OBJECTIVES/GOALS: The New Jersey Alliance for Clinical & Translational Science conducted an observational study of current clinical research training to establish a comprehensive infrastructure. The goal was to develop a cross training catalogue of available resources for trainees to fill gaps in their Clinical Research training. METHODS/STUDY POPULATION: The focus of this observational study is the evaluation of (1) available clinical research training programs, (2) training areas aligned with the Joint Task Force competency domains, (3) specific target audiences who utilize trainings offered nationally, and (4) availability of resource toolboxes. This assessment was extracted by clicking on each of the hubs Education & Training and Resources tabs. The determination of the training areas and competency skills that aligned with the JTFs eight domains was confirmed by reviewing the course description on each website. RESULTS/ANTICIPATED RESULTS: CTSA hub website analysis of each hub revealed that each CTSA hub region has their own regional focus on training areas targeted for specific audiences. The validation of the NJ ACTS Education and Offering Inventory study allowed authors to categorize available training programs which significantly showed that Basic Training Programs targeted 22% of Undergraduate Students, Community Engagement Training Programs targeted 15% of Early Career Faculty, Experiential Training targeted 20% of Early Career Faculty and Undergraduate Students, Scholarly & Certificate Training targeted 20.5% of Graduate Students, and Graduate/Post Graduate Programs targeted 22.5% of Graduate Students and KL2 scholars. DISCUSSION/SIGNIFICANCE: This information helps build the infrastructure of a National Cross-Training Resource Platform in aid to encourage trainees to take advantage of available trainings across the CTSA Consortium.

OBJECTIVES/SPECIFIC AIMS: In the context of skeletal muscle, IL-6 plays a major role in muscle quality. The goal of this project was to study the influence of systemic IL-6 on skeletal muscle mitochondrial physiology, most notably mitochondrial function (respiration and ROS production) and mitochondrial content. METHODS/STUDY POPULATION: To determine the influence of interleukin-6 (IL-6) on skeletal muscle mitochondria, high-resolution respirometry was performed to simultaneously measure oxygen consumption (JO2) and ROS production in differentiated myotubes incubated with increasing IL-6 (0, 10, 50, 100 ng/mL) for 18 hours in serum free conditions. To evaluate the impact of IL-6 on mitochondrial content we performed western blots on cell lysates from treated cells, measuring proteins of the mitochondrial electron transport chain (ETC) using a cocktail antibody and PGC-1α/PGC-1ß for mitochondrial biogenesis. To determine the role of mitochondrial ROS production on JO2 and mitochondrial content, we co-treated differentiated myotubes for 18 hours with 50 and 100ng/mL IL-6 and the mitochondrial specific antioxidant, MitoQ and performed respirometry for mitochondrial functional measurements and western blots for mitochondrial content.Statistical significance was evaluated by using a 2-tailed Student’s t-test and two-way ANOVA. Post hoc all-group analyses were conducted to determine which groups were different when the model was significant. RESULTS/ANTICIPATED RESULTS: Mitochondrial functional measurements show increased JO2 and increased ROS production in an IL-6 dose-dependent manner. Targeting mitochondrial ROS production with 0.5µm MitoQ attenuated IL-6 induced increases in JO2 and ROS production. Complexes I and II (CI, CII) of the ETC increased significantly in an IL-6 dose-wise fashion, and co-treatment with MitoQ normalized increases at 100ng/mL Il-6. 100ng/mL IL-6 significantly increased protein expression of PGC-1α and PGC-1ß. Co-treatment with MitoQ normalized IL-6 induced increase in PGC-1α. DISCUSSION/SIGNIFICANCE OF IMPACT: Our data suggest that when treated chronically at a high dose, IL-6 increases mitochondrial respiration, ROS production, and content. Targeting mitochondrial ROS production normalizes these mitochondrial adaptations. The present study provides new insights into mitochondrial physiology in the context of inflammation. Therapeutically targeting mitochondrial ROS production may impact skeletal muscle quality in certain populations.

OBJECTIVES/GOALS: Severe malarial anemia due to Plasmodium falciparum is often accompanied by thrombocytopenia. Treatment includes transfusion of whole blood, which contains erythrocytes, platelets, and other blood components. The objective of the study was to assess the effect of whole blood transfusion on survival in children with severe falciparum malaria and to examine the potential interaction of thrombocytopenia with malaria mortality and transfusion response. METHODS/STUDY POPULATION: We analyzed a retrospective cohort of 842 hospitalized children in Zambia with severe malarial anemia (703 transfused, 139 not transfused due to stock-out or other reason). Severe malarial anemia was defined as a positive rapid diagnostic test or blood smear in combination with an admission hemoglobin concentration ≤5 g/dL. RESULTS/ANTICIPATED RESULTS: Mortality was 13% (94/703) in the transfused group and 24% (34/139) in the non-transfused group. Kaplan-Meier survival estimates stratified by transfusion status and thrombocytopenia (150,000/μL threshold) showed increased mortality in children with thrombocytopenia who did not undergo transfusion, with no differences in mortality among the other transfused and non-transfused groups (log-rank test P = 0.0001). Effect modification analysis by Cox proportional hazards regression adjusted for age, sex, hemoglobin concentration, blood group type, and eosinophilia showed a significant interaction between platelet count and transfusion status (P = 0.028). Children with thrombocytopenia who were transfused and died had little or no post-transfusion increase in platelets, in contrast to those who survived. Freshness of transfused whole blood, construed from expiration dates, correlated with greater platelet recovery and improved survival. DISCUSSION/SIGNIFICANCE OF IMPACT: The role of platelets in malaria pathophysiology is complex and incompletely understood; prior studies describe preferential binding of platelets to parasitized erythrocytes and direct parasitocidal activity, whereas others detailed deleterious effects in malaria involving the central nervous system vasculature. These findings point to a potential clinical role for platelet-directed transfusion strategies to improve survival in children with severe falciparum malaria, which should be further assessed in randomized interventional studies.

OBJECTIVES/GOALS: Many researchers aim to build trust with communities and participants. Trust building is meant to achieve greater representation across aspects of research whether in participation, or more comprehensively as partners from design to dissemination. We provide practical guidance for trust building activities and the ethical issues that can arise. METHODS/STUDY POPULATION: While trust itself is inherently seen as an ethical good, often little attention is paid to the ethical aspects of trust building exercises themselves and the fact that trust can vary in type. Using a bioethical analysis of trustworthiness, we discuss how to approach trust in different relationships and settings. Explicit communication about the supports/constraints and potential outcomes of new trusted relationships is required for ethical practice. Where relationships are built without appropriate transparency and follow through, or with misunderstandings about potential shared values, priorities, or desired outcomes, significant harms can occur in the short- and long term. Using a bioethical framework and practical examples we provide guidance on how to engage in ethical trust building activities. RESULTS/ANTICIPATED RESULTS: While many people are good at the trust building work they do, this work is often not shared as best practices and is ascribed to individual skill. This is slowly changing and an evidence-base is being developed that can support those new to these activities. Ethical guidance to support trust building practices, especially for those new to these activities, is currently lacking. By providing both a conceptual and normative bioethical analysis grounded in practice, we provide the foundations for new activities and the necessary support for work that explores and determines best practices. This analysis provides an understanding of trust including a taxonomy and a discussion of how different types of trust can be built and can support research activities, as well as problems that can arise. DISCUSSION/SIGNIFICANCE: Trust building activities with communities and participants are crucial to much of translational science and research, but ethical guidance on how to engage in these activities well is lacking. We provide bioethical guidance and offer practical recommendations.

OBJECTIVES/SPECIFIC AIMS: Our objective is to create a Resistant Hypertension (RHTN) computable phenotype from electronic health record (EHR)-based data, and to determine the characteristics associated with RHTN within a large, diverse, EHR-based database. METHODS/STUDY POPULATION: The OneFlorida Clinical Research Consortium includes 10 unique health care systems providing care for approximately half of the state (48%, ~10 million). OneFlorida houses a Data Trust which contains longitudinal EHR data and claims data from these providers in a common format, the PCORnet common data model v3.0. For the current project, data from 5 health care systems were considered. All of the adult hypertension (HTN) patients with a HTN diagnosis from an outpatient encounter were extracted from the OneFlorida Data Trust. Additional data such as demographics, prescribing, and vitals information were also extracted. The RHTN computable phenotype was created by constructing a drug exposure variable that took into consideration the number of antihypertensive medications an individual was prescribed at any point in time over the course of the OneFlorida dataset. RHTN was defined as any blood pressure requiring four or more antihypertensive drugs, or uncontrolled blood pressure (≥140/90) on 3 antihypertensive drugs. RHTN cases had to meet the definition criteria twice during the data period, at least 30 days apart. All data extraction, computation phenotype coding, and statistical analyses were conducted using SQL or SAS. RESULTS/ANTICIPATED RESULTS: Our preliminary results show that there were n=342,026 adults with a HTN diagnosis from an outpatient visit in the data set. After the RHTN computable phenotype was constructed, n=11,670 RHTN cases were identified from the n=130,901 HTN individuals with all of the required variables in the data set (8.9% RHTN prevalence). In all, 55% of RHTN cases were Black or African American, compared with the total HTN population (25% Black/African American). RHTN cases also had more prescriptions for loop diuretics, centrally acting agents, α-blockers, and vasodilators compared with the total HTN population. Not surprisingly, the RHTN cases had 26% of the antihypertensive prescriptions in the data set, and the RHTN cases had fewer blood pressure readings that were in control (only 49.4% of readings <140/90). DISCUSSION/SIGNIFICANCE OF IMPACT: Overall, our preliminary data shows that it is possible to create the very complicated computable phenotype of RHTN within the OneFlorida Data Trust. We found that the RHTN prevalence in OneFlorida is 8.9% which is consistent with previous studies from NHANES. Although promising, these results require further validation of the computable phenotype and replication in other similar data sets in order to ascertain their true meaning. Once validated, the experience gained from this computable phenotype can be applied to many other phenotypes.

OBJECTIVES/SPECIFIC AIMS: Our objective is to study the role of soluble adenylyl cyclase in the melanocyte regulation of pigment in response to ultraviolet radiation. Melanocytes are specialized cells that produce melanin in organelles called melanosomes, and melanin determines the pigmentation of hair and skin. cAMP is a master regulator of pigmentation and transmembrane class of adenylyl cyclases are essential for expression of important enzymes involved in melanogenesis. However, pigmentation is also controlled by melanosomal pH, which regulates melanogenesis, tyrosinase activity, and melanosome maturation. The relationship between melanosomal pH and cAMP has been elusive. Soluble adenylyl cyclase is a noncanonical source of cAMP that is not responsive to G proteins but rather functions as a pH sensor. We recently demonstrated that loss of soluble adenylyl cyclase (sAC) activity leads to increased melanosomal pH as well as increased pigmentation in cells and hair. We expanded our research to investigate the role of sAC in the intrinsic response of melanocytes to ultraviolet radiation. METHODS/STUDY POPULATION: We utilized sACfl/fl (wild type) and sACKO mouse melanocytes and compared their change in pigmentation in response to ultraviolet radiation. Melanin was used as a measure of pigmentation. We irradiated these cells at differing doses of UVB (0, 1, 2, or 3 mJ/cm2) daily for 3 days. After UVB treatment, cells were observed and the surviving cell numbers were determined. Cells were then analyzed for melanin content using spectroscopy. RESULTS/ANTICIPATED RESULTS: We found that while both sACfl/fl and sACKO cells had increased melanin content in response to UVB, the melanin content of sACKO cells increased more compared with sACfl/fl cells (p=0.001 at daily dose of 3 mJ/cm2). In addition, sACKO cells required less UVB dose to induce a response. We also observed that sACKO cells show increased cell death compared with sACfl/fl cells. DISCUSSION/SIGNIFICANCE OF IMPACT: Although both sACfl/fl and sACKO cells can induce melanin production in response to UV, our results suggest that sACKO cells are more sensitive. We believe that this increased response in sACKO cells is due to increased melanosomal pH. In addition, sACKO cells show increased cell death, suggesting that sAC is important in the damage response secondary to UV exposure. UV plays a wide range of roles in skin biology such as contributing to cancer risk and pigmentation. Since pigmentation is essential for the protection of the skin from UV insult, further investigation of possible mechanisms in which sAC can influence pigmentation in response to UV is warranted.

OBJECTIVES/SPECIFIC AIMS: The promise and potential of connected personal health records (PHRs) has not come to fruition. This may be, in part, due to the lack of user-centered design and of a patient-centric approach to curating personal health data for use by patients. Co-design with end-users could help mitigate these issues by ensuring the software meets user’s needs, and also engages patients in informatics research. Our team partnered with patients with multiple chronic conditions to co-design a patient-centric PHR. This abstract will describe our experience with the co-design process, highlight functionalities desired by patients, and showcase the final prototype. METHODS/STUDY POPULATION: We conducted 3 design sessions (90 min per session) with patients as co-designers and employed an iterative process for software development. Patients were recruited from Chapel Hill and surrounding areas. The initial design session laid the foundation for future sessions, and began with brainstorming about what patients thought their ideal version of an engaging connected PHR would look like in terms of features and functionalities. After each software iteration, our entire design team, including our patient co-designers, was shown the prototype during a subsequent design session. Once the final prototype was developed, usability testing was conducted with patient participants. Our team then conducted a final design session to debrief about the final prototype. RESULTS/ANTICIPATED RESULTS: We started with an initial group of 12 patients (6 males) who all had diabetes and an additional comorbidity such as hypertension and hyperlipidemia. Age of participants ranged from 30 to 77 years with an average age of 56. The majority of participants were Caucasian with 1 Asian and 2 African Americans. Hemoglobin A1c values ranged from 6.0% to 9.2% with approximately half having A1c values less than the goal of 7.0%. Half the patients were aware of PHRs, majority had smartphones, and all participants had access to the Internet and used email. Two of the patients were retired engineers who had prior experience with software design. The other sessions had between 7 and 8 participants at each session, and 7 patients completed the 90-minute usability testing session. There was a core group of 7 patients who were engaged in the design and testing sessions throughout the entire 9-month study. Key features of the PHR that emerged from design sessions included the following: (1) allow for annotation of data by patients (particularly important for lab values like glucose or for physical activity); (2) calendars, to do list, and reminder functions should be linked so that an entry in one of these allows for auto-population of this data within the other sections; (3) notifications whenever new data from the electronic health record or other sources are pushed to the PHR account; (4) allow for drag and drop of photos of pills/medications taken via smartphone or from other sources so that medication list has photo of actual pills or pill bottle; (5) allow for patients to customize the order of sections in the PHR dashboard so that the sections most important to the individual patient can be displayed more prominently; (6) allow for notifications from pharmacies to be pushed to the PHR (eg, confirmation of receipt of prescription requests or alert that prescription is ready to pick up); and (7) graphical display of trends over time (patients would like to select the measures and time frames to plot for display). Patients cited the importance of data provenance so that patient-entered data Versus provider or electronic health record data could be easily differentiated. Patients also highlighted the importance of having this PHR be a “one-stop shop for all their health data” and to have meaningful data dashboards for the different types of information needed to comprehensively manage their health. Patients wished for a single PHR that could easily bring together data from multiple patient portal accounts to avoid having to manage multiple accounts and passwords. They felt that heat map displays such as those used on popular fitness tracking websites were not intuitive and that the color-coding made interpretation challenging. Participants noted that engagement in the design process made them feel that they contributed towards developing software that could not only positively impact them individually but others as well. Every patient indicated the desire to participate on future design projects. Of the 19 tasks evaluated during usability testing, only 5 tasks could not be completed (eg, adding exercise to the calendar, opening the heat map, etc.). Patients felt that the overall PHR design was clean and aesthetically pleasing. Most patients felt that the site was “pretty easy to use” (6 out of 7). The majority of participants would like to use this PHR in the future (5) and would recommend this PHR to their friends/family to use (6). DISCUSSION/SIGNIFICANCE OF IMPACT: Involving patients directly in the design process for creating a patient-centric connected PHR was essential to sustaining engagement throughout the software life cycle and to informing the design of features and functionalities desired by patients with chronic conditions.

Community health needs assessments (CHNAs) are important tools to determine community health needs, however, populations that face inequities may not be represented in existing data. The use of mixed methods becomes essential to ensure the needs of underrepresented populations are included in the assessment. We created an in-school public health course where students acted as citizen scientists to determine health needs in New Brunswick, New Jersey adults. By engaging members of their own community, students reached more representative respondents and health needs of the local community than a CHNA completed by the academic hospital located in the same community as the school which relies on many key health statistics provided at a county level. New Brunswick adults reported significantly more discrimination, fewer healthy behaviors, more food insecurity, and more barriers to accessing healthcare than county-level participants. New Brunswick participants had significantly lower rates of health conditions but also had significantly lower rates of health screenings and higher rates of barriers to care. Hospitals should consider partnering with local schools to engage students to reach populations that face inequities, such as individuals who do not speak English, to obtain more representative CHNA data.

The Accelerating COVID-19 Therapeutic Interventions and Vaccines Therapeutic-Clinical Working Group members gathered critical recommendations in follow-up to lessons learned manuscripts released earlier in the COVID-19 pandemic. Lessons around agent prioritization, preclinical therapeutics testing, master protocol design and implementation, drug manufacturing and supply, data sharing, and public–private partnership value are shared to inform responses to future pandemics.

OBJECTIVES/SPECIFIC AIMS: The objective of this research was to identify and evaluate published research articles that highlight the use of CTSA institutional websites as a research tool or data source for translational science research. METHODS/STUDY POPULATION: A multifaceted systematic search process was engaged for this literature review process using standard literature database searching, digital journal database searching, and pearl growing. All U.S. based studies and reports from 2006 through the present that addressed the application of websites of CTSA institutions for translational science purposes were included in this review. Identified articles were collected, organized, and analyzed using an excel spreadsheet. There were 2 different data collection and organization protocols, one for studies the other for reports. The first data collection protocol was for identified studies that used individual CTSA Institutional websites as a data source for a research topic. The organization processes for each relevant study article included a customized data extraction process that looked to identify a standard group of key elements from each study: (1) The study’s NCATS CTSA Goal. (2) The type of data searched in the CTSA institutional website. (3) The number of CTSA institutional websites searched. (4) The number of sites that had the needed data. (6) The outcomes reported from the research. The second data collection protocol was for identified reports that referenced single CTSA Institutional websites as performing a specific translational informatics functionality either as a portal to Clinical and Translational Science Award tools and resources or as a direct information source. The organizational process for each relevant report article also included a customized data extraction process that looked to identify a standard group of key elements from each report: (1) NCATS / CTSA Goal (2) Tool or Functionality Promoted (3) Description (4) Website used as portal or direct tool. (5) Target Audience. RESULTS/ANTICIPATED RESULTS: The studies were summarized using the standard group of key elements identified for data extraction and summarized in a table. In 5 of the 6 studies, researchers relied on CTSA member individual website content to mine necessary data. One (1) of the studies employed a mixed methods approach to data acquisition and only relied on CTSA member individual website content for CTSA institutions that did not respond to a user survey. One (1) study used a survey to learn about CTSA website content rather than review the websites. In 5 of the 6 studies, researchers reviewed individual CTSA websites for the purposes of determining the number or percentages of CTSA institutions had specific data. One (1) study instead reviewed the individual websites to develop a broader picture of what the CTSA Consortium offered as a group. The percentage of CTSA websites that had the needed data of the researchers ranged from 32% to 100%. The median and mean scores for CTSA websites having the needed data was 66% and 66.5% respectively. One study did not provide specific information for assessment. All 6 studies included research that fell within at least 2 categories of the 5 NCATS CTSA Goal topics. The category most investigated was translational research processes where 5 of the 6 studies investigated how CTSA websites looked to improve the quality and efficiency of translational research. Three (3) studies investigated how CTSA’s cultivated and trained the clinical and translational science workforce. Two (2) studies investigated how CTSA’s engaged patients and communities in the translational research process. Two (2) studies investigated how CTSA’s promoted the integration of underserved populations. One (1) study investigated ways the CTSA’s used their websites to advance the use of cutting-edge informatics. The outcomes reported included (1) the percentage CTSA individual websites that provided information regarding patient recruitment. (2) A list of generic services provided across the CTSA Individual website medium. (3) The number of CTSA individual website education and training programs. (4) The number and quality of informed consent forms presented online. (5) Investigational New Drug (IND) / Investigational Device Exemption (IDE) training methods for CTSA Investigators. (6) The percentage of KL2 Awards used by Child Health Investigators at CTSA Institutions. The reports (rn=9) were also summarized using the standard group of key elements identified for data extraction and summarized in a table. All six articles reported using their Institutional CTSA website as either a portal or a tool to promote clinical and translational science as outlined through NCATS goals. A CTSA website is used as a portal when it provides links to other sites, tools, or programs. A CTSA Website is used as a tool when it provides the functionality within its web design like providing an online application or database, or interactive training pages. In 8 of the 9 articles, authors reported on CTSA institutional website as either a translational informatics portal or providing informatics functionalities. Four (4) of the articles reported the use of their website for engagement, on either the collaborator or patient level, such as advocacy, education, or subject enrollment. Two (2) articles reported the use of their CTSA website for the cultivation and training of a clinical and translational science workforce. Four (4) articles reported on the use of their CTSA website for the purposes of increasing the quality and efficiency of translational research. None of the articles reported how their sites were used to promote the integration of underserved populations. All the reports identified a CTSA institutional website as a tool to leverage or disseminate CTSA capabilities and functionality. The access point and or warehousing of these capabilities was the CTSA institutional website. The target audience for these publications included researchers, clinical research administrators, IT programmers, community collaborators, and research subjects. The articles that reported on the use of CTSA institutional websites for clinical and translational functionality included topics such as: (1) the introduction of an informatics tool that searches clinical notes to identify clinical data for research. (2) the promotion of an online research subject advocacy program. (3) the introduction of an informatics tool portal that allows researchers flexible, efficient and effective means of collaboration and interaction with data. (4) the promotion of a team development project tool. (5) the introduction of a research participant registry and study promotion and education tool. (6) the promotion of an independent informatics tool registry that could connect to all CTSA websites. DISCUSSION/SIGNIFICANCE OF IMPACT: This research shows that CTSA institutional website functionality and content contributes to the CTSA body of research and the advancement NIH translational science goals.

ABSTRACT IMPACT: This qualitative study describes health system barriers to high-quality care for Latino older adults with Alzheimer’s Disease and Related Dementias OBJECTIVES/GOALS: Compared to non-Latino Whites, Latino older adults are more likely to receive low-quality dementia care such as high-risk medications or services. Caregivers play a critical role in managing medical care for persons with dementia (PWD). Yet little is known about the perceptions and knowledge of dementia quality of care among Latino caregivers of PWD. METHODS/STUDY POPULATION: We used a qualitative research design and conducted interviews with Latino caregivers of PWD and caregiver advocates. We recruited both from community organizations, senior centers, and clinics. Our interview guide focused on experiences of caregiving, interactions with medical system, and knowledge and experiences managing behavioral and eating problems. We used Grounded Theory methodology for coding and analysis, focusing on contrasting and comparing experiences within and between caregivers and caregiver advocates. RESULTS/ANTICIPATED RESULTS: Preliminary results from interviews with two caregivers and two caregiver advocates illustrate that caregivers of persons with dementia have a difficult time receiving high quality care from primary care clinicians. All participants noted that many primary care doctors didn’t know how to diagnose ADRD and dismissed critical symptoms as part of old age. Caregivers also reported that they wished they had more information on what to expect with ADRD disease progression, noting they received little information from the formal medical care system. With respect to behavioral problems, caregiver advocates noted that primary care doctors often did not provide non-pharmacological alternatives to behavioral problems. DISCUSSION/SIGNIFICANCE OF FINDINGS: Findings from our pilot study demonstrate that there is a clear need to train primary care physicians who serve Latino older adults on ADRD care. Improved diagnosis and management could improve outcomes among Latino older adults with dementia.

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.

ABSTRACT IMPACT: A one-stage Bayesian multilevel model for meta-analysis integrating different survival data is introduced to complete the information synthesis without assuming proportional hazard. OBJECTIVES/GOALS: To develop a general modeling approach to perform efficient and robust meta-analyses using aggregated data (AD) for survival type endpoint and apply to a meta-analysis to examine the association between measurable residual disease (MRD) and disease-free survival (DFS) and overall survival (OS) in patients with acute myeloid leukemia (AML). METHODS/STUDY POPULATION: A Bayesian semi-parametric hierarchical model with a time-varying HR effect was presented. Three common types of survival information, including reconstructed survival data, the hazard ratio (HR) estimates with corresponding CIs and survival rates at specific time points, are synthesized such that all literature from the systematic review can contribute properly to the estimation and uncertainty quantification of the model parameters. The time-varying effects was modeled by assuming piecewise hazard risk and piecewise constant hazard ratio. The heterogeneity across studies was expressed by an additive random study effect and a random treatment-by-study interaction. The method was applied to a systematic review of 81 publications reporting on 11,151 AML patients. RESULTS/ANTICIPATED RESULTS: In simulation studies that the proportional hazard assumption is either valid or violated, the proposed method was efficient to achieve comparable performance to IPD meta-analysis, a gold standard approach, in estimating the survival rates, the restricted mean survival time at specific time points and median survival time with the point estimates close to the true values. When HR is not proportional over time, the proposed method was robust in estimating HR and significantly outperformed the classical random-effects meta-analysis. In the application to AML study, the average HR for achieving MRD negativity was 0.36 (95% CrI, 0.33-0.39) for OS and 0.37 (95% CrI, 0.34-0.40) for DFS. The association of MRD negativity with OS and DFS was significant and consistent across all subgroups. DISCUSSION/SIGNIFICANCE OF FINDINGS: The proposed novel method provided a flexible framework for meta-analysis of survival data, to accommodate various types of survival data in one model without assuming proportional hazards assumption. The findings of AML meta-analysis suggest that achievement of MRD negativity is associated with superior DFS and OS in patients with AML.

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.