OBJECTIVES/GOALS: Participants will be able to identify how partnering with state health departments for a CTSA initiative assists in meeting shared goals by building infrastructure and sharing resources and list key components of a successful county engagement process that can be replicated. METHODS/STUDY POPULATION: Connections IN Health is a collaborative project with the Indiana Clinical and Translational Sciences Institute, Indiana Department of Health, Indiana University Simon Comprehensive Cancer Center, and community partners. We address chronic disease in Indiana with coalition-based engagement at the grassroots level, and partnering to provide technical assistance, resources, connections and evidence-based strategies to address the health challenges. Our methods of county engagement include surveying the broad community, conducting listening sessions with key community stakeholders, compiling, analyzing and sharing data, collaborating with existing local coalitions, assessing community readiness and suggesting evidence-based practices to implement. RESULTS/ANTICIPATED RESULTS: As a result of county engagement, local coalitions have current, local data to drive their efforts in improving local health rankings and outcomes. Community partners in eight counties have selected and implemented evidence-based strategies to manage and/or prevent diabetes, cardiovascular disease and/or stroke. Some examples include: starting a community garden with cooking classes in a food desert to provide fresh produce and nutrition/cooking knowledge, creating a mobile kitchen on hand for organizations to use to provide education and cooking skills, providing a passport for wellness at existing community events with food samples and health screenings and offering evidence-based educational programming such as Dining with Diabetes and Be Heart Smart. DISCUSSION/SIGNIFICANCE: Moving county health coalitions to evidence-based programming that has the greatest likelihood for success is a critical translational sciences challenge. Our rigorous and well defined approach yields significant improvement in local health coalition activities, sustaining their activities through long-term trusted relationships.

OBJECTIVES/GOALS: Translational Science includes the social responsibility to improve health outcomes and reduce disparities. This study aims to determine how scientists and community members perceive the social responsibility of translational science. METHODS/STUDY POPULATION: Methods include a series of 12 one-hour semi-structured focus groups. Six groups were held with a total of 34 scientists and four with approximately 32 community members (community focus groups still ongoing). Sample includes scientists and community members affiliated to one of three research fields: HIV/AIDS, Maternal Health, and Mental Health/Substance Use. Inclusion criteria for scientists were based on their scholarly contributions to a field. Community members included individuals who self-identified as affiliated to any above fields. Using reflexive thematic analysis, we analyzed the transcripts against existing frameworks on social responsibility. RESULTS/ANTICIPATED RESULTS: Literature on social responsibility suggests that translational science should be relevant, usable and sustainable for end-users. Scientists and community members identified the same groups for whom research is relevant. Scientists often conceptualized social responsibility through the sustainability lens, focusing on results that might have long-term societal impacts. Due to this, they saw limitations to social responsibility in academia and funding structures. Community members often conceptualized social responsibility through the usability lens, focusing on the complexity of research use and access. They saw barriers to social responsibility in systemic disparities. DISCUSSION/SIGNIFICANCE: Although participants emphasized different practices in focus groups, participants seemed generally interested in pursuing future discussions to develop best practices and commitments regarding social responsibility. Further discussions will take place in a deliberative dialogue activity in January 2024.

OBJECTIVES/SPECIFIC AIMS: To study the role functional capacity plays in surgical outcomes for head and neck cancers. METHODS/STUDY POPULATION: In this single-institution cohort study, we combined preoperative anesthesia assessment information with oncology registry data for newly-diagnosed patients with squamous cell carcinoma of the oral cavity, pharynx, and larynx (HNSCC) treated with definitive surgery at Siteman Cancer Center from 2012 to 2016. Patient-reported exercise capacity was assessed as metabolic equivalents. Metabolic equivalents<4 was defined as poor functional capacity. The primary outcome measure was overall survival (OS). Kaplan-Meir survival analysis was used to compare the survival of patients with poor functional capacity (PFC) and patients with normal functional capacity (NFC). Cox proportional hazard regression was used to explore the independent prognostic role of functional capacity on overall survival after controlling for other factors. RESULTS/ANTICIPATED RESULTS: A total of 671 patients underwent surgical treatment for HNSCC. The average age was 62 years (range: 19–94 years). Majority of the patients were male (n=481; 72%), White race (n=589; 88%), and smokers (n=528; 79%). Of 671 patients, 22% (n=146) had PFC. Two-year OS rate in PFC patients was 70% compared with 85% in NFC patients (15% difference; 95% CI: 7%–23%). Unadjusted Cox proportional hazard analysis showed that PFC patients had 2.2 times higher risk of death (95% CI: 1.5–3.2) than NFC patients. After adjustment for age at surgery, BMI, preoperative weight loss, comorbidity score, tumor site, and TNM stage the magnitude of the association between functional capacity and OS decreased (aHR=1.3; 95% CI: 0.88–1.98). DISCUSSION/SIGNIFICANCE OF IMPACT: Poor functional capacity is associated with decreased overall survival, but the magnitude of the association, while clinically meaningful, decreases after controlling for other important patient and tumor factors. Nevertheless, we believe preoperative functional capacity status is an important patient factor to consider when discussing prognosis and attempting risk stratification. We also believe that functional capacity may be associated with 30-day unplanned readmissions and 90-day complications and are currently performing chart review to ascertain this information.

OBJECTIVES/SPECIFIC AIMS: Infants with single ventricle congenital heart disease (CHD) who undergo staged surgical reconstruction are among the pediatric patients at highest risk for thrombotic complications. Despite improvements in survival due to medical and surgical advancements, thrombotic complications are common and lead to increased morbidity and mortality, especially during the first two stages of surgical reconstruction. The burden of disease caused by thrombosis is not fully known, and the risk factors associated with thrombosis are not clear. Due to this knowledge gap, prevention of thrombosis with medication, a strategy called thromboprophylaxis, has not been standardized, leading to inadequate prevention of thrombosis. In order to understand the burden of thrombosis and then provide targeted thromboprophylaxis for thrombosis prevention, better characterization of thrombotic complications and the associated factors is needed. Hypothesis: I hypothesize that in infants with single ventricle CHD, the incidence of thrombosis will be more frequent after stage I Versus stage II reconstruction, despite the type of shunt used. Specific demographic, clinical, and surgical variables will be associated with an increased risk for thrombotic complications, and a model to predict which subset of infants is at increased risk will be developed. Specific Aim 1: Characterize the incidence of thrombotic complications at different time points from stage I through stage II of the single ventricle reconstruction (SVR) pathway and determine the demographic, clinical, and surgical factors associated with thrombosis in infants with single ventricle CHD. (1) Determine the incidence of thrombosis in infants with single ventricle CHD. (2) Compare the rate of thrombotic complications between the 2 most commonly used approaches for stage I reconstruction for the group of patients with hypoplastic left heart type of anatomy [modified Blalock-Taussig shunt (MBTS) vs. right ventricle to pulmonary artery shunt (RVPAS)]. (3) Determine the factors (demographic, clinical, and surgical) associated with thrombosis in infants with single ventricle CHD. Specific Aim 2: Determine which subset of infants with single ventricle CHD is at increased risk of developing thrombotic complications across the first 2 stages of surgical reconstruction. (1) Test the identified demographic, clinical, and surgical variables including, but not limited to, gestational age, sex, CHD diagnosis, baseline oxygen saturation, stage of reconstruction, shunt type, and other clinical data available in a univariable and multivariable analysis and study their potential interactions to construct a novel risk predictive model specific for single ventricle CHD. METHODS/STUDY POPULATION: To address the specific aims, I will utilize data from the SVR clinical trial public use data set. This data set includes a prospective cohort of infants, 0–14 months of age, enrolled from any of the 15 participating clinical centers from the years 2005 to 2009. Inclusion criteria for enrollment were diagnosis of hypoplastic left heart syndrome or related single, morphologic right systemic ventricle anomaly, planned Norwood procedure, and informed consent of parent or legal guardian. No additional subjects outside of this data set will be included. Exclusion criteria were a diagnosis of single, morphologic left ventricle anomaly, preoperative identification of anatomy rendering the MBTS or RVPAS technically impossible, and any other major abnormality or acquired extra-cardiac disorder that could independently affect the likelihood of the subject meeting the primary endpoint. The complication of stroke will be excluded from the analyses of factors associated with thrombosis. The complication of thrombosis as defined in this dataset is a composite of events that include arterial or venous thrombosis, thromboembolism, and pulmonary embolism. The data was collected in such a way that it will not be possible to separate these sub-types of thrombosis. Additional thrombotic events of interest are superior vena cava occlusion and inferior vena cava occlusion. Specific Aim 1: Patient data will be extracted from the SVR clinical trial public use dataset to characterize the incidence of thrombotic complications at different time points from stage I through stage II of the SVR pathway and determine the demographic, clinical, and surgical factors associated with thrombosis in infants with single ventricle CHD. In addition, I will compare the rates of thrombotic complications between the 2 most commonly used approaches for stage I palliation for the group of patients with hypoplastic left heart type of anatomy (MBTS vs. RVPAS) and will test the hypothesis that the risk of thrombotic complications is associated with the stage of palliative surgery (stage I vs. stage II). Specific Aim 2: We will test identified demographic, clinical, surgical, and newly identified variables in a univariable and multivariable analysis and study their potential interactions to construct a novel risk predictive model specific for single ventricle CHD. RESULTS/ANTICIPATED RESULTS: To determine feasibility for adequate numbers to be able to address the research aims, a preliminary analysis dataset was performed using a dataset from the Pediatric Heart Network. The PHN is a collaborative group of hospitals that participates in clinical research studies in children with CHD. For the SVR clinical trial, the PHN conducted a randomized clinical trial at 15 centers in North America between 2005 and 2009, prospectively enrolling infants with HLHS or single right ventricle anomalies who were to undergo the Stage I Norwood procedure. A total of 920 newborns were screened; 664 were medically eligible and 549 patients were randomized. The primary aim of the trial was to compare survival of infants randomized to receive either the Norwood procedure with the MBTS or the RVPAS. These patients were followed at specific time points, including from baseline (pre-Norwood), at the time of the Norwood procedure, between stage I and II, following stage II reconstruction, and at 14 months of age. At these time points, data were collected that includes demographic, radiologic, clinical, and surgical outcomes. Included in the clinical outcomes are complications, such a thrombosis. There was no screening process to assess for asymptomatic thromboses, suggesting that most, if not all, discovered thromboses were due to clinically relevant effects. A newer iteration of this study (SVRIII) expands the monitoring of this cohort until the Fontan stage at 2–6 years of age, but these data have not yet been released in the public use data set. A descriptive analysis of the frequency of thrombotic complications was assessed at each time point, as well as in aggregate. Data were extracted from the specific time periods of interest, identified as Pre-Norwood, during Norwood Hospitalization, in-between visits, and during Stage II Hospitalization. There were 549 infants who were randomized with available data to analyze. During the Norwood hospitalization, 37 infants had a thrombotic complication. Between Stage I and Stage II outpatient visits, 8 infants had a thrombotic complication. During Stage II hospitalization, 16 infants had a thrombus. Overall, 61 individual patients (11%) had a thrombotic complication. DISCUSSION/SIGNIFICANCE OF IMPACT: This study utilizing data from the Pediatric Heart will be the largest cohort ever utilized for characterizing thrombotic complications and determining the factors associated with thrombosis across the first and second stages of surgical reconstruction. More than 500 (n=549) subject’s data will be analyzed through the first two stages of reconstruction, while the largest analysis before this proposed analysis only included a total of 195 children. Notably, these prior studies did not include a comparison between the 2 shunt types in stage I reconstruction, leaving a gap in knowledge regarding the incidence of thrombosis comparing these groups. The analysis will be the first to address this gap and update the current literature. Preliminary data show that the overall incidence of thrombosis across the first 2 stages of surgical reconstruction was 11%, which is lower than the previously reported overall rates of 40%–50%. Despite the continued lack of evidence-based guidelines for thromboprophylaxis methods, the decreased overall rate is most likely due to more widespread practice of anticoagulation in general. Determining the factors associated with thrombosis across the first and second stages of surgical reconstruction will help identify those at risk. An innovative aspect of this analysis will be the use of disease-specific factors to develop a model to predict thrombosis. Unique factors include cardiac variables like ejection fraction, baseline oxygen saturation, shunt type (MBTS vs. RVPAS), and other echocardiographic parameters. While the use of thromboprophylaxis has been associated with decreased risk of thrombosis, there is no general consensus to guide thromboprophylaxis in this population, which can be burdensome and costly. Determining which subset of infants with single ventricle CHD are at increased risk of developing thrombotic complications will allow for the development of a prediction model to predict those at highest risk of developing a thrombotic complication. Developing a predictive model will be a novel way to identify patients at risk for thrombosis and will set the stage for targeted prevention of thrombosis.

OBJECTIVES/GOALS: This research project aims to isolate and identify bioprospects capable of metabolizing estrogen using culture-dependent, culture independent methods and the identification of the gene/genes responsible for the metabolization of estrogen by the bioprospects. METHODS/STUDY POPULATION: For the culture dependent technique, samples were collected from the water treatment plant in Mayagüez, cultivated on TSA medium and selected specific and diverse colonies were patched on M-9NC (no carbon sources), M-9-glucose (M9G) and M-9-hormone mixture (M9H: 17-beta-Estradiol and 17-alpha-Ethynylestradiol). After the 48hrs incubation at 25 and 37 Celsius, growth was scored on the different media, to choose those potential bioprospects that use the hormones as the sole carbon source. For the culture independent approach, metagenomic clones from libraries generated from the Guajatacas water reservoir and Cabo Rojos Saltern microbial mats were cultivated on the appropriate M9NC, M-9G and M-9H, supplemented with Leucine and Thiamine for 48 hours at 37 Celsius. RESULTS/ANTICIPATED RESULTS: The culture-dependent approach showed a total of 6 potential bioprospects capable of growing on hormones as a sole carbon source on M9H at 25 and 37 Celsius and no-growth on the M-9 media used. Currently, we are in the process of determining the identities of the cultivable isolates genetically, any preference on hormone metabolization, monitoring a larger number of metagenomic clones and optimizing the selection conditions. DISCUSSION/SIGNIFICANCE: The identification of bioprospects capable of metabolizing hormones could potentially lead to the generation of new water treatments that could help remove unwanted chemicals, such as high concentrations of estrogens.

OBJECTIVES/GOALS: While there are many well-documented factors for racial/ethnic variation in discharge destination, less is known about the role hospital processes play. We hypothesize that variation in hospital processes -defined as the patient length of stay (LOS) adjusted for known confounders - explains racial/ethnic variation in discharge destination. METHODS/STUDY POPULATION: Our sample was 176,686 discharges from 165 hospitals in 2014 using the New York State Inpatient Dataset from the Healthcare Cost and Utilization Project, merged with the 2014 American Hospital Association Annual Survey to build a file of inpatient discharges with patient, disease and socio-economic characteristics. We excluded patients under 18 years, those with LOS of zero, those who died, those admitted to critical access hospitals, and patients from hospitals that lacked sufficient number of minority patients. We used a generalized linear mixed effects model to create an in-hospital risk-adjusted LOS by modelling the relationship between the interaction of race and discharge destination and LOS, controlling for known confounders such as patient, disease and between-hospital characteristics. RESULTS/ANTICIPATED RESULTS: Mean age of sample was 56.5 years, 57.3 % female, 54.9% white, 18.9% black and 13.1% Hispanic; 64.3% were discharged home, 15.8% to a skilled nursing or other intermediate care facility, 15.5% to home with home care and 2.4% left against medical advice. The top 3 discharge diagnoses were vaginal delivery (6.3% of discharges), psychosis (4.7%), and major joint replacement (2.9%). In adjusted analysis compared to white patients, black and Hispanic patients did not have an risk of increased LOS after being discharged to non-home destinations vs. discharged home, (black patients, adjusted OR [AOR], 0.97; 95% CI: 0.94-1.00, p = 0.08; Hispanic patients, AOR, 1.01; 95% CI: 0.98 – 1.05, p = 0.5). However, being black compared to white and discharge to non-home destinations significantly increased LOS. DISCUSSION/SIGNIFICANCE OF IMPACT: In this large sample of patients admitted for inpatient care in 2014 in New York, we found no independent effect between race and discharge destination on a patient’s LOS after controlling for patient, disease and between-hospital characteristics. However race/ethnicity increased LOS, suggesting its effect may play a role on in-hospital processes CONFLICT OF INTEREST DESCRIPTION: Dr. Ghosh has no relevant relationships with commercial interests to disclose Dr. Ibrahim has no relevant relationships with commercial interests to disclose

OBJECTIVES/GOALS: Our objective is to establish a proteomic protein labeling method from tumor tissue and blood samples obtained from patients undergoing surgery for pancreatic cancer in Puerto Rico. Our goal is to discover potential biomarkers in the patient tumor/blood samples that are not expressed in normal control samples obtained from potential organ donors. METHODS/STUDY POPULATION: A pilot study with ten patients undergoing surgery for pancreatic cancer will obtain tumor tissue and blood samples. Protein extracts isolated from tissue/cells will be reduced, alkylated, and digested overnight. Samples will be labeled with TMT reagents and mixed before fractionation and cleanup. Labeled samples will be analyzed with a high-resolution Orbitrap LC-MS/MS before data analysis to identify peptides and quantify the reporter ions. The altered proteins will be analyzed by ELISA to confirm their presence. The protein arrangements will be compared with results from proteomic profile banks to assess their prevalence. As controls, parallel protein analyses will be performed on normal tissue/blood samples from organ donors, facilitated by our local organ procurement organization. RESULTS/ANTICIPATED RESULTS: We anticipate finding proteogenomic material defining PC and new proteomic subtypes not previously described in this population. In addition, studying protein overexpression and underexpression can identify relevant genes and potential biomarkers. We hypothesize that PC in the Hispanic population will show slight variations in tumor protein expression than in other populations, which could lead to the discovery of a new Hispanic-specific biomarker. DISCUSSION/SIGNIFICANCE: We expect to provide essential information that will influence the next steps in developing future screening tests. Identifying specific proteins with the potential to become a preventive test should eventually lead to a reduction in morbidity and mortality of PC. The results of this work should lay the foundation that can guide future research.

OBJECTIVES/GOALS: This study utilizes a Black Feminist metatheoretical approach in conjunction with the Social Amplification of Risk Framework to: i) assess the role of communication with clinicians on Black women’s perceptions of risk and ii) outline recommendations for empowering communication that attenuates Black women’s perceptions of pregnancy risk. METHODS/STUDY POPULATION: Semi-structured in-depth interviews were conducted with 28 self-identified Black women in 2022 and 2023 to gain insights into their conceptualizations of pregnancy risk, and the role of communication with clinicians in the amplification and/or attenuation of pregnancy risk perceptions.An IRB approved flier was used for both in-person and online recruitment of participants from 12 US states.Each participant signed a consent form and received $20 as compensation for their time. Interviews were recorded and transcribed using a digital transcription tool, and then reviewed and edited to ensure accuracy. This study’s metatheoretical underpinning in Black Feminist Theory informed the use of reflexive thematic analysis in the qualitative analysis of the in-depth interviews. RESULTS/ANTICIPATED RESULTS: This study found thatunclear communication (including insufficiently contextualized history taking), obstetric violence, anddiagnoses with insufficient explanation,led to the amplification of concerns and worries about pregnancy as well as erosion of trust in healthcare. In contrast,clinicians lessenedconcerns about pregnancy through clear communication (including appropriately contextualized history-taking), demonstration of empathy, and by fostering patient agency.The study thus highlights the importance of clinicians' clear communication,demonstration ofempathy and fostering of patient agencyas critical factors to empowering communication that attenuates Black women’s pregnancy-related risk perceptions. DISCUSSION/SIGNIFICANCE: Given the unjust dangers Black women face during pregnancy, this study demonstrates how patient-clinician communication influences Black women’s pregnancy risk perceptions, providing recommendations for clinician communication practices that empower Black women and attenuate their perceptions of pregnancy risk.

OBJECTIVES/SPECIFIC AIMS: The primary objective of this study was to assess the interest in using mobile technology to manage hypertension and assessing medication adherence among African Americans and Hispanics living in a low-income urban community in Central PA. METHODS/STUDY POPULATION: This qualitative research study was designed using structured interviews with 30 African American participants with hypertension. The study survey consisted of 43 questions which included demographics, use of technology, technology literacy, health literacy, and medication adherence. Participants self-reported their responses about use of technology, literacy, and adherence. The data was examined using summary statistics. RESULTS/ANTICIPATED RESULTS: Out of 30 participants, 61% identified as African American and 30% identified as Hispanic. Overall, participants reported high use of technology; with 63.3% using the internet occasionally, 73.3% having a cell phone, and 66.7% accessing the internet using a mobile handheld device. Participants expressed an interest in measuring blood pressure, accessing health information, and managing medication on their cellphone or tablet. Twenty-five percent of participants self-reported not being confident at all in managing their medication without help and remembering to take their medication as prescribed. Fewer participants (54.2%) were very confident with using technology to help manage medication and treatment. DISCUSSION/SIGNIFICANCE OF IMPACT: This study provides important insights on the use of technology for managing hypertension in an urban low-income community. Results suggest that medication adherence, the use of technology, and the willingness to use mobile applications for hypertension management is high within this low-income community. This study gives future researchers a framework on how to assess these specific areas in their own population.

The survey investigates COVID-19 information source trust levels and Vietnamese Americans’ willingness to participate in clinical trials. An analysis of 212 completed surveys revealed that trust in coronavirus disease 2019 (COVID-19) clinical trial information from university hospitals and drug companies was associated with willingness to participate in clinical trials. Trust in COVID-19 information from federal governments and state governments was also associated with willingness to participate in clinical trials. However, trust in local health facilities was linked to trial participation reluctance. The results suggest that Vietnamese Americans’ participation in clinical trials can be increased by identifying and using trusted sources of information.

The COVID-19 pandemic laid bare the inequities in U.S. healthcare in ways that captured public attention and reinforced the need to view all of healthcare through an equity lens. It also exposed global inequities in access to healthcare technologies. At Rockefeller University, we participate in the entire spectrum of translational research, but our focus is in the areas of basic research and new methods to prevent, diagnose, and treat disease, extending to proof of concept preclinical and Phase 1 studies. Since we believe that all phases of translational research should have an equity lens, we have instituted an initiative to encourage thought and planning about global equitable access to discoveries made by our trainee Clinical Scholars and faculty, even at the earliest phases of basic research. Assuring global equitable access to new technologies requires addressing at least 3 different aspects of new technology: 1. Patenting and licensing, 2. Manufacturing, and 3. Dissemination and implementation in low- and middle-income countries. In this review, I focus on patenting and licensing and offer ten questions for inventors to consider in discussing licensing their technologies with technology transfer officers to maximize equitable global access to the technologies they create.

OBJECTIVES/GOALS: 1) illustrate the varied challenges individuals with a cocaine use disorder experience in daily life, 2) demonstrate techniques for empathizing and building rapport with potential subjects, and 3) identify recruitment obstacles and solutions. METHODS/STUDY POPULATION: Methods: We use a multi-source strategy to recruit our participants and employ practical techniques to enhance protocol adherence. Methods include a welcoming environment, establishing a routine with flexibility, personalized attention, and incentives for participation. Study population: Individuals with a cocaine use disorder. RESULTS/ANTICIPATED RESULTS: Understanding the life of an individual with a cocaine use disorder is paramount to successful recruitment and retention in addiction research studies. Our clinicians have been able to recruit and retain participants successfully by employing empathetic interpersonal skills, personalized attention, and health-related incentives. DISCUSSION/SIGNIFICANCE OF IMPACT: The Centers for Disease Control and Prevention estimated that 69,029 people died of a drug overdose during the period from February 2018 to February 2019, with 23%, due to cocaine. While methadone and buprenorphine-naloxone maintenance treatment allow opioid-dependent individuals achieve a sense of physical and mental stability, there is no pharmaceutical treatment to help a cocaine-dependent individual cope with cravings or the depression and anxiety that typically follow a cocaine binge. The development of a cocaine use disorder is multi-factorial and presents a significant challenge in terms of discovering treatments, identifying efficient recruitment and retention strategies is the first step for effective research.

OBJECTIVES/SPECIFIC AIMS: The purpose of this study was to examine factors associated with Latina immigrant mothers’ hesitancy in having their 9-12 year old daughters vaccinated against HPV despite a physician recommendation. METHODS/STUDY POPULATION: The data analyzed for this study was from a previous effort that examined the efficacy of an intervention to promote HPV vaccination among daughters (9-12 years of age) of Latina immigrants (N=317) through a randomized trial. Baseline data among Latina immigrant mothers with unvaccinated daughters was collected prior to this intervention. Participants were surveyed on sociodemographic characteristics, knowledge and perceptions of cervical cancer and HPV, and intention to vaccinate their daughters with the HPV vaccine if recommended by the daughter’s physician. RESULTS/ANTICIPATED RESULTS: Out of 317 participants, 205 reported willingness to vaccinate following a physician recommendation (64.7%) while 112 reported hesitancy (defined as an answer of “maybe”) to vaccinate their daughters (35.3%). None of the participants indicated “no”. No sociodemographic factors were significantly associated with vaccine hesitancy except for the daughter’s health insurance status (p = 0.03). A significant difference existed in the mother’s perceived risk of cervical cancer in herself based on hesitancy and willingness to vaccination (p < 0.001). Mother’s awareness of HPV (p < 0.0001), knowledge of HPV (p < 0.01), her perceived risk of HPV infection in herself (p < 0.01) and in her daughter (p < 0.0001), and her worry about her daughter being infected with HPV (p = 0.02) were also significant. Finally, there were differences among mothers in confidence of being able to have their daughters complete all three doses of the vaccine (p < 0.0001), and having the time (p < 0.0001) and the money (p < 0.0001) to complete the vaccination series. Factors that were significant in the univariate analysis were then incorporated into a binary logistic multivariable regression. HPV knowledge score was excluded from this analysis due to its limited sample size (n = 169). The five variables that were strongly associated with the outcome of vaccine hesitancy included: HPV awareness, mother’s perceived risk of HPV infection in their daughter, confidence in the ability to receive all three shots in vaccine series, confidence in being able to afford the vaccine series, and daughter’s health insurance. All were positively correlated with intention to vaccinate except for daughter’s health insurance status. DISCUSSION/SIGNIFICANCE OF IMPACT: Despite research showing Latinos are pro-vaccination and the association between HCP provider recommendation and vaccine acceptability among parents, over 35% of Latina immigrant mothers in our study were still hesitant about having their daughters vaccinated against HPV following a physician recommendation. Factors that strongly contributed to this hesitancy included HPV awareness, mother’s perceived risk of their daughter being infected with HPV, self-efficacy (ability to receive all required shots and finding time to complete the HPV vaccination series), and daughter’s health insurance status. These results indicate that HCP recommendation may be not enough of a driving factor to motivate Latina immigrant mothers to vaccinate their daughters against HPV. Further research efforts should focus on heightening perceived risk of HPV infection, improving knowledge of HPV, and boosting their self-efficacy to get their children vaccinated against HPV.

OBJECTIVES/GOALS: Many researchers aim to build trust with communities and participants. Trust building is meant to achieve greater representation across aspects of research whether in participation, or more comprehensively as partners from design to dissemination. We provide practical guidance for trust building activities and the ethical issues that can arise. METHODS/STUDY POPULATION: While trust itself is inherently seen as an ethical good, often little attention is paid to the ethical aspects of trust building exercises themselves and the fact that trust can vary in type. Using a bioethical analysis of trustworthiness, we discuss how to approach trust in different relationships and settings. Explicit communication about the supports/constraints and potential outcomes of new trusted relationships is required for ethical practice. Where relationships are built without appropriate transparency and follow through, or with misunderstandings about potential shared values, priorities, or desired outcomes, significant harms can occur in the short- and long term. Using a bioethical framework and practical examples we provide guidance on how to engage in ethical trust building activities. RESULTS/ANTICIPATED RESULTS: While many people are good at the trust building work they do, this work is often not shared as best practices and is ascribed to individual skill. This is slowly changing and an evidence-base is being developed that can support those new to these activities. Ethical guidance to support trust building practices, especially for those new to these activities, is currently lacking. By providing both a conceptual and normative bioethical analysis grounded in practice, we provide the foundations for new activities and the necessary support for work that explores and determines best practices. This analysis provides an understanding of trust including a taxonomy and a discussion of how different types of trust can be built and can support research activities, as well as problems that can arise. DISCUSSION/SIGNIFICANCE: Trust building activities with communities and participants are crucial to much of translational science and research, but ethical guidance on how to engage in these activities well is lacking. We provide bioethical guidance and offer practical recommendations.

ABSTRACT IMPACT: T cell dysfunction is a dominant suppressor of anti-tumor immunity, reducing immunotherapeutic efficacy and benefit to patients; our work will identify novel mediators of this process for both therapeutic potential and underlying mechanism, allowing for both potential immediate clinical utility and identification of future targets based on new mechanistic insights. OBJECTIVES/GOALS: T cell dysfunction is a dominant suppressor of anti-tumor immunity, reducing immunotherapeutic efficacy and clinical benefit to the majority of patients. We aim to interrogate a novel mediator of dysfunction identified from transcriptome analyses, pyruvate kinase muscle isozyme isoform 2 (PKM2), for therapeutic utility and underlying mechanism. METHODS/STUDY POPULATION: Transcriptome analyses of CD8+ lymphocytes from tumor-bearing lungs from both murine KrasG12D p53-/- and human non-small cell lung cancer (NSCLC) patients were performed, and differentially expressed genes identified. Flow cytometric analyses for PKM isoform expression and effects of target knockdown on accumulation of dysfunctional characteristics, including checkpoint and transcription factor expression, proliferation, and cytokine production, were performed using an in vitro co-culture of murine antigen-specific T (OT-I) cells and antigen-expressing NSCLC (HKP1-ova) cells. In vivo examination of the same was performed using adoptive transfer of OT-I cells into immunocompetent recipient mice with engraftment of HKP1-ova cells, and subsequent evaluation of mouse survival and T cell phenotypes. RESULTS/ANTICIPATED RESULTS: Transcriptome analyses demonstrated that PKM expression was upregulated in dysfunctional T cells from both murine and human samples. This was confirmed both in vitro with co-culture and in vivo with adoptive transfer approaches, with both activated and dysfunctional OT-I cells expressing higher levels of isoform 2 of PKM than naive OT-I cells. Expression of PKM2 mimicked the kinetics of the transcription factor Tox, a known driver of dysfunction, and knockdown of PKM2 resulted in reduced granzyme B expression, and increased proportions of progenitors with fewer terminally differentiated dysfunctional cells. Knockdown of PKM2 in adoptively-transferred OT-I cells led to enhanced tumor control; results are being extended to other tumor models, and T cells metabolically profiled with PKM2 manipulation. DISCUSSION/SIGNIFICANCE OF FINDINGS: This work identified a novel mediator of dysfunction whose targeting has the potential to enhance anti-tumor immunity. Mechanistically, targeting PKM2 led to altered T cell differentiation to a dysfunctional state, linking metabolic phenotypes to these traits and underlining the importance and therapeutic potential of T cell metabolic pathways.

OBJECTIVES/GOALS: Diabetes is a group of chronic metabolic diseases and significant gaps remain in our understanding of disease etiology, treatment regimens, and diabetes-related complications. The objective of study is to demonstrate how informatics techniques can leverage real-world data for diabetes research and identify barriers for implementation. METHODS/STUDY POPULATION: We evaluated informatics applications of real-world data in diabetes research conducted by the Facelli Research Group. The types of real-world data were categorized into clinical records, diabetes-related repositories, wearable sensors, and other data sources. Translational informatics applications were characterized into thematic groups of 1.) use of electronic health records, registries, and claims and other data sources to generate real-world evidence, 2.) evolution of novel methods to accelerate generation and use of real-world data, and 3.) infrastructure to support the generation and use of real-world data in translational science. A literature review is being conducted to identify additional articles meeting these themes focused on diabetes research. RESULTS/ANTICIPATED RESULTS: 6 research projects were included for analysis. The diabetes-focus spanned type 1 diabetes, type 2 diabetes, and general diabetes mellitus. Informatics methods included machine learning and data mining while real-world data sources included electronic medical records, the Environmental Determinants of Diabetes in the Young (TEDDY) study, continuous glucose monitors, and the U.S. Environmental Protection Agency (EPA) air pollution monitors. Overall, computability of real-world data, linkage of medical concepts to standardized terminologies, volume of data, and adoption of novel artificial intelligence methods were major determinants of successful implementation. Future work will systematically evaluate informatics applications of real-world data in diabetes from the academic community at large. DISCUSSION/SIGNIFICANCE: Translational informatics approaches are poised to leverage real-world data and better understand diabetes etiology, treatment regimens, and diabetes-related complications. By understanding barriers and opportunities for informatics methods, we can expedite translational applications in diabetes research.