OBJECTIVES/GOALS: The Translational Science Benefits Model (TSBM), developed at Washington University in St. Louis, was used to create a survey to collect group-level data on the real-world impacts of research. It was used with two cohorts of CTSA-supported pilot studies to compare the benefits of campus-community partnerships to campus-only projects. METHODS/STUDY POPULATION: Investigators from two funding streams were surveyed: a campus-based cohort (n=31), and a campus-community partnership cohort (n=6). All studies were related to COVID-19. The Translational Benefits Survey collected quantitative and qualitative data for each of the 30 TSBM benefits, in 4 benefit categories: clinical, community, economic and policy. Text provided by investigators to support each reported benefit was evaluated by two coders through a process that required coder consensus to verify a benefit as realized. Verified benefits were aggregated for each cohort, and the percentage of projects per cohort with realized clinical, community, economic and policy benefits were calculated. RESULTS/ANTICIPATED RESULTS: Campus-community partnerships did not realize any clinical benefits, whereas 26% of campus-based projects realized at least one clinical benefit. In contrast, campus-community partnerships were more likely to realize community health benefits (17% vs 10% of campus projects) and economic benefits (17% vs 13% of campus projects). We identified a substantial amount of self-reported benefits (64% across all categories) that were unable to be confirmed as realized using the provided text, which either described activities not relevant to the selected benefit, or lacked critical details needed to verify that the benefit was realized. DISCUSSION/SIGNIFICANCE: This project demonstrates that the TSBM can be utilized to collect group-level data and to compare cohorts’real-world benefits. It also illuminates the need to improve the process for verifying self-reported benefits. Sharing data on these real-world impacts has the potential to convey the strengths of translational science to the public.

ABSTRACT IMPACT: The proposed research study will provide critical pilot data on the effect of using the prebiotic (HAMS-AB) on the gut microbiome profile, Beta-cell function and immune markers in humans with T1D. OBJECTIVES/GOALS: The overall objective of this study is to assess how the prebiotic high amylose maize starch that has been acetylated and butyrylated (HAMS-AB) impacts the gut microbiome profile, short chain fatty acid (SCFA) production, glycemia, Beta-cell function/health and immune responses in newly diagnosed youth with type 1 diabetes (T1D). METHODS/STUDY POPULATION: We are performing a pilot randomized cross-over trial. We plan to recruit 12 newly-diagnosed T1D youth with residual Beta-cell function between 12-16 years of age. We will profile the gut microbiome using metagenomics, measure stool SCFA levels using mass spectrometry, assess glycemia using continuous glucose monitoring, assess insulin production using mixed meal tolerance testing, assess Beta-cell stress using proinsulin/C-peptide levels, and test immune responses by examining cytokine levels and frequency, phenotype and function of T cell markers in peripheral blood. RESULTS/ANTICIPATED RESULTS: Thus far, we have enrolled 3 participants, 1 has completed the study. Baseline assessments indicate that we have technical feasibility of performing the above studies and measurements. Recruitment and enrollment are ongoing. We hypothesize that the use of HAMS-AB in newly diagnosed youth with T1D will (i) improve the gut microbiome profile, (ii) increase SCFA production, (iii) improve overall glycemia and Beta-cell function and (iv) modulate the immune system and mitigate autoimmunity. DISCUSSION/SIGNIFICANCE OF FINDINGS: Given the failure to develop a cure for T1D despite multiple completed intervention studies and the unknown long-term effects of immune-modulatory therapy on those at risk for or those diagnosed with T1D, prebiotics such as HAMS-AB may offer a simple, safe, yet inexpensive and tolerated dietary alternative approach to mitigating disease.

OBJECTIVES/SPECIFIC AIMS: A hallmark of progressive HIV-1 infection is the massive activation and depletion of the gut barrier protective CD4 T helper subsets (Th17 and Th22) in the intestinal mucosa. The loss of these cells is thought to contribute to microbial translocation and systemic immune activation that occurs during chronic infection. In addition to the loss of protective Th subsets, we previously showed that chronically HIV-1 infected individuals have an altered colonic mucosal microbiome, which is in part characterized by a lower relative abundance of bacteria that produce the short-chain fatty acid butyrate in conjunction with increased relative abundance of gram-negative pathobionts. This dysbiosis was linked to markers of mucosal and systemic immune activation in these individuals. Following up on these clinical observations, we sought to understand how a loss of butyrate might contribute to HIV-associated inflammation. Initial studies showed that the addition of butyrate to cultured lamina propria mononuclear cells (LPMC) resulted in decreased pathobiont-driven gut T cell activation, HIV-1 infection levels and production of IL-17 and IFNy. Since the gut barrier protective Th17 and Th22 subsets are preferentially infected and depleted, which is critical to HIV-1 pathogenesis, we wanted to determine the mechanism by which butyrate modulates activation of these important Th subsets in the gut. METHODS/STUDY POPULATION: Total LPMCs or purified LP CD4 T cells were isolated from human jejunal tissue (n=3–6), labeled with CFSE and cultured with TCR/CD28 beads to mimic APC driven T cell activation, with the addition of butyrate at physiologic doses(0–2 mM). Four days after culture, secreted cytokine(IL-17 and IFNy) levels were measured by ELISA. Cells were then short-term (4 hr) mitogenically stimulated (PMA/Ionomycin) in the presence of a golgi transport inhibitor. Total CD4 T cell activation (CD38+/HLA-DR+, CD25+), proliferation (CFSElow), and frequencies of intracellular cytokines were measured by multi-color flow cytometry. Paired t-tests were performed to determine statistical significance. RESULTS/ANTICIPATED RESULTS: Butyrate inhibited LP CD4 T cell activation (p=0.013) and proliferation (p=0.015) within total LPMCs stimulated with TCR/CD28 beads in a dose-dependent manner, with significant activity starting at 0.125 mM. Quantification of total secreted cytokines revealed that butyrate significantly decreased both IL-17 and IFNy production after 4 days of culture at 0.0625 mM and 0.25 mM of butyrate, respectively. Assays using purified LP CD4 T cells demonstrated that butyrate directly decreased LP CD4 T cell activation, proliferation and cytokine production in response to TCR/CD28 stimulation. Studies on specific T helper subsets revealed that butyrate inhibited proliferation of Th17 cells at lower concentrations (IC50:0.147 mM) compared with Th1 (IC50:0.229 mM) and Th22 (IC50:0.258 mM) and Th non-IL-22/IL-17/IFNy producing (IC50:2.14 mM) subsets. In addition, it appeared there was a paradoxical increase of HIV-1 infection levels at lower concentrations of butyrate (0.125 mM). DISCUSSION/SIGNIFICANCE OF IMPACT: The addition of butyrate to activated LP CD4 T cells decreases TCR-mediated activation in a dose-dependent manner, and butyrate acts directly on purified LP CD4 T cell populations independent of other cell populations. Butyrate differentially inhibited the proliferation of Th17, Th1, and Th22 subsets, with Th17 cells being the most sensitive to butyrate but increased the infection levels of all T helper subsets at low concentrations. Further studies are needed to determine the mechanism of butyrate’s actions on LP Th cells and the sensitivity of Th17 cells to the inhibitory effects of butyrate. These results could help direct targeted manipulation of the colonic microbiome of HIV-1 infected individuals to help resolve inflammation and limit the impact of the infection in the gut mucosa and systemically.

Availability of trained professionals to assist researchers navigating regulatory pathways for new drug and device development is limited within academic institutions. We created ReGARDD (Regulatory Guidance for Academic Research of Drugs and Devices), a regional forum initially involving regulatory professionals from four Clinical and Translational Science Award (CTSA)-funded institutions, to build and capitalize on local expertise and to develop a regulatory guidance website geared toward academic researchers. Since 2015, members organized 15 forums covering topics such as FDA premarket submissions, gene therapy, and intellectual property for devices and therapeutics. Through user feedback, targeted surveys, and ongoing iterative processes, we refined and maintained a shared regulatory website, which reached 6000+ users in 2019. Website updates improved navigation to drug versus device topic areas, provided new educational content and videos to address commonly asked questions, and created a portal for posting upcoming training opportunities. Survey respondents rated the website favorably and endorsed expanding ReGARDD as a centralized resource. ReGARDD strengthened the regional regulatory workforce, increased regulatory efficiency, and promulgated best organizational and operational practices. Broad-scale deployment of the ReGARDD model across the CTSA consortium may facilitate the creation of a network of regional forums and reduce gaps in access to regulatory support.

Extensive health inequities exist for persons with criminal-legal involvement in the USA. Researchers, both novice and experienced, are critical in documenting these inequities and implementing programs that address the many health and social problems of this population. However, working with currently or formerly incarcerated persons brings new challenges to researchers that may have not been previously considered as necessary. Because incarcerated persons were systemically exploited by biomedical researchers until reform following the Civil Rights Movement, resulting in their designation as a vulnerable population in the Code of Federal Regulations, enhanced protections are necessary in implementing contemporary research involving incarcerated persons. These enhanced protections can delay or prolong the regulatory approval process, particularly to the novice carceral system researcher, which may discourage some from engaging with this important population. Drawing on the many years of experience working with incarcerated persons accumulated by the Sexual Health Empowerment (S)HE Team at the University of Kansas Medical Center (KUMC), this article offers some concrete steps toward getting started in this work.

OBJECTIVES/GOALS: Mobile health applications are widely used by the public but vary in how they are classified and regulated. This study examines the evidence of the safety and efficacy of mobile medical applications specifically focusing on those that are used to manage diabetes. METHODS/STUDY POPULATION: To understand the current regulatory landscape of mobile health applications (mHealth apps) for diabetes, a literature survey was conducted using the Pubmed database. Top mHealth apps were identified by searching the Apple store website using 10 key terms associated with diabetes management applications. A maximum of ten results, when available for each key term, were studied by exploring the FDA databases to understand how the products were regulated and if any were subject to recalls. These selected mHealth apps were also searched on clinicaltrials.gov to see if there were ongoing or completed clinical trials and if the trials were designed to include efficacy and safety outcome measures. RESULTS/ANTICIPATED RESULTS: Of the 71 mHealth apps for diabetes management that were identified, 16 were regulated. These products spanned a diverse range of functions including device data and decision support systems. Although 11 had clinical trial data demonstrating efficacy, only 4 had data demonstrating both efficacy and safety. Two of the regulated applications were subject to product recalls due to programming errors that resulted in incorrect insulin dose recommendations. These two applications had clinical trials evaluating efficacy but not safety. The companies noted that the incorrect insulin calculation from their respective mHealth app could cause either a low- or high-impact hypoglycemic event. DISCUSSION/SIGNIFICANCE OF IMPACT: With little to no clinical trial data to support their safety and efficacy, mHealth apps in the diabetes marketplace pose risks for patients as evidenced by recent safety-related recalls. The results of this study indicate that these products may need to be more tightly regulated.

OBJECTIVES/GOALS: The new CLIC Education & Career Development Gateway aims to be a translational science workforce ecosystem for CTSAs to share learning and training resources and career opportunities. The Gateway also provides individualized assistance to identify and implement TS learning and training resources. METHODS/STUDY POPULATION: The CLIC Education & Career Development Gateway, located on the CLIC website, is an entry way to: 1) the Education Clearinghouse, a platform where CTSA Program hubs can find and share educational resources individually or as part of resource kits; 2) the Opportunities Board, which includes jobs and mini-sabbaticals from CTSA Program hubs; and 3) the Education & Training Navigator, a personalized approach to education and training requests. These approaches help empower and support a cooperative learning and training community that is inclusive and collaborative, facilitating and amplifying opportunities for the sharing of educational resources throughout the translational science workforce. RESULTS/ANTICIPATED RESULTS: Through a person-centered, direct engagement approach, the anticipated outcomes of these efforts are to promote increased collaboration across CTSA Program Hubs and partners, and the amplification of accessible, relevant existing resources. Another anticipated outcome is increased production of educational materials through the reduction of work duplication and identification of gaps in education and training resources. The Gateway also provides an opportunity to communicate the work and efforts that consortium-level special groups (working groups, special interest groups, etc.) produce. Ongoing evaluations and suggestions will help determine future improvements and functionalities. DISCUSSION/SIGNIFICANCE OF IMPACT: CLIC’s education and training ecosystem promotes education as a community space to facilitate opportunities for collaboration and partnerships, amplifying visibility of the work created by members of the CTSA community, and encouraging a transformative career trajectory for trainees and scholars.

ABSTRACT IMPACT: We are adapting a global telehealth platform and model of care to the U.S. context in order to solve the problem of undertreatment of age-related hearing loss and, in turn, facilitate healthy aging and social engagement among older adults. OBJECTIVES/GOALS: Intelehealth is a nonprofit startup that provides medical care to last-mile populations in India by equipping frontline health workers with an open-source digital assistant and telemedicine platform. Here, we explore how this technology and model of care might be adapted to address health inequities in the context of the U.S. healthcare system. METHODS/STUDY POPULATION: We first sought to identify a specific healthcare need that we could address as a case study on applying the Intelehealth model more broadly in the U.S. context. We began with a needs assessment, wherein we conducted primary ethnographic research, expert interviews, and literature review to identify problems in the general areas of health disparities, community health workers, and telemedicine accessibility. We then scored each need on clinical impact, feasibility, business potential, and strategic fit. After a top need was selected, a root cause analysis was performed. Brainstorming and solution concepting will be followed by prototyping, iterative design with primary stakeholder feedback, usability testing, and finally implementation and validation of the solution. RESULTS/ANTICIPATED RESULTS: Of 106 needs, the most highly scored was undertreatment of age-related hearing loss (ARHL). The third most common chronic condition in the U.S., ARHL presents a significant barrier to healthy aging and the single largest modifiable risk factor for dementia; yet only 15% of those with ARHL regularly use hearing aids. Thus, a large market segment - nearly 30 million Americans - is underserved by the current hearing care paradigm. Root cause analysis revealed that the primary reasons for hearing aid non-use include stigma around aging, denial of hearing loss, poor awareness of resources, and insufficient education around proper use and maintenance. These barriers, being primarily sociocultural in nature, may be optimally addressed by community health workers, making ARHL an ideal fit for the Intelehealth model. DISCUSSION/SIGNIFICANCE OF FINDINGS: We have identified ARHL as an optimal test market for Intelehealth in the U.S. By developing a targeted intervention to improve hearing aid access and acceptability among older adults, we will create a generalizable model for delivering care through community health workers equipped with a decision support and telemedicine platform.

Funding for large research initiatives, such as those funded through the National Institutes of Health U mechanism, has increased since 2010; however, there is little published research on how to evaluate the success of such initiatives. Here, we describe the collaborative evaluation planning process undertaken by the Interactions Core of the Collaborating for the Advancement of Interdisciplinary Research in Benign Urology (CAIRIBU) research community, a clinical and translational research initiative funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Evaluation is necessary to measure the impact of our work and to allow for continuous improvement efforts of CAIRIBU activities and initiatives. We developed and implemented an iterative seven-step process that engaged the Interactions Core, NIDDK program staff, and grantees at each step of the planning process. Challenges faced in planning and implementing the evaluation plan included the time burden on investigators to submit new data for evaluations, finite time and resources for evaluation work, and the development of infrastructure for the evaluation plan. We call on funding agencies to include more explicit requirements for evaluation participation from grantees, as well as dedicated funding to support the evaluation process, in future funding opportunity announcements for large research consortia.

ABSTRACT IMPACT: This real-world study of what students value in crisis leadership fills an important gap in the literature and may inform future leadership development programs in undergraduate medical education. OBJECTIVES/GOALS: Leadership training is of growing importance and prevalence in medical education. The COVID-19 pandemic provides a unique insight into the qualities students value in leaders. Our qualitative study examined these leadership themes and provides a grounding for future development of leadership programs. METHODS/STUDY POPULATION: A conventional qualitative approach was used in order to allow open expression of ideas related to leadership in a pandemic. The authors developed a 5 free-text question survey instrument aimed to uncover student perceptions of leadership both during the current pandemic and in crises in general. A participant pilot was performed in order to ensure readability and ease of understanding. We used thematic analysis to examine the content of the survey responses, and inductive coding of the responses allowed identification of emerging themes. Medical students at the University of Michigan were surveyed. RESULTS/ANTICIPATED RESULTS: In total, 162 students completed the survey. The demographic characteristics of participants are shown in Table 1. Median age was 25 years old (range, 22-39). There was good representation from the 4 classes in the medical school with 20-30% from each medical school class and 5% of dual degree students. Thematic analysis demonstrated that students value personal characteristics of excellence in their leaders with an orientation towards helping other people. Students believe that leaders must know how to interpret and use information and then that these leaders must be able to communicate expertly to guide organizations. The final theme that emerged is that effective leaders must commit to decisive action. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study took place at a time of unprecedented crises and response examples were grounded in this real-world practice of leadership. These results and themes that emerged fill a critical gap and may facilitate future curriculum development for medical students and trainees.

Despite having the same underlying genetic etiology, individuals with the same syndromic form of intellectual developmental disability (IDD) show a large degree of interindividual differences in cognition and IQ. Research indicates that up to 80% of the variation in IQ scores among individuals with syndromic IDDs is attributable to nongenetic effects, including social-environmental factors. In this narrative review, we summarize evidence of the influence that factors related to economic stability (focused on due to its prevalence in existing literature) have on IQ in individuals with syndromic IDDs. We also highlight the pathways through which economic stability is hypothesized to impact cognitive development and drive individual differences in IQ among individuals with syndromic IDDs. We also identify broader social-environmental factors (e.g., social determinants of health) that warrant consideration in future research, but that have not yet been explored in syndromic IDDs. We conclude by making recommendations to address the urgent need for further research into other salient factors associated with heterogeneity in IQ. These recommendations ultimately may shape individual- and community-level interventions and may inform systems-level public policy efforts to promote the cognitive development of and improve the lived experiences of individuals with syndromic IDDs.

OBJECTIVES/GOALS: Degenerative cervical myelopathy (DCM) can lead to pain, disability, and permanent spinal cord impairment. Timely diagnosis and surgical intervention is essential to optimize functional outcomes for patients with CSM. Here, we compared patients who were admitted through clinic versus the emergency department (ED) for surgical management of DCM. METHODS/STUDY POPULATION: Patients aged ≥18 years admitted for surgery for DCM through clinic (elective cohort) were compared to a surgical cohort who were evaluated through the ED (call cohort). Basic demographics included age, gender, race, ethnicity, and insurance payor. Sociodemographic characteristics were estimated using the Social Deprivation Index (SDI) and the Area Deprivation Index (ADI) for the state of California, which were obtained through aggregated Zip Code Tabulation Area (ZCTA). Cervical MRI was reviewed to assess severity of spinal cord compression. Other outcomes included number of motion segments operated on, functional outcome using the Nurick classification, length of stay (LOS), disposition, and 30-day reoperation and readmission rates. RESULTS/ANTICIPATED RESULTS: From 2015 to 2021, 327 DCM patients received surgery (227 Elective Cohort, 100 Call Cohort). Elective cohort was mainly female (48.0 vs 30.0%, p=0.002) and white (72.7 vs 51.0%, p=0.0001). Call cohort was mainly uninsured/covered by Medicare/Medicaid (78.0 vs 67.0%, p=0.04), had higher SDI (68.0 vs 56.2, p=0.0003), ADI (7.9 vs 7.2, p=0.009), and cervical cord compression on MRI (78.0 vs 42.3% Grade III, p DISCUSSION/SIGNIFICANCE: Compared to DCM patients undergoing elective surgery, those admitted through the ED were more likely to be male, non-White, and socioeconomically disadvantaged, as measured by SDI and ADI. Postoperative outcomes were less favorable for these patients, including longer hospital stay, discharge disposition, and less Nurick grading improvement.

OBJECTIVES/GOALS: The goal of U-LINK is to bring together diverse scholars from multiple disciplines to address complex and challenging problems in healthcare, climate change, social equity, and community, through innovative team science, and aligned with the University of Miami’s strategic plans. METHODS/STUDY POPULATION: The U-LINK program has supported developmental and implementation projects through a competitive selection process. Developmental funding was intended for teams to develop and refine ideas and to become established as an effective team. Additional funding was provided to teams to advance their projects by conducting data collection and feasibility testing. In addition, U-LINK has supported fellowship for pre-doctoral and affiliated doctoral trainees. Team science training was provided to all teams through didactic lectures and hands-on training. Teams were tracked longitudinally by using surveys and bibliometrics to measure success and impact including scholarly output and follow on funding. Network analysis was performed to analyze research collaboration networks before and after ULINK funding. RESULTS/ANTICIPATED RESULTS: U-LINK has funded pilot programs and initial phases for 57 projects and 13 fellowships in the last three years. Over 400 individuals on teams from 16 schools/academic units collaborated on these projects on topics such as resilience, climate change, social equity and societal challenges, health, and impact of recent legislation on LGBTQ+ community. While data collection and analysis are ongoing, initial results show successful outcomes from U-LINK projects including publications and $29.5m in follow-on external funding. We anticipate network analysis to demonstrate increased and continued multi-disciplinary collaborations among U-LINK teams through co-authorship networks and increase in collaborative grants being submitted and/or funded. DISCUSSION/SIGNIFICANCE: The University of Miami’s U-LINK program has demonstrated success in forming interdisciplinary teams that have produced real-world solutions to complex problems by harnessing the inherent diversity and strength across UM’s programs.

OBJECTIVES/SPECIFIC AIMS: Black women experience discrimination that targets their intersecting gender and ethnic identities, termed gendered racism (Essed, 1991). The gendered racism Black women experience has been linked to negative mental health outcomes (Thomas etal., 2008). The ‘strong Black woman’ is a cultural symbol of strength depicting the Black woman as unwavered by hardships, such as gendered racism (Shorter-Gooden & Washington, 1996). However, recent research suggests that belief in the strong Black woman cultural construct is associated with negative mental health outcomes (Watson & Hunter, 2015). The goals of the current study were to (1) replicate previous findings suggesting that experiences with gendered racism is positively correlated with psychological distress, (2) replicate previous findings suggesting that belief in the strong Black woman construct is positively correlated with psychological distress, and (3) explore how experiences with gendered racism and belief in the strong Black woman construct might interact to predict distress. METHODS/STUDY POPULATION: A national sample of 112 Black women completed an online survey via MTurk. Survey measures included the Gendered Racial Microaggressions Scale, Strong Black Woman Cultural Construct Scale, and Psychological Distress Scale. RESULTS/ANTICIPATED RESULTS: Pearson correlation revealed that experiences with gendered racism was positively correlated with psychological distress, r = 0.23, p = .02. Pearson correlation also revealed that belief in the strong Black woman cultural construct was positively correlated with psychological distress, r = 0.39, p < .001. Multiple linear regression revealed an interaction between experiences with gendered racism and belief in the strong Black woman construct (β = -0.18, p = .04) that predicted psychological distress, R2 = .20, F(3,108) = 8.63, p < .01. Namely, for those with high belief in the strong Black woman construct, experiences with gendered racism did not predict distress, β = -0.31, t = -0.29, p = .78. However, for those with low belief in the construct, experiences with gendered racism positively predicted distress, β = -2.57, t = 2.31, p = .02. DISCUSSION/SIGNIFICANCE OF IMPACT: The results underscore the harmful effects of gendered racism and gendered racial stereotypes on Black women’s mental health outcomes. Striving to appear as the strong Black woman is not likely to help Black women overcome daily hardships. In fact, belief in the strong Black woman construct is likely to add extra difficulties.