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The mammalian intestine is colonized by trillions of microorganisms that have co-evolved with the host in a symbiotic relationship. Although the influence of the gut microbiota on intestinal physiology and immunity is well known, mounting evidence suggests a key role for intestinal symbionts in controlling immune cell responses and development outside the gut. Although the underlying mechanisms by which the gut symbionts influence systemic immune responses remain poorly understood, there is evidence for both direct and indirect effects. In addition, the gut microbiota can contribute to immune responses associated with diseases outside the intestine. Understanding the complex interactions between the gut microbiota and the host is thus of fundamental importance to understand both immunity and human health.

Ultraviolet (UV) assisted printing has emerged as a promising additive manufacturing (AM) technology, which puts UV light sources with focused emission in high demand. Unfortunately, current ultraviolet light-emitting diodes (UV LEDs) are not able to provide adequately focused UV emission required for printing. Thus, a UV LED package with focused UV emission was proposed and fabricated using microelectromechanical system (MEMS) technology in this study. An optical model of the UV LED package with focused UV emission was developed. Based on the designed model, a silicon reflector stacked on another was achieved. By assembling the stacked silicon reflector and hemispherical quartz lenses, the UV LED package with focused UV emission was successfully achieved. A narrow beam with a beam angle of 16° between half maximum intensity was achieved, while the intensity at 0° was greater than 1000 mW/cm2 at the focal point. The UV LED curing system using two focused UV LED packages was successfully developed based on the optical simulation results. Polymer pillars were fabricated by instantaneous UV curing process with synchronized UV curable polymer jetting process in one shot, and micro-scale polymer pillars with a diameter of $20~\mu \text{m}$ were achieved. Thanks to the high intensity and focused UV emission, polymer pillars can be formed in as little as 100 ms. 13600 polymer pillars were printed on a silicon wafer with uniform diameter and geometry in a single dispensing cycle. The UV LED assisted printing platform was successfully demonstrated for fabrication of micro-scale 3D structures in a fast speed with smooth printing process. [2020-0303]

COVID-19 respiratory disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly become a global health issue since it emerged in December 2019. While great global efforts are underway to develop vaccines and to discover or repurpose therapeutic agents for this disease, as of this writing only the nucleoside drug remdesivir has been approved under Emergency Use Authorization to treat COVID-19. The RNA-dependent RNA polymerase (RdRP), a viral enzyme for viral RNA replication in host cells, is one of the most intriguing and promising drug targets for SARS-CoV-2 drug development. Because RdRP is a viral enzyme with no host cell homologs, selective SARS-CoV-2 RdRP inhibitors can be developed that have improved potency and fewer off-target effects against human host proteins and thus are safer and more effective therapeutics for treating COVID-19. This review focuses on biochemical enzyme and cell-based assays for RdRPs that could be used in high-throughput screening to discover new and repurposed drugs against SARS-CoV-2.

Resume Un patient est hospitalise dans un etablissement psychiatrique pour decompensation de schizophrenie. Un traitement par clozapine est initie ; un mois plus tard, le patient presente une hypereosinophilie. Il est decide de ne pas interrompre le traitement sur des arguments cliniques, au vu de la balance benefice-risque du traitement. Une erreur medicamenteuse a ete declaree par le service de soin : dix jours plus tot, des comprimes de clozapine doses a 100 mg ont ete dispenses et administres a la place de comprimes doses a 25 mg. Cette erreur a pu entrainer le trouble biologique une dizaine de jours apres.

Objective To investigate associations of adolescents’ time spent on homework/studying with nocturnal time for sleep and depression symptoms, in a competitive academic environment. Design Cross-sectional, anonymous survey of sleep habits, school life, and health-related measures. Setting Eight schools in Singapore. Participants Total 1225 adolescents aged 13–19 years. Measurements Self-reported sleep behavior and time use data were collected separately for school days and weekends. Multiple regression models were used to test covariation of time spent on homework/studying with other activities, and associations of homework/studying duration with depression symptoms. Results Time in bed for sleep and media use were inversely related with homework/studying duration on both school days and weekends, adjusting for time spent on other activities and demographic variables. Face-to-face family time and hanging out with friends were also reciprocally related with homework/studying duration on weekends. Depression scores were higher in adolescents who spent long hours on homework/studying. On school days, this was mediated by reduced time in bed for sleep. On weekends, homework/studying duration associated with depression symptoms, adjusting for time in bed and other covariates. Adolescents who spent ≥5 hours on homework/studying per day on weekends had greater symptoms of anhedonia and anxiety. Conclusions In a competitive academic setting, adolescents who spent more time on homework/studying spent less time on sleep, media use, and social activities. Independent of effects on sleep, long hours on homework/studying on weekends may be a risk factor for depression. Reducing adolescents’ workload outside of class may benefit their sleep, schoolwork-life balance, and mental well-being.

The dynamic compressive strength of a commercial alumina was determined by five participants using the Split-Hopkinson pressure bar (SHPB) method with a dumbbell-shaped specimen. Each participant used their own SHPB test apparatus and imaging set-up to conduct the tests and capture the fracture process. The dumbbell-shaped specimen was designed to increase the likelihood of fracture commencing in the specimen gage section rather than at the interface of the specimen and the SHPB bars. The participants had a good success rate (between 40 and 80%) of tests being deemed valid, even though this was the first time several of the participants had used this specimen geometry. The average dynamic compression strength from the five participants were in excellent agreement with each other and ranged from 4.40 to 4.92 GPa with a grand average of 4.61 GPa ± 0.25 GPa (the average of the laboratory averages). The high success rate and remarkable consistency of the results show that the dumbbell-shaped specimen is the most optimum specimen geometry investigated to-date to determine the dynamic compression strength of advanced ceramics using the SHPB test methodology.

BACKGROUND: Clinician-educator (CE) careers in academic medicine are heterogeneous. Expectations for CEs have grown, along with a need to better prepare CEs for these roles. OBJECTIVE: To assess whether advanced education training is associated with productivity and success. DESIGN: We used a sequential mixed methods approach, collecting quantitative survey data and qualitative focus groups data. We developed a three-tiered categorization of advanced training to reflect intensity by program type. PARTICIPANTS: We surveyed CEs in the Society of General Internal Medicine (SGIM) and conducted two focus groups at an SGIM annual meeting. MAIN MEASURES: Primary outcomes were academic productivity (manuscripts, presentations, etc.) and leadership role attainment. Secondary analysis examined the interactive effect of gender and training intensity on these outcomes. KEY RESULTS: A total of 198 completed the survey (response rate 53%). Compared with medium- or low-intensity training, high-intensity training was associated with a greater likelihood of publishing ≥ 3 first- or senior-author manuscripts (adjusted OR 2.6; CI 0.8–8.6; p = 0.002), teaching ≥ 3 lectures/workshops at the regional/national/international level (adjusted OR 5.7; CI 1.5–21.3; p = 0.001), and having ≥ 3 regional/national committee memberships (adjusted OR 3.4; CI 1.0–11.7; p = 0.04). Among participants in the “no training” and “high-intensity training” categories, men were more likely to have ≥ 3 publications (OR 4.87 and 3.17, respectively), while women in the high intensity category had a likelihood similar to men with no training (OR 4.81 vs. OR 4.87). Participants felt the value of advanced training exists not only in content but also in networking opportunities that programs provide. CONCLUSIONS: While opinions were divided as to whether advanced training is necessary to position oneself for education roles, it is associated with greater academic productivity and reduced gender disparity in the publication domain. Institutions should consider providing opportunities for CEs to pursue advanced education training. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-020-06049-w) contains supplementary material, which is available to authorized users.

Primary hyperparathyroidism has deleterious effects on health and causes nephrolithiasis and osteoporosis. However, it remains unclear whether parathyroidectomy benefits kidney function among patients with primary hyperparathyroidism. In this retrospective study, patients with primary hyperparathyroidism receiving parathyroidectomy in a tertiary medical center between 2003 and 2017 were followed up until December 31 2017, death, or requiring renal replacement therapy. Impact of parathyroidectomy on kidney function was examined using longitudinal estimated glomerular filtration rate (eGFR) change scales: single, average, absolute difference, percent change, annual decline rate, and slope. We applied linear mixed-effect model to determine the effect of parathyroidectomy on kidney function. During study period, 167 patients with primary hyperparathyroidism were identified from 498 parathyroidectomized patients, and finally, 27 patients fulfilled our stringent criteria. Median follow-up duration was 1.50 years (interquartile range 1.05–1.81) before surgery and 2.47 years (1.37–6.43) after surgery. Although parathyroidectomy did not affect amount of proteinuria and distribution of eGFR, parathyroidectomy significantly slowed decline rate of eGFR compared with that before surgery (− 1.67 versus − 2.73 mL/min/1.73 m2/year, p

This study asked what happens as the proportion of immigrants on states’ Temporary Assistance for Needy Families (TANF) rolls changes, employing the group threat hypothesis to analyze data dating 2...

We surveyed a sample of young adults in the United States to determine (1) whether/how depression is affected by violent victimization during childhood and/or by recent stressful events, as well as (2) whether any observed links between depression and violent victimization and/or stressful events would be uniform across racial/ethnic groups. Using data from the National Longitudinal Survey of Youth 1997 cohort, we measured respondent depression in 5 interview waves dating 2004–2015. Our final sample for analysis numbered 22,549 person-waves. Our study showed that violent victimization in childhood, and recent stressful events, as well, alike exacerbated depression. Moreover, as we analyzed, in turn, the data for each ethnic subsample, we observed differential patterns in depression’s associations with victimization. Childhood violent victimization—and also recently encountered stress—has a significant role in the development of depression in adulthood; this role appears to be moderated by race/ethnicity.

The CD34 cell surface antigen is widely expressed in tissues on cells with progenitor-like properties and on mature vascular endothelia. In adult human bone marrow, CD34 marks hematopoietic stem and progenitor cells (HSPCs) starting from the bulk of hematopoietic stem cells with long-term repopulating potential (LT-HSCs) throughout expansion and differentiation of oligopotent and unipotent progenitors. CD34 protein surface expression is typically lost as cells mature into terminal effectors. Because of this expression pattern of HSPCs, CD34 has had a central role in the evaluation or selection of donor graft tissue in HSC transplant (HSCT). Given its clinical importance, it is surprising that the biological functions of CD34 are still poorly understood. This enigma is due, in part, to CD34's context-specific role as both a pro-adhesive and anti-adhesive molecule and its potential functional redundancy with other sialomucins. Moreover, there are also critical differences in the regulation of CD34 expression on HSPCs in humans and experimental mice. In this review, we highlight some of the more well-defined functions of CD34 in HSPCs with a focus on proposed functions most relevant to HSCT biology.

Adolescents throughout the world do not obtain adequate sleep. A recent proliferation of experimental and quasi-experimental studies on teens concur in finding that multiple successive nights of restricted sleep can impair multiple cognitive functions. These effects cumulate over successive nights, may not achieve complete restitution after weekend recovery sleep, and may even be compounded by re-exposure to sleep restriction. An hour-long afternoon nap reduces sleepiness and improves vigilance, memory encoding and mood without interfering with nocturnal sleep when the latter is deficient. The very technologies that disrupt sleep can be used to improve it by providing novel avenues to personalize sleep recommendations by monitoring the effects of deficient sleep duration, quality, regularity and continuity.

Recent advances in deep learning and reinforcement learning have made it possible to create an agent that is capable of mimicking human behaviours. In this paper, we are interested in how the reinforcement learning agent behaves under different learning strategies and whether it is able to complete the task similar to human performance in principle. To study the effect of different reward types, two reward schemes which include immediate reward and pure-delayed reward are introduced. To build a more human-like agent when interacting with the environment, we propose a goal-driven design that forces the agent to achieve a level close to human ability and a training mechanism that learns only from good trajectories. Q-learning is one of the most popular reinforcement learning algorithms and we employ it for our study. As the sorting problem is a classical topic in theoretical computer science with widespread applications, it is used for the empirical evaluation. We compare our results against the algorithmic solutions.

A sample of Americans in early adulthood was surveyed to determine (1) whether and how victimization shapes future offending among non-Hispanic Whites, non-Hispanic Blacks, and Hispanics and to exa...

Bisphosphonates (BP) are used to treat osteoporosis, although rare atypical femur fractures have occurred with long-term exposure, especially among Asians. Metatarsal fractures have also been reported with atypical femur fracture. We examined the epidemiology of metatarsal fractures among 48,390 females aged ≥50 years who initiated oral BP and were followed for a median 7.7 years, including 68 females who experienced an atypical femur fracture. Incident metatarsal fractures after BP initiation were identified by clinical diagnoses and validated by record review. The association of BP, clinical risk factors, race/ethnicity, and metatarsal fracture was examined by using Cox proportional hazard analyses. Among 1123 females with incident metatarsal fracture, 61.0% had an isolated fifth metatarsal fracture. The incidence of metatarsal fracture was 312 per 100,000 person-years of follow-up and was substantially lower for Asians. The adjusted relative rate for metatarsal fractures was 0.5 (95% confidence interval 0.4 to 0.6) for Asians compared with whites. Younger age, prior fracture, other risk factors, and current BP were associated with an increased relative rate of metatarsal fracture, but BP duration was not. Females with atypical femur fracture were not more likely to experience metatarsal fracture (2.9% versus 2.3%, p = .7), but only 68 females had an atypical fracture and stress fracture of the metatarsals was not examined. Except for age, the demographic profile for metatarsal fracture after initiating BP was similar to that for osteoporotic fracture, with Asians at a much lower risk. Although metatarsal fractures were not associated with BP duration or atypical femur fracture, the subset of metatarsal stress fractures was not specifically examined.

While health’s relationship to SES is well established by research, relevant studies in the literature display little uniformity in their conceptualization of SES. The present study sought a tempor...

MDM2 and MDMX, negative regulators of the tumor suppressor p53, can work separately and as a heteromeric complex to restrain p53's functions. MDM2 also has pro-oncogenic roles in cells, tissues, and animals that are independent of p53. There is less information available about p53-independent roles of MDMX or the MDM2–MDMX complex. We found that MDM2 and MDMX facilitate ferroptosis in cells with or without p53. Using small molecules, RNA interference reagents, and mutant forms of MDMX, we found that MDM2 and MDMX, likely working in part as a complex, normally facilitate ferroptotic death. We observed that MDM2 and MDMX alter the lipid profile of cells to favor ferroptosis. Inhibition of MDM2 or MDMX leads to increased levels of FSP1 protein and a consequent increase in the levels of coenzyme Q10, an endogenous lipophilic antioxidant. This suggests that MDM2 and MDMX normally prevent cells from mounting an adequate defense against lipid peroxidation and thereby promote ferroptosis. Moreover, we found that PPARα activity is essential for MDM2 and MDMX to promote ferroptosis, suggesting that the MDM2–MDMX complex regulates lipids through altering PPARα activity. These findings reveal the complexity of cellular responses to MDM2 and MDMX and suggest that MDM2–MDMX inhibition might be useful for preventing degenerative diseases involving ferroptosis. Furthermore, they suggest that MDM2/MDMX amplification may predict sensitivity of some cancers to ferroptosis inducers.

This longitudinal study applied general strain theory to elaborate specific stressful events’ lagged effects on risk of illicit substance use among non-Hispanic White, non-Hispanic Black, and Hispanic adolescents, and relatedly evaluated the moderating role of race/ethnicity in explaining illicit use. Data were drawn from five waves representing 9 years (2002–2010) of the 1997 National Longitudinal Survey of Youth (NLSY), totaling 16,868 person-waves, and we engaged temporal ordering and generalized estimating equations (GEE) for panel data in STATA for data analysis. Results showed specific events affected risk of illicit substance use differentially across racial/ethnic groups. Strains commonly encountered in disorganized spaces affected non-Hispanic White’s risk. Measured strains did not affect non-Hispanic Black respondents and findings for Hispanic respondents point to the family as a possible strain. Results indicated legal drug use and depression increased risk of illicit use greatly. Race/ethnicity’s role in illicit use’s associations with several variables illustrates differential implications for racial/ethnic groups in policy and preventive interventions.

Few studies have examined factors that determine bisphosphonate (BP) continuation beyond 5 years in clinical practice.To investigate factors associated with BP continuation among women who completed 5 years of BP therapy.Women who received 5 consecutive years of oral BP treatment entered the cohort during 2002-2014 and were followed up to 5 additional years. Multivariable logistic regression was used to evaluate the association of demographic and clinical factors with adherent treatment continuation.The cohort included 19,091 women with a median age of 72 years. Baseline and time-varying factors associated with increased odds of BP continuation after 5 years were (a) most recent bone mineral density (BMD) T-score -2 to -2.4 (OR = 1.31, 95% CI = 1.25-1.38), T-score -2.5 to -2.9 (OR = 1.48, 95% CI = 1.39-1.57), and T-score ≤ -3.0 (OR = 1.57, 95% CI = 1.47-1.68) versus T-scores above -2.0; (b) index date before 2008 (OR =1.35, 95% CI = 1.29-1.41); and (c) diabetes mellitus (OR = 1.08, 95% CI = 1.01-1.16). In contrast, factors associated with decreased odds of BP continuation were (a) recent hip (OR = 0.61, 95% CI = 0.52-0.71) or humerus (OR = 0.79, 95% CI = 0.66-0.94) fracture or fracture other than hip, wrist, spine, or humerus (OR = 0.90, 95% CI = 0.84-0.97); (b) Charlson Comorbidity Index score2 (OR = 0.91, 95% CI = 0.84-0.98); (c) history of rheumatoid arthritis (OR = 0.89, 95% CI = 0.80-0.99); (d) Hispanic (OR = 0.89, 95% CI=0.85-0.94) or Asian (OR = 0.90, 95% CI = 0.85-0.94) race/ethnicity; and (e) use of proton pump inhibitors (OR = 0.65, 95% CI = 0.59-0.71). Patient age and fracture before BP initiation were not associated with treatment continuation.Clinical factors predicting continued BP treatment beyond 5 years include low BMD T-score, absence of recent fracture, and earlier era of treatment. Use of proton pump inhibitors was associated with lower likelihood of BP continuation. Other clinical and demographic factors were also noted to have variable effects on BP treatment continuation.This study was supported by a grant from the National Institute on Aging and National Institute of Arthritis, Musculoskeletal and Skin Diseases at the National Institutes of Health (NIH; R01AG047230, S1). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or Kaiser Permanente. Lo has received previous research funding from Amgen and Sanofi, unrelated to the current study. Adams has received previous research funding from Merck, Amgen, Otsuka, and Radius Health, unrelated to the current study. Ettinger has served as an expert witness for Teva Pharmaceuticals, unrelated to the current study. Ott previously attended a scientific advisory meeting for Amgen but declined the honorarium. The other authors have nothing to disclose. These data were presented at the 2018 Annual Meeting of the American Society of Bone and Mineral Research (ASBMR), September 28-October 1, 2018, Montreal, Quebec, Canada.

CT-based computations of fractional flow reserve (FFR) have been widely utilized for evaluating functional severity of a coronary artery stenosis. Whilst this approach has been successful clinically, assumptions involved in the analysis still need to be investigated for further improvement in predictive accuracy. To better understand the sensitivity of computational FFRs on outflow boundary condition – typically reflecting patient's own physiology only through anatomical features – FFR computations for 10 patients with different degree of stenosis was conducted. The computations were based on 3D anatomical model reconstructed from CT images and patient-specific in/outflow boundary conditions (BC). Two outflow BCs were considered: (1) conventional morphology-based and (2) PET perfusion-based conditions. The results showed that the FFRs derived from the two boundary conditions agree in general. It was also found that the FFRs computed with the morphology-based BC tend to estimate higher functional severity, especially in patients with reduced vasodilatory response under hyperaemia – an essential physiological condition in FFR measurement. Further investigation was made by varying hyperaemic resistances (30%-90% of the baseline) in the morphology-based BC. The variation of FFR for the varied resistances was narrow for patients with mild stenosis and wider for those who have severe stenosis. This latter approach confirmed that variability of FFR due to outflow condition tends to come from overestimation of vasodilatory response, especially those who have abnormal myocardial perfusion. The results suggest that outflow conditions that are more representative of each patient could be an effective way to improve CT-based FFR computation.

Background Asymptomatic carriage of Plasmodium falciparum is widespread in adults and children living in malaria-endemic countries. This study identified the prevalence of malaria parasites and the corresponding levels of naturally acquired anti-parasite antibody levels in afebrile adults living in two communities in the Greater Accra Region of Ghana. Methods Two cross-sectional studies conducted in January and February 2016 and repeated in July and August 2016 recruited subjects aged between 6 and 75 years from high parasite prevalence (Obom) and low parasite prevalence (Asutsuare) communities. Whole blood (5 ml) was collected from each volunteer, plasma was aliquoted and frozen until needed. An aliquot (10 µl) of the blood was used to prepare thick and thin blood smears, 100 µl was preserved in Trizol and the rest was separated into plasma and blood cells and each stored at − 20 °C until needed. Anti-MSP3 and Pfs230 antibody levels were measured using ELISA. Results Asexual parasite and gametocyte prevalence were higher in Obom than Asutsuare. Antibody (IgG, IgG1, IgG3, IgM) responses against the asexual parasite antigen MSP3 and gametocyte antigen Pfs230 were higher in Obom during the course of the study except for IgM responses against Pfs230, which was higher in Asutsuare than in Obom during the rainy season. Antibody responses in Asutsuare were more significantly associated with age than the responses measured in Obom. Conclusion The pattern of antibody responses measured in people living in the high and low malaria transmission setting was similar. All antibody responses measured against the asexual antigen MSP3 increased, however, IgG and IgG1 responses against gametocyte antigen Pfs230 decreased in moving from the dry to the peak season in both sites. Whilst asexual and gametocyte prevalence was similar between the seasons in the low transmission setting, in the high transmission setting asexual parasite prevalence increased but gametocyte prevalence decreased in the rainy season relative to the dry season.

The mammalian intestine is colonized by trillions of microorganisms that have co-evolved with the host in a symbiotic relationship. The presence of large numbers of symbionts near the epithelial surface of the intestine poses an enormous challenge to the host because it must avoid the activation of harmful inflammatory responses to the microorganisms while preserving its ability to mount robust immune responses to invading pathogens. In patients with inflammatory bowel disease, there is a breakdown of the multiple strategies that the immune system has evolved to promote the separation between symbiotic microorganisms and the intestinal epithelium and the effective killing of penetrant microorganisms, while suppressing the activation of inappropriate T cell responses to resident microorganisms. Understanding the complex interactions between intestinal microorganisms and the host may provide crucial insight into the pathogenesis of inflammatory bowel disease as well as new avenues to prevent and treat the disease.

There is a compelling need for new therapeutic strategies for glioblastoma multiforme (GBM). Preclinical target and therapeutic discovery for GBMs is primarily conducted using cell lines grown in serum-containing media, such as U-87 MG, which do not reflect the gene expression profiles of tumors found in GBM patients. To address this lack of representative models, we sought to develop a panel of patient-derived GBM models and characterize their genomic features, using RNA sequencing (RNA-seq) and growth characteristics, both when grown as neurospheres in culture, and grown orthotopically as xenografts in mice. When we compared these with commonly used GBM cell lines in the Cancer Cell Line Encyclopedia (CCLE), we found these patient-derived models to have greater diversity in gene expression and to better correspond to GBMs directly sequenced from patient tumor samples. We also evaluated the potential of these models for targeted therapy, by using the genomic characterization to identify small molecules that inhibit the growth of distinct subsets of GBMs, paving the way for precision medicines for GBM.

Not all sources of inequality in educational achievements are fair. But how strong and persistent is the burden of unequal opportunities that each person carries on in their life? In this paper, we define individual indices of the burden of circumstances, which measure the effect that the accumulation of factors outside individual control, has on individual educational achievements in the short and long run. As our findings suggest, the effect of these circumstances tends to persist over time. This effect has been particularly strong for the generation of students who experienced the 1997 Asian Financial Crisis. Lastly, we do not find evidence of a sizeable effect of local non-routine education expenditure on the inequality of opportunity, causing us to question the effectiveness of educational policies in accurately targeting equity.

This study sought associations between maltreated children’s receipt of needed health care and five other variables or sets of variables: medical need, social structural factors, access to care, demographic factors, and child welfare intervention. Data for this study came from longitudinal records derived for a sample of 1,465 children (extracted from all records in a national data set) for whom maltreatment had been substantiated. Children in the sample had, following substantiation, either remained in the home or been placed in kinship care or other out-of-home setting. Generalized estimating equations were applied to the data. The results supported a negative association between the sample’s receipt of needed health care and three factors: general physical health, age, and remaining in the home after substantiation. Data analysis also supported a positive association between receiving needed care and Medicaid receipt, family income of between 100 percent and 200 percent of federal poverty level, family income above 200 percent of federal poverty level, needed health care services included in child welfare case plan, and wave 2 interview. The study’s implications for social work practice include the necessity of accurately identifying children’s health problems, of addressing health needs in the case plan, and of coordinating meaningfully with health professionals.

Let \(u\) and \(\varphi\) be two analytic functions on the unit disk \(\mathbb{D}\) such that \(\varphi(\mathbb{D}) \subset \mathbb{D}\). A weighted composition operator \(uC_{\varphi}\) induced by \(u\) and \(\varphi\) is defined on \(H^2\), the Hardy space of \(\mathbb{D}\), by \(uC_{\varphi}f := u \cdot f \circ \varphi\) for every \(f\) in \(H^2\). We obtain sufficient conditions for Hilbert-Schmidtness of \(uC_{\varphi}\) on \(H^2\) in terms of function-theoretic properties of \(u\) and \(\varphi\). Moreover, we characterize Hilbert-Schmidt difference of two weighted composition operators on \(H^2\).

Adherence to 24h movement guidelines of ≥60min of physical activity, ≤2h of screen time, and 9-11h of sleep has been shown to benefit cognition, physical and psychosocial health in children aged 5-13y. However, these findings are largely based on cross-sectional studies or small samples. Here we utilize data from the Adolescent Brain Cognitive Development (ABCD) study of 10000+ children aged 9-11y to examine whether adherence to 24h movement guidelines benefit cognition, BMI, psychosocial health and brain morphometric measures at baseline (T1) and 2 years later (T2). After adjustment for sociodemographic confounders in multivariable linear mixed models, we observed better cognitive scores, fewer behavioural problems, lower adiposity levels and greater gray matter volumes in children who met both sleep and screen time recommendations compared to those who met none. Longitudinal follow up further supports these findings; participants who met both recommendations at T1 and T2 evidenced better outcome measures than those who met none, even after controlling for T1 measures. These findings support consideration of integrated rather than isolated movement recommendations across the day for better cognitive, physical, psychosocial and brain health.

Membranous nephropathy (MN) is determined by deposition of autoantibodies targeting glomerular podoyctes antigens. MN progression to renal failure remains a central issue: antibodies modifying the inflammatory course after the first antibody hit may be involved. We investigated sera of MN patient using a high-density peptide array covering the whole coding sequences of the human genome encompassing 7,499,126 tiled peptides. A panel of 258 proteins reactive with MN sera were identified. We focused on Formin-like 1 (FMNL1) protein expressed by macrophages. High levels of anti-FMNL1 IgG4 were demonstrated in sera of MN patient with orthogonal methodologies (ELISA) and were observed co-staining with CD68 in glomeruli. High levels of circulating anti-FMNL1 IgG4 were associated with lack of remission of proteinuria, strengthening the concept that, autoantibodies directed to cells of the tissue repair, might have a definite role in determining the disease outcome. High serum levels of anti-FMNL1 IgGs were also observed in other non-autoimmune glomerolonephrites, ie. idiopathic and genetic FSGS, IgAGN, stressing the non-specificity for MN and suggesting their involvement in glomerular conditions affecting many patients worldwide.

Non-alcoholic fatty liver disease (NAFLD) disproportionally affects US children of Latino descent, who also have a higher burden of obesity and type 2 diabetes. We previously found significant associations between diet and sedentary behaviors and weight status, but it is unclear if these measured behaviors are associated with suspected NAFLD among Latino adolescents with obesity, which was the objective of this study. We used cross-sectional data from 10,087 Latino adolescents ages 13-17 years in northern California with a well-child visit in 2016-2019, health behavior assessment, and BMI ≥95th percentile. Adolescents self-reported on 4 daily obesogenic behaviors at the visit: 1) consuming 2 hours of screen time. Suspected NAFLD was classified by serum alanine transaminase level ≥44 U/L (girls) and ≥52 U/L (boys). We used logistic regression to examine the associations of obesogenic behaviors with NAFLD, adjusting for age, gender, household language preference (English/Spanish), neighborhood deprivation index (quartiles), and Class 1, 2, and 3 obesity. Among 10,087 Latino adolescents with obesity, 88% (8,877) had ≥1 obesogenic behaviors and 10% (1012) had suspected NAFLD. None of the obesogenic behaviors were associated with NAFLD in unadjusted or adjusted models. Boys (vs girls) had higher odds of NAFLD (OR 2.2; 95% CI: 1.9-2.5), as did older adolescents (ages 16-17 vs 13-15, OR 1.7; 1.5-1.9) and those with more severe obesity (OR 2.2; 1.9-2.5, and OR 3.0; 2.5-3.6 for Class 2 and 3 (vs Class 1) obesity, respectively). In summary, older age, male gender and severe obesity were risk factors for suspected NAFLD while binary assessment of diet and sedentary behaviors were not, suggesting that more precise diet and exercise assessment tools are needed. The high burden of obesogenic behaviors and strong association of severe obesity with NAFLD point to important actionable targets for pediatric primary care.

A key public health question during any disease outbreak when limited vaccine is available is who should be prioritized for early vaccination. Most vaccine prioritization analyses only consider variation in risk of infection and death by a single risk factor, such as age. We provide a more granular approach with stratification by demographics, risk factors, and location. We use this approach to compare the impact of different COVID-19 vaccine prioritization strategies on COVID-19 cases, deaths and disability-adjusted life years (DALYs) over the first 6 months of vaccine rollout, using California as a case example. We estimate the proportion of cases, deaths and DALYs averted relative to no vaccination for strategies prioritizing vaccination by a single risk factor and by multiple risk factors (e.g. age, location). When targeting by a single risk factor, we find that age-based targeting averts the most deaths (62% for 5 million individuals vaccinated) and DALYs (38%) and targeting essential workers averts the least deaths (31%) and DALYs (24%) over the first 6 months of rollout. However, targeting by two or more risk factors simultaneously averts up to 40% more DALYs. Our findings highlight the potential value of multiple-risk-factor targeting of vaccination against COVID-19 and other infectious diseases, but must be balanced with feasibility for policy.

ImportanceDespite widespread vaccination against COVID-19 in the United States, there are limited empirical data quantifying the public health impact in the population.ObjectiveTo estimate the number of cases of COVID-19 averted due to COVID-19 vaccinationDesign, Setting, and ParticipantsThe California Department of Public Health (CDPH) provided person-level data on COVID-19 cases and COVID-19 vaccine administration. To estimate the number of COVID-19 cases that would have occurred in the vaccine era in absence of vaccination, we applied a statistical model that estimated the relationship of COVID-19 cases in the pre-vaccine era between the unvaccinated age group (InterventionCOVID-19 vaccinationMain Outcomes and MeasuresCOVID-19 casesResultsThere were 4,585,248 confirmed COVID-19 cases in California from January 1, 2020 to October 16, 2021, during which 27,164,680 vaccine-eligible individuals ≥12 years were reported to have received at least 1 dose of a COVID-19 vaccine in the vaccine era (79.5% of the eligible population). We estimated that 1,523,500 [95% prediction interval (976,800-2,230,800)] COVID-19 cases were averted and there was a 34% [95% prediction interval (25-43)] reduction in cases due to vaccination in the primary model. Approximately 66% of total cases averted occurred after the delta variant became the dominant strain of SARS-CoV-2 circulating in California. Our alternative model identified comparable findings.Conclusions and RelevanceThis study provides robust evidence on the public health impact of COVID-19 vaccination in the United States and further supports the urgency for continued vaccination.Key PointsQuestionHow many COVID-19 cases have been prevented by COVID-19 vaccination in California?FindingsIn this empirical analysis of California using data from the Department of Public Health, we estimated that COVID-19 vaccination has prevented over 1.5 million COVID-19 cases from the introduction of vaccination through October 16, 2021.MeaningThese findings support that COVID-19 vaccination had a large public health impact in California in terms of averted cases of COVID-19 and can be generalized across the United States.

Meticillin-resistant Staphylococcus aureus (MRSA) infections are rampant in hospitals and residential care homes for the elderly (RCHEs).To analyse the prevalence of MRSA colonization among residents and staff, and degree of environmental contamination and air dispersal of MRSA in RCHEs.Epidemiological and genetic analysis by whole-genome sequencing (WGS) in 12 RCHEs in Hong Kong.During the COVID-19 pandemic (from September to October 2021), 48.7% (380/781) of RCHE residents were found to harbour MRSA at any body site, and 8.5% (8/213) of staff were nasal MRSA carriers. Among 239 environmental samples, MRSA was found in 39.0% (16/41) of randomly selected resident rooms and 31.3% (62/198) of common areas. The common areas accessible by residents had significantly higher MRSA contamination rates than those that were not accessible by residents (37.2%, 46/121 vs. 22.1%, 17/177, P=0.028). Of 124 air samples, nine (7.3%) were MRSA-positive from four RCHEs. Air dispersal of MRSA was significantly associated with operating indoor fans in RCHEs (100%, 4/4 vs. 0%, 0/8, P=0.002). WGS of MRSA isolates collected from residents, staff and environmental and air samples showed that ST 1047 (CC1) lineage 1 constituted 43.1% (66/153) of all MRSA isolates. A distinctive predominant genetic lineage of MRSA in each RCHE was observed, suggestive of intra-RCHE transmission rather than clonal acquisition from the catchment hospital.MRSA control in RCHEs is no less important than in hospitals. Air dispersal of MRSA may be an important mechanism of dissemination in RCHEs with operating indoor fans.

Study Objectives Gains in cognitive test performance that occur during adolescence are associated with brain maturation. Cortical thinning and reduced sleep slow wave activity (SWA) are markers of such developmental changes. Here we investigate whether they mediate age-related improvements in cognition. Methods 109 adolescents aged 15–19 years (49 males) underwent magnetic resonance imaging, polysomnography (PSG), and a battery of cognitive tasks within a 2-month time window. Cognitive tasks assessed nonverbal intelligence, sustained attention, speed of processing and working memory and executive function. To minimize the effect of sleep history on SWA and cognitive performance, PSG and test batteries were administered only after at least 8 nights of 9-h time-in-bed (TIB) sleep opportunity. Results Age-related improvements in speed of processing (r = 0.33, p = 0.001) and nonverbal intelligence (r = 0.24, p = 0.01) domains were observed. These cognitive changes were associated with reduced cortical thickness, particularly in bilateral temporoparietal regions (rs = −0.21 to −0.45, ps < 0.05), as well as SWA (r = −0.35, p < 0.001). Serial mediation models found that ROIs in the middle/superior temporal cortices, together with SWA mediated the age-related improvement observed on cognition. Conclusions During adolescence, age-related improvements in cognition are mediated by reductions in cortical thickness and sleep SWA.

Telehealth visits have become an integral model of healthcare delivery since the COVID-19 pandemic. This rapid expansion of telehealthcare delivery has forced faculty development and trainee education in telehealth to occur simultaneously. In response, academic medical institutions have quickly implemented clinical training to teach digital health skills to providers across the medical education continuum. Yet, learners of all levels must still receive continual assessment and feedback on their skills to align with the telehealth competencies and milestones set forth by the Association of American Medical Colleges (AAMC) and the Accreditation Council for Graduate Medical Education (ACGME). This paper discusses key educational needs and emerging areas for faculty development in telehealth teaching and assessment of telehealth competencies. It proposes strategies for the successful integration of the AAMC telehealth competencies and ACGME milestones into medical education, including skills in communication, data gathering, and patient safety with appropriate telehealth use. Direct observation tools in the paper offer educators novel instruments to assess telehealth competencies in medical students, residents, and peer faculty. The integration of AAMC and ACGME telehealth competencies and the new assessment tools in this paper provide a unique perspective to advance clinical practice and teaching skills in telehealthcare delivery.

Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).

Background: Little epidemiological research has investigated the associations of air pollutant exposure over various time windows with older adults' symptoms of depression. This study aimed to analyze the relationships of long- and short-term ambient air pollution exposure (to coarse particulate matter, O3, SO2, CO, and NOx) with depressive symptoms in a sample of community-dwelling older adults.Methods: A sample of older adults (n = 1,956) was recruited from a nationally representative multiple-wave study (Taiwan Longitudinal Study on Aging). Between 1996 and 2007, four waves of surveys investigated depressive symptoms by using the 10-item Center for Epidemiologic Studies Depression questionnaire. We approximated air pollutant concentrations from 1995 to 2007 by using daily concentration data for five air pollutants at air quality monitoring stations in the administrative zone of participants' residences. after adjusting for covariates, we applied generalized linear mixed models to analyze associations for different exposure windows (7-, 14-, 21-, 30-, 60-, 90-, and 180-day and 1-year moving averages).Results: In a one-pollutant model, long- and short-term exposure to CO and NOx was associated with heightened risks of depressive symptoms; the odds ratio and corresponding 95% confidence interval for each interquartile range (IQR) increment in CO at 7-, 14-, 21-, 30-, 60-, 90-, and 180-day and 1-year moving averages were 1.232 (1.116, 1.361), 1.237 (1.136, 1.348), 1.216 (1.128, 1.311), 1.231 (1.133, 1.338), 1.224 (1.124, 1.332), 1.192 (1.106, 1.285), 1.228 (1.122, 1.344), and 1.180 (1.102, 1.265), respectively. Those for each IQR increment in NOx were 1.312 (1.158, 1.488), 1.274 (1.162, 1.398), 1.295 (1.178, 1.432), 1.310 (1.186, 1.447), 1.345 (1.209, 1.496), 1.348 (1.210, 1.501), 1.324 (1.192, 1.471), and 1.219 (1.130, 1.314), respectively. The exposure to PM10, O3, and SO2 over various windows were not significant. In the two-pollutant model, only the associations of NOx exposure with depressive symptoms remained robust after adjustment for any other pollutant.Conclusions: Exposure to traffic-associated air pollutants could increase depression risks among older adults.

This paper investigates gender inequality in vulnerable employment: forms of employment typically featuring high precariousness, inadequate earnings, and lack of decent working conditions. Using a large collection of harmonized household surveys from developing countries, we measure long-term trends, describe geographical patterns, and estimate correlates of gender inequalities in vulnerable employment. Conditional on individual and household characteristics, women are 7 percentage points more likely to be in vulnerable employment than men. The experiences of marriage and parenthood are important drivers of this gender gap. Across countries, the gender gap is smaller in richer countries, with lower fertility rates, and more gender-egalitarian laws, particularly those laws regulating marriage, parenthood, access to assets, and access to entrepreneurship. Since the 1990s, rising levels of female education and rapidly falling fertility have pulled women away from vulnerable employment at a faster rate than men. However, that process is largely exhausted, with current levels of the gender gap in vulnerable employment being almost entirely unexplained by standard labour supply factors.