OBJECTIVES/GOALS: While CTSA hubs have contributed to the successes in COVID-19 clinical research, understanding the role of the CTSA consortium in translating vaccine efficacy and availability to awareness and implementation. The goal of this study is to quantitatively assess the use of social media in the dissemination of COVID 19 vaccine content across 60+ CTSA Hubs. METHODS/STUDY POPULATION: Structured search terms in the CTSA Search Solutions database were used to identify CTSA Hub website pages highlighting “COVID-19 Vaccination Information.” Each link identified was manually reviewed for vaccination content. The links and content identified by CTSA Search Solutions were then validated by advanced Google search operator “vaccine site” and manual review of CTSA Hub websites. Official CTSA Hub social media platforms were searched for vaccine proliferation content from January 1, 2020 to November 11, 2021. Data points collected included Community Targeted Vaccine Content, Vaccine Awareness, Vaccine Distribution, Vaccine Clinical Trial, Vaccine Related Media, Social Media Presence, and Social Media Vaccine Proliferation. RESULTS/ANTICIPATED RESULTS: In examining content, of the 64 listed CTSA Hubs, 52 of (67.2%) hosted one or more categories of COVID-19 vaccine information, and 16 (25%) hosted three or more categories. The most common category was “Community Targeted Information” with 27 (42.2%) hubs; the least common category was “Vaccine Distribution” with 5 (7.8%) hubs. Examining social media for vaccine proliferation, 41 (64.1%) hubs had connected social media and 23 (35.9%) hubs had vaccine proliferation posts. The most common platform was Twitter with 37 hubs; the least common platform was Instagram with 5 hubs. DISCUSSION/SIGNIFICANCE: Our investigation demonstrated varying Phase 4 translational efforts via social media among the CTSA Hubs for COVID-19 vaccine implementation. These novel findings identify promising opportunities for enhancement while emphasizing proven strategies from CTSA hubs nationwide. Further research will elucidate granular trends among CTSA hubs.

OBJECTIVES/GOALS: Writers with high self-efficacy perform better than writers with low self-efficacy regardless of writing ability. We investigated whether Shut Up & Write® (SUAW), a less-intensive writing intervention, produced gains in writing self-efficacy similar to those reported by intensive, longer-term interventions. METHODS/STUDY POPULATION: Meetings were held 2x/wk for 5 wks via Zoom, for 1 hour. Participants were encouraged to attend at least 1x/wk. The 1st few mins were devoted to a discussion of what each person planned to work on. Then, a timer was set and each writer muted themselves, shuttered their webcam, and wrote. When the alarm sounded, everyone returned to the group, and discussed what was accomplished. We measured writing self-efficacy before & after participating in SUAW using a pre-post survey design and used two-tailed paired t-tests to test for significant differences between pre- and post-test means. SUAW participants (n=23) were in 1 of 2 categories: 10 were self-selected LEADS scholars from MSIs, and 13 were medical students in a palliative care program. 86% were URB, 78% were female. RESULTS/ANTICIPATED RESULTS: Seven (30%) SUAW participants completed both the pre- and post-survey. Individuals showed significantly higher agreement from pre-to-post on the self-efficacy item “I have a generally positive attitude toward writing” (p=0.047) using a 5-point Likert scale from “completely agree” to “completely disagree.” Most other items did not indicate significant change between pre- and post-survey. The mean of the question “How satisfied were you with this Shut Up & Write activity?” which appeared only on the post-survey (n=10) was 1.10 (1=extremely satisfied, 5=extremely dissatisfied). Anticipated result: We suspect that the benefits of SUAW are best actualized by ongoing attendance, and that benefits are cumulative. DISCUSSION/SIGNIFICANCE: We found that participation in SUAW promotes writing self-efficacy in early-career URB researchers. This is an exciting finding because publishing ones research is essential for academic advancement, and research supports a relationship between writing self-efficacy and writing production. This may curtail URB scientists’ rate of attrition.

OBJECTIVES/SPECIFIC AIMS: Identify objective neurological substrates of cognitive fatigue in Parkinson’s disease and in aging. METHODS/STUDY POPULATION: Structural and diffusion MRI. Behavioral assessments for aged adults and Parkinson’s disease. RESULTS/ANTICIPATED RESULTS: Gray and white matter deficits that correlate with deficits in the basal ganglia for fatigued Parkinson’s disease patients Versus anterior cingulate cortex in healthy aged adults with fatigue. DISCUSSION/SIGNIFICANCE OF IMPACT: Over 50% of patients with Parkison’s disease and 38% of healthy older adults suffer from cognitive fatigue. However, diagnostics are limited to subjective surveys and there are no treatments for either population. Therefore, objective measures are greatly needed for better diagnosis and development of treatment targets.

OBJECTIVES/SPECIFIC AIMS: Cesarean delivery is typically performed in the extremely preterm period (23 to 28 weeks) when the fetus is in breech presentation to avoid the potential risk of head entrapment by an insufficiently dilated cervix during a vaginal delivery. Assessment of the prevalence of extremely preterm breech cesarean delivery would help to appropriately guide future clinical interventions designed to increase the feasibility of vaginal delivery for this sub-group of patients. METHODS/STUDY POPULATION: We performed a cross-sectional study of the 2106 U.S. National Vital Statistics birth certificate database to estimate the prevalence of cesarean deliveries performed during the period of gestation from 23 to 28 weeks with a fetus in breech presentation. RESULTS/ANTICIPATED RESULTS: An analysis of the total births in the 2016 registry (3,945,875) was performed. The gestational age was limited to the target range of 23 0/7 to 27 6/7 weeks. Multiple gestation deliveries were excluded. This yielded 16,092 births of which 4,849 were noted to have breech presentation. The proportion of cesarean deliveries performed for singleton breech fetuses at this gestational range was 87% (4,203/4,849). DISCUSSION/SIGNIFICANCE OF IMPACT: The probability of undergoing a cesarean delivery for an extremely preterm fetus in breech presentation is notably higher (87%) when compared to an overall cesarean delivery rate of 31.9%. Specific interventions to allow for vaginal delivery in this particular sub-group of the obstetric population would be useful to reduce maternal morbidity by increasing vaginal deliveries. Future work will attempt to address innovative solutions to prevent head entrapment by the cervix in this particular population and ultimately avoid cesarean delivery.

Every research study that includes volunteer participants requires safety assurances in proportion to the risks of the study. Investigator-initiated clinical research can present unique regulatory challenges particularly for studies with a risk profile that warrants more oversight than minimal risk but less than for large, commercial, or high-risk research. The use of an independent safety officer (ISO) offers a middle way of right-sizing oversight to match the risk. ISOs are clinicians or researchers with relevant expertise who are independent of the investigator and the research study. Their relationship to the study is defined by a formal charter which is aligned with the protocol and Data and Safety Monitoring Plan to address the oversight process, responsibilities of the ISO, and clearly describe the variables to be monitored. The ISO responsibilities include reviewing safety data, adverse events, recruitment, demographics, study progress, data quality, protocol changes, and any new scientific information that pertains to the trial. Finally, the ISO reports in their review on any significant findings may propose modifications to the study or a need to stop the trial.

OBJECTIVES/SPECIFIC AIMS: Determine whether GABA-A receptor binding is abnormal and linked to dystonia symptoms in cervical dystonia (CD). METHODS/STUDY POPULATION: There is increasing evidence that a key pathophysiological mechanism in adult-onset focal dystonia is a reduction in inhibitory control over the sensorimotor network. Results from a recent 11C-flumazenil PET imaging study suggest that abnormal inhibitory signaling in genetic and sporadic forms of dystonia may be due to reduced GABA-A binding. It remains unknown whether CD, the most common form of adult-onset focal dystonia, is associated with abnormal GABA-A binding. The goal of this research is to determine if GABA-A receptor binding is abnormal and linked to dystonia symptoms in CD. RESULTS/ANTICIPATED RESULTS: We investigated whole brain GABA-A binding in 15 CD patients (11F; 64±8 y) and 15 healthy controls (10F; 64±9 y) using 60-minute dynamic 11C-flumazenil PET scans. GABA-A receptor binding potential (BP) was estimated using a simplified reference tissue model. A 2-sample t-test was used to identify voxel-wise GABA-A BP differences between groups, and a regression analysis used to test for correlations between GABA-A BP and disease severity as measured with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). A conventional region of interest analysis was also conducted to quantify BP changes within the sensorimotor network using the automated anatomical labeling atlas. DISCUSSION/SIGNIFICANCE OF IMPACT: CD patients have reduced GABA-A receptor binding compared with healthy controls, with the greatest reduction seen within the sensorimotor region of the thalamus. Furthermore, reductions in GABA-A binding in brain regions associated with coupling sensory and motor information predict motor severity. These findings support that reduced GABAergic signaling within sensorimotor integration regions is a key mechanism underlying dystonic symptoms in CD and could help inform the development of better, more targeted treatment options.

OBJECTIVES/GOALS: The extent that Clinical and Translational Science Award (CTSA) programs offer resources accessible online for training in community-engaged research (CEnR) core competencies is unknown. This study cataloged CEnR resources accessible online from CTSAs and mapped resources to CEnR core competencies. METHODS/STUDY POPULATION: Eight domains of CEnR core competencies were identified: knowledge/perceptions of CEnR; personal traits necessary for CEnR; knowledge of/relationships with communities; training for performing CEnR; CEnR methods; program evaluation; resource sharing and communication; and dissemination and advocacy. A systematic review of CEnR resources accessible online from CTSAs was conducted between July 2018 and May 2019. Resource content was independently reviewed by two reviewers and scored for inclusion of each domain of CEnR core competencies. Domain scores across all resources and inter-rater reliability in scoring domains were assessed using descriptive statistics and Cohen’s kappa coefficients. RESULTS/ANTICIPATED RESULTS: Overall, 214 resources available from 24 CTSAs were eligible for full review. Scoring discrepancies for at least one domain within a resource initially occurred in 51% of resources. “CEnR methods” (50.5%; 108 of 214) and “Knowledge of/relationships with the community” (40.2%; 86 of 214) were most frequently addressed and “Program evaluation” (12.1%; 26 of 214) and “Dissemination and advocacy” (11.2%; 24 of 214) were least frequently addressed domains. Additionally, challenges were noted in navigating CTSA websites to access CEnR resources, and CEnR competency nomenclature was not standardized. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings guide CEnR stakeholders to identify CEnR resources accessible online and gaps to address in CEnR resource development. Standardized nomenclature for CEnR competencies is needed for effective CEnR resource classification. Uniform organization of CTSA websites may maximize navigability. CONFLICT OF INTEREST DESCRIPTION: In addition to the funding information listed previously (see above), within the last three years, R.J. Piasecki has been employed as: Project Coordinator, CEnR Online Learning Project, Johns Hopkins University School of Nursing (Current) Temporary Employee (Doctoral Student Intern), Michigan State University Institute for Health Policy (Current) Clinical RN, Intrastaff at the Johns Hopkins Health System (Past) Research Data Analysis Assistant, Maryland Institute for Emergency Medical Services (Past - contracted)

OBJECTIVES/GOALS: This project has two linked aims. (1) It seeks to integrate the TSBM into specific practices and processes to advance its integration into translational research and translational science processes. (2) Via this integration, it aims to determine ways to expand the TSBM as a conceptual model. Ultimately, we aim to advance the TSBM framework and use. METHODS/STUDY POPULATION: We developed a process that implemented and integrated the TSBM within three intentionally-distinct processes. First, we expanded the use of the TSBM case study from a focus on research studies to a focus on translational research programs, and specifically workforce development programs. Second, we integrated TSBM domains and indicators into a new Duke CTSA-wide database used to track, monitor, and assess activities and achievements across the CTSA. Third, we embedded TSBM and its indicators into our Pilots projects application and review process as well as ongoing reporting. RESULTS/ANTICIPATED RESULTS: We were able to successfully integrate the TSBM model into the processes indicated in methods, yet this integration identified opportunity to improve the model to enhance its applicability and value. We found the TSBM applies in distinct ways to translational science programs compared to research studies, with added indicators better accommodating TSBM application to programs. To properly integrate TSBM into progress monitoring systems, we found added needs to ensure comprehensibility for a wide array of researchers and program implementers. Across uses, we identified challenge distinguishing between TSBM benefits as demonstrated versus potential and ambiguity in potential as based on time to benefit realization, likelihood of realization, or centrality of a specific project to realization. DISCUSSION/SIGNIFICANCE: Our session contributes significantly to the field of translational research and science through its focus on advancement and implementation of an innovated model in its early stages, including how researchers and translation science entities can incorporate this model into their own work beyond the traditional use of case studies.

OBJECTIVES/SPECIFIC AIMS: Stakeholder engagement has been proposed to help realign clinical and translational research with the needs of clinicians, patients, and policymakers. Increasingly, funders and researchers seek to partner with stakeholders to inform study design, execution and dissemination of results. Kids and families Impacting Disease through Science (KIDS) is a program of the American Academy of Pediatrics that seeks to engage youth in clinical research. United States KIDS programs participate in International Children’s Advisory Network activities. The Chicago KIDS Advisory Board program at Walter Payton College Preparatory School, a Chicago Public School, was initiated in 2015 to foster and develop interest in careers in science, research and healthcare and provide youth perspectives to academic and industry researchers on the design and development of pediatric research studies. This project engaged youth advisors in creation and evaluation of a video explaining clinical research and informed consent for Ann & Robert H. Lurie Children’s Hospital, a clinical partner of the Northwestern University Clinical and Translational Sciences Institute. METHODS/STUDY POPULATION: The Payton program advisory board sessions are 1.5hr interactive seminars held on 1–2 school days each month. During the 2016–2017 school year, students participated in 3 stakeholder sessions, led by Lurie Children’s hospital researchers, to advise development of a script, storyboards, and ultimately an animated video that informs children and families about participation in clinical research to aid in the decision-making process. Qualitative research methods were used to examine attitudes towards clinical research and assess the video on content objectives, clarity of concept, and appropriateness for a pediatric audience. Following production, students from the 2017–2018 advisory board viewed the final video and presurvey and postsurvey were administered to assess the effect of video on the comprehension of 8 key concepts of informed consent on a 5-point Likert scale. The Wilcoxon signed-rank test was used to compare median pretest and post-test ranks. Results of this analysis were reviewed in seminar and students provided written contribution to this abstract. RESULTS/ANTICIPATED RESULTS: In total, 11 Walter Payton high school students participated in video development and 27, who were naïve to development, participated in the pre and post evaluation sessions. Students ranged from Freshman to Seniors and reflected the diverse ethnic and racial background of Chicago. A positive change from pre to post-test survey was observed in all questions presented assessing comprehension of key concepts of informed consent. The median post-test ranks were statistically significantly higher than the median pre-test ranks for all questions (p<0.01 in all). DISCUSSION/SIGNIFICANCE OF IMPACT: Chicago KIDS youth advisors were engaged in all aspects of the design of the research tool and gained experience in stakeholder contribution from study design to evaluation and publication. The students will next be involved in the design of a prospective randomized study to test the efficacy of the video compared with standard recruitment and consent practices. Given the difficulty of recruiting youth for clinical trials, development of effective engagement practices in is critically important. Our findings demonstrate the feasibility of utilizing youth advisors in a public school based setting.

OBJECTIVES/SPECIFIC AIMS: Over 80% of CTSA programs have a community advisory board (CAB), an effective strategy to increase community engagement (CE) in research. Little is known about how the research discussed with CABs aligns with community priorities (i.e., bi-directionality). This program evaluation assessed the health topics presented by researchers to the CABs linked to our CE Program at all three Mayo Clinic sites (MN, AZ, and FL) for relevance to local community needs. METHODS/STUDY POPULATION: Two coders classified Mayo researcher presentations to our CABs from 2014-2018 for relevance to needs identified in the local 2013 and/or 2016 County Health Needs Assessments and specific topic(s); with high levels of agreement (Kappa=0.90). RESULTS/ANTICIPATED RESULTS: Overall, of the 65 presentations 41 (63%) addressed one or more local health needs (47% MN, 60% FL, 80% AZ). Cross-cutting health topics addressed at 2 sites were physical activity/obesity/nutrition and mental health. DISCUSSION/SIGNIFICANCE OF IMPACT: Findings were shared with our CABs to obtain input on future directions. The FL and AZ CABs are systematic in seeking out or initiating research projects that address local health needs, an approach the MN site is interested in adopting. Ultimately, it is important to demonstrate improved health outcomes with CTSA-based CE research strategies. Understanding community health needs and depth of researchers in those areas may help to focus priorities for demonstrating such outcomes.

OBJECTIVES/SPECIFIC AIMS: Chromosome 22q11.2 deletion syndrome (22q) has a prevalence almost as common as Down syndrome. 22q is well known for medical complications, including congenital heart disease and immune dysfunction. However, children with 22q also have borderline cognitive abilities, are at high risk for ADHD and anxiety, and have poor independent living skills (adaptive function). Parenting is one modifiable factor that has been found in typically developing populations to promote independent functioning and protect against the development of anxiety disorders. This study investigates the associations between parenting, anxiety, and adaptive functioning in 22q. METHODS/STUDY POPULATION: Parent-child (ages 4–11) dyads participated in an ongoing study involving observed parenting during challenging tasks plus questionnaires of parenting, child anxiety, and child functioning. In total, 52 dyads [22q=25; typical development (TD)=27] have enrolled to date. Parents completed questionnaires, including the Parenting Styles and Dimensions Questionnaire (PSDQ), Spence Children’s Anxiety Scale, and Adaptive Behavior Assessment System for Children (ABAS-II). PSDQ dimensions of interest included Parental Psychological Control (PPC: the management of child behavior through the manipulation of emotions, expectations, and independence), Authoritative, Authoritarian, and Permissive, and the subscales of these broad dimensions. Scores were compared using t-tests and multiple regression models were used to investigate the relationships between 1-parenting and anxiety and 2-parenting and adaptive function. RESULTS/ANTICIPATED RESULTS: Mean age was 7.8+2.1 years. Full Scale IQ (TD: 112.3 vs. 22q: 82; p<0.001) and ABAS-II Global Adaptive Composite (TD: 102.7 vs. 22q: 69.2; p<0.001) were significantly higher in the TD group. Parents in the 22q group reported higher levels of PSDQ PPC (22q: 2.3 vs. TD: 2.1; p=0.06), specifically overprotection (22q: 3.7 vs. TD: 3.3; p=0.04), and lower Authoritative parenting (22q: 4.1 vs. TD: 4.4; p=0.03), across the subscales. There were no differences in Authoritarian or Permissive parenting. Children with 22q had higher Spence Total Anxiety scores (22q: 62.5 vs. TD: 47.4; p<0.001). Self-reported PPC and group (R2=0.3, F3,48=8.1, p<0.001) predicted child anxiety with a main effect of PPC (β=16, p=0.02). Group tended to moderate the association between PPC and anxiety (β=−17.5, p<0.10), with PPC predicting anxiety for the 22q group (r=0.35, p<0.09), but not the TD group (r=−0.08, ns). At this time, a relationship between PPC and child ABAS-II GAC in 22q (r=−0.14; p=0.5) is not identified. DISCUSSION/SIGNIFICANCE OF IMPACT: Children with 22q are at high risk for anxiety and poor adaptive outcomes. These results suggest that parents of children with 22q use higher levels of PPC, which is correlated with increased child anxiety. These analyses also provide support for parenting interventions to improve anxiety in children with 22q and possibly mitigate the serious mental health risk in this population.

Infants with congenital heart disease (CHD) may have impaired cerebral autoregulation (CA) associated with cerebral fractional tissue oxygen extraction (FTOE). We conducted a pilot study in nine CHD neonates to validate a noninvasive CA measure, cerebrovascular stability index (CSI), by eliciting responses to postural tilts. We compared CSI to an invasive measure of CA and to FTOE collected during tilts (FTOESpot). FTOESpot correlated with CSI, as did the change in FTOE during tilts, but CSI’s correlation with impaired CA did not reach significance. Larger trials are indicated to validate CSI, allowing for noninvasive CA measurements and measurements in outpatient settings.

OBJECTIVES/SPECIFIC AIMS: To create the instrument, we employed a modified Delphi approach by conducting a thorough literature review on Leadership to help concretize the relevant constructs, and then usied these extracted constructs as a springboard for the Rockefeller Team Science Educators (TSE’s) to discuss and refine the leadership domain areas, collectively creating domain-specific survey items, and then further discussed and refining the number, grouping, and wording of the items. METHODS/STUDY POPULATION: We piloted the Leadership Survey by having all of the Rockefeller TSEs rate Clinical Scholars. Each item was answered using a six-point Likert scale where a low score indicated poor expression of the specific leadership attribute and a high score represented excellent expression of the specific leadership attribute. RESULTS/ANTICIPATED RESULTS: Means, medians, standard deviations, and ranges of each item were calculated and tabulated. A complete (Pearson) correlation matrix was computed so that the raw inter-item relationships can be observed. For each a priori Domain an equal weighted summary scale was created and tabulated for review. The internal consistency of each a priori scale was assessed by calculating Cronbach’s Alpha (α). Items with low Item to Construct coefficients were candidates for elimination or modification, and overall scales with low’s will undergo further discussion. To challenge our assumptions of the construction and integrity of each domain, we employed exploratory Principal Components Analysis (PCA), followed by orthogonally rotated Factor Analysis (FA). We also forced the PCA / FA analysis to extract the a priori dimensions that allowed us to compare if the empirical and a priori structures match. DISCUSSION/SIGNIFICANCE OF IMPACT: We are partnering with the CTSA programs at Penn and Yale to assess issues of generalizability and scalability. We are working with Vanderbilt to install survey onto REDCap for ease of dissemination. Will continue to assess psychometric properties and refine as we receive more input.

Contracting delays remain a challenge to the successful initiation of multisite clinical research in the US. The Clinical and Translational Science Awards (CTSA) Contracts Processing Study showed average contract negotiation duration of > 100 days for industry-sponsored or investigator-initiated contracts. Such delays create enormous costs to sponsors and to patients waiting to use new evidence-based treatments. With support from the National Institutes of Health’s National Center for Advancing Translational Sciences, the Accelerated Clinical Trial Agreement (ACTA) was developed by 25 major academic institutions and medical centers engaged in clinical research in collaboration with the University-Industry Demonstration Partnership and with input from pharmaceutical companies. The ACTA also informed the development of subsequent agreements, including the Federal Demonstration Partnership Clinical Trial Subaward Agreement (FDP-CTSA); both ACTA and the FDP-CTSA are largely non-negotiable agreements that represent pre-negotiated compromises in contract terms agreed upon by industry and/or medical center stakeholders. When the involved parties agree to use the CTSA-developed and supported standard agreement templates as a starting point for negotiations, there can be significant time savings for trials. Use of the ACTA resulted in an average savings of 48 days and use of the FDP-CTSA saved an average of 57 days of negotiation duration.

OBJECTIVES/GOALS: To facilitate the development of innovative injection products by providing translational researchers with a regulatory and manufacturing road map for producing small batch sterile products for Phase 1 research use. To leverage recent AMC investments in facility improvements and pharmacy training in the areas of sterile product production, testing, and environmental controls, that can be used to support production of phase 1 clinical trial supplies METHODS/STUDY POPULATION: Searching and organizing relevant data and information from web portals and databases in the following: areas: FDA, EMA, USP regulations, regulatory science, pharmaceutical formulation and analytics, supply vendors, analytical testing laboratories, and product testing laboratories. Present the information using a user friendly format including flow charts and development timelines, taking the perspective of the translational investigator. RESULTS/ANTICIPATED RESULTS:

• Choosing AMC resources vs outside consultants and vendors, leveraging local resources where possible

• Qualifying and monitoring suppliers, testing laboratories, in-house departments, and Contract Drug Manufacturing Organizations (CDMO)

• Bringing together the deliverables for the IND CMC section

• Where and how to leverage available products and science to simplify safe and reliable production

DISCUSSION/SIGNIFICANCE OF IMPACT: Use and utility of injectable drug products, both small molecule and biologics, is growing rapidly, and is projected to continue to escalate well into the next decade. This is due not only to advances in medicine, but also to improvements in AMC-based sterile product production, and a better understanding of small batch manufacturing methods. All three trends align in academic medical centers (AMC) and can be utilized by translational researchers, if they can understand the potential and regulatory requirements.