OBJECTIVES/GOALS: We developed a non-invasive test of ocular alignment (OA) as a measure of otolith asymmetry, which impacts vestibular function. This test has also been administered on commercial astronauts to study the effect of microgravity on vestibular function. We will assess OA test performance in ground subjects, which has not yet been characterized. METHODS/STUDY POPULATION: Subjects were recruited from visitors to Space Center Houston from June to October 2022. Participants wore red-blue glasses in a darkened room and aligned two vertically or torsionally misaligned line segments, one red and one blue, on a tablet. Each subject underwent 11 vertical and torsional trials. The remaining misalignment was used to calculate ocular misalignment. Subjects self-reported demographic and health data. We calculated descriptive statistics and explored the distribution of overall vertical and torsional OA and distributions by age. Next steps will establish the reliability of the outcome measures with intraclass correlation coefficients and analyze associations between demographic variables and health status with OA performance using linear regression analysis. RESULTS/ANTICIPATED RESULTS: A total of 143 participants (67 female) with a median age of 21 (range 5-74 years old) completed OA testing. Of participants, 64% identified as white, 10% as black, 14% as Asian, 3% as Native American, and 8% as unknown. This test battery was feasible to implement in this mixed-age sample, with a 95% completion rate. Median absolute vertical OA was 0.08 degrees (IQR = 0.17 degrees), and median absolute torsional OA was 0.80 degrees (IQR = 1.20 degrees). Visual analysis of plots of OA by trial number reveals no apparent learning effect within subjects, though some individuals had considerable variation in performance. Average absolute vertical ocular misalignment increased modestly when plotted by age (fitted regression line b = 0.0032 degrees per year of age, p = 0.004), unadjusted for potential confounders. DISCUSSION/SIGNIFICANCE: Ocular alignment testing was feasible in a mixed-age general population sample. Our findings will expand understanding of how OA varies with age. These results will be used to create a normative database to compare and inform analysis of OA results from commercial spaceflights, which include individuals of varying age and health statuses.

OBJECTIVES/GOALS: In 2010, an estimated 65% of antipsychotic prescriptions were given to youth for off-label indications. It is unclear whether subsequent calls for reduced pediatric prescribing led to a decrease in off-label use. This study examined the diagnostic characteristics of the current pediatric population using antipsychotics in the United States. METHODS/STUDY POPULATION: Data from the Clinformatics Data Mart, a database containing longitudinal patient information between 2010-2019 from commercial healthcare insurance claims in the United States was used in this study. We conducted a case-control study, in which antipsychotic initiators were matched 1:1 to non-initiators on age, sex, and insurance enrollment. There were 26,375 included antipsychotic initiators with matched non-initiator controls between the ages of 6-17. Conditional logistic regression was used to examine the odds of being an antipsychotic user among those with past-year psychiatric diagnoses that have been previously found to be associated with antipsychotic use. RESULTS/ANTICIPATED RESULTS: Disorders with psychotic features were associated with the greatest differences in odds of antipsychotic prescription receipt. Specifically, children with bipolar or manic disorders had 145-fold greater odds of antipsychotic receipt than did those without bipolar or manic disorders (OR = 145.45, 95% CI = [95.64, 221.22]), whereas those with schizophrenia had 106-fold greater odds (OR = 105.89, CI = [67.40, 166.37]). However, these disorders occurred in only 12% and 8%, respectively, of the antipsychotic recipients. The most common disorders among those with antipsychotic receipt were depressive disorders and ADHD, which occurred in 46% and 43% of the recipients, respectively. Additionally, conduct disorder was present in 20% of recipients. DISCUSSION/SIGNIFICANCE: As expected, bipolar disorder and schizophrenia were strongly associated with initiation of pediatric antipsychotic treatment. Yet, most initiators did not have a diagnosis for either psychotic disorder or any other FDA-approved indications. This study highlights the critical need for further research on antipsychotic use among youth.

OBJECTIVES/GOALS: We aimed to find the histology-specific markers that were predictive of post-operative long-term chordoma recurrence (≤1 year) using trained multiple tree-based machine learning (ML) algorithms. METHODS/STUDY POPULATION: We reviewed the records of patients who had treatment for clival and spinal chordomas between January 2017 and June 2021 across the Mayo Clinic enterprise (Minnesota, Florida, and Arizona). Patients were excluded if they had no histopathology or recurrence as an outcome. Demographics, type of treatment, clinical and radiological follow-up duration, histopathology, and other relevant clinical factors were abstracted from each patient record. Decision tree and random forest classifiers were trained and tested to predict the long-term recurrence based on unseen data using an 80/20 split. The performance of the model was optimized using tenfold cross-validation. RESULTS/ANTICIPATED RESULTS: One hundred fifty-one patients were identified: 58 chordomas from the clivus, 48 chordomas of the mobile spine, and 45 sacrococcygeal. Subtotal Resection followed by radiation therapy, was the most common treatment modality, followed by Gross Total resection, then radiation therapy. The multivariate analysis defines the molecular predictors of recurrence following resection. S100 and pan-cytokeratin is more likely to increase the risk of post-operative recurrence (OR= 3.67; CI= [1.09,12.42], p=0.03). In the decision tree analysis, a clinical follow-up > 1897 days was found in 37 % of encounters and a 90% chance of being classified for recurrence (Accuracy= 77%). Factors predicting long-term recurrence are the patient’s age, type of surgical treatment, location of the tumor, S100, pan-cytokeratin, and EMA. DISCUSSION/SIGNIFICANCE: Our molecular and clinicopathological variables combined with tree-based ML tools successfully demonstrate a high capacity to individually identify the patient’s recurrence pattern with an accuracy of 77%. S100, pan-cytokeratin, and EMA were the histologic drivers of recurrence.

OBJECTIVES/GOALS: The rapid spread of Monkeypox (MPV) across the US may trigger stress reactions that increase the risk of developing secondary trauma among those most at risk of exposure. The present study aimed to investigate the degree to which vicarious MPV exposure (i.e., knowing people who acquired MPV), was associated with symptoms of secondary traumatization. METHODS/STUDY POPULATION: An online survey was administered to 253 participants enrolled in Keeping it LITE, a prospective U.S. cohort study of ethnically diverse, sexually active, sexual, and gender minority persons aged 19–39 in September 2022. Multiple linear regression was used to examine the association between proximity to MPV and secondary traumatic stress (STS) symptoms. RESULTS/ANTICIPATED RESULTS: Study findings demonstrated that MPV morbidity was low (1%); however, 37% of participants reported knowing at least one person diagnosed with MPV. For most individuals, this person was a friend (28%). 16% of participants were found to have at least one indicator of MPV-related STS. Our multiple linear regression results demonstrated a positive association between an individual’s indirect exposure to MPV via their interpersonal relationships and STS symptoms. DISCUSSION/SIGNIFICANCE: Findings suggest that the more adults’interpersonal relationships are saturated with people who have acquired MPV, the more likely they are to develop symptoms of secondary traumatization. These findings provide initial evidence that secondary exposure to MPV via one’s social network may undermine adults’mental health.

OBJECTIVES/GOALS: METHODS/STUDY POPULATION: This study utilizes the IeDEA W. Africa cohort to evaluate the prevalence and burden of hypertension and diabetes type II among people living with HIV (PLWH) in sub-Saharan Africa (SSA), and to assess how sex and aging impact the development of these NACM. The cohort is a large, international collaboration across eight countries and 19 treatment centers. Established by the National Institute of Allergy and Infectious Diseases in 2006, the W. Africa cohort is now in its fourth renewal (2021-2026). Participating countries include Senegal, Mali, Cote d’Ivoire, Burkina Faso, Ghana, Togo, Benin, and Nigeria. Data are collected from affiliated cohorts in the regional data center every 24 months. The cohort currently includes >65,000 adult PLWH on anti-retroviral therapy. RESULTS/ANTICIPATED RESULTS: The prevalence of several NACM, such as hypertension and cardiovascular disease, have significantly increased among PWH over time, surpassing prevalence observed in the general population. We therefore expect similar patterns in the W. Africa IeDEA cohort and a high prevalence and burden of both hypertension and diabetes type II in this sample. Additionally, evidence suggests that increasing age and female sex serve as independent risk factors for the development of NACM in PLWH. We anticipate that both increased age and female sex, separately and synergistically, are associated with increased prevalence and burden of hypertension and diabetes type II in this cohort. DISCUSSION/SIGNIFICANCE: With more than 37 million people currently living with HIV, the HIV/AIDS epidemic continues to pose a serious threat to global public health. SSA bears a disproportionate burden of the epidemic with greater than two-thirds of global cases. NACM are now driving morbidity and mortality among PLWH, and increased age and female sex may modify this effect.

OBJECTIVES/GOALS: The prevalence of combusted cigarette (CC) smoking among older adults is stagnant, with zero declines attributable to e-cigarette (EC) use. Normative beliefs predict quitting and switching to ECs (a behavior likely to yield health benefits for those unable to quit), so this study seeks to characterize the role of age in norms about CC and EC use. METHODS/STUDY POPULATION: Data come from Wave 5 (2018-2019) of the adult Population Assessment of Tobacco Use and Health (PATH) study, a nationally-representative, U.S. longitudinal cohort. Analyses were restricted to people with established CC use (smoked CCs in the past year, currently smoke regularly, and smoked ≥100 lifetime CCs; n=8,590). Cross-sectional weighted estimates of the prevalence of normative beliefs about CCs and ECs were calculated by age using the Balanced Repeated Replication (BRR) method with Fay=0.3. We used chi-square tests to examine the association of age group (18-24, 25-34, 35-44, 45-54, 55-64, or ≥65) with the prevalence of 2 descriptive and 4 personal social norms. RESULTS/ANTICIPATED RESULTS: The prevalence of the normative belief that most people disapprove of CCs (p DISCUSSION/SIGNIFICANCE: Older adults are more likely than younger adults to endorse anti-tobacco norms, which prior work shows is associated with quitting smoking. These beliefs could be leveraged to create targeted communications towards older adults encouraging smoking cessation. More research is needed to assess age-related tobacco beliefs and switching from CC to EC.

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: Decoding the origins of cell-free DNA (cfDNA) released from dying cells in a liquid biopsy sample (e.g. blood) can provide insight into the dynamic, organism-wide changes reflective of health and disease state. Making cfDNA an ideal target for genomic monitoring of disease-related changes. METHODS/STUDY POPULATION: Methylome-wide sequencing (WGBS) data present unique statistical challenges. To this end, we developed a novel statistical method using an Expectation-Maximization algorithm to decode the cellular origins of cfDNA fragments in liquid biopsies. Our flexible, probabilistic method leverages the co-regulation of neighboring CpG sites on the individual sequencing read to facilitate tissue of origin analysis, as opposed to prior methods that focus on the methylation rate of a single CpG site. We assess the performance of our model in various simulated settings and apply our model to an important clinical example in which we are able to detect early off-target tissue damage from radiation therapy via minimally invasive blood draws. RESULTS/ANTICIPATED RESULTS: We found our model more effective at capturing the range of biologically plausible methylation patterns on cfDNA read fragments compared to prior models that use single CpG sites. We also show our model is robust to high levels of noise inherent with WGBS data. We demonstrate the accuracy of cell-type proportion estimation on in-silico mixed cfDNA samples from real WGBS data. Finally, we use our model in a clinical application. We detect significant (p < 0.05) increases in cellular contributions from lung and cardiac tissue in breast cancer patients (n=15) undergoing radiation therapy compared to baseline. We also detect novel signals of radiation induced toxicity to the liver in right-sided breast cancer patients (n=8) receiving radiation treatment compared to matched left-sided breast cancer patients (n=7). DISCUSSION/SIGNIFICANCE: Here we address an unmet need in developing novel statistical methodologies that can handle the unique complexities of methylated cfDNA obtained from liquid biopsy samples. We also demonstrate the far-ranging clinical utility of serial liquid biopsy sampling to complement and advance standards of clinical care in oncology and other pathologies.

Although team science has expanded with far-reaching benefits, universities generally have not established criteria to recognize its value in faculty promotion and tenure. This paper recommends how institutions might weigh a faculty member’s engagement in team science in the promotion and tenure process. Seventeen team science promotion and tenure criteria are recommended based on four sources – an evaluation framework, effectiveness metrics, collaborative influences, and authorship criteria. Suggestions are made for adaptation of the 17 criteria to committee guidelines, faculty team science portfolios, and the roles of individuals and institutions participating in large, cross-disciplinary research projects. Future research recommendations are advanced.

OBJECTIVES/GOALS: Motoric cognitive risk (MCR) is a pre-dementia syndrome characterized by slow gait and subjective cognitive complaints. In the Atherosclerosis Risk in Communities (ARIC) study, we aim to (1) identify plasma proteins and protein modules associated with MCR and (2) compare the proteomic signature of MCR to that of mild cognitive impairment (MCI). METHODS/STUDY POPULATION: Nondemented ARIC participants were classified by MCR status (yes/no) according to a memory questionnaire and 4-meter walk. MCI status (yes/no) was classified by expert diagnosis using standardized criteria. We measured 4,877 proteins in plasma collected at ARIC Visit 5 (late-life) and Visit 2 (midlife) utilizing the SomaScan4 proteomic assay. Multivariable logistic regression”adjusted for demographic variables, kidney function, cardiovascular risk factors, and APOE4 status”related each protein to MCR at late-life. An FDR corrected P RESULTS/ANTICIPATED RESULTS: Proteome-wide association study among 4076 ARIC participants (mean age=75; 58% women, 17% Black, 4% MCR+, 21% MCI+; MCR+ and MCI+ groups overlapped) at late-life identified 26 MCR-associated proteins involved in metabolism, vascular/visceral smooth muscle, and extracellular matrix organization. At an uncorrected P DISCUSSION/SIGNIFICANCE: This proteomic characterization of MCR identifies novel plasma proteins and networks, both distinct from and overlapping with those of MCI, thus highlighting the partially divergent mechanisms underlying these pre-dementia syndromes. These findings may be leveraged toward dementia prognostication and targeted therapeutic approaches.

OBJECTIVES/GOALS: Children with Down syndrome are at increased risk of respiratory diseases including asthma. Prenatal antibiotic exposure has been shown to be associated with the development of childhood asthma. We aim to estimate the association between prenatal antibiotic exposure and childhood asthma among children with Down syndrome. METHODS/STUDY POPULATION: We conducted a retrospective cohort study of mother-child dyads of children with Down syndrome who were born 1995-2013. Both children and mothers were continuously enrolled in the Tennessee Medicaid Program (TennCare). Prenatal antibiotic exposure was measured using mother’s prescription fill records. Childhood asthma was defined between age 4.5-6 years by asthma-related healthcare encounters and asthma-specific medication fills. We assessed the association between prenatal antibiotic exposure and childhood asthma among children with Down syndrome using modified Poisson regression adjusting for maternal age, race, residence, education, marital status, smoking during pregnancy, maternal asthma status, delivery method, number of siblings, and children’s sex. RESULTS/ANTICIPATED RESULTS: Among 346 mother-child dyads of children with Down syndrome, 273 (78.9%) children were exposed prenatally to antibiotics and 104 (30.0%) had asthma by age 4.5-6 years. Among those who were exposed to at least one course, the median antibiotic course equaled 2 (interquartile range: 1-4). Prenatal antibiotic exposure was associated with a 20% increase in risk of childhood asthma in the unadjusted analysis (risk ratio [RR] 1.20, 95% confidence interval [CI] 0.78, 1.83) and a 26% increase in risk after adjustment (adjusted RR 1.26, 95% CI 0.79, 2.01). DISCUSSION/SIGNIFICANCE: In our study population, the majority of children with Down syndrome were exposed to antibiotics prenatally and the prevalence of asthma was high. Prenatal antibiotic exposure was associated with an increased risk of childhood asthma among children with Down syndrome; however, this increase was not statistically significant.

Clinical trials continue to disproportionately underrepresent people of color. Increasing representation of diverse backgrounds among clinical research personnel has the potential to yield greater representation in clinical trials and more efficacious medical interventions by addressing medical mistrust. In 2019, North Carolina Central University (NCCU), a Historically Black College and University with a more than 80% underrepresented student population, established the Clinical Research Sciences Program with support from the Clinical and Translational Science Awards (CTSA) program at neighboring Duke University. This program was designed to increase exposure of students from diverse educational, racial, and ethnic backgrounds to the field of clinical research, with a special focus on health equity education. In the first year, the program graduated 11 students from the two-semester certificate program, eight of whom now hold positions as clinical research professionals. This article describes how leveraging the CTSA program helped NCCU build a framework for producing a highly trained, competent, and diverse workforce in clinical research responsive to the call for increased diversity in clinical trial participation.

OBJECTIVES/GOALS: There is evidence that lesbian, gay, and bisexual (LGB) adults have poorer cardiovascular health than their heterosexual peers, but studies of the association between sexual orientation (SO) and diabetes mellitus (DM) have been few with mixed findings. To further investigate this association, large cohorts with objective data capture are needed. METHODS/STUDY POPULATION: We used data from the Veterans Healthcare Administration Lesbian, Gay, Bisexual, Transgender EHR cohort which includes veterans with at least 2 encounters October 1, 2009-September 30, 2019. The first clinic visit in this window was the index date with the baseline date one year later; the intervening year served as a baseline period for observation of prevalent disease and comorbidities. We did not include transgender veterans in this analysis in order to focus on SO rather than on the intersection of SO with gender identity. The SO of 1,108,990 veterans was identified using a natural language processing tool; 185,788 veterans were classified as LGB. We first examined sample characteristics by sex and SO and then used logistic regression to assess the association between SO and prevalent DM. RESULTS/ANTICIPATED RESULTS: DM was present among 193,330 veterans (32,986 LGB). Mean age was similar across SO in women (41) and men (53). Distribution of race was similar across groups, but LGB veterans were more likely to be Hispanic (11%, both sexes) than non-LGB men (6%) and women (8%). Current smoking was more prevalent among LGB (44% men, 39% women) than non-LGB veterans (40% men, 30% women). Adjusting for age, sex, race, Hispanic ethnicity, BMI, smoking status, health insurance, marital status, and enrollment priority, LGB veterans had 1.12 [1.10, 1.13] times the odds of DM vs. non-LGB veterans. Bisexual (0.87 [0.74, 1.01]) or lesbian (1.03 [0.97, 1.10]) women did not have significantly different DM odds than non-LGB women. Bisexual men had lower DM odds (0.86 [0.80, 0.93]) while gay men had higher odds (1.04 [1.01, 1.06]) than non-LGB men. DISCUSSION/SIGNIFICANCE: This is one of the first studies to report DM in a veteran cohort stratified by SO. Our findings highlight the importance of examining SO groups separately and jointly, as to further elucidate the association between SO, cardiovascular risk factors, and general cardiovascular health. Future work will examine the intersection of SO and gender identity.