OBJECTIVES/GOALS: Biomedical research fields are facing the challenges of demand for skilled workers as well as challenges related to diversity in that workforce. It is important that the healthcare workforce reflect the population it serves. The Exposures Internship seeks to address this by building pathways for youth to pursue careers in research and medicine. METHODS/STUDY POPULATION: In 2021, the Yale Cultural Ambassadors expressed concern about the lack of free high quality, educational offerings for youth that summer. They asked YCCI to consider developing a summer program for students aged 15 and older that focused on spurring interest in careers in healthcare, medicine, and clinical and translational research. The result was a 4-week virtual learning experience for 34 interns who met daily via Zoom and participated in course work, lectures, journal clubs, group projects, and virtual lunches with internationally renowned clinical research and healthcare leaders. Sessions were designed to help interns gain knowledge of and exposure to current topics in clinical and translational science and to observe the various steps of proposing, designing, undertaking, and analyzing clinical trials. RESULTS/ANTICIPATED RESULTS: YCCI received over 900 inquiries from around the world with more than 200 completed applications for participation in the internship for the pilot year. Since then, YCCI leadership has worked with community partners to engage young scholars from 17 different states, Canada, Mexico and Puerto Rico. Of those, we estimate 75% are minority, ~50% female and 20% from rural areas with limited similar opportunities. During the four weeks of the program these highly motivated students worked on projects aimed at increasing participation in pediatric research through a revised Informed consent and adolescent assent process and a youth centered awareness campaign. Interns were so inspired that they requested the program be continued beyond the initial four weeks. As such, YCCI continued to offer sessions throughout the year. DISCUSSION/SIGNIFICANCE: In evaluation of the pilot program 95% of respondents strongly agreed that the program exposed them to new information about clinical and translational research. One intern shared, This program has unquestionably made me consider becoming a researcher in the future with the goal of becoming a principal investigator within my interest in medicine.

OBJECTIVES/GOALS: To improve early career faculty members’ NIH grant writing skills, Clinical and Translational Science Awards (CTSA) hubs have developed a variety of workshop-style programs. However, few articles have evaluated the impact of grant writing workshops on NIH grant submission and award rates. METHODS/STUDY POPULATION: The K Writing program was developed by the Michigan Institute for Clinical and Health Research (MICHR) at the University of Michigan. Since 2012, 435 scholars have participated in the program. The MICHR K Writing program is a three-part workshop series that prepares scholars by providing them with guidelines to write all sections of a career development grant application. Each session focuses on different sections of the K award proposal. During the workshop sessions, participants break into small groups and exchange drafts of their proposal sections and receive peer critique and feedback from senior faculty facilitators who have experience with NIH study sections. RESULTS/ANTICIPATED RESULTS: Between 2012-2018, 273 scholars participated and 57% were female. Our two primary outcomes of interest are submission rates and success rates (the number of grants awarded divided by the number of applications). We plan to examine the effects of several characteristics, including number of sessions attended, cohort year, and faculty vs. postdoctoral status. We will also examine whether there were differences in submission and success rates between female and male researchers and between underrepresented minority scholars and those who identified as white or Asian. Lastly, we will report submission and success rates for each grant mechanism and compare them to the national averages. DISCUSSION/SIGNIFICANCE: Obtaining external research funding is an important part of a faculty career, especially at its early stages. This research has important implications for the design of similar programs intended to increase submission and success rates for federal grant applications.

OBJECTIVES/SPECIFIC AIMS: Treatment of acute myeloid leukemia (AML) is challenging, as apoptosis-resistant AML cells often persist within the bone marrow microenvironment despite chemotherapy. The overall goal of our laboratory is to identify and ultimately target the bone marrow factors that protect AML cells. METHODS/STUDY POPULATION: Using cell cultures, we previously reported that SDF-1 (CXCL12), an abundant bone marrow chemokine, induces apoptosis of isolated CXCR4+ AML cells, including freshly isolated bone marrow-derived AML cells from approximately one-third of AML patients. However, co-culture of AML cells with differentiating osteoblasts protected AML cells from apoptosis. RESULTS/ANTICIPATED RESULTS: Histone deacetylase inhibitors (HDACi) abrogated the ability of osteoblasts to protect AML cells and altered expression of matrix mineralization genes including tissue nonspecific alkaline phosphatase (TNAP). A different drug, cyclosporine A (CSA), similarly inhibited osteoblast-mediated protection of AML cells and reduced TNAP expression. Specifically targeting osteoblast TNAP via siRNA was sufficient to prevent osteoblasts from protecting AML cells in co-cultures. In addition, we are targeting TNAP enzymatically. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate that targeting TNAP may be useful in AML treatment to render the bone marrow microenvironment more hostile to leukemic cell survival.

OBJECTIVES/SPECIFIC AIMS: Glaucoma is a leading cause of irreversible blindness worldwide; in the United States alone, over 2.7 million individuals are affected. Various risk factors for glaucoma are known and include age, race/ethnicity, genetics, and ocular measures. Despite numerous studies, molecular and environmental factors that contribute to glaucoma remain elusive. Our objective was to conduct a genome-wide association for glaucoma among black and white HRS respondents, and to determine the feasibility for future analyses examining shared genetic markers between glaucoma and other comorbidities, behaviors, and environmental risk factors. METHODS/STUDY POPULATION: The University of Michigan Health and Retirement Study (HRS) is a longitudinal survey of a representative sample of Americans over the age of 50. Supported by the National Institute on Aging and the Social Security Administration, the HRS is designed to provide reliable data on the decisions, choices, and behaviors of people as they age and respond to changes in public policy, the economy, and health. The study obtains information every two years about income and wealth, health and use of health services, work and retirement, and family connections. Through its unique and in-depth interviews, the HRS provides an invaluable and growing body of multidisciplinary data that researchers can use to address important questions about the challenges and opportunities of aging. Because of its innovation and importance, the HRS has become the model and hub for a growing network of harmonized longitudinal aging studies around the world. Saliva was collected on half of the HRS sample each wave starting in 2006 and respondents were genotyped on the Illumina Human Omni2.5-Quad (Omni2.5) BeadChip at the NIH Center for Inherited Disease Research. We accessed survey results to evaluate prevalence of glaucoma in this dataset and performed a genome-wide association study (GWAS) adjusting for age, sex, and significant Principal Components and stratifying by self-reported race (White / Black). RESULTS/ANTICIPATED RESULTS: Of 8179 respondents passing quality filters, 6409 (78.40%) were white and 985 (12.05%) were black. Self-reported glaucoma prevalence was 7.85% and 16.34% in white and black respondents, respectively. White respondents had a mean age of 76.97 (SD 7.53) and were 57.25% female. Black respondents had a similar mean age of 74.96 (SD 7.27) and were 62.54% female. More than 87% of both groups were assessed in 2012. Preliminary GWAS analyses did not replicate known glaucoma loci and no variants attained genome-wide significance. A suggestive variant (p<1e-05) in the black population was within 10kb of a known locus, rs1196998. Future analyses will evaluate genetic association with combinations of glaucoma and comorbidities. DISCUSSION/SIGNIFICANCE OF IMPACT: Glaucoma risk is higher in minority groups than in whites, and the majority of reported genetic studies of glaucoma have been performed in individuals of European descent. It is imperative to better understand the role of genetics, environment, and health behavior in glaucoma risk. Further, understanding common mechanisms underlying diseases that co-occur with glaucoma could illuminate novel disease mechanisms that can be targeted for early intervention and/or treatment.

OBJECTIVES/GOALS: Our objective was to investigate racial differences in experiencing multiple categories of childhood trauma (CT) and the differential impact on alcohol use in individuals with alcohol use disorder (AUD). We hypothesized that there would be a differential additive effect of CT categories endorsed and drinking behaviors between racial groups. METHODS/STUDY POPULATION: Participants were recruited through the NIAAA screening protocol where they completed alcohol-related assessments including a 90-day Timeline Followback (TLFB) and the Alcohol Use Disorder Identification Test (AUDIT). Structured Clinical Interviews for DSM disorders were conducted to identify participants with lifetime alcohol dependence (DSM-IV) or AUD (DSM-5) (N = 1152). Participants self-identified as Black or White completed the Childhood Trauma Questionnaire (CTQ) which assesses 5 types of CT: emotional abuse, physical abuse, sexual abuse, physical neglect, and emotional neglect, and were classified into 3 CT groups: no trauma, 1 type of trauma, and 2+ types of trauma endorsed. RESULTS/ANTICIPATED RESULTS: For Black participants (N = 583), 21.6% experienced no trauma, 21% experienced 1 type, and 57.4% experienced 2 or more types, with the most common being physical abuse and emotional neglect. For White participants (N = 569), 32.1% experienced no trauma, 20.6% experienced 1 type, and 47.3% experienced 2 or more types, with the most common being emotional neglect and emotional abuse. There were significant associations between CT groups, TLFB, and AUDIT measures. For Black participants, AUDIT-Harm and AUDIT Total were significantly different across the 3 CT groups (all p values <0.05). For White participants, Heavy Drinking Days was significantly different across the 3 CT groups (p = 0.028), with trends for AUDIT-Harm (p = 0.061) and AUDIT-Dependence (p<0.065). DISCUSSION/SIGNIFICANCE OF IMPACT: In individuals with AUD, there were significant positive associations between the number of CT categories endorsed and alcohol use across race, suggesting a cumulative effect of CT on risky alcohol use. Future work includes exploring personality and behavioral mediators of the relationship between cumulative trauma load and drinking.

OBJECTIVES/SPECIFIC AIMS: Sudden death in the young (SDY) occurs in people between 1 and 40 years of age who do not have a known premortem risk factor for early death. Cardiovascular diseases account for the majority of causes of SDY. Sequencing of genes associated with congenital arrhythmia susceptibility and familial cardiomyopathy reveals pathogenic variants in 30% of postmortem cases (often called “molecular autopsy”). However, better data are needed to determine the prevalence of phenotype and genotype abnormalities in surviving relatives. METHODS/STUDY POPULATION: A retrospective cohort study was performed at a tertiary pediatric center including all subjects with a family history of SDY. Cases were identified using ICD-9 codes (798.1 or .9, V17.41, V17.49, V19.8, V61.07), search of cardiology databases, and by recursive identification of all family members of a subject. Phenotype data was independently reviewed by a pediatric cardiologist. Genotype results were available when obtained by the original treating physician. RESULTS/ANTICIPATED RESULTS: Cardiac evaluations were performed in 279 subjects from 175 families, of whom 117 subjects (42%) were first-degree relatives of the proband. Mean age of the subject at time of evaluation was 9 years (SD 5.9). Most probands were over 18 years at the time of SDY: 1–4 years of age (9%); 5–12 (5%); 13–17 (16%); 18–24 (18%); 25–40 (42%). A final diagnosis was determined in 55 families (20%), and a variant in a gene potentially causative of SDY was discovered in 20/55 (36%) of those families. Variants were classified as 50% pathogenic/likely pathogenic, 50% variants of unknown significance. Cardiac testing (ECG, echo, EST, signal averaged ECG, cardiac MRI, or EP study) was abnormal in 124/279 subjects (44%). Among those with abnormal studies, 57/124 (46%) were from a family where a final diagnosis could be determined (LQT 43%, HCM 21%, ARVC 4%, other cardiomyopathy 19%, WPW 5%, CPVT 2%). However, 67/279 of total subjects (24%) had at least 1 abnormal study and a final diagnosis was not determined in the family. DISCUSSION/SIGNIFICANCE OF IMPACT: An abnormal phenotype is common among relatives referred for cardiac evaluation after SDY. While testing identifies a family diagnosis in 20% of families, many patients have abnormal cardiac testing and no clear diagnosis can be made. An improved postmortem protocol for phenotype testing in relatives of a SDY victim and improved postmortem genetic testing may lead to a higher diagnosis rate and improved risk determination in surviving family members.

OBJECTIVES/GOALS: To truly improve health equity and accessibility, we must develop a diverse and inclusive workforce. The BUILD EXITO program developed as a collaboration between a network of undergraduate programs and a CTSA hub and now has become a sustainable resource that will outlive NIH funding. We will disseminate our successful model. METHODS/STUDY POPULATION: The BUILD EXITO program has completed 10 years of NIH funding, a partnership between OCTRI and Portland State University (PSU), to create a new model of research training for underrepresented and disadvantaged students. This model provides an opportunity to learn about clinical and translational research academic careers; participate in a research enhancement and professional development curriculum;have a long-term authentic research experience; and receive enhanced mentorship. BUILD EXITO includes PSU, and local and 3 US Pacific territory 2-year colleges. We have developed a sustainable plan that includes these core elements after NIH support for the program ends. We have tracked long-term student outcomes for entry into graduate programs and the research workforce. RESULTS/ANTICIPATED RESULTS: We will describe the experimental model and the network of university and community colleges in BUILD EXITO, including PSU, U of Alaska, and colleges in US territories of Guam, Northern Mariana Islands, and American Samoa. All these universities and colleges have high proportions of underrepresented and disadvantaged students. We will present data on characteristics of the >600 students who have participated in BUILD EXITO to demonstrate the diversity of the cohort. We will also describe 4-year degree completion, engagement in the research workforce, and entry into graduate or professional programs. We will show how this has positively affected faculty inclusion of students in research, institutional policies at the 2-year and 4-year programs, and how this model has become sustainable. DISCUSSION/SIGNIFICANCE: The BUILD EXITO program developed as a collaboration of the CTSA hub at OHSU and a highly diverse undergraduate programs. We have developed a successful model for training a diverse research workforce and will disseminate this sustainable model.

OBJECTIVES/GOALS: Our goal is three-fold: (1) to enhance protections for research participants in decentralized clinical trials (DCT) by (2) identifying the ethical and regulatory challenges posed by DCT and (3) considering possible solutions to the ethical and regulatory challenges of DCT. METHODS/STUDY POPULATION: A literature review was conducted to identify the ethical and regulatory challenges of DCT. The review showed that, with few exceptions, the publications on DCT have been written by IT experts, researchers or representatives of the pharma industry. There are hardly any independent or multidisciplinary analyses of DCT, e.g., by ethicists, medical sociologists or patients. This suggests that, currently, the potential advantages of digitized clinical research are still to be tested empirically and confirmed independently. Ethical analyses of DCT are particularly scant, which points to a gap in the current understanding of the ethical and regulatory implications of DCT and the issues they raise. Our research used the method of ethical analysis to examine the ethical challenges and to consider possible solutions. RESULTS/ANTICIPATED RESULTS: We identify the following ethical challenges of DCT: (1) challenges related to modifications of research protocols to allow for decentralized activities; (2) lack of expertise for ethical review and approval of digital tools; (3) different regulatory standards of privacy for clinical trials and for commercial digital tools, (4) risks to participants privacy and confidentiality involving both data and physical privacy; (5) the impact of the digital divide on DCT, (6) technology-related subject selection bias and marginalization of vulnerable groups, (7) imposing new burdens on research subjects and caregivers due to technology needs and smaller research teams, (8) restricted access to the study team, and (9) impact of digital technology on informed consent and participant understanding. DISCUSSION/SIGNIFICANCE: DCT became the primary form of clinical research during the COVID-19 pandemic. DCT rely on a wide range of internet-based tools for recruitment, informed consent, data collection, health monitoring, and communication with participants. The tools pose ethical and regulatory challenges, which should be addressed to ensure participant well-being.

Strategies are needed to ensure greater participation of underrepresented groups in diabetes research. We examined the impact of a remote study protocol on enrollment in diabetes research, specifically the Pre-NDPP clinical trial. Recruitment was conducted among 2807 diverse patients in a safety-net healthcare system. Results indicated three-fold greater odds of enrolling in remote versus in-person protocols (AOR 2.90; P < 0.001 [95% CI 2.29–3.67]). Priority populations with significantly higher enrollment included Latinx and Black individuals, Spanish speakers, and individuals who had Medicaid or were uninsured. A remote study design may promote overall recruitment into clinical trials, while effectively supporting enrollment of underrepresented groups.

The emphasis on team science in clinical and translational research increases the importance of collaborative biostatisticians (CBs) in healthcare. Adequate training and development of CBs ensure appropriate conduct of robust and meaningful research and, therefore, should be considered as a high-priority focus for biostatistics groups. Comprehensive training enhances clinical and translational research by facilitating more productive and efficient collaborations. While many graduate programs in Biostatistics and Epidemiology include training in research collaboration, it is often limited in scope and duration. Therefore, additional training is often required once a CB is hired into a full-time position. This article presents a comprehensive CB training strategy that can be adapted to any collaborative biostatistics group. This strategy follows a roadmap of the biostatistics collaboration process, which is also presented. A TIE approach (Teach the necessary skills, monitor the Implementation of these skills, and Evaluate the proficiency of these skills) was developed to support the adoption of key principles. The training strategy also incorporates a “train the trainer” approach to enable CBs who have successfully completed training to train new staff or faculty.

Translational research should examine racism and bias and improve health equity. We designed and implemented a course for the Master of Science in Clinical Investigation program of the Northwestern University Clinical and Translational Sciences Institute. We describe curriculum development, content, outcomes, and revisions involving 36 students in 2 years of “Anti-Racist Strategies for Clinical and Translational Science.” Ninety-six percent of students reported they would recommend the course. Many reported changes in research approaches based on course content. A course designed to teach anti-racist research design is feasible and has a positive short-term impact on learners.

OBJECTIVES/GOALS: Early life pain/stress impacts infants’ neurodevelopmental outcomes. Mitochondrial dysfunction may interface between infants’ stress and neurodevelopment. The study aims to investigate the associations between pain/stress, proteins associated with mitochondrial dysfunction, and neurobehavioral responses in preterm infants. METHODS/STUDY POPULATION: A prospective cohort study was conducted with 33 preterm infants enrolled between September 2017 and July 2022 at two affiliated NICUs in Hartford and Farmington, CT. Daily pain/stress experienced during NICU was documented. At 36-38 weeks post-menstrual age (PMA), neurobehavioral outcomes were evaluated using the NICU Network Neurobehavioral Scale (NNNS) and buccal swabs for Mass spectrometry-based proteomics analysis. Lasso statistical methods were conducted to study the association between protein abundance and infants’ NNNS summary scores. Multiple linear regression and Gene Ontology (GO) enrichment analyses were performed to examine how clinical characteristics and neurodevelopmental outcomes may be associated with protein levels and underlying molecular pathways. RESULTS/ANTICIPATED RESULTS: During NICU hospitalization, preterm premature rupture of membrane (PPROM) was negatively associated with neurobehavioral outcomes. The protein functions, including leptin receptor binding activity, glutathione disulfide oxidoreductase activity, and response to oxidative stress, lipid metabolism, phosphate, and proton transmembrane transporter activity, were negatively associated with neurobehavioral outcomes. In contrast, cytoskeletal regulation, epithelial barrier, and protection function were found to be positively associated with neurodevelopmental outcomes. In addition, mitochondrial dysfunction-related proteins (SPRR2A, PAIP1, S100A3, MT-CO2, PiC, GLRX, PHB2, and BNIPL-2, ABLIM1, UNC45A, Keratins, MUC1, and CYB5B) were found to be associated with neurobehavioral outcomes. DISCUSSION/SIGNIFICANCE: Mitochondrial dysfunction-related proteins were observed to be associated with early life pain/stress and neurodevelopmental outcomes in infants. Buccal proteins could be used to predict potential neurobehavioral outcomes. In addition, individualized skin integrity protection should be provided to preterm infants during their NICU stay.

OBJECTIVES/SPECIFIC AIMS: To assess the association between probable OSA and the sudden unexpected death in epilepsy (SUDEP-7) risk profiling index in monitored adult inpatients with epilepsy. METHODS/STUDY POPULATION: We analyzed 49 consecutive adults (>18 years) with refractory epilepsy admitted to our inpatient epilepsy monitoring unit. The SUDEP-7 inventory was performed for all subjects. Probable OSA was identified using overnight oximetry, the Sleep Apnea Sleep Disorder Questionnaire (SA-SDQ), and STOP-BANG inventory. RESULTS/ANTICIPATED RESULTS: Thirty-nine percent of participants screened positive for probable sleep apnea. Patients with high SUDEP-7 scores were more likely to have a positive screen for OSA. DISCUSSION/SIGNIFICANCE OF IMPACT: OSA is an independent risk factor for sudden cardiac death. OSA may be a hitherto unrecognized contributor to sudden death risk in epilepsy. Further studies determining the relationship between OSA, neural circulatory control and SUDEP are warranted.

OBJECTIVES/GOALS: Early pediatric intensive care unit (PICU) mobilization is safe and associated with improved outcomes. Nursing-specific mobility training is desired and improves mobilization compliance. Thus, our aim is to implement a nurse-targeted, simulation-based early mobility curriculum to determine if it increases the frequency of PICU mobilizations. METHODS/STUDY POPULATION: We will conduct a single center pre-post interventional study of an in situ nurse-targeted, simulation-based early mobility curriculum. We will prospectively evaluate mobilization events in 100 patients admitted during the pre-intervention phase (n=50) and the post-intervention phase (n=50). Inclusion criteria are children ages 1 day to 17 years old admitted to the PICU for ≥3 days. Exclusion criteria include specific mobility contraindications. PICU-wide deployment will be complete when >80% of nurses have participated in the curriculum. Demographic and clinical information will be obtained. Mobility data obtained will include number of nursing-led mobilizations, highest level of mobility achieved, and potential safety events. Data will be collected from the EMR and the nurse caring for the patient. RESULTS/ANTICIPATED RESULTS: The primary endpoint will be the change in the number of nursing-led mobilization events per patient day. The secondary effectiveness outcome is the highest level of mobility achieved by patients during mobilization events in a day. A final secondary end point will be safety events defined as unplanned extubations, medical device dislodgement, falls, and cardiac arrests. Descriptive statistics for continuous variables will be presented as the median and interquartile range and categorical variables will be expressed as percentages. The effect of the simulation curriculum on the clinical outcomes will be assessed using mixed-effects models. Due to the lack of normality in number of nurse-led mobilizations and highest level of mobility achieved, the analysis will be performed using log-normal models. DISCUSSION/SIGNIFICANCE: We hypothesize that we will demonstrate the crucial importance of hands-on nursing education to improve and increase early mobility of critically ill children

OBJECTIVES/GOALS: Mothers with cancer who have young children experience life disruptions when treatment procedures limit mother-child interactions. This study proposes the development of an intervention combining the Coaching approach with the Model of Playfulness to improve Quality of Life (QoL) and wellbeing of these patients and their young children. METHODS/STUDY POPULATION: This embedded mixed method study will be guided by the two initial phases of the ORBIT Model for the development of behavioral interventions for patients with chronic diseases. Participants will be mothers in the post-acute treatment stage of cancer (n = 6) and their children who are between 2 years and a half and 6 years, 11 months. Phase 1A, Definition, builds on qualitative data from a concurrent study exploring the experiences of mothers with cancer playing with their young children. As part of this phase, we will develop a play-based coaching intervention. In Phase 1B, Refinement, we will employ in-depth semi-structured interviews and standardized tools to evaluate acceptability of the intervention and preliminary outcomes. This will serve to further refine the intervention. RESULTS/ANTICIPATED RESULTS: Phase 1A will yield a plan for the intervention and data to enhance its initial implementation. Phase 1B will yield data, from the perspective of the mothers, about acceptability of the intervention procedures (e.g., delivery strategy, place for the intervention, time devoted, and outcome measures). This will enable modifications to the intervention. Additionally, Phase IB will yield preliminary data from specific QoL and wellbeing measures. For the mother, data about anxiety and depression symptoms, stress levels, and parental self-efficacy; for the child, emotional and behavioral indicators; for both: playfulness. DISCUSSION/SIGNIFICANCE OF IMPACT: This study entails the development of an intervention to enhance QoL and wellbeing of mothers with cancer and their children. Play moments as the centerpiece of the intervention, represent an innovative approach. Findings will guide the design of future feasibility studies to advance the development of this outcome driven intervention.

OBJECTIVES/SPECIFIC AIMS: The goals of our study are: (1) To test the hypothesis that the presence of any autoimmune cytopenia (ITP, AIHA, or ES) at time of cSLE diagnosis is associated with decreased risk of developing LN. (1b) To test the hypothesis that there is a lower risk of LN in patients with cSLE and any co-existing autoimmune cytopenia (ITP, AIHA, or ES) who had treatment with immunomodulatory or immunosuppressive therapy (intravenous immunoglobulin, corticosteroids, rituximab, or cyclophosphamide) before diagnosis of cSLE. (2) To test the hypothesis that in patients with cSLE who develop LN, the presence of any co-existing autoimmune cytopenia (ITP, AIHA, or ES) at time of cSLE diagnosis is associated with less severe LN. (3) To test the hypothesis that at the time of cSLE diagnosis, there is a lower incidence of double-stranded DNA (dsDNA) and a higher incidence of ribonucleoprotein autoantibodies in those with co-existing autoimmune cytopenias (ITP, AIHA, or ES). METHODS/STUDY POPULATION: This is a retrospective study of a large cohort of patients from the Emory Children’s Center, Children’s Healthcare of Atlanta (CHOA) satellite clinics and pediatric rheumatology inpatient services at any of the 3 CHOA hospitals (Egleston, Scottish Rite, and Hughes Spalding) with ICD 9 or ICD 10 codes corresponding to a diagnosis of SLE between January 1, 2000 and January 31, 2015. We will include patients diagnosed at age 2–16 years who meet at least 4 of the 11 American College of Rheumatology (ACR) classification criteria for SLE. We will consider these patients as having cSLE. We will exclude patients with less than 2 years of follow-up data and patients with a pre-existing diagnosis of cSLE who transferred care to our Emory/CHOA center. We will define time of diagnosis as time from initial evaluation for cSLE by a pediatric rheumatologist up to 28 days post cSLE diagnosis. We will define co-existing autoimmune cytopenia as preceding diagnosis of a primary autoimmune cytopenia or the presence of an autoimmune cytopenia at the time of initial evaluation for cSLE and up to 28 days post cSLE diagnosis. We will define AIHA as hemoglobin ≤10 g/dL with positive direct Coombs and/or reticulocytosis. We will define ITP as thrombocytopenia <100,000/mm3 and Evans syndrome as concurrent or sequential AIHA and ITP. We will define lupus nephritis (LN) as the presence of urine protein to creatinine ratio>0.5 in a patient with cSLE and/or biopsy demonstrating LN. IRB approval of the study protocol with waiver of informed consent has been obtained from the CHOA IRB. RESULTS/ANTICIPATED RESULTS: We have approximately 40 newly diagnosed cSLE patients annually; therefore, a study population of 400 patients with cSLE is possible. Therefore, assuming 50% of cSLE patients without autoimmune cytopenias have LN and 22% of cSLE patients with autoimmune cytopenias have LN, at an alpha of 0.05, we will have > 80% power to detect significant differences. We expect to show phenotypic differences in patients with co-existing autoimmune cytopenia and cSLE from other newly diagnosed cSLE patients. We expect that the presence of a co-existing autoimmune cytopenia and cSLE is associated with decreased risk of developing LN. We expect that there will be a decreased prevalence of LN in cSLE patients pretreated with immunosuppression further highlighting that earlier indicators of LN risk and early interventions are necessary. We expect to find decreased severity of LN in patients with a co-existing autoimmune cytopenia at time of cSLE diagnosis. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study will be conducted on one of the largest single-center cohorts of cSLE patients. We will determine whether pediatric patients with SLE and autoimmune cytopenias have a distinct clinical or serological phenotype and less severe disease. Our results will be significant in developing hypothesis for further retrospective or prospective multi-center or large database and immunological studies to understand the relationship of each individual autoimmune cytopenia to cSLE. It will provide the necessary background for further clinical and immunological studies to identify predictive biomarkers of cSLE severity.

OBJECTIVES/GOALS: The goal of the Translational Research Program (TRP) at the University of Toronto is to provide structured and adaptive competency-based training around the translation, mobilization, implementation, and commercialization of research for the current and future Canadian healthcare workforce. METHODS/STUDY POPULATION: Guided by the Toronto Translational Framework, the TRP is a two-year hybrid master’s degree program that integrates courses, case-studies, mentorship, and experiential learning to facilitate real-world student-led translational projects. Focusing on skills development and competency-based assessment, the curriculum emphasizes ongoing reflection, interprofessional collaboration, and multidisciplinary problem-solving using human-centered principles. Learners identify problems using contextual inquiry to define unmet needs and frame design requirements. Systematic ideation is used to generate, select, and validate promising concepts for further iterative prototyping and evaluation. RESULTS/ANTICIPATED RESULTS: Throughout the program, students demonstrate a range of collaborative skills and activities around developing, assessing, and implementing new health interventions. Learners apply the Toronto Translational Framework and refine their professional competencies during the final year of the program in a student-led Capstone project. The unconventional combination of a guided framework and a learner-driven curriculum has produced over 120 graduates in a variety of careers within government, industry, clinical settings, and start-ups. The program’s focus on problem-solving and lifelong learning is growing Canada’s translational workforce and advancing translational health science education. DISCUSSION/SIGNIFICANCE: The TRP addresses the need to educate healthcare professionals in Canada about translational research and accelerate the transformation of scientific discoveries into tangible interventions that benefit human health, improve clinical medicine, and enhance patient care.