In 2020, Baylor College of Medicine held a datathon to inform potential users of a new data warehouse, allow users to address clinical questions, identify warehouse capabilities and limitations, foster collaborations, and engage trainees. Senior faculty selected proposals based on feasibility and impact. Selectees worked with Information Technology for 2 months and presented findings. A survey of participants showed diverse levels of experience, high perceived value of the datathon, high rates of collaboration, and significant increases in knowledge. A datathon can promote familiarity with a new data warehouse, guide data warehouse improvement, and promote collaboration.

OBJECTIVES/SPECIFIC AIMS: The aim of the study is to examine the relation between dental fluorosis, serum and water levels of fluoride and Chronic Kidney Disease (CKD) among children. A link between dental fluorosis, fluoride level and CKD can be an indicator of the blind danger of fluoride toxicity that poses a great threat to the human health. METHODS/STUDY POPULATION: Dental fluorosis, serum and water levels of fluoride and CKD were examined in children 6-19 years old, using data from the National Health and Nutrition Examination Survey1999-2012 and 2013-2016. We used multiple logistic regression to adjust for the confounders (demographics, insurance, dental visit, and co-morbidity) to assess the relation between dental fluorosis, serum and water levels of fluoride and CKD. STATA 14.0 was used to analyze the data (sample design and weight). P < 0.05 is statistically significant. RESULTS/ANTICIPATED RESULTS: The prevalence of CKD was 13.9% and dental fluorosis was 34.3%. In the multivariate model, plasma fluoride level was independently associated with CKD (Adjusted Odds Ratio (AOR) = 1.68, 95% Confidence Interval (CI) = 1.06-2.68, p = 0.029) but not with dental fluorosis (AOR = 1.4, 95% CI = 0.87-2.2, p = 0.17) or water fluoride level (AOR = 0.91, 95% CI = 0.59-1.396, p = 0.659). DISCUSSION/SIGNIFICANCE OF IMPACT: Results indicated that serum fluoride level is independently associated with CKD but dental fluorosis and water fluoride level were not related to CKD. Increase awareness and screening for fluorosis in children are needed for early detection and prevention of organ damage. Prospective studies related to fluorosis and tissue damage are needed.

Objectives/Goals: This study aims to harmonize quality indicators (QIs) across University of Toronto-affiliated microbiology labs to establish universal benchmarks that enhance performance, patient safety, and health outcomes. Harmonized QIs will enable effective comparisons and enhance the consistency of care. Methods/Study Population: The study employed the Delphi method, a structured and iterative process to build consensus. An expert panel of clinical microbiology trainees, medical microbiologists, trainees, and site leads from five University of Toronto-affiliated microbiology labs was assembled. Initial insights were gathered through surveys and a comprehensive scoping review of the literature. The study involved two rounds of feedback, a SurveyMonkey-based survey, with a defined consensus of 75% agreement among participants. Followed by an implementation survey conducted through REDCap to assess how these QIs were adopted in practice and identify barriers to implementation. Results/Anticipated Results: The study achieved consensus on nine high-impact quality indicators, including blood culture volume and contamination rates, cerebrospinal fluid transport time, and turnaround times for Gram stain results. Blood culture contamination and positivity rates garnered the highest agreement, at 100% and 91%, respectively. While some indicators were widely accepted and implemented, others faced resistance due to feasibility concerns. The study also identified significant variability in the level of adoption across the participating laboratories, pointing to operational challenges and the need for further efforts to address these barriers. Discussion/Significance of Impact: This study highlights the importance of QI harmonization in improving lab services and patient safety. It reveals challenges in standardizing practices but promotes uniformity in QIs, laying the groundwork for better inter-lab collaboration, consistent outcomes, and improvements in microbiology.

ABSTRACT IMPACT: Correctly identifying and documenting patients’ primary care physicians in community hospital settings may improve clinical care and coordination for patients, potentially leading to a reduction in hospitalizations, while simultaneously increasing patient education and expanding the limits of electronic health record systems. OBJECTIVES/GOALS: Clinical research infrastructure can be leveraged to detect inaccuracies in primary care physician (PCP) identification and documentation in a community hospital. As a result, collaboration between clinical research and hospital clinical operations can produce long-term solutions required by patient-centered, learning health care systems. METHODS/STUDY POPULATION: Hospitalized patients at a community hospital were asked to verify the name of their PCP. The PCP name given by the patient was then compared to the PCP on file in the EHR system. A corrected list of PCP names for each patient was sent by a clinical research program to hospital management on a weekly basis and used to update the EHR. RESULTS/ANTICIPATED RESULTS: A total of 272 hospitalized patients were screened on the basis of eligibility and asked to verify their PCP name. Overall, 35.3% (N=96) of patients had incorrectly listed PCPs in the EHR system. DISCUSSION/SIGNIFICANCE OF FINDINGS: Accurate PCP identification processes may enable broader clinical communication and potentially reduce future hospitalizations by improving coordination of care. The benefits of collaboration between research and clinical activities may provide an opportunity to justify greater investment in clinical research in community settings.

OBJECTIVES/GOALS: Specific Aim 1 To examine sex distribution of psoas cross sectional area (CSA) on CT imaging in a cohort of trauma patients age 55 and older. We will use three methods of assessing psoas CSA: psoas CSA averaged between left and right, average psoas CSA adjusted for height, and average psoas CSA adjusted for body surface area (psoas index). Specific Aim 2 Use multivariable logistic regression prediction modeling to compare the 3 methods of CT psoas muscle measurement widely used in the literature in their ability to predict a composite of in-hospital morbidity and mortality in trauma patients ages 55 and older. METHODS/STUDY POPULATION: The Maine Medical Center Trauma Registry is maintained by the Trauma Surgery Service at Maine Medical Center in Portland, Maine, the only Level-1 trauma center in the state. After receiving approval from the Institutional Review Board of Maine Medical Center for this retrospective cohort study, we queried the Maine Medical Center Trauma Registry for all adults 55 years and older who underwent evaluation by the Trauma Service between January 1, 2015 and January 1, 2019. In the case of multiple admissions within the study time period, only a patient’s index admission was used. MaineHealth IMPACS imaging software was used to measure bilateral psoas CSA on each patient CT. The Maine Medical Center electronic medical record was queried for additional clinical information including the ICD codes associated with each patient encounter. Data analysis was performed using R statistical software (R project, Vienna, Austria). Data is reported as median + IQR for CSA measurements. The agreement between the three methods of quantifying psoas CSA was evaluated using Pearson correlation (R package “stats”). Inter-rater reliability of psoas muscle measurements was evaluated using intra-class correlation (R package “irr”). Prediction models for the composite outcome of in-hospital morbidity and mortality were constructed using multivariable logistic regression. Bootstrapping was used for internal validation and shrinkage to avoid overfitting. Models including psoas CSA were compared to a baseline model without psoas CSA to evaluated incremental added predictive ability. RESULTS/ANTICIPATED RESULTS: This cohort provides a basis for examining the population distribution of psoas CSA in adults 55 years and older. IN addition to a high level of agreement between the three methods of measuring psoas CSA (Spearman coefficient > 0.9), there was also high level of inter rater reliability in psoas muscle assessment (intraclass correlation 0.9). We anticipate that psoas CSA adjusted for body surface area will add the most incremental predictive ability to a model predicting in-hospital morbidity and mortality. DISCUSSION/SIGNIFICANCE OF IMPACT: Given the heterogeneity of health status amongst elderly trauma patients, a major challenge lies in the rapid objective identification of those elderly trauma patients who are frail. Due to the limitations in current frailty measures, there has been a surge of interest in surrogate markers of frailty, such as muscle mass, as predictive factors of poor outcomes after trauma.Several studies have found that sarcopenia is associated with post injury morbidity and mortality. Estimates of the prevalence of sarcopenia among trauma patients vary across studies due to differences in definition and sample characteristics. In order to appropriately categorize patients as sarcopenic, the population distribution of psoas CSA on CT must be established. The psoas measurement that best correlates with outcomes has yet to be determined, and it is unclear which measurement should be implemented in usual practice. Our main objective is to improve the outcomes of sarcopenic patients hospitalized with trauma by implementing in the future patient-centered interventions which will account for sarcopenia.

OBJECTIVES/SPECIFIC AIMS: The Johns Hopkins University Clinicaltrials.gov (CT.gov) Program has previously reported on a study showing reduction of “Late Results – per FDAAA” from 111 to 0. What we hope to do here is to focus on non-late results records. Over the years, some institutions spend their efforts solely on late results in order to avoid any penalties from the Food and Drug Administration (FDA). However, there are a number of variables that labels “problem records” within the Protocol and Registration System (PRS). These records are also subject to penalties. Our goal has been to minimize problem records and establish processes to improve and maintain our institutional compliance in regards to regulations governing clinical trials registration and results reporting. METHODS/STUDY POPULATION: The Johns Hopkins University implemented a Clinicaltrials.gov program solely mandated to assist Principal Investigators (PIs) and other study team members with clinical trial registration and results reporting. The program has developed processes in its duty towards reducing problem records in the PRS. Full-time staff have been assigned to assist research teams with registration and results reporting, while ensuring compliance with all relevant regulations. Several methods have been utilized to track metrics, such as monthly reports and internal databases. Features within the PRS have also been used to draw attention to newly-identified problem records on a daily basis in order to rectify these issues with the study team promptly. In order to ensure compliance, our office communicates with study teams regarding the problems within their CT.gov record that requires attention. In challenging cases, our program will also collaborate with the CT.gov PRS Team at the NIH to facilitate the process and avoid multiple review cycles, which can delay registration or the posting of results. Our Program has also formed internal collaborations with the Institutional Review Board (IRB) which allows us to verify study status and view active study team members. This is especially useful in cases where the study team members who are listed on the CT.gov record cannot be reached or the contact information is outdated (a common occurrence with older studies). With access in the IRB, we can contact the current study team members who may not be listed in CT.gov and assist them to resolve any outstanding issues of non-compliance within their CT.gov record. RESULTS/ANTICIPATED RESULTS: From September 2015 (before our program was established) to September 2016 (three months after the institution of our program), the total amount of problem records increased from 44% (339/774) to 45% (383/852). Since then, the processes we have developed resulted in a decline in problem records to 30% (282/955) in September 2017, and a further decline to 8% (83/1075) as of September 2018. The short rise that was observed in 2016, was a potential indicator that if our program was not instituted, it would have been more difficult to maintain compliance. DISCUSSION/SIGNIFICANCE OF IMPACT: According to the FDA Draft Guidance released in September 2018 referring to the Civil Money Penalties Relating to the ClinicalTrials.gov Data Bank, there are a number of ways to violate the FDA regulations, resulting in potential monetary penalties, which include “failing to submit required clinical trial information or submitting clinical trial information that is false or misleading”. These regulations apply to results as well as registration and study status updates. By paying attention to all problems that are identified by the PRS, institutions can rectify errors and remain complaint with all regulations that govern clinical trial registration and results reporting.

OBJECTIVES/GOALS: The primary aim of this observational study was to explore minute by minute differences in children’s in-school PA accumulation while attending a nature-based compared to a traditional Pre-K program. METHODS/STUDY POPULATION: Participants from a single Pre-K program wore an accelerometer at the waist during school for two consecutive weekdays in the winter, chosen for consistent weather conditions. In this program, one day was spent at a nature-based site, and one day at a traditional classroom location. Accelerometer data was analyzed using Butte (2014) vector magnitude activity thresholds summed by minute across each day. Paired-sample t-tests were applied on a minute-by-minute basis at a significance of p<0.001 to determine the point(s) at which PA accumulation diverged between settings. Direct observation (DO) conducted by a trained researcher also documented activities children engaged in each school day. RESULTS/ANTICIPATED RESULTS: In-school PA differed significantly between settings beginning at minute 37 of classroom time. Based on results obtained through DO, this coincided with the end of unstructured free play time and the start of structured activities across both days. In a traditional classroom setting, structured activities included classroom-based learning, while the nature-based setting incorporated a 10-minute outdoor walk prior to the start of classroom learning. This walking period altered the trajectory of total in-school PA accumulation between program locations, with participants maintaining a significantly greater PA accumulation while in a nature-based setting through the end of the school period. DISCUSSION/SIGNIFICANCE OF IMPACT: Compared to a traditional setting, nature-based programs allow for more active structured periods in school. A 10-minute teacher-led walk can significantly improve the trajectory of children’s PA accumulation throughout the remainder of a school day.

OBJECTIVES/GOALS: Selinexor is a novel XPO1 inhibitor that blocks nuclear export, thus impairing DNA repair and causing apoptosis. Our goal was to conduct preclinical and clinical studies to test our hypothesis that selinexor’s efficacy is boosted by priming with temozolomide and is associated with a tissue biomarker. METHODS/STUDY POPULATION: We leveraged a team science approach through the NCI Cancer Therapy Evaluation Program (CTEP) to design preclinical experiments, develop a novel RNAseq analysis pipeline, and use pre-existing clinical experience to open an early phase clinical trial for recurrent glioblastoma. Team members included a CTEP medical officer, cancer biologist, pharmacist, industry scientist, translational scientist, and early career clinician scientist mentored by an expert clinician scientist. Based on preclinical results, participants in the clinical trial experimental arm will receive sequential temozolomide 150mg/m2 on days 1-5 and a starting dose of selinexor 60mg on days 8 and 15 of a 28-day cycle. Participants in the control arm will receive monotherapy temozolomide. RESULTS/ANTICIPATED RESULTS: Sequential treatment of U87 cells and intracranial xenografts had superior DNA damage (É£H2A.X, cleaved PARP) and overall survival compared to combination or single-agent (HR 0.25 [95% CI, 0.07-0.84]; p=0.01, log-rank). We used the top-scoring gene pair method to identify an RNAseq signature associated with response to selinexor. We then designed a trial for first recurrent MGMT methylated glioblastoma. Primary objectives are safety and preliminary efficacy. Secondary objectives are overall response rate, efficacy, and validation of a molecular signature. Phase 1 dose finding (n=12) will be followed by a randomized phase 2 (n=72); using proportional hazards regression, RHR 0.5 with p DISCUSSION/SIGNIFICANCE: The NCI CTEP Project Team employs team science as a framework to successfully develop multidisciplinary collaborations, build investigator trial experience, and lead the way to future research opportunities. Our trial addresses a significant unmet need to offer novel therapies and molecular biomarkers in glioblastoma.

ABSTRACT IMPACT: Being explicit about the prevention of falls throughout an older adults’ episode of care may further help reinforce the role of physical therapy providers in falls prevention and improve dissemination of this knowledge. OBJECTIVES/GOALS: The purpose of this study was to determine older adults’ awareness of and perspectives about the role of physical therapy providers for falls prevention and determine potential barriers and facilitators to utilization of preventive rehabilitation services METHODS/STUDY POPULATION: We used a qualitative descriptive phenomenological approach to emphasize participants’ perceptions and lived experiences. Four focus groups were conducted with 27 community-dwelling older adults (average age = 78 years). Focus groups were recorded, transcribed, condensed, and coded using thematic analysis. RESULTS/ANTICIPATED RESULTS: Surveys indicated 37% of participants experienced a fall in the last year and 26% reported suffering an injury. Four main themes and six subthemes surrounding older adults’ perceptions of physical therapy providers’ roles for falls prevention emerged: (1) Awareness of Falls Prevention (subthemes: I Don’t Think About It, I Am More Careful); (2) Being Able to Get Up from the Floor; (3) Limited Knowledge about the Role of Physical Therapy Providers in Falls Prevention (subtheme: Physical Therapy Services are for After a Fall, Surgery, or for a Specific Problem); and 4). Barriers to Participating in Preventive Physical Therapy Services (subthemes: Perceived Need and Costs, Access Requires a Doctor’s Prescription). DISCUSSION/SIGNIFICANCE OF FINDINGS: Older adults lack awareness about the role of physical therapy services in falls prevention, perceiving services are only to treat a specific problem or after a fall. Physical therapists should be explicit about the role of physical therapy in falls prevention for all older adults undergoing rehabilitation, regardless of the reason.

Objectives/Goals: Novel therapeutics to control Staphylococcus aureus (S. aureus) infections are needed for people with cystic fibrosis (CF, PwCF). In this study, our objective is to determine if the pharmacologic MEK1/2 inhibitor compound ATR-002 can restrict the growth of S. aureus clinical isolates and modulate infection in a murine model of S. aureus infection. Methods/Study Population: To evaluate the anti-inflammatory effects of ATR-002 on human macrophages, cells were stimulated with TLR2 agonists FSL1 or Pam3CSK4 with a dose range of ATR-002, and secretion of proinflammatory cytokines were measured by ELISA. To determine the direct antibacterial effect of ATR-002, minimum inhibitory concentration (MIC) assays were performed with the community-associated methicillin-resistant S. aureus strain USA300 and 40 S. aureus isolates from PwCF. To validate our results in vivo, mice were provided i.p. treatment with either vehicle, the MEK1/2 inhibitor compound PD0325901 (20 mg/kg), or ATR-002 (10 mg/kg) prior to intranasal infection with 1x10^7 CFU of USA300. Bacterial burdens at 4- and 24-hour post-infection (p.i.) and inflammatory cell recruitment at 24 hours p.i. were quantified. Results/Anticipated Results: Macrophages treated with ATR-002 exhibited a dose-dependent decrease in secretion of proinflammatory cytokines TNF and IL-8 following TLR stimulation. Our studies identified that ATR-002, but not PD0325901 or other MEK1/2 inhibitors, had direct antibacterial effects, and ATR-002 had an MIC range of 8 to above 64 ug/mL on CF S. aureus isolates. In the murine pulmonary infection model, delivery of ATR-002 and PD0325901 significantly prevented infection-induced loss of body mass and decreased neutrophil inflammation. However, when bacterial burdens were quantified 4-hours p.i., only ATR-002 treatment reduced lung bacterial burden compared to vehicle or PD0325901-treated groups. Discussion/Significance of Impact: These results are the first demonstration of the in vivo anti-inflammatory and antibacterial effects of ATR-002. Our results further demonstrate that ATR-002 exhibits direct antibacterial effects across a collection of clinical isolates of S. aureus. Future studies will continue to investigate the therapeutic potential of ATR-002.

OBJECTIVES/GOALS: The objective of our research is to define unique molecular and immune markers in benign breast tissue to better identify women at risk of node-positive breast cancer (BC). The goal of the work is to improve individualized risk assessment, to guide targeted prevention and screening recommendations, and to reduce disease incidence and mortality. METHODS/STUDY POPULATION: From the Mayo Clinic’s Benign Breast Disease (BBD) cohort, we matched women who developed node-positive breast cancer after a BBD biopsy (cases; n=42) with women who remained cancer-free (controls; n=37), considering patient age and biopsy date. We used NanoString gene expression profiling to identify differentially expressed genes (DEGs) between cases and controls. We optimized a multiplex immunofluorescence (mIF) approach to simultaneously detect multiple markers within single FFPE tissue slides to correlate cells expressing DEGs in relation to innate and adaptive immune effectors. We used tissue segmentation, cell phenotyping, and spatial relationships to define molecular and immune differences between cases and controls. RESULTS/ANTICIPATED RESULTS: We discovered higher gene expression levels of IRF8 (interferon regulatory factor 8, a factor involved in immune cell differentiation) in controls as compared to cases (p = 0.0024) and found that IRF8 expression is also associated with longer cancer onset times among cases (p = 0.0012). Our pilot mIF experiments revealed higher frequencies of CD4+, CD8+, CD68+, CD20+ and CD11c+ cells in controls compared to cases. We predict that higher IRF8 expression and increased frequencies of immune cells in BBD biopsies indicate a proactive immune environment that may act to prevent cancer development. Furthermore, we predict that our analyses of the spatial localization of these markers by mIF may offer further predictive insight. DISCUSSION/SIGNIFICANCE: Deciphering the relationship between immune alterations in BBD and risk of node positive BC has the potential to improve individualized risk prediction. These insights will foster improved surveillance and informed screening and prevention, ultimately reducing BC incidence and mortality.

OBJECTIVES/GOALS: The goal of U-LINK is to bring together diverse scholars from multiple disciplines to address complex and challenging problems in healthcare, climate change, social equity, and community, through innovative team science, and aligned with the University of Miami’s strategic plans. METHODS/STUDY POPULATION: The U-LINK program has supported developmental and implementation projects through a competitive selection process. Developmental funding was intended for teams to develop and refine ideas and to become established as an effective team. Additional funding was provided to teams to advance their projects by conducting data collection and feasibility testing. In addition, U-LINK has supported fellowship for pre-doctoral and affiliated doctoral trainees. Team science training was provided to all teams through didactic lectures and hands-on training. Teams were tracked longitudinally by using surveys and bibliometrics to measure success and impact including scholarly output and follow on funding. Network analysis was performed to analyze research collaboration networks before and after ULINK funding. RESULTS/ANTICIPATED RESULTS: U-LINK has funded pilot programs and initial phases for 57 projects and 13 fellowships in the last three years. Over 400 individuals on teams from 16 schools/academic units collaborated on these projects on topics such as resilience, climate change, social equity and societal challenges, health, and impact of recent legislation on LGBTQ+ community. While data collection and analysis are ongoing, initial results show successful outcomes from U-LINK projects including publications and $29.5m in follow-on external funding. We anticipate network analysis to demonstrate increased and continued multi-disciplinary collaborations among U-LINK teams through co-authorship networks and increase in collaborative grants being submitted and/or funded. DISCUSSION/SIGNIFICANCE: The University of Miami’s U-LINK program has demonstrated success in forming interdisciplinary teams that have produced real-world solutions to complex problems by harnessing the inherent diversity and strength across UM’s programs.

OBJECTIVES/GOALS: * Patients with skin of color (SOC) are disproportionately affected by systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE). In this study, we aim to address this disparity and characterize the real-world efficacy and tolerability of anifrolumab in CLE patients using validated disease activity instruments. METHODS/STUDY POPULATION: This single-center, prospective observational cohort study includes SLE patients with severe or refractory CLE who have received ≥ 1 dose of anifrolumab. Cutaneous disease activity is assessed periodically at 2, 6, 9, 12, and 18 months using the Cutaneous Lupus Disease Area and Severity Index (CLASI). Adverse events and concurrent treatments are also routinely evaluated. To date, 22 patients have been enrolled, with 6-month follow-up data available for 15. At the time of anifrolumab initiation, 95% of participants had discoid LE (DLE), 60% had mucosal DLE, and 13% had subacute CLE. Nine patients identified as SOC, two as White, and four did not report race/ethnicity. RESULTS/ANTICIPATED RESULTS: A Friedman test showed statistically significant changes over time in CLASI activity score (CLASI-A) (χ2(2) =20, p<0.0001) (Figure 1) and CLASI damage score (CLASI-D) (χ2(2) =9.5789, p=0.0083) (Figure. To estimate effect sizes, we employed linear mixed models, which demonstrated statistically significant reductions in the CLASI-A score from baseline by an average of 14 points at 2 months (p<0.001) and 18 points at 6 months (p<0.001); notably, a reduction in CLASI-A of 4 is considered clinically meaningful. At 2 months, 20% of patients experienced a 50% or more reduction in CLASI, which increased to 60% of patients at 6 months. Patients on systemic corticosteroids could taper off. Adverse events were minimal and did not lead to treatment discontinuation. Fig. 1:[blob:https://acts.slayte.com/045319b4-7272-4351-a771-78ba9ee57f5c] Fig. 2:[blob:https://acts.slayte.com/67df7653-0cd8-4e8e-a3e1-d5c565b19dce] DISCUSSION/SIGNIFICANCE: As SOC patients with CLE have significant potential for permanent pigmentary alternations, early treatment is imperative. Effective treatments for refractory CLE are elusive. Our study represents the largest single-center cohort of CLE patients treated with anifrolumab and suggests that it is a promising therapeutic option for patients with SOC.

OBJECTIVES/SPECIFIC AIMS: Helping researchers assess and effectively translate innovations into healthcare improvements is a complex process (Terry et. al., 2013). The Clinical Translational Science Awards (CTSA)—supported by the National Institute of Health (NIH) under the auspices of the National Center for Advancing Translational Sciences (NCATS)— provide the resources and support needed to strengthen our nation’s clinical and translational research (CTR) enterprise. In 2008, Stanford University was awarded a CTSA from the NIH, establishing Spectrum (the Stanford Center for Clinical and Translational Research and Education). Under the Spectrum umbrella, the Byers Center for Biodesign manages the MedTech Pilot Program with the goal of translating discoveries into novel health technologies that address important unmet health needs. The MedTech Pilot Program is an innovative funding mechanism that seeks to (1) stimulate clinical translational research, (2) help promising projects bridge the gap between the bench and the patients’ bedside, and (3) encourage collaborative, transdisciplinary work. Specifically, the Pilot Program offers up to $50,000 to support projects involving medical devices and mobile technologies used for (1) therapeutic applications and (2) device-based patient-specific (or POC) diagnostic applications. This analysis of the MedTech Pilot Program will: 1) describe the Program’s structure and process; 2) highlight the intensive, hands-on mentorship and practical guidance awardees receive that enables them to more efficiently and effectively advance their projects toward patient care; and 3) characterize the progress of the 36 funded projects. METHODS/STUDY POPULATION: Key elements of the Pilot Program’s infrastructure and mentoring processes as they relate to project outcomes were identified. Additionally, outcomes data were collected from two sources: (1) annual survey of Pilot Awardees and (2) publicly available information relevant to the pilot projects. RESULTS/ANTICIPATED RESULTS: The Pilot Program’s framework and infrastructure has supported a diverse group of transdisciplinary projects. These projects were evaluated using both traditional and non-traditional metrics (e.g., patents, startups, publications). The initial investment of $1.5 million to fund 36 projects has led to over $88 million dollars in additional funding. Additionally, taking full advantage of the expertise in Silicon Valley, strong mentorship has helped advance projects along the clinical and translational path. DISCUSSION/SIGNIFICANCE OF IMPACT: The Pilot Program has benefited Stanford innovators and researchers by providing seed funding to help promising projects bridge the gap between the bench and the bedside. The intensive, hands-on mentorship, early pilot funding, and practical guidance pilot awardees receive effectively help translate their technologies into patient care.

OBJECTIVES/GOALS: This study aimed to investigate the mechanistic effects of the omega-6-derived eicosanoid 12-HETrE on platelets of cardiovascular patients at risk for a recurrent cardiovascular event triggered by thrombosis. 12-HETrE negatively regulates platelet reactivity through binding to the prostacyclin receptor in platelets. METHODS/STUDY POPULATION: Healthy donors were recruited from the Ann Arbor community and the University of Michigan Medicine Center. Cardiovascular patients with elevated cardiovascular risk were recruited from the Cardiac Catheterization Laboratory at Michigan Medicine Hospital. All subjects were recruited under study protocols approved by the University of Michigan IRB. Healthy donors were matched with the cardiovascular patients regarding age, sex, race, and BMI. Whole blood was collected via venipuncture into vacutainers containing sodium citrate. Platelets were isolated via serial centrifugation and treated ex vivo with vehicle control, 12-HETrE, or Iloprost. RESULTS/ANTICIPATED RESULTS: Based on our previous studies, we chose to treat platelets ex vivo with 25uM of 12-HETrE for 10 minutes. Using platelets of healthy donors, we have shown that treatment with 25uM of 12-HETrE for 10 minutes inhibited platelet aggregation and activation, and activated protein kinase A, suggesting activation of the prostacyclin receptor. We conducted a preliminary study to demonstrate that ex vivo treatment of 12-HETrE regulated signaling pathways in platelets such as cell-to-cell interaction, platelet activation and cytoskeleton rearrangements. In this study, we have demonstrated that treatment with 12-HETrE regulated receptors and intraplatelet proteins in platelets of cardiovascular patients. Furthermore, these proteins are involved in critical pathways in the platelet. DISCUSSION/SIGNIFICANCE: Dual antiplatelet therapy has significantly decreased mortality due to thrombotic events. However, cardiovascular events triggered by thrombosis persist as the leading cause of death in the US. This study may uncover key regulators to be targeted for the long-term goal of providing additional protection to reduce future incidence of thrombosis.

Objectives/Goals: People with insulin-treated diabetes face hypoglycemia risk due to imperfect insulin replacement and impaired counterregulation. We identified the dopamine antagonist, metoclopramide, as a potential treatment. Hypothesis: Treatment with metoclopramide will prevent the development of impaired counterregulatory response to hypoglycemia. Methods/Study Population: In a pre-clinical model, diabetes was induced in 10-week-old Sprague-Dawley rats with streptozotocin (STZ, 65 mg/kg IP). Rats were divided into three groups: 1) diabetic controls (STZ+RS, n = 6), 2) recurrent hypoglycemia (STZ+RH, n = 7), and 3) recurrent hypoglycemia + metoclopramide (STZ+RH+MET, 3 mg/kg IP, n = 7). After 3 days, all rats underwent a hyperinsulinemic (50 mU/kg/min) and hypoglycemic (~45 mg/dl) clamp. In the clinical trial, adults with Type 1 diabetes (age 20–60, ≥5 years duration) were enrolled in a phase II, double-blinded, placebo-controlled trial. Awareness status was assessed via Gold score, and subjects maintained drug regimens and underwent two hyperinsulinemic-hypoglycemic clamps (where blood glucose was lowered to 100, 65, 55, and 45 mg/dl) to assess counterregulation. Results/Anticipated Results: In the pre-clinical model, glucose infusion rates (GIR) to maintain hypoglycemia were higher in STZ+RH (27±0.9 mg/kg/min) than STZ+RS (19±0.8 mg/kg/min, p Discussion/Significance of Impact: Metoclopramide improves glucoregulatory, sympathoadrenal, and counterregulatory responses to hypoglycemia in pre-clinical models, suggesting dopaminergic regulation. While clinical data are still blinded, increased epinephrine and growth hormone responses suggest treatment may preserve or restore counterregulation.