OBJECTIVES/SPECIFIC AIMS: Alcohol craving, particularly in response to stress and alcohol cues, can lead to relapse in alcohol-dependent individuals. Hypothalamus-pituitary-adrenal (HPA) axis markers such as the cortisol to corticotrophin (CORT:ACTH) ratio have been shown to be a significant predictor of alcohol relapse. Our objective was to evaluate the influence of HPA-axis measures on intravenous alcohol self-administration (IV-ASA) in binge and nonbinge drinkers. METHODS/STUDY POPULATION: Healthy, non-dependent binge drinkers (n=14) and nonbinge drinkers (n=11) participated in this study. They underwent 3 personalized imagery sessions, where they heard 5-minute personalized audio scripts designed to trigger stress, alcohol craving, and neutral-relaxation states. Immediately following these cues, participants were given access to alcohol using a novel IV-ASA paradigm for 120 minutes. Serial blood samples were collected for cortisol and ACTH levels. Subjective measures were collected serially using the Subjective Units of Distress Scale (SUDS), Drug Effects Questionnaire (DEQ), and Alcohol Urge Questionnaire (AUQ). Analyses were conducted using linear regression. RESULTS/ANTICIPATED RESULTS: Results showed that peak and average ACTH levels as well as the CORT:ACTH ratio during the early phase of the IV-ASA session following the stress and alcohol cues were significantly higher than the neutral script; this effect was seen primarily in binge drinkers. After script administration, a greater change from baseline for ACTH predicted time to peak BrAC during IV-ASA. Gender and binge group predicted AUQ MAX (peak alcohol craving over the entire study session) and WANT MAX (peak “want more alcohol” scores over the session). There was a significant correlation between IV-ASA and increased ACTH peak and average values in binge drinkers. The DEQ and AUQ measures were positively correlated with ACTH peak and ACTH change from baseline. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings, to our knowledge, are the first demonstration that exposure to both stress and alcohol cues lead to an increase in ACTH during cue-induced IV-ASA, particularly in binge drinkers. These results suggest that changes in HPA-axis reactivity following stress and alcohol may be important determinants of alcohol consumption in non-dependent binge drinkers.

OBJECTIVES/SPECIFIC AIMS: Clostridium difficile is the most common cause of infectious antibiotic associated diarrhea. It is often refractory to antimicrobial therapy and fecal microbiota transplantation (FMT) is emerging as a therapeutic option. The objective is to characterize the direct effects of FMT on the gut microbiota. METHODS/STUDY POPULATION: Fecal specimens were obtained from a cohort of 29 subjects with recurrent C. difficile infection who received FMTs from 1 of 4 healthy donors as part of a phase 2 trial (Rebiotix). Fecal specimens were collected from the subject before FMT and up to 6 months post FMT. 16S rRNA sequencing and whole-genome shotgun sequencing were used to assess microbial community composition as compared by weighted Unifrac. RESULTS/ANTICIPATED RESULTS: Before treatment, the microbial community of subjects with C. difficile infection was highly distinct from the composition of the healthy donors in terms of metabolic profile. Quantification of phylogenetic community distance from donor by weighted Unifrac distance showed a significant decrease within the 1st week (Wilcoxon rank sum, p<0.01). This metric was predictive of both treatment failures and antibiotic resistance gene count (LR=22.45, p<0.0001). DISCUSSION/SIGNIFICANCE OF IMPACT: We conclude that distance from donor is a useful metric to quantify FMT success and that FMTs are a promising treatment for otherwise untreatable carriage of antibiotic resistance genes and organisms.

OBJECTIVES/SPECIFIC AIMS: Background: Renal transplantation (tx) is the optimal treatment for end-stage renal disease (ESRD) in children, but post-tx urinary tract infections (UTIs) may cause morbidity and reduce allograft survival. Objectives: To quantify the number and risk factors for UTIs in pediatric kidney tx recipients in preparation for an analysis of the morbidity and impact of UTIs on allograft survival. METHODS/STUDY POPULATION: Methods: We identified all patients who underwent kidney tx between 2001 and 2016 (n=390) at Children’s Healthcare of Atlanta (CHOA). Patients were included if they had >1 year of follow-up at CHOA. We conducted an IRB-approved, retrospective review of patient demographics, medical history, and tx outcomes in the 5 years following tx. RESULTS/ANTICIPATED RESULTS: Results: Of the 205 records reviewed to date, we identified 176 eligible patients (61.9% male). Mean age at tx was 11.7±5.5 years. In total, 58.5% had a deceased and 41.5% had a living kidney donor. Obstructive uropathy was the etiology of ESRD in 21.0%. Mean UTIs in all patients was 1.1/patient±2.7. On preliminary analysis, patients with a history of obstructive uropathy were more likely to develop a UTI than patients without (45.9% vs. 25.2%, p=0.014). There is a trend to more UTIs in patients with a history of obstructive uropathy compared with patients without (2.1±3.5 vs. 0.9±2.4, p=0.055). In males, there were more UTIs in patients with a history of obstructive uropathy compared to patients without (1.7±2.9 vs. 0.5±1.5, p=0.024). In all, 23.2% of all patients were on UTI prophylaxis post-tx; trimethoprim-sulfamethoxazole was the prophylactic antibiotic in 54.5%. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusions: UTIs are common post kidney tx in children, especially in those with a history of obstructive uropathy. The associated morbidity and impact on graft survival are unknown.

OBJECTIVES/GOALS: Assistive technology (AT) can improve older adults’ function in daily activities. However, Latinos are among the least likely to use AT. Given that primary health care physicians (PCPs) have low awareness about AT, this study aims to evaluate the usability and acceptability of an AT WebAPP among PCPs to increase older Latinos’ access to AT. METHODS/STUDY POPULATION: A team of an established researcher, a sub-graduate faculty and student, and a graduate student will recruit ten PCPs in Puerto Rico and will interview them to explore their current practice in addressing the functional needs of older Spanish-speaking Latinos. The researchers will then train PCPs in the use of a Spanish evidence-based AT WebAPP developed in one of our earlier studies. PCP participants will use the APP with their older patients for 30 days. At the end of the usage period, the analysis will include a mixed method design, consisting of the simultaneous collection of quantitative data using a validated scale followed by qualitative data through individual interviews. Quantitative data will be analyzed with descriptive statistics and qualitative data with thematic content analysis. RESULTS/ANTICIPATED RESULTS: We expect that the AT WebAPP will be rated as particularly useful and acceptable by the PCPs to increase older Latinos’ access to information about AT that could compensate for their physical function disabilities. We also expect that PCPs will offer recommendations for enhancing the design and usability of the AT WebAPP. DISCUSSION/SIGNIFICANCE: Studying the usability and acceptability of this AT WebAPP among PCPs will advance our understanding of its feasibility in enhancing PCPs AT knowledge and recommendations of AT devices for older adults with disabilities in Puerto Rico and in Latino communities in the continental United States.

OBJECTIVES/GOALS: The goal of this study was to perform a comparative, multi-reader, retrospective clinical evaluation of prostate multiparametric MRI (mpMRI) at 3 Tesla (3T) vs. 7 Tesla (7T) primarily in terms of prostate cancer localization. Subjective measures of image quality and artifacts were also evaluated. METHODS/STUDY POPULATION: Nineteen subjects were imaged at 3T and 7T between March 2016 and October 2018 under IRB-approved protocols. Four radiologists retrospectively and independently reviewed the data, and completed a two-part assessment for each dataset. First, readers assessed likelihood of cancer using Prostate Imaging Reporting & Data System (PI-RADS) guidelines. Accuracy of cancer detection was compared to findings from prostate biopsy. The numbers of correctly or incorrectly classified sextants were summed across all four readers, then used to summarize detection performance. Second, readers assigned a score on a five-point Likert scale to multiple image quality characteristics for the 3T and 7T datasets. RESULTS/ANTICIPATED RESULTS: Sensitivity and specificity of 3T and 7T datasets for sextant-wise cancer detection were compared by paired two-tailed t-tests. Readers identified more sextants harboring cancer with the 3T datasets while false-positive rates were similar, resulting in significantly higher sensitivity at 3T with no significant differences in specificity. Likert scores for image quality characteristics for 3T and 7T datasets were compared by applying paired two-tailed t-tests to mean scores of the four radiologists for each dataset. Readers generally preferred the 3T datasets, in particular for staging and assessment of extraprostatic extension as well as overall quality of the contrast-enhanced data. DISCUSSION/SIGNIFICANCE OF IMPACT: Readers agreed 7T prostate mpMRI produced images with more anatomic detail, though with equivocal clinical relevance and more pronounced artifacts. Reader unfamiliarity with 7T images is a major extenuating factor. Forthcoming technological developments are anticipated to improve upon the results.

OBJECTIVES/GOALS: This poster shares a case study on how a group at The Johns Hopkins University formed a translational lab missioned to reinvent currently existing treatments for acute spinal cord injuries, implanting in humans within a five-year window. The poster showcases how a project funded by the Defense Advanced Research Projects Agency has been implemented. METHODS/STUDY POPULATION: The translational team; Holistic Electrical; ultrasonic and Physiological Interventions Unburdening those with Spinal cord injury• (HEPIUS) Lab is composed of many parts as listed below: neurosurgeons; engineers; radiologists; public health specialists; statisticians; patient advocates; ethicists; sonographers; researchers; academic collaborators; and specialized industry partners. Sometimes physically separated; the team has videoconferencing carts across locations to stay connected at every step in the process. The lab facilities were organized with several key facets in mind: research and development (R&D); prototyping; fabrication; verification; and validation (V&V); animal model testing; cadaveric testing accessibility; mock operating room for simulations; and collaboration hubs. RESULTS/ANTICIPATED RESULTS: Due to communications with the US Food and Drug Administration (FDA), DARPA, patient advocates, ethicists, internal review boards, and other bodies, the team has a clear path towards clinical translation. The team has the following stages in progress or scheduled: manufacturing devices, benchtop testing, rat and pig models, biocompatibility testing, cadaveric testing, and clinical use. The lab space was designed to achieve these core functions. For rapid, in-house manufacturing, the lab has unique capabilities including 3D metal printing. For experiments, industry collaborations and equipment acquisitions enable the highest quality research. These technologies are assembled into diagnostic, therapeutic, testing, and manufacturing hubs to drive real change in the lives of many; the patient comes first. DISCUSSION/SIGNIFICANCE: This laboratory, team, and system of operation is aimed to enable novel practices for the clinical translation of spinal cord medical solutions. For researchers interested in launching their own translational work, this poster may serve as a reference, example, and inspiration for similar hopeful university-centered hubs.

OBJECTIVES/SPECIFIC AIMS: In an effort to elucidate the role of potentially cancer chemopreventive drugs, we leveraged the Mayo Clinic-Karolinska Institute collaboration to create a multidisciplinary team that included an epidemiologist, statisticians, and physicians. We performed a population-based cohort study to examine the association between low dose aspirin, non-aspirin NSAIDs, statins, metformin, other risk factors and the risk of biliary tract cancer (BTC), while assessing confounding by sex. METHODS/STUDY POPULATION: We conducted a nationwide Swedish population-based cohort study using the Swedish Prescribed Drug Registry, which virtually completely enumerates use of prescribed medications nationwide since 2005. BTC diagnosis (intrahepatic cholangiocarcinoma [iCCA], extrahepatic cholangiocarcinoma [eCCA] or gallbladder cancer [GBC]) was ascertained from the Swedish Cancer Registry. Age-scaled Cox models, with exposure as time-varying covariates, were used to calculate hazard ratios (HRs), separately for men and women. RESULTS/ANTICIPATED RESULTS: In the 5.7 million person cohort, the risk of iCCA was significantly lower in men using statins (HR 0.62,95%CI 0.39-1.00, p = 0.05), with a non-significant reduction in women. Statin use was associated with a significantly decreased risk of eCCA in both women (HR 0.60,0.38-0.94, p = 0.03) and men (HR 0.47,0.28-0.80, p = 0.01). Low dose aspirin (HR 0.76,0.60-0.97, p = 0.03) was associated with a lower risk of GBC only in women, while statins (HR 0.72,0.55-0.93, p = 0.01) showed a significantly decreased risk of GBC in women and a non-significant reduction in men. For all BTC subtypes, combined use of low dose aspirin and statins did not confer additional risk reductions beyond those achieved by statins alone. Male and female users of non-aspirin NSAIDs appeared to be at increased risk of BTC and its subtypes. Metformin did not significantly affect risk of BTC. DISCUSSION/SIGNIFICANCE OF IMPACT: Our collaborative efforts allowed us to develop the largest population-based cohort evaluating risk and protective factors for BTC. Our results provide strong evidence in favor of the chemopreventive roles of low dose aspirin and statins in a subtype- and sex-specific manner. Individual risk factors contribute to development of BTC subtypes in different magnitudes. The next steps to translate these findings into clinical practice require randomized clinical trials that validate our results and provide a more complete picture of the risk-benefit ratio.

OBJECTIVES/GOALS: Establishing a career trajectory geared towards undergraduates interested in a biomedical career has led to the development of a Clinical Research Training (CRT) Program. The purpose of this study is to evaluate the student experience of the program. It is our hopes to train the next generation of clinical researchers straight out of undergrad. METHODS/STUDY POPULATION: Establishing the success of the recently established Clinical Research Training Program and creating quality improvement measures has been analyzed with a focus on 5 domains. Outcome quality measurements and evaluation of the following domains have been completed from a student’s experience. These domains include: 1) the capstone course, 2) the internship experience, 3) career development opportunities, 4) hands-on training opportunities, and 5) post-baccalaureate career plans or career attainment. Each of these outcomes have been collected from students who have completed the program as well as students currently enrolled. Data will be obtained via qualitative measures such as course surveys, Likert scale ratings, and evaluation of data-based outcomes. RESULTS/ANTICIPATED RESULTS: In this ongoing study, results will demonstrate there is a percentage of students who were directed into clinical research positions due to their exposure to the clinical research world during their undergraduate training. Transferable skills such as CITI training, knowledge of good clinical practice, and familiarity of current research topics are associated with a higher likelihood to pursue a career in clinical research. Students placed within an associated internship slot with the community partners has also led to an increase in career placement in clinical research. Other factors provided by the course such as establishment of an extensive network, exposure to career pathways related to clinical research, and an increase in cross-trainings that lead to increased advancement in the scientific domain. DISCUSSION/SIGNIFICANCE: To address clinical research workforce gaps by training students during their undergraduate education. Also, by addressing this gap, we can begin to strengthen the career trajectory and goals of students interested in a career in the life sciences. By targeting this workforce, it can lead to an increase in diversity and retention in the workforce.

OBJECTIVES/GOALS: Prenatal cannabinoid use is increasing and more studies are needed to describe the neurodevelopmental impact on the fetus. However, pregnant cannabinoid users are a “hidden population,” which makes identification of these individuals for research difficult. Our study will employ three methods of recruitment and evaluate the success of each method. METHODS/STUDY POPULATION: We will recruit a total of 40 women in the third trimester of pregnancy who regularly use cannabinoid products thought to contain tetrahydrocannabinol (THC) and/or cannabidiol (CBD) throughout their pregnancies, and 20 control pregnant women who do not use those products. The purpose of this study is to evaluate the effects of prenatal cannabinoid use on the neurodevelopment of their offspring over the first year of life. We will employ three recruitment methods. First, targeted recruitment will occur in two university-based obstetrical clinics, where the obstetrician will present the study material and contact information. Second, we will utilize social media advertisements targeted to a specific demographic of Facebook users. Finally, we will employ the traditional method of distributing flyers in a non-targeted manner. We will track methods of recruitment success and gather information from the mothers on their preferences for recruitment approaches. RESULTS/ANTICIPATED RESULTS: Recruitment will start in January 2020 and continue for several months. We anticipate that the targeted method will yield the highest number of participants, and participants with the best fit for the inclusion criteria. However, it is possible that those women will be deterred by fear of having their drug use status revealed to their care providers, even though all research activity will occur independently from clinic visits and will not be transmitted to the electronic health record. The inclusion of a control group will also help foster “anonymity” for participants. The social media method has the potential for the greatest reach, but we expect many of these potential participants will fail to meet inclusion/exclusion criteria, as this is not as targeted as the first method. We anticipate a similar issue with the flyer-based approach. DISCUSSION/SIGNIFICANCE OF IMPACT: Optimizing recruitment of hidden and sensitive populations is crucial for clinical and translational research. Our goal is to identify strategies that can lead to best practices for engagement of those populations. Our conclusions could be applied in recruitment of sensitive populations for other clinical and translational research projects.

ABSTRACT IMPACT: The findings suggest that targeting parenting stress in combination with psychoeducation on nutrition and physical activity may have positive effects in improving healthy food choices such as reduction of fast food intake, which may in turn impact the health of toddlers and their families. OBJECTIVES/GOALS: Parent stress is associated with a myriad of unhealthy behaviors including overeating, decreased physical activity, which contribute to increased weight. Several programs have aimed to increase education of nutrition, but few have focused on parent stress to improve healthy food intake. The present study assessed parent stress and fast food intake. METHODS/STUDY POPULATION: Parents who have obesity and had a toddler in the age group of 2-5 years were enrolled for a preventive intervention study to assess the effect of a parent-based intervention to improve family health choices and reduce childhood obesity risk. The sample included 105 participants, mean age 34.80 (6.27) years old, mean body mass index (BMI) 35.51 kg/m2, 39.0% Non-Hispanic White, 20.0% Non-Hispanic Black, 22.9% multiracial, 12.4% Hispanic, and 5.7% other. Stress was assessed using the Perceived Stress Scale (PSS) to assess overall general stress and the Parenting Stress Index (PSI) to assess parent-specific stress. Chaos in the home and fast food intake were also assessed using self-report surveys. RESULTS/ANTICIPATED RESULTS: Preliminary results are based on available data as of October 2020, data collection and recruitment are still in progress. There was a significant correlation between fast food intake with PSS (r=.18, p=.04), chaos (r=.24, p=.02), and PSI (r=.25, p=.01). Using a hierarchical regression model, we entered home chaos in the first block which explained a significant amount of the variability (R2= .06, p=.04). PSS was entered in the second block, which was not significant (R2 change=.01, p=.50), and in the final block PSI was entered and was significant (R2 change=.13, p <.01). DISCUSSION/SIGNIFICANCE OF FINDINGS: The data indicate that parenting stress uniquely predicts fast food intake above and beyond what could be explained by home chaos and general perceived stress. Future analyses will assess a parent-based intervention targeting stress reduction to improve weight and health for the parent and their toddlers in order to reduce childhood obesity risk.

ABSTRACT IMPACT: Impaired neuromuscular control could lead to the failure in activation and deactivation of the target muscles in a timely manner, with the concurrence of activities of non-targeted muscles. OBJECTIVES/GOALS: Stroke leads to impaired capacity to manipulate objects with the hand in terms of timing and strength of grasp. The influence of abnormal coupling across more proximal arm muscles post stroke on the failure in normal functioning of finger flexor muscle activity is of interest to investigate. METHODS/STUDY POPULATION: We have recruited 12 participants with stroke hemiparesis in the sub-acute or chronic stage. Motor impairment of the arm was assessed using electromyography (EMG) and the Fugl-Meyer Upper Extremity (FMUE) assessment. Participants were requested to flex and relax the metacarpophalangeal (MCP) joints against motorized resistance in response to audible tones to determine timing and strength during flexion. They were asked to flex maximally, as quickly as possible, in response to the first of a pair of tones, and relax as quickly as possible after the second tone. Delays in initiation and termination were evaluated using EMG responses versus a predefined threshold. RESULTS/ANTICIPATED RESULTS: We anticipate greater delays in grasp initiation as well as in grasp termination in participants with a greater extent of abnormal coupling across more proximal muscles of the upper extremity in comparison to participants with a less extent, using the results of the FMUE assessment. Also it is expected that participants with a greater extent of the flexion synergy produce a less extent of force generation. The EMG results will show that activities of more proximal arm muscles precede the initiation of MCP flexion and their activity termination precedes that of MCP flexion, significantly more in participants with a greater extent of the flexion synergy. DISCUSSION/SIGNIFICANCE OF FINDINGS: The flexion synergy over the arm following stroke affects the timing and strength of hand grasp. Impaired neuromuscular control could lead to the failure in activation and deactivation of the target muscles in a timely manner, with the concurrence of activities of non-targeted muscles.

OBJECTIVES/GOALS: As question complexity in science and medicine increase, the need for teams with diverse skill sets grows as well. We identify essential roles and barriers that define the team environment within the National COVID Cohort Collaborative (N3C), an initiative grounded in interdisciplinary team science. METHODS/STUDY POPULATION: This work was compiled through a combination of observations, interviews, and survey responses involving members of the N3C research community, specifically those involved in N3C workstreams and clinical domain teams. Observational data was obtained through participation in N3C workstream activities and domain team research and meetings. The survey included five questions related to team science elements and barriers, as well as contrasting science-based teams and non-science-based teams, such as “What elements are common between both Team-Science and non-Team-Science teams?”, and was sent to members of two domain teams: Immunosuppressed and Compromised and Social Determinants of Health. RESULTS/ANTICIPATED RESULTS: Team science within N3C has a unique structure of roles and barriers that define the team environment of each project. Within each group, team and role management within team science is an ongoing process that occurs even after a team is formed. We obtained 8 survey responses that indicated communication, attribution, team management, collaboration, interdisciplinary diversity, and problem solving were key aspects to successful team science. Additionally, survey respondents identified prominent barriers to successful team science that included bandwidth constraints, lack of a shared scientific language, learning curves, funding, and lack of communication. DISCUSSION/SIGNIFICANCE: Communication was identified as a key component of team science and a prominent barrier, which indicates that successful team science relies on communication between team members. Thus, it is vital that teams identify and commit to using predefined methods of communication to function effectively.

OBJECTIVES/GOALS: There is a need to develop a workforce of translational research professionals with the skills to innovate, mobilize, and commercialize research for unmet needs in the Canadian health system. The objective of this study is to evaluate the impact and value of the master’s degree on the Translational Research Program (TRP) alumni. METHODS/STUDY POPULATION: This study will use a cross-sectional approach and an electronic survey will be administered to alumni. The TRP was established in 2015 and has graduated over 150 students since its inception. Participants will be recruited through convenience sampling via email, social media platforms, and personal communication. Eligible participants must have a conferred Master of Health Science in Translational Research from the University of Toronto. All collected data will remain anonymous and include demographic information about graduation year, race, ethnicity, gender, and employment status. Descriptive statistics will be used to analyze and report the findings. RESULTS/ANTICIPATED RESULTS: The results of this survey will be used to evaluate how the TRP graduate degree helps alumni contribute to healthcare, learn to think differently, and establish their professional networks. The findings will also be used to inform curriculum improvements, enhance competency-based assessments, and understand demographic differences in student cohorts to promote equity, diversity, and inclusion. Investigating the perspectives of alumni reflecting on their degree will support validating the program’s objectives and advance the integration of translational science principles in the healthcare workforce and community. DISCUSSION/SIGNIFICANCE: This research addresses the need to evaluate health sciences education to ensure the program’s novel pedagogical approaches are equipping the next generation of health professionals with the skills to accelerate the transformation of discoveries into interventions that benefit human health, improve clinical medicine, and enhance patient care.

OBJECTIVES/GOALS: Launch a case-based learning collaborative on best practices that meet social, emotional and physical health needs of underserved communities as they relate to environmental toxins—specifically those related to the train derailment in OH. Topics discussed could also include disasters and spills, air quality, extreme heat, and water. METHODS/STUDY POPULATION: In response to a call for action delivered by PA’s Acting Secretary of Health, we established a partnership between Penn State CTSI, Project ECHO at Penn State, and Primary Health Network (PHN). PHN is the largest Federally Qualified Health Center in PA, making it uniquely qualified to reach rural providers diagnosing and treating patients impacted by environmental events. Utilizing the ECHO model, we are hosting monthly, 1-hour sessions on environmental determinants of health starting October 2023. Experts in pulmonology, toxicology, atmospheric science, and rural medicine (whom many participants would have limited access to outside of the ECHO platform) and participants have the opportunity to share and learn from their varied experiences exemplifying a culture of ‘all teach, all learn’. RESULTS/ANTICIPATED RESULTS: Project ECHO is an ideal model for upscaling workforce quickly, allowing participants to be responsive in the care of their community, regardless of location and access to specialty clinics. 74 participants across 26 PA counties registered for the series, ranging from PCPs, medical directors, and state officials. Upon registration, nearly half of our direct patient-care participants do not routinely conduct an environmental exposure history and almost 70% report receiving questions from their patients related to how the environment might impact their health. More than half of those providers reported feeling unprepared to answer patients’ questions related to the environment’s impact on their health. Evaluation data will be collected at enrollment, after each session, and post-series. DISCUSSION/SIGNIFICANCE: This series could result in: * Reduction of health disparities caused by environmental events (no cost, virtual learning) * Increased preparedness to quickly address health questions/symptoms related to environmental exposures * Increased awareness of the environmental impacts on health. * Improved testing/treatment for patients

OBJECTIVES/GOALS: Our goal is to explore and collaboratively identify the team science competencies essential for Clinical Research Professionals at all experience levels and how these competencies relate to the Joint Task Force for Clinical Translational Research Professionals Competencies. METHODS/STUDY POPULATION: Team science competencies for clinical research professionals are poorly defined. The JTF Clinical Trial Competencies lack sufficient emphasis on team science, though it is briefly included in two JTF competency domains: Leadership & Professionalism, and Communication & Teamwork. The competencies primarily focus on tasks related to clinical research and basic knowledge of product development; however, a conceptual model for applying the competencies using a team science lens is needed. Currently, the JTF competency figure is often thought of as sequential, given the competencies are numbered, creating the misconception that the last competencies are less important. We support a new figure showing the permeability of team science across competencies and the connectedness and equality of the competencies. RESULTS/ANTICIPATED RESULTS: Our anticipated results are to show the integral nature of team science in clinical research professional communities of practice. Once complete, we will have identified measurable team science competency-based skills essential for clinical research professionals at various levels of expertise. Understanding the multi-dimensional team science competencies will inform targeted team science education and training for clinical research professionals. Our revised competency framework provides an improved team science conceptual model for clinical translational science. DISCUSSION/SIGNIFICANCE: Our work will define team science competencies as related to clinical research professionals at all experience levels. The interdependence of teams across clinical trial activities necessitates a consideration of an improved conceptual framework for clinical translational team science competencies.

OBJECTIVES/SPECIFIC AIMS: Congenital heart disease (CHD) is the most frequently occurring birth defect in the United States affecting about 40,000 infants born every year. Despite significant advances in postsurgical survival, developmental outcomes remain disproportionately poor. Therapeutic hypothermia has been used for neuroprotection during cardiac surgery since the 1950s. Infants undergoing cardiac surgery are typically cooled to 28–33°C during the operation and then rapidly rewarmed to normothermia following surgery at a rate of 1°C every 3–5 minutes to minimize concerns surrounding the risks associated with prolonged bypass exposure. However, emerging evidence from animal models has shown rapid temperature changes following surgery may diminish or even negate the neuroprotective effect of intraoperative hypothermia. No prospective studies have assessed the safety or impact of alternative approaches to postoperative temperature management on the outcome of infants with CHD undergoing cardiac surgery. Therefore, we conducted a pilot study to examine the safety of a novel application of a temperature-regulating device to slowly rewarm infants with congenital heart disease over the 12 hours following cardiac surgery. METHODS/STUDY POPULATION: From November 2014 to July 2016, infants with CHD requiring surgery with cardiopulmonary bypass before the age of 12 months were prospectively recruited. Infants were randomized in blocks of 3 with 1 allocated to standard of care and 2 to the experimental protocol. Infants assigned to the standard of care were rewarmed in the operating room while on bypass at a rate of 1°C every 3–5 minutes back to a temperature of 37°C. Infants assigned to the experimental intervention, were rewarmed on bypass to 35°C and then over the subsequent 12 hours following surgery, gradually rewarmed using an FDA approved “cooling blanket” to increase temperature by 0.3°C every 2 hours for 6 hours and then by 0.2°C every 2 hours for 6 hours until the goal temperature of 36.5°C was achieved. Frequency of serious, moderate and other adverse events were tracked. Detailed vital sign data was collected hourly for the first 12 hours after surgery and then every 6 hours for the next 36 hours and included temperature, highest and lowest heart rate, highest and lowest systolic blood pressure, and highest and lowest diastolic blood pressure. Presence or absence of abnormal cardiac rhythms was recorded per 24-hour interval. Chest tube output was recorded in cc/kg/8 hours for as long as the chest tube was in place. Laboratory data points included serum creatinine level, serum glucose level, liver function tests (AST and ALT), platelet count, hematocrit level, PTT, INR, fibrinogen, white blood cell count and lactate. Blood samples for biomarkers of brain injury (s100b and NSE) were obtained on all infants at the following 4 intervals; the preoperative setting for baseline, postoperatively after bypass, on postoperative day 1, and on postoperative day 2. For this safety study, the primary outcome measure was a composite outcome of the frequency of serious adverse events as well as the frequency of any adverse events and was compared among treatment groups. Data were analyzed using an intent to treat analysis. The study was approved by the Maine Medical Center Institutional Review Board. RESULTS/ANTICIPATED RESULTS: Seven infants were randomized to the standard of care group and 9 were randomized to the experimental group. There were 2 exclusions after randomization in the standard of care group with 1 death in the operating room and 1 unsuccessful attempt to wean from bypass. The mean temperature upon arrival to the PICU for the experimental infants was 35.2°C (range 34–36°C) and for the standard of care infants was 37.5°C (range 36.9–38.9°C). For the first 8 hours after surgery, infants in the standard of care group had mean temperatures over 37.0°C. There were no significant differences in the frequency of serious, moderate, or other adverse events between the standard of care group and experimental group. No infant in either group had need for cardiopulmonary resuscitation or exploratory surgery within 48 hours following surgery nor did any infant experience any clinically appreciated adverse neurological events such as stroke or seizure. No infant in either group experienced clinically significant bradycardia of less than 100 beats per minute or sustained tachycardia of greater than 160 beats per minute. There was a trend toward lower heart rates in the experimental group. Junctional Ectopic tachycardia (JET) occurred in 2 patients in the experimental group and 1 in the standard of care group. The mean highest INR in both groups was 1.4 (range 1.2–1.6). The mean lowest recorded platelet level in the first 48 hours was 128.8 (range 87–160) in the standard of care group and 123.8 (range 49–229) in the experimental group. Infants in the experimental group had lower chest tube output overall than the standard of care infants. The mean days of intubation for standard of care infants was 5 days (range 1–15 days) and for experimental infants the mean was 3.7 days (range 0–16 d). The PICU length of stay was shorter for the experimental infants (6.9 vs. 12 d for standard of care). The total length of stay was also shorter for experimental infants (12.4 vs. 16.4 d for standard of care). Serum biomarkers of brain injury (s100b and Neuron specific enolase) were elevated in the immediate postoperative period for infants in the standard of care group compared with the experimental group but normalized more quickly for standard of care. DISCUSSION/SIGNIFICANCE OF IMPACT: This small pilot study suggests that mild hypothermia following congenital heart surgery in infants under the age of 12 months is safe as there was no increase in the rate of severe, moderate, or other adverse outcomes in infants who received the experimental treatment of delayed rewarming. This study provides evidence for the efficacy of the cooling blanket in regulating the temperature of infants after surgery. Trends toward lower chest tube output, shorter intubation and decreased length of stay are possibly the result of improved hemodynamic stability in the absence of postoperative fever. Future studies will need to assess the effect of mild hypothermia compared with a normothemic control group.

ABSTRACT IMPACT: This study helps translate investigational bedside optical coherence tomography into improved diagnosis and care of preterm infants at risk for retinopathy of prematurity. OBJECTIVES/GOALS: In retinopathy of prematurity screening, fundus photography may be of limited quality in eyes with dark fundus pigmentation (FP). The goal of this study was to evaluate the impact of FP on overall scan quality and retinal layer visibility on investigational bedside optical coherence tomography (OCT) in preterm infants. METHODS/STUDY POPULATION: We analyzed 846 OCT scans captured prospectively from 188 eyes of 94 preterm infants enrolled in the BabySTEPS study (NCT02887157). Trained ophthalmologists, masked to OCT findings, determined FP (blond, medium, or dark). Expert graders, masked to FP, evaluated OCT images for: 1) overall OCT quality (excellent, acceptable, poor, or unusable); and 2) all age-appropriate retinal layers visible (yes or no). To assess the association of FP with OCT quality (excellent/acceptable or poor/unusable) and retinal layer visibility, we performed multivariable logistic regression modeling, adjusting for biologic and demographic confounders and correlations from repeated OCT scans and paired eyes. RESULTS/ANTICIPATED RESULTS: Mean birthweight was 964 (SD=283) grams, mean gestational age was 27.8 (SD=2.6) weeks, 48 (51%) infants were male, and 51 (54%) were non-white. On exam, 72 (38%) eyes had blond FP, 92 (49%) had medium, and 24 (13%) had dark. OCT quality was excellent or acceptable in 725 scans (86%) and all age-appropriate retinal layers were visible in 781 scans (92%). Compared to eyes with blond FP, eyes with medium and dark FP did not have higher odds of poor/unusable OCT scan quality (adjusted OR 0.87 [95% CI 0.50-1.48] and 0.49 [95% CI 0.16-1.55], respectively) or not all age-appropriate retinal layers visible on OCT (adjusted OR 1.17 [95% CI 0.39-3.51] and 0.57 [95% CI 0.15-2.20], respectively). DISCUSSION/SIGNIFICANCE OF FINDINGS: Medium and dark FP did not impact overall scan quality or age-appropriate retinal layer visibility on investigational bedside OCT in preterm infants. This study supports the feasibility of using OCT to analyze retinal microanatomy in diverse populations of preterm infants with a range of FP.

OBJECTIVES/SPECIFIC AIMS: There are currently no established blood-based biomarkers of recovery and neural repair following stroke in humans. Such biomarkers would be extremely valuable for aiding in stroke prognosis, timing rehabilitation therapies, and designing drugs to augment natural repair mechanisms. Metabolites, including lipids and amino acids, are engaged in many cellular processes and cross the blood-brain barrier more easily than proteins. Recent advances in liquid chromatography / mass spectrometry (LCMS) allow researchers to obtain a biochemical fingerprint of the metabolites in various biofluids. Thus, metabolite biomarkers of neural repair after brain injury are a promising avenue for future research. Objective: Design and conduct a study to identify metabolite changes in the blood associated with good and poor motor recovery following stroke. METHODS/STUDY POPULATION: We launched the Biomarkers of Stroke Recovery (BIOREC) study, which seeks to enroll 70 participants suffering arm motor impairment following stroke and 35 matched controls. BIOREC is a longitudinal observational study. Fasting blood samples are collected at 5, 15, and 30 days post-stroke, processed, and stored in the Georgetown Lombardi biorepository. Outcome measures, including measures of motor impairment, cognition and language, are assessed at 5, 15, 30, and 90 days post-stroke. The primary outcome measure is the upper extremity Fugl-Meyer score. Control participants are matched for age +/− 1 yr, race, gender, cardiovascular comorbities, and statin use through a computer algorithm that screens the entire MedStar electronic health record (EHR). Control participants provide 2 fasting blood samples one month apart. Once all samples are collected and sent for LCMS analysis, logistic regression analysis will identify potential metabolite biomarkers by comparing participants with good recovery to those with poor recovery as well as stroke participants to controls. RESULTS/ANTICIPATED RESULTS: To date, forty stroke participants have enrolled from 4 acute care hospitals in the Washington, DC metro region and completed all study procedures. Twenty stroke participants either dropped out or were withdrawn due to other medical concerns. Stroke patients ended up at a variety of venues following their acute hospitalization including the acute rehabilitation hospital, skilled nursing facilities, and home. We learned to overcome these logistical challenges by traveling to wherever the patients were sent and notifying medical providers of their study participation. In rare cases we have paid to transport patients from skilled nursing facilities to the clinic, which has reduced dropouts. In addition to the stroke participants, we have enrolled 7 healthy control participants using the EHR screening algorithm. DISCUSSION/SIGNIFICANCE OF IMPACT: Performing a longitudinal study in the early recovery phase following stroke is logistically challenging, but feasible. Difficulty in identifying participants with isolated motor impairment requires added effort to eliminate dropouts. Screening the EHR is an effective method to identify matched controls. Future metabolomics analysis of stored blood samples holds promise to identify biomarkers of stroke recovery and neural repair.

OBJECTIVES/GOALS: Previous research has shown acute and chronic alcohol effects on cardiac function, including elevated heart rate (HR) and lowered heart rate variability (HRV). This study aimed to examine the relationship between cardiac reactivity and subjective response following intravenous (IV) alcohol in non-dependent drinkers. METHODS/STUDY POPULATION: Non-dependent drinkers (N = 46, average age = 25.2) completed a human laboratory IV alcohol self-administration (IV-ASA) session. Subjective response to alcohol was assessed using the Drug Effects Questionnaire (DEQ) and Alcohol Urge Questionnaire (AUQ). Drinking behavior was assessed using the Alcohol Timeline Followback (TLFB) and Alcohol Use Disorders Identification Test (AUDIT). HR was recorded using the Polar Pro Heart Rate monitor throughout the session. HRV measures were calculated using guidelines determined by the Task Force of the European Society of Cardiology and The North American Society of Pacing and Electrophysiology. RESULTS/ANTICIPATED RESULTS: Recent drinking history as measured by the AUDIT and TLFB was not significantly different by sex. Results showed heavier drinking measures (AUDIT and TLFB) were positively associated with HRV measures (all p-values < 0.02). Those who reported a greater increase in alcohol craving (AUQ score) and wanted more alcohol (DEQ) following an alcohol prime, showed a greater change in HRV (p < 0.005). When examining HRV change from baseline throughout the priming session, there was a significant sex interaction for NN50 (p < 0.03) and a trend for PNN50 (p-value < 0.07). DISCUSSION/SIGNIFICANCE OF IMPACT: Acute IV alcohol alters cardiac reactivity measures in non-dependent drinkers. Future directions include examining the role of sex in HRV changes during alcohol consumption during IV-ASA. Understanding the effect of alcohol on cardiac reactivity and physiology may help characterize those at risk for alcohol use disorders.

OBJECTIVES/SPECIFIC AIMS: The purpose of this study was to provide individuals who have experience with cognitive behavioral therapy (CBT) with a demonstration of how using their therapeutic strategies affects their brain activity. Two challenges that face CBT and other cognitive therapies are (1) sustaining the gradual, incremental behavioral changes characteristic of the treatment and (2) measuring associated biological changes. These challenges may impede treatment efficacy and may negatively affect treatment outcomes, including patient discontinuation of CBT. Ideas for addressing these issues include providing patients with (1) a more immediate indicator of therapy effectiveness as well as (2) a biological index of behavioral change. In this study, we aimed to provide participants with an index of biological change based on therapeutic experiences via use of real-time functional magnetic resonance imaging (rtfMRI) neurofeedback. METHODS/STUDY POPULATION: We recruited participants who had already completed cognitive therapy as part of a clinical trial for depression at the University of North Carolina at Greensboro (n=13). In the present experiment, participants were asked to provide a list of negative autobiographical memories or worries as well as cognitive strategies they use to cope with negative moods. The task consisted of COUNT, MEMORY, and STRATEGY trials (30 s each). During baseline COUNT trials, participants counted backwards (e.g., 300–4). During MEMORY trials, they viewed phrases previously developed describing their negative autobiographical memories/worries. During STRATEGY trials participants viewed a strategy they use to help them process the memory/worry. First, a localizer run was completed to determine a unique region of interest for each participant. We identified peak activation within the cingulate cortex to the contrast of MEMORY (STRATEGY+COUNT). Although the task was the same, no neurofeedback was displayed during the localizer run. During the feedback runs, participants were shown neurofeedback from the cingulate cortex following both the MEMORY and STRATEGY trials. This activation was represented on a signal bar display and represented the average cingulate activation during the trial. Unlike many rtfMRI studies, the purpose here was not for participants to interact with the neurofeedback directly. Rather, a feedback summary was shown to participants after each MEMORY and STRATEGY trial as an index of how brain activity changed in response to negative memories/worries and therapeutic strategies. Our goal was not for participants to learn to self-regulate the cingulate cortex, but rather to provide participants with a metacognitive demonstration of strategy efficacy. Participants were given detailed instructions regarding the task design, the role of the cingulate cortex in depression, as well as the hypothesized direction of activation during the MEMORY and STRATEGY phases to help them interpret the neurofeedback. RESULTS/ANTICIPATED RESULTS: Results revealed that “stronger neurofeedback” (defined as the difference between STRATEGY vs. MEMORY trials) correlated with self-reported strategy efficacy ratings immediately following the scan session (p<0.05). More importantly, stronger neurofeedback predicted both self-reported strategy efficacy and frequency of use 1 month following the MRI session (p<0.05). Importantly, this relationship was specific to only those strategies used inside the scanner; and no such relationship was observed at baseline. Neuroimaging results revealed that during the MEMORY phase, activation within inferior frontal gyrus and supramarginal gyrus correlated with baseline BDI score (whole brain, cluster corrected with FSL Flame 1 to p<0.05). During the STRATEGY phase, the periaqueductal gray nucleus, insula, and temporal pole predicted self-reported frequency of strategy use 1 month post-scan session (whole brain, cluster corrected with FSL Flame 1 to p<0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: We believe this study holds promise to provide a powerful demonstration for individuals that strategies used to cope with negative moods can produce significant changes in their brain.