OBJECTIVES/SPECIFIC AIMS: Despite aggressive chemotherapy, surgical resection, and radiation therapy, glioblastoma remains almost universally fatal. In a pilot, randomized, and blinded clinical trial, we recently demonstrated that administration of RNA-loaded DC vaccines was associated with significantly improved progression-free and overall survival in patients with glioblastoma (Mitchell et al., Nature, 2015). Furthermore, clinical outcomes correlated with DC migration to vaccine-site draining lymph nodes measured by Indium-111 labeling of RNA-loaded DCs and SPECT/CT imaging. Although these studies demonstrated that tracking DC migration may be an important clinical biomarker for response to DC vaccination, the complexity and regulatory requirements associated with nuclear labelling to track DC migration limits widespread application of this technique. We have therefore developed RNA-loaded magnetic nanoparticles (RNA-NPs) to enhance DC migration to LNs and track that migration with a widely available imaging modality (i.e., MRI). METHODS/STUDY POPULATION: Cationic liposomes were loaded with iron oxide nanoparticles with or without cholesterol. The resulting nanoparticles were complexed with RNA and used to transfect DCs ex vivo. RNA-NP-loaded DsRed+ DCs were then injected intradermally into mice and tracked noninvasively with T2-weighted 11T MRI before excision and quantification with flow cytometry. RESULTS/ANTICIPATED RESULTS: In vitro experiments demonstrate that iron oxide loading does not reduce RNA-NP-mediated transfection of DCs. Additionally, replacement of cationic lipids with cholesterol increased RNA-NP transfection of the DC2.4 cell line and enhanced the T cell stimulatory capacity of treated bone marrow-derived dendritic cells (BMDCs). Compared to electroporation, RNA-NPs enhanced DC migration to lymph nodes and reduced T2 MRI intensity in DC-bearing lymph nodes. DISCUSSION/SIGNIFICANCE OF IMPACT: This data suggests that iron oxide-loaded RNA-NPs enable noninvasive cell tracking with MRI and enhance DC migration to lymph nodes. We have further shown that inclusion of cholesterol in RNA-NPs augments the stimulatory capacity of transfected DCs. Future work will consider effects of RNA-NPs on antitumor immune responses and the utility of MRI-detected DC migration as a biomarker of vaccine efficacy.

OBJECTIVES/SPECIFIC AIMS: The goal of this study is to further evaluate underlying disease parameters in respiratory syncytial virus (RSV) infection, that is reduction in antioxidant potential, and determining if supplementation of the antioxidant enzyme catalase could be employed as a potential therapeutic. METHODS/STUDY POPULATION: Nasopharyngeal secretions were obtained from patients (<2 years old) verified for RSV infection, and assessed for catalase activity and correlated with disease parameters. In addition, the BALB/c animal model of RSV infection was utilized to directly study the effect of supplemental catalase on RSV-related disease parameters in vivo. The catalase formulation used in these studies is pegylated, and has been tested to provide long-term increased catalase activity in vivo. We are also currently working on designing an in vitro model of catalase supplementation in A549 bronchial epithelial cells. RESULTS/ANTICIPATED RESULTS: Our preliminary data shows that patients with more severe disease (based on hospitalization, oxygen supplementation) have significantly lower levels of catalase activity (p<0.02). Additionally, when pegylated-Catalase (PG-CAT) treatment is utilized in RSV infection of mice, there is significant improvement in several disease parameters. PG-CAT-treated mice show an attenuated body weight loss (p<0.001) and clinical disease (p<0.02), and also have lower levels of key pro-inflammatory cytokines including CXCL1 and TNF-α. PG-CAT treatment also resulted in a minor decrease in viral titer, which is being further evaluated. In addition, PG-CAT treatment resulted in an improvement in airway hyperresponsiveness observed at baseline, we are further characterizing this improvement and also conducting methacholine challenges. Currently, we are working to determine the underlying mechanism through which PG-CAT results in these improvements, and whether it is through changes in immune cell populations, cellular signaling or apoptosis signaling pathways (i.e., caspases). DISCUSSION/SIGNIFICANCE OF IMPACT: RSV is the leading cause of viral pneumonia and bronchiolitis in infants, with no vaccines or effective therapeutics available currently. Our study indicates that catalase activity could be used as a potential correlate for disease severity and be used as an indicator of disease during patient treatment. Additionally, and more importantly supplementation of catalase could be used as a potential therapeutic for treatment of RSV.

OBJECTIVES/SPECIFIC AIMS: This research examined 3 aims to address the need to understand and quantify exertion in infants. Aim 1: Develop a schema to identify and code exertional behaviors in infants during treadmill stepping. Aim 2: Establish feasibility for the schema’s use with clinical populations. Aim 3: Pilot the schema in a study designed to induce infant exertion. METHODS/STUDY POPULATION: Aims 1 and 2 were achieved using existing treadmill stepping data. The data used in Aim 1 included eight typically-developing infants (age 7-10 months) who were able to sit independently, but not walk. The data used in Aim 2 came from two separate data sets from infants who took more than 10 steps in a 30-second trial: Data set A included six typically-developing infants (age 2-5 months) who were unable to sit independently (developmentally comparable to atypical populations who might receive treadmill interventions). Data set B included six infants with Spina Bifida (age 3-10 months). Aim 3 was addressed with a prospective study using an exertion model. Pre-walking, typically developing infants (age 8-10 months) underwent five total stepping trials. Trial 1 determined the infant’s individualized maximum stepping speed; trials 2-5 were each 60 seconds and alternated between a baseline stepping speed of.20 m/s and the infant’s maximum stepping speed determined in trial 1. All video data were coded for step type, step frequency, and exertional behavior. RESULTS/ANTICIPATED RESULTS: Aim 1: Two behaviors were identified and determined to capture infant exertion: foot dragging and leg crossing. Aim 2: The feasibility of capturing exertion with these two behaviors was established for young infants and infants with neuromotor delays, with exertional behaviors increasing with stepping exposure (p< 0.05). Aim 3: Total exertion (foot dragging + leg crossing) was higher in the maximum speed trials compared to baseline trials (p = 0.005). DISCUSSION/SIGNIFICANCE OF IMPACT: Exertion in infants can be quantified. The exertion schema developed with this study will support the development of dosing guidelines for infant treadmill intervention. The next step in this line of research is to examine the correlation between infant exertion and heart rate, in effort to move from behaviorally-informed protocols to more precise, individualized protocols based on the physiological response of the infant.

OBJECTIVES/SPECIFIC AIMS: (1) Characterize the prevalence and initial pharmacological management of chronic pain syndromes during pregnancy in a women’s mental health program. (2) Describe the severity and qualitative characteristics of chronic pain during pregnancy and the acute postpartum period. (3) Compare obstetrical and neonatal outcomes between pregnant women with and without chronic pain syndromes. METHODS/STUDY POPULATION: A chart review was conducted to identify all pregnant women who presented for an initial evaluation to the Women’s Mental Health Program (WMHP) at the University of Arkansas for Medical Sciences from July 2013 to June 2016. We excluded respondents <18 years of age or who did not consent to having their information used for research purposes. Demographic information, past and current medical histories, and medication history were obtained from written and electronic medical records. Chronic pain complaints and medication history are presented as counts and percentages. In an ongoing prospective, longitudinal study of pregnant women with chronic pain, women are enrolled before 20 weeks gestation and followed throughout pregnancy and the first 3 months postpartum. Study visits occur at 4-week intervals; and pain characteristics, analgesic exposures, other medications, and depressive measures are collected. Obstetrical and neonatal outcomes are obtained following delivery. Subjects will be compared based on pain types (ie, neuropathic pain, non-neuropathic pain, and controls) and treatment exposures (eg, +/− opioids). Primary outcome measures include visual analog scale (VAS). Secondary outcome measures include other pain and depression assessments. Data will be analyzed using SAS 9.4. A p-value of<0.05 was considered statistically significant. RESULTS/ANTICIPATED RESULTS: (1) Chronic pain conditions were reported by 28.2% (44/156) of the initial referrals to the WMHP. (2) 95.5% of respondents with chronic pain were taking at least 1 medication, and 59.5% were taking 2 or more medications. Mean number of medications used were 2.6±2.1.3. The most common medications reported were acetaminophen (43.2%), opioids (43.2%), and sedative/hypnotics (36.4%). Non-pharmacological therapy (eg, physical therapy and transcutaneous electrical nerve stimulation) was reported by 20.5% of respondents. (4) We anticipate that measures of pain severity will increase in pregnancy, peak in the third trimester, and decline in the postpartum period. (5) We foresee that the prospective results will confirm the chart review as indicated by a higher rate of medication exposures during pregnancy, including non-analgesic medications in the women with chronic pain syndromes. (6) We expect women with chronic pain syndromes to have a higher rate of obstetrical complications, specifically pre-term delivery and operative delivery. (7) Finally, we anticipate that chronic pain syndromes and management will result in a higher rate of neonatal complications, specifically neonatal intensive care unit admission, neonatal respiratory problems, and small for gestational age infants. DISCUSSION/SIGNIFICANCE OF IMPACT: Chronic pain syndromes are prevalent in more than one-quarter of pregnant women in our study with the majority of women using pharmacological agents to manage their condition. This prevalence is greater or equal to than other common obstetrical conditions, such as gestational diabetes or preterm delivery. The novel prospective data will be germane to the clinical care of pregnant women with chronic pain disorders. Clinical practice will be better informed by our data regarding the potential impact of chronic pain and its management on pregnancy course and perinatal outcomes. These data will provide the initial foundation for the development of treatment guidelines for the management of chronic pain syndromes during the perinatal period.

OBJECTIVES/GOALS: BURRITO is an efficient strategy that provides full disclosure in the electronic medical record of a patient’s preference in real time. BURRITO uses printed materials only to inform patients and has a <50% rates of consent. We hypothesized that adding an informational video to the printed materials would increase donations. METHODS/STUDY POPULATION: This study was IRB-approved and was considered minimal risk. The BURRITO self-consent workflow process (Soares et. al, Biopreservation and Biobanking, IN PRINT) was developed in an outpatient cardiology clinic. In the same clinic, patients were randomized to receiving printed materials only (standard procedure) or the printed materials plus a 2.5-minute informational video (intervention) while waiting for the physician in the exam room. Randomization occurred at the level of the day in clinic. Patients were blinded to the nature of the study. Following the presentation of information, the patient’s decision on consent for donation was documented in the electronic record by ancillary clinical staff. Rates of consent were analyzed by a statistician not involved in the experiment and after completion of trial. RESULTS/ANTICIPATED RESULTS: Thirty-five clinic days were randomized to either intervention (17 days) or standard (18 days), and a total of 255 patients decided during their visit to either “opt-in” or “opt-out” to donating remnant biospecimens for future research. One hundred patients opted to defer deciding (28%). No significant demographic differences were noted between the study arms. The rate of consent was 73% vs. 58% in the intervention group and the control group, respectively (p-value = 0.014). This represents an increase in the odds of consenting with an informational video by 96% (OR = 1.96, 95% CI = 1.15 to 3.34). DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first randomized trial to show that an informational video with printed materials is superior for when patients are self-consenting to opt-in for clinical remnant biospecimen donation. This result adds to the evidence that the BURRITO process plus video (BURRITOv) is an effective approach for biospecimen universal consenting.

OBJECTIVES/GOALS: Test the validity of a system for subgrouping people with CLBP by comparing lumbar spine alignment in two CLBP subgroups and sexes during clinical tests of maximum flexed and extended sitting and a functional test of preferred sitting. METHODS/STUDY POPULATION: Using the Movement System Impairment classification system, 154 participants with CLBP were subgrouped based on the predominant direction of altered movement and alignment patterns and symptoms during a standardized examination. Participants performed a functional test of preferred sitting followed by clinical tests of maximum flexed and extended sitting in random order. Reflective markers were place superficial to T12, L3 and S1 spinous processes. 3D marker co-ordinate data were collected using an 8 camera motion capture system. Sagittal plane lumbar curvature angle (LCA), defined as the angular distance between T12, L3, and S1 landmarks was calculated for each test. A three-way mixed effect ANOVA model was used to examine the following effects: test, subgroup, sex, test*subgroup, test*sex, subgroup*sex. RESULTS/ANTICIPATED RESULTS: Test: Lumbar alignment patterns were different for flexed [LCA = 7.4° (6.1, 8.7)], extended [LCA = −22.6° (−23.9,−21.3)], and preferred [LCA = −3.8° (−5.2,−2.5)] sitting tests. LBP subgroup: Rotation-extension [LCA = −7.5° (−8.7,−6.3)] had more extended lumbar alignment than rotation [LCA = −5.2° (−6.2,−4.2)]. Sex: Women had more extended lumbar alignment [LCA = −10.3° (−11.2,−9.3)] than men [LCA = −2.5° (−3.7,−1.2)]. Test*sex: The difference in lumbar alignment between women and men was smaller during the flexed sitting test [women = 4.2° (2.5, 5.9), men = 9.9° (7.8, 12.1)], compared to extended [women = −27.5° (−29.2, −25.8), men = −17.0° (−9.2, −14.8)] and preferred [women = −7.4° (−9.1, −5.8), men = −0.3° (−2.5, 1.8)]. The test*subgroup (p = 0.84) and subgroup*sex (p = 0.87) interactions were not significant.

ABSTRACT IMPACT: Given the association between lower time to treatment and better clinical outcomes in stroke patients, identifying factors correlated with reduced proximity and thus greater time to stroke care can aid efforts to reduce disparities in stroke outcomes. OBJECTIVES/GOALS: The objective of this study is to quantify the relationship between distance to the nearest certified stroke hospital and census-derived demographics of age, race/ethnicity, income, and insurance status. METHODS/STUDY POPULATION: This is a cross-sectional study. Population data for all census tracts in the contiguous United States were obtained from the US Census Bureau’s 2014-2018 American Community Survey. Stroke hospitals were identified from national or state level certification databases and were required to offer at least IV tPA. The main outcome is driving distance in kilometers from each census tract to the nearest certified stroke center, which was calculated using OSMnx, a Python package to retrieve, model and analyze real-world street networks. Quantile regression analysis was used to compare relationships between distances and tract-level demographics of age, race/ethnicity, income, and insurance status. RESULTS/ANTICIPATED RESULTS: 2,423 stroke centers and 71,929 census tracts containing 316,995,649 individuals were included. 49,918 (69%) tracts were urban. Demographic disparities in proximity to certified stroke care were greater in non-urban areas than in urban areas. Higher representation of individuals with age ≤65 years were associated with increased median distance to a certified stroke center in non-urban areas, but not urban areas. Median distance was greater with greater representation of American Indian or uninsured populations in urban and non-urban census tracts. Higher median income was associated with decreased median distance in non-urban census tracts and greater median distance in urban census tracts. DISCUSSION/SIGNIFICANCE OF FINDINGS: Reduced proximity to stroke care exists in areas with greater representation of elderly, American Indian, or uninsured persons; and low median income. These disparities are magnified in non-urban settings. Such knowledge can aid efforts to address and reduce disparities in stroke outcomes.

OBJECTIVES/GOALS: To increase diversity in clinical and translational research (CTR), to strengthen protections for uninsured and under-insured study participants from vulnerable groups by addressing their medical, ancillary care and psycho-social needs and to develop a systematic ethically sound approach to addressing such needs in the study protocol and budget. METHODS/STUDY POPULATION: We conducted) ethical analyses of: (1) the regulatory and ethics scholarship concerning protections and duty of care to research participants from vulnerable groups, and 2) arguments concerning the nature and scope of ancillary care obligations of researchers, as well as 3) a review of the applicable local, federal, and international regulations and practices concerning the duty of care to CTR participants and potential participants who are uninsured, under-insured and/or undocumented members of vulnerable groups. RESULTS/ANTICIPATED RESULTS: Uninsured and underinsured study participants pose major ethical challenges for CTR as medical needs arising during a study are usually covered by the participants own insurance. Lack of health insurance increases vulnerability and creates (1) a barrier to research participation for members of socially disenfranchised groups, (2) risk of discriminatory exclusion of such participants from clinical studies, and (3) inter-institutional inconsistencies in meeting their medical needs; thus limiting diversity in CTR. To address the challenges, we propose an inclusive, systematic, ethically sound approach, which deliberately plans for and provides resources within a study protocol to address the medical and psycho-social needs of uninsured participants during and beyond the study. DISCUSSION/SIGNIFICANCE: Including diverse participants in CTR ensures data quality and social justice. PIs and IRBs should adopt an inclusive approach to the medical needs of vulnerable uninsured participants, plan for their medical and ancillary care needs in the protocol and budget, list community resources, provide follow-up support and note assistance in their files.

OBJECTIVES/SPECIFIC AIMS: To study the biology of Phosholamban (PLN) in a human relevant model. METHODS/STUDY POPULATION: State of the art stem-cell technologies using iPSC-CMs derived from carriers of a lethal PLN mutation. RESULTS/ANTICIPATED RESULTS: Our preliminary data demonstrate that this particular PLN mutation (L39) results in reduced expression and mis-localization of PLN as well as increased incidence of early after depolarization in isolated iPSC-CMs. DISCUSSION/SIGNIFICANCE OF IMPACT: Phospholamban (PLN) is a critical regulator of Ca++ homeostasis yet many uncertainties still remain regarding its role in humans. Our study will provide unique insights into the pathophysiology of this protein in HF.

ABSTRACT IMPACT: Our work helps show universities that embedding dedicated sexual health clinics within university health and wellness clinics may expand the amount of students they see for sexual health screenings during a time of increased sexual behavior and exploration. OBJECTIVES/GOALS: The National College Health Association reports that college students have frequent, condomless sex. Student health and wellness clinics (SHWC) offer sexual health services, but few have dedicated sexual health clinics (SHC). We evaluated sexual health service use at a university SHWC after implementation of a dedicated SHC two half-days per week. METHODS/STUDY POPULATION: This was a retrospective analysis of data collected from patients receiving sexual health screening at the University of Alabama at Birmingham (UAB) SHWC between January 2015 and June 2019. Demographic variables, sexual behaviors, reason for testing, and rates of STIs were extracted from the electronic medical record and were compared by clinic (SHC vs. SHWC). Data on screening visits of patients over 18 were included in the final analysis. Variables were summarized with frequencies and percentages. Univariate models were fit, and multi-variable models will be fit, selecting variables with p values of 0.1 or less. Odds ratios with corresponding 95% confidence intervals for univariate analysis are presented. The study was approved by the UAB Institutional Review Board. RESULTS/ANTICIPATED RESULTS: A total of 5025 STI screenings were performed. Males (OR 4.13; 3.61-4.72), undergraduates (OR 1.33; 1.15-1.54), and persons reporting sex with the same sex (OR 1.88; 1.56-2.28), were significantly more likely to seek care at the SHC. Students with symptoms were more likely to seek care at the SHWC (OR 0.53; 0.47-0.61), while persons who reported contact with STIs were more likely to seek care at the SHC (OR 2.88; 2.22-3.74). The overall percentage of positive screenings was 9.3% for chlamydia (CT), 3.0% for gonorrhea (GC), 0.8% for trichomoniasis (TV), 0.7% for syphilis, and 0.3% for HIV with higher percentages of positive for CT (OR 1.60; 1.30-1.96) and GC (OR 2.02; 1.44-2.85) in the SHC. A greater percentage of positives for TV (OR 0.37; 0.14-0.96) was found in the SHWC. DISCUSSION/SIGNIFICANCE OF FINDINGS: Based on demographics of persons utilizing services, embedding a dedicated SHC within a university SHWC may expand populations reached for STI screening. With higher percentages of patients testing positive for CT and GC, a SHC may allow for greater diagnosis and treatment of STIs in general screening and persons presenting as contacts.

OBJECTIVES/SPECIFIC AIMS: Deficits in reward-based learning have been shown in youth at risk for developing substance use disorders (SUD). Here, we investigated whether computational models can be used to more precisely delineate the additive effects of such risk loading (i.e., the comparison between youth with ADHD, and those with ADHD and familial SUD) on reward-based learning in youth. METHODS/STUDY POPULATION: In total, 41 drug-naïve youth, stratified into 3 groups based on ADHD diagnosis and parental SUD: healthy controls (HC, n=13; neither ADHD nor parental SUD), low risk (LR, n=13; ADHD only), and high risk (HR, n=15; both ADHD and parental SUD), performed a reward task. Learning rates, prediction and congruence t-scores were computed using a reinforcement learning model and analyzed via a multivariate ANOVA. RESULTS/ANTICIPATED RESULTS: The analyses showed a significant linear effect in task accuracy, which decreased with increasing risk profiles. Analyses of the model-derived variables also showed similar significant linear effects in learning rates and the congruence t-score, but not in the prediction t-score. These effects were primarily driven by significantly higher learning rate and congruence t-score in HC compared with HR youth. DISCUSSION/SIGNIFICANCE OF IMPACT: These results show most profound deficits in reward-learning in HR youth. These findings also show that computational analyses can offer added value over conventional behavioral analyses by more precisely evaluating group differences in relation to SUD risk.

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

OBJECTIVES/SPECIFIC AIMS: Individuals with autism spectrum disorder (ASD) and developmental coordination disorder (DCD) share overlap in their motor symptom profile and underlying neurology (Sumner, Leonard, & Hill, 2016, JADD). DSM-5 guidelines allow these 2 disorders to be independent or co-occurring (APA, 2013), but common clinical practice does not include systematic assessment to determine the presence or absence of co-occurring DCD in children with ASD, or vice versa. Furthermore, in many cases DCD is managed in a nonspecific manner, with schools making accommodations for a child’s motor challenges without formally assigning a diagnosis of DCD. Thus, somewhat subjective, qualitative judgments are made by clinicians to classify children as DCD, ASD, or ASD+DCD in the absence of a reliable, valid, quantitative measure to distinguish between these profiles. As a first step toward developing such a measure, researchers must tease apart the nuanced differences in the motor symptoms of these 2 developmental disorders using methods that are scalable to clinical and educational settings. These methods must also be developed with consideration for logistical variables such as cost, clinical utility of data output, and ease-of-use if they are to be transferrable to physicians, school nurses, and other community health workers outside of academic laboratory settings. To that end, we conducted 2 complementary studies: 1 in the lab and 1 in the community. METHODS/STUDY POPULATION: In the community-based study, we used an affordable, user-friendly, portable balance testing system to assess postural stability during quiet standing (feet shoulder-width apart) with eyes open for 30 seconds. Data were generated from a single force plate in the balance platform. Potential participants were screened for other medical and neurological conditions that might impact their postural stability, and those with significant comorbidities were excluded. We tested 15 children with a reported diagnosis of ASD, 8 children with suspected or diagnosed DCD who were enrolled in a motor intervention program, and 30 typically-developing (TD) children with no significant developmental history reported. The ASD group ranged in age from 7 to 20, the DCD group ranged from 7 to 10, and the TD group ranged from 7 to 19. In the lab-based study, we again obtained force plate data during quiet standing (feet shoulder-width apart) with eyes open for 30 seconds, in our system that also included full-body motion capture, virtual reality, and mobile eye tracking. (Data from these additional sources are not discussed in this disseminaton, as our current focus is on identifying a simple, scalable metric that can be used to distinguish ASD from DCD.) We tested 10 children with a diagnosis of ASD that was confirmed by the research team, 10 children with a diagnosis of DCD that was confirmed by the research team, and 5 TD children with no significant developmental history reported. The ASD group ranged in age from 7 to 18, the DCD group ranged from 8 to 12, and the TD group ranged from 9 to 18. RESULTS/ANTICIPATED RESULTS: Primary outcome measures in both studies were related to Center of Pressure (CoP), including CoP sway, CoP velocity, and amount of sway relative to the base of support. Data analysis from both studies is ongoing, but preliminary trends suggest that CoP metrics may effectively differentiate between ASD, DCD, and TD. During quiet standing, individuals with DCD exhibited the greatest postural sway. Individuals with ASD followed, having greater instability than the TD group. Differences were also evident in the velocity profiles of postural sway. DISCUSSION/SIGNIFICANCE OF IMPACT: Preliminary findings suggest that CoP offers a means of differentiating between typical and atypical development specifically with respect to motor symptoms. This simple, quantifiable measure may prove a sensitive and specific means of systematically assessing co-occurrence of ASD and DCD in clinical and educational settings, leading to more accurate diagnostic classification and tailored intervention. Future directions include conducting analyses that account for participant age and developmental stage with respect to motor skills, determining whether trends hold in a larger sample, and using advanced statistical methods to determine whether CoP variables have predictive validity in discriminating between classifications of ASD, DCD, ASD+DCD, and TD. Eye-movement data were also obtained during these tasks, and may further aid in understanding the factors contributing to atypical postural control. These 2 studies also yielded methodological findings, namely that the portable force platform carries the benefit of high ease-of-use, low cost, and portability, but also has important drawbacks. Specifically, it is not capable of registering accurate CoP data for participants who weigh <40 lbs, and the error variance for the load cells is greater than that of most nonportable, higher-end plates like those embedded in our laboratory’s platform. As technological advances continue to facilitate development of more portable, higher-resolution systems, these drawbacks may be significantly reduced. Future directions include further assessment of portable, affordable solutions for this type of testing to identify whether higher-resolution options are available, whether this added resolution increases classification accuracy, and how ease-of-use is perceived by clinical and community health workers.

OBJECTIVES/GOALS: To evaluate the incidence of brachial plexus birth injury (BPBI) and its associations with maternal demographic factors. Additionally, we sought to determine whether longitudinal changes in BPBI incidence differed by maternal demographics. METHODS/STUDY POPULATION: We conducted a retrospective cohort study of over 8 million maternal-infant pairs using California’s Office of Statewide Health Planning and Development Linked Birth Files from 1991-2012. Descriptive statistics were used to determine BPBI incidence and the prevalence of maternal demographic factors (race, ethnicity, age). Multivariable logistic regression was used to determine associations of year, maternal race, ethnicity, and age with BPBI. Excess population level risk associated with these characteristics was determined by calculating population attributable fractions. RESULTS/ANTICIPATED RESULTS: The incidence of BPBI between 1991-2012 was 1.28 per 1000 live births, with peak incidence of 1.84 per 1000 in 1998 and low of 0.9 per 1000 in 2008. Incidence varied by demographic group, with infants of Black (1.78 per 1000) and Hispanic (1.34 per 1000) mothers having the highest incidences. Controlling for relevant covariates, infants of Black (AOR=1.88, 95% CI 1.70, 2.08), Hispanic (AOR=1.25, 95% CI 1.18, 1.32) and advanced-age mothers (AOR=1.16, 95% CI 1.09, 1.25) were at increased risk. Disparities in risk experienced by Black, Hispanic, and advanced-age mothers contributed to a 5%, 10%, and 2% excess risk at the population level, respectively. Longitudinal trends in incidence did not vary among demographic groups. Population-level changes in maternal demographics did not explain changes in incidence over time. DISCUSSION/SIGNIFICANCE: Although BPBI incidence has decreased in California, demographic disparities exist. Infants of Black, Hispanic, and advanced-age mothers are at increased BPBI risk compared to White, Non-Hispanic, and younger mothers.

OBJECTIVES/GOALS: The Clinical Research Coordinator (CRC) Intern Program was developed to increase knowledge and awareness of CRC’s vital role in conducting clinical studies. Program outcomes are to provide students with marketable skills and knowledge leading to employment within the clinical research ecosystem. METHODS/STUDY POPULATION: The CRC Intern Program is available to college students for health-related academic courses requiring an internship component. Didactic and experiential learning are incorporated into the program with students imbedded within well-established clinical research teams. Activities include attending IRB meetings, recruitment and enrollment, data collection and entry, and regulatory items. Students complete knowledge pre- and post-assessments (Competency Index for Clinical Research Professionals-CIRCP) via REDCap surveys to assess learner knowledge acquisition and program effectiveness. Demographic, program evaluation, and 3-month follow up survey data are analyzed using descriptive statistics. RESULTS/ANTICIPATED RESULTS: Beginning in Spring 2022, the Intern Program has accepted 9 students with 5 completing the program, with 2 of this 5 having been offered employment as CRCs. Preliminary CIRCP assessment data indicates increased CRC knowledge upon Intern Program completion. Demographic data shows that students are mostly female and non-white (43% African American, 29% Hispanic). Additional results from the current cohort will be shared upon program completion. Of note is the development of partnerships with local colleges, including community colleges, to build awareness of the CRC career path and to provide opportunities for CRC exploration resulting in expansion and diversification of the clinical research workforce. DISCUSSION/SIGNIFICANCE: There is an industry wide shortage of CRCs. Our internship program has provided an effective method to expand and diversify the CRC workforce through knowledge acquisition and application building CRC skills and competencies. Lessons learned and future plans for intern expansion will be discussed.

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

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

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

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

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