Clinicians who are interested in becoming principal investigators struggle to find and complete training that adequately prepares them to conduct safe, well-designed clinical and translational research. Degree programs covering these skills require a significant time investment, while online trainings lack engagement and may not be specific to local research contexts. Staff at Tufts Clinical and Translational Science Institute sought to fill the gap in junior investigator training by designing an eight-module, noncredit certificate program to teach aspiring clinician-investigators about good clinical practice, clinical research processes, and federal and local regulatory requirements. The first iteration of this program was evaluated using pre- and posttest questionnaires and by gathering clinician learner feedback in a focus group. Based on the pre- and posttest questionnaires, learners experienced an increase in self-efficacy and confidence related to clinical research competencies. Feedback from learners also highlighted important program strengths, including an engaging program format, a manageable time commitment, and an emphasis on identifying crucial research resources. This article describes one approach to creating a meaningful and efficient clinical trial training program for clinicians.

The COVID-19 pandemic accelerated the development of decentralized clinical trials (DCT). DCT’s are an important and pragmatic method for assessing health outcomes yet comprise only a minority of clinical trials, and few published methodologies exist. In this report, we detail the operational components of COVID-OUT, a decentralized, multicenter, quadruple-blinded, randomized trial that rapidly delivered study drugs nation-wide. The trial examined three medications (metformin, ivermectin, and fluvoxamine) as outpatient treatment of SARS-CoV-2 for their effectiveness in preventing severe or long COVID-19. Decentralized strategies included HIPAA-compliant electronic screening and consenting, prepacking investigational product to accelerate delivery after randomization, and remotely confirming participant-reported outcomes. Of the 1417 individuals with the intention-to-treat sample, the remote nature of the study caused an additional 94 participants to not take any doses of study drug. Therefore, 1323 participants were in the modified intention-to-treat sample, which was the a priori primary study sample. Only 1.4% of participants were lost to follow-up. Decentralized strategies facilitated the successful completion of the COVID-OUT trial without any in-person contact by expediting intervention delivery, expanding trial access geographically, limiting contagion exposure, and making it easy for participants to complete follow-up visits. Remotely completed consent and follow-up facilitated enrollment.

OBJECTIVES/GOALS: Improving physical activity of African American women experiencing disproportionate health risks from sedentarism, educational and socio-environmental barriers. BeFit: Building Empowerment through Fitness is based on “What I Learned At Home” project, run by Women Under Construction Network, for residents of the Birmingham Housing Authority. METHODS/STUDY POPULATION: A qualitative study design to understand unique cultural context and challenges faced by African American women residing in the Birmingham Housing Authority, regarding physical activity engagement, including sedentarism. A needs assessment approach will help determine barriers, support systems, and social networks. Semi-structured, pre, mid, and post program focus groups will identify challenges and opportunities for health, such as diet and exercise, and will be analyzed by hand with a thematic analysis. The project framework uses exercise and home repair tools with a life-building/life repair curriculum to influence health, self-efficacy, and program engagement. The Study enrollment will include 50 women over two cohorts in a 12-week project. RESULTS/ANTICIPATED RESULTS: This research addresses the urgent health needs of African American women in low-income communities. These women face heightened health risks due to sedentary lifestyles, educational gaps, and socio-environmental barriers. This project targets the pronounced prevalence of allostatic burden in this population by applying a culturally sensitive, bottom-up approach. Our goal of incorporating healthy lifestyles to improve health in at-risk women and their families requires multiple projects. This project is a necessary first step in engaging with a community to identify local environmental circumstances and barriers to increasing the relevance of physical activity within the home. These barriers can then be addressed by adapting an exercise promotion program to the needs of this community. DISCUSSION/SIGNIFICANCE: Black women in under-resourced communities are more likely to be sedentary and have poor health. Exercise programs can be a powerful tool to address disparities and help prioritize health. The circumstances of women in public housing in Birmingham, AL, need community partners to adapt exercise engagement programs to meet environmental challenges.

OBJECTIVES/SPECIFIC AIMS: Our objective was to assess and compare the attitudes of patients with head and neck cancer and their clinicians regarding the commercialization of genetic research data. We explored whether such opinions changed when profits from such transactions were used to fund 1) cancer research, 2) academic research generally, or 3) if patients were given personalized genetic information in return. METHODS/STUDY POPULATION: This qualitative analysis was nested within a prospective precision oncology genomic sequencing study in an NCI-designated cancer center. We conducted paired, semi-structured interviews with enrolled participants with head & neck cancer and with their doctors (medical oncologists, surgical oncologists, and radiation oncologists). Interviews were recorded, transcribed, and coded for analysis. Codes were developed through an iterative process until saturation was reached, and all transcripts were double-coded (and discrepancies reconciled) to ensure reliability. RESULTS/ANTICIPATED RESULTS: We identified three main themes from the patients and clinicians: (1) Both clinicians and their patients were unclear about how the study protocol and informed consent form authorized patients’ genetic data to be used and commercialized in the future. (2) Patients with cancer were generally more comfortable than their clinician thought they were regarding the ongoing research use of their genetic data and commercialization thereof. (3) There is a strong interest among patients and clinicians in focusing academic medical center profits from commercialization back into the research program from which the data was acquired, rather than being invested into academic research more broadly. DISCUSSION/SIGNIFICANCE OF IMPACT: Given patients’ strong feelings about the commercialization of their data, our results highlight the need for greater transparency—both with patients and with their clinicians—about potential future use of research data. Clinicians appear inclined to be particularly cautious regarding access to and commercialization of patients’ data, however patients generally hope that their data may be used to help future cancer patients. Explicit discussions with patients about specific future uses of profits derived from commercialization of research data can ensure both transparency and participation in future primary and secondary precision health research programs.

ABSTRACT IMPACT: Our results reveal a limited amount of breast cancer survivorship print materials as both understandable and actionable, and indicate a need to supplement material with personalized teaching. OBJECTIVES/GOALS: Using educational print material for young women breast cancer survivors (YBCS) is considered a best practice in patient teaching. Little is known about how well YBCS understand or act upon the material. The purpose of this study was to assess the understandability and actionability of commonly distributed breast cancer survivorship print materials. METHODS/STUDY POPULATION: We used an environmental scan approach to obtain breast cancer survivorship print materials available in eight outpatient oncology clinics and one electronic medical record used in a Midwestern state. Print materials were included if they were freely available to patients, were specific to breast cancer, provided detailed information about survivorship, and were directly given to patients by physicians or nurses. Print materials were excluded if topics were related to treatment, diagnosis, or prevention. All brochures, drug advertisements, and advertisements for support services were excluded. The understandability and actionability analyses of the breast cancer survivorship print materials were analyzed using Patient Education Materials Assessment Tool for Printable Materials (PEMAT-P). RESULTS/ANTICIPATED RESULTS: The environmental scan resulted in 82 individual print materials. After applying the inclusion and exclusion criteria, eight breast cancer survivorship print materials were included in the final sample. The final sample included two books, two patient education handouts from the electronic medical record, two multi-page booklets, and two pamphlets. The overall mean understandability score of the print materials was 68.9% ? 11.3 with a range of 47% to 80%. Five materials scored above the recommended 70% in understandability. The overall mean actionability score of the print materials was much higher at 81.3% ? 21.6 with a range of 67% to 100%. Five materials scored above 70% in actionability. However, only three of the eight materials scored above the recommended 70% in both understandability and actionability. DISCUSSION/SIGNIFICANCE OF FINDINGS: Limited breast cancer survivorship print materials exist as both understandable and actionable. Personalized instruction provided by oncology team members may be indicated to supplement the material. This additional teaching may help ensure survivors comprehend messages and act upon specific tasks as indicated in survivorship print material.

OBJECTIVES/SPECIFIC AIMS: To investigate the performance of a metric for passive localization of central sulcus. METHODS/STUDY POPULATION: We studied 7 patients with intractable epilepsy undergoing intra-cranial EEG (icEEG) monitoring at Yale, in whom central sulcus (CS) localization was obtained by standard methods. Our method takes advantage of inherent properties of the primary motor cortex (MC), which exhibits enhanced icEEG band-power and coherence across the CS. For each contact x we calculated the z-score of a composite power and synchrony value log10(px)x;cx, where px is sum of the root mean square of the icEEG in the high gamma band (80–115 Hz) for contact x over the 6–10 minutes of NREM sleep studied, and cx is the mean magnitude squared coherence in the same band using a 500-ms Hamming window between contact x and all other contacts. z-score values lower than threshold (th) were set to 0. Finally, we calculated a metric m=z/d, where d is the mean Euclidian distance of each contact from contacts with z scores greater than 0. The last step was implemented to emphasize local network activity. RESULTS/ANTICIPATED RESULTS: We report the results of a pilot study to test the performance of a new operator independent method for passive identification of CS with intractable epilepsy undergoing icEEG monitoring at Yale, in whom CS localization was obtained by standard methods. The sensori-motor (SM) cortex exhibited higher EEG-gamma power compared with non-SM cortex (p<0.0002). There was no significant difference between the motor/premotor and sensory cortex (p<0.47). CS was successfully localized in all patients with thresholds between 0.4 and 0.6. In 2 patients, knowledge of anatomy was needed to distinguish the MC from adjacent epileptic foci. The primary hand and leg motor areas exhibited the highest metric values consistently followed by the tongue motor area. Higher threshold values were very specific (94%) for the anterior bank of the CS but not sensitive. Intermediate threshold values achieved a reasonable trade-off (0.4: 89% specific and 70% sensitive). DISCUSSION/SIGNIFICANCE OF IMPACT: We present and successfully implement a rapid procedure for task-free and stimulation free localization of the central sulcus during sleep based on intrinsic electrophysiological properties of the primary motor strip which exhibits increased power and enhanced local connectivity. We successfully localized the central sulcus in all patients. When implementing appropriate thresholds, our proposed metric M is very specific for the anterior lip of the central sulcus which may make it ideal to identify this important anatomical landmark. Our method is sensitive for epileptogenic regions as well, therefore basic knowledge about central sulcus anatomy may be needed in cases where there is an epileptogenic lesion in the vicinity of the central suclus. Our method makes a few a priori assumptions: The regions around the central sulcus are adequately sampled and the occipital or parieto-occipital regions are not included in the analysis. In order for the method to function properly, nonsensori-MC should be sampled adequately as well. In the future, normative data could be generated for the composite product of connectivity×power which may replace within-patient z-scoring. Our method is rapid and can be implemented on short segments of ECoG data. The proposed method may be potentially used for identification of seeds in the motor cortex for subsequent network analysis and further studies may delineate its potential use in the operating room.

OBJECTIVES/SPECIFIC AIMS: Compare effectiveness of a patient case-based, interactive teaching approach that included optional student genotyping with traditional didactic teaching strategies for increasing students’ knowledge and ability to effectively use pharmacogenomic data in clinical decision making. METHODS/STUDY POPULATION: The UF College of Pharmacy offers a required Personalized Medicine (PM) course for pharmacy students as well as an elective course, Clinical Applications of Personalized Medicine (CAPM). Students dual enrolled in the PM and elective CAPM courses comprised the intervention (INT) group, with interactive patient case-based teaching and the option to undergo personal genotyping, whereas students enrolled in PM alone comprised the control (CTR) group, which primarily used a traditional didactic teaching format and did not include personal genotyping. Both groups completed a pre- and post-course patient case-based test (15 questions/1 point each) to evaluate their knowledge and abilities to apply genotype and other patient-specific data to drug therapy recommendations. Pre- and post-course test scores for knowledge were compared between the INT and CTR groups using the Student t-test. RESULTS/ANTICIPATED RESULTS: In total, 52 students completed surveys (INT group, n=21; CTR group, n=31). Race was similar between groups, but there were fewer females in the INT compared with CTR group (8 vs. 22, p=0.02). Pre-course knowledge scores did not differ between INT and CTR groups (6.8±2.2 vs. 6.3±1.6 respectively, p=0.34), however, post-course scores were significantly higher in the INT Versus CTR group (10.0±2.3 vs. 7.5±1.7, p<0.0001). DISCUSSION/SIGNIFICANCE OF IMPACT: There have been significant advancements in the clinical applications of pharmacogenomic and genomic data, however, barriers to routine clinical adoption of genomic medicine persist. Developing education and training methods that equip practitioners to effectively translate genomic data into evidence-based clinical recommendations has been identified as a key strategy to overcome such barriers. Our data suggest that a personalized medicine course that employs patient-centered, case-based teaching strategies and includes optional personal genotyping for students compared with traditional didactic instruction improves students’ knowledge and abilities to apply pharmacogenomic data in practice-based scenarios. These results can inform future strategies for educating healthcare professionals on the clinical use of pharmacogenomic and genomic data.

OBJECTIVES/SPECIFIC AIMS: Histones are nuclear proteins that associate with DNA to facilitate packaging into condensed chromatin. Histones are dynamically decorated with post-translational modifications (PTMs), which regulate such processes as DNA repair, gene expression, mitosis, and meiosis. Histone 3 Family 3 (H3F3) histones (H3.3), encoded by H3F3A and H3F3B, mark active genes, maintain epigenetic memory, and maintain heterochromatin and telomeric integrity. Specific somatic mutations in H3F3A and H3F3B have been strongly associated with pediatric glia and other tumors, but no germline mutations have been reported. The goal of our study was to further understand the functional effects of germline mutations of H3F3A and H3F3B. METHODS/STUDY POPULATION: We analyzed 32 patients bearing de novo germline missense mutations in H3F3A or H3F3B with core phenotypes of progressive neurologic dysfunction and congenital anomalies, but no malignancies. Patient histones were analyzed by quantitative mass spectrometry (qMS). RESULTS/ANTICIPATED RESULTS: qMS results revealed that the mutant histone proteins are present at a concentration similar to that of wild-type H3.3. qMS analysis showed strikingly aberrant PTM patterns that suggested local dysregulation. These patterns are distinct from the dominant negative somatic mutations, which cause more global PTM dysregulation. Patient cells also demonstrated upregulation of the expression of genes related to mitosis and cell division, and had a greater proliferative capacity. DISCUSSION/SIGNIFICANCE OF IMPACT: Our data suggests that the pathogenic mechanism of germline histone mutations is distinct from that of the published cancer-associated somatic histone mutations, but may converge on control of cell proliferation. Further clarification of the pathophysiology in these patients can elucidate the roles of histones and histone PTMs in human development and non-syndromic neurodegeneration. In addition, it provides a framework for targeted therapy development for this and related progressive neurologic disorders.

OBJECTIVES/SPECIFIC AIMS: This study aims to understand the factors influencing engagement with out-patient services from pregnancy to 1 year postpartum among women in recovery from opioid use disorders (OUD). METHODS/STUDY POPULATION: We conducted semi-structured qualitative interviews and a brief survey with 20 mothers in OUD recovery recruited from health care and community organizations in Western MA. Transcripts were coded by two independent coders and analyzed using a qualitative descriptive approach. RESULTS/ANTICIPATED RESULTS: The average duration of any addiction treatment among the 20 participants was 5.6 years with 80% receiving medication-assisted treatment during a pregnancy. Approximately two-thirds experienced relapse during pregnancy or the first year postpartum. We identified 3 themes elucidating women’s experiences around service engagement: “How I see myself” (personal development), “How services see me” (service delivery quality), and “Are you with me?” Personal development included response to past trauma, coping strategies and self-advocacy, and adjusting to parenthood. Service delivery quality was influenced by service design, efficacy of individual providers, and cultural norms (organizational and societal). In the final theme, intersection of individual and service-level factors influenced the degree and quality of the women’s experience engaging with services. DISCUSSION/SIGNIFICANCE OF IMPACT: Women describe successful engagement when they experience service providers as being emotionally supportive, delivering relevant services, and advocating on their behalf. To best support and engage families affected by OUD, relevant and timely services should be linked with compassionate delivery.

OBJECTIVES/SPECIFIC AIMS: This study aims to assess the safety, feasibility, clinical benefits and pharmacodynamics of adding allopurinol to standard maintenance therapy that includes 6-mecaptopurine (6-MP) in pediatric patients with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma. Our goal is to investigate if allopurinol improves hepatotoxicity and GI toxicity, if it safely decreases acute neutrophil count (ANC), if it reduces the 6-MP dose required during chemotherapy, and if it works through our hypothesized mechanism by lowering the levels of the toxic metabolite, 6-methylmecaptopurine (6-MMP) and by raising the levels of the active metabolite, 6-thioguanine (6-TGN). METHODS/STUDY POPULATION: This is a single arm, nonblinded pilot study of patients under age 30 years who were being treated in the maintenance phase of therapy for ALL or lymphoblastic lymphoma, and had adverse effects such as high 6-MMP:6-TGN ratio, high ANC, and high liver enzymes. Patients enrolled were started with allopurinol in addition to ongoing oral chemotherapy. Data from beginning maintenance to end of chemotherapy was collected in the electronic medical record, EPIC for the 13 patients enrolled at Johns Hopkins, and data analysis was conducted using STATA and Excel. RESULTS/ANTICIPATED RESULTS: Initial data analysis reveals that the required dose of 6-MP after addition of allopurinol to the chemotherapy regimen was significantly lower compared with that before the addition of allopurinol in 11 out of the 12 patients assessed (p<0.05). Among the 10 patients that were assessed for 6MMP:6TG ratio, all had lower average 6MMP:6TGN ratios after allopurinol compared to before allopurinol; the percentage of weeks that goal 6MMP:6TGN ratio (<40) were maintained were statistically significant in 6 patients (p<0.05) and close to significance in 2 other patients (p=0.057). The percentage of weeks that patients maintained alanine aminotransferase levels below 120 was significantly greater after addition of allopurinol compared to before the addition of allopurinol in 9 out of 13 patients assessed, suggesting that allopurinol may be associated with reduced hepatotoxicity. Further data analysis is ongoing to assess the percentage of weeks that patients maintained goal total bilirubin, direct bilirubin, and ANC, as well as average number of admissions for infections and average number of therapy holds after allopurinol addition compared to before allopurinol addition. DISCUSSION/SIGNIFICANCE OF IMPACT: Allopurinol is associated with reduction in required 6-MP dose, decrease in the percentage of weeks that patients have hepatotoxicity, and reduction in the ratio of toxic metabolite to active anti-leukemic metabolite in several patients. We hope that the results of this study can be used for further research and for guiding clinical practice since there are no established guidelines in pediatric oncology regarding addressing side effects of oral chemotherapy using 6-MP. If allopurinol indeed is safe and effective, adding it to the standard chemotherapy regimen can lead to better tolerance and compliance to oral maintenance chemotherapy, and hopefully improved outcomes for children with ALL and lymphoblastic leukemia.

OBJECTIVES/SPECIFIC AIMS: The objective of this partnership was to create a global network of clinical and public health researchers and communities conducting technology-assisted research in noncommunicable disease. METHODS/STUDY POPULATION: The University of Rochester’s Clinical and Translational Science Institute (CTSI) has successfully leveraged the informatics core’s capacity into an emerging network of organizations that focus on technology and health in settings outside of the mainland United States. The CTSI coordinated with another NIH-funded infrastructure program [the RCMI Translational Research Network (RTRN)] to identify partner institutions interested in technology and health. RTRN identified the University of Puerto Rico and the University of Hawaii, both of which serve as hubs for common research interests in technology and health throughout the Caribbean and the Pacific. This network was formalized as the CDC’s Coordinating Center for its Global and Territorial Health Research Network (the “Global Network”), with additional US partners (Yale, University of Illinois at Chicago, University of North Caroline Chapel Hill, and the University of South Florida) within a wider scope of the CDC’s Prevention Research Centers (PRC) program. RESULTS/ANTICIPATED RESULTS: Through combining 2 main NIH-funded research infrastructure networks (CTSA and RTRN), with a large CDC-funded PRC, the University of Rochester’s Informatics Core was successful in establishing a new productive global health network throughout Latin America and the Caribbean, and in the Pacific, garnering additional research support from NIH Fogarty and other programs. The resulting network not only supports locally-important research in technology and health on compelling health issues (eg, diabetes, ZIka, participation in research), but also facilitates community engagement through local partnerships and the cores of the involved networks. In addition, much of the information and communications technology (ICT)-related research and learnings from the Global Network activity is immediately applicable to populations in the United States, served by the various collaborative networks. In total, while new, the Global Network supports a wide range of projects and engagements throughout the world that expand local informatics capacity and use of technology in the research process and to address global health problems, further enhancing the CTSI’s informatics core to serve the needs of its own constituency and promote research engagement with technology within this population. Local research collaborative projects reinforce the utility of the network and its resources, evidenced by tools, publications, partnerships, and conference presentations that have arisen. Lessons to date from this Global Network collaboration include: specific global research projects provide opportunities for partnership building and meaningful collaboration, team science is of central importance in distributing the work of the network, synergy is multidirectional with expertise and need flowing in all directions, and project team members in all locales learned and contributed substantially in ways that carried into their other responsibilities. DISCUSSION/SIGNIFICANCE OF IMPACT: The overall partnership has created opportunity for South-South collaboration, for adaptation of projects among locales, and has helped boost reputational value for all partners involved. Implications for other CTSA awardees include: global collaboration can serve core research and technical needs for the CTSA itself and its local partners, CTSA status can be leveraged to access resources to support local research, and collaboration in other federally-funded research networks helps expand the insight, scope, and potential for new research.

OBJECTIVES/SPECIFIC AIMS: We aim to leverage our analysis of the scientific collaboration network at a research university to design an innovative pilot program and foster scientific productivity. We test the impact of creating a new collaboration in a research community, which decreases the average network distance and accelerates the diffusion of information and expertise among the community’s investigators. METHODS/STUDY POPULATION: We mapped the whole network of co-authorship on publications and co-participation on extramurally awarded grants at the University of Florida (UF) between 2013 and 2015. We used network science methods to identify research communities of investigators who have consistently worked together and/or have other collaborators in common with at least one researcher based in the UF Health Science Center. We selected pairs of communities with (i) similar productivity levels, research interests, and network structures and (ii) no research projects in common. Communities in each pair were randomly assigned to a treatment or control group. In each treatment community, we selected 1 pair of investigators who had not collaborated in the past 3 years and whose connection would maximally reduce average network distance in the community. The pair was provided with an economic incentive to collaborate for the submission of a CTSA pilot proposal. RESULTS/ANTICIPATED RESULTS: We successfully identified 15 pairs of treatment/control communities. In each of 8 treatment communities, a pair of potential collaborators agreed to participate in the intervention. DISCUSSION/SIGNIFICANCE OF IMPACT: Network-informed Clinical Translational Science Awards (CTSA) pilot programs can identify research communities and create innovative collaborations. Statistical experiments can establish the programs’ causal effects on scientific productivity.

OBJECTIVES/SPECIFIC AIMS: MicroRNAs are small, non-coding RNAs that control gene expression by inhibiting protein translation. Preclinical studies in rodent stroke models suggest that changes in microRNA expression contribute to neural repair mechanisms. To our knowledge, no one has previously assessed microRNA changes during the recovery phase of human stroke. Our goal was to determine whether patients with significant upper limb recovery following stroke have alteration of neural repair-related microRNA expression when compared to those with poor recovery. METHODS/STUDY POPULATION: Plasma was collected at 19 days post-stroke from 27 participants with mild-moderate upper extremity impairment enrolled in the Critical Periods After Stroke Study. MicroRNA expression was assessed using TaqMan microRNA assays (Thermo Fisher Scientific). Good recovery was defined as ≥6 point change in the Action Research Arm Test (ARAT) score from baseline to 6 months. Bioinformatics analysis compared the plasma microRNA expression profiles of participants with good Versus poor recovery. Candidate biomarkers were identified after correcting for multiple comparisons using a false discovery rate <0.05. RESULTS/ANTICIPATED RESULTS: Eleven microRNAs had significantly altered expression in the good (n=22) Versus poor (n=5) recovery groups, with 2 showing increased expression—miR-371-3p and miR-520g, and 9 showing decreased expression—miR-449b, miR-519b, miR-581, miR-616, miR-892b, miR-941, miR-1179, miR-1292, and miR1296. Three of these could be implicated in neural repair mechanisms. Elevated miR-371-3p levels increase the likelihood that pluripotent stem cells will differentiate into neural progenitors. MiR-892b decreases levels of amyloid precursor protein, which has been implicated as a regulator of synapse formation. Finally miR-941, the only known human-specific microRNA, downregulates the CSPα protein which is involved in neurotransmitter release. DISCUSSION/SIGNIFICANCE OF IMPACT: This preliminary study suggests that circulating microRNAs in the plasma may help serve as biomarkers of neural repair and aid in understanding human neural repair mechanisms. If validated in larger studies with appropriate controls, these markers could aid in timing rehabilitation therapy or designing recovery-based therapeutics.

The rate at which the coronavirus disease (COVID-19) spread required a rapid response across many, if not all, industries. Academic medical centers had to rapidly evaluate, prioritize, and coordinate the multiple requests for clinical trial participation. This involved redirecting resources and developing a collaborative system for assessment, decision making, and implementation. Our institution formed a team with diverse representation from multiple stakeholders to review and prioritize all research protocols related to COVID-19. To accomplish this, a prioritization matrix was developed to help determine the order in which the protocols should be placed for consideration by the treating clinician. The purpose of the team was to review the COVID-19 clinical trials in the pipeline, prioritize those trials that best met the needs of our patients, oversee training and resource needs, and lead the formulation of procedures for integration with clinical care. Resources from the Clinical Research Unit were then allocated to support the swift execution of such studies. This manuscript describes that process, the challenges encountered, and the lessons learned on how to make all clinical trials more successful in a complex and dynamic environment.

OBJECTIVES/GOALS: Our goal is to develop a non-invasive stimulation technique using magneto-electric nanoparticles (MENs) for inducing and enhancing neuronal activity with high spatial and temporal resolutions and minimal toxicity, which can potentially be used as a more effective approach to brain stimulation. METHODS/STUDY POPULATION: MENs compose of core-shell structures that are attracted to strong external magnetic field (~5000 Gauss) but produces electric currents with weaker magnetic field (~450 Gauss). MENs were IV treated into mice and drawn to the brain cortex with a strong magnetic field. We then stimulate MENs with a weaker magnetic field via electro magnet. With two photon calcium imaging, we investigated both the temporal and spatial effects of MENs on neuronal activity both in vivo and in vitro. We performed mesoscopic whole brain calcium imaging on awake animal to assess the MENs effects. Furthermore, we investigated the temporal profile of MENs in the vasculatures post-treatment and its toxicities to CNS. RESULTS/ANTICIPATED RESULTS: MENs were successfully localized to target cortical regions within 30 minutes of magnetic application. After wirelessly applying ~450 G magnetic field between 10-20 Hz, we observed a dramatic increase of calcium signals (i.e. neuronal excitability) both in vitro cultured neurons and in vivo treated animals. Whole brain imaging of awake mice showed a focal increase in calcium signals at the area where MENs localized and the signals spread to regions further away. We also found MENs stimulatory effects lasted up to 24 hours post treatment. MEN stimulation increases c-Fos expression but resulted in no inflammatory changes, up to one week, by assessing microglial or astrocytes activations. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study shows, through controlling the applied magnetic field, MENs can be focally delivered to specific cortical regions with high efficacy and wirelessly activated neurons with high spatial and temporal resolution. This method shows promising potential to be a new non-invasive brain modulation approach disease studies and treatments.

OBJECTIVES/SPECIFIC AIMS: The study aims to (1) investigate the structural patterns of professional communication that exist at the Mount Sinai Health Hackathon (2) explore if and how the professional networks of the participants change after engaging in the Mount Sinai Health Hackathon (3) explore any associations between the characteristics of participants’ professional networks and successful innovation development. METHODS/STUDY POPULATION: The recruitment pool consists of all 78 Mount Sinai Health Hackathon 2018 participants. Characteristics of the social network of Health Hackathon participants are assessed via an SNA data collection instrument at three time points: T1 directly before the Health Hackathon event, T2 directly after the event, T3 six months post-event. The Icahn School of Medicine at Mount Sinai Institutional Review Board approved this study as exempt. In order to explore patterns of communication between Health Hackathon participants during event, whole network data is collected at T2. Participants are provide with a roster of Mount Sinai Health hackathon participant names and asked to report the nature, frequency and perceived importance of their interaction with each of the other participants over the duration of the 48 hour event. In order capture any network change in the wider professional networks of the individual participants, known as “ego networks”, participants are asked to complete an SNA ego network survey at time points T1, T2 and T3. Open ended questions asked participants to report up to 20 people they consider being most important to them in their professional network and record the professional background of each person, the nature of the communication and the importance of each person to their success. Finally, at T3 participants are also asked to report on their project success (determined by businesses formed, filed provisional patents, financial income generation). This will be reviewed in relation to their social network data, to see if there is any relationship between the two. Data is analyzed using the specialized SNA software, UCiNET, which creates network sociograms to visualize network data. Descriptive statistics are used to report individual-level characteristics of respondents.RESULTS/ANTICIPATED RESULTS: To describe the structural patterns of communication at each time point, the following network-level indices are calculated: density (a measure of network cohesion), degree centrality (how many connections the individual has), betweenness centrality (whether the individual provides connections to other people in a network) and closeness centrality (how close the individual is to other people in the network). Network sociograms are generated for each time point to provide a visualization of the network. To explore the hypothesis that participating in the Mount Sinai Health Hackathon increases diversity of a professional network, analysis will focus on whether and how network-level indices change pre- and post- Hackathon. It will also explore any association between network characteristics and project success. DISCUSSION/SIGNIFICANCE OF IMPACT: Social Network Analysis of the Mount Sinai Health Hackathon provides an understanding about the structure of relationships that are formed as a result of participation in this event. Although, the design of this study does not allow for inferences of causality, the SNA approach enables an in-depth exploration of Hackathon participants’ professional networks, how these evolve over time and how certain network characteristics may be associated with project success. This information will be used to inform the development, content and delivery of future Health Hackathon initatives.

OBJECTIVES/GOALS: Health care systems are complex, dynamic, and varied. Advances in artificial intelligence (AI) are enabling healthcare systems to use their own data to elicit patterns and design suitable interventions. To realize this potential, computer scientists and clinicians need an effective, practical, and replicable approach to collaboration METHODS/STUDY POPULATION: In this study, computer scientists partnered with clinicians to investigate predictors of avoidable emergency department use. The team sought an approach to computational medicine that could increase the relevance and impact of prediction to solve pressing problems in the health system. The team adopted an emergent architecture that engaged system leaders, computer scientists, data scientists, health services researchers, and practicing clinicians with deep ambulatory and inpatient knowledge to form the initial questions that shaped the prediction model; to understand nuances of coding and recording in source data and the implications for models; and to generate insights for promising points of intervention. The team recorded decisions and challenges as it progressed to analyze its function. RESULTS/ANTICIPATED RESULTS: Most avoidance models focus on a narrow time period around target events, or on high cost patients and events. This interdisciplinary team used their insights into the health system’s workflows and patient population to adopt a longitudinal approach to their prediction models. They used AI to build models of behavior in the system and consider prevention points across clinical units, time, and place. The holistic, systemwide focus enabled the team to generate insights that the system leaders and subsequently specific clinical units could apply to improve value and outcomes. A facilitated team process using learning system and cooperative network principles allowed a large and modular interdisciplinary team to build a transparent AI modeling process that yielded actionable insights into hypercomplex workflows. DISCUSSION/SIGNIFICANCE OF IMPACT: An architecture for involving diverse stakeholders in computational medicine projects can increase the relevance and impact of AI for solving care delivery problems in complex health systems. Translational science and computational medicine programs can foster this type of engagement and encourage a whole system perspective.

OBJECTIVES/SPECIFIC AIMS: Because clinical trial results are instrumental in the approval of a new drug or changes to the practice of medicine, ensuring the accuracy and validity of collected data is critical in the clinical trial process. This function, routinely carried out by clinical trial monitors in industry-sponsored trials, is often lacking in investigator-initiated trials (IITs) conducted in academia. To address this challenge, we have developed a self-study module that can be used to cross-train academic researchers in essential concepts and practical approaches to monitoring. Furthermore, we are applying a framework drawn from implementation science in the development and launch of this initiative. This framework, as used in other educational programs, is employed here to close the gap between initiative and practice, thereby effectively disseminating this training would improve the quality of clinical trials in academia. METHODS/STUDY POPULATION: This research project applied exploration, installation and implementation stages of the implementation science process by 1) exploring the need for a new initiative, 2) disseminating results, 3) engaging stakeholders, 4) creating standard operating procedures (SOPs) for installation and implementation, 5) studying user satisfaction and effectiveness, 6) addressing feedback and 7) conducting implementation. RESULTS/ANTICIPATED RESULTS: From literature review and internet searches we determined that although numerous GCP training resources exist, most are too broad and lack the practical approaches to meet the complex requirements of monitoring. Moreover, most of the offerings identified are costly or inaccessible. With only about 65% of IITs reported as being monitored (Figures 1 and 2), it appears that there is a clear need for training tools that are easily available to a broader audience. And because monitoring skills are substantially different from those associated with research coordination, it is not surprising that research professionals believed that they would need additional training to become proficient. To address this need, we began developing a monitoring module. We engaged key stakeholders from academia and industry to gain insights into their needs. The results indicated that although our training module was effective, supplementary information on the fundamentals of clinical trials should be included for those new to the field. After incorporating suggested changes and completing the module, we conducted user testing to determine if our module is ready to be broadly disseminated (Figures 3 and 4). Following positive feedback from the group, we are currently in the process of disseminating our module and studying its impact. DISCUSSION/SIGNIFICANCE OF IMPACT: IITs are instrumental in translating academic research into product development. Deficiencies in the quality control of these trials can lead to inadequacies in data accuracy and validity that could lead to significant delays in bringing innovative therapies to patients. Recent NIH policies require data and safety monitoring for all of the trials it supports. The latest addendum to ICH GCP, E6(R2), discusses a need for quality management across the clinical trial lifecycle. As we continue to disseminate and share information during the development of our self-study monitoring module, we are engaging key stakeholders from academia, government, and private institutions to understand and address quality challenges in conducting clinical trials. Finally, this research informs dissemination and implementation research, specifically for creating training for academic research professionals.