OBJECTIVES/SPECIFIC AIMS: Fifty percent of adolescents have tried an illicit drug and 70% have tried alcohol by the end of high school. Further, despite 7-9% of youth 12-17 meeting criteria for a substance use disorder only 1 in 10 actually receive it. Screening, Brief Intervention, and Referral to Treatment (SBIRT) is an evidence based process that facilitates early identification and treatment for adults and adolescents in community (primary care) facilities. Despite the documented effectiveness of SBIRT, no research has examined the implementation of SBIRT in school settings by school-based mental health personnel. The purpose of the present study was to identify facilitators and barriers to SBIRT implementation by school-based personnel in secondary schools. METHODS/STUDY POPULATION: Participants included 30 school and community service providers including: teachers, school counselors, school psychologists, school administrators (principals and central office staff), city council members, school board members, community mental health services providers as well as state level individuals from the department of Adolescent Substance Use and the Office of Drug Control Policy. Interview guides were developed using the Consolidated Framework for Implementation Research (CFIR) to identify facilitators and barriers regarding the following: inner setting, outer setting, individuals involved, and intervention (SBIRT). The six-phase framework of Thematic Analysis (TA) was employed to analyze the data. We specifically used the deductive method to analyze the data with a pre-determined theory in mind (CFIR) to move to hypothesis building, and coding the data. RESULTS/ANTICIPATED RESULTS: Contrary to research conducted outside of the schools under the auspices that schools do not have the time or interest in providing school-based substance use interventions, several themes emerged identifying a receptivity, willingness, and eagerness to provide these services. Specifically, school-based mental health professionals (i.e., school counselors, school psychologists) being aware of adolescent substance use in their schools, but not knowing how to appropriately handle such disclosures. Further, school-based mental health personnel indicated that they would want additional training on how to identify and provide services to adolescents with substance use needs. School-based administrators also indicated a receptivity to addressing substance use with an acknowledgement that schools would need to move from a punitive model for substance use infractions to a treatment model. Some identified barriers to implementation included lack of awareness of community treatment settings for referrals and anonymity or lack thereof of substance use screening. DISCUSSION/SIGNIFICANCE OF IMPACT: While the data analyzed come from a limited sample in one school district, the present study found that schools could be potential settings for the early identification and intervention of adolescent substance use. Findings from this study contribute to our understanding of school and community receptivity to school-based interventions. Future research should identify training needs of school-based mental health personnel to assist in the early identification and prevention of substance use disorders.

OBJECTIVES/GOALS: Myocarditis is an inflammatory cardiomyopathy commonly caused by viral infections. The residual burden of this disease after guideline-based therapies is substantial, as there are no pathway-specific therapies. Our long-term goal is to find and translate treatments that reduce acute myocarditis severity and prevent progression of disease. METHODS/STUDY POPULATION: Of available therapies, extracellular vesicles (EVs) are ideally suited to the task of simultaneous, specific reprogramming of multiple pathogenesis mechanisms necessary in diseases like myocarditis, without similar immunosuppressive risks as their pharmacologic counterparts. We obtained plasma from healthy men and women and isolated nanoparticles, which were analyzed for physiochemical markers of human EVs. After confirming presence of EVs, we injected these plasma-derived extracellular vesicles (PEV) into male BALB/c mice vs. PBS control intraperitoneally on days -1, 0, 1 of viral infection (day 0) in a highly translational, mouse model of myocarditis. Hearts were examined at day 10 at the peak of acute myocarditis, using standard histological and cell composition analyses. RESULTS/ANTICIPATED RESULTS: Mice treated with PEV had significantly less myocardial inflammation both histologically and by gene expression of immune markers in the heart. The immunoregulation by PEV treatment decreased many key components of innate immune response networks that are known to be upregulated during acute myocarditis: TLR4+ mast cells and macrophages and complement. These pathways drive the profibrotic gene and protein changes that lead to remodeling, fibrosis, and disease progression observed in patients. We anticipate that when we analyze later timepoints in this model (day 35 post infection) which are normally associated with development of chronic myocarditis, dilated cardiomyopathy, we will see reduction of this fibrosis and of damage-associated changes. DISCUSSION/SIGNIFICANCE: These data suggest that EVs from plasma may be a novel treatment for viral myocarditis, but translation of EVs is hindered by their heterogeneity. We demonstrate characterization both physiochemically and functionally in a well-defined model. Such practices are necessary as these contemporary products challenge current regulation standards.

OBJECTIVES/SPECIFIC AIMS: Atrial fibrillation (AF) is the most commonly encountered arrhythmia in clinical practice, and has widely varying treatments for stroke prevention and rhythm management. Some of these therapies are increasingly being prescribed by primary care physicians (PCPs). We therefore sought to investigate if healthcare plans with PCP gatekeeping for access to specialists are associated with different pharmacologic treatment strategies for the disease. In particular, we focused on oral anticoagulants (OACs), non-vitamin K-dependent oral anticoagulants (NOACs), rate control, and rhythm control medications. METHODS/STUDY POPULATION: We examined a commercial pharmaceutical claims database (Truven Marketscan™) to compare the prescription frequency of OAC, rate control, and rhythm control medications used to treat AF between patients with PCP-gated health plans (where the PCP is the gatekeeper to specialist referral—i.e., HMO, EPO, POS) and patients with non-PCP-gatekeeper health plans (i.e., comprehensive, PPO, CHDP, HDHP). To control for potential confounders, we also used multivariable logistic regression models to calculate adjusted odds ratios which accounted for age, sex, region, Charlson comorbidity index, CHADS2Vasc score, hypertension, diabetes, stroke/transient ischemic attack, prior myocardial infarction, peripheral artery disease, and antiplatelet medication use. We also calculated median time to therapy to determine if there was a difference in time to new prescription of these medications. RESULTS/ANTICIPATED RESULTS: We found only small differences between patients in PCP-gated and non-PCP-gated plans regarding prescription proportion of anticoagulants at 90 days following new AF diagnosis (OAC 44.2% vs. 42%, p<0.01; warfarin 39.1% vs. 37.1%, p<0.01; NOAC 5.9% vs. 6.0%, p=0.64). We observed similar trends for rate control agents (76.4% vs. 73.4%, p<0.01) and rhythm control agents (24.4% vs. 24.6%, p=0.83). We found similar odds of OAC prescription at 90 days following new AF diagnosis between patients in PCP-gated and non-PCP-gated plans (adjusted OR for PCP-gated plans relative to non-gated plans: OAC 1.006, p=0.84; warfarin 1.054, p=0.08; NOAC 0.815, p=0.001; dabigatran 0.833, p=0.004; and rivaroxaban 0.181, p=0.02). We observed similar trends for rate control agents (1.166, p<0.0001) and rhythm control agents (0.927, p=0.03). Elapsed time until receipt of medication was similar between PCP-gated and non-gated groups [OAC 4±14 days (interquartile range) vs. 5±16 days, p<0.0001; warfarin 4±14 vs. 5±14, p<0.0001; NOAC 7±26 vs. 6±23, p=0.2937; rhythm control 13±35 vs. 13±34, p=0.8661; rate control 10±25 vs. 11±30, p<0.0001]. DISCUSSION/SIGNIFICANCE OF IMPACT: We found that plans with PCP gatekeeping to specialist referrals were not associated with clinically meaningful differences in prescription rates or delays in time to prescription of oral anticoagulation, rate control, and rhythm control drug therapy. In some cases, PCP gatekeeping plans had very small but statistically significant lower odds of being prescribed NOACs. These findings suggest that PCP gatekeeping does not appear to be a major structural barrier in receipt of medications for AF, although non-PCP-gated plans may vary slightly favor facilitating the prescription of NOACs. Our findings that overall OAC prescriptions did not differ by PCP gating status may suggest completion of the rapid dissemination and uptake phase for most AF treatments. The small but statistically significant odds ratios favoring the non-PCP-gated populations in NOACs further suggests that in this newer drug group, the process is ongoing, with more specialists representing early adopters. Interestingly, the low primary care odds ratio of rivaroxaban use, relative to dabigatran, may be indicative of a gradient of uptake of later-generation NOACs, although interpretability is limited by the small number of patients in the rivaroxaban group.

OBJECTIVES/SPECIFIC AIMS: The central goal is to predict the metabolites of varenicline and predictively evaluate their propensities for eliciting an increased binding effect in the brain. METHODS/STUDY POPULATION: Molecular modeling computational software and other cheminformatic tools present a strategic in silico strategy to predict a complete metabolic transformation for the varenicline molecule. Molecular docking tools help to highlight key interactions of the varenicline with key metabolizing enzymes that are differentially expressed across a population. This will assist in validating clinical models for smoking cessation. RESULTS/ANTICIPATED RESULTS: Differentialized binding results depending on whatever metabolite is produced. DISCUSSION/SIGNIFICANCE OF IMPACT: Products of metabolism of varenicline may differ in individuals and across groups, thus, binding effects and the propensity for adverse effects may differ in individuals.

OBJECTIVES/GOALS: The goal of this project was to inform four chronic disease initiatives, working together on the team Connections IN Health, and counties in Indiana on certain areas of need to assist them in collaborative planning. The chronic diseases focused on include diabetes, cardiovascular disease, stroke, asthma, lung cancer and obesity. METHODS/STUDY POPULATION: Chronic disease health outcomes and social determinants of health indicators were identified in all 92 Indiana counties. Counties were compared by composite z scores in a matrix to determine the 23 counties with the poorest health statistics for diabetes, cardiovascular disease, stroke, asthma, lung cancer, obesity and life expectancy. Qualitative data were used to identify local health coalitions that have the capacity and desire to work with Connections IN Health to improve these health outcomes. With input from partners, the counties were narrowed to 10 that were identified as those with the most need in the specific areas of chronic disease that the initiatives focus on. The team will begin listening sessions with two of these counties to identify strategic partnerships, funding sources, and evidence-based programs to address community-identified health priorities. RESULTS/ANTICIPATED RESULTS: The 23 counties with the poorest health outcomes related to chronic disease and factors were Blackford, Clark, Clay, Fayette, Fulton, Grant, Greene, Howard, Jay, Jennings, Knox, Lake, LaPorte, Madison, Marion, Pike, Scott, Starke, Sullivan, Vanderburgh, Vermillion, Vigo, and Washington. There was significant overlap in low z score rankings for individual health and social determinants of health measures among these 23 counties. The following 10 counties were selected for focus in the next five years based on partner input: Blackford, Clay, Grant, Jennings, Lake, Madison, Marion, Starke, Vermillion, and Washington. The Connections IN Health team has initiated listening sessions in Grant and Vermillion Counties (with data for presentation at the ACTS meeting). DISCUSSION/SIGNIFICANCE OF IMPACT: This mixed methods approach using existing data and partner input on county capacity/readiness directed Connections IN Health to counties with the most need for coalition efforts. Engagement within each county will inform next steps (e.g., capacity building, partnership development, applications for funding, implementation of evidence-based programs) and specific health focus area(s).

Objectives/Goals: Adults from minority groups report more severe and pervasive pain than those in majority groups, resulting in a disproportionate burden of pain. Whether race disparities in pain outcomes exist in persons with multiple sclerosis (MS) is unknown. We examined the association of race with pain intensity, pain interference, and pain phenotypes in MS. Methods/Study Population: Ambulatory adults with medically documented MS completed a comprehensive survey battery including demographics and clinical data. Pain outcomes were assessed with four measures: Patient Reported Outcome Measurement Information System (PROMIS) pain intensity and pain interference short forms, the American College of Rheumatology Fibromyalgia Survey Criteria (a surrogate of degree of nociplastic pain), and the PainDETECT (a surrogate of neuropathic pain). Participants were categorized as either Black/African American or White based on their self-reported race. Four sets of unadjusted and adjusted (including sex, age, years since diagnosis, MS subtype and Patient Determined Disease Steps—PDDS score) linear regression models were built to examine the associations between race and pain outcomes. Results/Anticipated Results: A total of 258 participants (200 White and 58 Black), with a mean age of 51 ± 12 years, mostly female (77%), an average of 15 ± 10 years since diagnosis, a PDDS score ranging from 0 to 6, and mostly diagnosed with RRMS (79%), were included in the analyses. Unadjusted regression models indicated that pain intensity (β  =  5.20; 95% CI 2.73 – 7.66, p < 0.001), pain interference (β  =  5.17; 95% CI 2.29 – 8.06, p < 0.001), and nociplastic pain (β  =  2.41; 95% CI 0.40 – 4.42, p  =  0.019) were all higher for Black/African American participants compared to White participants. The differences remained statistically significant in adjusted models. No differences in neuropathic pain were observed between Black/African American and White participants in both unadjusted and adjusted models. Discussion/Significance of Impact: We highlight an increased burden of pain in Black/African American with MS compared with their White counterparts. The findings illuminate potential future targets of interventions to reduce disparities in the experience and impact of pain. A comprehensive examination of the role of social determinants in pain outcomes in MS is further warranted.

Gaps in the implementation of effective interventions impact nearly all cancer prevention and control strategies in the US including Massachusetts. To close these implementation gaps, evidence-based interventions must be rapidly and equitably implemented in settings serving racially, ethnically, socioeconomically, and geographically diverse populations. This paper provides a brief overview of The Implementation Science Center for Cancer Control Equity (ISCCCE) and describes how we have operationalized our commitment to a robust community-engaged center that aims to close these gaps. We describe how ISCCCE is organized and how the principles of community-engaged research are embedded across the center. Principles of community engagement have been operationalized across all components of ISCCCE. We have intentionally integrated these principles throughout all structures and processes and have developed evaluation strategies to assess whether the quality of our partnerships reflects the principles. ISCCCE is a comprehensive community-engaged infrastructure for studying efficient, pragmatic, and equity-focused implementation and adaptation strategies for cancer prevention in historically and currently disadvantaged communities with built-in methods to evaluate the quality of community engagement. This engaged research center is designed to maximize the impact and relevance of implementation research on cancer control in community health centers.

Community advisory boards (CABs) have traditionally been formed in the context of discrete projects and served to support community protections within the confines of the associated investigation(s). However, as funding bodies increasingly prioritize health equity, CABs have shifted – evolving into long-running organizations with broader scope and value. An emerging cornerstone of these project-independent boards (PICABs) has been the formation of “Research Review Boards” (RRBs). While unified in their goal of promoting community protection and representation in health research, it is unknown to what degree RRBs differ on key features including membership, leadership, service reach, and – crucially – impact. A scoping review was conducted according to PRISMA-ScR guidelines to analyze current practices for RRBs. Of screened articles (n= 1878), 25 were included, corresponding to 24 unique RRBs. Findings indicated overlaps in the stated missions, funding structures, and processes of most RRBs. Differences in membership composition, location, service-reach, leadership structures, evaluation procedures, and perceived impact were evident. Where data is available, RRBs receive positive endorsement from both internal members and external users. Standardization of evaluation procedures is needed to fully quantify impact. Additional challenges to sustainability, communication, and conflicts (e.g., of interest, commitment, and power differentials) merit further consideration.

Availability of trained professionals to assist researchers navigating regulatory pathways for new drug and device development is limited within academic institutions. We created ReGARDD (Regulatory Guidance for Academic Research of Drugs and Devices), a regional forum initially involving regulatory professionals from four Clinical and Translational Science Award (CTSA)-funded institutions, to build and capitalize on local expertise and to develop a regulatory guidance website geared toward academic researchers. Since 2015, members organized 15 forums covering topics such as FDA premarket submissions, gene therapy, and intellectual property for devices and therapeutics. Through user feedback, targeted surveys, and ongoing iterative processes, we refined and maintained a shared regulatory website, which reached 6000+ users in 2019. Website updates improved navigation to drug versus device topic areas, provided new educational content and videos to address commonly asked questions, and created a portal for posting upcoming training opportunities. Survey respondents rated the website favorably and endorsed expanding ReGARDD as a centralized resource. ReGARDD strengthened the regional regulatory workforce, increased regulatory efficiency, and promulgated best organizational and operational practices. Broad-scale deployment of the ReGARDD model across the CTSA consortium may facilitate the creation of a network of regional forums and reduce gaps in access to regulatory support.

OBJECTIVES/SPECIFIC AIMS: Due to increased experience and favorable outcomes, the use of partial nephrectomy (PN) to treat renal cell carcinoma has grown in the past decade, with expansion to larger tumors. Performing PN for larger tumors could potentially increase the number of patients up-staged to pT3a after surgery, who may have instead been treated with radical nephrectomy (RN), if known preoperatively. We aimed to estimate the proportion of patients up-staged to T3a disease after PN stratified by size. We also compared size-stratified survival outcomes of up-staged patients to those with T1a, T1b, or T2 kidney cancer. METHODS/STUDY POPULATION: From 1998 to 2013, patients undergoing PN or RN were identified from Surveillance Epidemiology and End Results registries. The proportion of patients receiving PN found to have pT3a disease was quantified by size. Cox proportional hazards models compared cancer-specific (CSS) and overall survival (OS) for PN patients with pT1a, pT1b, and pT2 disease with appropriately size-stratified pT3a patients. Also, PN patients with pT3a disease were compared to size-stratified RN patients with pT3a disease. Comparisons by size were performed within pT3a patients receiving PN. RESULTS/ANTICIPATED RESULTS: From a total of 28,854 patients undergoing PN, the estimated proportion up-staged to pT3a increased along with increasing tumor size: 4.2% for T1a, 9.5% for T1b, and 19.5% for T2. Among patients receiving PN, adjusted survival analysis demonstrated worse CSS for up-staged pT3a patients Versus appropriately stratified pT1a (CSS: HR=1.87, p=0.02), pT1b (CSS: HR=1.91, p=0.01), and pT2 (CSS: HR=2.33, p=0.01) patients. However, when assessing OS, only the size-stratified comparison of up-staged pT3a Versus pT1a disease demonstrated worse OS for the up-staged cohort (OS: HR=1.25, p=0.04). Comparing PN and RN for pT3a disease, size-adjusted analysis revealed no statistical difference in CSS or OS. Lastly, among patients undergoing PN with pT3a disease, patients with larger tumors, measuring 4–7 cm (CSS: HR=2.83, p<0.01; OS: HR=1.44, p=0.04) or 7–16 cm (CSS: HR=8.22, p<0.01; OS: HR=2.64, p<0.01), experienced worse survival than those with smaller pT3a tumors, <4 cm. DISCUSSION/SIGNIFICANCE OF IMPACT: A greater proportion of patients appear to experience T3a up-staging after PN with increasing initial T stage. Up-staged pT3a patients have worse cancer specific survival after PN compared to those with similarly sized localized tumors. Furthermore, the up-staged pT3a patients after PN appear to experience similar survival to pT3a patients undergoing RN. However, pT3a patients undergoing PN had worse survival with increasing tumor size, reinforcing the need for improvements in preoperative staging and identifying patients at risk of up-staging.

OBJECTIVES/SPECIFIC AIMS: To outline 4 categories of ethics needs identified at a translational science center. To map how research ethics has been further integrated into the center’s culture in response to these needs. To provide insights into how research ethics can be integrated into the translational team science environment. METHODS/STUDY POPULATION: The Institute for Translational Sciences (ITS) at the University of Texas Medical Branch is studied on an organizational level using polyphonic organizational theory and the results of an ethics needs assessment completed in 2010. RESULTS/ANTICIPATED RESULTS: The results will be a map indicating how research ethics has been further integrated into the culture of the ITS in response to the needs identified to ensure the responsible practice of translational science. DISCUSSION/SIGNIFICANCE OF IMPACT: Successful translational science requires shared understanding of communication and values. Achieving agreement in these areas requires the development of strategies for communicating and reinforcing common goals. Research ethics has often been considered an “add on” rather than a “part of” science. Through integrating ethics into various aspects of translational science, the ITS has taken important steps toward achieving the goal of culture change. The map of how the ITS has integrated ethics into organizational activities and structures will serve as a model for other organizations and institutions.

OBJECTIVES/GOALS: People engaging in high-risk substance use or experiencing food insecurity or housing instability are at increased risk to develop end-stage kidney disease. This study will examine associations between these risk factors, patient indicators of socioeconomic position, and hospitalization rates and quality of life after initiation of hemodialysis. METHODS/STUDY POPULATION: The proposed study will leverage a prospective cohort design. We will enroll a convenience sample of 330 participants from the same large dialysis organization. Participants will complete measures of socioeconomic position (age, gender, race, ethnicity, education, income, occupation and community poverty); substance use; food insecurity; housing instability; and quality of life at baseline. We will follow participants for 6 months and extract hospitalization counts from the dialysis facility medical record. RESULTS/ANTICIPATED RESULTS: We will generate risk scores (low, medium, high) from measures of substance use, food insecurity and housing instability. We will conduct multiple logistic regression to generate odds ratios comparing risk group membership by indicators of socioeconomic position. We anticipate that low or medium-risk groups will differ from high risk groups by indicators of socioeconomic position. We will conduct Poisson regression to generate incidence rate ratios for 6-month hospitalization rates comparing low or medium-risk and high-risk groups. Lastly, we will conduct multiple linear regression to generate beta coefficients for changes in quality of life scores comparing low or medium-risk and high-risk groups. We anticipate that high-risk groups will have higher hospitalization rates and lower quality of life scores. DISCUSSION/SIGNIFICANCE OF IMPACT: As the prevalence of end-stage kidney disease continues to increase, there is a need for tertiary prevention interventions that reduce costly inpatient utilization and improve health-related quality of life. The proposed study will lay groundwork for the development of interventions to improve patient outcomes and reduce Medicare spending.

ABSTRACT IMPACT: The broad goal of this investigation is to inform the development of culturally sensitive HIV prevention strategies to reduce specific challenges pertaining to PrEP uptake and utilization for Latino men. OBJECTIVES/GOALS: HIV is a significant public health concern affecting Latinos in the U.S. Daily use of pre-exposure prophylaxis (PrEP) effectively prevents HIV infection and has the potential to curb HIV epidemics. The objective of this study is to examine how sociocultural variables impact PrEP-related services among HIV-negative Latinxs. METHODS/STUDY POPULATION: The current study is a mixed-method investigation. Participants will include Latinx adult patients seeking services at an HIV community clinic. Approximately 150 participants will be recruited for the study. Participants who are eligible will complete sociocultural, mental health and PrEP-related measures. For the applied aim, community stakeholders will be recruited who serve the Latinx community. Upon completion of data collection, the data analytic plan is as follows: Aim 1, to establish the relationship between each sociocultural variable and PrEP uptake/utilization, preliminary analyses (i.e., correlations and regression analyses considering co-variates) will be conducted. Aim 2, grounded theory techniques will be conducted to establish community-informed practices to increase the use of PrEP. RESULTS/ANTICIPATED RESULTS: Relatively little is known about cultural factors that may impede PrEP uptake among Latinx MSM. Several researchers have identified specific factors such as language, acculturation, familismo, and similar cultural norms as significant barriers to care (Page et al., 2017). It is expected that each of these variables will contribute significant variance to willingness to use PrEP. Specifically, negative relationships are expected between fatalism and machismo and lower stages on the PrEP Contemplation Ladder. Comparably, a negative relationship is expected between the Hispanic acculturation subscale and lower stages on the PrEP Contemplation Ladder. It is however, hypothesized that there will be a positive relationship between familism and the non-Hispanic acculturation sub-scale. DISCUSSION/SIGNIFICANCE OF FINDINGS: Despite important advances in health to prevent HIV infection, HIV rates among Latinx MSM continue to rise. This investigation will have the potential to inform the development of culturally sensitive prevention strategies. By collecting qualitative data from key community stakeholders, this project will also directly inform a CBPR prevention.

OBJECTIVES/GOALS: Using a cell culture model, we will determine the effects of phosphate on primary lung cell cultures and use our results to delineate a pathway through which these changes are carried out. Using animal models, we will determine the effects of phosphate on inflammatory and fibrotic lung injury, both in the presence and absence of CKD. METHODS/STUDY POPULATION: For our in vitro experiments, human lung fibroblasts were treated with concentrations of 1 to 5 mM sodium phosphate and FGFR inhibitors. Expression levels of interleukin (IL)-1beta, IL-6, and IL-8 were analyzed by qPCR and secretion of these cytokines was measured by ELISA. Phosphorylation of PLCy and ERK was measured by western blot. Using an in vivo approach, we placed C57Bl/6 mice on a high phosphate (3%) diet to elevate serum phosphate levels in the absence of kidney injury and administered bleomycin via oropharyngeal aspiration to generate an acute inflammatory response. Serum FGF23 levels were measured by ELISA and serum analysis for phosphate and renal function were obtained. Furthermore, expression of FGF23 pathway and inflammatory markers were analyzed in murine lung tissue using qPCR and western blotting. RESULTS/ANTICIPATED RESULTS: Augmented phosphate concentrations led to increased cytokine expression and secretion from human lung fibroblasts as well as a concomitant increase in PLCy and ERK phosphorylation. Inhibition of FGFR1 reversed the effects of phosphate on the inflammatory cytokines and PLCy/ERK phosphorylation. Serum FGF23 levels were significantly upregulated in mice on a high phosphate diet and further increased in mice subjected to a high phosphate diet with exposure to bleomycin. Both serum phosphate and creatinine levels were significantly elevated as well. Additionally, high phosphate and bleomycin increased local FGF23 expression in murine lung tissue, when compared to controls or each stimulus alone. DISCUSSION/SIGNIFICANCE: Phosphate has a significant impact on inflammation and fibrosis in the lung, indicating that the existence of pulmo-renal crosstalk exaggerates pulmonary injury and that there are biological pathways that may be targeted therapeutically to mediate these effects. These results could have a substantial impact on the quality of life for CKD patients.

OBJECTIVES/SPECIFIC AIMS: ClinicalTrials.gov (CTgov) compliance has received much international attention as a significant regulatory, scientific, and ethical responsibility. Compliance rates for both industry and academia are held up for scrutiny by transparency advocates, but solutions for achieving compliance in academia have proven to be—because of its focus on innovation and multiple disciplines—significantly more complex than those employed by industry. Added challenges for academic medical centers (AMCs) are both increased researcher responsibilities under the new NIH Policy on Clinical Trial Dissemination and system-wide changes to requirements for “clinical trial only” Funding Opportunity Announcements. At Stanford University, a multifaceted approach toward improving CTgov outreach, education, and reporting led to a dramatic turnaround in compliance over 17-month period. METHODS/STUDY POPULATION: Stanford University School of Medicine’s Senior Associate Dean for Research and PI of Stanford’s CTSA applied a 3-part strategy to address unacceptable rates of results reporting. The strategy included (1) regular compliance reports to department chairs, (2) establishment of a central office, Clinical Research Quality (CRQ), to provide consistent training and support, and (3) interdepartmental cooperation across the school and university. Compliance reports, identifying all studies late for results reporting were sent monthly to all department chairs, with heightened focus on departments that conduct the most clinical trials. Senior leadership described the process in executive meetings and set improvement goals. Reports included multiple data points to help departments mobilize resources and identify trends; half-way through the period, soon-to-be late study records were included. CRQ hired 2 fulltime employees tasked with all aspects of managing the CTgov process and designed a portfolio of activities including: (1) a master list of all Stanford studies in the CTgov system; (2) a process for generating and distributing monthly reports; (3) an education program; and (4) support services, including an administrator working group. RESULTS/ANTICIPATED RESULTS: Since December 2015, Stanford has had the second-highest compliance rate improvement out of the 20 schools of medicine that receive the most NIH funding (+ 62%). DISCUSSION/SIGNIFICANCE OF IMPACT: Managing ClinicalTrials.gov compliance requires a high degree of technical knowledge of regulations, NIH policy, and the CTgov system. But without an equally high degree of engagement from senior leadership, results would not have been achieved. Central resources are critical to set policy and establish consistent processes, but without regular and repeated interactions between faculty, a multitude of administrators and staff, more central resources would have been required. By working simultaneously “down from the top” and “up from the bottom,” communication and education expanded rapidly, ineffective efforts were quickly transformed, and what began as an irritating and cumbersome problem became an occasion for collaboration and celebration of increased transparency.

OBJECTIVES/GOALS: The aim of this study is to analyze electronic health record (EHR) data using Mapper PLUS (MP), a new mathematical model, to classify acute myocardial infarction (MI) patients by risk of major adverse events (AE). We tested MP’s ability to define patient subgroups with distinctive risk for death, heart failure or recurrent MI after revascularization. METHODS/STUDY POPULATION: An EHR retrospective analysis of 797 MI patients and 29 variables (i.e., laboratory tests, imaging, vitals, and clinical traits) collected at the time of hospitalization was conducted. All patients received percutaneous coronary intervention and standard pharmacotherapy. MP analysis produced a multi-dimensional nodal graph of the patients based on similarities found within variables. Two algorithms, Walk Likelihood and Walk Likelihood Community Finder were applied to the graph which formed joint clusters according to spatial distance within nodes. The final output was three clusters for risk level evaluation. Risk level (low vs. high) was relative to the average risk of AEs for the entire cohort one year post MI. RESULTS/ANTICIPATED RESULTS: Of three patient subgroups, one (n= 318) had a >1 fold change for the probability of survival without AE when compared to the overall cohort and thus was defined as the low-risk group. The second group (n=304) had DISCUSSION/SIGNIFICANCE: MP stratifies patients into three groups according to predictive variables which relate to the risk for AE following an acute MI treatment. This is a new topological method for patient classification based on minimal input strictly from pre-collected EHR data. More cohort studies are needed to validate MP to classify patients for precision medicine.

ABSTRACT IMPACT: This study will be used to culturally tailor interventions to reduce maternal and infant health disparities in a Marshallese community. OBJECTIVES/GOALS: Inadequate prenatal care is associated with adverse birth outcomes including preterm births, low birth weight infants, and neonatal mortality. Marshallese Pacific Islanders are less likely to receive early and consistent prenatal care compared to other racial/ethnic groups and are thus at a higher risk for maternal and infant health disparities. METHODS/STUDY POPULATION: This article used a qualitative comparative analysis method to compare and contrast the perceived barriers to prenatal care for the prospective of Marshallese mothers and Maternal Health Care Providers (MHCPs). RESULTS/ANTICIPATED RESULTS: Marshallese mothers and MHCPs identified the same structural barriers to prenatal care: health insurance, transportation, and language. The socio-cultural barriers to prenatal care were depicted quite differently by Marshallese mothers verses MHCPs. DISCUSSION/SIGNIFICANCE OF FINDINGS: While the description of structural barriers were consistent among Marshallese mothers and MHCPs, the socio-cultural barriers and the value assigned to those barriers was quite different. Understanding the perspectives from both lenses is an important step towards addressing the barriers to prenatal care among Marshallese.