OBJECTIVES/GOALS: Single-cell and spatial transcriptomics have revealed high heterogeneity in the tumor and microenvironment. Identifying populations of cells that impact a patient’s prognosis is an important research goal, so researchers can generate hypotheses and clinicians can provide targeted treatment. METHODS/STUDY POPULATION: DEGAS uses deep-transfer-learning to identify patterns between patient tumor RNA-seq and clinical outcomes and map these associations on to higher-resolution data like spatial and single-cell transcriptomics. We apply DEGAS to prostate and pancreatic cancer spatial transcriptomics samples, as well as one normal sample of prostate tissue. We used the TCGA prostate cancer cohort to with the accompanying survival information and publicly accessible prostate cancer ST data from 10X Genomics to predict survival associations in the ST slides derived from the TCGA patients. Based on these survival associations, we identify higher risk subsections of ST slides which can be further studied. RESULTS/ANTICIPATED RESULTS: We were able to validate our method by comparing it to Scissor and were able to show that the number of high-risk regions in prostate cancer slides increased with the stage of disease. Furthermore, we identify transcriptomic signatures enriched for ontology terms associated with growth regulation and apoptosis, inflammation, immune signaling, and autophagy in histologically normal prostate tissues and adjacent normal pancreatic cancer tissues that were identified as high-risk by DEGAS. The regions highlighted by DEGAS could reflect transcriptional precursors to intraepithelial neoplasia–a well-recognized premalignant morphological change in glandular epithelium. DISCUSSION/SIGNIFICANCE: Identifying biomarkers of tissue stress that precede morphologic diagnosis of high-grade pre-malignant lesions by a pathologist may help triage patients at high risk for future development of cancer, or aid in better understanding whether histologically normal pre-malignant tissues at tumor margins contribute to recurrence.

The rate at which the coronavirus disease (COVID-19) spread required a rapid response across many, if not all, industries. Academic medical centers had to rapidly evaluate, prioritize, and coordinate the multiple requests for clinical trial participation. This involved redirecting resources and developing a collaborative system for assessment, decision making, and implementation. Our institution formed a team with diverse representation from multiple stakeholders to review and prioritize all research protocols related to COVID-19. To accomplish this, a prioritization matrix was developed to help determine the order in which the protocols should be placed for consideration by the treating clinician. The purpose of the team was to review the COVID-19 clinical trials in the pipeline, prioritize those trials that best met the needs of our patients, oversee training and resource needs, and lead the formulation of procedures for integration with clinical care. Resources from the Clinical Research Unit were then allocated to support the swift execution of such studies. This manuscript describes that process, the challenges encountered, and the lessons learned on how to make all clinical trials more successful in a complex and dynamic environment.

Racism shapes the distribution of the social determinants of health (SDoH) along racial lines. Racism determines the environments in which people live, the quality of housing, and access to healthcare. Extensive research shows racism in its various forms negatively impacts health status, yet few studies and interventions seriously interrogate the role of racism in impacting health. The C2DREAM framework illuminates how exposure to racism, in multiple forms, connects to cardiovascular disease, hypertension, and obesity. The goal of the C2DREAM framework is to guide researchers to critically think about and measure the role of racism across its many levels of influence to better elucidate the ways it contributes to persistent health inequities. The conceptual framework highlights the interconnectedness between forms of racism, SDoH, and the lifecourse to provide a greater context to individual health outcomes. Utilizing this framework and critically contending with the effects of racism in its multiple and cumulative forms will lead to better research and interventions.

ABSTRACT IMPACT: This abstract presents a generalizable process to evaluate, and act on, community advisory board perceptions of collaboration effectiveness to improve clinical and translational research network function. OBJECTIVES/GOALS: Community advisory boards (CAB) play an important role in facilitating relevant and externally valid, clinical and translational research (CTR). The objective of this presentation is to describe a participatory process to derive collaboration metrics that can be used to assess CAB effectiveness. METHODS/STUDY POPULATION: During the 4th and 5th years of the Great Plains IDeA CTR award, we used a mixed-methods approach that included CAB (1) discussions related to the need to assess collaboration effectiveness, (2) review of the validated Wilder Collaboration Inventory to identify factors that, if maximized, would improve a sense of team science and enhance productivity, (3) planning for assessment frequency and follow-up processes, and (4) review of collaboration data to determine necessary actions for improvement. Qualitative data were gathered across components of the mixed-methods approach. Quantitative data were collected and reviewed by the CAB (n=11 members) during the 1st quarter of award year 5. RESULTS/ANTICIPATED RESULTS: CAB members expressed an interest in assessing collaboration effectiveness, identified important factors to assess, and agreed that annual assessment and follow-up would be appropriate. Key factors identified and assessed (5-point agreement scale--higher score reflects stronger agreement) were 1) mutual respect/trust (m=4.2); 2) appropriate cross section of members (m=3.6); 3) a shared stake in the process and outcomes (m=3.9); 4) flexibility in decision-making/collaboration (m=4.1); 5) roles and policy guidelines (m=3.6); 6) open communication (m=3.9); 7) goal achievement (m=4.0); 8) shared vision (m=4.0); and 9) skilled leadership (m=4.4). DISCUSSION/SIGNIFICANCE OF FINDINGS: CAB reflection on the initial collaboration assessment resulted in developing plans to broaden membership and clarify roles and policy guidelines related to CAB participation. There was strong consensus related to the utility of this assessment approach.

OBJECTIVES/GOALS: Building community-engaged research capacity is imperative to improve translation, but not everyone exhibits capacity to conduct research, especially community. We modified the research institute planning and implementation process between 2022 and 2023 to increase community appeal and engagement. METHODS/STUDY POPULATION: The 2022 and 2023 Community-Engaged Research Institutes (CERI) varied in their formats. For 2022, we hosted a one-hour planning session with community-academic dyads from our Community Advisory Board facilitated by the CEO director and co-director. The 2022 CERI consisted of five sessions totaling 12 hours. The first session was hybrid, followed by four virtual sessions. For 2023, we hosted two, facilitated one-hour planning sessions with community partners who attended the 2022 CERI, based on feedback and attendance from 2022. The 2023 CERI was consolidated to a seven-hour, one-day hybrid session. RESULTS/ANTICIPATED RESULTS: In 2022, two community partners participated as CERI panelists. There were 95 unique attendees spanning five days. Of the 95 attendees, 67% (n=64) were researchers and 33% (n=31) were community members. In 2023, eight community partners participated as CERI panelists and presenters. There were 57 unique attendees, of which 61% (n=34) were researchers and 39% (n=23) were community members. When comparing attendance for 2022 (29%, n=28) and 2023 (86%, n=49), in-person attendance was increased by 57%. DISCUSSION/SIGNIFICANCE: In 2023, we focused on research capacity building for community partners to align with community engagement principles and increasing research impact across the translational spectrum. Partnering with community elevated appeal for community participation and an increase in-person attendance.

OBJECTIVES/SPECIFIC AIMS: The National Institutes of Health (NIH) has provided continual support for the Georgia Clinical and Translational Science Alliance (CTSA) since 2006. An overarching goal of the Georgia CTSA is to accelerate clinical and translational research to impact health in Georgia and beyond. Toward these ends, a primary objective has been to support interdisciplinary research projects encompassing 2 or more disciplinary domains. The goal of the present study is to evaluate the degree to which interdisciplinary research projects increased in prevalence during the first decade of funding. METHODS/STUDY POPULATION: We began by using PubMed to identify all publications citing the Georgia CTSA hub (n=1865), categorizing each article as encompassing 1 or more research domain using a taxonomy derived from the Web of Science. We created 1 network for each of the 10 years with nodes representing research areas and ties between pairs of nodes representing the presence of 1 or more publication integrating both research areas. We conducted longitudinal network analyses using an approach called MCMC MLE Temporal Exponential Random Graph Models, which models the antecedents of networks over time. RESULTS/ANTICIPATED RESULTS: Supporting Georgia CTSA objectives, results suggest the probability of publications connecting multiple research areas increased over time, with substantially greater increases appearing initially as compared to later years. DISCUSSION/SIGNIFICANCE OF IMPACT: This study advances an innovative approach to modeling the system-wide impact of CTSA hub funding.

OBJECTIVES/GOALS: A negative circumferential resection margin (CRM) after surgical resection of rectal cancer decreases local recurrence and increases overall survival. While MRI is used to predict this risk, there is no predictive model that incorporates clinical factors to predict the risk of CRM positivity. METHODS/STUDY POPULATION: Utilizing the National Cancer Database from 2010-2014, we performed a retrospective study evaluating factors predictive for positive CRM after surgical resection of rectal cancer. The primary outcome was positive CRM (tumor≤1 mm from the surgical margin). Our population included patients with clinical stage I-III rectal cancer who underwent total mesorectal excision. For the primary outcome, multivariable logistic models were used to estimate the probability of a positive CRM. Model performance was evaluated by using the area under the receiver operating characteristic curve (AUC). Model calibration was assessed by examining the calibration plot. Bootstrapping method (300-iteration) was used to internally validate and estimate optimism-adjusted measures of discrimination and overall model fit. RESULTS/ANTICIPATED RESULTS: There were 28,790 patients included. 2,245 (7.8%) had positive CRM. Older age, race, larger tumor size, higher tumor grade, mucinous and signet tumor histology, APR, open operative approach, facility location, higher T stage, lymphovascular invasion, lack of neoadjuvant chemotherapy/radiation, and perineural invasion were all significantly associated with positive CRM (p DISCUSSION/SIGNIFICANCE: An objective model that predicts positive CRM and associated poor clinical outcomes is possible to be used in conjunction with MRI. Positive CRM is associated with specific patient demographics, tumor characteristics, and operative approach. These factors can be used to predict CRM positivity in the preoperative period and plan accordingly.

OBJECTIVES/GOALS: Identify and stratify clinical presentations of thrombotic pathology in PCOS patients. This will be accomplished by 1) evaluating clinical assays for the detection of hypofibrinolysis, and 2) analyzing clinical symptomology of thrombosis in PCOS via Symptom-Disease Pair Analysis of Diagnostic Error (SPADE). METHODS/STUDY POPULATION: Preliminary study populations include n=3 for each of the following groups PCOS with thrombotic complications, PCOS without thrombotic complications, healthy controls, and healthy control samples treated ex vivo with PAI-1. Coagulation assays include ACL coagulation panel, antiphospholipid antibody assays, viscoelastic testing with TEG and Quantra devices, and global fibrinolytic capacity. Coagulation assays will be performed on three samples taken at 4-week intervals. The SPADE techniques will be used to evaluate symptomology of thrombosis in the study period and patient electronic medical history. Molecular testing will be performed for pro-thrombotic polymorphisms (PAI-1 and Apo E) and mutations (Factor V Leiden and Prothrombin). RESULTS/ANTICIPATED RESULTS: We anticipate PCOS and ex vivo PAI-1 samples to show signs of hypofibrinolysis on TEG and Quantra devices outside of reference ranges and with statistical significance. We also anticipate seeing a statistical significance with ACL coagulation panels, however, these results are expected to still be within the reference ranges, as seen in previous studies. We believe the SPADE method will identify clinical presentations of hypofibrinolysis in PCOS patients coinciding with patterns in laboratory tests that were misdiagnosed due to being within reference ranges. We hope to stratify clinical presentations predictive of thrombosis in PCOS patients with standard clinical assays and with increased precision using viscoelastic assays. DISCUSSION/SIGNIFICANCE: The incidence rate of thrombosis is 40x higher in PCOS compared to healthy populations. However, the mechanisms of thrombosis in PCOS are unknown and are undetectable with current clinical assays. We hypothesize that chronic cellular stress in PCOS disrupts the regulation of interconnected immune pathways, causing hypofibrinolysis.

OBJECTIVES/SPECIFIC AIMS: Approximately 80% of adolescents do not meet the current national guidelines of engaging in 60 minutes or more of physical activity daily. Physical activity is widely recognized as being beneficial for healthy growth as well as important for good mental health and fitness. Interventions are needed that promote and encourage physical activity among this population to reduce the risk of obesity and to encourage maintenance of a healthy weight. Since adolescents enjoy digital technologies, robotic-assisted platforms might be a novel, innovative and engaging mechanism to deliver physical activity interventions. The objective of this study was to assess the potential acceptability of robotic-assisted exercise coaching among diverse youth. METHODS/STUDY POPULATION: This was a pilot study that used a cross-sectional survey design. Adolescents ages 12-17 were recruited at 3 community-based sites. We obtained written informed consent from participants’ parents and guardians as well as assent from participants. We demonstrated the robotic system human interface (also known as the robotic human trainer) to groups of adolescents. We delivered the exercise coaching in real time via an iPad tablet placed atop a mobile robotic wheel base and controlled remotely by the coach using an iOS device or computer. After the demonstration participants were asked to complete a 28- item survey that included questions about socio demographics, smoking history, weight, exercise habits, and depression history. The survey also included the 8- item Technology Acceptance Scale (TAS). RESULTS/ANTICIPATED RESULTS: Participants (N = 190) were 55% (103/189) male, 43% (81/190) racial minority, 6% (11/190) Hispanic, and 28% (54/190) lived in a lower-income community. The mean age of participants was 15.0 years (SD=2.0). Approximately 25% (47/190) of participants met national recommendations for physical activity. Their mean body mass index (BMI) was 21.8(SD_4.0) kg/m2. Of note, 18% (35/190) had experienced depression now or in the past. The mean Technology Acceptance Scale (TAS) total score was 32.8 (SD 7.8) of a possible score of 40, indicating high potential receptivity to the technology. No significant associations were detected between TAS score and gender, age, racial minority status, median income of participant’s neighborhood, BMI, meeting national recommendations for physical activity levels, or depression history. Of interest, 68% (129/190) of participants agreed that they and their friends were likely to use the robot to help them exercise. DISCUSSION/SIGNIFICANCE OF IMPACT: This pilot survey study demonstrated that among a racially and socioeconomically diverse group of adolescents, robotic-assisted exercise coaching is likely acceptable. The discovery that all demographic groups represented in this sample had similarly high receptivity to the robotic human exercise trainer is encouraging for ultimate considerations of intervention scalability and reach among diverse adolescent populations. Next steps include a study to assess the impact of robotic-assisted exercise coaching on adolescents’ exercise and health outcomes.

OBJECTIVES/GOALS: The major objective of this project is two points. First, is to repeat and confirm previous observations that there is elevated cytosolic Line1 DNA in the cytoplasm of cells derived from old mice compared to young. Second is to identify which Line1s in the genome are contributing to this free DNA and test if targeting them rescues the age-related phenotype. METHODS/STUDY POPULATION: This project will focus on data collected from both tissues and primary cells derived from multiple tissues. Using cellular/tissue fractionation kits, we isolate specifically from the cytoplasm. This specificity is confirmed by western blotting. Measurement of the Line1 levels is measured by quantitative PCR. Subsequently, these cytoplasmic samples are sent off for sequencing in order to quantify the length of the free DNA in the cytoplasm and to identify which Line1 genomic families the cytosolic DNA originates. Additionally, FISH is utilized to visualize Line1 DNA in the cytoplasm of aged versus young cells RESULTS/ANTICIPATED RESULTS: We anticipate this research to confirm the hypothesis that extranuclear Line1 DNA accumulates with age in both tissues and primary fibroblasts. Additionally, we expect to be able to determine which specific families of genomic Line1 is driving this extranuclear DNA, which would suggest the active retrotransopable elements that are directly involved in this aging related phenotype. Assuming successful identification of such families, we can then target and silence these specific elements to determine not only if cytoplasmic Line1 in aged mice decreases, but additionally if the healthspan and/or lifespan of these mice improves DISCUSSION/SIGNIFICANCE: Dereoressed Line1s have been shown to be involved in detrimental phenotypes, including autoimmune disease, cancer, and inflammaging. Targeting retrotransposons, either directly through degradation of transcriptional product of LINE1s or indirectly by improving function of regulators, will be crucial in ablating aging phenotypes

Objectives/Goals: Primary care physicians (PCPs) have limited awareness of assistive technology (AT) devices that can improve the daily functioning of older adults. This study aimed to assess the quality of the My Assistive Technology Guide (MATG), an informative web app, among PCPs and to describe their experiences using it. Methods/Study Population: In this pilot project, our team – comprising an established researcher, an undergraduate faculty member, and a graduate student – enrolled ten PCPs. In Phase I, the PCPs received training on how to use the MATG and were encouraged to utilize it for 30 days. At the end of this usage period, we implemented a concurrent parallel mixed-method design to collect both quantitative and qualitative data. Quantitative data were gathered using the User Mobile Application Scale (uMARS), while qualitative data was obtained through interviews. Data analysis involved descriptive statistics and thematic content analysis. Results/Anticipated Results: The mean score for the subjective quality of the MATG was high, 4.1 ± 1.1. The information domain received the highest rating, with a mean score of 4.6 ± 0.51, while the engagement domain received the lowest rating, at 3.3 ± 1.5. Overall, subjective quality was rated moderately high (mean 3.9, interquartile range 1.2), with perceived impact rated the highest at 4.8 ± 0.4. PCPs reported increased awareness, knowledge, attitude, intention, and behaviors to learn about AT and to inform and recommend AT devices to older adults. In addition, PCPs provided suggestions to improve the MGAT and its integration into their medical practice. Discussion/Significance of Impact: The results demonstrated the high quality and utility of the MATG, indicating that it could serve as a valuable resource for PCPs in addressing functional disabilities among older adults. Future research should evaluate the effectiveness of the MATG in enhancing older adults’ function in daily living activities.

OBJECTIVES/SPECIFIC AIMS: Approximately 50% of people who have been diagnosed with HIV are either not linked to a care provider or not retained in medical care. This has substantial implications for both individual and public health outcomes. On an individual level, being retained in care is necessary for continuous receipt of antiretroviral therapy and sustained viral suppression. The public health implications of poor retention in HIV care are also serious, as it is estimated that people with HIV who are not retained in medical care are responsible for a majority of HIV transmissions, even more than the number of transmissions attributable to those who are HIV infected but undiagnosed. State departments of health routinely collect surveillance data including positive HIV test results, CD4 counts and viral load measures for monitoring trends in HIV infection. A shift in the use of these surveillance measures, guided by the CDC, has brought forth the opportunity to use these data for direct patient services and, more specifically, to direct re-engagement and retention in care efforts. Although the risk factors for poor retention in HIV care have been characterized using information from individual or multiple clinics, this study seeks to incorporate state surveillance data into the retention measures. METHODS/STUDY POPULATION: This retrospective cohort study was performed at the University of Alabama at Birmingham 1917 HIV/AIDS Clinic among patients with at least one attended HIV primary care visit during the calendar year of 2015. Retention during the calendar year of 2016 was then measured as whether or not a patient had 2 or more completed clinic visits which were separated by more than 90 days (in accordance with the Health Resources and Services Administration or HRSA guidelines, a National HIV Quality Indicator). For patients who did not have any primary care visit in 2016, the Alabama Department of Public Health will provide a status of care (out of care, in care elsewhere, died, moved out of state, and cannot locate) based on HIV laboratory results reported from all clinics and labs across the state and/or mortality information. A multinominal regression model of the status of care will be fitted to demographic, clinical, laboratory, and behavioral patient reported outcomes captured during an index visit in 2015. RESULTS/ANTICIPATED RESULTS: Data were recently obtained and is currently being analyzed on 3107 patients included in this study. We anticipate that there will be differences in the factors significantly associated with patients classified as out of care, poorly retained (patients who have only one completed clinic visit), and retained in care by the HRSA measure during calendar year 2016. DISCUSSION/SIGNIFICANCE OF IMPACT: By incorporating state surveillance data into our analysis, we expect to obtain a more precise picture of the risk factors for poor retention among HIV patients. For the first time, we will be able to determine if patients lost to our HIV clinic (~10% annually) are entirely lost to medical care or are seeking care elsewhere as indicated by HIV lab data reported to public health via surveillance. Identified risk factors will then be able to better inform the efforts to proactively improve the efficiency for HIV patient retention and re-engagement, and therefore lead to better individual outcomes for HIV patients and reduce the incidence of new HIV cases.

OBJECTIVES/GOALS: This project aims to elucidate the mechanism by which LRP1 governs hippocampal neurogenesis with a particular focus on its relevance in brain aging and memory loss. We are specifically interested in further discerning the intricacies of a novel relationship we have discovered between LRP1 and CXCR4 in adult neural stem cells. METHODS/STUDY POPULATION: For the in vivo studies, we are using a triple-transgenic mouse model in which we knockout LRP1 in adult neural stem cells. This is accomplished using a nestin-driven Cre-ER system in animals with floxed LRP1 and a floxed stop codon preceding a td-tomato reporter. The reporter allows for visualization of cells with the knockout and for trafficking and differentiation assays to be easily accomplished. We study stroke recovery using the middle cerebral artery occlusion model and brain aging by inducing the knockout and allowing the mice to age. We perform behavioral batteries and histological analysis on these mice to elucidate functional changes in neurogenesis. We also incorporate in vitro studies using primary neural stem cell cultures to mechanistically test the role of LRP1 in neural stem cell function. RESULTS/ANTICIPATED RESULTS: We have discovered that neural stem cell LRP1 knockout caused a 10-fold loss of CXCR4 expression in conjunction with deficits in ischemia-stimulated migration from the subventricular zone. We also found that uninjured aged mice lacking neural stem cell LRP1 displayed spatial memory deficits at 9 months of age (6 months after knockout), suggesting dysregulated hippocampal function. Given this, we hypothesize that LRP1 regulates CXCR4 in the subgranular zone NSCs to enhance hippocampal memory function. Ongoing research is testing our hypothesis via hippocampal functional tests and in vitro trafficking/expression assays. We expect our research to elucidate a previously unknown link between three independently identified effectors of neurodegenerative disease: LRP1, CXCR4, and neurogenesis. DISCUSSION/SIGNIFICANCE: The role of LRP1 in Alzheimers disease has long eluded clarity despite its known role in trafficking many major disease players – ApoE, amyloid beta and tau. Elucidating its role in hippocampal neurogenesis, a potential disease-modifying process, could lead to novel therapeutic approaches in diseases that cause the death of 1/3 of senior citizens.

OBJECTIVES/SPECIFIC AIMS: Expanded Access is an avenue for patients with no available treatment options to access investigational drugs and devices for clinical therapy. This process requires physicians treating these patients to submit requests to the FDA and the local IRB, processes which are typically unfamiliar to clinicians. METHODS/STUDY POPULATION: With the goal of reducing burden and ensuring access to investigational products, Michigan Medicine established the Expanded Access Oversight Committee in January 2015. This committee brought together key stakeholders to develop appropriate policy and infrastructure to support these requests. RESULTS/ANTICIPATED RESULTS: Outcomes from this committee have resulted in a uniform process with a single point of entry for interested physicians and patients. With standardized policy implemented across the institution, a revised IRB application has been developed that is more tailored to Expanded Access and an informed consent document has been developed specific to the clinical use of investigational therapies. To ensure timely execution of these agreements, the contracts office has streamlined the process for negotiating Expanded Access agreements with manufacturing companies. Further development has begun with the Michigan Clinical Research Unit to provide space for clinical visits in Expanded Access cases, allowing for initiation of outpatient therapy. These changes have allowed Michigan Medicine to support triple the number of Expanded Access requests, including more than 45 Expanded Access requests in fiscal year 2018. DISCUSSION/SIGNIFICANCE OF IMPACT: Institutional support for Expanded Access requests within a large academic medical center is feasible and can increase access to investigational therapies bfor patients.

ABSTRACT IMPACT: The mobilization of a CTSA-sponsored team with multi-disciplinary translational science expertise enabled the university to provide a range of T1-T4 expertise to a large, complex school district that resulted in permanent learning and data science infrastructure. OBJECTIVES/GOALS: The Clinical Translational Science Institute (CTSI) formed a multidisciplinary science team to provide expertise in support of the re-opening of in-person learning in the second-largest U.S. school district during the COVID-19 pandemic. METHODS/STUDY POPULATION: The assembled interdisciplinary science team provided expertise in epidemiology, machine learning, causal inference and agent-based modeling, data and improvement science, biostatistics, clinical and laboratory medicine, health education, community engagement, and experience in outbreak investigation and management. The team included TL1 pre and postdoctoral fellows and mobilized scientists from multiple professional schools and T1-T4 stages of translational research. RESULTS/ANTICIPATED RESULTS: Tangible outcomes achieved using this team approach included the development of practical metrics for use in the school community, a learning process, the integration of preventive design elements into a testing and tracing program, and targeted and data-driven health education. The team, for example, generated new data displays for community engagement and collaborated with the school district in their use to visualize, learn from, and act on variation across a 700 square mile region. DISCUSSION/SIGNIFICANCE OF FINDINGS: Novel translational methods can be used to establish a learning environment and data science infrastructure that complements efforts of public health agencies to aid schools in the COVID-19 pandemic. These new capabilities apply to COVID-19 testing and vaccines and can be mobilized for future population health challenges faced by school districts.

OBJECTIVES/SPECIFIC AIMS: (1) To explain and discuss minority health and health disparities and the mechanisms, for example, individual behaviors and lifestyle, genetics and epigenetics, physical and cultural environment, and clinical events and health care, that lead to health disparities. (2) To explore the intersection between health disparity science and clinical and translational science. (3) To present and discuss the NIMHD Framework and how it can be used to guide multilevel research to address minority health and health disparities. (4) To highlight examples of NIMHD-funded novel and innovative research relevant to clinical and translational research from a health disparities perspective. METHODS/STUDY POPULATION: The NIMHD Research Framework will be introduced that is currently being used by NIMHD to address minority health and health disparity research. The Framework looks at targeted populations in relation to biological, behavioral, physical, and sociocultural environmental domains of influence as well as the health care system. These domains have different levels of influence: individual, family/interpersonal, community, and population. Targeted populations include NIH-designated health disparity populations, that include racial/ethnic minorities, socioeconomically disadvantaged populations, underserved rural populations, and sexual and gender minorities. The following research opportunities are among the many opportunities offered by NIMHD: Disparities in Surgical Care and Outcomes Social Epigenomics for Minority Health and Health Disparities Addressing Health Disparities Among Immigrant Populations. RESULTS/ANTICIPATED RESULTS: Select examples of NIMHD supported minority health and health disparities research that intersects with clinical and translational research will be presented. Candidate examples include: Genetic Architecture of Lupus (SLE) in individuals with Asian ancestry; A Novel Racial Disparity Marker for Risk Prediction in Triple Negative Breast Cancer Patients; Self-Applied Wearable Ultrasound Therapy for Osteoarthritis Management in Rural Central NY; Design and Development of a Multifunctional Self-service Health Screening Kiosk. DISCUSSION/SIGNIFICANCE OF IMPACT: Despite notable improvements gained as a result of medical and scientific advances, there continues to be an alarming disproportionate burden of illness and lack of representation in research among minority and other socially disadvantaged and underserved populations. To meet this challenge, NIMHD is committed to supporting a wide range of clinical and translational research aimed at the development of innovative strategies and approaches to reduce and, eventually, eliminate health disparities. NIMHD’s mission, research priorities, and funding opportunities are relevant to the efforts and interests of clinical and translational scientists, especially those interested in the translation of research findings into interventions, products, and tools that may improve minority health and quality of life, increase adherence to medication and treatment regimens, increase access, and improve the delivery of health services.

Objectives/Goals: Chronic stress may accelerate biological aging yet is often overlooked in clinical settings. Many tools to assess stress exist, but a comprehensive measure of cumulative stress across the lifespan is unavailable. This study validates a novel measure of lifetime stress for use as a screening tool in clinical practice. Methods/Study Population: Patients (n > 220) enrolled in brain health research registry at the Washington University St. Louis Knight Alzheimer Disease Research Center completed in-person surveys at baseline and after six months. Baseline measures included the everyday discrimination scale (EDS), total adverse experience (TAE), and demographics. Age and evaluating life course stress experience (ELSE) scores were measured six months later. Ongoing analysis includes age-adjusted correlations of ELSE scores with TAE and EDS scores. We will investigate the correlation with race and ethnicity and sex assigned at birth. We will explore the relationship between ELSE score and multidimensional intersectionality. Results/Anticipated Results: The sample was 87% Black or African American, 8% White, 4% Hispanic, 82% female, and 18% male, with a mean age of 66 ± 10 years. Age-adjusted relationships between patient characteristics and ELSE scores will be analyzed. Additionally, ELSE responses will be compared against age, EDS, and TAE measurements. Intersectionality between race-ethnicity, sex, and gender will be examined. We hypothesize ELSE scores will vary by demographic. Preliminary results indicate the ELSE scale correlates with established life stress measures, accounting for cumulative stress exposure across a lifespan independent of specific stressor topics. Discussion/Significance of Impact: The ELSE scale is a viable tool for clinical screening of chronic stress exposure over a lifespan. Its implementation will allow clinicians to identify patients at high risk for accelerated aging, facilitating targeted interventions and advancing equity in healthcare delivery.