ABSTRACT IMPACT: Understanding how perceived discrimination affects Asian Americans can help stakeholders target subgroups that are at highest risk of discrimination-related behaviors and design culturally appropriate interventions to ensure equitable access to healthcare. OBJECTIVES/GOALS: The COVID-19 pandemic has exposed longstanding anti-Asian racism in the US. Yet, effects of discrimination on Asian American health are unknown, partly because diverse Asian American populations are analyzed in aggregate. We aim to understand how perceived discrimination affects healthcare utilization among different Asian American subgroups. METHODS/STUDY POPULATION: We examine the association of perceived discrimination with healthcare utilization using the California Health Interview Survey (CHIS). In the CHIS, respondents reported whether they would’ve gotten better medical care if they belonged to a different race. We examine the association between these responses and physician visits within the past year, in the survey years 2003, 2004 and 2016-2017. We adjust for covariates based on the Andersen Health Behavior model. Subsequent modeling examines potential mediating and moderating factors such as limited English proficiency, immigration status, income, and survey year. Asian American subgroups analyzed include Asian Indian, Korean, Chinese, Filipino, Vietnamese, Japanese, and other Asian. RESULTS/ANTICIPATED RESULTS: Results will highlight how perceived discrimination incentivizes or disincentivizes certain Asian subgroups to utilize healthcare. Asian American subgroups have differing and diverse experiences with discrimination due to their historical and cultural differences; results will elucidate how discrimination affects these subgroups. Results will be compared to non-Hispanic Whites, who represent the racial group least likely to experience discrimination in the US. Mediation and moderation analysis will help understand how traditionally cited factors for healthcare utilization interact with perceived discrimination on Asian Americans. DISCUSSION/SIGNIFICANCE OF FINDINGS: Asian American subgroups are understudied, despite Asian Americans being one of the fastest growing racial groups in the US. Understanding how perceived discrimination affects Asian Americans can help stakeholders target subgroups that are at highest risk of discrimination-related behaviors and design culturally appropriate interventions.

OBJECTIVES/GOALS: Community and other stakeholder engagement (CSE) is critical for relevant and equitable clinical research, yet implementation poses challenges. This study delineates the perspectives of scientists and diverse stakeholders regarding facilitators and challenges in CSE, its perceived value, and their recommendations for successful CSE. METHODS/STUDY POPULATION: The Tufts CTSI Pilot Studies Program requires applicants to propose a plan for CSE while implementing the award, including which stakeholders (SHs)—community members, clinicians, and others affected by the research--will be involved and at what stages. This qualitative study assessed the experiences of both Principal Investigators (PIs) and SHs engaged in pilot projects from three cohorts of awardees (2019-21). Recruitment targeted one PI and one SH per project. Semi-structured interviews explored their CSE experiences, including facilitators, challenges, meaningfulness, perceived impact, intent to participate in CSE in future studies, as well as recommendations for funders, research support organizations, and investigators. Inductive consensus-based coding and thematic analysis was employed. RESULTS/ANTICIPATED RESULTS: Fourteen PIs from different pilot projects and a SH from five of these projects participated. Almost all PIs (92%) had over six years of experience, but two-thirds (67%) had little or no experience with CSE. Four SHs self-identified as representatives of community organizations and one as a clinician scientist. CSE was a “win-win” for both PIs and SHs, and all PIs intended to involve SHs in other research studies. Three facilitators were identified as fostering effective CSE (e.g., PI access to CSE expertise while conducting the project), while four challenges hindered it (e.g., limits on SH capacity and CSE funding). SHs advised scientists to build authentic, sustained relationships, and PIs and SHs provided three actionable recommendations for funders and research support organizations to deepen and expand CSE. DISCUSSION/SIGNIFICANCE: Perspectives of scientists and SHs engaged in research projects are vital for expanding and sustaining effective CSE in research. Funders and research support organizations can enhance their strategies for CSE integration in clinical and translational research by incorporating these diverse views to ensure the research achieves maximal impact.

OBJECTIVES/SPECIFIC AIMS: Opioid prescribing is common and increasing in certain areas of the country with known risk of misuse and dependence. Our study examined the association of opioid prescription at discharge after hospitalization for acute coronary syndrome (ACS) or acute decompensated heart failure (ADHF) with emergency department (ED) care or all-cause readmission, intended healthcare utilization (follow-up with physician within 30 d of discharge and cardiac rehab participation), and all-cause mortality. METHODS/STUDY POPULATION: The Vanderbilt Inpatient Cohort Study is a prospective cohort of hospitalized patients age >18 enrolled with either ACS or ADHF between 2011 and 2015 (index hospitalization). We then excluded those who died during the index hospitalization, patients with hospitalization <24 hours, patients discharged to hospice care, or those who underwent coronary artery bypass surgery because of the high probability of receiving opioids. In addition, we limited the analyses to patients whom we had complete covariate data. The primary predictor variable was an opioid prescription at the time of hospital discharge. We collected healthcare utilization behavior for 90 days after discharge, and mortality data until March 8, 2017. Time-to-event analysis using Cox proportional hazard models was performed for both unintended healthcare utilization behavior and mortality outcomes. Logistic regression was performed for intended healthcare utilization (adherence to follow-up appointments and cardiac rehabilitation). All models were adjusted for demographic data, opioid use prior to index hospitalization, severity of illness, and healthcare utilization prior to the index hospitalization. RESULTS/ANTICIPATED RESULTS: There were 501 patients discharged with an opioid prescription and 1994 with no opioid prescription at discharge. Among patients with opioids at discharge 235 (47%) experienced unplanned healthcare events (71 ED visits and 164 readmissions) and among nonopioids patients 775 (39%) experienced unplanned healthcare events (254 ED visits and 521 readmissions) (aHR: 1.06, 95% CI: 0.87, 1.28). Patient mortality in the opioid group was 131 Versus 432 in the nonopioid group (aHR: 1.08, 95% CI 0.84, 1.39). Patients in the opioid at discharge group were less likely to attend follow up visits or participate in cardiac rehab (OR: 0.69, 95% CI 0.52, 0.91, p=0.009) compared with those not discharged on opioid medications. Sensitivity analysis of patients who were prescribed prehospital opioids (including prehospital opioids in the exposure group with postdischarge opioids) did not reveal a statistically significant increase in mortality (aHR: 1.09, 95% CI 0.91, 1.31) or unintended healthcare utilization (aHR: 1.12, 95% CI 0.89, 1.41) among opioid users. DISCUSSION/SIGNIFICANCE OF IMPACT: Morbidity and mortality related to opioid use is a public health concern. Our study demonstrates a statistically significant reduction in physician follow-up and participation in cardiac rehab among opioid users, both of which are known to decrease patient mortality. We did not find a statistically significant increase in unplanned healthcare utilization or mortality. Sensitivity analysis combining prehospital and posthospital opioid prescriptions did not reveal a statistically significant association between opioid use, hospital readmissions, or mortality. The hospital provides unique patient interactions where providers can make significant medical changes based on their patient’s clinical status. Continuing to understand the association between opioid use, healthcare utilization, morbidity, and mortality in recently hospitalized cardiac patients will provide data to support reduction in total opioid dose to improve clinical outcomes.

OBJECTIVES/GOALS: Real-world data (RWD) may offer insights into mental health treatment as usual and illuminate targets for implementation and translation. This requires strong research-community partnerships (RCP). In this presentation, we will highlight key components of an ongoing RCP in leveraging RWD to advance translational science. METHODS/STUDY POPULATION: The RCP was formed to develop an infrastructure for NAMI Chicago, a community-based organization that oversees a city-wide social services helpline, to support collection of RWD data to understand whether NAMI helpline support services and referrals meet callers’ emotional and physical needs. This RCP includes three entities: NAMI Chicago, UIC’s Center for Clinical and Translational Science’s Community Engagement and Collaboration (CEC) Core, and UIC’s Institute for Health and Research Policy’s Data Management Core (DMC). From a preliminary review of case notes, this case study details concrete examples that fit into Brookman-Frazee etal. (2012)’s RCP framework to illustrate the trajectory of this partnership through its formation, execution of activities, and sustaining NAMI Chicago’s data capacity. RESULTS/ANTICIPATED RESULTS: In the formation of this RCP, we identified our joint goal of creating a database infrastructure to link NAMI Chicago’s existing helpline data with a database co-created in REDCap through APIs. Based on the identified joint goal, we defined our roles/responsibilities that best aligned with our own individual expertise to execute the necessary operational processes. The RCP is currently executing the activities to create this data infrastructure. Barriers included delays in securing a computing environment and enablers included an established long-standing relationship between NAMI Chicago and CEC. Distal outcomes of this RCP include increasing NAMI Chicago’s capacity to systematically use RWD to better inform their practices and identify barriers in accessing social service resources in Chicago. DISCUSSION/SIGNIFICANCE: The identification of enablers, barriers, and the necessary operational processes and activities will outline a “blueprint” for other institutions and community organizations to successfully utilize RWD to understand mental health practices and advance translational research.

OBJECTIVES/GOALS: Understanding the mechanism of transcriptional adaptation may contribute to an explanation for variation in clinical manifestations of Amyotrophic lateral sclerosis patient phenotypes. METHODS/STUDY POPULATION: To examine transcriptional adaptation, we utilized gene editing tools in HT1080 cells and patient samples with known CHCHD10 mutations causative for Amyotrophic lateral sclerosis. Frameshift mutations were performed via CRISPR-Cas9. Ribonucleoprotein electroporation was used to transfect cells and DNA sequencing was conducted to validate gene editing. To validate transcriptional adaption, changes in levels of protein and gene expression will be measured via immunoblot and quantification of CHCHD10 and CHCHCD2 from whole cells lysates of the edited cells. RESULTS/ANTICIPATED RESULTS: We anticipate that CHCHD2 transcriptional adaptation can functionally compensate for the locus loss of function of CHCHD10. This mechanism of transcriptional adaptation may contribute to an explanation for variation in clinical manifestations of patient phenotypes. DISCUSSION/SIGNIFICANCE: Our approach would advance discovery science towards by exploring CHCHD10/2 transcriptional adaptation mechanism that can lead to novel therapies for rare Amyotrophic lateral sclerosis, such as CHCHD10-R15L.

OBJECTIVES/GOALS: In triple negative breast cancer (TNBC), obesity is associated with poor outcomes. Adipose stem cells (ASCs) from obese patients (obASCs) secrete higher levels of adipokines compared to ASCs from lean individuals. Leptin, one of these adipokines, has been implicated in many cancers. This study seeks to examine the role of leptin signaling in TNBC. METHODS/STUDY POPULATION: Previous work in conjunction with a collaborating lab has shown that leptin signaling promotes metastasis and increased expression of epithelial-mesenchymal transition (EMT) markers in triple negative breast cancer cell lines. This project expands upon this work through using both patient-derived cell lines and and patient-derived xenografts (PDX), and examines the role of leptin signaling both in vitro and in vivo. To determine the effects of obesity upon a PDX model of TNBC, a high fat diet was used to induce obesity in vivo. A pharmacological inhibitor of the leptin receptor was used to test the requirement for leptin signaling both in vivo and in vitro. RESULTS/ANTICIPATED RESULTS: Exposure to conditioned media harvested from obASCs increased the percentage of TNBC cells that expressed cancer stem cell markers, whereas exposure to an inhibitor of the leptin receptor decreased the percentage of cells with cancer stem cell markers. PDX tumors implanted into mice with diet-induced obesity had an increased volume compared to tumors implanted into lean controls. Further analysis will be conducted on metastasis, circulating tumor cells, and survival in both lean and obese mice. DISCUSSION/SIGNIFICANCE: Understanding the complex signaling events in the obese tumor microenvironment is essential, as these molecular differences may contribute to different outcomes for obese and lean individuals with triple negative breast cancer. Therefore, study of the crosstalk between obASCs and TNBC cells is critical.

OBJECTIVES/GOALS: Neonatal hypoxic-ischemic encephalopathy (HIE) is an acute neurologic syndrome where decreased blood flow and oxygen to the brain causes acute and chronic brain dysfunction. The only proven neuroprotective intervention for HIE is hypothermia treatment started within 6 hours of birth and 50% of survivors have long-term deficits. METHODS/STUDY POPULATION: Pre-clinical adult stroke studies demonstrated that vagus nerve stimulation (VNS) has anti-inflammatory effects and attenuates brain damage. Transcutaneous auricular VNS (taVNS) is safe and feasible in infants and may improve the motor skill of bottle feeding. We hypothesize that a combined hypothermia-taVNS treatment shortly after HIE birth will have neuroprotective effects, improve motor function, attenuate infarct volume inflammation compared to hypothermia alone. The HIE model includes ligation of the right common carotid artery in postnatal day 7 (P7) rats followed by 90min hypoxia (8% oxygen) and 2hr hypothermia. taVNS or sham taVNS was administered using a bipolar electrode placed on the auricular concha region for 30min, [30sec trains, 0.5msec duration, 20Hz frequency, followed by 4.5min breaks] RESULTS/ANTICIPATED RESULTS: Experimental groups include +HIE/+taVNS, +HIE/-taVNS, and -HIE/-taVNS. To assess motor function, grasping reflex and forelimb grip strength tasks were assessed prior to surgery through P10. Infarct volume was assessed at 72h after injury by staining coronal sections with cresyl-violet. Thirty-four rat pups underwent surgery with an 8.82% mortality rate. taVNS was well tolerated by the P7 rats when delivered below perceptual threshold (0.4-1.1mA). There was no difference in elementary motor function or infarct volume between any group. DISCUSSION/SIGNIFICANCE: Future studies will include 2.5hr hypoxia for a more severe brain injury and a -HIE/+taVNS control group. These initial pre-clinical studies in neonates are important in determining whether taVNS may translate as a treatment to improve outcomes after neonatal HIE.

OBJECTIVES/SPECIFIC AIMS: Community-engaged research can provide important input to researchers to understand the impact of health services on diverse communities. In emergency (911) dispatch research, most studies have focused on specific health conditions, especially on identifying and managing those conditions remotely and identifying the most appropriate resources to send. Community-engaged research can add a needed component to these studies, identifying not only what happens when someone calls 911, but who calls and who doesn’t, what barriers community members encounter when they call, and what they expect from their 911 service. METHODS/STUDY POPULATION: A recent study published in the Journal of Clinical and Translational Science outlined a method for identifying and evaluating the needed competencies and readiness of individual researchers to do effective community-engaged research. The investigators involved in an ongoing study on community attitudes toward 911 propose to use the methods outlined in that study to receive feedback from their Community Advisory Board on their own competencies and readiness. RESULTS/ANTICIPATED RESULTS: It is anticipated that 13 people will be involved in providing feedback to the investigators, including all official member of the Community Advisory Boards and all supportive academic staff and faculty. The feedback will be gathered using a survey instrument developed from the recently-published study and will include questions about the purpose of the research, openness to feedback, communication, cultural sensitivity, community presence, power sharing, recognizing partner contributions, and developing community capacity. DISCUSSION/SIGNIFICANCE OF IMPACT: Identifying the most appropriate resources to send to any given emergency is the primary role of the emergency dispatcher. However, they are also public servants, providing care and comfort in a time of stress to members of many diverse communities. As such, it is critical that they understand the needs and expectations of those communities, as well as the barriers they face in calling 911. The proposed study adds value to an ongoing community-engaged research project by providing feedback about readiness and competency to the investigators.

OBJECTIVES/GOALS: Low-dose aspirin is an established treatment to prevent preeclampsia, a leading cause of maternal and perinatal complications. Nevertheless, aspirin failure is not uncommon. We are investigating whether a gain-of-function genetic polymorphism in a platelet thrombin receptor is associated with aspirin failure in the prevention of preeclampsia. METHODS/STUDY POPULATION: Women who had preeclampsia in an initial pregnancy who then received low-dose aspirin in a subsequent pregnancy will be evaluated. We will compare between women who developed preeclampsia despite aspirin (aspirin non-responders) to women who did not develop preeclampsia with aspirin treatment (aspirin responders). Specifically, we will evaluate the allelic frequency of a single nucleotide variant (rs773902) in PAR4 thrombin receptor on platelets. This variant is associated with increased platelet function and potentially aspirin resistance. In addition, we will analyze the platelet response to PAR4 activation before and 1 hour after administering a single 81 mg enteric-coated aspirin tablet. RESULTS/ANTICIPATED RESULTS: We hypothesize that the prevalence of the PAR4 variant will be significantly higher among women who had recurrence of preeclampsia despite aspirin therapy. We also postulate that women who developed preeclampsia despite aspirin prophylaxis and have the polymorphism will have increased platelet aggregation in response to activation of PAR4, either by thrombin or peptides that activate the receptor, both at baseline and 1 hour after aspirin administration. DISCUSSION/SIGNIFICANCE: If our hypothesis that aspirin failure in preeclampsia prevention is associated with the gain-of-function polymorphism in the platelet PAR4 thrombin receptor, there may be justification for additional experimental studies to assess whether better pregnancy outcomes can be obtained by targeting thrombin itself using low molecular weight heparin.

OBJECTIVES/SPECIFIC AIMS: Previous studies suggest that prenatal exposure to environmental pollutants can have an adverse effect on brain development. We examine the association between prenatal near roadway air pollution (NRAP) exposure and early neurodevelopment. METHODS/STUDY POPULATION: The Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) Study is a prospective birth cohort that began in 1999 with 605 mother-child pairs of primarily Mexican-American descent. Maternal residence during pregnancy was geocoded using ArcGIS and prenatal NRAP exposure was assigned using the CALINE4 line source dispersion model. We used composite Bayley Scale scores for cognitive and motor development, and created separate linear regression models at 6, 12, and 24 months of age. RESULTS/ANTICIPATED RESULTS: After adjusting for relevant maternal and child characteristics, preliminary estimates suggest that prenatal NRAP exposure is associated with a nonsignificant increase in Bayley Scale scores at 6 and 24 months (cognitive: β=0.13, p-value=0.20 and motor: β=0.08, p-value=0.58 at 6 months; cognitive: β=0.16, p-value=0.42 and motor: β=0.20, p-value=0.25 at 24 months) and a nonsignificant decrease at 12 months (cognitive: β=−0.07, p-value=0.64 and motor: β=−0.12, p-value=0.56). DISCUSSION/SIGNIFICANCE OF IMPACT: Our preliminary findings do not suggest that prenatal NRAP exposure is associated with early cognitive development. Additional exploration of co-exposures known to effect neurodevelopment should be examined in this rural population.

ABSTRACT IMPACT: This work is intended to improve community engagement salons both virtually and generally in order to maximize the benefit of this vital research tool. OBJECTIVES/GOALS: The Meharry-Vanderbilt Community Engaged Research Core (CERC) provides a protocol to maintain high standards in community engagement studios, even in a virtual setting amidst a pandemic. A virtual community engagement salon was selected as a case study to evaluate outcomes. METHODS/STUDY POPULATION: A virtual salon regarding sun safety in the Latinx community was observed live via Zoom and as a recording afterward. Following dissemination and completion of the post-meeting surveys, authors compiled and reviewed the results. An assessment was developed to determine the salon’s alignment with the Meharry-Vanderbilt CERC guidelines in a virtual setting; this was designated as the primary outcome. Data from the session were compared to the available literature on the topic, which produced three subheadings to the secondary outcome essential to the success of virtual community engagement salons: researcher preparedness, participant selection, and survey importance. RESULTS/ANTICIPATED RESULTS: The CERC guidelines of the community engagement salon were met and were effectively translated into a virtual setting. The presentation given by the researcher followed all technical instructions, yet it was clear that the researcher’s demeanor and conversational soft-skills were lacking. Instead of the recommended bi-directional flow of conversation, the conversation flow shifted to a unidirectional state controlled by the participants. Following the session, only three participants completed the survey along with the researcher. This completion rate of under 50% provides limited feedback on participants’ perspectives on the session’s quality and points to improve future sessions. DISCUSSION/SIGNIFICANCE OF FINDINGS: Pre-meeting researcher preparation is necessary to engage community stakeholders effectively. The lack of completed surveys from participants suggests potential fatigue from leading a majority of the conversation. Results demonstrate that solely meeting the requirements of the CERC does not suffice.

OBJECTIVES/GOALS: In March 2019, Duke updated recruitment guidelines and adopted an “Engagement” policy that requires patients to ‘opt-out’ of communications regarding potential research participation. This created an opportunity to evaluate recruitment for ongoing clinical studies pre and post implementation. METHODS/STUDY POPULATION: Implementation of the new policy required new training for study teams, modification to recruitment plans, and expansion of ongoing efforts to improve direct-to-patient messaging through EPIC/MyChart tools. The impact of this new policy on overall recruitment was monitored and characterized both prior to and after implementation of the policy. Customized MyChart messages have been generated for over 22 studies, with a total of 41,386 messages sent to potential participants. RESULTS/ANTICIPATED RESULTS: Only a small number of study teams have modified their recruitment plans with transition to the new policy. This may be related to lack of understanding about policy implementation, potential recruitment opportunities, required training, resource limitations, etc. However, our case study, TMIST, had an 48% improvement in average enrollment within the first 2 months of implementation, and an almost 40% improvement in recruitment efficiency. Since becoming an “opt-out” institution, 11 study teams have implemented direct-to-patient recruitment via the MyChart patient portal. One unintended consequence we’ve noted is several different study invitations to potential participants within some patient populations. DISCUSSION/SIGNIFICANCE OF IMPACT: The new policy allows study teams to engage in direct-to-patient outreach, leading to an increase in enrollment for some studies. Incorporation of direct-to-patient messaging strategies can be a cost and resource saving measure to improve recruitment. The need to recruit similar populations demonstrated that strategic, thoughtful approaches are needed.

OBJECTIVES/GOALS: Healthcare costs for falls are expected to reach nearly 55 billion dollars annually in the US by 2020. Leveraging 911 calls as trigger events to activate fall prevention solutions could transform our ability to identify high-risk individuals and significantly improve fall prevention strategies globally. METHODS/STUDY POPULATION: An innovative pilot program entitled Community-centered Fall Intervention Team (Community FIT). Community FIT that leverages 911 calls, implementation science approaches, community partnerships, and collaboration among multiple healthcare disciplines including physical therapists, community paramedics, physicians, and social service coordinators was used to design and implement a community paramedicine fall intervention program. 911 call reports from February 2016 – August 2019 were analyzed using time series analyses to measure community level outcomes in fall-related calls and transports. RESULTS/ANTICIPATED RESULTS: 224 grab bars were installed free of charge to local residents (averaging approximately $125 per home for modifications).Over an 18-month period, time series analysis indicated an approximate demonstrated a consistent drop in the average fall-related 911 calls per month from 11.6 to 4.5 calls (a change of 61.21%) and a decrease of 58% in the transport rates to the hospital for fall-related 911 calls. 911 referrals to the community paramedicine program have also increased by 83%, demonstrating increased activation of fall prevention strategies with Community FIT. DISCUSSION/SIGNIFICANCE OF IMPACT: Collectively, these pilot study results provide preliminary support for individual and system level improvements in fall prevention by leveraging 911 calls to activate a community medicine fall prevention program. Future studies are needed to determine reach, long-term effectiveness, and sustainability of the program. CONFLICT OF INTEREST DESCRIPTION: Johnson & Johnson Hip Fracture Advisory Board (not related to project submission)

OBJECTIVES/GOALS: Smoking is a well-established risk factor for lung cancer, but never smokers account for up to 25% of lung cancer cases. There is mounting evidence that lung cancer in never smokers is biologically distinct. We aim to characterize the genomic and immunologic features of lung adenocarcinoma in never smokers versus smokers. METHODS/STUDY POPULATION: We examined clinical, genomic, and bulk-RNA sequencing data from 499 patients in the TCGA lung adenocarcinoma cohort. Tumor mutation burden was analyzed using maftools (R package). Tumor immune characterization was completed using CIBERSORTx, a digital cytometry tool that uses single cell reference profiles to determine immune cell type frequencies from bulk-RNA sequencing data. Single cell reference profiles for 19 different immune cell types were constructed from sequencing of freshly resected lung tumor tissue from UCSF patients. Partitioning Around Medoids (PAM; R package) was used to identify distinct immune phenotypes based on immune cell composition. Fisher’s exact test was used to evaluate for associations between immune phenotypes and smoking status. RESULTS/ANTICIPATED RESULTS: Of the 499 TCGA lung adenocarcinoma patients, 75 were never smokers, 269 were female, and 246 were over the age of 65. Never smokers had lower tumor mutation burden and lower predicted neoantigen burden compared to smokers (p < 0.001). There was no difference in total tumor immune cell infiltration between never smokers and smokers. PAM yielded 2 distinct clusters/immune phenotypes. The first was enriched in M1 Macrophages, cytotoxic T Cells, helper T Cells, regulatory T Cells, and Plasma Cells. The second was enriched in plasmacytoid Dendritic Cells, M2 Macrophages, and exhausted cytotoxic T Cells. Never smoking status was associated with an increased odds of having the first immune phenotype (OR 1.95, 95% CI: 1.15 - 3.35) and this association was statistically significant (p = 0.0086). DISCUSSION/SIGNIFICANCE: Our findings suggest that never smokers have an immune phenotype that is distinct from that observed in smokers. The distinct immune characteristics we observed could explain clinical trial data suggesting immune checkpoint inhibitors are less effective in never smokers and hold implications for tailoring therapy.

OBJECTIVES/GOALS: This study examines psychological resilience in adults living with Sickle Cell Disease (SCD) in the U.S. aiming to explore how psychological resilience is defined by this community. METHODS/STUDY POPULATION: Participants were recruited between 2014 – 2018, from across the U.S. as part of an ongoing cross-sectional study: Insights into Microbiome and Environmental Contributions to Sickle Cell Disease and Leg Ulcers Study (INSIGHTS). Inclusion criteria included age of 18 or older, with a clinical history of SCD, and were interviewed if they completed the Brief Resilience Scale (BRS) as part of INSIGHTS. 150 study participants were separated by their BRS scores into “High” and “Low” scoring quartiles. 30 participants were randomly selected, 15 from the lowest quartile and 15 from the highest. All participants completed the Connor Davidson Resilience (CD) measure at the end of their qualitative interview. All identified as Black with an average age of 42.5 (13 F, 17 M). RESULTS/ANTICIPATED RESULTS: Three main concepts emerged within both groups in response to the question “How do you define resilience?” (a) not giving up (b) how one deals with challenges and (c) moving forward. DISCUSSION/SIGNIFICANCE: Our analysis shows that the BRS may not be a precise or accurate indicator of the resilience of adults living with SCD. Therefore, it remains to be seen if these measures are descriptive of these individuals true psychological or physiological state as they have not been used in this community until now.

OBJECTIVES/SPECIFIC AIMS: The goal of this study is to characterize traumatic events and post-traumatic stress symptom severity experienced by caregivers of children with hydrocephalus. Results will eventually be evaluated and compared with demographic and medical characteristics. This study is part of a larger research project that aims to (1) determine the prevalence and risk factors for post-traumatic stress symptoms in pediatric hydrocephalus patients and their caregivers; (2) develop a targeted intervention to mitigate its effects and pilot test the intervention. METHODS/STUDY POPULATION: Caregivers of children with hydrocephalus that have received surgical treatment (CSF shunt or ETV/CPC) were enrolled during routine follow up visit in a pediatric neurosurgery clinic. Caregivers completed the PTSD Checklist for DSM-5 (PCL-5), a 20-item self-report measure that assesses the presence and severity of post-traumatic stress disorder (PTSD) symptoms. RESULTS/ANTICIPATED RESULTS: Participant responses (n=56) revealed that 57.14% of caregivers indicated that their most traumatic event was directly related to their child’s medical condition. In total, 23.21% of caregivers did not specify their most traumatic event and 1.79% of caregivers indicated that they had never experienced a traumatic event. Median Total Symptom Severity Score was 11 (mean: 15.32±14.92), and scores ranged from 0 to 67; 32.14% of caregivers scored 19 or greater, and 16.07% of caregivers scored 33 or greater, a value suggestive of a provisional diagnosis of PTSD. Severity scores by DSM-V clusters were as follows: cluster B—intrusion symptoms (mean: 4.91±4.77, median: 4, range: 0–20), cluster C—avoidance symptoms (mean: 1.27±1.87, median: 0.5, range: 0–8), cluster D—negative alterations in cognition and mood (mean: 4.86±6.07, median: 2, range: 0–22), and cluster E—alterations in arousal and reactivity (mean: 4.29±4.07, median: 3, range: 0–17). DISCUSSION/SIGNIFICANCE OF IMPACT: Preliminary results from this study indicate that post-traumatic stress symptoms are prevalent among caregivers of children with hydrocephalus. These results suggest that psychosocial issues such as PTSS may be a significant problem in need of treatment, that is not traditionally addressed as part of routine care for families of children with hydrocephalus. Characterizing post-traumatic stress symptoms in this population sets the foundation for the development of screening and treatment protocols for post-traumatic stress symptoms in caregivers of children with hydrocephalus. This study is the first step towards fundamentally improving routine clinical care and quality of life for patients with hydrocephalus and their caregivers by understanding and addressing the effects of traumatic stress.