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.

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.

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/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: 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/GOALS: Objectives: The study goal is to identify discriminating symptom characteristics of PAD versus non-ischemic conditions to improve recognition. Just as nausea, back, and jaw pain were once thought to be unrelated to myocardial infarction and coronary artery disease, patient-reported symptoms of PAD are frequently overlooked as being a sign of PAD. METHODS/STUDY POPULATION: Methods: Using a prospective de novo population-based cross-sectional design we will link symptom descriptors to PAD disease status using diagnostic testing in individuals who report lower extremity or buttock symptoms (n = 100). Symptom descriptors will be obtained via questionnaires and structured interviews will be completed pre and post physical function tests. Using near infrared spectroscopy, we will measure calf muscle tissue oxygenation levels to further differentiate ischemic vs. non-ischemic symptoms during exercise. The primary outcome will be the diagnostic accuracy of patient-reported symptoms which discriminate between PAD and non-PAD conditions. Positive predictive value and accuracy will be calculated using receiver operating characteristic (ROC) curve and chi-square analysis. RESULTS/ANTICIPATED RESULTS: Results: Previous studies from which symptom descriptors have been obtained were from patients with known PAD, of which 85-88% of participants were male.1–2 Seventy-six percent of this sample thus far is female. Nationally, PAD prevalence is 20% in those over the age of 70 years, however 58% of our study participants tested positive for PAD (via ankle brachial index test).3 The most commonly reported symptoms of PAD are “numbness” and “aching” vs. those without PAD most commonly reporting “cramping”. These results trend against our current understanding of PAD symptomatology, which is that cramping is the cardinal symptom of PAD.4 Preliminary analysis suggests that balance is a sensitive and specific predictor of PAD. Recruitment is ongoing, therefore results are preliminary. DISCUSSION/SIGNIFICANCE OF IMPACT: Translation of the results will impact primary care and community health. Improved disease detection will position providers to refer patients to exercise therapy before symptoms become disabling. Understanding the diagnostic accuracy of symptoms prepares us to apply novel techniques, such as statistical modeling, to systematically predict PAD.

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.

ABSTRACT IMPACT: Identifying differential COVID-19 progression across the disease continuum may help policymakers and service providers better identify or predict gaps in services and resources and develop precision strategies to support COVID-19 patients where the need is mostly needed. OBJECTIVES/GOALS: Single institution studies have documented COVID-19 disproportionally affected US racial and ethnic minority groups compared to Whites. However, few population-wide data studied severity and death in multiracial populations. We aim to examine the current disparity in the COVID-19 continuum, including hospitalizations, severity, and death. METHODS/STUDY POPULATION: Data on 67,094 laboratory documented COVID-19 cases nested from the state-wide ‘OneFlorida’ research consortium through August 3, 2020, were assessed to decide differences and disparities in COVID-19 outcomes. A COVID-19 outcome continuum outlining the proportions of cases transitioning from diagnosis to death was constructed (Figure 1). OneFlorida partners provide health care to more than 40% of Floridians in the nation’s third-largest and very diverse state. OneFlorida partners encompass hospitals, practice/clinic settings, and physicians, which provide care for 15 million patients across all of Florida’s 67 counties. It is part of the Patient-Centered Outcomes Research Institute (PCORI). RESULTS/ANTICIPATED RESULTS: Among cases, 25,443 (37.9%) were non-Hispanic Whites, 11,709 (17.5%) were non-Hispanic Blacks, and 16,119 (24.0%) were Hispanics. Among COVID-19 patients, Blacks and Hispanics had a higher frequency of emergency department (ED) visits (45.7% and 46.0%, respectively), whereas admission rates were higher in Blacks (15.6%) and Whites (15.9%) than in Hispanics (11.5%). Blacks had the highest rates of intubation (3.6%) and in-hospital deaths (2.7%) compared to Whites (2.5% and 2.3%, respectively) and Hispanics (1.3% and 1.4%, respectively), Figure 1. When rates were indexed to the state census data, Blacks had the worst rates across the disease continuum (infection to death). In comparison, Hispanics had higher rates of ED visits but lower rates of intubation and death, Table 1. DISCUSSION/SIGNIFICANCE OF FINDINGS: Outcomes continuum is a useful tool at an individual-level to assess care outcomes and at population-level as a framework to analyze the proportion of population with COVID-19 that progress to each successive disease stage. This will help policymakers to better identify gaps in services and develop precision strategies to support COVID-19 patients.

OBJECTIVES/GOALS: The goals of the proposed project are to 1) identify the critical components of trust required by Black Women to build a visible expression of trust within their reproductive health space, and 2) incorporate the elements of trust identified into a mindfulness-based communication tool, for reproductive health care providers. METHODS/STUDY POPULATION: We will be applying a mixed-methods approach inclusive of questionnaires and focus groups. Aim 1: Our study population consists of persons who identify as 18+ Black Women in Alachua County, Florida.Aim 2: Our Population within the reproductive health space (e.g., ob-gyn, midwives, nurse practitioners, etc…) at the University of Florida Shands Hospital. RESULTS/ANTICIPATED RESULTS: We anticipate that our results will fully engage with our Black Women in dialogues about key components of trust they want to experience and have within their reproductive space. This will inform the development of the mindfulness-based tool which will be incorporated with continuous insights with our Black Women. The proposed research project will contribute to the call for health equity. We aim to address this barrier by recognizing the agency of Black women to conceptualize trust on their terms, which we then would incorporate into applied trainings of reproductive health providers to establish trust. Health equity will take a considerable amount of social change at many levels and this study aims to better understand the process. DISCUSSION/SIGNIFICANCE: Structural racism and health disparities are linked with the disproportionate loss of Black women and associated negative birth outcomes. Our work will provide needed insights regarding mistrust in patient-provider relationships. Inform the development of a feasible tool challenging implicit bias in health provider spaces.

ABSTRACT IMPACT: This study will be the first to explore the relationship between preeclampsia and breast cancer risk using the largest cohort of Black women in the US, and it will guide future research and potentially inform clinical practice to reduce breast cancer disparities in this population. OBJECTIVES/GOALS: Black women are disproportionately impacted by preeclampsia. This disorder induces hormonal changes that may contribute to diseases such as breast cancer. However, there is a lack of clear data on the relationship between preeclampsia and breast cancer, and few previous studies included Black women. This study will work to fill this knowledge gap. METHODS/STUDY POPULATION: We prospectively assessed the association between preeclampsia during pregnancy and risk of breast cancer in 43,040 parous women in the Black Women’s Health Study, a nationwide cohort of Black women who were ages 21 -69 at enrollment in 1995. Through 2017, we confirmed 1,968 incident diagnoses of invasive breast cancer. Approximately 6% of parous women reported a diagnosis of preeclampsia; characteristics of the population at baseline are shown in Table 1. We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of breast cancer overall. We used age as the time scale and adjusted for breast cancer risk factors including parity, age at first birth, age at menarche, and body mass index (BMI) at age 18. RESULTS/ANTICIPATED RESULTS: : Compared to parous women without a history of preeclampsia, women with a history of preeclampsia in any pregnancy were not at an increased risk of breast cancer overall (HR 0.98; 95% CI 0.81, 1.18). These preliminary results suggest that history of preeclampsia is not an important risk factor for breast cancer overall in Black women. Our analyses are ongoing to evaluate whether the association may vary by estrogen receptor status or within subgroups of the population defined by age, menopausal status, BMI, and time since last pregnancy. DISCUSSION/SIGNIFICANCE OF FINDINGS: Findings from this study will provide unprecedented knowledge on the association between hypertensive diseases during pregnancy and incidence of breast cancer in the largest cohort of Black women in the U.S.

OBJECTIVES/GOALS: The Indiana CTSI Strategy Committee charged the Racial Justice and Health Equity Taskforce to identify priorities with short-term and long-term goals consistent with the I-CTSI mission. In addition, I-CTSI leadership asked for a general description of current state and the resources necessary to achieve the proposed goals. METHODS/STUDY POPULATION: The Taskforce applied an inclusive excellence model to the way we look at the I-CTSI structure, policies, and programs while performing an environmental scan within and across I-CTSI partner institutions. In order to reach equitable solutions and consensus, listening tours were held with partner stakeholders guided by the SOAR framework for strategic planning. This approach allowed us to assess current resources, needs, and gaps across the system, along with a baseline of measures currently monitored. Taskforce members openly discussed strengths and opportunities for enhancement of current programs and services. In addition, these conversations offered an opportunity to disrupt existing practices and through collective agency we identified priority areas that promote equity, diversity and inclusion. RESULTS/ANTICIPATED RESULTS: The Taskforce identified recurring themes in conversations with all partners, which led to the formation of three working groups that examined recruitment broadly: workforce, staffing, and research participation; professional development across all stakeholders from community members to I-CTSI staff; and data-centered metrics informing current state, decision-making, and accountability. Recommendations included these priorities, content, and implementation strategies. The Taskforce delivered a report to the I-CTSI leadership fostering the promotion of diversity, equity and inclusion along with a systematic collection of gender, race, and ethnicity data for individuals utilizing I-CTSI services and resources requiring additional metrics and tracking. DISCUSSION/SIGNIFICANCE: The pandemic shed light on the manner in which marginalized groups are rendered particularly vulnerable to death and disease by systemic and structural racism. The I-CTSI recognized that we cannot advance population health without attending to root causes of inequity and that includes our internal structure. We offer a potential model for other CTSAs.

OBJECTIVES/SPECIFIC AIMS: Pre-clinical and clinical observations have noted that increased aortic dilation is associated with male sex. Using an experimental model of severe, syndromic thoracic aortic aneurysms, we quantify aortic dilation and elastin stability in male Versus female mice. METHODS/STUDY POPULATION: Ascending aortas from male and female FBN1mgR/mgR mice and their wild type littermates were assessed every 4 weeks from 6 to 18 weeks of age by ultrasound. Measurements were taken luminal edge to luminal edge in diastole. At termination, aortas were harvested for RT-PCR analysis of extracellular matrix genes. Aortas were serially sectioned and elastin fragmentation was imaged by auto-fluorescence. RESULTS/ANTICIPATED RESULTS: At 12 weeks of age, differences of aortic diameters between male and female FBN1mgR/mgR mice were significantly different (2.24±0.43 vs. 1.57±0.22 mm; p=0.002), while there were no significant differences between sexes of wild type littermates (1.29±0.13 vs. 1.23±0.08 mm; p=0.71). Male sex was associated with increased elastin but not fibrillin-1 mRNA expression. Ascending aortas from male and female FBN1mgR/mgR mice significantly differed in the degree of elastin fragmentation (2.76 vs. 1.85 breaks/ 100 µm aorta; p=0.03). DISCUSSION/SIGNIFICANCE OF IMPACT: Sexual dimorphism of thoracic aortic dilation observed in human TAA patients was recapitulated in the fibirllin-1 hypomorphic mouse model of syndromic thoracic aortic aneurysms. Differences in this mouse model could be explained by the differential expression of extracellular matrix genes.

OBJECTIVES/SPECIFIC AIMS: This study aims to identify genetic biomarkers of GDM and facilitate the understanding of its molecular underpinnings. METHODS/STUDY POPULATION: We identified a cohort of mothers diagnosed with GDM in our longitudinal birth study by mining Electronic Health Records of participants utilizing PheCode map with ICD-9 and ICD-10 codes. We verified each case using ACOG’s GDM diagnosis criteria. RESULTS/ANTICIPATED RESULTS: Whole genome sequencing (WGS) data were available for 111 confirmed cases (out of 205) and 706 controls (out of 1,429) from different ancestries (412 EUR, 256 AMR, 56 EAS, 26 SAS and 18 AFR; 49 OTHER). SAS had the highest incidence of GDM at 38.46% and EUR had the lowest at 6.55%. We performed logistic regression using computed ancestry, age and BMI as covariates to determine if any variants are associated with GDM. The top variant (rs139014401) was found in an intron of DFFB gene, which is p53-bound and regulates DNA fragmentation during apoptosis. We will investigate the robustness of 49 identified variants and will separate the cohort by ancestry to detect population-specific differences in the top loci. DISCUSSION/SIGNIFICANCE OF IMPACT: Identification of molecular biomarkers in GDM across different ancestral backgrounds will address a gap in current GDM research. Findings may enhance screening and enable clinicians to identify those at risk for developing GDM earlier in the pregnancy. Early management of mothers at risk may lead to better health outcomes for mother and baby.