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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/SPECIFIC AIMS: The goal of this study is to develop an effective and efficient STI preventive intervention among college students following the principles and phases of MOST. METHODS/STUDY POPULATION As part of the preparation phase, an explicit conceptual model, drawing heavily on theory and prior research, was used to translate the existing science into 5 candidate intervention components (ie, descriptive norms, injunctive norms, expectancies, perceived benefits of protective behavioral strategies, and self-efficacy). For the optimization phase, in Fall 2016 all firstyear students (n = 3547) from 4 universities were recruited to participate. Students were randomized to 1 of 32 different experimental conditions that included a combination of the candidate intervention components. Component effectiveness was evaluated using data from an immediate post-intervention survey on respective component mediators (eg, alcohol and sex-related descriptive norms). After a second factorial experiment (Fall 2017), only those intervention components that meet the pre-specified criteria of day ≥0.15 will be included in the optimized intervention. The evaluation phase will evaluate the effectiveness of the optimized STI preventive intervention via a randomized-control trial (Fall 2018). RESULTS/ANTICIPATED RESULTS: Preliminary results from the first factorial experiment suggest that descriptive norms and injunctive norms intervention components were significantly effective in reducing post-intervention perceived alcohol prevalence (β = −0.28, p < 0.001) and approval of alcohol (β = −0.33, p < 0.001), and sex-related norms (β = −0.23, p < .001). These results, in combination with process data, are being used to inform revisions of the intervention components to be included in a second factorial screening experiment. DISCUSSION/ SIGNIFICANCE OF IMPACT: This study demonstrates how an iterative approach to engineering an STI preventive intervention using MOST can affect the behaviors of college students and serve as a foundation for other translational science.

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A community-academic partnership to understand the correlates of successful aging in place Many seniors served by CBCA are racial/ethnic minorities, live in poverty, suffer from multiple chronic conditions, depression, and food insecurity; there is no simple measure routinely used to characterize the health/health risks of program participants. Multiple biological, musculoskeletal, psychosocial and nutritional factors collectively contribute to frailty a construct that is variously defined, and has been used as a surrogate or predictor for health outcomes. Aim 1: We will engage seniors, CBCA leadership, New York City Department for the Aging, staff and other stakeholders in research priority-setting, joint protocol writing, research conduct, analysis and dissemination to cultivate a population of elder stakeholders interested in designing and participating in this and future research. Aim 2: We will characterize the health status of the resident and nonresident populations by collecting data across 3 sessions to include validated cardio-metabolic, musculoskeletal, chronic condition prevalence, quality of life, psychosocial, and nutritional assessments. METHODS/ STUDY POPULATION: Stakeholders will be engaged through the process of Community Engaged Research Navigation and a series of meetings and exercises to refine priorities and research design, co-write the protocol, provide feedback on conduct, analyze and disseminate results of the project. RESULTS/ANTICIPATED RESULTS: Outcomes will include rates of participation and retention in assessments and engagement activities, themes from qualitative research, contributions to study design, placement of aims on the T0-T48 spectrum, social network analysis, classification of engagement on the spectrum of Community-based Participatory Research (CBPR) and partnership assessment. The primary outcome is frailty (6-minute walk test); We will examine associations among these measures with services utilization data captured electronically by CBCA. A key deliverable of this project will be a REDCap data capture platform that integrates and displays these measures that will be sustainable for CBCA. DISCUSSION/SIGNIFICANCE OF IMPACT: This practice-based research partnership will allow us to extract, replicate and extend the lessons learned about engaging stakeholders in generating hypotheses, operationalizing research, collecting and analyzing data, and disseminating results. The collaboration is built around generating and testing rigorous clinical an health services hypotheses that are derived from real-world practice-based needs and also incorporate basic science measures to embed and examine mechanistic hypotheses. Testing a simple to implement validated surrogate frailty measure will accelerate progress on evidence-based practices to test interventions that enhance healthy aging and serve as a model for future similar partnerships to form a network for community-based senior research. This work aligns with the RU-CCTS grant Hub Research goal to engage populations across the life span, including hard-to-reach and underserved populations, such as minority seniors.

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Predictive metabolism studies of varenicline and implications of its metabolites in nicotine addiction Keeshaloy Thompson and Milton Brown Georgetown -Howard Universities, Washington, DC, USA 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 82 cambridge.org/jcts varenicline may differ in individuals and across groups, thus, binding effects and the propensity for adverse effects may differ in individuals.

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Artificial urinary sphincter (AUS) placement after failed urethral sling: Impact of sling removal and proximal cuff placement Arnav Srivastava, Gregory Joice, Madeline Manka, Nikolai Sopko and Edward Wright Johns Hopkins University School of Medicine, Baltimore, MD, USA OBJECTIVES/SPECIFIC AIMS: Perineal urethral sling placement is an option for men with mild to moderate post-prostatectomy stress urinary incontinence (SUI). However, men with persistent incontinence after sling placement often require secondary artificial urinary sphincter (AUS) placement, made difficult by the sling occupying the proximal bulbar urethra. This proximal section has a thicker corpus spongiosum which may mitigate cuff-induced ischemia and subsequent urethral atrophy. The authors report a series of AUS placements after failed sling, using sling revision or removal to access the proximal urethra. METHODS/STUDY POPULATION: Cutting the sling arms during urethral cuff placement increased urethral exposure and mobility. If feasible, completely removing the sling allowed the most proximal cuff site; but if dissection was felt unsafe, the mesh was left in situ and the cuff placed distally. This study is a retrospective cohort design of patients with SUI who underwent AUS placement after failed sling from 2010 to 2016. Variables included baseline patient characteristics, SUI severity, intraoperative variables, and postoperative outcomes. AUS failure, defined as infection, erosion or urethral atrophy, was analyzed at 12 and 96 months using univariate and multivariable logistic regression. RESULTS/ANTICIPATED RESULTS: Over the study period, 29 patients underwent AUS placement after failed sling. At the time of AUS placement, mean urethral circumference was 6.2 cm and 68% of patients had a 4.5 cm cuff placed; no cases required a 3.5 cm cuff. Seventy-three percent of cases were after transobturator sling placement (27% bone-anchored) and 45% of slings were explanted. AUS failure rate at 12 and 96 months was 17.8% and 45%, respectively; atrophy was the most common indication. Prior transobturator sling placement had lower rates of both 12 month (9.1% vs. 57%, p = 0.006) and 96 month (36% vs. 71%, p = 0.11) failure, though the latter was not statistically significant. Sling explant was not a significant predictor of 12 month (p = 0.12) or 96 month failure (p = 0.17). DISCUSSION/SIGNIFI-CANCE OF IMPACT: Sling revision during AUS placement helps expose the wider proximal urethra, allowing larger cuff size placement. This procedure appears safe, with low rates of erosion and short-term failure-albeit with high rates of long-term urethral atrophy possibly due to more significant dissection causing devascularization. However, sling removal was not a significant predictor of failure. The transobturator sling's smaller profile may result in less trauma to urethra-possibly explaining the improved outcomes.

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Incidence of T3a up-staging and survival after partial nephrectomy: Size-stratified rates and implications for prognosis Arnav Srivastava, Hiten Patel, Max Kates, Zeyad Schwen, Gregory Joice, Alice Semerjian, Michael Gorin, Phillip Pierorazio and Mohammad E. Allaf Johns Hopkins University School of Medicine, Baltimore, MD, USA 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 upstaged 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. cambridge.org/jcts