The development of depression and social anxiety symptoms in adolescents and the negative impact of the COVID-19 pandemic and desire for peer contact.

Introduction: Adolescence is a dynamic developmental phase in which contact with peers is crucial for socio-emotional development and wellbeing. Depression and social anxiety show patterns of high onset during this period, and more for girls than boys. Here we examine this development among Dutch adolescents, as well as how desire for more peer contact as a result of social distancing measures during the COVID-19 pandemic contributed to this increase. Methods: We used a longitudinal three-wave design to examine 406 typically developing Dutch adolescents across two consecutive cohorts; Cohort 1: 2016-2019 (N = 138, 53.6% girls, age at T0 M = 13.00, SD = 0.42), Cohort 2: 2017-2020 (N = 268, 63.1% girls, age at T0 M = 13.05, SD = 0.39), final wave during spring 2020 during the first COVID-19 lockdown. Self-report questionnaires were used to measure depression and social anxiety symptoms, desire for change in the amount of peer contact during lockdowns, and emotion regulation. Parallel process dual latent growth models and autoregressive cross-lagged models were used to test the hypotheses. Results: Results showed that symptoms of both depression and social anxiety increase during adolescence. Gender analysis reveal a higher initial level and increase in depression symptoms for girls, while levels for boys decreased. Adolescents exposed to the pandemic showed a steeper increase in depression but not in social anxiety. Desire for more peer contact was related to an increase in depression and social anxiety, though only in girls. No evidence was found for moderation of emotion regulation skills concerning COVID evoked emotions on the association between desire for peer contact and anxiety and depression symptom development. Discussion: Symptoms of social anxiety increased during adolescence in boys and girls. Symptoms of depression increased for girls, but decreased for boys. The increase in depression was greater in a cohort who experienced the COVID-19 pandemic. For girls, a desire for more peer contact was associated with an increase of depression and social anxiety symptoms in times of social restrictions.

Maternal symptoms of depression and anxiety as modifiers of the relationship between prenatal phthalate exposure and infant neurodevelopment in the Atlanta African American maternal-child cohort.

Background: Prenatal exposure to phthalates, a group of synthetic chemicals widely used in consumer products, has previously been associated with adverse infant and child development. Studies also suggest that maternal depression and anxiety, may amplify the harmful effects of phthalates on infant and child neurodevelopment. Study design: Our analysis included a subset of dyads enrolled in the Atlanta African American Maternal-Child Cohort (N = 81). We measured eight phthalate metabolites in first and second trimester (8-14 weeks and 24-32 weeks gestation) maternal urine samples to estimate prenatal exposures. Phthalate metabolite concentrations were averaged across visits and natural log-transformed for analysis. Maternal symptoms of depression and anxiety were assessed using validated questionnaires (Edinberg Postnatal Depression Scale and State Trait Anxiety Inventory, respectively) and the total score on each scale was averaged across study visits. The NICU Network Neurobehavioral Scale (NNNS) was administered at two weeks of age. Our primary outcomes included two composite NNNS scores reflecting newborn attention and arousal. Linear regression was used to estimate associations between individual phthalate exposures and newborn attention and arousal. We assessed effect modification by maternal depression and anxiety. Results: Higher levels of urinary phthalate metabolites were not associated with higher levels of infant attention and arousal, but true associations may still exist given the limited power of this analysis. In models examining effect modification by maternal depression, we observed that an interquartile range increase in mono (2-ethlyhexyl) phthalate (MEHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was associated with a significant increase in newborn arousal only among those with high depressive symptoms (MEHP: ß = 0.71, 95% confidence interval [CI] = 0.10, 1.32 for high, ß = -0.30, 95% CI = -0.73, 0.12 for low; MEOHP: ß = 0.60, 95% CI = -0.03, 1.23 for high, ß = -0.12, 95% CI = -0.58, 0.33 for low; MEHHP: ß = 0.54, 95% CI = -0.04, 1.11 for high, ß = -0.11, 95% CI = -0.54, 0.32 for low). Similar patterns were observed in models stratified by maternal anxiety, although CIs were wide. Conclusion: Our results suggest maternal anxiety and depression symptoms may exacerbate the effect of phthalates on infant neurodevelopment. Future studies are needed to determine the optimal levels of attention and arousal in early infancy.

Longitudinal Changes in Bone Mineral Density in Adults with Cystic Fibrosis.

BACKGROUND: Improved survival in people with cystic fibrosis (pwCF) presents new complexities of care, including CF-related bone disease, a common complication in older pwCF. The trajectory of bone loss with age in this population remains unclear. The objective of this study was to estimate the average rate of change in bone mineral density (BMD) in adults with CF. METHODS: This retrospective study included adults with CF, aged 25-48 years, followed between January 2000 and December 2021. Subjects with at least one dual-energy X-ray absorptiometry (DXA) scan were included. Scans obtained post-transplantation, after the initiation of bisphosphonates or cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy were excluded. The primary outcome was BMD (g/cm2) at the lumbar spine (LS) and femoral neck (FN). A linear mixed-effects model with both random intercept and random slope terms was used to estimate the average annual change in BMD. RESULTS: A total of 1502 DXA scans in 500 adults (average age 28.4y) were included. There was a statistically significant annual decline in BMD of -0.008 gm/cm2/year (95% CI -0.009, -0.007) at the FN and -0.006 gm/cm2/year (95% CI -0.007, -0.004) at the LS. Relative to BMD at age 25, there was a -18.8% decline at the FN by age 48 years and a -11% decline at the LS. Pancreatic insufficient (PI) subjects had a faster rate of decline in BMD compared to pancreatic sufficient (PS) subjects. After adjusting for markers of disease severity, the annual rate of decline remained significant. CONCLUSIONS: Individuals with CF experience bone loss at an age when it is not anticipated, thereby entering early adulthood, where further bone loss is inevitable especially with the decrease in estrogen during menopause, with suboptimal BMD. As the CF population ages, it will become very important to consider interventions to maximize bone health.

Improved survival in people with cystic fibrosis (pwCF) presents new complexities of care, including CF-related bone disease, a common complication in older pwCF. The objective of this study was to estimate how bone mineral density (BMD) changes over time in adults with CF. The study included 500 adults with CF, aged 25-48 years, followed between January 2000 and December 2021 who underwent a scan to assess BMD. On average, BMD decreased over time both at the spine and the hip. People who have pancreatic insufficiency had a faster rate of decline in BMD than people with pancreatic sufficiency. Individuals with CF experience bone loss at an age when bone density is expected to be stable. As the CF population ages, interventions to maximize bone health should be emphasized to prevent fractures in the future.

User experience with HIV molecular epidemiology in research, surveillance, and cluster detection and response: a needs assessment.

OBJECTIVE: HIV molecular epidemiology (HIV ME) is a tool that aims to improve HIV research, surveillance, and cluster detection and response. HIV ME is a core pillar of the U.S. initiative to End the HIV Epidemic but faces some challenges and criticisms from stakeholders. We sought to assess user experience to identify the current needs for HIV ME. METHODS: Users of HIV ME, including researchers and public health practitioners, were engaged via a structured survey. Needs were assessed via open-ended questions about HIV ME. Data were analyzed using reflexive thematic analysis; the concordance of results was assessed semi-quantitatively. RESULTS: Of 90 possible HIV-ME end-users, 57 completed the survey (response rate = 63%), which included users engaged in research (n = 29) and public health (n = 28). Respondents identified current imperatives, challenges, and strategies to improve HIV ME. Imperatives included characterization of the virus, identification of HIV hotspots, and tailoring of HIV interventions. Challenges encompassed technological issues, ethical concerns, and implementation difficulties. Strategies to improve HIV ME involved improving data access and analysis, enhancing implementation guidance and resources, and fostering community engagement and support. Researchers and public health practitioners prioritized different imperatives, but similarly emphasized the ethical concerns with HIV ME. CONCLUSION: The imperatives identified by users underscore the necessity of HIV ME, while the challenges highlight the hurdles to be overcome, including ethical concerns which emerged as a shared emphasis across user groups. The strategies outlined offer a roadmap for overcoming these challenges. These insights, drawn from user experience, present a valuable opportunity to inform the development of guidelines for the ethical application of HIV ME in research, surveillance, and cluster detection and response.

Effectiveness of a Just-In-Time Adaptive App to Increase Daily Steps: An RCT.

INTRODUCTION: Addressing the public health problem of physical inactivity, this study evaluates "SNapp", a just-in-time adaptive app intervention to promote walking through dynamically tailored coaching content. It assesses SNapp's impact on daily steps and how users' perceptions regarding ease of use and usefulness moderated its effectiveness. STUDY DESIGN: SNapp was evaluated in an RCT from February 2021 to May 2022. Analyses were conducted in November 2022. SETTING/PARTICIPANTS: 176 adults (76% female, mean age of 56 years) were randomized to a control group receiving a step counter app (n = 89) or an intervention group receiving the app plus coaching content (n = 87). INTERVENTION: SNapp's coaching content encompasses individually tailored feedback on step counts and advice to engage in more walking, taking preferences regarding behavior change techniques into account. Additionally, SNapp provides contextualized content calling attention to suitable walking locations in the user's environment. MAIN OUTCOME MEASURES: The primary outcome was daily step count as recorded by the step counter app. User perceptions regarding ease of use and usefulness were assessed via survey at 3-month follow-up. RESULTS: Mixed models indicated that the intervention did not significantly impact step counts on average over time (B = -202.30, 95% CI = -889.7, 485.1), with the coefficient indicating that the intervention group walked fewer steps per day on average, though this difference was not statistically significant. Perceived ease of use did not moderate the intervention effect (B group x perceived ease of use = 38.60, 90% CI = -276.5, 353.7). Perceived usefulness significantly moderated the intervention effect (B group x perceived usefulness = 344.38, 90% CI = 40.4, 648.3). CONCLUSIONS: SNapp increased steps only in users who deemed the app useful, underscoring the importance of user perceptions in app-based interventions. TRIAL REGISTRATION: This trial was preregistered in the Dutch Trial Register (NL7064).

Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children's Oncology Group study.

Limited prognostic factors have been associated with overall survival (OS) post-relapse in childhood Acute Lymphoblastic Leukemia (ALL). Patients enrolled on 12 Children's Oncology Group frontline ALL trials (1996-2014) were analyzed to assess for additional prognostic factors associated with OS post-relapse. Among 16,115 patients, 2053 (12.7%) relapsed. Relapse rates were similar for B-ALL (12.5%) and T-ALL (11.2%) while higher for infants (34.2%). Approximately 50% of B-ALL relapses occurred late (≥36 months) and 72.5% involved the marrow. Conversely, 64.8% of T-ALL relapses occurred early (<18 months) and 47.1% involved the central nervous system. The 5-year OS post-relapse for the entire cohort was 48.9 ± 1.2%; B-ALL:52.5 ± 1.3%, T-ALL:35.5 ± 3.3%, and infant ALL:21.5 ± 3.9%. OS varied by early, intermediate and late time-to-relapse; 25.8 ± 2.4%, 49.5 ± 2.2%, and 66.4 ± 1.8% respectively for B-ALL and 29.8 ± 3.9%, 33.3 ± 7.6%, 58 ± 9.8% for T-ALL. Patients with ETV6::RUNX1 or Trisomy 4 + 10 had median time-to-relapse of 43 months and higher OS post-relapse 74.4 ± 3.1% and 70.2 ± 3.6%, respectively. Patients with hypodiploidy, KMT2A-rearrangement, and TCF3::PBX1 had short median time-to-relapse (12.5-18 months) and poor OS post-relapse (14.2 ± 6.1%, 31.9 ± 7.7%, 36.8 ± 6.6%). Site-of-relapse varied by cytogenetic subtype. This large dataset provided the opportunity to identify risk factors for OS post-relapse to inform trial design and highlight populations with dismal outcomes post-relapse.

Building decolonial nursing curricula to address disparities in Indigenous women's maternal health.

BACKGROUND: Social and health inequities and inequalities are rising all over the world (Chinn & Falk-Rafael, 2018; McGibbon et al., 2014; Smtih, 2012). Nursing students should therefore be educated to understand the multifaceted factors creating health inequities and the degree to which non-biological elements can be embodied and become biological (e.g., environmental stress leading to changes in health.). PURPOSE: We suggest pathways to decolonize nursing curricula and pedagogy through decentering the colonial knowledge structures and practices that harm Indigenous health and wellbeing. METHODS: This discursive analysis utilizes decolonial theory and postcolonial feminism. DISCUSSION: Colonization, broadly speaking, characterizes the Eurocentric project to "civilize" the rest of the world utilizing various forms of violence (McGibbon et. al., 2014). The persistent and ongoing reproduction and recurrence of colonialism, enacting cycles of disenfranchisement and oppression, creates significant inequities in physical, mental, and emotional health and well-being for historically marginalized groups of people (Smith, 2012). CONCLUSION: The need for innovative undergraduate nursing curricula reform is apparent. The lack of nursing courses highlighting the effects of colonization, environmental justice, upstream structural and social determinants of health, globalization, and state violence must be addressed. Because gaps in nursing curricula and outdated teaching practices may support persistent inequities, scholars and students have advocated for decolonization of nursing curricula (Chinn & Falk-Rafael, 2018; McGibbon et al., 2014; Smtih, 2012).

Investigating the association between household exposure to Anopheles stephensi and malaria in Sudan and Ethiopia: A case-control study protocol.

BACKGROUND: Endemic African malaria vectors are poorly adapted to typical urban ecologies. However, Anopheles stephensi, an urban malaria vector formerly confined to South Asia and the Persian Gulf, was recently detected in Africa and may change the epidemiology of malaria across the continent. Little is known about the public health implications of An. stephensi in Africa. This study is designed to assess the relative importance of household exposure to An. stephensi and endemic malaria vectors for malaria risk in urban Sudan and Ethiopia. METHODS: Case-control studies will be conducted in 3 urban settings (2 in Sudan, 1 in Ethiopia) to assess the association between presence of An. stephensi in and around households and malaria. Cases, defined as individuals positive for Plasmodium falciparum and/or P. vivax by microscopy/rapid diagnostic test (RDT), and controls, defined as age-matched individuals negative for P. falciparum and/or P. vivax by microscopy/RDT, will be recruited from public health facilities. Both household surveys and entomological surveillance for adult and immature mosquitoes will be conducted at participant homes within 48 hours of enrolment. Adult and immature mosquitoes will be identified by polymerase chain reaction (PCR). Conditional logistic regression will be used to estimate the association between presence of An. stephensi and malaria status, adjusted for co-occurrence of other malaria vectors and participant gender. CONCLUSIONS: Findings from this study will provide evidence of the relative importance of An. stephensi for malaria burden in urban African settings, shedding light on the need for future intervention planning and policy development.

Validation of a machine learning algorithm for identifying infants at risk of hypoxic ischaemic encephalopathy in a large unseen data set.

OBJECTIVE: To validate a hypoxic ischaemic encephalopathy (HIE) prediction algorithm to identify infants at risk of HIE immediately after birth using readily available clinical data. DESIGN: Secondary review of electronic health record data of term deliveries from January 2017 to December 2021. SETTING: A tertiary maternity hospital. PATIENTS: Infants >36 weeks' gestation with the following clinical variables available: Apgar Score at 1 min and 5 min, postnatal pH, base deficit, and lactate values taken within 1 hour of birth INTERVENTIONS: Previously trained open-source logistic regression and random forest (RF) prediction algorithms were used to calculate a probability index (PI) for each infant for the occurrence of HIE. MAIN OUTCOME: Validation of a machine learning algorithm to identify infants at risk of HIE in the immediate postnatal period. RESULTS: 1081 had a complete data set available within 1 hour of birth: 76 (6.95%) with HIE and 1005 non-HIE. Of the 76 infants with HIE, 37 were classified as mild, 29 moderate and 10 severe. The best overall accuracy was seen with the RF model. Median (IQR) PI in the HIE group was 0.70 (0.53-0.86) vs 0.05 (0.02-0.15), (p<0.001) in the non-HIE group. The area under the receiver operating characteristics curve for prediction of HIE=0.926 (0.893-0.959, p<0.001). Using a PI cut-off to optimise sensitivity of 0.30, 936 of the 1081 (86.5%) infants were correctly classified. CONCLUSION: In a large unseen data set an open-source algorithm could identify infants at risk of HIE in the immediate postnatal period. This may aid focused clinical examination, transfer to tertiary care (if necessary) and timely intervention.

Managing neonatal hyperbilirubinemia: An updated guideline.

ABSTRACT: More than 80% of newborn infants experience jaundice as a result of elevated bilirubin during the first few weeks after birth. In most cases, hyperbilirubinemia is physiologic, but persistent and extreme elevations can lead to serious long-term complications, such as kernicterus. To avoid these complications and help clinicians in the successful assessment, evaluation, and treatment of hyperbilirubinemia, the American Academy of Pediatrics updated its clinical practice guideline for neonatal hyperbilirubinemia. This article reviews the guideline and highlights significant updates, such as an elevation in the threshold for phototherapy and exchange transfusion, inclusion of gestational age, and removal of racially based norms.

BMP4 and Temozolomide Synergize in the Majority of Patient-Derived Glioblastoma Cultures.

One of the main causes of poor prognoses in patient with glioblastoma (GBM) is drug resistance to current standard treatment, which includes chemoradiation and adjuvant temozolomide (TMZ). In addition, the concept of cancer stem cells provides new insights into therapy resistance and management also in GBM and glioblastoma stem cell-like cells (GSCs), which might contribute to therapy resistance. Bone morphogenetic protein-4 (BMP4) stimulates astroglial differentiation of GSCs and thereby reduces their self-renewal capacity. Exposure of GSCs to BMP4 may also sensitize these cells to TMZ. A recent phase I trial has shown that local delivery of BMP4 is safe, but a large variation in survival is seen in these treated patients and in features of their cultured tumors. We wanted to combine TMZ and BMP4 (TMZ + BMP4) therapy and assess the inter-tumoral variability in response to TMZ + BMP4 in patient-derived GBM cultures. A phase II trial could then benefit a larger group of patients than those treated with BMP4 only. We first show that simultaneous treatment with TMZ + BMP4 is more effective than sequential treatment. Second, when applying our optimized treatment protocol, 70% of a total of 20 GBM cultures displayed TMZ + BMP4 synergy. This combination induces cellular apoptosis and does not inhibit cell proliferation. Comparative bulk RNA-sequencing indicates that treatment with TMZ + BMP4 eventually results in decreased MAPK signaling, in line with previous evidence that increased MAPK signaling is associated with resistance to TMZ. Based on these results, we advocate further clinical trial research to test patient benefit and validate pathophysiological hypothesis.

Large-scale deep learning identifies the antiviral potential of PKI-179 and MTI-31 against coronaviruses.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to the global pandemic of Coronavirus Disease (2019) (COVID-19), underscoring the urgency for effective antiviral drugs. Despite the development of different vaccination strategies, the search for specific antiviral compounds remains crucial. Here, we combine machine learning (ML) techniques with in vitro validation to efficiently identify potential antiviral compounds. We overcome the limited amount of SARS-CoV-2 data available for ML using various techniques, supplemented with data from diverse biomedical assays, which enables end-to-end training of a deep neural network architecture. We use its predictions to identify and prioritize compounds for in vitro testing. Two top-hit compounds, PKI-179 and MTI-31, originally identified as Pi3K-mTORC1/2 pathway inhibitors, exhibit significant antiviral activity against SARS-CoV-2 at low micromolar doses. Notably, both compounds outperform the well-known mTOR inhibitor rapamycin. Furthermore, PKI-179 and MTI-31 demonstrate broad-spectrum antiviral activity against SARS-CoV-2 variants of concern and other coronaviruses. In a physiologically relevant model, both compounds show antiviral effects in primary human airway epithelial (HAE) cultures derived from healthy donors cultured in an air-liquid interface (ALI). This study highlights the potential of ML combined with in vitro testing to expedite drug discovery, emphasizing the adaptability of AI-driven approaches across different viruses, thereby contributing to pandemic preparedness.

Neighborhood Food Access in Early Life and Trajectories of Child Body Mass Index and Obesity.

Importance: Limited access to healthy foods, resulting from residence in neighborhoods with low food access, is a public health concern. The contribution of this exposure in early life to child obesity remains uncertain. Objective: To examine associations of neighborhood food access during pregnancy or early childhood with child body mass index (BMI) and obesity risk. Design, Setting, and Participants: Data from cohorts participating in the US nationwide Environmental Influences on Child Health Outcomes consortium between January 1, 1994, and March 31, 2023, were used. Participant inclusion required a geocoded residential address in pregnancy (mean 32.4 gestational weeks) or early childhood (mean 4.3 years) and information on child BMI. Exposures: Residence in low-income, low-food access neighborhoods, defined as low-income neighborhoods where the nearest supermarket is more than 0.5 miles for urban areas or more than 10 miles for rural areas. Main Outcomes and Measures: BMI z score, obesity (age- and sex-specific BMI ≥95th percentile), and severe obesity (age- and sex-specific BMI ≥120% of the 95th percentile) from age 0 to 15 years. Results: Of 28 359 children (55 cohorts; 14 657 [51.7%] male and 13 702 [48.3%] female; 590 [2.2%] American Indian, Alaska Native, Native Hawaiian, or Other Pacific Islander; 1430 [5.4%] Asian; 4034 [15.3%] Black; 17 730 [67.2%] White; and 2592 [9.8%] other [unspecified] or more than 1 race; 5754 [20.9%] Hispanic and 21 838 [79.1%] non-Hispanic) with neighborhood food access data, 23.2% resided in low-income, low-food access neighborhoods in pregnancy and 24.4% in early childhood. After adjusting for individual sociodemographic characteristics, residence in low-income, low-food access (vs non-low-income, low-food access) neighborhoods in pregnancy was associated with higher BMI z scores at ages 5 years (ß, 0.07; 95% CI, 0.03-0.11), 10 years (ß, 0.11; 95% CI, 0.06-0.17), and 15 years (ß, 0.16; 95% CI, 0.07-0.24); higher obesity risk at 5 years (risk ratio [RR], 1.37; 95% CI, 1.21-1.55), 10 years (RR, 1.71; 95% CI, 1.37-2.12), and 15 years (RR, 2.08; 95% CI, 1.53-2.83); and higher severe obesity risk at 5 years (RR, 1.21; 95% CI, 0.95-1.53), 10 years (RR, 1.54; 95% CI, 1.20-1.99), and 15 years (RR, 1.92; 95% CI, 1.32-2.80). Findings were similar for residence in low-income, low-food access neighborhoods in early childhood. These associations were robust to alternative definitions of low income and low food access and additional adjustment for prenatal characteristics associated with child obesity. Conclusions: Residence in low-income, low-food access neighborhoods in early life was associated with higher subsequent child BMI and higher risk of obesity and severe obesity. We encourage future studies to examine whether investments in neighborhood resources to improve food access in early life would prevent child obesity.

"Treat people with human dignity": the perspective of older adults on the quality of geriatric rehabilitation.

PURPOSE: The aim of this study was to gain insight into the perspectives of older adults on the quality of geriatric rehabilitation (GR) during the trajectory of GR from admission until six weeks after discharge. METHODS: We conducted a longitudinal qualitative study. Participants were interviewed three times: at the start of rehabilitation, at discharge, and six weeks after discharge. The data were analysed using a thematic analysis. RESULTS: In total, 50 interviews were conducted, with 18 participants being interviewed multiple times. The following themes emerged: 1. A bond of trust with health care professionals (HCPs), 2. Being prepared and informed at all stages of GR, 3. Participants emphasise physical and occupational therapy rather than other aspects of care as comprising GR 4. Changing needs regarding (the extent of) involvement in decision-making, 5. Contact with family and peers. CONCLUSION: For older adults, preparation for and good organisation of rehabilitation and social interaction with HCPs and other older adults were found to be important for the perceived quality of GR. Social interaction is influenced by how HCPs engage with older adults in all the phases of the rehabilitation process. Older adults have varying preferences about involvement in decision-making during GR. These perspectives should be acknowledged and acted upon in clinical practice to further improve the quality of care in GR.

A New Era of Ophthalmology Leadership? A Descriptive and Comparative Analysis of Ophthalmology Department Chairs in 2024.

PURPOSE: To (1) characterize and analyze the demographics and scholarly achievements of United States (US) academic ophthalmology department chairs, and (2) to elucidate trends in the academic and demographic profiles of newly hired department chairs. DESIGN: Cross-sectional study. METHODS: none SETTING: Online search of publicly available resources conducted January 1, 2024. PATIENT OR STUDY POPULATION: 107 ophthalmology chairs of accredited US departments. MAIN OUTCOME MEASURES: Department chair demographic and academic data. RESULTS: Of the 107 chairs analyzed, 83% (89/107) are male. The mean age of chairs is 60.9 ± 7.9 years and the mean age at appointment is 51.9 ± 7.6 years. There has been significant turnover in department chairs recently, with 47 (44%, 47/107) chairs newly appointed in the past seven years. Approximately 40% (41/107) of current chairs completed at least one component of their medical training at the program where they are currently chair. Approximately 1/3 (31%, 33/107) of current chairs earned an additional graduate degree, most frequently a PhD (16%, 17/107), MBA (8%, 10/107), and MS (4%, 8/107). More than 96% (103/107) of chairs completed a clinical fellowship, often in vitreoretinal surgery (28%, 30/107), cornea (25%, 27/107), or glaucoma (22%, 24/107). The average number of peer-reviewed publications amongst chairs is 214.9 ± 294.7 (range 0-1901), and the mean h-index is 35.0 ± 25.4 (range 0-147). When comparing profiles of newly appointed chairs in the past 7 years to chairs appointed prior to 2017, there was not a statistically significant difference in gender distribution (21% female vs. 13% female, respectively, p = 0.276). Newly hired chairs were significantly older at the time of their appointment to chair (54 years vs. 50 years, respectively, p = 0.008) and averaged significantly more years from residency completion to appointment as chair (23 years vs. 19 years, respectively, p = 0.005). CONCLUSIONS: Ophthalmology department chairs remain predominantly fellowship-trained males who have frequently trained at the institution they currently chair. Newly hired chairs have accumulated more experience prior to their appointment, starting the role later in their careers, with implications for the frequency of future chair turnover. While females compose a higher proportion of newly hired chairs in the past 7 years compared to prior, females remain underrepresented in ophthalmology chair positions.

Leukemia-derived apelin selects endothelial niche clones to promote tumorigenesis.

Hematopoietic stem cells are regulated by endothelial and mesenchymal stromal cells in the marrow niche1-3. Leukemogenesis was long believed to be solely driven by genetic perturbations in hematopoietic cells but introduction of genetic mutations in the microenvironment demonstrated the ability of niche cells to drive disease progression4-8. The mechanisms by which the stem cell niche induces leukemia remain poorly understood. Here, using cellular barcoding in zebrafish, we found that clones of niche endothelial and stromal cells are significantly expanded in leukemic marrows. The pro-angiogenic peptide apelin secreted by leukemic cells induced sinusoidal endothelial cell clonal selection and transcriptional reprogramming towards an angiogenic state to promote leukemogenesis in vivo. Overexpression of apelin in normal hematopoietic stem cells led to clonal amplification of the niche endothelial cells and promotes clonal dominance of blood cells. Knock-out of apelin in leukemic zebrafish resulted in a significant reduction in disease progression. Our results demonstrate that leukemic cells remodel the clonal and transcriptional landscape of the marrow niche to promote leukemogenesis and provide a potential therapeutic opportunity for anti-apelin treatment.

Do small effects matter more in vulnerable populations? an investigation using Environmental influences on Child Health Outcomes (ECHO) cohorts.

BACKGROUND: A major challenge in epidemiology is knowing when an exposure effect is large enough to be clinically important, in particular how to interpret a difference in mean outcome in unexposed/exposed groups. Where it can be calculated, the proportion/percentage beyond a suitable cut-point is useful in defining individuals at high risk to give a more meaningful outcome. In this simulation study we compute differences in outcome means and proportions that arise from hypothetical small effects in vulnerable sub-populations. METHODS: Data from over 28,000 mother/child pairs belonging to the Environmental influences on Child Health Outcomes Program were used to examine the impact of hypothetical environmental exposures on mean birthweight, and low birthweight (LBW) (birthweight < 2500g). We computed mean birthweight in unexposed/exposed groups by sociodemographic categories (maternal education, health insurance, race, ethnicity) using a range of hypothetical exposure effect sizes. We compared the difference in mean birthweight and the percentage LBW, calculated using a distributional approach. RESULTS: When the hypothetical mean exposure effect was fixed (at 50, 125, 167 or 250g), the absolute difference in % LBW (risk difference) was not constant but varied by socioeconomic categories. The risk differences were greater in sub-populations with the highest baseline percentages LBW: ranging from 3.1-5.3 percentage points for exposure effect of 125g. Similar patterns were seen for other mean exposure sizes simulated. CONCLUSIONS: Vulnerable sub-populations with greater baseline percentages at high risk fare worse when exposed to a small insult compared to the general population. This illustrates another facet of health disparity in vulnerable individuals.