Objectives/Goals: Physical activity (PA) is a well-documented protective factor against many cardiovascular diseases. PA guidelines to reduce these risks and the impact of variability are unclear, and most studies only examine a 7-day activity window. This study aimed to examine factors related to variability in step counts in a 3-year study of adults aged ≥18 years. Methods/Study Population: Included were 6,525 participants from the Michigan Predictive Ability and Clinical Trajectories study, a prospective cohort of community-dwelling adults enrolled between 8/14/2018 and 12/19/2019 who received care at Michigan Medicine and were followed for 3 years. Data were collected from Apple Watches provided to participants via the HealthKit. This secondary analysis included those with ≥4 valid weeks of data (≥4 days with at least 8 hours of wear time). Season was defined as Spring (March 20–June 20), Summer (June 21–September 21), Fall (September 22–December 20), and Winter (December 21–March 19). GEE models against the outcome of variability, defined as weekly standard deviation of step counts, and the predictor of season were adjusted for age, sex, race/ethnicity, weekly average step count, diabetes, and body mass index. Results/Anticipated Results: The average (standard deviation (SD) step counts by season were 7101 (3434) in Spring, 7263 (3354) in Summer, 6863 (3236) in Fall, and 6555 (3211) in Winter. Compared to winter, there was statistically significantly higher variability in all other seasons (p Discussion/Significance of Impact: In this cohort of community-dwelling adults, we found significant differences in variability of physical activity by season, age, and BMI. Future work will examine how this variability impacts the risk of development of cardiovascular disease, incorporating the impact and recovery trajectories of COVID-19 and other acute respiratory infections.

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 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/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: 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.

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: Approximately 250,000 anterior cruciate ligament (ACL) tears occur annually in the USA. Symptoms generally improve after ACL reconstruction (ACLR), but 20% of athletes do not return to sport. It is not clear how biomechanical function and mental health impact return to activity, so the purpose of this study is to evaluate their effect on return to activity following ACLR. Methods/Study Population: Patients age 18 years and older who have undergone primary ACLR at a single institution who are one year out from their initial procedure will be recruited by email. Patients will be excluded if they had a concomitant or subsequent ligamentous knee injury in the follow-up period since their index procedure. Additionally, patients will be excluded if they do not have access to a mobile phone with video recording capability. The primary outcome will be joint angle kinematics and postural balance metrics derived from patient recorded mobile-phone videos while performing several provocative exercises (sit-to-stand, Star Excursion Balance test). Patients will also be given surveys assessing knee symptoms, psychological readiness for return to sport, mental health, athletic history, and current return to sport level. Results/Anticipated Results: We predict that psychological readiness for return to sport following ACL injury and biomechanical postural stability will each be independently associated with return to sport timing following ACLR. Additionally, we anticipate that psychological readiness, as measured by higher ACL-Return to Sport Index scores, will be more strongly associated with return to sport compared to biomechanical movement quality (better gross postural control on skeletal modeling). In other words, higher psychological readiness for return to sport will have a stronger independent association with return to sport level compared to biomechanical movement quality measures. Discussion/Significance of Impact: This study also aims to define return to sport in terms of biomechanics and psychological readiness in an athletically heterogenous population. Additionally, we will test the feasibility of patient-led, remote, mobile, marker less motion capture for assessment of biomechanical function and distribution of patient-reported outcome measures.

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: 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.

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/SPECIFIC AIMS: The prevalence of BPH, coupled with associated disability ranging from quality of life impairments to hospitalization, has spurred decades of research into its pathophysiology, diagnosis, treatment, and outcomes. For these reasons, we conducted a study to characterize the current landscape of BPH literature, including the most commonly cited articles impacting the field. METHODS/STUDY POPULATION: We used the Web of ScienceTM databases to conduct a bibliometric analysis of the top 100 leading BPH articles. Bibliometric analyses are quantitative approaches examining the impact of academic literature. We used the following search terms: ‘benign prostatic hyperplasia’ and ‘benign prostatic enlargement.’ We identified and characterized the 100 most-cited BPH articles including their citations, journal, author, year, and country through September 2018. RESULTS/ANTICIPATED RESULTS: The top 100 BPH articles were published between 1978 and 2012. The number of citations ranged from 143 to 2,158 across 26 different journals, including 9 urology-specific journals. The Journal of Urology (5-year impact factor: 4.91) was the most published journal with 26 articles, followed by European Urology (5-year impact factor: 15.66) with 16, and Urology (5-year impact factor: 2.39) with 13. The oldest 10 articles in the top 100 mainly focused on BPH etiology/pathogenesis, while the newest 10 articles mainly focused on medical treatment. The 1990’s was the most productive decade accounting for nearly half of the top 100 articles (n=46). Eight authors had two or more first author publications, and 8 institutions had five or more publications in the top 100. Thirteen different countries were represented in the top 100 articles, with the US (n = 64), Italy (n=7), and Germany (n=5) being the most common. The articles were published in the following Web of Science Categories: Urology & Nephrology (n=68), Medicine, General & Internal (n=15), and Endocrinology & Metabolism (n=7). DISCUSSION/SIGNIFICANCE OF IMPACT: This study represents the first bibliometric analysis of the leading 100 BPH articles impacting the academic literature. The literature focus has evolved from BPH pathogenesis/etiology to treatment, and was primarily published in 3 specialty journals. Our findings highlight the most impactful BPH literature, and may be used to guide research and funding priorities for this increasingly common condition.

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.

OBJECTIVES/SPECIFIC AIMS: The purpose of this study is to understand factors that are associated with identifying which eligible pregnant women in Baltimore City accept a referral for HV services. Taking into account demographic and obstetrical variables, we will examine the extent to which 13 medical and 14 psychosocial risk factors differentiate pregnant women who (1) accepted a HV referral, (2) could not be located, or (3) refused a HV referral. METHODS/STUDY POPULATION: In this observational study, we will use secondary data on 8172 pregnant women collected by Health Care Access Maryland (HCAM) between 2014 and 2016. HCAM is the single point of entry for all pregnant women in Baltimore City into HV. HV eligibility includes being a pregnant woman, residing in Baltimore City, being uninsured or receiving Medicaid, and being identified by a prenatal care provider who completed an assessment profile of the woman’s medical and psychosocial risk (prenatal risk assessment). The outcome variable, HV engagement status (ie, accepted referral, could not be located, refused referral), will be based on HCAM discharge codes. Medical risk factors include BMI, hypertension, anemia, asthma, sickle cell, diabetes, vaginal bleeding, genetic risk, sexually transmitted disease, last dental visit >1 year ago, and taking prescription medications. Psychosocial risk factors include current pregnancy unintended; <1 year since last delivery; late entry to prenatal care (>20 wk gestation); mental, physical, or developmental disability; history of abuse or violence within past 6 months; tobacco use; alcohol use; illegal substance use within the past 6 months; resides in home built before 1978; homelessness; lack of social/emotional support; exposure to long-term stress; lack of transportation; and history of depression or mental illness. All risk factor variables are categorical (yes/no). Control variables will include demographics (eg, age, race, ethnicity, marital status, educational level) and OB history (eg, history of preterm labor, history of fetal or infant death). We will conduct descriptive statistics to characterize the sample and look for interrelatedness among the risk factors. Where there is a high level of inter-relatedness we will consider combining or omitting variables to reduce redundancy. We will use multinomial regression to examine which medical and psychological factors are associated with referral category. RESULTS/ANTICIPATED RESULTS: We hypothesize that (a) women with more medical risk factors will be more likely to accept a referral for HV services, (b) women with more psychosocial risk factors will be more likely to refuse HV or not be located, and (c) certain risk factors, such as depression/mental illness, history of abuse/violence, illegal substance use, homelessness, and exposure to long-term stress will be the strongest predictors of not accepting HV referral and/or not being located. DISCUSSION/SIGNIFICANCE OF IMPACT: The translation of effective randomized control trials (RCTs) to successful implementation in community-based programs can be challenging. Community-based programs serving low-income communities typically lack the same resources available to recruit and retain participants in RCTs. And, exclusion criteria applied in RCTs are often not applied in real world implementation which can open program to participants with more complex social and medical characteristics. Findings from this study will inform the translation of evidence-based HV programs into real world settings through an enhanced understanding of the characteristics of women who are not engaged by HV programs. This will inform development of improved outreach methods that may more effectively engage at-risk women for prenatal HV services.

OBJECTIVES/GOALS: Underrepresented (UR) biomedical researchers leave research positions at a disproportionate rate. We aim to identify factors associated with confidence in career progression and intent to continue clinical research training in UR post-doctoral fellows and early-career faculty. METHODS/STUDY POPULATION: Building Up is a cluster-randomized trial at 25 academic institutions. In September-October 2020, 224 participants from the Building Up study completed the pre-intervention assessment, which included questions on demographics, science identity, mentoring competency, confidence in career progression, and intent to continue clinical research training. Using multinomial logistic regression controlling for gender and race/ethnicity, we identified factors associated with confidence in career progression, and intent to continue clinical research training. Statistically significant findings are reported. RESULTS/ANTICIPATED RESULTS: The cohort (N=219) is 80% female, 33% non-Hispanic Black, and 34% Hispanic. Having mentors that address diversity was associated with belief that career advancement is as open to them as anyone else (OR=1.7) and confidence in ability to overcome professional barriers (OR=1.4). Higher science identity (OR=4.0) and having mentors who foster independence (OR=1.7) were associated with confidence in ability to progress in career. Higher science identity was also associated with confidence in ability to overcome professional barriers (OR=2.2) and intent to continue studying biomedical sciences (OR=3.4). Being faculty (OR=3.8), higher science identity (OR=3.8), and having mentors that align expectations (OR=2.3) were associated with intent to continue clinical research training. DISCUSSION/SIGNIFICANCE: These findings suggest that science identity and mentoring play key roles in confidence in career progression and intent to continue clinical research training. These factors are important to consider in retaining UR early-career biomedical researchers.

OBJECTIVES/SPECIFIC AIMS: The goal of the study is to evaluate the prognostic importance and accuracies of a biomarker, human epidermal receptor 2 (Her2), for breast cancer recurrence in a cohort study, namely Lifetime after Cancer Epidemiology (LACE). We specifically interested in the role that Her2 plays in prognosis of breast tumor recurrence for women after a previously diagnosed and treated breast cancer. METHODS/STUDY POPULATION: The study cohort includes 2267 women enrolled in LACE who had previously diagnosed breast cancer. Patients were enrolled from each of the 2 LACE registries in California and Utah. The main endpoint of the study is the right-censored time to breast cancer recurrence. Patients’ enrollments were, on average, 2 years after diagnosis of the first breast cancer. The patients’ characteristics at baseline were obtained through self-administered questionnaires. Cox proportional hazard model with time-varying covariates was used to relate the Her2 status (Her2+ and Her2−) to the primary end point (time to breast cancer recurrence). Hazard ratios (HRs) and their 95% confidence interval comparing Her2+ and Her2− arms were estimated. Time-dependent sensitivity and specificity were used to investigate the performance of using Her2 for classifying patients into high and low risk (Her2 + is classified as hi risk and Her− as low risk) of future breast cancer recurrence at time points after baseline. The time-dependent sensitivity was calculated as the proportion of patients being classified as high risk of recurrence who had breast cancer recurrence before a series of pre-specified time points after baseline, and the time-dependent specificity was calculated as the proportion of subjects being classified as low risk of recurrence who did not have breast cancer recurrence at the same time points. RESULTS/ANTICIPATED RESULTS: The average patient follow-up time was 9.8 years, and 18% of the women got positive Her2 test results at baseline. Among 2267 patients in the study cohort, 2031 had records on their Her2 status, among whom 326 (16.1%) patients were Her2+ and 1705 (83.9%) were Her2−. The mean tumor size among the 2031 patient was 2.10±1.22 cm. A majority of the patients (78.9%) were White. Over one-half of these patients were neither current nor past smokers. Only 3% of the patient had a baseline stage IIIA or higher. About 49% of the patients underwent a mastectomy. Radiation therapy was used by 63.5% of the patients, and Tamoxifen users accounted for 78% of the study cohort. We found a statistically significant association between Her2 and breast cancer recurrence (HR=1.33, log-ran p-value=0.006). However, the HRs of breast cancer recurrence comparing Her2+ and Her2− patients decreased over time. We also investigate the effect of combined Her2, estrogen (ER), and progesterone (PR) on breast cancer recurrence and found that patients with Her2+/ER+/PR− had the highest risk of breast cancer recurrence. The hazard of recurrence for this group of patients was 85% higher than patients with Her2−/ER+/PR+. We also investigate the prognostic accuracies of Her2 in terms of time-dependent sensitivity and specificity. Using Her2 as the prognostic biomarker resulted in a specificity consistently over 80% from baseline up until 15 years post-baseline. The time-dependent sensitivity of Her2 was above 90% between baseline and 1.5 years. Then, the sensitivity dropped gradually to 40% from 1.5 years to 3 years post-baseline. For prognosis of breast cancer over 3 years from baseline, the sensitivity was between 30% and 40%. DISCUSSION/SIGNIFICANCE OF IMPACT: As a single biomarker and risk factor, Her2 was statistically significantly associated with the recurrence of breast cancer among patients in the LACE cohort. A composite biomarker by combining Her2, ER, and PR status was also significantly associated with the breast cancer recurrence. However, the HRs of breast cancer recurrence comparing Her2+ and Her2− patients decreased over time, implying that the Her2 status had a high impact on early recurrent breast tumors. Single biomarkers, usually, have very limited ability for prognosis of future events. However, we found that using HER2 as a single biomarker can give a relatively larger specificity consistently over 15 years of the study period. The sensitivity of Her2 is high for detecting early breast cancer recurrence. However, after 2.5 years from baseline, using Her2 for breast cancer recurrence detection is not reliable. Due to the relatively high accuracies of using Her2 status for prognosis of breast cancer recurrence, we conclude that Her2 should be considered in clinical studies related to prognosis of breast cancer recurrence. Future studies will investigate if prognostic accuracies can be improved by combining Her2 with baseline clinical risk factors such as age, tumor size and lymph nodes. In conclusion, our study has the clinical impact on prognosis (or early detection) of breast cancer recurrence among women with previously diagnosed and treated breast cancers.