Objectives/Goals: To strengthen postdocs’ skills in developing and reviewing competitive proposals, advancing translational research by leveraging core facilities at Indiana University, Purdue University, and the University of Notre Dame, fostering collaboration, and preparing participants of the program for future funding success. Methods/Study Population: The Postdoc Challenge is a state-wide program for postdoctoral scholars across Indiana to gain hands-on experience in developing and reviewing competitive grant proposals. Participants compete for a $5,000 award to use any of the Indiana Clinical and Translational Science Institute (CTSI)-approved core facilities. Through workshops and following NIH guidelines for the review process, participants refine their proposal-writing skills and serve as reviewers for peers’ proposals. The program is designed to support translational research, utilizing the core facilities at Indiana University, Purdue University, and the University of Notre Dame. Participants are trained in grant proposal writing, reviewing using NIH criteria, and engaging in peer discussions, developing critical skills necessary for future funding success. Results/Anticipated Results: Since its launch in 2014, the Indiana CTSI Postdoc Challenge has funded 54 postdoctoral researchers, with 276 applications reviewed. The program has strengthened participants’ grant proposal writing skills and peer review capabilities. Career outcomes include several postdocs securing assistant professor positions and other prestigious roles, such as an Associate Principal Investigator at the National Biodefense Analysis and Countermeasures Center, and a Toxicologist at the CDC. Participants also report enhanced collaboration, greater access to core facilities, and significant career advancement, including support for international postdocs seeking permanent residency. Discussion/Significance of Impact: The Postdoc Challenge has significantly improved postdoctoral researchers’ grant proposal writing and peer review skills, helping them secure faculty and research positions. By fostering collaboration across Indiana’s top universities and utilizing core facilities, the program accelerates translational research and career success.

The trace element selenium is known to protect against oxidative damage which is known to contribute to cognitive impairment with ageing (1,2). The aim of this study was to explore the association between selenium status (serum selenium and selenoprotein P (SELENOP)) and global cognitive performance at baseline and after 5 years in 85-year-olds living in the Northeast of England.

Serum selenium and SELENOP concentrations were measured at baseline by total reflection X-ray fluorescence (TXRF) and enzyme-linked immunosorbent assay (ELISA), respectively, in 757 participants from the Newcastle 85+ study. Global cognitive performance was assessed using the Standardized Mini-Mental State Examination (SMMSE) where scores ≤25 out of 30 indicated cognitive impairment. Logistic regressions explored the associations between selenium status and global cognition at baseline. Linear mixed models explored associations between selenium status and global cognition prospectively after 5 years. Covariates included sex, body mass index, physical activity, high sensitivity C-reactive protein, alcohol intake, self-rated health, medications and smoking status.

At baseline, in fully adjusted models, there was no increase in odds of cognitive impairment with serum selenium (OR 1.004, 95% CI 0.993-1.015, p = 0.512) or between SELENOP (OR 1.006, 95% CI 0.881-1.149, p = 0.930). Likewise, over 5 years, in fully adjusted models there was no association between serum selenium and cognitive impairment (β 7.20E-4 ± 5.57E-4, p = 0.197), or between SELENOP and cognitive impairment (β 3.50E-3 ± 6.85E-3, p = 0.610).

In this UK cohort of very old adults, serum selenium or SELENOP was not associated with cognitive impairment at baseline and 5 years. This was an unexpected finding despite SELENOP’s key role in the brain and the observed associations in other studies. Further research is needed to explore the effect of selenium on global cognition in very old adults.

Background: We evaluated vorasidenib (VOR), a dual inhibitor of mIDH1/2, in patients with mIDH1/2 glioma (Phase 3; NCT04164901). Methods: Patients with residual/recurrent grade 2 mIDH1/2 oligodendroglioma or astrocytoma were enrolled (age ≥12; Karnofsky Performance Score ≥80; measurable non-enhancing disease; surgery as only prior treatment; not in immediate need of chemoradiotherapy). Patients were stratified by 1p19q status and baseline tumor size and randomized 1:1 to VOR 40 mg or placebo (PBO) daily in 28-day cycles. Endpoints included imaging-based progression-free survival (PFS), time to next intervention (TTNI), tumor growth rate (TGR), health-related quality of life (HRQoL), neurocognition and seizure activity. Results: 331 patients were randomized (VOR, 168; PBO, 163). The median age was 40.0 years. 172 and 159 patients had histologically confirmed oligodendroglioma and astrocytoma, respectively. Treatment with VOR significantly improved PFS and TTNI. Median PFS: VOR, 27.7 mos; PBO, 11.1 mos (P=0.000000067). Median TTNI: VOR, not reached; PBO, 17.8 mos (P=0.000000019). Treatment with VOR resulted in shrinkage of tumor volume. Post-treatment TGR: VOR, -2.5% (95% CI: -4.7, -0.2); PBO, 13.9% (95% CI: 11.1, 16.8). HRQoL and neurocognition were preserved and seizure control was maintained. VOR had a manageable safety profile. Conclusions: VOR was effective in mIDH1/2 diffuse glioma not in immediate need of chemoradiotherapy.

Providing access to food in schools can serve as a platform for food system transformation, while simultaneously improving educational outcomes and livelihoods. Locally grown and procured food is a nutritious, healthy, and efficient way to provide schoolchildren with a daily meal while, at the same time, improving opportunities for smallholder farmers(1). While there is significant potential for school food provision activities to support healthy dietary behaviours in the Pacific Islands region, there is limited evidence of these types of activities(2), including scope and links to local food production in the region. Therefore, the aim of this scoping study was to understand the current state of school food activities (school feeding, gardening and other food provision activities) and any current, and potential links to local agriculture in the Pacific Islands. A regional mapping activity was undertaken, initially covering 22 Pacific Island countries. The mapping included two steps: 1) a desk based scoping review including peer-reviewed and grey literature (2007-2022) and 2) One-hour semi-structured online Zoom interviews with key country stakeholders. Twelve sources were identified, predominately grey literature (n = 9). Thirty interviews were completed with at least 1 key stakeholder from 15 countries. A variety of school food provision activities were identified, including school feeding programs (n = 16, of varying scale), programs covering both school feeding and school gardens (n = 2), school garden programs (n = 12), and other school food provision activities (n = 4, including taste/sensory education, food waste reduction, increasing canteen capacity for local foods, supply chain distribution between local agriculture and schools). Existing links to local agriculture varied for the different programs. Of the 16 school feeding programs, 8 had a requirement for the use of local produce (policy requirement n = 6, traditional requirement from leaders n = 2). Of the 12 school garden programs, 6 used local or traditional produce in the garden and 5 involved local farmers in varying capacities. Challenges to linking local agriculture into school food provision programs were reported for 17 activities and were context dependent. Common challenges included limited funding, inflation, Covid-19, inadequate produce supply for the scale of program, limited farmer capacity, limited institutional support for local produce, low produce storage life, climatic conditions and disasters, water security, delayed procurement process, and limited professional development and upskilling opportunities. Modernisation and colonisation of food systems resulting in a preference for hyperpalatable foods and challenges in incorporating local produce in a way that is accepted by students was also identified as a challenge. This evidence can be used to develop a pathway to piloting and implementing models of school food provision programs and promoting opportunities for shared learning and collaboration with key stakeholders across the Pacific Islands region.

Improvements in computational and experimental capabilities are rapidly increasing the amount of scientific data that are routinely generated. In applications that are constrained by memory and computational intensity, excessively large datasets may hinder scientific discovery, making data reduction a critical component of data-driven methods. Datasets are growing in two directions: the number of data points and their dimensionality. Whereas dimension reduction typically aims at describing each data sample on lower-dimensional space, the focus here is on reducing the number of data points. A strategy is proposed to select data points such that they uniformly span the phase-space of the data. The algorithm proposed relies on estimating the probability map of the data and using it to construct an acceptance probability. An iterative method is used to accurately estimate the probability of the rare data points when only a small subset of the dataset is used to construct the probability map. Instead of binning the phase-space to estimate the probability map, its functional form is approximated with a normalizing flow. Therefore, the method naturally extends to high-dimensional datasets. The proposed framework is demonstrated as a viable pathway to enable data-efficient machine learning when abundant data are available.

The 2022 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for Acute Stroke Management, 7th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for use by an interdisciplinary team of healthcare providers and system planners caring for persons with an acute stroke or transient ischemic attack. These recommendations are a timely opportunity to reassess current processes to ensure efficient access to acute stroke diagnostics, treatments, and management strategies, proven to reduce mortality and morbidity. The topics covered include prehospital care, emergency department care, intravenous thrombolysis and endovascular thrombectomy (EVT), prevention and management of inhospital complications, vascular risk factor reduction, early rehabilitation, and end-of-life care. These recommendations pertain primarily to an acute ischemic vascular event. Notable changes in the 7th edition include recommendations pertaining the use of tenecteplase, thrombolysis as a bridging therapy prior to mechanical thrombectomy, dual antiplatelet therapy for stroke prevention,1 the management of symptomatic intracerebral hemorrhage following thrombolysis, acute stroke imaging, care of patients undergoing EVT, medical assistance in dying, and virtual stroke care. An explicit effort was made to address sex and gender differences wherever possible. The theme of the 7th edition of the CSBPR is building connections to optimize individual outcomes, recognizing that many people who present with acute stroke often also have multiple comorbid conditions, are medically more complex, and require a coordinated interdisciplinary approach for optimal recovery. Additional materials to support timely implementation and quality monitoring of these recommendations are available at www.strokebestpractices.ca.

OBJECTIVES/GOALS: The goal was to develop foundational research knowledge and skills for clinicians interested in conducting clinical research. Emphasis was on the development of a research question and the iterative process necessary to transform a research question into a well-designed study and well-articulated research proposal for pilot grant funding. METHODS/STUDY POPULATION: The course took place over 10 sessions, May - September 2021. The application process required participants to provide an initial self-assessment of research skills and a proposed research question. 25 clinicians applied to the program, 11 were accepted, and 9 enrolled. All clinicians in the initial cohort were clinical faculty physicians. Because of the geographical distance of participants as well as the ongoing pandemic, the course used a blended learning approach with both synchronous and asynchronous learning. Participants viewed online lectures on core content coupled with live virtual sessions with opportunities for discussion and application of the content. Relevant CTSI and institutional resources were highlighted in each session. RESULTS/ANTICIPATED RESULTS: Of the 9 clinician participants who enrolled in Research 101, the average attendance per session was 67% or 6 people. 89% or 8 participants attended five or more sessions. 5 participants submitted a letter of intent for the annual CTSI Pilot grant program, and of the five, two were invited to submit a grant application. Formal evaluation of the program is currently ongoing and will close on November 30th, at which time full results will be available. Research competencies will be assessed through a pre-post comparison, each self-rated by course participants. Additionally, participants were asked to provide input on the most and least valuable components of the course, as well as any open-ended feedback. Research 101 leadership will use these results to improve the course for future participants. DISCUSSION/SIGNIFICANCE: A learning health system (LHS) is recognized as an essential means by which research evidence is translated into practice. Important to realizing the LHS vision is the engagement of clinicians into the generation and translation of research into practice. Research 101 is an important way to bolster clinician engagement in translational research.

One pathway by which environments of socioeconomic risk are thought to affect cognitive development is through stress physiology. The biological systems underpinning stress and attention undergo a sensitive period of development during infancy. Psychobiological theory emphasizes a dynamic pattern of context-dependent development, however, research has yet to examine how basal cortisol and attention dynamically covary across infancy in ecologically valid contexts. Thus, to address these gaps, we leveraged longitudinal, multilevel analytic methods to disentangle between- from within-person associations of hypothalamic–pituitary–adrenal (HPA) axis activity and executive attention behaviors across infancy. We use data from a large longitudinal sample (N = 1,292) of infants in predominantly low-income, nonurban communities at 7-, 15-, and 24-months of age. Using multilevel models, we investigated longitudinal associations of infant attention and basal cortisol levels and examined caregiving behaviors as moderators of this relationship. Results indicated a negative between- and within-person association between attention and cortisol across infancy and a within-person moderation by caregiver responsiveness. In other words, on the within-person level, higher levels of cortisol were concomitantly associated with lower infant attention across the first 2 years of life. However, variation in the caregiver's level of responsiveness either buffered or sensitized the executive attention system to the negative effects of physiological stress.

This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.

Megan Gunnar's pubertal stress recalibration hypothesis was supported in a recent study of previously institutionalized (PI) youth such that increases in pubertal stage were associated with increases in cortisol stress reactivity. This work provides evidence that puberty may open up a window of recalibration for PI youth, resulting in a shift from a blunted to a more typical cortisol stress response. Using the same sample (N = 132), the current study aimed to elucidate whether increases in cortisol are associated with increases in adaptive functioning or whether they further underlie potential links to developmental psychopathology. Specifically, we examined the bidirectional associations between cortisol stress reactivity and both internalizing and externalizing symptoms across three timepoints during the pubertal period. Youth reported on their own internalizing symptoms and parents reported on youths’ externalizing symptoms. Cortisol reactivity was assessed during the Trier social stress test. Analyses revealed no associations between cortisol reactivity and externalizing symptoms across puberty for PI youth. However, longitudinal bidirectional associations did emerge for internalizing symptoms such that increases in cortisol reactivity predicted increases in internalizing symptoms and increases in internalizing symptoms predicted increases in cortisol reactivity. Findings suggest that recalibrating to more normative levels of cortisol reactivity may not always be associated with adaptive outcomes for PI youth.

Environmental adversity increases child susceptibility to disrupted developmental outcomes, but the mechanisms by which adversity can shape development remain unclear. A translational cross-species approach was used to examine stress-mediated pathways by which poverty-related adversity can influence infant social development. Findings from a longitudinal sample of low-income mother–infant dyads indicated that infant cortisol (CORT) on its own did not mediate relations between early-life scarcity-adversity exposure and later infant behavior in a mother-child interaction task. However, maternal CORT through infant CORT served as a mediating pathway, even when controlling for parenting behavior. Findings using a rodent “scarcity-adversity” model indicated that pharmacologically blocking pup corticosterone (CORT, rodent equivalent to cortisol) in the presence of a stressed mother causally prevented social transmission of scarcity-adversity effects on pup social behavior. Furthermore, pharmacologically increasing pup CORT without the mother present was not sufficient to disrupt pup social behavior. Integration of our cross-species results suggests that elevated infant CORT may be necessary, but without elevated caregiver CORT, may not be sufficient in mediating the effects of environmental adversity on development. These findings underscore the importance of considering infant stress physiology in relation to the broader social context, including caregiver stress physiology, in research and interventional efforts.