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Background and Aims: Steatotic liver disease (SLD) is the most common chronic liver disease strongly associated with metabolic dysfunction, but its pathogenesis remains incompletely understood. Exploring plasma circulating metabolites may help in elucidating underlying mechanisms and identifying new biomarkers for SLD. Methods: We examined cross-sectionally the association between plasma metabolites and SLD as well as liver enzymes using data from 4 population-based cohort studies (Rotterdam study, Avon Longitudinal Study of Parents and Children, The Insulin Resistance Atherosclerosis Family Study, and Study of Latinos). Metabolites were assessed in the Nightingale platform (n = 225 metabolites) by nuclear magnetic resonance spectroscopy and in the Metabolon platform (n = 991 metabolites) by ultra-high-performance liquid chromatography-mass spectrometry. Serum levels of liver enzymes (alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase) were measured and SLD was diagnosed by ultrasound or computed tomography scan. Logistic and linear regression models were performed per cohort and meta-analyzed. A false discovery rate < 0.05 was considered as significant threshold. Results: Several metabolites were significantly associated with SLD and liver enzymes, of which 21 metabolites were associated with both traits. The most significant associations were observed with phenylalanine, triglycerides in (high-density lipoprotein, intermediate-density lipoprotein, and small low-density lipoprotein), fatty acid (FA) ratios of (18:2 linoleic acid-to-total FA, omega 6 FA-to-total FA, and polyunsaturated FA-to-total FA) from the Nightingale and glutamate and sphingomyelin from the Metabolon platform. Other associated metabolites were mainly involved in lipid, amino acid, carbohydrates, and peptide metabolism. Conclusion: Our study indicates a landscape of circulating metabolites associated with SLD. The identified metabolites may contribute to a better understanding of the metabolic pathways underlying SLD and hold promising for potential biomarkers in early diagnosis and monitoring of the disease.

BackgroundReproductive health conditions such as polycystic ovary syndrome (PCOS), endometriosis, and uterine fibroids pose a significant burden to people who menstruate, health care systems, and economies. Despite clinical guidelines for each condition, prolonged delays in diagnosis are commonplace, resulting in an increase to health care costs and risk of health complications. Symptom checker apps have the potential to significantly reduce time to diagnosis by providing users with health information and tools to better understand their symptoms. ObjectiveThis study aims to study the prevalence and predictive importance of self-reported symptoms of PCOS, endometriosis, and uterine fibroids, and to explore the efficacy of 3 symptom checkers (developed by Flo Health UK Limited) that use self-reported symptoms when screening for each condition. MethodsFlo’s symptom checkers were transcribed into separate web-based surveys for PCOS, endometriosis, and uterine fibroids, asking respondents their diagnostic history for each condition. Participants were aged 18 years or older, female, and living in the United States. Participants either had a confirmed diagnosis (condition-positive) and reported symptoms retrospectively as experienced at the time of diagnosis, or they had not been examined for the condition (condition-negative) and reported their current symptoms as experienced at the time of surveying. Symptom prevalence was calculated for each condition based on the surveys. Least absolute shrinkage and selection operator regression was used to identify key symptoms for predicting each condition. Participants’ symptoms were processed by Flo’s 3 single-condition symptom checkers, and accuracy was assessed by comparing the symptom checker output with the participant’s condition designation. ResultsA total of 1317 participants were included with 418, 476, and 423 in the PCOS, endometriosis, and uterine fibroids groups, respectively. The most prevalent symptoms for PCOS were fatigue (92%), feeling anxious (87%), BMI over 25 (84%); for endometriosis: very regular lower abdominal pain (89%), fatigue (85%), and referred lower back pain (80%); for uterine fibroids: fatigue (76%), bloating (69%), and changing sanitary protection often (68%). Symptoms of anovulation and amenorrhea (long periods, irregular cycles, and absent periods), and hyperandrogenism (excess hair on chin and abdomen, scalp hair loss, and BMI over 25) were identified as the most predictive symptoms for PCOS, while symptoms related to abdominal pain and the effect pain has on life, bleeding, and fertility complications were among the most predictive symptoms for both endometriosis and uterine fibroids. Symptom checker accuracy was 78%, 73%, and 75% for PCOS, endometriosis, and uterine fibroids, respectively. ConclusionsThis exploratory study characterizes self-reported symptomatology and identifies the key predictive symptoms for 3 reproductive conditions. The Flo symptom checkers were evaluated using real, self-reported symptoms and demonstrated high levels of accuracy.

In Brazil, leprosy is endemic and concentrated in high-risk clusters. Internal migration is common in the country and may influence leprosy transmission and hamper control efforts. We performed a cross-sectional study with two separate analyses evaluating factors associated with migration in Brazil’s Northeast: one among individuals newly diagnosed with leprosy and the other among a clinically unapparent population with no symptoms of leprosy for comparison. We included 394 individuals newly diagnosed with leprosy and 391 from the clinically unapparent population. Of those with leprosy, 258 (65.5%) were birth migrants, 105 (26.6%) were past five-year migrants, and 43 (10.9%) were circular migrants. In multivariate logistic regression, three independent factors were found to be significantly associated with migration among those with leprosy: (1) alcohol consumption, (2) separation from family/friends, and (3) difficulty reaching the healthcare facility. Separation from family/friends was also associated with migration in the clinically unapparent population. The health sector may consider adapting services to meet the needs of migrating populations. Future research is needed to explore risks associated with leprosy susceptibility from life stressors, such as separation from family and friends, access to healthcare facilities, and alcohol consumption to establish causal relationships.

Abstract We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare “clumping-and-thresholding” (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs developed from multiple independent GWAS, perform best across all race/ethnic backgrounds. Stratified analysis in All of Us shows that PRSs are better predictive of BP in females compared to males, individuals without obesity, and middle-aged (40-60 years) compared to older and younger individuals.

Abstract Background Alterations in gut microbiota have been implicated in HIV infection and cardiovascular disease. However, how gut microbial alterations relate to host inflammation and metabolite profiles, and their relationships with atherosclerosis, have not been well-studied, especially in the context of HIV infection. Here, we examined associations of gut microbial species and functional components measured by shotgun metagenomics with carotid artery plaque assessed by B-mode carotid artery ultrasound in 320 women with or at high risk of HIV (65% HIV +) from the Women’s Interagency HIV Study. We further integrated plaque-associated microbial features with serum proteomics (74 inflammatory markers measured by the proximity extension assay) and plasma metabolomics (378 metabolites measured by liquid chromatography tandem mass spectrometry) in relation to carotid artery plaque in up to 433 women. Results Fusobacterium nucleatum, a potentially pathogenic bacteria, was positively associated with carotid artery plaque, while five microbial species (Roseburia hominis, Roseburia inulinivorans, Johnsonella ignava, Odoribacter splanchnicus, Clostridium saccharolyticum) were inversely associated with plaque. Results were consistent between women with and without HIV. Fusobacterium nucleatum was positively associated with several serum proteomic inflammatory markers (e.g., CXCL9), and the other plaque-related species were inversely associated with proteomic inflammatory markers (e.g., CX3CL1). These microbial-associated proteomic inflammatory markers were also positively associated with plaque. Associations between bacterial species (especially Fusobacterium nucleatum) and plaque were attenuated after further adjustment for proteomic inflammatory markers. Plaque-associated species were correlated with several plasma metabolites, including the microbial metabolite imidazole-propionate (ImP), which was positively associated with plaque and several pro-inflammatory markers. Further analysis identified additional bacterial species and bacterial hutH gene (encoding enzyme histidine ammonia-lyase in ImP production) associated with plasma ImP levels. A gut microbiota score based on these ImP-associated species was positively associated with plaque and several pro-inflammatory markers. Conclusion Among women living with or at risk of HIV, we identified several gut bacterial species and a microbial metabolite ImP associated with carotid artery atherosclerosis, which might be related to host immune activation and inflammation. Video Abstract

Abstract Background Understanding human genetic influences on the gut microbiota helps elucidate the mechanisms by which genetics may influence health outcomes. Typical microbiome genome-wide association studies (GWAS) marginally assess the association between individual genetic variants and individual microbial taxa. We propose a novel approach, the covariate-adjusted kernel RV (KRV) framework, to map genetic variants associated with microbiome beta-diversity, which focuses on overall shifts in the microbiota. The KRV framework evaluates the association between genetics and microbes by comparing similarity in genetic profiles, based on groups of variants at the gene level, to similarity in microbiome profiles, based on the overall microbiome composition, across all pairs of individuals. By reducing the multiple-testing burden and capturing intrinsic structure within the genetic and microbiome data, the KRV framework has the potential of improving statistical power in microbiome GWAS. Results We apply the covariate-adjusted KRV to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) in a two-stage (first gene-level, then variant-level) genome-wide association analysis for gut microbiome beta-diversity. We have identified an immunity-related gene, IL23R, reported in a previous microbiome genetic association study and discovered 3 other novel genes, 2 of which are involved in immune functions or autoimmune disorders. In addition, simulation studies show that the covariate-adjusted KRV has a greater power than other microbiome GWAS methods that rely on univariate microbiome phenotypes across a range of scenarios. Conclusions Our findings highlight the value of the covariate-adjusted KRV as a powerful microbiome GWAS approach and support an important role of immunity-related genes in shaping the gut microbiome composition. Video Abstract

Most genetic association studies have been done on single nucleotide polymorphisms and small indels, while other types of variants have been less studied. Here, the authors use whole genome sequencing in a diverse population to identify and provide experimental evidence for associations between structural variants and blood-cell traits.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

Abstract Background Cryopreserved peripheral blood mononuclear cells (PBMCs) are frequently collected and provide disease- and treatment-relevant data in clinical studies. Here, we developed combined protein (40 antibodies) and transcript single-cell (sc)RNA sequencing (scRNA-seq) in PBMCs. Results Among 31 participants in the Women’s Interagency HIV Study (WIHS), we sequenced 41,611 cells. Using Boolean gating followed by Seurat UMAPs (tool for visualizing high-dimensional data) and Louvain clustering, we identified 50 subsets among CD4+ T, CD8+ T, B, NK cells, and monocytes. This resolution was superior to flow cytometry, mass cytometry, or scRNA-seq without antibodies. Combined protein and transcript scRNA-seq allowed for the assessment of disease-related changes in transcriptomes and cell type proportions. As a proof-of-concept, we showed such differences between healthy and matched individuals living with HIV with and without cardiovascular disease. Conclusions In conclusion, combined protein and transcript scRNA sequencing is a suitable and powerful method for clinical investigations using PBMCs.

Polygenic risk scores have potential to predict an individual’s risk of disease based on genetic markers. Here, the authors develop a polygenic risk score for hypertension and test it in a multi-ethnic cohort, finding that the score is associated with higher likelihood of hypertension development 4-6 years later.

Abstract Background Non-genetic factors contribute to differences in diabetes risk across race/ethnic and socioeconomic groups, which raises the question of whether effects of predictors of diabetes are similar across populations. We studied diabetes incidence in the primarily non-Hispanic White Framingham Heart Study (FHS, N = 4066) and the urban, largely immigrant Hispanic Community Health Study/Study of Latinos (HCHS/SOL, N = 6891) Please check if the affiliations are captured and presented correctly. Methods Clinical, behavioral, and socioeconomic characteristics were collected at in-person examinations followed by seven-day accelerometry. Among individuals without diabetes, Cox proportional hazards regression models (both age- and sex-adjusted, and then multivariable-adjusted for all candidate predictors) identified predictors of incident diabetes over a decade of follow-up, defined using clinical history or laboratory assessments. Results Four independent predictors were shared between FHS and HCHS/SOL. In each cohort, the multivariable-adjusted hazard of diabetes increased by approximately 50% for every ten-year increment of age and every five-unit increment of body mass index (BMI), and was 50–70% higher among hypertensive than among non-hypertensive individuals (all P

Objective: To determine the prevalence and determinants of electronic nicotine delivery systems (ENDS) use among Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods: Cross-sectional data collected between the years 2015–2017 were analyzed to assess ENDS use (ever (current: use ≤ past 30 days; former: use > past 30 days) and never) among 11,623 adults (mean age 47 years±0.3 years; 52% women). Weighted prevalence estimates were reported, and age-adjusted logistic regression models were used to examine associations between sociodemographic and clinical exposures with ENDS use. Results: The prevalence of current and former ENDS use was 2.0% and 10.4%, respectively. Having ever used ENDS was associated with prevalent coronary artery disease. Current ENDS use was higher in males and associated with higher education, English language preference, and Puerto Rican background compared with nonsmokers and cigarette-only smokers (all p

Abstract Background While large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify low frequency and rare genetic variants within previously reported linkage regions on chromosomes 1 and 19 in African American families from the Trans-Omics for Precision Medicine (TOPMed) program. Genetic association analyses weighted by linkage evidence were completed with whole genome sequencing data within and across TOPMed ancestral groups consisting of 60,388 individuals of European, African, East Asian, Hispanic, and Samoan ancestries. Results Associations of low frequency and rare variants in RCN3 and multiple other genes were observed for blood pressure traits in TOPMed samples. The association of low frequency and rare coding variants in RCN3 was further replicated in UK Biobank samples (N = 403,522), and reached genome-wide significance for diastolic blood pressure (p = 2.01 × 10− 7). Conclusions Low frequency and rare variants in RCN3 contributes blood pressure variation. This study demonstrates that focusing association analyses in linkage regions greatly reduces multiple-testing burden and improves power to identify novel rare variants associated with blood pressure traits.

IntroductionUnderstanding how abundance, productivity and distribution of individual species may respond to climate change is a critical first step towards anticipating alterations in marine ecosystem structure and function, as well as developing strategies to adapt to the full range of potential changes.MethodsThis study applies the NOAA (National Oceanic and Atmospheric Administration) Fisheries Climate Vulnerability Assessment method to 64 federally-managed species in the California Current Large Marine Ecosystem to assess their vulnerability to climate change, where vulnerability is a function of a species’ exposure to environmental change and its biological sensitivity to a set of environmental conditions, which includes components of its resiliency and adaptive capacity to respond to these new conditions.ResultsOverall, two-thirds of the species were judged to have Moderate or greater vulnerability to climate change, and only one species was anticipated to have a positive response. Species classified as Highly or Very Highly vulnerable share one or more characteristics including: 1) having complex life histories that utilize a wide range of freshwater and marine habitats; 2) having habitat specialization, particularly for areas that are likely to experience increased hypoxia; 3) having long lifespans and low population growth rates; and/or 4) being of high commercial value combined with impacts from non-climate stressors such as anthropogenic habitat degradation. Species with Low or Moderate vulnerability are either habitat generalists, occupy deep-water habitats or are highly mobile and likely to shift their ranges.DiscussionAs climate-related changes intensify, this work provides key information for both scientists and managers as they address the long-term sustainability of fisheries in the region. This information can inform near-term advice for prioritizing species-level data collection and research on climate impacts, help managers to determine when and where a precautionary approach might be warranted, in harvest or other management decisions, and help identify habitats or life history stages that might be especially effective to protect or restore.

Metformin is considered as first-line treatment for type 2 diabetes and an effective treatment for polycystic ovary syndrome (PCOS). However, evidence regarding its safety in pregnancy is limited. We conducted a systematic review and meta-analysis of major congenital malformations (MCMs) risk after first-trimester exposure to metformin in women with PCOS and pregestational diabetes mellitus (PGDM). Randomized controlled trials (RCTs) and observational cohort studies with a control group investigating risk of MCM after first-trimester pregnancy exposure to metformin were searched until December 2021. ORs and 95% CIs were calculated separately according to indications and study type using Mantel-Haenszel method; outcome data were combined using random-effects model. Eleven studies (two RCTs; nine observational cohorts) met the inclusion criteria: four included pregnant women with PCOS, four included those with PGDM and three evaluated both indications separately and were considered in both indication groups. In PCOS group, there were two RCTs (57 exposed, 52 control infants) and five observational studies (472 exposed, 1892 control infants); point estimates for MCM rates in RCTs and observational studies were OR 0.93 (95% CI 0.09 to 9.21) (I2=0%; Q test=0.31; p value=0.58) and OR 1.35 (95% CI 0.37 to 4.90) (I2=65%; Q test=9.43; p value=0.05), respectively. In PGDM group, all seven studies were observational (1122 exposed, 1851 control infants); the point estimate for MCM rates was OR 1.05 (95% CI 0.50 to 2.18) (I2=59%; Q test=16.34; p value=0.01). Metformin use in first-trimester pregnancy in women with PCOS or PGDM do not meaningfully increase the MCM risk overall. However, further studies are needed to characterize residual safety concerns.

Abstract Background Obesity and related comorbidities are major health concerns among many US immigrant populations. Emerging evidence suggests a potential involvement of the gut microbiome. Here, we evaluated gut microbiome features and their associations with immigration, dietary intake, and obesity in 2640 individuals from a population-based study of US Hispanics/Latinos. Results The fecal shotgun metagenomics data indicate that greater US exposure is associated with reduced ɑ-diversity, reduced functions of fiber degradation, and alterations in individual taxa, potentially related to a westernized diet. However, a majority of gut bacterial genera show paradoxical associations, being reduced with US exposure and increased with fiber intake, but increased with obesity. The observed paradoxical associations are not explained by host characteristics or variation in bacterial species but might be related to potential microbial co-occurrence, as seen by positive correlations among Roseburia, Prevotella, Dorea, and Coprococcus. In the conditional analysis with mutual adjustment, including all genera associated with both obesity and US exposure in the same model, the positive associations of Roseburia and Prevotella with obesity did not persist, suggesting that their positive associations with obesity might be due to their co-occurrence and correlations with obesity-related taxa, such as Dorea and Coprococcus. Conclusions Among US Hispanics/Latinos, US exposure is associated with unfavorable gut microbiome profiles for obesity risk, potentially related to westernized diet during acculturation. Microbial co-occurrence could be an important factor to consider in future studies relating individual gut microbiome taxa to environmental factors and host health and disease.

Abstract Background The hygiene hypothesis posits that microbial exposure reduces risk of asthma and other respiratory-related diseases. Helicobacter pylori and hepatitis A virus (HAV) are common fecal–oral infections. Our study aimed to examine associations of seropositivity to these agents with asthma in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods A total of 12,471 HCHS/SOL participants with baseline data on self-reported physician-diagnosed asthma, and antibodies anti-H. pylori and anti-HAV were included in this cross-sectional analysis. Multivariable logistic regression models were used to estimate the odds ratios and 95% confidence intervals for the overall associations of seropositivity to each agent with asthma. Analyses were also stratified by Hispanic/Latino background. Effect modification by smoking status and nativity were tested. An analysis restricted to individuals with spirometry-defined chronic obstructive pulmonary disease (COPD) was also considered. Results The weighted overall prevalence of asthma was 16.6%. The weighted seroprevalence of H. pylori was 56.6% and of HAV was 76.6%, and they significantly differed by Hispanic/Latino background. After accounting for age, sex, education and other key confounders, we found no associations between H. pylori or HAV seropositivity with asthma (with and without COPD), either for all individuals combined or for any of the six specific backgrounds. There were no significant interactions by smoking and nativity. Conclusion Our findings did not provide support for the role of H. pylori or HAV, as evidence of the hygiene hypothesis in asthma among the large and diverse Hispanic/Latino populations of the HCHS/SOL. Trial registration NCT02060344

Abstract Background Sleep-disordered breathing is a common disorder associated with significant morbidity. The genetic architecture of sleep-disordered breathing remains poorly understood. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we performed the first whole-genome sequence analysis of sleep-disordered breathing. Methods The study sample was comprised of 7988 individuals of diverse ancestry. Common-variant and pathway analyses included an additional 13,257 individuals. We examined five complementary traits describing different aspects of sleep-disordered breathing: the apnea-hypopnea index, average oxyhemoglobin desaturation per event, average and minimum oxyhemoglobin saturation across the sleep episode, and the percentage of sleep with oxyhemoglobin saturation

Yang et al. examine whether genetic ancestry is associated with genetic variation in fatty acid desaturases and plasma phospholipid levels of long chain polyunsaturated fatty acids (LC-PUFAs) in Hispanic Americans. They find strong associations between Amerind genetic ancestry and LC-PUFA levels; and report that the well-known FADS rs174537 variant was associated with several metabolic, inflammatory and anthropomorphic traits including circulating triglycerides.

The present study was conducted to evaluate the effect of dietary supplementation of the herbal extract on growth performance, carcass yield, and meat quality in quails raised under thermal-neutral (TN) and heat stress (HS) conditions. For this purpose, a total of 384 one-day-old Japanese quail chicks (Coturnix coturnix japonica) were randomly allocated to 4 treatments in a 2 × 2 factorial arrangement with two levels of dietary herbal extract (Digestarom® Poultry; 0 and 100 mg/kg of diet) and two thermal environments (TN and GS). A corn-soybean meal-based diet was prepared for starter and grower phases according to NRC (1994) recommendations. Growth performance along with carcass and meat quality characteristics including color, pH levels, L* , a* , and b* values, cooking loss, and water holding capacity were recorded. Heat stress negatively affected the feed intake of birds during the second phase of the experiment (P < 0.001). Meat pH levels were decreased at the 15th minute postmortem in quails subjected to HS (P < 0.05), while other meat quality parameters were not affected. The HS also had no significant effect on blood stress indicators such as heterophil/lymphocyte ratio or malondialdehyde concentration. The herbal extract could not extremely improve growth performance and meat quality in quails, but it helped to some extent to buffer the negative effects of HS. In conclusion, it seems quails have a high tolerant capacity and the beneficial effect of dietary herbal extract addition might be achieved when quails are subjected to higher thermal conditions.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

Obesity is associated with twofold increased risk of neural tube defects (NTD). Research has repeatedly shown that about 70% of NTD are folic-acid dependent. Yet, there is controversy whether folic acid status is the main determinant of the increased risk of obesity-induced NTD. The rational for this review is to update and discuss the evidence on the link between obesity, folic acid and NTD, in an attempt to shed light on the question whether optimal folic acid dose schedule can mitigate this risk. During pregnancy maternal folate requirements increase by 5–10-fold, as folate is diverted towards the placenta and fetus, as well as supporting different maternal organs. Correspondingly, low maternal folate status has been associated with birth defects in fetal anatomical regions particularly sensitive to reduced folate intake including oral cleft, cardiovascular defects and NTD. A recent study has documented decreased placental folate transporter expression and activity in the first and second trimesters among obese mothers. This may explain the higher incidence on NTD in infants of obese women, as less folate may find its way to the developing fetus during the sensitive periods for creating NTD. Recent pharmacokinetic results indicate that steady state levels of folate are almost perfectly defined by the dose per lean body weight (LBW). The mean dose per kg LBW that would be expected to result in steady state serum folate level of > 15.9 nmol/L was identified as 0.0073 mg/kg LBW. A large study found no differences in dietary supplementations of folic acid, yet obese women exhibited lower median serum folate as well as lower mean serum B12 levels, but no differences in mean RBC folate levels. There was a negative correlation between increasing BMI and both serum folate and plasma B12. Future research will be needed to incorporate more fully, in addition to evidence of NTD, obesity and folic acid intake, also direct measurements of serum and RBC folate, as well as other confounders, in order to create a model that will shed light on these complex interactions.

Abstract Background Intravaginal practices (IVPs), methods used by women most often to manage vaginal hygiene and address perceived disruptions to vaginal health, may increase the risk of contracting human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). This qualitative study explores the social, professional, and peer context surrounding IVPs, the experiences of self-cleaning or getting cleaned from a health professional, and the perceived impacts of IVPs among female entertainment workers (FEWs) in Cambodia. Methods In 2017, we conducted 27 focus group discussions from four provinces, and 16 follow-up semi-structured in-depth interviews with purposively selected participants in two provinces. Data collection occurred over three weeks, with concurrent data transcription and translation. The data from the transcripts were analyzed using Dedoose, an online, open-access qualitative analysis software. Two researchers independently labeled sections of transcripts associated with broader categories and subcategories based on the initial content analysis matrix and created codes. This process continued iteratively until a final coding schema and conceptual model was created. Results We found that IVPs are widely practiced among FEWs in Cambodia and are associated with internalized and enacted stigma. Stigma was an overarching theme that impacted the sub-themes of (1) messages about cleaning, (2) the cleaning process, and (3) the impact of cleaning. Experiences of enacted stigma and internalized stigma permeated conversations about IVP, including feeling pressured by peers to keep themselves clean, practicing internal cleaning after transactional sex, and being called dirty by health providers. Conclusions FEWs who practice IVP talk about it in the context of their lived experiences stigma and discrimination. Highly stigmatized practices such as IVP among FEWs may benefit from a harm reduction approach that emphasizes positive changes without judgment, coercion, or discrimination.

Chronic obstructive pulmonary disease is a leading cause of morbidity and mortality. Here, the authors analyse whole genome sequence data and find new loci associated with lung function and COPD.

Abstract Background Whether physical activity can reduce cardiometabolic risk particularly in understudied populations such as US Hispanics/Latinos is of public health interest. We prospectively examined the association of physical activity and cardiometabolic biomarkers in n = 8049 participants of the Hispanic Community Health Study/Study of Latinos, a community-based cohort study of 16,415 adults aged 18–74 yr who self-identified as Hispanic/Latino from four US urban centers. Methods We assessed physical activity using accelerometry in 2008–2011 at visit 1. We assessed cardiometabolic biomarkers twice: once at visit 1 and collected a second measure in 2014–2017 at visit 2. We used survey linear regression models with changes in cardiometabolic markers as the dependent variables and quartiles of sedentary behavior or whether adults met guidelines for moderate-to-vigorous physical activity as the independent variables. Results In normoglycemic adults without cardiovascular disease, but not in adults with evidence of cardiometabolic disease, those who were in the lowest quartile for sedentary behavior (

ABSTRACT Menopause is a pivotal period during which loss of ovarian hormones increases cardiometabolic risk and may also influence the gut microbiome. However, the menopause-microbiome relationship has not been examined in a large study, and its implications for cardiometabolic disease are unknown. In the Hispanic Community Health Study/Study of Latinos, a population with high burden of cardiometabolic risk factors, shotgun metagenomic sequencing was performed on stool from 2,300 participants (295 premenopausal women, 1,027 postmenopausal women, and 978 men), and serum metabolomics was available on a subset. Postmenopausal women trended toward lower gut microbiome diversity and altered overall composition compared to premenopausal women, while differing less from men, in models adjusted for age and other demographic/behavioral covariates. Differentially abundant taxa for post- versus premenopausal women included Bacteroides sp. strain Ga6A1, Prevotella marshii, and Sutterella wadsworthensis (enriched in postmenopause) and Escherichia coli-Shigella spp., Oscillibacter sp. strain KLE1745, Akkermansia muciniphila, Clostridium lactatifermentans, Parabacteroides johnsonii, and Veillonella seminalis (depleted in postmenopause); these taxa similarly differed between men and women. Postmenopausal women had higher abundance of the microbial sulfate transport system and decreased abundance of microbial β-glucuronidase; these functions correlated with serum progestin metabolites, suggesting involvement of postmenopausal gut microbes in sex hormone retention. In postmenopausal women, menopause-related microbiome alterations were associated with adverse cardiometabolic profiles. In summary, in a large U.S. Hispanic/Latino population, menopause is associated with a gut microbiome more similar to that of men, perhaps related to the common condition of a low estrogen/progesterone state. Future work should examine similarity of results in other racial/ethnic groups. IMPORTANCE The menopausal transition, marked by declining ovarian hormones, is recognized as a pivotal period of cardiometabolic risk. Gut microbiota metabolically interact with sex hormones, but large population studies associating menopause with the gut microbiome are lacking. Our results from a large study of Hispanic/Latino women and men suggest that the postmenopausal gut microbiome in women is slightly more similar to the gut microbiome in men and that menopause depletes specific gut pathogens and decreases the hormone-related metabolic potential of the gut microbiome. At the same time, gut microbes may participate in sex hormone reactivation and retention in postmenopausal women. Menopause-related gut microbiome changes were associated with adverse cardiometabolic risk in postmenopausal women, indicating that the gut microbiome contributes to changes in cardiometabolic health during menopause.

Abstract Background Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment. Results Amplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA. Conclusions Our analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.

Abstract Previous research has shown that genes play a substantial role in determining a person’s susceptibility to age-related hearing impairment. The existing studies on this subject have different results, which may be caused by difficulties in determining the phenotype or the limited number of participants involved. Here, we have gathered the largest sample to date (discovery n = 9,675; replication n = 10,963; validation n = 356,141), and examined phenotypes that represented low/mid and high frequency hearing loss on the pure tone audiogram. We identified 7 loci that were either replicated and/or validated, of which 5 loci are novel in hearing. Especially the ILDR1 gene is a high profile candidate, as it contains our top SNP, is a known hearing loss gene, has been linked to age-related hearing impairment before, and in addition is preferentially expressed within hair cells of the inner ear. By verifying all previously published SNPs, we can present a paper that combines all new and existing findings to date, giving a complete overview of the genetic architecture of age-related hearing impairment. This is of importance as age-related hearing impairment is highly prevalent in our ageing society and represents a large socio-economic burden.

Climate change may impact ocean ecosystems through a number of mechanisms, including shifts in primary productivity or plankton community structure, ocean acidification, and deoxygenation. These processes can be simulated with global Earth system models (ESMs), which are increasingly being used in the context of fisheries management and other living marine resource (LMR) applications. However, projections of LMR-relevant metrics such as net primary production can vary widely between ESMs, even under identical climate scenarios. Therefore, the use of ESM should be accompanied by an understanding of the structural differences in the biogeochemical sub-models within ESMs that may give rise to these differences. This review article provides a brief overview of some of the most prominent differences among the most recent generation of ESM and how they are relevant to LMR application.

Management strategy evaluation (MSE) is a simulation approach that serves as a “light on the hill” (Smith, 1994) to test options for marine management, monitoring, and assessment against simulated ecosystem and fishery dynamics, including uncertainty in ecological and fishery processes and observations. MSE has become a key method to evaluate trade-offs between management objectives and to communicate with decision makers. Here we describe how and why MSE is continuing to grow from a single species approach to one relevant to multi-species and ecosystem-based management. In particular, different ecosystem modeling approaches can fit within the MSE process to meet particular natural resource management needs. We present four case studies that illustrate how MSE is expanding to include ecosystem considerations and ecosystem models as ‘operating models’ (i.e., virtual test worlds), to simulate monitoring, assessment, and harvest control rules, and to evaluate tradeoffs via performance metrics. We highlight United States case studies related to fisheries regulations and climate, which support NOAA’s policy goals related to the Ecosystem Based Fishery Roadmap and Climate Science Strategy but vary in the complexity of population, ecosystem, and assessment representation. We emphasize methods, tool development, and lessons learned that are relevant beyond the United States, and the additional benefits relative to single-species MSE approaches.

One of the significant challenges to using information and ideas generated through ecosystem models and analyses for ecosystem-based fisheries management is the disconnect between modeling and management needs. Here we present a case study from the U.S. West Coast, the stakeholder review of NOAA’s annual ecosystem status report for the California Current Ecosystem established by the Pacific Fisheries Management Council’s Fisheries Ecosystem Plan, showcasing a process to identify management priorities that require information from ecosystem models and analyses. We then assess potential ecosystem models and analyses that could help address the identified policy concerns. We screened stakeholder comments and found 17 comments highlighting the need for ecosystem-level synthesis. Policy needs for ecosystem science included: (1) assessment of how the environment affects productivity of target species to improve forecasts of biomass and reference points required for setting harvest limits, (2) assessment of shifts in the spatial distribution of target stocks and protected species to anticipate changes in availability and the potential for interactions between target and protected species, (3) identification of trophic interactions to better assess tradeoffs in the management of forage species between the diet needs of dependent predators, the resilience of fishing communities, and maintenance of the forage species themselves, and (4) synthesis of how the environment affects efficiency and profitability in fishing communities, either directly via extreme events (e.g., storms) or indirectly via climate-driven changes in target species availability. We conclude by exemplifying an existing management process established on the U.S. West Coast that could be used to enable the structured, iterative, and interactive communication between managers, stakeholders, and modelers that is key to refining existing ecosystem models and analyses for management use.

Despite the success of antiretroviral therapy (ART), people living with HIV (PLWH) are still at higher risk for cardiovascular diseases (CVDs) that are mediated by chronic inflammation. Identification of novel inflammatory mediators with the inherent potential to be used as CVD biomarkers and also as therapeutic targets is critically needed for better risk stratification and disease management in PLWH. Here, we investigated the expression and potential role of the multi-isoform proinflammatory cytokine IL-32 in subclinical atherosclerosis in PLWH (n=49 with subclinical atherosclerosis and n=30 without) and HIV- controls (n=25 with subclinical atherosclerosis and n=24 without). While expression of all tested IL-32 isoforms (α, β, γ, D, ϵ, and θ) was significantly higher in peripheral blood from PLWH compared to HIV- controls, IL-32D and IL-32θ isoforms were further upregulated in HIV+ individuals with coronary artery atherosclerosis compared to their counterparts without. Upregulation of these two isoforms was associated with increased plasma levels of IL-18 and IL-1β and downregulation of the atheroprotective protein TRAIL, which together composed a unique atherosclerotic inflammatory signature specific for PLWH compared to HIV- controls. Logistic regression analysis demonstrated that modulation of these inflammatory variables was independent of age, smoking, and statin treatment. Furthermore, our in vitro functional data linked IL-32 to macrophage activation and production of IL-18 and downregulation of TRAIL, a mechanism previously shown to be associated with impaired cholesterol metabolism and atherosclerosis. Finally, increased expression of IL-32 isoforms in PLWH with subclinical atherosclerosis was associated with altered gut microbiome (increased pathogenic bacteria; Rothia and Eggerthella species) and lower abundance of the gut metabolite short-chain fatty acid (SCFA) caproic acid, measured in fecal samples from the study participants. Importantly, caproic acid diminished the production of IL-32, IL-18, and IL-1β in human PBMCs in response to bacterial LPS stimulation. In conclusion, our studies identified an HIV-specific atherosclerotic inflammatory signature including specific IL-32 isoforms, which is regulated by the SCFA caproic acid and that may lead to new potential therapies to prevent CVD in ART-treated PLWH.

As ecosystem-based fisheries management becomes more ingrained into the way fisheries agencies do business, a need for ecosystem and multispecies models arises. Yet ecosystems are complex, and model uncertainty can be large. Model ensembles have historically been used in other disciplines to address model uncertainty. To understand the benefits and limitations of multispecies model ensembles (MMEs), cases where they have been used in the United States to address fisheries management issues are reviewed. The cases include: (1) development of ecological reference points for Atlantic Menhaden, (2) the creation of time series to relate harmful algal blooms to grouper mortality in the Gulf of Mexico, and (3) fostering understanding of the role of forage fish in the California Current. Each case study briefly reviews the management issue, the models used and model synthesis approach taken, and the outcomes and lessons learned from the application of MMEs. Major conclusions drawn from these studies highlight how the act of developing an ensemble model suite can improve the credibility of multispecies models, how qualitative synthesis of projections can advance system understanding and build confidence in the absence of quantitative treatments, and how involving a diverse set of stakeholders early is useful for ensuring the utility of the models and ensemble. Procedures for review and uptake of information from single-species stock assessment models are well established, but the absence of well-defined procedures for MMEs in many fishery management decision-making bodies poses a major obstacle. The benefits and issues identified here should help accelerate the design, implementation, and utility of MMEs in applied fisheries contexts.

Summary: Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP, taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from five ancestry groups. In the combined meta-analyses of stages 1 and 2, we identified 59 loci (p value < 5e−8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A and PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5 and CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.

Changing ecosystem conditions present a challenge for the monitoring and management of living marine resources, where decisions often require lead-times of weeks to months. Consistent improvement in the skill of regional ocean models to predict physical ocean states at seasonal time scales provides opportunities to forecast biological responses to changing ecosystem conditions that impact fishery management practices. In this study, we used 8-month lead-time predictions of temperature at 250 m depth from the J-SCOPE regional ocean model, along with stationary habitat conditions (e.g., distance to shelf break), to forecast Pacific hake (Merluccius productus) distribution in the northern California Current Ecosystem (CCE). Using retrospective skill assessments, we found strong agreement between hake distribution forecasts and historical observations. The top performing models [based on out-of-sample skill assessments using the area-under-the-curve (AUC) skill metric] were a generalized additive model (GAM) that included shelf-break distance (i.e., distance to the 200 m isobath) (AUC = 0.813) and a boosted regression tree (BRT) that included temperature at 250 m depth and shelf-break distance (AUC = 0.830). An ensemble forecast of the top performing GAM and BRT models only improved out-of-sample forecast skill slightly (AUC = 0.838) due to strongly correlated forecast errors between models (r = 0.88). Collectively, our results demonstrate that seasonal lead-time ocean predictions have predictive skill for important ecological processes in the northern CCE and can be used to provide early detection of impending distribution shifts of ecologically and economically important marine species.

Background Underuse of cardiovascular medications for secondary prevention among individuals with peripheral artery disease (PAD) has been reported. Little is known about PAD treatment status in the Hispanic/Latino population in the United States, who may have limited access to health care and who have worse clinical outcomes than non‐Hispanic individuals. Methods and Results We studied the use of cardiovascular therapies in 1244 Hispanic/Latino individuals recruited from 4 sites in the United States, including 826 individuals who reported diagnosis of PAD by physician and 418 individuals with coronary artery disease alone, in the Hispanic Community Health Study/Study of Latinos. We compared the prevalence of using antiplatelet therapy, lipid‐lowering therapy and antihypertensive therapy by PAD and coronary artery disease status. Among those with PAD, we studied factors associated with taking cardiovascular medications, including demographic and socioeconomic factors, acculturation, access to health care and comorbidities, using multivariable regression models. The overall prevalence for individuals with PAD taking antiplatelet therapy, lipid‐lowering therapy and, among hypertensive individuals, antihypertensive therapy was 31%, 26% and 57%, respectively. Individuals of Mexican background had the lowest use for all classes of cardiovascular medications. Older age, number of doctor visits and existing hypertension and diabetes mellitus were significantly associated with taking cardiovascular therapies in adjusted models. Compared with those with PAD alone, individuals with PAD and concurrent coronary artery disease were 1.52 (95% CI, 1.20–1.93) and 1.74 (1.30–2.32) times more likely to use antiplatelet agents and statins according to multivariable analysis. No significant difference of antihypertensive medication use was found among PAD patients with or without coronary artery disease. Conclusions Hispanic/Latino individuals with known PAD underuse cardiovascular medications recommended in clinical guidelines. More efforts should be directed to improve treatment in this important group.

Management strategy evaluation (MSE) provides a simulation framework to test the performance of living marine resource management. MSE has now been adopted broadly for use in single-species fishery management, often using a relatively simple “operating model” that projects population dynamics of one species forward in time. However, many challenges in ecosystem-based management involve tradeoffs between multiple species and interactions of multiple stressors. Here we use complex operating models, multi-species ecosystem models of the California Current and Nordic and Barents Seas, to test threshold harvest control rules that explicitly address the linkage between predators and prey, and between the forage needs of predators and fisheries. Specifically, within Atlantis ecosystem models we focus on how forage (zooplankton) availability affects the performance of harvest rules for target fish, and how these harvest rules for fish can account for environmentally-driven fluctuations in zooplankton. Our investigation led to three main results. First, consistent with studies based on single-species operating models, we found that compared to constant F = FMSY policies, threshold rules led to higher target stock biomass for Pacific hake (Merluccius productus) in the California Current and mackerel (Scomber scombrus) in the Nordic and Barents Seas. Performance in terms of catch of these species varied depending partly on the biomass and recovery trajectory for the simulated stock. Secondly, the multi-species operating models and the harvest control rules that linked fishing mortality rates to prey biomass (zooplankton) led to increased catch variability; this stemmed directly from the harvest rule that frequently adjusted Pacific hake or mackerel fishing rates in response to zooplankton, which are quite variable in these two ecosystems. Thirdly, tests suggested that threshold rules that increased fishing when productivity (zooplankton) declined had the potential for strong ecosystem effects on other species. These effects were most apparent in the Nordic and Barents Seas simulations. The tests of harvest control rules here do not include uncertainty in monitoring of fish and zooplankton, nor do they include uncertainty in stock assessment and implementation; these would be required for full MSE. Additionally, we intentionally chose target fish with strong mechanistic links to particular zooplankton groups, with the simplifying assumption that zooplankton biomass followed a forced time series. Further developing and testing of ecosystem-level considerations can be achieved with end-to-end ecosystem models, such as the Atlantis models applied here, which have the added benefit of tracking the follow-on effects of the harvest control rule on the broader ecosystem.

Background To identify reasons for increased atherosclerotic risk among women living with HIV (WLWH), we evaluated the associations between psychosocial risk factors (depressive symptoms, perceived stress, and posttraumatic stress disorder symptoms) and subclinical atherosclerosis among WLWH and HIV‐negative women. Methods and Results Carotid artery focal plaque (localized intima‐media thickness >1.5 mm) was measured using B‐mode ultrasound imaging in 2004–2005 and 2010–2012 in the Women's Interagency HIV Study. We created psychosocial risk groups using latent class analysis and defined prevalent plaque at the final measurement. We also examined repeated semiannual depression measures with respect to focal plaque formation throughout follow‐up. The associations between latent class and prevalent plaque, and between depressive symptom persistence and plaque formation, were assessed separately by HIV status using multivariable logistic regression. Among 700 women (median age 47 years), 2 latent classes were identified: high (n=163) and low (n=537) psychosocial risk, with corresponding prevalence of depression (65%/13%), high stress (96%/12%), and probable posttraumatic stress disorder (46%/2%). Among WLWH, plaque prevalence was 23% and 11% in high versus low psychosocial risk classes (adjusted odds ratio [aOR], 2.12; 95% CI, 1.11–4.05) compared with 9% and 9% among HIV‐negative women (aOR, 1.07; 95% CI, 0.24–4.84), respectively. New plaque formation occurred among 17% and 9% of WLWH who reported high depressive symptoms at ≥45% versus

Immunologic function is an important determinant of cognition. Here we examined the contribution of early immune signatures to cognitive performance among HIV-infected, virally suppressed women (HIV+VS) and in HIV-uninfected (HIV-) women. Specifically, we measured serum inflammatory markers, developed combinatory immune signatures, and evaluated their associations with cognition. Forty-nine HIV+VS women in the Women’s Interagency HIV Study (WIHS) who achieved viral suppression shortly after effective antiretroviral therapy (ART) initiation, and 56 matched HIV− women were selected. Forty-two serum inflammatory markers were measured within 2 years of effective ART initiation for HIV+VS women, and at an initial timepoint for HIV− women. The same inflammatory markers were also measured approximately 1, 7, and 12 years later for all women. Of the 105 women with complete immune data, 83 (34 HIV+VS, 49 HIV−) also had cognitive data available 12 years later at ≥1 time points (median = 3.1). We searched for combinatory immune signatures by adapting a dynamic matrix factorization analytic method that builds upon Tucker decomposition followed by Ingenuity® Pathway Analysis to facilitate data interpretation. Seven combinatory immune signatures emerged based on the Frobenius residual. Three signatures were common between HIV+VS and HIV− women, while four signatures were unique. These inflammatory signatures predicted subsequent cognitive performance in both groups using mixed-effects modeling, but more domain-specific associations were significant in HIV+VS than HIV− women. Leukocyte influx into brain was a major contributor to cognitive function in HIV+VS women, while T cell exhaustion, inflammatory response indicative of depressive/psychiatric disorders, microglial activity, and cytokine signaling predicted both global and domain-specific performance for HIV− women. Our findings suggest that immune signatures may be useful diagnostic, prognostic, and immunotherapeutic targets predictive of subsequent cognitive performance. Importantly, they also provide insight into common and distinct inflammatory mechanisms underlying cognition in HIV− and HIV+VS women.

Background: Gut microbiota alteration has been implicated in HIV infection and metabolic disorders. The relationship between gut microbiota and diabetes has rarely been studied in HIV-infected individuals, who have excess risk of metabolic disorders. Methods: Our study during 2015–2016 enrolled predominantly African Americans and Hispanics in the Women's Interagency HIV Study. We studied 28 women with long-standing HIV infection under antiretroviral therapy and 20 HIV-uninfected, but at high risk of infection, women (16 HIV+ and 6 HIV- with diabetes). Fecal samples were analyzed by sequencing prokaryotic16S rRNA gene. Plasma metabolomics profiling was performed by liquid chromatography-tandem mass spectrometry. Findings: No significant differences in bacterial α- or β-diversity were observed by diabetes or HIV serostatus (all P > .1). Relative abundances of four genera (Finegoldia, Anaerococcus, Sneathia, and Adlercreutzia) were lower in women with diabetes compared to those without diabetes (all P 0.05). Anaerococcus, known to produce butyrate which is involved in anti-inflammation and glucose metabolism, showed an inverse correlation with kynurenine/tryptophan ratio (r = −0.38, P

Abstract Background The importance of contextual factors in influencing quality improvement and implementation (QI&I) initiatives is broadly acknowledged. Existing treatments of context have primarily viewed it as static and distinct from interventions themselves. The objective of this study was to advance understanding of the complex and dynamic interaction between context, intervention, and implementation strategies. Using the Model for Understanding Success in Quality (MUSIQ), we aimed to better understand the roles of, and inter-relationships between, contextual factors within QI&I initiatives. Methods Secondary analysis was performed on qualitative data collected as part of two studies: (1) an evaluation of a state-wide obstetrical quality improvement (QI) initiative, and (2) a study of the use of Plan-Do-Study-Act cycle method in QI projects. Electronic coding databases from each study were reviewed jointly. Data analysis was initiated deductively using MUSIQ as a template. Codes were added in an inductive manner. Results All original factors in MUSIQ were observed to be important in the QI initiatives studied and new factors were identified. Three distinct types of context were identified; the setting(s) of care in which QI&I takes place (Type 1); the context of the team conducting a specific project (Type 2); and the wider context supporting general QI&I (Type 3). The picture of context emerging from this study is a dynamic one with multiple, closely-linked factors operating at different levels in a system that is constantly changing in response to QI&I initiatives. To capture this complexity, a revised model (MUSIQ v2.0) was created positioning use of structured QI&I approaches as the focal point and demonstrating how context influenced effective use of these approaches, and in turn, how these approaches supported teams in navigating context by adapting interventions to fit local settings. Conclusions MUSIQ is a useful tool to explore the roles of, and inter-relationships between, contextual factors within QI&I initiatives. The revised model may help address some existing controversies about how context influences QI&I success and help ensure that future research efforts consider context not as static background, but as a complex system that is constantly changing, tightly-linked, and governed by feedback loops.

Pulmonary function is influenced by environmental factors, lifestyle, and genetics. Here, in a multiethnic GWAS meta-analysis for pulmonary function traits, the authors identify over 50 additional genetic loci, a subset of which are specific for European, African, Asian, or Hispanic/Latino ancestry.

Abstract Background In Cambodia, HIV prevalence is concentrated in key populations including among female entertainment workers (FEWs) who may engage in direct or indirect sex work. Reaching FEWs with sexual and reproductive health (SRH) services has been difficult because of their hidden and stigmatized nature. Mobile-phone-based interventions may be an effective way to reach this population and connect them with the existing services. This article describes study design and implementation of a randomized controlled trial (RCT) of a mobile health intervention (the Mobile Link) aiming to improve SRH and related outcomes among FEWs in Cambodia. Methods A two-arm RCT will be used to determine the effectiveness of a mobile-phone-based text/voice messaging intervention. The intervention will be developed through a participatory process. Focus group discussions and in-depth interviews have been conducted to inform and tailor behavior change theory-based text and voice messages. During the implementation phase, 600 FEWs will be recruited and randomly assigned into one of the two arms: (1) a control group and (2) a mobile phone message group (either text messages [SMS] or voice messages [VM], a delivery method chosen by participants). Participants in the control group will also receive a weekly monitoring survey, which will provide real-time information to implementing partners to streamline outreach efforts and be able to quickly identify geographic trends. The primary outcome measures will include self-reported HIV and sexually transmitted infections (STI) testing and treatment, condom use, contraceptive use, and gender-based violence (GBV). Discussion If the Mobile Link trial is successful, participants will report an increase in condom use, linkages to screening and treatment for HIV and STI, and contraception use as well as a reduction in GBV. This trial is unique in a number of ways. First, the option of participation mode (SMS or VM) allows participants to choose the message medium that best links them to services. Second, this is the first RCT of a mobile-phone-based behavior change intervention using SMS/VMs to support linkage to SRH services in Cambodia. Lastly, we are working with a hidden, hard-to-reach, and dynamic population with which existing methods of outreach have not been fully successful. Trial registration Clinical trials.gov, NCT03117842. Registered on 31 March 2017.