Objectives/Goals: Cognitive decline is a known sequalae of intracranial radiation in the treatment of brain metastases. In this study, we investigate global structural changes in the brain akin to accelerated aging and compare aging kinetics between patients treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS). Methods/Study Population: This retrospective study consists of patients with brain metastases treated with WBRT and SRS at our institution. Brain MRI images collected prior to radiation therapy and at approximately three and six months following radiation will be analyzed, excluding patients with evidence of worsening disease burden in the brain. Surface morphology of the cerebral cortex and sub-cortical structures will be extracted using Freesurfer and converted to graphs. Data will then be input into a validated graph convolutional neural network model to estimate brain age at each time point. A generalized linear model will be used to estimate the aging pace between baseline and follow-up for each subject within the whole brain as well as the sub-cortical structures, which will be compared between WBRT and SRS treatment groups. Results/Anticipated Results: We anticipate that intracranial radiation will accelerate brain aging to a greater extent following WBRT compared to SRS. Additionally, this accelerated aging will occur globally in the whole brain as well as within individual substructures, including the cerebral cortex, nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Discussion/Significance of Impact: This study will demonstrate structural changes in the brain analogous to accelerated aging, supporting its potential use as an imaging biomarker to monitor cognitive decline after radiation therapy. Future work will explore the relationship between structural brain aging and assessments of neurocognitive function.

Objectives/Goals: The goal of the RC2 Systems Marketing Analysis for Research Translation (SMART) special innovation program is to develop and test a structured approach for working with research teams and communities to accelerate the translation of clinical and community innovations to address health inequities by integrating social marketing with community-based system dynamics. Methods/Study Population: The SMART program is a consultancy service for CTS teams focused on selecting and tailoring implementation strategies for advancing equity. We use social marketing for understanding the alignment of practice innovation feature sets with community priorities for advancing health equity; and community-based system dynamics to understand and refine the dynamics of scaling up and sustaining the implementation of innovations with sufficient reach to address regional health inequities. The program is implemented as community-engaged group model-building workshops with research teams, with follow-up marketing analyses and computer simulation of implementation strategies of innovations and development of implementation roadmaps. We use developmental program evaluation to revise the SMART program. Results/Anticipated Results: Anticipated results from piloting the SMART innovation program with four research teams include (1) design matrices pre and post-workshop for each innovation; (2) system dynamics simulation models and analyses of implementation and scale-up of innovations; (3) analysis of the SMART program for highest impact, with priors for estimating subsequent SMART program performance; and (4) a revised SMART program based on results from the developmental program evaluation. Discussion/Significance of Impact: This work highlights the feasibility and benefits of combining methods that have been cited in implementation science for understanding the complexity of implementation to accelerate the translation of innovations into clinical and community settings for advancing health equity.

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.

This paper presents a simple random procedure for selecting subsets of stimulus pairs for presentation to subjects. The resulting set of ratings from the group of subjects allows the construction of a group (average) space through the use of the computer program TORSCA-9 or equivalent programs. The procedure is applied to both real and simulated data. It is found that subjects need only make between 20% and 50% of the usual judgements to reconstruct a reasonably accurate group space.

Following the application of MCPA/MCPB at 1.7 kg ae ha−1 at a field site near Dresden, ON, Canada, poor control (<50% visible control) of green pigweed (Amaranthus powellii S. Watson) was observed. Amaranthus powellii is a common weed in Ontario crop production, and its evolution of resistance to synthetic auxin herbicides (SAHs) could pose a risk to crop yields. The suspected resistant A. powellii population (R) was used in dose–response and field experiments to determine resistance to SAHs. The objective of these studies was to determine whether this population of A. powellii is resistant to MCPA and cross-resistant to other SAHs. The GR50 (herbicide dose that causes a 50% reduction in plant aboveground biomass) values were determined by fitting plant dry weight data, obtained following application with seven SAHs, to a four-parameter log-logistic equation and were compared between the suspected-resistant (R) population and a known susceptible (S) population of A. powellii. The field trial was conducted in 2017, 2018, 2019, and 2021 in corn (Zea mays L.) and consisted of 11 postemergence SAH treatments. The GR50 values differed between the R and S populations following application with MCPA, aminocyclopyrachlor, dichlorprop-p, and mecoprop, resulting in resistance factors of 4.4, 3.0, 2.5, and 2.4, respectively. In the field study, dicamba and MCPA ester controlled A. powellii 84% and 30%, respectively, at 8 wk after treatment application (WAA). The control of Amaranthus powellii with all SAHs applied POST in corn was poor (<90% visible control) at 8 WAA. Both studies confirmed resistance to SAHs in this population of A. powellii, which will create limitations for farmers aiming to control this weed.

Demand for student mental health services is growing, as is the complexity of presentations to university student wellbeing services. There is a need for innovative service delivery models to prevent students falling in the gaps of existing provision, where outcomes from traditional talking therapies services have been shown to be poorer for students than non-student peers. In 2018, Newcastle University established a pilot in-house cognitive behavioural therapy (CBT) service to provide high-intensity CBT for students at the university, harnessing the expertise of qualified and training staff from the psychological professions. This subsequently expanded into the Psychological Therapies Training and Research Clinic, appointing additional clinical staff. Here we present the journey of the clinic, from inception to implementation and expansion. We also present a descriptive evaluation of the first three years of operation, reporting on clinical activity, clinical outcomes and client experiences of the service. Data are presented from 605 referrals. Over 70% of referrals were assessed and over 60% transitioned into treatment. The treatment completion rate was 50%, with an overall recovery rate of 47.3% [using the same definition of recovery as NHS Talking Therapies for Anxiety and Depression (NHS TTAD)]. Satisfaction, measured by the Patient Evaluation Questionnaire, was high. These outcomes are commensurate or better than seen in NHS TTAD services for students and young adults. Overall, the clinic has been a successful addition to the wellbeing offer of the university and has provided a number of positive further opportunities for both research and the clinical training programmes.

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.

OBJECTIVES/GOALS: Renal vascular resistance (RVR) is the opposition to blood flow by renal arteries. At the population level, dietary salt increases RVR and blood pressure (BP), which are associated with cardiovascular disease. Recent data indicate exogenous ketones may offset adverse cardiorenal effects of salt. METHODS/STUDY POPULATION: Our registered clinical trial (NCT05545501) is a double-blinded, placebo-controlled, crossover study. Participants are being randomized to three 10-day conditions: A) control; B) high salt; C) high salt and ketone supplementation. Ten participants are enrolled (target 30 participants). Renal blood velocity (RBV) in the renal and segmental arteries will be measured in the decubitus position using Doppler ultrasound during a 3-minute baseline and 3-minute cold pressor test. We will measure brachial BP with an automated oscillometric BP monitor. RVR will be calculated as mean BP divided by RBV. Statistical analyses will include ANOVA and correlations with α set at ≤ 0.05. RESULTS/ANTICIPATED RESULTS: We anticipate attenuated RBV and increased BP during the cold pressor test, particularly following high salt loading, leading to greater RVR. We hypothesize ketone supplementation will attenuate the high salt induced increase in RVR during the cold pressor test. In addition to RVR we will examine renal vascular conductance which is the ease with which blood flows through arteries, calculated as RBV divided by mean BP. Additional hemodynamics such as heart rate and systolic and diastolic BP will be reported and correlated with primary outcomes. DISCUSSION/SIGNIFICANCE: Dietary salt plays a role in hypertension, cardiovascular disease, and chronic kidney disease, which are leading causes of death. Ketone supplementation may be a promising approach to counteract the detrimental effects of high dietary salt and improve cardiovascular health in adults.