OBJECTIVES/GOALS: To describe how the UCLA Clinical and Translational Science Institute (CTSI) assembled and deployed a science team in support of a local jurisdictions effort to manage and control COVID-19 outbreaks in one of the nations largest metropolitan regions, Los Angeles County (LAC). METHODS/STUDY POPULATION: During the COVID-19 pandemic (2020-21), building an efficient data infrastructure to support outbreak management became a priority for the local health department. In response, the UCLA CTSI assembled a science team with expertise across the translational continuum: epidemiology, laboratory and microbiology, machine learning, health policy, medicine and clinical care, and community engagement. The team partnered with a new LAC Data Science Team to foster a collaborative learning environment for scientists and public health personnel, employing improvement and implementation science to help mitigate COVID-19 outbreaks in sectors including healthcare, skilled nursing facilities, and K-12 education. The goal was a public health workforce that is prepared to problem-solve complex, evolving outbreaks. RESULTS/ANTICIPATED RESULTS: The science team created a learning environment with data modeling and visualization, problem-based learning, and active knowledge and skills acquisition. First, control charts and time series methods were used to visualize COVID-19 data and find signals for action. Second, a series of 16 Grand Rounds offered interactive sessions on problem-solving of outbreak challenges in different sectors. Third, a biweekly Public Health Digest provided fieldworkers with the latest scientific studies on COVID-19. All three elements guided and empowered the workforce to implement timelier, efficient outbreak mitigation strategies in the field. The partnered team also identified barriers to adoption of selected new data and management techniques, revealing areas for further skill-building and data-driven leadership. DISCUSSION/SIGNIFICANCE: The UCLA CTSI science team offered a backbone science infrastructure for helping public health and other sector agencies manage COVID-19 outbreaks and mitigation. It showed promise in bringing and translating science into public health practice. It revealed future priorities for CTSI innovation and scientific support of public agencies.

Fair inclusion of research subjects is necessary to ensure that post-acute sequelae COVID-19 (PASC) research results benefit all members of society. Scientists should conduct research on a broad sample of individuals who represent clinically relevant factors influencing a disease. Without demographic diversity and sociological and environmental variability, research outputs are less likely to apply to different populations and would thus increase health disparities. The goal of this narrative literature review and ethical analysis is to apply fair selection criteria to PASC research studies. We briefly highlight the importance of fair subject selection in translational research and then identify features of PASC, as well as PASC research, that hinder fair inclusion of research participants. We will demonstrate that determining an adequate and representative sample is not simply a matter of ensuring greater diversity; rather, fairness requires a broader evaluation of risks, burdens, and benefits specific to underrepresented populations. We provide recommendations to ensure fair subject selection in PASC research and promote translation toward positive health outcomes for all individuals, including the most vulnerable.

OBJECTIVES/GOALS: This poster summarizes the development and implementation of research exploring the relationship between sleep and brain health. METHODS/STUDY POPULATION: Three pilot studies and two secondary data analyses were conducted on 20 older adults with coronary artery disease and 30 older adults without major cardiovascular disease. They were recruited for 10 older adults with multiple chronic conditions. The study included interviews, magnetic resonance imaging, and sleep assessment of participants. Data were also gathered from two secondary sources on multiple chronic conditions, sleep, neuroimaging, cognition, and Alzheimers biomarkers. RESULTS/ANTICIPATED RESULTS: The multidisciplinary team was from nursing, medicine, cardiology, psychology, neuroscience, radiology, and data science to address the separate research aims. The pilot studies and secondary data analyses were successfully implemented. The University of Iowa Institute for Clinical and Translational Science, Center for Advancing Multimorbidity Science, and Iowa Neuroscience Consortium supported the collaboration. The teams have found that sleep and circadian rhythms characteristics may be associated with not only coronary artery disease, but also multiple chronic conditions. Having sleep disorders and reduced circadian amplitude can be associated with white matter microstructure and functional connectivity. These collaborations provided multiple funding and publication opportunities. DISCUSSION/SIGNIFICANCE: Interdisciplinary team research is important to enhance translational science. Although challenges were identified, using multiple methods and dataset sources with multidisciplinary team members enabled opportunities to explore multifaced topics related to sleep and brain aging.

OBJECTIVES/GOALS: For patients suffering from respiratory failure there are limited options to support gas exchange aside from mechanical ventilation. Our goal is to design, investigate, and refine a novel device for extrapulmonary gas exchange via peritoneal perfusion with perfluorocarbons (PFC) in an animal model. METHODS/STUDY POPULATION: Hypoxic respiratory failure will be modeled using 50 kg swine mechanically ventilated with subatmospheric (10-12%) oxygen. Through a midline laparotomy, two cannulas, one for inflow and one for outflow, will be placed into the peritoneal space. After abdominal closure, the cannulas will be connected to a device capable of draining, oxygenating, regulating temperature, filtering, and pumping perfluorodecalin at a rate of 3-4 liters per minute. During induced hypoxia, the physiologic response to PFC circulation through the peritoneal space will be monitored with invasive (e.g. arterial and venous blood gases) and non-invasive measurements (e.g. pulse oximetry). RESULTS/ANTICIPATED RESULTS: We anticipate that the initiation of oxygenated perfluorocarbons perfusion through the peritoneal space during induced hypoxia will create an increase in hemoglobin oxygen saturation and partial pressure of oxygen in arterial blood. As we expect gas exchange to be occurring in the microvascular beds of the peritoneal membrane, we expect to observe an increase in the venous blood oxygen content sampled from the inferior vena cava. Using other invasive hemodynamic measures (e.g. cardiac output) and blood samples taken from multiple venous sites, a quantifiable rate of oxygen delivery will be calculable. DISCUSSION/SIGNIFICANCE: Peritoneal perfluorocarbon perfusion, if able to deliver significant amounts of oxygen, would provide a potentially lifesaving therapy for patients in respiratory failure who are unable to be supported with mechanical ventilation alone, and are not candidates for extracorporeal membrane oxygenation.

OBJECTIVES/GOALS: Youth with comorbid asthma and overweight/obesity (OW/OB) are at risk for increased morbidity. Physical activity (PA) engagement can mitigate risks, but the majority of youth do not meet national PA guidelines. This study examines caregiver and youth perspectives about ways physicians can promote PA in this population. METHODS/STUDY POPULATION: Participants included 20 adolescents (M age = 16.0; 55% male) with asthma and OW/OB and a primary caregiver (90% mothers). Caregivers and adolescents participated in separate semi-structured interviews about adolescent PA engagement, including questions regarding strategies for physicians to promote PA. Interviews were audio recorded, transcribed, and analyzed using NVivo. Two authors assigned conceptual codes to the transcripts to identify key concepts and then met to create a codebook. Authors independently coded 4 transcripts and met to resolve discrepancies. Authors then independently coded 2 additional transcripts (final kappa = .62) and met to reach consensus before dividing the remainder for coding. Codes were collapsed and sorted into themes, and attributes of each theme were determined. RESULTS/ANTICIPATED RESULTS: Dyads discussed the importance of physicians providing general (positive statements) and PA-specific encouragement. Dyads also stated that physicians should encourage teens to set and reach PA-related goals. Caregivers and youth reported that physicians should provide education about the importance of PA and ways to engage in PA, awareness about adolescents weight and its impact on health, and resources (camps, events, and locations). Additionally, caregivers and a teen noted that physicians should talk directly to and address questions toward teens. Dyads mentioned the importance of focusing on overall health (instead of weight) as well. Dyads also noted that physicians should avoid judgmental and shaming statements when talking about weight. DISCUSSION/SIGNIFICANCE: Results provide information about strategies physicians can use to promote PA among adolescents with asthma and OW/OB, a population that is at risk for low PA and poor health outcomes. Findings suggest that physicians may effectively motivate behavior change by providing health guidelines, encouragement, resources, and positive reinforcement.

The Recruitment Innovation Center (RIC) has created a toolkit of novel strategies to engage potential participants in response to recruitment and retention challenges associated with COVID-19 studies. The toolkit contains pragmatic, generalizable resources to help research teams increase awareness of clinical trials and opportunities to participate; produce culturally sensitive and engaging recruitment materials; improve consent and return of results processes; and enhance recruitment of individuals from populations disproportionately impacted by COVID-19. This resource, the “RIC COVID-19 Recruitment and Retention Toolkit,” is available free online. We describe the toolkit and the community feedback used to author and curate this resource.

OBJECTIVES/GOALS: Infants of diabetic mothers (IDMs) may exhibit decreased oral intake, requiring nasogastric feedings and prolonged hospitalization. We hypothesize that increased insulin exposure and resulting overgrowth in utero disrupts hypothalamic regulation of food intake, correlates to body composition and impacts feeding in IDMs. METHODS/STUDY POPULATION: Infants born at ≥ 35 weeks gestation to mothers with gestational or type II diabetes (IDM cohort), and normoglycemic mothers (control cohort) were recruited. Infants born to mothers with Type I DM or preeclampsia and with a history of intrauterine growth restriction, opioid exposure, or major congenital anomalies were excluded. Salivary expression of known hunger signaling genes 5AMP-activated protein kinase (AMPK), Neuropeptide Y receptor Y2 (NPY2R), leptin (LEP), ghrelin (GHRL), proopiomelanocortin (POMC), and adiponectin (ADIPOQ) were quantified using RT-qPCR. Body composition was assessed via skinfold measurements and compared and correlated between cohorts. Feeding outcomes were recorded. RESULTS/ANTICIPATED RESULTS: 23 infants were recruited in each cohort. POMC and AMPK were expressed by 71% and 88% of infants respectively in both cohorts. NPY2R was expressed by 79% and 83% of the diabetic cohort and normoglycemia cohort respectively, while GHRL was expressed by 75% and 79% of the diabetic cohort and normoglycemia cohort, respectively. LEP and ADIPOQ were not reliably expressed in either cohort. Infants with a higher body fat percentage were less likely to express NPY2R (OR= 0.76). There was no significant association between body fat percentage and expression of AMPK, POMC, or GHRL. Only 3 IDMs were noted by providers to exhibit poor oral intake, limiting our ability to correlate gene expression and body composition with feeding outcomes. DISCUSSION/SIGNIFICANCE: Non-invasive assessment of hunger signaling gene expression is possible through salivary analysis of AMPK, POMC, NPY2R, and GHRL. Given the paucity of IDMs with poor feeding in our study, future studies should target IDMs requiring feeding support to understand mechanisms driving aberrant feeding behavior.

Evidence-based psychotherapies (EBPs) are underused in health care settings. Aligning implementation of EBPs with the needs of health care leaders (i.e., operational stakeholders) can potentially accelerate their uptake into routine practice. Operational stakeholders (such as hospital leaders, clinical directors, and national program officers) can influence development and oversight of clinical programs as well as policy directives at local, regional, and national levels. Thus, engaging these stakeholders during the implementation and dissemination of EBPs is critical when targeting wider use in health care settings. This article describes how research–operations partnerships were leveraged to increase implementation of an empirically supported psychotherapy – brief Cognitive Behavioral Therapy (brief CBT) – in Veterans Health Administration (VA) primary care settings. The partnered implementation and dissemination efforts were informed by the empirically derived World Health Organization’s ExpandNet framework. A steering committee was formed and included several VA operational stakeholders who helped align the brief CBT program with the implementation needs of VA primary care settings. During the first 18 months of the project, partnerships facilitated rapid implementation of brief CBT at eight VA facilities, including training of 12 providers who saw 120 patients, in addition to expanded program elements to better support sustainability (e.g., train-the-trainer procedures).

Translation of research discoveries into health impact can take many years, creating delays in improving clinical outcomes. One approach to promoting timely translation is to examine successful cases in order to understand facilitators and strategies for overcoming barriers. We examined the development of evidence-based management for neonatal abstinence syndrome (NAS) at one academic medical center, with a primary focus on pharmacologic treatment. Despite a substantial increase in NAS case incidence starting in the early 2000s, significant sociocultural, policy, and regulatory barriers limited collaborative NAS research. Facilitators for translation encompassed: 1) pursuing research of societal interest, 2) building an effective interdisciplinary team, 3) intentionally linking clinical, research, and advocacy efforts, 4) broad stakeholder engagement across clinical, policy, and research arenas, and 5) leveraging local resources. Challenges included lack of commercially available U.S. Food and Drug Administration approved neonatal drug formulations, legal and regulatory barriers related to off-label and illicit use of opioids, recruitment for a treatment associated with drug withdrawal syndromes, misalignment of research design needs with real-world scenarios, and episodic funding. Benefits of successful translation included improvements in clinical care, reduced healthcare costs related to NAS, and enhanced legislative, policy, and research strategies to support broader neonatal investigations.

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/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.

The Translational Science TS22 conference in Chicago in April 2022 was the first time post-pandemic that members of the Association of Clinical and Translational Science were able to meet up in person to share scientific advances. Given the remaining level of risk due to COVID-19, the meeting was designed as hybrid allowing virtual participation to some of the presentations. Prior to the meeting, JCTS Junior Editors were invited to report on the plenary sessions of the meeting. The present perspective constitutes a summary of three plenary sessions.

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/GOALS: The New Jersey Alliance for Clinical and Translational Science (NJ ACTS) interest in developing a comprehensive education and training program for enhancing the quality, efficacy, and safety of the clinical research enterprise led to the release of a survey distributed nationwide to assess initiatives in the translational science workforce. METHODS/STUDY POPULATION: Twenty-one hubs responded to the survey and data was exported from REDCap to Excel. Respondent demographics were categorized to formalize roles and data was categorically divided into sections based on training type (engagement, basic, postgraduate etc…) utilizing conditional formatting. The limitation in this survey was a branching logic defect aligned with questions on competency tool usage and the roles that they play which led to only six hubs having the advantage to respond to all questions. RESULTS/ANTICIPATED RESULTS: Summary findings showed that the majority of respondents for the survey (30%) were the Director of Operations’. Further; the Joint Task Force (JTF) domain Scientific Concepts and Research Design’ was the most preferred Hard Skill (81%) while the least preferred was Investigational Product Development and Regulation’ (29%). In spite of only six hubs receiving the short competency assessment; 50% of those hubs stated they would utilize ‘In House Assessment Tools’ and 83% stated they used the tools to ‘Develop Personalized Training Plans’. The assessment of this Inventory was indeed necessary to identify trends in available trainings across the CTSA consortium. DISCUSSION/SIGNIFICANCE: The internal cross training catalogue will help to develop an infrastructure for the NJ ACTS community to work along with other CTSA hubs while creating comprehensive clinical research training initiatives and programs.

OBJECTIVES/GOALS: Whole-genome viral sequencing is vital to inform public health and study evolution. Arboviruses evolve in vectors, reservoir hosts, and humans, and require surveillance at all points. We developed a new rigorous method of sequencing that captures whole viral genomes in field-collected and clinical samples. METHODS/STUDY POPULATION: ClickSeq is a novel method of Next Generation Sequencing (NGS) library synthesis using azido-nucleotides to terminate reverse transcription. The cDNA generated can be ligated to sequencing and indexing primers at room temperature using copper (Cu I) and vitamin C. With this approach, we designed primers located ~250 bp apart along the genomes of the arboviruses Chikungunya 37797, Zika Dakar, Yellow Fever Asibi, Dengue serotype 2, West Nile 385-99, and St. Louis Encephalitis Virus (SLEV) clade II. We tested this method with varying viral titers: lab-infected mosquito pools, field-collected mosquito pools from a Texas West Nile and SLEV outbreak, and patient isolates from a Pakistani CHIKV outbreak. The cDNA was sequenced in the UTMB NGS Core and aligned using bowtie. RESULTS/ANTICIPATED RESULTS: The use of a single protocol to capture whole viral genomes including UTRs for multiple viruses from different sample collection styles is ideal for arboviruses. Primers for multiple viruses were pooled and used to sequence mosquito pools. The Tiled ClickSeq method captured whole viral genomes without the need for host depletion. UTRs were captured even when the viral strain used for primer design differed from the resulting strain. Discreet variants were captured in both the hypervariable nsP3 region and the UTR in the patient isolates from the CHIKV outbreak compared to the 2017 outbreak. Texas WNV and SLEV outbreaks are now defined from the 2020 outbreak and can be further tracked to update public health measures and understand viral evolution. DISCUSSION/SIGNIFICANCE: UTRs impact both human and mosquito fitness, leading to further outbreaks. Tiled ClickSeq aims to capture whole viral genomes with a method and cost that can be implemented by public health researchers to understand disease evolution as it happens to update both public health and basic virology to the effects of evolution on arboviruses.