OBJECTIVES/SPECIFIC AIMS: To improve translational research, we have developed a program called Duke Multidisciplinary Education and Research in Translational Sciences (Duke MERITS). Duke MERITS will facilitate cross-disciplinary collaboration among faculty involved in foundational, clinical and/or health care research and in turn also prepare them to train the next generation of translational researchers. METHODS/STUDY POPULATION: The program aims are (1) to define metrics and outcomes measures so faculty can track their progress and identify impact of their collaborative research in translational sciences; (2) to offer a multi-modal faculty development series to promote team science, improve didactic teaching, and incorporate innovative resources to promote interdisciplinary approach to translational research; (3) to provide module-based hands-on-training sessions in bench to bedside research and training in translational grant writing to facilitate the development of multidisciplinary research collaborations. The present study describes results from Aim 1 and includes (a) development of baseline outcome assessment tools necessary to gauge the impact of our programs on both the participating faculty and the research culture within Duke University, (b) impact of a specific course offering in Translational Medicine. In order to achieve this, we conducted multiple focus group sessions with faculty self-identified as junior-, mid-, or advanced-career, a mixed group at any career level and included a group of graduate students and postdoctoral trainees to study the impact of a graduate level course in Translational Aspects of Pathobiology. The activities during these translational science focus groups were designed to define what successful translational science is, to determine what resources support translational Science at Duke, and to decide what resources we need in order to enhance Duke’s position as a leader in research and scientific education. RESULTS/ANTICIPATED RESULTS: We identified that translational science is changing standards while incorporating leadership, teamwork, collaborations, and movement primarily focusing on the overall goal of improving all aspects of health. Participants categorized their field of study and the fields of their coparticipants most frequently as basic discovery and a combination of intervention and health services. The most frequently identified pros/benefits of performing translational science at Duke include industry connections, collaborations with other departments resulting in disciplines being bridged, improving patient care, and access to resources as well as money. The most frequently identified cons/barriers of performing translational science includes the expensiveness, silos, and lack of resources willing to absorb risks. DISCUSSION/SIGNIFICANCE OF IMPACT: The identification of these defined factors from the focus groups has allowed us to issue a comprehensive, sliding Likert scale-based anonymous survey from the secure RedCap system and is being rolled out throughout Duke University, including schools of medicine, nursing, Trinity, biomedical engineering. We envision that Duke MERITS education program will facilitate interprofessional efforts, which we define as a team science approach to identify the clinical “roadblock” and then seek an innovative approach or technology to help overcome this “roadblock”? It can facilitate institutional and departmental recognition in faculty career development. The common goal is to gain fundamental new insights that will result in significant improvement of the existing “standard of care” and meet the challenges of dwindling extramural support.

OBJECTIVES/SPECIFIC AIMS: Central neuropathic pain is a severely disabling consequence of conditions that cause tissue damage in the central nervous system (CNS) such as multiple sclerosis (MS) and neuromyelitis optica (NMO). It impacts mood, mobility and quality of life, but is often refractory to common treatments. Scrambler Therapy is an emerging non-invasive pain modifying technique that utilizes transcutaneous electrical stimulation of nociceptive fibers with the intent of re-organizing maladaptive signaling pathways. It has been examined for treatment of peripheral neuropathy with favorable safety and efficacy outcomes, but its use in central neuropathic pain has not been reported. We aim to explore acceptability and safety of Scrambler Therapy through a Phase II sham-controlled trial in NMO, and describe its use to date in central neuropathic pain. METHODS/STUDY POPULATION: Two patients with longstanding central neuropathic pain who failed multiple drug trials were treated as proof-of-concept, supporting the recent launch of a Phase II randomized controlled trial in NMO where patients receive 10 daily Scrambler treatments versus sham. Safety and acceptability from those recruited to date will be reported. Acceptability is measured by adherence and responses to patient surveys. RESULTS/ANTICIPATED RESULTS: We plan to recruit 22 patients, randomized 1:1 into experimental and sham arms. We will present acceptability and safety data for Scrambler use in patients with NMO who have been recruited by the time of this conference, as well as effectiveness data from two cases that have been completed outside of the trial. One case involved a 65-year-old woman with a 4-year history of central neuropathic pain following a C3-C5 TM. Her numerical rating scale (NRS) pain score was reduced to 0/10 from a baseline score of 5/10. The second case involved a 52-year-old woman with a 13-year history of pain following a medullary cavernoma bleed. Her baseline NRS pain score was 9/10, which was reduced to 0.5/10 post-treatment. No adverse events were reported. Pain relief was sustained at 30 days’ post-treatment. DISCUSSION/SIGNIFICANCE OF IMPACT: We are investigating the acceptability and efficacy of Scrambler Therapy for central neuropathic pain treatment in NMO. Proof-of-concept was supported by two patients whose pain scores improved considerably more in response to this treatment than with previous pharmacologic and non-pharmacologic interventions. Results from this trial may support future investigation in other disorders that cause damage in the CNS, including MS and TM.

Objectives/Goals: Developing an online platform for the clinical research coordinator (CRC) mentoring program aimed to create an accessible space for professional development and peer support using Microsoft Teams. The platform fosters communication, community, and connection to share best practices and resources, enhancing competencies and growth within the CRC research learning community. Methods/Study Population: The CRC group mentoring program was developed using the ADDIE model. In the analysis phase, CRC needs were assessed to identify gaps in professional development, leading to the choice of Microsoft Teams for its effective communication and resource-sharing capabilities. The Design phase established objectives and content outlines for mentors and mentees. During development, training materials and interactive activities were created. Implementation involved onboarding participants and facilitating scheduled sessions. Finally, the Evaluation phase employed the Kirkpatrick model to assess program effectiveness: Level 1 gathered participant feedback, Level 2 measured knowledge gains, Level 3 tracked skill application, and Level 4 evaluated overall CRC performance and professional development impact. Results/Anticipated Results: Building and maintaining a learning community in Microsoft Teams with 16 mentors and 34 mentees across two health locations offers benefits and challenges. Benefits include the structured organization that facilitates collaboration, resource sharing, and real-time communication, regardless of location. Specific channels can focus discussions and virtual meeting scheduling streamlines coordination. Teams allow easy access to training materials and assessments. Challenges include maintaining engagement and fostering community. Asynchronous communication may lead to uneven participation, while digital literacy levels can hinder involvement. Sustaining meaningful interactions requires intentional facilitation and consistent encouragement to keep discussions dynamic and supportive. Discussion/Significance of Impact: The online Microsoft Teams mentoring platform boosts professional development, enhances community, and provides a vital space for resource sharing and discussion, thereby improving CRC competencies. Despite challenges like digital literacy and asynchronous communication, effective facilitation is crucial for empowering future leaders.

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.

ABSTRACT IMPACT: This is the first study to use QUINT analyses to examine heterogeneity of treatment effect for group medical visits among individuals with type 2 diabetes. QUINT is a data driven method that assumes no a priori assumptions regarding effect moderators - an important step in the path towards personalized medicine. OBJECTIVES/GOALS: To examine heterogeneity of treatment effect (HTE) in Jump Start, a trial that compared the effectiveness of group medical visits (GMVs) focused on medication management only versus the addition of intensive weight management (WM) on glycemic control for patients with type 2 diabetes and body mass index >=27kg/m^2. METHODS/STUDY POPULATION: Jump Start patients (n=263) were randomized to a GMV-based medication management plus low carbohydrate diet-focused WM program (WM/GMV; n = 127) or GMV-based medication management only (GMV; n = 136) for diabetes control. We used QUalitative INteraction Trees (QUINT), a tree-based clustering method, to determine if there were subgroups of patients who derived greater benefit from either WM/GMV or GMV. Subgroup predictors included 32 baseline demographic, clinical, and psychosocial factors. Outcome was hemoglobin A1c (HbA1c). We conducted internal validation via bootstrap resampling to estimate bias in the range of mean outcome differences among arms. RESULTS/ANTICIPATED RESULTS: QUINT analyses indicated that for patients who had not previously attempted weight loss, WM/GMV resulted in better glycemic control than GMV alone (mean difference in HbA1c improvement = 1.48%). For patients who had previously attempted weight loss and had lower cholesterol and blood urea nitrogen levels, GMV alone was better than WM/GMV (mean difference in HbA1c improvement = 1.51%). Internal validation resulted in moderate corrections in the mean HbA1c differences between arms; however, differences remained in the clinically significant range. DISCUSSION/SIGNIFICANCE OF FINDINGS: Among patients with diabetes and BMI>=27kg/m^2, a low-carbohydrate, weight loss focus may better improve HbA1c in those who have never attempted weight loss. A medication management focus may be better in those who have attempted weight loss and have lower cholesterol and blood urea nitrogen.

OBJECTIVES/GOALS: CEnR plays a crucial role in rapidly translating science to improve health by bridging gaps between research and practice although skills development is critical to enable successful community/academic partnerships. We have developed a curriculum mapped to CEnR domains and competencies that meets the needs of community partners and investigators. METHODS/STUDY POPULATION: We located three comprehensive efforts to identify CEnR domains and competencies that we aligned to develop our curriculum, which we then mapped to these competencies. The first was undertaken by a NCATS Joint Workgroup which identified curricula, resources, tools, strategies, and models for innovative training programs. Using Competency Mapping, they developed a framework for curriculum mapping that included eight domains, each with two to five competencies of knowledge, attitudes, and skills. The second aligned CEnR competencies with online training resources across the CTSA consortium, while the third focused on Dissemination and Implementation training. Informed by a conceptual model to advance health equity, we adapted and integrated these frameworks into a set of six educational modules. RESULTS/ANTICIPATED RESULTS: Although many CEnR training programs have been developed, few curricula are mapped to identified domains and competencies, and fewer still address institutional and community barriers to effective CEnR training. However, many outstanding curricula effectively address these competencies, and our curriculum draws from and builds upon these programs of excellence, including those from our sister CTSA hubs. Our modules serve our local community by educating and empowering faculty, students, and community partners. To date, no CEnR curriculum has been implemented at our institution that meets the needs of all parties who play a significant role in community-engaged research (e.g., IRB members, investigators, and community-based partners). This curriculum thus fills an important gap in our workforce training. DISCUSSION/SIGNIFICANCE: This educational program is designed to educate and empower investigators, trainees, students, and community partners to engage in effective CEnR that promotes community projects and fosters relationships and trust. Following evaluation, we will offer the curriculum for use by others interested in using or adapting it for their own programming.

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/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/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: We reorganized the University of Illinois Chicago, Center for Clinical and Translational Science education programs in part to extend assessment beyond funding success. We evaluated the impact of early career grant coaching on applicants’ perceived preparedness for grant submission, confidence in securing grants, and self-reported benefits. Methods/Study Population: Modeled after the National Research Mentoring Network, groups of ~5 investigators who wanted to submit a career development grant proposal met weekly for ~12 weeks with a senior faculty coach to refine aims pages, biosketches, and career development plans using a real-time peer review process. To evaluate impact, we assessed perceived preparedness (“How prepared do you feel to submit your grant proposal?”) and funding confidence (“How confident do you feel in your proposal’s funding chances?”) on entrance and exit surveys using a visual analog scale (max 100 points). Exit surveys also included an open-ended question: “What did you learn or accomplish during the coaching group?” We used paired t-tests to evaluate pre-to-post participation changes and reviewed free responses for additional context. Results/Anticipated Results: From June 2023 to September 2024, 21 people (12 postdocs/1 research assistant professor/7 tenure-track assistant professors/1 other; 13 female) were enrolled in 4 sessions. Seven people did not finish the sessions and were lost to follow-up. For the 14 participants who completed both the entry and exit survey, perceived preparedness for grant submission increased from 30.1 ± 23.5 to 67.1 ± 24.6 (p  =  0.001). Funding confidence in securing funding also increased from 40.8 ± 19.1 to 64.0 ± 20.7 (p  =  0.003). Participants valued the structure and accountability of the groups and reported other benefits, such as improved writing skills. Opportunities for feedback were also appreciated, with one participant stating, “I learned to face my fear of constructive criticism.” Discussion/Significance of Impact: Coaching improved perceived preparedness for grant submission and confidence in securing funding for participants’ current submissions and provided potentially durable benefits such as receiving and positively responding to constructive feedback. The impact of such programs likely exceeds the short-term financial return on investment.

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.