Understanding place-based contributors to health requires geographically and culturally diverse study populations, but sharing location data is a significant challenge to multisite studies. Here, we describe a standardized and reproducible method to perform geospatial analyses for multisite studies. Using census tract-level information, we created software for geocoding and geospatial data linkage that was distributed to a consortium of birth cohorts located throughout the USA. Individual sites performed geospatial linkages and returned tract-level information for 8810 children to a central site for analyses. Our generalizable approach demonstrates the feasibility of geospatial analyses across study sites to promote collaborative translational research.

OBJECTIVES/GOALS: This study explored whether gabapentin (GBN) differentially impacted heart rate variability (HRV) and whether HRV was associated with opioid withdrawal ratings among participants with opioid use disorder (OUD) undergoing a randomized, double blind placebo-controlled, trial (RCT) of GBN during a buprenorphine (BUP)-assisted taper. METHODS/STUDY POPULATION: Participants (ages 18-64) with OUD, no recent use of benzodiazepines/barbiturates, and no major psychiatric disorders or unstable medical conditions were enrolled in the RCT, inducted onto BUP starting week 1 day 1 and randomly assigned to receive adjunct GBN or placebo starting week 1 day 3. All participants began a 10-day BUP-taper beginning week 2 day 3. HRV measures were assessed on week 1 day 2 (before GBN/placebo induction), week 2 day 2, and week 3 day 5 (end of BUP taper). HRV metrics were analyzed using Two Sample T-Test to determine differences between GBN vs. Placebo. Correlations between HRV metrics and opioid withdrawal ratings administered at the above timepoints will be analyzed using Spearman correlation. RESULTS/ANTICIPATED RESULTS: 28 participants underwent at least 1 HRV session that resulted in usable data. Preliminary statistical analyses revealed that HRV trended lower for GBN subjects during PB exercises than Placebo subjects, demonstrated by a higher mean heart rate for GBN subjects compared to Placebo subjects (p=0.0506) at the end of the BUP-taper (week 3 day 5). We expect future analyses to demonstrate a negative correlation between certain HRV metrics indicative of parasympathetic tone and opioid withdrawal rating assessment scores indicative of withdrawal severity. Such findings would demonstrate an association between opioid withdrawal severity and lower parasympathetic tone and HRV. DISCUSSION/SIGNIFICANCE: Individuals with OUD have previously been shown to have a lower parasympathetic tone than individuals without OUD. Additionally, opioid withdrawal has been shown to be associated with reduced parasympathetic tone. Our initial findings suggest that adjunct GBN administration was not associated with lower parasympathetic tone during PB exercises.

OBJECTIVES/SPECIFIC AIMS: Determine timing of risk of readmissions within 30 days among patients first discharged to a skilled nursing facilities (SNF) after heart failure hospitalization and subsequently discharged home. METHODS/STUDY POPULATION: This was a retrospective cohort study of patients with SNF stays of 30 days or less following discharge from a heart failure hospitalization. Patients were followed for 30 days following discharge from SNF. We categorized patients based on SNF length of stay (LOS): 1–6 days, 7–13 days, 14–30 days. We then fit a piecewise exponential Bayesian model with the outcome as time to readmission after discharge from SNF for each group. Our event of interest was unplanned readmission; death and planned readmissions were considered as competing risks. Our model examined 2 different time intervals following discharge from SNF: 0–3 days post SNF discharge and 4–30 days post SNF discharge. We reported the hazard rate (credible interval) of readmission for each time interval. We examined all Medicare fee-for-service (FFS) patients 65 and older admitted from July 2012 to June 2015 with a principal discharge diagnosis of HF, based on methods adopted by the Centers for Medicare and Medicaid Services (CMS) for hospital quality measurement. RESULTS/ANTICIPATED RESULTS: Our study included 67,585 HF hospitalizations discharged to SNF and subsequently discharged home [median age, 84 years (IQR; 78–89); female, 61.0%]; 13,257 (19.2%) were discharged with home care, 54,328 (80.4%) without. Median length of SNF admission was 17 days (IQR; 11–22). In total, 16,333 (24.2%) SNF discharges to home were readmitted within 30 days of SNF discharge; median time to readmission was 9 days (IQR; 3–18). The hazard rate of readmission for each group was significantly increased on days 0–3 after discharge from SNF compared with days 4–30 after discharge from SNF. In addition, the hazard rate of readmission during the first 0–3 days after discharge from SNF decreased as the LOS in SNF increased. DISCUSSION/SIGNIFICANCE OF IMPACT: The hazard rate of readmission after SNF discharge following heart failure hospitalization is highest during the first 6 days home. Length of stay at SNF also has an effect on risk of readmission immediately after discharge from SNF; patients with a longer length of stay in SNF were less likely to be readmitted in the first 3 days after discharge from SNF.

OBJECTIVES/SPECIFIC AIMS: The objective of this study is to determine predictors and motives for sustained opioid use, prescription misuse, and nonmedical opioid use in the adolescent trauma population. METHODS/STUDY POPULATION: This is a prospective cohort study that will follow patients for 1 year and administer surveys to patients on prescription opioid usage; substance use; utilization of pain management and mental health services; mental and physical health conditions; and behavioral and social risk factors. Patient eligibility criteria include: (1) patient is 12–18 years of age; (2) admitted for trauma; (3) english speaking; (4) resides within Indianapolis, IN metropolitan area; and (5) consent can be obtained from a parent or guardian. Patients with severe brain injuries or other injuries that prevent survey participation will be excluded. The patient sample will comprise of 50 traumatically injured adolescents admitted for trauma who will be followed for 12 months after discharge. RESULTS/ANTICIPATED RESULTS: We expect that the results of this study will identify multiple risk factors for sustained opioid use that can be used to create targeted interventions to reduce opioid misuse in the adolescent trauma population. Clinical predictors such as opioid type, dosage, and duration that can be modified to reduce the risk of long-term opioid use will be identified. We expect to elucidate clinical, behavioral, and social risk factors that increase the likelihood adolescents will misuse their medication and initiate nonmedical opioid use. DISCUSSION/SIGNIFICANCE OF IMPACT: Trauma is a surgical specialty that often has limited collaboration with behavioral health providers. Collaborative care models for trauma patients to adequately address the psychological impact of a traumatic injury have become more common in recent years. These models have primarily been concerned with the prevention of post-traumatic stress disorder. We would like to apply the findings of our research to better understand what motivates adolescents to misuse pain medications as well as how clinical, individual, behavioral, and social factors affect medication usage. This may help identify patients at greater risk of developing a SUD by asking questions not commonly addressed in the hospital setting. For example, similar to how trauma centers have mandated brief interventions on alcohol use be performed for center verification, screening patients’ on their social environment may identify patients at greater risk for SUD than assumed. The long-term goal would be to prevent opioid use disorders in injured adolescents by providing better post-acute care support, possibly by developing and implementing a collaborative care model that addresses opioid use. Additionally, we believe our findings could be applied in the acute care setting as well to help inform opioid prescribing and pain management methods in the acute phase of an injury. Genetic testing to determine which opioid to prescribe pediatric surgical patients is starting to be done at some pediatric hospitals. Certain genes determine which specific opioid is most effective in controlling a patient’s pain and, further, using the optimal opioid medication can also reduce overdose. Our findings may help refine prescribing patterns that could increase or decrease the likelihood of developing SUD in patients with certain genetic, clinical, behavioral, and social characteristics.

Objectives/Goals: This study aimed to identify preferences for nutrient-dense foods with critical nutrients associated with reduced neuroinflammation and perinatal depression risk. Aim two evaluated the acceptability of daily intake and preparation methods of select foods in Black American pregnant and postpartum people living in food apartheid in St. Louis. Methods/Study Population: The study included a mixed-methods sequential explanatory design with data collection at the YWCA of Metro St. Louis during Early Head Start programming with 21 participants living in geographies with low grocery-to-convenience store ratios. We conducted an open-ended online survey to determine participants’ preferences for specific foods with high nutrient density. Food preferences were subjected to nutrient analyses using FoodData Central, and foods with the highest concentrations of critical nutrients associated with reduced neuroinflammation and perinatal depression risk were identified. We presented results during a focus group with participants who completed the survey and evaluated the acceptability of daily intake and preparation methods. Results/Anticipated Results: Preferred food choices with the highest concentrations of critical nutrients associated with reduced neuroinflammation and perinatal depression risk included dark red kidney beans, black beans, pinto beans, black-eyed peas, peanuts, almonds, pistachios, walnuts, pecans, carrots, spinach, red bell pepper, sweet potatoes, and salmon. Participant justifications for low acceptance of daily intake included allergic reactions, “dry” or “slimy” texture, undesirable taste or appearance, absence of cravings, preferring alternatives, complicated preparation methods, and financial tradeoffs. Participant justifications for high acceptance included desirable taste and texture, diverse modification and preparation options, and nutrient composition critical for anemia treatment. Discussion/Significance of Impact: The study identified nutrient-dense food preferences within a sample vulnerable to nutrient-poor alternatives and health consequences. Participant acceptance of nutrient-dense intake was contingent upon recipes fulfilling cravings, acceptance among persons preparing meals, and diverse options to prevent boredom with preparation methods.

OBJECTIVES/GOALS: A quarter of Puerto Rican pediatric population are overweight or obese. Pediatric obesity is established as a global public health concern that will develop liver complication as a Non-alcoholic fatty liver disease (NAFLD). This study aims to determine the association between body weight, liver size and texture in Puerto Rican pediatric population. METHODS/STUDY POPULATION: Twenty-nine (n=29) pediatric participants (20 unhealthy weight and 9 healthy weight) between 7 to 19 years underwent panoramic ultrasound imaging of the RLL. Craniocaudal RLL measurement and liver texture were evaluated. Body mass index and waist circumference were also compared. Shapiro-Wilk test and students t-tests were attained with significance at p < 0.05. RESULTS/ANTICIPATED RESULTS: Statistical differences were detected between healthy weight and unhealthy weight pediatric patients: (1) RLL craniocaudal diameter (p=0.006); (2) waist circumference (p < 0.001); (3) BMI (p < 0.001). Unhealthy weight (overweight and obese) pediatric patients presented a greater number of livers with fat infiltration (13) and hepatomegaly (15). DISCUSSION/SIGNIFICANCE: This preliminary results showed that liver size was larger and fatty infiltration are relatively frequent among overweight and obese pediatric patients. Prevention of unhealthy weight and the diagnosis of changes in liver texture and size among pediatric patients is important to prevent progressing of liver disease and avoid irreversible damage.

OBJECTIVES/GOALS: We have shown that glioblastoma upregulates blood-brain barrier drug efflux transporters via a mechanism that likely involves TNFα and PI3K/Akt. Our goal is to repurpose FDA-approved PI3K/Akt inhibitors to increase anticancer drug brain concentrations, which holds the potential for translation into the neuro-oncology clinic. METHODS/STUDY POPULATION: GL261 Red-FLuc and MBR525-1 Red-FLuc cells (2μl; 2.5K cells/μl; 1μl/min) were injected into the right hemisphere of 8-week old female J:NU mice (coordinates relative to bregma: AP -2 mm, ML -2 mm, DV -3 mm). Tumor burden was assessed weekly with IVIS® Spectrum in vivo imaging; tumor volume and invasiveness were measured by MRI and histopathology, respectively. On day 14 post-injection, mice received 5-ALA (200 mg/kg ip), and tumors were resected with a 2 mm punch biopsy tool and surgical fluorescence microscope (ex/em: 405/635nm). Drug efflux transporter expression and activity in isolated brain capillaries were determined by Western blot and substrate fluorescence assays, respectively. Cytotoxicity was assessed after 48-hour drug incubation using CyQuant MTT Cell Proliferation Assay kits. RESULTS/ANTICIPATED RESULTS: IC50 values of temozolomide, lapatinib, alpelisib, and miltefosine were N/A, 32, 20, and 190 μM for GL261 Red-FLuc cells and N/A, 49, 36, and 148 μM for MBR525-1 Red-FLuc cells, respectively. Median survival of GL261 Red-FLuc mice was 26.5d and significantly increased to 34d with resection (p=0.116). In GBM mice, drug efflux transporter expression and activity levels in brain capillaries isolated from the contralateral hemisphere were significantly upregulated compared to sham controls. Furthermore, treatment with FDA-approved PI3K/Akt inhibitors, alpelisib and miltefosine, significantly reduced drug efflux transporter expression and activity to control levels. In PK and survival studies, we expect that PI3K/Akt inhibition will increase brain uptake of anticancer drugs and prolong GBM mouse survival. DISCUSSION/SIGNIFICANCE: We have previously shown that PI3K/Akt inhibition reduces P-gp/BCRP levels in brain capillaries. Here, we vertically extend this strategy by repurposing the FDA-approved PI3K/Akt inhibitors alpelisib/miltefosine to improve brain uptake of anticancer drugs in GBM resection models.

ABSTRACT IMPACT: Understanding gene expression changes after viral vaccination and booster may help predict vaccine efficacy. OBJECTIVES/GOALS: Utilize a systems biology approach to identify gene expression changes after administration of Zaire Ebola virus glycoprotein expressed in a Chimp Adeno3 vector (ChAd3-EBOZ) and either boosted ˜7 weeks later with modified vaccinia Ankara MVA expressing Zaire and Marburg GPs plus Tai forest NP (MVA-BN ®Filo) or given saline (placebo). METHODS/STUDY POPULATION: As part of the phase 1b, open-label vaccination trial of ChAd3-EBO-Z in Mali, West Africa, peripheral blood mononuclear cells were isolated from eight volunteers for whole genome transcriptomics analysis. Four subjects received the MVA-BN ®-Filo booster and four received saline. Samples were taken prior to receipt of the booster or placebo, as well as 1, 7, and 14 days afterwards. Significant differentially expressed genes were identified using RNA-seq between baseline and post-MVA-BN ®Filo. Functional enrichment analysis against the GO Ontology Database and the Immune Signatures C7 collection of MSigDB (ImmuneSigDB) was performed. These differentially expressed genes were also examined for associations with Ebola antibody titers and cell-mediated immune responses. RESULTS/ANTICIPATED RESULTS: The majority of gene expression changes occurred on day 1 post-MVA-BN ®-Filo administration. 870 genes had significantly different expression when day 1 samples were compared to pre-booster baseline (791 upregulated/79 downregulated). Those upregulated genes are mainly involved type I interferon and regulation of viral life cycle pathways. The downregulated genes are involved in regulation of cellular defense response, lymphocyte mediated immunity. Comparing to the C7 Immune Signatures collection datasets, we identified more than 100 upregulated genes from 6 studies of yellow fever vaccination that were also significantly upregulated in our study. The top enriched ontological pathway of those genes is cellular response to type I Interferon. DISCUSSION/SIGNIFICANCE OF FINDINGS: The use of a systems biology approach to compare gene expression changes among vaccine studies utilizing whole genome transcriptomics data allows the identification of genes involved in the immune response to vaccination and might aid in predicting vaccine efficacy.

OBJECTIVES/SPECIFIC AIMS:.Outline the development and purpose of the partnership brokering database in REDCap. Provide an overview of the tool and how it works. Discuss how this tool facilitates partnership-brokering activities and discuss plans for future use METHODS/STUDY POPULATION: Research Electronic Data Capture (REDCap) is a secure, web-based application developed at Vanderbilt University to assist with systematic data management of small and medium sized projects. CCH utilized REDCap to build a custom data management warehouse entitled the Partnership Brokering Tool. Information compiled in various formats (handwritten notes, spreadsheets, etc.) over the past 10 years by CCH staff, was then systematically organized and entered into the Partnership Brokering Tool. The tool captures information such as individual contact information, organizational affiliation (academic, community, faith, government etc.), research interests (35 categories - asthma, diabetes, heart disease, etc.), communities of foci (children, elderly, LGBTQ, ethnicity, etc.), and target geographic community served (Chicago north, south, suburban, Illinois, etc.). RESULTS/ANTICIPATED RESULTS: Data was compiled on 451 community groups and organizations and 77 partners in academia thus far. Community organizations represent a range of community sectors including advocacy and policy groups, community-based, faith-based organizations, foundations, media, schools, etc. throughout the Chicagoland area. Data analysis activities are underway, however, results will also be shared regarding characteristics of the communities these organizations serve including:. Age range. Special populations (as defined by the CSTI grant). Underrepresented racial and ethnic communities. DISCUSSION/SIGNIFICANCE OF IMPACT: The Partnership Brokering Tool has provided a format for CCH to systematically gather information about the relationships staff have cultivated with community groups and organizations. Unlike an email management system, this REDCap project is highly useful in capturing the parameters of our partner pool, identifying partnership gaps, and matching individuals interested in collaborating with researchers or community organizations that have a particular skill set or research interest. The Partnership Brokering Tool has also facilitated stakeholder engagement dedicated to guiding the centers’ overall goals, objectives, and programming. Finally, utilizing REDCap has streamlined efforts in reporting quantitative and qualitative data about these organizations. In the next phase of this project, CCH will utilize the database to assess the nature of the relationship between CCH and community groups and organizations.

OBJECTIVES/GOALS: Theater has always served as a means of reflecting and understanding the human condition. Participatory theater further offers the option for viewers to participate in and thus additionally benefit from the performance itself. We use Playback Theater for outreach and research, eliciting information to guide research, education, and engagement. METHODS/STUDY POPULATION: Playback Theater is a type of improvisation that involves audience members recounting personal experiences which are then enacted by a theater troupe. Playback has evolved to include storytelling as a means of expressing and understanding difficult life experiences such as violence, bullying, incarceration, disaster, illness, etc. While not intended as therapy, it has been found to provoke insight and catharsis when used by trained practitioners. We are conducting Playback theater with LGBTQ+ and African American women to elucidate health disparities related to HIV/AIDS. Black/African Americans accounted for 42.1% of cases in 2019, and African American females are 15 times more likely to develop AIDS than white females. We hope to elucidate barriers to screening and treatment to inform early intervention. RESULTS/ANTICIPATED RESULTS: In community engagement, we employ a variety of strategies involving storytelling, since this simple act fosters multiple positive outcomes. For example, by talking about their experiences participants might find clarity about a difficult experience, facilitating coping or healing, or even letting go. By sharing their stories, others (clinicians, researchers, other patients, or the public) can learn what it is like to go through a particular illness or event. This knowledge can be used to allay patient fears or help researchers or clinicians to develop programming that better responds to needs. This novel approach to knowledge sharing also allows communication that may not otherwise be possible. Discussions about sensitive topics are enabled, often leading to shared understanding and potential solutions. DISCUSSION/SIGNIFICANCE: Through Playback Theater, we hope to identify and thus be able to address barriers to early screening and treatment for African American women and the LGBTQ+ population. We are also planning an event with children with cancer and their families to better understand their experiences and needs in both the clinical and familial settings.

OBJECTIVES/GOALS: While anti-seizure medications are effective, nearly one third of patients have seizures that go untreated. Prior studies using evoked seizure models have shown that activation of the Superior Colliculus (SC) display anti-seizure effects. Here we monitored and modulated the DLSC to suppress spontaneous seizures in a genetic model of epilepsy. METHODS/STUDY POPULATION: WAG/Rij rats (4 months old) were employed as study subjects. Animals were surgically prepared for virus injection (ChR2 excitatory opsin, or control vector), fiber optic implantation and cortical EEG for optogenetic studies. For In vivo electrophysiology, animals were implanted with a 16 wire multi-electrode array into the DLSC. In optogenetic experiments, we compared the efficacy of continuous neuromodulation to that of on-demand neuromodulation (real time detection of seizures) paradigms on a within-subject basis. We compared three stimulation frequencies on a within-subject basis (5, 20, 100 Hz). We quantified the number and duration of each spike wave discharge (SWD) during each two-hour-long trial. Electrode array single units were sorted and analyzed for activity before, during and after seizures. RESULTS/ANTICIPATED RESULTS: In vivo electrophysiology found there to be a significant decrease in single unit activity leading up to the start of SWDs. Interestingly, on-demand neuromodulation was effective in both females and males – where the greatest reduction in seizure duration was under 100 Hz light delivery. As expected, male and female animals injected with a control vector did not show a reduction in seizures in response to light delivery. In the open-loop (continuous) stimulation paradigm, optogenetic activation of the DLSC was without effect on the number or duration of SWDs at any of the frequencies examined. DISCUSSION/SIGNIFICANCE: SC activity is significantly decreased prior to the start of seizures. Furthermore, activation of the SC displays anti-seizure effects in a model of spontaneous seizures. A striking difference between open and closed-loop neuromodulation approaches underscores the importance of stimulation paradigm in determining therapeutic effect.

OBJECTIVES/GOALS:

• The podcasts highlight work from our partners: Indiana University, Purdue University and the University of Notre Dame.

• Our goal is to expand our podcast reach to include work from at least three additional CTSAs, as well as highlighting the benefits of translational research to the public.

METHODS/STUDY POPULATION:

• Aaron E. Carroll, is the director of Education and Workforce Development for the Indiana CTSI and a popular writer covering health, research, and policy for The New York Times. He is host of the Indiana CTSI-sponsored Healthcare Triage podcasts as well as the Healthcare Triage YouTube show, with 340,000 subscribers. We will leverage his audience and research expertise to grow the Indiana CTSI podcast participation and increase audience engagement.

• We will eventually allow the nation-wide network of CTSAs to pitch guests and shows covering Translational Research, and invite local CTSA leadership or faculty to participate in the podcast.

RESULTS/ANTICIPATED RESULTS:

• Utilizing quantitative analytics, we expect to see a significant increase in podcast downloads and listeners as we expand our offering to other CTSAs, beyond Indiana

• We expect that the CTSA-wide podcast will increase the nationwide level of knowledge and understanding of NCATS, translational research, and its benefits to society and healthcare.

• We anticipate, through this expanded podcast offering, a growing number of community members who are informed and engaged on the topics of translational research, clinical and translational sciences and beyond.

DISCUSSION/SIGNIFICANCE OF IMPACT:

• Podcasts are a convenient, portable, and efficient form of science communication.

• Podcasts also make information personal and offer us an excellent and innovative communications vehicle to spread the word about translational research, as well as the excellent work happening at each of our CTSAs.

OBJECTIVES/GOALS: The goal of theIntegrating Special Populations (ISP) Studiosis tointegrate communityvoice into research design and en hance diversity, equity, and inclusion in research, and disseminate findings in ways that improve health literacy and equity. METHODS/STUDY POPULATION: Based on the Vanderbilt Community Engagement Studio model, the ISP Studiowas designed through multiple phases, including Designand PilotStudioSessions. Stakeholders were diverse representatives of community and academic organizations serving special populations, as well asself-identified persons within special populations as defined by the NIH.Each phase of development and implementation of the Studio included an evaluation consisting of Likert scale and open-ended survey questions for process improvement and to integrate voices of the ISP community continuously. Demographic information and program outcomes were also collected via the evaluation survey. RESULTS/ANTICIPATED RESULTS: All Design Session (N=9) and Pilot Studio (N=10) participants indicated that the Design and Pilot were positive, relevant, bidirectionally useful, and fostered respect, trust, and inclusion. 100% of the panel strongly agreed the Studio met its goals and that the ISP Studios have potentialtobenefitspecial and under represented populations. Qualitative data and discussion on design will also be shared. Additi onaland relevant pointsincludepanelisttraining,compensation for community panelists, and ensuring accessibility. Evaluation outcomes from initial implementation of the ISP Studio will be discussed. DISCUSSION/SIGNIFICANCE: The ISP Studio is an innovative model that may increase engagement of special populations in the research process through co-creation and integration of lived experiences.It has the potential to improve research design, implementation, and impact.

OBJECTIVES/SPECIFIC AIMS: Children with medical complexity (CMC) comprise less than 5% of the pediatric population and over 40% of pediatric spending, yet receive poorer quality health care compared with other children. The American Academy of Pediatrics recently identified shared decision making (SDM) as a key quality indicator for CMC, but there is no consensus model for SDM in CMC. Objective: To create a model of SDM from perspectives of parents of CMC. METHODS/STUDY POPULATION: Interviews with parents of CMC explored SDM preferences and experiences. Eligible parents were ≥18 years old, English-speaking or Spanish-speaking, with a CMC <12 years old. Interviews were recorded, transcribed, and analyzed by 3 independent coders for shared themes using grounded theory. RESULTS/ANTICIPATED RESULTS: Interviews were with 31 parents [26 English speakers, median parent age 33 years (SD 11), median child age 3 years (SD 3.6)] in inpatient and outpatient settings. We identified specific, unique components of SDM that affect decision quality, the alignment of a decision with the parent’s preferences and values. Themes included: concerns about uncertainty of the child’s life trajectory, conflict during parent-provider communication, health system factors such as provider schedule; parent agency, and the influence of the source of information. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings provide specific components of SDM unique to CMC that can inform future research and interventions to support SDM for parents and providers of CMC.

Objectives/Goals: Community engagement is critical to promoting equity for those affected by clinical and translational research. Despite its importance, investigators rarely involve community stakeholders in ancillary projects such as secondary analyses. I use a study example to demonstrate how to meaningfully partner with communities in ancillary research. Methods/Study Population: Using data collected in a previous study, the aim of this secondary analysis was to examine whether pregnant women’s reports of social adversity during the third trimester were associated with their infant’s resting cortisol level at 1, 6, and 12 months of age. Community engagement at the study design phase included consultation with an institutional Community Advisory Board (CAB) whose expertise included lived experiences relevant to the context of the study (i.e., social adversity and pregnancy). Community engagement at the analysis and dissemination stage included deeper collaboration with three community research consultants (CRCs) from the CAB; all identified as women of color and mothers with relevant lived experiences. CRCs received compensation for time and effort and an invitation for co-authorship. Results/Anticipated Results: Consultations included written review as well as a live presentation and discussion with the CAB for feedback on the study proposal prior to submission for IRB approval. The focus of discussion was around the use of inclusive terminology and ensuring respectful and equitable representation of all participants in the original study, including those who reported experiences with social adversity during pregnancy. After receiving study approval, statistical analyses were finalized and CRCs actively engaged in discussions with the PI around the interpretation of results. CRCs significantly contributed to the development of solutions-oriented implications for practice, policy, and future research. All CRCs were co-authors on the study manuscript that was published in a top-tier international journal. Discussion/Significance of Impact: Community engagement in ancillary research is feasible and essential. True equitable collaboration requires partnership during all study activities, including critical phases (e.g., developing aims, data analysis). Researchers also should prioritize the use of datasets from studies that incorporated community partnership and engagement.

OBJECTIVES/SPECIFIC AIMS: The goals in this project were two-fold:. Develop metrics that assessed community engagement support the center provides, and. Systematically document the fluid and time-intensive nature of providing community engaged research support, as well as key outcomes. METHODS/STUDY POPULATION: The CCH utilized REDCap software in combination with Excel, to create and implement a data collection system to monitor and report on the full spectrum of engagement activities offered by the center. Center staff collaborated in identifying relevant metrics, developing the data collection instruments, and beta-testing instruments with real examples. This facilitated the integration of contextual factors (defined as factors such as the history, size, and diversity of the community, the organizational mission, the structure and size of the CE team, the number of years a university has been supporting community-engaged research work, etc.). Taking a collaborative approach in developing the center’s evaluation plan offered the added benefit of facilitating staff/faculty buy-in, building staff capacity, and engaging the team in understanding concepts related to performance measurement versus management. RESULTS/ANTICIPATED RESULTS: Key benefits of these engagement tracking systems include: consolidating data into a central location, standardizing tracking processes and critical definitions, and supporting more automated reporting systems (e.g., dashboards) that facilitate quality improvement and highlight success stories. Data were compiled and reported via on-line dashboard (REDCap and Tableau) to help center leadership and staff analyze:. Quality improvement issues (How quickly are we responding to a request for support? Are we providing resources that meet the needs of community partners? Academics? Community-academic partnerships?);. Qualitative process analysis (In what research phase are we typically receiving requests for support (e.g. proposal development phase, implementation phase, etc.)? What types of projects are applying for seed grants? After the seed grant ends, are the community-academic partnerships continuing to partner on research activities?);. Outcomes (Are new partnerships stemming from our support? Are supported research projects leading to new policies, practices, programs?). DISCUSSION/SIGNIFICANCE OF IMPACT: There is a gap in the literature regarding meaningful, actionable, and feasible community engaged metrics that capture critical processes and outcomes. This project identified many more relevant metrics and demonstrates that it is worthwhile to take a collaborative, inclusive approach to identifying, tracking, and reporting on key process and outcome metrics in order to convey a more comprehensive picture of community engagement activities and to inform continuous improvement efforts. Community engagement centers across CTSIs offer a similar range of programs and services. At the same time, much of the community-engaged research literature describes metrics related to community-academic grant submissions, funds awarded, and peer-reviewed publications. Experts that work in the arena of providing community engagement support recognize that these metrics are sufficient in understanding the spectrum of engagement opportunities. Community engagement (CE) teams nationally can utilize these metrics in developing their evaluation infrastructure. At the national level, NCATS can utilize the metrics for CE common metrics related to these programs and services. Critical to this process:. Leveraging resources that will facilitate collecting generalizable data (national metrics) while allowing sites to continue collecting nuanced data (local programs and services). Gathering input from CE teams, stakeholders, and researchers to further refine these metrics and data collection methods. Utilizing REDCap, Tableau and other resources that can facilitate data collection and analysis efforts.

OBJECTIVES/GOALS: Glioblastoma (GBM) is the most common and aggressive adult primary brain malignancy. Clinically, GBM is refractory to T cell immune checkpoint blockade (ICB), in part due to its dense immune suppressive myeloid stroma. Here we show that myeloid-targeting STING agonists can repolarize the GBM microenvironment to cure ICB-refractory GBM models. METHODS/STUDY POPULATION: Using the synthetic cyclic di-nucleotide STING agonist IACS-8803 (8803) we treated orthotopic ICB-refractory QPP8 orthotopic murine GBM tumors intratumorally. We then analyzed survival and performed high parameter flow cytometry profiling of the tumor immune microenvironment following STING agonist treatment. To assess the contribution of adaptive immunity to STING agonist therapeutic efficacy, we treated orthotopic QPP8 tumors implanted in RAG1 KO mice and monitored survival. RESULTS/ANTICIPATED RESULTS: We found that STING agonist therapy cured murine orthotopic QPP8 tumors, in contrast to ICB that showed no survival benefit. In RAG1-/- mice bearing QPP8 tumors STING agonist therapy extended survival, however, the curative effect observed in wild-type mice was lost in the absence of adaptive immunity. STING agonist-treated QPP8 tumors displayed increased counts of CD8 T cells and NK cells, and decreased CD8 T cell PD1 expression. Infiltration of STING-treated gliomas by Ly6C+ F4/80+ Mono-MDSC substantially increased; however, these cells expressed reduced CD206 and CD163, suggestive of reduced immuno-suppression. Finally, in the cervical LN of QPP8-treated mice the frequency and CD80/CD86 expression of cDC1 cells increased.​ DISCUSSION/SIGNIFICANCE: ICB has failed in GBM, and the suppressive myeloid stroma remains a major barrier to generating anti-GBM T cell responses. Our work shows that STING activation, which primarily targets innate immunity myeloid cells 'upstream' of T cells in the antitumor immunity cycle, can cure ICB-refractory GBM tumors in an adaptive immunity-dependent manner.

Objectives/Goals: To facilitate engagement between university researchers and Appalachian Kentucky communities, the UK Rural Research Hub (RRH) promotes Community Engaged Research (CEnR) and academic–community partnerships that have the greatest potential to conduct impactful research to improve health and reduce regional health disparities. Methods/Study Population: Through the UK RRH, a wealth of expertise and a range of services sustain successful CEnR. Hub coordinators provide research consultations, accelerate researchers’ engagement with the community, and facilitate the success of studies through study coordination, assistance with participant recruitment, data collection and interventions, and through dissemination back to the community. Results/Anticipated Results: UK RRH coordinators have supported numerous studies across the region. For example, RRH staff facilitated recruitment of and collected data from 40 Appalachian caregivers of patients with Alzheimer’s disease and related dementias (ADRD) in a study to improve home environments for patient well-being. The study provided pilot data for a successful K23 application. Other examples of supported research include studies to improve cancer screening uptake, self-management of diabetes, and cardiovascular disease risk reduction, resulting in improved care in the community and often providing pilot data leading to larger national grants. Discussion/Significance of Impact: Research addressing the complex health issues that burden Appalachian Kentucky requires community engagement to be successful. The UK RRH is at the heart of successful CEnR that benefits researchers and communities alike.

OBJECTIVES/GOALS: One of the most significant challenges to community engagement experienced by Clinical and Translational Science Award (CTSA) institutions is inadequate capacity of academic and community partners to engage in collaborative research. Several CTSAs within the consortium provide consultation services to help address this gap. METHODS/STUDY POPULATION: For over 10 years, the Michigan Institute for Clinical and Health Research (MICHR), a CTSA at the University of Michigan, has provided CEnR-specific consultations to partners seeking support for a variety of needs. Consultations can be requested for assistance with identifying potential partners, developing partnership infrastructure, finding CEnR funding opportunities, and incorporating CEnR approaches into research plans. When a consultation is requested, MICHR’s Community Engagement (CE) Program responds by planning a meeting with staff and faculty who have relevant skills, expertise, and connections. After the initial meeting, the CE Program provides follow-up communication and support based on the needs of the specific request, and often facilitates connections with potential partners. RESULTS/ANTICIPATED RESULTS: The two most frequent types of consultation requests involve 1) making connections with potential researchers or community partner organizations, and 2) providing guidance on research grant applications that involve community engagement. MICHR provides approximately 50 CEnR consultations each year, which have resulted in development of new partnerships, grant submissions, and research projects that utilize CEnR principles and address community-identified health priorities. DISCUSSION/SIGNIFICANCE OF IMPACT: This presentation will describe the evolution of MICHR’s CEnR consultation process and highlight successful outcomes and lessons learned over its 12-year history. CONFLICT OF INTEREST DESCRIPTION: NA