OBJECTIVES/GOALS: Our purpose is to promote traffic toward the NJ ACTS Regulatory Cores recently launched website and increase investigator engagement through marketing strategies on LinkedIn. Landscaping to characterize the profiles of researchers on LinkedIn was also completed to estimate the feasibility of engaging with a target population on LinkedIn. METHODS/STUDY POPULATION: Insight gathering was performed to analyze what percentage of researchers possessed a LinkedIn profile and actively used their accounts. A sample population consisting of 284 NJ ACTS members were analyzed to summarize the type of researchers on LinkedIn, and their likelihood of responding to LinkedIn marketing campaigns. Efforts to launch a company LinkedIn page and collect followers were completed. Different methods of promotion were evaluated, including direct vs. mass email outreach to over 600+ researchers at Rutgers. Effectiveness of our platform was measured by comparing/overlaying Regulatory website traffic with LinkedIn traffic, as well as tracking the metrics of LinkedIn posts. RESULTS/ANTICIPATED RESULTS: Among 284 NJ ACTS members, 76% (n=215) possess a LinkedIn profile, but only 21% (n=59) are actively interacting with material on LinkedIn, such as creating, commenting, or sharing posts. Among the NJ ACTS LinkedIn users, 27% of individuals (n=57/215) responded to a direct outreach. Retention of the created organizational page was strong, as most users who visited the Regulatory Core page were likely to become followers. Massive email outreach to 600+ researchers within RBHS did not yield a strong LinkedIn following, however it did result in strong signals of website traffic during the days after the promotion was sent. Engagement with posts on LinkedIn can also be amplified and messaging proliferated when colleagues reshare Regulatory posts on their personal feeds. DISCUSSION/SIGNIFICANCE: 3/4 of academic researchers are likely to be on LinkedIn but may not be active users of the platform. The most effective outreach is through direct messaging as opposed to broader, less individualized tactics (including mass email outreach). Evidence suggests potential to utilize LinkedIn to proactively engage in regulatory-related activities.

OBJECTIVES/GOALS: While mutant TP53 is an attractive therapeutic target in TNBC, attempts to target the mutant p53 protein directly have failed. Thus, we aim to identify pathways critical for the survival of TP53 mutant cells that can be targeted in TNBC. We have identified Kif11 as one such target and aim to further investigate its function in TP53 mutant TNBC. METHODS/STUDY POPULATION: We conducted a dual in silico/in vivo screen that identified Kif11 inhibition as preferentially inhibiting the growth of TP53 mutant TNBC. We obtained data on TP53 mutational status, KIF11 mRNA expression levels, and clinical characteristics from TCGA, METABRIC, and CCLE datasets. We treated breast cancer cell lines with the KIF11 inhibitor SB-743921. Cell counts were obtained through staining with DAPI or Hoechst and imaging on the ImageXPress PICO. We detected cell death by DRAQ7 staining and flow cytometry analysis following Annexin V-PI staining. To investigate mitotic spindle organization, we performed immunofluorescent staining with an anti-tubulin antibody and DAPI co-staining. Cell cycle analysis was performed through flow cytometry. RESULTS/ANTICIPATED RESULTS: KIF11 is highly expressed in TP53 mutant and TNBC clinical samples. High KIF11 expression is associated with poorer clinical outcomes. Kif11 inhibition suppresses growth of both TP53 mutant and wild-type breast cancer cells, but preferentially induces the death of TP53 mutant cells as detected by DRAQ7 and Annexin V/PI staining. Kif11 inhibition induces a G2-M block and growth inhibition in TP53 wild-type cells. On the other hand, following treatment with the Kif11 inhibitor SB-743921, TP53 mutant cells undergo mitotic spindle dysfunction leading to the formation of multinucleated cells and cell death. DISCUSSION/SIGNIFICANCE: These results demonstrate that Kif11 is a promising therapeutic target in aggressive, TP53 mutant TNBCs. Kif11 inhibitors, including SB-743921, have been tested in human trials, and are well tolerated, but it is unclear which patients would most benefit. Our studies show that Kif11 inhibitors may be most useful in patients with TP53 mutant TNBCs.

ABSTRACT IMPACT: This work investigates C. difficile strains in soil as a potential exposure for gut colonization and community-acquired infection of C. difficile. OBJECTIVES/GOALS: Identifying environmental sources of C. difficile can inform how non-hospital reservoirs can potentially contribute to C. difficile exposure and subsequent gastrointestinal colonization. The objective of the study was to identify C. difficile and toxin genes across various soil sources. METHODS/STUDY POPULATION: This was a cross-sectional study utilizing soil samples obtained throughout Texas, USA. All samples were collected between August and November of 2019 and 2020. Samples were taken from human and animal high contact areas, such as recreational parks. Samples were stored at -80oC until processing. DNA extractions were performed using the DNeasy Powersoil Pro Kit (Qiagen) per manufacturer’s instructions. Real-time PCR was also performed on extracted DNA using the Microbial DNA qPCR Multi-Assay Kit for Clostridium difficile Pathogenicity (Qiagen) for the identification of C. difficile, toxin A (TcdA), and toxin B (TcdB) genes. RESULTS/ANTICIPATED RESULTS: A total of 137 soil samples including dry dirt, sand, and wet soil near water sources were collected and processed for the presence of C. difficile. These included samples from parks and trails (42.3%), water sources (36.5%), and other public spaces (21.2%). C. difficile was identified in 59 (43.1%) soil samples: 6 (4.4%) with Toxin A and 2 (1.5%) with toxin B production. C. difficile was most prevalent among samples taken from parks and trails (50.0%), followed by other public spaces (48.3%), and water sources (32.0%). The median (IQR) Cq value for the C. difficile gene was 39.24 (33.45-40.47) among samples that tested positive. DISCUSSION/SIGNIFICANCE OF FINDINGS: We identified a high prevalence of Clostridioides difficile in soil samples, though toxin gene detection prevalence was low. Future studies will analyze other sources, including water and varying surface samples to obtain a comprehensive view of C. difficile in the environment.

Identifying and disseminating actionable intelligence is a challenging task that requires thoughtful planning. The National Center for Advancing Translational Sciences instituted the Common Metrics Initiative with the goal of evaluating the Clinical and Translational Science Awards (CTSA) Programs using a standard set of metrics. Initially managed by Tufts University, the Center for Leading Innovation and Collaboration (CLIC) at the University of Rochester began leading this initiative in 2017. In directing this work, CLIC created a framework for communicating and disseminating data insights. Insights to Inspire emerged from the need to share strategies and lessons learned to improve metric performance at the local level to a network of 60+ academic research institutions. Insights to Inspire employs a mixed methods approach for translating data into actionable intelligence. A series of blogs, webinars, and webcasts were designed to communicate metric-specific strategies used by individual sites to the broader CTSA consortium. A dissemination plan to expand the reach beyond metric stakeholders utilized focused communications including social media channels, network newsletters, and presentations at national meetings. This framework serves as a blueprint for other national evaluation programs interested in a systematic approach to using data insights for continuous improvement.

OBJECTIVES/GOALS: Stress is amplified in parents of children with Down syndrome (DS). However, little is known about caregivers’use of coping strategies in relation to stress-related eating and their child with DS. The purpose of this study is to explore stressors and coping resources that increase or decrease stress-related eating among caregivers of children with DS. METHODS/STUDY POPULATION: This descriptive qualitative study sought to understand and describe the lived experiences of caregivers of children with DS. Fifteen caregivers of children, ages 2-6-years with DS, completed an online survey and individual interview. The Transactional Model of Stress and Coping was used to develop the interview guide and to assess related constructs using the Mindful Eating Questionnaire (MEQ), Perceived Stress Scale (PSS), Salzburg Stress Eating Scale (SSES), and a subscale of the Eating and Appraisal Due to Emotions and Stress Questionnaire (EADES). Interviews were audio-recorded, transcribed verbatim, coded using NVivo 12, and analyzed using deductive thematic analysis based on theoretical constructs and content analysis approaches. RESULTS/ANTICIPATED RESULTS: Thirteen of the 15 participants reported moderate to high perceived stress on the PSS. Stressors identified by caregivers included caring for a child with DS, feeding difficulties, physical and mental health, family and social interactions, and finances. Caregivers utilized various interpersonal resources to cope, including family, friends, and social media groups. In the interviews, stress-related eating was revealed as a coping mechanism for 9 caregivers. Also, 13 caregivers reported eating more or eating less when stressed on the SSES and 7 caregivers reported increased emotional eating as measured on the sub-scale of the MEQ. Only two caregivers described using mindfulness strategies throughout the interview. DISCUSSION/SIGNIFICANCE: Overall, caregivers of children with DS report increased perceived stress related to their role as a caregiver of a child with DS, which may be related to changes in caregivers’dietary intake. Dietary interventions developed for these families should include mindful eating and stress management strategies.

Despite understanding its impact on organizational effectiveness, practical guidance on how to train translational team (TT) leaders is lacking. Previously, we developed an evolutionary learning model of TT maturation consisting of three goal-directed phases: (1). team assembly (Formation); (2). conducting research (Knowledge Generation); and (3). dissemination and implementation (Translation). At each phase, the team acquires group-level knowledge, skills, and attitudes (KSAs) that enhance its performance. Noting that the majority of team-emergent KSAs are promoted by leadership behaviors, we examine the SciTS literature to identify the relevant behaviors for each phase. We propose that effective team leadership evolves from a hierarchical, transformational model early in team Formation to a shared, functional leadership model during Translation. We synthesized an integrated model of TT leadership, mapping a generic “functional leadership” taxonomy to relevant leadership behaviors linked to TT performance, creating an evidence-informed Leadership and Skills Enhancement for Research (LASER) training program. Empirical studies indicate that leadership behaviors are stable across time; to enhance leadership skills, ongoing reflection, evaluation, and practice are needed. We provide a comprehensive multi-level evaluation framework for tracking the growth of TT leadership skills. This work provides a framework for assessing and training relevant leadership behaviors for high-performance TTs.

OBJECTIVES/GOALS: Team science competencies are not well-defined for nonfaculty staff of Clinical Research Professionals (CRPs) who conduct research. Using an existing framework, our work has determined skills associated with team science competencies as related to CRPs. Our team also outlined examples of those skills on a fundamental, skilled, and advanced level. METHODS/STUDY POPULATION: The team consists of both CRPs and those working in the Team Science space. This team used a modified Delphi approach to determine the skills and leveling examples of each team science competency. The team broke into four groups and was assigned 3-4 competencies each. Each group determined skills needed to support (exhibit, promote) each competency and then described an example of this skill at the fundamental, skilled, and advanced levels. Once each group was finished with their assigned competencies, they were re-assigned to a different group for review and changes. Finally, team science and CRP experts reviewed the skills and levels. RESULTS/ANTICIPATED RESULTS: Our results are a rubric that defines 3-5 practical skills per described competency. These skills are needed to support and promote each competency as a CRP. An additional outcome from this work includes examples of each skill at the fundamental, skilled, and advanced levels in a CRP’s career. Each leveled example is described in a concise, actionable way using Bloom’s taxonomy. This rubric is meant to be easily understood, very useable and able to be used in conjunction with existing CRP competency frameworks. By using Bloom’s taxonomy, we set the stage for future educational programming in Team Science skill-building for clinical research professionals. DISCUSSION/SIGNIFICANCE: Team science concepts and competencies have been increasingly integrated into translational science teams. However, team science competencies related to CRPs have remained largely undefined. Our work helps to define these competencies for CRPs in a practical way. Our rubric fills gaps in, and builds on, existing CRP competency frameworks.

Physician parents encounter unique challenges in balancing new parenthood with work responsibilities, especially upon their return from parental leave. We designed a pilot program that incorporated 1:1 parental coaching to expectant and new physician parents and provided stipends for lactation support and help at home. Additional initiatives included launching a virtual new parent group during the COVID-19 pandemic and starting an emergency backup pump supplies program. There was positive feedback for our Parental Wellness Program (PWP), which was used to secure expanded funding. Pilot results showed that our program had a meaningful impact on parental wellness, morale, productivity, and lactation efforts.

OBJECTIVES/GOALS: Illuminate processes and findings of the Environmental Scan of Adaptive Capacity and Preparedness of CTSAs done by the CTSA Working Group. Share challenges, strategies, and lessons learned for CTSAs to build Capacity to address clinical and translational barriers while responding to emergencies. METHODS/STUDY POPULATION: An Environmental Scan approach for searching, collecting, analyzing and using information from diverse sources regarding CTSA hubs experiences during emergency as related to research implementation, translation, support, adaptation, and preparedness: - Triangulating multiple data sources and mixed methods (e.g., literature review, document/RPPR analysis, and expert review); - Secondary analysis of the JCTS COVID-19 Survey of the CTSAs: challenges, lessons learned, and practices that work in various program components/areas; - Using feedback of CTSA professionals from multiple disciplines to enhance our knowledge of emergency preparedness and efficient adaptation to public health and other crises. RESULTS/ANTICIPATED RESULTS: The E-scan approach helped identify challenges, successful practices, and evidence-based strategies for building adaptive capacity and preparedness of CTSAs across various scientific sectors of the translational science spectrum. Some of the findings include: - Roadmaps for the creation of new collaborative research resources (biobanks; data repositories, etc.); - Rapid clinical and research decision making during public health crises; - New community-based research strategies to facilitate communication, research dissemination, and participant recruitment based on existing trust-based networks; - Innovative resource allocation to guarantee continuity of training and research opportunities for trainees. DISCUSSION/SIGNIFICANCE: The Environmental Scan of the Adaptive Capacity of CTSA hubs provides useful knowledge and tools to diverse clinical research stakeholders for mitigating the impact of a disaster via adjusting programs, practices, and processes, and building capacity for effective, emergency-ready and responsive research, training, and community engagement.

OBJECTIVES/SPECIFIC AIMS: As pediatric care becomes more concentrated in large urban hospitals, smaller rural hospitals with reduced pediatric care capacity may opt to transfer pediatric patients to higher levels of care even if the patient has a condition that is manageable in a general ED. Up to 20-40% of pediatric transfers are considered avoidable, placing a burden on the patient, their family and the health care system. The aim of this study is to determine the association between pediatric readiness (as measured by the National Pediatric Readiness Project score) and risk of interfacility transfer. We hypothesized that emergency departments with higher measures of pediatric readiness would be less likely to transfer pediatric patients to another facility. METHODS/STUDY POPULATION: The most recent and complete National Pediatric Readiness Project data were from 300 California hospitals in 2012. These data include the overall pediatric readiness score, presence of inter-facility guidelines (written protocols on patients needing care not available at the hospital), presence of interfacility agreements (written agreements with other hospitals regarding transfer patients), and other variables on the facility’s capacity to care for pediatric patients. We linked these hospital data with patient encounter data from the California Office of Statewide Health Planning and Development Emergency Department (ED) Database (OSHPD) using hospital name and zip code. To be eligible for the study, the patient must have a documented ED encounter and be less than 18 years old during the encounter. A patient was considered a transfer patient if they were transferred to a separate general hospital, children’s hospital, federal health care facility, rehabilitation facility, Critical Access Hospital or psychiatric hospital. Chi-square tests and t-tests were used for descriptive statistics. For non-normal data, we used the non-parametric Kruskall-Wallis test. We also used logistic regression to compare the odds of transfer between comparison groups. Statistical analyses were conducted in the R environment version 3.4.4. RESULTS/ANTICIPATED RESULTS: In 2012, there were 2,604,723 pediatric ED encounters, of which 10,966 resulted in a transfer (0.4%). Transferred patients on average were older (15 vs. 5 years, p < 0.001) and more likely to be female (58.6% vs 46.6%, p < 0.001). The transfer group originated from hospitals with a lower median pediatric readiness score (76.0 vs 78.3, p < 0.001). Patients were less likely to be transferred if they were seen at a hospital with written guidelines with transfer protocols (OR 0.89, 95% CI 0.83—0.95, p < 0.001). Patients were more likely to be transferred if they were seen at a hospital with written interfacility agreements with other hospitals (OR 1.17, 95%CI 1.10—1.25, p < 0.001). We anticipate, that even with more sophisticated multilevel statistical models, pediatric readiness scores will remain associated with odds of transfer. DISCUSSION/SIGNIFICANCE OF IMPACT: These preliminary data suggest that hospitals with higher levels of pediatric readiness and written guidelines with transfer protocols are less likely to transfer pediatric patients. There may be actionable policy and procedural items that a hospital could enact to lower the rate of transfer patients. Future analyses will include more complex statistical modeling to adjust for confounders, will include inpatient data, and will compare the risk of potentially avoidable transfers between hospitals with varying levels of pediatric readiness.

OBJECTIVES/SPECIFIC AIMS: Community stakeholder engagement along the translational spectrum of biomedical research has been identified as a potentially crucial factor for encouraging participation among underrepresented groups, improving research relevance, and adoption of evidence into practice. Although we have developed various methods to improve communication between researchers and community stakeholders, we have not focused much attention on the manner by which community stakeholders choose to communicate with researchers in scientific feedback settings. In our PCORI funded study using Community Engagement Studios to elicit feedback on research from community stakeholders, we found that feedback from participants was frequently provided in the form of stories. This presentation aims to describe these narratives, examine their function in the feedback process and consider how a focus on these narratives enhances our understanding of community engagement for clinical and translational research. METHODS/STUDY POPULATION: The present study comes from a larger randomized, controlled methodological study. We randomized 20 investigators seeking input on their research to either a Community Engagement Studio (a panel of community members or patients) or a Translational Studio (a panel of researchers). Any faculty member or research trainee at Vanderbilt University or Meharry Medical College was eligible to participate. Each Studio panel was convened to provide project-specific input. The 153 stakeholders who participated in CE Studios were patients, caregivers, or patient advocates identified by health status, health condition, or demographic variables based on the project-based needs of the 20 researchers randomized in this project. Stakeholders include individuals with diabetes, heart failure, Parkinson’s disease, sickle cell disease, and ICU survivors. All stakeholders had experience as a partner or consultant on a research project or through serving on a research advisory board or committee. All Studios were recorded and transcribed, and experienced qualitative researchers analyzed the data. For this paper, we focus on the narrative feedback in the form of stories elicited in the CE Studios. Using qualitative methods, we coded the transcripts from the 20 CE Studios to identify stories and their functions in the feedback. Stories were defined as narratives with (a) at least one actor (b) action that unfolds over time, and (c) a realization, destination, or conflict resolution (i.e., a point of the story). For example, “I refilled my mother’s pillbox on Sunday and on Friday I found the pillbox still completely full” would be a story, however, “my mother doesn’t take her meds correctly” would not. We coded the stories for how they facilitated communication in the Studio using an open-coding style, that is we did not apply a specific theoretical framework of interaction or communication. It was possible for any given story to have more than one code applied to it; that is they were not classified in a mutually exclusive way. RESULTS/ANTICIPATED RESULTS: We found 5 major functions of stories in the Studios. Basic sender-receiver functions were noted, including responding to queries and seeking mutual understanding. The other functions served to move or add to the conversation, including adding expansion and depth, characterizing abstract concepts, and providing context, with the latter being the most frequent function of stories. Speakers provided context in a wide variety of dimensions, ranging from the context of the body to spatial and institutional contexts. These stories served to help others understand the speakers’ lived experiences. DISCUSSION/SIGNIFICANCE OF IMPACT: We often engage community members in research for their expertise with regards to their lived experiences as patients or community members, and for their experiences of healthcare and social determinants of health in particular community contexts. Yet we may expect them to share their expertise in a manner that is consistent with a scientific, explanatory framing and language. However, we know there is a difference in the way that professional researchers discuss research Versus how community members discuss research. In our PCORI study, we found that our Community Studio participants relied on storytelling as an important means to communicate their lived experiences. Their stories were often key to communicating the complex contexts of their experiences. We focus on examining these narrative practices and their functions in how community members engaged with and provided advice to researchers. This understanding may help us in: (1) Characterizing the contexts, processes, and meanings associated with community stakeholder experiences that are otherwise difficult to access. (2) Identifying community priorities relevant to research that are embedded in community narratives to better align research priorities with community needs and to improve patient outcomes. (3) Collecting insights for improving the design of community engagement activities in research. (4) Harnessing more fully the potential of community engagement in research.

Health systems currently underutilize systematic reviews. Here, we describe a proof of concept project designed to augment the standard systematic review process by presenting qualitative information as a companion to a review on deprescribing interventions. We conducted a thematic analysis of semi-structured interviews with Veterans Health Administration clinicians and Veterans to describe first-hand experiences of engaging in the deprescribing process. Qualitative findings were incorporated into an interactive, web-based product designed to supplement the systematic review report. Preliminary evaluation suggests that integration of narratives as a companion to systematic reviews is of interest to frontline clinicians, researchers, and health system administrators.

Composite endpoints can encode multiple pieces of information and are increasingly adopted in clinical trials. Advocacy for using composite endpoints began decades ago in cardiovascular trials, leading to incorporation of patient-oriented outcomes and consideration of a hierarchical ranking system. The use of composite endpoints in coronavirus disease (COVID-19) trials has evolved similarly. We conducted a literature review to investigate the use of composite endpoints in acute heart failure and COVID-19 clinical trials. The results showed more frequent use of patient-oriented outcomes and ordinal composite endpoints in COVID-19 trials, which might be driven by global consensus on a set of common outcome measures.

Attacks on minoritized communities and increasing awareness of the societal causes of health disparities have combined to highlight deep systemic inequities. In response, academic health centers have prioritized justice, equity, diversity, and inclusion (JEDI) in their strategic goals. To have a sustained impact, JEDI efforts cannot be siloed; rather, they must be woven into the fabric of our work and systematically assessed to promote meaningful outcomes and accountability. To this end, the University of Pittsburgh’s Institute for Clinical Research Education assembled a task force to create and apply a rubric to identify short and long-term JEDI goals, assess the current state of JEDI at our Institute, and make recommendations for immediate action. To ensure deep buy-in, we gathered input from diverse members of our academic community, who served on targeted subcommittees. We then applied a three-step process to ensure rapid forward progress. We emerged with concrete actions for priority focus and a plan for ongoing assessment of JEDI institutionalization. We believe our process and rubric offer a scalable and adaptable model for other institutions and departments to follow as we work together across academic medical institutions to put our justice, equity, diversity, and inclusion goals into meaningful action.