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Exposure to social adversity has been associated with cortisol dysregulation during pregnancy and in later childhood; less is known about how prenatal exposure to social stressors affects postnatal cortisol of infants. In a secondary analysis of data from a longitudinal study, we tested whether a pregnant woman's reports of social adversity during the third trimester were associated with their infant's resting cortisol at 1, 6, and 12 months postnatal. Our hypothesis was that prenatal exposure to social adversity would be associated with elevation of infants' cortisol. Measures included prenatal survey reports of social stressors and economic hardship, and resting cortisol levels determined from infant saliva samples acquired at each postnatal timepoint. Data were analyzed using linear mixed effects models. The final sample included 189 women and their infants (46.56% assigned female sex at birth). Prenatal economic hardship was significantly associated with infant cortisol at 6 months postnatal; reports of social stressors were not significantly associated with cortisol at any time point. Factors associated with hardship, such as psychological distress or nutritional deficiencies, may alter fetal HPA axis development, resulting in elevated infant cortisol levels. Developmental changes unique to 6 months of age may explain effects at this timepoint. More work is needed to better comprehend the complex pre- and post-natal physiologic and behavioral factors that affect infant HPA axis development and function, and the modifying role of environmental exposures.

To assess the actual presence of underlying depressed skull fractures and traumatic brain injuries (TBI) on computed tomography (CT) in children with and without palpable skull fractures on physical examination following minor head trauma. This was a secondary analysis of a prospective, observational multicenter study enrolling 42,412 children

Lifelong, guideline-based monitoring for late effects is recommended for childhood cancer survivors (CCS). We examined rates of receiving surveillance tests among at-risk young adult CCS in a population-based study (n = 253; 50% Hispanic/Latino; mean post-treatment interval 14.5 years, range: 5-22). Adherence rates were 36.1%, 31.9%, and 36.4% among those indicated for cardiac (n = 119), thyroid (n = 68), and breast (n = 66) surveillance, respectively, indicating that poor surveillance among long-term CCS is widespread. Receipt of any of these surveillance tests was positively associated with being in follow-up care, having any health insurance (vs. none), and receiving education about need for follow-up with surveillance (all p-values less than .05).

The Zika virus (ZIKV) epidemic in Latin America (2015-2016) has primarily been studied in urban centers, with less understanding of its impact on smaller rural communities. To address this gap, we analyzed ZIKV seroepidemiology in 6 rural Ecuadorian communities (2018-2019) with varying access to a commercial hub. Seroprevalence ranged from 19% to 54%, measured by nonstructural protein 1 blockade of binding enzyme-linked immunosorbent assay. We observed a decline in ZIKV seroprevalence between 2018 and 2019 that was greater among younger populations, suggesting that the attack rates in the 2015-2016 epidemic were significantly higher than our 2018 observations. These data indicate that the 2015-2016 epidemic included significant transmission in rural and more remote settings. Our observations of high seroprevalence in our area of study highlights the importance of surveillance and research in rural areas lacking robust health systems to manage future Zika outbreaks and vaccine initiatives.

BACKGROUND: School physical education is an important population-level health intervention for improving youth fitness. This study estimated the impact of New York Citys PE Works program - which included providing PE teachers, training for classroom teachers, and administrative/ teacher support for PE - on student cardiorespiratory fitness as measured by the FitnessGrams 15-meter PACER test for aerobic capacity. METHODS: This longitudinal study (2014/15-2018/19) includes 581 elementary schools (n = 315,999 4th /5th -grade students; 84% non-white; 74% who qualify for free or reduced-price meals, a proxy for socioeconomic status). We apply the parametric g-formula to address schools time-varying exposure to intervention components and time-varying confounding. RESULTS: After four years of staggered PE Works implementation, 49.7% of students/school (95% CI: 42.6%, 54.2%) met age/sex-specific Healthy Fitness Zone (HFZ) aerobic capacity standards set by the FitnessGram. Had PE Works not been implemented, we estimate 45.7% (95% CI: 36.9%, 52.1%) would have met aerobic capacity HFZ standards. Had PE Works been fully implemented in all schools from the programs inception, we estimate 57.4% (95% CI: 49.1%, 63.3%) would have met aerobic capacity HFZ standards. Adding a PE teacher, alone, had the largest impact (6.4% (95% CI: 1.0, 12.0) increase). CONCLUSION: PE Works positively impacted student cardiorespiratory fitness. Mandating and funding multicomponent PE programs is an important public health intervention to increase childrens cardiorespiratory fitness.

Tools for rapid identification of novel and/or emerging viruses are urgently needed for clinical diagnosis of unexplained infections and pandemic preparedness. Here we developed and clinically validated a largely automated metagenomic next-generation sequencing (mNGS) assay for agnostic detection of respiratory viral pathogens from upper respiratory swab and bronchoalveolar lavage samples in

BACKGROUND: Patients with hereditary hemorrhagic telangiectasia (HHT) are at risk for organ vascular malformations including arteriovenous malformations (AVMs) in the brain and lungs. North American HHT Centers of Excellence (CoEs) routinely screen for brain and lung AVMs, with the primary goal of detecting AVMs which can be treated before complications arise. Current international HHT guidelines provide recommendations for initial screening for brain and lung AVMs among children and adults with the disease, but rescreening recommendations are not comprehensively addressed and have not been reported. We determined current rescreening practices for brain and lung AVMs for children and adults with HHT among North American HHT CoEs. METHODS: We surveyed North American HHT CoEs regarding rescreening practices for new brain and lung AVMs in children and adults with initial negative screening. RESULTS: All thirty CoEs responded; 28 regarding pediatric (93.3%) and 30 (100%) regarding adult HHT care. The median duration of practice experience in HHT was 11.5 (range 3-30) years for providers of pediatric HHT care and 11.5 (range 3-35) years for providers of adult HHT care. The median number of patients followed at each CoE was 60 for children (range 8-500) and 375 for adults (range 30-1500). 25/28 CoEs (89.3%) reported rescreening children for brain AVMs, most commonly with enhanced MRI (21/25, 84%). 25 CoEs rescreen children for lung AVMs, most commonly every 5 years (15/25). Only 4/30 CoEs (13.3%) rescreen adults for brain AVMs. 26/30 CoEs (86.7%) reported rescreening adults for lung AVMs, most commonly every 5 years (18/26, 69.2%). CONCLUSIONS: Most HHT CoEs routinely rescreen children for brain and lung AVMs and adults for lung AVMs when initial screening is negative, but adults are infrequently rescreened for brain AVMs. Long-term data regarding risk for new brain and lung AVMs are required to establish practice guidelines for rescreening.

Prior literature has debated whether syntax is separable from semantics in the brain. Using functional magnetic resonance imaging and multi-voxel pattern analysis, our previous studies investigated brain activity during morpho-syntactic versus semantic processing. These studies only detected semantic specialization in activation patterns and no syntactic specialization in 5- to 6-year-old and 7- to 8-year-old children. To examine if older children who have mastered morpho-syntactic skills would show specialization for syntax, the current study examined 64 9- to 10-year-old children using the same design and analyses. We observed that only the left IFG pars opercularis was sensitive to syntactic but not semantic information, supporting the hypothesis that this region serves as a core region for syntax. In addition, the left STG which has been implicated in the integration of semantics and syntax, as well as the left MTG and IFG pars triangularis which have been implicated in semantics, were sensitive to both semantic and syntactic information with no evidence of specialization. These findings suggest a lexicalized view of syntax, which argues that semantically sensitive regions are also critical regions for syntactic processing during language comprehension.

Human inborn errors of thymic T cell tolerance underlie the production of autoantibodies (auto-Abs) neutralizing type I IFNs, which predispose to severe viral diseases. We analyze 131 female patients with X-linked dominant incontinentia pigmenti (IP), heterozygous for loss-of-function (LOF) NEMO variants, from 99 kindreds in 10 countries. Forty-seven of these patients (36%) have auto-Abs neutralizing IFN-α and/or IFN-ω, a proportion 23 times higher than that for age-matched female controls. This proportion remains stable from the age of 6 years onward. On imaging, female patients with IP have a small, abnormally structured thymus. Auto-Abs against type I IFNs confer a predisposition to life-threatening viral diseases. By contrast, patients with IP lacking auto-Abs against type I IFNs are at no particular risk of viral disease. These results suggest that IP accelerates thymic involution, thereby underlying the production of auto-Abs neutralizing type I IFNs in at least a third of female patients with IP, predisposing them to life-threatening viral diseases.

Rocky mountain spotted fever (RMSF) causes significant illness and death in children. Although historically rare in California, USA, RMSF is endemic in areas of northern Mexico that border California. We describe 7 children with RMSF who were hospitalized at a tertiary pediatric referral center in California during 2017-2023. Five children had recent travel to Mexico with presumptive exposure, but 2 children did not report any travel outside of California. In all 7 patients, Rickettsia rickettsii DNA was detected by plasma microbial cell-free next-generation sequencing, which may be a useful diagnostic modality for RMSF, especially early in the course of illness, when standard diagnostic tests for RMSF are of limited sensitivity. A high index of suspicion and awareness of local epidemiologic trends remain most critical to recognizing the clinical syndrome of RMSF and initiating appropriate antimicrobial therapy in a timely fashion.

Natural disasters trigger complex chains of events within human societies1. Immediate deaths and damage are directly observed after a disaster and are widely studied, but delayed downstream outcomes, indirectly caused by the disaster, are difficult to trace back to the initial event1,2. Tropical cyclones (TCs)-that is, hurricanes and tropical storms-are widespread globally and have lasting economic impacts3-5, but their full health impact remains unknown. Here we conduct a large-scale evaluation of long-term effects of TCs on human mortality in the contiguous United States (CONUS) for all TCs between 1930 and 2015. We observe a robust increase in excess mortality that persists for 15 years after each geophysical event. We estimate that the average TC generates 7,000-11,000 excess deaths, exceeding the average of 24 immediate deaths reported in government statistics6,7. Tracking the effects of 501 historical storms, we compute that the TC climate of CONUS imposes an undocumented mortality burden that explains a substantial fraction of the higher mortality rates along the Atlantic coast and is equal to roughly 3.2-5.1% of all deaths. These findings suggest that the TC climate, previously thought to be unimportant for broader public health outcomes, is a meaningful underlying driver for the distribution of mortality risk in CONUS, especially among infants (less than 1 year of age), people 1-44 years of age, and the Black population. Understanding why TCs induce this excess mortality is likely to yield substantial health benefits.

Previous studies have reported alterations in cortical thickness in autism. However, few have included enough autistic females to determine if there are sex specific differences in cortical structure in autism. This longitudinal study aimed to investigate autistic sex differences in cortical thickness and trajectory of cortical thinning across childhood. Participants included 290 autistic (88 females) and 139 nonautistic (60 females) individuals assessed at up to 4 timepoints spanning ~2-13 years of age (918 total MRI timepoints). Estimates of cortical thickness in early and late childhood as well as the trajectory of cortical thinning were modeled using spatiotemporal linear mixed effects models of age-by-sex-by-diagnosis. Additionally, the spatial correspondence between cortical maps of sex-by-diagnosis differences and neurotypical sex differences were evaluated. Relative to their nonautistic peers, autistic females had more extensive cortical differences than autistic males. These differences involved multiple functional networks, and were mainly characterized by thicker cortex at ~3 years of age and faster cortical thinning in autistic females. Cortical regions in which autistic alterations were different between the sexes significantly overlapped with regions that differed by sex in neurotypical development. Autistic females and males demonstrated some shared differences in cortical thickness and rate of cortical thinning across childhood relative to their nonautistic peers, however these areas were relatively small compared to the widespread differences observed across the sexes. These results support evidence of sex-specific neurobiology in autism and suggest that processes that regulate sex differentiation in the neurotypical brain contribute to sex differences in the etiology of autism.

A hallmark of fetal alcohol spectrum disorders (FASD) is neurobehavioral deficits that still do not have effective treatment. Here, we present that reduction of Apolipoprotein E (APOE) is critically involved in neurobehavioral deficits in FASD. We show that prenatal alcohol exposure (PAE) changes chromatin accessibility of Apoe locus, and causes reduction of APOE levels in both the brain and peripheral blood in postnatal mice. Of note, postnatal administration of an APOE receptor agonist (APOE-RA) mitigates motor learning deficits and anxiety in those mice. Several molecular and electrophysiological properties essential for learning, which are altered by PAE, are restored by APOE-RA. Our human genome-wide association study further reveals that the interaction of PAE and a single nucleotide polymorphism in the APOE enhancer which chromatin is closed by PAE in mice is associated with lower scores in the delayed matching-to-sample task in children. APOE in the plasma is also reduced in PAE children, and the reduced level is associated with their lower cognitive performance. These findings suggest that controlling the APOE level can serve as an effective treatment for neurobehavioral deficits in FASD.

Meningeal solitary fibrous tumors (SFT) are rare and have a high frequency of local recurrence and distant metastasis. In a cohort of 126 patients (57 female, 69 male; mean age at surgery 53.0 years) with pathologically confirmed meningeal SFTs with extended clinical follow-up (median 9.9 years; range 15 days-43 years), we performed extensive molecular characterization including genome-wide DNA methylation profiling (n = 80) and targeted TERT promoter mutation testing (n = 98). Associations were examined with NAB2::STAT6 fusion status (n = 101 cases; 51 = ex5-7::ex16-17, 26 = ex4::ex2-3; 12 = ex2-3::exANY/other and 12 = no fusion) and placed in the context of 2021 Central Nervous System (CNS) WHO grade. NAB2::STAT6 fusion breakpoints (fusion type) were significantly associated with metastasis-free survival (MFS) (p = 0.03) and, on multivariate analysis, disease-specific survival (DSS) when adjusting for CNS WHO grade (p = 0.03). DNA methylation profiling revealed three distinct clusters: Cluster 1 (n = 38), Cluster 2 (n = 22), and Cluster 3 (n = 20). Methylation clusters were significantly associated with fusion type (p

PURPOSE: There is variability in clinical outcomes with vertebral body tethering (VBT) partly due to a limited understanding of the growth modulation (GM) response. We used the largest sample of patients with 3D spine reconstructions to characterize the vertebra and disc morphologic changes that accompany growth modulation during the first two years following VBT. METHODS: A multicenter registry was used to identify idiopathic scoliosis patients who underwent VBT with 2 years of follow-up. Calibrated biplanar X-rays obtained at longitudinal timepoints underwent 3D reconstruction to obtain precision morphological measurements. GM was defined as change in instrumented coronal angulation from post-op to 2-years. RESULTS: Fifty patients (mean age: 12.5 ± 1.3yrs) were analyzed over a mean of 27.7 months. GM was positively correlated with concave vertebra height growth (r = 0.57, p  10°) experienced an additional 1.6 mm (229% increase) of mean concave vertebra growth during study period compared to the Poor Modulators (GM

Most studies of developing visual attention are conducted using screen-based tasks in which infants move their eyes to select where to look. However, real-world visual exploration entails active movements of both eyes and head to bring relevant areas in view. Thus, relatively little is known about how infants coordinate their eyes and heads to structure their visual experiences. Infants were tested every 3 months from 9 to 24 months while they played with their caregiver and three toys while sitting in a highchair at a table. Infants wore a head-mounted eye tracker that measured eye movement toward each of the visual targets (caregiver's face and toys) and how targets were oriented within the head-centered field of view (FOV). With age, infants increasingly aligned novel toys in the center of their head-centered FOV at the expense of their caregiver's face. Both faces and toys were better centered in view during longer looking events, suggesting that infants of all ages aligned their eyes and head to sustain attention. The bias in infants' head-centered FOV could not be accounted for by manual action: Held toys were more poorly centered compared with non-held toys. We discuss developmental factors-attentional, motoric, cognitive, and social-that may explain why infants increasingly adopted biased viewpoints with age.

AimThe current study investigated the prospective relationships between parental monitoring, family conflict, and screen time across six screen time modalities in early adolescents in the USA.MethodsWe utilised prospective cohort data of children (ages 10-14 years) from the Adolescent Brain Cognitive Development (ABCD) Study (years baseline to Year 2 of follow-up; 2016-2020; N = 10 757). Adjusted coefficients (B) and 95% confidence intervals (CIs) were estimated using mixed-effect models with robust standard errors.ResultsA higher parental monitoring score was associated with less total screen time (B = -0.37, 95% CI -0.58, -0.16), with the strongest associations being with video games and YouTube videos. Conversely, a higher family conflict score was associated with more total screen time (B = 0.08, 95% CI 0.03, 0.12), with the strongest associations being with YouTube videos, video games, and watching television shows/movies in Years 1 and 2.ConclusionThe current study found that greater parental monitoring was associated with less screen time, while greater family conflict was linked to more screen time. These results may inform strategies to reduce screen time in adolescence, such as improving communication between parents and their children to strengthen family relationships.

C1q deficiency is a rare inborn error of immunity characterized by increased susceptibility to infections and autoimmune manifestations mimicking SLE, with an associated morbidity and mortality. Because C1q is synthesized by monocytes, to date, four patients treated with allogeneic HSCT have been reported, with a positive outcome in three. We conducted an international retrospective study to assess the outcome of HSCT in C1q deficiency. Eighteen patients, fourteen previously unreported, from eleven referral centres, were included. Two patients had two HSCTs, thus 20 HSCTs were performed in total, at a median age of 10 years (range 0.9-19). Indications for HSCT were autoimmune manifestations not controlled by ongoing treatment in seventeen, and early development of MALT lymphoma in one patient. Overall survival (OS) was 71% and event-free survival was 59% at two years (considering an event as acute GvHD ≥ grade III, disease recurrence and death). In eleven patients HSCT led to resolution of autoimmune features and discontinuation of immunosuppressive treatments (follow-up time range 3-84 months). Five patients died due to transplant-related complications. Patients with a severe autoimmune phenotype, defined as neurological and/or renal involvement, had the worst OS (40% vs 84%; p = 0.034). Reviewing data of 69 genetically confirmed C1q deficient patients, we found that anti-Ro antibodies are associated with neurologic involvement, and anti-RNP and anti-DNA antibodies with renal involvement. In conclusion, HSCT may be a valid curative option for C1q deficiency, but careful selection of patients, with an accurate assessment of risk and benefit, is mandatory.

BACKGROUND: The COVID-19 pandemic led to dramatic changes in the lives of children that impact cardiometabolic health. Cities and counties had varying policies with respect to school closure, recreational programs, and efforts to mitigate food insecurity and economic distress. Our objective was to evaluate changes in BMI-z score and prevalence of overweight/obesity prior to and during the pandemic among children in San Francisco, CA, where public schools were closed for 18-months. METHODS: This was an electronic medical record-based retrospective cohort study. We included 15,401 children, 4-17 years of age at study onset. Our exposure was time into each of three time periods: (1) March 2018-February 2019; (2) March 2019-February 2020; (3) March 2020-August 2021 (the pandemic period of school closure). Generalized estimating equations (GEE) were used to assess changes in BMI-z score and overweight/obesity across the three time periods. We assessed for effect modification by age-category, insurance status, and race/ethnicity. RESULTS: Mean BMI-z score increased by 0.06 per year in time period 2, the year prior to the pandemic (p

BACKGROUND: Cancer is the leading cause of disease-related mortality in children. Causes of leukemia, the most common form, are largely unknown. Growing evidence points to an origin in-utero, when global redistribution of DNA methylation occurs driving tissue differentiation. METHODS: Epigenome-wide DNA methylation was profiled in surrogate (blood) and target (bone marrow) tissues at birth, diagnosis, remission and relapse of pediatric pre-B acute lymphoblastic leukemia (pre-B ALL) patients. Double-blinded analyses was performed between prospective cohorts extending from birth to diagnosis and retrospective studies backtracking from clinical disease to birth. Validation was carried out using independent technologies and populations. RESULTS: The imprinted and immuno-modulating VTRNA2-1 was hypermethylated (FDR

BACKGROUND: Family dynamics play an important role in determining the glycemic outcomes of type 1 diabetes (T1D) in children. The time interval immediately following T1D diagnosis is particularly stressful for families, and interventions to support families in adjusting their family practices to support adjustment to and management of T1D in the months following diagnosis may improve glycemic outcomes. Self-guided digital interventions offer a sustainable model for interventions to support caregivers in learning evidence-based family management skills for adjustment to and management of T1D. OBJECTIVE: We hypothesized that a self-guided, web-based, family skills management program (addressing caregiver social support as well as family problem-solving, communication, and supportive behavior change strategies) initiated at the time of T1D diagnosis would improve glycemic outcomes in children with T1D. In this study, we report on the feasibility and acceptability of this program. METHODS: We prospectively evaluated a sample of 37 children newly diagnosed with T1D recruited from a pediatric endocrinology clinic. Parent participants were asked to complete web-based modules addressing social support, family problem-solving, communication, and supportive behavior change strategies. Module completion was analyzed for percentage completion, patterns of completion, and differences in completion rates by coparenting status. Qualitative open-ended feedback was collected at the completion of each module. RESULTS: A total of 31 (84%) of the 37 participants initiated the web-based program. Of those 31 participants, 25 (81%) completed some content and 15 (48%) completed all 5 modules. Completion rates were higher when coparenting partners engaged in the intervention together (P=.04). Of the 18 participants given a choice about the spacing of content delivery, 15 (83%) chose to have all sessions delivered at once and 3 (17%) chose to space sessions out at 2-week intervals. Qualitative feedback supported the acceptability of the program for delivery soon after T1D diagnosis. Families reported on positive benefits, including requesting future access to the program and describing helpful changes in personal or family processes for managing T1D. CONCLUSIONS: In this study, we found that a self-guided digital family support intervention initiated at the time of a childs T1D diagnosis was largely feasible and acceptable. Overall, rates of participation and module completion were similar to or higher than other self-guided digital prevention interventions for mental and physical health outcomes. Self-guided digital programs addressing family management skills may help prevent challenges common with T1D management and can decrease cost, increase access, and add flexibility compared to traditional interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03720912; https://clinicaltrials.gov/study/NCT03720912.

BACKGROUND: Malaria continues to represent an important public health problem in Ethiopia. The expansion of irrigated agricultural development projects turns out to be a major impediment to long-lasting and sustainable malaria prevention and control efforts in the country. The aim of this study was to determine the micro-epidemiology of malaria and associated risk factors in and around Gojeb Horizon Irrigation Plantation in southwest Ethiopia. METHODS: A community-based comparative cross-sectional study was conducted from May to June 2018 in Gimbo District, southwest Ethiopia. A total of 186 households (94 from irrigated village and 92 from non-irrigated village) were randomly selected from among the communities living around the Gojeb Horizon plantation. In total, 718 individuals (368 from irrigated village and 350 from non-irrigated village) were recruited from the selected households. A finger-prick blood sample was obtained from each participant. Socio-demographic data from the households and individual study participants were collected using a semi-structured questionnaire. Multivariate regression was used to assess factors associated with micro-epidemiology of malaria. P-value

BACKGROUND: Problematic Internet use (i.e., Internet use that disrupts functioning in other important domains; PIU) is increasingly prevalent worldwide, particularly among youth. One form of PIU relates specifically to interpersonal interaction and communication, deemed social PIU. Social PIU has been linked to various forms of psychopathology, including attention-deficit/hyperactivity disorder (ADHD). Yet with limited longitudinal research, the direction of this association remains unclear. Moreover, little research investigates whether social PIU is linked to one or both symptom dimensions of ADHD (inattention vs. hyperactivity/impulsivity). METHODS: The present study utilized data from the largest extant longitudinal study of girls with childhood-diagnosed ADHD (N = 228). Linear regression and structural equation models were used to analyze social PIU as both a prospective predictor and outcome of ADHD symptoms. RESULTS: Inattentive ADHD symptoms were positively associated with concurrent social PIU in initial regression models but were non-significant in path analyses. Social PIU was only marginally significant in predicting subsequent inattention six years later. Symptoms of hyperactivity/impulsivity were unrelated to social PIU among girls at either time point. CONCLUSIONS: Inattentive ADHD symptoms were initially positively linked to concurrent problems with social Internet use, but bidirectional associations were non-significant in path analyses. Relations between PIU and ADHD in girls may be less robust than previously thought, although further longitudinal research with clinical samples is needed to clarify which groups of adolescents are particularly vulnerable to social PIU and its long-term effects.

BACKGROUND: In 2022-2023, 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recommended for infants. We aimed to estimate the incidence of outpatient visits and antibiotic prescriptions in US children (≤17 years) from 2016-2019 for acute otitis media, pneumonia, and sinusitis associated with PCV15- and PCV20-additional (non-PCV13) serotypes to quantify PCV15/20 potential impacts. METHODS: We estimated the incidence of PCV15/20-additional serotype-attributable visits and antibiotic prescriptions as the product of all-cause incidence rates, derived from national health care surveys and MarketScan databases, and PCV15/20-additional serotype-attributable fractions. We estimated serotype-specific attributable fractions using modified vaccine-probe approaches incorporating incidence changes post-PCV13 and ratios of PCV13 versus PCV15/20 serotype frequencies, estimated through meta-analyses. RESULTS: Per 1000 children annually, PCV15-additional serotypes accounted for an estimated 2.7 (95% confidence interval, 1.8-3.9) visits and 2.4 (95% CI, 1.6-3.4) antibiotic prescriptions. PCV20-additional serotypes resulted in 15.0 (95% CI, 11.2-20.4) visits and 13.2 (95% CI, 9.9-18.0) antibiotic prescriptions annually per 1000 children. PCV15/20-additional serotypes account for 0.4% (95% CI, 0.2%-0.6%) and 2.1% (95% CI, 1.5%-3.0%) of pediatric outpatient antibiotic use. CONCLUSIONS: Compared with PCV15-additional serotypes, PCV20-additional serotypes account for > 5 times the burden of visits and antibiotic prescriptions. Higher-valency PCVs, especially PCV20, may contribute to preventing pediatric pneumococcal respiratory infections and antibiotic use.

Mozambique is making progress towards elimination of trachoma as a public health problem, but in some districts trachomatous inflammation-follicular (TF) prevalence remains above the 5% elimination threshold despite years of various interventions, including antibiotic mass drug administration. To characterize transmission in four districts, we incorporated testing of ocular infection and serology into routine trachoma impact surveys (TIS) in August 2022. We examined residents aged ≥ 1 year for trachoma and collected information on household water, sanitation, and hygiene. Among children aged 1-9 years, we tested conjunctival swabs for Chlamydia trachomatis nucleic acid and dried blood spots for C. trachomatis antibodies. We modeled age-dependent seroprevalence to estimate seroconversion rate (SCR). We examined 4841 children aged 1-9 years. TF prevalence ranged between 1.1 and 6.0% with three districts below the 5% threshold. PCR-confirmed infection prevalence ranged between 1.1 and 4.8%, and Pgp3 seroprevalence ranged between 8.8 and 24.3%. Pgp3 SCR was 1.9 per 100 children per year in the district with the lowest TF prevalence. Two other districts with TF

OBJECTIVES: This study aimed to evaluate pulmonary diffusing capacity for nitric oxide (DLNO) and pulmonary diffusing capacity for carbon monoxide (DLCO) in Mexican Hispanics born and raised at 2240 m altitude (midlanders) compared with those born and raised at sea level (lowlanders). It also aimed to assess the effectiveness of race-specific reference equations for pulmonary diffusing capacity (white people vs Mexican Hispanics) in minimising root mean square errors (RMSE) compared with race-neutral equations. METHODS: DLNO, DLCO, alveolar volume (VA) and gas transfer coefficients (KNO and KCO) were measured in 392 Mexican Hispanics (5 to 78 years) and compared with 1056 white subjects (5 to 95 years). Reference equations were developed using segmented linear regression (DLNO, DLCO and VA) and multiple linear regression (KNO and KCO) and validated with Least Absolute Shrinkage and Selection Operator. RMSE comparisons between race-specific and race-neutral models were conducted using repeated k-fold cross-validation and random forests. RESULTS: Midlanders exhibited higher DLCO (mean difference: +4 mL/min/mm Hg), DLNO (mean difference: +7 mL/min/mm Hg) and VA (mean difference: +0.17 L) compared with lowlanders. The Bayesian information criterion favoured race-specific models and excluding race as a covariate increased RMSE by 61% (DLNO), 18% (DLCO) and 4% (KNO). RMSE values for VA and KCO were comparable between race-specific and race-neutral models. For DLCO and DLNO, race-neutral equations resulted in 3% to 6% false positive rates (FPRs) in Mexican Hispanics and 20% to 49% false negative rates (FNRs) in white subjects compared with race-specific equations. CONCLUSIONS: Mexican Hispanics born and raised at 2240 m exhibit higher DLCO and DLNO compared with lowlanders. Including race as a covariate in reference equations lowers the RMSE for DLNO, DLCO and KNO and reduces FPR and FNR compared with race-neutral models. This study highlights the need for altitude-specific and race-specific reference equations to improve pulmonary function assessments across diverse populations.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) that affects approximately 4% of males and 1% of females in the United States. While causes of ASD are multi-factorial, single rare genetic variants contribute to around 20% of cases. Here, we report a case series of seven unrelated probands (6 males, 1 female) with ASD or another variable NDD phenotype attributed to de novo heterozygous loss of function or missense variants in the gene LARP1 (La ribonucleoprotein 1). LARP1 encodes an RNA-binding protein that post-transcriptionally regulates the stability and translation of thousands of mRNAs, including those regulating cellular metabolism and metabolic plasticity. Using lymphocytes collected and immortalized from an index proband who carries a truncating variant in one allele of LARP1, we demonstrated that lower cellular levels of LARP1 protein cause reduced rates of aerobic respiration and glycolysis. As expression of LARP1 increases during neurodevelopment, with higher levels in neurons and astrocytes, we propose that LARP1 haploinsufficiency contributes to ASD or related NDDs through attenuated metabolic activity in the developing fetal brain.

BACKGROUND: Malaria prevention and control strategies have been hampered by urbanization and the spread of Anopheles stephensi. The spread of this vector into Africa further complicates the already complex malaria situation, that could put about 126 million Africans at risk of infection. Hence, this study aimed to assess the determinants of urban malaria, focusing on the role of urbanization and the distribution of An. stephensi in Eastern Ethiopia. METHODS: A matched case control study was conducted among febrile urban residents of Dire Dawa (malaria positive as cases and negative as a control). A capillary blood sample was collected for parasite identification using microscopic examination and an interviewer administered questionnaire was used to collect additional data. Centers for Disease Control and Prevention miniature light traps (CDC-LT) and Prokopack aspirator were used to collect adult mosquito vectors from the selected cases and control houses to identify the mosquito vector species. Then, the data were exported to STATA for analysis. Conditional logistic regression was done to identify determinants, and principal component Analysis (PCA) was done for some independent variables. RESULTS: This study enrolled 132 cases and 264 controls from urban setting only. Of the 132 cases, 90 cases were positive for Plasmodium falciparum, 34 were positive for Plasmodium vivax and 8 had mixed infections. All cases and controls were similar with regard to their respective age and sex. Travel history (AOR: 13.1, 95% CI 2.8-61.4), presence of eves and holes on walls (AOR: 2.84, 95% CI 1.5-5.5), history of malaria diagnosis (AOR: 2.4, 95% CI 1.1-5.3), owning any livestock (AOR: 7.5, 95% CI 2.4-22.8), presence of stagnant water in the area (AOR: 3.2, 95% CI 1.7-6.1), sleeping under bed net the previous night (AOR: 0.21, 95% CI 0.1-0.6) and knowledge on malaria and its prevention (AOR: 2.2, 95% CI 1.2-4.1) were determinants of urban malaria infection. About 34 adult Anopheles mosquitoes were collected and identified from those selected cases and control houses and 27 of them were identified as An. stephensi. CONCLUSION: Among the cases, the dominant species were P. falciparum. This study identified travel history, house condition, past infection, livestock ownership, stagnant water, bed net use, and malaria knowledge as determinants of infection. This study also found the dominance of the presence of An. stephensi among the collected mosquito vectors. This suggests that the spread of An. stephensi may be impacting malaria infection in the study area. Hence, strengthening urban-targeted malaria interventions should be enhanced to prevent and control further urban malaria infection and spread.

Seasonal influenza epidemics result in high levels of healthcare utilization. Vaccination is an effective strategy to reduce the influenza-related burden of disease. However, reporting vaccine effectiveness does not convey the population impacts of influenza vaccination. We aimed to calculate the burden of influenza-related hospitalizations and emergency department (ED) attendance averted by influenza vaccination in Victoria, Australia, from 2017 to 2019, and associated economic savings. We applied a compartmental model to hospitalizations and ED attendances with influenza-specific, and pneumonia and influenza (P&I) with the International Classification of Diseases, 10th Revision, Australian Modification (ICD-10-AM) diagnostic codes of J09-J11 and J09-J18, respectively. We estimated an annual average of 7657 (120 per 100000 population) hospitalizations and 20560 (322 per 100000 population) ED attendances over the study period, associated with A$85 million hospital expenditure. We estimated that influenza vaccination averted an annual average of 1182 [range: 556 - 2277] hospitalizations and 3286 [range: 1554 - 6257] ED attendances and reduced the demand for healthcare services at the influenza season peak. This equated to approximately A13 [range: A6 - A25] million of savings over the study period. Calculating the burden averted is feasible in Australia and auseful approach to demonstrate the health and economic benefits of influenza vaccination.

BACKGROUND/OBJECTIVES: School meals are an important source of nutrition for children and have been found to help mitigate food insecurity. This study evaluated the association between food insecurity and school meal participation and whether parental perceptions about school meals differ by food security status. METHODS: In May 2022, 1110 Californian parents of K-12 students shared their perceptions about school meals, including meal quality, healthiness, stigma, and benefits, as well as their childs participation in school meals, in an online survey. Household food security was determined using the USDA 6-item module. Logistic and Poisson regression models were used for analysis. RESULTS: The prevalence of household food insecurity was 56.2% (69.6% in households of students eligible for free meals, 55.9% in reduced-price, and 38.3% in non-eligible). Many of the reported benefits of school meals (saving families money and time) were equally highly endorsed by parents with and without food insecurity (p > 0.05). Parents reporting food insecurity had less favorable perceptions of school meals and perceived more stigma (p < 0.05). Food insecurity was positively associated with breakfast participation, especially among elementary school students and students not eligible for free or reduced-price meals (FRPMs) (p < 0.05). CONCLUSIONS: Food insecurity is prevalent among California families with school-age children, even in families not eligible for federal FRPMs. Food-insecure households have more negative perceptions of school meals and experience more stigma, though they also report higher breakfast participation. Improving school meal quality and appeal, ensuring parents are familiar with meal quality and healthfulness, and reducing stigma may ease food insecurity while improving childrens health.

School nurses are pivotal to the safety of school-aged children, particularly those who receive medications in the school setting. The purpose of this study was to explore factors associated with medication administration errors in North Carolina school districts between 2012/2013 and 2017/2018. A longitudinal study using repeated measures analysis of school health services data collected in the North Carolina Annual School Health Services and Programs Survey was conducted. Over time, the number of medication errors (p = .001) and number of medication corrective action plans (p

INTRODUCTION: Reducing cardiopulmonary bypass (CPB) induced inflammatory injury is a potentially important strategy for children undergoing multiple operations for single ventricle palliation. We sought to characterize the soluble receptor for advanced glycation end products (sRAGE), a protein involved in acute lung injury and inflammation, in pediatric patients with congenital heart disease and hypothesized that patients undergoing single ventricle palliation would have higher levels of sRAGE following bypass than those with biventricular physiologies. METHODS: This was a prospective, observational study of children undergoing CPB. Plasma samples were obtained before and after bypass. sRAGE levels were measured and compared between those with biventricular and single ventricle heart disease using descriptive statistics and multivariate analysis for risk factors for lung injury. RESULTS: sRAGE levels were measured in 40 patients: 19 with biventricular and 21 with single ventricle heart disease. Children undergoing single ventricle palliation had a higher factor and percent increase in sRAGE levels when compared to patients with biventricular circulations (4.6 vs. 2.4, p = 0.002) and (364% vs. 181%, p = 0.014). The factor increase in sRAGE inversely correlated with the patients preoperative oxygen saturation (Pearson correlation (r) = -0.43, p = 0.005) and was positively associated with red blood cell transfusion (coefficient = 0.011; 95% CI: 0.004, 0.017; p = 0.001). CONCLUSIONS: Children with single ventricle physiology have greater increase in sRAGE following CPB as compared to children undergoing biventricular repair. Larger studies delineating the role of sRAGE in children undergoing single ventricle palliation may be beneficial in understanding how to prevent complications in this high-risk population.

Malaria-elimination interventions aim to extinguish hotspots and prevent transmission to nearby areas. Here, we re-analyzed a cluster-randomized trial of reactive, focal interventions (chemoprevention using artemether-lumefantrine and/or indoor residual spraying with pirimiphos-methyl) delivered within 500 m of confirmed malaria index cases in Namibia to measure direct effects (among intervention recipients within 500 m) and spillover effects (among non-intervention recipients within 3 km) on incidence, prevalence and seroprevalence. There was no or weak evidence of direct effects, but the sample size of intervention recipients was small, limiting statistical power. There was the strongest evidence of spillover effects of combined chemoprevention and indoor residual spraying. Among non-recipients within 1 km of index cases, the combined intervention reduced malaria incidence by 43% (95% confidence interval, 20-59%). In analyses among non-recipients within 3 km of interventions, the combined intervention reduced infection prevalence by 79% (6-95%) and seroprevalence, which captures recent infections and has higher statistical power, by 34% (20-45%). Accounting for spillover effects increased the cost-effectiveness of the combined intervention by 42%. Targeting hotspots with combined chemoprevention and vector-control interventions can indirectly benefit non-recipients up to 3 km away.

Outbreaks of monkeypox (mpox) have historically resulted from zoonotic spillover of clade I monkeypox virus (MPXV) in Central Africa and clade II MPXV in West Africa. In 2022, subclade IIb caused a global epidemic linked to transmission through sexual contact. Here we describe the epidemiological and genomic features of an mpox outbreak in a mining region in eastern Democratic Republic of the Congo, caused by clade I MPXV. Surveillance data collected between September 2023 and January 2024 identified 241 suspected cases. Genomic analysis demonstrates a distinct clade I lineage divergent from previously circulating strains in the Democratic Republic of the Congo. Of the 108 polymerase chain reaction-confirmed mpox cases, the median age of individuals was 22 years, 51.9% were female and 29% were sex workers, suggesting a potential role for sexual transmission. The predominance of APOBEC3-type mutations and the estimated emergence time around mid-September 2023 imply recent sustained human-to-human transmission.

BackgroundDespite elevated rates of trauma exposure, substance misuse, mental health problems, and suicide, systems-impacted teens and their caregivers have limited access to empirically supported behavioral health services. Family-based interventions are the most effective for improving mental health, education, substance use, and delinquency outcomes, yet the familial and placement disruption that occurs during child welfare involvement can interfere with the delivery of family-based interventions.ObjectiveTo address this gap in access to services, we adapted an in-person, empirically supported, family-based affect management intervention using a trauma-informed lens to be delivered via telehealth to families impacted by the child welfare system (Family Telehealth Project). We describe the intervention adaptation process and an open trial to evaluate its feasibility, acceptability, and impact.MethodsAdaptations to the in-person, family-based affect management intervention were conducted iteratively with input from youth, caregivers, and systems partners. Through focus groups and collaborative meetings with systems partners, a caregiver-only version of the intervention was also developed. An open trial of the intervention was conducted to assess family perspectives of its acceptability and feasibility and inform further refinements prior to a larger-scale evaluation. Participants included English-speaking families involved in the child welfare system in the past 12 months with teens (aged 12-18 years). Caregivers were eligible to participate either individually (caregivers of origin, kinship caregivers, or foster parents; n=7) or with their teen (caregiver of origin only; n=6 dyads). Participants completed session feedback forms and surveys at pretreatment, posttreatment, and 3-month posttreatment time points. Qualitative exit interviews were conducted with a subset of participants (12/19, 63%) to further understand their experiences with the intervention.ResultsSession attendance was high, and both caregivers and teens reported high acceptability of clinicians and sessions on feedback forms. Families were comfortable with video technology, with very few (

OBJECTIVE: To evaluate the reliability, responsiveness, and validity of the Scale for the Assessment and Rating of Ataxia (SARA) in patients with lysosomal storage disorders (LSDs) who present with neurological symptoms, and quantify the threshold for a clinically meaningful change. METHODS: We analyzed data from three clinical trial cohorts (IB1001-201, IB1001-202, and IB1001-301) of patients with Niemann-Pick disease type C (NPC) and GM2 Gangliosidoses (Tay-Sachs and Sandhoff disease) comprising 122 patients and 703 visits. Reproducibility was described as re-test reliability between repeat baseline visits or baseline and post-treatment washout visits. Responsiveness was determined in relation to the Investigators, Caregivers, and Patients Clinical Global Impression of Improvement (CGI-I). The CGI-I data was also used to quantify a threshold for a clinically meaningful improvement on the SARA scale. Using a qualitative methods approach, patient/caregiver interviews from the IB1001-301 trial were further used to assess a threshold of meaningful change as well as the breadth of neurological signs and symptoms captured and evaluated by the SARA scale. RESULTS: The Inter-Class Correlation (ICC) was 0.95 or greater for all three trials, indicating a high internal consistency/reliability. The mean change in SARA between repeat baseline and post-treatment washout visit assessments in all trials was -0.05, SD 1.98, i.e., minimal, indicating no significant differences, learning effects or other systematic biases. For the CGI-I responses and change in SARA scores, Area Under the Curve (AUC) values were 0.82, 0.71, and 0.77 for the Investigators, Caregivers, and Patients CGI-I respectively, indicating strong agreement. Further qualitative analyses of the patient/caregiver interviews demonstrated a 1-point or greater change on SARA to be a clinically meaningful improvement which is directly relevant to the patients everyday functioning and quality of life. Changes captured by the SARA were also paralleled by improvement in a broad range of neurological signs and symptoms and beyond cerebellar ataxia. CONCLUSION: Qualitative and quantitative data demonstrate the reliability and responsiveness of the SARA score as a valid measure of neurological signs and symptoms in LSDs with CNS involvement, such as NPC and GM2 Gangliosidoses. A 1-point change represents a clinically meaningful transition reflecting the gain or loss of complex function.

BACKGROUND: Provisional Tic Disorder (PTD) is common in childhood. The received wisdom among clinicians is that PTD is short-lived and mild, with at most a few tics, and rarely includes complex tics, premonitory phenomena or comorbid illnesses. However, such conclusions come from clinical experience, with biased ascertainment and limited follow-up. METHODS: Prospective study of 89 children with tics starting 0-9 months ago (median 4 months), fewer than half from clinical sources. Follow-up at 12 (± 24, 36, 48) months after the first tic. RESULTS: At study entry, many children had ADHD (39), an anxiety disorder (27), OCD (9) or enuresis (17). All had at least two current tics, with a mean total since onset of 6.9 motor and 2.0 phonic tics. Forty-one had experienced a complex tic, and 69 could suppress some tics. Tics were clinically meaningful: 64 had tics severe enough for a clinical trial, and 76 families sought medical attention for the tics. At 12 months, 79 returned, and 78 still had tics. Of these, 29 manifested no tics during history and extended examination, but only via audio-visual monitoring when the child was seated alone. Only 12/70 now had plans to see a doctor for tics. Most who returned at 2-4 years still had tics known to the child and family, but medical impact was low. CONCLUSIONS: Our results do not contradict previous data, but overturn clinical lore. The data strongly argue against the longstanding but arbitrary tradition of separating tic disorders into recent-onset versus chronic.

The fundamental organization of the human brain is established before birth, with rapid growth continuing over the first postnatal years. Children exposed before or after birth to various biological (e.g., substance exposure) or psychosocial hazards (e.g., maltreatment) are at elevated likelihood of deviating from a typical developmental trajectory, which in turn can be associated with psychological, behavioral, and physical health sequelae. In the HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, brain, physical, biological, cognitive, behavioral, social, and emotional development is being examined starting in pregnancy and planned through age 10 (data are sampled at varying degrees of granularity depending on age, with more dense sampling earlier in life). HBCD aims to determine the short- and long-term impacts of a variety of both harmful and protective factors, including prenatal substance use, on developmental trajectories through early childhood. Organized as a nationwide consortium across 27 sites, the HBCD Study will collect multimodal data that will be made publicly available on a yearly basis, through a data use application and approval process. Here we provide an overview of the HBCD Study design, sampling, protocol development, and data management. Data collected through HBCD will be fundamental to informing future prenatal and early childhood interventions and policies to promote wellbeing and resilience in all children.

PURPOSE: In the past few decades, the prevalence of myopia, where the eye grows too long, has increased dramatically. The visual environment appears to be critical to regulating the eye growth. Thus, it is very important to determine the properties of the environment that put children at risk for myopia. Researchers have suggested that the intensity of illumination and range of distances to which a childs eyes are exposed are important, but this has not been confirmed. METHODS: We designed, built, and tested an inexpensive, child-friendly, head-mounted device that can measure the intensity and spectral content of illumination approaching the eyes and can also measure the distances to which the central visual field of the eyes are exposed. The device is mounted on a childs bicycle helmet. It includes a camera that measures distances over a substantial range and a six-channel spectral sensor. The sensors are hosted by a light-weight, battery-powered microcomputer. We acquired pilot data from children while they were engaged in various indoor and outdoor activities. RESULTS: The device proved to be comfortable, easy, and safe to wear, and able to collect very useful data on the statistics of illumination and distances. CONCLUSIONS: The designed device is an ideal tool to be used in a population of young children, some of whom will later develop myopia and some of whom will not. TRANSLATIONAL RELEVANCE: Such data would be critical for determining the properties of the visual environment that put children at risk for becoming myopic.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The HBCD Study aims to reflect the sociodemographic diversity of pregnant individuals in the U.S. The study will also oversample individuals who use substances during pregnancy and enroll similar individuals who do not use to allow for generalizable inferences of the impact of prenatal substance use on trajectories of child development. Without probability sampling or a randomization-based design, the study requires innovation during enrollment, close monitoring of group differences, and rigorous evaluation of external and internal validity across the enrollment period. In this article, we discuss the HBCD Study recruitment and enrollment data collection processes and potential analytic strategies to account for sources of heterogeneity and potential bias. First, we introduce the adaptive design and enrollment monitoring indices to assess and enhance external and internal validity. Second, we describe the visit schedule for in-person and remote data collection where dyads are randomly assigned to visit windows based on a jittered design to optimize longitudinal trajectory estimation. Lastly, we provide an overview of analytic procedures planned for estimating trajectories.

Child abuse has intergenerational consequences for psychopathology, however, there remains a paucity of research regarding how these experiences affect Latinx families, particularly those at risk for additional negative life events, such as racial discrimination. This study aims to contribute to this gap in the literature by examining the impact maternal child abuse exposure has on youth and maternal psychopathology, as well as whether these associations are moderated by racial discrimination, in a sample of 224 Latinx mother-youth dyads. Hierarchical regressions revealed small but significant maternal child abuse exposure x racial discrimination interactions for youth depression and anxiety, but not maternal depression or anxiety, which were solely positively associated with maternal child abuse exposure. Findings highlight the multifarious, and at times convergent, nature of trauma and oppression among Latinx families, as well as the impact across generations. Future work is needed to further elucidate developmental pathways of intergenerational trauma in understudied populations.

PurposeTraumatic brain injury (TBI) and potentially traumatic events (PTEs) contribute to increased substance use, mental health issues, and cognitive impairments. However, there's not enough research on how TBI and PTEs combined impact mental heath, substance use, and neurocognition.MethodsThis study leverages a subset of The National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) multi-site dataset with 551 adolescents to assess the combined and distinctive impacts of TBI, PTEs, and TBI+PTEs (prior to age 18) on substance use, mental health, and neurocognitive outcomes at age 18.ResultsTBI, PTEs, and TBI+PTEs predicted greater lifetime substance use and past-year alcohol and cannabis use. PTEs predicted greater internalizing symptoms, while TBI+PTEs predicted greater externalizing symptoms. Varying effects on neurocognitive outcomes included PTEs influencing attention accuracy and TBI+PTEs predicting faster speed in emotion tasks. PTEs predicted greater accuracy in abstraction-related tasks. Associations with working memory were not detected.ConclusionThis exploratory study contributes to the growing literature on the complex interplay between TBI, PTEs, and adolescent mental health, substance use, and neurocognition. The developmental implications of trauma via TBIs and/or PTEs during adolescence are considerable and worthy of further investigation.

BACKGROUND: Malaria is a major disease burden in Ethiopia. Migration can influence malaria transmission dynamics, with individuals relocating from malaria-free highland regions to malarious lowlands potentially facing elevated risks of contracting malaria. Migrants may find it difficult to protect themselves against malaria and have limited access to diagnosis or treatment. Settlers in gold mining sites are one type of migrant and are often neglected in malaria research yet may have particularly high malaria risk. This study was a malaria prevalence survey among settlers in a new gold mining settlement in the highly malarious Gambella Region, Ethiopia. METHODS: n = 590 people were surveyed for demographic information and their knowledge and practices of malaria. Participants were tested for malaria using rapid diagnostic tests and microscopy. Using logistic regressions, the influence of demographic characteristics on malaria infections and bed net access were analysed. A sub-sample of participants was interviewed to comprehend settlement living conditions and healthcare accessibility. RESULTS: The overall prevalence of Plasmodium falciparum was 37.5% (CI 32.4-42.3%). Young children were most likely to have malaria, with individuals aged 15-24 having 67% lower odds (aOR: 0.33; CI 0.13-0.86) of infection compared to those aged 1-4 years old. Meanwhile, those age 25-plus had 75% decreased odds of malaria infection (aOR 0.25; CI 0.10-0.65). Individuals with bed nets had ~ 50% decreased odds of testing positive for falciparum malaria than those reporting having no bed net (aOR: 0.47; CI 0.22-0.97). Individuals who relocated from low elevation with high malaria test positivity rate areas were more prone to testing positive for malaria, as were those residing in densely populated households with multiple malaria cases. Conversely, individuals from higher elevations with low malaria test positivity rates, and those living in households with 5-10 occupants and

BACKGROUND: Phenotypic heterogeneity in early language, intellectual, motor, and adaptive functioning (LIMA) features are amongst the most striking features that distinguish different types of autistic individuals. Yet the current diagnostic criteria uses a single label of autism and implicitly emphasizes what individuals have in common as core social-communicative and restricted repetitive behavior difficulties. Subtype labels based on the non-core LIMA features may help to more meaningfully distinguish types of autisms with differing developmental paths and differential underlying biology. METHODS: Unsupervised data-driven subtypes were identified using stability-based relative clustering validation on publicly available Mullen Scales of Early Learning (MSEL) and Vineland Adaptive Behavior Scales (VABS) data (n = 615; age = 24-68 months) from the National Institute of Mental Health Data Archive (NDA). Differential developmental trajectories between subtypes were tested on longitudinal data from NDA and from an independent in-house dataset from UCSD. A subset of the UCSD dataset was also tested for subtype differences in functional and structural neuroimaging phenotypes and relationships with blood gene expression. The current subtyping model was also compared to early language outcome subtypes derived from past work. RESULTS: Two autism subtypes can be identified based on early phenotypic LIMA features. These data-driven subtypes are robust in the population and can be identified in independent data with 98% accuracy. The subtypes can be described as Type I versus Type II autisms differentiated by relatively high versus low scores on LIMA features. These two types of autisms are also distinguished by different developmental trajectories over the first decade of life. Finally, these two types of autisms reveal striking differences in functional and structural neuroimaging phenotypes and their relationships with gene expression and may highlight unique biological mechanisms. LIMITATIONS: Sample sizes for the neuroimaging and gene expression dataset are relatively small and require further independent replication. The current work is also limited to subtyping based on MSEL and VABS phenotypic measures. CONCLUSIONS: This work emphasizes the potential importance of stratifying autism by a Type I versus Type II distinction focused on LIMA features and which may be of high prognostic and biological significance.

Cash transfer policies have been widely discussed as mechanisms to curb intergenerational transmission of socioeconomic disadvantage. In this paper, we take advantage of a large casino-funded family transfer program introduced in a Southeastern American Indian Tribe to generate difference-in-difference estimates of the link between childrens cash transfer exposure and third grade math and reading test scores of their offspring. Here we show greater math (0.25 standard deviation [SD], p =.0148, 95% Confidence Interval [CI]: 0.05, 0.45) and reading (0.28 SD, p = .0066, 95% CI: 0.08, 0.49) scores among American Indian students whose mother was exposed ten years longer than other American Indian students to the cash transfer during her childhood (or relative to the non-American Indian student referent group). Exploratory analyses find that a mothers decision to pursue higher education and delay fertility appears to explain some, but not all, of the relation between cash transfers and childrens test scores. In this rural population, large cash transfers have the potential to reduce intergenerational cycles of poverty-related educational outcomes.

BACKGROUND: Extending the dosing interval of a primary series of mRNA COVID-19 vaccination has been employed to reduce myocarditis risk in adolescents, but previous evaluation of impact on vaccine effectiveness (VE) is limited to risk after second dose. METHODS: We quantified the impact of the dosing interval based on case notifications and vaccination uptake in Hong Kong from January to April 2022, based on calendar-time proportional hazards models and matching approaches. RESULTS: We estimated that the hazard ratio (HR) and odds ratio (OR) of infections after the second dose for extended (28 days or more) versus regular (21-27 days) dosing intervals ranged from 0.86 to 0.99 from calendar-time proportional hazards models, and from 0.85 to 0.87 from matching approaches, respectively. Adolescents in the extended dosing groups (including those who did not receive a second dose in the study period) had a higher hazard of infection than those with a regular dosing interval during the intra-dose period (HR 1.66; 95% CI 1.07, 2.59; p = 0.02) after the first dose. CONCLUSIONS: Implementing an extended dosing interval should consider multiple factors including the degree of myocarditis risk, the degree of protection afforded by each dose, and the extra protection achievable using an extended dosing interval.

Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), viral infections, and bacterial infections. We developed machine learning models based on these cfRNA profiles, which effectively differentiated KD from MIS-C-two conditions presenting with overlapping symptoms-with high performance [test area under the curve = 0.98]. We further extended this methodology into a multiclass machine learning framework that achieved 80% accuracy in distinguishing among KD, MIS-C, viral, and bacterial infections. We further demonstrated that cfRNA profiles can be used to quantify injury to specific tissues and organs, including the liver, heart, endothelium, nervous system, and the upper respiratory tract. Overall, this study identified cfRNA as a versatile analyte for the differential diagnosis and characterization of a wide range of pediatric inflammatory syndromes.

BACKGROUND: Fragile X syndrome (FXS) and autism spectrum disorder (ASD) are neurodevelopmental conditions that often have a substantial impact on daily functioning and quality of life. FXS is the most common cause of inherited intellectual disability (ID) and the most common monogenetic cause of ASD. Previous literature has shown that electrophysiological activity measured by electroencephalogram (EEG) during resting state is perturbated in FXS and ASD. However, whether electrophysiological profiles of participants with FXS and ASD are similar remains unclear. The aim of this study was to compare EEG alterations found in these two clinical populations presenting varying degrees of cognitive and behavioral impairments. METHODS: Resting state EEG signal complexity, alpha peak frequency (APF) and power spectral density (PSD) were compared between 47 participants with FXS (aged between 5-20), 49 participants with ASD (aged between 6-17), and 52 neurotypical (NT) controls with a similar age distribution using MANCOVAs with age as covariate when appropriate. MANCOVAs controlling for age, when appropriate, and nonverbal intelligence quotient (NVIQ) score were subsequently performed to determine the impact of cognitive functioning on EEG alterations. RESULTS: Our results showed that FXS participants manifested decreased signal complexity and APF compared to ASD participants and NT controls, as well as altered power in the theta, alpha and low gamma frequency bands. ASD participants showed exaggerated beta power compared to FXS participants and NT controls, as well as enhanced low and high gamma power compared to NT controls. However, ASD participants did not manifest altered signal complexity or APF. Furthermore, when controlling for NVIQ, results of decreased complexity in higher scales and lower APF in FXS participants compared to NT controls and ASD participants were not replicated. CONCLUSIONS: These findings suggest that signal complexity and APF might reflect cognitive functioning, while altered power in the low gamma frequency band might be associated with neurodevelopmental conditions, particularly FXS and ASD.

Konzo is a neglected paralytic neurological disease associated with food (cassava) poisoning that affects the worlds poorest children and women of childbearing ages across regions of sub-Saharan Africa. Despite understanding the dietary factors that lead to konzo, the molecular markers and mechanisms that trigger this disease remain unknown. To identify potential protein biomarkers associated with a disease status, plasma was collected from two independent Congolese cohorts, a discovery cohort (n = 60) and validation cohort (n = 204), sampled 10 years apart and subjected to multiple high-throughput assays. We identified that Glutathione Peroxidase 3 (GPx3), a critical plasma-based antioxidant enzyme, was the sole protein examined that was both significantly and differentially abundant between affected and non-affected participants in both cohorts, with large reductions observed in those affected with konzo. Our findings raise the notion that reductions in key antioxidant mechanisms may be the biological risk factor for the development of konzo, particularly those mediated through pathways involving the glutathione peroxidase family.

Single-dose azithromycin is being considered by the WHO as an intervention for prevention of child mortality. However, concerns have emerged related to longer term unintended consequences of early life antibiotic use, particularly among infants. We conducted a long-term follow-up in a random sample of children who had been enrolled in a trial of neonatal azithromycin versus placebo for prevention of mortality to assess whether neonatal azithromycin exposure led to differences in child growth up to 4 years of age. We found no evidence of a difference in any anthropometric outcome among children who had received a single oral dose of azithromycin compared with placebo during the neonatal period. These results do not support long-term growth-promoting or deleterious effects of early life azithromycin exposure.