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The INDDEX24 Dietary Assessment Platform (INDDEX24) was developed to facilitate the collection of 24-h dietary recall (24HR) data. Alongside validation studies in Viet Nam and Burkina Faso in 2019–2020, we conducted activity-based costing studies to estimate the cost of conducting a 24HR among women of reproductive age using INDDEX24 compared with the pen-and-paper interview (PAPI) approach. We also modelled alternative scenarios in which: (1) 25–75 % of dietary reference data were borrowed from the INDDEX24 Global Food Matters Database (FMDB); (2) all study personnel were locally based and (3) national-scale surveys. In the primary analysis, in Viet Nam, the 24HR cost US $111 004 ($755/respondent, n 147) using INDDEX24 and $120 483 ($820/respondent, n 147) using PAPI. In Burkina Faso, the 24HR cost $78 105 ($539/respondent, n 145) using INDDEX24 and $79 465 ($544/respondent, n 146) using PAPI. In modelled scenarios, borrowing dietary reference data from the FMDB decreased the cost of INDDEX24 by 17–34 % (Viet Nam) and 5–15 % (Burkina Faso). With all locally based personnel, INDDEX24 cost more than PAPI ($498 v. $448 per respondent in Viet Nam and $456 v. $410 in Burkina Faso). However, at national scales (n 4376, Viet Nam; n 6500, Burkina Faso) using all locally based personnel, INDDEX24 was more cost-efficient ($109 v. $137 per respondent in Viet Nam and $123 v. $148 in Burkina Faso). In two countries and under most circumstances, INDDEX24 was less expensive than PAPI. Higher INDDEX24 survey preparation costs (including purchasing equipment) were more than offset by higher PAPI data entry, cleaning and processing costs. INDDEX24 may facilitate cost-efficient dietary data collection.

The Centers for Medicare & Medicaid Services’ Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) measure has appropriately established sepsis as a national priority. However, the Infectious Diseases Society of America (IDSA and five additional endorsing societies) is concerned about SEP-1’s potential to drive antibiotic overuse because it does not account for the high rate of sepsis overdiagnosis and encourages aggressive antibiotics for all patients with possible sepsis, regardless of the certainty of diagnosis or severity of illness. IDSA is also concerned that SEP-1’s complex “time zero” definition is not evidence-based and is prone to inter-observer variation. In this position paper, IDSA outlines several recommendations aimed at reducing the risk of unintended consequences of SEP-1 while maintaining focus on its evidence-based elements. IDSA’s core recommendation is to limit SEP-1 to septic shock, for which the evidence supporting the benefit of immediate antibiotics is greatest. Prompt empiric antibiotics are often appropriate for suspected sepsis without shock, but IDSA believes there is too much heterogeneity and difficulty defining this population, uncertainty about the presence of infection, and insufficient data on the necessity of immediate antibiotics to support a mandatory treatment standard for all patients in this category. IDSA believes guidance on managing possible sepsis without shock is more appropriate for guidelines that can delineate the strengths and limitations of supporting evidence and allow clinicians discretion in applying specific recommendations to individual patients. Removing sepsis without shock from SEP-1 will mitigate the risk of unnecessary antibiotic prescribing for noninfectious syndromes, simplify data abstraction, increase measure reliability, and focus attention on the population most likely to benefit from immediate empiric broad-spectrum antibiotics.

Sudden unexpected death of an individual with epilepsy (SUDEP) can pose a challenge to death investigators, as most deaths are unwitnessed and the individual is commonly found dead in bed. Anatomic findings (e.g., tongue/lip bite) are commonly absent and of varying specificity, limiting the evidence to implicate epilepsy as a cause of or contributor to death. Thus, it is likely that death certificates significantly underrepresent the true number of deaths in which epilepsy was a factor. To address this, members of the National Association of Medical Examiners, North American SUDEP Registry, Epilepsy Foundation SUDEP Institute, American Epilepsy Society, and the Centers for Disease Control and Prevention convened an expert panel to generate evidence-based recommendations for the practice of death investigation and autopsy, toxicological analysis, interpretation of autopsy and toxicology findings, and death certification to improve the precision of death certificate data available for public health surveillance of epilepsy-related deaths. The recommendations provided in this paper are intended to assist medical examiners, coroners, and death investigators when a sudden, unexpected death in a person with epilepsy is encountered.

PURPOSE: To assess time requirements for patient encounters and estimate after-hours demands of paper-based clinical workflows in ophthalmology. DESIGN: Time-and-motion study with a structured survey METHODS: Setting: Single academic ophthalmology department. Participants and Observation Procedures: Convenience sample of seven attending ophthalmologists from six subspecialties observed during 414 patient encounters for the time-motion analysis and twelve attending ophthalmologists for the survey. Main Outcome Measures: Total time spent by attending ophthalmologists per patient, and time spent on documentation, examination, and talking with patients. The survey assessed time requirements of documentation-related activities performed outside of scheduled clinic hours. RESULTS: Among the 7 attending ophthalmologists observed (6 men and 1 woman, mean (SD) age, 43.9 (7.1) years) during encounters with 414 patients (mean (SD) age of 57.8 (24.6) years), the mean (SD) total time spent per patient was 8.1 (4.8) minutes, with 2.8 (1.4) minutes (38%) for documentation, 1.2 (0.9) minutes (17%) for examination, and 3.3 (3.1) minutes (37%) for talking with patients. New patient evaluations required significantly more time than routine follow-up visits and postoperative visits. Higher clinical volumes were associated with less time per patient. Survey results indicated that paper-based documentation was associated with minimal after-hours work on weeknights and weekends. CONCLUSIONS AND RELEVANCE: Paper-based documentation comprises a substantial portion of the total time spent for patient care in outpatient ophthalmology clinics but is associated with minimal after-hours work. Understanding paper-based clinical workflows may help inform targeted strategies for improving electronic health record use in ophthalmology.

Breakthrough invasive fungal infections (IFI) have emerged as a significant problem in patients receiving systemic antifungals; however, consensus criteria for defining breakthrough IFI are missing. This position paper establishes broadly applicable definitions of breakthrough IFI for clinical research. Representatives of the Mycoses Study Group Education and Research Consortium (MSG-ERC) and the European Confederation of Medical Mycology (ECMM) reviewed the relevant English literature for definitions applied and published through 2018. A draft proposal for definitions was developed, and circulated to all members of the two organizations for comment and suggestions. The authors addressed comments received, and circulated the updated document for approval. Breakthrough IFI was defined as any IFI occurring during exposure to an antifungal drug, including fungi outside the spectrum of activity of an antifungal. The time of breakthrough IFI was defined as the first attributable clinical sign or symptom, mycological finding or radiological feature. The period defining breakthrough IFI depends on pharmacokinetic properties and extends at least until one dosing interval after drug discontinuation. Persistent IFI describes IFI that is unchanged/stable since treatment initiation with ongoing need for antifungal therapy. It is distinct from refractory IFI, defined as progression of disease and therefore similar to non-response to treatment. Relapsed IFI occurs after treatment, and is caused by the same pathogen at the same site, although dissemination can occur. These proposed definitions are intended to support the design of future clinical trials and epidemiological research in clinical mycology, with the ultimate goal of increasing the comparability of clinical trial results.

Copyright © 2018 Burla et al. Published by The American Society for Biochemistry and Molecular Biology, Inc. Human blood is a self-regenerating lipid-rich biological fluid that is routinely collected in hospital settings. The inventory of lipid molecules found in blood plasma (plasma lipidome) offers insights into individual metabolism and physiology in health and disease. Disturbances in the plasma lipidome also occur in conditions that are not directly linked to lipid metabolism; therefore, plasma lipidomics based on MS is an emerging tool in an array of clinical diagnostics and disease management. However, challenges exist in the translation of such lipidomic data to clinical applications. These relate to the reproducibility, accuracy, and precision of lipid quantitation, study design, sample handling, and data sharing. This position paper emerged from a workshop that initiated a community-led process to elaborate and define a set of generally accepted guidelines for quantitative MS-based lipidomics of blood plasma or serum, with harmonization of data acquired on different instrumentation platforms across independent laboratories as an ultimate goal. We hope that other fields may benefit from and follow such a precedent.

Acute respiratory distress syndrome (ARDS) is a heterogeneous clinical syndrome. Understanding of the complex pathways involved in lung injury pathogenesis, resolution, and repair has grown considerably in recent decades. Nevertheless, to date, only therapies targeting ventilation-induced lung injury have consistently proven beneficial, and despite these gains, ARDS morbidity and mortality remain high. Many candidate therapies with promise in preclinical studies have been ineffective in human trials, probably at least in part due to clinical and biological heterogeneity that modifies treatment responsiveness in human ARDS. A precision medicine approach to ARDS seeks to better account for this heterogeneity by matching therapies to subgroups of patients that are anticipated to be most likely to benefit, which initially might be identified in part by assessing for heterogeneity of treatment effect in clinical trials. In October 2019, the US National Heart, Lung, and Blood Institute convened a workshop of multidisciplinary experts to explore research opportunities and challenges for accelerating precision medicine in ARDS. Topics of discussion included the rationale and challenges for a precision medicine approach in ARDS, the roles of preclinical ARDS models in precision medicine, essential features of cohort studies to advance precision medicine, and novel approaches to clinical trials to support development and validation of a precision medicine strategy. In this Position Paper, we summarise workshop discussions, recommendations, and unresolved questions for advancing precision medicine in ARDS. Although the workshop took place before the COVID-19 pandemic began, the pandemic has highlighted the urgent need for precision therapies for ARDS as the global scientific community grapples with many of the key concepts, innovations, and challenges discussed at this workshop.

HIV/HCV risk behavior among women who use drugs is often exacerbated within high risk networks. The use of social media platforms such as Facebook to identify sex partners within these high-risk networks has not been examined among rural Appalachian women who use drugs. This paper provides an exploratory examination of Facebook use to identify sex partners among rural Appalachian women who use drugs, as well as associated risky sexual practices. Rural Appalachian women were randomly selected from two rural jails, consented, screened for eligibility (including drug use), and interviewed prior to jail release. Findings indicated that using Facebook to meet sex partners was associated with exchanging sex for drugs or money and having a male casual partner during the same time frame. These study findings suggest that the use of social media for high-risk sexual practices may provide a valuable platform for intervention delivery, particularly in resource-deprived areas where formal prevention and treatment services are limited.

Deep-water access is arguably the most effective, but under-studied, mechanism that plants employ to survive during drought. Vulnerability to embolism and hydraulic safety margins can predict mortality risk at given levels of dehydration, but deep-water access may delay plant dehydration. Here, we tested the role of deep-water access in enabling survival within a diverse tropical forest community in Panama using a novel data-model approach. We inversely estimated the effective rooting depth (ERD, as the average depth of water extraction), for 29 canopy species by linking diameter growth dynamics (1990-2015) to vapor pressure deficit, water potentials in the whole-soil column, and leaf hydraulic vulnerability curves. We validated ERD estimates against existing isotopic data of potential water-access depths. Across species, deeper ERD was associated with higher maximum stem hydraulic conductivity, greater vulnerability to xylem embolism, narrower safety margins, and lower mortality rates during extreme droughts over 35years (1981-2015) among evergreen species. Species exposure to water stress declined with deeper ERD indicating that trees compensate for water stress-related mortality risk through deep-water access. The role of deep-water access in mitigating mortality of hydraulically-vulnerable trees has important implications for our predictive understanding of forest dynamics under current and future climates.

Introduction: As their name suggests, ‘psychedelic’ (mind-revealing) compounds are thought to catalyse processes of psychological insight; however, few satisfactory scales exist to sample this. This study sought to develop a new scale to measure psychological insight after a psychedelic experience: the Psychological Insight Scale (PIS). Methods: The PIS is a six- to seven-item questionnaire that enquires about psychological insight after a psychedelic experience (PIS-6) and accompanied behavioural changes (PIS item 7). In total, 886 participants took part in a study in which the PIS and other questionnaires were completed in a prospective fashion in relation to a planned psychedelic experience. For validation purposes, data from 279 participants were analysed from a non-specific ‘global psychedelic survey’ study. Results: Principal components analysis of PIS scores revealed a principal component explaining 73.57% of the variance, which displayed high internal consistency at multiple timepoints throughout the study (average Cronbach’s α = 0.94). Criterion validity was confirmed using the global psychedelic survey study, and convergent validity was confirmed via the Therapeutic-Realizations Scale. Furthermore, PIS scores significantly mediated the relationship between emotional breakthrough and long-term well-being. Conclusion: The PIS is complementary to current subjective measures used in psychedelic studies, most of which are completed in relation to the acute experience. Insight – as measured by the PIS – was found to be a key mediator of long-term psychological outcomes following a psychedelic experience. Future research may investigate how insight varies throughout a psychedelic process, its underlying neurobiology and how it impacts behaviour and mental health.

Background. Burgeoning evidence suggests that loneliness during the COVID-19 pandemic is tied to high levels of depression and anxiety. The current study is unique, though, in examining which facets of social behavior and perceived social quality are most tied to internalizing symptoms using longitudinal data, including a pre-pandemic baseline, collected from a community sample of adults with pre-existing mental health concerns (analyzed n = 144). Methods. Participants completed measures of depressive and anxious symptoms pre-pandemic, followed by three weekly surveys during the pandemic. We distinguished four social variables: in-person social engagement, remote social engagement, social disruption, and social distress. OLS and mixed-effects regression models examined 1) pre-pandemic baseline symptoms as predictors of social functioning during the pandemic and 2) time-lagged associations between symptoms and social functioning during the pandemic. Results. Social behavior and social perceptions were dissociable. Baseline depressive, but not anxious, symptoms predicted greater social distress during the pandemic. Both anxious and depressive symptoms were predicted by social variables, but the specific associations differed: depressive symptoms were related to perceived social quality, whereas anxious symptoms were more tied to reported social behavior. Limitations. We relied on self-report indices, and causality should not be inferred directly from these correlational data. Conclusions. Overall, our results indicate that it is possible to follow social guidelines and even to spend relatively few hours socializing with close others, while still feeling connected and rewarded; however, people who struggle with depression and anhedonia were particularly vulnerable to distressing feelings of social disconnection amid the pandemic.

An oral antiviral against SARS-CoV-2 that also attenuates inflammatory instigators of severe COVID-19 is not available to date. Herein, we show that the apoA-I mimetic peptide 4 F inhibits Spike mediated viral entry and has antiviral activity against SARS-CoV-2 in human lung epithelial Calu3 and Vero-E6 cells. In SARS-CoV-2 infected Calu3 cells, 4 F upregulated inducers of the interferon pathway such as MX-1 and Heme oxygenase 1 (HO-1) and downregulated mitochondrial reactive oxygen species (mito-ROS) and CD147, a host protein that mediates viral entry. 4 F also reduced associated cellular apoptosis and secretion of IL-6 in both SARS-CoV-2 infected Vero-E6 and Calu3 cells. Thus, 4 F attenuates in vitro SARS-CoV-2 replication, associated apoptosis in epithelial cells and secretion of IL-6, a major cytokine related to COVID-19 morbidity. Given established safety of 4 F in humans, clinical studies are warranted to establish 4 F as therapy for COVID-19., GRAPHICAL ABSTRACT

In this paper, a generalized fractional-order SEIR model is proposed, denoted by SEIQRP model, which divided the population into susceptible, exposed, infectious, quarantined, recovered and insusceptible individuals and has a basic guiding significance for the prediction of the possible outbreak of infectious diseases like the coronavirus disease in 2019 (COVID-19) and other insect diseases in the future. Firstly, some qualitative properties of the model are analyzed. The basic reproduction number \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{ R }}_{0}$$\end{document}R0 is derived. When \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{ R }}_{0}1$$\end{document}R0>1, the endemic equilibrium point is also unique. Furthermore, some conditions are established to ensure the local asymptotic stability of disease-free and endemic equilibrium points. The trend of COVID-19 spread in the USA is predicted. Considering the influence of the individual behavior and government mitigation measurement, a modified SEIQRP model is proposed, defined as SEIQRPD model, which is divided the population into susceptible, exposed, infectious, quarantined, recovered, insusceptible and dead individuals. According to the real data of the USA, it is found that our improved model has a better prediction ability for the epidemic trend in the next two weeks. Hence, the epidemic trend of the USA in the next two weeks is investigated, and the peak of isolated cases is predicted. The modified SEIQRP model successfully capture the development process of COVID-19, which provides an important reference for understanding the trend of the outbreak.

Over the last year, the coronavirus disease 2019 (COVID-19) pandemic has resulted in profound disruptions across the globe, with school closures, social isolation, job loss, illness, and death affecting the lives of children and families in myriad ways. In an Editors' Note in our June 2020 issue, 1 our senior editorial team described this Journal's role in advancing knowledge in child and adolescent mental health during the pandemic and outlined areas we identified as important for science and practice in our field. Since then, the Journal has published articles on the impacts of the pandemic on child and adolescent mental health and service systems, 2-5 which are available in a special collection accessible through the Journal's website. 6 Alongside many opinion papers, the pace of publication of empirical research in this area is rapidly expanding, covering important issues such as increased frequency of mental health symptoms among children and adolescents 3,5,7-10 and changes in patterns of clinical service use such as emergency department visits. 11-14 As the Senior Editors prepared that Editors’ Note, they were acutely aware that the priorities that they identified were broad and generated by only a small group of scientists and clinicians. Although this had the advantage of enabling us to get this information out to readers quickly, we decided that a more systematic approach to developing recommendations for research priorities would be of greater long-term value. We were particularly influenced by the efforts of the partnership between the UK Academy of Medical Scientists and a UK mental health research charity (MQ: Transforming Mental Health) to detail COVID-19−related research priorities for “Mental Health Science” that was published online by Holmes et al. in The Lancet Psychiatry in April 2020. 15 Consistent with its focus on mental health research across the lifespan, several recommendations highlighted child development and children's mental health. However, a more detailed assessment of research priorities related to child and adolescent mental health was beyond the scope of that paper. Furthermore, the publication of that position paper preceded the death of George Floyd at the hands of Minneapolis police on May 25, 2020, which re-energized efforts to acknowledge and to address racism and healthcare disparities in the United States and many other countries. To build upon the JAACAP Editors’ Note 1 and the work of Holmes et al., 15 we conducted an international survey of professionals—practitioners and researchers—working on child and adolescent development and pediatric mental health to identify concerns about the impact of the pandemic on children, adolescents, and their families, as well as what is helping families navigate these impacts, and the specific research topics that are of greatest importance.

Latino day laborers in the United States are socially and economically vulnerable due to exclusionary immigration policies. Using data from a multi-mode survey, we examine the relationship between immigration policy legal vulnerability and mental health outcomes among 138 Latino, male day laborers (mean age = 45.65, SD = 12.05). Multivariable linear and logistic regression models separately estimated the effect of legal vulnerability, as measured by the Perceived Immigration Policy Effects Scale, on anxiety and depression symptoms and a positive depression and anxiety screening, respectively. Approximately 26.1% and 27.9% of day laborers reported depression and anxiety symptoms, respectively. In each adjusted model, we find a positive relationship between legal vulnerability and adverse mental health. Immigration policy legal vulnerability is associated with more depression and anxiety symptoms among Latino day laborers. Policies to reduce legal vulnerability, such as pathways to citizenship and employment authorization, may support Latino day laborers' mental health outcomes.

Currently, there are a few detailed guidelines on the overall management of children and adolescents with moderate-severe atopic dermatitis. AD ​​is a complex disease presenting with different clinical phenotypes, which require an individualized and multidisciplinary approach. Therefore, appropriate interaction between primary care pediatricians, pediatric allergists, and pediatric dermatologists is crucial to finding the best management strategy. In this manuscript, members of the Italian Society of Pediatric Allergology and Immunology (SIAIP), the Italian Society of Pediatric Dermatology (SIDerP), and the Italian Society of Pediatrics (SIP) with expertise in the management of moderate-severe atopic dermatitis have reviewed the latest scientific evidence in the field. This narrative review aims to define a pathway to appropriately managing children and adolescents with moderate-severe atopic dermatitis.

Globally, depressive symptoms among pregnant and postpartum (i.e., perinatal) women living with HIV (WLWH) are alarmingly high and associated with poor outcomes such as suboptimal adherence to antiretroviral therapy (ART), and early cessation of exclusive breastfeeding (EBF). Few qualitative studies have described the experience of perinatal depression among WLWH to identify the underlying social-structural determinants of poor mental health and potential strategies to intervene. We conducted a longitudinal qualitative study applying semi-structured interviews with 30 WLWH at three timepoints (28–38 weeks pregnant, 6-weeks postpartum and 5–7 months postpartum) to understand mental health experiences of perinatal WLWH in western Kenya. Financial insecurity emerged as the central theme impacting the mental health of women across time. Financial insecurity was often attributed to the loss of employment, related to pregnancy and the demands of breastfeeding and caring for an infant, as well as a lack of support from male partners. The loss of income and subsequent financial strain contributed to worsening levels of food insecurity and relationship stress and challenged engagement in HIV care. In this way, increased financial strain during the perinatal period negatively impacted the mental health of perinatal WLWH. Our findings suggest support to meet basic needs and remain engaged in HIV care during pregnancy and postpartum could improve perinatal mental health for WLWH in this setting.

HIV-negative individuals in serodiscordant partnerships experience reduced risk of HIV acquisition when their partners adhere to ART and achieve undetectable viral loads. Partnership support may encourage ART adherence, reducing viral load and the risk of HIV transmission. This study aims to determine whether HIV viral suppression is associated with partnership status and partnership support among 201 HIV positive (HIV+ individuals in serodiscordant partnerships and 100 HIV+ unpartnered individuals receiving care at Hospital Nossa Senhora da Conceição in Porto Alegre, Brazil between 2014 and 2016. Clinical data and patient-reported questionnaire data were assessed, and propensity scores were used to control for confounding variables in adjusted logistic regression models. Viral suppression did not significantly differ between HIV+ partnered (78.5% virally suppressed) and unpartnered (76.0% virally suppressed) individuals. Among individuals in partnerships, viral suppression was significantly associated with having a partner who attended monthly clinic visits (AOR 2.99; 95% CI 1.00–8.93). Instrumental social support—attending monthly visits—may improve the odds of viral suppression among HIV+ individuals in serodiscordant relationships. Supplementary Information The online version of this article (10.1007/s10461-020-03124-5) contains supplementary material, which is available to authorized users.

HIV-1 is a major global health challenge. The development of an effective vaccine and a therapeutic cure are top priorities. The creation of vaccines that focus an antibody response toward a particular epitope of a protein has shown promise, but the genetic diversity of HIV-1 stymies this progress. Therapeutic strategies that provide effective and broad‐spectrum neutralization against HIV-1 infection are highly desirable. Methods: We investigated the potential of nanoengineered CD4+ T cell membrane-coated nanoparticles (TNP) encapsulating the DIABLO/SMAC mimetics LCL-161 or AT-406 (also known as SM-406 or Debio 1143) to both neutralize HIV-1 and selectively kill HIV-1-infected resting CD4+ T cells and macrophages. Results: DIABLO/SMAC mimetic-loaded TNP displayed outstanding neutralizing breadth and potency, and selectively kill HIV-1-infected cells via autophagy-dependent apoptosis while having no drug-induced off-target or cytotoxic effects on bystander cells. Genetic inhibition of early stages of autophagy abolishes this effect. Conclusion: DIABLO/SMAC mimetic loaded TNP have the potential to be used as therapeutic agents to neutralize cell-free HIV-1 and to kill specifically HIV-1-infected cells as part of an HIV-1 cure strategy.

Background Genetic variation in the guidance cue DCC gene is linked to psychopathologies involving dysfunction in the prefrontal cortex. We created an expression-based polygenic risk score (ePRS) based on the DCC coexpression gene network in the prefrontal cortex, hypothesizing that it would be associated with individual differences in total brain volume. Methods We filtered single nucleotide polymorphisms (SNPs) from genes coexpressed with DCC in the prefrontal cortex obtained from an adult postmortem donors database (BrainEAC) for genes enriched in children 1.5 to 11 years old (BrainSpan). The SNPs were weighted by their effect size in predicting gene expression in the prefrontal cortex, multiplied by their allele number based on an individual’s genotype data, and then summarized into an ePRS. We evaluated associations between the DCC ePRS and total brain volume in children in 2 community-based cohorts: the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) and University of California, Irvine (UCI) projects. For comparison, we calculated a conventional PRS based on a genome-wide association study of total brain volume. Results Higher ePRS was associated with higher total brain volume in children 8 to 10 years old (β = 0.212, p = 0.043; n = 88). The conventional PRS at several different thresholds did not predict total brain volume in this cohort. A replication analysis in an independent cohort of newborns from the UCI study showed an association between the ePRS and newborn total brain volume (β = 0.101, p = 0.048; n = 80). The genes included in the ePRS demonstrated high levels of coexpression throughout the lifespan and are primarily involved in regulating cellular function. Limitations The relatively small sample size and age differences between the main and replication cohorts were limitations. Conclusion Our findings suggest that the DCC coexpression network in the prefrontal cortex is critically involved in whole brain development during the first decade of life. Genes comprising the ePRS are involved in gene translation control and cell adhesion, and their expression in the prefrontal cortex at different stages of life provides a snapshot of their dynamic recruitment.

Background older HIV-positive adults experience a significant burden of geriatric conditions. However, little is known about the association between geriatric conditions and healthcare utilisation in this population. Setting outpatient safety-net HIV clinic in San Francisco. Methods in 2013, HIV-positive adults ≥50 years of age underwent geriatric assessment including functional impairment, fall(s)in past year, cognitive impairment (MOCA Results among 192 participants, 81% were male, 51% were white, the median age was 56 (range 50–74), and the median CD4 count was 508 (IQR 338–688) cells/mm3. Sixteen percent of participants had ≥1 activities of daily living (ADL) dependency, 58% had ≥1 instrumental activities of daily living IADL dependency, 43% reported ≥1 falls, 31% had cognitive impairment, and 58% had low social support. Over 4 years, 90 participants (46%) had ≥1 ER visit (total of 289 ER visits), 39 (20%) had ≥1 hospitalisation (total of 68 hospitalisations), and 15 (8%) died. In unadjusted and adjusted analyses, IADL dependency and falls were associated with healthcare utilisation (adjusted incidence rate ratios IADL (95%CI): 1.73 (1.33–2.25); falls: 1.51 (1.21–1.87)). Conclusion IADL dependency and history of falls were associated with healthcare utilisation among older HIV-positive adults. Although our results are limited by sample size, improved understanding of the association between geriatric conditions and healthcare utilisation could build support for geriatric HIV care models.

Aims This study explored the association of coronary artery calcium (CAC) with incident cancer subtypes in the Multi-Ethnic Study of Atherosclerosis (MESA). CAC is an established predictor of cardiovascular disease (CVD), with emerging data also supporting independent predictive value for cancer. The association of CAC with risk for individual cancer subtypes is unknown. Methods and results We included 6271 MESA participants, aged 45–84 and without known CVD or self-reported history of cancer. There were 777 incident cancer cases during mean follow-up of 12.9 ± 3.1 years. Lung and colorectal cancer (186 cases) were grouped based on their strong overlap with CVD risk profile; prostate (men) and ovarian, uterine, and breast cancer (women) were considered as sex-specific cancers (in total 250 cases). Incidence rates and Fine and Gray competing risks models were used to assess relative risk of cancer-specific outcomes stratified by CAC groups or Log(CAC+1). The mean age was 61.7 ± 10.2 years, 52.7% were women, and 36.5% were White. Overall, all-cause cancer incidence increased with CAC scores, with rates per 1000 person-years of 13.1 [95% confidence interval (CI): 11.7–14.7] for CAC = 0 and 35.8 (95% CI: 30.2–42.4) for CAC ≥400. Compared with CAC = 0, hazards for those with CAC ≥400 were increased for lung and colorectal cancer in men [subdistribution hazard ratio (SHR): 2.2 (95% CI: 1.1–4.7)] and women [SHR: 2.2 (95% CI: 1.0–4.6)], but not significantly for sex-specific cancers across sexes. Conclusion CAC scores were associated with cancer risk in both sexes; however, this was stronger for lung and colorectal when compared with sex-specific cancers. Our data support potential synergistic use of CAC scores in the identification of both CVD and lung and colorectal cancer risk.

Poor sleep is common among older adults, affecting a wide range of health outcomes. However, little is known about sleep issues among older Korean immigrants, the fastest growing Asian American subgroup in the United States. We aimed to explore multiple factors associated with sleep among this group. We analyzed cross-sectional survey data from 43 older immigrants living in two large Korean communities in Southern California. Perceived sleep quality was significantly associated with gender, living arrangement, employment status, mental health, and sleep-related beliefs (all p-values

Summary Mutations sometimes increase contagiousness for evolving pathogens. During an epidemic, scientists use viral genome data to infer a shared evolutionary history and connect this history to geographic spread. We propose a model that directly relates a pathogen’s evolution to its spatial contagion dynamics—effectively combining the two epidemiological paradigms of phylogenetic inference and self-exciting process modeling—and apply this phylogenetic Hawkes process to a Bayesian analysis of 23 421 viral cases from the 2014 to 2016 Ebola outbreak in West Africa. The proposed model is able to detect individual viruses with significantly elevated rates of spatiotemporal propagation for a subset of 1610 samples that provide genome data. Finally, to facilitate model application in big data settings, we develop massively parallel implementations for the gradient and Hessian of the log-likelihood and apply our high-performance computing framework within an adaptively pre-conditioned Hamiltonian Monte Carlo routine. Supplementary information Supplementary data are available at Bioinformatics online.

Acculturation may limit HIV-positive Asian Americans' active interactions with patient-healthcare providers (HCP) and utilization of HIV healthcare services; however, the specific mediation effect of acculturation still unknown. A bias-corrected factor score path analysis was performed to examine the proposed model of relations among acculturation, stigma, stress, and patient-HCP relationships. A convenience sample of 69 HIV-positive Asian Americans in San Francisco, Los Angeles, and New York City were recruited and collect data were collected on demographics, HIV-related stigma, stress, and patient-HCP relationships. HIV stigma and stress had a direct, negative effect on patient-HCP relationships. Acculturation had a positive total effect on patient-HCP relationships, and was mediated by HIV stigma and stress. A acculturation also had a direct impact on stigma and stress. Acculturation, HIV-related stigma, and stress are key elements to achieving good patient-HCP relationships, and provide insights on the design of culturally sensitive interventions to improve patient-HCP relationships.

Type 1 diabetes is a rare immune-related adverse event (irAE) caused by checkpoint inhibitors with serious risk for diabetic ketoacidosis (DKA). Using our electronic medical record, we identified 1327 adult patients who received PD-(L)1 or CTLA-4 inhibitors from 2013 to 2018. Of the patients who received immunotherapy, 5 (0.38%) patients were found to have type 1 diabetes, all of whom presented with DKA requiring insulin at 20 to 972 days from their first anti-PD-(L)1 dose. All patients were treated with anti-PD-1 therapy (nivolumab or pembrolizumab). Four patients had new onset diabetes with mean HbA1c of 9.1% on DKA presentation and persistent elevations over time. Two patients who tested positive for glutamic acid decarboxylase (GAD) antibodies presented with DKA at 20 and 106 days from first anti-PD-1 administration whereas patients who were autoantibody negative had DKA more than a year later. Type 1 diabetes occurs within a wide time frame after anti-PD-1 initiation and commences with an abrupt course. Our case series suggests that monitoring glycemia in patients on PD-1 inhibitors is not predictive for diabetes occurrence. GAD autoantibodies could portend earlier onset for diabetes, although further prospective studies are needed to elucidate their diagnostic utility and contribution in therapeutic interception.

Objective:Women in South Asia, including Nepal, have some of the poorest nutritional indicators globally, leading to poor maternal and child health outcomes. Nepal also suffers from high levels of household food insecurity, and newly married women are at high risk. Intra-household relationships may mediate the relationship between food insecurity and women’s nutrition in Nepal for newly married women. Our aim is to understand how newly married, preconception, women’s food consumption changes when she enters her husband’s home, compared with her natal home. We also explore whether relationship quality with husbands and mothers-in-law mediates the association between food insecurity and eating less high-quality food, using structural equation modelling.Design:Cross-sectional survey data.Setting:Rural Nepal in 2018.Participants:Data were collected from 200 newly married, preconception women.Results:Women had poor diet quality, and most ate fewer high-quality foods important for pregnancy in their marital, compared with natal, home. Higher quality relationships with mothers-in-laws mediated the association between food insecurity and a woman eating fewer high-quality foods in her marital, compared with natal, home. Relationship quality with husbands was not associated with changes in food consumption.Conclusions:Preconception, newly married women in Nepal are eating less high-quality foods important for women’s health during the preconception period – a key period for avoiding adverse maternal and infant health outcomes. Relationships with mothers-in-law are key to women’s access to high-quality food, suggesting that interventions aiming to improve maternal and child nutrition should target all household members.