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.

The stars of the Milky Way carry the chemical history of our Galaxy in their atmospheres as they journey through its vast expanse. Like barcodes, we can extract the chemical fingerprints of stars from high-resolution spectroscopy. The fourth data release (DR4) of the Galactic Archaeology with HERMES (GALAH) Survey, based on a decade of observations, provides the chemical abundances of up to 32 elements for 917 588 stars that also have exquisite astrometric data from the Gaia satellite. For the first time, these elements include life-essential nitrogen to complement carbon, and oxygen as well as more measurements of rare-earth elements critical to modern-life electronics, offering unparalleled insights into the chemical composition of the Milky Way. For this release, we use neural networks to simultaneously fit stellar parameters and abundances across the whole wavelength range, leveraging synthetic grids computed with Spectroscopy Made Easy. These grids account for atomic line formation in non-local thermodynamic equilibrium for 14 elements. In a two-iteration process, we first fit stellar labels to all 1 085 520 spectra, then co-add repeated observations and refine these labels using astrometric data from Gaia and 2MASS photometry, improving the accuracy and precision of stellar parameters and abundances. Our validation thoroughly assesses the reliability of spectroscopic measurements and highlights key caveats. GALAH DR4 represents yet another milestone in Galactic archaeology, combining detailed chemical compositions from multiple nucleosynthetic channels with kinematic information and age estimates. The resulting dataset, covering nearly a million stars, opens new avenues for understanding not only the chemical and dynamical history of the Milky Way but also the broader questions of the origin of elements and the evolution of planets, stars, and galaxies.

We present a chemo-dynamical study conducted with 2dF$+$AAOmega of $\sim 6\,000$ Gaia DR3 non-variable candidate metal-poor stars that lie in the direction of the Galactic plane. Our spectral analysis reveals 15 new extremely metal-poor (EMP) stars, with the lowest metallicity at $\left[\text{Fe/H}\right] = -4.0 \pm 0.2$ dex. Two of the EMP stars are also carbon enhanced, with the largest enhancement of $\left[\text{C/Fe}\right] = 1.3 \pm 0.1$ occurring in a dwarf. Using our $\left[\text{C/Fe}\right]$ results, we demonstrate that the number of carbon-depleted stars decreases with lower metallicities, and the fraction of carbon-enhanced stars increases, in agreement with previous studies. Our dynamical analysis reveals that the fraction of prograde and retrograde disk stars, defined as $z_{\mathrm{max}} \lt 3$ kpc, with $J_{\phi}/J_{\mathrm{tot}} \gt 0.75$ and $J_{\phi}/J_{\mathrm{tot}} \lt -0.75$, respectively, changes as metallicities decrease. Disk stars on retrograde orbits make up $\sim 10$% of all the stars in our sample with metallicities below $-2.1$ dex. Interestingly, the portion of retrograde disk stars compared with the number of kinematically classified halo stars is approximately constant at $4.6$% for all metallicities below $-1.5$ dex. We also see that $J_{\phi}$ increases from $380 \pm 50$ to $1320 \pm 90$ km s$^{-1}$ kpc across metallicity range $-1.5$ to $-1.1$, consistent with the spin-up of the Galactic disk. Over the metallicity range $-3.0 \lt \left[\text{Fe/H}\right] \lt -2.0$, the slopes of the metallicity distribution functions for the prograde and retrograde disk stars are similar and comparable to that for the halo population. However, detailed chemical analyses based on high-resolution spectra are needed to distinguish the accreted versus in situ contributions. Finally, we show that our spectroscopic parameters reveal serious systematics in the metallicities published in recent studies that apply various machine learning techniques to Gaia XP spectra.

Vaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology.

Almost half of countries globally are implementing national strategies to lower population salt intake towards the World Health Organization’s target of a 30% reduction by 2025(1). However, most are yet to lower population salt intake(1). We conducted process evaluations of national salt reduction strategies in Malaysia and Mongolia to understand the extent to which they were implemented and achieving their intended outcomes, using the findings to generate insights on how to strengthen strategies and accelerate population salt reduction. Mixed methods process evaluations were conducted at the mid-point of implementation of the strategies in Malaysia (2018-19) and Mongolia (2020-21)(2). Guided by theoretical frameworks, information on the implementation, mechanism and contextual barriers and enablers of the strategies were collected through desk-based reviews of documents related to salt reduction, interviews with key stakeholders (n = 12 Malaysia, n = 10 Mongolia), and focus group discussions with health professionals in Malaysia (n = 43) and health provider surveys in Mongolia (n = 12). Both countries generated high-quality evidence about salt intake and salt levels in foods, and culturally-specific education resources in 3 and 5 years respectively. However, in Malaysia there was moderate dose delivered and low reach in terms of education and reformulation activities. Within 5 years, Mongolia implemented education among schools, health professionals and food producers on salt reduction with high reach but with moderate dose and reach among the general population. There were challenges in both countries with respect to implementing legislative interventions and both could improve the scaling up of their reformulation and education activities to have population-wide reach and impact. In the first half of Malaysia’s and Mongolia’s strategies, both countries generated necessary evidence and education materials, mobilised health professionals to deliver salt reduction education and achieved small-scale salt reformulation in foods. However, both faced challenges in implementing regulatory policies and the scaling up of their reformulation and education activities to have population-wide reach and impact could be strengthened. Similar process evaluations of existing salt reduction strategies are needed to strengthen intervention delivery and inform areas for adaptation, to aid achievement of the WHO’s global target of a 30% reduction in population salt intake by 2025.

Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.

OBJECTIVES/SPECIFIC AIMS: Clostridium difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and an increasingly common infection in children in both hospital and community settings. Between 20% and 30% of pediatric patients will have a recurrence of symptoms in the days to weeks following an initial infection. Multiple recurrences have been successfully treated with fecal microbiota transplantation (FMT), though the body of evidence in pediatric patients is limited primarily to case reports and case series. The goal of our study was to better understand practices, success, and safety of FMT in children as well as identify risk factors associated with a failed FMT in our pediatric patients. METHODS/STUDY POPULATION: This multicenter retrospective analysis included 373 patients who underwent FMT for CDI between January 1, 2006 and January 1, 2017 from 18 pediatric centers. Demographics, baseline characteristics, FMT practices, C. difficile outcomes, and post-FMT complications were collected through chart abstraction. Successful FMT was defined as no recurrence of CDI within 60 days after FMT. Of the 373 patients in the cohort, 342 had known outcome data at two months post-FMT and were included in the primary analysis evaluating risk factors for recurrence post-FMT. An additional six patients who underwent FMT for refractory CDI were excluded from the primary analysis. Unadjusted analysis was performed using Wilcoxon rank-sum test, Pearson χ2 test, or Fisher exact test where appropriate. Stepwise logistic regression was utilized to determine independent predictors of success. RESULTS/ANTICIPATED RESULTS: The median age of included patients was 10 years (IQR; 3.0, 15.0) and 50% of patients were female. The majority of the cohort was White (89.0%). Comorbidities included 120 patients with inflammatory bowel disease (IBD) and 14 patients who had undergone a solid organ or stem cell transplantation. Of the 336 patients with known outcomes at two months, 272 (81%) had a successful outcome. In the 64 (19%) patients that did have a recurrence, 35 underwent repeat FMT which was successful in 20 of the 35 (57%). The overall success rate of FMT in preventing further episodes of CDI in the cohort with known outcome data was 87%. Unadjusted predictors of a primary FMT response are summarized. Based on stepwise logistic regression modeling, the use of fresh stool, FMT delivery via colonoscopy, the lack of a feeding tube, and a lower number of CDI episodes before undergoing FMT were independently associated with a successful outcome. There were 20 adverse events in the cohort assessed to be related to FMT, 6 of which were felt to be severe. There were no deaths assessed to be related to FMT in the cohort. DISCUSSION/SIGNIFICANCE OF IMPACT: The overall success of FMT in pediatric patients with recurrent or severe CDI is 81% after a single FMT. Children without a feeding tube, who receive an early FMT, FMT with fresh stool, or FMT via colonoscopy are less likely to have a recurrence of CDI in the 2 months following FMT. This is the first large study of FMT for CDI in a pediatric cohort. These findings, if confirmed by additional prospective studies, will support alterations in the practice of FMT in children.

Survivors of adolescent and young adult (AYA) central nervous system (CNS) neoplasms are at risk for late effects (LE) - treatment-related health problems occurring more than 5 years after therapy). Since, in Canada, AYA survivors are usually followed in the community, information must be conveyed to primary care providers to guide risk-based follow-up care. Objective: To assess documentation of LE risks and screening recommendations (SR) in medical records of AYA CNS tumor survivors treated with radiation therapy. Methods: The medical records of all patients diagnosed with a CNS neoplasm (benign or malignant) at ages 15-39 years, treated between 1985 and 2010 in the province of British Columbia, surviving >5 years and discharged to the community were assessed. Documentation of LE and SR were extracted, and analyzed descriptively. Results: Among 132 survivors (52% female), treated with radiation therapy (95% partial brain, 10% craniospinal, 8% partial spine, and 4% whole brain) and chemotherapy (17%), 19% of charts included no documentation of LE risks, 26% included only non-specific documentation, and 55% had minimal documentation (1 or 2 LE). Documentation of at least one specific LE increased from 24% in 1980-1989, to 54% in 1990-1999, to 86% in 2000 – 2010. Based on treatment information, all survivors were at high-risk for LE, such as radiation induced neoplasm, meningioma and cerebrovascular events. Yet, SR were documented in only 25% of charts. Conclusions: The documentation of LE risks and screening recommendations has been limited, highlighting the need to improve written communication with primary care providers.

The term radiosurgery has been used to describe a variety of radiotherapy techniques which deliver high doses of radiation to small, stereotactically defined intracranial targets in such a way that the dose fall-off outside the targeted volume is very sharp. Proton, charged particle, gamma unit, and linear accelerator-based techniques appear to be equivalent from the standpoint of accuracy, dose distributions, and clinical results. However, capital and operating costs associated with the use of linear accelerators in general clinical use are much lower. Radiosurgery has an established role in the treatment of arteriovenous malformations and acoustic neurinomas. Interest in these techniques is increasing in neurosurgical and radiation oncological communities, as radiosurgery is rapidly assuming a place in the management of several other conditions, including craniopharyngiomas, meningiomas, and selected malignant lesions.

Background: To examine stereotactic radiosurgery (SRS) following whole brain radiotherapy for metastases in eloquent, central brain locations: brainstem, thalamus, and basal ganglia. Methods: We conducted a retrospective review of patients with metastases in eloquent, central brain locations who were treated with SRS between January 2000 and April 2012. All patients had whole brain radiotherapy. Patients eligible for SRS had one to three brain metastases, metastasis size ≤4 cm, and Karnofsky performance status ≥70. Local progression-free survival and overall survival were calculated using the Kaplan-Meier method. Results: For 24 patients, the median age was 50 years (range, 36-73). Metastases by location were: 11 brainstem, 9 thalamus, and 5 basal ganglia. The median metastasis size was 15 mm (range, 2-33) and the median SRS dose prescription was 15 Gy (range, 12-24). The median local progression-free survival was 13.7 months and median overall survival was 16.4 months. Compared with a cohort of 188 patients with noneloquent brain metastases receiving a median dose of 24 Gy, overall survival of 10.8 months was not significantly different (p=0.16). The only symptomatic complication was grade 2 headache in 8.3%. Asymptomatic adverse radiologic events were radionecrosis in two (8.3%), peritumoural edema in four (16.7%), and hemorrhage in one patient (4.2%). Conclusions: Lower SRS marginal doses do not appear to compromise survival in patients with eloquently located brain metastases compared with higher doses for other brain metastases, with minimal symptomatic complications.