OBJECTIVES/GOALS: The Mission: Health Equity Challenge Series is a four-part multimedia, interdisciplinary series that raises awareness about health disparities and health equity, cultivates environments for collaboration, and encourages participants to apply learnings via film screenings, a book discussion, community research panel, and un-meeting. METHODS/STUDY POPULATION: Methods used to collect data include: REDCap for participant profile storage and surveys, Zoom polls and chats, and informal, unsolicited feedback from e-mail communications. Our primary study population includes researchers and healthcare professionals. Secondary populations include: administrative staff and community members. We had approximately 500 individuals, across four of our hospital institution stakeholders (Cleveland Clinic, University Hospitals, MetroHealth, and the VA Northeast Ohio Health Care System), the community at-large, and others from CTSA hubs and related entities participated in one or more of the challenges. RESULTS/ANTICIPATED RESULTS: We anticipate that participants in the Mission: Health Equity Challenge Series, whether they participated in one or more of the challenges, will gain increased awareness about health disparities and how research can help close preventable gaps in health outcomes amongst underserved communities as well as advance health equity. Additionally, we suspect that due to the diverse nature of each challenge and attraction of nontraditional audiences to spaces with researchers and healthcare professionals, we will foster environments where cross-institutional, interdisciplinary collaboration can thrive. This is the type of collaboration needed to address complex problems that prevent health equity. DISCUSSION/SIGNIFICANCE: This challenge series elevates the relationship between advancing health equity and clinical and translational science and is one way to create opportunities for the existing research community to meet and collaborate with individuals that are not typically included in the ideation, design, implementation, and dissemination of research.

OBJECTIVES/GOALS: We aimed to explore the students’ assessments of workload distribution by comparing personal reflective commentaries and team documents defining division of labor in a team science setting. METHODS/STUDY POPULATION: The Interprofessional Research Design course models the team science experience by bringing together MD and PhD students to write a research grant. Four teams of 13 students were tasked with both individual and team-based assignments: 1) Each week, each student reported their perception of their own and their team members’ effort over the week (totalling 100%). 2) Iterative work contracts for each team were submitted at four time-points; assigned work toward project completion totalled 100%. 3) Lastly, each student submitted a short commentary reflecting on the prior week’s team dynamics and teamwork. We retrospectively performed a mixed-methods analysis of the workload data. RESULTS/ANTICIPATED RESULTS: Group-reporting in the team contracts remained static throughout the course, often stating equal distribution of workload, whereas individual reporting was more dynamic. Of 13 students, 8 rated more than 50% of the weeks as balanced. Among some students, there was a discordance of workload distribution when comparing the group document to the individual perceptions of work performed by their teammates. Reflective writing mapped more closely to individual quantitative reports. The data also revealed within team variations, where one student may report a higher proportion of their contributions, while the rest of the team attributed that student a lower percentage of the total work. DISCUSSION/SIGNIFICANCE OF IMPACT: An important aspect of team function is workload distribution. Group-based workload discussions may be a useful framework, but does not provide insight into team dynamics, whereas individually reported workload distributions and short reflections seem to more accurately inform us on team function.

OBJECTIVES/GOALS: MgSO4 is a frequently used to treat asthma exacerbations. Its role in the management of pediatric asthma remains controversial. Our objective is to demonstrate that the response of the small (peripheral) airways depends on airway de novo sphingolipid synthesis, clinically and experimentally. The small airways are the main site of asthma pathology. METHODS/STUDY POPULATION: We investigated airway reactivity in response to MgSO4 in murine small airways and children 1. Precision-cut lung slices (PCLS): Using heterozygous knockouts mice of one of the Sptlc2 subunit of the serine palmitoyl-CoA transferase (SPT) which results in reduced tissue sphingolipid levels compared to wild-type control littermates (Sptlc2+/+). We compared small airway dilation to MgSO4 in Sptlc2+/- and Sptlc2+/+ mice. This was assessed by directly visualization of small airway contractility in PCLS from Sptlc2+/- mice using video phase-contrast microscopy 2. Clinical response to MgSO4 in children by using a respiratory score before and after the treatment. The response to MgSO4 was the correlated to asthma-associated 17q21 specific single nucleotide polymorphisms (SNPs) from DNA isolated from buccal swabs RESULTS/ANTICIPATED RESULTS: Sphingolipid-mediated activity alters magnesium response in small airways. We assessed whether downregulation of SPT could lead to alterations in MgSO4-induced small airway dilation and in MgSO4 responsiveness in mouse tracheal rings and found that the magnesium-induced relaxation of airways pre-contracted with methacholine was impaired in Sptlc+/- mice compared to the control group (p=<0.05) Clinical response to MgSO4 in children with status asthmaticus. A respiratory score was assessed in a cohort of 5 to 21-year-old who received IV MgSO4. An increase of 3 or more points was considered positive. Only 32% of the patients showed a favorable improvement to the medication, showing variability of response between individuals. The correlation of sphingolipid-deficient SNPs and MgSO4 responsiveness is ongoing DISCUSSION/SIGNIFICANCE: This suggest that decreased SPT activity in the respiratory track alters the response of the airways to magnesium. Connecting decreased de novo SL synthesis to alterations in cellular magnesium homeostasis provides a mechanistic link to differential airway reactivity to MgSO4 in pediatric asthma management.

OBJECTIVES/SPECIFIC AIMS: The Clinical Research Operations Program is a free educational program designed to educate clinical research personnel on the conduct of clinical research (CR). The participant completes 16 required core sessions (24 h), 4 elective sessions (4 h), and passes the final exam to receive a certification in CR operations at Stanford. Sessions focus on the 9 domains of CR (established by the Joint Task Force for Clinical Trial Competency), such as Ethical & Participant Safety Considerations, Clinical Study Operations, & Data Management/Informatics. METHODS/STUDY POPULATION: Sessions are taught by volunteer lecturers. Participants may also attend the sessions without pursuing the certification. The program objective is to provide easy-access education in CR in order to increase regulatory compliance, staff retention, and improve CR at Stanford. The program targets CR coordinators, however, staff, postdocs, fellows, and faculty also participate. RESULTS/ANTICIPATED RESULTS: Since the program’s launch in January 2017, 119 individuals have enrolled in the certification program. The most represented group is the Department of Medicine. Sessions consistently reach their maximum with a waiting list. Each core session requires that the participant complete an evaluation (Likert scale, 1–5) of the registration process (4.5/5), the class environment (4.6/5), the presented content (4.5/5), and the instructor (4.6/5). Data from these evaluations are positive to date and is used to continually refine the program. DISCUSSION/SIGNIFICANCE OF IMPACT: N/A.

OBJECTIVES/GOALS: The NC Translational and Clinical Sciences (NC TraCS) Institute’s Latine Community Review Board (CRB) provides expertise to researchers seeking to culturally adapt interventions and improve language access in clinical and translational science. Early efforts aimed to expand CRB membership, build member capacity, and assess CRB impact. METHODS/STUDY POPULATION: Founded in 2021, the NC TraCS Latine CRB is an advisory group of natively Spanish-speaking, Latine North Carolinians who contract with research teams (RTs) to review Latine community-facing study materials (e.g., decision aids, scales, recruitment scripts) and provide feedback for improving or validating materials’ linguistic accuracy and cultural relevance. Bilingual staff facilitate members’ review of materials, use focus group methods to solicit feedback, and report key findings and suggested revisions to RTs. In 2023, we recruited new age-, gender-, and racially diverse members; and implemented process and impact evaluation, via (1) post surveys of RTs and (2) assessment of members’ experiences and visions for growth utilizing the Focused Conversation Method (Top-network, 2021). RESULTS/ANTICIPATED RESULTS: Since 2021, NC TraCS has conducted 11 Latine CRB review sessions to support 7 research studies. Current CRB members (n=8) report that (1) their work effectively supports Latine inclusion in research; (2) increased group size and diversity help ensure study materials are comprehensible to heterogenous Latine populations; and (3) an hourly member compensation rate equal to the hourly rate of TraCS’ staff accurately represents member contributions. Members also cited that they value open communication, continuous improvement, communication via email and group chat, periodic programming meetings, and RT updates on study outcomes. Post-session RT surveys to date (n=3) show that RTs would recommend this program to other researchers (pending survey responses from RTs this year will provide additional impact data). DISCUSSION/SIGNIFICANCE: Early data highlight the value of fairly compensated, bilingually coordinated input from diverse Latine community members for improving studies’ inclusion of heterogeneous, multilingual communities. Our approach can inform the development, growth, and continuous improvement of multilingual review boards at other research institutions.

OBJECTIVES/GOALS: Greater blood pressure (BP) reactivity and socioeconomic deprivation (e.g., area deprivation index; ADI) are associated with poor vascular health [1-3]. However, it is unclear if ADI is associated with BP reactivity. Thus, we sought to examine if ADI is associated with BP reactivity in young adults. METHODS/STUDY POPULATION: Participants completed questionnaires used to derive lifetime ADI averaged from early-, mid-childhood, and adolescence. Participants completed a handgrip (HG) exercise protocol including 10 minutes of rest, 2 minutes of static HG at 40% of their maximal voluntary contraction, 3 minutes of post-exercise ischemia (PEI), and 2 minutes of recovery (REC). Beat-to-beat BP (photoplethysmography) and heartrate (HR; electrocardiogram) were continually assessed. We used the Shapiro-Wilk test to assess data for normality. We examined associations between ADI, BP reactivity, and HR using unadjusted and body mass index (BMI), sex, and race-adjusted Pearson’s correlation (set a priori to 0.05). RESULTS/ANTICIPATED RESULTS: This study included 53 (27Males/26Females; 21 ± 1 years; 24Black/29White; BP 107 ± 9/64 ± 9 mmHg) participants. There were racial differences (Black compared to White adults) for several BP reactivity metrics (e.g., PEI minute 3 diastolic BP: 96 ± 15 vs. 84 ± 19 mmHg, p=0.014) and lifetime ADI (p0.050). DISCUSSION/SIGNIFICANCE: Our data suggest racial differences exist in socioeconomic deprivation in a modestly sized young adult sample living in the southeast. While additional data are needed for other stressors, socioeconomic deprivation was not independently associated with BP or HR reactivity during acute exercise.

OBJECTIVES/SPECIFIC AIMS: Objectives/goals: Describe the process used to develop leveled competencies and associated examples. Discuss the final leveled competencies and their potential use in clinical research professional workforce initiatives. METHODS/STUDY POPULATION: The revised JTFCTC Framework 2.0 has 51 competency statements, representing 8 domains. Each competency statement has now been refined to delineate fundamental, skilled or advanced levels of knowledge and capability. Typically, the fundamental level describes the competency for a professional that requires some coaching and oversight, but is able to understand and identify basic concepts. The skilled level of the competency reflects the professional’s solid understanding of the competency and use of the information to take action independently in most situations. The advanced level embodies high level thinking, problem solving, and the ability to guide others in the competency. The process for developing both the three levels and examples involved 5 workgroups, each chaired by a content expert and comprising of national/international clinical research experts, including representatives from research sites, professional associations, government, and industry and academic sponsors. RESULTS/ANTICIPATED RESULTS: The committee developed 51 specific competencies arrayed across 3 levels and examples of each to demonstrate an appropriate application of the competency. The competencies and examples, and potential utilization, will be described. DISCUSSION/SIGNIFICANCE OF IMPACT: The use of competencies in the context of workforce development and training initiatives is helping to create standards for the clinical research profession. These leveled competencies allow for an important refinement to the standards that can be used to enhance the quality and safety of the clinical research enterprise and guide workforce development.

OBJECTIVES/SPECIFIC AIMS: To determine if altered sphingolipid metabolism and composition are associated with childhood-onset asthma. METHODS/STUDY POPULATION: Sphingolipid profiles and composition were analyzed in a pilot cohort of pediatric with asthma (n=22), and in nonasthmatic controls (n=17). The cohort includes males and females, ages 5–17 years with no prior history of asthma or wheezing, and those who have been previously diagnosed with asthma by a pediatric pulmonologist. Subjects who have a history of prematurity, chronic lung disease, acute respiratory infection, malignancy, autoimmune disorders, immunodeficiency, or sickle cell anemia were excluded. Asthma and nonasthma phenotypes were determined through clinical history, standardized asthma symptom checklists, medical record review and spirometry. Masses of sphingolipids were quantified by mass spectrometry (HPLC-MS/MS) in serum and exhaled breath condensates (EBC). Allergy status was determined through clinical questionnaire, blood IgE (>150 IU/mL) and blood eosinophils (>0.3×103/mcl). RESULTS/ANTICIPATED RESULTS: Multiple species of sphingolipids and ceramides were found to be higher in the serum and EBC of asthmatics compared with controls in the overall cohort. In serum, these species include C16 (p=0.05), C16DH (p=0.05), C18:1DH (p=0.002), C20 (p=0.05), Sphingosine (p=0.05), and S1P (p=0.04). In EBC, asthma was associated with higher levels of C18:1DH (p=0.05), C20 (p=0.05), C22 (p=0.05), Sphinganine (p=0.05), Sphingosine (p=0.04), and S1P (p=0.06). When data were stratified for allergic status, the increases in serum sphingolipids were largely associated with total IgE levels greater than 150 IU/mL. Sphingolipids which were increased in allergic asthma (n=13) compared with allergic controls (n=5) included C16 (p=0.006), C16DH (p=0.006), C18:1DH (p=0.06), C20 (p=0.048), C22 (p=0.02), C24 (p=0.02), C24:1 (p=0.02), Sphinganine (p=0.02), Sphingosine (p=0.01), and S1P (p=0.02). Notably, only C18:1DH remained increased in asthmatics regardless of allergic status, in both low and high total IgE subjects. DISCUSSION/SIGNIFICANCE OF IMPACT: Data from this pilot cohort suggest that sphingolipids are altered in asthmatic compared with nonasthmatic children, particularly in association with a history of allergy and elevated blood IgE. This trend was also demonstrated in exhaled breath condensate, suggesting that sphingolipids are altered both in serum and airway fluid. Only 1 species of sphingolipid measured, C18:1DH, was elevated in asthmatics regardless of allergic status. Notably, this sphingolipid was recently identified to be associated with exercise induced wheezing (EIW) and asthma persistence overtime, in a large case-control study of children with and without asthma (Perzanowski et al., in press). EIW has been identified as a specific phenotype of asthma, and can be present with or without allergy/atopy. Taken together, these data suggest that altered sphingolipids may contribute towards the underlying pathophysiology of asthma, the understanding of which can lead to improved characterization of asthma phenotypes.

Reference Perzanowski M, et al. Distinct serum sphingolipid profiles among school-age children with exercise-induced wheeze and asthma persistence. American Journal of Respiratory and Critical Care Medicine 2017 (in press).

Objectives/Goals: The ITHS KL2 Seminar Fellows program creates a larger cohort by inviting additional early career faculty to join the tailored career development curriculum. The implementation of this program seeks to increase collaboration and innovation by amplifying diverse perspectives and increased networking. Methods/Study Population: In addition to the funded KL2 Scholars awarded each year, 13–15 Seminar Fellows are invited to be full participants in the KL2 curriculum, which includes monthly career development seminars and opportunities for feedback on their research. Invited Fellows are early career investigators who were promising KL2 applicants, faculty with alternative career development funding, and/or new underrepresented faculty in Washington, Wyoming, Alaska, Montana, and Idaho. Fellows commit to one year of participation, which can be renewed on a case-by-case basis. Fellows have been integrated into the ITHS implementation of Flight Tracker (Vanderbilt) to follow the career pathways alongside funded KL2 award recipients. Results/Anticipated Results: The key measures of success will be the rate of seminar fellows transitioning into K-level or similar career development awards and securing other subsequent funding. Preliminary data demonstrates significant collaborations between KL2 Scholars with different areas of scientific inquiry and promotion of at least half of our past KL2 Scholars into leadership positions at prestigious medical schools in the USA and Canada. We suspect that the trends evidenced by the career progression of early KL2 recipients will be expanded into newer and different translational research projects with the addition of the KL2 Fellows program. Discussion/Significance of Impact: The Seminar Fellows program presents a cost-effective way to increase the impact of an existing career development program by amplifying cross-boundary interactions to form a strong, diverse translational research workforce.

OBJECTIVES/GOALS: The aim of this project is to assess the usability and acceptance of a web-based educational resource for early career researchers. The Emerging Investigators website is designed to bring together resources, provide educational support and foster a community of early career researchers throughout the Mount Sinai Health System (MSHS). Locally designed and built, this web-based platform is developed using the principles of Community of Inquiry (COI), which considers how the design of online learning environments might best create and sustain a sense of community among learners. Developing a resource that meets the needs of this cohort of researchers requires an iterative implementation strategy guided by user feedback. A formal website roll-out strategy and accompanied evaluation aims to determine the design, navigability, content, relevance and educational value of this online resource from a user perspective. METHODS/STUDY POPULATION: In order to ensure this resource effectively meets the needs of this cohort of researchers, a mixed process of evaluation and design was utilized. An initial phase 1 survey was conducted with TL1 and KL2 scholars. Surveys consisted of standardized questions with answers arranged as Likert-type scales and additional written responses to collect valuable qualitative data. A convenience sample of early career researchers at Mount Sinai were contacted for initial survey participation (N = 10). A total of 3 junior faculty KL2 scholars, 3 TL1 post-doc and 4 TL1 pre-doc scholars responded to the survey. Participants were initially asked to comment on design, functionality and usefulness of content on a Likert scale with qualitative comments to support the given scores. They were subsequently asked to consider what key topics or resources were missing from the website. Based on the initial survey, changes were made to the format and content of the Emerging Investigators website to improve content relevance and usability. For phase 2, an evaluation rubric was developed to assess design, navigability, content, relevance, along with three key COI criteria to determine the educational value of this online resource. The rubric will be utilized to collect feedback in the wider phase 2 roll out of the website. RESULTS/ANTICIPATED RESULTS: The first phase of survey feedback shaped overall design of the resource. The second phase will comprehensively evaluate the value of the website in the context of teaching and learning for emerging investigators. Ten surveys were captured in the first phase. Data collection is ongoing for the second phase. Phase 1 feedback was primarily qualitative, and valuable in informing overall design choices and content. Overall the website was well received, with participants commenting on the value of the resource in terms of content and educational value. Participants particularly appreciated the regularly updated calendar function and the links provided to a wide range of resources. Functionality issues, such as broken links, were reported by participants and repaired for phase 2. Further topics of content were identified, and additional links and multimedia resources were added to address this feedback. The second phase evaluation is ongoing with data collection being conducted via an evaluation rubric. DISCUSSION/SIGNIFICANCE OF IMPACT: The Emerging Investigators website, developed using the principles of COI provides key learning, reading and resources for early career investigators in a format that is well received by a sample group of early career researchers at Mount Sinai. The website has aimed to address the reported need for communication, collaboration and social interaction with peers and other researchers across the MSHS through the addition of further web-based resources such as a LinkedIn page, a blog to feature research and provide a sounding board for research efforts, and a calendar of events targeted specifically at early career researchers. These were highlighted as areas of particular value by the participants. We anticipate the results of phase 2 rubric-based evaluations will provide actionable data that will lead to further refinement of the website, an optimized interface, and improved usability.

OBJECTIVES/SPECIFIC AIMS: Intestinal stem cells (ISC) primarily act in the repair of ulcerated epithelium, and their proliferative capacity relies on Wnt/β-catenin signaling. However, the role of GCs on basal epithelial cell signaling has not been fully characterized. The objective of this study was to interrogate a mechanism by which steroids may limit ISC activation. GCs inhibit NFκB signaling, which has been shown to play a role in nuclear β-catenin activation in epithelial cells. We hypothesized that GCs limit Wnt/β-catenin signaling required for ISC activation and epithelial restitution by inhibiting NFκB activation in epithelial cells. METHODS/STUDY POPULATION: To examine the effects of GCs on intestinal epithelial cells, we treated a nontransformed human colonic epithelial cell line (NCM460) with dexamethasone and observed the effects on NFκB and Wnt/β-catenin signaling events. We isolated mouse epithelial cells from the distal colon for stem cell culture as 3D “organoids.” We obtained pure epithelial cell preparations from mucosal biopsies isolated from patients treated at GI clinics at the University of Kentucky Chandler Hospital and VA Medical Center, Lexington. Steroid treated patients with equivalent levels of inflammation, but no mucosal ulceration were used as controls. RESULTS/ANTICIPATED RESULTS: In steroid-treated NCM460 cells, we saw an increase in steroid-responsive genes GILZ and SGK1. We saw a significant decrease in transcripts for Wnt target genes, including Axin2 and cmyc; NFκB target genes, including IFNG and IL6; and the shared NFκB and Wnt pathway co-activator CREBBP, despite unchanged transcript levels for β-catenin (CTNNB1). This data was corroborated in 3D stem cell cultures from cells isolated from mouse colon tissue, which had significant decreases in transcripts for stem cell markers Lgr5 and Ascl2, proliferative markers KI67 and PCNA, and Wnt target Axin2. NCM460s transfected with a lentivirus carrying a TCF/LEF luciferase construct showed a 2.5-fold decrease in TNF-stimulated luciferase activity with dexamethasone treatment. Interestingly, this effect can be rescued by glucocorticoid receptor (GR) blockade with RU-486. Intestinal epithelial cells from patient biopsies showed significant decreases in colitis-induced Axin2, p-LRP6 (a positive marker of Wnt Signaling) and nuclear β-catenin, which correlated with decreased p-p65 protein levels. DISCUSSION/SIGNIFICANCE OF IMPACT: Together, these data suggest that steroid therapy inhibits Wnt/β-catenin signaling at multiple levels, and effects stem cell proliferation in pure stem cell cultures. Decreases in TCF/LEF transcriptional activation (nuclear β-catenin’s DNA binding target) can be reversed with steroid receptor blockade with RU-486, suggesting that a receptor level interaction may be occurring. Interestingly, the required co-activator CBP, shared between NFκB and Wnt pathways, has decreased transcription following steroid treatment, which may provide a mechanism for limited Wnt activation following steroid therapy. Although steroids play a significant role in regulating the amount of inflammatory damage that occurs during IBD treatment, our data suggest that they may be limiting pathways required for effective healing as well.

OBJECTIVES/GOALS: The CHW TAB is exploring pre-diabetes knowledge and perceived needs in south Texas to facilitate the role of CHWs to increase the capacity of community members to better manage their prediabetes diabetes risk. The long-term goal of this project is to show how the diagnosis of pre-diabetes can be managed to prevent type 2 diabetes. METHODS/STUDY POPULATION: We selected a two-pronged approach to gather quantitative and qualitative data. CHW TAB members collected data participated in different aspects of the project (e.g., study design, survey development, etc.). Data collection procedures include Quantitative - a 9-item survey in English and Spanish administered by each participating CHW in 2022 at community events. One hundred surveys were collected. In Phase 2: Qualitative, participants attended focus groups to gather in-depth data about pre-diabetes management, including challenges and opportunities, which will inform CHW-led intervention development. Eight English and one Spanish focus groups, with 65 participants in 6 counties were completed. RESULTS/ANTICIPATED RESULTS: This project is still in progress. Preliminary results show that most survey participants identify as Hispanic, and half have been diagnosed with pre-diabetes. Additionally, 87.8% report that prediabetes is a problem in their community. Preliminary focus group findings indicate that knowledge and support for managing prediabetes is missingin South Texas. Many participants report feeling “doomed” to develop type 2 diabetes but are eager to share their experiences. Additionally, participants report that family and culture play a huge part in their ability to eat healthier foods. DISCUSSION/SIGNIFICANCE: These findings can help identify knowledge gaps, strengths, and areas for promoting and empowering better health behaviors among those who have pre-diabetes. Participant feedback and focus group responses will inform a CHW-led educational intervention through our TAB.

Objectives/Goals: We developed an educational online module to equip researchers with knowledge, skills, and resources for conducting community-engaged research, aiming to foster meaningful collaboration between academia and communities. Methods/Study Population: A working group was formed, including three research faculty, four staff members, and four community partners who have partnered with researchers on community engaged projects. The working group first identified three objectives for the module and outlined what should be covered for each objective. The working group identified existing resources, texts, and videos that would address the objectives and worked in small groups to create additional content for the module. A smaller subgroup then took this content, organized it, and worked with the Office of Online Education to put the content into an interactive online format. Results/Anticipated Results: The three objectives identified for the online module are 1) Describe community engaged research, the purpose it serves, and why researchers do it; 2) Identify how to seek and collaboratively engage with a community partner; and 3) Identify and connect with resources for conducting community engaged research in Indiana. Each objective contains text, interactive figures and images, links to external resources or further reading, and videos of researchers and community partners talking about their own experiences and lessons learned. Each objective also includes activities and prompts for the learner to complete to apply the module content to the work they want to do. Discussion/Significance of Impact: Community engagement ensures research addresses real-world needs, builds trust, and includes diverse perspectives. Many researchers lack best practices to do this ethically. This module teaches skills needed to foster trust through transparency, respect, and by incorporating community voices.

ABSTRACT IMPACT: By understanding Junior investigator characteristics and CTSA support services which strongly influence scientific productivity and impact, we will inform and improve research training and enhance the career development of future generations of clinical and translational science researchers. OBJECTIVES/GOALS: In the field of clinical and translational science, the career trajectory and definition of Junior Investigators (JIs) vary greatly. This study aims to investigate JI characteristics, training, and support that contribute to career development at the University of California Los Angeles (UCLA) Clinical and Translation Science Institute (CTSI). METHODS/STUDY POPULATION: Every 18 months, the UCLA CTSI administers the Longitudinal Scientific Achievement Survey, which collects information on the predictors of scientific productivity and impact. In 2018, a special supplement was added to survey JIs who received CTSA support between 2011 and 2017 (n=305), including questions on knowledge, use, and effectiveness of CTSA specific support, barriers and facilitators of research, scientific productivity, and perceived scientific impact. A literary analysis was conducted to explore previous categorizations of JIs. The JIs in our sample conducted bench to bedside, population and policy research at our four partner sites. Bivariate and logistic regression analysis were conducted to examine the significant predictors of a new grant award attributed to the CTSA support/services. RESULTS/ANTICIPATED RESULTS: The survey response rate was 82% (n=250). Respondents include core voucher co-investigators, enrollees in the Training Program in Translational Science, and K- and K-to-R workshop participants. Bivariate results showed new grant awardees significantly more likely to have the following characteristics: physician scientist with an MD and PhD (47%), pilot grant awardee (42%), core voucher awardee (49%), four or more types of CTSI support (48%), prior affiliation with an NIH institute/center other than NCATS (42%), and reported at least one impact in science, health, and/or the community (72%). Multivariate results showed that investigators with a prior core voucher award, a prior NIH affiliation, or reported one or more impacts were the strongest predictors of obtaining a new grant (each with OR>=4.0). DISCUSSION/SIGNIFICANCE OF FINDINGS: The most successful investigators consulted with NIH program officers and received feedback on their research plans and methods. Sufficient funding is crucially important to research progression. In our CTSA hub, vouchers and grants to initiate new studies or offset costs of existing research are consistent predictors of new extramural funding.

OBJECTIVES/SPECIFIC AIMS: Our aim was to assess the feasibility and acceptability of a VW-based cardiac rehabilitation (CR) program (Destination Rehab) as an extension of a face-to-face conventional CR program. We hypothesized that a VW-based CR program could be successfully implemented as an extension of conventional CR and would have high acceptability among cardiac patients. METHODS/STUDY POPULATION: We recruited 30 adult cardiac patients (10/site) hospitalized at Mayo Clinic Hospitals in Rochester, MN, Jacksonville, FL or Scottsdale, AZ with a diagnosis for CR (eg, acute coronary syndrome (ACS), heart failure, elective percutaneous coronary intervention (PCI)). Other inclusion criteria included at least 1 modifiable, lifestyle risk factor target: sedentary lifestyle (< 3 hours physical activity (PA)/week), unhealthy diet (< 5 servings fruits and vegetables/day) or current smoking (>1 year). Patients participated in an 8-week, health education program using a VW platform from a prior proof-of-concept study and provided intervention usability, usefulness and satisfaction feedback. We assessed cardiovascular (CV) health behaviors (diet, PA) and risk factors (eg, blood pressure (BP), lipids) at baseline and immediate post-intervention. RESULTS/ANTICIPATED RESULTS: Among 30 patients enrolled (mean age; 59 years; 50% women; 65% <college graduate; 32% annual household income <$50,000), 28 (98%) completed the study. The majority (64%) were enrolled in conventional CR with a high session completion rate (median 36 sessions, interquartile range 8-36). The most common CR indication was PCI (68%). There were statistically significant improvements in PA from baseline to post-intervention: vigorous PA, +10.7 (SD 11.7) minutes/day (p = 0.05) and flexibility exercises +0.9 (SD 0.9) days/week for men (p=0.05). There were favorable trends in risk factors: systolic BP (−6.8 mmHg, SD 29.8), total cholesterol (−31.6 mg/dL, SD 46.2) and LDL (−26 mg/dL, SD 44.8) from baseline to post-intervention, although not statistically significant. The majority reported that they would continue to use VW as a resource (76%) and agreed/strongly agreed that the program improved their heart health knowledge (86%) and assisted with adapting healthier lifestyle (100%). Overall, the VW CR program received a rating of 8 (scale 0-10). DISCUSSION/SIGNIFICANCE OF IMPACT: VW-based CR program is a feasible, highly acceptable and innovative platform to influence health behaviors and CV risk and can increase accessibility to disadvantaged populations with higher CVD burdens.

OBJECTIVES/SPECIFIC AIMS: To establish a conceptual framework todevelop a CTS-IDP with data analytics, and an e-Learning Faculty DevelopmentGuide on best practices and use of the IDP over the CTS academic life-course.METHODS/STUDY POPULATION: To accomplish our goal, we propose thefollowing methods: (1) an online survey, using a convenience sample of the 24KL2 CTSA IDP Collaborative members (conducted in 2017), to assess perceivedneeds for a universal CTS-IDP, current IDP practices, barriers to IDP use, andto discern and align each CTSA Hub’s interests, expertise andcommitment to specific areas of the study; (2) A scoping narrative literaturereview, utilizing the Arksey and O’Malley framework covering the timeperiod corresponding to the initiation of funding (1999) of the original K30Clinical Research Curriculum Awards through to the present CTSA funding period,incorporating Medical Subject Heading (MeSH) keywords (career development;career development plan; employee plan; mentoring plans; compacts; researchcontracts; career planning; mentor guide), initially delineated by USC referencelibrarian and to be expanded by reference librarian services from the IcahnSchool of Medicine at Mount Sinai and University of Rochester, and performed onNIH searchable databases including NCBI PubMed, Central and Medline &Worldwide Science; Web of Science, ProQuest, ProQuest Abi/Inform,Google Scholar, Cochrane, Ovid MEDLINE databases, as well as Google forpublished papers in English and Spanish. For this portion of the work, we willdescribe and characterize (1) research career development or progressionconstructs, domains, and milestones; (2) establish the presence or absence ofdefined and/or pre-specified timed milestone objectives and inclusionof SWOT analytics (strengths, weaknesses, opportunities, and threats)and/or Gantt chart approaches; (3) delineate IDPs structure, toolkitsand their key features (competencies, skills acquisition and processesutilized); (4) and identify specific gaps to best address the need forpersonalized career development education. Based on this review, we willsynthesize CTS milestones, develop a time frame for meeting RCD expectations,and establish RCD benchmarks for achieving these milestones, all in consensuswith the IDP Collaborative Workgroup. RESULTS/ANTICIPATED RESULTS:Seventy-seven percent of the IDP CTSA’s responded to the onlinesurvey, led by University of Rochester, and the results can be summarized asfollows: (1) 100% agreed that the IDP process is important and shouldbe considerably improved to optimize effectiveness; (2) a range of diverse IDPformats are utilized, making comparisons across programs difficult; (3)50% of CTSA hubs report only fair to good compliance with the IDPprocess; (4) a major barrier to the IDP process is lack of instruction regardinghow best to utilize; (5) poor alignment of currently available IDPs designed forbasic science PhDs with CTS investigators; (6) an absence of a CTS specific IDPto best foster RCD for this specific career trajectory. When asked: What are thebarriers to writing a detailed and thoughtful IDP, responses in order ofagreement from greatest to least were: No verification of acquired competencies,beyond self-report (56%), Static platform (38%), Notconstructed for clinical and translational researcher (31%), Noanalytical or documentation on use (31%), No instruction given toscholars on how to use it effectively and efficiently (31%), The IDPwe are using is more constructed for PhD students and postdoctoral fellows(25%), No instruction given to the scholars on why it is important asadult learners (19%), and Not constructed for early careerphysicians/scientist (13%). Additional progress has beenmade on our Scoping review: An initial ABI/Inform and PubMed USCresearch librarian conducted search using Author names yielded 72 articles, ofwhich only 2 were relevant to the topic at hand. A ProQuest™ searchyielded 19 potentially relevant articles, 11 of which were of relevance to thetopic of IDPs; and a Google Scholar search yielded 18 and 25 on careerdevelopment and self-management, respectively. This has enabled us to put forthan initial model of factors that impact the purpose and design of IDPs thatincludes? DISCUSSION/SIGNIFICANCE OF IMPACT: Discussion: Our initialdata suggests that many CTSA institutions see the need to further enhance thementoring process with a more informed and personalized IDP template andprocess. Furthermore, our initial scoping review suggests a framework upon whichto build specific components of a more ideal and useful IDP to best guidementored research career development of CTS trainees. Significance: Developingand evaluating collaborative evidence-based CTS IDP and corresponding e-LearningGuide could potentially prevent or reduce important delays in RCD, a commonroadblock for the translation of clinical interventions. Ultimately, the CTS-IDPserves not only to support and frame a scholar’s RCD“habits of mind” during training and early careerdevelopment but to also to achieve a sustainable long-term career at a CTSresearcher equipped to meet the ever challenging and dynamic researchlandscape.

Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.

Pragmatic trials aim to generate timely evidence while ensuring feasibility, minimizing practice burden, and maintaining real-world conditions. We conducted rapid-cycle qualitative research in the preimplementation period of a trial evaluating a community paramedic program to shorten and prevent hospitalizations. Between December 2021 and March 2022, interviews (n = 30) and presentations/discussions (n = 17) were conducted with clinical and administrative stakeholders. Two investigators analyzed interview and presentation data to identify potential trial challenges, and team reflections were used to develop responsive strategies. Solutions were implemented prior to the commencement of trial enrollment and were aimed at bolstering feasibility and building ongoing practice feedback loops.