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.

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.

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 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.

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.

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.

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.

Molecular and Functional Networks Linked to Sarcopenia Prevention by Caloric Restriction in Rhesus Monkeys.

Caloric restriction (CR) improves survival in nonhuman primates and delays the onset of age-related morbidities including sarcopenia, which is characterized by the age-related loss of muscle mass and function. A shift in metabolism anticipates the onset of muscle-aging phenotypes in nonhuman primates, suggesting a potential role for metabolism in the protective effects of CR. Here, we show that CR induced profound changes in muscle composition and the cellular metabolic environment. Bioinformatic analysis linked these adaptations to proteostasis, RNA processing, and lipid synthetic pathways. At the tissue level, CR maintained contractile content and attenuated age-related metabolic shifts among individual fiber types with higher mitochondrial activity, altered redox metabolism, and smaller lipid droplet size. Biometric and metabolic rate data confirm preserved metabolic efficiency in CR animals that correlated with the attenuation of age-related muscle mass and physical activity. These data suggest that CR-induced reprogramming of metabolism plays a role in delayed aging of skeletal muscle in rhesus monkeys.

ActEarly: a City Collaboratory approach to early promotion of good health and wellbeing.

Economic, physical, built, cultural, learning, social and service environments have a profound effect on lifelong health. However, policy thinking about health research is dominated by the 'biomedical model' which promotes medicalisation and an emphasis on diagnosis and treatment at the expense of prevention. Prevention research has tended to focus on 'downstream' interventions that rely on individual behaviour change, frequently increasing inequalities. Preventive strategies often focus on isolated leverage points and are scattered across different settings. This paper describes a major new prevention research programme that aims to create City Collaboratory testbeds to support the identification, implementation and evaluation of upstream interventions within a whole system city setting. Prevention of physical and mental ill-health will come from the cumulative effect of multiple system-wide interventions. Rather than scatter these interventions across many settings and evaluate single outcomes, we will test their collective impact across multiple outcomes with the goal of achieving a tipping point for better health. Our focus is on early life (ActEarly) in recognition of childhood and adolescence being such critical periods for influencing lifelong health and wellbeing.

Targeted HIV testing at birth supported by low and predictable mother-to-child transmission risk in Botswana.

INTRODUCTION: Most African countries perform infant HIV testing at 6 weeks or later. The addition of targeted testing at birth may improve retention in care, treatment outcomes and survival for HIV-infected infants. METHODS: HIV-exposed infants were screened as part of the Early Infant Treatment (EIT) study in Botswana. Screened infants were ≥35 weeks gestational age and ≥2000 g at birth. Risk factors for mother-to-child transmission (MTCT) were assessed by maternal obstetric card or verbally. Risk factors included <8 weeks ART in pregnancy, last known CD4 <250 cells/mm3 , last known HIV RNA >400 copies/mL, poor maternal ART adherence, lack of maternal zidovudine (ZDV) in labour, or lack of infant post-exposure prophylaxis. Infants underwent dried blood spot testing by Roche Cobas Ampliprep/Cobas Taqman HIV-1 qualitative PCR. RESULTS: From April 2015 to April 2016, 2303 HIV-exposed infants were tested for HIV in the EIT study. Of these, 369 (16%) were identified as high risk for HIV infection by information available at birth, and 12 (0.5% overall, 3.25% of high risk) were identified as HIV positive at birth. All 12 positive infants were identified as high risk at the time of screening, and only 2 risk factors were required to identify all positive infants: either <8 weeks of maternal ART in pregnancy (75%) or lack of maternal HIV suppression at last test (25%). CONCLUSIONS: In utero MTCT occurred only among infants identified as high risk at delivery, using information available from the mother or obstetric record. Birth testing that targets high-risk infants based on maternal ART receipt is likely to identify the majority of in utero HIV transmissions, and allows early ART initiation for these infants.

Linkage and association analysis of circulating vitamin D and parathyroid hormone identifies novel loci in Alaska Native Yup'ik people.

BACKGROUND: Vitamin D deficiency is a well-documented public health issue with both genetic and environmental determinants. Populations living at far northern latitudes are vulnerable to vitamin D deficiency and its health sequelae, although consumption of traditional native dietary pattern rich in fish and marine mammals may buffer the effects of reduced sunlight exposure. To date, few studies have investigated the genetics of vitamin D metabolism in circumpolar populations or considered genediet interactions with fish and n-3 fatty acid intake. METHODS: We searched for genomic regions exhibiting linkage and association with circulating levels of vitamin D and parathyroid hormone (PTH) in 982 Yup'ik individuals from the Center for Alaska Native Health Research Study. We also investigated potential interactions between genetic variants and a biomarker of traditional dietary intake, the δ15N value. RESULTS: We identified several novel regions linked with circulating vitamin D and PTH as well as replicated a previous linkage finding on 2p16.2 for vitamin D. Bioinformatic analysis revealed multiple candidate genes for both PTH and vitamin D, including CUBN, MGAT3, and NFKBIA. Targeted association analysis identified NEBL as a candidate gene for vitamin D and FNDC3B for PTH. We observed significant associations between a variant in MXD1 and vitamin D only when an interaction with the δ15N value was included. Finally, we integrated pathway level information to illustrate the biological validity of the proposed candidate genes. CONCLUSION: We provide evidence of linkage between several biologically plausible genomic regions and vitamin D metabolism in a circumpolar population. Additionally, these findings suggest that a traditional dietary pattern may modulate genetic effects on circulating vitamin D.

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.

Linkage and association analysis of obesity traits reveals novel loci and interactions with dietary n-3 fatty acids in an Alaska Native (Yup'ik) population.

OBJECTIVE: To identify novel genetic markers of obesity-related traits and to identify gene-diet interactions with n-3 polyunsaturated fatty acid (n-3 PUFA) intake in Yup'ik people. MATERIAL AND METHODS: We measured body composition, plasma adipokines and ghrelin in 982 participants enrolled in the Center for Alaska Native Health Research (CANHR) Study. We conducted a genome-wide SNP linkage scan and targeted association analysis, fitting additional models to investigate putative gene-diet interactions. Finally, we performed bioinformatic analysis to uncover likely candidate genes within the identified linkage peaks. RESULTS: We observed evidence of linkage for all obesity-related traits, replicating previous results and identifying novel regions of interest for adiponectin (10q26.13-2) and thigh circumference (8q21.11-13). Bioinformatic analysis revealed DOCK1, PTPRE (10q26.13-2) and FABP4 (8q21.11-13) as putative candidate genes in the newly identified regions. Targeted SNP analysis under the linkage peaks identified associations between three SNPs and obesity-related traits: rs1007750 on chromosome 8 and thigh circumference (P=0.0005), rs878953 on chromosome 5 and thigh skinfold (P=0.0004), and rs1596854 on chromosome 11 for waist circumference (P=0.0003). Finally, we showed that n-3 PUFA modified the association between obesity related traits and two additional variants (rs2048417 on chromosome 3 for adiponectin, P for interaction=0.0006 and rs730414 on chromosome 11 for percentage body fat, P for interaction=0.0004). CONCLUSIONS: This study presents evidence of novel genomic regions and gene-diet interactions that may contribute to the pathophysiology of obesity-related traits among Yup'ik people.

Differential Gene Expression Landscape of Co-Existing Cervical Pre-Cancer Lesions Using RNA-seq.

Genetic changes occurring in different stages of pre-cancer lesions reflect causal events initiating and promoting the progression to cancer. Co-existing pre-cancerous lesions including low- and high-grade squamous intraepithelial lesion (LGSIL and HGSIL), and adjacent "normal" cervical epithelium from six formalin-fixed paraffin-embedded samples were selected. Tissues from these 18 samples were isolated using laser-capture microdissection, RNA was extracted and sequenced. RNA-sequencing generated 2.4 billion raw reads in 18 samples, of which ~50.1% mapped to known and annotated genes in the human genome. There were 40 genes up-regulated and 3 down-regulated (normal to LGSIL) in at least one-third of the sample pairs (same direction and FDR p < 0.05) including S100A7 and KLK6. Previous studies have shown that S110A7 and KLK7 are up-regulated in several other cancers, whereas CCL18, CFTR, and SLC6A14, also differentially expressed in two samples, are up-regulated specifically in cervical cancer. These differentially expressed genes in normal to LGSIL progression were enriched in pathways related to epithelial cell differentiation, keratinocyte differentiation, peptidase, and extracellular activities. In progression from LGSIL to HGSIL, two genes were up-regulated and five down-regulated in at least two samples. Further investigations using co-existing samples, which account for all internal confounders, will provide insights to better understand progression of cervical pre-cancer.

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.

Where in the genome are we? A cautionary tale of database use in genomics research.

With the advent of high throughput data genomic technologies the volume of available data is now staggering. In addition databases that provide resources to annotate, translate, and connect biological data have grown exponentially in content and use. The availability of such data emphasizes the importance of bioinformatics and computational biology in genomics research and has led to the development of thousands of tools to integrate and utilize these resources. When utilizing such resources, the principles of reproducible research are often overlooked. In this manuscript we provide selected case studies illustrating issues that may arise while working with genes and genetic polymorphisms. These case studies illustrate potential sources of error which can be introduced if the practices of reproducible research are not employed and non-concurrent databases are used. We also show examples of a lack of transparency when these databases are concerned when using popular bioinformatics tools. These examples highlight that resources are constantly evolving, and in order to provide reproducible results, research should be aware of and connected to the correct release of the data, particularly when implementing computational tools.