OBJECTIVES/SPECIFIC AIMS: Incomplete spinal cord injury (iSCI) is a life-long disability that typically results in a profound loss of locomotion capability. Current rehabilitation methods rarely restore full community ambulation, which in turn limits quality of life. Most individuals with iSCI exhibit persistent deficits in eccentric muscle control and reach recovery plateaus below the levels necessary for independent community ambulation. Eccentric motor control is essential during the weight acceptance phase of gait, which is emphasized during downhill walking. METHODS/STUDY POPULATION: The overground locomotion of subjects with chronic iSCI was analyzed both prior to and following a 12-week downhill body-weight-supported treadmill training regimen and compared to that of matched healthy controls in terms of kinematics, kinetics, and EMG activation. RESULTS/ANTICIPATED RESULTS: We expect to find significant differences between the controls and subjects with iSCI, with deficits in eccentric motor control accounting for some of these differences. In addition, we expect the downhill training to yield significant improvement in eccentric muscle control that translates into improvements in functional, overground walking for the subjects with iSCI. DISCUSSION/SIGNIFICANCE OF IMPACT: The goal is to determine if downhill training can improve eccentric motor control and extend recovery beyond established plateaus. OpenSim modeling of the experimental data will help quantify changes in eccentric control of individual muscles to clarify where specific gains are made.

OBJECTIVES/SPECIFIC AIMS: Sexual violence (SV) is a public health crisis. High rates of SV are observed among college-age youth, yet holistic interventions are currently lacking. The purpose of this study was to conduct a pilot feasibility and acceptability test of a WebApp, MKit, which translates a clinical life skills approach to influence the health and well-being of university students. METHODS/STUDY POPULATION: We randomized two residence halls at a public university in the Midwest into a control group (n=139) that received typical university programming around SV and healthy relationships, or an intervention group (n=122) receiving MKit and the usual SV programming. We used online surveys to assess acceptability, feasibility, and usability at 3- and 5-months. Focus groups were conducted with a subsample of participants at 5-months to further investigate safety. RESULTS/ANTICIPATED RESULTS: The mean number of uses of MKit was 2.84 in a 5-month period. The majority of intervention participants endorsed the acceptability and usability of MKit as easy to use, well integrated, accessible, and easy to learn quickly. There were no concerns regarding personal safety. DISCUSSION/SIGNIFICANCE OF IMPACT: MKit provides a promising resource platform to deliver messages regarding healthy relationships and SV within the university context. By delivering SV-related content through a holistic life skills approach, MKit may offer new opportunities to reach and engage a wide range of students on how to foster healthy relationships.

OBJECTIVES/GOALS: To identify insights and challenges in community engaged research for the academy and community. To develop an online platform to match academic and community partners; promote networking; and provision of key resources. METHODS/STUDY POPULATION: Using a human-centered design approach, 19 interviews were conducted with academics, community organizations and members, and other CTSAs. The interviews focused on understanding CEnR challenges and processes in partnership formation. RESULTS/ANTICIPATED RESULTS: Findings revealed the following 10 challenges to and insights about CEnR: (1) time intensive; (2) lack of knowledge; (3) differing motivations; (4) connections occur through networking; (5) topic area, proximity, and readiness influence partnerships; (6) organizational turnover; (7) promotion pressure; (8) collaboration throughout; (9) navigator for partnership; and (10) lack of shared language. Also, a CEnR system flowchart revealed the following five phases of an effective partnership: 1) generating interest; 2) learning process; 3) connecting with the right partner; 4). Defining the research question; and 5) implementing research as a partnership. DISCUSSION/SIGNIFICANCE: In conclusion, input from academicians and community members support the need for an online platform like M-REACH to facilitate CEnR partnerships, networking, and resources to address significant public health issues through translational research.

OBJECTIVES/GOALS: Family health history is widely recognized as an important step of genetic counseling; however, <50% of adults collect family health history due to implementation gaps such as suboptimal collection tools. Our objective is to create KIT, an interactive chatbot to administer a family history survey in comparison to a form-based data collection tool. METHODS/STUDY POPULATION: Both family health history collection tools were designed by adapting the NIH All of Us Research Family History Survey. The study population consists of 1000 individuals recruited from the crowdsourcing platforms, subreddits r/Health, r/SampleSize, and r/GeneticCounseling and Amazon Mechanical Turk. Eligible participants must be U.S. adults who know at least two first-degree relatives with at least one condition. Study participants are randomized to interact with either tool and complete a survey that measures the usability, engagement, accuracy, and impact of the two data collection strategies. We will use an independent t-test to compare differences in our outcome variables between the two family health history collection tools with demographic variables as covariates. RESULTS/ANTICIPATED RESULTS: The hypothesis of this study is that KIT will be more usable, more engaging, with similar accuracy in comparison to form-based tools, which are currently being used for family healthy history collection at low rates. The primary outcome of this study is usability, which will be measured based on standardized surveys. Secondary metrics of this study include engagement, accuracy, and impact. Engagement metrics include time to completion and number of resource link clicks. To assess accuracy and impact, we have included survey questions about the quality of the final summary report provided by both tools. Additionally, we ask users to rank areas for design feature improvement and feature importance; these features were determined by shared-decision-making concepts. DISCUSSION/SIGNIFICANCE: This study provides recommendations for design features important for the usability, engagement, and impact of future family health history collection tools. With a more usable and engaging tool, we can maximize rates of collection and support both patients and genetic counselors by ensuring features align with shared-decision-making frameworks.

OBJECTIVES/SPECIFIC AIMS: The objectives for the Rigor, Reproducibility, and Transparency course within KAIZEN-Edu was to provide a platform that allows essential training, in a novel and customizable approach, for a large number of students across the multiple institutions within the UAB CCTS Partner Network. Successful implementation across this geographically diverse of partner institutions would serve as proof of concept to future dissemination across the CTSA consortium. METHODS/STUDY POPULATION: We used the “build a game” tools within Kaizen-Edu to design the “Rigor and Reproducibility Game.” The games consisted of four modules, with 20 questions designed to test participant knowledge, and edify learners on particular concepts through a multimedia approach (embedded video, text, and hyperlinks to articles) with content provided as questions released over 4 weeks. Researchers from across the UAB CCTS Partner Network developed comprehensive modules for (1) How Scientists Fool Themselves/Scientific Premise, (2) Authentication of Chemical and Biologic Resources and Sex and Other Biologic Variables, (3) Statistical Rigor, and (4) Comprehensive Review. A typical week began with review articles (1–2) sent to each participant. The participants are informed that 5 questions will be released midweek testing the key concepts from the papers. When ready, the participant logs into Kaizen-Edu and starts to answer questions/play the game. Immediately, the articles are opened for reference, followed by a brief 4–5 minute video which reinforces key concepts and then timed questions begin. A typical question is allowed 3 minutes (visible countdown clock). Accurate responses result in the addition of points, with double points awarded for correct answers within the questions time limit. No points are awarded for incorrect answers. After each question, a detailed explanation reviews and reinforces the key concepts. Each participants’ points contribute to both their individual score and team scores, which influences their position on the Rigor and Reproducibility game leaderboard. RESULTS/ANTICIPATED RESULTS: Within 2017, the Rigor Reproducibility, and Transparency course was conducted 5 times. A total of 126 researchers across 9 institutions were enrolled. A total of 87 enrollees completed the full course, with 80% passing (answering ≥75% of questions correctly) on their first attempt and an additional 20% passing on a second attempt. The distribution of completers across the CCTS Network was UAB=48, Auburn=13, Pennington=10, University of Alabama=5, Hudson Alpha=5, Tulane=4, University of South Alabama=1, LSU=2, and Southern Research=1. Researchers throughout at Partner Institutions represent 46% of the total population trained. DISCUSSION/SIGNIFICANCE OF IMPACT: This software based, gamification-enhanced course was broadly accepted with each session fully enrolled, and learners spread almost evenly between our institution and various Partner Network sites. Our pilot proved that gamification was an effective technique to engage users and produced a high pass rate, suggesting that the content both engaged learners and was effectively internalized. Educational interventions, imbued with principles of gamification provide educators powerful tools that use competition and/or collaboration to disseminate knowledge, engage learners with content, and save educator time as created game content can be reused in additional educational sessions. Analyses of the data trail provided by users engaging with such electronic learning tools will provide educators will insights on how to maximize learning, opening the door to an era of educational analytics.

ABSTRACT IMPACT: We report a novel metric for assessing clinical informatics fellows relative to their personal goals, using standardized milestones that have been approved for the field by ACGME. OBJECTIVES/GOALS: ACGME has defined 20 milestones that serve as the goals for fellows in clinical informatics. Each fellow is rated from 1 to 5 on the achievement of each milestone, where 1 is entry-level, 4 is the level expected of a graduating fellow, and 5 is aspirational. We assessed fellows’ progress toward the personal goal levels that they set for each milestone. METHODS/STUDY POPULATION: At the start of the fellowship, we asked each fellow to rate the personal target levels that they want to achieve for each milestone. Since the default target level of achievement for a graduating fellow is a 4, we asked fellows to document exceptions from this target. We calculated a metric for each fellow’s achievement of each milestone as their achievement rating (assigned by mentors and rotation leaders during the semi-annual Clinical Competency Committee meeting) divided by the fellow’s desired level of achievement. In summarizing across the milestones, we counted those milestones having achievement metrics >=1.0 as ‘achieved,’ and then for milestones that were not achieved, we calculated an average for the fellow. RESULTS/ANTICIPATED RESULTS: As of June, 2020, our two graduating 2nd-year fellows had fully met 9/20 and 18/20 milestones, respectively. For the unmet milestones they averaged 81% and 85% achievement. The largest shortfalls were 75% achievements in Assessing User Needs for one fellow, and in Recognition of Errors for the other. One of our three 1st-year fellows had fully met 3/20 milestones; the other two had met none at 1st-year’s end. For unmet milestones, the 1st-year fellows’ average achievement metrics were 69%, 67%, and 52%. The greatest shortfalls were in Resource Utilization (creating job descriptions, budgeting etc.) and in Communication with Patients and Families. However, the rotations that would expose them to project management and to patient-facing systems such as MyChart come in our 2nd-year. DISCUSSION/SIGNIFICANCE OF FINDINGS: Assessing milestones met plus the percent achievement for those not yet met provides a useful metric for comparing fellows and identifying areas in need of more training. Although milestones will soon change to reflect the recent practice analysis for clinical informatics, we expect that this approach to assessing fellows will remain equally useful.

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/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: 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: 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/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/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/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/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 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/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.

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: To establish a conceptual framework to develop a CTS-IDP with data analytics, and an e-Learning Faculty Development Guide on best practices and use of the IDP over the CTS academic life-course. METHODS/STUDY POPULATION: To accomplish our goal, we propose the following methods: (1) an online survey, using a convenience sample of the 24 KL2 CTSA IDP Collaborative members (conducted in 2017), to assess perceived needs for a universal CTS-IDP, current IDP practices, barriers to IDP use, and to discern and align each CTSA Hub’s interests, expertise and commitment to specific areas of the study; (2) A scoping narrative literature review, utilizing the Arksey and O’Malley framework covering the time period corresponding to the initiation of funding (1999) of the original K30 Clinical 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; research contracts; career planning; mentor guide), initially delineated by USC reference librarian and to be expanded by reference librarian services from the Icahn School of Medicine at Mount Sinai and University of Rochester, and performed on NIH 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 for published papers in English and Spanish. For this portion of the work, we will describe and characterize (1) research career development or progression constructs, domains, and milestones; (2) establish the presence or absence of defined and/or pre-specified timed milestone objectives and inclusion of SWOT analytics (strengths, weaknesses, opportunities, and threats) and/or Gantt chart approaches; (3) delineate IDPs structure, toolkits and their key features (competencies, skills acquisition and processes utilized); (4) and identify specific gaps to best address the need for personalized career development education. Based on this review, we will synthesize CTS milestones, develop a time frame for meeting RCD expectations, and establish RCD benchmarks for achieving these milestones, all in consensus with the IDP Collaborative Workgroup. RESULTS/ANTICIPATED RESULTS: Seventy-seven percent of the IDP CTSA’s responded to the online survey, led by University of Rochester, and the results can be summarized as follows: (1) 100% agreed that the IDP process is important and should be considerably improved to optimize effectiveness; (2) a range of diverse IDP formats are utilized, making comparisons across programs difficult; (3) 50% of CTSA hubs report only fair to good compliance with the IDP process; (4) a major barrier to the IDP process is lack of instruction regarding how best to utilize; (5) poor alignment of currently available IDPs designed for basic science PhDs with CTS investigators; (6) an absence of a CTS specific IDP to best foster RCD for this specific career trajectory. When asked: What are the barriers to writing a detailed and thoughtful IDP, responses in order of agreement from greatest to least were: No verification of acquired competencies, beyond self-report (56%), Static platform (38%), Not constructed for clinical and translational researcher (31%), No analytical or documentation on use (31%), No instruction given to scholars on how to use it effectively and efficiently (31%), The IDP we are using is more constructed for PhD students and postdoctoral fellows (25%), No instruction given to the scholars on why it is important as adult learners (19%), and Not constructed for early career physicians/scientist (13%). Additional progress has been made on our Scoping review: An initial ABI/Inform and PubMed USC research librarian conducted search using Author names yielded 72 articles, of which only 2 were relevant to the topic at hand. A ProQuest™ search yielded 19 potentially relevant articles, 11 of which were of relevance to the topic of IDPs; and a Google Scholar search yielded 18 and 25 on career development and self-management, respectively. This has enabled us to put forth an initial model of factors that impact the purpose and design of IDPs that includes? DISCUSSION/SIGNIFICANCE OF IMPACT: Discussion: Our initial data suggests that many CTSA institutions see the need to further enhance the mentoring process with a more informed and personalized IDP template and process. Furthermore, our initial scoping review suggests a framework upon which to build specific components of a more ideal and useful IDP to best guide mentored research career development of CTS trainees. Significance: Developing and evaluating collaborative evidence-based CTS IDP and corresponding e-Learning Guide could potentially prevent or reduce important delays in RCD, a common roadblock for the translation of clinical interventions. Ultimately, the CTS-IDP serves not only to support and frame a scholar’s RCD “habits of mind” during training and early career development but to also to achieve a sustainable long-term career at a CTS researcher equipped to meet the ever challenging and dynamic research landscape.

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.