Community-Based Cluster-Randomized Trial to Reduce Opioid Overdose Deaths.

BACKGROUND: Evidence-based practices for reducing opioid-related overdose deaths include overdose education and naloxone distribution, the use of medications for the treatment of opioid use disorder, and prescription opioid safety. Data are needed on the effectiveness of a community-engaged intervention to reduce opioid-related overdose deaths through enhanced uptake of these practices. METHODS: In this community-level, cluster-randomized trial, we randomly assigned 67 communities in Kentucky, Massachusetts, New York, and Ohio to receive the intervention (34 communities) or a wait-list control (33 communities), stratified according to state. The trial was conducted within the context of both the coronavirus disease 2019 (Covid-19) pandemic and a national surge in the number of fentanyl-related overdose deaths. The trial groups were balanced within states according to urban or rural classification, previous overdose rate, and community population. The primary outcome was the number of opioid-related overdose deaths among community adults. RESULTS: During the comparison period from July 2021 through June 2022, the population-averaged rates of opioid-related overdose deaths were similar in the intervention group and the control group (47.2 deaths per 100,000 population vs. 51.7 per 100,000 population), for an adjusted rate ratio of 0.91 (95% confidence interval, 0.76 to 1.09; P = 0.30). The effect of the intervention on the rate of opioid-related overdose deaths did not differ appreciably according to state, urban or rural category, age, sex, or race or ethnic group. Intervention communities implemented 615 evidence-based practice strategies from the 806 strategies selected by communities (254 involving overdose education and naloxone distribution, 256 involving the use of medications for opioid use disorder, and 105 involving prescription opioid safety). Of these evidence-based practice strategies, only 235 (38%) had been initiated by the start of the comparison year. CONCLUSIONS: In this 12-month multimodal intervention trial involving community coalitions in the deployment of evidence-based practices to reduce opioid overdose deaths, death rates were similar in the intervention group and the control group in the context of the Covid-19 pandemic and the fentanyl-related overdose epidemic. (Funded by the National Institutes of Health; HCS ClinicalTrials.gov number, NCT04111939.).

Overlapping neural correlates underpin theory of mind and semantic cognition: Evidence from a meta-analysis of 344 functional neuroimaging studies.

Key unanswered questions for cognitive neuroscience include whether social cognition is underpinned by specialised brain regions and to what extent it simultaneously depends on more domain-general systems. Until we glean a better understanding of the full set of contributions made by various systems, theories of social cognition will remain fundamentally limited. In the present study, we evaluate a recent proposal that semantic cognition plays a crucial role in supporting social cognition. While previous brain-based investigations have focused on dissociating these two systems, our primary aim was to assess the degree to which the neural correlates are overlapping, particularly within two key regions, the anterior temporal lobe (ATL) and the temporoparietal junction (TPJ). We focus on activation associated with theory of mind (ToM) and adopt a meta-analytic activation likelihood approach to synthesise a large set of functional neuroimaging studies and compare their results with studies of semantic cognition. As a key consideration, we sought to account for methodological differences across the two sets of studies, including the fact that ToM studies tend to use nonverbal stimuli while the semantics literature is dominated by language-based tasks. Overall, we observed consistent overlap between the two sets of brain regions, especially in the ATL and TPJ. This supports the claim that tasks involving ToM draw upon more general semantic retrieval processes. We also identified activation specific to ToM in the right TPJ, bilateral anterior mPFC, and right precuneus. This is consistent with the view that, nested amongst more domain-general systems, there is specialised circuitry that is tuned to social processes.

Conceptual framework for preterm birth review in San Francisco.

Preterm birth persists as a leading cause of infant mortality and morbidity despite decades of intervention effort. Intervention null effects may reflect failure to account for social determinants of health (SDH) or jointly acting risk factors. In some communities, persistent preterm birth trends and disparities have been consistently associated with SDH such as race/ethnicity, zip code, and housing conditions. Health authorities recommend conceptual frameworks for targeted action on SDH and precision public health approaches for preterm birth prevention. We document San Francisco, California's experience identifying the need, rationale, methods, and pilot work for developing a conceptual framework for preterm birth review (PTBR) in San Francisco. The PTBR conceptual framework is intended to enable essential public health services in San Francisco that prevent a range of preterm birth phenotypes by guiding plans for data collection, hypothesis testing, analytical methods, reports, and intervention strategy. Key elements of the PTBR conceptual framework are described including, 10 domains of SDH, 9 domains at the whole person level, such as lived experience and health behaviors, 8 domains at the within-person level, such as biomarkers and clinical measures, 18 preterm birth phenotypes, and the interconnections between domains. Assumptions for the PTBR conceptual framework were supported by a scoping review of literature on SDH effects on preterm birth, health authority consensus reports, and PTBR pilot data. Researcher and health authority interest in each of the domains warrants the framework to prompt systematic consideration of variables in each proposed domain. PTBR pilot data, illustrated in heatmaps, confirm the feasibility of data collection based on the framework, prevalence of co-occurring risk factors, potential for joint effects on specific preterm birth phenotypes, and opportunity for intervention to block SDH effects on preterm birth. The proposed PTBR conceptual framework has practical implications for specifying (1) population groups at risk, (2) grids or heatmap visualization of risk factors, (3) multi-level analyses, and (4) multi-component intervention design in terms of patterns of co-occurring risk factors. Lessons learned about PTBR data collection logistics, variable choice, and data management will be incorporated into future work to build PTBR infrastructure based on the PTBR conceptual framework.

Association of antenatal or neonatal SARS-COV-2 exposure with developmental and respiratory outcomes, and healthcare usage in early childhood: a national prospective cohort study.

Background: Perinatal exposure to SARS-CoV-2 may affect neurodevelopment before 12 months of age, but longer-term outcomes remain unknown. We examined whether antenatal or neonatal SARS-CoV-2 exposure compared with non-exposure is associated with neurodevelopment, respiratory symptoms, and health care usage in early childhood. Methods: This prospective national population-based cohort study was conducted in England and Wales, United Kingdom. We enrolled term-born children (≥37 weeks' gestation) with and without antenatal or neonatal exposure to SARS-CoV-2 infection by approaching parents of eligible children who were cared for in 87 NHS hospitals. Potential participants were identified through the national active surveillance studies of pregnant women and newborn infants hospitalised with confirmed SARS-CoV-2 infection conducted through the UK Obstetric Surveillance System and the British Paediatric Surveillance Unit. We defined antenatal and neonatal SARS-CoV-2 exposure as infants born to mothers hospitalised with confirmed SARS-CoV-2 infection between 14 + 0 and 36 + 6 weeks gestation and infants admitted to hospital with confirmed SARS-CoV-2 infection within the first 28 days after birth. Children born preterm or with major congenital anomaly or who were not residing in the UK were excluded. We assessed children's development (Ages and Stages Questionnaire 3rd Edition (ASQ-3); Ages and Stages Questionnaire Social-Emotional 2nd Edition (ASQ:SE-2)), respiratory symptoms (Liverpool Respiratory Symptom Questionnaire (LRSQ)) and health care usage (parent-completed questionnaire) at 21-32 months of age. Primary outcome: total ASQ-3 score, converted to z-scores. Secondary outcomes: ASQ:SE-2 z-scores; risk of delay in ASQ-3 domains; total LRSQ scores, converted to z-scores. Analyses were adjusted for children's age, sex, maternal ethnicity, parental education, and index of multiple deprivation. Findings: Between October 20, 2021 and January 27, 2023, we approached 668 and 1877 families out of 712 and 1917 potentially eligible participants in the exposed and comparison cohort. Of the 125 and 306 participants who were enrolled to the exposed and comparison cohort 121 and 301 participants completed the questionnaires and 96 and 243 participants were included in the analysis. In the age adjusted analysis, the mean total ASQ-3 z-score was lower in the exposed than the comparison cohort (-0.3, 95% CI: -0.6 to -0.05), however, when adjusted for sex, parental education, ethnicity and IMD quintile, there was no significant difference (difference in mean z-score = -0.2 95% CI: -0.5 to 0.03). SARS-CoV-2 exposure was associated with increased risk of delayed personal-social skills (odds ratio = 3.81; 95% CI: 1.07-13.66), higher ASQ:SE-2 total z-scores (difference in mean z-score = 0.4; 95% CI: 0.2-0.6) and increased risk of delayed social-emotional development (OR = 3.58, 95% CI: 1.30-9.83), after adjusting for sex, age at assessment, parental education, ethnicity and IMD quintile. The exposed cohort had a higher mean total LRSQ z-score than the comparison cohort (0.3 95% CI: 0-0.6) and higher inpatient (38% vs. 21%, p = 0.0001), outpatient (38% vs. 30%, p = 0.0090), and General Practitioner appointments (60% vs. 50%, p = 0.021) than the comparison cohort, after adjusting for sex, age at assessment, parental education, ethnicity and IMD quintile. No differences in other secondary outcomes between the exposed and comparison cohorts were found. Interpretation: Although the exposed cohort did not differ from the comparison cohort on the primary outcome, total ASQ-3 score, the exposed cohort were at greater risk of delayed social-emotional development, had a greater prevalence of respiratory symptoms and increased health care usage relative to the comparison cohort. The study is limited by the smaller sample size due to the low response rate and lack of clinical developmental assessments. Given the association of poor social-emotional development with antenatal or neonatal SARS-CoV-2 exposure, developmental screening, and follow-up of children with confirmed antenatal or neonatal SARS-CoV-2 infection may be warranted to identify those in need of early intervention. Funding: Action Medical Research for Children.

Time-to-Event Genome-Wide Association Study for Incident Cardiovascular Disease in People With Type 2 Diabetes.

OBJECTIVE: To identify genetic risk factors for incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We conducted a multiancestry time-to-event genome-wide association study for incident CVD among people with T2D. We also tested 204 known coronary artery disease (CAD) variants for association with incident CVD. RESULTS: Among 49,230 participants with T2D, 8,956 had incident CVD events (event rate 18.2%). We identified three novel genetic loci for incident CVD: rs147138607 (near CACNA1E/ZNF648, hazard ratio [HR] 1.23, P = 3.6 × 10-9), rs77142250 (near HS3ST1, HR 1.89, P = 9.9 × 10-9), and rs335407 (near TFB1M/NOX3, HR 1.25, P = 1.5 × 10-8). Among 204 known CAD loci, 5 were associated with incident CVD in T2D (multiple comparison-adjusted P < 0.00024, 0.05/204). A standardized polygenic score of these 204 variants was associated with incident CVD with HR 1.14 (P = 1.0 × 10-16). CONCLUSIONS: The data point to novel and known genomic regions associated with incident CVD among individuals with T2D.

Graded and sharp transitions in semantic function in left temporal lobe.

Recent work has focussed on how patterns of functional change within the temporal lobe relate to whole-brain dimensions of intrinsic connectivity variation (Margulies et al., 2016). We examined two such 'connectivity gradients' reflecting the separation of (i) unimodal versus heteromodal and (ii) visual versus auditory-motor cortex, examining visually presented verbal associative and feature judgments, plus picture-based context and emotion generation. Functional responses along the first dimension sometimes showed graded change between modality-tuned and heteromodal cortex (in the verbal matching task), and other times showed sharp functional transitions, with deactivation at the extremes and activation in the middle of this gradient (internal generation). The second gradient revealed more visual than auditory-motor activation, regardless of content (associative, feature, context, emotion) or task process (matching/generation). We also uncovered subtle differences across each gradient for content type, which predominantly manifested as differences in relative magnitude of activation or deactivation.

Fatty Acid Intake and Polyunsaturated Fatty Acid Biomarkers and Risk of Total Knee or Hip Arthroplasty Among Older Women in the Women's Health Initiative.

OBJECTIVE: The objective was to determine whether baseline fatty acid intake and erythrocyte omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) can predict risk of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in older women. METHODS: This was a prospective analysis of 34,990 women in the Women's Health Initiative. Dietary fatty acids were estimated from food frequency questionnaires. Imputed erythrocyte PUFAs were available in a subcohort of 3,428 women. Arthroplasty (THA and TKA), used as a surrogate of severe osteoarthritis, was identified via linked Medicare data. Cox proportional hazards models were constructed to estimate risk of arthroplasty. RESULTS: Risk of THA was associated with higher intake of arachidonic acid, (multivariable hazard ratio [HR] quartile 4 [Q4] vs Q1: 1.16; 95% confidence interval [CI] 1.01-1.34; P = 0.03) and higher intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA; HR Q4 vs Q1: 1.20; 95% CI 1.05-1.39; P = 0.003). There was a linear trend (P = 0.04) for patients to have a higher risk of THA with higher erythrocyte EPA and DHA in body mass index-adjusted models; however, there was no significant difference in patients who had THAs by quartiles of erythrocyte EPA and DHA (P = 0.10). Dietary fatty acids and erythrocyte PUFAs were not significantly associated with risk of TKA. CONCLUSION: Higher baseline intakes of arachidonic acid and EPA and DHA were associated with a modestly higher risk of THA. No association was found between fatty acids and patients who had TKAs. Further research in populations with direct measures of osteoarthritis severity is needed to better understand the importance of PUFAs in modulating osteoarthritis and arthroplasty risk.

Virome analysis of New Zealand's bats reveals cross-species viral transmission among the Coronaviridae.

The lesser short-tailed bat (Mystacina tuberculata) and the long-tailed bat (Chalinolobus tuberculatus) are Aotearoa New Zealand's only native extant terrestrial mammals and are believed to have migrated from Australia. Long-tailed bats arrived in New Zealand an estimated two million years ago and are closely related to other Australian bat species. Lesser short-tailed bats, in contrast, are the only extant species within the Mystacinidae and are estimated to have been living in isolation in New Zealand for the past 16-18 million years. Throughout this period of isolation, lesser short-tailed bats have become one of the most terrestrial bats in the world. Through a metatranscriptomic analysis of guano samples from eight locations across New Zealand, we aimed to characterise the viromes of New Zealand's bats and determine whether viruses have jumped between these species over the past two million years. High viral richness was observed among long-tailed bats with viruses spanning seven different viral families. In contrast, no bat-specific viruses were identified in lesser short-tailed bats. Both bat species harboured an abundance of likely dietary- and environment-associated viruses. We also identified alphacoronaviruses in long-tailed bat guano that had previously been identified in lesser short-tailed bats, suggesting that these viruses had jumped the species barrier after long-tailed bats migrated to New Zealand. Of note, an alphacoronavirus species discovered here possessed a complete genome of only 22,416 nucleotides with entire deletions or truncations of several non-structural proteins, thereby representing what may be the shortest genome within the Coronaviridae identified to date. Overall, this study has revealed a diverse range of novel viruses harboured by New Zealand's only native terrestrial mammals, in turn expanding our understanding of bat viral dynamics and evolution globally.

Development and validation of a community-level social determinants of health index for drug overdose deaths in the HEALing Communities Study.

INTRODUCTION: Social determinants of health (SDoH), such as socioeconomic status, education level, and food insecurity, are believed to influence the opioid crisis. While global SDoH indices such as the CDC's Social Vulnerability Index (SVI) and Area Deprivation Index (ADI) combine the explanatory power of multiple social factors for understanding health outcomes, they may be less applicable to the specific challenges of opioid misuse and associated outcomes. This study develops a novel index tailored to opioid misuse outcomes, tests the efficacy of this index in predicting drug overdose deaths across contexts, and compares the explanatory power of this index to other SDoH indices. METHODS: Focusing on four HEALing Communities Study (HCS) states (Kentucky, Massachusetts, New York and Ohio; encompassing 4269 ZIP codes), we identified multilevel SDoH potentially associated with opioid misuse and aggregated publicly available data for each measure. We then leveraged a random forest model to develop a composite measure that predicts age-adjusted drug overdose mortality rates based on SDoH. We used this composite measure to understand HCS and non-HCS communities in terms of overdose risk across areas of varying racial composition. Finally, we compared variance in drug overdose deaths explained by this index to variance explained by the SVI and ADI. RESULTS: Our composite measure included 28 SDoH measures and explained approximately 89 % percent of variance in age-adjusted drug overdose mortality across HCS states. Health care measures, including emergency department visits and primary care provider availability, were top predictors within the index. Index accuracy was robust within and outside of HCS communities and states. This measure identified high levels of overdose mortality risk in segregated communities. CONCLUSIONS: Existing SDoH indices fail to explain much variation in area-level overdose mortality rates. Having tailored composite indices can help us to identify places in which residents are at highest risk based on their composite contexts. A comprehensive index can also help to develop effective community interventions for programs such as HCS by considering the context in which people live.

Antenatal and neonatal exposure to SARS-CoV-2 and children's development: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review of the impact of antenatal and neonatal exposure to SARS-CoV-2 on developmental outcomes in preterm and term-born infants. METHODS: We searched Embase, Emcare, MEDLINE, PsycINFO, Web of Science and grey literature on May 27, 2022 and updated on May 8, 2023. Studies defining exposure with a positive SARS-CoV-2 protein or genetic material, used a contemporaneous non-exposed cohort, and reported developmental outcomes up to 2 years of age were included. RESULTS: Four out of 828 screened studies were included. Meta-analysis included 815 infants screened for developmental delay (n = 306 exposed; n = 509 non-exposed) between 3- and 11-months of age. Among term-born infants, we did not find an increased risk of delay in communication (odd's ratio: 0.73 (95% CI: 0.24-2.24)), gross motor (1.50 (0.62, 3.62)), fine motor (2.90 (0.58, 14.43)), problem-solving (1.19 (0.54, 2.66)) or personal-social development (1.93 (0.78, 4.75)) in exposed infants. The number of preterm-born infants in the exposed (n = 37) and comparison cohorts (n = 41) were too few to report meaningful comparisons. CONCLUSION: Evidence regarding the potential impact of antenatal or neonatal exposure to SARS-CoV-2 infection on developmental outcomes in early infancy is limited and inconsistent. Larger cohorts with outcomes beyond the first year of life are needed. IMPACT: The current evidence examining associations between SARS-CoV-2 exposure during the neonatal period and developmental outcomes in infancy is limited by there being few studies with extremely small sample sizes. Based on sparse data there was no consistent association between antenatal or neonatal exposure to SARS-CoV-2 infection and an adverse impact on developmental outcomes below 12 months of age for babies born preterm or at term. This study highlights that larger cohorts with outcomes assessed beyond the first year are needed to determine the potential longer-term impact of SARS-CoV-2 infection exposure on child development.

Differences in perceptions of community stigma towards opioid use disorder between community substance use coalition members and the general public.

INTRODUCTION: To examine differences in perceptions about community stigma towards individuals with opioid use disorder (OUD) between community members involved in the opioid response (i.e., coalition members) and the general public, and how community geography may moderate this relationship. METHODS: This study administered identical cross-sectional surveys about perceived community opioid-related stigma to two distinct populations in 66 communities participating in the HEALing Communities Study prior to the intervention period (i.e., coalition members, November 2019-January 2020; residents, March-April 2020). Linear-mixed models compared survey responses of populations, including the moderating effect of community rural/urban location. RESULTS: A total of 826 coalition members and 1131 residents completed the surveys. The study found no differences between the coalition members and residents for general perceived community opioid-related stigma. In both urban and rural communities, coalition members reported greater perceived community stigma than residents reported towards medication for opioid use disorder (MOUD), naloxone, and drug treatment as an alternative to incarceration. CONCLUSION: Our findings suggest similar perceived community opioid-related stigma between coalition members and residents, yet differences emerge related to evidence-based practices (i.e., MOUD, naloxone, and drug treatment as an alternative to incarceration) to reduce opioid overdose deaths. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04111939.

A cluster randomised controlled trial to assess the effectiveness of a multi-strategy sustainability intervention on teachers' sustained implementation of classroom physical activity breaks (energisers): study protocol.

BACKGROUND: Governments internationally have invested hugely in the implementation and scale-up of school-based physical activity interventions, but have little evidence of how to best sustain these interventions once active implementation support ceases. This study will assess the effectiveness of a multi-strategy sustainability intervention on classroom teachers' sustainment of energisers (short 3-5 min physical activity breaks during class-time) scheduled across the school day from baseline to 12 and 24-month follow-up. METHODS: A cluster randomised controlled trial will be conducted in 50 primary schools within the Hunter New England, Illawarra Shoalhaven, Murrumbidgee and Northern New South Wales (NSW) Local Health Districts of NSW Australia. Schools will be randomly allocated to receive either usual support or the multi-strategy sustainability intervention that includes: centralised technical assistance from a trained project officer; formal commitment and mandated change obtained from school principals; training in-school champions; reminders for teachers; educational materials provided to teachers; capturing and sharing local knowledge; and engagement of parents, carers and the wider school community. The primary trial outcome will be measured via a teacher logbook to determine the between-group difference in the change in mean minutes of energisers scheduled across the school day at 12 and 24-month follow-up compared to baseline. Analyses will be performed using an intention to treat framework. Linear mixed models will be used to assess intervention effects on the primary outcome at both follow-up periods. DISCUSSION: This study will be one of the first randomised controlled trials to examine the impact of a multi-strategy sustainability intervention to support schools' sustainment of a physical activity intervention. The proposed research will generate new evidence needed for the partnering organisations to protect their considerable investments to date in physical activity promotion in this setting and will provide seminal evidence for the field globally. TRIAL REGISTRATION: ACTRN12620000372987 version 1 registered 17th March 2020. Version 3 (current version) updated 4th August 2023.

Graded functional organization in the left inferior frontal gyrus: evidence from task-free and task-based functional connectivity.

The left inferior frontal gyrus has been ascribed key roles in numerous cognitive domains, such as language and executive function. However, its functional organization is unclear. Possibilities include a singular domain-general function, or multiple functions that can be mapped onto distinct subregions. Furthermore, spatial transition in function may be either abrupt or graded. The present study explored the topographical organization of the left inferior frontal gyrus using a bimodal data-driven approach. We extracted functional connectivity gradients from (i) resting-state fMRI time-series and (ii) coactivation patterns derived meta-analytically from heterogenous sets of task data. We then sought to characterize the functional connectivity differences underpinning these gradients with seed-based resting-state functional connectivity, meta-analytic coactivation modeling and functional decoding analyses. Both analytic approaches converged on graded functional connectivity changes along 2 main organizational axes. An anterior-posterior gradient shifted from being preferentially associated with high-level control networks (anterior functional connectivity) to being more tightly coupled with perceptually driven networks (posterior). A second dorsal-ventral axis was characterized by higher connectivity with domain-general control networks on one hand (dorsal functional connectivity), and with the semantic network, on the other (ventral). These results provide novel insights into an overarching graded functional organization of the functional connectivity that explains its role in multiple cognitive domains.

Melting of glacier ice enhanced by bursting air bubbles.

Feedbacks between ice melt, glacier flow and ocean circulation can rapidly accelerate ice loss at tidewater glaciers and alter projections of sea-level rise. At the core of these projections is a model for ice melt that neglects the fact that glacier ice contains pressurized bubbles of air due to its formation from compressed snow. Current model estimates can underpredict glacier melt at termini outside the region influenced by the subglacial discharge plume by a factor of 10-100 compared with observations. Here we use laboratory-scale experiments and theoretical arguments to show that the bursting of pressurized bubbles from glacier ice could be a source of this discrepancy. These bubbles eject air into the seawater, delivering additional buoyancy and impulses of turbulent kinetic energy to the boundary layer, accelerating ice melt. We show that real glacier ice melts 2.25 times faster than clear bubble-free ice when driven by natural convection in a laboratory setting. We extend these results to the geophysical scale to show how bubble dynamics contribute to ice melt from tidewater glaciers. Consequently, these results could increase the accuracy of modelled predictions of ice loss to better constrain sea-level rise projections globally.

Reliable change in developmental outcomes of Brain Balance® participants stratified by baseline severity.

The effects of comprehensive multimodal programs on developmental outcomes have not been well-studied. Emerging evidence suggests a possible role for the Brain Balance® (BB) program, a multimodal training program, in serving as a nonpharmacologic approach to addressing cognitive, attentional, and emotional issues in youth. In this analysis, we examined the effects of 3 months of participation in the BB program on the outcomes of children and adolescents with developmental difficulties (N = 4,041; aged 4-18 years; 69.7% male). Parent-rated scores on the Brain Balance-Multidomain Developmental Survey (BB-MDS) were used to assess six areas at baseline and post-program: (1) negative emotionality; (2) reading/writing difficulties; (3) hyperactive/disruptive behavior; (4) academic disengagement; (5) motor/coordination problems; and (6) social communication problems. To estimate change from pre- to post-program, we calculated effect size (Cohen's d) and the Reliable Change Index (RCI) for groups stratified by baseline severity. There was a very large effect size for the moderate/high severity (d = 1.63) and extreme severity (d = 2.08) groups, and a large effect size for the mild severity group (d = 0.87). The average percentage of participants who observed reliable change over all BB-MDS domains was 60.1% (RCICTT) for extreme severity, 46.6% (RCICTT) for moderate/high severity, and 21.1% (RCICTT) for baseline mild severity. In additional assessments of primitive reflexes and sensory motor activity, students demonstrated significantly diminished primitive reflexes from pre- to post-participation and significant improvements in sensory motor skills including fine motor skills, gait and aerobic ability, proprioception, rhythm and timing, and eye-gaze stability. Overall, these results demonstrate improvements in primitive reflex integration and sensory motor skills, as well as statistically significant reliable change in emotionality, reading/writing, behavior, academic engagement, motor skills, and social communication in BB participants from pre- to post-program, with the probability and degree of change increasing as the participants' baseline severity increases. These results contribute to the growing literature on the need for evidence-based nonpharmacologic approaches to addressing developmental issues. Future research with well-controlled designs, longitudinal follow-up, implementation across settings, and participant groups in which diagnoses are known, will help to more fully characterize the effects of the BB program.

Evaluating the scaling up of an effective implementation intervention (PACE) to increase the delivery of a mandatory physical activity policy in primary schools.

BACKGROUND: Physically Active Children in Education (PACE) is an effective implementation intervention for increasing the number of minutes classroom teachers schedule physical activity each week. To date, evaluations of PACE have included a smaller number of schools from only one region in New South Wales Australia. If PACE is to have population-wide benefits we must be able to deliver this support to a larger number of schools across multiple regions. This study aimed to evaluate the scale-up of PACE. METHODS: An uncontrolled before and after study, with 100 schools from three regions was conducted. Participating schools received PACE for approximately 12 months. We assessed the following outcomes: delivery of the evidence-based intervention (EBI) (i.e. minutes of physical activity scheduled by classroom teachers per week); delivery of the implementation strategies (i.e. reach, dose delivered, adherence and indicators of sustainability); and key determinants of implementation (i.e. acceptability of strategies and cost). Data were collected via project officer records, and principal and teacher surveys. Linear mixed models were used to assess EBI delivery by evaluating the difference in the mean minutes teachers scheduled physical activity per week from baseline to follow-up. Descriptive data were used to assess delivery of the implementation strategies and their perceived acceptability (i.e. PACE). A prospective, trial-based economic evaluation was used to assess cost. RESULTS: Delivery of the EBI was successful: teachers increas their average minutes of total physical activity scheduled across the school week by 26.8 min (95% CI: 21.2, 32.4, p < 0.001) after receiving PACE. Indicators for delivery of implementation strategies were high: 90% of consenting schools received all strategies and components (reach); 100% of strategies were delivered by the provider (dose); >50% of schools adhered to the majority of strategies (11 of the 14 components); and acceptability was > 50% agreement for all strategies. The incremental cost per additional minute of physical activity scheduled per week was $27 per school (Uncertainty Interval $24, $31). CONCLUSIONS: PACE can be successfully delivered across multiple regions and to a large number of schools. Given the ongoing and scalable benefits of PACE, it is important that we continue to extend and improve this program while considering ways to reduce the associated cost.

WHOLE GENOME SEQUENCING ANALYSIS OF BODY MASS INDEX IDENTIFIES NOVEL AFRICAN ANCESTRY-SPECIFIC RISK ALLELE.

Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups. We discovered 18 BMI-associated signals (P < 5 × 10-9). Notably, we identified and replicated a novel low frequency single nucleotide polymorphism (SNP) in MTMR3 that was common in individuals of African descent. Using a diverse study population, we further identified two novel secondary signals in known BMI loci and pinpointed two likely causal variants in the POC5 and DMD loci. Our work demonstrates the benefits of combining WGS and diverse cohorts in expanding current catalog of variants and genes confer risk for obesity, bringing us one step closer to personalized medicine.

Marine diatoms record Late Holocene regime shifts in the Pikialasorsuaq ecosystem.

The Pikialasorsuaq (North Water polynya) is an area of local and global cultural and ecological significance. However, over the last decades, the region has been subject to rapid warming, and in some recent years, the seasonal ice arch that has historically defined the polynya's northern boundary has failed to form. Both factors are deemed to alter the polynya's ecosystem functioning. To understand how climate-induced changes to the Pikialasorsuaq impact the basis of the marine food web, we explored diatom community-level responses to changing conditions, from a sediment core spanning the last 3800 years. Four metrics were used: total diatom concentrations, taxonomic composition, mean size, and diversity. Generalized additive model statistics highlight significant changes at ca. 2400, 2050, 1550, 1200, and 130 cal years BP, all coeval with known transitions between colder and warmer intervals of the Late Holocene, and regime shifts in the Pikialasorsuaq. Notably, a weaker/contracted polynya during the Roman Warm Period and Medieval Climate Anomaly caused the diatom community to reorganize via shifts in species composition, with the presence of larger taxa but lower diversity, and significantly reduced export production. This study underlines the high sensitivity of primary producers to changes in the polynya dynamics and illustrates that the strong pulse of early spring cryopelagic diatoms that makes the Pikialasorsuaq exceptionally productive may be jeopardized by rapid warming and associated Nares Strait ice arch destabilization. Future alterations to the phenology of primary producers may disproportionately impact higher trophic levels and keystone species in this region, with implications for Indigenous Peoples and global diversity.