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Objective: To compare the proportion of children and adolescents with incident psychotropic medication use from 2019 through 2022. Methods: This cross-sectional study used the IQVIA PharMetrics ® Plus for Academics health plan claims database. Our study sample consisted of children and adolescents ages 6-18 who had at least one psychotropic medication in March 2019-February 2022. We examined psychotropic medication use in three distinct study periods: pre-pandemic (March 2019 to February 2020), pandemic-year-1 (March 2020-February 2021), and pandemic-year-2 (March 2021-February 2022). Incident use was defined as no evidence of psychotropic medication in the 12 months preceding the child and adolescent's first psychotropic dispensing in each study period. We estimated incident psychotropic use in the three study periods. Average marginal effects tested for significant differences in psychotropic initiation, overall and stratified by age and sex. Results: In our sample of 42,346 children and adolescents who were dispensed any psychotropic medication during the study period, incident psychotropic users were 27.8% in pre-pandemic, 26.0% in pandemic-year-1, and 27.8% in pandemic-year-2. Incident use of antidepressants was 51.4% in pandemic-year-1 and 54.6% in pandemic-year-2. The probability of incident psychotropic use was 2.4% lower in pandemic-year-1 than in the pre-pandemic year ( p < 0.001). The proportion of 6-11-year-olds and females initiating a psychotropic was higher in pandemic-year-2 than pre-pandemic. Conclusion: Incident psychotropic use was most notable in younger and female children 2 years after the pandemic onset.

Background/objective: Intracranial epidermoid tumors (ETs) are rare, benign lesions that present significant challenges in neurosurgical management due to their propensity to encase vital neurovascular structures. We aimed to evaluate the impact of clinical, demographic, and tumor-specific factors on surgical decisions (gross total resection [GTR] vs. subtotal resection [STR]) and outcomes and identify patient clusters with distinct profiles and outcomes post-resection., Methods: We retrospectively analyzed 72 patients with ET treated from 1998 to 2022, employing multivariable logistic regression for GTR versus STR predictors and Kaplan-Meier curves for progression-free survival (PFS). K-prototype clustering classified patients based on clinical data., Results: The mean age of our cohort was 39.8 ± 20.1 years. About 13.9% of patients had a recurrence, with a median PFS of 108 months (interquartile range: 57 -206). Seizures significantly predicted GTR (P < 0.05), whereas adherence to critical structures reduced GTR likelihood (P < 0.05). Initial surgeries more often achieved GTR, correlating with longer PFS (P < 0.0001) and reduced recurrence (P < 0.01) versus re-operations. Cluster analysis identified three distinct groups, with the initial GTR cluster showing superior PFS and the lowest recurrence (P < 0.0001 and P < 0.01, respectively). Statistically significant predictors of PFS included age and preoperative seizure presence, with older age favoring longer PFS (P < 0.01) and seizures associated with reduced PFS (P < 0.01). In addition, patients with previous surgeries showed a trend toward shorter PFS (P < 0.05)., Conclusions: This study emphasizes the importance of tailored surgical strategies in managing intracranial ETs, advocating for GTR to optimize long-term outcomes where possible. Future prospective studies are essential to further refine treatment approaches, enhancing survival for ET patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: Many trials have demonstrated the efficacy of specific therapy modalities for individuals with attenuated psychosis symptoms (APS). Less is known regarding mechanisms behind positive outcomes, including the role of nonspecific therapeutic factors. This study explored working alliance (WA) in a clinic serving individuals with APS to see how WA changed across the course of treatment and its relation to APS., Methods: Session level APS and WA data was available for 12 individuals of diverse racial and gender identity, (M = 48 sessions each). Multilevel models with random intercepts tested change in WA and APS over time, and cross-sectional and prospective relations., Results: WA increased and APS decreased over time. Cross sectionally, WA and APS were inversely related. Prospective relations were non-significant., Conclusion: When symptoms increase, therapists for individuals with APS should be attentive to potential disruptions in WA, though strong WA may be a cross-sectional protective factor., (© 2024 John Wiley & Sons Australia, Ltd.)

Suspended animation states allow organisms to survive extreme environments. The African turquoise killifish has evolved diapause as a form of suspended development to survive a complete drought. However, the mechanisms underlying the evolution of extreme survival states are unknown. To understand diapause evolution, we performed integrative multi-omics (gene expression, chromatin accessibility, and lipidomics) in the embryos of multiple killifish species. We find that diapause evolved by a recent remodeling of regulatory elements at very ancient gene duplicates (paralogs) present in all vertebrates. CRISPR-Cas9-based perturbations identify the transcription factors REST/NRSF and FOXOs as critical for the diapause gene expression program, including genes involved in lipid metabolism. Indeed, diapause shows a distinct lipid profile, with an increase in triglycerides with very-long-chain fatty acids. Our work suggests a mechanism for the evolution of complex adaptations and offers strategies to promote long-term survival by activating suspended animation programs in other species., Competing Interests: Declaration of interests A.B. is a scientific advisory board member of Calico. M.P.S. is a co-founder and the scientific advisory board member of Personalis, Qbio, January AI, SensOmics, Filtricine, Protos, Mirvie, Onza, Marble Therapeutics, Iollo, and NextThought AI. He is also on the scientific advisory board of Jupiter, Applied Cognition, Neuvivo, Mitrix, and Enovone. K.C. is currently an AstraZeneca employee., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To streamline the cataract surgery pathway to improve the time from first specialist assessment (FSA) to surgery, while reducing the clinical priority assessment criteria (CPAC) score from 55 to 50., Method: A quality improvement project using Lean Six Sigma tools and the Model for Improvement. Most data were collected from the i.Patient Manager (iPM) system and analysed using statistical process control charts. Change interventions included combining FSA and pre-admission clinics (PAC); post-operative telephone review by non senior medical officers (SMO); and using our own surgeons in private theatres., Results: The standard cataract pathway was reduced from 5 to 3 appointments. This removed 1,514 hours of appointments, released 113 SMO hours and saved patients NZ$156,000 in indirect costs over a year. The average waiting time from FSA to surgery decreased from 90 to 77 days (-13.5%). The number of overdue patients reduced from 127 to 44 (-35%). The average number of patients on the FSA waiting list dropped from 322 to 205 (-40%). There was no change to the proportions of surgeries or appointment attendance rates by ethnicity. Average monthly cataract surgeries increased from 192 to 215 (+12%), and the CPAC score threshold was decreased to 50 in February 2021., Conclusion: Despite significant demand pressures, and the disruptions of COVID-19, we were able to reduce the CPAC score for accessing cataract surgery by optimising the clinical pathway to better utilise staff capacity and maximise value for patients., Competing Interests: Nil., (© PMA.)

The state of genome-wide chromatin accessibility in cells, tissues, or organisms can be investigated with a technique called assay for transposase-accessible chromatin using sequencing (ATAC-seq). ATAC-seq is a powerful approach for profiling the epigenomic landscape of cells using very low input materials. Analysis of chromatin accessibility data allows for prediction of gene expression and identification of regulatory elements such as potential enhancers and specific transcription-factor binding sites. Here, we describe an optimized ATAC-seq protocol for the preparation of isolated nuclei and subsequent next-generation sequencing from whole embryos and tissues of the African turquoise killifish ( Nothobranchius furzeri ). Importantly, we provide an overview of a pipeline for processing and analyzing ATAC-seq data from killifish., (© 2024 Cold Spring Harbor Laboratory Press.)

Background: In studies of the association of adiposity with disease risk, widely used anthropometric measures of adiposity (e.g. body-mass-index [BMI], waist circumference [WC], waist-hip ratio [WHR]) are simple and inexpensive to implement at scale. In contrast, imaging-based techniques (e.g. magnetic resonance imaging [MRI] and dual x-ray absorptiometry [DXA]) are expensive and labour intensive, but can provide more accurate quantification of body fat composition. There is, however, limited evidence about the relationship between conventional and imaging-derived measures of adiposity., Methods: We searched Scopus and Web of Science for published reports in English of conventional versus imaging-derived measurements of adiposity. We identified 42 articles (MRI = 22; DXA = 20) that met selection criteria, involving 42,556 (MRI = 15,130; DXA = 27,426) individuals recruited from community or hospital settings. Study-specific correlation coefficients (r) were transformed using Fisher's Z transformation, and meta-analysed to yield weighted average correlations, both overall and by ancestry, sex and age, where feasible. Publication bias was investigated using funnel plots and Egger's test., Results: Overall, 98% of participants were 18 + years old, 85% male and 95% White. BMI and WC were most strongly correlated with imaging-derived total abdominal (MRI-derived: r = 0.88-; DXA-derived: 0.50-0.86) and subcutaneous abdominal fat (MRI-derived: 0.83-0.85), but were less strongly correlated with visceral abdominal fat (MRI-derived: 0.76-0.79; DXA-derived: 0.80) and with DXA-derived %body fat (0.76). WHR was, at best, strongly correlated with imaging-derived total abdominal (MRI-derived: 0.60; DXA-derived: 0.13), and visceral abdominal fat (MRI-derived: 0.67; DXA-derived: 0.65), and moderately with subcutaneous abdominal (MRI-derived: 0.54), and with DXA-derived %body fat (0.58). All conventional adiposity measures were at best moderately correlated with hepatic fat (MRI-derived: 0.36-0.43). In general, correlations were stronger in women than in men, in Whites than in non-Whites, and in those aged 18 + years., Conclusions: In this meta-analysis, BMI and WC, but not WHR, were very strongly correlated with imaging-derived total and subcutaneous abdominal fat. By comparison, all three measures were moderately or strongly correlated with imaging-based visceral abdominal fat, with WC showing the greatest correlation. No anthropometric measure was substantially correlated with hepatic fat. Further larger studies are needed to compare these measures within the same study population, and to assess their relevance for disease risks in diverse populations., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Stroke is a significant cause of death, and the leading cause of severe long-term disability for individuals over 80 (the very old), yet few studies of such risk factors for ischemic stroke, or the known mitigation techniques, in this population, and the evidence base regarding risk modification strategies in this susceptible population can be inconsistent and incomplete. This article examines current guidelines and evidence regarding medical management, lifestyle changes, and psychosocial interactions that can contribute to the primary and secondary prevention of ischemic stroke in the very old., Areas Covered: The authors conducted a literature search for ischemic stroke prevention and risk assessment in the elderly via PubMed. Furthermore, they describe current strategies for monitoring risk and preventing ischemic stroke in the elderly population., Expert Opinion: Ischemic stroke poses a significant health risk to the elderly, with prevention relying on managing modifiable risk factors such as hypertension, atrial fibrillation, diabetes, and high cholesterol, as well as promoting healthy lifestyle choices like quitting smoking, regular physical activity and a heart-healthy diet. Healthcare providers must adopt a multifaceted approach, addressing individual and population-level factors while remaining vigilant in monitoring and managing risk factors to reduce the incidence and impact of stroke in older adults.

Background: The aim of this study was to determine the extent to which socioeconomic characteristics of the home and neighborhood are associated with racial inequalities in brain outcomes., Methods: We performed a cross-sectional analysis of the baseline dataset (v.2.0.1) from the Adolescent Brain and Cognitive Development (ABCD) Study. Cognitive performance was assessed using the National Institutes of Health Toolbox (NIH-TB) cognitive battery. Standard socioeconomic indicators of the family and neighborhood were derived from census-related statistics. Cortical morphometric measures included MRI-derived thickness, area, and volume., Results: 9638 children were included. Each NIH-TB cognitive measure was negatively associated with household and neighborhood socioeconomic characteristics. Differences in cognitive scores between Black or Hispanic children and other racial groups were mitigated by higher household income. Most children from lowest-income families or residents in impoverished neighborhoods were Black or Hispanic. These disparities were associated with racial differences in NIH-TB measures and mediated by smaller cortical brain volumes., Conclusions: Neighborhood socioeconomic characteristics are associated with racial differences in preadolescent brain outcomes and mitigated by greater household income. Household income mediates racial differences more strongly than neighborhood-level socioeconomic indicators in brain outcomes. Highlighting these socioeconomic risks may direct focused policy-based interventions such as allocation of community resources to ensure equitable brain outcomes in children., Impact: Neighborhood socioeconomic characteristics are associated with racial differences in preadolescent brain outcomes and mitigated by greater household income. Household income mediates racial differences more strongly than neighborhood-level socioeconomic indicators in brain outcomes. Highlighting these disparities related to socioeconomic risks may direct focused policy-based interventions such as allocation of community resources to ensure equitable brain outcomes in children., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have the following interests to declare. TG is a member of the Academic and Research Committee for the Association of Breast Surgery, the Clinical Advisory Panel for Cancer Research UK, and National Audit of Primary Breast Cancer Audit Advisory Committee. RIC is a trustee and chair of the Academic and Research Committee for the Association of Breast Surgery, a committee member for the National Institute for Health and Care Excellence, joint lead investigator for the EndoNET Trial, and has received research support from SECA and Astra-Zeneca. DD and KH are the oncology and surgical leads for the National Audit of Primary Breast Cancer. KH is the chair of the EndoNet Trial Steering Committee. GKR is a committee member for the National Institute for Health and Care Excellence. TG, SS, SWK, and/DD are funded in part by Cancer Research UK (C16077/A29186, C8225/A21133).

C 4 photosynthesis has evolved by repurposing enzymes found in C 3 plants. Compared with the ancestral C 3 state, accumulation of C 4 cycle proteins is enhanced. We used de-etiolation of C 4 Gynandropsis gynandra and C 3 Arabidopsis thaliana to understand this process. C 4 gene expression and chloroplast biogenesis in G. gynandra were tightly coordinated. Although C 3 and C 4 photosynthesis genes showed similar induction patterns, in G. gynandra . In vivo binding of TGA and homeodomain as well as light-responsive elements such as G- and I-box motifs were associated with the rapid increase in transcripts of C 4 genes. Deletion analysis confirmed that regions containing G- and I-boxes were necessary for high expression. The data support a model in which accumulation of transcripts derived from C A. thaliana . In vivo binding of TGA and homeodomain as well as light-responsive elements such as G- and I-box motifs were associated with the rapid increase in transcripts of C 4 genes. Deletion analysis confirmed that regions containing G- and I-boxes were necessary for high expression. The data support a model in which accumulation of transcripts derived from C 4 photosynthesis genes in C 4 leaves is enhanced because modifications in cis allowed integration into ancestral transcriptional networks.

Background: Current or recent use of combined oral contraceptives (containing oestrogen+progestagen) has been associated with a small increase in breast cancer risk. Progestagen-only contraceptive use is increasing, but information on associated risks is limited. We aimed to assess breast cancer risk associated with current or recent use of different types of hormonal contraceptives in premenopausal women, with particular emphasis on progestagen-only preparations., Methods and Findings: Hormonal contraceptive prescriptions recorded prospectively in a UK primary care database (Clinical Practice Research Datalink [CPRD]) were compared in a nested case-control study for 9,498 women aged <50 years with incident invasive breast cancer diagnosed in 1996 to 2017, and for 18,171 closely matched controls. On average, 7.3 (standard deviation [SD] 4.6) years of clinical records were available for each case and their matched controls prior to the date of diagnosis. Conditional logistic regression yielded odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer by the hormonal contraceptive type last prescribed, controlled for age, GP practice, body mass index, number of recorded births, time since last birth, and alcohol intake. MEDLINE and Embase were searched for observational studies published between 01 January 1995 and 01 November 2022 that reported on the association between current or recent progestagen-only contraceptive use and breast cancer risk in premenopausal women. Fixed effects meta-analyses combined the CPRD results with previously published results from 12 observational studies for progestagen-only preparations. Overall, 44% (4,195/9,498) of women with breast cancer and 39% (7,092/18,171) of matched controls had a hormonal contraceptive prescription an average of 3.1 (SD 3.7) years before breast cancer diagnosis (or equivalent date for controls). About half the prescriptions were for progestagen-only preparations. Breast cancer ORs were similarly and significantly raised if the last hormonal contraceptive prescription was for oral combined, oral progestagen-only, injected progestagen, or progestagen-releasing intrauterine devices (IUDs): ORs = 1.23 (95% CI [1.14 to 1.32]; p < 0.001), 1.26 (95% CI [1.16 to 1.37]; p < 0.001), 1.25 (95% CI [1.07 to 1.45]; p = 0.004), and 1.32 (95% CI [1.17 to 1.49]; p < 0.001), respectively. Our meta-analyses yielded significantly raised relative risks (RRs) for current or recent use of progestagen-only contraceptives: oral = 1.29 (95% CI [1.21 to 1.37]; heterogeneity χ25 = 6.7; p = 0.2), injected = 1.18 (95% CI [1.07 to 1.30]; heterogeneity χ28 = 22.5; p = 0.004), implanted = 1.28 (95% CI [1.08 to 1.51]; heterogeneity χ23 = 7.3; p = 0.06), and IUDs = 1.21 (95% CI [1.14 to 1.28]; heterogeneity χ24 = 7.9; p = 0.1). When the CPRD results were combined with those from previous published findings (which included women from a wider age range), the resulting 15-year absolute excess risk associated with 5 years use of oral combined or progestagen-only contraceptives in high-income countries was estimated at: 8 per 100,000 users from age 16 to 20 years and 265 per 100,000 users from age 35 to 39 years. The main limitation of the study design was that, due to the nature of the CPRD data and most other prescription databases, information on contraceptive use was recorded during a defined period only, with information before entry into the database generally being unavailable. This means that although our findings provide evidence about the short-term associations between hormonal contraceptives and breast cancer risk, they do not provide information regarding longer-term associations, or the impact of total duration of contraceptive use on breast cancer risk., Conclusions: This study provides important new evidence that current or recent use of progestagen-only contraceptives is associated with a slight increase in breast cancer risk, which does not appear to vary by mode of delivery, and is similar in magnitude to that associated with combined hormonal contraceptives. Given that the underlying risk of breast cancer increases with advancing age, the absolute excess risk associated with use of either type of oral contraceptive is estimated to be smaller in women who use it at younger rather than at older ages. Such risks need be balanced against the benefits of using contraceptives during the childbearing years., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Fitzpatrick et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Extensive research has demonstrated racial disparities, particularly among Black individuals, in both presentation and course of psychosis spectrum disorders. Few studies, however, have examined racial differences in the clinical high-risk (CHR) phase of illness. It is unclear if functional deficits seen in association with CHR symptoms generalize to marginalized racial groups, or whether race may play a role in the link between symptoms and functioning. In a sample of youth at CHR (N = 46), the present study examined the effect of race (Black and White represented in this sample) on the relation between CHR symptoms and social/role functioning. Race had a moderating effect on the relation between CHR symptoms and social functioning for total positive symptom score (p < .04, f 2  = 0.10). Although positive symptoms were associated with worse social functioning for White participants, no association was found for Black participants. Follow up analyses indicated suspiciousness was a statistically significant predictor of social functioning for White participants but was unrelated to functioning for Black participants. Results may be indicative of phenomenon experienced by individuals within racial minority groups (e.g., "healthy suspiciousness") or potential measurement validity concerns. Findings further the understanding of racial differences in the CHR phase of illness among White and Black youth and highlight limitations of the existing CHR literature and assessment tools for diverse youth., Competing Interests: Declaration of competing interest The authors do not have any conflicts of interest, including financial relationships, to disclose., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: As patients with heart failure experience worsening of their condition, including acute decompensated heart failure, quality of life deteriorates. However, the trajectory of quality of life changes and their determinants in the context of the Rehabilitation Therapy in Older Acute Heart Failure Patients trial physical rehabilitation intervention are unknown., Methods: Patients ≥60 years old admitted for acute decompensated heart failure (n=349) were randomized to either attention control or intervention. Quality of life outcomes (Kansas City Cardiomyopathy Questionnaire; 12-Item Short-Form Health Survey) were measured at baseline (inpatient), 1 month, and 3 months. Intervention effects were assessed using linear mixed effects regression, including covariates to model the main effects of the intervention and timing of outcome assessments. Mediation analysis determined if changes in Kansas City Cardiomyopathy Questionnaire were due to improvement in physical function (short physical performance battery, 6-minute walk distance)., Results: Baseline Kansas City Cardiomyopathy Questionnaire summary score was similarly poor in the intervention and control arms (40.2±20.6 versus 41.5±20.6). Although the intervention experienced nominally greater Kansas City Cardiomyopathy Questionnaire improvement than control at 1 month (64.7±1.9 versus 61.1±1.9, P =0.13), the difference was not statistically significant until 3 months (67.7±1.9 versus 60.8±1.9, P =0.004). Twelve-Item Short-Form Health Survey Physical and Mental Composite Scores increased in both arms at 1 month and continued improvement only in the intervention. The 3-month improvement in short physical performance battery score explained 64.1% of the improvement in Kansas City Cardiomyopathy Questionnaire ( P <0.001)., Conclusions: In older patients hospitalized for acute decompensated heart failure, quality of life improves in the first month after discharge. The quality of life benefit of a post-discharge physical rehabilitation intervention is detected early with large significant improvements at 3 months achieved primarily through improvement in short physical performance battery., Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT02196038.

Background: Older patients hospitalized with acute decompensated heart failure (ADHF) have marked functional impairments, which may contribute to their delayed and incomplete recovery and persistently poor outcomes. However, whether impairment severity differs by race and sex is unknown., Methods: REHAB-HF trial participants (≥60 years) were assessed just before discharge home from ADHF hospitalization. Physical function [Short Physical Performance Battery; 6-min walk distance (6MWD)], frailty (Fried criteria), cognition [Montreal Cognitive Assessment (MoCA)], quality-of-life [Kansas City Cardiomyopathy Questionnaire, Short-Form-12, EuroQol-5D-5L], and depression [Geriatric Depression Scale (GDS)] were examined by race and sex., Results: This prespecified subgroup cross-sectional analysis included 337 older adults (52% female, 50% Black). Black participants were on average younger than White participants (70.3 ± 7.2 vs. 74.7 ± 8.3 years). After age, body mass index, ejection fraction, comorbidity, and education adjustment, and impairments were similarly common and severe across groups except: Black male and Black and White female participants had more severely impaired walking function compared with White male participants [6MWD (m) 187 ± 12, 168 ± 9170 ± 11 vs. 239 ± 9, p < 0.001]; gait speed (m/s) (0.61 ± 0.03, 0.56 ± 0.02, 0.55 ± 0.02 vs. 0.69 ± 0.02, p < 0.001); White female participants had the highest frailty prevalence (72% vs. 47%-51%, p = 0.007); and Black participants had lower MoCA scores compared with White participants (20.9 ± 4.5 vs. 22.8 ± 3.9, p < 0.001). Depressive symptoms were common overall (43% GDS ≥5), yet underrecognized clinically (18%), especially in Black male participants compared with White male participants (7% vs. 20%)., Conclusion: Among older patients hospitalized for ADHF, frailty and functional impairments with high potential to jeopardize patient HF self-management, safety, and independence were common and severe across all race and sex groups. Impairment severity was often worse in Black participant and female participant groups. Formal screening across frailty and functional domains may identify those who may require greater support and more tailored care to reduce the risk of adverse events and excess hospitalizations and death., (© 2022 The American Geriatrics Society.)

Dropout events are dramatic decreases in radiation belt electron populations that can occur in as little as 30 minutes. Loss to magnetopause due to a combination of magnetopause shadowing and outward radial transport plays a significant role in these events. We examine the dropout of relativistic electron populations during the October 2012 geomagnetic storm using simulated electron phase space density, evaluating the contribution of different processes to losses across the magnetopause. We compare loss contribution from outward transport calculated using a standard empirical radial diffusion model that assumes a dipolar geomagnetic field to an event-specific radial diffusion model evaluated with a non-dipolar geomagnetic field. We additionally evaluate the contribution of Shabansky type 1 particles, which bounce along magnetic field lines with local equatorial maxima, to the loss calculated during this event. We find that the empirical radial diffusion model with a dipolar background field underestimates the contribution of radial diffusion to this dropout event by up to 10% when compared to the event-specific, non-dipolar radial diffusion model. We additionally find that including Shabansky type 1 particles in the initial electron phase space density, that is, allowing some magnetic field lines distorted from the typical single-minima configuration in drift shell construction, increases the calculated loss by an average of 0.75%. This shows that the treatment of the geomagnetic field significantly impacts the calculation of electron losses to the magnetopause during dropout events, with the non-dipolar treatment of radial diffusion being essential to accurately quantify the loss of outer radiation belt populations., (©2022. The Authors.)

Objective: Peer victimization is a substantial early life stressor linked to psychiatric symptoms and poor academic performance. However, the sex-specific cognitive or behavioral outcomes of bullying have not been well-described in preadolescent children., Methods: Using the baseline dataset of the Adolescent Brain Cognitive Development (ABCD) Study 2.0.1 data repository ( N  = 11,875), we evaluated associations between parent-reported bullying victimization, suicidality (suicidal ideation, intent, and/or behavior), and non-suicidal self-injury (NSSI), as well as internalizing and externalizing behavioral problems, cognition, and academic performance., Results: Of the 11,015 9-10-year-old children included in the analyses (5,263 girls), 15.3% experienced bullying victimization, as reported by the primary caregiver. Of these, boys were more likely to be bullied than girls (odds ratio [OR], 1.2 [95% CI, 1.1-1.3]; p  = 0.004). Children who were bullied were more likely to display NSSI or passive suicidality (OR, 2.4 [95% CI, 2.0-2.9]; p  < 0.001) and active suicidality (OR, 3.4 [95% CI, 2.7-4.2]; p  < 0.001). Bullied children also had lower cognitive scores, greater behavioral problems, and poorer grades ( p  < 0.001). Across all participants, boys had poorer grades and greater behavioral problems than girls; however, bullied boys had greater behavioral problems than girls in several areas ( p  < 0.001). Compared to their non-bullied peers, bullied children with greater non-suicidal self-injury or suicidality also had greater behavioral problems and poorer grades ( p  < 0.001)., Conclusion: These findings highlight the sex-specific effects of bullying, and the negative associations of bullying victimization with cognitive performance, behavioral problems, and academic performance. Future longitudinal studies will identify the natural history and neural correlates of these deficits during adolescence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Menken, Isaiah, Liang, Rodriguez Rivera, Cloak, Reeves, Lever and Chang.)

Existing evidence shows positive effects of being in nature on wellbeing, but we know little about the mental health benefits of spending time near canals and rivers specifically. This study investigates the association between visits to canals and rivers and mental wellbeing. We addressed the following questions: Are visits to canals and rivers associated with higher levels of mental wellbeing? Does this association depend on age and gender? Does this association vary between people with and without a diagnosis on mental illness? We used Urban Mind, a flexible smartphone application for examining the impact of different aspects of the built and social environment on mental wellbeing, a strong predictor of mental health. Participants were invited to complete an ecological momentary assessment three times a day for fourteen days. Each assessment included questions about their surrounding environment and mental wellbeing. A total of 7,975 assessments were completed by 299 participants including 87 with a diagnosis of mental illness. Multilevel regression models were used to analyse the data. We found positive associations between visits to canals and rivers and mental wellbeing (p < .05) when compared to being anywhere else and when compared to being in green spaces. Increases in mental wellbeing were still evident after the visit had taken place. These effects remained significant after adjusting for age, gender, ethnicity and education, and were consistent in people with and without a diagnosis of mental illness. Spending time near canals and rivers is associated with better mental wellbeing. These findings have potential implications for mental health as well as urban planning and policy. Visits to canals and rivers could become part of social prescribing schemes, playing a role in preventing mental health difficulties and complementing more traditional interventions., Competing Interests: The study was part-funded by the Canal and River Trust, which is a registered charity in the United Kingdom. Jenny Shepherd and Graham Reeves are both employed by The Canal and River Trust. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: To examine trends in off-label antipsychotic use for youth with attention-deficit/hyperactivity disorder with and without a comorbid disruptive behavior disorder., Method: This cross-sectional study of annual trends from 2007 through 2015 used the IQVIA PharMetrics® Plus for Academics data. We identified 165 794 commercially-insured youth 3-18-year-old who had a diagnosis of attention-deficit/hyperactivity disorder and classified them into subgroups with and without disruptive behavior disorders comorbidities. Antipsychotic use, with or without a stimulant, was the primary dependent outcome. Logistic regression estimated the odds of antipsychotic use associated with comorbid attention-deficit/hyperactivity disorder and disruptive behavior disorders, adjusting for age, sex, study year, and other psychotropic use., Results: Over 70% of the 165 794 youth with attention-deficit/hyperactivity disorder were 5-14-year-old and male, and 12% had disruptive behavior disorders. Antipsychotic prevalence, with or without a stimulant, was 4.4% in 2007 and 3.4% in 2015. Stimulants with antipsychotics increased significantly from 2007 to 2015 for females (19.5%-28.7%) and youth 15-18-year-old (25.9%-32.7%). Adjusting for age, sex, study year, and other psychotropic use, youth with a comorbid disruptive behavior had a 2.5 (95% CI: 2.3, 2.7) higher likelihood of receiving an antipsychotic than youth with attention-deficit/hyperactivity disorder and no comorbidities., Conclusions: Antipsychotic use was associated with comorbid disruptive behaviors in youth with attention-deficit/hyperactivity disorder. Off-label antipsychotic use has increased for females and older adolescents., (© 2022 John Wiley & Sons Ltd.)

The current cross-sectional study aimed to extend the literature on childhood adversity by examining the unique associations between potentially traumatic events (PTEs) and a range of mental health concerns, including domain-specific versus comorbid concerns. Participants were 11,877 preadolescents (47.8% female, 15.0% Black, 20.3% Hispanic/Latinx, M age  = 9.5 years) taking part in the Adolescent Brain and Cognitive Development (ABCD) Study ® . The Kiddie Schedule for Affective Disorders and Schizophrenia was used to measure PTEs and caregiver- and child-reported mental health concerns. Adjusted odds ratios (aORs) were used for the outcomes of interest. Overall, PTEs were consistently associated with increased odds of experiencing comorbid posttraumatic stress disorder (PTSD), internalizing disorders, and externalizing disorders, significant AORs = 1.34-4.30, after accounting for children's experiences of other PTEs and polyvictimization. In contrast, PTEs were generally not associated with meeting the criteria for diagnoses within only one domain (i.e., internalizing-only or externalizing-only diagnoses). We also found PTEs to be differentially related to the various mental health outcomes. In particular, witnessing domestic violence was consistently associated with children's psychopathology. Other PTEs, such as witnessing community violence, were not associated with children's psychopathology in the final model. Associations between PTEs and mental health concerns did not differ as a function of sex. Overall, the results support the notion that PTEs are associated with comorbid concerns rather than individual disorders. These findings have important implications for the screening of PTEs, continued research on the conceptualization of traumatic stress, and the importance of accounting for comorbidities across mental health domains., (© 2022 International Society for Traumatic Stress Studies.)

Reducing photorespiration in C3 crops could significantly increase rates of photosynthesis and yield. One method to achieve this would be to integrate C4 photosynthesis into C3 species. This objective is challenging as it involves engineering incompletely understood traits into C3 leaves, including complex changes to their biochemistry, cell biology, and anatomy. Quantitative genetics and selective breeding offer underexplored routes to identify regulators of these processes. We first review examples of natural intraspecific variation in C4 photosynthesis as well as the potential for hybridization between C3 and C4 species. We then discuss how quantitative genetic approaches including artificial selection and genome-wide association could be used to better understand the C4 syndrome and in so doing guide the engineering of the C4 pathway into C3 crops., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Background/objectives: Chronic noncancer pain (CNCP) affects millions of individuals in the United States but evidence of its prevalence among caregivers of children with special health care needs is sparse. We sought to estimate the prevalence of CNCP and its association with caregiver burden, in a nationally representative sample., Methods: Retrospective cross-sectional study using pooled Medical Expenditure Panel Survey data for 2010-2015. Within interviewed households, family groups consisting of at least 1 parent and 1 child (0-17 y) were identified. CNCP was identified by one or more International Classification of Diseases, Ninth Revision (ICD-9)-CM codes utilizing previously published approaches. Level of caregiver burden was defined using a validated screener questionnaire identifying children with high burden of care (ie, special health care needs), for example, high or low burden. We estimated prevalence of CNCP as a function of caregiver burden, as well as the association of risk factors with CNCP, including parent sociodemographic features, clinical diagnoses, and family level characteristics., Results: We identified 46,525 caregivers of whom 3.6% reported experiencing high caregiving burden. The prevalence of CNCP was 25.5% and 14.0% among parents with high compared with low caregiving burden, respectively. Odds of CNCP were higher among parents with high compared to those with lower caregiver burden (odds ratio=1.29, 95% confidence interval=1.06-1.55). Being obese, experiencing disability, and having a mental health diagnosis were associated with higher odds of CNCP., Conclusions: Chronic pain is more common among caregivers with high caregiver burden. Our findings highlight the need to further explore the nature and impact of risk factors on caregiver health and disability., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To identify antidepressant dose trajectories in the first 6-months of antidepressant initiation and to evaluate the association between antidepressant dose trajectories and augmentation with another psychotropic medication., Methods: Using the IQVIA PharMetrics® Plus database, we identified 5655 commercially insured youth (3-18 years) with depression who newly initiated an antidepressant anytime from January 2007 to June 2015. No antidepressant use within 1 year prior to the index prescription defined new use. Latent class growth analysis of antidepressant dosing in the 6 months after initiation defined the exposure groups. The outcome was any regimen change, that is, antidepressant augmentation with another psychotropic or discontinuation of the antidepressant, with and without switching to another psychotropic. Baseline covariates measured in the 6 months before antidepressant initiation included demographic factors, psychiatric comorbidities, and health service use. Multinomial logistic regression tested the association between antidepressant dose trajectories and the odds of an antidepressant regimen change., Results: Five dose trajectories were sharp decline (n = 897; 16%), slow decline (n = 1029; 18%), stable minimum dose (n = 1397; 25%), stable maximum dose (n = 1783; 32%), and increasing high dose (n = 549; 10%). Relative to the stable minimum dose group, the sharp and slow decline groups were more likely to discontinue the antidepressant, either switch to another psychotropic (OR [odds ratio]: 5.91; 95%CI: 3.23-10.80 and OR: 1.67; 95%CI: 1.04-2.68, respectively) or stop all psychotropic medication (OR: 6.64; 95%CI: 4.24-10.39 and OR: 1.62; 95%CI: 1.22-2.13, respectively). However, the stable maximum and increasing high-dose groups were less likely to discontinue, either switch (OR: 0.38; 95%CI: 0.24-0.61 and OR: 0.30; 95%CI: 0.16-0.59, respectively) or stop all psychotropic medications (OR: 0.15; 95%CI: 0.12-0.20 and OR: 0.02; 95%CI: 0.01-0.03 respectively) than augment with another psychotropic., Conclusions: The findings from this cross-sectional study demonstrate an association between antidepressant dose trajectories within 6 months of initiating treatment and the odds of augmenting with another psychotropic., (© 2021 John Wiley & Sons Ltd.)

Grafting is possible in both animals and plants. Although in animals the process requires surgery and is often associated with rejection of non-self, in plants grafting is widespread, and has been used since antiquity for crop improvement 1 . However, in the monocotyledons, which represent the second largest group of terrestrial plants and include many staple crops, the absence of vascular cambium is thought to preclude grafting 2 . Here we show that the embryonic hypocotyl allows intra- and inter-specific grafting in all three monocotyledon groups: the commelinids, lilioids and alismatids. We show functional graft unions through histology, application of exogenous fluorescent dyes, complementation assays for movement of endogenous hormones, and growth of plants to maturity. Expression profiling identifies genes that unify the molecular response associated with grafting in monocotyledons and dicotyledons, but also gene families that have not previously been associated with tissue union. Fusion of susceptible wheat scions to oat rootstocks confers resistance to the soil-borne pathogen Gaeumannomyces graminis. Collectively, these data overturn the consensus that monocotyledons cannot form graft unions, and identify the hypocotyl (mesocotyl in grasses) as a meristematic tissue that allows this process. We conclude that graft compatibility is a shared ability among seed-bearing plants., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

The Van Allen Probes mission operations materialized through a distributed model in which operational responsibility was divided between the Mission Operations Center (MOC) and separate instrument specific SOCs. The sole MOC handled all aspects of telemetering and receiving tasks as well as certain scientifically relevant ancillary tasks. Each instrument science team developed individual instrument specific SOCs proficient in unique capabilities in support of science data acquisition, data processing, instrument performance, and tools for the instrument team scientists. In parallel activities, project scientists took on the task of providing a significant modeling tool base usable by the instrument science teams and the larger scientific community. With a mission as complex as Van Allen Probes, scientific inquiry occurred due to constant and significant collaboration between the SOCs and in concert with the project science team. Planned cross-instrument coordinated observations resulted in critical discoveries during the seven-year mission. Instrument cross-calibration activities elucidated a more seamless set of data products. Specific topics include post-launch changes and enhancements to the SOCs, discussion of coordination activities between the SOCs, SOC specific analysis software, modeling software provided by the Van Allen Probes project, and a section on lessons learned. One of the most significant lessons learned was the importance of the original decision to implement individual team SOCs providing timely and well-documented instrument data for the NASA Van Allen Probes Mission scientists and the larger magnetospheric and radiation belt scientific community., (© The Author(s) 2022.)

This paper presents the highlights of joint observations of the inner magnetosphere by the Arase spacecraft, the Van Allen Probes spacecraft, and ground-based experiments integrated into spacecraft programs. The concurrent operation of the two missions in 2017-2019 facilitated the separation of the spatial and temporal structures of dynamic phenomena occurring in the inner magnetosphere. Because the orbital inclination angle of Arase is larger than that of Van Allen Probes, Arase collected observations at higher L -shells up to L ∼ 10 . After March 2017, similar variations in plasma and waves were detected by Van Allen Probes and Arase. We describe plasma wave observations at longitudinally separated locations in space and geomagnetically-conjugate locations in space and on the ground. The results of instrument intercalibrations between the two missions are also presented. Arase continued its normal operation after the scientific operation of Van Allen Probes completed in October 2019. The combined Van Allen Probes (2012-2019) and Arase (2017-present) observations will cover a full solar cycle. This will be the first comprehensive long-term observation of the inner magnetosphere and radiation belts., (© The Author(s) 2022.)

Aim: Early psychosis is typically operationalized as a categorical construct by dividing people into one of three diagnostic statuses: low-risk, clinical high-risk, and first episode psychosis. We empirically assess whether an alternative dimensional approach focused on observed symptom severity may be more desirable for clinical and research purposes., Methods: Participants were 152 help-seeking youths ages 12-22 years old. Structured interview for psychosis risk syndromes interviews were used to obtain dimensional psychosis symptom severity ratings, and to classify participants by categorical psychosis risk status. Twenty-five participants were classified as having a diagnosable psychotic disorder, 52 participants as clinical high-risk, and 75 participants as help-seeking controls. We assessed the relation between categorical and dimensional measurements of psychosis severity, and then compared categorical versus dimensional psychosis severity in their ability to predict social and role functioning., Results: On average, dimensional psychosis symptom severity increased along with categorical risk status (help-seeking control < clinical high-risk < diagnosable psychotic disorder). There was, however, considerable overlap between categories, with people at clinical high-risk being particularly hard to distinguish from people with diagnosable psychotic disorders on the basis of symptom severity. Dimensional symptom severity was more predictive of functioning than categorical risk status., Conclusions: Categorical risk status and psychosis symptom severity are related but not interchangeable, and dimensional models of psychosis may be more predictive of functional outcomes. Adopting a dimensional rather than categorical approach to the psychosis risk spectrum may facilitate better predictive models and a richer theoretical understanding of early psychosis., (© 2021 John Wiley & Sons Australia, Ltd.)

The Adolescent Brain Cognitive Development (ABCD) Study ® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Ethnic minority women are commonly reported to have more aggressive breast cancer than White women, but there is little contemporary national evidence available., Methods: We analysed data from the National Cancer Registration and Analysis Service on women diagnosed with invasive breast cancer during 2013-2018. Multivariable logistic regression yielded adjusted odds ratios (and 95% confidence intervals) of less favourable tumour characteristics (high stage, high grade, ER negative, Her2 positive) by ethnicity (black African, black Caribbean, Indian, Pakistani and white) in younger (30-46 years) and older (53-70 years) women., Results: In 24,022 women aged 30-46 at diagnosis, all ethnic minority groups apart from Indian women had a significantly greater odds of certain less favourable tumour characteristics compared to white women in fully adjusted models. In 92,555 women aged 53-70, all ethnic minorities had a significantly greater adjusted odds of several of the less favourable tumour characteristics. These differences were most marked in black African and black Caribbean women., Conclusions: Ethnic minority women are at greater risk of breast cancers with less favourable characteristics, even after allowing for age and other potential confounders. These differences are greater in older than younger women, and in the Black rather than South Asian ethnic groups., (© 2021. The Author(s).)

Background: Older patients with acute decompensated heart failure (ADHF) have severely impaired physical function (PF) and quality of life (QOL). However, relationships between impairments in PF and QOL are unknown but are relevant to clinical practice and trial design., Methods: We assessed 202 consecutive patients hospitalized with ADHF in the multicenter Rehabilitation Therapy in Older Acute HF Patients (REHAB-HF) Trial. PF measures included Short Physical Performance Battery (SPPB) and 6-min walk distance (6MWD). Disease-specific QOL was assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ). General QOL was assessed by the Short Form-12 (SF-12) and EuroQol-5D-5L. PF was evaluated as a predictor of QOL using stepwise regression adjusted for age, sex, race, and New York Heart Association class., Results: Participants were 72 ± 8 years, 54% women, 55% minority race, 52% with reduced ejection fraction, and body mass index 33 ± 9 kg/m 2 . Participants had severe impairments in PF (6MWD 185 ± 99 m, SPPB 6.0 ± 2.5 units) and disease-specific QOL (KCCQ Overall Score 41 ± 21 and Physical Score 47 ± 24) and general QOL (SF-12 Physical Score 28 ± 9 and EuroQol Visual Analog Scale 57 ± 23). There were modest, statistically significant correlations between 6MWD and KCCQ Overall, KCCQ Physical Limitation, and SF-12 Physical Scores (r = 0.23, p < 0.001; r = 0.30, p < 0.001; and r = 0.24, p = 0.001, respectively); and between SPPB and KCCQ Physical and SF-12 Physical Scores (r = 0.20, p = 0.004, and r = 0.19, p = 0.007, respectively). Both 6MWD and SPPB were correlated with multiple components of the EuroQol-5D-5L. 6MWD was a significant, weak predictor of KCCQ Overall Score and SF-12 Physical Score (estimate = 0.05 ± 0.01, p < 0.001 and estimate = 0.05 ± 0.02, p = 0.012, respectively). SPPB was a significant, weak predictor of KCCQ Physical Score and SF-12 Physical Score (estimate = 1.37 ± 0.66, p = 0.040 and estimate = 0.54 ± 0.25, p = 0.030, respectively)., Conclusion: In older, hospitalized ADHF patients, PF and QOL are both severely impaired but are only modestly related, suggesting that PF and QOL provide complementary information and assessment of both should be considered to fully assess clinically meaningful patient-oriented outcomes., (© 2021 The American Geriatrics Society.)

Posterior computation for high-dimensional data with many parameters can be challenging. This article focuses on a new method for approximating posterior distributions of a low- to moderate-dimensional parameter in the presence of a high-dimensional or otherwise computationally challenging nuisance parameter. The focus is on regression models and the key idea is to separate the likelihood into two components through a rotation. One component involves only the nuisance parameters, which can then be integrated out using a novel type of Gaussian approximation. We provide theory on approximation accuracy that holds for a broad class of forms of the nuisance component and priors. Applying our method to simulated and real data sets shows that it can outperform state-of-the-art posterior approximation approaches.

Background: Youth treated with antipsychotic medications are high risk for weight gain, increased lipids/glucose, and development of metabolic syndrome. Little is known about the dietary intake/nutritional adequacy in this vulnerable population, and effect on weight gain. This secondary data analysis describes the baseline intake and changes in diet after receiving healthy lifestyle education/counseling over 6 months, in a sample of youth with antipsychotic-induced weight gain. Methods: The U.S. Department of Agriculture (USDA) Automated Multiple-Pass Method 24-hour dietary recall was administered to 117 youth at baseline, 3 months, and 6 months. Parent/child received personalized healthy lifestyle education sessions over 6 months. Baseline intake was compared with the USDA Recommended Daily Allowance using independent samples t -tests. Individual dietary covariates were examined for change over 6 months using longitudinal linear mixed modeling. Influence of each on body mass index (BMI) z -score change was tested in a pooled group analysis and then compared by treatment group. Results: Pooled analysis revealed baseline consumption high in carbohydrates, fat, protein, sugar, and refined grains, while low in fruit/vegetables, whole grains, fiber, and water. Change over 6 months demonstrated a statistically significant decrease in daily calories ( p  = 0.002), carbohydrates ( p  = 0.003), fat ( p  = 0.012), protein ( p  = 0.025), sugar ( p  = 0.008), refined grains ( p  = 0.008), total dairy ( p  = 0.049), and cheese ( p  = 0.027). Small increases in fruits/vegetables were not statistically significant, although the Healthy Eating Index subscores for total vegetables ( p  = 0.013) and dark green/orange vegetables ( p  = 0.034) were. No dietary covariates were predictors of change in BMI z -score. Nondietary predictors were parent weight/BMI and treatment group, with the metformin and switch groups experiencing significant decreases in BMI z -score. Conclusions: Further pediatric studies are necessary to assess the effects of antipsychotic medications on dietary intake, and test efficacy of healthy lifestyle interventions on change in nutrition. The relationship of nutrition to cardiometabolic health in this population must be further investigated. Clinical Trial Registration number: NCT02877823.

Background: Limited information is available about patterns of surgical management of early breast cancer by ethnicity of women in England, and any potential inequalities in the treatment received for breast cancer., Methods: National Cancer Registration and Analysis Service data for women diagnosed with early invasive breast cancer (ICD-10 C50) during 2012-2017 were analysed. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95 per cent confidence intervals for the risk of mastectomy versus breast-conserving surgery by ethnicity (black African, black Caribbean, Indian, Pakistani and white), adjusting for age, region, deprivation, year of diagnosis, co-morbidity and stage at diagnosis., Results: Data from 164 143 women were included in the analysis. The proportion of women undergoing mastectomy fell by approximately 5 per cent between 2012 and 2017 across all the ethnic groups examined. In unadjusted analyses, each ethnic minority group had a significantly higher odds of mastectomy than white women; however, in the fully adjusted model, there were no significantly increased odds of having mastectomy for women of any ethnic minority group examined. For example, compared with white women, the unadjusted and fully adjusted ORs for mastectomy were 1·14 (95 per cent c.i. 1·05 to 1·20) and 1·04 (0·96 to 1·14) respectively for Indian women, and 1·45 (1·30 to 1·62) and 1·00 (0·89 to 1·13) for black African women. This attenuation in OR by ethnicity was largely due to adjustment for age and stage., Conclusion: Allowing for different patterns of age and stage at presentation, the surgical management of early breast cancer is similar in all women, regardless of ethnicity., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

Importance: Incidental findings (IFs) are unexpected abnormalities discovered during imaging and can range from normal anatomic variants to findings requiring urgent medical intervention. In the case of brain magnetic resonance imaging (MRI), reliable data about the prevalence and significance of IFs in the general population are limited, making it difficult to anticipate, communicate, and manage these findings., Objectives: To determine the overall prevalence of IFs in brain MRI in the nonclinical pediatric population as well as the rates of specific findings and findings for which clinical referral is recommended., Design, Setting, and Participants: This cohort study was based on the April 2019 release of baseline data from 11 810 children aged 9 to 10 years who were enrolled and completed baseline neuroimaging in the Adolescent Brain Cognitive Development (ABCD) study, the largest US population-based longitudinal observational study of brain development and child health, between September 1, 2016, and November 15, 2018. Participants were enrolled at 21 sites across the US designed to mirror the demographic characteristics of the US population. Baseline structural MRIs were centrally reviewed for IFs by board-certified neuroradiologists and findings were described and categorized (category 1, no abnormal findings; 2, no referral recommended; 3; consider referral; and 4, consider immediate referral). Children were enrolled through a broad school-based recruitment process in which all children of eligible age at selected schools were invited to participate. Exclusion criteria were severe sensory, intellectual, medical, or neurologic disorders that would preclude or interfere with study participation. During the enrollment process, demographic data were monitored to ensure that the study met targets for sex, socioeconomic, ethnic, and racial diversity. Data were analyzed from March 15, 2018, to November 20, 2020., Main Outcomes and Measures: Percentage of children with IFs in each category and prevalence of specific IFs., Results: A total of 11 679 children (52.1% boys, mean [SD] age, 9.9 [0.62] years) had interpretable baseline structural MRI results. Of these, 2464 participants (21.1%) had IFs, including 2013 children (17.2%) assigned to category 2, 431 (3.7%) assigned to category 3, and 20 (0.2%) assigned to category 4. Overall rates of IFs did not differ significantly between singleton and twin gestations or between monozygotic and dizygotic twins, but heritability analysis showed heritability for the presence or absence of IFs (h2 = 0.260; 95% CI, 0.135-0.387)., Conclusions and Relevance: Incidental findings in brain MRI and findings with potential clinical significance are both common in the general pediatric population. By assessing IFs and concurrent developmental and health measures and following these findings over the longitudinal study course, the ABCD study has the potential to determine the significance of many common IFs.

Objectives: To investigate the risk of cardiovascular events associated with concomitant use of stimulants and atypical antipsychotics (AAPs) among youth and evaluate whether AAP dose and duration of concomitant use modifies the risk. Methods: We used IQVIA PharMetrics® Plus data from 2006 to 2015 to construct a retrospective cohort of commercially-insured youth aged 5-17 years old who initiated a stimulant medication. Time-varying concomitant stimulant/AAP use was defined as current, past and no concomitant use based on person months. The primary time-varying Cox proportional hazard regression analysis evaluated the risk of cardiovascular events comparing current concomitant use with past and no concomitant use, adjusted for baseline cardiovascular risk. A secondary analysis assessed the risk of cardiovascular events comparing AAP daily doses (<1, 1-2, >2 mg) and duration (<3, 3-6, >6 months) of current concomitant use to no concomitant use. Cardiovascular outcomes included severe (i.e., stroke, acute myocardial infarction, ischemic heart disease) and less severe (i.e., angina pectoris, cardiac dysrhythmias, transient cerebral ischemia, hypertensive disease, tachycardia, palpitations, syncope). Results: For this cohort of 61,438 youths, the incidence rate of severe cardiovascular events was 0.18 per 10,000 person-months, and all events occurred in no concomitant use months. The risk of less severe cardiovascular events was significantly higher in current concomitant users compared with no [HR: 2.59 (95%CI: 1.72, 3.90)] and past [HR: 1.89 (95%CI: 1.10, 3.24)] concomitant users. Compared to no concomitant use, the risk of less severe cardiovascular events was significantly higher at all AAP daily doses [HR: <1 mg: 2.82 (95%CI: 1.72, 4.61); 1-2 mg: 2.22 (95%CI: 1.16, 4.25); >2 mg: 2.65 (95%CI: 1.50, 4.71)]. The risk of less severe cardiovascular events significantly elevated for all duration of use and was higher for <3 months of concomitant use [HR: <3 months: 3.45 (95%CI: 2.17, 5.47) relative to 3-6 months: 2.60 (95%CI: 1.29, 5.25) or >6 months: 2.61 (95%CI: 1.59, 4.30)]. Conclusions: Severe cardiovascular events are rare. Concomitant stimulant/AAP use elevates the risk of less severe cardiovascular events. Periodic heart rate or blood pressure monitoring for youth on stimulant/AAP treatment may be warranted., Competing Interests: CZ is a Maryland Center of Excellence in Regulatory Science and Innovation (CERSI) Scholar with the US Food and Drug Administration. SD received grant funding from the National Institute of Mental Health (NIMH), the Patient Centered Outcomes Research Institute (PCORI), GSK, and the Pharmaceutical Research Manufacturers of America (PhRMA) Foundation. O'MS was a recipient of a Maryland CERSI Scholar award from the Food and Drug Administration and is currently a PhRMA Foundation pre-doctoral fellow in health outcomes. GR received grant funding from NIMH and PCORI., (Copyright © 2021 Zhang, Spence, Reeves and DosReis.)

Aim: To examine individual variability between perceived physical features and hormones of pubertal maturation in 9-10-year-old children as a function of sociodemographic characteristics., Methods: Cross-sectional metrics of puberty were utilized from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study-a multi-site sample of 9-10 year-olds (n = 11,875)-and included perceived physical features via the pubertal development scale (PDS) and child salivary hormone levels (dehydroepiandrosterone and testosterone in all, and estradiol in females). Multi-level models examined the relationships among sociodemographic measures, physical features, and hormone levels. A group factor analysis (GFA) was implemented to extract latent variables of pubertal maturation that integrated both measures of perceived physical features and hormone levels., Results: PDS summary scores indicated more males (70%) than females (31%) were prepubertal. Perceived physical features and hormone levels were significantly associated with child's weight status and income, such that more mature scores were observed among children that were overweight/obese or from households with low-income. Results from the GFA identified two latent factors that described individual differences in pubertal maturation among both females and males, with factor 1 driven by higher hormone levels, and factor 2 driven by perceived physical maturation. The correspondence between latent factor 1 scores (hormones) and latent factor 2 scores (perceived physical maturation) revealed synchronous and asynchronous relationships between hormones and concomitant physical features in this large young adolescent sample., Conclusions: Sociodemographic measures were associated with both objective hormone and self-report physical measures of pubertal maturation in a large, diverse sample of 9-10 year-olds. The latent variables of pubertal maturation described a complex interplay between perceived physical changes and hormone levels that hallmark sexual maturation, which future studies can examine in relation to trajectories of brain maturation, risk/resilience to substance use, and other mental health outcomes., Competing Interests: In the interest of full disclosure, DG is founder and chief scientific and strategy advisor at Salimetrics LLC and Salivabio LLC (Carlsbad, CA) and these relationships are managed by the policies of the committee’s on conflict of interest at Johns Hopkins University School of Medicine and the University of California at Irvine. ND and DF have a financial interest in Nous Imaging Inc. and may financially benefit if the company is successful in marketing FIRMM software products. DF is a patent holder on the Framewise Integrated Real-Time Motion Monitoring (FIRMM) software and is a co-founder of Nous Imaging Inc. KG provides consultation to Pfizer, Inc. MP is an advisor to Spring Care, Inc., a behavioral startup and has received royalties for an article about methamphetamine in Uptodate. Authors AG and FB were employed by the company SRI International. SW has stock ownership in GE and Merck. All other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Herting, Uban, Gonzalez, Baker, Kan, Thompson, Granger, Albaugh, Anokhin, Bagot, Banich, Barch, Baskin-Sommers, Breslin, Casey, Chaarani, Chang, Clark, Cloak, Constable, Cottler, Dagher, Dapretto, Dick, Dosenbach, Dowling, Dumas, Edwards, Ernst, Fair, Feldstein-Ewing, Freedman, Fuemmeler, Garavan, Gee, Giedd, Glaser, Goldstone, Gray, Hawes, Heath, Heitzeg, Hewitt, Heyser, Hoffman, Huber, Huestis, Hyde, Infante, Ivanova, Jacobus, Jernigan, Karcher, Laird, LeBlanc, Lisdahl, Luciana, Luna, Maes, Marshall, Mason, McGlade, Morris, Nagel, Neigh, Palmer, Paulus, Potter, Puttler, Rajapakse, Rapuano, Reeves, Renshaw, Schirda, Sher, Sheth, Shilling, Squeglia, Sutherland, Tapert, Tomko, Yurgelun-Todd, Wade, Weiss, Zucker and Sowell.)

Measurements from NASA's Van Allen Probes have transformed our understanding of the dynamics of Earth's geomagnetically-trapped, charged particle radiation. The Van Allen Probes were equipped with the Magnetic Electron Ion Spectrometers (MagEIS) that measured energetic and relativistic electrons, along with energetic ions, in the radiation belts. Accurate and routine measurement of these particles was of fundamental importance towards achieving the scientific goals of the mission. We provide a comprehensive review of the MagEIS suite's on-orbit performance, operation, and data products, along with a summary of scientific results. The purpose of this review is to serve as a complement to the MagEIS instrument paper, which was largely completed before flight and thus focused on pre-flight design and performance characteristics. As is the case with all space-borne instrumentation, the anticipated sensor performance was found to be different once on orbit. Our intention is to provide sufficient detail on the MagEIS instruments so that future generations of researchers can understand the subtleties of the sensors, profit from these unique measurements, and continue to unlock the mysteries of the near-Earth space radiation environment., Supplementary Information: The online version contains supplementary material available at 10.1007/s11214-021-00855-2., Competing Interests: Conflicts of interest/Competing interestsThe authors declare that they have no conflict of interest that could have direct or potential influence or impart bias on this work., (© The Author(s) 2021.)

This paper explores some applications of a two-moment inequality for the integral of the r th power of a function, where 0

Purpose: To evaluate spillover effects of Medicaid antipsychotic prior authorization (PA) policies among commercially insured youth., Methods: Commercially insured youth residing in nine US states that implemented PA exclusively for antipsychotics in 2011 or 2012 were identified using a 10% random sample of enrollees in the IQVIA PharMetrics Plus database spanning 2007 to 2015. Youth were included if they were ≤18 years, met the age criteria of the PA at the time of dispensing, and had at least 1 month of prescription drug coverage from 2007 to 2015. The primary outcome of interest was the monthly prevalence of antipsychotics. We implemented segmented regression of interrupted time series analysis to estimate changes in the monthly prevalence of targeted medications, overall and stratified by age. Trends were compared in the 4-year period before and the 3-year period after implementation of PA policies., Results: Antipsychotics prescribing significantly decreased 6.74/10 000 (95% CI, -9.04 to -4.44) enrollees per month immediately after PA implementation. However, PA was not associated with significant long-term trend changes (-0.06; 95% CI, -0.16 to 0.03). Antipsychotic prescribing in children <12 years-old significantly decreased 0.14/10 000 (95% CI, -0.21 to -0.07) enrollees per month after PA implementation, while prescribing in adolescents 12 to 18 years-old significantly increased 0.32/10 000 (95% CI, 0.16 to 0.47) enrollees per month., Conclusion: While Medicaid PA polices for antipsychotic oversight did not affect overall prescribing, there were spillover effects in U.S. commercially insured children <12 years-old. This suggests that state-level Medicaid policies intended to improve the quality of care and safe use of antipsychotics can have broad reach., (© 2020 John Wiley & Sons Ltd.)

Four closely located satellites at and inside geosynchronous orbit (GEO) provided a great opportunity to study the dynamical evolution and spatial scale of premidnight energetic particle injections inside GEO during a moderate substorm on 23 December 2016. Just following the substorm onset, the four spacecraft, a LANL satellite at GEO, the two Van Allen Probes (also called "RBSP") at ~5.8 R E , and a THEMIS satellite at ~5.3 R E , observed substorm-related particle injections and local dipolarizations near the central meridian (~22 MLT) of a wedge-like current system. The large-scale evolution of the electron and ion (H, He, and O) injections was almost identical at the two RBSP spacecraft with ~0.5 R E apart. However, the initial short-timescale particle injections exhibited a striking difference between RBSP-A and -B: RBSP-B observed an energy dispersionless injection which occurred concurrently with a transient, strong dipolarization front (DF) with a peak-to-peak amplitude of ~25 nT over ~25 s; RBSP-A measured a dispersed/weaker injection with no corresponding DF. The spatiotemporally localized DF was accompanied by an impulsive, westward electric field (~20 mV m -1 ). The fast, impulsive E  ×  B drift caused the radial transport of the electron and ion injection regions from GEO to ~5.8 R E . The penetrating DF fields significantly altered the rapid energy- and pitch angle-dependent flux changes of the electrons and the H and He ions inside GEO. Such flux distributions could reflect the transient DF-related particle acceleration and/or transport processes occurring inside GEO. In contrast, O ions were little affected by the DF fields., (©2020. The Authors.)

Background: For decades, nursing programs have worked to address the need for a culturally diverse workforce and student body to better reflect the populations they serve. The development of a diversity and inclusivity statement is a first step in ameliorating this issue., Problem: A clearly communicated diversity and inclusivity statement should demonstrate a nursing organization's commitment to the value of people from all backgrounds. It should include language that emphasizes the value of diverse cultures, experiences, thoughts, and contributions., Approach: Nursing faculty can benefit from an organized and literature-supported model for writing meaningful diversity and inclusivity statements., Conclusions: Such an approach will communicate a nursing program's commitment to diversity and inclusion in the organization's mission, policies, practices, relationships, and curricula. This article provides nursing faculty with evidence-supported guidelines for writing meaningful diversity, inclusion, and equity statements for their nursing programs.

Objective: To determine if adverse family factors are associated with a higher likelihood of psychotropic polypharmacy among US youth with a mental health condition., Methods: The 2009-2015 Medical Expenditure Panel Survey data were used to identify family characteristics of 5136 youth aged ≤18 years with an emotional or behavioral health condition. Family adversity was based on family size, number of parents in the household, parental education and income, and parent-reported physical and/or cognitive or mental health disability. Cluster analysis identified family adversity subgroups. Polypharmacy was defined as 3 or more psychotropic classes (eg, stimulants, antipsychotics, antidepressants, mood stabilizers, and sedatives) in at least 1 interview round in a calendar year. Weighted logistic regression evaluated associations between family adversity and psychotropic polypharmacy among youth., Results: Nearly half (47.8%) of youth lived with parents who had a disability. Parents in the least socioeconomically disadvantaged cluster mainly had a mental illness, and 94% of parents in the most socioeconomically disadvantaged cluster had a parent-reported physical and/or cognitive disability and mental illness. Among youth, mood disorder (24.2%; 95% confidence interval [CI]: 12.6%-16.0%), antidepressant use (16.0%; 95% CI: 10.6%-21.5%), and antipsychotic use (7.5%; 95% CI: 5.4%-9.6%) were higher in the most socioeconomically disadvantaged cluster relative to the other clusters. Approximately 3% of youth received psychotropic polypharmacy. The odds of psychotropic polypharmacy were 2.7 (95% CI: 1.1-6.4) times greater among youth in the most relative to the least socioeconomically disadvantaged cluster., Conclusions: Higher use of psychotropic polypharmacy among youth with parents who have multiple disabilities raises concerns about oversight and monitoring of complex psychotropic treatment., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr dosReis has received grant funding from the National Institute of Mental Health, the Patient-Centered Outcomes Research Institute, the Food and Drug Administration, the Pharmaceutical Research and Manufacturers of America Foundation, and GlaxoSmithKline. Dr Reeves has received grant funding from the National Institute of Mental Health and Patient-Centered Outcomes Research Institute. Dr Camelo Castillo has received funding from the Food and Drug Administration and Patient-Centered Outcomes Research Institute. Dr Qato has received funding from the National Institutes of Health; Ms Zhang has indicated she has no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Objective: Caregivers of a child with a coexisting cognitive/intellectual and an emotional/behavior/developmental disability have difficult decisions regarding care management options for their child. This study aimed to pilot and refine an instrument to elicit caregivers' preferences in managing their child's care needs., Methods: Subjects were 38 caregivers of a child aged 21 and younger with a coexisting cognitive/intellectual and an emotional/behavior/developmental disability. A mixed-methods design was used to develop and pilot a discrete choice experiment (DCE) to elicit care management preferences for their child. Six attributes of care management decisions were tested in the DCE: medication use, parental custody, time cost, social interactions, medication effects, and school placement. Subjects completed a paper-and-pencil survey after which a debriefing discussion was held to obtain feedback that would aid in refining the attribute descriptions. Conditional logistic regression generated mean scores for each attribute. Comments from the debriefing sessions were audio-recorded and used to modify the attribute descriptions., Results: The majority (84%) of subjects were aged 40 years or older and a female caregiver. Common diagnoses of the children were autism spectrum disorder (55%) and attention-deficit/hyperactivity disorder (76%). Subjects preferred using fewer medications and maintaining decision-making authority as opposed to delegating authority to a third party. Medication effects on the child's mood were more important than effects on personality or body weight., Conclusions: The DCE was sensitive to caregivers' preferences for managing their child's coexisting cognitive/intellectual and emotional/behavior/developmental disability. Findings may help providers gauge treatment in a broader context of health outcomes., (Copyright © 2019 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Diapause is a state of suspended development that helps organisms survive extreme environments. How diapause protects living organisms is largely unknown. Using the African turquoise killifish ( Nothobranchius furzeri ), we show that diapause preserves complex organisms for extremely long periods of time without trade-offs for subsequent adult growth, fertility, and life span. Transcriptome analyses indicate that diapause is an active state, with dynamic regulation of metabolism and organ development genes. The most up-regulated genes in diapause include Polycomb complex members. The chromatin mark regulated by Polycomb, H3K27me3, is maintained at key developmental genes in diapause, and the Polycomb member CBX7 mediates repression of metabolism and muscle genes in diapause. CBX7 is functionally required for muscle preservation and diapause maintenance. Thus, vertebrate diapause is a state of suspended life that is actively maintained by specific chromatin regulators, and this has implications for long-term organism preservation., (Copyright © 2020, American Association for the Advancement of Science.)

Antipsychotics are used for many psychiatric conditions in youth. Although developmentally inappropriate weight gain and metabolic abnormalities, which are risk factors for premature cardiovascular mortality, are especially frequent in youth, optimal strategies to reduce pediatric antipsychotic-induced overweight/obesity are unclear. The Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) was a randomized, parallel group, 24-week clinical trial which enrolled overweight/obese, psychiatrically stable youth, aged 8-19 years, with a DSM-IV diagnosis of severe mental illness (schizophrenia spectrum disorder, bipolar spectrum disorder or psychotic depression), at four US universities. All of them had developed substantial weight gain following treatment with a second-generation antipsychotic. The centralized, computer-based randomization system assigned participants to unmasked treatment groups: metformin (MET); antipsychotic switch (aripiprazole or, if already exposed to that drug, perphenazine or molindone; SWITCH); or continued baseline antipsychotic (CONTROL). All participants received healthy lifestyle education. The primary outcome was body mass index (BMI) z-score change from baseline, analyzed using estimated least squares means. Altogether, 127 participants were randomized: 49 to MET, 31 to SWITCH, and 47 to CONTROL. BMI z-score decreased significantly with MET (week 24: -0.09±0.03, p=0.002) and SWITCH (week 24: -0.11±0.04, p=0.003), while it increased non-significantly with CONTROL (week 24: +0.04±0.03). On 3-way comparison, BMI z-score changes differed significantly (p=0.001). MET and SWITCH were each superior to CONTROL (p=0.002), with effect sizes of 0.68 and 0.81 respectively, while MET and SWITCH did not differ. More gastrointestinal problems occurred in MET than in SWITCH or CONTROL. The data safety monitoring board closed the perphenazine-SWITCH arm because 35.2% of subjects discontinued treatment due to psychiatric worsening. These data suggest that pediatric antipsychotic-related overweight/obesity can be reduced by adding metformin or switching to a lower risk antipsychotic. Healthy lifestyle education is not sufficient to prevent ongoing BMI z-score increase., (© 2020 World Psychiatric Association.)

We investigate the longitudinal structure of the oxygen torus in the inner magnetosphere for a specific event found on 12 September 2017, using simultaneous observations from the Van Allen Probe B and Arase satellites. It is found that Probe B observed a clear enhancement in the average plasma mass ( M ) up to 3-4 amu at L  = 3.3-3.6 and magnetic local time (MLT) = 9.0 h. In the afternoon sector at MLT ~ 16.0 h, both Probe B and Arase found no clear enhancements in M . This result suggests that the oxygen torus does not extend over all MLT but is skewed toward the dawn. Since a similar result has been reported for another event of the oxygen torus in a previous study, a crescent-shaped torus or a pinched torus centered around dawn may be a general feature of the O + density enhancement in the inner magnetosphere. We newly find that an electromagnetic ion cyclotron (EMIC) wave in the H + band appeared coincidently with the oxygen torus. From the lower cutoff frequency of the EMIC wave, the ion composition of the oxygen torus is estimated to be 80.6% H + , 3.4% He + , and 16.0% O + . According to the linearized dispersion relation for EMIC waves, both He + and O + ions inhibit EMIC wave growth and the stabilizing effect is stronger for He + than O + . Therefore, when the H + fraction or M is constant, the denser O + ions are naturally accompanied by the more tenuous He + ions, resulting in a weaker stabilizing effect (i.e., larger growth rate). From the Probe B observations, we find that the growth rate becomes larger in the oxygen torus than in the adjacent regions in the plasma trough and the plasmasphere., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)