OBJECTIVES/SPECIFIC AIMS: We hypothesized that increasing percent calories from MUFA (%MUFA) would be associated an increased FFM/FM index. METHODS/STUDY POPULATION: Nine consecutive HFpEF patients with obesity participated in a 12-week pilot feasibility trial of UFA supplementation (NCT03310099). Subjects were educated at baseline by a dietitian on UFA rich foods including high MUFA choices such as extra-virgin olive oil, canola oil and avocados. Participants were given a list of items, corresponding serving sizes and asked to eat at least one serving of these UFA rich foods per day for 12 weeks. Adherence was encouraged through weekly phone calls by the dietitian. Standardized 5-pass 24-hour dietary recall was performed by a dietitian at baseline and 12 weeks. The recalls were analyzed to establish intake of MUFA in percent calories (%kcals) with Nutrition Data Systems for Research software (NDSR). Body composition including FM%, fat free mass percent of body weight (FFM%) and ratio of FFM to FM (FFM/FM Index) was measured with bioelectrical impedance analysis (RJL systems) at baseline and 12 weeks. Statistical analysis was performed with SPSS (24.0). Spearman rank test was used for correlations. Values are expressed as numbers and percentages or as median and interquartile range (IQR). RESULTS/ANTICIPATED RESULTS: Subjects were mostly female (56%) with a median age 56 (IQR 50-59). Baseline median body mass index (kg/m2) was 36.7 (36.2-48.0), median FM% was 44.5 (IQR 32.5-53.4), median FFM% was 55.5 (IQR 46.7-67.5) and median FFM/FM Index was 1.25 (IQR 0.88-2.1).The only significant change was an increase in %MUFA from baseline 12.4% (IQR 6.9-14.3) to 12 weeks 21.8% (17.6-36.9) (p = 0.008). Increased %MUFA was highly associated with increased FFM% (r = 0.783, p = 0.013) (Figure 1A), decreased FM%(r = −0.783, p = 0.013)(Figure 1B) and increased FFM/FM index (r = 0.800, p = 0.010) (Figure 1C). All correlations remained statistically significant after adjustment for changes in energy intake. DISCUSSION/SIGNIFICANCE OF IMPACT: Increasing dietary %MUFA is protective against negative changes in body composition in patients with obesity and HFpEF, independent of changes in caloric intake. Future work should focus on whether the correlation found in this pilot study translate in improved body composition and finally, exercise tolerance and clinical outcomes.

OBJECTIVES/SPECIFIC AIMS: Provide an innovative, integrative, and interdisciplinary training program which will leverage a unique and internationally recognized strength of BU and establish an environment that facilitates translational team science interactions with MD scientists and clinicians, thereby synergistically bridging research strengths with interdisciplinary approaches. METHODS/STUDY POPULATION: This overall mission of the RMTP is pursued through 2 independent aims. Aim 1: Provide an innovative, integrative, and interdisciplinary training program which will leverage a unique and internationally recognized strength of BU. Aim 2: Establish an environment that facilitates translational team science interactions with MD scientists and clinicians, thereby synergistically bridging research strengths with interdisciplinary approaches. To achieve these aims, we have developed a specialized didactic curriculum that is fully integrated in graduate school training and can be shared for the benefit of others outside of the BU community. We are also developing online iPSC practicum workshops for more efficient distribution of didactic content. Interdisciplinary team science approaches to stem cell research related to cures for human diseases are fostered across investigators across diverse hubs at BU, BU Medical Center, the Charles River Campus and the Framingham Heart Study. All methodology, data and materials are provided in a transparent and open-source manner to benefit the greater scientific community and ensure rigorous reproducibility. RESULTS/ANTICIPATED RESULTS: As a nascent TL1 training program, we are just arriving at the end of our second year. At this point, 5 out of a total of 11 appointed trainees have concluded RMTP support, all of whom have transitioned into biomedical science-related pursuits; 2 predoctoral trainees were awarded F31 fellowships, 2 postdoctoral trainees were awarded career transition grants (K99/R00 and LERN fellowship), and 1 postdoctoral trainee became a Senior Scientist at a Biopharmaceutical company. Given the quality of our trainees and their RMTP mentors, we anticipate that close to 100% of those supported by this mechanism will continue their career development in the biomedical sciences. DISCUSSION/SIGNIFICANCE OF IMPACT: Implementation of the RMTP TL1 would not only serve to increase the capacity of trainees within the CReM, but would also extend the scope of regenerative medicine research to other CTSI-participating hubs and more broadly to other scientific disciplines.

OBJECTIVES/SPECIFIC AIMS: Emotional processing theory and some observations suggest that activation of subjective and physiological distress during therapeutic exposure and habituation across exposure sessions are key to improvement. This study sought to determine whether initial subjective and physiological activation and between-session habituation would predict PTSD symptom reduction after a series of written trauma narrative exposure sessions. METHODS/STUDY POPULATION: In total, 29 urban-residing African-American participants with PTSD participated in four 30-minute writing sessions. Writing sessions 1 and 2 were 12 hours apart and session 3 and 4 were performed 1 week later, also 12 hours apart. PTSD symptoms were measured at baseline, after session 2, and 1 week after all 4 writing sessions with the Clinician Administered PTSD Scale. During each session, Subjective Units of Distress Scores (SUDS) were assessed 4 times and heart rate was measured continuously. RESULTS/ANTICIPATED RESULTS: Participants exhibited PTSD symptom improvement and habituation of subjective distress, but not physiological arousal, across writing sessions. First session baseline-corrected SUDS maximum and SUDS decrease from the initial to the final writing session were both positively associated with symptom improvement. DISCUSSION/SIGNIFICANCE OF IMPACT: Increased subjective, but not physiological, distress in the first exposure session and diminished subjective distress across sessions may be a helpful marker of emotional processing for clinicians and predictor of symptom improvement after written trauma narrative exposure.

OBJECTIVES/GOALS: Flavorings differ between brands and tobacco products, potentially altering the sensory perceptions. This study aimed to examine discrepancies in flavor preference across various non-cigarette tobacco products among a national representative sample of US adult regular tobacco users. METHODS/STUDY POPULATION: Data from the Population Assessment of Tobacco and Health (PATH) Study Wave 3 (W3) were used. Weighted prevalence of flavor preference for various tobacco products, including electronic nicotine delivery systems (ENDS), traditional cigars, cigarillos/filtered cigars, hookah and snus/smokeless, was presented for 9,037 adult current and new former users of multiple flavored tobacco products. Within-subject flavor discrepancies were assessed using generalized estimating equations (GEE) models considering the complex sampling design of the PATH study. RESULTS/ANTICIPATED RESULTS: Most regular users of a flavored tobacco products reported using one flavor category per product. Fruit flavors, followed by tobacco, were the most common flavor categories among ENDS (32% and 25%, respectively) and hookah users (44% and 36%, respectively). Tobacco flavor was the most common among regular users of traditional cigars (80%), cigarillos/filtered cigars (55%), and smokeless tobacco (79%). Polytobacco users of ENDS and traditional cigars had the largest discrepancy, where about 68-76%% used different flavor categories when switching products. Conversely, polytobacco users of traditional cigars and cigarillos/filtered cigars had the lowest discrepancy (23-25%). DISCUSSION/SIGNIFICANCE OF IMPACT: Many consumers of multiple tobacco products had different flavor preferences when switching between products. In the event of a partial or full flavor ban for ENDS, these findings raise questions about consumer loyalty to a particular tobacco product or a particular flavor category. Conflict of Interest Description: MLG serves as a paid consultant for Johnson & Johnson and has received research grant from Pfizer, manufacturers of smoking cessation medications. The other authors have no conflicts to declare. CONFLICT OF INTEREST DESCRIPTION: MLG serves as a paid consultant for Johnson & Johnson and has received research grant from Pfizer, manufacturers of smoking cessation medications. The other authors have no conflicts to declare.

ABSTRACT IMPACT: Our findings could potentially identify CVD at-risk persons living with HIV who might benefit from aggressive risk-reduction. OBJECTIVES/GOALS: PWH have higher rates of CVD than the general population yet CVD risk prediction models rely on traditional risk factors and fail to capture the heterogeneity of CVD risk in PWH. Here we identify protein biomarkers that are able to discriminate between CVD cases and controls in PWH, and we assess their added benefit beyond traditional risk factors. METHODS/STUDY POPULATION: We analyzed 459 baseline protein expression levels from five OLINK panels in a matched CVD (MI, coronary revascularization, stroke, CVD death) case-control study with 390 PWH from INSIGHT trials (131 cases, 259 controls). We formed 200 datasets via bootstrap. For each bootstrap set, a two-component partial least squares discriminant model (PLSDA) was fit. The importance of each variable in the discrimination of cases and controls in the PLSDA projection was assessed by the variable importance in projection (VIP) score. Proteins with average VIP scores > 1 were used in penalized logistic regression models with elastic net penalty, and proteins were ranked based on the number of times the protein had a nonzero coefficient. Proteins in the top 25th percentile were considered to have high discrimination. RESULTS/ANTICIPATED RESULTS: Participants had mean age 47 years, 13% were females, 4.9% had CVD at baseline and 69% were on ART at baseline. Eight proteins including the hepatocyte growth factor and interleukin-6 were identified as able to distinguish between CVD cases and controls within PWH. A protein score (PS) of the top-ranked proteins was developed using the bootstrap (for weights) and the entire data. The PS was found to be predictive of CVD independent of established CVD and HIV factors (Odds ratio: 2.17 CI: 1.58-2.99). A model with the PS and traditional risk factors had a 5.9% improvement in AUC over the baseline model (AUC=0.731 vs 0.69), which is an increase in model predictive power of 18%. Individuals with a PS above the median score were 3.1 (CI: 1.83- 5.41) times more likely to develop CVD than those with a protein score below the median score. DISCUSSION/SIGNIFICANCE OF FINDINGS: A protein score developed improved discrimination of PWH with CVD and those without, and helped identify PWH with high risk for developing CVD. If validated, this score and/or the individual proteins could be used in addition with established factors to identify CVD at-risk individuals who might benefit from aggressive risk-reduction.

OBJECTIVES/SPECIFIC AIMS: Addressing Disparities in Asian Populations through Translation research (ADAPT) is a community-research partnership funded by the Tufts Clinical Translational Sciences Institute (CTSI). Founded in 2011, this collaborative brings together 7 Chinatown-serving community-based organizations and academic researchers with the goal of improving health for the local Chinatown community and beyond. The goal of this research project was to document the best practices, lessons learned, and process through which ADAPT has developed and grown. The aim of this project is to disseminate the model to other CTSAs who are currently engaged in METHODS/STUDY POPULATION: We used a combination of qualitative interviews and content analysis to gather data on the evolution of ADAPT over the last 5 years. Current members from both community organizations and the university/medical center were interviewed about their experiences participating in ADAPT. When possible, interviews were recorded and transcribed verbatim. Deidentified transcripts and administrative documents including meeting minutes, conference summaries, bylaws, and mission statements were coded using Dedoose analytic software. RESULTS/ANTICIPATED RESULTS: Established community-based participatory research (CBPR) principles, including mutual respect, transparency, and commitment, are viewed as necessary, but not sufficient. Patience—both with other members and with the group as a work in progress—is highlighted as being a necessary characteristic of participants. Time and funding are 2 of the most important resources, and the majority of members agree that there is no substitute for “skin in the game.” Attempts at last minute, opportunistic engagement were provided as examples of what had not worked. One ongoing tension is the balance between process and product. Individual members are beholden to organizations to different degrees, and the need to produce something in the form of publications or grant money can limit the amount of time members can commit to the collaborative. At the same time, these products are unlikely to materialize if members are not invested in the process of growing and sustaining the collective. DISCUSSION/SIGNIFICANCE OF IMPACT: Out of the 7 community organizations who currently participate in ADAPT, only 1 is explicitly focused on health in the traditional sense. The others are primary service organizations, but because they understand the impact of the social determinants of health on the local community—including housing, employment, education, nutrition, among other factors—the research collaborative is able to leverage the knowledge and expertise of the academic researchers and the community partners to focus on health topics most salient to the local Chinatown community.

OBJECTIVES/GOALS: Transgender, non-binary, and gender expansive (TGE) patients experience significant barriers to high-quality care including limited provider expertise and pathologization within health documentation. This study aimed to evaluate the use of gender-affirming language within free text medical notes of TGE patients. METHODS/STUDY POPULATION: We conducted a qualitative analysis of free text medical notes in adult (> age 18 years) TGE patients seen in inpatient and outpatient medicine and general surgery clinics between January 2019 and January 2022 at three independent health systems in San Francisco. TGE patients were identified based on self-identified gender identity, sex assignment at birth, and legal sex. We conducted a thematic analysis to assess use of gender-affirming language, including self-identified pronouns, chosen names, gendered and gender-neutral descriptors, sex-related traits, and pathologizing language. RESULTS/ANTICIPATED RESULTS: Within pilot data, we found inconsistent use of gender-affirming language within notes, with pronounced variability within the history of present illness, the clinical one liner, and the problem list. Within one liners, many did not include patient-identified pronouns (81%), omitted chosen names (53%), and utilized gendered language that was misaligned with patient self-identified gender identity (27%) - frequently including the use of outdated terms i.e. female-to-male and transsexual. Many problem lists included gender-related care, with some describing hormonal and surgical interventions and others utilizing language to pathologize trangender status. DISCUSSION/SIGNIFICANCE: Our study identifies gaps in the use of gender-affirming language in medical notes. Of particular significance in the era of open notes wherein patients can view their medical records, our study offers a framework for assessing and increasing gender-affirming language use within free text medical notes that can be applied across health systems.

OBJECTIVES/SPECIFIC AIMS: The objective of the study is to examine the ability of iTBS to improve depression and executive impairment in depressed older adults. If effective, this treatment will have the potential to improve the quality of life in LLD. METHODS/STUDY POPULATION: From 12- 2016 to date older adults (60 – 85 y/o) in a major depressive episode, with evidence of executive dysfunction (on the NIH Tool Box battery) were enrolled. iTBS protocol: This brief paradigm (3 min 9 seconds duration) was administered on weekdays for four weeks (20 sessions total). Stimulation intensity was set up to 120% of the observed motor threshold. Depression primary outcome: Change in the Montgomery Asberg Depression Rating Scale (MADRS) from baseline to the end of iTBS course. Executive function primary outcome: Change in executive measures from the electronic NIH Tool Box cognitive domain battery8. Executive secondary outcome: Change in scores from baseline to the end of iTBS on the Frontal Systems Behavior Scale (FrSBe), this self reported instrument measures dys-executive behavior. Statistical Analysis: paired t-test examined changes in depression and executive variables from baseline to post iTBS. Pearson correlation examined the association between degree of mood improvement and degree of improvement in executive function. SPSS v 24 was used for all analyses. RESULTS/ANTICIPATED RESULTS: We examined 11 subjects. Primary outcomes: Patients showed a significant decrease in scores on the Montgomery Asberg Depression Rating Scale (MADRS) from baseline Mean (M) = 27.73, Standard Deviation (SD) 8.2 to the end of 4 weeks of iTBS: M = 15.91, SD = 10.05, t = 7.4, p < .001. The Flanker Inhibitory Control and attention test significantly improved from baseline M = 91.0, SD = 7 to the end of iTBS M = 98.7, SD = 12.8, t = −2.9, p = .014 (higher scores at week 4 denote improvement). The List Sorting Working Memory test and the Dimensional Change Card sort a measure of cognitive flexibility improved but did not reach statistical significance. The self reported executive measure improved from baseline M = 48.6, SD = 9.4 to post iTBS M = 39.4, SD = 8.5, t = 3.8, p = .003 (lower scores at week 4 denote improvement). We also examined whether the degree of improvement in depression related to the degree of improvement in executive function. We found positive correlations between change in mood scores with iTBS with change in executive scores with iTBS, with a strong relationship with working memory r = 0.34. Tolerability and Side effects: Common side effects were twitching in facial muscles during the stimulation (n =11), headaches (n =10) and pain or discomfort at the stimulation site and face (n =4). One participant withdrew due to intolerance to the stimulation. DISCUSSION/SIGNIFICANCE OF IMPACT: The iTBS paradigm was effective in improving mood and executive function in older adults. Both the psychometric measure and the self reported executive function measure (indicative of dysexecutive behavior) reflected improvements post iTBS. Improvement in executive function was correlated with depression improvement. We targeted the Dorso Lateral Prefrontal cortex, which exhibits decreased connectivity with the dorsal anterior cingulate in depressed elderly and is a key in orchestration of executive function. Our findings are consistent with the conceptualization of depression as a circuit level disorder affecting interconnected networks involving mood and cognition. Although we demonstrated potential therapeutic effects, the mechanism of action of iTBS remains unknown. We are presently conducting a randomized controlled trial to examine the effects of iTBS on brain connectivity using functional MRI. Results of this study underway will hopefully demonstrate engagement of the TMS target and contribute to a neurocircuitry based approach treatment of geriatric depression.

OBJECTIVES/SPECIFIC AIMS: Peer groups are one of the strongest determinants of alcohol use and misuse. Furthermore, social influence plays a significant role in alcohol use across the lifespan. One of the factors that most consistently predicts successful treatment outcomes for alcohol use disorders is one’s ability to change their social network. However, the concept of social influence as defined by suggestibility or susceptibility to social influence has not yet been studied as it relates to drinking behavior and acute subjective response to alcohol. Our objective was to examine the relationship between suggestibility and alcohol consumption and responses, using an intravenous alcohol self-administration (IV-ASA) paradigm in social drinkers. METHODS/STUDY POPULATION: Healthy, social drinkers (n=20) completed a human laboratory session in which they underwent the IV-ASA paradigm. This consisted of an initial 25-minute priming phase, where participants were prompted to push a button to receive individually standardized IV alcohol infusions, followed by a 125-minute phase during which they could push the button for additional infusions. IV-ASA measures included the peak and average breath alcohol concentration (BrAC) and number of button presses. Subjective responses were assessed using the Drug Effects Questionnaire (DEQ) and Alcohol Urge Questionnaire (AUQ) collected serially during the session. Participants completed the Multidimensional Iowa Suggestibility Scale (MISS) to assess suggestibility. The Alcohol Effects Questionnaire (AEFQ) was used to assess alcohol expectancies and the Timeline Followback questionnaire measured recent drinking history. RESULTS/ANTICIPATED RESULTS: After controlling for drinking history, greater suggestibility significantly predicted greater average BrAC, greater peak BrAC, and a greater number of button presses (p=0.03, p=0.02, p=0.04, respectively) during the early open bar phase. Suggestibility significantly predicted subjective alcohol effects following the priming phase which included “Feel,” “Want,” “High,” and “Intoxicated” and was trending for “Like” (p=0.02, p=0.03, p=0.01, p=0.03, p=0.054, respectively) as well as AUQ (p=0.03). After controlling for drinking history, suggestibility significantly predicted “Feel,” “Like,” “High,” and “Intoxicated” peak scores during the open bar phase (p=0.03, p=0.009, p=0.03, p=0.03, respectively). There was no association between suggestibility and “Want More” alcohol. Suggestibility was positively associated with three positive expectancies (global positive; p=0.04, social expressiveness; p=0.005, relaxation; p=0.03), and one negative expectancy (cognitive and physical impairment; p=0.02). DISCUSSION/SIGNIFICANCE OF IMPACT: These results indicate that social drinkers that were more suggestible had higher alcohol consumption, greater acute subjective response to alcohol, and more positive alcohol expectancies. As such, susceptibility to social influence may be an important determinant of alcohol consumption, and may provide insight into harmful drinking behavior such as binge drinking. Future analyses should examine the impact of suggestibility on alcohol-related phenotypes across the spectrum of drinking from social to binge and heavy drinking patterns.

Successful social media recruitment requires specific expertise and constant upkeep, placing an inordinate burden on study teams. Over half of the study teams at the University of Michigan (U-M) surveyed about recruitment assistance needs indicated that they wanted to use social media as a recruitment strategy, but lacked the expertise to do so. We thus built a service to centralize social media recruitment across the university. This involved assembling the right expertise, creating a centralized social media profile, creating linkages to other digital recruitment platforms, building the financial structure, and operationalizing the service. So far, we have helped 94 study teams launch social media campaigns on Facebook and Instagram. These campaigns resulted in 1,653,675 users being reached, of which 20,546 users actively showed interest in participating in the corresponding studies. We followed 18 studies further, who reported a total of 345 social media participants as being enrolled, resulting in an average cost-per-contact (CPC) of $8.72 and an average cost-per-enrollee (CPE) of $55.21. The combination of communication expertise, streamlined administrative processes, and linkages to a centralized research participation registry has allowed us to help a large number of study teams seamlessly engage broad and diverse populations.

OBJECTIVES/GOALS: We will reduce the number of research staff by 50% within 6 months that are non-compliant with completing the Good Clinical Practice (GCP) course without increasing costs as measured by salary and benefits for staff involved in the tracking and assignment process. We will also introduce a GCP policy to define the education requirements for GCP training METHODS/STUDY POPULATION: We touted focus groups to stakeholders for input on workflows with graphs, surveys, and meetings in the onset and throughout the project. This input prompted us to develop a staff guide outlining the modification process of removing a staff name from an IRB trial if they are no longer active in the trial. A workflow and root cause analysis were done resulting in the implementation of one gatekeeper for assigning and tracking completions, instead of three staff. Successfully reconciling the non-compliant report, which extracted data from three databases, allowed us to eliminate 174 names from the report, which originally comprised 792 names. IRB modifications were entered into the IRB system for these 174 names. We also put into effect a GCP policy for the institution, where none had previously existed. RESULTS/ANTICIPATED RESULTS: * In 3.5 months, we decreased the GCP non-compliance rate by 50% from 792 to 399. * We removed 22% of names from the 792 from the report due to their status of being non-employees, or Emeritus, or not in research anymore. * We discovered a data type issue in the non-compliance report that shuffled the MAX calculation, therefore not requiring some staff to complete the training. * We developed a new process for assigning training, resulting in faster compliance rates for the institution. It included sending emails to users two months before their training expired before we assigned the course to them. * We reconciled the non-compliance report, and it decreased the effort with staff involved in GCP for grant renewals and audits in numerous other departments. * Developed an escalation procedure for non-compliant staff. DISCUSSION/SIGNIFICANCE: Failure to address our GCP non-compliance rates could have put our institution at risk for potential penalties. With 4400+ research personnel listed on active trials the interventions we implemented accelerated our compliance rate by assigning the refresher course monthly and this also resulted in no disruption to staff completing the training.

OBJECTIVES/SPECIFIC AIMS: Screening the general population for prostate cancer with prostate specific antigen (PSA) continues to be controversial. Patients with advanced heart failure undergoing evaluation for suitability for cardiac transplantation are often requested to undergo prostate cancer screening, with guiding evidence generated from the general population. The objective of this study is to determine the clinical implications of a positive prostate cancer screen result in this patient population. METHODS/STUDY POPULATION: A retrospective cohort study was performed on all men that were referred to a tertiary care cardiac transplant center between January 2000 and December 2015. Patients were classified as having either a “positive screen” (PSA≥4 ng/mL) or a “negative screen” (PSA<4 ng/mL) at the point of evaluation. The primary outcome of time to listing for cardiac transplant (days) was calculated from the date of referral to the date of listing. A multivariable Cox proportional hazards model was developed to assess the association between a positive prostate cancer test result and listing for cardiac transplantation. RESULTS/ANTICIPATED RESULTS: Among the 704 patients included in this study, 66 men (9.4%) had a positive prostate cancer screen result. Men with a positive prostate cancer screen were approximately 4 year older (mean 58.5 vs. 54.1 years), more likely to have a diagnosis of Ischemic Cardiomyopathy (74% vs. 53%) and require continuous mechanical support (61% vs. 16%) at the point of transplant evaluation. The median time for listing for cardiac transplant was greater in patients with a positive PSA (119 vs. 48 days, p<0.05). After adjusting for age, renal function, clinical status at evaluation, history of COPD, and year of referral, patients with a positive prostate cancer screen had a reduced hazards ratio (HR) for progressing to cardiac transplant listing compared with those with a negative screen (HR 0.58, 95%CI: 0.38–0.91). DISCUSSION/SIGNIFICANCE OF IMPACT: Screening patients undergoing cardiac transplant evaluation for prostate cancer with PSA has a low diagnostic yield. An individual’s PSA value is influenced by their age and clinical status at the time of screening, with a positive screen being associated with a reduced likelihood for progressing to listing for cardiac transplant.

OBJECTIVES/SPECIFIC AIMS: The objective of the study is to test the effect of oral inorganic nitrate on the primary outcomes of exercise capacity and quality of life in patients who have undergone TAVR for severe aortic stenosis. We will also test the effect of the study drug on various physiology endpoints, including systemic vasodilator response to exercise, LV diastolic function and myocardial strain, late systolic LV load and pulsatile arterial wave reflections. METHODS/STUDY POPULATION: This is a randomized double-blind crossover clinical trial, in which 24 subjects who underwent TAVR for severe AS 3 or more months before enrollment will receive the following 2 interventions, in randomized order: (1) Potassium nitrate (KNO3), at a dose of 12–18 mmol/day by mouth for ~4 weeks, or (2) Potassium chloride (KCl), at a dose of 12–18 mmol/day by mouth for ~4 weeks. A 1-week washout period will be introduced between the 2 interventions. RESULTS/ANTICIPATED RESULTS: We hypothesize that sustained oral administration of potassium nitrate will lead to improvement of exercise capacity and quality of life in this population.DISCUSSION/SIGNIFICANCE OF IMPACT: His study will have a significant impact on assessment and management of patients after TAVR. We will gain a better understanding of physiologic abnormalities leading to exercise intolerance after TAVR. In addition, there are currently no proven therapies that improve exercise capacity in this population.

ABSTRACT IMPACT: The described framework will enable other sites with a well-defined apparatus for enabling the secondary analysis of EHR data for research through education, team science, and resource consolidation. OBJECTIVES/GOALS: EHR’s potential to improve healthcare outcomes extends far beyond the clinic. This vast repository of clinical insights has dramatic potential for biomedical research. To enhance accessibility for busy clinicians and underserved populations, we describe a framework for interfacing with EHR locally and through national network participation. METHODS/STUDY POPULATION: The Institutional Development Award (IDeA) program, which began in 1993, broadens NIH funding’s geographic distribution for biomedical research. Included in this is the IDeA Networks for Clinical and Translational Research, which focuses on enhancing clinical and translational science across a network of IDeA-states with traditionally underserved communities and rural providers. A prior survey of the needs and capabilities of IDeA-CTR centers identified the need for improved research support. Based on our annual member survey we developed a process for supporting distributed research projects across the GP-CTR. NIH also recently made a funding announcement for the IDeA-CTR community identifying EHR research as a major priority in responding to the COVID-19 pandemic. RESULTS/ANTICIPATED RESULTS: Results from site interviews and member surveys show a clear need for dedicated resources to navigate the process of EHR-derived research. Most described a different set of requirements for increasing accessibility to EHR for research and a strong desire to participate in research networks. Local investigators cited a lack of tools, educational materials, and accessibility. Initial efforts demonstrate strong research questions but limited technical, statistical, and terminological capabilities to succeed. In response, a pipeline for team science and promotion of projects from local phenotypes to national studies. We created a facilitator training program to expand the number of facilitators (n=22), quarterly training for investigators (n=104), and ongoing efforts to advance COVID-19 research. DISCUSSION/SIGNIFICANCE OF FINDINGS: As evidenced in the expanding number of EHR-based research networks there is a need for a system to promote project development and best practices. The proposed model promotes education, resource sharing, and team formation to advance clinical questions from the idea stage toward national research network participation.

OBJECTIVES/GOALS: Despite the importance of stakeholder engagement in research, there remains a critical need for methods that facilitate the engagement of diverse stakeholders throughout the research process. We describe dissemination and capacity building for the SEED Method, which was created to involve stakeholders in the research development process. METHODS/STUDY POPULATION: In order to raise greater awareness of the SEED Method and to build capacity among research teams, we received funding from the Patient-Centered Outcomes Research Institute (PCORI) for a 2-year project to implement a plan of outreach, training, interactive learning, and technical assistance, as well as an innovative partnership with the Extension Foundation. Tools created for this project include an internet site providing tools and materials, live and on-demand webinars, training videos, SEED materials, a blog, and an interactive course/toolkit. In addition, we created a monthly learning collaborative and provided direct technical assistance to teams using the SEED Method in their research engagement projects. We evaluated user satisfaction with the tools and support provided through online surveys. RESULTS/ANTICIPATED RESULTS: We highlight the routes to reaching potential users and diverse approaches to capacity building, including multi-media training materials, interactive learning sessions, and customized technical assistance. As a result of outreach and capacity building, there are currently 13 research teams using the SEED Method to engage stakeholders in research development across various topics. We link this result to the dissemination and capacity building strategies utilized and the paths through which teams learned about the SEED Method. We also look at how the teams are using the method in terms of project goals and approaches to adapting the SEED Toolkit. DISCUSSION/SIGNIFICANCE: The use of PHR continues to increase, and with it the emergence of new approaches to involve patients, stakeholders, and communities. Innovations in engagement need to reach potential users and build capacity among researchers and communities.

OBJECTIVES/GOALS: To date, no reviews have been published combining the topics of pre-operative mental illness and postoperative atrial fibrillation (POAF). For adult cardiac surgical procedures, therefore, this scoping review provides an overview of the published evidence for this novel topic. METHODS/STUDY POPULATION: A combination of MESH terms and text words were used to capture all papers analyzing any risk factors for atrial fibrillation development after any cardiovascular surgery, and thus, 4,203 search results were initially identified. Papers were manually screened for relevance, resulting in 69 articles that analyzed risk factors associated with POAF. As a separate analytical step, all included publications were used to identify additional citations and Web of Science PubMed identification number-based (i.e., PMID) specific backwards citation searches were performed to ensure comprehensive coverage. For each of the three articles analyzed, moreover, these PMIDs were further evaluated using individual google scholar searches to assure no other relevant literature was inadvertently found. RESULTS/ANTICIPATED RESULTS: For the 69 relevant articles found with multivariable risk models predicting new onset POAF during this scoping review, a wide variety of patient risk factors were reported. The statistically significant predictors reported for new POAF included age (57 papers), hypertension (22 papers), tobacco use (15 papers), LVEF-related characteristics (14 papers), COPD (13 papers), and patient gender (13 papers). All other factors were found to be significant 10 times or fewer; importantly, no multivariable models evaluated mental illness-related factors as predictors of new onset POAF. Only 3 articles even considered the potential influence of mental illnesses. DISCUSSION/SIGNIFICANCE: Mentally ill patients have been documented to have increased incidence of cardiovascular disease and adverse cardiac outcomes, however, very few articles evaluated mental illness associations with POAF. This comprehensive review has demonstrated the urgent need for new research focused on mental illness impacts.