OBJECTIVES/GOALS: Use an easily accessible medium to educate life science researchers and academic innovators interested in the commercialization of academic research at the University of Michigan (UM). METHODS/STUDY POPULATION: Life science research investigators and academic innovators interested in research commercialization and technology development from across the state of Michigan were invited to attend the Idea to Impact: The Translation & Commercialization of Academic Research webinar series, presented by Fast Forward Medical Innovation at the University of Michigan. The webinar series outlined the significance and critical milestones of developing novel therapeutics, medical devices, diagnostics, and digital health innovations, as well as essential collaborations with industry partners to translate a research-based idea into a product of impact. RESULTS/ANTICIPATED RESULTS: 113 investigators and innovators from 28 different institutions, organizations, and companies, registered for the webinar series. Results (N=24) of an evaluation immediately following each webinar revealed that 100% of respondents strongly agreed or agreed that the series was effective in helping them to identify and describe commercialization resources, including funding, education, and mentorship, available at the University of Michigan and within the state. Participants stated that they “loved the practical information” “shared” and that the series was a “great overview that inspired a lot more questions.” The Fast Forward Medical Innovation team was then able to consult with participants to connect them with additional resources. DISCUSSION/SIGNIFICANCE: The data suggests that easily accessible and digestible commercialization education can make navigating the academic entrepreneurial ecosystem easier for investigators and innovators. The recorded webinar series, Idea to Impact: The Translation & Commercialization of Academic Research, serves this purpose.

OBJECTIVES/GOALS: The goal of the CTSA consortium is to move scientific discoveries to clinical application. Translational science (TS) focuses on the process by which this happens, and NCATS supports pilot projects that propose TS questions. We are developing a rubric to guide program managers’ability to discriminate between TS and translational research (TR). METHODS/STUDY POPULATION: The CTSA External Review Exchange Consortium (CEREC) and CEREC II are reciprocal review collaborations between CTSA hubs that identify reviewers for each other’s pilot grant applications. CEREC and CEREC II partners developed a 31-item rubric, based on NIH’s Translational Science Principles, for discriminating pilot TS grant applications from those proposing TR. The hubs contributed proposals pre-selected as either TS or TR projects. Then, experienced reviewers and/or program administrators from the hubs used the rubric to score each of the proposals. Reliability of the rubric will be assessed using inter-rater reliability (% agreement and kappa). To identify which of the items in the rubric best discriminate between TS and TR, Item Response Theory analysis will be employed. RESULTS/ANTICIPATED RESULTS: Ten CEREC participating hubs submitted 30 applications: 20 TS proposals and 10 TR proposals. Twenty-two reviewers from 12 CEREC hubs evaluated the applications by using the scoring rubric; at least two reviewers evaluated each proposal. The results of the analyses will describe the reliability of the rubric and identify which of the seven TS Principles are most useful for distinguishing between TS and TR pilot grant proposals. Ultimately, this work will yield a scoring rubric that will be disseminated throughout the CTSA network to facilitate the screening of TS applications. DISCUSSION/SIGNIFICANCE: Optimizing research processes is critical to ensure that scientific discoveries are integrated into clinical practice and public health policy as rapidly, efficiently, and equitably as possible. By appropriately identifying and funding TS projects, CTSA hubs can accelerate the impact of clinical and translational research.

OBJECTIVES/SPECIFIC AIMS: To examine and compare the claims in Bzdok, Altman, and Brzywinski under a broader set of conditions by using unbiased methods of comparison. To explore how to accurately use various machine learning and traditional statistical methods in large-scale translational research by estimating their accuracy statistics. Then we will identify the methods with the best performance characteristics. METHODS/STUDY POPULATION: We conducted a simulation study with a microarray of gene expression data. We maintained the original structure proposed by Bzdok, Altman, and Brzywinski. The structure for gene expression data includes a total of 40 genes from 20 people, in which 10 people are phenotype positive and 10 are phenotype negative. In order to find a statistical difference 25% of the genes were set to be dysregulated across phenotype. This dysregulation forced the positive and negative phenotypes to have different mean population expressions. Additional variance was included to simulate genetic variation across the population. We also allowed for within person correlation across genes, which was not done in the original simulations. The following methods were used to determine the number of dysregulated genes in simulated data set: unadjusted p-values, Benjamini-Hochberg adjusted p-values, Bonferroni adjusted p-values, random forest importance levels, neural net prediction weights, and second-generation p-values. RESULTS/ANTICIPATED RESULTS: Results vary depending on whether a pre-specified significance level is used or the top 10 ranked values are taken. When all methods are given the same prior information of 10 dysregulated genes, the Benjamini-Hochberg adjusted p-values and the second-generation p-values generally outperform all other methods. We were not able to reproduce or validate the finding that random forest importance levels via a machine learning algorithm outperform classical methods. Almost uniformly, the machine learning methods did not yield improved accuracy statistics and they depend heavily on the a priori chosen number of dysregulated genes. DISCUSSION/SIGNIFICANCE OF IMPACT: In this context, machine learning methods do not outperform standard methods. Because of this and their additional complexity, machine learning approaches would not be preferable. Of all the approaches the second-generation p-value appears to offer significant benefit for the cost of a priori defining a region of trivially null effect sizes. The choice of an analysis method for large-scale translational data is critical to the success of any statistical investigation, and our simulations clearly highlight the various tradeoffs among the available methods.

Housing is an environmental social determinant of health that is linked to mortality and clinical outcomes. We developed a lexicon of housing-related concepts and rule-based natural language processing methods for identifying these housing-related concepts within clinical text. We piloted our methods on several test cohorts: a synthetic cohort generated by ChatGPT for initial infrastructure testing, a cohort with substance use disorders (SUD), and a cohort diagnosed with problems related to housing and economic circumstances (HEC). Our methods successfully identified housing concepts in our ChatGPT notes (recall = 1.0, precision = 1.0), our SUD population (recall = 0.9798, precision = 0.9898), and our HEC population (recall = N/A, precision = 0.9160).

This case study presents an analysis of community-driven partnerships, focusing on the nonprofit Baltimore CONNECT (BC) network and its collaborative efforts with a Community-Engaged Research (CEnR) team of the Johns Hopkins Institute for Clinical and Translational Research (ICTR). BC has built a network of over 30 community-based organizations to provide health and social services in Baltimore City. The study emphasizes the role of CEnR in supporting community-led decision-making, specifically in the planning and implementation of community health resource fairs. These fairs address social determinants of health by offering a variety of services, including health education, screenings, vaccinations, and resource distribution. The paper details the methods, resource mobilization, and collaborative framing processes in the execution of these fairs in a community-academic collaboration with the ICTR. Results from a 2.5-year period show the positive impact of the fairs on individuals, families, and the community at large in East Baltimore. The findings underscore the importance of community-led collaborations in addressing health disparities and improving overall community well-being. It concludes by reflecting on the sustained engagement, trust-building, and shared learning that emerges from such partnerships, suggesting a model for future community-academic health initiatives.

OBJECTIVES/GOALS: Healthcare sectors are rushing to develop AI models. Yet, a dearth of coordinated practices leaves many teams struggling to implement models into practice. The Enterprise AI Translation Advisory Board uses across-disciplinary team to facilitate AI translation. METHODS/STUDY POPULATION: The Mayo Clinic Enterprise AI Translation Advisory Board was established to assess AI solutions lever aging cross-disciplinary team science to accelerate AI innovation and translation. The 23-member board reflects expertise in data science, qualitative research, user experience, IT, human factors, informatics, regulatory compliance,ethics, and clinical care, with members spanning thought leadership, decision-making, and clinical practice. Taking an approach of respectful communication, transparency, scientific debate, and open discussion, the Board has consulted onover two dozen projects at various stages of the AI life cycle. RESULTS/ANTICIPATED RESULTS: Common issues identified for projects earlier in the AI life cycle, sometimes fatal but often address able once identified, include a lack of buy-in from potential product users, a lack of planningabout integration into clinical workflow, inadequately labeled data, and attempting to use machine learning when what is desired is really a causal model for intervening. Recommendations for projects later in the AI life cycle include details of a testing plan (silent evaluation, pragmatic clinical trials), advice about clinical integration, both post-hoc and on going auditing for performance disparities, and planning for regulatory clearance. DISCUSSION/SIGNIFICANCE: Advising is more valuable for projects at the ideation phase, when multi disciplinary interrogation can identify weaknesses. But at all phases, projects have gaps related to a lack of specific disciplinary expertise. A multi disciplinary cluster like the AI Translation Advisory Board seeks to address these gaps.

OBJECTIVES/GOALS: Introduction: Between 2014 and 2019 the National Institute of Health (NIH) through the National Center for the Advancement of Translational Science (NCATS) has awarded about $2.7 billion to U.S. Academic Medical Centers to build a national network of clinical and translational science program hubs that serve to meet their key goals and initiatives. Today there are about 60 Clinical and Translational Science Award (CTSA) program hubs. Each CTSA program hub has a corresponding website highlighting its clinical and translational science centered programs and activities. These websites are a critical communication gateway to promote NCATS goals and initiatives. Objective: The objective of this research is to evaluate the NIH funded Clinical and Translational Science Award (CTSA) program hub websites for NCATS goals and initiative content alignment, navigability, and interactivity. METHODS/STUDY POPULATION: Methods: Each CTSA program hub website was systematically evaluated for information or tools that align with the five NCATS / CTSA Goals and eight CTSA nationally identified program initiatives. Each NCATS goal and CTSA initiative was subsequently ranked by information diversity level (text, tool, interactivity) and navigation level (click distance from the home page). RESULTS/ANTICIPATED RESULTS: Results: Four of the five NCATS goals are thoroughly and consistently represented among the CTSA Consortium with workforce development, patient and community engagement, and quality and efficiency of research being the top three. Informatics is thoroughly and consistently represented, but not always clearly identified on the home page. The most underrepresented goal is integration of special and underserved populations which was identified on only 60% of CTSA program hub websites. The most common focus of the eight CTSA program initiatives is the Trial Innovation Network in CTSA program hub websites. The Smart IRB comes in a distant second. The remaining six initiatives are severely underrepresented. DISCUSSION/SIGNIFICANCE OF IMPACT: Discussion: The identification of these gaps among the CTSA program hubs presents an understanding of content management and website functionality among the consortium from 3 principal approaches. First it creates an understanding of CTSA program hub content alignment with its funding source goals and initiatives. Such an understanding presents an opportunity to promote ways to create a better aligned consortium with improved collaboration pathways by the funding source through program hub website content standards. Second, it creates an opportunity for program hubs to understand and respond to the messaging their websites are presenting as it relates to the funding source. Third, it provides an opportunity to identify specific program initiatives and goals the CTSA institutions independently chose to highlight which can open a dialog to the better understanding the value of the program initiatives as they relate to the needs of CTSA program hubs. Ultimately, CTSA websites through content alignment should lead to an improved user experience.

OBJECTIVES/SPECIFIC AIMS: To study the role of OSA as an independent predictor of perioperative outcomes. METHODS/STUDY POPULATION: For this single-institution cohort study, we included data from patients who were enrolled into 1 of 3 prospective parent studies. All participants underwent in-patient surgeries, excluding neurosurgeries, which required general anesthesia and a postoperative stay of at least 1 day. Patients included in this study were assessed daily for postoperative delirium and pain severity as part of the parent studies. In the current study, determination of delirium diagnosis was based on the 3-minute Diagnostic Confusion Assessment Method (3D-CAM), and the Visual Analogue Pain Scale (VAS) was used for pain severity. Data on OSA diagnosis (determined by sleep study); OSA risk (determined by the STOP-Bang tool; snoring, tiredness, observed apnea, high blood pressure, body mass index>35 kg/m2, age>50, neck circumference, male gender); and compliance with treatment were obtained from the preoperative assessment record. Participants were grouped into 1 of 3 categories: high risk of OSA (HR-OSA; including patients with a previous positive sleep study or STOP-Bang score ≥5); intermediate risk of OSA (IR-OSA; including patients with a STOP-Bang score of 3 or 4); and low risk of OSA (LR-OSA; including patients with a previous negative sleep study or STOP-Bang score <3). Candidate risk factors for delirium and pain were also extracted from this record. RESULTS/ANTICIPATED RESULTS: Logistic regression will be used to test whether OSA independently predicts postoperative delirium and linear regression to assess OSAs relationship to acute pain severity. We hypothesize that patients in the HR-OSA category will experience a higher incidence of postoperative delirium and greater postoperative pain severity. We also predict a step-wise increase in risk of these adverse outcomes when analyzing patients stratified by OSA risk (HR-OSA vs. IR-OSA vs. LR-OSA). For our secondary analyses, we anticipate these outcomes are modified by compliance with CPAP treatment. We believe patients with OSA who do not use prescribed CPAP will experience a higher incidence of postoperative delirium as well as increased pain severity. DISCUSSION/SIGNIFICANCE OF IMPACT: OSA is a common and frequently undiagnosed perioperative problem associated with altered pain processing and a high incidence of postoperative delirium. While likely providing stronger evidence of OSA’s reported impact on postoperative delirium and pain, our findings might also help discern points of intervention for treatment and prevention. Since OSA’s presumed impact poses challenges to clinicians and patients, prospective, randomized trials testing preventative or mitigating interventions are necessary. We hope to use these results to design such trials and clinical plans, with the goal of reducing postoperative delirium and acute postsurgical pain severity for the large number of patients at risk due to OSA.

OBJECTIVES/GOALS: The Colorado Community Engagement Alliance Against COVID-19 Disparities (CO-CEAL) Team has worked with 5 racial/ethnic communities in Colorado to understand COVID-19 vaccine hesitancy and develop messages, materials and dissemination strategies to impact vaccine hesitancy. Relationships have been key facilitators of this work. METHODS/STUDY POPULATION: CO-CEAL was funded for one year as a part of the national CEAL Teams effort. CO-CEAL engaged urban Hispanic/LatinX, rural Hispanic/LatinX, urban African/American, rural African Immigrant and urban American Indian/Alaska Native communities through Community Connectors in each community. Our Community Connectors led recruitment of community members for our community survey data collection (goal of 200 surveys from each community) and participation in our 5 Community (Boot Camp) Translations. Where possible we worked with Community Connectors and leveraged community relationships with whom we had worked over multiple years and projects. In two communities we worked to quickly build and establish new relationships with Community Connectors and their communities. RESULTS/ANTICIPATED RESULTS: The rapid nature of the CO-CEAL project, its timeline and the unusual nature of the funding mechanism required adaptations to usual ways of working on both the academic and community side.In our CO-CEAL partner communities where there was a history of working together, concerns, possible barriers and other issues tended to be rapidly addressed. The prior existing, long-standing relationships fostered trust that enabled open airing of concerns and an ability to address issues as they arose. In CO-CEAL partner communities where new relationships were being forged, trust needed to be build from the ground up. This made adaptations more challenging and the ability to address concerns and issues as they arose more problematic. Although the work has moved forward in all communities, extra care has been required in some. DISCUSSION/SIGNIFICANCE: When crises necessitate rapid action in communities, the depth of prior investments in building and maintaining relationships makes a difference in how rapidly and successfully partners can work together to address a crisis like the COVID-19 pandemic. Funders and Academic researchers should invest broadly in communities to enable rapid responses.

Translation is the process of turning observations in the research laboratory, clinic, and community into interventions that improve people’s health. The Clinical and Translational Science Awards (CTSA) program is a National Center for Advancing Translational Sciences (NCATS) initiative to advance translational science and research. Currently, 64 “CTSA hubs” exist across the nation. Since 2006, the Houston-based Center for Clinical Translational Sciences (CCTS) has assembled a well-integrated, high-impact hub in Texas that includes six partner institutions within the state, encompassing ∼23,000 sq. miles and over 16 million residents. To achieve the NCATS goal of “more treatments for all people more quickly,” the CCTS promotes diversity and inclusion by integrating underrepresented populations into clinical studies, workforce training, and career development. In May 2023, we submitted the UM1 application and six “companion” proposals: K12, R25, T32-Predoctoral, T32-Postdoctoral, and RC2 (two applications). In October 2023, we received priority scores for the UM1 (22), K12 (25), T32-Predoctoral (20), and T32-Postdoctoral (23), which historically fall within the NCATS funding range. This report describes the grant preparation and submission approach, coupled with data from an internal survey designed to assimilate feedback from principal investigators, writers, reviewers, and administrative specialists. Herein, we share the challenges faced, the approaches developed, and the lessons learned.

At least 70% of premature adult deaths result from behaviors starting and reinforced in adolescence. The use of adolescent-centered outcomes and the necessity of creating space for the adolescent voice regarding research that directly impacts them is often overlooked. These omissions result in proposals and solutions that lack consideration of adolescent ingenuity, preferences, and needs. In 2021, Penn State PRO Wellness was awarded a Patient-Centered Outcomes Research Institute Engagement Award with the goal of addressing the gap in the inclusion of adolescents in research focused on teenage health. The resultant Adolescent Health Network (AHN) was developed in partnership with a stakeholder advisory board comprised of adolescents, parents, health researchers, and school staff. The AHN currently consists of 12 schools and 43 adolescents who have completed stakeholder training. For adolescents, the AHN simulates a school club or career enrichment activity with incoming freshmen replacing graduating seniors over time. For health researchers, the AHN provides rapid, easy access to a pool of adolescents with stakeholder training who are available to provide input on various aspects of a study from recruitment plans, to survey tools to dissemination strategies. This manuscript details the development, execution, and data from this novel program.

OBJECTIVES/GOALS: To describe how the Community Engagement (CE) Program at the Michigan Institute for Clinical & Health Research (MICHR), a Clinical & Translational Science Award (CTSA) site at the University of Michigan, is adopting human-centered design (HCD) to advance the science of community engagement in translational research and CE’s programmatic efforts. METHODS/STUDY POPULATION: The MICHR CE Program supports academic-community partnerships to transform translational research across the state of Michigan. As the team aims to better engage partners to help guide the direction of their work, CE is collaborating with MICHR’s Design and Innovation Core to incorporate human-centered design (HCD). HCD is an approach that prioritizes the needs, values, and perspectives of direct users during the creation of a new product or service. The MICHR team created interactive HCD activities for two statewide retreats to elicit feedback from community and academic members on ways to enhance community-engaged research (CEnR). Retreat participants worked on a variety of problems, such as barriers to partnering and defining impact for CEnR. These activities generated authentic, contextual, and multi-view data captured in various artifacts for systematic analysis. RESULTS/ANTICIPATED RESULTS: In the first retreat, a HCD activity had participants reflect on their own barriers to partnering in research and potential solutions. In the second retreat, an HCD activity facilitated participants interviewing each other on their views of the impact in CEnR. Results from the first activity identified a set of common barriers to CEnR, some related to partnership formation, communication, and partner equity, among others. These led the CE Program to specific programmatic efforts, such as designing a statewide partnership platform, hiring a communication program manager, and sponsoring community partners to join national conferences. The second retreat activity produced rich data to identify overlaps between different perspectives to inform how impact can be defined and measured in CEnR. DISCUSSION/SIGNIFICANCE OF IMPACT: HCD activities provide means to include community and academic members in the science of CEnR. They allow systematic ways to gather information directly from the diverse set of current or prospective partners of community engagement programs about their needs, experiences, and values, which can be translated to programmatic innovation.

OBJECTIVES/SPECIFIC AIMS: To mobilize and engage CHWs/promotores as stakeholders, we aim to promote the capacity for CHWs participate in patient centered research (PCOR) by locally implementing a structured research training curriculum for CHWs. Main Questions: How the process of mobilization and engagement would be implemented at local/state level? What would be project challenges, risks and barriers at each and across sites? What modifications would be made to the initial PCOR for CHWs training curriculum and toolkit based on local feedback from collaborators, in both English and Spanish? What would be lessons learned on mobilization, engagement of, and sustainability for CHW training organizations as partners in PCOR? METHODS/STUDY POPULATION: Measures: Monthly calls and quarterly reports from local organizations on activities, deliverables status, modifications, project implementation challenges/barriers and solutions (experienced and potential) to achieve goals of training 10 PCOR CHW Champions and a total of 360 CHWs/promotores trained in PCOR. Input from Note taker reports, Feedback and Evaluation Forms from training attendees at each session. Co-authorship of team members on dissemination activities (submissions for presentations, posters, blogs entries, webinars). Activities/Procedures: Via a highly participatory, consensus-driven decision-making approach, each of the organizations in the target states provide input into refining the toolkit for local use, select the training champions and develop CHW/promotor outreach and recruitment plans, and deliver the PCOR training to CHWs. In addition, the organizations will also set up a local stakeholder CHW/promotores advisory group. Environmental scan and literature review continues on training content areas to complement field experience in implementing the trainings at local sites. Project information tools developed (info sheet for local organizations, informational slide set to be used at calls and statewide seminars, a templates for flyer for training recruitment, agenda, certificates). FL and TN pilot of the translation of the curriculum, addressing problematic concepts and terms, collecting feedback forms eliciting input on terminology variations across Spanish speaking populations and literacy levels. Project Collaborators: Día de la Mujer Latina, a patient advocacy group in Texas with CHW trainings in several states and Puerto Rico Chula Vista Community Collaborative, a community health empowerment organization in Southern California Progresso Community Center, a Latino-focused health coalition based in Tennessee Florida Community Health Worker Coalition, a statewide partnership dedicated to the support and promotion of the CHW profession in Florida. RESULTS/ANTICIPATED RESULTS: Results: Trainings per State - Y1 Jan- October 2018 Totals: 11 PCOR Champions and 252 PCOR-Trained CHWs in CA-TX-TN Y2 Plans (October 2018-September 2019): Will continue to collect CHW trainee demographic data, CHW certification and patient/patient advocate status. Will conduct qualitative and quantitative analysis of all quarterly reports, Note taker, and trainee Feedback and Evaluation forms. Will reach goal of 360 PCOR-trained CHWs in FL, CA, TX and TN. Will continue to submit abstracts on our story on building patient and stakeholder capacity to participate as partners in patient-centered outcomes research, engagement and mobilization, from topic generation through the dissemination of research results. From evaluation analysis of content and process measures, we will discuss sustainability strategies as shared learning collaborative. DISCUSSION/SIGNIFICANCE OF IMPACT: Challenges/Decision Points Y1: On Mobilization and Engagement: Across partners, different levels of readiness/capacities/structures, and access to local resources Process application for request for content and guest instructor approvals to the Texas Department of State Health Services (DSHS) for CHW and CHW Instructor credit Co-branding of informational products (recruitment flyers, agendas, certificates), slides of Welcome section On Content and Curriculum Development: Address different levels of literacy Format (1-day vs spread, in person/online, prescriptive vs open) Clear distinction between service provision and research; paradigm shift of transfer of skills Inserting examples of unethical health research past activities with both African American and Hispanic/Latino populations Reinstating phases of clinical studies basic information Creating a study research design activity in Chapter 1 CHW role as member of research team Adding PCORI-funded project summary fact sheet per state On translations: Diversity of nuances of meaning in vocabulary for concepts On sustainability: Different degrees of organizational and personal involvement Next for newly PCOR-trained CHWs Meaningfully engaging patients and other stakeholders is increasingly recognized as requisite to generate research findings that are trusted, meaningful, and useful to clinicians, patients, and their families. One key engagement strategy used for engaging specific patients/caregivers and patient advocates in underserved communities is leveraging our partnerships with Community Health Workers (CHWs). Moreover, there is a documented need for higher level of training skills to undertake activities such as community health assessments, program evaluations and clinical studies. University of Miami (UM) along FL partners has successfully developed a 7-hr specialized toolkit on patient-centered research for CHWs and trained 148 CHWs/promotores (original plans were for 100) across the six major statewide regions. Evaluation data resulted in 100% of attendees responses’ as excellent and 99% would recommend it to others. Qualitative comments included “even though the training was tailored for research, I feel that it applies to many other aspects of the CHW role” and “I feel more empowered in my role after hearing explicitly the opportunities…for a CHW to be more involved in the research process”. UM has partnered with stakeholders in FL, Texas, southern California and Tennessee to develop a Spanish version of the PCOR for CHWs Training Toolkit (including a slide deck, Facilitator’s Guide and Student Workbook) that can be culturally and linguistically appropriate, to train local CHWs/promotores as PCOR CHW Champions. Attendees will receive lunch and a certificate of participation upon completion of the module. In turn, they agree to train local CHWs in their region. These 7 credit hrs could be used as credits towards state certification requirements, in states with CHW certification programs. This partnership for the mobilization and engagement of CHWs/promotores aims to strengthen their capacity to be involved in PCOR at the local and national level and increase the organizational capacity of CHW representative organizations in their promotion of PCOR. This type of research aims to help patients and those who care for them make better-informed decisions about the healthcare choices they face every day, guided by those who will use that information. In doing so, CHWs/promotores are contributing to PCOR in addressing health disparities and achieving health equity as a more culturally and linguistically diverse healthcare workforce and PCOR research team members.

OBJECTIVES/SPECIFIC AIMS: The study aims to develop and test a biocompatible 3D-printed IVRs for the mechanical and release properties of a model drug, β-estradiol, then translate these methods to the target drug, progesterone. The goals include demonstrating decoupling of mechanical and release properties of the rings, release profiles driven by geometry and efficacy in sheep animal models to evaluate device safety. METHODS/STUDY POPULATION: A novel 3D-printing platform, continuous liquid interface production (CLIP), pioneered by Carbon, enables the fabrication of complex designs on a timescale that is amenable to manufacturing. The process utilizes computational-aided design (CAD), specifying shape and geometry, which is recreated via a photopolymerization process. IVRs are fabricated with CLIP using a biocompatible resin at a rate of approximately 15 min. per ring. Rings were fabricated and assessed for the release of a model drug, β-estradiol. The process was then translated to the target drug, progesterone. Rings were evaluated for radial compression and in vitro release in simulated vaginal fluid (SVF). RESULTS/ANTICIPATED RESULTS: Intravaginal rings (IVRs) were designed and fabricated to be geometrically complex in an effort to control release. Ring geometry and subsequent pore size was achieved through the use of unit cells. Several design parameters were explored including unit cell type, size, and band presence in two resins of differing mechanical properties. Through design, a wide range of radial compressive properties were achieved which spanned values covered by commercially available rings. The release of β-estradiol in SVF was found to span 57 – 115 days and resulted in near or complete release of the total loaded drug. Changing the internal geometric design of the ring was found to have minimal influence on the compression properties, thus the mechanical and release characteristics of the rings were largely decoupled. DISCUSSION/SIGNIFICANCE OF IMPACT: This is a novel approach to the design and fabrication of intravaginal rings for the treatment of infertility. The use of CAD and the decoupling of release from mechanical properties allows for us to move away from the one-size one-dose fits all approach to IVRs.

Despite their documented benefits, the widespread adoption of community-engaged and participatory approaches among health researchers remains limited. Institutional practices and policies influence the uptake of community engagement and participatory approaches. We examine the role of financial arrangements between university researchers and community partners, by exploring efforts to bridge the gap between research administration and researchers at two research-intensive institutions. The type of financial arrangement a researcher has with a community partner plays an important role in setting the stage for the structure of the partnership as it relates to shared decision-making and ownership of the research. Continued efforts to clarify and streamline subcontracting processes are needed as is infrastructure to support community partners and researchers as they navigate financial arrangements if progress is to be made.

OBJECTIVES/SPECIFIC AIMS: Purpose - The goal of this study is to understand how loss of the membrane protein SLC4A11 alters endothelial cell metabolism thereby producing Corneal Endothelial Dystrophy. Studies from our lab indicated that glutamine-dependent mitochondrial dysfunction is one of the outcomes of SLC4a11 loss. In the current study, we ask if autophagy and mitophagy pathways and the signaling pathways that regulate these processes are altered in SLC4a11 KO cells. METHODS/STUDY POPULATION: Methods – Immortalized mouse WT and SLC4a11 KO cell lines were incubated in DMEM with and without 0.5mM glutamine for 6 hours. In order to assess mitophagy, cells were stained using Lysotracker Red and Mitotracker Green. Colocalization co-efficients of red and green channels were obtained for at least 35 cells using Zeiss-Zen Pro software. Student’s t-test was used to determine statistical significance. For Western Blots, antibodies against LC3b, AMPK, pAMPK, and b-actin were used to examine autophagy flux and potential signaling pathways that regulate autophagy. RESULTS/ANTICIPATED RESULTS: Results – In the presence of glutamine, the colocalization co-efficient of Lysotracker Red and Mitotracker Green channels was significantly increased in KO cells (0.74 ±0.18) relative to WT (0.58±0.20) with a p-value ≤0.0024. In the absence of glutamine, the colocalization co-efficient was reversed, for KO cells 0.54 ±0.14 and for WT cells 0.77±0.0.16 with a p-value ≤0.0001, suggesting increased mitophagy by glutamine in KO cells. Western Blots indicated that glutamine increased autophagy flux, as indicated by increased levels of LC3b following bafilomycin A treatment in KO cells. Concomitantly, there was an increase in pAMPK/AMPK levels suggesting a potential mechanism for increased mitophagy. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusion and Future studies –Our data indicates enhanced mitophagy as well as autophagy in SLC4a11 KO cells. Future studies will determine whether these processes regulate cell survival in mouse models of corneal endothelial dystrophies.

OBJECTIVES/SPECIFIC AIMS: Our objectives with this project are to engage communities through technology creating a communication channel with affected communities and stakeholders about mosquito-borne illness, vector control and environmental health risk. Furthermore, engaging communities to electronically map ecological risks that impact mosquito-borne illness with the goal of creating a mobile application that will work as an ecological surveillance against mosquito proliferation and potential mosquito population reduction, and finally pilot test and evaluate potential benefits in communities where the application was used. METHODS/STUDY POPULATION: We propose a methodology to perform formative community work that will underscore a distributed, democratized ecological surveillance through an integration of multidimensional health behavior theories that address the challenges of ZIKV in Culebra, a marginalized island community off the coast of the main island of Puerto Rico. Using participatory design, we will develop, test, and evaluate users’ experiences towards mobile applications using qualitative (interviews) and quantitative (survey) methodologies. A mobile application with the capacity of mapping, use of social-media, crowdsourcing, and photo-voice in a dynamic and simple way will allow community members to alert “hot-zone” locations to the stakeholders interested in creating ecological action in their community. This multidimensional concept integrates explanatory and prospective approaches and will generate systematic short-term solutions for mosquito control and long-term solutions providing the necessary tools for community empowerment. RESULTS/ANTICIPATED RESULTS: Our proposed design will facilitate better understanding of the interactions between community members and socio-environmental determinants of mosquito-borne diseases. Furthermore, our proposed project will not only facilitate communication among members of a community, but also it will provide a platform for engagement and empowerment, establishing a change in the preventive paradigm of how communities face the negative impacts of micro-ecologies that surround them. DISCUSSION/SIGNIFICANCE OF IMPACT: Our proposed community collaboratory mHealth tool mZAP! (Zonas, Accion y Proteccion) will address the lack of community participation efforts against mosquito-borne diseases contributed simultaneously by the disengagement and disempowerment of community members. mZAP! will serve as an innovative tool to engage marginalized and communities made vulnerable in Puerto Rico. This approach should be successful as Puerto Rico is one of the most digitally connected countries in Latin America, with high mobile phone usage rates and social media use. Using mZAP!, communities will report and map breeding sites, use social media and crowd sensing, targeting against powerful tools against mosquito ecologies in their own environments. This application could result in an effective way to change the paradigms for public health approaches to use Information Communications Technologies (ICTs) to empower communities.

OBJECTIVES/GOALS: Limited specialty care within safety net health systems reduces availability of follow-up appointments for chronic conditions. We evaluated patient acceptability of a 6 month series of telemedicine group medical visits for chronic migraine at a county hospital-based clinic as a potential method to improve access to specialty care in this setting. METHODS/STUDY POPULATION: We developed and implemented a pilot program of monthly physician-led telemedicine group visits to provide routine follow-up care for adults with chronic migraine. Visits were conducted through the neurology clinic at LAC+USC medical center, a safety net hospital in Los Angeles and included an educational component, peer support, and the opportunity to address individual needs or refill medications. We assessed headache severity (HIT-6) and mood (PHQ-9) through telephone surveys before and 6 months after patients’ first telemedicine group visit and compared timepoints using paired t-tests. Patient acceptability of the group visits was elicited through focus groups and key themes identified using grounded field theory. RESULTS/ANTICIPATED RESULTS: Baseline data was available for 18/20 pilot participants. Patients were predominantly female (89%) with mean age of 46 (SD 8.6). Mean HIT-6 was 65/78 reflecting a very severe impact on daily life, and mean PHQ-9 was 8.7 reflecting mild depressive symptoms. There was no statistically significant change in either HIT-6 (mean difference 2.36, p=0.34) or PHQ-9 (mean difference 2.09, p=0.12) after group participation. Key themes from the focus groups included lack of prior exposure to other people with similar headache burden and logistical barriers to care, such as difficulty contacting a provider or extended clinic wait times. Primary patient-reported benefits included more frequent access to a provider and peer support. DISCUSSION/SIGNIFICANCE: Telemedicine group visits for chronic migraine are feasible in a safety net context and were well-received by patients. However, this pilot study did not show a benefit of telemedicine group visits for headache control or mood symptoms.