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Many questions remain about the prevalence and effects of SARS-CoV-2 infection in malaria-endemic African countries like Uganda, particularly in vulnerable groups such as pregnant women. We describe SARS-CoV-2 immunoglobulin (Ig)G and IgM antibody responses and clinical outcomes in mother-infant dyads enrolled in malaria chemoprevention trials in Uganda. From December 2020-February 2022, among 400 unvaccinated pregnant women enrolled at 12-20 weeks gestation and followed through delivery, 128 (32%) were seronegative for anti-SARS-CoV-2 IgG and IgM at enrollment and delivery, 80 (20%) were infected prior to or early in pregnancy, and 192 (48%) were infected or re-infected with SARS-CoV-2 during pregnancy. We observed preferential binding of plasma IgG to Wuhan-Hu-1-like antigens in individuals seroconverting up to early 2021, and to Delta variant antigens in a subset of individuals in mid-2021. Breadth of IgG binding to all variants improved over time, consistent with affinity maturation of the antibody response in the cohort. No women experienced severe respiratory illness during the study. SARS-CoV-2 infection in early pregnancy was associated with lower median length-for-age Z-score at age 3 months compared with no infection or late pregnancy infect (-1.54 versus -0.37 and -0.51, P = 0.009). These findings suggest that pregnant Ugandan women experienced high levels of SARS-CoV-2 infection without severe respiratory illness. Variant-specific serology testing demonstrated evidence of antibody affinity maturation at the population level. Early gestational SARS-CoV-2 infection was associated with transient shorter stature in early infancy. Further research should explore the significance of this finding and define targeted measures to prevent infection in pregnancy.

Purpose: Conceptual models provide frameworks to illustrate relationships among patient-, provider-, system-, and community-level factors that inform care delivery and research. Existing models of cancer survivorship care focus largely on pediatric or adult populations whose needs differ from adolescents and young adults (AYAs). We developed a patient-centered conceptual model of AYA survivorship care. Methods: We conducted a narrative literature review of current conceptual and theoretical models of care. We engaged AYA cancer survivors (n = 25) in semi-structured one-hour telephone interviews. Most participants were in their 20s and 30s, and the majority (84%) were women. Recruitment was stratified by age and time since cancer diagnosis. We conducted a thematic analysis of interview transcripts to identify themes that exemplified patient-centered care. Results: Most participants identified as white and female. Leukemia and breast cancer were the most common cancer types. Main themes included the need for (1) care coordination, (2) ongoing mental health support, (3) connection to AYA peer support, (4) support during fertility preservation efforts, (5) support with financial burden, (6) support for quality of life, (7) information about and support with side effects and late effects, and (8) attention to the unique needs of young adults. Conclusions: We present a patient-centered conceptual model of AYA survivorship care needs that can inform future cancer care delivery and research.

We aimed to identify unique constellations of sensory phenotypes for genetic etiologies associated with diagnoses of autism spectrum disorder (ASD) and intellectual disability (ID). Caregivers reported on sensory behaviors via the Sensory Profile for 290 participants (younger than 25 years of age) with ASD and/or ID diagnoses, of which [approximately] 70% have a known pathogenic genetic etiology. Caregivers endorsed poor registration (i.e., high sensory threshold, passive behaviors) for all genetic subgroups relative to an "idiopathic" comparison group with an ASD diagnosis and without a known genetic etiology. Genetic profiles indicated prominent sensory seeking in "ADNP," "CHD8," and "DYRK1A," prominent sensory sensitivities in "SCN2A," and fewer sensation avoidance behaviors in "GRIN2B" (relative to the idiopathic ASD comparison group).

Abstract: Objective Our objective was to describe clinical characteristics and course of pediatric bupropion ingestions requiring extracorporeal membrane oxygenation (ECMO) life support. Desgin The study included a retrospective cohort of patients ≤18 years of age reported to a regional poison control (PC) system covering three states in the upper Midwest United States. All bupropion exposures ≤18 years of age, coded as receiving ECMO to treat toxicity, were included. Clinical presentation and management including ECMO are presented as descriptive statistics. Results During the study period, 4,951 bupropion exposures were reported; 1,145 (23.1%) were children. Nine patients were coded as undergoing ECMO; four (44.4%) were ≤18 years of age (median 16, range 14–17). All were treated with venoarterial ECMO. The median time from ingestion to presentation was 2.25 hours (range: 1–3.5). Median first systolic blood pressure and pulse were 100 mm Hg (range: 70–124) and 119.5 (range: 70–175). The median time from ingestion to ECMO was 17.63 hours (range: 7.25–33.75); median number of vasopressors was 2.5 (range: 2–3). All experienced multiple seizures, ventricular dysrhythmias, and hypotension. Three of four sustained cardiac arrest. All but one required transfer to an ECMO-capable facility for definitive care. Three patients survived with full neurologic recovery; one died. Conclusion Pediatric bupropion cases requiring ECMO were rare in this study. Time to initiation and duration of EMCO suggest that the variable onset of hemodynamic instability may delay ECMO initiation. It is incumbent on PCs and medical toxicologists to educate prescribers and pediatricians about bupropion's potential lethality and to consider early transfer to an ECMO center.

INTRODUCTION: As malaria declines, low-density malaria infections (LMIs) represent an increasing proportion of infections and may have negative impacts on child health and cognition, necessitating development of targeted and effective solutions. This trial assesses the health, cognitive and socioeconomic impact of two strategies for detecting and treating LMI in a low transmission setting. METHODS AND ANALYSIS: The study is a 3-arm open-label individually randomised controlled trial enrolling 600 children aged 6 months to 10 years in Bagamoyo district, Tanzania. Children are randomised to one of three arms: active case detection with molecular (ACDm) testing by high volume quantitative PCR (qPCR), passive case detection also with molecular testing (PCDm) and a control of standard PCD using rapid diagnostics tests (RDTs). Over the 2-year trial, ACDm participants receive malaria testing using RDT and qPCR three times annually, and malaria testing by RDT only when presenting with fever. PCDm and PCD participants receive malaria testing by RDT and qPCR or RDT only, respectively, when presenting with fever. RDT or qPCR positive participants with uncomplicated malaria are treated with artemether lumefantrine. The primary outcome is cumulative incidence of all-cause sick visits. Secondary outcomes include fever episodes, clinical failure after fever episodes, adverse events, malaria, non-malarial infection, antibiotic use, anaemia, growth faltering, cognition and attention, school outcomes, immune responses, and socioeconomic effects. Outcomes are assessed through monthly clinical assessments and testing, and baseline and endline neurodevelopmental testing. The trial is expected to provide key evidence and inform policy on health, cognitive and socioeconomic impact of interventions targeting LMI in children. ETHICS AND DISSEMINATION: Study is approved by Tanzania NatHREC and institutional review boards at University of California San Francisco and Ifakara Health Institute. Findings will be reported on ClinicalTrials.gov, in peer-reviewed journals and through stakeholder meetings. TRIAL REGISTRATION NUMBER: NCT05567016.

Tororo District, Uganda experienced a dramatic decrease in malaria burden from 2015-19 during 5 years of indoor residual spraying (IRS) with carbamate (Bendiocarb) and then organophosphate (Actellic) insecticides. However, a marked resurgence occurred in 2020, which coincided with a change to a clothianidin-based IRS formulations (Fludora Fusion/SumiShield). To quantify the magnitude of the resurgence, investigate causes, and evaluate the impact of a shift back to IRS with Actellic in 2023, we assessed changes in malaria metrics in regions within and near Tororo District. Malaria surveillance data from Nagongera Health Center, Tororo District was included from 2011-2023. In addition, a cohort of 667 residents from 84 houses was followed from August 2020 through September 2023 from an area bordering Tororo and neighboring Busia District, where IRS has never been implemented. Cohort participants underwent passive surveillance for clinical malaria and active surveillance for parasitemia every 28 days. Mosquitoes were collected in cohort households every 2 weeks using CDC light traps. Female Anopheles were speciated and tested for sporozoites and phenotypic insecticide resistance. Temporal comparisons of malaria metrics were stratified by geographic regions. At Nagongera Health Center average monthly malaria cases varied from 419 prior to implementation of IRS; to 56 after 5 years of IRS with Bendiocarb and Actellic; to 1591 after the change in IRS to Fludora Fusion/SumiShield; to 155 after a change back to Actellic. Among cohort participants living away from the border in Tororo, malaria incidence increased over 8-fold (0.36 vs. 2.97 episodes per person year, p

IntroductionMaternal intervillous monocytes (MIMs) and fetal Hofbauer cells (HBCs) are myeloid-derived immune cells at the maternal-fetal interface. Maternal reproductive history is associated with differential risk of pregnancy complications. The molecular phenotypes and roles of these distinct monocyte/macrophage populations and the influence of gravidity on these phenotypes has not been systematically investigated.MethodsHere, we used RNA sequencing to study the transcriptional profiles of MIMs and HBCs in normal term pregnancies.ResultsOur analyses revealed distinct transcriptomes of MIMs and HBCs. Genes involved in differentiation and cell organization pathways were more highly expressed in MIMs vs. HBCs. In contrast, HBCs had higher expression of genes involved in inflammatory responses and cell surface receptor signaling. Maternal gravidity influenced monocyte programming, as expression of pro-inflammatory molecules was significantly higher in MIMs from multigravidae compared to primigravidae. In HBCs, multigravidae displayed enrichment of gene pathways involved in cell-cell signaling and differentiation.DiscussionOur results demonstrated that MIMs and HBCs have highly divergent transcriptional signatures, reflecting their distinct origins, locations, functions, and roles in inflammatory responses. Furthermore, maternal gravidity influences the gene signatures of MIMs and HBCs, potentially modulating the interplay between tolerance and trained immunity. The phenomenon of reproductive immune memory may play a novel role in the differential susceptibility of primigravidae to pregnancy complications.

This study addresses the measurement of high school students' epistemic knowledge associated with scientific experimentation (EKSE) which concerns "how" scientific experimentation generates knowledge and "why" that knowledge is justified. Based on philosophical, educational standards, and literature analyses, an EKSE construct is characterized as (1) underlying students' decisions and reasoning elicited during experiment design, data collection/measurement, and data analysis/interpretation and (2) progressing in five levels of sophistication: no information, nascent, dogmatic, contextualized, and reflective. This study psychometrically examined the structure of the EKSE construct using the construct modeling approach. An instrument was designed to ask students decisions and reasoning encountered while carrying out the activities embedded in experimental inquiry. High school students took the instrument as a pretest and a posttest to a physics curriculum where they learned to carry out independent scientific experiments. Results indicate that (1) all decisions and reasoning taking place during experiment design, data collection/measurement, and data analysis/interpretation contribute to the EKSE construct, (2) epistemic knowledge develops in the hypothesized order, (3) scientifically aligned decisions are likely to occur when students' epistemic knowledge is at or higher than the dogmatic level, and (4) students' EKSE can improve after engaging in a curriculum that encourages independent scientific experimentation with materials. Implications of these results and further research are discussed.

States vary widely in their approaches to charter school regulation. We administered online surveys to charter school leaders in four of the most stringently regulated states and three of the least stringently regulated states to examine how their approach might influence perceived school goals and levels of goal agreement. Generally, survey responses reveal that leaders in both settings perceive similar priorities from school stakeholders. However, charter leaders in low regulation states ascribe greater relative importance to satisfying enrolled families, report that charter authorizers are comparatively less concerned about test scores, and report less clarity regarding school goals. Implications are discussed.

This study highlights opportunities for developing programs and initiatives to assist Black men in understanding leadership and seeing themselves as leaders, and for decreasing low college retention and persistence rates. The themes from this qualitative narrative inquiry highlight leader identity, capacity, and efficacy for undergraduate Black men. Narrative inquiry was appropriate for this study because the researchers sought to better understand how Black undergraduate male student leaders make meaning of their experience in higher education related to their comprehension of leadership and identity as leaders.

Studies of educational games often treat them as "black boxes" (Black and Wiliam in Phi Delta Kappan 80: 139-48, 1998; Buckley et al. in Int J LearnTechnol 5:166-190, 2010; Buckley et al. in J Sci Educ Technol 13: 23-41, 2010) and measure their effectiveness by exposing a treatment group of students to the game and comparing their performance on an external assessment to that of a control group taught the same material by some other method. This precludes the possibility of monitoring, evaluating, and reacting to the actions of individual students as they progress through the game. To do that, however, one must know what to look for because superficial measures of success are unlikely to identify unproductive behaviors such as "gaming the system." (Baker in Philipp Comput J, 2011; Downs et al. in Proceedings of the SIGCHI Conference on Human Factors in Computing Systems, USA, 2010) The research reported here advances the ultimate goal of creating educational games that can provide real time, meaningful feedback on the progress of their users, enabling teachers or the game itself to intervene in a timely manner. We present the results of an in-depth analysis of students' actions in "Geniventure," an interactive digital game designed to teach genetics to middle and high school students. "Geniventure" offers a sequence of challenges of increasing difficulty and records students' actions as they progress. We analyzed the resulting log files, taking into account not only whether a student achieved a certain goal, but also the quality of the student's performance on each attempt. Using this information, we quantified students' performance and correlated it to their learning gain as estimated by scores on identical multiple-choice tests administered before and after exposure to "Geniventure." This analysis was performed in classes taught by teachers who had participated in professional development as part of a research project. A two-tailed paired-sample t-test of mean pre-test and post-test scores in these classes indicates a significant positive difference with a large effect size. Multivariate regression analysis of log data finds no correlation between students' post-test scores and their performance on "practice" challenges that invite experimentation, but a highly significant positive correlation with performance on "assessment" challenges, presented immediately following the practice challenges, that required students to invoke relevant mental models. We repeated this analysis with similar results using a second group of classes led by teachers who implemented "Geniventure" on their own after the conclusion of, and with no support from, the research project.

IntroductionMaps of malaria risk are important tools for allocating resources and tracking progress. Most maps rely on cross-sectional surveys of parasite prevalence, but health facilities represent an underused and powerful data source. We aimed to model and map malaria incidence using health facility data in Uganda.MethodsUsing 24 months (2019-2020) of individual-level outpatient data collected from 74 surveillance health facilities located in 41 districts across Uganda (n=445 648 laboratory-confirmed cases), we estimated monthly malaria incidence for parishes within facility catchment areas (n=310) by estimating care-seeking population denominators. We fit spatio-temporal models to the incidence estimates to predict incidence rates for the rest of Uganda, informed by environmental, sociodemographic and intervention variables. We mapped estimated malaria incidence and its uncertainty at the parish level and compared estimates to other metrics of malaria. To quantify the impact that indoor residual spraying (IRS) may have had, we modelled counterfactual scenarios of malaria incidence in the absence of IRS.ResultsOver 4567 parish-months, malaria incidence averaged 705 cases per 1000 person-years. Maps indicated high burden in the north and northeast of Uganda, with lower incidence in the districts receiving IRS. District-level estimates of cases correlated with cases reported by the Ministry of Health (Spearman's r=0.68, p

African children are at risk of malaria and malnutrition. We quantified relationships between malaria and malnutrition among young Ugandan children in a high malaria transmission region. Data were used from a randomized controlled trial where Ugandan HIV-unexposed (n = 393) and HIV-exposed (n = 186) children were randomized to receive no malaria chemoprevention, monthly sulfadoxine-pyrimethamine, daily trimethoprim-sulfamethoxazole, or monthly dihydroartemisinin-piperaquine (DP) from age 6-24 months, and then were followed off chemoprevention until age 36 months. Monthly height and weight, and time of incident malaria episodes were obtained; 89 children who received DP contributed piperaquine (PQ) concentrations. Malaria hazard was modeled using parametric survival analysis adjusted for repeated events, and height and weight were modeled using a Brody growth model. Among 579 children, stunting (height-for-age z-score [ZHA]