Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.

Objectives/Goals: The objective of this study is to explore strategies for AI-physician collaboration in diagnosing acute respiratory distress syndrome (ARDS) using chest X-rays. By comparing the diagnostic accuracy of different AI deployment methods, the study aims to identify optimal strategies that leverage both AI and physician expertise to improve outcomes. Methods/Study Population: The study analyzed 414 frontal chest X-rays from 115 patients hospitalized between August 15 and October 2, 2017, at the University of Michigan. Each X-ray was reviewed by six physicians for ARDS presence and diagnostic confidence. We developed a deep learning AI model for detecting ARDS and explored the strengths, weaknesses, and blind spots of both physicians and AI systems to inform optimal system deployment. We then investigated several AI-physician collaboration strategies, including: 1) AI-aided physician: physicians interpret chest X-rays first and defer to the AI model if uncertain, 2) physician-aided AI: the AI model interprets chest X-rays first and defers to a physician if uncertain, and 3) AI model and physician interpreting chest X-rays separately and then averaging their interpretations. Results/Anticipated Results: While the AI model (84.7% accuracy) had higher accuracy than physicians (80.8%), we found evidence that AI and physician expertise are complementary. When physicians lacked confidence in a chest X-ray’s interpretation, the AI model had higher accuracy. Conversely, in cases of AI uncertainty, physicians were more accurate. The AI excelled with easier cases, while physicians were better with difficult cases, defined as those where at least two physicians disagreed with the majority label. Collaboration strategies tested include AI-aided physician (82.4%), physician-aided AI (86.9%), and averaging interpretations (86%). The physician-aided AI approach had the highest accuracy, could off-load the human expert workload on the reading of up to 79% chest X-rays, allowing physicians to focus on challenging cases. Discussion/Significance of Impact: This study shows AI and physicians complement each other in ARDS diagnosis, improving accuracy when combined. A physician-aided AI strategy, where the AI defers to physicians when uncertain, proved most effective. Implementing AI-physician collaborations in clinical settings could enhance ARDS care, especially in low-resource environments.

Objectives/Goals: Manual skin assessment in chronic graft-versus-host disease (cGVHD) can be time consuming and inconsistent (>20% affected area) even for experts. Building on previous work we explore methods to use unmarked photos to train artificial intelligence (AI) models, aiming to improve performance by expanding and diversifying the training data without additional burden on experts. Methods/Study Population: Common to many medical imaging projects, we have a small number of expert-marked patient photos (N = 36, n = 360), and many unmarked photos (N = 337, n = 25,842). Dark skin (Fitzpatrick type 4+) is underrepresented in both sets; 11% of patients in the marked set and 9% in the unmarked set. In addition, a set of 20 expert-marked photos from 20 patients were withheld from training to assess model performance, with 20% dark skin type. Our gold standard markings were manual contours around affected skin by a trained expert. Three AI training methods were tested. Our established baseline uses only the small number of marked photos (supervised method). The semi-supervised method uses a mix of marked and unmarked photos with human feedback. The self-supervised method uses only unmarked photos without any human feedback. Results/Anticipated Results: We evaluated performance by comparing predicted skin areas with expert markings. The error was given by the absolute difference between the percentage areas marked by the AI model and expert, where lower is better. Across all test patients, the median error was 19% (interquartile range 6 – 34) for the supervised method and 10% (5 – 23) for the semi-supervised method, which incorporated unmarked photos from 83 patients. On dark skin types, the median error was 36% (18 – 62) for supervised and 28% (14 – 52) for semi-supervised, compared to a median error on light skin of 18% (5 – 26) for supervised and 7% (4 – 17) for semi-supervised. Self-supervised, using all 337 unmarked patients, is expected to further improve performance and consistency due to increased data diversity. Full results will be presented at the meeting. Discussion/Significance of Impact: By automating skin assessment for cGVHD, AI could improve accuracy and consistency compared to manual methods. If translated to clinical use, this would ease clinical burden and scale to large patient cohorts. Future work will focus on ensuring equitable performance across all skin types, providing fair and accurate assessments for every patient.

OBJECTIVES/GOALS: To determine whether cardioprotective effects observed in individuals taking dietary supplementation with eicosapentaenoic acid (EPA), an ω-3 polyunsaturated fatty acid, are realized by altering platelet function, and if these effects are mediated through the 12-lipoxygenase derived metabolite, 12-hydroxyeicosapentaenoic acid (12-HEPE). METHODS/STUDY POPULATION: Washed platelets or platelet rich plasma from healthy human donors were treated with EPA and 12-HEPE to assess their ability to inhibit platelet activation. Platelets were stimulated with agonists targeting different steps of the hemostatic response to vascular injury. Platelet aggregation, dense granule secretion, surface expression of integrin αIIbβ3 and P-selectin, and clot retraction were analyzed. To assess signaling through Gαs-GPCRs and protein kinase A activity, phosphorylation of vasodilator-stimulated phosphoprotein (VASP) was examined via western blot following treatment with EPA or 12-HEPE. RESULTS/ANTICIPATED RESULTS: EPA and 12-HEPE dose-dependently inhibit both collagen and thrombin-induced platelet aggregation. Furthermore, 12-HEPE more potently attenuates dense granule secretion and surface expression of platelet activation markers, integrin αIIbβ3 and P-selectin, in comparison to EPA. Plasma treated with EPA delayed thrombin-induced clot retraction, while 12-HEPE had no effect. Additionally, treatment with 12-HEPE increases phosphorylation of VASP, suggesting it could signal through the activation of the eicosanoid Gαs-GPCRs. DISCUSSION/SIGNIFICANCE: Here, we show for the first time that EPA directly inhibits platelet activation through its 12-LOX metabolite, 12-HEPE. These findings provide further insight into the mechanisms underlying the cardioprotective effects of EPA. A better understanding of current PUFA supplementations can inform treatment and prevention of cardiovascular diseases.

Wyoming bentonite, Fithian illite, and basalt from the Umtanum Formation, Washington, were treated hydrothermally at 200° to 460°C and 260 to 500 bars for 71 to 584 days. No change was detected for the bentonite and basalt, except for the loss of calcite and exchange of Ca for K in the smectite and the growth of a small amount of smectite (presumably from a glass phase) in the basalt. Calcite in the initial bentonite may have stabilized the smectite by Ca/K exchange; thus, if the latter is used as a packing material in a nuclear waste repository, limestone should be added. No change was detected in the illite samples treated <300°C; however, at 360°C, euhedral crystals of berthierine and illite grew at the expense of original illite/smectite, apparently by a solution-crystallization process. Significant changes involving the dissolution of starting phases and the formation of illite and chlorite were also detected in mixtures of basalt and bentonite at 400°C; at temperatures <400°C, no changes were observed.

The newly formed mineral phases (berthierine, illite, and chlorite) observed by transmission electron microscopy showed euhedral to subhedral shapes. These shapes are the same as those observed in hydrothermally altered sediments from the Salton Sea field and different from those from burial metamorphic environments, such as Gulf Coast sediments. The reaction mechanism is apparently the dissolution of reactants followed by the crystallization of products from solution, without conservation of structural elements of the reactants. Reactions apparently required temperatures greater than those for analogous changes in nature, suggesting that the degree of reaction was controlled by kinetics. The lack of dissolution in experimental runs at low temperatures, however, does not necessarily imply long-term stabilities of these clay minerals.

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.

The reading the mind in the eyes test (RMET) – which assesses the theory of mind component of social cognition – is often used to compare social cognition between patients with schizophrenia and healthy controls. There is, however, no systematic review integrating the results of these studies. We identified 198 studies published before July 2020 that administered RMET to patients with schizophrenia or healthy controls from three English-language and two Chinese-language databases. These studies included 41 separate samples of patients with schizophrenia (total n = 1836) and 197 separate samples of healthy controls (total n = 23 675). The pooled RMET score was 19.76 (95% CI 18.91–20.60) in patients and 25.53 (95% CI 25.19–25.87) in controls (z = 12.41, p < 0.001). After excluding small-sample outlier studies, this difference in RMET performance was greater in studies using non-English v. English versions of RMET (Chi [Q] = 8.54, p < 0.001). Meta-regression analyses found a negative association of age with RMET score and a positive association of years of schooling with RMET score in both patients and controls. A secondary meta-analysis using a spline construction of 180 healthy control samples identified a non-monotonic relationship between age and RMET score – RMET scores increased with age before 31 and decreased with age after 31. These results indicate that patients with schizophrenia have substantial deficits in theory of mind compared with healthy controls, supporting the construct validity of RMET as a measure of social cognition. The different results for English versus non-English versions of RMET and the non-monotonic relationship between age and RMET score highlight the importance of the language of administration of RMET and the possibility that the relationship of aging with theory of mind is different from the relationship of aging with other types of cognitive functioning.

Animal welfare encompasses all aspects of an animal's life and the interactions between animals. Consequently, welfare must be measured across a variety of factors that consider aspects such as health, behaviour and mental state. Decisions regarding housing and grazing are central to farm management. In this study, two beef cattle systems and their herds were compared from weaning to slaughter across numerous indicators. One herd (‘HH’) were continuously housed, the other (‘HG’) were housed only during winter. Inspections of animals were conducted to assess body condition, cleanliness, diarrhoea, hairlessness, nasal discharge and ocular discharge. Hair and nasal mucus samples were taken for quantification of cortisol and serotonin. Qualitative behaviour assessments (QBA) were also conducted and performance monitored. Physical health indicators were similar between herds with the exception of nasal discharge which was more prevalent in HH (P < 0.001). During winter, QBA yielded differences between herds over PC1 (arousal) (P = 0.032), but not PC2 (mood) (P = 0.139). Through summer, there was a strong difference across both PC1 (P < 0.001) and PC2 (P = 0.002), with HG exhibiting more positive behaviour. A difference was found in hair cortisol levels, with the greatest concentrations observed in HG (P = 0.011), however such a pattern was not seen for nasal mucus cortisol or for serotonin. Overall, providing summer grazing (HG) appeared to afford welfare benefits to the cattle as shown with more positive QBA assessments, but also slightly better health indicators, notwithstanding the higher levels of cortisol in that group.

We extend Venkatesh’s proof of the converse theorem for classical holomorphic modular forms to arbitrary level and character. The method of proof, via the Petersson trace formula, allows us to treat arbitrary degree $2$ gamma factors of Selberg class type.

Hierarchical Bayesian methods offer a principled and comprehensive way to relate psychological models to data. Here we use them to model the patterns of information search, stopping and deciding in a simulated binary comparison judgment task. The simulation involves 20 subjects making 100 forced choice comparisons about the relative magnitudes of two objects (which of two German cities has more inhabitants). Two worked-examples show how hierarchical models can be developed to account for and explain the diversity of both search and stopping rules seen across the simulated individuals. We discuss how the results provide insight into current debates in the literature on heuristic decision making and argue that they demonstrate the power and flexibility of hierarchical Bayesian methods in modeling human decision-making.

The purpose of this document is to highlight practical recommendations to assist acute care hospitals to prioritize and implement strategies to prevent ventilator-associated pneumonia (VAP), ventilator-associated events (VAE), and non-ventilator hospital-acquired pneumonia (NV-HAP) in adults, children, and neonates. This document updates the Strategies to Prevent Ventilator-Associated Pneumonia in Acute Care Hospitals published in 2014. This expert guidance document is sponsored by the Society for Healthcare Epidemiology (SHEA), and is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America, the American Hospital Association, the Association for Professionals in Infection Control and Epidemiology, and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise.

The Variables and Slow Transients Survey (VAST) on the Australian Square Kilometre Array Pathfinder (ASKAP) is designed to detect highly variable and transient radio sources on timescales from 5 s to $\sim\!5$ yr. In this paper, we present the survey description, observation strategy and initial results from the VAST Phase I Pilot Survey. This pilot survey consists of $\sim\!162$ h of observations conducted at a central frequency of 888 MHz between 2019 August and 2020 August, with a typical rms sensitivity of $0.24\ \mathrm{mJy\ beam}^{-1}$ and angular resolution of $12-20$ arcseconds. There are 113 fields, each of which was observed for 12 min integration time, with between 5 and 13 repeats, with cadences between 1 day and 8 months. The total area of the pilot survey footprint is 5 131 square degrees, covering six distinct regions of the sky. An initial search of two of these regions, totalling 1 646 square degrees, revealed 28 highly variable and/or transient sources. Seven of these are known pulsars, including the millisecond pulsar J2039–5617. Another seven are stars, four of which have no previously reported radio detection (SCR J0533–4257, LEHPM 2-783, UCAC3 89–412162 and 2MASS J22414436–6119311). Of the remaining 14 sources, two are active galactic nuclei, six are associated with galaxies and the other six have no multi-wavelength counterparts and are yet to be identified.

Eggs contain important compounds related to enhanced cognition, but it is not clear if egg consumption, as a whole, has a direct impact on memory decline in older adults. This study aimed to determine whether egg intake levels predict the rate of memory decline in healthy older adults after sociodemographic and dietary controls. We conducted a secondary analysis of data from 470 participants, age 50 and over, from the Biospsychosocial Religion and Health Study. Participants completed a food frequency questionnaire, which was used to calculate egg intake and divide participants into Low (<23 g/week, about half an egg), Intermediate (24–63 g/week, half to 1½ eggs) and High (≥63 g/week, about two or more eggs) tertiles. Participants were administered the California Verbal Learning Test – 2nd Edition (CVLT-II) Short Form in 2006–2007, and 294 of them were again tested in 2010–2011. Using linear mixed model analysis, no significant cross-sectional differences were observed in CVLT-II performance between egg intake levels after controlling for age, sex, race, education, body mass index, cardiovascular risk, depression and intake of meat, fish, dairy and fruits/vegetables. Longitudinally, the Intermediate egg group exhibited significantly slower rates of decline on the CVLT-II compared to the Low egg group. The High egg group also exhibited slower rates of decline, but not statistically significant. Thus, limited consumption of eggs (about 1 egg/week) was associated with slower memory decline in late life compared to consuming little to no eggs, but a dose-response effect was not clearly evident. This study may help explain discrepancies in previous research that did not control for other dietary intakes and risk factors.

ABSTRACT IMPACT: This work may provide new targets for vaccine and immunotherapeutic development against MRSA infections. OBJECTIVES/GOALS: Staphylococcus aureus is the leading cause of skin and skin structure infection (SSSI), a primary portal of entry for invasive infection. Patients with SA SSSI have a high 1-year recurrence. We have shown innate memory protects mice against SA SSSI. The goal of this project is to determine epigenetic mechanisms of protective memory against SA SSSI. METHODS/STUDY POPULATION: We have shown macrophages (Mf) afford protective memory against recurrent SA SSSI in mice. Priming by prior infection reduced skin lesion size and MRSA burden, which correlated with increased Mf in abscesses and lymph nodes. Priming potentiated the opsonophagocytic killing of SA by bone-marrow derived Mf (BMDM) in vitro, and their adoptive transfer into naive skin afforded protective efficacy in vivo. Here, we investigated epigenetic mechanisms of anti-SA efficacy in BMDMs. BMDM from naive (uninfected) or primed (SA SSSI) wild-type C57Bl/6 mice were cultured ex vivo. DNA from BMDM groups were isolated and analyzed for methylation changes using reduced representation bisulfite sequencing (RRBS). Pathway analyses of methylation changes were determined with Panther. RESULTS/ANTICIPATED RESULTS: Present findings indicate the protective memory afforded by BMDM was mediated by epigenetic modifications of the DNA. Using RRBS, we profiled differentially methylated regions (DMR) in DNA from naive vs. primed BMDM. Primed BMDM exhibited significantly different DMRs as compared to naive BMDM. Proximity to known genes were mapped using GREAT. Pathway analyses revealed DMRs predominant in genes integral to immune modulation, such as integrin signaling, cytokine/chemokine networks, and growth regulation. For example, SA-primed BMDM were hypermethylated proximate to GIMAP8 versus naive BMDM, suggesting repression of this protein. Gimap family ligands are small GTPase immune-associated proteins expressed in immune cells known to regulate macrophage lysosomal fusion during parasite infection. DISCUSSION/SIGNIFICANCE OF FINDINGS: These findings reveal epigenetic mechanisms of macrophage innate memory against recurrent MRSA infection. Functional testing of these genes in response to SA infection is needed to confirm their protective role. These insights may provide new targets for vaccine and immunotherapeutic development against MRSA.

Subglacial hydrological systems require innovative technological solutions to access and observe. Wireless sensor platforms can be used to collect and return data, but their performance in deep and fast-moving ice requires quantification. We report experimental results from Cryoegg: a spherical probe that can be deployed into a borehole or moulin and transit through the subglacial hydrological system. The probe measures temperature, pressure and electrical conductivity in situ and returns all data wirelessly via a radio link. We demonstrate Cryoegg's utility in studying englacial channels and moulins, including in situ salt dilution gauging. Cryoegg uses VHF radio to transmit data to a surface receiving array. We demonstrate transmission through up to 1.3 km of cold ice – a significant improvement on the previous design. The wireless transmission uses Wireless M-Bus on 169 MHz; we present a simple radio link budget model for its performance in cold ice and experimentally confirm its validity. Cryoegg has also been tested successfully in temperate ice. The battery capacity should allow measurements to be made every 2 h for more than a year. Future iterations of the radio system will enable Cryoegg to transmit data through up to 2.5 km of ice.