Optical Control of Adaptive Nanoscale Domain Networks.

Adaptive networks can sense and adjust to dynamic environments to optimize their performance. Understanding their nanoscale responses to external stimuli is essential for applications in nanodevices and neuromorphic computing. However, it is challenging to image such responses on the nanoscale with crystallographic sensitivity. Here, the evolution of nanodomain networks in (PbTiO3)n/(SrTiO3)n superlattices (SLs) is directly visualized in real space as the system adapts to ultrafast repetitive optical excitations that emulate controlled neural inputs. The adaptive response allows the system to explore a wealth of metastable states that are previously inaccessible. Their reconfiguration and competition are quantitatively measured by scanning x-ray nanodiffraction as a function of the number of applied pulses, in which crystallographic characteristics are quantitatively assessed by assorted diffraction patterns using unsupervised machine-learning methods. The corresponding domain boundaries and their connectivity are drastically altered by light, holding promise for light-programable nanocircuits in analogy to neuroplasticity. Phase-field simulations elucidate that the reconfiguration of the domain networks is a result of the interplay between photocarriers and transient lattice temperature. The demonstrated optical control scheme and the uncovered nanoscopic insights open opportunities for the remote control of adaptive nanoscale domain networks.

The Diagnostic Utility of Cervical Spine Proprioception for Adolescent Concussion.

OBJECTIVE: Cervical spine proprioception may be impaired after concussion. Our objective was to determine the diagnostic utility of cervical spine proprioception for adolescent concussion. DESIGN: Cross-sectional. SETTING: Research laboratory. PARTICIPANTS: Adolescents ≤18 days of concussion and uninjured controls. INTERVENTIONS: N/A. MAIN OUTCOMES: Head repositioning accuracy (HRA) testing, a measure of cervical spine proprioception. The HRA test involved patients relocating their head back to a neutral starting position with eyes closed after maximal cervical spine flexion, extension, and right and left rotations. The overall HRA error score was the mean error (distance from the starting point to self-reported return to neutral) across 12 trials: 3 trials in each direction. We used t-tests to compare group means and logistic regression (outcome = group, predictor = HRA, covariates) to calculate odds ratios. We used a receiver operator characteristic curve to evaluate area under the curve (AUC) and calculate the optimal HRA cutpoint to distinguish concussion from controls. RESULTS: We enrolled and tested 46 participants with concussion (age = 15.8 ± 1.3 years, 59% female, mean = 11.3 ± 3.3 days postconcussion) and 83 uninjured controls (age = 16.1 ± 1.4 years, 88% female). The concussion group had significantly worse HRA than controls (4.3 ± 1.6 vs 2.9 ± 0.7 degrees, P < 0.001, Cohen d = 1.19). The univariable HRA model AUC was 0.81 (95% CI = 0.73, 0.90). After adjusting for age, sex, and concussion history, the multivariable model AUC improved to 0.85 (95% CI = 0.77, 0.92). The model correctly classified 80% of participants as concussion/control at a 3.5-degree cutpoint. CONCLUSIONS: Adolescents with concussion demonstrated worse cervical spine proprioception than uninjured controls. Head repositioning accuracy may offer diagnostic utility for subacute concussion.

Improving the direct air capture capacity of grafted amines via thermal treatment.

This study investigates the effects of elevated temperature thermal treatments on the direct air capture of CO2 by aminosilane-grafted SBA-15 silica sorbents. Exposing samples to high temperatures (200-250 °C compared to 80-120 °C) in an inert environment resulted in improved CO2 capacity (5-21%) that was sustained over multiple adsorption/desorption cycles.

The Prevalence of Hip Dysplasia on Radiographs for Adolescent Idiopathic Scoliosis.

BACKGROUND: During radiographic assessment of adolescent idiopathic scoliosis (AIS), upright images frequently capture the hip. The purpose of this study was to assess the prevalence of radiographic hip dysplasia on postero-anterior (PA) scoliosis radiographs, as defined as a lateral center edge angle (LCEA) ≤25 degrees. METHODS: All patients with upright PA scoliosis radiographs over a one-year study period at a single tertiary academic medical center (2020 to 2021) were included in the study. Radiographs containing the hip joints were annotated by 3 reviewers for left and right LCEA, and triradiate cartilage (TRC) status. Inter-rater reliability was determined among the 3 reviewers. RESULTS: Two hundred fifty patients {500 hips, 75.6% female, median age 14 [interquartile range (IQR)=3]} had PA scoliosis radiographs that captured the hip, which qualified for analysis. Seventy-four hips (14.8%) demonstrated evidence of dysplasia (LCEA ≤25 deg) in 55/250 patients (22%). The median LCEA was significantly lower in the dysplastic hip cohort (23.9 deg, IQR=4.8 deg), compared with those without dysplasia (33 deg IQR=7.3 deg; P=0.001). A higher percentage of dysplastic hip patients were female than male (72.7% vs. 27.3%). Patients with bilateral dysplasia had a similar LCEA ( 22.9 deg) [to those with unilateral dysplasia (22.9 deg left, 23.9 deg right, P=0.689)]. CONCLUSIONS: In a cohort of 250 AIS patients, 22% demonstrated evidence of hip dysplasia, as defined as an LCEA ≤2 degrees. The dysplastic patients were more likely to be female. Screening for hip symptomatology in AIS patients may be of benefit, considering the frequency of radiographic hip dysplasia in this population. LEVEL OF EVIDENCE: III. Type of Evidence: diagnostic.

Twenty Years of Get With The Guidelines-Stroke: Celebrating Past Successes, Lessons Learned, and Future Challenges.

The Get With The Guidelines-Stroke program which, began 20 years ago, is one of the largest and most important nationally representative disease registries in the United States. Its importance to the stroke community can be gauged by its sustained growth and widespread dissemination of findings that demonstrate sustained increases in both the quality of care and patient outcomes over time. The objectives of this narrative review are to provide a brief history of Get With The Guidelines-Stroke, summarize its major successes and impact, and highlight lessons learned. Looking to the next 20 years, we discuss potential challenges and opportunities for the program.

Sex Differences in Trends in Stroke Recurrence and Postrecurrence Mortality 2000-2020: Population-Based Brain Attack Surveillance in Corpus Christi Project.

OBJECTIVE: This study was undertaken to delineate 21-year sex-specific trends in recurrence and postrecurrence mortality. METHODS: Between 2000 and 2020, first-ever ischemic stroke (IS) patients, ascertained from the population-based BASIC (Brain Attack Surveillance in Corpus Christi) project in South Texas, were followed for recurrent stroke and all-cause mortality until December 31, 2020. Multivariable regression models with an interaction between calendar year and sex were used to estimate sex-specific trends and sex differences in recurrence and postrecurrence mortality. RESULTS: Of the 6,057 IS patients (median age = 69 years, 49.8% women), 654 (10.8%) had a recurrence and 399 (47.7%) had postrecurrence mortality during 5 years of follow-up. In 2000, women had 2.5% higher albeit non-statistically significant 5-year risk of recurrence than men in absolute scale. With the trend declining in women by 7.6% (95% confidence interval [CI] = -10.8 to -4.5%) and in men by 3.6% (95% CI = -6.5% to -0.7%), the risk at the end of the study period was 1.5% (95% CI = -0.3% to 3.6%) lower among women than men. For postrecurrence mortality, the risk was 10.2% lower among women in 2000, but the sex difference was 3.3% by the end of the period, which was due to a larger overall increase in the risk among women than men over the entire time period. INTERPRETATION: The declines in recurrent stroke suggest successful secondary stroke prevention, especially in women. However, the continued high postrecurrence mortality among both sexes at the end of study period emphasizes the need for ongoing interventions to improve prognosis in those who have had recurrent cerebrovascular events. ANN NEUROL 2024;96:332-342.

Mapping the Ecological Terrain of Stroke Prehospital Delay: A Nationwide Registry Study.

BACKGROUND: Delays in hospital presentation limit access to acute stroke treatments. While prior research has focused on patient-level factors, broader ecological and social determinants have not been well studied. We aimed to create a geospatial map of prehospital delay and examine the role of community-level social vulnerability. METHODS: We studied patients with ischemic stroke who arrived by emergency medical services in 2015 to 2017 from the American Heart Association Get With The Guidelines-Stroke registry. The primary outcome was time to hospital arrival after stroke (in minutes), beginning at last known well in most cases. Using Geographic Information System mapping, we displayed the geography of delay. We then used Cox proportional hazard models to study the relationship between community-level factors and arrival time (adjusted hazard ratios [aHR] <1.0 indicate delay). The primary exposure was the social vulnerability index (SVI), a metric of social vulnerability for every ZIP Code Tabulation Area ranging from 0.0 to 1.0. RESULTS: Of 750 336 patients, 149 145 met inclusion criteria. The mean age was 73 years, and 51% were female. The median time to hospital arrival was 140 minutes (Q1: 60 minutes, Q3: 458 minutes). The geospatial map revealed that many zones of delay overlapped with socially vulnerable areas (https://harvard-cga.maps.arcgis.com/apps/webappviewer/index.html?id=08f6e885c71b457f83cefc71013bcaa7). Cox models (aHR, 95% CI) confirmed that higher SVI, including quartiles 3 (aHR, 0.96 [95% CI, 0.93-0.98]) and 4 (aHR, 0.93 [95% CI, 0.91-0.95]), was associated with delay. Patients from SVI quartile 4 neighborhoods arrived 15.6 minutes [15-16.2] slower than patients from SVI quartile 1. Specific SVI themes associated with delay were a community's socioeconomic status (aHR, 0.80 [95% CI, 0.74-0.85]) and housing type and transportation (aHR, 0.89 [95% CI, 0.84-0.94]). CONCLUSIONS: This map of acute stroke presentation times shows areas with a high incidence of delay. Increased social vulnerability characterizes these areas. Such places should be systematically targeted to improve population-level stroke presentation times.

Symptoms, concerns, and experiences of women living with and beyond breast cancer in Africa: A mixed-methods systematic review.

OBJECTIVE: A mixed-methods systematic review to determine reported symptoms, concerns, and experiences of women living with and beyond breast cancer in Africa. METHODS: Literature searches were conducted in Medline, Embase, PsycINFO, Global Health, Web of Science, CINAHL, and the Cochrane Library. Quantitative and qualitative studies that comprised study populations of women with breast cancer from countries in Africa, detailing symptoms, concerns, and experiences of living with and beyond breast cancer were included. Inductive framework analysis was applied to organise existing literature with the Adversity, Restoration, and Compatibility framework and quality was assessed using the Mixed Methods Appraisal Tool. RESULTS: In total, 48 studies were included, comprising quantitative (n = 24), qualitative (n = 23) and mixed method (n = 1) studies. Women reported multiple complex and burdensome symptoms at all stages of the breast cancer disease trajectory. Multiple pervasive factors influencing participants' experiences included a lack of cancer knowledge, being removed from decision-making, religion, and the presence and use of traditional medicines. Literature relating to benefit finding, understanding identity for the future, and broader perspectives of well-being was absent. CONCLUSIONS: This review contributes insights and mapping of symptoms, concerns, and experiences of women with breast cancer in Africa. There is a great necessity to increase an understanding of the needs and experiences of women with breast cancer in Africa following cancer treatment, stages of remission, and longer-term monitoring and follow-up. This is required to ensure access to prompt and timely clinical and individualized supportive care for women with breast cancer in Africa.

Tibial and femoral articular cartilage exhibit opposite outcomes for T1ρ and T2* relaxation times in response to acute compressive loading in healthy knees.

Abnormal loading is thought to play a key role in the disease progression of cartilage, but our understanding of how cartilage compositional measurements respond to acute compressive loading in-vivo is limited. Ten healthy subjects were scanned at two timepoints (7 ± 3 days apart) with a 3 T magnetic resonance imaging (MRI) scanner. Scanning sessions included T1ρ and T2* acquisitions of each knee in two conditions: unloaded (traditional MRI setup) and loaded in compression at 40 % bodyweight as applied by an MRI-compatible loading device. T1ρ and T2* parameters were quantified for contacting cartilage (tibial and femoral) and non-contacting cartilage (posterior femoral condyle) regions. Significant effects of load were found in contacting regions for both T1ρ and T2*. The effect of load (loaded minus unloaded) in femoral contacting regions ranged from 4.1 to 6.9 ms for T1ρ, and 3.5 to 13.7 ms for T2*, whereas tibial contacting regions ranged from -5.6 to -1.7 ms for T1ρ, and -2.1 to 0.7 ms for T2*. Notably, the responses to load in the femoral and tibial cartilage revealed opposite effects. No significant differences were found in response to load between the two visits. This is the first study that analyzed the effects of acute loading on T1ρ and T2* measurements in human femoral and tibial cartilage separately. The results suggest the effect of acute compressive loading on T1ρ and T2* was: 1) opposite in the femoral and tibial cartilage; 2) larger in contacting regions than in non-contacting regions of the femoral cartilage; and 3) not different visit-to-visit.

Single nucleus and spatial transcriptomic profiling of healthy human hamstring tendon.

The molecular and cellular basis of health in human tendons remains poorly understood. Among human tendons, hamstring tendon has markedly low pathology and can provide a prototypic healthy tendon reference. The aim of this study was to determine the transcriptomes and location of all cell types in healthy hamstring tendon. Using single nucleus RNA sequencing, we profiled the transcriptomes of 10 533 nuclei from four healthy donors and identified 12 distinct cell types. We confirmed the presence of two fibroblast cell types, endothelial cells, mural cells, and immune cells, and identified cell types previously unreported in tendons, including different skeletal muscle cell types, satellite cells, adipocytes, and undefined nervous system cells. The location of these cell types within tendon was defined using spatial transcriptomics and imaging, and potential transcriptional networks and cell-cell interactions were analyzed. We demonstrate that fibroblasts have the highest number of potential cell-cell interactions in our dataset, are present throughout the tendon, and play an important role in the production and organization of extracellular matrix, thus confirming their role as key regulators of hamstring tendon homeostasis. Overall, our findings underscore the complexity of the cellular networks that underpin healthy human tendon function and the central role of fibroblasts as key regulators of hamstring tendon tissue homeostasis.

Who is the majority group? Signaling majority group membership with name-based treatments in multilingual contexts: The case of Catalonia.

An increasing body of work has shown how the selection of names shapes patterns of ethnic and racial discrimination in hiring observed in correspondence audit studies. A clear limitation of the existing research on name perceptions and ethnic discrimination in employment is that is predominantly based in the US, which limits its applicability to contexts with high linguistic diversity among the majority population. These territories confront a reality where language preferences and uses, social class, and ancestry are associated with specific names among the native majority group. The result is notable diversity in the labor market (dis)advantages conferred by different names within the majority population. To fill this gap, this article focuses on Catalonia, a diverse multilingual region and Spain's second most populated area. Using two complementary studies, this work identifies the direct influence of names in the hiring process (Study 1) and evaluates the associations between names and perceptions of geographic origin, social class, and linguistic competence (Study 2). The results show that having a Catalan name confers an advantage in the labour market via three mechanisms. First, names inform a perception of language proficiency, which is tied to an expectation of productivity. Second, names signal social class and certain names in the majority group (applicants with two Catalan surnames, a minority within the region), indicate higher social class, which affords an advantage. Third, some advantage could be linked to tastes that favor an ingroup for reasons of assumed cultural, historical, or political compatibility. The approach adopted in this article holds significant relevance to other research on ethnic discrimination conducted in multilingual contexts with comparable autochthonous diversity.

Overcoming barriers to single-cell RNA sequencing adoption in low- and middle-income countries.

The advent of single-cell resolution sequencing and spatial transcriptomics has enabled the delivery of cellular and molecular atlases of tissues and organs, providing new insights into tissue health and disease. However, if the full potential of these technologies is to be equitably realised, ancestrally inclusivity is paramount. Such a goal requires greater inclusion of both researchers and donors in low- and middle-income countries (LMICs). In this perspective, we describe the current landscape of ancestral inclusivity in genomic and single-cell transcriptomic studies. We discuss the collaborative efforts needed to scale the barriers to establishing, expanding, and adopting single-cell sequencing research in LMICs and to enable globally impactful outcomes of these technologies.

Factors Associated With Premature Termination of Hyperacute Stroke Trials: A Review.

BACKGROUND: We performed a review of acute stroke trials to determine features associated with premature termination of trial enrollment, defined by the authors as not meeting preplanned sample size. METHODS AND RESULTS: MEDLINE was searched for randomized clinical stroke trials published in 9 major clinical journals between 2013 and 2022. We included randomized clinical trials that were phase 2 or 3 with a preplanned sample size ≥100 and a time-to-treatment within 24 hours of onset for transient ischemic attack, ischemic stroke, or intracerebral hemorrhage. Data were abstracted on trial features including trial design, inclusion criteria, imaging, location and number of sites, masking, treatment complexity, control group (standard therapy, placebo), industry involvement, and preplanned stopping rules (futility and efficacy). Least absolute shrinkage and selection operator regression was used to select the most important factors associated with premature termination; then, a multivariable logistic regression was fit including only the least absolute shrinkage and selection operator selected variables. Of 1475 studies assessed, 98 trials met eligibility criteria. Forty-five (46%) trials were prematurely terminated, of which 27% were stopped for benefit/efficacy, 20% for lack of money/slow enrollment, 18% for futility, 16% for newly available evidence, 17% for other reasons, and 4% due to harm. Complex trials (adjusted odds ratio [aOR], 2.76 [95% CI, 1.13-7.49]), presence of a futility rule (aOR, 4.43 [95% CI, 1.62-17.91]), and exclusion of prestroke dependency (none/slight disability only; aOR, 2.19 [95% CI, 0.84-6.72] versus dependency allowed) were identified as the strongest predictors. CONCLUSIONS: Nearly half of acute stroke trials were terminated prematurely. Broadening inclusion criteria and simplifying trial design may decrease the likelihood of unplanned termination, whereas planned futility analyses may appropriately terminate trials early, saving money and resources.

Deficiency of the paternally-expressed imprinted Peg3 gene in mice has sexually dimorphic consequences for offspring communication and social behaviour.

Introduction: Imprinted genes are expressed from one parental allele as a consequence of epigenetic processes initiated in the germline. Consequently, their ability to influence phenotype depends on their parent-of-origin. Recent research suggests that the sex of the individual expressing the imprinted gene is also important. We have previously reported that genetically wildtype (WT) dams carrying and caring for pups mutant for PEG3 exhibit anxiety-like behaviours and their mutant pups show a reduction in ultrasonic vocalisation when separated from their mothers. Sex-specificity was not examined. Methods: WT female mice were mated with WT, heterozygous Peg3-/+ or homozygous Peg3-/- studs to generate all WT (control), 50:50 mixed or 100% mutant litters, respectively, followed by behavioural assessment of both dams and their pups. Results: We reproduced our original finding that WT dams carrying and caring for 100% mutant litters exhibit postpartum anxiety-like symptoms and delayed pup retrieval. Additionally, these WT dams were found to allocate less time to pup-directed care behaviours relative to controls. Male Peg3-deficient pups demonstrated significantly reduced vocalisation with a more subtle communication deficit in females. Postweaning, male mutants exhibited deficits across a number of key social behaviours as did WT males sharing their environment with mutants. Only modest variations in social behaviour were detected in experimental females. Discussion: We have experimentally demonstrated that Peg3 deficiency confined to the offspring causes anxiety in mouse mothers and atypical behaviour including deficits in communication in their male offspring. A male-specific reduction in expression PEG3 in the fetally-derived placenta has previously been associated with maternal depression in human pregnancy. Maternal mood disorders such as depression and anxiety are associated with delays in language development and neuroatypical behaviour more common in sons. Peg3 deficiency could drive the association of maternal and offspring behavioural disorders reported in humans.

Active and Transfer Learning of High-Dimensional Neural Network Potentials for Transition Metals.

Classical molecular dynamics (MD) simulations represent a very popular and powerful tool for materials modeling and design. The predictive power of MD hinges on the ability of the interatomic potential to capture the underlying physics and chemistry. There have been decades of seminal work on developing interatomic potentials, albeit with a focus predominantly on capturing the properties of bulk materials. Such physics-based models, while extensively deployed for predicting the dynamics and properties of nanoscale systems over the past two decades, tend to perform poorly in predicting nanoscale potential energy surfaces (PESs) when compared to high-fidelity first-principles calculations. These limitations stem from the lack of flexibility in such models, which rely on a predefined functional form. Machine learning (ML) models and approaches have emerged as a viable alternative to capture the diverse size-dependent cluster geometries, nanoscale dynamics, and the complex nanoscale PESs, without sacrificing the bulk properties. Here, we introduce an ML workflow that combines transfer and active learning strategies to develop high-dimensional neural networks (NNs) for capturing the cluster and bulk properties for several different transition metals with applications in catalysis, microelectronics, and energy storage, to name a few. Our NN first learns the bulk PES from the high-quality physics-based models in literature and subsequently augments this learning via retraining with a higher-fidelity first-principles training data set to concurrently capture both the nanoscale and bulk PES. Our workflow departs from status-quo in its ability to learn from a sparsely sampled data set that nonetheless covers a diverse range of cluster configurations from near-equilibrium to highly nonequilibrium as well as learning strategies that iteratively improve the fingerprinting depending on model fidelity. All the developed models are rigorously tested against an extensive first-principles data set of energies and forces of cluster configurations as well as several properties of bulk configurations for 10 different transition metals. Our approach is material agnostic and provides a methodology to transfer and build upon the learnings from decades of seminal work in molecular simulations on to a new generation of ML-trained potentials to accelerate materials discovery and design.

Novel WRN Helicase Inhibitors Selectively Target Microsatellite Unstable Cancer Cells.

Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due to expanded DNA (TA)n-dinucleotide repeats. WRN is a promising synthetic lethal target for MSI tumours, and WRN inhibitors are in development. Here, we used CRISPR-Cas9 base editing to map WRN residues critical for MSI cells, validating the helicase domain as the primary drug target. Fragment-based screening led to the development of potent and highly selective WRN helicase covalent inhibitors. These compounds selectively suppressed MSI model growth In vitro and In vivo by mimicking WRN loss, inducing DNA double-strand breaks at expanded TA-repeats and DNA damage. Assessment of biomarkers in preclinical models linked TA-repeat expansions and mismatch repair (MMR) alterations to compound activity. Efficacy was confirmed in immunotherapy-resistant organoids and patient-derived xenograft (PDX) models. The discovery of potent, selective covalent WRN inhibitors provides proof of concept for synthetic-lethal targeting of WRN in MSI cancer and tools to dissect WRN biology.

Antibody-mediated rejection in pediatric kidney transplant recipients: A report from the Pediatric Nephrology Research Consortium.

BACKGROUND: Antibody-mediated rejection (AMR) is a major cause of kidney allograft loss. There is a paucity of large-scale pediatric-specific data regarding AMR treatment outcomes. METHODS: Data were obtained from 14 centers within the Pediatric Nephrology Research Consortium. Kidney transplant recipients aged 1-18 years at transplant with biopsy-proven AMR between 2009 and 2019 and at least 12 months of follow-up were included. The primary outcome was graft failure or an eGFR <20 mL/min/1.73 m2 at 12 months following AMR treatment. AMR treatment choice, histopathology, and DSA class were also examined. RESULTS: We reviewed 123 AMR episodes. Median age at diagnosis was 15 years at a median 22 months post-transplant. The primary outcome developed in 27.6%. eGFR <30 m/min/1.73 m2 at AMR diagnosis was associated with a 5.6-fold higher risk of reaching the composite outcome. There were no significant differences in outcome by treatment modality. Histopathology scores and DSA class at time of AMR diagnosis were not significantly associated with the primary outcome. CONCLUSIONS: In this large cohort of pediatric kidney transplant recipients with AMR, nearly one-third of patients experienced graft failure or significant graft dysfunction within 12 months of diagnosis. Poor graft function at time of diagnosis was associated with higher odds of graft failure.

Road vehicle collision suicide in Australia: Trends, collision types, and individual characteristics.

BACKGROUND: Suicide by road vehicle collision in Australia is under-explored with mixed findings. We aimed to address this research gap by examining time trends, different types of vehicle collision, and individual characteristics related to vehicle-collision suicide. METHOD: We retrospectively analyzed deaths by suicide between 1st January 2001 and 31st December 2017 in Australia, using coronial records from the National Coronial Information System. The travel mode used and collision counterpart were retrieved from records of death by vehicle-collision suicide using all available information. We conducted negative binomial regression analysis to examine annual changes in suicide rate by vehicle collision on a public road (N = 640) and other methods of suicide (N = 41,890), and logistic regression analysis to examine individual characteristics associated with the likelihood of dying by suicide via road vehicle collision. RESULTS: Overall, the national suicide rate involving road vehicle collision significantly increased, while the rate by other methods significantly decreased. Drivers accounted for 61% of suicide events by vehicle collision, of which 72% were single-vehicle collisions (commonly involving a tree). For multiple-vehicle collision suicide events, 82% involved collision with a truck. Pedestrians accounted for more than one-third of suicide events, of which 58% involved collision with a truck and 23% involved collision with a car/van. Individuals who were male (odds ratio 1.15; 95% CI 0.88-1.50), aged <25 years old (odds ratio 5.27; 95% CI 3.05-9.10), non-Indigenous (odds ratio 3.36; 95% CI 1.71-6.62), and born overseas (odds ratio 1.40; 95% CI 1.10-1.79) were more likely to die by vehicle-collision suicide than by other methods of suicide. CONCLUSIONS: This study provides a better understanding of road vehicle collision suicide in Australia and informs future research directions on topic. Our findings can be used to inform suicide prevention initiatives to reduce vehicle-collision suicide deaths.

Study protocol for a pilot clinical trial to understand neural mechanisms of response to a psychological treatment for pain and anxiety in pediatric functional abdominal pain disorders (FAPD).

BACKGROUND: Functional abdominal pain disorders (FAPD) are the most common chronic pain conditions of childhood and are made worse by co-occurring anxiety. Our research team found that the Aim to Decrease Pain and Anxiety Treatment (ADAPT), a six-session coping skills program using cognitive behavioral therapy strategies, was effective in improving pain-related symptoms and anxiety symptoms compared to standard care. In follow-up, this current randomized clinical trial (RCT) aims to test potential neural mechanisms underlying the effect of ADAPT. Specifically, this two-arm RCT will explore changes in amygdalar functional connectivity (primary outcome) following the ADAPT protocol during the water loading symptom provocation task (WL-SPT). Secondary (e.g., changes in regional cerebral blood flow via pulsed arterial spin labeling MRI) and exploratory (e.g., the association between the changes in functional connectivity and clinical symptoms) outcomes will also be investigated. METHODS: We will include patients ages 11 to 16 years presenting to outpatient pediatric gastroenterology care at a midwestern children's hospital with a diagnosis of FAPD plus evidence of clinical anxiety based on a validated screening tool (the Generalized Anxiety Disorder-7 [GAD-7] measure). Eligible participants will undergo baseline neuroimaging involving the WL-SPT, and assessment of self-reported pain, anxiety, and additional symptoms, prior to being randomized to a six-week remotely delivered ADAPT program plus standard medical care or standard medical care alone (waitlist). Thereafter, subjects will complete a post assessment neuroimaging visit similar in nature to their first visit. CONCLUSIONS: This small scale RCT aims to increase understanding of potential neural mechanisms of response to ADAPT. TRIAL REGISTRATION: ClinicalTrials.gov registration: NCT03518216.