in this area.

A Systematic Review of Studies Describing the Effectiveness, Acceptability, and Potential Harms of Place-Based Interventions to Address Loneliness and Mental Health Problems.

Given the links between the built environment and loneliness, there is interest in using place-based approaches (addressing built environment characteristics and related socio-spatial factors) in local communities to tackle loneliness and mental health problems. However, few studies have described the effectiveness, acceptability, or potential harms of such interventions. This review aimed to synthesize the literature describing local community-based interventions that target place-based factors to address loneliness and mental health problems, informing the development of future public health approaches. We searched PsycINFO, Medline, and Embase using a structured search strategy to identify English-language studies evaluating the effectiveness, acceptability, and potential harms of place-based community interventions in addressing loneliness and mental health problems, both in general and clinical populations. Seven studies met the inclusion criteria, classified as evaluating provision of community facilities (such as clubhouses), active engagement in local green spaces, and housing regeneration. None were randomised trials. Quantitative and qualitative findings suggested promising effects and/or acceptability of six interventions, with minimal potential harms. There is a clear need for randomised trials or quasi-experimental studies of place-based interventions to describe their effectiveness in addressing loneliness and mental health problems, as well as complementary qualitative work investigating acceptability. This will inform future policy development.

A 360 degree mixed-methods evaluation of a specialized COVID-19 outpatient clinic and remote patient monitoring program.

BACKGROUND: Our goals are to quantify the impact on acute care utilization of a specialized COVID-19 clinic with an integrated remote patient monitoring program in an academic medical center and further examine these data with stakeholder perceptions of clinic effectiveness and acceptability. METHODS: A retrospective cohort was drawn from enrolled and unenrolled ambulatory patients who tested positive in May through September 2020 matched on age, presence of comorbidities and other factors. Qualitative semi-structured interviews with patients, frontline clinician, and administrators were analyzed in an inductive-deductive approach to identify key themes. RESULTS: Enrolled patients were more likely to be hospitalized than unenrolled patients (N = 11/137 in enrolled vs 2/126 unenrolled, p = .02), reflecting a higher admittance rate following emergency department (ED) events among the enrolled vs unenrolled, though this was not a significant difference (46% vs 25%, respectively, p = .32). Thirty-eight qualitative interviews conducted June to October 2020 revealed broad stakeholder belief in the clinic's support of appropriate care escalation. Contrary to beliefs the clinic reduced inappropriate care utilization, no difference was seen between enrolled and unenrolled patients who presented to the ED and were not admitted (N = 10/137 in enrolled vs 8/126 unenrolled, p = .76). Administrators and providers described the clinic's integral role in allowing health services to resume in other areas of the health system following an initial lockdown. CONCLUSIONS: Acute care utilization and multi-stakeholder interviews suggest heightened outpatient observation through a specialized COVID-19 clinic and remote patient monitoring program may have contributed to an increase in appropriate acute care utilization. The clinic's role securing safe reopening of health services systemwide was endorsed as a primary, if unmeasured, benefit.

Anti-nucleocapsid antibody levels and pulmonary comorbid conditions are linked to post-COVID-19 syndrome.

BACKGROUNDProlonged symptoms after SARS-CoV-2 infection are well documented. However, which factors influence development of long-term symptoms, how symptoms vary across ethnic groups, and whether long-term symptoms correlate with biomarkers are points that remain elusive.METHODSAdult SARS-CoV-2 reverse transcription PCR-positive (RT-PCR-positive) patients were recruited at Stanford from March 2020 to February 2021. Study participants were seen for in-person visits at diagnosis and every 1-3 months for up to 1 year after diagnosis; they completed symptom surveys and underwent blood draws and nasal swab collections at each visit.RESULTSOur cohort (n = 617) ranged from asymptomatic to critical COVID-19 infections. In total, 40% of participants reported at least 1 symptom associated with COVID-19 six months after diagnosis. Median time from diagnosis to first resolution of all symptoms was 44 days; median time from diagnosis to sustained symptom resolution with no recurring symptoms for 1 month or longer was 214 days. Anti-nucleocapsid IgG level in the first week after positive RT-PCR test and history of lung disease were associated with time to sustained symptom resolution. COVID-19 disease severity, ethnicity, age, sex, and remdesivir use did not affect time to sustained symptom resolution.CONCLUSIONWe found that all disease severities had a similar risk of developing post-COVID-19 syndrome in an ethnically diverse population. Comorbid lung disease and lower levels of initial IgG response to SARS-CoV-2 nucleocapsid antigen were associated with longer symptom duration.TRIAL REGISTRATIONClinicalTrials.gov, NCT04373148.FUNDINGNIH UL1TR003142 CTSA grant, NIH U54CA260517 grant, NIEHS R21 ES03304901, Sean N Parker Center for Allergy and Asthma Research at Stanford University, Chan Zuckerberg Biohub, Chan Zuckerberg Initiative, Sunshine Foundation, Crown Foundation, and Parker Foundation.

A unified framework for multi-locus association analysis of both common and rare variants.

BACKGROUND: Common, complex diseases are hypothesized to result from a combination of common and rare genetic variants. We developed a unified framework for the joint association testing of both types of variants. Within the framework, we developed a union-intersection test suitable for genome-wide analysis of single nucleotide polymorphisms (SNPs), candidate gene data, as well as medical sequencing data. The union-intersection test is a composite test of association of genotype frequencies and differential correlation among markers. RESULTS: We demonstrated by computer simulation that the false positive error rate was controlled at the expected level. We also demonstrated scenarios in which the multi-locus test was more powerful than traditional single marker analysis. To illustrate use of the union-intersection test with real data, we analyzed a publically available data set of 319,813 autosomal SNPs genotyped for 938 cases of Parkinson disease and 863 neurologically normal controls for which no genome-wide significant results were found by traditional single marker analysis. We also analyzed an independent follow-up sample of 183 cases and 248 controls for replication. CONCLUSIONS: We identified a single risk haplotype with a directionally consistent effect in both samples in the gene GAK, which is involved in clathrin-mediated membrane trafficking. We also found suggestive evidence that directionally inconsistent marginal effects from single marker analysis appeared to result from risk being driven by different haplotypes in the two samples for the genes SYN3 and NGLY1, which are involved in neurotransmitter release and proteasomal degradation, respectively. These results illustrate the utility of our unified framework for genome-wide association analysis of common, complex diseases.

Genes linked to energy metabolism and immunoregulatory mechanisms are associated with subcutaneous adipose tissue distribution in HIV-infected men.

OBJECTIVE: Genetic studies may help explain abnormalities of fat distribution in HIV-infected patients treated with antiretroviral therapy (ARV). METHODS: Subcutaneous adipose tissue (SAT) volume measured by MRI in the leg, the lower trunk, the upper trunk, and the arm was examined in 192 HIV-infected White men, ARV-treated from the Fat Redistribution and Metabolic Change in HIV infection study. Single-nucleotide polymorphisms were assayed using the Illumina Human CNV370-quad beadchip. Multivariate and univariate genome-wide association analyses of the four SAT depots were implemented in PLINK software adjusted for age and ARV duration. Functional annotation analysis using Ingenuity Systems Pathway Analysis tool was carried out for markers with P lower than 10(-3) near known genes identified by multivariate analysis. RESULTS: Loci (rs10504906, rs13267998, rs921231) in or near the anion exchanger solute carrier family 26, member 7 isoform a (SLC26A7) were strongly associated with the upper trunk and the arm SAT (9.8×10(-7) ≤P<7.8×10(-6)). Loci (rs193139, rs7523050, rs1761621) in and near a gene-rich region including G-protein-signaling modulator 2 (GPSM2) and syntaxin-binding protein 3 (STXBP3) were significantly associated with the lower body SAT depots (9.9×10(-7) ≤P<9.5×10(-6)). GPSM2 is associated with cell division and cancer whereas STXBP3 is associated with glucose metabolism in adipoctyes. Ingenuity Systems Pathway Analysis identified atherosclerosis, mitochondrial function, and T-cell-mediated apoptosis as processes related to SAT volume in HIV-infected individuals (P<5×10(-3)). CONCLUSION: Our results are limited by the small sample size and replication is needed; however, this genomic scan uncovered new genes associated with metabolism and inflammatory pathways that may affect SAT volume in ARV-treated HIV-infected patients.

Comparing self-reported ethnicity to genetic background measures in the context of the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Questions remain regarding the utility of self-reported ethnicity (SRE) in genetic and epidemiologic research. It is not clear whether conditioning on SRE provides adequate protection from inflated type I error rates due to population stratification and admixture. We address this question using data obtained from the Multi-Ethnic Study of Atherosclerosis (MESA), which enrolled individuals from 4 self-reported ethnic groups. We compare the agreement between SRE and genetic based measures of ancestry (GBMA), and conduct simulation studies based on observed MESA data to evaluate the performance of each measure under various conditions. RESULTS: Four clusters are identified using 96 ancestry informative markers. Three of these clusters are well delineated, but 30% of the self-reported Hispanic-Americans are misclassified. We also found that MESA SRE provides type I error rates that are consistent with the nominal levels. More extensive simulations revealed that this finding is likely due to the multi-ethnic nature of the MESA. Finally, we describe situations where SRE may perform as well as a GBMA in controlling the effect of population stratification and admixture in association tests. CONCLUSIONS: The performance of SRE as a control variable in genetic association tests is more nuanced than previously thought, and may have more value than it is currently credited with, especially when smaller replication studies are being considered in multi-ethnic samples.

Use of home pulse oximetry with daily short message service messages for monitoring outpatients with COVID-19: The patient's experience.

Studies have shown COVID-19 patients may have a low oxygen saturation (SpO2) independent of visible respiratory distress, a phenomenon termed "silent hypoxia." Silent hypoxia creates uncertainty in the outpatient setting for clinicians and patients alike. In this study, we examined the potential for pulse oximeters in identifying early signs of clinical deterioration. We report descriptive results on COVID-positive patients' experiences with a comprehensive home monitoring tool comprised of home SpO2 measurements with a novel symptom-tracking short message service/text messaging application. Of patients who required hospitalization, 83% sought care as a result of low pulse oximeter readings. Nearly all patients who did not require hospitalization reported that having a pulse oximeter provided them with the confidence to stay at home. Essentially all patients found a home pulse oximeter useful. Keeping COVID-19-positive patients at home reduces the potential for disease spread and prevents unnecessary costs and strain on the healthcare system.

Measuring the Built Environment in Studies of Child Health-A Meta-Narrative Review of Associations.

Although the built environment (BE) is important for children's health, there is little consensus about which features are most important due to differences in measurement and outcomes across disciplines. This meta-narrative review was undertaken by a multi-disciplinary team of researchers to summarise ways in which the BE is measured, and how this links to children's health. A structured search of four databases across the relevant disciplines retrieved 108 relevant references. The most commonly addressed health-related outcomes were active travel, physical activity and play, and obesity. Many studies used objective (GIS and street audits) or standardised subjective (perceived) measurements of the BE. However, there was a wide variety, and sometimes inconsistency, in their definition and use. There were clear associations between the BE and children's health. Objective physical activity and self-reported active travel, or obesity, were positively associated with higher street connectivity or walkability measures, while self-reported physical activity and play had the strongest association with reduced street connectivity, indicated by quieter, one-way streets. Despite the high heterogeneity found in BE measures and health outcomes, the meta-narrative approach enabled us to identify ten BE categories that are likely to support children's health and be protective against some non-communicable disease risk factors. Future research should implement consistent BE measures to ensure key features are explored. A systems approach will be particularly relevant for addressing place-based health inequalities, given potential unintended health consequences of making changes to the BE.

Implementing Value-Added Medical Education: Lessons Learned From the Student-Initiated Stanford Frontline COVID-19 Consult Service.

PROBLEM: Value-added medical education (VAME) has been difficult to implement due to student and educator constraints. The COVID-19 pandemic caused mass transitions to online learning, removed students from clinical settings, and underscored students' desires for meaningful VAME opportunities. The authors introduced the Stanford Frontline COVID-19 Consult Service (SFCS), through which off-service medical and physician assistant (PA) students provided assistance to clinicians in the form of rapid research regarding COVID-19 clinical questions. APPROACH: The SFCS, a student-derived VAME initiative, was implemented from March to May 2020 by Stanford University medical students, PA students, and faculty. SFCS aligned with not only the interests of clinicians and students but also national accreditation standards. Students attended weekly editorial meetings, didactic sessions on literature reviews and information management, and they underwent rigorous training on the peer review process. After 2 months, the authors expanded the service to local community clinicians. OUTCOMES: The SFCS enrolled 16 students, was supported by 13 faculty members, and produced 87 peer-reviewed evidence syntheses. Of the 16 SFCS students, 13 (81%) completed evaluations; of 128 Stanford Primary Care and Population Health clinicians, 48 (38%) completed evaluations. Overall student satisfaction with the SFCS was 4.9/5 (standard deviation [SD] 0.3). Self-assessed achievement of SFCS learning objectives exceeded 90% for all objectives. Overall faculty satisfaction with the SFCS was 4.4/5 (SD 0.8). Most faculty (40/46 [87%]) planned to use the database to answer future COVID-19 questions. NEXT STEPS: The SFCS is a novel, student-initiated VAME curriculum focused on increasing students' meaningful contributions to patient care. The authors will track SFCS students throughout their clerkships to gauge clerkship performance/preparedness, and they will develop training for integrating VAME into preclerkship curricula at other institutions. Given its adaptive, student-driven design, the VAME framework used to develop the SFCS empowers students to create their own personalized, experiential learning.

Is dietary fat "fattening"? A comprehensive research synthesis.

The goal of this research synthesis was to separate and articulate questions that had clear meaning, were empirically addressable, and were germane to the broad question "Is fat fattening?" Four such questions addressing the effect of varying the proportion of dietary fat on body weight and body fat were formulated. A comprehensive review of electronic citation databases was conducted to identify studies that addressed each question. The results of the studies addressing each question were tabulated and summarized, and an answer for each question was formulated. The results indicated that whether "fat is fattening" depends on exactly what one means by the question. It is apparent that under conditions of energy deficit, high-fat diets lead to greater weight loss than low-fat diets, but under ad libitum feeding conditions, instructing persons to follow a low-fat diet promotes loss of body weight and body fat. For one question, studies were few but convincing that altering the proportion of energy from fat in daily snacks has no effect on weight, while for another there were not enough studies available to answer the question with confidence. General recommendations to reduce dietary fat to promote weight loss or maintenance in all circumstances may merit reconsideration.

Commonality of functional annotation: a method for prioritization of candidate genes from genome-wide linkage studies.

Linkage studies of complex traits frequently yield multiple linkage regions covering hundreds of genes. Testing each candidate gene from every region is prohibitively expensive and computational methods that simplify this process would benefit genetic research. We present a new method based on commonality of functional annotation (CFA) that aids dissection of complex traits for which multiple causal genes act in a single pathway or process. CFA works by testing individual Gene Ontology (GO) terms for enrichment among candidate gene pools, performs multiple hypothesis testing adjustment using an estimate of independent tests based on correlation of GO terms, and then scores and ranks genes annotated with significantly-enriched terms based on the number of quantitative trait loci regions in which genes bearing those annotations appear. We evaluate CFA using simulated linkage data and show that CFA has good power despite being conservative. We apply CFA to published linkage studies investigating age-of-onset of Alzheimer's disease and body mass index and obtain previously known and new candidate genes. CFA provides a new tool for studies in which causal genes are expected to participate in a common pathway or process and can easily be extended to utilize annotation schemes in addition to the GO.