Deep continental roots and cratons.

The formation and preservation of cratons-the oldest parts of the continents, comprising over 60 per cent of the continental landmass-remains an enduring problem. Key to craton development is how and when the thick strong mantle roots that underlie these regions formed and evolved. Peridotite melting residues forming cratonic lithospheric roots mostly originated via relatively low-pressure melting and were subsequently transported to greater depth by thickening produced by lateral accretion and compression. The longest-lived cratons were assembled during Mesoarchean and Palaeoproterozoic times, creating the stable mantle roots 150 to 250 kilometres thick that are critical to preserving Earth's early continents and central to defining the cratons, although we extend the definition of cratons to include extensive regions of long-stable Mesoproterozoic crust also underpinned by thick lithospheric roots. The production of widespread thick and strong lithosphere via the process of orogenic thickening, possibly in several cycles, was fundamental to the eventual emergence of extensive continental landmasses-the cratons.

Cut-and-Run: A Distinct Mechanism by which V(D)J Recombination Causes Genome Instability.

V(D)J recombination is essential to generate antigen receptor diversity but is also a potent cause of genome instability. Many chromosome alterations that result from aberrant V(D)J recombination involve breaks at single recombination signal sequences (RSSs). A long-standing question, however, is how such breaks occur. Here, we show that the genomic DNA that is excised during recombination, the excised signal circle (ESC), forms a complex with the recombinase proteins to efficiently catalyze breaks at single RSSs both in vitro and in vivo. Following cutting, the RSS is released while the ESC-recombinase complex remains intact to potentially trigger breaks at further RSSs. Consistent with this, chromosome breaks at RSSs increase markedly in the presence of the ESC. Notably, these breaks co-localize with those found in acute lymphoblastic leukemia patients and occur at key cancer driver genes. We have named this reaction "cut-and-run" and suggest that it could be a significant cause of lymphocyte genome instability.

Thermal displacement by marine heatwaves.

Marine heatwaves (MHWs)-discrete but prolonged periods of anomalously warm ocean temperatures-can drastically alter ocean ecosystems, with profound ecological and socioeconomic impacts1-8. Considerable effort has been directed at understanding the patterns, drivers and trends of MHWs globally9-11. Typically, MHWs are characterized on the basis of their intensity and persistence at a given location-an approach that is particularly relevant for corals and other sessile organisms that must endure increased temperatures. However, many ecologically and commercially important marine species respond to environmental disruptions by relocating to favourable habitats, and dramatic range shifts of mobile marine species are among the conspicuous impacts of MHWs1,4,12,13. Whereas spatial temperature shifts have been studied extensively in the context of long-term warming trends14-18, they are unaccounted for in existing global MHW analyses. Here we introduce thermal displacement as a metric that characterizes MHWs by the spatial shifts of surface temperature contours, instead of by local temperature anomalies, and use an observation-based global sea surface temperature dataset to calculate thermal displacements for all MHWs from 1982 to 2019. We show that thermal displacements during MHWs vary from tens to thousands of kilometres across the world's oceans and do not correlate spatially with MHW intensity. Furthermore, short-term thermal displacements during MHWs are of comparable magnitude to century-scale shifts inferred from warming trends18, although their global spatial patterns are very different. These results expand our understanding of MHWs and their potential impacts on marine species, revealing which regions are most susceptible to thermal displacement, and how such shifts may change under projected ocean warming. The findings also highlight the need for marine resource management to account for MHW-driven spatial shifts, which are of comparable scale to those associated with long-term climate change and are already happening.

Prevalence of adolescent mental disorders in Kenya, Indonesia, and Viet Nam measured by the National Adolescent Mental Health Surveys (NAMHS): a multi-national cross-sectional study.

BACKGROUND: Mental disorders are the leading global cause of health burden among adolescents. However, prevalence data for mental disorders among adolescents in low-income and middle-income countries are scarce with often limited generalisability. This study aimed to generate nationally representative prevalence estimates for mental disorders in adolescents in Kenya, Indonesia, and Viet Nam. METHODS: As part of the National Adolescent Mental Health Surveys (NAMHS), a multinational cross-sectional study, nationally representative household surveys were conducted in Kenya, Indonesia, and Viet Nam between March and December, 2021. Adolescents aged 10-17 years and their primary caregiver were interviewed from households selected randomly according to sampling frames specifically designed to elicit nationally representative results. Six mental disorders (social phobia, generalised anxiety disorder, major depressive disorder, post-traumatic stress disorder, conduct disorder, and attention-deficit hyperactivity disorder) were assessed with the Diagnostic Interview Schedule for Children, Version 5. Suicidal behaviours and self-harm in the past 12 months were also assessed. Prevalence in the past 12 months and past 4 weeks was calculated for each mental disorder and collectively for any mental disorder (ie, of the six mental disorders assessed). Prevalence of suicidal behaviours (ie, ideation, planning, and attempt) and self-harm in the past 12 months was calculated, along with adjusted odds ratios (aORs) to show the association with prevalence of any mental disorder in the past 12 months. Inverse probability weighting was applied to generate national estimates with corresponding 95% CIs. FINDINGS: Final samples consisted of 5155 households (ie, adolescent and primary caregiver pairs) from Kenya, 5664 households from Indonesia, and 5996 households from Viet Nam. In Kenya, 2416 (46·9%) adolescents were male and 2739 (53·1%) were female; in Indonesia, 2803 (49·5%) adolescents were male and 2861 (50·5%) were female; and in Viet Nam, 3151 (52·5%) were male and 2845 (47·4%) were female. Prevalence of any mental disorder in the past 12 months was 12·1% (95% CI 10·9-13·5) in Kenya, 5·5% (4·3-6·9) in Indonesia, and 3·3% (2·7-4·1) in Viet Nam. Prevalence in the past 4 weeks was 9·4% (8·3-10·6) in Kenya, 4·4% (3·4-5·6) in Indonesia, and 2·7% (2·2-3·3) in Viet Nam. The prevalence of suicidal behaviours in the past 12 months was low in all three countries, with suicide ideation ranging from 1·4% in Indonesia (1·0-2·0) and Viet Nam (1·0-1·9) to 4·6% (3·9-5·3) in Kenya, suicide planning ranging from 0·4% in Indonesia (0·3-0·8) and Viet Nam (0·2-0·6) to 2·4% (1·9-2·9) in Kenya, and suicide attempts ranging from 0·2% in Indonesia (0·1-0·4) and Viet Nam (0·1-0·3) to 1·0% (0·7-1·4) in Kenya. The prevalence of self-harm in the past 12 months was also low in all three countries, ranging from 0·9% (0·6-1·3) in Indonesia to 1·2% (0·9-1·7) in Kenya. However, the prevalence of suicidal behaviours and self-harm in the past 12 months was significantly higher among those with any mental disorder in the past 12 months than those without (eg, aORs for suicidal ideation ranged from 7·1 [3·1-15·9] in Indonesia to 14·7 [7·5-28·6] in Viet Nam). INTERPRETATION: NAMHS provides the first national adolescent mental disorders prevalence estimates for Kenya, Indonesia, and Viet Nam. These data can inform mental health and broader health policies in low-income and middle-income countries. FUNDING: The University of Queensland in America (TUQIA) through support from Pivotal Ventures, a Melinda French Gates company.

Temporal analyses reveal a pivotal role for sense and antisense enhancer RNAs in coordinate immunoglobulin lambda locus activation.

Transcription enhancers are essential activators of V(D)J recombination that orchestrate non-coding transcription through complementary, unrearranged gene segments. How transcription is coordinately increased at spatially distinct promoters, however, remains poorly understood. Using the murine immunoglobulin lambda (Igλ) locus as model, we find that three enhancer-like elements in the 3' Igλ domain, Eλ3-1, HSCλ1 and HSE-1, show strikingly similar transcription factor binding dynamics and close spatial proximity, suggesting that they form an active enhancer hub. Temporal analyses show coordinate recruitment of complementary V and J gene segments to this hub, with comparable transcription factor binding dynamics to that at enhancers. We find further that E2A, p300, Mediator and Integrator bind to enhancers as early events, whereas YY1 recruitment and eRNA synthesis occur later, corresponding to transcription activation. Remarkably, the interplay between sense and antisense enhancer RNA is central to both active enhancer hub formation and coordinate Igλ transcription: Antisense Eλ3-1 eRNA represses Igλ activation whereas temporal analyses demonstrate that accumulating levels of sense eRNA boost YY1 recruitment to stabilise enhancer hub/promoter interactions and lead to coordinate transcription activation. These studies therefore demonstrate for the first time a critical role for threshold levels of sense versus antisense eRNA in locus activation.

Real-time pandemic surveillance using hospital admissions and mobility data.

Forecasting the burden of COVID-19 has been impeded by limitations in data, with case reporting biased by testing practices, death counts lagging far behind infections, and hospital census reflecting time-varying patient access, admission criteria, and demographics. Here, we show that hospital admissions coupled with mobility data can reliably predict severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission rates and healthcare demand. Using a forecasting model that has guided mitigation policies in Austin, TX, we estimate that the local reproduction number had an initial 7-d average of 5.8 (95% credible interval [CrI]: 3.6 to 7.9) and reached a low of 0.65 (95% CrI: 0.52 to 0.77) after the summer 2020 surge. Estimated case detection rates ranged from 17.2% (95% CrI: 11.8 to 22.1%) at the outset to a high of 70% (95% CrI: 64 to 80%) in January 2021, and infection prevalence remained above 0.1% between April 2020 and March 1, 2021, peaking at 0.8% (0.7-0.9%) in early January 2021. As precautionary behaviors increased safety in public spaces, the relationship between mobility and transmission weakened. We estimate that mobility-associated transmission was 62% (95% CrI: 52 to 68%) lower in February 2021 compared to March 2020. In a retrospective comparison, the 95% CrIs of our 1, 2, and 3 wk ahead forecasts contained 93.6%, 89.9%, and 87.7% of reported data, respectively. Developed by a task force including scientists, public health officials, policy makers, and hospital executives, this model can reliably project COVID-19 healthcare needs in US cities.

Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States.

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.

Molecular characterization of 13 patients with PIK3CA-related overgrowth spectrum using a targeted deep sequencing approach.

Activating variants in the PIK3CA gene cause a heterogeneous spectrum of disorders that involve congenital or early-onset segmental/focal overgrowth, now referred to as PIK3CA-related overgrowth spectrum (PROS). Historically, the clinical diagnoses of patients with PROS included a range of distinct syndromes, including CLOVES syndrome, dysplastic megalencephaly, hemimegalencephaly, focal cortical dysplasia, Klippel-Trenaunay syndrome, CLAPO syndrome, fibroadipose hyperplasia or overgrowth, hemihyperplasia multiple lipomatosis, and megalencephaly capillary malformation-polymicrogyria (MCAP) syndrome. MCAP is a sporadic overgrowth disorder that exhibits core features of progressive megalencephaly, vascular malformations, distal limb malformations, cortical brain malformations, and connective tissue dysplasia. In 2012, our research group contributed to the identification of predominantly mosaic, gain-of-function variants in PIK3CA as an underlying genetic cause of the syndrome. Mosaic variants are technically more difficult to detect and require implementation of more sensitive sequencing technologies and less stringent variant calling algorithms. In this study, we demonstrated the utility of deep sequencing using the Illumina TruSight Oncology 500 (TSO500) sequencing panel in identifying variants with low allele fractions in a series of patients with PROS and suspected mosaicism: pathogenic, mosaic PIK3CA variants were identified in all 13 individuals, including 6 positive controls. This study highlights the importance of screening for low-level mosaic variants in PROS patients. The use of targeted panels with deep sequencing in clinical genetic testing laboratories would improve diagnostic yield and accuracy within this patient population.

Prediction of post-hemorrhagic ventricular dilatation trajectory using a growth mixture model in preterm infants.

BACKGROUND: Early intervention for post-hemorrhagic ventricular dilatation (PHVD), guided by ventricular size measurements from cranial ultrasound (cUS), is associated with improved neurodevelopmental outcomes in preterm infants but benefits must be balanced against intervention risks. METHODS: Anterior horn width (AHW) and ventricular index (VI) were measured from cUS for preterm infants (<29 weeks) with intraventricular hemorrhage admitted from 2010-2018. PHVD was defined as AHW > 6 mm or VI >97th percentile for postmenstrual age. Individual ventricular size trajectories were plotted, and a growth mixture model (GMM) used to identify latent trajectory classes and compare these to predetermined outcome of neurosurgical intervention. RESULTS: Measurements were obtained from 1543 cUS in 249 infants, of whom 39 had PHVD without and 17 PHVD with neurosurgical intervention based on signs of raised intracranial pressure. The GMM predicted trajectory identified: 93.3% of infants without PHVD, 88.2% and 30.8% of infants with PHVD with and without intervention using AHW; 100% of infants without PHVD, 52.9% and 59.0% of infants with PHVD with and without intervention using VI. CONCLUSIONS: The AHW GMM identified a significant proportion of infants with severe PHVD. Model refinement offers a promising approach for identifying differences in PHVD trajectory at an early stage to guide management. IMPACT: It is difficult to distinguish the trajectory of PHVD in the early stage of development, in particular PHVD that spontaneously arrests from slowly progressive PHVD which eventually requires intervention. We report the first modeling-based evaluation of PHVD trajectory for the prediction of short-term outcome of PHVD progression and neurosurgical intervention. With additional clinical validation and optimization to increase accuracy, predictive modeling has the potential to identify important differences in PHVD trajectory at an early stage in the clinical course, allowing for more individualized data-driven risk-benefit assessments to guide decisions on early intervention.

Iron Supplementation in Management of Neurodevelopmental Disorders: Systematic Review, Meta-Analysis, and Qualitative Synthesis.

OBJECTIVE: The authors sought to explore the role of iron supplementation in the management of neurodevelopmental disorders among children and youths. METHODS: A systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was undertaken. A subset of results was suitable for meta-analysis. The quality of the evidence and strength of the clinical recommendations were assessed by using the Grading of Recommendations, Assessment, Development, and Evaluation method, and critical appraisal was conducted with the Joanna Briggs Institute critical appraisal tools. RESULTS: Nine articles met inclusion criteria. These articles included studies of attention-deficit hyperactivity disorder (ADHD) (N=7), autism spectrum disorder (N=1), and Tourette's syndrome (N=1). Three randomized controlled trials evaluating iron supplementation for ADHD hyperactivity symptom severity (124 participants: placebo, N=56; supplement, N=68) met inclusion criteria for a meta-analysis. Effect sizes for the placebo and supplement groups were moderate (Cohen's d=0.76) and large (Cohen's d=1.70), respectively, although these differences were not significant. The impact of iron supplementation on inattentive ADHD symptom severity was examined in two trials (75 participants: placebo, N=31; supplement, N=44). Large, nonsignificant effect sizes were demonstrated for the placebo (Cohen's d=1.66) and supplementation (Cohen's d=3.19) groups. The quality of the evidence and strength of the clinical recommendations were considered very low. CONCLUSIONS: Further research is needed to examine the role of iron supplementation in the management of ADHD and neurodevelopmental disorders more generally. Additionally, iron supplementation comes with risks, including death in the case of overdose.

Size Isn't Everything: Geometric Tuning in Polycyclic Aromatic Hydrocarbons and Its Implications for Carbon Nanodots.

Recent developments in light-emitting carbon nanodots and molecular organic semiconductors have seen renewed interest in the properties of polycyclic aromatic hydrocarbons (PAHs) as a family. The networks of delocalized π electrons in sp2-hybridized carbon grant PAHs light-emissive properties right across the visible spectrum. However, the mechanistic understanding of their emission energy has been limited due to the ground state-focused methods of determination. This computational chemistry work, therefore, seeks to validate existing rules and elucidate new features and characteristics of PAHs that influence their emissions. Predictions based on (time-dependent) density functional theory account for the full 3-dimensional electronic structure of ground and excited states and reveal that twisting and near-degeneracies strongly influence emission spectra and may therefore be used to tune the color of PAHs and, hence, carbon nanodots. We particularly note that the influence of twisting goes beyond torsional destabilization of the ground-state and geometric relaxation of the excited state, with a third contribution associated with the electric transition dipole. Symmetries and peri-condensation may also have an effect, but this could not be statistically confirmed. In pursuing this goal, we demonstrate that with minimal changes to molecular size, the entire visible spectrum may be spanned by geometric modification alone; we have also provided a first estimate of emission energy for 35 molecules currently lacking published emission spectra as well as clear guidelines for when more sophisticated computational techniques are required to predict the properties of PAHs accurately.

Associations between neighborhood socioeconomic status, parental education, and executive system activation in youth.

Socioeconomic status (SES) can impact cognitive performance, including working memory (WM). As executive systems that support WM undergo functional neurodevelopment during adolescence, environmental stressors at both individual and community levels may influence cognitive outcomes. Here, we sought to examine how SES at the neighborhood and family level impacts task-related activation of the executive system during adolescence and determine whether this effect mediates the relationship between SES and WM performance. To address these questions, we studied 1,150 youths (age 8-23) that completed a fractal n-back WM task during functional magnetic resonance imaging at 3T as part of the Philadelphia Neurodevelopmental Cohort. We found that both higher neighborhood SES and parental education were associated with greater activation of the executive system to WM load, including the bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and precuneus. The association of neighborhood SES remained significant when controlling for task performance, or related factors like exposure to traumatic events. Furthermore, high-dimensional multivariate mediation analysis identified distinct patterns of brain activity within the executive system that significantly mediated the relationship between measures of SES and task performance. These findings underscore the importance of multilevel environmental factors in shaping executive system function and WM in youth.

Organophosphate ester flame retardants and plasticizers in house dust and mental health outcomes among Canadian mothers: A nested prospective cohort study in CHILD.

Organophosphate ester flame retardants and plasticizers (OPEs) are common exposures in modern built environments. Toxicological models report that some OPEs reduce dopamine and serotonin in the brain. Deficiencies in these neurotransmitters are associated with anxiety and depression. We hypothesized that exposure to higher concentrations of OPEs in house dust would be associated with a greater risk of depression and stress in mothers across the prenatal and postpartum periods. We conducted a nested prospective cohort study using data collected on mothers (n = 718) in the CHILD Cohort Study, a longitudinal multi-city Canadian birth cohort (2008-2012). OPEs were measured in house dust sampled at 3-4 months postpartum. Maternal depression and stress were measured at 18 and 36 weeks gestation and 6 months and 1 year postpartum using the Centre for Epidemiologic Studies for Depression Scale (CES-D) and Perceived Stress Scale (PSS). We used linear mixed models to examine the association between a summed Z-Score OPE index and continuous depression and stress scores. In adjusted models, one standard deviation increase in the OPE Z-score index was associated with a 0.07-point (95% CI: 0.01, 0.13) increase in PSS score. OPEs were not associated with log-transformed CES-D (ß: 0.63%, 95% CI: -0.18%, 1.46%). The effect of OPEs on PSS score was strongest at 36 weeks gestation and weakest at 1 year postpartum. We observed small increases in maternal perceived stress levels, but not depression, with increasing OPEs measured in house dust during the prenatal and early postpartum period in this cohort of Canadian women. Given the prevalence of prenatal and postpartum anxiety and the ubiquity of OPE exposures, additional research is warranted to understand if these chemicals affect maternal mental health.

Gender differences in cardiovascular disease risk: Adolescence to young adulthood.

BACKGROUND AND AIMS: Gender differences in cardiovascular disease (CVD) have been well documented but rarely for young adults and the extent to which gender related lifestyle differences may contribute to gender differences in CVD risk experienced by young adults have not been reported. METHODS AND RESULTS: Data are from a long-running cohort study, the Mater-University of Queensland Study of Pregnancy (MUSP). We track gender differences in CVD related behaviours at 21 and 30 years (consumption of a Western Diet/Health-Oriented Diet, cigarette smoking, vigorous physical exercise, heavy alcohol consumption). At 30 years we compare males and females for CVD risk, and the extent to which lifestyle behaviours at 21 and 30 years contribute to CVD risk. At both 21 and 30 years of age, males more frequently consume a Western Diet and less often a Health Oriented Diet. By contrast, males are also much more likely to report engaging in vigorous physical activity. On most CVD markers, males exhibit much higher levels of risk than do females at both 21 and 30 years. At 30 years of age males have about five times the odds of being at high risk of CVD. Some lifestyle behaviours contribute to this additional risk. CONCLUSION: Young adult males much more frequently engage in most CVD related risk behaviours and males have a higher level of CVD risk. Gender differences in CVD risk remain high even after adjustment for CVD lifestyles, though dietary factors independently contribute to CVD risk at 30 years.

The effectiveness and tolerability of pharmacotherapy for psychosis in 22q11.2 Deletion Syndrome: A systematic review.

OBJECTIVE: The 22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion in humans with over 180 phenotypic expressions. Approximately 30-40% of affected individuals will develop psychosis and 25% meet the criteria for schizophrenia. Despite this, pharmacotherapy for managing psychosis in 22q11.2DS is poorly understood and 22q11.2DS psychosis is frequently labelled as treatment resistant. The objectives of this paper are to evaluate the effectiveness and tolerability of pharmacotherapy for 22q11.2DS psychosis and evaluate the evidence for treatment resistance. METHOD: A systematic search was performed using CINAHL, The Cochrane Library (Cochrane Database of Systematic Reviews; Cochrane Central Register of Controlled Trials and Cochrane Clinical Answers), EMBASE, PsycINFO, PubMed, Scopus and Web of Science Core Collection from inception to December 2022. It yielded 39 case reports, 6 case series and 1 retrospective study which met the inclusion criteria. RESULTS: Based on the current literature, individuals with 22q11.2DS psychosis experience a greater rate of medical co-morbidities such as cardiac arrhythmias, seizures and movement disorders, which complicate pharmacotherapy. Poor tolerability rather than poor clinical response motivates the switching of antipsychotics, which may explain the labelling of treatment resistance in the literature. CONCLUSION: There are insufficient data to recommend a single antipsychotic for 22q11.2DS psychosis. Nonetheless, with proactive management of co-morbidities, antipsychotic medication in 22q11.2DS psychosis is an effective treatment commonly resulting in improvement in quality of life.

Electroconvulsive therapy in a tertiary Australian mental health facility between 2009 and 2020.

BACKGROUND: Despite electroconvulsive therapy being one of the most effective treatments in psychiatry, few studies report trends in the provision of electroconvulsive therapy over time. This study aims to investigate the use of electroconvulsive therapy between 2009 and 2020 in an Australian public tertiary mental health facility, and to describe the electroconvulsive therapy patient population and change in courses of treatment. METHODS: Routinely collected data for 677 patients who received 1669 electroconvulsive therapy courses of treatment at an Australian public tertiary mental health facility between 2009 and 2020 were examined. RESULTS: The provision of acute electroconvulsive therapy was stable across the study period; however, the number of maintenance electroconvulsive therapy courses commenced declined over the study. Schizophrenia was the most common indication for index treatment (37.4%). The majority of patients (85.7%) received acute electroconvulsive therapy only. Voluntary provision of electroconvulsive therapy declined over the study period, reducing from 44.9% in 2009 to 16.3% in 2020. CONCLUSION: Over the study period, there was a significant reduction in the number of maintenance electroconvulsive therapy courses commenced, and a large increase in involuntary treatment. The provision of electroconvulsive therapy was more likely to occur in males with a diagnosis of schizophrenia. Further studies are needed to generate a greater understanding of the factors influencing the provision of electroconvulsive therapy within differing geographical, social and healthcare landscapes.

The Kessler Psychological Distress Scale in Australian adolescents: Analysis of the second Australian Child and Adolescent Survey of Mental Health and Wellbeing.

INTRODUCTION: The 10-item Kessler Psychological Distress Scale (K10) is used to screen adolescents for mental disorders in Australian clinical practice; however, there are no Australian adolescent normative data. METHODS: Data were drawn from a nationally representative sample (N = 2964) of Australian adolescents (11-17 years). This study had three aims: (1) to examine concurrent validity between the K10 and Strengths and Difficulties Questionnaire (SDQ) emotional symptoms subscale, (2) to establish normative Australian adolescent K10 data and (3) to determine optimal K10 cut-off scores for screening for major depressive disorder (MDD) via receiver operator characteristic curve analysis and stratum-specific likelihood ratios. RESULTS: The K10 and SDQ emotional symptoms scales were moderately correlated (rs = 0.63, p < 0.001). Older female adolescents reported higher total K10 scores compared with younger female adolescents (15-17 years: M = 20.2, standard error [SE] = 0.3; 11-14 years: M = 16.8, SE = 0.3) and male adolescents (11-14 years: M = 16.6, SE = 0.2; 15-17 years: M = 16.0, SE=0.2). K10 scores to optimally discriminate those with and without MDD varied by age and sex and had low specificities. Stratum-specific likelihood ratios indicated adolescents with a K10 score of ≥30 will have a 12.9 (95% confidence interval = [10.2, 16.2]) increased likelihood of MDD. CONCLUSION: The K10 has utility for assessing psychological distress in health care and epidemiological research in Australian adolescents. Adolescents with K10 scores in the 'very high' range are at increased risk of MDD. Further assessment of these young people is indicated to identify those with or at risk of developing MDD.

Documenting and modeling the acoustic variability of intervocalic alveolar taps in conversational Peninsular Spanish.

This study constitutes an investigation into the acoustic variability of intervocalic alveolar taps in a corpus of spontaneous speech from Madrid, Spain. Substantial variability was documented in this segment, with highly reduced variants constituting roughly half of all tokens during spectrographic inspection. In addition to qualitative documentation, the intensity difference between the tap and surrounding vowels was measured. Changes in this intensity difference were statistically modeled using Bayesian finite mixture models containing lexical and phonetic predictors. Model comparisons indicate predictive performance is improved when we assume two latent categories, interpreted as two pronunciation variants for the Spanish tap. In interpreting the model, predictors were more often related to categorical changes in which pronunciation variant was produced than to gradient intensity changes within each tap type. Variability in tap production was found according to lexical frequency, speech rate, and phonetic environment. These results underscore the importance of evaluating model fit to the data as well as what researchers modeling phonetic variability can gain in moving past linear models when they do not adequately fit the observed data.

Provision of Medications for Self-Managed Abortion Before and After the Dobbs v Jackson Women's Health Organization Decision.

Importance: The Supreme Court decision in Dobbs v Jackson Women's Health Organization overturned the right to choose abortion in the US, with at least 16 states subsequently implementing abortion bans or 6-week gestational limits. Prior research indicates that in the 6 months following Dobbs, approximately 32 360 fewer abortions were provided within the US formal health care setting. However, trends in the provision of medications for self-managed abortion outside the formal health care setting have not been studied. Objective: To determine whether the provision of medications for self-managed abortion outside the formal health care setting increased in the 6 months after Dobbs. Design, Setting, and Participants: Cross-sectional study using data from sources that provided abortion medications outside the formal health care setting to people in the US between March 1 and December 31, 2022, including online telemedicine organizations, community networks, and online vendors. Using a hierarchical bayesian model, we imputed missing values from sources not providing data. We estimated the change in provision of medications for self-managed abortion after the Dobbs decision. We then estimated actual use of these medications by accounting for the possibility that not all provided medications are used by recipients. Exposure: Abortion restrictions following the Dobbs decision. Main Outcomes and Measures: Provision and use of medications for a self-managed abortion. Results: In the 6-month post-Dobbs period (July 1 to December 31, 2022), the total number of provisions of medications for self-managed abortion increased by 27 838 (95% credible interval [CrI], 26 374-29 175) vs what would have been expected based on pre-Dobbs levels. Excluding imputed data changes the results only slightly (27 145; 95% CrI, 25 747-28 246). Accounting for nonuse of medications, actual self-managed medication abortions increased by an estimated 26 055 (95% CrI, 24 739-27 245) vs what would have been expected had the Dobbs decision not occurred. Conclusions and Relevance: Provision of medications for self-managed abortions increased in the 6 months following the Dobbs decision. Results suggest that a substantial number of abortion seekers accessed services despite the implementation of state-level bans and restrictions.

A bovine antibody possessing an ultralong complementarity-determining region CDRH3 targets a highly conserved epitope in sarbecovirus spike proteins.

Broadly neutralizing antibodies have huge potential as novel antiviral therapeutics due to their ability to recognize highly conserved epitopes that are seldom mutated in viral variants. A subset of bovine antibodies possess an ultralong complementarity-determining region (CDR)H3 that is highly adept at recognizing such conserved epitopes, but their reactivity against Sarbecovirus Spike proteins has not been explored previously. Here, we use a SARS-naïve library to isolate a broadly reactive bovine CDRH3 that binds the receptor-binding domain of SARS-CoV, SARS-CoV-2, and all SARS-CoV-2 variants. We show further that it neutralizes viruses pseudo-typed with SARS-CoV Spike, but this is not by competition with angiotensin-converting enzyme 2 (ACE2) binding. Instead, using differential hydrogen-deuterium exchange mass spectrometry, we demonstrate that it recognizes the major site of vulnerability of Sarbecoviruses. This glycan-shielded cryptic epitope becomes available only transiently via interdomain movements of the Spike protein such that antibody binding triggers destruction of the prefusion complex. This proof of principle study demonstrates the power of in vitro expressed bovine antibodies with ultralong CDRH3s for the isolation of novel, broadly reactive tools to combat emerging pathogens and to identify key epitopes for vaccine development.