OBJECTIVES/SPECIFIC AIMS: This study will elucidate what percent of unnecessary ED visits for chronic conditions can be reduced by extant telemedicine devices, and which telemedicine devices can yield the greatest reduction in unnecessary ED visits for chronic conditions. METHODS/STUDY POPULATION: We intend to use the Nationwide Emergency Department Sample (NEDS) to estimate the percent of ED visits, with a chronic condition as the principal diagnosis, were only evaluation and management services were rendered. The NEDS is the largest publicly available, all-payer ED database, providing national estimates of ED visits. The NEDS contains information on patient demographics, principal diagnosis (captured by ICD-9-CM codes and defined as the main reason for bringing the patient to the hospital), and procedure codes using Current Procedural Terminology, Fourth Edition (CPT-4). Patients with a chronic condition will be identified using Chronic Condition Indicator developed by the Agency for Healthcare Research and Quality and, from them, patients who only received “evaluation and management” services will be extracted using the CPT-4 codes 99281–99283 and G0380–G0383. Then using our previously developed database, wherein FDA-approved OTC medical devices were allied to chronic conditions by applying the transitive property of equality between telemedicine devices – measurement and measurement – conditions pairs, we will elucidate what percent of unnecessary ED visits for chronic conditions which can be reduced by extant telemedicine devices. RESULTS/ANTICIPATED RESULTS: We anticipate multiple OTC telemedicine devices will be necessary to evaluate and manage common principal conditions. DISCUSSION/SIGNIFICANCE OF IMPACT: Telemedicine is seen as a potentially powerful tool for improving healthcare and reducing cost. UnitedHealthcare, the largest US insurance provider, has partnered with Doctors on Demand, the largest players in the telemedicine app space, and other app-based telemedicine services to provide on-demand access to physicians. However, to reach the full potential of telemedicine, and more specifically towards reducing unnecessary ED visits for chronic conditions, telemedicine services need to include capabilities that will allow for the evaluation and management of chronic conditions. This study is a pragmatic first step towards understanding what telemedicine devices would best augment existing telemedicine services to reduce unnecessary ED utilization.

OBJECTIVES/SPECIFIC AIMS: Upper-extremity (UE) impairment affects 88% of stroke survivors due to dysfunctional shoulder-hand coordination. Patients may be able to grasp with the arm at rest, but unable to grasp in a functional context (eg, from a high shelf) because shoulder use elicits involuntary hand muscle activity. Further, much rehabilitation research is directed at unsuccessful stroke recovery (patients with persistent UE impairment) but very little towards patients who show successful clinical recovery (such as those with mild UE impairment) even though these patients have attained the desired rehabilitation outcome. We examined the neurophysiological trajectory of successful compared to unsuccessful post-stroke recovery in the context of functional UE movements to clearly identify what factors are necessary for successful recovery of functional UE movements after stroke. METHODS/STUDY POPULATION: We studied 3 populations: (1) mildly-impaired patients, early (at <17 d, 30 d, 90 d, and 180 d) after stroke as a model of successful post-stroke recovery, (2) moderately-impaired, chronic patients (>6-months post stroke) with persistent hand function impairment, as a model of incomplete post-stroke recovery (unsuccessful recovery), and (3) Healthy age-range matched controls. We used transcranial magnetic stimulation (TMS) in all 3 groups at the given time points to measure corticomotor excitability (motor evoked potentials, recruitment curve), corticomotor inhibition (short-interval intracortical inhibition, long-interval intracortical inhibition), and intracortical facilitation of hand muscles with the shoulder positioned in different degrees of flexion or abduction (these shoulder positions are known to elicit involuntary, undesired hand muscle activation, which leads to UE dysfunction and impairment in individuals with stroke). RESULTS/ANTICIPATED RESULTS: Data collection are in process and will be presented. Preliminary data from controls shows that corticomotor excitability of selected hand muscles is affected by changes in shoulder position. Preliminary findings in controls are consistent with clinical findings in stroke that certain shoulder positions elicit involuntary and undesired hand muscle activation, leading to UE dysfunction and disability. Findings from the stroke groups will be presented. DISCUSSION/SIGNIFICANCE OF IMPACT: We hypothesize that this centrally-facilitated coupling between shoulder and hand muscles is disrupted after stroke, which may play a central role in the inability of patients to perform functional UE movements. By comparing the TMS metrics in mildly-impaired Versus moderately-impaired chronic patients, we will be able to identify the longitudinal change in neurophysiology underlying shoulder-hand coordination that is associated with successful or unsuccessful clinical recovery of UE function after stroke. Thus, these findings will help us distinguish between the neurophysiology underlying successful from unsuccessful UE recovery leading to more mechanism-based interventions for UE dysfunction post stroke in the future.

OBJECTIVES/SPECIFIC AIMS: The TL1 Team approach aims to train translational investigators capable of tackling complex and multifaceted diseases, such as hypertension, by beginning multidisciplinary, team-based training early in their graduate programs. METHODS/STUDY POPULATION: Leanne Dumeny is a graduate student in Genetics and Genomics studying how pharmacogenomics can be applied to improve clinical care and cardiovascular outcomes. Chu Hsiao is a graduate student in Anthropology studying how sociocultural experiences become biologically embodied. Both are in the Ph.D. phase of M.D.-Ph.D. training. Joining the seemingly disparate but complementary fields of anthropology and genomics facilitates understanding of the intersection between socially driven experiences and genetics on nocturnal blood pressure. Understanding both social determinants, such as racial discrimination, and biological determinants, such as genetics, is important because an interplay of gene-environment interactions influences many complex diseases. Rarely can 1 individual, or 1 discipline, tackle all the perspectives necessary to answer these types of complex questions. The TL1 Team curriculum teaches students to navigate the spectrum of translational research as a team, reflect on disciplinary limitations, and embrace collaborative research. RESULTS/ANTICIPATED RESULTS: This team project will investigate the relationship between racial discrimination and genetics using a large epidemiological cohort of African Americans in Mississippi. The data request application is currently under review. By the project’s end, the team anticipates their investigation will reveal novel associations between racial discrimination, genetic polymorphisms, and nocturnal blood pressure measurements. The investigators will have gained experience obtaining and analyzing large external data sets, working in diverse team settings, collaborating across state-lines, and publishing articles. Through this team approach, the students will also understand the barriers to working in multidisciplinary groups, and develop a foundation for approaching future collaborations. DISCUSSION/SIGNIFICANCE OF IMPACT: By joining anthropology with genomics, it becomes possible to understand the intersection between socially driven experiences of racial discrimination and genetics on nocturnal blood pressure. The successful training of this first cohort of team-applicants to the TL1 funding mechanism can impact how graduate education will be structured and could reframe graduate education to emphasize a team-based approach.

OBJECTIVES/GOALS: Lymphedema is a chronic, debilitating disease characterized by progressive swelling due to lymphatic dysfunction. Lymphedema affects 5+ million people in the US, commonly as a consequence of cancer treatment. We identified the most relevant needs within lymphedema based on clinical impact, commercial viability, and technological feasibility. METHODS/STUDY POPULATION: A narrative review of lymphedema management was performed through a combination of literature review via English language PubMed, landscape determination for current solutions and primary ethnography. Lymphedema-focused physicians, patients, physical therapists and researchers were interviewed on Needs were identified and clustered based on common themes. These clusters were further refined through an iterative process of systematic scoring and expert evaluation. Clusters were evaluated on their potential for clinical and commercial impact as well as technical feasibility. RESULTS/ANTICIPATED RESULTS: General clusters identified included improved diagnostic modalities, curative treatment, disease knowledge among non-specialized clinicians and increased insurance coverage. 3 primary needs were determined to represent the best opportunities for technological innovation. There is a need for a quantitative method of evaluating lymphedema. This would allow for both improved tracking of progression for patients undergoing conservative management, and for better evaluation of surgical outcomes. Oncologists and surgeons need a method of prophylaxis in order to decrease the rate of lymphedema development following cancer treatment. Physicians need a method for early diagnosis of subclinical lymphedema to enable early intervention through proactive screening rather than reactive management. DISCUSSION/SIGNIFICANCE: Increasingly medical device design has moved towards a “bedside to benchtop” model where technology development is targeted based on critical needs within the clinical environment. Identification of these critical needs will serve as to guide future technological innovation in creating clinically impactful advancements.

OBJECTIVES/SPECIFIC AIMS: The purpose of this study was to summarize the existing literature on clinical research competencies and determine what competency assessments currently exist. We also wished to assess which competencies should be included in a research competency assessment tool and to evaluate the validity of current competency assessments. We also examined whether these competency assessments can be used for the purposes of formative and summative evaluation. METHODS/STUDY POPULATION: Prior to conducting our search of the literature, we first compiled a list of search terms (e.g., clinical, research, training, competencies) that could be used to locate articles. We then entered these search terms, in various combinations, on several relevant databases. We evaluated abstracts of the articles revealed by this search to determine whether they met three criteria. The first criterion was that the subjects of the article must be clinical investigators or clinical investigators in training. Relevant disciplines included medicine, public health, nursing, pharmacy, dentistry, and other related fields. The second criterion was that articles should focus on research-based (as opposed to clinical) skills. The last criterion was that research-based competencies (or related terms like skills, abilities, mastery, knowledge) must be assessed in some way. If the abstract suggested that the article met all three criteria, the full article was retrieved and analyzed in-depth. To identify articles that eluded literature search, we then examined the reference section of these articles and examined articles that cited these articles. When no additional articles could be located, the search for articles stopped. Once a pool of potentially eligible articles was identified, the articles underwent peer review by several researchers experienced with clinical research and competency-based education and assessment. Articles that were unanimously judged to meet the criteria were included in the systematic review. RESULTS/ANTICIPATED RESULTS: Approximately 75 articles were selected and reviewed for eligibility. After peer review, we found that only a small fraction of these articles met our criteria for inclusion in the systematic literature review. Our preliminary findings suggest that there are few assessments of clinical research competency and that many of these assessments are poorly validated. DISCUSSION/SIGNIFICANCE OF IMPACT: The findings of the present study suggest that the validation methods used thus far are limited and so the validity of many of these assessments is effectively unproven. Future research on assessments of clinical research competency ought to address these limitations by sampling clinical researchers, using more rigorous validation methods, and by confirming hypothesized factor structures in new samples. The use of better-validated instruments may enhance measurement of trainees’ knowledge and skill levels for the purposes of formative and summative assessment.

OBJECTIVES/SPECIFIC AIMS: The goal of this research is to use circulating tumor cells (CTC) enumeration and characterization to monitor anticancer treatment response. Emerging evidence strongly suggests the implications that epithelial-to-mesenchymal transition may have in cancer metastasis. Consequently, we hope to elucidate the significance of mesenchymal and stem-like CTCs in the peripheral blood of metastatic pancreatic cancer patients by analyzing the prevalence and frequency trends of CD133+ CTCs, as they relate to clinical events. We also hope to determine if there is a correlation between EpCAM+ CTCs and CD133+ CTCs numbers with tumor size, disease stage, and patient clinical outcome. METHODS/STUDY POPULATION: Blood samples of patients with metastatic pancreatic cancer (stage IV) were obtained from the University of Florida Health Cancer Center after informed consent through an IRB-approved protocol. CTC capture, characterization, and enumeration was performed on the blood of these cancer patients during their anticancer treatment. Patients had blood drawn for this purpose at time points aligned with clinical phlebotomy (every 2 weeks). CTC capture was performed by introducing treated patient blood samples into antibody-functionalized microdevices. The PDMS devices were functionalized by immobilizing either anti-EpCAM or anti-CD133, through an avidin-biotin complex. After capture, cells were fixated and permeabilized with 4% paraformaldehyde and 0.2% Triton X-100, respectively. Three-color immunocytochemistry (anti-cytokeratin-FITC, anti-CD45-PE, and DAPI) was performed to identify CTCs from nonspecifically captured blood cells. To be counted as a CTC, based on the FDA-approved technical definition, a cell with the appropriate cell size and morphology must be nucleated (DAPI+), express cytokeratin (CK+), and lack the leukocytic CD45 marker (CD45−). RESULTS/ANTICIPATED RESULTS: We tested the clinical utility of the device for monitoring the response of patients with advanced pancreatic cancer to a chemotherapy treatment consisting of anticancer drugs including 5-fluorouracil, leucovorin, oxaliplatin, and dasatinib. We have detected EpCAM+ CTCs in 47/47 (100%) and CD133+ CTCs in 41/47 (87.2%) of blood samples, coming from a cohort of 16 patients. We studied the correlation between the CTC numbers and the clinical result of patients in the study. We found that the size and changes in the size of the primary tumor (confirmed by CT scans) correlated with the frequency and increase/decrease trends in the number of CTCs detected. We expect to find some relationship between the number of detected CD133+ CTCs, or rather stem-like CTCs, and the clinical outcome of patients (eg, disease progression leading to withdrawal from study). DISCUSSION/SIGNIFICANCE OF IMPACT: Enumeration of patient CTCs and stem-like CTCs at different stages of a patient’s treatment may correlate with disease stage and prognosis, and prove useful in monitoring early recurrence, patient-specific treatment response, and newly acquired resistances; all of which would aid in providing guidance for the next step in clinical intervention. This type of liquid biopsy technology has great potential to make an impact in the future of personalized medicine and point-of-care diagnostics, as well as become a sturdy tool for translational research.

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

OBJECTIVES/GOALS: Diffusion basis spectrum imaging (DBSI) allows for detailed evaluation of white matter microstructural changes present in cervical spondylotic myelopathy (CSM). Our goal is to utilize multidimensional clinical and quantitative imaging data to characterize disease severity and predict long-term outcomes in CSM patients undergoing surgery. METHODS/STUDY POPULATION: A single-center prospective cohort study enrolled fifty CSM patients who underwent surgical decompression and twenty healthy controls from 2018-2021. All patients underwent diffusion tensor imaging (DTI), DBSI, and complete clinical evaluations at baseline and 2-years follow-up. Primary outcome measures were the modified Japanese Orthopedic Association score (mild [mJOA 15-17], moderate [mJOA 12-14], severe [mJOA 0-11]) and SF-36 Physical and Mental Component Summaries (PCS and MCS). At 2-years follow-up, improvement was assessed via established MCID thresholds. A supervised machine learning classification model was used to predict treatment outcomes. The highest-performing algorithm was a linear support vector machine. Leave-one-out cross-validation was utilized to test model performance. RESULTS/ANTICIPATED RESULTS: A total of 70 patients – 20 controls, 25 mild, and 25 moderate/severe CSM patients – were enrolled. Baseline clinical and DTI/DBSI measures were significantly different between groups. DBSI Axial and Radial Diffusivity were significantly correlated with baseline mJOA and mJOA recovery, respectively (r=-0.33, p<0.01; r=-0.36, p=0.02). When predicting baseline disease severity (mJOA classification), DTI metrics alone performed with 38.7% accuracy (AUC: 72.2), compared to 95.2% accuracy (AUC: 98.9) with DBSI metrics alone. When predicting improvement after surgery (change in mJOA), clinical variables alone performed with 33.3% accuracy (AUC: 0.40). When combining DTI or DBSI parameters with key clinical covariates, model accuracy improved to 66.7% (AUC: 0.65) and 88.1% (AUC: 0.95) accuracy, respectively. DISCUSSION/SIGNIFICANCE: DBSI metrics correlate with baseline disease severity and outcome measures at 2-years follow-up. Our results suggest that DBSI may serve as a valid non-invasive imaging biomarker for CSM disease severity and potential for postoperative improvement.

OBJECTIVES/GOALS: Communities of color often report that their concerns are ignored and desire a means to facilitate effective community-academic engagement, especially during a crisis. The objective is to share lessons learned and challenges faced in the development of an online portal designed to meet this need. METHODS/STUDY POPULATION: The Michigan Institute for Clinical & Health Research (MICHR) worked with community and academics to develop an online tool, the Michigan Research Engaging the Academy and Community in Health (M-REACH) platform. The community-engaged research (CEnR) project involved conducting qualitative interviews exploring connectivity to community and academic organizations and pilot testing of the novel platform. Following development, efforts were made to implement the statewide use of M-REACH. We will report on the challenges encountered and lessons learned from development and optimization of the platform. RESULTS/ANTICIPATED RESULTS: Authors will review the timeline of the launch of M-REACH. Steps to promote engagement of the locally developed platform to statewide utilization will be shared. Challenges encountered with scaling, matching the needs of differing communities both rural and urban, and navigating connections between remote geographies will be presented. Lessons learned and potential solutions will be discussed. DISCUSSION/SIGNIFICANCE: M-REACH can connect partners by increasing understanding of the CEnR process, enhancing alignment, and building a foundation for well-functioning research partnerships. Further work is required to address the challenges encountered in development and implementation.

ABSTRACT IMPACT: We plan to measure the impact of integrating 3D printed models in the planning process of endovascular procedures with the goal of making a case for using this resource more often. OBJECTIVES/GOALS: To measure the impact of using 3D printed models of patient specific anatomy for pre-procedure planning and as an intra-procedure reference. Impact will be measured by: a. Radiation exposure ; b. Contrast dosage; c. Fluoroscopy time; d. Time to procedural completion; e. ‘Attempts at access,’ when applicable to the procedure METHODS/STUDY POPULATION: Retrospective data will be collected on every patient that received one of prostate artery embolism, transjugular intrahepatic portosystemic shunt placement, or endovascular stent repair in the 3 years prior to the first prospective case. An attempt will be made to create a procedure planning model for every patient that receives one of the three procedures of interest in the 5 months following the first prospective case and those that have a model included in their procedure planning process will be included as part of the experimental group. We anticipate this to not include every patient as there will need to be adequate time between the scheduling of the procedure and the procedure start time to be able to create a 3D model. This will make it impossible to include every patient. Our first prospective case was 11/12/20. RESULTS/ANTICIPATED RESULTS: At the time of submission we have very limited data and cannot confidently make a statement regarding results. We anticipate to measure a reduced time to procedural completion, and as a result, decreased radiation exposure, decreased contrast dosage, and decreased fluoroscopy time in the cases that included a 3D printed model in the planning of the procedures when compared to the procedures that did not include a model. DISCUSSION/SIGNIFICANCE OF FINDINGS: Few hospitals are using 3D printing as a regular tool that physicians can access as a part of their procedure preparation. If we are able to measure a significant impact on the efficiency and safety of procedures in interventional radiology, a much more robust argument can be made for including this technique in procedure planning with regularity.

OBJECTIVES/GOALS: We assessed the relationship between C-peptide preservation and a serum exocrine pancreatic enzyme (trypsin) in a recently concluded clinical trial. We hypothesized that immunomodulatory treatment resulting in improved beta-cell function would be associated with improved trypsin levels in subjects with recent-onset type 1 diabetes (T1D). METHODS/STUDY POPULATION: In a three-arm, randomized, double-masked, placebo-controlled trial 'Antithymocyte Globulin (ATG) and pegylated granulocyte colony stimulating factor (GCSF) in New Onset Type 1 Diabetes’ 89 subjects with recent-onset T1D (duration <100 days) were enrolled and randomized to 3 groups: low-dose ATG (2.5 mg/kg IV) followed by pegylated GCSF (6 mg subcutaneously every 2 weeks for 6 doses), low-dose ATG alone, and placebo. We compared longitudinal serum levels of an exocrine enzyme (trypsin) in a subset of responders to therapy (defined as subjects with at least 60% of baseline area under the curve (AUC) C-peptide levels at 96 weeks, n=4) versus placebo 'responders’ (n=2) and non-responders (n=25), and treated (n=19) versus placebo (n=12) subjects at baseline, 2 weeks, and 6 months after treatment. RESULTS/ANTICIPATED RESULTS: There was no observed difference in treated (n=20) versus placebo (n=12) longitudinal trends in trypsin levels when compared to baseline levels. However, responders to immunotherapy (n=4) had 6 month trypsin levels that were 114% of baseline whereas placebo subject 'responders’ (n=2), placebo subjects (n=10), and non-responders to immunotherapy (n=15) had trypsin levels that were 81-93% of baseline (unpaired T test p=0.05). Overall, we found that serum trypsin, a marker of exocrine pancreatic function, had a normal upward trend in new-onset T1D subjects who responded clinically to immunotherapy but declined in subjects who did not respond or who were not treated. These results were bordering on statistical significance but did not reach significance, likely due to the small sample size. DISCUSSION/SIGNIFICANCE: An improvement in trypsin, a marker of exocrine function, after response to immunotherapy in new-onset T1D may be due to a direct impact on exocrine function versus an indirect effect from improved beta cell function. Future studies will be needed to confirm our findings in a larger sample and evaluate the mechanism for improved exocrine function.

OBJECTIVES/SPECIFIC AIMS: The Indiana CTSI is investigating innovative approaches to integrate resources that will enrich scientific investigators. Our goals are to enhance the availability and communication among CTSI resources, for example internal funding, and to expand existing mentorship. METHODS/STUDY POPULATION: Developed a reviewer database that serves to streamline reviewer identification, decrease reviewer fatigue, and promote collaboration among disciplines. We started with a pool of NIH-funded investigators from across the Indiana CTSI core institutions and merged this list with previous CTSI reviewers and internal funding awardees. To expand this list, names and expertise from new faculty hires were added. RESULTS/ANTICIPATED RESULTS: Though this tool is relatively new, we have already observed an increase in junior faculty awareness and engagement with the CTSI. This database allows for increased opportunities of junior faculty to serve as reviewers and to refine grant writing skills and provides a platform for networking and collaborating across disciplines. It also allows for increased integration of programs with a shared reviewer database and promotes grant review standardization. DISCUSSION/SIGNIFICANCE OF IMPACT: Our database utilization seeks to decrease the time for junior faculty to obtain their first extramural grant, to enhance promotion and tenure packages, strengthen integration among CTSI programs, increase interactions between clinical and basic science investigators, and promote team science.

OBJECTIVES/SPECIFIC AIMS: Precise biomarkers are urgently needed to characterize the tumor immune microenvironment in primary melanoma tumors both for prognostication and to predict the benefit of immuno-therapeutic intervention. The goal of this work is to define spatial relationships between CD8+ T cells, CD68+ macrophages and Sox10+ melanoma cells in order to define features correlating with prolonged survival METHODS/STUDY POPULATION: Five micrometer slides from either the primary biopsy or subsequent wide local excision procedure were stained using Opal multiplex IHC for DAPI, CD3 (LN10, Leica), CD8 (4B11, Leica), CD68 (KP1, Biogenex), SOX10 (BC34, Biocare), HLA-DR (LN-3, Abcam), and Ki67 (MIB1, Abcam). Cell phenotypes within representative fields preselected by a trained dermato-pathologist and were visualized using the Mantra quantitative pathology workstation (PerkinElmer), and analysis of spatial distribution of CD3+ CD8+ cells analyzed using inForm® image analysis software (PerkinElmer), and Spotfire software (TIBCO). In order to test whether mIHC can better characterize the tumor immune microenvironment, we screened databases at the Herbert Irving Cancer Center (HICC) at Columbia University for stage II/III melanoma patients diagnosed between 2000 and 2012, with available FFPE of primary melanoma tissue and documented clinical follow-up. We identified a preliminary population of 57 patients to begin our analysis. Clinical follow-up was available on 35 patients of whom 21 patients were alive with no evidence of recurrence or died with no evidence of recurrence and 14 had died of melanoma. Twenty-four patients had more than 24 months of survival information available but no detailed clinical information to determine cause of death. RESULTS/ANTICIPATED RESULTS: First, we evaluated whether density of immune cells in tumor and stroma predicted prognosis in 35 patients with disease specific survival information. We find that high number of CD3+CD8+ cells in tumor correlates with Disease Specific Survival (DSS) (p=0.0323*) and CD3+CD8+ cells in stroma may also correlate with DSS (p=0.0671). This is consistent with what is known in the literature regarding tumor infiltrating lymphocytes (TILs). We also found that CD68+ cells in stroma predict poor prognosis (0.0259*). This is consist with the proposed deleterious role for macrophages in tumor progression. Next, using nearest neighbor analysis we examined the effect of HLA-DR and Ki67 expression on spatial distribution of CD3+CD8+ T cells. We find that CD8+ T cells are closer to myeloid (CD68+) cells expressing HLA-DR. This is consistent with the potential of HLA-DR expressing cells to present antigens to T cells, and suggests that T cells may preferentially interact with HLA-DR expressing myeloid cells. Conversely, we find that Ki67 expression on tumor (SOX10+) cells correlates with increased distance from CD3+CD8+ T cells relative to SOX10+Ki67-tumor cells. This finding is consistent with the observation that more advanced tumors with higher mitotic rates have decreased T cell infiltrates, and suggests that dividing melanoma cells are less likely to interact with T cells. In addition, we performed analysis to determine whether spatial relationships defined above impact prognosis. Clinical oncology follow-up was available on 35 of the 57 patients evaluated above. We compared proximity of CD3+CD8+ cells to both myeloid (CD68+) and tumor (SOX10+) cells in patients who recurred and those with no evidence of recurrence. We found that CD3+CD8+ cells in patients who had recurrence were closer to CD68+ HLA-DR− cells than in patients who had no recurrence (t-test, p=0.0377), this correlated with DSS (p=0.003). Conversely, distance from CD3+CD8+ to CD68+ HLA-DR+ in relationship to recurrence was not significant with a trend towards CD3+CD8+ T cells being closer in nonrecurrent patients (t-test, p=0.1362). DISCUSSION/SIGNIFICANCE OF IMPACT: Consistent with the literature, we find that densities of CD8+ T cells correlates with favorable outcomes in early stage melanoma. We also find that density of CD68+ macrophages in stroma correlates with poor outcome. If proximity is a surrogate for interaction, these data indicate that dividing, Ki67+, melanoma cells interact less with CD8+ T cells than do Ki67+ melanoma cells. Further, HLA-DR expression on CD68+ infiltrating cells likely enhances their interaction with T cells. Interestingly, on further analysis, CD3+CD8+ cells were significantly closer to CD68+ HLA-DR− cells in patients who recurred, implying that interactions between these cell types may not be favorable. This analysis demonstrates that spatial analysis may be useful in predicting prognosis in early stage melanoma, and this is the first report of this type of analysis predicting outcomes in primary tumor specimens to our knowledge. Further staining and analysis of the complete patient cohort (n=120) is ongoing.

OBJECTIVES/GOALS: This study explored personal recovery support, including social determinants of health and psychosocial needs to understand factors for sustaining recovery among parenting and pregnant women with opioid use disorder. METHODS/STUDY POPULATION: This study used a mixed method quantitative/qualitative design and recruited women from residential/transitional facilities in an urban area. We used the Accountable Health Communities Health-Related Social Needs tool to assess social determinants of health factors, level of physical activity, family/community support, and mental health (stress). Through focus groups, we interviewed women to describe challenges to recovery and to resources including access to providers, housing, childcare, and food assistance from lived experiences. RESULTS/ANTICIPATED RESULTS: Survey analysis showed social determinants of health factors such as food and transportation were partially mitigated by residential living; however, parenting and pregnant women with opioid use disorder remained concerned about housing and finances; and encountered low levels of physical activity and significant stress. Preliminary results from the focus groups revealed a theme of positive recovery and retention experiences from residential living. DISCUSSION/SIGNIFICANCE: Evidence from studies suggests focused interventions for recovering women to reduce relapse risk factors and adverse maternal outcomes. Opportunities for improving personal recovery capital are accessible in residential facilities, however, further exploration of unmet social determinants of health factors are needed for recovery retention.

OBJECTIVES/GOALS: Improve infrastructure, resources, partnerships, and metrics to enhance the research environment for Hispanic researchers as a Minority Serving Institution. To support the research infrastructure in our Campus to encourage a research culture of sustainability and productivity. METHODS/STUDY POPULATION: Development of four research capacity-building models to enhance the pathway of junior researchers as independent researchers:1. MSc Phase I-Scholar Award 2 years in a Post Doctoral Master in CTR ; 2. Advanced CTR Award 1 year to support research infrastructure development in submitting a grant to NIH with the mentoring of a Visiting Endowed Chair; 3. Mini Infrastructure Research Award 1 year provides funds to increase research productivity; 4. Award on Excellence in CTR recognizes a faculty member with a distinguished research portfolio that support HiREC Career Coach and Mentoring approach. HiREC targets junior faculty, early and mid-career researchers from our two partners Schools. RESULTS/ANTICIPATED RESULTS: HiREC has been recognize as support for research infrastructure development. Since 2011, 10 MSc Phase I-Scholar Awards have been granted increasing the pool of trained Hispanics researchers in P. R., the Advanced CTR Award of $50,000 each, from March, 2019, was granted to 2 women researchers from the SoM and 2 Visiting Endowed Chair were accepted as candidates. The Mini Infrastructure Research Award, since 2017, supported the development of 2 Science labs, data analysis, 3 peer review publications and other research capacity building. Two researchers from the SoM were honored with the HiREC 2018 Award on Excellence in CTR heighten the institutional recognition of top researchers’ endeavors. DISCUSSION/SIGNIFICANCE OF IMPACT: It’s imperative to pursue specific strategies that lead to successful research capacity-building models. By acknowledging institutional research infrastructure needs, trendy scientific and technological knowledges and researchers’ needs, HiREC have been able to successfully accomplish its mission. CONFLICT OF INTEREST DESCRIPTION: Authors have no conflict of interest in this research.

OBJECTIVES/GOALS: At the Saturday Clinic for the Uninsured (SCU), a Milwaukee student-run free clinic affiliated with the Medical College of Wisconsin, we screened patients for food insecurity and evaluated associations of food security status with nine separate social determinants of health (SDOH) needs and eight chronic medical conditions influenced by diet. METHODS/STUDY POPULATION: This cross-sectional study took place from October 2021-April 2022 at SCU, which only sees uninsured patients. We added the USDA six-item food insecurity form to the clinic’s larger SDOH survey, which screens for medication financing, housing stability, energy assistance, legal issues, educational/work opportunities, substance use, mental health, health insurance options, and dental care needs. We then completed chart review for demographic, diagnostic, lab, and medication information pertaining to obesity, hypertension, diabetes, dyslipidemia, chronic kidney disease (CKD), gastroesophageal reflux disease (GERD), anxiety, and depression. We conducted descriptive statistics on demographics and measured associations using both Kendall’s tau correlation and odds ratios from binomial regression. RESULTS/ANTICIPATED RESULTS: Of the 157 patients seen during this time, most were middle-aged (mean age = 49.4 years ± 14.5 years), female (n = 98, 62.4%), Black or African American (n = 66, 42%) and resided in Milwaukee County (n = 144, 92.9%). 22 (16%) screened as food insecure and had greater odds and positively correlated with needing resources for medication financing (OR = 7.28, I2 = 0.33), housing (OR = 129.99, I2 = 0.28), energy assistance (OR = 3.94,I2= 0.2), mental health (OR = 4.54, I2= 0.28), insurance (OR = 2.86, I2= 0.18), and dental care (OR=3.65,I2= 0.28), but not legal concerns, education/work opportunities, or substance use. Food insecure patients had higher odds and positively correlated with having anxiety (OR = 3.26,I2= 0.23) or depression (OR = 2.88,I2= 0.19), but not obesity, hypertension, diabetes, dyslipidemia, CKD, or GERD. DISCUSSION/SIGNIFICANCE: Patients without health insurance and experiencing food insecurity were more likely to have multiple SDOH needs and mental health diagnoses. Risk factors separate from food security status may explain associations with other chronic medical conditions, including uninsured status, socioeconomic status, eating behaviors, or food accessibility.

A translational team (TT) is a specific type of interdisciplinary team that seeks to improve human health. Because high-performing TTs are critical to accomplishing CTSA goals, a greater understanding of how to promote TT performance is needed. Previous work by a CTSA Workgroup formulated a taxonomy of 5 interrelated team-emergent competency “domains” for successful translation: 1). affect, 2). communication, 3). management, 4). collaborative problem-solving, and 5). leadership. These Knowledge Skills and Attitudes (KSAs) develop within teams from the team’s interactions. However, understanding how practice in these domains enhance team performance was unaddressed. To fill this gap, we conducted a scoping literature review of empirical team studies from the broader Science of Team Science literature domains. We identified specific team-emergent KSAs that enhance TT performance, mapped these to the earlier “domain” taxonomy, and developed a rubric for their assessment. This work identifies important areas of intersection of practices in specific competencies across other competency domains. We find that inclusive environment, openness to transdisciplinary knowledge sharing, and situational leadership are a core triad of team-emergent competencies that reinforce each other and are highly linked to team performance. Finally, we identify strategies for enhancing these competencies. This work provides a grounded approach for training interventions in the CTSA context.