Next generation high-power laser facilities are expected to generate hundreds-of-MeV proton beams and operate at multi-Hz repetition rates, presenting opportunities for medical, industrial and scientific applications requiring bright pulses of energetic ions. Characterizing the spectro-spatial profile of these ions at high repetition rates in the harsh radiation environments created by laser–plasma interactions remains challenging but is paramount for further source development. To address this, we present a compact scintillating fiber imaging spectrometer based on the tomographic reconstruction of proton energy deposition in a layered fiber array. Modeling indicates that spatial resolution of approximately 1 mm and energy resolution of less than 10% at proton energies of more than 20 MeV are readily achievable with existing 100 μm diameter fibers. Measurements with a prototype beam-profile monitor using 500 μm fibers demonstrate active readouts with invulnerability to electromagnetic pulses, and less than 100 Gy sensitivity. The performance of the full instrument concept is explored with Monte Carlo simulations, accurately reconstructing a proton beam with a multiple-component spectro-spatial profile.

Success of atrioventricular septal defect repair is defined by post-operative atrioventricular valve function and presence of residual intracardiac shunting. We evaluated differences in interpretation of atrioventricular valve function and residual defects between transesophageal and transthoracic echocardiography in a contemporary cohort of infants undergoing atrioventricular septal defect repair. Among 106 patients, we identified an increase in left and right atrioventricular valve regurgitation, right atrioventricular valve inflow gradient, and increased detection rate of residual intracardiac shunting on transthoracic compared to transesophageal echocardiograms, although residual shunts identified only on transthoracic echocardiogram were not haemodynamically significant. Findings may help inform expectation of post-operative transthoracic echocardiogram findings based on intraoperative assessment.

Sperlingite, (H2O)K(Mn2+Fe3+)(Al2Ti)(PO4)4[O(OH)][(H2O)9(OH)]⋅4H2O, is a new monoclinic member of the paulkerrite group, from the Hagendorf-Süd pegmatite, Oberpfalz, Bavaria, Germany. It was found in corrosion pits of altered zwieselite, in association with columbite, hopeite, leucophosphite, mitridatite, scholzite, orange–brown zincoberaunite sprays and tiny green crystals of zincolibethenite. Sperlingite forms colourless prisms with pyramidal terminations, which are predominantly only 5 to 20 μm in size, rarely to 60 μm and frequently are multiply intergrown and are overgrown with smaller crystals. The crystals are flattened on {010} and slightly elongated along [100] with forms {010}, {001} and {111}. Twinning occurs by rotation about c. The calculated density is 2.40 g⋅cm–3. Optically, sperlingite crystals are biaxial (+), α = 1.600(est), β = 1.615(5), γ = 1.635(5) (white light) and 2V (calc.) = 82.7°. The optical orientation is X = b, Y = c and Z = a. Neither dispersion nor pleochroism were observed. The empirical formula from electron microprobe analyses and structure refinement is A1[(H2O)0.96K0.04]Σ1.00 A2(K0.52□0.48)Σ1.00 M1(Mn2+0.60Mg0.33Zn0.29Fe3+0.77)Σ1.99 M2+M3(Al1.05Ti4+1.33Fe3+0.62)Σ3.00(PO4)4 X[F0.19(OH)0.94O0.87]Σ2.00[(H2O)9.23(OH)0.77]Σ10.00⋅3.96H2O. Sperlingite has monoclinic symmetry with space group P21/c and unit-cell parameters a = 10.428(2) Å, b = 20.281(4) Å, c = 12.223(2) Å, β = 90.10(3)°, V = 2585.0(8) Å3 and Z = 4. The crystal structure was refined using synchrotron single-crystal data to wRobs = 0.058 for 5608 reflections with I > 3σ(I). Sperlingite is the first paulkerrite-group mineral to have co-dominant divalent and trivalent cations at the M1 sites; All other reported members have Mn2+ or Mg dominant at M1. Local charge balance for Fe3+ at M1 is achieved by H2O → OH– at H2O coordinated to M1.

Clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) for treatment of treatment-resistant depression (TRD) vary widely and there is no mood rating scale that is standard for assessing rTMS outcome. It remains unclear whether TMS is as efficacious in older adults with late-life depression (LLD) compared to younger adults with major depressive disorder (MDD). This study examined the effect of age on outcomes of rTMS treatment of adults with TRD. Self-report and observer mood ratings were measured weekly in 687 subjects ages 16–100 years undergoing rTMS treatment using the Inventory of Depressive Symptomatology 30-item Self-Report (IDS-SR), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item, and Hamilton Depression Rating Scale 17-item (HDRS). All rating scales detected significant improvement with treatment; response and remission rates varied by scale but not by age (response/remission ≥ 60: 38%–57%/25%–33%; <60: 32%–49%/18%–25%). Proportional hazards models showed early improvement predicted later improvement across ages, though early improvements in PHQ and HDRS were more predictive of remission in those < 60 years (relative to those ≥ 60) and greater baseline IDS burden was more predictive of non-remission in those ≥ 60 years (relative to those < 60). These results indicate there is no significant effect of age on treatment outcomes in rTMS for TRD, though rating instruments may differ in assessment of symptom burden between younger and older adults during treatment.

In 2016, the National Center for Advancing Translational Science launched the Trial Innovation Network (TIN) to address barriers to efficient and informative multicenter trials. The TIN provides a national platform, working in partnership with 60+ Clinical and Translational Science Award (CTSA) hubs across the country to support the design and conduct of successful multicenter trials. A dedicated Hub Liaison Team (HLT) was established within each CTSA to facilitate connection between the hubs and the newly launched Trial and Recruitment Innovation Centers. Each HLT serves as an expert intermediary, connecting CTSA Hub investigators with TIN support, and connecting TIN research teams with potential multicenter trial site investigators. The cross-consortium Liaison Team network was developed during the first TIN funding cycle, and it is now a mature national network at the cutting edge of team science in clinical and translational research. The CTSA-based HLT structures and the external network structure have been developed in collaborative and iterative ways, with methods for shared learning and continuous process improvement. In this paper, we review the structure, function, and development of the Liaison Team network, discuss lessons learned during the first TIN funding cycle, and outline a path toward further network maturity.

Background: We aimed to develop an efficient and reliable artificial intelligence solution to automate prediction of neurosurgical intervention using acute traumatic brain injury computed tomography (CT) scans. Methods: TBI patients were identified from 2005 - 2022 at a Level 1 Canadian trauma center. Model training, validation, and testing was performed using head CT scans with patient-level labels corresponding to whether the patient received neurosurgical intervention. The finalized model was then deployed in a simulated prospective fashion on all TBI patients presenting to our center over an 18-month epoch. Results: 2,806 TBI scans were utilized for development of the Automated Surgical Intervention Support Tool (ASIST-TBI). 612 additional consecutive scans were used for simulated prospective model deployment. Prediction of neurosurgical intervention exhibited an area under receiver operating curve (AUC) of 0.92, accuracy of 0.87, sensitivity of 0.87, and specificity of 0.88 on the test dataset. On simulated prospective data, the results were: AUC 0.89, sensitivity 0.85, specificity 0.84 and accuracy of 0.84. Conclusions: We demonstrate the development and validation of ASIST-TBI, a machine learning model that accurately predicts whether TBI patients will need neurosurgical intervention. This model has potential application to optimize decision support and province-wide efficiency of inter-facility TBI triage to tertiary care centers.

Optimizing research on the developmental origins of health and disease (DOHaD) involves implementing initiatives maximizing the use of the available cohort study data; achieving sufficient statistical power to support subgroup analysis; and using participant data presenting adequate follow-up and exposure heterogeneity. It also involves being able to undertake comparison, cross-validation, or replication across data sets. To answer these requirements, cohort study data need to be findable, accessible, interoperable, and reusable (FAIR), and more particularly, it often needs to be harmonized. Harmonization is required to achieve or improve comparability of the putatively equivalent measures collected by different studies on different individuals. Although the characteristics of the research initiatives generating and using harmonized data vary extensively, all are confronted by similar issues. Having to collate, understand, process, host, and co-analyze data from individual cohort studies is particularly challenging. The scientific success and timely management of projects can be facilitated by an ensemble of factors. The current document provides an overview of the ‘life course’ of research projects requiring harmonization of existing data and highlights key elements to be considered from the inception to the end of the project.

Since the advent of direct-acting antiviral therapy, the elimination of hepatitis c virus (HCV) as a public health concern is now possible. However, identification of those who remain undiagnosed, and re-engagement of those who are diagnosed but remain untreated, will be essential to achieve this. We examined the extent of HCV infection among individuals undergoing liver function tests (LFT) in primary care. Residual biochemistry samples for 6007 patients, who had venous blood collected in primary care for LFT between July 2016 and January 2017, were tested for HCV antibody. Through data linkage to national and sentinel HCV surveillance databases, we also examined the extent of diagnosed infection, attendance at specialist service and HCV treatment for those found to be HCV positive. Overall HCV antibody prevalence was 4.0% and highest for males (5.0%), those aged 37–50 years (6.2%), and with an ALT result of 70 or greater (7.1%). Of those testing positive, 68.9% had been diagnosed with HCV in the past, 84.9% before the study period. Most (92.5%) of those diagnosed with chronic infection had attended specialist liver services and while 67.7% had ever been treated only 38% had successfully cleared infection. More than half of HCV-positive people required assessment, and potentially treatment, for their HCV infection but were not engaged with services during the study period. LFT in primary care are a key opportunity to diagnose, re-diagnose and re-engage patients with HCV infection and highlight the importance of GPs in efforts to eliminate HCV as a public health concern.

The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.

Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.

OBJECTIVES/GOALS: Using the covariate-rich Veteran Health Administration data, estimate the association between Proton Pump Inhibitor (PPI) use and severe COVID-19, rigorously adjusting for confounding using propensity score (PS)-weighting. METHODS/STUDY POPULATION: We assembled a national retrospective cohort of United States veterans who tested positive for SARS-CoV-2, with information on 33 covariates including comorbidity diagnoses, lab values, and medications. Current outpatient PPI use was compared to non-use (two or more fills and pills on hand at admission vs no PPI prescription fill in prior year). The primary composite outcome was mechanical ventilation use or death within 60 days; the secondary composite outcome included ICU admission. PS-weighting mimicked a 1:1 matching cohort, allowing inclusion of all patients while achieving good covariate balance. The weighted cohort was analyzed using logistic regression. RESULTS/ANTICIPATED RESULTS: Our analytic cohort included 97,674 veterans with SARS-CoV-2 testing, of whom 14,958 (15.3%) tested positive (6,262 [41.9%] current PPI-users, 8,696 [58.1%] non-users). After weighting, all covariates were well-balanced with standardized mean differences less than a threshold of 0.1. Prior to PS-weighting (no covariate adjustment), we observed higher odds of the primary (9.3% vs 7.5%; OR 1.27, 95% CI 1.13-1.43) and secondary (25.8% vs 21.4%; OR 1.27, 95% CI 1.18-1.37) outcomes among PPI users vs non-users. After PS-weighting, PPI use vs non-use was not associated with the primary (8.2% vs 8.0%; OR 1.03, 95% CI 0.91-1.16) or secondary (23.4% vs 22.9%;OR 1.03, 95% CI 0.95-1.12) outcomes. DISCUSSION/SIGNIFICANCE: The associations between PPI use and severe COVID-19 outcomes that have been previously reported may be due to limitations in the covariates available for adjustment. With respect to COVID-19, our robust PS-weighted analysis provides patients and providers with further evidence for PPI safety.

The end-Cretaceous (K/Pg) mass extinction event is the most recent and well-understood of the “big five” and triggered establishment of modern terrestrial ecosystem structure. Despite the depth of research into this event, our knowledge of upper Maastrichtian terrestrial deposits globally relies primarily on assemblage-level data limited to a few well-sampled formations in North America, the Hell Creek and Lance Formations. These assemblages disproportionally affect our interpretations of this important interval. Multiple investigations have quantified diversity patterns within these assemblages, but the potential effect of formation-level size-dependent taphonomic biases and their implications on extinction dynamics remains unexplored. Here, the relationship between taphonomy and body size of the Hell Creek Formation and Lance Formation dinosaurs and mammals are quantitatively analyzed. Small-bodied dinosaur taxa (<70 kg) are consistently less complete, unlikely to be articulated, and delayed in their description relative to their large-bodied counterparts. Family-level abundance (particularly skeletons) is strongly tied to body mass, and the relative abundance of juveniles of large-bodied taxa similarly is underrepresented. Mammals show similar but nonsignificant trends. The results are remarkably similar to those from the Campanian-aged Dinosaur Park Formation, suggesting a widespread strong taphonomic bias against the preservation of small taxa, which will result in their seemingly depauperate diversity within the assemblage. This taphonomically skewed view of diversity and abundance of small-bodied taxa amid our best late Maastrichtian samples has significant implications for understanding speciation and extinction dynamics (e.g., size-dependent extinction selectivity) across the K/Pg boundary.

Introduced mammalian predators are responsible for the decline and extinction of many native species, with rats (genus Rattus) being among the most widespread and damaging invaders worldwide. In a naturally fragmented landscape, we demonstrate the multi-year effectiveness of snap traps in the removal of Rattus rattus and Rattus exulans from lava-surrounded forest fragments ranging in size from <0.1 to >10 ha. Relative to other studies, we observed low levels of fragment recolonization. Larger rats were the first to be trapped, with the average size of trapped rats decreasing over time. Rat removal led to distinct shifts in the foraging height and location of mongooses and mice, emphasizing the need to focus control efforts on multiple invasive species at once. Furthermore, because of a specially designed trap casing, we observed low non-target capture rates, suggesting that on Hawai‘i and similar islands lacking native rodents the risk of killing non-target species in snap traps may be lower than the application of rodenticides, which have the potential to contaminate food webs. These efforts demonstrate that targeted snap-trapping is an effective removal method for invasive rats in fragmented habitats and that, where used, monitoring of recolonization should be included as part of a comprehensive biodiversity management strategy.

Healthcare personnel with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection were interviewed to describe activities and practices in and outside the workplace. Among 2,625 healthcare personnel, workplace-related factors that may increase infection risk were more common among nursing-home personnel than hospital personnel, whereas selected factors outside the workplace were more common among hospital personnel.