OBJECTIVES/SPECIFIC AIMS: 1.Assess changes in clinical research workforce landscape at Duke 2.Optimize and evaluate efficacy of a tier advancement process for clinical research career progression at Duke 3.Implement CRP engagement as a change management mechanism for workforce innovation METHODS/STUDY POPULATION: We evaluated 857 clinical research positions at Duke to understand changes in the workforce (demographics, numbers in each position and tier) since implementing the tier advancement process in 2016. To understand the efficacy of the tier assessment process, data from a subset of this population (n=84) who underwent the advancement process was examined for success rate. Individual employees and their managers were surveyed to understand their perception of the advancement process and identify areas for improvement. We also describe implementation of multiple mechanisms of community engagement to manage expectations around the tier advancement process and to provide opportunities for employees to self-manage their career planning, including portfolio planning and leadership opportunities. RESULTS/ANTICIPATED RESULTS: Whereas the clinical research workforce has grown by 5.5% since tiering began (2016, n=810; 2018 n=857). Nearly 13% of that growth has been in managerial or senior positions (2016, n=111; 2018 n=127). Distributions across job classifications changed only slightly, representing realignment of positions with study-level responsibilities over department-level responsibilities. Notably, clinical research nurses (CRNC & CRNC Sr.) was the only category including tiered and non-tiered positions to drop overall numbers between 2016 (n = 136) and 2018 (n=115), representing a shift in the workforce from research nurses to research coordinators. General demographics (gender, age) remained largely the same. A total of 359 positions have been hired during this time frame, nearly half of which were entry-level positions (175/359): 47 of these positions represent expansion of the workforce. Of 359 new hires since 2016, 271 currently still work in one of the research roles. Of the 84 employees who underwent the tier advancement process, 84% (43/51) succeeded in tier 2 advancement, 70% (14/20) succeeded in tier 3 advancement (CRC, CRNC, and regulatory coordinators), and 77% (10/13) of research program leaders (RPLs) succeeded in achieving tier two, which is the highest tier for this group. Fifty-five employees (65%) and 32 managers responded to a voluntary feedback survey. Overall confidence in the process improved in both groups from 2016 to 2018, most notably with managers. Both groups indicated a 10 hour reduction (employees = 35hr, 2016 and 25hr 2018; managers 25hr, 2016 and 15hr 2018) in time required to complete the tier advancement process. DISCUSSION/SIGNIFICANCE OF IMPACT: The use of objectively-assessed competencies is an important step in the development of a workforce. By 1) maintaining alignment with industry standards for competencies, 2) upholding high standards, and 3) offering a consistent approach to career growth, Duke is working to develop and maintain a workforce that supports high quality research. Since the implementation of standardized job classifications and competency-based tier advancement, the positions have undergone rigorous competency-based needs evaluation. This leads to better matched jobs to study needs as well as increased standardization across the clinical research workforce. We believe that the subtle workforce shifts represent alignment of our positions with the business needs of our clinical research enterprise. Additionally, approximately 15% of our clinical research workforce has taken advantage of the opportunity to advance their own careers. We have made significant improvements in the following tier advancement processes: standardization of assessments, scoring guides, and modes; changes from LMS to a REDCap delivery of the knowledge assessments; streamlined the utilization of electronic documentation; and additional guidance for employees and managers regarding portfolio inclusions. These improvements have increased satisfaction and acceptance with the advancement process and were made possible through strategic communication across the workforce. Regular town hall meetings and focus group feedback sessions have included the clinical research community in discussions of WE-R initiatives and provided a much-needed feedback loop for process improvement and change management. Moreover, inclusion of WE-R discussion in our Research Professional Network events has provided opportunities to discuss career advancement strategies as well as volunteer opportunities to grow and demonstrate leadership competencies.

OBJECTIVES/GOALS: The COVID-19 pandemic limited family caregivers’ in-person visits to their loved one’s healthcare appointments, and many switched to phone and video calls with their loved one’s healthcare providers. We sought to determine the relationship between virtual communication with their loved one’s healthcare providers and caregiver’s mental stress. METHODS/STUDY POPULATION: This research utilizes cross-sectional retrospective data from the National Study of Caregiving (NSOC) Round VI (June 2021 – January 2022), a nationally representative cohort of caregivers of Medicare enrollees ages 65+. Caregivers reported the frequency of contact with their loved one’s healthcare providers and the healthcare provider’s rated helpfulness. Univariate, bivariate, and multivariate analyses will be performed in Stata to characterize how communication frequency between caregivers and their loved one’s healthcare providers may be associated with outcome variables including symptoms of anxiety and depression, as measured by the Generalized Anxiety Disorder-2 (GAD-2) and Patient Health Questionnaire-2 (PHQ-2) scales. RESULTS/ANTICIPATED RESULTS: Analysis is ongoing. We anticipate that this research will help in determining significant symptoms of anxiety and depression as measured by the GAD-2 and PHQ-2 scales amongst caregivers according to their virtual communication use. In addition, we anticipate that results may vary based on sociodemographic characteristics including gender, age, race, ethnicity, socioeconomic status, and level of education. Other possible covariates that might be associated with varying levels of stress in using virtual communication include caregiver’s health status and comfort with technology. DISCUSSION/SIGNIFICANCE: This research is important as many caregivers cannot attend their loved one’s healthcare appointments in-person, like in situations of geographic distance or inflexible work hours. Further, study results may identify stress disparities among caregiver sociodemographic groups for future targeted intervention.

Retrospective case studies of initiatives supported by the National Institutes of Health’s Clinical and Translational Science Award (CTSA) hubs can be used to identify facilitators and barriers of translational science. This case study investigates how a CTSA Expanded Access program adapted to changing FDA guidance issued in 2020 to support clinicians’ treatment of COVID-19 patients in Michigan. We studied how this program changed throughout the pandemic to support physicians’ requests for remdesivir, convalescent plasma, and other uses of unapproved drugs and novel medical devices. A protocol for retrospective translational science case studies of health interventions developed by CTSA evaluators was used for this case study. Data collection methods included seven interviews and a review of institutional data, peer-reviewed publications, news stories, and other public records. The barriers identified include evolving guidance, misalignment of organizational operations, and the complexity of the research infrastructure. The facilitators of translation include collaboration between research and care teams, increasing engagement with a broad network of supporters, and ongoing professional development for research staff. The findings of this case study can be used to inform future investigations of the principles underlying the translational process.

OBJECTIVES/SPECIFIC AIMS: (1) Develop a concept map of ideas from diverse stakeholders on how to best improve training programs. (2) Assess the degree of consensus amongst stakeholders regarding importance and feasibility. (3) Identify which ideas are both important and feasible to inform policy and curricular interventions. METHODS/STUDY POPULATION: Concept mapping is a 4 step approach to data gathering and analysis. (1) Stakeholders [pediatricians (peds), MH professionals (MHPs), trainees, parents] were recruited to brainstorm ideas in response to this prompt: “To prepare future pediatricians for their role in caring for children and adolescents with mental and behavioral health conditions, residency training needs to...”. (2) Content analysis was used to edit and synthesize ideas. (3) A subgroup of stakeholders sorted ideas into groups and rated for importance and feasibility. (4) A large group of anonymous participants rated ideas for importance and feasibility. Multidimensional scaling and hierarchical cluster analysis grouped ideas into clusters. Average importance and feasibility were calculated for each cluster and were compared statistically in each cluster and between subgroups. Bivariate plots were created to show the relative importance and feasibility of each idea. The “Go-Zone” is where statements are feasible and important and can drive action planning. RESULTS/ANTICIPATED RESULTS: Content analysis was applied to 497 ideas resulting in 99 that were sorted by 40 stakeholders and resulted in 7 clusters: Modalities, Prioritization of MH, Systems-Based, Self-Awareness/Relationship Building, Clinical Assessment, Treatment, and Diagnosis Specific Skills. In total, 216 participants rated statements for importance, 209 for feasibility: 17% MHPs, 82% peds, 55% trainees. There was little correlation between importance and feasibility for each cluster. Compared with peds, MHPs rated Modalities, and Prioritization of MH higher in importance and Prioritization of MH as more feasible, but Treatment less feasible. Trainees rated 5 of 7 clusters higher in importance and all clusters more feasible than established practitioners. DISCUSSION/SIGNIFICANCE OF IMPACT: Statements deemed feasible and important should drive policy changes and curricular development. Innovation is needed to make important ideas more feasible. Differences between importance and feasibility in each cluster and between stakeholders need to be addressed to help training programs evolve.

OBJECTIVES/GOALS: To identify the role of sialoglycans in the mechanisms underlying cancer-associated fibroblast-derived exosomes (CAFEX) immuno-regulatory properties. The central hypothesis is that CAFEX manipulates the immune response to allow immunoevasion and glycomic approaches can identify the signaling factors involved. METHODS/STUDY POPULATION: Cancer associated fibroblasts (CAFs) were isolated from primary head and neck tumors, expanded, characterized and cryopreserved prior to experimentation and isolation of CAFEX. Sialoglycan expression was determined using lectin-specific staining of cells and bead-captured CAFEX in combination with flow cytometry analysis. Siglec expression and expression of M2-macrophage markers were also determined by flow cytometry analysis and cytokine bead arrays. Inhibition studies involved either the enzymatic removal of cell-surface sialoglycans or alternatively, a specific small molecule analog inhibitor of sialoglycan transferases. RESULTS/ANTICIPATED RESULTS: Both CAFs and CAFEX expressed abundant levels of cell-surface sialoglycans. CAFEX induced an M2-macrophage phenotype in primary monocytes, based on surface marker expression and cytokine secretion profiles. The induction of the M2 phenotype in macrophages was attenuated upon the removal of sialoglycans from the surface of CAFEX either by enzymatic removal or via a small molecule inhibitor. CAFEX were also able to directly bind members of the Siglec family, which are sialoglycan specific lectin receptors expressed on immune cells, including macrophages. DISCUSSION/SIGNIFICANCE: Collectively, these studies suggest that surface presentation of sialoglycans by CAFEX may induce an immunosuppressive phenotype in monocytes/macrophages. Consequently, this may be a novel mechanism by which cells within the tumor bed facilitate immunoevasion during tumor progression.

OBJECTIVES/GOALS: The extent that Clinical and Translational Science Award (CTSA) programs offer resources accessible online for training in community-engaged research (CEnR) core competencies is unknown. This study cataloged CEnR resources accessible online from CTSAs and mapped resources to CEnR core competencies. METHODS/STUDY POPULATION: Eight domains of CEnR core competencies were identified: knowledge/perceptions of CEnR; personal traits necessary for CEnR; knowledge of/relationships with communities; training for performing CEnR; CEnR methods; program evaluation; resource sharing and communication; and dissemination and advocacy. A systematic review of CEnR resources accessible online from CTSAs was conducted between July 2018 and May 2019. Resource content was independently reviewed by two reviewers and scored for inclusion of each domain of CEnR core competencies. Domain scores across all resources and inter-rater reliability in scoring domains were assessed using descriptive statistics and Cohen’s kappa coefficients. RESULTS/ANTICIPATED RESULTS: Overall, 214 resources available from 24 CTSAs were eligible for full review. Scoring discrepancies for at least one domain within a resource initially occurred in 51% of resources. “CEnR methods” (50.5%; 108 of 214) and “Knowledge of/relationships with the community” (40.2%; 86 of 214) were most frequently addressed and “Program evaluation” (12.1%; 26 of 214) and “Dissemination and advocacy” (11.2%; 24 of 214) were least frequently addressed domains. Additionally, challenges were noted in navigating CTSA websites to access CEnR resources, and CEnR competency nomenclature was not standardized. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings guide CEnR stakeholders to identify CEnR resources accessible online and gaps to address in CEnR resource development. Standardized nomenclature for CEnR competencies is needed for effective CEnR resource classification. Uniform organization of CTSA websites may maximize navigability. CONFLICT OF INTEREST DESCRIPTION: In addition to the funding information listed previously (see above), within the last three years, R.J. Piasecki has been employed as: Project Coordinator, CEnR Online Learning Project, Johns Hopkins University School of Nursing (Current) Temporary Employee (Doctoral Student Intern), Michigan State University Institute for Health Policy (Current) Clinical RN, Intrastaff at the Johns Hopkins Health System (Past) Research Data Analysis Assistant, Maryland Institute for Emergency Medical Services (Past - contracted)

OBJECTIVES/GOALS: Inflammation-promoting exposures, including hyperglycemia and inflammatory cytokines, are common in the development and progression of multiple cancers. Here, we determine if high glucose drives the dysregulation of XRCC1, changing BER/SSBR capacity, and increasing resistance to DNA damaging agents. METHODS/STUDY POPULATION: Here, we acutely exposed cell lines models with 30 mM glucose to mimic hyperglycemic changes and monitored the gene and protein expression of STAT3 and XRCC1. We selected the osteosarcoma cell line U2OS, with high STAT3 activation before glucose challenge, and the non-tumorigenic human embryonic kidney cell line HEK293T, with low STAT3 activation before glucose challenge, to dissect the role STAT3 plays in dysregulating DNA repair. We also examined changes in STAT3 occupancy at the XRCC1 promoter following glucose challenge using chromatin immunoprecipitation (ChIP). Finally, we measured changes in the sensitivity to the alkylating agent methyl methanesulfonate (MMS) induced by the glucose challenge using cell survival and DNA strand break analysis. RESULTS/ANTICIPATED RESULTS: High glucose challenge increases the phosphorylation and activation of STAT3 and subsequently increases XRCC1 gene and protein content in the cell. Acute high glucose activated STAT3, driving the subsequent expression of XRCC1 in U2OS and HEK293T cells through increased STAT3 occupancy at the XRCC1 promoter. High glucose also reduced sensitivity to MMS, increasing cell survival. The most significant increase in resistance to MMS occurred in the HEK293T, which also showed the largest increase in XRCC1 protein expression following the glucose challenge. Increased survival correlated with the faster resolution of DNA strand breaks in glucose-challenged cell lines. DISCUSSION/SIGNIFICANCE: This work has identified a novel regulatory mechanism by which high glucose drives the expression of XRCC1 through STAT3 activation, increasing DNA repair and resistance to the DNA damaging agent MMS. These data suggest dietary choices induce sustained XRCC1 expression and may contribute to chemoresistance and poor survival outcomes in cancers.

OBJECTIVES/SPECIFIC AIMS: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft tissue infections (SSTIs) recurrence ranges from 16% to 43% and presents significant challenges to clinicians, patients, and families. The number of emergency department visits for SSTIs increased from 1993 to 2005 from 0.48 to 1.16 ED visits per 100 US residents (95% CI 0.94 to 1.39; p<0.001); high safety-net status EDs saw a 4-fold increase in visits. The CA-MRSA Project (CAMP2) comparative effectiveness research (CER) study aims to evaluate a home-based intervention implemented by Community Health Workers (CHWs) or “promotoras” to prevent recurrence and transmission of CA-MRSA in primarily low-income, minority patients presenting to primary care with SSTIs. The intervention disseminates and implements methods found effective in the REDUCE MRSA trial. The present analysis was conducted using publically available data set to characterize the national patterns of healthcare utilization for treatment of SSTIs. METHODS/STUDY POPULATION: An analysis was conducted using data downloaded from the CDC National Ambulatory Medical Care Survey (NAMCS) and the CDC National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2012 (most recent data available) to evaluate the addition of Emergency Departments (EDs) as compared to Ambulatory Care as recruitment sources for a clinical trial to reduce CA-MRSA SSTI recurrence and household transmission. “Low-income” population was defined using “Expected Source of Payment” categories “Medicaid” and “Uninsured,” and ICD-9-CM dermatologic diagnosis codes for SSTIs and ICD-9-CM Procedure Codes for Incision and Drainage (I&D) were used to define a visit for SSTI treatment. RESULTS/ANTICIPATED RESULTS: In all patients, I&D was performed at a higher rate in EDs as compared with the ambulatory care setting (49.57 vs. 1.44 per 10,000 US residents in Medicaid and Uninsured; 44.48 vs. 5.24 per 10,000 US residents in all other insurance types). Nationally, low-income patients are 4 times more likely to have I&D procedure performed (OR 4.05, 95% CI 0.614–26.759, p<0.0001) and 5 times more likely to be diagnosed with an SSTI (OR 5.10, 95% CI 2.987–8.707, p<0.001) in the ED setting. DISCUSSION/SIGNIFICANCE OF IMPACT: These results confirm that low income patients seek primary care for SSTIs in both EDs and ambulatory care, such as Federally Qualified Health Centers (FQHCs). This also confirms the trend we have experienced in FQHCs in NYC, many of whom refer patients to the ED for the I&D procedure, and those patients return to the FQHC for follow-up. Thus, the most comprehensive test of using CHWs to disseminate and implement the findings from the REDUCE MRSA trial would engage both EDs and Ambulatory Care/FQHCs for patient identification and recruitment.

OBJECTIVES/SPECIFIC AIMS: Analyze data from the first 30 children enrolled in a prospective cohort study evaluating the ability of specific serum biomarkers to distinguish children with traumatic brain injuries (TBI) from children with orthopedic injuries (OI). METHODS/STUDY POPULATION: Children ages 0<5 years were eligible if they presented to the emergency department within 6 hours of injury. Children were identified as having a TBI if they sustained a head injury and were found to have an acute injury on head CT. Children were identified as having an OI if they sustained a musculoskeletal injury significant enough to necessitate radiography per clinical care. Individual (eg, age) and clinical (eg, radiography findings) factors, as well as serum biomarkers [eg, ubiquitin C-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP)] were collected at time of enrollment. TBI and OI groups were compared using Wilcoxon rank-sum and Kruskal-Wallis tests. RESULTS/ANTICIPATED RESULTS: This cohort consisted of 13 children with TBI (7 with isolated skull fractures, 1 with intracranial injury, and 5 with both a skull fracture and an intracranial injury) and 17 with OI (12 with fractures). Most patients were male (67%) and White (67%), and this did not differ between groups (p>0.1). Children with TBI were significantly younger than children with OI, with an average (±standard deviation) age of 15±13 and 39±13 months, respectively (p<0.01). There was not a significant difference in time from injury to biomarker collection between TBI and OI patients at 4.1±1.8 and 5.8±2.6 hours, respectively (p=0.07). Median (IQR) levels of GFAP were significantly higher (p<0.01) in children with TBI, relative to children with OI: 220 (67–421) pg/mL Versus 37 (25–74) pg/mL, respectively. Median (IQR) levels of UCH-L1 were also significantly higher (p<0.01) in the TBI group, relative to children with OI: 444 (377–449) pg/mL Versus 248 (140–417) pg/mL, respectively. In a subanalysis comparing median biomarker levels across three study groups (ie, TBI with an isolated skull fracture, TBI with an intracranial injury, and OI), group differences remained significant for both biomarkers with TBI patients having higher levels, relative to OI patients, of both GFAP (p<0.01) and UCH-L1 (p=0.02). DISCUSSION/SIGNIFICANCE OF IMPACT: GFAP and UCH-L1 hold promise to improve the diagnosis of TBI in very young children. Identification of a marker of TBI that can be done in the acute care setting would advance the diagnosis of TBI in very young children, a vulnerable population for whom identification of neurological symptoms can be challenging.

OBJECTIVES/GOALS: Familial Hypercholesterolemia (FH) is a common disorder that is vastly underdiagnosed and causes an increased risk for sudden cardiac death. Cardiology providers (CHCPs) are in an ideal position to care for patients with FH. This research aimed to understand the practice behaviors of CHCPs in the screening, diagnosis, and management of FH. METHODS/STUDY POPULATION: An explanatory mixed methods design was utilized for this study. Adaptation of an existing FH knowledge tool guided survey development. The results of the quantitative survey, along with the Knowledge to Action framework and Theory of Planned Behavior, guided development of the interview protocol. Convenience and snowball sampling recruited CHCPs in the Division of Cardiology at Columbia University Irving Medical Center (CUIMC). Descriptive statistical analysis was performed on survey data. Qualitative interviews were conducted with survey respondents who volunteered to participate. Interviews were audio recorded, transcribed, and analyzed thematically. A descriptive review of the educational materials offered by the Division of Cardiology was conducted to identify FH knowledge domains presented. RESULTS/ANTICIPATED RESULTS: CHCPs with MDs, at CUIMC for 6-10 years, in clinical practice for 1-5 years, and in Inpatient Services had the highest average total FH knowledge scores. CHCPs with RNs, at CUIMC for less than 1 year, in clinical practice for 6-10 years, and in Cath Lab had the lowest average FH knowledge scores. Twenty interviews were completed, and four themes emerged- variability in FH care; issues related to addressing FH at institutional, practice setting and individual levels; importance of identifying FH early; and intervention approaches to overcome barriers to caring for FH patients in cardiology. CHCPs with MDs or with experiential FH knowledge were the only CHCPs to describe FH care beyond the point of screening. The document review revealed that only MDs were provided four lectures over the course of 4 years pertaining to FH. DISCUSSION/SIGNIFICANCE: CHCPs with didactic or experiential FH knowledge provided care beyond screening. Future interventions should increase didactic and experiential FH knowledge by incorporating institutional, local, and national FH resources. Improving the FH care CHCPs provide, can reduce FH-related morbidity and mortality as well as improve FH health outcomes.

OBJECTIVES/GOALS: The Michigan Institute for Clinical & Health Research Community Engagement (MICHR CE) has collaborated for 15+ years with underserved communities on public health issues. As Michigan’s sole CTSA institution, we aim to advance the science of community engagement in translational science statewide. METHODS/STUDY POPULATION: MICHR CE PACE (Promoting Academic-Community Engagement) will advance clinical and translational science. Key steps include: 1) form a PACE Steering Committee; 2) PACE Trainings with community-academic partner Detroit Urban Research Center; 3) PACE Training Manual; 4) community Grand Rounds to bridge academic-community insights; and 5) community resources (e.g., toolkits). PACE projects will spotlight community-engaged research (CEnR) via diverse media including social media and community-level communications. The PACE ScienCE initiative will embody cultural humility by addressing power imbalances, emphasizing trust. We will utilize assessments and root cause analyses to navigate CEnR barriers. RESULTS/ANTICIPATED RESULTS: Anticipated results from MICHR CE’s planned approach with PACE include strengthened academic-community relationships. Formation of the PACE Steering Committee and collaborations are expected to foster more structured and impactful CEnR trainings. The PACE Training Manual will become a foundational resource for CEnR best practices. Community Grand Rounds will reveal increased interdisciplinary insights and community trust. All PACE projects will utilize diverse media to enhance CEnR visibility and community-level access. Lastly, by addressing power disparities via PACE ScienCE, we foresee enhanced trust, reduced barriers, and more transparent community-academic collaborations. DISCUSSION/SIGNIFICANCE: This strategy, based on co-planned efforts and community consultations, aims to reshape Michigan’s CEnR landscape and offers a replicable model for other regions. The insights gained will guide community-academic collaborations promoting translational, inclusive, and efficient community engagement.

OBJECTIVES/SPECIFIC AIMS: Community health coalitions (CHC) aim to improve local cultures of health, health behaviors, and health outcomes. However, challenges sustaining partnerships and activities limit CHC impact. Traditional CHC evaluations survey members about perceived effectiveness, failing to capture underlying network structures and community health outcomes. Thus, we applied a mixed-methods evaluation in eight rural Indiana CHC, triangulating social network analysis [(SNA), conducted in 2017], functioning effectiveness [Coalition Self-Assessment Survey (CSAS), also 2017], and latest county health statistics (2015–2016) to assess existing CHC building efforts, inform best practices, and facilitate the adoption of evidence-based programming. METHODS/STUDY POPULATION: Across the eight rural Indiana CHC, relationships between the three evaluation components were analyzed using Pearson’s correlations. We are now collaborating with Purdue’s Nutrition Education Program Community Wellness Coordinators to scale up evaluation efforts throughout Indiana. RESULTS/ANTICIPATED RESULTS: CHC effectiveness was positively correlated with the average number of connections CHC members held in the network (mean indegree) and negatively correlated with the presence of a network broker (eigenvector centrality). However, effective leadership was positively correlated with opioid deaths and treatment, food insecurity, smoking during pregnancy, lack of healthcare coverage, and fair/ poor health status, and negatively correlated with prenatal care. Effective operating norms was positively correlated with smoking during pregnancy and preterm births, and negatively correlated with prenatal care. Effective action outcomes was positively correlated with opioid deaths and treatments, smoking during pregnancy, preterm births, and fair/ poor health status, and negatively correlated with respondents reporting they had no personal doctor. DISCUSSION/SIGNIFICANCE OF IMPACT: Interestingly, CHC effectiveness was positively correlated with poor county health outcomes related to infant well-being. Thus, CHC may develop in counties with a high unmet need for effective pregnancy and infant services. Alternatively, the prevalent CHC focus on obesity prevention may eclipse programmatic efforts to improve infant well-being. Longitudinal evaluations and scaling up evaluation efforts across Indiana are being pursued to clarify trajectories and inform best practices, which in turn should provide recommendations for network structures to improve CHC effectiveness and county health.

ABSTRACT IMPACT: This poster will demonstrate how input from a CTSI Community Advisory Board was used to develop a large, annual dissemination event focused on health disparities, health equity, and community engagement. OBJECTIVES/GOALS: The NYU Langone Annual Health Disparities Symposium began in response to the NYU-H+H CTSI’s Community Advisory Board, which expressed a desire to 1) learn about health disparities research at NYU, H+H, and beyond; 2) build connections and interdisciplinary collaborations; 3) support bidirectional dissemination between community and researchers. METHODS/STUDY POPULATION: The annual symposium, a collaboration between NYU Langone’s CTSI, Department of Population Health, Office of Diversity Affairs, and the NYU-CUNY Prevention Research Center, features a keynote, a series of rapid-fire talks, panels on current controversies in population health and the work of the Community Engagement Cores of NYC-based CTSAs, and poster sessions. Each year the event is focused around a specific theme, with the 2020 theme being ‘Research Into Action’. Audience members include faculty, staff, students, health care providers, community health workers, and representatives from community-based organizations, health care facilities, and the NYC Department of Health and Mental Hygiene. For the very first time, the event was held virtually days and CME/CNE credits were provided free of cost. RESULTS/ANTICIPATED RESULTS: The conference explored how institutions have turned research into action, and speakers addressed the ways in which COVID-19 has highlighted structural inequities that have existed across time. 585 attendees participated in the event, with 63 claiming an average of 7.8 hours of continuing education credits. 46 individuals completed the post-event evaluation, with 95% agreeing/strongly agreeing that the symposium increased their awareness of health disparities research taking place at NYU, H+H, and beyond, 91% agreeing/strongly agreeing that they are likely to apply the information learned to their own work, and 91% agreeing/strongly agreeing that the symposium increased their interest in health disparities research. 86% were very/extremely satisfied with the quality of the meeting overall. DISCUSSION/SIGNIFICANCE OF FINDINGS: The 2020 event had the greatest proportion of health care provider attendees (24%), likely due to the opportunity to earn CME/CNE credits. Attendance also grew over the years, from 150 in 2015 to 585 in 2020. This increase is likely due to increased awareness of the event, as well as well as virtual the format, which made it more convenient for attendees.

OBJECTIVES/GOALS: The primary goals of this study are 1) expand our understanding of the neural circuitry influenced by the neuropeptide Neuromedin U (NMU) via its receptor Neuromedin U Receptor 2 (NMUR2), and 2) provide alternative top-down mechanisms for how NMU regulates high fat food intake and cocaine taking. METHODS/STUDY POPULATION: Immunohistochemistry (IHC) for NMUR2 and cell markers was performed on rat brain tissue containing the medial prefrontal cortex (mPFC). To identify the source of the presynaptic NMUR2, anterograde tracing from the paraventricular nucleus or dorsal raphe nucleus to the mPFC utilizing an AAV2- dsRed-synaptobrevin fusion protein were performed (n=3) and will be followed by IHC. Using in vivo calcium imaging technology (InScopix nVista), neuronal activity (calcium transients) was recorded from the mPFC of two awake, freely behaving rats. Each animal underwent a single session of 30 minutes baseline activity, intraperitoneal NMU administration, and 30 minutes of post-treatment activity. Activity was then processed and recorded as distinct events using the InScopix data acquisition software. RESULTS/ANTICIPATED RESULTS: Medial prefrontal cortex staining for NMUR2 revealed a characteristic “beads on a string” motif, consistent with presynaptic receptor expression. Furthermore, we expect the anterograde tracing experiment will show colocalization of the dsRed-synaptobrevin fusion protein with NMUR2 on synaptic inputs into the medial prefrontal cortex. Following quantification of pre- and post- treatment events using the InScopix data acquisition software, total events during the pre- and post-treatment time periods were calculated. In these studies, both animals demonstrated a clear increase in calcium transient activity between pre- and post- treatment evaluations, suggesting that NMU administration increases the neuronal activity of neurons in the prefrontal cortex. DISCUSSION/SIGNIFICANCE: This research provides a new site of action for the known therapeutic effects of NMU. We demonstrate the presence of presynaptic NMUR2 in the mPFC and show that systemic administration of NMU increases mPFC neuronal activity. This illustrates NMU may act as a top-down mediator for substance use disorders and binge eating behaviors.

OBJECTIVES/SPECIFIC AIMS: Cervical fusion is commonly performed for the management of degenerative disc disease, which can cause spinal stenosis and radiculopathy. Adjacent segment disease (ASD) is an adverse postsurgical outcome experienced by some patients as new radiculopathy, stenosis, or other symptomatic sequelae. We sought to assess whether fusion extension past the cervicothoracic junction reduces the risk of distal ASD after multilevel fusions ending at C7-T3. METHODS/STUDY POPULATION: We retrospectively reviewed all first-time patients undergoing instrumented cervical fusion of at least 2 spinal levels and whose distal level of fusion ranged from C7-T3, at the Johns Hopkins Medical Institutions, from 1999 to 2013. The primary outcome was reoperation for distal ASD. Using multiple logistic regression, ANOVA, and χ2 analysis, we determined the odds of ASD due to age, gender, distal level of fusion, surgical approach (anterior, posterior, or combined), smoking status, and race. RESULTS/ANTICIPATED RESULTS: Of the 158 patients who met the selection criteria, the mean age was 58.7±13.8 years, and 95 (60.1%) were female. Ten patients (6.3%) underwent reoperation for ASD. Patients whose fusions ended at C7 were significantly more likely to develop ASD and undergo reoperation (70%, p=0.007) than those whose fusions ended at T1. There were no differences in age, proximal fusion level, smoking status, BMI, gender, and patient-reported race between the reoperation and non-reoperation groups. Following a multivariable analysis, extending the distal fusion to T1 was again found to be protective against reoperation (OR=0.07, p=0.020). DISCUSSION/SIGNIFICANCE OF IMPACT: Our study shows that for multilevel instrumented cervical fusions that terminate within the cervicothoracic junction, fusion distal to the C7 vertebra is associated with decreased odds of reoperation for symptomatic ASD. Therefore, this study provides clinical evidence that may help surgeons determine the optimal distal fusion segment for multilevel fusions ending at C7-T3.

OBJECTIVES/GOALS: The effect of the Direct-Acting Antiviral (DAA) on hepatic histopathological features from patients treated for HCV has not been thoroughly evaluated. The goals of this retrospective study were to determines differences between the liver biopsies collected before and after DAA treatment and correlated the histopathology with clinical outcome. METHODS/STUDY POPULATION: Spectral imaging was used to evaluate differences in intrahepatic macrophage (CD68, CD14, CD16, MAC 387, and CD163) and T cell (CD3, CD4, CD8, CD45, and FoxP3) phenotypes in paired liver biopsies collected from the same patient before (n=10) and after (n=10) achieving SVR (Figure 1). Imaging analysis and machine learning algorithms were used to evaluate changes in these key immune cells. We also compared differential gene expression of over 700 genes using RNA isolated from liver biopsies with NanoString. RESULTS/ANTICIPATED RESULTS: Multispectral imaging analysis showed a significant increase of proinflammatory/M1-like (e.g., CD14+) and anti-inflammatory/M2-like macrophage (e.g., CD163+) phenotypes in pre-treatment versus post-treatment biopsies, respectively. Gene expression analysis revealed enrichment of inflammatory (HLA-B, STAT1, CXCL10) and interferon induced-antiviral (ISG15, OAS3, MX1 and IFIT1) genes in the pre-treatment vs the post-treatment group. Cell deconvolution analysis also showed a significant increase of M1-like macrophages in the pre-treatment group when compared to the post-treatment group or controls. Upregulation of genes associated with cell proliferation and differentiation (c-KIT and Fos) was observed in the post-treatment biopsies of patients with persistent inflammatory infiltrates. DISCUSSION/SIGNIFICANCE: Protein and gene expression profiles observed in patients before DAA therapy showed a strong macrophage-mediated inflammatory response against HCV infection in the liver that shifted significantly to a tissue remodeling microenvironment after treatment.