OBJECTIVES/SPECIFIC AIMS: (1) To explain and discuss minority health and health disparities and the mechanisms, for example, individual behaviors and lifestyle, genetics and epigenetics, physical and cultural environment, and clinical events and health care, that lead to health disparities. (2) To explore the intersection between health disparity science and clinical and translational science. (3) To present and discuss the NIMHD Framework and how it can be used to guide multilevel research to address minority health and health disparities. (4) To highlight examples of NIMHD-funded novel and innovative research relevant to clinical and translational research from a health disparities perspective. METHODS/STUDY POPULATION: The NIMHD Research Framework will be introduced that is currently being used by NIMHD to address minority health and health disparity research. The Framework looks at targeted populations in relation to biological, behavioral, physical, and sociocultural environmental domains of influence as well as the health care system. These domains have different levels of influence: individual, family/interpersonal, community, and population. Targeted populations include NIH-designated health disparity populations, that include racial/ethnic minorities, socioeconomically disadvantaged populations, underserved rural populations, and sexual and gender minorities. The following research opportunities are among the many opportunities offered by NIMHD: Disparities in Surgical Care and Outcomes Social Epigenomics for Minority Health and Health Disparities Addressing Health Disparities Among Immigrant Populations. RESULTS/ANTICIPATED RESULTS: Select examples of NIMHD supported minority health and health disparities research that intersects with clinical and translational research will be presented. Candidate examples include: Genetic Architecture of Lupus (SLE) in individuals with Asian ancestry; A Novel Racial Disparity Marker for Risk Prediction in Triple Negative Breast Cancer Patients; Self-Applied Wearable Ultrasound Therapy for Osteoarthritis Management in Rural Central NY; Design and Development of a Multifunctional Self-service Health Screening Kiosk. DISCUSSION/SIGNIFICANCE OF IMPACT: Despite notable improvements gained as a result of medical and scientific advances, there continues to be an alarming disproportionate burden of illness and lack of representation in research among minority and other socially disadvantaged and underserved populations. To meet this challenge, NIMHD is committed to supporting a wide range of clinical and translational research aimed at the development of innovative strategies and approaches to reduce and, eventually, eliminate health disparities. NIMHD’s mission, research priorities, and funding opportunities are relevant to the efforts and interests of clinical and translational scientists, especially those interested in the translation of research findings into interventions, products, and tools that may improve minority health and quality of life, increase adherence to medication and treatment regimens, increase access, and improve the delivery of health services.

OBJECTIVES/GOALS: The process of decision making in serious illness and end-of-life care needs to be culturally appropriate, relevant, and equitable. For Chinese Americans, family and filial piety have been shown to impact this process, yet it remains poorly understood how. The purpose of our study is to explore this decision-making process qualitatively. METHODS/STUDY POPULATION: We created semi-structure interview guides, based on a literature review of values salient to serious illness and end of life care for Chinese Americans. The guides will be used to conduct three focus groups, each with ten participants who identify as Chinese American stratified by highest attained familial role (grandparents, parents, and adult children). This will be done in partnership with Greater Boston Chinese Golden Age Center, a local community organization, in English, Cantonese, and Mandarin using our interview guides with live interpretation. Focus groups will be audiotaped, transcribed, and analyzed using thematic content analysis and modified grounded theory. RESULTS/ANTICIPATED RESULTS: We anticipate that we will identify how, by whom, and why Chinese Americans in Boston’s Chinatown make decisions during serious illness and end-of-life. We anticipate that we will clarify cultural values, the balance between individual and collective values, intergenerational processes, individual and family suffering, and themes salient to this process. We expect to elucidate the role of family and filial piety during serious illness and end-of-life decision making and compare how these processes differ by generation and familial role for this population. DISCUSSION/SIGNIFICANCE: Using the family as a unit of investigation and focusing on intergenerational processes represent a novel approach to understanding decision making during serious illness and end of life care for Chinese Americans.

OBJECTIVES/SPECIFIC AIMS: This study seeks to test the feasibility and effectiveness of a brief Acceptance and commitment therapy (ACT) treatment for patients with persistent pain in a patient-centered medical home. METHODS/STUDY POPULATION: Participants are recruited via secure messaging, clinic advertisements and clinician referral. Primary care patients age 18 and older with at least 1 pain condition for 12 weeks or more in duration are stratified based on pain severity ratings and randomized into (a) ACT intervention or (b) control group [Enhanced Treatment as Usual (E-TAU)]. Participants in the ACT arm attend 1 individual visit with an integrated behavioral health provider, followed by 3 weekly ACT classes and a booster class 2 months later. E-TAU participants will receive usual care plus patient education handouts informed by cognitive behavioral science. Currently, 17% of our overall goal of 60 patients have completed ACT or enhanced treatment as usual. Average participant age is 49 years old, 70% female, and 70% Hispanic/Latino. Most report multisite pain conditions (e.g., musculoskeletal, fibromyalgia) and 30% are taking opioid medications. Data analysis in this presentation will include early correlational findings from baseline assessments. Upon study completion, we will analyze data using a general linear mixed regression model with repeated measures. RESULTS/ANTICIPATED RESULTS: The overall hypothesis is that brief ACT treatment reduces physical disability in patients with persistent pain when delivered by an integrated behavioral health provider in primary care. By examining a subset of patients on opioid medications, we also anticipate a reduction in opioid misuse behaviors. Additionally, it is anticipated that improvements in patient functioning will be mediated by patient change in pain acceptance and patient engagement in values-consistent behaviors. DISCUSSION/SIGNIFICANCE OF IMPACT: This pilot study will establish preliminary data about the feasibility and effectiveness of addressing persistent pain in a generalizable, “real-world” integrated primary care setting. Data will help support a larger trial in the future. If effective, findings could improve treatment methods and quality of life for patients with persistent pain using a scalable approach.

OBJECTIVES/SPECIFIC AIMS: Examine mental health service use and its correlates among depressed group in a national sample of population≥20 years old. METHODS/STUDY POPULATION: Analysis of data for adult≥20 years old from the NHANES 2006–2012. Depression was assessed using the 9-item PHQ. The use of mental health and antidepressant drug were used to indicate the service use. We utilized multiple logistic regressions to determine the independent association between service use and each independent variable (demographics, health status, food security, chronic conditions, and depression severity) controlling for other independent variables. Data were presented as adjusted odds ratio (AOR), 95% confidence interval (95% CI), and p-value of statistical significance. p-value of<0.05 indicates statistical significance. RESULTS/ANTICIPATED RESULTS: Of the 17,824 subjects, 22% had mild to severe depression. Among the depressed group, 25% used antidepressant, 17% used mental health service. For the use of mental health services among the depressed group, African-American (AA), ≥60 years old, uninsured and foreign born were less likely to use the mental health service relative to other groups [AOR=0.58 (95% CI=0.45–0.75), 0.21 (95% CI=0.14–0.33), 0.61 (95% CI=0.45–0.83), 0.41 (95% CI=0.17–0.99), respectively, p<0.05]. For the use of antidepressant drug among the depressed group, AA, Hispanics, uninsured and foreign born were less likely to use antidepressant drug relative to other groups [OR=0.26 (95% CI=0.20–0.33), 0.42 (95% CI=0.31–0.57), 0.41 (95% CI=0.31–0.56), 0.20 (95% CI=0.10–0.78), respectively, p<0.05). For the use of mental health services and/or antidepressant drug among the depressed group, 40–59 years old, AA, Hispanics, uninsured, foreign born were less likely to use mental health services and/or antidepressant drug relative to other groups [OR=0.52 (95% CI=0.38–0.72), 0.35 (95% CI=0.28–0.43), 0.52 (95% CI=0.40–0.69), 0.53 (95% CI=0.41–0.68), 0.30 (95% CI=0.13–0.68), respectively, p<0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: Our study showed that minority (AA and Hispanics), foreign born and uninsured with depression were less likely to use mental health services and/or antidepressant drug relative to other groups. Culturally and linguistically adapted intervention that involves community and providers to increase awareness about depression and the available services/treatment among minority, immigrant, and uninsured population are needed.

OBJECTIVES/SPECIFIC AIMS: Our goals in developing adaptations to the Community Engagement Studio model have been to: (1) enable investigators to consult with as broad a range of community “experts” (stakeholders) as possible, (2) make Studio participation feasible for stakeholders from rural and frontier areas, (3) create a safe environment for stakeholders from communities facing health disparities, who have had low participation in research, and (4) enable stakeholders to speak in the language in which they are most comfortable. METHODS/STUDY POPULATION: We have used several strategies to enable investigators to gain input from stakeholders in rural and frontier areas. If the research focuses on rural populations, we hold the Studio at a central location, usually at a restaurant in a private room, if this is available. If the investigator wants to hear from both rural and urban residents, we use videoconferencing via Skype or FaceTime when individuals have enough bandwidth to support it and/or feel comfortable using this technology. For those who have dial-up or no internet access, we provide a conference call line Trusting relationships are essential to creating a safe space in which stakeholders from communities facing health disparities can provide consultations to researchers. When an investigator wishes to consult with stakeholders from one racial/ethnic community, we contract with a leader or trusted member of that community to recruit appropriate stakeholders. The Studio is co-facilitated by a CCET staff member and a community leader in the community’s preferred language, with the leader translating for the CCET staff member. For Studios that involve stakeholders from multiple communities and that are conducted in English, we provide translators, if appropriate. Stakeholders using translation may be present in the room with other Studio participants or may be on the phone. RESULTS/ANTICIPATED RESULTS: Of the 35 Studios we have held, five have been held in rural locations and another five have included one or more rural/frontier stakeholders participating via phone or videoconferencing. Six Studios have been co-facilitated with community leaders and four others have included translators. Almost all Studios we have held in English have included individuals representing diverse communities. Anonymous surveys completed at the end of Studios show that participants report the following on 5-point Likert scales:. The facilitator managed the allotted time so that my voice was heard (67% strongly agree; 33% agree). The relevant experts were present at the Studio (78% strongly agree; 22% agree). I was satisfied with the Studio session (78% strongly agree; 22% agree). The Studio process was worth my time (89% strongly agree; 11% agree). The feedback provided by the community experts will improve the research project (68% strongly agree; 44% agree). Participants were also asked what they felt was their contribution to the research project. Among the most common themes were: increased researcher’s understanding of the community, increased researcher’s sensitivity to the community, provided feedback on the feasibility of the project, provided ideas on recruiting research participants, provided ideas for how to use the project results to benefit the community, and provided ideas on how to inform the community about the project. All participants said that they would participate in a Studio again. DISCUSSION/SIGNIFICANCE OF IMPACT: Studies at all stages in the research life cycle can be strengthened through consultations with community experts. These stakeholders can inform needs assessments, provide input on study design, supply critical information on supports and barriers to research participation, review study instruments for readability and cultural appropriateness, provide feedback on recruitment and educational materials, and inform dissemination of research results, among others. These consultations provide the most benefit to researchers when they include the voices of as broad a range of stakeholders as possible. We have shown that it is feasible to include stakeholders who live in rural and frontier areas in Studio consultations. We also have developed successful methods for holding Studio consultations with stakeholders who are members of communities facing health disparities and who speak multiple languages. This expanded representation in Community Engagement Studios strengthens research studies.

OBJECTIVES/GOALS: The overall goal of the Community-Engaged Research Core, supported by the Penn State Clinical and Translational Science Institute, is to invest in opportunities that promote collaboration between researchers and communities. Research in which community members are participating in the research process will more likely lead to reducing health disparities when compared to more traditional approaches. This abstract describes a community research day that brought researchers and community-based organizational leaders together to discuss critical areas of research. We aim to highlight a successful approach for how to work with a community, particularly one that has been distrustful of research, to facilitate and support collaborations between academic researchers and community-based organizational leaders (CBOs). Community-based organizational leaders are often the most knowledgeable individuals when it comes to identifying and discerning the needs and research priorities of their communities and they are generally in the best positions to help build greater trust between academic researchers and communities. METHODS/STUDY POPULATION: A Community Research Day Steering Committee was formed in the spring of 2018 and consisted of 10 community-based organizational leaders from Harrisburg, Pennsylvania, two Penn State University staff, and one Penn State University faculty member. The Steering Committee’s purpose was to design, plan, and execute an event (Better Together: Community Driven Awareness) in which community-organizational leaders and faculty researchers came together to discuss possible research collaborations to improve community health. The Steering Committee participated in bi-monthly planning meetings leading up to the event, Better Together: Community-Driven Awareness. During these planning meetings, members determined that mental health and nutrition were two critical areas deserving of more attention from research within their geographical community. Organizations were asked to identify sub-categories within mental health and nutrition that they saw as most relevant to their communities. The sub-categories that they selected became the theme topics for round table discussions at the main event. This information was also used to determine which academic researchers to invite to the event, based on scientific expertise. In addition to selecting these topics for table discussions, the Steering Committee provided advice on the agenda and program materials. The agenda for Better Together: Community-Driven Awareness featured a presentation from a successful collaboration between a faculty member and a community-based organization whose project was centered around suicide prevention in the school system. After the presentation, researchers and CBOs sat at round tables for facilitated discussions about their table’s theme. The facilitated discussions fostered new relationships and led to collaborations outside of the event. Following the round-table discussions, there was a presentation about funding and next steps. Lastly, feedback forms were given to each attendee to assess their experience of the event and to better understand what to improve upon for the future. RESULTS/ANTICIPATED RESULTS: Following the Community-Driven Awareness event, the Community-Engaged Research Core at Penn State released a call for proposals for planning grants to be awarded to faculty/community-based organization teams. These grants were intended to build capacity for externally-funded research that seeks to address important community-identified research questions. The internal grants support meetings to discuss mutual interests, develop research questions, identify leaders, conduct literature reviews, and collect pilot data. A team must have included, at a minimum, one Penn State faculty researcher and one community-based organizational leader as co-principal investigators. In the proposal, the team was asked to describe its preliminary research question, the work to be accomplished during the planning period, anticipated outcome(s) and deliverables, and preliminary ideas for seeking future external funding. A two-page narrative briefly described how the team members’ expertise/experience/constituencies would address the specified research question. In addition, the team provided a budget and budget justification. Planning grants ranged from $500-$5,000. Funds were allocated for a 6-12 month period. After the call was sent out, seven proposals were submitted and three were selected for external funding. Proposal topics included: * Exploring the Mechanism of Engagement in HIV Testing, Prevention, and Care Among African American and Hispanic/Latino Men who Have Sex with Men * Educator Translation of a Universal Social-Emotional Learning Program in School Practice * Growing Nutritious Communities: Gardening to increase access to and knowledge about fresh fruits and vegetables among residents in South Harrisburg, Hall Manor community. DISCUSSION/SIGNIFICANCE OF IMPACT: There are several academic institutions that have implemented similar events whose goal is to bring together academic researchers and community-based organizational leaders. To our knowledge, this is one of a few examples of an event that was developed from the ground up by a committee comprised mostly of community organization leaders. The community leaders guided the decisions made in all phases of the event design from determining the research themes to providing input on program materials. Additionally, our Steering Committee garnered the interest and attendance from over 20 community participating organizations, which attests to their commitment and dedication to seeing this event through from beginning to end. The feedback received from the event was overwhelmingly positive. Both academic researchers and community-based organizational leaders expressed their appreciation for an event that brought both parties together in a space where they felt comfortable to share ideas and knowledge. When asked how we could improve this event in the future, most attendees shared that they wanted more time and more opportunities to connect. One limitation of the event noted by attendees was that attendees were not able to sign up for the round table discussions themselves but were placed strategically at them by our Steering Committee. Therefore, at our next event, attendees will be able to select their tables and determine which themed topic they prefer to participate in. Lastly, we are considering how to best summarize the ideas that are generated from these round table discussions in a way that can be shared with the larger group and in a way that might foster collaborations outside of the event.

ABSTRACT IMPACT: Using network analysis and a systems science lens, UTMB’s Institute for Translational Sciences is able to quantify the evolution of REACH (its Community-Campus Partnership) as measured by the creation of new partnerships among member entities, promoting the translation and sharing of ideas and resources, and formalization of relationships among members. OBJECTIVES/GOALS: o Present how network analysis and systems science can inform evaluation of community-campus partnerships o Describe results from our experience with evaluating the REACH coalition o Summarize lessons-learned and likely improvements we are considering for our methodology METHODS/STUDY POPULATION: In 2016, we administered a network survey to core members of the Research, Education, and Community Health (REACH) coalition. The survey captured attributes about each organization, including size, populations served, etc. The survey also captured data on the relationships among these organizations, including joint meeting attendance, joint event planning, shared tangible resources, shared information, and formal legal agreements between organizations. These data were analyzed using network analysis methods. The survey was again repeated in 2018, and comparisons were made to evaluate how the network structure had evolved from 2016 to 2018. RESULTS/ANTICIPATED RESULTS: Joint meeting attendance was high in both 2016 and 2018; however, there was evidence of increased sharing of information and tangible resources in 2018. We also observed an increase in joint event planning among partnering agencies. Most strikingly, we observed that the number of formalized agreements (in the form of Memoranda of Understanding or more formalized contracts) between agencies more than doubled between 2016 and 2018. By measuring the evolution of our network of partners, we are able to document the evolution of a community-campus partnership over time. DISCUSSION/SIGNIFICANCE OF FINDINGS: Over the course of 2 years, the coalition signaled an increase in deeper collaborations beyond simply meeting together. The use of network analysis demonstrated utility and provided another dimension for evaluating the development of teams, partnerships, and coalitions.

OBJECTIVES/GOALS: Goals: Engage in collaborative approaches that target health disparities, especially among communities experiencing poverty or ethnic/racial minorities. Develop and sustain effective community-academic partnerships that foster trust through bidirectional communication and shared leadership leading to improved translational research. METHODS/STUDY POPULATION: The Community Health Science model was developed at UTSW over the past 20 years in efforts to integrate practices across 3 component areas – clinical practice, population health, and community organizations – into a single collaborative effort to improve health and reduce disparities. As part of the CTSA Program’s translational science efforts, we have extended this model to promote community engagement in research as an additional strategy needed to achieve health equity. Our Office of Community Health & Research Engagement operates 9 programs that each fit within one or more of 4 overarching conceptual pillars - Education/Resources, Collaboration/Partnership, Outreach/Service, Priorities/Perspectives - serving to bridge the community-academic divide and build strong, trusting relationships. RESULTS/ANTICIPATED RESULTS: The implementation of our model has resulted in measurable outcomes. To date, we have hosted 23 HealthStreet community events resulting in 464 health screenings, 203 health needs assessments completed, and 123 individuals joining our Community Research Registry allowing for future contact to participate in research. Our Community Health Coalition, comprised of 32 organizations, provides a forum for co-learning between researchers and stakeholders. We have awarded 9 grants ($175,800) for community-engaged projects. Our Community Advisory Panel has participated in 8 sessions with research teams. A total of 13 projects utilized the Spanish Language Resource, for a total of 30,617 translated words. Finally, we have hosted 9 Community Engagement Grand Rounds lectures, which included a total of 559 attendees. DISCUSSION/SIGNIFICANCE: Our model strengthens our capacity to build trust with communities and facilitate sustained community-academic partnerships. By prioritizing community engagement in research, we improve health equity by understanding community perspectives and increasing diversity in trials. We hope our model can be disseminated and scaled for greater impact.

OBJECTIVES/SPECIFIC AIMS: Acculturation and discrimination are associated with negative health outcomes including functional disability. The effect of these on functional disability in older African immigrants in the United States is not well understood. The purpose of this study is to describe and examine the experiences of acculturation, racial discrimination and functional disability in older African immigrants. METHODS/STUDY POPULATION: This study will use cross-sectional quantitative and qualitative mixed methods design. We plan to recruit 150 older (>55 years) participants through the African Immigrant Health Study and community-based organizations serving African immigrants. We will use the PROMIS physical function measure to assess functional disability, the Everyday Discrimination scale and the Psychological Acculturation scale will be used to measure discrimination and acculturation respectively. Higher scores indicate greater severity. RESULTS/ANTICIPATED RESULTS: We have recruited 12 participants so far. The mean age is 57 years and mean length of stay in the United States is 23 years. Mean disability score is 6.5 (range 1–38). Mean discrimination is 8.2 (range 4–15). The prevalent acculturation strategy of these participants (7) is marginalization (neither identified with the American nor African cultures). DISCUSSION/SIGNIFICANCE OF IMPACT: Preliminary results indicate pervasive discrimination and marginalization of study participants. Exploring these experiences can inform preventive strategies of coping and health behaviors that can decrease the negative effects of discrimination, acculturation and functional disability in African immigrants.

OBJECTIVES/GOALS: Recent in vitro evidence suggests that diverse parasite protein families called RIFINs and STEVORs are displayed on the surface of infected red blood cells and may have a role in severe malaria, but they remain sparsely studied in natural infections. We measured the RNA expression of these antigens in Malian children with severe or mild malaria illness. METHODS/STUDY POPULATION: We collected blood samples from Malian children aged six months to five years, including 14 with cerebral malaria, 10 with severe malarial anemia, and demographic-matched controls with mild, uncomplicated malaria. We extracted total RNA from each patient and used a custom capture array to selectively enrich Plasmodium falciparum parasite RNA. We then performed Illumina next-generation RNA sequencing and reconstructed parasite transcriptomes using reference-free de novo assembly. We identified RNA encoding RIFINs and STEVORs using an in-house classifier, then measured the diversity and abundance of gene expression for each infection. Expression diversity was defined as the number of unique variants transcribed. Expression abundance was calculated as transcripts per million (TPM). RESULTS/ANTICIPATED RESULTS: Cerebral malaria cases, but not severe malarial anemia cases, had higher diversity and abundance of RIFIN expression compared to mild infections. Type A RIFINs predominated over Type B RIFINs, and the same two RIFINs were predominantly expressed in all disease phenotypes. We anticipate that predominantly expressed RIFINs share high sequence homology with variants previously shown to bind blood antigens or immune inhibitory receptors. STEVOR expression was also higher in cerebral malaria compared to mild malaria, but STEVOR transcripts were sparse overall. DISCUSSION/SIGNIFICANCE: Elevated RIFIN expression in cerebral malaria over mild malaria supports a role for these antigens in pathogenesis. Severe malarial anemia may progress through a different pathogenic mechanism. Predominantly expressed RIFIN variants may be promising targets for vaccines and therapeutics to protect children against cerebral malaria.

OBJECTIVES/GOALS: We aimed to determine if GLP-1 receptor agonists exert beneficial effects on surrogate measures of cardiovascular function independently of weight loss. Our objective was to compare the outcomes between GLP-1 receptor agonist treatment versus a similar drug without cardiovascular benefit versus weight loss through diet alone. METHODS/STUDY POPULATION: We enrolled 88 individuals with obesity (BMI ≥ 30kg/m2) and pre-diabetes and randomized them in a 2:1:1 ratio to 14 weeks of the GLP-1 receptor agonist liraglutide, the dipeptidyl peptidase-4 inhibitor sitagliptin, or hypocaloric diet. Sitagliptin blocks degradation of endogenous GLP-1 but does not cause weight loss or lower adverse cardiovascular outcomes. Treatment was double-blinded and placebo-controlled for drug, and unblinded for diet. Primary endpoints were flow-mediated dilation (FMD) to assess endothelial vasodilatory function, and plasminogen activator inhibitor-1 (PAI-1) to assess endothelial fibrinolytic function. We used a general linear model for each outcome and included gender as a covariate for FMD. Baseline characteristics were similar. Mean age was 50, with 32% men and 13% black. RESULTS/ANTICIPATED RESULTS: At 14 weeks, diet and liraglutide caused weight loss (diet -4.3 ± 3.2 kg, P<0.01; liraglutide -2.7 ± 3.2, P<0.01), while sitagliptin did not (-0.7 ± 2.0, P=0.17). Diet did not improve FMD at 14 weeks compared to baseline (+0.9%, 95% CI [-1.5, 3.3], P=0.46). FMD tended to increase after liraglutide and sitagliptin but was not significant (liraglutide +1.2 [-0.3, 2.8], P=0.12; sitagliptin +1.6 [-0.6, 3.8], P=0.15). Given that liraglutide and sitagliptin work through the same GLP-1 pathway, we combined the liraglutide and sitagliptin groups for overall effect on FMD, which was significantly improved from baseline (+1.4 [0.1, 2.8], P=0.04). Diet and liraglutide improved PAI-1 at 14 weeks (diet -4.4U/mL, [-8.5, -0.2], P=0.04; liraglutide -3.4 [-6.0, -0.7], P=0.01), while sitagliptin did not (-1.4 [-5.1, 2.3], P=0.46). DISCUSSION/SIGNIFICANCE: Activation of the GLP-1 pathway by liraglutide or sitagliptin improves FMD independent of weight loss, while PAI-1 improvement is weight-loss dependent and is only seen after liraglutide or diet. Our study suggests the cardiovascular benefit of liraglutide may be due to combined improvements in endothelial vasodilatory and fibrinolytic function.

The opioid crisis in the USA requires immediate action through clinical and translational research. Already built network infrastructure through funding by the National Institute on Drug Abuse (NIDA) and National Center for Advancing Translational Sciences (NCATS) provides a major advantage to implement opioid-focused research which together could address this crisis. NIDA supports training grants and clinical trial networks; NCATS funds the Clinical and Translational Science Award (CTSA) Program with over 50 NCATS academic research hubs for regional clinical and translational research. Together, there is unique capacity for clinical research, bioinformatics, data science, community engagement, regulatory science, institutional partnerships, training and career development, and other key translational elements. The CTSA hubs provide unprecedented and timely response to local, regional, and national health crises to address research gaps [Clinical and Translational Science Awards Program, Center for Leading Innovation and Collaboration, Synergy paper request for applications]. This paper describes opportunities for collaborative opioid research at CTSA hubs and NIDA–NCATS opportunities that build capacity for best practices as this crisis evolves. Results of a Landscape Survey (among 63 hubs) are provided with descriptions of best practices and ideas for collaborations, with research conducted by hubs also involved in premier NIDA initiatives. Such collaborations could provide a rapid response to the opioid epidemic while advancing science in multiple disciplinary areas.

Northwest Arkansas, particularly Benton and Washington counties, is one of the highest COVID-19 hot spots in the United States (US), with more than half of all reported cases in this area identifying as Latinx or Pacific Islander, even though these communities account for less than 20% of the overall population. The University of Arkansas for Medical Sciences (UAMS) leveraged their existing relationship with 18 key community partners. Partners collaboratively developed a COVID-19 Response Strategy to ensure coordinated effort for Latinx and Pacific Islander communities with four interrelated strategies: health education, testing, contact tracing, and supported quarantine/case management.

OBJECTIVES/GOALS: Tumor PDL1 signals to immune cells for tumor immune evasion but has cell-intrinsic signals that promote tumor virulence. We identify novel tumor PDL1 depleting drugs (PDDs) to interrupt tumor-intrinsic PDL1 signals and sensitize tumors to targeted therapy in vitro and in vivo. METHODS/STUDY POPULATION: We screened the Prestwick and LOPAC libraries for FDA-approved drugs reducing B16 melanoma PDL1 > 2.6-fold. ?-lactam antibiotics were used at 80 ?M and Chk1 inhibitor rabusertib as indicated in T24 human bladder cancer, and murine ID8agg ovarian cancer, 4T1 breast cancer and B16. Genetic PDL1 KO was by CRISPR or shRNA and re-expression by lentivirus. Viability was by MTT and protein by immunoblot. We challenged 5 NSG mice/group with 2x106 T24 (SQ) cells and 5 BALB/c mice/group with 5x105 4T1 cells (mammary fat pad) and treated with cefepime (200 mg/kg), rabusertib (2.5 mg/kg), vehicle, or combo daily from day 3. RESULTS/ANTICIPATED RESULTS: Structurally-related ?-lactam antibiotics cefepime and ceftazidime are tumor PDDs. Cefepime or ceftazidime reduced tumor PD-L1 and thus its cell-intrinsic signals to deplete the DNA damage sensing Chk2 protein and promote rabusertib synthetic lethality in vitro and in vivo in a tumor PDL1-dependent manner independent of immunity. Structurally distinct ?-lactam antibiotics did not sensitize tumor cells to rabusertib, suggesting ?-lactam antimicrobial functions did not promote PDL1 depletion or rabusertib treatment effects in vivo. Although rabusertib effects were immune-independent, both PDDs induced immunogenic tumor STING signaling, suggesting they can improve tumor immunotherapy. DISCUSSION/SIGNIFICANCE: We show a rapidly translatable way to deplete detrimental tumor-intrinsic PDL1 signals, and sensitize tumors to rabusertib. We are testing PDD structure activity relationships to improve PDD effects and testing PDD effects on other treatments, e.g., PARP inhibitors, immunotherapy.

OBJECTIVES/SPECIFIC AIMS: Over 80% of CTSA programs have a community advisory board (CAB), an effective strategy to increase community engagement (CE) in research. Little is known about how the research discussed with CABs aligns with community priorities (i.e., bi-directionality). This program evaluation assessed the health topics presented by researchers to the CABs linked to our CE Program at all three Mayo Clinic sites (MN, AZ, and FL) for relevance to local community needs. METHODS/STUDY POPULATION: Two coders classified Mayo researcher presentations to our CABs from 2014-2018 for relevance to needs identified in the local 2013 and/or 2016 County Health Needs Assessments and specific topic(s); with high levels of agreement (Kappa=0.90). RESULTS/ANTICIPATED RESULTS: Overall, of the 65 presentations 41 (63%) addressed one or more local health needs (47% MN, 60% FL, 80% AZ). Cross-cutting health topics addressed at 2 sites were physical activity/obesity/nutrition and mental health. DISCUSSION/SIGNIFICANCE OF IMPACT: Findings were shared with our CABs to obtain input on future directions. The FL and AZ CABs are systematic in seeking out or initiating research projects that address local health needs, an approach the MN site is interested in adopting. Ultimately, it is important to demonstrate improved health outcomes with CTSA-based CE research strategies. Understanding community health needs and depth of researchers in those areas may help to focus priorities for demonstrating such outcomes.

OBJECTIVES/SPECIFIC AIMS: The goal of this study is to develop an effective and efficient STI preventive intervention among college students following the principles and phases of MOST. METHODS/STUDY POPULATION As part of the preparation phase, an explicit conceptual model, drawing heavily on theory and prior research, was used to translate the existing science into 5 candidate intervention components (ie, descriptive norms, injunctive norms, expectancies, perceived benefits of protective behavioral strategies, and self-efficacy). For the optimization phase, in Fall 2016 all first-year students (n=3547) from 4 universities were recruited to participate. Students were randomized to 1 of 32 different experimental conditions that included a combination of the candidate intervention components. Component effectiveness was evaluated using data from an immediate post-intervention survey on respective component mediators (eg, alcohol and sex-related descriptive norms). After a second factorial experiment (Fall 2017), only those intervention components that meet the pre-specified criteria of day ≥0.15 will be included in the optimized intervention. The evaluation phase will evaluate the effectiveness of the optimized STI preventive intervention via a randomized-control trial (Fall 2018). RESULTS/ANTICIPATED RESULTS: Preliminary results from the first factorial experiment suggest that descriptive norms and injunctive norms intervention components were significantly effective in reducing post-intervention perceived alcohol prevalence (β=−0.28, p<0.001) and approval of alcohol (β=−0.33, p<0.001), and sex-related norms (β=−0.23, p<.001). These results, in combination with process data, are being used to inform revisions of the intervention components to be included in a second factorial screening experiment. DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrates how an iterative approach to engineering an STI preventive intervention using MOST can affect the behaviors of college students and serve as a foundation for other translational science.

OBJECTIVES/GOALS: The Michigan Institute for Clinical & Health Research (MICHR) Community Engagement (CE) Program fosters translational science and community-engaged research (CenR) through education, connecting, supporting, and funding efforts and opportunities. METHODS/STUDY POPULATION: In Michigan’s Upper Peninsula, CE partnered with the Michigan Health Endowment Fund to develop a 3-hour workshop that consisted of a panel discussion on best practices of community engagement and a presentation on community engaged nonprofit management. The workshop was designed from mapping 60 participants’ pre-workshop survey findings and reviewing themes from a planning meeting transcript with six community partners. Key themes that emerged included participatory budgeting, collaborative governance, communications, and community planning. RESULTS/ANTICIPATED RESULTS: A mix methods post-workshop evaluation feedback survey was completed. The 9-item survey assessed workshop content, satisfaction, and knowledge gained using a Likert scale as well as opened questions about key takeaway and value added. Quantitative results to be analyzed. Qualitatively, some participants described the workshop as helpful and thoughtful about how to strengthen community engagement within their organizations. Others expressed a desire for more time. Regarding impact, CE received an uptake in consultations and inquiries into statewide pilot grants. The workshop facilitated new collaborations with philanthropic and community organizations serving the Upper Peninsula. DISCUSSION/SIGNIFICANCE: Lessons learned highlight trust, understanding community culture, and moving slowly in a newly formed collaboration. The approach utilized in the Upper Peninsula can inform translational methods for additional partnerships underway across the state of Michigan.