OBJECTIVES/GOALS: The COVID-19 pandemic may have affected the relationship/experience of the mother-child dyad (Provenzi et al., 2021). Our objective is to identify the association of pandemic related maternal stress with child development. We will further evaluate the role of bonding, attachment, and trauma on this association. METHODS/STUDY POPULATION: We aim to recall a prospective cohort (n=200) of Latinx/Hispanic mothers from an ongoing study, power analysis will estimate minimum sample size (power=0.80 and alpha =0.05). Assessments of pandemic related maternal stress (PRMS) will be done with the COVID-19 and Perinatal Experiences Interview, perceived stress scale, and Parental Stress Index. Bonding, attachment, and trauma history will be assessed with psychological questionnaires and Childs behaviors with the Ackerman-CBCL questionnaire. Descriptive statistical analysis will be done. Correlations will identify associations and multivariate models will assess the role of parental bonding and effects of maternal attachment/trauma on associations to PRMS and child behavioral outcomes (controlling for confounding effects). RESULTS/ANTICIPATED RESULTS: First, we expect to find that mothers will report higher levels of stress (pandemic related, perceived, and parental) which will be associated with less bonding behaviors towards her child. Second, we expect that mothers levels of PRMS will be mediated by poorer bonding characteristics thus leading to negative child behavioral outcomes (i.e., poor regulation, crying spells, alterations in physiological patterns, and social-emotional developmental outcomes). Further mothers insecure attachment traits and trauma history will moderate perception of stress and negative child behavioral outcomes. DISCUSSION/SIGNIFICANCE: Results will describe stress in Latinx/Hispanics mothers during the pandemic and effects on child development. Identifying the role of maternal bonding/attachment will point to how this formative relationship has transformed during the pandemic, providing knowledge of mother-child resiliency.

OBJECTIVES/SPECIFIC AIMS: Mesh properties, such as stiffness, porosity, and weight have been shown to correlate with the degree of mesh integration with vaginal tissue. Previous research in rhesus macaques implanted with polypropylene mesh differing in stiffness, porosity, and weight showed differences in vaginal deterioration following mesh implantation. These differences were correlated with a foreign body response, consisting primarily of activated, proinflammatory M1 macrophages. Previous studies have determined that the early macrophage polarization profile following biomaterial implantation is a strong indicator of overall tissue integration downstream. However, these early responses have not been previously observed in the appropriate surgical models. Prior work from our laboratory in developing a cytokine delivery system has shown that shifting the macrophage response at the host-implant interface from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype in the first 14 days postimplantation resulted in enhanced integration of the mesh with the surrounding tissues. The present study develops an in vivo model clinically relevant surgical model to investigate the modulation of the host response to mesh. Utilizing a moderately-sized animal, we can feasibly implant mesh using the “gold standard” abdominal sacrocolpopexy procedure and evaluate the changes in the host immunologic response at early (14 d) and tissue remodeling outcomes at late stages (90 and 180 d) of implantation. METHODS/STUDY POPULATION: Commercially available heavyweight and lightweight mesh was used to investigate the modulation of the immune response. A custom MTI SILAR Automated Dip Coating machine is used to uniformly coat the mesh in a reproducible manner. An adapted radio frequency glow discharge method is used to create a stable negative charge on the surface of the mesh, followed by the sequential deposition of polycationic and polyanionic polymers to provide a stable, conformal, nanoscale coating. Chitosan served as the polycation, chosen because of its known antimicrobial and biocompatibility properties. Dermatan sulfate served as the polyanion, chosen for its important role in regulating extracellular matrix components and enhancing the activity of cytokines. Interleukin-4 (IL-4) is incorporated into the coating to be released in a controlled manner upon implantation. In vitro controlled release profiles were assessed to demonstrate efficient and local release of IL-4. Utilizing a New Zealand white rabbit surgical model, we implant mesh using the “gold standard” abdominal sacrocolpopexy procedure and evaluate the changes in the host immunologic response at early (14 d) and tissue remodeling outcomes at late stages (90 and 180 d) of implantation. The mesh-tissue complex was removed from each rabbit and processed for histological staining as well as immunolabeling of immune cells, such as macrophages. Determination of matrix metalloproteinases and fibrotic capsule formation also helps characterize the overall inflammatory response associated with each implant. RESULTS/ANTICIPATED RESULTS: We have developed a clinically relevant rabbit surgical model to implant different conditions of surgical mesh into 2 different sites, including the vagina and the abdomen. The results of this study show that implants into vaginal tissues elicited an increased host inflammatory response at 14 days as compared with those in the abdominal wall. However, at chronic time points the inflammatory response in the vagina was reduced as compared to that in the abdominal cavity. The present study also demonstrates the scale-up of a previous methodology for nano-scale coating. We present a nanometer thickness, tunable, and uniform coating capable of releasing bioactive IL-4. In vitro assays confirm the bioactivity and the controlled local release allowing for shifts in the immune response to promote implant integration. Improved remodeling has been observed to correlate with a shift in the early host response from an M1 to an M2 phenotype, however, there is limited information on the exact mechanism. Our strategy to achieve enhanced tissue remodeling demonstrate outcomes such as minimal changes to the structural properties of the mesh and a controlled release profile to sufficiently polarize macrophages around the mesh to a pro-remodeling state. DISCUSSION/SIGNIFICANCE OF IMPACT: Pelvic organ prolapse is a condition where the pelvic floor muscles weaken over time resulting in the downward shift of the pelvic organs into the vaginal canal. Moreover, factors such as obesity, age, and vaginal birth increase the susceptibility of being diagnosed with pelvic organ prolapse. Direct costs of reconstructive procedures exceed $1 billion each year in the United States. Synthetic mesh has been used to repair abdominal hernias for over half a century. Biomedical companies, through 510k and the 1976 Medical Device Amendments Act, were able to resell their hernia repair mesh as a treatment for pelvic organ prolapse. However, women who have had vaginal mesh implants have reported an increasing number of complications including chronic pain and mesh erosion/exposure at rates as high as 10%–20%. In fact, in 2008 and 2011, the US Food and Drug Administration issued warnings to doctors and patients about the mesh. In January 2016, the FDA officially had to reclassify surgical mesh for transvaginal repair of pelvic organ prolapse from a class II, moderate risk device, to a class III, high-risk device. Presently, data for the use of synthetic mesh has largely derived from abdominal hernia repair, instead of vaginal repair of prolapse. In the rodent model, the vagina is too small to implant mesh in an analogous manner to human implantation. Instead, implantations are done in the abdomen, a different tissue composition and host response profile than the vagina. Primate models of pelvic organ prolapse have been utilized, but are associated with high costs and investigation of acute immune responses are not considered ethical due to the short time of survival. Thus, our presented work will not only show the development of an improved material for implantation, but also the development of an in vivo model clinically relevant to understanding the early host response to mesh.

OBJECTIVES/GOALS: Accumulating evidence supports the involvement of immune and inflammatory pathways in Bipolar Disorder (BD) pathophysiology. This pilot study aims to determine if altered peripheral IL-2, TNF-a, IL-4, IL-6, IL-10, IFN-y, IL-17A levels are associated with BD across mood episodes (euthymic, manic, depressive), and worsen neurocognitive function. METHODS/STUDY POPULATION: Twenty-eight participants (17 cases and 11 controls) were recruited. We assessed the clinical features and cytokine plasma levels of participants. Cytokines were measured using Flow Cytometry. All subjects were interviewed by a trained psychiatrist. Each participant was fasting before the blood sample was taken. Neuropsychological tests were used to measure verbal fluency, speed processing, working memory/attention, visuospatial skills, verbal learning, executive functions, and motor skills. Descriptive statistics were used to calculate the demographic characteristics of the sample. An independent-sample Kruskal-Wallis Test and Mann-Whitney Test were carried out using SPSS version 21. RESULTS/ANTICIPATED RESULTS: Serum biomarker concentration showed a decrease in levels of IL-4 (anti-inflammatory) in BD patients vs healthy controls (p < .05). There was a major concentration of IL-6 (pro-inflammatory) on bipolar patients vs controls (p = .003). When we analyze the results with the mood episodes, we found that patients with bipolar depression showed decreased levels of IL-4 (p = .046) and increase levels of IL-6 (p = .020) in comparison to the manic or euthymic episodes. In the neurocognitive tests, we found that the control participants had better performance in the working memory domain (p = .038) and also in the general performance (p = .036) in comparison to bipolar patients. We found also a positive significant correlation between IL-4 and verbal learning in the control sample (.829, p = .003). DISCUSSION/SIGNIFICANCE: The findings evidence a significant immune activation in bipolar patients, in particular during the depressive episode. Participants with BD have a decrease in the protective levels of IL-4 combined with high levels of IL-6 when compared to healthy controls. Worse neurocognitive functioning was found in bipolar patients.

OBJECTIVES/GOALS: We sought to explore how the COVID-19 pandemic impacted community and stakeholder engagement in research from both researcher and stakeholder partner perspectives and to identify challenges, strategies, and other facilitators affecting their experience, including those related to virtual engagement. METHODS/STUDY POPULATION: We conducted semi-structured interviews with ten researchers and eight stakeholder partners who conducted or collaborated on stakeholder-engaged health research during the COVID-19 pandemic (March 2020 onwards). Potential participants were identified purposively and through snowball sampling. Interviews were conducted via Zoom, recorded, and transcribed for analysis. The transcribed data were qualitatively analyzed through an iterative process involving memoing and consensus coding using inductive and deductive codes. We reviewed memos and code reports to identify and describe key categories and themes. RESULTS/ANTICIPATED RESULTS: The challenges and facilitators identified varied based on factors such as geographic scope of the partnership (local vs national) and previous engagement type (virtual vs in-person). Many challenges were related to virtual engagement, such as dealing with distractions, limited access to Internet, or difficulty forming relationships online, or to wellbeing and personal circumstances, such as feeling burnt out, managing increased caregiving responsibilities, or concern about risk of illness if conducting in-person activities. Facilitators identified included having strong existing partnerships, utilizing strategies to enhance virtual engagement, adapting activities to manage risk of in-person interactions, and showing support to stakeholder partners. DISCUSSION/SIGNIFICANCE: By better understanding challenges and facilitators affecting experiences of both researchers and stakeholder partners engaging in research during the COVID-19 pandemic, we can develop strategies and resources to better support research partnerships during future health emergencies.

OBJECTIVES/SPECIFIC AIMS: Explore perceptions of Flint stakeholders on the water crisis regarding trust and the capacity of faith and community-based organizations providing public health services to address community needs. Analyze the community’s voice shared at (1) 17 key community communications (community/congressional meetings and events), and (2) during 9 focus group sessions, in which residents, faith-based leadership and other stakeholders discuss issues and concerns on the Flint Water Crisis, and recommend ways to address them. Develop a framework that defines core theories, concepts and strategies recommended by the community to help rebuild trust and the quality of life in Flint, Michigan, and support other communities experiencing environmental stress. METHODS/STUDY POPULATION: Study population: faith-based leaders, seniors, youth, Hispanic/Latino and African American stakeholders, and others experiencing inequities in the city of Flint. Convene 9 focus group sessions (recorded and transcribed) to learn community perceptions on trust and ways to address it. Validate accuracy of the transcriptions with community consultants to reconcile any inaccurate information. Through a community engaged research (CEnR) process, review and analyze qualitative data from the 9 focus group sessions, and quantitative data from 2 surveys documenting (1) demographic backgrounds of focus group participants, and (2) their perceptions on trust and mistrust. Prepare a codebook to qualitatively analyze the focus group data summarizing community input on trust, mistrust, changes in service delivery among community and faith-based organizations, and ways to re-build trust in the city of Flint. Transcribe the community’s voice shared during 17 key events, identified by a team of community-academic stakeholders (i.e., UM Flint water course, congressional and community events, etc.), in which residents and other stakeholders discuss issues and concerns on the Flint Water Crisis, and recommend ways to address it. Qualitatively analyze the transcriptions, using a CEnR process to prepare a codebook on key themes from the community’s voice shared at these events, and recommendations on ways to address it. Compare and contrast findings between the two codebooks developed from (1) the focus group data and (2) qualitative analysis of community voice during public meetings and events. Synthesize this information into a framework of core theories, concepts and rebuilding strategies for Flint, Michigan. RESULTS/ANTICIPATED RESULTS: It is important to note many undocumented immigrant populations in Flint fear deportation and other consequences, hampering their ability to obtain service and provide community voice. Through our purposive sampling approach, we will hear from community voices not often included in narratives (i.e., seniors, youth, Hispanic/Latino residents). The presentation will present findings documenting levels of trust and mistrust in the city of Flint; and a framework of recommendations, core theories and concepts on ways to reduce, rebuild and eliminate stress that will be helpful to other communities experiencing distress. DISCUSSION/SIGNIFICANCE OF IMPACT: To our knowledge, levels of trust and mistrust in Flint have not been documented thus far. We will compare and contrast common themes presented by the community at public meetings and events with themes presented in our focus group effort on trust. Faith and community-based providers were among the first responders to the Flint Water Crisis. The effort will also share perceptions on changes in public health service delivery, and observations on preparedness for these roles that occurred among community and faith-based providers. Finally, the effort will (1) support the design of a research agenda, (2) define a framework of core theories, concepts and recommendations developed by the community to help rebuild trust in Flint, Michigan; and (3) support other communities addressing environmental distress.

OBJECTIVES/GOALS: Characterize formal informatics methods and approaches for enabling reproducible translational research. Education of reproducible methods to translational researchers and informaticians. METHODS/STUDY POPULATION: We performed a scoping review [1] of selected informatics literature (e.g. [2,3]) from PubMed and Scopus. In addition we reviewed literature and documentation of translational research informatics projects [4–21] at the University of Utah. RESULTS/ANTICIPATED RESULTS: The example informatics projects we identified in our literature covered a broad spectrum of translational research. These include research recruitment, research data requisition, study design and statistical analysis, biomedical vocabularies and metadata for data integration, data provenance and quality, and uncertainty. Elements impacting reproducibility of research include (1) Research Data: its semantics, quality, metadata and provenance; and (2) Research Processes: study conduct including activities and interventions undertaken, collections of biospecimens and data, and data integration. The informatics methods and approaches we identified as enablers of reproducibility include the use of templates, management of workflows and processes, scalable methods for managing data, metadata and semantics, appropriate software architectures and containerization, convergence methods and uncertainty quantification. In addition these methods need to be open and shareable and should be quantifiable to measure their ability to achieve reproducibility. DISCUSSION/SIGNIFICANCE OF IMPACT: The ability to collect large volumes of data collection has ballooned in nearly every area of science, while the ability to capturing research processes hasn’t kept with this pace. Potential for problematic research practices and irreproducible results are concerns.

Reproducibility is a core essentially of translational research. Translational research informatics provides methods and means for enabling reproducibility and FAIRness [22] in translational research. In addition there is a need for translational informatics itself to be reproducible to make research reproducible so that methods developed for one study or biomedical domain can be applied elsewhere. Such informatics research and development requires a mindset for meta-research [23].

The informatics methods we identified covers the spectrum of reproducibility (computational, empirical and statistical) and across different levels of reproducibility (reviewable, replicable, confirmable, auditable, and open or complete) [24–29]. While there are existing and ongoing efforts in developing informatics methods for translational research reproducibility in Utah and elsewhere, there is a need to further develop formal informatics methods and approaches: the Informatics of Research Reproducibility.

In this presentation, we summarize the studies and literature we identified and discuss our key findings and gaps in informatics methods for research reproducibility. We conclude by discussing how we are covering these topics in a translational research informatics course.

1. 1. Pham MT, Rajić A, Greig JD, Sargeant JM, Papadopoulos A, McEwen SA. A scoping review of scoping reviews: advancing the approach and enhancing the consistency. Res Synth Methods. 2014 Dec;5(4):371–85.

2. 2. McIntosh LD, Juehne A, Vitale CRH, Liu X, Alcoser R, Lukas JC, Evanoff B. Repeat: a framework to assess empirical reproducibility in biomedical research. BMC Med Res Methodol [Internet]. 2017 Sep 18 [cited 2018 Nov 30];17. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604503/

3. 3. Denaxas S, Direk K, Gonzalez-Izquierdo A, Pikoula M, Cakiroglu A, Moore J, Hemingway H, Smeeth L. Methods for enhancing the reproducibility of biomedical research findings using electronic health records. BioData Min. 2017;10:31.

4. 4. Burnett N, Gouripeddi R, Wen J, Mo P, Madsen R, Butcher R, Sward K, Facelli JC. Harmonization of Sensor Metadata and Measurements to Support Exposomic Research. In: 2016 International Society of Exposure Science [Internet]. Research Triangle Park, NC, USA; 2017 [cited 2017 Jun 17]. Available from: http://www.intlexposurescience.org/ISES2017

5. 5. Butcher R, Gouripeddi RK, Madsen R, Mo P, LaSalle B. CCTS Biomedical Informatics Core Research Data Service. In Salt Lake City; 2016.

6. 6. Cummins M, Gouripeddi R, Facelli J. A low-cost, low-barrier clinical trials registry to support effective recruitment. In Salt Lake City, Utah, USA; 2016 [cited 2018 Nov 30]. Available from: //campusguides.lib.utah.edu/UtahRR16/abstracts

7. 7. Gouripeddi R, Warner P, Madsen R, Mo P, Burnett N, Wen J, Lund A, Butcher R, Cummins MR, Facelli J, Sward K. An Infrastructure for Reproducibile Exposomic Research. In: Research Reproducibility 2016 [Internet]. Salt Lake City, Utah, USA; 2016 [cited 2018 Nov 30]. Available from: //campusguides.lib.utah.edu/UtahRR16/abstracts

8. 8. Eilbeck K, Lewis SE, Mungall CJ, Yandell M, Stein L, Durbin R, Ashburner M. The Sequence Ontology: a tool for the unification of genome annotations. Genome Biol. 2005;6:R44.

9. 9. Gouripeddi R, Cummins M, Madsen R, LaSalle B, Redd AM, Presson AP, Ye X, Facelli JC, Green T, Harper S. Streamlining study design and statistical analysis for quality improvement and research reproducibility. J Clin Transl Sci. 2017 Sep;1(S1):18–9.

10. 10. Gouripeddi R, Eilbeck K, Cummins M, Sward K, LaSalle B, Peterson K, Madsen R, Warner P, Dere W, Facelli JC. A Conceptual Architecture for Reproducible On-demand Data Integration for Complex Diseases. In: Research Reproducibility 2016 (UtahRR16) [Internet]. Salt Lake City, Utah, USA; 2016 [cited 2017 Apr 25]. Available from: https://zenodo.org/record/168067

11. 11. Gouripeddi R, Lane E, Madsen R, Butcher R, LaSalle B, Sward K, Fritz J, Facelli JC, Cummins M, Shao J, Singleton R. Towards a scalable informatics platform for enhancing accrual into clinical research studies. J Clin Transl Sci. 2017 Sep;1(S1):20–20.

12. 12. Gouripeddi R, Deka R, Reese T, Butcher R, Martin B, Talbert J, LaSalle B, Facelli J, Brixner D. Reproducibility of Electronic Health Record Research Data Requests. In Washington, DC, USA; 2018 [cited 2018 Apr 21]. Available from: https://zenodo.org/record/1226602#.WtvvyZch270

13. 13. Gouripeddi R, Mo P, Madsen R, Warner P, Butcher R, Wen J, Shao J, Burnett N, Rajan NS, LaSalle B, Facelli JC. A Framework for Metadata Management and Automated Discovery for Heterogeneous Data Integration. In: 2016 BD2K All Hands Meeting [Internet]. Bethesda, MD; November 29-30 [cited 2017 Apr 25]. Available from: https://zenodo.org/record/167885

14. 14. Groat D, Gouripeddi R, Lin YK, Dere W, Murray M, Madsen R, Gestaland P, Facelli J. Identification of High-Level Formalisms that Support Translational Research Reproducibility. In: Research Reproducibility 2018 [Internet]. Salt Lake City, Utah, USA; 2018 [cited 2018 Oct 30]. Available from: //campusguides.lib.utah.edu/UtahRR18/abstracts

15. 15. Huser V, Kahn MG, Brown JS, Gouripeddi R. Methods for examining data quality in healthcare integrated data repositories. Pac Symp Biocomput Pac Symp Biocomput. 2018;23:628–33.

16. 16. Lund A, Gouripeddi R, Burnett N, Tran L-T, Mo P, Madsen R, Cummins M, Sward K, Facelli J. Enabling Reproducible Computational Modeling: The Utah PRISMS Ecosystem. In Salt Lake City, Utah, USA; 2018 [cited 2018 Oct 30]. Available from: //campusguides.lib.utah.edu/UtahRR18/abstracts

17. 17. Pflieger LT, Mason CC, Facelli JC. Uncertainty quantification in breast cancer risk prediction models using self-reported family health history. J Clin Transl Sci. 2017 Feb;1(1):53–9.

18. 18. Shao J, Gouripeddi R, Facelli J. Improving Clinical Trial Research Reproducibility using Reproducible Informatics Methods. In Salt Lake City, Utah, USA; 2018 [cited 2018 Oct 30]. Available from: //campusguides.lib.utah.edu/UtahRR18/abstracts

19. 19. Shao J, Gouripeddi R, Facelli JC. Semantic characterization of clinical trial descriptions from ClincalTrials.gov and patient notes from MIMIC-III. J Clin Transl Sci. 2017 Sep;1(S1):12–12.

20. 20. Tiase V, Gouripeddi R, Burnett N, Butcher R, Mo P, Cummins M, Sward K. Advancing Study Metadata Models to Support an Exposomic Informatics Infrastructure. In Ottawa, Canada; 2018 [cited 2018 Oct 30]. Available from: = http://www.eiseverywhere.com/ehome/294696/638649/?&t=8c531cecd4bb0a5efc6a0045f5bec0c3

21. 21. Wen J, Gouripeddi R, Facelli JC. Metadata Discovery of Heterogeneous Biomedical Datasets Using Token-Based Features. In: IT Convergence and Security 2017 [Internet]. Springer, Singapore; 2017 [cited 2017 Sep 6]. p. 60–7. (Lecture Notes in Electrical Engineering). Available from: https://link.springer.com/chapter/10.1007/978-981-10-6451-7_8

22. 22. Wilkinson MD, Dumontier M, Aalbersberg IjJ, Appleton G, Axton M, Baak A, Blomberg N, Boiten J-W, da Silva Santos LB, Bourne PE, Bouwman J, Brookes AJ, Clark T, Crosas M, Dillo I, Dumon O, Edmunds S, Evelo CT, Finkers R, Gonzalez-Beltran A, Gray AJG, Groth P, Goble C, Grethe JS, Heringa J, ’t Hoen PAC, Hooft R, Kuhn T, Kok R, Kok J, Lusher SJ, Martone ME, Mons A, Packer AL, Persson B, Rocca-Serra P, Roos M, van Schaik R, Sansone S-A, Schultes E, Sengstag T, Slater T, Strawn G, Swertz MA, Thompson M, van der Lei J, van Mulligen E, Velterop J, Waagmeester A, Wittenburg P, Wolstencroft K, Zhao J, Mons B. The FAIR Guiding Principles for scientific data management and stewardship. Sci Data. 2016 Mar 15;3:160018.

23. 23. Ioannidis JPA. Meta-research: Why research on research matters. PLOS Biol. 2018 Mar 13;16(3):e2005468.

24. 24. Stodden V, Borwein J, Bailey DH. Setting the default to reproducible. Comput Sci Res SIAM News. 2013;46(5):4–6.

25. 25. Stodden V, McNutt M, Bailey DH, Deelman E, Gil Y, Hanson B, Heroux MA, Ioannidis JPA, Taufer M. Enhancing reproducibility for computational methods. Science. 2016 Dec 9;354(6317):1240–1.

26. 26. Stodden V, McNutt M, Bailey DH, Deelman E, Gil Y, Hanson B, Heroux MA, Ioannidis JPA, Taufer M. Enhancing reproducibility for computational methods. Science. 2016 Dec 9;354(6317):1240–1.

27. 27. Stodden V. Reproducible Research for Scientific Computing: Tools and Strategies for Changing the Culture. Comput Sci Eng. 2012 Jul 1;14(4):13–7.

28. 28. Baker M. Muddled meanings hamper efforts to fix reproducibility crisis. Nat News Available from: http://www.nature.com/news/muddled-meanings-hamper-efforts-to-fix-reproducibility-crisis-1.20076

29. 29. Barba LA. Terminologies for Reproducible Research. ArXiv180203311 Cs 2018 Feb 9; Available from: http://arxiv.org/abs/1802.03311

OBJECTIVES/SPECIFIC AIMS: Translational researchers often require the use of informatics methods in their work. Lack of an understanding of key informatics principles and methods limits the abilities of translational researchers to successfully implement Findable, Accessible, Interoperable, Reusable (FAIR) principles in grant proposal submissions and performed studies. In this study we describe our work in addressing this limitation in the workforce by developing a competency-based, modular course in informatics to meet the needs of diverse translational researchers. METHODS/STUDY POPULATION: We established a Translational Research Informatics Education Collaborative (TRIEC) consisting of faculty at the University of Utah (UU) with different primary expertise in informatics methods, and working in different tiers of the translational spectrum. The TRIEC, in collaboration with the Foundation of Workforce Development of the Utah Center for Clinical and Translational Science (CCTS), gathered informatics needs of early investigators by consolidating requests for informatics services, assistance provided in grant writing, and consultations. We then reviewed existing courses and literature for informatics courses that focused on clinical and translational researchers [3–9]. Using the structure and content of the identified courses, we developed an initial draft of a syllabus for a Translational Research Informatics (TRI) course which included key informatics topics to be covered and learning activities, and iteratively refined it through discussions. The course was approved by the UU Department of Biomedical Informatics, UU Graduate School and the CCTS. RESULTS/ANTICIPATED RESULTS: The TRI course introduces informatics PhD students, clinicians, and public health practitioners who have a demonstrated interest in research, to fundamental principles and tools of informatics. At the completion of the course, students will be able to describe and identify informatics tools and methods relevant to translational research and demonstrate inter-professional collaboration in the development of a research proposal addressing a relevant translational science question that utilizes the state-of-the-art in informatics. TRI covers a diverse set of informatics content presented as modules: genomics and bioinformatics, electronic health records, exposomics, microbiomics, molecular methods, data integration and fusion, metadata management, semantics, software architectures, mobile computing, sensors, recruitment, community engagement, secure computing environments, data mining, machine learning, deep learning, artificial intelligence and data science, open source informatics tools and platforms, research reproducibility, and uncertainty quantification. The teaching methods for TRI include (1) modular didactic learning consisting of presentations and readings and face-to-face discussions of the content, (2) student presentations of informatics literature relevant to their final project, and (3) a final project consisting of the development, critique and chalk talk and formal presentations of informatics methods and/or aims of an National Institutes of Health style K or R grant proposal. For (3), the student presents their translational research proposal concept at the beginning of the course, and works with members of the TRIEC with corresponding expertise. The final course grade is a combination of the final project, paper presentations and class participation. We offered TRI to a first cohort of students in the Fall semester of 2018. DISCUSSION/SIGNIFICANCE OF IMPACT: Translational research informatics is a sub-domain of biomedical informatics that applies and develops informatics theory and methods for translational research. TRI covers a diverse set of informatics topics that are applicable across the translational spectrum. It covers both didactic material and hands-on experience in using the material in grant proposals and research studies. TRI’s course content, teaching methodology and learning activities enable students to initially learn factual informatics knowledge and skills for translational research correspond to the ‘Remember, Understand, and Apply’ levels of the Bloom’s taxonomy [10]. The final project provides opportunity for applying these informatics concepts corresponding to the ‘Analyze, Evaluate, and Create’ levels of the Bloom’s taxonomy [10]. This inter-professional, competency-based, modular course will develop an informatics-enabled workforce trained in using state-of-the-art informatics solutions, increasing the effectiveness of translational science and precision medicine, and promoting FAIR principles in research data management and processes. Future work includes opening the course to all Clinical and Translational Science Award hubs and publishing the course material as a reference book. While student evaluations for the first cohort will be available end of the semester, true evaluation of TRI will be the number of trainees taking the course and successful grant proposal submissions. References: 1. Wilkinson MD, Dumontier M, et al. The FAIR Guiding Principles for scientific data management and stewardship. Sci Data. 2016 Mar 15. 2. National Center for Advancing Translational Sciences. Translational Science Spectrum. National Center for Advancing Translational Sciences. 2015 [cited 2018 Nov 15]. Available from: https://ncats.nih.gov/translation/spectrum 3. Hu H, Mural RJ, Liebman MN. Biomedical Informatics in Translational Research. 1 edition. Boston: Artech House; 2008. 264 p. 4. Payne PRO, Embi PJ, Niland J. Foundational biomedical informatics research in the clinical and translational science era: a call to action. J Am Med Inform Assoc JAMIA. 2010;17(6):615–6. 5. Payne PRO, Embi PJ, editors. Translational Informatics: Realizing the Promise of Knowledge-Driven Healthcare. Softcover reprint of the original 1st ed. 2015 edition. Springer; 2016. 196 p. 6. Richesson R, Andrews J, editors. Clinical Research Informatics. 2nd ed. Springer International Publishing; 2019. (Health Informatics). 7. Robertson D, MD GHW, editors. Clinical and Translational Science: Principles of Human Research. 2 edition. Amsterdam: Academic Press; 2017. 808 p. 8. Shen B, Tang H, Jiang X, editors. Translational Biomedical Informatics: A Precision Medicine Perspective. Softcover reprint of the original 1st ed. 2016 edition. S.l.: Springer; 2018. 340 p. 9. Valenta AL, Meagher EA, Tachinardi U, Starren J. Core informatics competencies for clinical and translational scientists: what do our customers and collaborators need to know? J Am Med Inform Assoc. 2016 Jul 1;23(4):835–9. 10. Anderson LW, Krathwohl DR, Airasian PW, Cruikshank KA, Mayer RE, Pintrich PR, Raths J, Wittrock MC. A Taxonomy for Learning, Teaching, and Assessing: A Revision of Bloom’s Taxonomy of Educational Objectives, Abridged Edition. 1 edition. New York: Pearson; 2000.

There are numerous examples of translational science innovations addressing challenges in the translational process, accelerating progress along the translational spectrum, and generating solutions relevant to a wide range of human health needs. Examining these successes through an education lens can identify core principles and effective practices that lead to successful translational outcomes. The National Center for Advancing Translational Sciences (NCATS) is identifying and teaching these core principles and practices to a broad audience via online courses in translational science which teach from case studies of NCATS-led or supported research initiatives. In this paper, we share our approach to the design of these courses and offer a detailed description of our initial course, which focused on a preclinical drug discovery and development project spanning academic and government settings. Course participants were from a variety of career stages and institutions. Participants rated the course high in overall value to them and in providing a unique window into the translational science process. We share our model for course development as well as initial findings from the course evaluation with the goal of continuing to stimulate development of novel education activities teaching foundational principles in translational science to a broad audience.

A decline in routine vaccinations, attributed to vaccine hesitancy, undermines preventative healthcare, impacting health and exacerbating vaccine disparities. University-public health partnerships can improve vaccination services. This study describes and evaluates a university-public health use case employing social determinants of health (SDoH)-based strategies to address vaccination disparities. Guided by the Translational Science Benefits Logic Model, the partnership offered no-cost preventative vaccines at community-based organization (CBO) sites, collected CBO clientele’s vaccination interest, hesitancy, and demographic data, and conducted descriptive analyses. One hundred seven vaccination events were held, administering 3,021 vaccines. This partnership enhanced health outcomes by addressing disparities through co-located vaccination and SDoH services.

OBJECTIVES/GOALS: As the number of older adults (≥65 years) with T1D grows, there are limited data to guide care. In a six-month trial, CGM reduced hypoglycemia in older adults, yet there are challenges for widespread uptake. Our objective is to characterize older adults experiences with using CGM and define suboptimal responses signaling a need for resources or support. METHODS/STUDY POPULATION: The study will engage key stakeholders (i.e., older adults with T1D, caregivers [recruited as patient-caregiver dyads], and providers [endocrinologists, geriatricians, diabetes educators]) for a Group Model Building (GMB). GMB is a participatory approach to system dynamics in which participants share perceptions and experiences with a problem and collaboratively explore the system structure that shapes those trends. A series of 8 GMB workshops will be held with 3-8 participants. The final study n will be determined by thematic saturation. Workshops comprise 1) a questionnaire, 2) a GMB session, and 3) a focus group discussion. GMB will follow a replicable process to generate a model of the complex web of causal determinants affecting CGM-related experiences, including optimal and suboptimal CGM responses. RESULTS/ANTICIPATED RESULTS: To date, the study has enrolled 33 participants, including 28 older adults living with T1D and 5 caregivers (mean age = 74 years, range 67-83 years). Twenty-four patient participants will be active CGM users and 4 will be CGM non-users. The study will report on patient data capture from the questionnaire and EMR, including demographics, experiences, familiarity, and confidence surrounding CGM use; diabetes duration; insulin pump use; history of severe hypoglycemia. Analysis of aggregated data will generate causal loop diagrams that integrate pertinent theoretical frameworks, lived experiences, and CGM outcomes. Maps will be used to identify a set of suboptimal CGM responses (i.e., key outcome trajectories) that signal a need for action, with a diagram of factors that interact to produce each response. DISCUSSION/SIGNIFICANCE: Delivering CGM to older adults with T1D demands new approaches. This study will yield critical evidence to tailor support and resources for effective CGM use in older adults. Findings may be translated into suite of pragmatic interventions to bolster CGM use and matched to individual patients expected to benefit using a precision medicine framework.

OBJECTIVES/SPECIFIC AIMS: To determine the association between clinical characteristics and platelet reactivity in Hispanic patients on clopidogrel therapy. METHODS/STUDY POPULATION: A cross-sectional pilot study was performed in 58 Puerto Rican patients diagnosed with any type of vascular disease and actively receiving a maintenance dose of clopidogrel for at least 7 days. The study population was divided into 2 groups: Group I with non-high on-treatment platelet reactivity (TPR); Group II with high TPR. To determine the platelet function, P2Y12 reaction units (PRU) were obtained by VerifyNow® P2Y12 assay (Accumetrics, USA). RESULTS/ANTICIPATED RESULTS: We studied a heterogeneous cohort of patients with coronary artery disease (57%), peripheral artery disease (30%), carotid artery stenosis (7%), cerebral artery aneurysm (3%), and stroke (3%) on clopidogrel therapy for secondary prevention of thromboembolic events. The mean TPR was 205±49 PRU (range: 61–304), with a prevalence of 28% patients with high TPR (PRU≥230). No significant clinical differences were found between the non-high TPR and high-TPR groups (p>0.05). However, multivariable logistic regression analysis showed that both diabetes mellitus (OR=7.5; CI: 1.01–51.9) and proton-pump inhibitors (OR=13.6; CI: 1.3–142.0) were independently correlated with high TPR (p<0.05) after adjusting for other clinical variables. DISCUSSION/SIGNIFICANCE OF IMPACT: These results provide new insight into the importance of clinical characteristics on platelet reactivity in this Caribbean population. Further studies are warranted to determine whether important clopidogrel pharmacogenes are related with platelet function in Hispanics, as well as the role of TPR in guiding antiplatelet therapy and predicting future adverse cardiovascular events in this population.

OBJECTIVES/GOALS: To ameliorate the leaky pipeline of physician-scientists, we must address the factors that cause medical trainees to disengage from research. Here we describe the development of standardized Physician-Scientist Training Program guidelines that may be implemented across disciplines to address these challenges. METHODS/STUDY POPULATION: Maintenance of a robust pool of physician-scientists is critical to meet the rapidly growing need for novel therapeutics. A variety of factors contribute to the decline of this pool. Key among these are a lengthy training period that segregates research from clinical training, thus impeding research progress and milestones that allow for a successful research career. Through engagement of residency program directors and Vice Chairs of Research, we have created a series of guidelines that promote residency research tracks and enable better integration of research and clinical training time. Guidelines have been piloted in the Departments of Pediatrics, Medicine and Surgery in the context of 2 new R38-supported programs. RESULTS/ANTICIPATED RESULTS: Our physician-Scientist Training Program (PSTP) guidelines were developed by our central Office of Physician-Scientist Development (OPSD) after a successful pilot of an integrated research residency program in the Department of Pediatrics [Duke Pediatric Research Scholars (DPRS); Hurst, et al, 2019], which has included 36 resident and fellow scholars over 3 years. To date, eight clinical departments have adopted our PSTP guidelines as part of their R38-supported or pending programs. The OPSD has recently created a tracking database for scholar metrics, which will further promote PSTP development by enabling centralized reporting on scholar success to individual programs. DISCUSSION/SIGNIFICANCE OF IMPACT: PSTP guidelines enable effective implementation of new programs by sharing best practices and lessons learned, standardizing expectations, and defining metrics of success. By promoting proven strategies for integrated clinical and research training, PSTP guidelines may aid in retaining trainees pursuing research careers.

OBJECTIVES/GOALS: Assess the diagnostic yield and test utilization of WES in patients having complex traits. We aim to evaluate the use of the first genetic approach for the identification of primary variants that contribute to neurogenetic disease etiology and influence onset and progression in Puerto Ricans. METHODS/STUDY POPULATION: Prospective cohort of 45 Puerto Rican probands (19 months - 36 years old) with complex neurogenetic traits that underwent WES (2019 - 2021). WES was performed, including copy number variant analysis and mitochondrial genome sequencing. We evaluated several factors possibly influencing the rate of WES diagnosis including early age, consanguinity, and family history of neurogenetic diseases. In addition, we only evaluated probands rather than dyads/trios and the clinical phenotypes. Descriptive analysis was performed, including a catalog of all variants reported. Multivariate analysis was performed to estimate the statistical association between variants and phenotypes reported and adjusting for potential confounders (age, sex, family history, income, health insurance and zip code). RESULTS/ANTICIPATED RESULTS: Auspiciously, positive pathogenic findings altered the clinical management in 29% of the probands in this study. A likely genetic diagnosis was achieved in 53% of the probands including pathogenic, likely pathogenic and variants of uncertain significance. Intronic variants, copy number variants detection and mitochondrial genome was included in WES methodology. Despite these facts, a 47% of the reported WES were negative, which deserve re-analysis potentially genotype based. Multivariate analysis is expected to adjust for potential confounders to establish a genotype-phenotype correlations in neurogenetic complex traits in this Puerto Rican admixed population. DISCUSSION/SIGNIFICANCE: Clinical WES offers an alternative approach for identification of variants in patients with complex traits. WES is also applicable in genetically heterogeneous individuals when specific genetic tests are not available or unsuccessful. Variants reported contribute to understand complex neurogenetic disease in underrepresented Puerto Ricans.

ABSTRACT IMPACT: This work will help assess the effectiveness of the mentored career development programs. OBJECTIVES/GOALS: There is increased attention on assessing the impact of the CTSA in building a research workforce through mentored career development programs. We propose using data visualization to assess and communicate the impact of the programs on the scholars career development. METHODS/STUDY POPULATION: Evaluators from two CTSAs collaborated to visualize the KL2 data such as demographics, scholarly productivity (publications, grants, intellectual property), and time to promotion that is already tracked through REDCap at their institutions. Excel, Tableau, and Microsoft PowerBi were then used to generate trends in scholarly productivity over time. The goal was to compare how different tools can be used to visualize bibliometric data, based on what is available at the respective institutions. RESULTS/ANTICIPATED RESULTS: Longitudinal visual summary reports were produced for the entire program as well individual scholar progress. These reports can be used to identify trends such as how long after program completion do participants achieve their next milestone, what type of milestones are achieved, when in their career is their scholarly productivity the highest, etc. Answers to these questions could tell a story of the effectiveness of a mentored development program in the participants’ career. It can also highlight gaps and areas of opportunities that the program must address, either by adapting their curriculum or clarifying their intended outcomes. DISCUSSION/SIGNIFICANCE OF FINDINGS: Data visualization provides better understanding of the impact of the training programs on the scholars career development. Such insights are otherwise missing when evaluations are only focused on the percentage of scholars who were still engaged in research after completion of the program.

OBJECTIVES/SPECIFIC AIMS: Improving human papillomavirus (HPV) vaccination rates ultimately decreases the morbidity and mortality of HPV-associated diseases. A school-based program was piloted in the Rio Grande City Consolidated Independent School District (RGCCISD) to increase HPV vaccination. METHODS/STUDY POPULATION: We assessed baseline HPV vaccination; surveyed 622 parents of eligible children aged ≥9 years; and piloted and developed a school-based HPV education and vaccination program in 1 middle school in 2017 and 4 additional middle schools in 2018. The parent survey included (1) demographic information, (2) an assessment of parental knowledge about the HPV vaccine, and (3) information about their children and HPV vaccine experience. Results of the parent survey and pilot program are in progress. RESULTS/ANTICIPATED RESULTS: As of 9/1/2016, 20.4% of the 7527 RGCCISD eligible students (≥9 years) had completed the HPV vaccine. Baseline completion rates were higher for RGCCISD students aged 12–14 years compared with students aged 9–11 and ≥15 years (28.4% vs. 16.5%). Baseline completion rates for RGCCISD adolescents were substantially lower than those reported in NIS-Teen and for Texas (42% females and 28% males for NIS-Teen vs. 41% and 24% for the state of Texas). DISCUSSION/SIGNIFICANCE OF IMPACT: Initial results show that engagement with key stakeholders is important and schools are a great venue for delivering and increasing HPV vaccination.

OBJECTIVES/SPECIFIC AIMS: The DIAMOND project encourages study team workforce development through the creation of a digital learning space that brings together resources from across the CTSA consortium. This allows for widespread access to and dissemination of training and assessment materials. DIAMOND also includes access to an ePortfolio that encourages CRPs to define career goals and document professional skills and training. METHODS/STUDY POPULATION: Four CTSA institutions (the University of Michigan, the Ohio State University, University of Rochester, and Tufts CTSI) collaborated to develop and implement the DIAMOND portal. The platform is structured around eight competency domains, making it easy for users to search for research training and assessment materials. Contributors can upload links to (and meta-data about) training and assessment materials from their institutions, allowing resources to be widely disseminated through the DIAMOND platform. Detailed information about materials included in DIAMOND is collected through an easy to use submission form. DIAMOND also includes an ePortfolio designed for CRPs. This encourages workforce development by providing a tool for self-assessment of clinical research skills, allowing users to showcase evidence of experience, training and education, and fosters professional connections. RESULTS/ANTICIPATED RESULTS: To date, more than 100 items have been posted to DIAMOND from nine contributors. In the first 30 days there were 229 active users with more than 500 page views from across the U.S. as well as China and India. Training materials were viewed most often from four competency domains: 1) Scientific Concepts & Research Design, 2) Clinical Study Operations, 3) Ethical & Participant Safety, and 4) Leadership & Professionalism. Additionally, over 100 CRPs have created a DIAMOND ePortfolio account, using the platform to document skills, connect with each other, and search for internships and job opportunities. DISCUSSION/SIGNIFICANCE OF IMPACT: Lessons learned during development of the DIAMOND digital platform include defining relevant information to collect for the best user experience; selection of a standardized, user-friendly digital platform; and integration of the digital network and ePortfolio. Combined, the DIAMOND portal and ePortfolio provide a professional development platform for clinical research professionals to contribute, access, and benefit from training and assessment opportunities relevant to workforce development and their individual career development needs.

OBJECTIVES/GOALS: Methods for recruitment and retention of participants in research have been extensively discussed, but procedures to end studies in a way that is respectful to participants and keeps them engaged are seldom described. We relate the procedures to close a study focused on genomic DNA damage and DNA repair capacity in a longitudinal population sample. METHODS/STUDY POPULATION: Data collection, which included the provision of 30 ml blood sample along with a health status survey and anthropometric measurements, was discontinued earlier than anticipated during the fourth of a five-year Community Engaged Research (CEnR) study focused on residents of historically marginalized, low wealth communities. In collaboration with the project’s Community Advisory Board, we devised a strategy to inform study participants of the study closure, which included: 1) attempts at one-on-one contact via phone, 2) provision of a study closure packet, 3) periodic mailing of study updates through study year five, 4) sustained interaction with participants through invitations to participate in additional research projects. RESULTS/ANTICIPATED RESULTS: Among 149 participants (65% female, 99% of African American descent), 106 (71%) have been reached by phone. The communication included: 1) expressions of gratitude for their participation; 2) explanation of study findings to date; and 3) assurance that data analysis continued. Among those reached, 96% agreed to ongoing communication and 97% agreed to be contacted about future studies. We continue procedures to reach the remaining 43 participants. Over the study closure period, two qualitative studies offered opportunities for participants to join in focus groups (FG). The first one queried perceptions of community-based research. The response rate was 66% among 65 persons invited. The second study, focused on COVID-19 knowledge and invited 39 individuals with 24 scheduled to participate (62% response rate). DISCUSSION/SIGNIFICANCE: Translational research views the participant as an active partner. Study closure offers an opportunity to foster a long-lasting participant-research institution partnership, while also promoting participants’ broad engagement and familiarity with research. Respectful research closure is an important step in CEnR.