OBJECTIVES/GOALS: Our primary objective was to determine the demographic and linguistic characteristics of research coordinators (RCs) in a large pediatric emergency medicine research collaborative network. Our secondary objective was to determine if the RCs perceived any impact of those characteristics on their duties. METHODS/STUDY POPULATION: We conducted a 15-question electronic survey of RCs at the member institutions of the Pediatric Emergency Care Applied Research Network (PECARN). A total of 74 potential respondents were identified and received the survey. RESULTS/ANTICIPATED RESULTS: Fifty-three surveys (71.6%) were completed. Most respondents identified as female; white; and not Hispanic or Latino. Fourteen respondents (26.4%) identified as underrepresented minorities in medicine (UIM), which is similar to the percentage of UIM among the general population (30%). Twenty-eight respondents (52%) felt that their race/ethnicity positively impacted recruitment efforts. Twenty-three respondents (43%) felt that their ability to speak a language other than English positively impacted recruitment efforts. Four female respondents felt that their gender hindered their recruitment activities and impacted their sense of belonging within the research team. DISCUSSION/SIGNIFICANCE: RCs felt that their backgrounds and attributes positively impacted subject recruitment. However, some female coordinators felt negatively impacted by their gender. Increasing diversity amongst clinical research professionals and incorporating team cultural humility practices, may help increase diversity among clinical research subjects.

OBJECTIVES/SPECIFIC AIMS: Prostate cancer (PCa) is the most common noncutaneous malignancy in men in the United States. A significant fraction of advanced PCa treated with androgen deprivation therapy experience relentless progression to lethal metastatic castration-resistant prostate cancer (mCRPC). The PCa tumor microenvironment is comprised of a complex mixture of epithelial and stroma cell types engaged in multifaceted heterotypic interactions functioning to maintain tumor growth and immune evasion. We recently uncovered the important role played by myeloid-derived suppressor cells (MDSCs) to mediate tumor immune evasion in aggressive PCa (Wang, Lu et al., Cancer Discovery, 2016). Immune checkpoint blockade (ICB) has elicited durable therapeutic responses across a number of cancer types. However, the impact of ICB on mCRPC has been disappointing, which may signal the need to combine mechanistically-distinct ICB agents and/or override immunosuppression in the tumor microenvironment. Our objective is to determine if robust immunotherapy responses in mCRPC may be elicited by the combined actions of ICB agents together with targeted agents that neutralize MDSCs yet preserve T cell function. METHODS/STUDY POPULATION: We created a novel embryonic stem cell-based chimeric mouse model of mCRPC engineered with signature mutations to study the response to single and combination immunotherapy. The efficacy studies were followed with detailed mechanistic investigation and clinical validation. RESULTS/ANTICIPATED RESULTS: Consonant with early stage clinical trials experience, anti-CTLA4 or anti-PD1 monotherapy failed to impact disease progression. Similarly, modest anti-tumor activity was observed with combination ICB as well as monotherapy with targeted agents including Cabozantinib (tyrosine kinase inhibitor), Dactolisib (PI3K/mTOR inhibitor), and Dasatinib (tyrosine kinase inhibitor). In contrast, mCRPC primary and metastatic disease showed robust responses to dual ICB treatment together with either Cabozantinib or Dactolisib, but not with Dasatinib which impaired T cell infiltration in the tumor. Detailed intratumoral immune profiling with mass cytometry (CyTOF) showed that combined ICB and Cabozantinib or Dactolisib was associated with significant depletion of MDSCs. Cabozantinib and Dactolisib blocked the PI3K signaling activity in MDSCs and reduced their immunosupppresive activity. Mechanistically, the combination efficacy was due to the upregulation of IL-1RA and suppression of MDSC-promoting cytokines secreted by mCRPC cells. DISCUSSION/SIGNIFICANCE OF IMPACT: We demonstrated that an antibody cocktail targeting CTLA4 and PD1 was insufficient to generate effective anti-tumor response, but combination of ICB with targeted therapy that inactivates PI3K signaling displayed superior synergistic efficacy through impairing MDSCs in the tumor microenvironment. These observations illuminate a clinical path hypothesis for combining ICB with MDSC-targeted therapies in the treatment of mCRPC. Importantly, conclusions from the study on PCa may have implications in combination immunotherapy for aggressive breast cancer which is also largely resistant to immune checkpoint blockade and replete with immunosuppressive myeloid cells.

OBJECTIVES/SPECIFIC AIMS: The purpose of this study is to characterize children with nonalcoholic fatty liver disease (NAFLD) living in the Southeastern United States. METHODS/STUDY POPULATION: This retrospective electronic medical record chart review was conducted on a random sample of 206 children identified with NAFLD. Patients were included if they met the following criteria: confirmed NAFLD through either an ultrasound or liver biopsy or clinical suspicion of fatty liver disease alongside elevated alanine aminotransferase (ALT) in the absence of other etiologies causing elevated transaminases. Patients were excluded if they had hepatitis or other documented liver disease. Data collected at initial presentation included age, gender, ethnicity, height, weight, body mass index (BMI), BMI percentile, blood pressure, HbA1c, aspartate aminotransferase (AST), ALT, γ-glutamyl transferase (GGT), total cholesterol, total triglycerides, low-density lipoprotein, and high-density lipoprotein. Statistical analysis: for descriptive statistics, frequency counts and percentages alongside means, standard deviation, range, min/max values for the continuous variables were calculated. RESULTS/ANTICIPATED RESULTS: This study included 206 children diagnosed with NAFLD. Subjects were primarily male (n=136, 66%) and Caucasian (n=133, 66%), followed by Hispanic (n=42, 21%), Black (n=25, 12%), and Asian (n=2, 1%). Mean age at diagnosis was 12.3±3.5 years. Mean weight (lbs), height (in), and BMI (kg/m2) of subjects at diagnosis were 192±77 lbs, 61.7±6.6 in, 34.6±9.7 kg/m2, respectively. Patients had an average systolic blood pressure of 124±15.4 mmHg and diastolic blood pressure of 69.6±10.6 mmHg. Mean ALT was 91.8±67.2 U/L, AST was 61±38.8 U/L, and GGT was 55.1±64.6 U/L. Mean HbA1c was 5.8±1.4%, cholesterol was 176±36.3 mg/dL, triglycerides were 200±134 mg/dL, low-density lipoprotein was 107.6±32.1 mg/dL, and high-density lipoprotein was 39.9±8.4 mg/dL. DISCUSSION/SIGNIFICANCE OF IMPACT: In addition to having significantly elevated liver enzymes, children with NAFLD had several derangements in their metabolic profile, most notably high triglyceride levels and HbA1c values in the prediabetic range. Although lifestyle modification is the gold standard treatment for NAFLD, pharmacotherapy may need to be included to address metabolic syndrome.

OBJECTIVES/SPECIFIC AIMS: Incomplete spinal cord injury typically results in life-long disability, often in the form of profound loss of locomotion capability. Individuals who have experienced incomplete spinal cord injury exhibit persistent eccentric motor deficits, which are particularly prevalent in the weight acceptance phase of gait and emphasized in sagittal plane knee motion and frontal plane hip motion. METHODS/STUDY POPULATION: Motion analysis can capture the kinematic and joint-level deficits of these individuals, but it is impossible to directly calculate the contributions of individual muscles to weight acceptance due to the complexity of the musculoskeletal system. Instead, those muscle contributions must be simulated in order to approximate muscle power during locomotion. RESULTS/ANTICIPATED RESULTS: The traditional method for driving these simulations with electromyography readings is unavailable for individuals who have neuromuscular deficits (e.g., spasticity or paralysis), due to the need to generate reliable maximum voluntary isometric contractions for baseline purposes. Instead, this research develops a novel method for using resting electromyography data to drive musculoskeletal simulations using a muscle activation threshold paradigm. DISCUSSION/SIGNIFICANCE OF IMPACT: The simulation results of this method more closely resemble experimental results, but further simulation refinement is needed to fully capture the true muscle activity.

OBJECTIVES/SPECIFIC AIMS: The morbidity and mortality in adults with single ventricular hearts who have undergone Fontan palliation is poorly defined. These patients have a high burden of arrhythmia, heart failure, and re-operation. We hypothesized that age and type of Fontan predict occurrence of arrhythmia. METHODS/STUDY POPULATION: In total, 205 patients aged 18 years who had undergone a Fontan procedure were identified. Those with incomplete data were excluded. Demographic, anatomic, pharmacologic, imaging, hemodynamic, and electrophysiologic data were collected. The χ2 and Mann-Whitney U tests were used to test significance defined as p<0.05. RESULTS/ANTICIPATED RESULTS: Of the 205 patients identified, 59 had been lost to follow-up. Of the 146 patients (77, 53% female) actively followed 18 (12%) had died at a median (IQR) age of 27 (21–34.3); in patients alive as of 10/2016 the median age was 26 years (22–34). Fontan types were lateral tunnel (LT) (n=79, 54.1%), extracardiac (EC) (n=32, 22%), right atrial to pulmonary artery (RV-PA) (n=28, 19%), and Fontan with Bjork modification (n=4, 2.7%). Systemic left ventricle (n=96, 66%) was more common than systemic right ventricle (n=43, 30%). Of the 146 patients, 101 (69%) had significant morbidity or mortality: 86 (59%) were diagnosed with arrhythmia, 18 (12%) died, and 11 (8%) underwent heart transplants. Frequent procedures included: Fontan revisions/cryoablation in 28 (19%), electrophysiology studies with ablation in 73 (50%), and pacemakers in 53 (36%). Of the arrhythmia diagnoses, 57 (64%) were atrial tachyarrhythmias. RV-PA Fontan procedures were associated with significantly more atrial arrhythmia than all other Fontan types (70% vs. 30%; p<0.01). There was no statistical difference in occurrence of atrial arrhythmia in adults with LT Versus EC Fontans (p=0.3). While patients who had undergone RV-PA and Bjork Fontans were older with median age 34 years, there was no significant difference in age between LT and EC (median 24.0 and 24.5). DISCUSSION/SIGNIFICANCE OF IMPACT: Adult survivors of the Fontan procedure suffer from significant morbidity and mortality. The single most prevalent morbidity is atrial arrhythmia. We conclude that RV-PA Fontans, now obsolete, have the highest prevalence of arrhythmia and that there is no difference in arrhythmia burden between LT and EC Fontans. Given the high prevalence of morbidity and mortality in this population, it is imperative that they be followed by cardiologists with expertise in congenital heart disease.

OBJECTIVES/GOALS: Parental SES may influence the trajectory of students applying to orthopaedic surgery residency, perpetuating opportunistic disparities. Thus, we sought to examine the relationship between parental occupation/education and applicant match rate, education financing, and medical school background. METHODS/STUDY POPULATION: Data from the Association of American Medical Colleges (AAMC) documented parental occupation and education levels of 10,697 orthopedics applicants from 2011 to 2021. Parental occupations were categorized into physician vs non-physician, healthcare vs non-healthcare, working class vs non-working class, and STEMM (Science, Technology, Engineering, Mathematics, Medicine) vs non-STEMM. Parental education levels spanned from no college degree to doctorate degrees and were used as a proxy for SES. Outcomes analyzed included match success, premedical and medical school debt, total educational debt, scholarships, and representation from top 40 research medical schools as determined by NIH funding. RESULTS/ANTICIPATED RESULTS: Physician parent applicants (20.1%) had better match rates (75.5% vs. 73.5%), lower debts, lesser scholarships, and higher top 40 school representation. Healthcare parent applicants (37.0%) had similar match rates, less debt and scholarships. Working class parent applicants (6.0%) had more debt and scholarships. STEMM parent applicants (48.6%) had higher match rates, lesser debts and scholarships, and higher top 40 representation. Applicants with parents without college degrees had lower match rates (68.6% vs 74.5%), more debt and scholarships. Doctorate parent applicants had better match success (75.9% vs 72.9%), lesser debts, and higher top 40 school representation (34.9% vs 29.6%). DISCUSSION/SIGNIFICANCE: Parental SES was associated with substantial variation in applicant financial burden and educational pedigree. Notably, applicants with parents lacking degrees had lower match rates, underscoring the need for supportive strategies to ensure equitable opportunities for aspiring orthopaedic surgeons.

OBJECTIVES/SPECIFIC AIMS: More than half a million adult patients nationally undergo cardiac surgery each year. Reintubation following cardiac surgery is common and associated with higher short- and long-term mortality, increased cost, and longer lengths of stay. The reintubation incidence is estimated at 5-10%. Patients undergoing cardiac surgery are increasing in age and comorbidity burden, and receive increasingly complex cardiac surgical procedures, complicating decision making around when to extubate postoperative patients. Compounding this complexity are financial pressures to maintain high throughput and maximize ICU bed availability. Providers are often compelled to extubate high-risk patients earlier, despite the potential for an increased risk of reintubation. Understanding the risk factors for reintubation after cardiac surgery and identifying effective interventions to reduce these reintubations is of critical importance to optimize patient outcomes. High-flow nasal cannula (HFNC) provides up to 60 liters per minute of 100% oxygen, dead space washout, and humidification to improve secretion clearance, and has shown some benefits in improving hypoxia and reducing reintubation in select populations. However, its benefit in high-risk patients undergoing cardiac surgical procedures is not known and therefore clinicians may still be reluctant to extubate these patients early and introduce HFNC, despite the known risks of prolonged intubation. To address this important issue, we aim to develop and validate a model to predict postoperative reintubation after cardiac surgery using data readily available from the electronic health record (EHR) and use this data to complete a pilot randomized controlled trial (RCT) of post-extubation HFNC to prevent reintubation in cardiac surgery patients identified as at high risk for reintubation. METHODS/STUDY POPULATION: Based on retrospective data demonstrating a 4.7% reintubation incidence within 48 hours in our CVICU, we estimate that there will be 340 reintubations available for analysis of the risk factors for reintubation to develop our predictive model from November 2, 2017 (our EHR go-live). We require 15 events per predictive variable to avoid overfitting the model, giving us at least 22 variables for analysis and inclusion in the model. Model validation and calibration will be performed using a bootstrapped validation cohort. Next, we will prospectively study 120 patients with a greater than 10% predicted risk of reintubation (double the baseline risk of the overall population) and randomly assign them to either HFNC or usual care, to test the hypothesis that HFNC decreases the rate of reintubation in high-risk patients. RESULTS/ANTICIPATED RESULTS: In addition to developing a predictive model, refining it, and validating its ability to predict the primary outcome of reintubation within 48 hours, I will further assess whether HFNC reduces total duration of mechanical ventilation, hospital length of stay, and ICU length of stay in this high-risk population. I will use these data to establish the feasibility of EHR-integrated predictive modeling and randomization, as well as to guide a future multicenter clinical trial that will pragmatically leverage the EHR for patient selection, enrollment, randomization, and data collection. DISCUSSION/SIGNIFICANCE OF IMPACT: Assuming HFNC decreases reintubation rates by 50%, at a 1:1 ratio of cases to controls, we will require 435 patients in each group (970 total), to have an 80% power and alpha of 0.05 to detect a difference. As this will require a multicenter study, we will instead focus on using data from this pilot study to: 1) refine our sample size estimates. 2) demonstrate the feasibility of our novel EHR-integrated pragmatic trial design. 3) identify and screen collaborators at other institutions, including obtaining important regulatory and legal approval. 4) establish a data safety monitoring board for the trial. 5) refine the data collection infrastructure, leveraging commercially available resources in one of the largest enterprise EHR systems (Epic) and associated resource-sharing products, such as Epic’s App Orchard.

OBJECTIVES/GOALS: The inclusion of underrepresented racial and ethnic groups (URGs) in clinical research is critical for ethical and scientific reasons. This initiative aimed to assess the perspectives, barriers, needs, and recommendations encountered by research teams when enrolling and retaining URGs in clinical research. METHODS/STUDY POPULATION: An anonymous, web-based survey comprised of quantitative and qualitative questions was administered to individuals involved in clinical research at an academic medical center. The survey assessed three main domains: 1. Research teams' perceptions and experiences with enrolling URGs in clinical research, 2. Factors that discourage URGs from participating in clinical research, and 3. Research teams’ overall willingness to support URG enrollment. Demographics were also collected. The survey was reviewed by experts in clinical research, research ethics, and diversity, equity, inclusion, and accessibility (DEIA). The assessment was piloted among research professionals and edits were made accordingly prior to official dissemination. Data were analyzed using descriptive statistics. RESULTS/ANTICIPATED RESULTS: There was a total of 63 responses. A majority of respondents have more success enrolling patients whose primary language is the same as their own and that time arranging for an interpreter has negatively impacted enrollment efforts. Approximately half of the respondents believe that the race and/or ethnicity of the potential study participant influences enrollment success. Factors discouraging URGs from participating in clinical research include unavailability for follow-up visits due to transportation issues, distrust in doctors and/or researchers, fear of unknown side effects, and unavailability of medical interpreters. Respondents report that they are not discouraged from enrolling URGs and would utilize resources related to encouraging the inclusion of URGs DISCUSSION/SIGNIFICANCE: Language appears more influential than ethnicity or race when it comes to enrolling and retaining URGs. Additionally, it appears that enrolling is a bigger challenge than retaining. Major themes that emerge with respect to retaining enrolled participants include the inability to attend follow-up visits and the lack of incentives/compensation.

OBJECTIVES/GOALS: The use of Human Centered Design (HCD) to improve the quality of team science is a recent application, and HCDs benefits and challenges have not been rigorously evaluated. We conducted a qualitative study with health sciences researchers trained in HCD methods to determine how they applied HCD methods and perceived its benefits and challenges. METHODS/STUDY POPULATION: The University of Pittsburgh offered HCD training to three cohorts of research scientists (staff as well as faculty) over a three-year period. The training was provided by the LUMA Institute, a premier HCD design firm with a highly regarded training program. We then evaluated this training by conducting 1-hour, semi-structured interviews with trainees from three training cohorts. Interviews focused on perceptions of the training, subsequent uses of HCD, barriers and facilitators, and perceptions of the utility of HCD to science teams. Data analysis was conducted using Braun and Clarkes process for thematic analysis. RESULTS/ANTICIPATED RESULTS: We interviewed 18 researchers (nine faculty and nine staff) trained in HCD methods and identified distinct themes regarding HCD use and its perceived benefits and challenges. Trainees found HCD relevant to research teams for stakeholder engagement, research design, project planning, meeting facilitation, and team management. They also described benefits of HCD in five distinct areas: creativity, egalitarianism, structure, efficiency, and visibility. We also identified challenges, including tensions between HCD approaches and academic culture. DISCUSSION/SIGNIFICANCE: Our data suggest that HCD has the potential to help researchers work more inclusively and collaboratively on interdisciplinary teams and generate more innovative and impactful science. The application of HCD methods is not without challenges; however, we believe these challenges can be overcome with institutional investment.

OBJECTIVES/GOALS: The current opioid epidemic has placed post-operative pain management under scrutiny. Limiting post-operative pain can decrease overall opioid usage in the recovery period, especially after orthognathic surgery. Several studies have illustrated the efficacy of pregabalin in decreasing postoperative pain and opioid usage in adults undergoing orthognathic surgery. We aim to study the effects of a single dose of preoperative pregabalin on postoperative pain and total opioid consumption after orthognathic surgery in individuals with cleft lip and palate. METHODS/STUDY POPULATION: This was a retrospective cohort study of consecutive patients who received Le Fort I midface advancement between June 2012 and July 2019 by one of two surgeons at a single institution. We took advantage of our institution’s implementation, beginning in 2016, of a one-time dose of preoperative pregabalin for LeFort I midface advancement. All patients had diagnosed cleft lip and palate. The treatment group received a one-time preoperative dose of pregabalin. The control group did not receive pregabalin. Total morphine milligram equivalents (MME) consumption was calculated by adding intraoperative opioid administration and postoperative opioid consumption during admission. Postoperative pain control during admission consisted of oral oxycodone and intravenous (IV) hydromorphone or morphine. Duration of hospitalization and pain intensity assessed with the numeric pain rating scale (0-10) were also recorded. The mean postoperative pain assessment scores during admission was calculated for each patient. The median of these individual mean pain assessment scores for each group was subsequently computed. RESULTS/ANTICIPATED RESULTS: Twenty-three patients (14 males, 9 females) were included in this study; 12 patients received pregabalin (median dose: 150mg, range: 100-200mg). Mean age (years) at operation of the pregabalin (18.3 ± 1.9) and control groups (17.8 ± 1.9) were also equivalent (p = 0.571). Median hospital stay for both groups was 1.0 day. The pregabalin group had significantly lower consumption of total opioids during admission (total MME 70.95 MME; IQR: 24.65-150.17) compared to the control group (138.00 MME; IQR: 105.00-232.48) (MU = 31.00, p = 0.031). Although pain scores in the treatment group (3.21 ± 2.03) were lower than in the control group (3.71 ± 2.95), the difference was not statistically significant (p = 0.651, 95% Cl [−1.75, 2.75]). DISCUSSION/SIGNIFICANCE OF IMPACT: Based on the results, a one-time preoperative oral dose of pregabalin before orthognathic surgery in patients with cleft lip and palate reduced total opioid consumption during admission. However, there was no difference in length of stay or pain scores within the two groups. A single preemptive oral dose of pregabalin should be considered an effective adjunct to pain management protocols in patients undergoing orthognathic surgery.

ABSTRACT IMPACT: Younger patients receiving biologics for rheumatoid arthritis have higher medical expenditure. OBJECTIVES/GOALS: TNF inhibiting biologic disease modifying antirheumatic drugs are among the most highly regarded treatment options for rheumatoid arthritis (RA). We aimed at evaluating the medical and prescription costs associated with monoclonal antibody use vs. other RA treatment options in subjects diagnosed with RA. METHODS/STUDY POPULATION: Records from the Medical Panels Expenditure Survey (MEPS) database made available by the Agency for Healthcare Research and Quality were used to identify all RA subjects (n=_____). Demographics and MEPS-provided flags for RA were abstracted from the medical condition files for all the subjects surveyed (2008-2018). Prescribed biologics were identified based on generic and brand names following a manual review to detect any misspellings. Total medical expenses and prescription expenses were abstracted for all identified RA subjects. Subject were surveyed for two consecutive years, thus expenses were assessed for each of the two surveyed years. Costs were adjusted for inflation and expressed in 2018 dollars. The relationship between biologics use, cost and age or gender was evaluated by Fisher’s exact test. RESULTS/ANTICIPATED RESULTS: Most RA subjects did not use biologics. RA was more prevalent in women than in men with no significant correlation between sex and the use of biologics in year 1, year 2, or the combined years (p=.44, p=.63, and p=.65, respectively). Biologics users were found to be significantly younger (p<.001), with a mean of 52.8 years compared to 59 years in those who did not use biologics. The 95% confidence interval was 3.7 to 8.6 years younger than non-users. Total medical and prescription costs were higher for biologics users (p<.001) in all analyses. The mean prescription cost difference was $24,038 more per year for biologics users, and $26,296 more total medical expenses, CI $20,502-$27,230 and CI $21,947-$30,646, respectively. There was a trend for biologics users to have higher non-prescription medical expenses (p=.05). DISCUSSION/SIGNIFICANCE OF FINDINGS: Interestingly, biologics non-users had some extreme outliers with expenses far higher than any biologics users, possibly due to poorly controlled RA due to age and/or comorbidities. Yet, our most interesting findings are the higher use of biologics among younger RA subjects and the elevated costs of care being driven mainly by prescriptions cost.

OBJECTIVES/GOALS: A group of leading students was integrated as part of the collaborators of the Title V MSC Project with the objective of promoting UgS and GS from Puerto Rico to start and get involved in CTR with an interdisciplinary approach (IA) through the course of INTD 5998: Clinical and Translational Research: Introduction and Principles. METHODS/STUDY POPULATION: The Title V MSC Project of the UPR institutionalized the INTD 5998 course. This course offers UgS and GS the opportunity to start and get involved in CTR. Students with leadership from different universities and from different geographic regions of Puerto Rico were identified and recruited to collaborate in the recruitment of students interested in taking the INTD 5998 course. Since April 2022, the student leaders implemented different strategies to make known about the course and its benefits among their peers. RESULTS/ANTICIPATED RESULTS: For the course of INTD 5998 that began in August 2022, they achieved a contact list of 97 interested students from different geographic areas of Puerto Rico, 21 students applied for the course and 15 enrolled (71% of those who applied and 75% of the maximum course quota). DISCUSSION/SIGNIFICANCE: The student leaders have been an effective promotion and marketing strategy to make known the INTD 5998 course among their peers from the different Universities of Puerto Rico. Their integration as collaborators to the Title V MSC Project has been successful and valuable.

OBJECTIVES/SPECIFIC AIMS: About 75% of the estimated 2.5 million traumatic brain injuries (TBIs) diagnosed annually classify as mild TBI (mTBI); yet cognitive impairments associated with poor patient outcomes can persist for weeks to years. mTBI symptoms are difficult to measure objectively and often remain undiagnosed in the context of an unknown cognitive baseline. Formal neuropsychological exams hold limited utility due to their extensive resource burden. We aimed to define the clinical importance of a 4-question assessment of subjective cognitive complaints (SCC) in predicting return to work at 6 months following mTBI. METHODS/STUDY POPULATION: mTBI participants from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study were included. A self-report affirmation to at least 1 of 4 subjective cognitive symptoms yielded positive SCC. Regression analysis was used to determine factors associated with return to work by 6-months. RESULTS/ANTICIPATED RESULTS: Of 479 enrolled participants with mTBI, 271 (57%) had complete follow-up data. Of which, 156 (58%) had at least sheltered employment at enrollment. Thirty-four (22%) of workers had no return to work at 6-months. Demographics, prior education, presenting injury severity, work status, and post-traumatic stress disorder were associated with return to work. SCC was associated with lower odds of return to work by 6-months (OR=0.11, p=0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: We suggest a concise 4-question assessment of SCC may be clinically relevant in estimating the likelihood of return to work by 6 months post-mTBI.

OBJECTIVES/GOALS: In this study we sought to determine the role of glucagon-like peptide-1 (GLP-1), one of the main gut hormones in regulating glucose metabolism, after protein ingestion in patients with a history of Roux-en-Y gastric bypass (GB) and sleeve gastrectomy (SG). METHODS/STUDY POPULATION: We examined the glucose and islet-cell secretory responses to 50 g protein ingestion with and without a potent GLP-1 receptor antagonist, exendin-(9-39) [Ex-9], in 10 GB-treated subjects, 9 SG-treated, and 7 non-operated controls (CN). The groups were matched for age, BMI, fat-free mass, fasting glucose and insulin, and HbA1c. The surgical groups also were matched for weight loss and time post-surgery. No subjects had diabetes. RESULTS/ANTICIPATED RESULTS: Protein ingestion resulted in an early rise in glycemia (AUCGlucose1hr) in GB and SG, whereas CN had minimal change in glucose (p<0.05). Protein ingestion enhanced C-peptide responses in all groups, but to a larger extent in GB and SG when compared to CN (p<0.05). Early glucagon response to protein ingestion (AUCGlucagon1hr) tended to be larger in GB and SG subjects when compared to CN (p=0.07). Ex-9 increased premeal and prandial glycemia in all groups (p<0.05), but increase in early glycemia (AUCGlucose1hr) was most notable in GB (p=0.1, interaction). This glycemic effect of Ex-9 was associated with a ~25% reduction in prandial C-peptide secretion in GB and SG and ~8% increase in CN (p<0.05, interaction). Early prandial glucagon responses were larger during studies with Ex-9 compared to those without (p<0.05). DISCUSSION/SIGNIFICANCE: Our findings indicate that glucose metabolism after protein ingestion is altered after GB and SG. To our knowledge, this is the first report to demonstrate that endogenous GLP-1 contributes to glucose and islet-cell secretory response to protein ingestion, and that GB and SG exaggerate GLP-1 contribution to insulin secretion after protein ingestion.

OBJECTIVES/GOALS: Clinical research professionals (CRPs) are vital for high quality research. Professional development opportunities for CRPs help improve job satisfaction and retention. This poster will present data on peer-presenter satisfaction and their assessment of co-leading a workshop as an important professional development and networking activity. METHODS/STUDY POPULATION: Developing a Research Professionals Network Workshop is an important professional development opportunity for peer-presenters in a mentored, collaborative environment that encourages networking and inter-institutional teamwork. Presenters are connected by the leadership team and then work together to develop the workshop’s learning objectives, presentation, and activities. A summary of learner evaluations are provided to the presenting team to provide constructive feedback for future presentations. A survey to assess experience in leading the workshops is sent to presenters after the workshop to assess overall satisfaction and assessment of importance in their professional development. RESULTS/ANTICIPATED RESULTS: Presenter evaluation response data from the years of 2019-2022 showed high rates of agreement that presenters’ participation 1) increased their knowledge of the topic, 2) appreciated the support provided by the leadership team, 3) felt adequately prepared to lead the workshop, and 4) were overall satisfied with the experience. Questions specifically around the inter-institutional collaboration and professional development of the workshop experience were added in 2021 and similarly showed high marks of satisfaction. Qualitative response data showed that some presenters continued collaborations after workshop completion. DISCUSSION/SIGNIFICANCE: Overall results show that workshop presenters felt that leading an RPN workshop with collaborators from the other participating sites was a useful experience that supported their ongoing professional development. High marks on satisfaction by presenters is attributed to the multi-hub partnership and guidance from the leadership team.

OBJECTIVES/GOALS: Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing β-cells. Emerging data suggest that differences in intestinal microbiota might be critically involved both in autoimmunity and in glucose homeostasis. The prebiotic high amylose maize starch (HAMS) alters the gut microbiome profile and metabolites positively by increasing production of beneficial short chain fatty acids (SCFAs) that have significant anti-inflammatory effects. HAMS also improves glycemia, insulin sensitivity and secretion in healthy non-diabetic adults. Further, an acetylated and butyrylated form of HAMS (HAMS-AB) that increases beneficial SCFA production, namely acetate and butyrate, has been safe and effective in disease prevention in mouse T1D models. The objective of the proposed study is to assess the effect of administering a prebiotic, such as HAMS-AB, on the gut microbiome profile, SCFA production, glycemia and β-cell function in humans with T1D. METHODS/STUDY POPULATION: We hypothesize that administration of HAMS-AB will (i) improve the gut microbiome profile in humans with T1D, (ii) increase SCFA production, and (iii) improve β-cell health, β-cell function and overall glycemia. We propose a pilot randomized controlled cross-over trial of HAMS-AB in 12 youth with newly-diagnosed T1D. We will use state-of-the-art markers to profile the gut microbiome (using 16S rRNA sequencing), measure stool SCFA levels (using gas chromatography), asses β-cell stress/death (by measuring proinsulin to C-peptide ratios) and glycemia (assessed by continuous glucose monitoring and HbA1c measurements). RESULTS/ANTICIPATED RESULTS: We expect that the use of HAMS-AB in newly diagnosed youth with type 1 diabetes will alter the gut microbiome profile (thus increasing the number of fermenters and SCFA levels), β-cell function and glycemia in humans with T1D. DISCUSSION/SIGNIFICANCE OF IMPACT: Given the unknown long-term effects of immune-modulatory therapy on those at risk for or those diagnosed with T1D, the use of a prebiotic such as HAMS-AB offers a simple, safe, yet inexpensive and tolerated dietary alternative approach to mitigating disease.

OBJECTIVES/GOALS: To construct an assessment scale capable of evaluating a trial’s gender literacy or the extent to which biologically assigned “sex” is understood as separate from culturally defined and personally embodied “gender”. This scale in tandem with a policy brief will outline recommendations for inclusive medical nomenclature in the clinical space. METHODS/STUDY POPULATION: Using clinicaltrials.gov, inclusion/exclusion criteria was recorded for PrEP interventional trials (i.e., Truvada, Descovy). To evaluate these trials, an assessment scale for “gender literacy” is necessary. This scale relies on the fact that sex and gender are distinct elements to one’s identity and ought to be reported as such. As a form of content analysis, where literary information (eligibility criteria) is evaluated based on set rubric, this scale will require validation through inter-coder agreement. Evaluated in a group of 5 college-age students, this scale was used on selected PrEP clinical trials to verify if there was high agreement in the scores given. After validation, the dataset from clinicaltrials.gov underwent evaluation using the proposed assessment scale for gender literacy. RESULTS/ANTICIPATED RESULTS: The student coders had a Kalpha of 0.4 in the first round of grading. After retraining, their Kalpha increased to 0.68. The grading involved a subjective language rating (LIR), evaluating the usage of inclusive language, and a numerical score (GR) for the demographics of inclusion in a trial. After this inter-coder agreement validation, 216 active PrEP clinical trials (as of March 2023) were downloaded from clinicaltrials.gov. Grading of these trials showed that cisgender males represented 40% of participants, while 28% represented both transgender men and women, and less than 1% represented non-binary individuals. Moreover, more than half of the trials (52%) exhibited cisgender-oriented language or made no reference to gender identity. DISCUSSION/SIGNIFICANCE: It is a scientific imperative for clinical trials to have representative participant bases in order to derive data that is generalizable to afflicted populations. Especially for PrEP clinical trials, where gender-diverse individuals need visibility, trial design must be carefully crafted so as not to exclude through dated or exclusionary language.

Objectives/Goals: Discriminatory experiences within healthcare settings significantly hinder equitable health access for sexual minority groups (SMPs) in the USA. These discriminatory experiences can manifest in various forms (e.g., refusal of care). We aimed to explore different types of discrimination encountered by SMPs in the healthcare settings. Methods/Study Population: This study utilized secondary data from the NIH All of Us Research Program. For this analysis, we selected cohorts self-identifying as gay (n  =  9,454), bisexual (n  =  15,284), lesbian (n  =  5,267), and straight (n  =  349,748), enabling robust comparisons across SMPs and straight individuals. We employed analysis of variance and Chi-square analyses to assess group differences in healthcare discrimination, using key indicators from the Discrimination in Medical Settings Scale. These indicators captured experiences such as being treated with less respect or courtesy and feeling ignored by healthcare providers, providing a comprehensive view of discriminatory encounters in healthcare settings for SMPs. Results/Anticipated Results: Our analyses revealed that bisexual individuals reported the highest levels of healthcare discrimination (mean  =  3.64, SD  =  2.45), followed by lesbians (mean  =  3.37, SD  =  2.47), other SMPs (mean  =  3.36, SD  =  2.53), gay (mean  =  2.69, SD  =  2.47), and straight participants (mean  =  2.60, SD  =  2.42). Among the seven discrimination indicators, the most reported experience was feeling like a doctor or nurse was not listening, with 76.8% of bisexual participants, 72.3% of lesbians, 68.8% of other SMPs, and 56.9% of gay participants reporting this experience. This was followed by reports of being treated with less respect and being treated with less courtesy in healthcare settings. These findings highlight the pervasive nature of healthcare discrimination among SMPs, particularly bisexual individuals. Discussion/Significance of Impact: SMPs experience higher levels of discrimination in healthcare settings compared to their straight counterparts. Our results underscore the urgent need to foster respectful, inclusive healthcare environments and ensure that healthcare providers are adequately trained to address the unique health needs and experiences of SMPs.

OBJECTIVES/SPECIFIC AIMS: Characterize microbiome metadata describing specimens collected, genomic pipelines and microbiome results, and incorporate them into a data integration platform for enabling harmonization, integration and assimilation of microbial genomics with exposures as spatiotemporal events. METHODS/STUDY POPULATION: We followed similar methods utilized in previous efforts in charactering and developing metadata models for describing microbiome metadata. Due to the heterogeneity in microbiome and exposome data, we aligned them along a conceptual representation of different data used in translational research; microbiomes being biospecimen-derived, and exposomes being a combination of sensor measurements, surveys and computationally modelled data. We performed a review of literature describing microbiome data, metadata, and semantics [4–15], along with existing datasets [16] and developed an initial metadata model. We reviewed the model with microbiome domain experts for its accuracy and completeness, and with translational researchers for its utility in different studies, and iteratively refined it. We then incorporated the logical model into OpenFurther’s metadata repository MDR [17,18] for harmonization of different microbiome datasets, as well as integration and assimilation of microbiome-exposome events utilizing the UPIE. RESULTS/ANTICIPATED RESULTS: Our model for describing the microbiome currently includes three domains (1) the specimen collected for analysis, (2) the microbial genomics pipelines, and (3) details of the microbiome genomics. For (1), we utilized biospecimen data model that harmonizes the data structures of caTissue, OpenSpecimen and other commonly available specimen management platform. (3) includes details about the organisms, isolate, host specifics, sequencing methodology, genomic sequences and annotations, microbiome phenotype, genomic data and storage, genomic copies and associated times stamps. We then incorporated this logical model into the MDR as assets and associations that UPIE utilizes to harmonize different microbiome datasets, followed by integration and assimilation of microbiome-exposome events. Details of (2) are ongoing. DISCUSSION/SIGNIFICANCE OF IMPACT: The role of the microbiome and co-influences from environmental exposures in etio-pathology of various pulmonary conditions isn’t well understood [19–24]. This metadata model for the microbiome provides a systematic approach for integrating microbial genomics with sensor-based environmental and physiological data, and clinical data that are present in varying spatial and temporal granularities and require complex methods for integration, assimilation and analysis. Incorporation of this microbiome model will advance the performance of sensor-based exposure studies of the (UPIE) to support novel research paradigms that will improve our understanding of the role of microbiome in promoting and preventing airway inflammation by performing a range of hypothesis-driven microbiome-exposome pediatric asthma studies across the translational spectrum.

OBJECTIVES/GOALS: Mayo Clinic implemented a CRC Placement Hub to improve hiring experiences for candidates and hiring managers. Candidates apply to a centralized posting. A Placement Coordinator handles administrative and screening responsibilities, allowing hiring managers to focus on selecting best candidates. METHODS/STUDY POPULATION: The CRC Placement Hub was implemented in phases. Initially, first and second interviews were conducted using Zoom and hiring manager utilization of the Hub was voluntary. Positive candidate and hiring manager feedback shifted Hub utilization to the standard practice and hiring managers must request an exception to post separately for unique candidate requirements. The third phase progressed to utilizing the HireVue hiring platform. Qualified candidates are invited to complete an on-Demand interview at their convenience, which hiring managers utilize to select candidates to continue through the interview process. HireVue utilization has decreased time to fill metrics for CRC candidates. RESULTS/ANTICIPATED RESULTS: The intentions for the CRC Placement Hub are to offer a positive hiring experience for candidates and reduce administrative burden for the hiring managers, while maintaining autonomy of hiring decisions. Additional purposes for the Hub are to increase the candidate pool by developing recruitment pipelines and decrease overall timeline to fill an open position. Qualitative and quantitative metrics were established to monitor performance. Metrics depict positive experiences for candidates and hiring managers, and decreased timelines to fill open positions. Candidate pools continue to increase as the Hub Placement Coordinator holds off-campus and online recruitment events. DISCUSSION/SIGNIFICANCE: The CRC Placement Hub provides candidates a positive experience, allowing them to apply to one posting but considered for all open positions. The Hub decreases administrative burden for hiring managers, allowing them to focus on critical aspects of candidate selection and managing clinical research.