OBJECTIVES/GOALS: This investigation aimed to develop and validate a subject-specific finite element analysis (FEA) model with subject-specific mechanical loads during walking and to use this method to compare mechanical stresses between transfemoral and transtibial osseointegrated (OI) implants. METHODS/STUDY POPULATION: One patient with a unilateral transtibial OI prosthesis and one with a unilateral transfemoral OI prosthesis participated in motion analysis to collect kinematics and ground reaction forces during overground walking. Subject-specific musculoskeletal models were created, and static optimization was used to estimate muscle and joint reaction forces throughout walking. 3D FEA models of the tibia, femur, and implants were created using ScanIP and exported into ABAQUS CAE. Muscle forces were applied at corresponding origin/insertion locations, determined from the musculoskeletal models [7]. Fixed boundary conditions were applied at proximal joint centers, and bone stresses throughout gait were calculated. OpenSim and FEA derived estimates of joint reaction forces were compared for validation. RESULTS/ANTICIPATED RESULTS: A maximum stress of 65.53 MPa and 60.70 MPa was observed at the bone-implant interface for the transtibial and transfemoral patients (respectively) in the late stance phase of the walking task, corresponding to terminal stance and heel off. Averaged root mean squared errors of the walking task (in the anterior-posterior, inferior-superior, and medial-lateral directions, respectively) for the transtibial and transfemoral patients were (124, 152, 80) N, (71, 80, 30) N, and (190, 62, 30) N, respectively. DISCUSSION/SIGNIFICANCE: The purpose of the above study was to develop a methodology for determining subject-specific mechanical loads during walking using finite element analysis and compare mechanical stresses in patients with transfemoral and transtibial OI. Similar stresses between the two implant types were found.

OBJECTIVES/GOALS: To apply implementation science strategies to evaluate the impact of the 2016 Pennsylvania (PA) Medicaid payment policy change on hospital-level access to immediate postpartum long-acting reversible contraception (IPP LARC), an evidence-based strategy to increase contraceptive access; to identify differences by rurality and academic status. METHODS/STUDY POPULATION: We conducted a web-based, IRB-exempt survey of Labor and Delivery (L&D) leaders at all PA hospitals in Summer-Fall 2022, assessing hospital characteristics, contraceptive practices, and facilitators/barriers to IPP LARC implementation, using concepts from health services studies of small subsets of implementing hospitals; we translate these concepts into policy evaluation by sampling the complete population of Pennsylvania hospitals with active L&D units. L&D hospitals were characterized as sustainers if they implemented by 2019 and continued to provide IPP LARC, as implementers if they implemented IPP LARC in 2020-22, and non-implementers if they had not started the process. We use the Center for Rural Pennsylvania definition of rural: counties with RESULTS/ANTICIPATED RESULTS: We collected data from 48/74 (64.9%) hospitals with L&D units. Hospitals were heterogenous with 18/48 (37.5%) in rural counties and 15/48 (31.3%) identifying as academic. A minority of hospitals provide IPP LARC, with 17/48 (35.4%) offering implants and 16/48 (33.3%) offering intrauterine devices (IUD) immediately postpartum. Before the PA Medicaid payment policy change, few offered implants [4/48 (8.3%)] or IUDs [1/48 (2.1%)]. Non-rural hospitals implemented IPP LARC more often and on an earlier timeline than rural hospitals: [7/30 (23.3%) v 3/18 (16.7%)] sustainers, [5/30 (16.6%) v 2/18 (11.1%)] implementers. Common facilitators include clinical champions, meeting patient needs, and adequate knowledge. Planned analyses include implementation barriers, and impact of external implementation support. DISCUSSION/SIGNIFICANCE: Despite unmet need in rural populations for evidence-based contraception, rural hospitals were less likely to implement IPP LARC. Implementation support should be designed to meet the needs of rural hospitals. Implementation science methods can be translated to evaluate the impact of healthcare policy on access to care.

OBJECTIVES/GOALS: Increases in anxiety and depression during adolescence may be related to increased biological reactivity to negative social feedback (i.e., social threat sensitivity). Our goal was to identify biomarkers of social threat sensitivity, which may provide unique etiological insight to inform early detection and intervention efforts. METHODS/STUDY POPULATION: Adolescents aged 12-14 (N=84; 55% female; 80% White; 69% annual family income <$70,000) were recruited. Youth viewed a series of happy, neutral, and angry faces while eye-tracking and electroencephalogram (EEG) data were recorded to capture cognitive and neural markers of sensitivity to social threat (i.e., an angry face). Fixation time and time to disengage from angry faces were derived from eye-tracking and event-related potentials were derived from EEG, which index rapid attention capture (P1), attention selection and discrimination (N170), and cognitive control (N2). Adolescents also completed a social stress task and provided salivary cortisol samples to assess endocrine reactivity. Social anxiety and depressive symptoms were self-reported concurrently and one year later. RESULTS/ANTICIPATED RESULTS: Latency to disengage from threatening faces was associated with lower N2 amplitudes (indexing poor cognitive control; r= -.24, p = .03) and higher concurrent social anxiety (r = .28, p = .01). Higher N170 amplitudes, reflecting attentional selection and discrimination in favor of threatening faces, predicted increases in depressive symptoms one year later (b= .88, p = .02). No other neurophysiological measures were associated with each other or with concurrent or prospective symptomatology. DISCUSSION/SIGNIFICANCE: Eye-tracking and EEG measures indexing difficulty disengaging from social threat and poor cognitive control may be biomarkers of social anxiety, which could be utilized as novel intervention targets. High N170 amplitudes to social threat, derived from EEG, may have clinical utility as a susceptibility/risk biomarker for depressive symptoms.

OBJECTIVES/GOALS: Cancer survivors are at increased risk for type 2 diabetes mellitus.It is not clear if diabetes susceptibility is due to shared risk factors for cancer and diabetes, such as obesity, or if it is directly related to cancer and its treatment. We investigated the association between malignancy and insulin resistance, a major risk factor for diabetes. METHODS/STUDY POPULATION: 20 adult patients with treated hematological malignancies and 21 controls without cancer were included in the study. Individuals with pre-existing diabetes were excluded. All patients underwent a 2-hour 75-gram oral glucose tolerance test (OGTT). Hyperinsulinemic-euglycemic clamps were performed to measure the steady-state glucose infusion rate (M-value) as an indicator of whole-body glucose utilization during insulin stimulation. Insulin sensitivity index was calculated by dividing M-value over the steady-state plasma insulin (M/I). RESULTS/ANTICIPATED RESULTS: Fasting or postprandial plasma glucose levels during the OGTT did not differ significantly between malignancy patients and controls (Table 2). Difference in the insulin-stimulated glucose utilization (M-value) was not statistically significant among cancer patients and controls (median, 7.2 [IQR, 6.2-10.4] vs. 7.3 [IQR, 5.5-8.9] mg/kg/min; P = 0.261). M/I index was significantly higher in malignancy patients compared to controls (median, 42.4 mg/kg/min/(µU/ml) [IQR, 33.9-67.2] vs. 23.4 mg/kg/min/(µU/ml) [IQR, 12.9-29.2], P <0.001), however insulin clearance was also lower in the controls. In multivariate analysis, only BMI was significantly associated with M-value (β = −0.2 (95% CI −0.4, −0.1), P = 0.004), and M/I (β = −2 (95% CI −3.4, −0.5), P = 0.009). DISCUSSION/SIGNIFICANCE OF IMPACT: Our data suggest that the major contributor to diabetes development after diagnosis of cancer in adults is obesity-induced insulin resistance, not malignancy related factors. These findings emphasize the importance of obesity management in long-term survival of cancer patients, as diabetes is a risk factor for mortality in this patient population.

OBJECTIVES/GOALS: Prematurity and perinatal brain injury are known risk factors for strabismus. In this study, we sought to understand the link between neonatal neuroimaging measures in very preterm infants and the emergence of strabismus later in life. Study findings may inform if neonatal brain MRI could serve as a prognostic tool for this visual disorder. METHODS/STUDY POPULATION: This study draws from a longitudinal cohort of very preterm infants (VPT, < 30 weeks gestation, range 23 – 29 weeks) who underwent an MRI scan at 36 to 43 weeks postmenstrual age (PMA). Anatomic and diffusion MRI data were collected for each child . A subset of thirty-three patients in this cohort had records of an eye exam, which were reviewed for a history of strabismus. Patients with MRI scans demonstrating cystic periventricular leukomalacia or grade III/IV intraventricular hemorrhage were classified as having brain injury. Clinical variables with a known association to strabismus or diffusion metrics were included in a multivariable logistic regression model. Diffusion tractography metrics were screened for association with strabismus on univariable analysis prior to inclusion in the regression model. RESULTS/ANTICIPATED RESULTS: A total of 17/33 (51.5%) patients developed strabismus. A logistic regression model including gestational age, PMA at MRI, retinopathy of prematurity (ROP) stage, brain injury, and fractional anisotropy of the right optic radiation was significant at the .001 level according to the chi-square statistic. The model predicted 88% of responses correctly. Each decrease of 0.01 in the fractional anisotropy of the right optic radiation increased the odds of strabismus by a factor of 1.5 (95% CI 1.03 – 2.06; p = .03). Patients with brain injury had 15.8 times higher odds of strabismus (95% CI 1.1 – 216.5; p = .04). Gestational age (OR 1.7; 95% CI 0.9 – 3.3; p = .1) and stage of ROP (OR 0.6; 95% CI 0.2 – 2.0; p = .4) were not significant predictors of strabismus in the multivariable model. DISCUSSION/SIGNIFICANCE: Our findings suggest that strabismus in VPT patients may be related to specific changes in brain structure in the neonatal period. The identified association between neonatal optic radiation microstructure and strabismus supports the possibility of using brain MRI in very preterm infants to prognosticate visual and ocular morbidity.

OBJECTIVES/GOALS: To determine whether cardioprotective effects observed in individuals taking dietary supplementation with eicosapentaenoic acid (EPA), an ω-3 polyunsaturated fatty acid, are realized by altering platelet function, and if these effects are mediated through the 12-lipoxygenase derived metabolite, 12-hydroxyeicosapentaenoic acid (12-HEPE). METHODS/STUDY POPULATION: Washed platelets or platelet rich plasma from healthy human donors were treated with EPA and 12-HEPE to assess their ability to inhibit platelet activation. Platelets were stimulated with agonists targeting different steps of the hemostatic response to vascular injury. Platelet aggregation, dense granule secretion, surface expression of integrin αIIbβ3 and P-selectin, and clot retraction were analyzed. To assess signaling through Gαs-GPCRs and protein kinase A activity, phosphorylation of vasodilator-stimulated phosphoprotein (VASP) was examined via western blot following treatment with EPA or 12-HEPE. RESULTS/ANTICIPATED RESULTS: EPA and 12-HEPE dose-dependently inhibit both collagen and thrombin-induced platelet aggregation. Furthermore, 12-HEPE more potently attenuates dense granule secretion and surface expression of platelet activation markers, integrin αIIbβ3 and P-selectin, in comparison to EPA. Plasma treated with EPA delayed thrombin-induced clot retraction, while 12-HEPE had no effect. Additionally, treatment with 12-HEPE increases phosphorylation of VASP, suggesting it could signal through the activation of the eicosanoid Gαs-GPCRs. DISCUSSION/SIGNIFICANCE: Here, we show for the first time that EPA directly inhibits platelet activation through its 12-LOX metabolite, 12-HEPE. These findings provide further insight into the mechanisms underlying the cardioprotective effects of EPA. A better understanding of current PUFA supplementations can inform treatment and prevention of cardiovascular diseases.

ABSTRACT IMPACT: It is our hope that a better understanding of the relationship between genetic variants that influence heart failure precursor traits will not only inform clinical care, but enable better assessment of inherited risk and will identify new biological targets for drug development. OBJECTIVES/GOALS: In this project, using a large-scale human genomic dataset with extensive phenotype data available, we intend to interrogate the known MTSS1 variants that have been associated with heart failure (HF) in previous GWAS studies in order to understand the directionality and mechanisms of their effects. METHODS/STUDY POPULATION: Data was obtained from the UK Biobank, a large prospective cohort of ˜500,000 patients across the United Kingdom with extensive phenotype data, including ˜50,000 patients with cardiac MRI and ˜200,000 with whole exome sequencing. We test for associations between genetic variants at the MTSS1 locus and HF precursor traits using logistic regression or linear regression, adjusting for age, gender, and principal components (PCs) of ancestry. For rare variant analyses we ‘bin’ rare variants (MAF < 0.01) using the software tool BioBin to aggregate low frequency genetic variants into single genetic units. RESULTS/ANTICIPATED RESULTS: Preliminary data have shown that variants in the known MTSS1 enhancer region which reduce MTSS1 expression are associated with smaller, more contractile hearts. We anticipate that common variants known to reduce enhancer activity will attenuate heart failure precursor traits, will be associated with a reduced risk clinical heart failure, and will favorably impact clinical outcomes once HF is established. We also anticipate that rare exonic variants predicted to impair MTSS1 function will attenuate heart failure precursor traits. DISCUSSION/SIGNIFICANCE OF FINDINGS: Through this work, we intend to take advantage of multiple novel approaches to better understand a complex disease process, identify a new potential therapeutic target (namely one that targets cardiac function), and to determine which patient subgroups will benefit from this our therapeutic interventions and why.

OBJECTIVES/SPECIFIC AIMS: The purpose of the current study is to determine predictors of linkage-to-care (LTC) outcomes among patients screened for hepatitis C virus (HCV) infection in the emergency department (ED). The study is one of the first to report the impact of factors influencing medical eligibility for HCV treatment. By establishing predictors of linkage outcomes, we hope to characterize patients at highest risk of being lost to follow-up. This information can be used to guide the development of targeted interventions and optimize linkage efforts at institutions with similar programs. METHODS/STUDY POPULATION: In 2013, we implemented an opt-out HCV screening program targeting baby boomers presenting to the ED. The screening program was expanded in 2015, and all patients who presented to the ED (an academic ED with 73,000 annual visits) between 2015 and 2018 were offered an HCV antibody test. Confirmatory RNA tests were ordered for all patients with a positive screening test, and those with confirmed infection were contacted (when possible) by a linkage coordinator, who sought to facilitate linkage to outpatient care. Patients were followed until they had been successfully linked to care or were lost to follow-up; successful linkage was defined as a patient attending a scheduled HCV clinic visit. Linkage outcomes (linked vs. not linked) among confirmed cases were analyzed based on previously described LTC barriers, sociodemographic factors, and factors influencing HCV treatment eligibility. Binary multiple logistic regression was used to model the relationship between predictors and LTC outcomes. RESULTS/ANTICIPATED RESULTS: Between August 2015 and June 2018, 48,947 patients were screened for HCV, yielding 4,026 positive results. HCV infection was confirmed in 1,798 patients, 1,651 of whom were eligible for the current study. By July 2018, 884 eligible patients (53.5%) had been successfully linked to care. Odds of linkage failure were decreased among patients with known linkage barriers including mental health disorders (adjusted odds ratio [aOR], 0.28; 95% confidence interval [CI], 0.21-0.37), active substance abuse (aOR, 0.65; 95% CI, 0.47-0.91), and ‘competing’ medical comorbidities (aOR, 0.31; 95% CI, 0.21-0.47); however, odds of linkage failure were increased in the presence of medical comorbidities leading to ineligibility for HCV treatment (aOR, 21.71; 95% CI, 7.02-67.13). Decreased odds of linkage failure were also found among patients belonging to the baby boomer population (aOR, 0.64; 95% CI, 0.46-0.91) and individuals with HBV co-infection (aOR, 0.36; 95% CI, 0.14-0.94). Finally, odds of linkage failure were increased among patients without health insurance (aOR, 1.952; 95% CI, 1.01-3.79) and with public health insurance (aOR, 2.140; 95% CI, 1.08-4.24). While African-American patients exhibited decreased odds of linkage failure in bivariate analyses, this association was not significant in the multivariate analysis. Variables ultimately found not to be predictive of linkage outcome included race, ethnicity, gender, homelessness, and incarceration. DISCUSSION/SIGNIFICANCE OF IMPACT: In contrast with current trends in the literature, our analysis found that patients with any of three well-described linkage barriers (mental health disorder, active substance abuse, and ‘competing’ comorbidities) exhibited decreased odds of linkage failure. It is possible that knowledge of these barriers by linkage personnel led to increased persistence of efforts for such patients, resulting in improved linkage among patients with these barriers. However, another possibility is that individuals with factors such as a mental health disorder or medical comorbidity were more likely to experience a clinical encounter, during which discussions about HCV treatment could take place. It is also possible that other contributing factors were unaccounted for by our analysis, such as internal programmatic issues, patient education and income levels, marital status, or other ‘destabilizing’ factors that would reduce a patient’s likelihood of being contacted by a linkage coordinator. While patients with general medical comorbidities were less likely to experience linkage failure, patients who were ineligible for HCV treatment due to a medical comorbidity were significantly more likely to experience linkage failure. While this finding is intuitive, it is nonetheless troubling, as we would expect patients with severe medical comorbidities to benefit greatly from health counseling, mental health services, substance abuse treatment, or other resources available through linkage. As a result of this finding, we intend to adapt our approach to medically ineligible patients, emphasizing the availability and potential usefulness of such resources. It is unsurprising that uninsured and publicly insured patients were less likely to be successfully linked to care, as HCV treatment continues to be associated with significant financial costs for such patients. However, it is also possible that confounding factors such as education and income level, which were not included in our analysis, would be more predictive of patients’ ability or willingness to undergo HCV treatment. More research is needed to improve linkage-to-care for patients with HCV. In the near future, we intend to conduct an internal evaluation, as well as a positive deviance analysis of other LTC programs, to determine additional ways to improve linkage outcomes for all patients screened for HCV in the ED.

OBJECTIVES/GOALS: Non-Typhoidal Salmonella causes over 95 million infections globally each year, and no effective vaccine exists to combat infections in humans. The goal of this study is to determine the immune protection provided by a novel extracellular vesicle (EV)-based vaccine generated using lab-strain Salmonella against wastewater-derived Salmonella. METHODS/STUDY POPULATION: We isolated Non-Typhoidal Salmonella (NTS) from raw influent wastewater samples collected from two wastewater reclamation facilities (WRF) in Gainesville, FL. Whole genome sequencing was performed on each isolate and compared to sequences of clinically-derived isolates in FL during our study period to identify a clinical and subclinical isolate for assessing EV based vaccine protection. Mouse serum and stool samples were collected from a cohort of EV-vaccinated mice. Surrogates of protection against Salmonella used anti-Salmonella IgA in the feces of these mice, and anti-Salmonella IgG in serum of the mice, by using ELISAs coated with whole cell lysate collected from the two wastewater-derived isolates. RESULTS/ANTICIPATED RESULTS: We have previously shown that an EV vaccine provides protection against Salmonella enterica Serovar Typhimurium, the serovar used in the generation of the EV vaccine. We anticipate that the EV vaccine generates additional protection against the community-acquired strains, which will be characterized by increases in fecal IgA and serum IgG against two community Salmonella isolates that is similar to responses against the serovar used to generate the EV vaccine (Typhimurium). DISCUSSION/SIGNIFICANCE: This study will improve the translation of our vaccine studies by demonstrating the efficacy of our novel EV vaccine against circulating Salmonella isolates.

The fifth in a 5-part series on the clinical and translational sciences educational pipeline, this paper focuses on strategies for developing leadership capacity among senior faculty and administrators responsible for clinical and translational science (CTS) research. Although progression in academic rank recognizes scientific excellence in research or scholarship, neither disciplinary training nor experience alone prepare senior faculty for the leadership challenges they inevitably face. Yet these faculty are increasingly responsible for multidisciplinary teams working within complex organizations with unclear or conflicting incentives that demand innovation. In academic health centers with Clinical and Translational Science Awards (CTSAs), investing in leadership often includes career development support in the CTSA education and training pillar programs. Only a few CTSAs have taken an intentional approach to developing senior leadership capacity, however, and still fewer have focused specifically on building such capacity for current CTS leaders within the context of a growing emphasis on team science. This manuscript explains the need for senior leadership training and describes an established example of such a program, the year-long Leadership for Innovative Team Science program for senior CTS researchers at the University of Colorado. The development of the program over time, topical elements, and participant perspectives are provided.

Interim analyses in clinical trials can take on a multitude of forms. They are often used to guide Data and Safety Monitoring Board (DSMB) recommendations to study teams regarding recruitment targets for large, later-phase clinical trials. As collaborative biostatisticians working and teaching in multiple fields of research and across a broad array of trial phases, we note the large heterogeneity and confusion surrounding interim analyses in clinical trials. Thus, in this paper, we aim to provide a general overview and guidance on interim analyses for a nonstatistical audience. We explain each of the following types of interim analyses: efficacy, futility, safety, and sample size re-estimation, and we provide the reader with reasoning, examples, and implications for each. We emphasize that while the types of interim analyses employed may differ depending on the nature of the study, we would always recommend prespecification of the interim analytic plan to the extent possible with risk mitigation and trial integrity remaining a priority. Finally, we posit that interim analyses should be used as tools to help the DSMB make informed decisions in the context of the overarching study. They should generally not be deemed binding, and they should not be reviewed in isolation.

ABSTRACT IMPACT: This project demonstrates that addressing low-value care, which has the potential to cause patient harm, relies on novel data tools and collaboration between health system and research stakeholders. OBJECTIVES/GOALS: Reducing low-value care, or patient care that offers no net benefit in specific clinical scenarios, is an important approach to improving value as it can simultaneously lower health care spending and improve quality. We describe an initiative to identify such care in a large statewide employer. METHODS/STUDY POPULATION: Claims data for self-funded University of California (UC) Preferred Provider Organization (PPO) plan members during 2019 were abstracted from the University of California Health (UCH) Clinical Data Warehouse, a unique central database that includes electronic medical record data from >5 million patients across UC medical campuses and all claims from UC self-funded health plans. UCH spans six academic health systems across California. The Milliman MedInsight Health Waste Calculator, a proprietary algorithm-based software tool, was used to identify low-value care and estimate associated spending. The HWC measures 48 low-value services using recommendations from the Choosing Wisely Campaign, the US Preventive Services Task Force, and other clinical specialty guidelines. RESULTS/ANTICIPATED RESULTS: Of 43,882 members of the UC PPO, 11,174 (25.4%) received at least one low-value service. The HWC identified 50,103 eligible services and classified 35% as low-value. Total spending on low-value services ranged between $2,209,516 and $5,089,866, based on a more or less conservative estimate. Across the five sites, the proportion of low-value services ranged from 31% to 39%. Five services comprised 65% of costs from low-value care: annual EKGs, preoperative baseline labs for low-risk surgeries, vitamin D deficiency screening, imaging for eye disease, and headache imaging. The top five services by order frequency were annual EKGs, vitamin D tests, preoperative labs, antibiotics for upper respiratory infections, and imaging for eye disease. DISCUSSION/SIGNIFICANCE OF FINDINGS: Low-value care is prevalent and costly within a large statewide employer. Collaborative multidisciplinary partnerships between employers, health systems, informatics, and researchers can leverage existing data to identify opportunities for improving the value of care for covered populations.

OBJECTIVES/GOALS: We prioritize Chlamydia’s public health impact, aim to develop rVCG-MECA for practical use, study robust immunity for effective strategies, and assess animal models for human vaccination adaptation. Our work highlights rVCG-MECA’s translational significance in public health. METHODS/STUDY POPULATION: Female Mice C57BL/6J mice (N=8) were immunized intramuscularly(IM) and intranasally(IN) and boosted twice, two weeks apart, with rVCG-MECA, once with live Chlamydia (C. trachomatis serovar D elementary bodies) and PBS. Specific mucosal and systemic immune responses were characterized. Vaccine efficacy was determined from chlamydia shedding following the transcervical challenge. Additionally, Chlamydia-specific cytokine (IFN-γ and IL-4) production by splenic and ILN T cells was assessed after 16 weeks RESULTS/ANTICIPATED RESULTS: Immunization with rVCG-MECA via intramuscular and intranasal routes triggered notable humoral responses in systemic and mucosal tissues. Intramuscular vaccination produced higher IgG2c levels in both tissues, while intranasal vaccination led to elevated IgA levels in mucosal tissues. rVCG-MECA-immunized mice exhibited significantly higher IFN-γ (Th1) secretion compared to IL-4 (Th2), with intramuscular immunization showing the highest IFN-γ levels. These findings anticipate robust immune responses, promising protection against Chlamydia, particularly through the intra muscular route. Overall, our results support rVCG-MECA as a promising Chlamydia vaccine, aligned with public health goals. DISCUSSION/SIGNIFICANCE: This study suggests that IM and IN immunization with rVCG-MECA induces immune effectors such as IFN-gamma and IgG2c that mediate chlamydial clearance in the genetical tract.

OBJECTIVES/GOALS: Research on the safety of perinatal kratom use - an herb that acts on opioid receptors - is scarce. Our transdisciplinary clinical and translational science (CTS) team is conducting parallel qualitative analyses of subreddit posts related to kratom use during (1) pregnancy and (2) breastfeeding. METHODS/STUDY POPULATION: Pregnancy- and breastfeeding-related keywords are being used to extract posts and selected metadata from the following subreddit communities: r/kratom, r/quittingkratom, r/pregnant, and/or r/breastfeeding. After the removal of duplicate posts, posts written in a non-English language and those that state in the post text and/or title that they were published by minors ( RESULTS/ANTICIPATED RESULTS: Among the eligible posts, the number of unique usernames of the sources publishing the posts; the range of publication dates; and the mean, median, & range of the number of comments per post will be presented. Inter-rater concordance in thematic coding will be computed. A word cloud will be created with the most used nouns from the eligible posts. Verbatim quotes will be shown to illustrate themes depicted in the sample. The quantitative and qualitative analyses will be conducted separately for the posts related to kratom use during pregnancy and breastfeeding. DISCUSSION/SIGNIFICANCE: These findings could assist clinicians in identifying questions that obstetric patients may have regarding the perinatal use of this emerging substance of concern. Further research is needed to validate these findings using other social media data, such as Twitter.

OBJECTIVES/GOALS: Fetal glucose dynamics mediate many of the adverse outcomes seen in infants of diabetic mothers (IDM). The goals of this study are to identify: (1) rates of blood glucose change in normoglycemic and hypoglycemic IDM; (2) their relation to in-utero insulin exposure; and (3) their transcriptional impacts on placental and umbilical vasculature. METHODS/STUDY POPULATION: Using a longitudinal prospective study design, placental/umbilical cord tissue and maternal hemoglobin A1c (HbA1c) are being collected from mothers diagnosed with Type 1, Type 2, or gestational diabetes mellitus. Blood glucose levels are also collected from their infants at birth, and every 3-4 hours for up to 9 hours to determine the rate of change. Linear regression modeling will be used to determine associations between placental and umbilical endothelial RNA expression, umbilical cord insulin levels, and maternal HbA1c within each diabetic sub-type. Gene expression from endothelial specimens will be compared between diabetic sub-types and between normoglycemic and hypoglycemic infants via paired t-tests using Benjamini-Hochberg procedure for false discovery rate correction. RESULTS/ANTICIPATED RESULTS: We hypothesize the following; (1) glucose levels will have a steeper rate of change in hypoglycemic infants; (2) maternal HbA1c and in-utero insulin levels will correlate with the level of transcriptional change identified in placental and umbilical endothelial samples; (3) a negative association will exist between cord insulin levels and the rate of change in infant glucose levels; and (4) a positive association will exist between cord insulin level and transcriptional change on the placental and umbilical endothelium. DISCUSSION/SIGNIFICANCE: Identifying gene expression changes in diabetic placental/umbilical endothelium, and the role of insulin/glucose in these changes, is key to managing diabetic vasculopathy and its adverse outcomes. Understanding infant insulin response may also guide management of hypoglycemia and decrease the risk for neonatal intensive care unit admission.

OBJECTIVES/GOALS: Artificial intelligence (AI) depends on quality machine learning (ML) algorithms constructed with high-quality training data. This TL1 trainee project develops a disease-agnostic computable phenotype framework for ML algorithm construction, modeling male puberty as a case example. METHODS/STUDY POPULATION: A computable phenotype of male puberty was constructed to answer the question: “Does early pubertal timing increase the risk of developing type II diabetes (T2D) in males?” A computable phenotype of males < 18 years old was created in the TriNetX© Diamond Network utilizing Boolean operator data queries. TriNetX© contains patient electronic health record information (ICD-10 diagnoses, anthropometric measures). An exploratory analysis of patient counts reflecting various computable phenotypes allowed for outcome (T2D) comparison of males diagnosed with precocious puberty (E30.1, ICD code for early pubertal timing) to those without, controlling for body mass index (BMI). RESULTS/ANTICIPATED RESULTS: Subjects (n=12,996,132) displayed the following computable phenotype: Male, < 18 years old, without ever having a BMI documented >85th percentile. Males diagnosed with precocious puberty (E30.1) were 6.89 times more likely to develop T2D when aged 14-18 years old than those without (OR 6.89, 95% CI: 5.17-9.19, p<0.0001). Next steps involve training a ML model on each computable phenotype groupings’ health data, with anticipated results identifying underlying salient pathophysiologic variables. A generalized computable phenotype approach is further developed to: 1) explore clinical questions in large databases like TriNetX©, and 2) model disease development with AI/ML algorithm construction. DISCUSSION/SIGNIFICANCE: Computed phenotypes reveal males with precocious puberty may have increased T2D risk. Next steps utilize subject data to train an AI/ML algorithm, model development to identify salient pathophysiologic variables, and synthesize a generalized AI/ML developmental research framework for dissemination.

OBJECTIVES/SPECIFIC AIMS: 1. To evaluate the effects of masculinizing chest reconstruction on the quality of life of female-to-male transgender individuals. 2. To develop and validate a quality of life survey for female-to-male transgender individuals undergoing masculinizing chest reconstruction gender-affirming surgery. METHODS/STUDY POPULATION:. We developed and refined the GENDER-Q using focus groups and exploratory interviews with FTM individuals that were recorded, transcribed, and coded. All consenting FTM patients undergoing chest reconstruction at UCSF Parnassus Medical center between 2017-2019 who meet World Professional Association for Transgender Health (WPATH) criteria for gender dysphoria will be enrolled in the study. The GENDER-Q will be co-administered with the WHO Quality of Life-BREF survey pre-operatively, 6 weeks post-operatively, and one year post-operatively through REDCAP, an online survey database. RESULTS/ANTICIPATED RESULTS: Approximately 70 patients will be enrolled in the study. Preliminary results detect statistically significant mean quality of life post-operative improvements in all three sections (Physical Health, Gender Presentation, Psychological Health) of the GENDER-Q at 6-week follow up that is maintained at one-year (p< 0.005). Statistically significant improvements were similarly achieved and maintained with the WHO QOL-BREF survey (p< 0.05). The mean reported improvement from baseline to follow-up appears to be more pronounced in the GENDER-Q survey compared to WHO QOL-BREF. The median time to complete the pre and post-operative surveys was 10 minutes. Calculation of Cronbach’s (0.67-0.81) and the Pearson Correlation Coefficient for each section revealed excellent internal validity. DISCUSSION/SIGNIFICANCE OF IMPACT: There are few studies assessing quality of life outcomes in transgender patients undergoing gender-affirming surgeries. A standardized and validated assessment tool will provide the means for which data can be pooled in large multi-center studies. Providing further evidence to support the positive health outcomes of gender-affirming surgeries can lead to broader access and reduce healthcare disparities among transgender populations.

ABSTRACT IMPACT: Limited research has been conducted on the survival of men with castration-resistance prostate cancer (CRPC) with a pre-existing history of cardiovascular disease, receiving oral androgen signaling inhibitors. This study highlights all-cause and prostate cancer-specific mortality for elderly patients with CRPC with pre-existing history of cardiovascular disease. OBJECTIVES/GOALS: Inadequate knowledge is known about the survival of men with castration-resistance prostate cancer (CRPC) with pre-existing history of cardiovascular disease (CVD), receiving oral androgen signaling inhibitors (OASI). We compared all-cause and prostate cancer-specific mortality for elderly patients with CRPC with pre-existing history of CVD. METHODS/STUDY POPULATION: An active comparator, new user design, was used to identify 2,608 men older than age 65 years with CRPC using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database from 2011 to 2015. Patients were grouped into two analytical cohorts by CVD history. Within each analytical cohort patients were divided into two arms based on their new-user status (OASI vs. chemotherapy). All demographics and clinical characteristics were adjusted by inverse probability treatment weights (IPTWs). Unadjusted and IPTW-adjusted time-dependent Cox models, and Fine and Gray’s models were conducted to evaluate associations between OASI and all-cause and prostate cancer-specific mortality. RESULTS/ANTICIPATED RESULTS: Nearly 64.5% of patients had pre-existing CVD. We observed a lower all-cause mortality in the pre-existing CVD cohort compared to the no pre-existing CVD cohort (IPTW-adjusted hazard ratio [AHR], 0.59; 95% Confidence Interval [CI], 0.54 to 0.64; IPTW-AHR, 0.68; 95% CI, 0.59 to 0.78, respectively). Similarly, the prostate cancer specific-mortality was showed to be lower in the pre-existing CVD cohort compared to the no pre-existing CVD cohort when comparing OASI versus chemotherapy by the IPTW-adjusted time-dependent Fine and Gray’s models (IPTW-AHR, 0.60; 95% CI, 0.55 to 0.66; IPTW-AHR, 0.68; 95% CI, 0.59 to 0.80, respectively). DISCUSSION/SIGNIFICANCE OF FINDINGS: OASI showed a significant protective effect against all-cause and prostate cancer-specific mortality compared with chemotherapy; however, were less protective among patients without pre-existing CVD. Further studies are needed to investigate OASI in patients with and without pre-existing CVD.