OBJECTIVES/GOALS: METHODS/STUDY POPULATION: This study utilizes the IeDEA W. Africa cohort to evaluate the prevalence and burden of hypertension and diabetes type II among people living with HIV (PLWH) in sub-Saharan Africa (SSA), and to assess how sex and aging impact the development of these NACM. The cohort is a large, international collaboration across eight countries and 19 treatment centers. Established by the National Institute of Allergy and Infectious Diseases in 2006, the W. Africa cohort is now in its fourth renewal (2021-2026). Participating countries include Senegal, Mali, Cote d’Ivoire, Burkina Faso, Ghana, Togo, Benin, and Nigeria. Data are collected from affiliated cohorts in the regional data center every 24 months. The cohort currently includes >65,000 adult PLWH on anti-retroviral therapy. RESULTS/ANTICIPATED RESULTS: The prevalence of several NACM, such as hypertension and cardiovascular disease, have significantly increased among PWH over time, surpassing prevalence observed in the general population. We therefore expect similar patterns in the W. Africa IeDEA cohort and a high prevalence and burden of both hypertension and diabetes type II in this sample. Additionally, evidence suggests that increasing age and female sex serve as independent risk factors for the development of NACM in PLWH. We anticipate that both increased age and female sex, separately and synergistically, are associated with increased prevalence and burden of hypertension and diabetes type II in this cohort. DISCUSSION/SIGNIFICANCE: With more than 37 million people currently living with HIV, the HIV/AIDS epidemic continues to pose a serious threat to global public health. SSA bears a disproportionate burden of the epidemic with greater than two-thirds of global cases. NACM are now driving morbidity and mortality among PLWH, and increased age and female sex may modify this effect.

ABSTRACT IMPACT: The described framework will enable other sites with a well-defined apparatus for enabling the secondary analysis of EHR data for research through education, team science, and resource consolidation. OBJECTIVES/GOALS: EHR’s potential to improve healthcare outcomes extends far beyond the clinic. This vast repository of clinical insights has dramatic potential for biomedical research. To enhance accessibility for busy clinicians and underserved populations, we describe a framework for interfacing with EHR locally and through national network participation. METHODS/STUDY POPULATION: The Institutional Development Award (IDeA) program, which began in 1993, broadens NIH funding’s geographic distribution for biomedical research. Included in this is the IDeA Networks for Clinical and Translational Research, which focuses on enhancing clinical and translational science across a network of IDeA-states with traditionally underserved communities and rural providers. A prior survey of the needs and capabilities of IDeA-CTR centers identified the need for improved research support. Based on our annual member survey we developed a process for supporting distributed research projects across the GP-CTR. NIH also recently made a funding announcement for the IDeA-CTR community identifying EHR research as a major priority in responding to the COVID-19 pandemic. RESULTS/ANTICIPATED RESULTS: Results from site interviews and member surveys show a clear need for dedicated resources to navigate the process of EHR-derived research. Most described a different set of requirements for increasing accessibility to EHR for research and a strong desire to participate in research networks. Local investigators cited a lack of tools, educational materials, and accessibility. Initial efforts demonstrate strong research questions but limited technical, statistical, and terminological capabilities to succeed. In response, a pipeline for team science and promotion of projects from local phenotypes to national studies. We created a facilitator training program to expand the number of facilitators (n=22), quarterly training for investigators (n=104), and ongoing efforts to advance COVID-19 research. DISCUSSION/SIGNIFICANCE OF FINDINGS: As evidenced in the expanding number of EHR-based research networks there is a need for a system to promote project development and best practices. The proposed model promotes education, resource sharing, and team formation to advance clinical questions from the idea stage toward national research network participation.

OBJECTIVES/GOALS: The limited treatment options for ischemic stroke patients have resulted in stroke being a leading cause of death and the primary cause of long-term disability in the U.S. Finding effective treatment options requires a better fundamental understanding of the ongoing processes that contribute to poor long-term outcome. METHODS/STUDY POPULATION: Expression of Apolipoprotein E4 predisposes stroke patients to poor long-term outcome. This study aims to test one possible mechanism by which ApoE4 contributes to cognitive decline after stroke. Here, we examine the effect of a major ApoE4 receptor, low-density lipoprotein receptor related protein 1 (LRP1) on sensitivity to stress in astrocytes. LRP1 binds and moves extracellular ligands and plasma membrane proteins into the endocytic system. Others have shown that LRP1 regulates cell-surface TNF receptor (TNFR1) in non-astrocytic cells. We propose That LRP1 similarly regulates TNFR1 in the central nervous system to attenuate inflammatory response after stroke. Studies have shown that ApoE4 slows the recycling of endocytic LDL receptors. We hypothesize that ApoE4 inhibits the ability of LRP1 to remove TNFR1 from the plasma membrane. This is expected to increase cytokine sensitivity, resulting in worse outcome after stroke. We investigated the effect of LRP1 on astrocyte TNFα signaling and response in immortalized ApoE null mouse astrocytes subjected to lentiviral-mediated knockdown of LRP1. The astrocyte response to TNFα stimulation was tested in a time dependent manner using Western blotting of NFkB pathway components, which are the downstream mediators of TNFα signaling. We also tested astrocyte viability after prolonged TNFα stimulation using Alamar Blue reagent. We found that LRP1 deficient cells have increased phosphorylation of NFkB upon TNFα stimulation, and that loss of LRP1 resulted in significant loss of astrocyte viability after prolonged stimulation. RESULTS/ANTICIPATED RESULTS: Altogether, our results indicate that loss of LRP1 renders astrocytes more sensitive to TNFα. Future experiments will focus on testing the influence of LRP1 on recovery after middle cerebral artery occlusion in mice. DISCUSSION/SIGNIFICANCE OF IMPACT: These studies will elucidate how astrocyte-LRP1 contributes to outcome after stroke, and helps us to understand one potential way that ApoE4 exerts pathological effects. A better understanding of the long-term processes after stroke will allow identification of therapies which improve the morbidity and mortality associated with stroke. CONFLICT OF INTEREST DESCRIPTION: NA.

OBJECTIVES/GOALS: To facilitate the development of innovative injection products by providing translational researchers with a regulatory and manufacturing road map for producing small batch sterile products for Phase 1 research use. To leverage recent AMC investments in facility improvements and pharmacy training in the areas of sterile product production, testing, and environmental controls, that can be used to support production of phase 1 clinical trial supplies METHODS/STUDY POPULATION: Searching and organizing relevant data and information from web portals and databases in the following: areas: FDA, EMA, USP regulations, regulatory science, pharmaceutical formulation and analytics, supply vendors, analytical testing laboratories, and product testing laboratories. Present the information using a user friendly format including flow charts and development timelines, taking the perspective of the translational investigator. RESULTS/ANTICIPATED RESULTS:

• Choosing AMC resources vs outside consultants and vendors, leveraging local resources where possible

• Qualifying and monitoring suppliers, testing laboratories, in-house departments, and Contract Drug Manufacturing Organizations (CDMO)

• Bringing together the deliverables for the IND CMC section

• Where and how to leverage available products and science to simplify safe and reliable production

DISCUSSION/SIGNIFICANCE OF IMPACT: Use and utility of injectable drug products, both small molecule and biologics, is growing rapidly, and is projected to continue to escalate well into the next decade. This is due not only to advances in medicine, but also to improvements in AMC-based sterile product production, and a better understanding of small batch manufacturing methods. All three trends align in academic medical centers (AMC) and can be utilized by translational researchers, if they can understand the potential and regulatory requirements.

Contracting delays remain a challenge to the successful initiation of multisite clinical research in the US. The Clinical and Translational Science Awards (CTSA) Contracts Processing Study showed average contract negotiation duration of > 100 days for industry-sponsored or investigator-initiated contracts. Such delays create enormous costs to sponsors and to patients waiting to use new evidence-based treatments. With support from the National Institutes of Health’s National Center for Advancing Translational Sciences, the Accelerated Clinical Trial Agreement (ACTA) was developed by 25 major academic institutions and medical centers engaged in clinical research in collaboration with the University-Industry Demonstration Partnership and with input from pharmaceutical companies. The ACTA also informed the development of subsequent agreements, including the Federal Demonstration Partnership Clinical Trial Subaward Agreement (FDP-CTSA); both ACTA and the FDP-CTSA are largely non-negotiable agreements that represent pre-negotiated compromises in contract terms agreed upon by industry and/or medical center stakeholders. When the involved parties agree to use the CTSA-developed and supported standard agreement templates as a starting point for negotiations, there can be significant time savings for trials. Use of the ACTA resulted in an average savings of 48 days and use of the FDP-CTSA saved an average of 57 days of negotiation duration.

OBJECTIVES/GOALS: The Association of Clinical and Translational Science (ACTS) chartered a Diversity, Equity, and Inclusion (DEI) Committee to prioritize activities to support, develop and report on metrics for measuring progress toward DEI goals. This poster aims to describe the formative process toward prioritizing DEI in society’s efforts. METHODS/STUDY POPULATION: In 2021, the ACTS chartered the DEI Committee. Two ACTS Board of Directors members chair the committee, and members represent 10 academic institutions committed to prioritizing DEI. Members participated in a Human-Centered Design process to develop the committee’s mission, goals, and activities. The committee determined areas of opportunity for ACTS to increase DEI by identifying challenges to support DEI in clinical and translational science. The chairs facilitated a discussion using Mural to foster an interactive strategy to engage members in conversations that respected individual experiences, promoted a discussion of actions that ACTS as a society, and determining metrics for measuring DEI. RESULTS/ANTICIPATED RESULTS: We plan to present the committee’s efforts to create the ACTS mission statement and strategies to priority to DEI. We will describe current and future activities to engage historically underrepresented members and academic institutions in ACTS programs. Based on the committee’s work, ACTS has taken systematic approaches toward social justice and is beginning to determine new ways of engaging members. DISCUSSION/SIGNIFICANCE: Scientific societies that prioritize DEI increases equity and belonging across members. ACTS is at the forefront of advocacy, policy, and social justice effort. The DEI committee is positioned to aid ACTS in increasing DEI across the clinical and translational science spectrum.

OBJECTIVES/GOALS: The extent that Clinical and Translational Science Award (CTSA) programs offer resources accessible online for training in community-engaged research (CEnR) core competencies is unknown. This study cataloged CEnR resources accessible online from CTSAs and mapped resources to CEnR core competencies. METHODS/STUDY POPULATION: Eight domains of CEnR core competencies were identified: knowledge/perceptions of CEnR; personal traits necessary for CEnR; knowledge of/relationships with communities; training for performing CEnR; CEnR methods; program evaluation; resource sharing and communication; and dissemination and advocacy. A systematic review of CEnR resources accessible online from CTSAs was conducted between July 2018 and May 2019. Resource content was independently reviewed by two reviewers and scored for inclusion of each domain of CEnR core competencies. Domain scores across all resources and inter-rater reliability in scoring domains were assessed using descriptive statistics and Cohen’s kappa coefficients. RESULTS/ANTICIPATED RESULTS: Overall, 214 resources available from 24 CTSAs were eligible for full review. Scoring discrepancies for at least one domain within a resource initially occurred in 51% of resources. “CEnR methods” (50.5%; 108 of 214) and “Knowledge of/relationships with the community” (40.2%; 86 of 214) were most frequently addressed and “Program evaluation” (12.1%; 26 of 214) and “Dissemination and advocacy” (11.2%; 24 of 214) were least frequently addressed domains. Additionally, challenges were noted in navigating CTSA websites to access CEnR resources, and CEnR competency nomenclature was not standardized. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings guide CEnR stakeholders to identify CEnR resources accessible online and gaps to address in CEnR resource development. Standardized nomenclature for CEnR competencies is needed for effective CEnR resource classification. Uniform organization of CTSA websites may maximize navigability. CONFLICT OF INTEREST DESCRIPTION: In addition to the funding information listed previously (see above), within the last three years, R.J. Piasecki has been employed as: Project Coordinator, CEnR Online Learning Project, Johns Hopkins University School of Nursing (Current) Temporary Employee (Doctoral Student Intern), Michigan State University Institute for Health Policy (Current) Clinical RN, Intrastaff at the Johns Hopkins Health System (Past) Research Data Analysis Assistant, Maryland Institute for Emergency Medical Services (Past - contracted)

OBJECTIVES/SPECIFIC AIMS: To create the instrument, we employed a modified Delphi approach by conducting a thorough literature review on Leadership to help concretize the relevant constructs, and then usied these extracted constructs as a springboard for the Rockefeller Team Science Educators (TSE’s) to discuss and refine the leadership domain areas, collectively creating domain-specific survey items, and then further discussed and refining the number, grouping, and wording of the items. METHODS/STUDY POPULATION: We piloted the Leadership Survey by having all of the Rockefeller TSEs rate Clinical Scholars. Each item was answered using a six-point Likert scale where a low score indicated poor expression of the specific leadership attribute and a high score represented excellent expression of the specific leadership attribute. RESULTS/ANTICIPATED RESULTS: Means, medians, standard deviations, and ranges of each item were calculated and tabulated. A complete (Pearson) correlation matrix was computed so that the raw inter-item relationships can be observed. For each a priori Domain an equal weighted summary scale was created and tabulated for review. The internal consistency of each a priori scale was assessed by calculating Cronbach’s Alpha (α). Items with low Item to Construct coefficients were candidates for elimination or modification, and overall scales with low’s will undergo further discussion. To challenge our assumptions of the construction and integrity of each domain, we employed exploratory Principal Components Analysis (PCA), followed by orthogonally rotated Factor Analysis (FA). We also forced the PCA / FA analysis to extract the a priori dimensions that allowed us to compare if the empirical and a priori structures match. DISCUSSION/SIGNIFICANCE OF IMPACT: We are partnering with the CTSA programs at Penn and Yale to assess issues of generalizability and scalability. We are working with Vanderbilt to install survey onto REDCap for ease of dissemination. Will continue to assess psychometric properties and refine as we receive more input.

Infants with congenital heart disease (CHD) may have impaired cerebral autoregulation (CA) associated with cerebral fractional tissue oxygen extraction (FTOE). We conducted a pilot study in nine CHD neonates to validate a noninvasive CA measure, cerebrovascular stability index (CSI), by eliciting responses to postural tilts. We compared CSI to an invasive measure of CA and to FTOE collected during tilts (FTOESpot). FTOESpot correlated with CSI, as did the change in FTOE during tilts, but CSI’s correlation with impaired CA did not reach significance. Larger trials are indicated to validate CSI, allowing for noninvasive CA measurements and measurements in outpatient settings.

OBJECTIVES/GOALS: Environmental factors may significantly increase the risk of or buffer against Alzheimer’s disease and related dementias, yet strategies to address cognitive decline and impairment to date largely overlook the role of neighborhoods. This mixed-methods study is the first to examine potential links between access to eateries and cognitive function. The goal is to inform place-specific interventions to help aging individuals reduce risk for cognitive impairment through neighborhood community and design. METHODS/STUDY POPULATION: Following an exploratory sequential mixed-methods design, seated and mobile interviews with 125 adults aged 55-92 (mean age 71) living in the Minneapolis (Minnesota) metropolitan area suggest that eateries, including coffee shops and fast-food restaurants, represent popular neighborhood destinations for older adults and sources of wellbeing. To test the hypothesis that these sites, and the benefits they confer, are associated with cognitive welfare, we analyzed data from urban and suburban dwelling participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study, a national racially diverse sample of older Americans followed since 2003 (n = 16,404, average age at assessment 72 years). RESULTS/ANTICIPATED RESULTS: Qualitative thematic analysis of how older adults perceived and utilized local eateries include sites of familiarity and comfort; physical and economic accessibility; sociability with friends, family, staff, and customers; and entertainment (e.g., destinations for outings and walks, free newspapers to read). Quantitative results from multilevel linear regression models demonstrate a positive association between density of eateries and cognitive functioning. Taken together, these results complicate our understanding of fast-food settings as possible sites of wellbeing through social interaction and leisure activities. DISCUSSION/SIGNIFICANCE OF IMPACT: The results contribute new evidence towards an emerging ecological model of cognitive health. Understanding whether and how retail food environments can help buffer against cognitive decline among older adults provides novel opportunities to promote wellbeing in later life through community interventions and neighborhood design.