OBJECTIVES/SPECIFIC AIMS: The primary goal of the project was to conduct a narrative review of the published literature to identify and summarize best practices for developing oncology-focused research and training experiences for AI/AN undergraduate, graduate and professional students. A secondary goal was to identify methodological limitations and areas for future research related to rigorous educational program evaluation. METHODS/STUDY POPULATION:. Published literature was searched using databases relevant to oncology (PubMed, Web of Science) and sociology (PsychINFO, SocIndex). The bibliographies of identified relevant papers were searched for additional references by title. Search terms included synonyms and commonly used terms for three general areas: (1) target population (e.g., American Indian), (2) training area (e.g., oncology), and (3) educational program (e.g., undergraduate). RESULTS/ANTICIPATED RESULTS:. A current total of 107 original publications and 33 review papers that are relevant to the project goals have been identified. Key areas of program development and implementation relate to advertising and recruitment; didactic curriculum in research methods, cancer health disparities, and professional development and career planning; research immersion experiences through shadowing, networking, application of research skills, and opportunities to develop oral and written communication skills; ongoing career development support; mentoring by faculty, advanced trainees, and peers; and culture-specific enrichment. Important areas for program evaluation relate to measures of reaction, knowledge, practice and long-term outcomes. Evaluation design approaches include observational and experimental designs with recommendations for identifying relevant control groups. Strategies to ensure complete long-term follow-up are also summarized. DISCUSSION/SIGNIFICANCE OF IMPACT:.Successful programs address barriers related to perceived lack of abilities, lack of AI role models, limited culture-specific enrichment, and limited mentoring and ongoing career development support. Program directors should work with local tribal and community leaders when creating a new program. A high degree of coordination is needed to create a bicultural program to interest students in a research career and avoid the creation of barriers hidden to the program director. There are opportunities to improve the rigor of educational program evaluation in this setting by including measures beyond self-reported reaction and knowledge to focus on educational program enrollment and completion and long-term career outcomes. Methodologic challenges include identification of relevant control groups for comparison and the use of experimental designs.

OBJECTIVES/SPECIFIC AIMS: Emergency department (ED) length of stay (LOS) is one of the important indicators of quality and efficiency of ED service delivery and is reported to be both cause and result of ED crowding. Increased ED LOS is associated with ED crowding, increases service cost and sometimes poor patient outcome. Substance abuse is one of the major determinants of morbidity, mortality and healthcare needs. Substance abuse may confound the healthcare and service needs of patients in the ED irrespective of primary purpose of their ED visit and may lengthen the ED LOS. The aim of this study was to evaluate the effect of patients’ demographic and clinical characteristics and of different patient-related activities such as screening brief intervention and referral to treatment (SBIRT) on the ED LOS of patients discharged from the ED with a diagnosis of substance abuse. METHODS/STUDY POPULATION: We conducted a retrospective data analysis of electronic health records. The study population included 26971 patients who visited our hospital ED between 2013 and 2017, had a history of substance abuse and were discharged from the ED. An accelerated failure time (AFT) model was used to analyze the influence of covariates on patient ED LOS. The predictor factors in the model included age, gender, ED arrival shift and weekday, diagnosis history of mental health and drug use, acuity triage level from 1 to 5, with 1 being worse severity, and whether any lab tests were ordered, SBIRT intervention and whether patient was homeless. The AFT model is an alternative to the Cox Proportional Hazard Ratio model, which directly models the log of ED LOS as a function of a vector of covariates. The model defines the increase or decrease in LOS with the changes in the covariate levels as an acceleration factor or time ratio (TR). RESULTS/ANTICIPATED RESULTS: The overall median ED LOS was 4 hours with IQR of 4.2 hours. The average age of the study population was 39.3 years, 58.6% of the patients were male and 57% where White; 63.4% had a history of drug use; 43% had a history of mental health issue, and 0.4% were homeless. In the analysis using the AFT model, increased age (a year increase, TR =1.01, p =0.008), female sex (TR=1.044, P<0.001), SBIRT (TR=1.525, P <0.001), history of mental health issue (TR=1.117, P<0.00), evening arrival (evening vs night, TR=1.04, p=0.006), history of drug use (drug vs alcohol only, TR=1.04, p=0.001), higher acuity (triage level 1 vs 5, TR=2.795, p <0.001) and homelessness (TR=1.073, P = 0.021) lengthened the ED LOS. In contrast, weekend arrival (TR=0.956, p=0.004) and day shift arrival (day vs night, TR=0.958, p=0.004) shortened the ED LOS. DISCUSSION/SIGNIFICANCE OF IMPACT: We identified gender, age, SBIRT, arrival shift, weekend arrival, mental health status, substance abuse, acuity level and homelessness to be significant predictor of ED LOS. The fact that SBIRT increased the LOS should be balanced with the advantages of engaging patients into substance use disorder treatment. Understanding the determinants of ED LOS in this population may provide useful information for physicians or patients to better anticipate an individual’s LOS and to help administrators plan the ED staffing and other resources mobilization.

OBJECTIVES/GOALS: Our preclinical data demonstrate that the principal effects of nilotinib, a multi-tyrosine kinase inhibitor, in models of neurodegeneration is clearance of misfolded proteins via autophagy. Here we aimed to evaluate the effects of nilotinib on microRNAs in the cerebrospinal fluid of Parkinson’s disease patients. METHODS/STUDY POPULATION: Cerebrospinal fluid (CSF) was collected as part of an open label phase I (NCT02281474) (n = 12, 300 mg nilotinib taken orally once daily for 6 months), and a phase II randomized, double-blind, placebo-controlled study (NCT02954978) (n = 75, randomized 1:1:1 into placebo, 150 mg or 300 mg nilotinib taken orally once daily for 12 months). RNA was isolated from CSF and Indexed sequencing libraries were prepared from total RNA plus miRNA. Next generation whole-genome sequencing (single-end 1x75 bp, 25 million raw reads per sample) was performed to identify miRNAs significantly differentially expressed (fold-change ≥ 2, Benjamini-Hochberg FDR p-value ≤ 0.05 or Empirical Bayes FDR ≤ 0.05) with treatment compared to baseline. RESULTS/ANTICIPATED RESULTS: Next generation whole-genome sequencing of microRNAs in the CSF demonstrated that nilotinib significantly increases microRNAs that specifically regulate expression of autophagy and ubiquitination genes in individuals with Parkinson’s disease. In the open label phase I, samples, 28 microRNAs found to regulate autophagy and ubiquitination genes, were significantly altered with treatment (Benjamini-Hochberg FDR p-value ≤ 0.05). In the phase II randomized, double-blind, placebo-controlled study samples, we verified several of those 28 candidate microRNAs had been significantly deferentially expressed with treatment (Empirical Bayes FDR p-value ≤ 0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: Our data provide robust evidence that nilotinib’s effects on misfolded protein clearance is via autophagy and CSF miRNA sequencing is a valid biomarker of nilotinib’s effects in a definitive phase III study to investigate nilotinib in Parkinson’s and other neurodegenerative diseases. CONFLICT OF INTEREST DESCRIPTION: Charbel Moussa is listed as an inventor on several Georgetown University patents for the use of tyrosine kinase inhibitors as a treatment for neurodegenerative diseases

OBJECTIVES/GOALS: Biliary atresia (BA) is a progressive congenital disease that is characterized by periductular inflammation and fibrosis that leads to bile duct destruction and cholestasis in neonates. Galectin-3 (Gal3) plays a key role in inflammation and fibrosis. The aim of this study was to evaluate plasma Gal3 levels in early and late BA. METHODS/STUDY POPULATION: Samples from our institutional Pediatric Liver Biobank were used for this study. Patients were categorized as early BA (at diagnosis), late BA (at liver transplant), early other cholestatic liver disease (CLD), late other CLD, or controls without cholestasis or structural liver disease. Plasma Gal3 levels were measured by standard ELISA. Inflammatory cytokines were measured in a subset of samples using MSD Proinflammatory Panel 1 multiplex ELISA. Liver fibrosis was categorized as none (Ishak or METAVIR 0), mild (Ishak 1-2 or METAVIR 1), moderate (Ishak 3-4 or METAVIR 2-3), and severe (Ishak 5-6 or METAVIR 4) based on histology. Data are presented as median (IQR) and compared using Kruskal-Wallis test. Spearmans correlation was used to assess the relationship between Gal3 and clinical and inflammatory markers. RESULTS/ANTICIPATED RESULTS: Samples from 10 controls, 26 early BA, 24 late BA, 13 early other CLD, and 8 late other CLD patients were used for this study. Gal3 levels in late BA (20.8 [12.4-30.5] ng/mL) and late other CLD (21.8 [16.9 – 27.2] ng/mL) were significantly higher than in controls (10.2 [7.6 – 14.5] ng/mL, p < 0.02) and early BA (11.3 [8.7 – 16.8] ng/mL, p < 0.01), but not significantly different from early other CLD (15.7 [11.9 – 21.4] ng/mL, p > 0.05). Gal3 positively correlated with fibrosis score (rho 0.3, p = 0.01), total bilirubin (rho 0.3, p = 0.002), ALT (rho 0.3, p = 0.01), AST (rho 0.3, p = 0.005), and APRI score (rho 0.3, p = 0.009), and negatively correlated with albumin (rho -0.3, p = 0.01). Out of the 10 cytokine proinflammatory panel, Gal3 was significantly correlated with IL-6 (rho 0.3, p = 0.006). DISCUSSION/SIGNIFICANCE: Gal3 is elevated in late BA and other CLD at time of transplant and correlated with degree of fibrosis, suggesting it may play a role in disease progression to cirrhosis. If targeted in the early disease stage, blocking Gal3 in pediatric cholestatic liver diseases may help delay the progression to cirrhosis and need for transplant.

OBJECTIVES/GOALS: High cholesterol is among the major causes of cardiometabolic complications. People with high cholesterol have about twice the risk of heart disease as people with lower levels. Approximately every 40 seconds, an American will have a heart attack. Costs related to Heart Attack exceed 60 Billion USA dollars per year. Renin-Angiotensin-Aldosteron System (RAAS) is implicated in the genesis of coronary heart disease and in the perpetuation of heart failure. Angiotensin-Converting Enzyme inhibitors (ACE-I) have emerged as the treatment of choice for patients with all degrees of heart failure. Many clinical trials (Consensus, 1987; Save 1990) provide the evidence that ACE-I preserves cardiac function, prevents cardiovascular death, myocardial infarction & stroke and limit remodeling after myocardial infarction. However, there are still controversies in cardiology and a debate over cardioprotection is continuing:

• Do ACE Inhibitors have unique properties, beyond their antihypertensive effect?

• Can we protect the heart during hypercholesterolemia?

• In which way hypercholesterolemia affects mitochondria bioenergetics?

• How does ramipril affect mitochondrial bioenergetics during the course of experimental hypercholesterolemia?

Objectives/Goals were: To evaluate the mitochondrial actions of chronically administered ramipril (non-SH-containing ACE inhibitor) in cholesterol-fed rabbits by determining the influence of ramipril on:

• myocardial oxygen consumption (State 4, State 3), Respiratory Control Ratio (RCR), and adenosine diphosphate - oxygen index (ADP/O) and

• oxidative stress biomarkers

METHODS/STUDY POPULATION: Animal treatments. In the course of twelve-week the male Chinchilla rabbits (n = 10/group) received once a day a single dose, in group: A - sunflower oil (control animals); B – atherogenic 2% hypercholesterolemic diet; C - atherogenic diet and ramipril (1 mg/kg) and D - ramipril (1 mg/kg) only. Animals were terminated in accordance with the U.K. “Animals (Scientific Procedures) Act.” Isolation of mitochondria - Mitochondria from rabbit heart were isolated by tissue digestion (trypsin), fractionation and differential centrifugation. Mitochondrial respiratory functional measures (State 4 - Basal; State 3 - ADP-stimulated respiration, RCR and ADP/O) and biochemical markers of oxidative damage (the nitrite level) were measured polarographically (Clark electrode, YSI, USA) and spectrophotometrically, respectively, in isolated heart mitochondrial suspensions. Statistics - All results are reported as means ± SD. Comparisons between ramipril treated and control animals were performed by unpaired t-test or one-way ANOVA with a Tukey adjustment for multiple comparisons. A P value < 0.05 was considered significant for all tests. RESULTS/ANTICIPATED RESULTS: Plasma cholesterol levels: After a period of 12 weeks

• Plasma cholesterol levels in control rabbits (A) were low (1.36 ± 0.23 mmol/l).

• Cholesterol-fed rabbits became hypercholesterolemic and their plasma total cholesterol level was higher even than 10 mmol/l. The level of total cholesterol in the high-cholesterol-diet group was significantly increased compared with the level in the normal-diet group (p < 0.01).

• In the high-cholesterol-diet group treated with ramipril (C), the plasma cholesterol level was not affected by the drug ramipril (10.54 ± 1.31 mmol/l). ACE-I ramipril did not infuence the concentration of total cholesterol.

• Plasma cholesterol levels in group D were low (1.46 ± 0.29 mmol/l).

• Atherogenic 2% cholesterol diet (B) caused a decline in mitochondrial function (in both, State 3 and 4) (−25%).

• Mitochondria from group C animals (treatment with ramipril along with 2% cholesterol diet) exhibited higher State 3 respiratory rates compared with group B.

• Mild inhibition of mitochondrial respiration was recorded in group D, in both respiratory states (V4&V3).

• In cholestrerol-supplemented hearts myocardial oxygen consumption was markedly reduced (State 4 and State 3) compared to controls. Administration of high-cholesterol diet decreased not only the respiratory activity of rabbit heart mitochondria (RHM), but also the sensitivity of respiratory chain to ADP (ADP/O), while concomitantly caused an increase in nitrite production. Possible explanation: high-fat diet affects the fluidity of mitochondrial membrane – Electron transport chain (ETC) may be damaged, and unable to support high rates of respiration (e.g. substantial cytochrome c could be lost).

• Administration of ACE-I ramipril along with cholesterol diet partially abolish reduction in MQO2 and improved coupling efficiency (ADP/O). Possible explanation: reduced coupling efficiency means the coupling mechanism itself is altered (e.g. the respiratory complexes slip and pump fewer protons than normal and less ATP is produced per oxygen consumed. Ramipril partially improved coupling efficiency and increased the amount of ATP per oxygen consumed.

• RCR - No significant difference between the groups were found. High RCR indicates good function (a high capacity for substrate oxidation and ATP turnover). Low RCR usually indicates dysfunction. However, there is no absolute RCR value that is diagnostic of dysfunctional mitochondria, because values are substrate- and tissue-dependent.

• NO• exerts metabolic control over mitochondrial respiration. Group B: The lowered state 3-respiration in heart mitochondria seems to contribute to the increased NO production, and elevated nitrite level.

• In a system as complex as OXPHOS, conclusions about overall efficiency must involve measurements of: mito membrane potential, proton transport, ATP synthesis and modular kinetic analisys.

OBJECTIVES/SPECIFIC AIMS: The purpose of this study is to evaluate the extent of publication bias in anesthesia and to evaluate the characteristics of studies that are registered and unpublished. METHODS/STUDY POPULATION: We used the advanced search option and the key word “anesthesia” to identify anesthesia related studies in the ClinicalTrials.gov registry. For the purpose of this analysis we have randomly selected 50% of the anesthesia related studies from the year 2008–2013. We have collected information pertaining to drug/device study, origin, type, design, subspecialty, enrollment target, anesthesia type, and adult/ pediatric, sponsored/ investigator initiated, population studied and start and end date. Studies with an ongoing, terminated, or unknown status were excluded from the analysis. For results, we initially searched the results section associated with each study; also we searched for any publication link at the study result area of the registry. For studies with no results and publication links we searched on PubMed, Google Scholar, and Embase by trial registration number, study title, and investigators name for matching manuscripts. In addition, we also analyzed the proportion of studies with positive and negative conclusions. We used descriptive and univariate statistics to report the results. RESULTS/ANTICIPATED RESULTS: Overall, 5448 studies were identified within the queried timeframe. We have included 2649 studies in our final analysis and detailed analysis were performed for 1778 studies with the status “completed.” The mean, standard deviation of subjects enrolled in completed trials was 392.47±6378. Only 162 (9.9%) studies registered were in the pediatric population, and 1616 (90.9%) were in the adult population. Finally, of the reviewed studies, 1486 (83.6%) were investigator-initiated, 207 (11.6%) were sponsored, and 85 (4.8%) were registered as collaborated studies. Among the completed studies only 296 (16.6%) studies posted results to the result section of the registry. Additionally, a link associated with a publication was posted in only 393 (22.1%) of the studies. The proportion of studies with posted results were 208 (14%), 61 (29%) and 27 (31.8%) in investigator-initiated, sponsored, and collaborated studies p<0.001 respectively. In the 1778 studies we reviewed, 954 (53.7%) studies were associated with one publication. In the published studies, 721 (75.6%) studies reported a positive conclusion for their publication. DISCUSSION/SIGNIFICANCE OF IMPACT: Only, 53.7% of anesthesia related studies with a “complete” status in ClinicalTrials.gov were published. Furthermore, investigators fail to fulfill the requirement of making the results available in the results section of the registry. Lack of availability of published literature and the nonavailability of the results from these studies contributes to publication bias and also failure to honor the ethical responsibility of the investigator to share the results of the study with subjects and with the medical community around the world.

OBJECTIVES/GOALS: To test whether implementing DASH-aligned meals in a congregate meal program, combined with Self-Measured Blood Pressure (SMBP) monitoring, lowers systolic blood pressure in community-living seniors at two senior centers. Secondary Aims included cognitive and behavioral change, and attention to client preferences. METHODS/STUDY POPULATION: The Carter Burden Network (CBN) provides services and congregate meals to older adults in NYC, many with low income, and unmet health needs. Eligible participants at two CBN sites, aged 60 or older and consuming >4 congregate meals/week, were recruited. After baseline assessments, participants received DASH-aligned meals onsite, education on nutrition and BP management, and personal devices and support for self-measured blood pressure (SMBP) monitoring. Primary outcome data (BP measured by health professional) was collected at Month 1, with secondary assessments at Months 3 and 6. Staff downloaded SMBP data regularly. Study surveys tracked cognitive and behavioral changes. Qualitative feedback from a project Advisory Committee, participants and study partners was collected throughout implementation. RESULTS/ANTICIPATED RESULTS: 97 Participants enrolled (49% White, 32% Black, 19% Other races; mean age 73). At Baseline, 67% were overweight/obese; 80% were hypertensive (32% Stage I; 48% Stage 2). Primary outcome: Mean change in systolic BP at Month 1 compared to Baseline, was -4.41 mmHg (n= 61; p=0.07). By multiple regression analysis, change in BP at Month 1 was associated with BMI, age, and baseline blood pressure (p= .02, .04, .00, respectively). SMBP: Mean change in systolic SMBP by End-of-Study was -6.9 mmHg (p=.003). 56% participants completed SMBP through Month 1 and 30% to End-of-Study. Mean frequency of > 1 SMBP measure/day was 3 days/week. Women (n= 22, 88%) and Black participants (n= 15, 60%) were more likely to continue taking their home blood pressure measurements to End-of-Study (p=.002, p=.037, respectively). DISCUSSION/SIGNIFICANCE: This study provides the first data to support the potential of DASH as part of an effective community-implemented program for seniors and demonstrates the feasibility of implementing a multi-component intervention using existing congregate meal programs at senior centers that can reach minority and low-income communities.

ABSTRACT IMPACT: Obesity is a quickly growing pandemic that negatively impacts health, and clinicians and clinics must employ all evidence-based tools (such as self-monitoring) to help patients control their weight. OBJECTIVES/GOALS: The objective of this study was to understand patient and parent perspectives on using daily self-weighing for adolescents with obesity who are seeking obesity treatment. The secondary objective was to understand perspectives on connecting smart-scales to the electronic medical record for messaging, feedback, and reminders between visits. METHODS/STUDY POPULATION: Thirty adolescents with obesity who were seeking obesity treatment at a tertiary pediatric weight management clinic were recruited into a single-arm feasibility study to create and assess a connection between blue-tooth scales and the electronic medical record. These adolescents and their parents were then approached about conducting exit interviews about their experience in the feasibility study -- their perspectives on connecting bluetooth scales connected to the electronic health record and using daily self-weighing at home to help them reach their healthy weight goals. The interviews were conducted by a trained interviewer who was not a PI or Co-I on the feasibility study, recorded, and transcribed. The interviews were organized on themes including technical challenges, mood, stress, clinic feedback. RESULTS/ANTICIPATED RESULTS: The main theme expressed by participants and parents was related to past experiences of their weight loss journey. Sub-themes included: technical challenges with apps, parental involvement in weighing, being told by clinicians to weigh, and intervention impact. Most parents desired more directions and help with setting up the app connection to the EHR. Most parents did not ask their child daily about their weight status as they did not want to cause stress. Some adolescents found it stressful when parents asked about daily weight status; others found it helpful or at least not stressful. Most participants had never been advised by their clinician to regularly self-weigh. Most found it helpful to monitor their weight regularly. Most asked for reminders from clinic to weight and for feedback on weight between visits. DISCUSSION/SIGNIFICANCE OF FINDINGS: Overall, adolescents with obesity reported self-weighing as being helpful and most wanted some, but not daily, involvement from parents. Most parents wanted additional technological support to create the scale set-up. Nearly all parents and adolescents wanted the weights to be connected to clinic, and for there to be feedback from clinic on weight.

OBJECTIVES/SPECIFIC AIMS: The objective of this study is to assess the efficacy of combined AF and NP repairs to prevent degenerative changes and restore native disc morphology in an in vivo large animal model. We hypothesize that combined repairs will prevent disc degeneration following injury to a greater extent than the individual repairs after 6 weeks in vivo, as demonstrated through disc height measurements and disc morphology. METHODS/STUDY POPULATION: A total of 8 skeletally mature female Finn sheep were used in this study. Following a previously described method, IVDs from L1 to L6 of the lumbar spine were exposed using a lateral access, extraperitoneal approach5. IVDs were randomized into 5 treatment groups: 1) intact discs, 2) discs injured via a 3 cm x 1 cm box annulotomy and partial nucleotomy, 3) injury followed by a high density collagen (HDC) AF patch, 4) injury followed by injection of a modified hyaluronic acid (HA) into the NP, and 5) injury followed by both the HDC AF patch and HA NP injection. The HDC treatment was 15 mg/mL type-I collagen mixed with 0.06mM riboflavin, injected at the defect site and crosslinked in situ with blue light. The NP injection was HA modified with C16 side chains to increase the viscosity of the hydrogel (HYADD 4®)6. At 6 weeks post-operatively, sheep were sacrificed and had 3T magnetic resonance images (MRI) taken of their lumbar spine. Disc height analysis and Pfirrmann grading were performed on each segment using MR images. Additionally, quantitative MRI analyses were performed using a custom MATLAB algorithm that segments NP from the surrounding tissue and directly measures the NP volume. ANOVA with Tukey’s HSD was used to determine statistical significance between groups for disc height and quantitative MRI analyses, and the Kruskal-Wallis test with Mann-Whitney tests was used to statistically analyze Pfirrmann Grades. All animal use followed approved IACUC protocol. RESULTS/ANTICIPATED RESULTS: As shown in axial MR images (Figure 1A), intact discs had hyperintense NP with a distinct border to the AF. The discs receiving injury with no treatment had hypointense NP with no distinct border between the AF and NP. Individual and combined treatment with the HA NP injection and HDC AF patch appeared to preserve the hyperintense NP signal and AF/NP border. Intact control discs were not degenerated and had an average Pfirrmann grade of 1 (Figure 1B), while injured, untreated discs had significant degeneration with an average Pfirrmann grade of 3. Discs receiving the HA NP injection and collagen AF patch individually showed fewer signs of degeneration than the injured alone, and the combined treatment resulted in the least amount of degeneration with Pfirrmann grades not significantly different than the intact controls. Disc height index confirmed the trends seen in the Pfirrmann grades (Figure 1C), where injured discs lost 20% of the intact disc height, the individual NP and AF repairs restored 5-10% of intact disc height, and the combined repairs preserved 90% of the intact disc height. The NP voxel count of all treatment groups were similar to the intact controls (Figure 1D). DISCUSSION/SIGNIFICANCE OF IMPACT: The objective of this study was to determine how combined AF and NP can prevent degenerative changes to the disc in a large animal in vivo model. Pfirrmann grading and disc height index results show that the greatest preservation of disc morphology was seen with combined AF and NP repairs, while the individual strategies prevented degenerative changes better than injury with no treatment. It appears the HA NP injection restores lost water content to the disc following injury, and the AF collagen patch plays a role in maintaining the NP repair within the disc. This is the first study to our knowledge to attempt combined AF and NP repairs in an in vivo large animal model. Combining NP and AF repairs leads to significantly improved outcomes following disc injury, which warrants the translation of combined repairs into the clinic to improve patient outcomes with degenerative disc disease involving NP and AF.

OBJECTIVES/SPECIFIC AIMS: Our overall goals are: 1. To engage, inform and educate children and families on clinical research and increase their understanding of the goals and process of participation in research studies/clinical trials; 2. To Increase participation of children, especially those who are disproportionately underrepresented, in clinical research in the Western New York region and beyond. METHODS/STUDY POPULATION: The University at Buffalo Clinical Translational Science Institute conducted meetings in schools, community coalitions while holding focus groups with children with chronic conditions and their families and community health workers to identify the general perceptions of research. These conversations then informed the development of a children’s activity book about research. Completed in 2017, our “Sofia Learns about Research” activity book presents research in a non-threatening way by presenting a child with asthma who walks through the process of learning about research, being recruited and participating in research. The book explains basic concepts about research coupled with fun games and the possibility to color. Over 1,000 copies of the activity book have been disseminated to second to fourth graders via afterschool programs, community events, and medical practice waiting rooms. Recipients of the book are directed to short surveys to provide feedback on the book and their perception of research. The parents are also given the option to sign-up for the Buffalo Research Registry in order to be contacted about research opportunities. RESULTS/ANTICIPATED RESULTS: Response has been very positive, with parents and community participants saying “It’s not just a storybook. The activities keep kids entertained while learning new concepts.” In children informally polled via a brief questionnaire pre and post story reading at an afterschool program, there was an increase in those interested in participating in a research study. In a recent event sponsored by the CTSI Community Engagement Core and other UB organizations, a group of fifty children from diverse background colored with enthusiasm several activity pages and obtained stickers for their “Research Passport”. In a recent teacher focus group we learned that the book content may fit the Science Curriculum and plan on reading sessions in inner-city schools after approval from the district. A pilot reading activity in a Montessori program revealed that second grade children were able to understand and complete the activities in the book. We are obtaining further feedback form teachers and parents in order to design simple protocol to be submitted for IRB approval to obtain more formal feed-back and outcomes in future readings. In parents and focus groups several respondents have indicated its relevance to older populations and English-language learners as well. The book has recently been translated into Spanish and Arabic through a partnership with the International Institute of Buffalo, which “welcomes, connects and empowers the foreign born”. Some of the book’s images have been modified in order to be sensitive to the readers’ culture and we are in the process of collaborating with the International Institute to disseminate it to their clients. We are in the initial phase of planning a mobile application which we anticipate will significantly enhance dissemination. DISCUSSION/SIGNIFICANCE OF IMPACT: This presentation will describe the development process, the underpinning concepts and our plans and current progress towards a more formal community and school dissemination and evaluation. This project was made possible by Team Science in that the expertise of a millennial pre-medical student and an anthropologist with high community involvement was coupled with that of a senior clinical translational researcher. Moreover, much research and attention was devoted to the creation of images that are culturally inclusive. To this end, with the exception of the cover page, we have intentionally created the book in black and white so that the child may use his/her imagination and color the way he/she sees the protagonists and the environment. Great attention was devoted to names of the protagonists with the names of the two main characters being among the most common in the world in numerous countries. Also, the book lends itself to a mobile application which will allow the reader to change colors and shapes of the protagonists to fit his/her cultural background. We are in the early planning stages and will share our progress as part of this presentation. We have strived to disseminate the book with a broad approach in our community. This phase is being followed by a more formal dissemination phase via libraries, schools and community events. This part of the project exemplifies the challenge between wanting to disseminate the book broadly while obtaining formal feedback and outcomes in compliance with regulations protecting the anonymity and/or confidentiality of children and families. Therefore for this second phase of dissemination IRB approval is being sought in order to collect more quantitative and qualitative data on the impact of the book. We have already conducted a focus group with teachers to overcome the challenges around informed consent, especially in the public school system. Our initial findings suggest this resource will improve knowledge and perception of research among children and their families. To our knowledge most of the materials explaining research to children are geared to older children and are often sponsored by pharmaceutical companies for a specific trial. If successful, this book can have a profound impact in reaching out to children outside of the research and medical environments, with the ultimate goal of increasing the child’s and family’s willingness to participate in clinical research and clinical trials.

OBJECTIVES/SPECIFIC AIMS: Alcohol use disorder (AUD) has been associated with greater discounting of delayed rewards relative to healthy controls. The relationship, however, has been inconsistent, likely because previous studies had relatively small sample sizes and inadequately controlled for comorbid psychopathology and substance use. In the present study, we analyzed one of the largest clinical research samples to date to assess the influence of alcohol use on delay discounting, and examine the influence of confounding variables including substance use disorder. METHODS/STUDY POPULATION: In total, 801 participants completed a delay discounting task where they chose between smaller, immediately available monetary amounts ($0–$90) and $100 available after a delay of 7–30 days. Delay discounting behavior was summarized as the natural log of k, a constant derived from a hyperbolic discounting equation. Participants also completed Structured Clinical Interviews for DSM-IV disorders, 90-day Timeline Followback interviews, and the Fagerström Test for Nicotine Dependence. Participants were divided into 4 groups: healthy controls (n=298), past AUD (n=69), and current AUD with (n=224) and without (n=210) comorbid psychopathology or substance use disorder. Kruskal-Wallis test was used to examine the effect of group on delay discounting. RESULTS/ANTICIPATED RESULTS: There were significant differences in the distribution of delay discounting scores by group (H=80.195, p<0.001). Healthy controls and past AUD showed lower levels of delay discounting than current AUD and current AUD+comorbidity groups with medium effect sizes (Cohen’s d=−0.635 and Cohen’s d=−0.614, respectively). There were nearly no differences between current AUD with and without comorbid psychopathology groups (Cohen’s d=−0.024). The past AUD group showed almost no difference relative to the healthy control group (Cohen’s d=0.007). DISCUSSION/SIGNIFICANCE OF IMPACT: Individuals with current AUD were shown to discount rewards greater than those without current AUD, although comorbid psychopathology did not significantly affect discounting. Surprisingly, individuals with past AUD were more similar to controls than to those with current AUD. Our findings suggest that current problematic alcohol use is related to greater discounting of delayed rewards, but comorbid diagnoses do not significantly impact this relationship. However, once problematic patterns of alcohol use cease, delay discounting appears to return to levels comparable to healthy controls.

OBJECTIVES/GOALS: There is no objective, biologic tool to detect concussion or guide clinical management. We previously showed that saliva microRNA (miRNA) levels differ in children with concussion and may predict symptom duration. The purpose of this study was to validate the utility of saliva miRNA and define longitudinal trends during the recovery period. METHODS/STUDY POPULATION: We collected concussion symptom burden (SCAT-5), cognitive performance (DANA), balance measures (ClearEdge), and saliva from 150 children (7-21 years) with concussion over 5 time-points: 0-2, 3-6, 7-14, 15-29, and 30-60 days post-injury. Saliva miRNA levels within the 443 concussion samples were quantified with RNA sequencing and compared to 218 samples from age- and sex-matched controls (healthy and post-exercise participants). Non-parametric ANOVA assessed RNA levels across time-points, and between concussions/controls. Machine learning was used to build logistic regression algorithms differentiating concussions/controls, and symptomatic/recovered concussion participants. Relationships between miRNAs and concussion phenotypes were explored with Spearman’s Rank correlations. RESULTS/ANTICIPATED RESULTS: Fifteen miRNAs differed across control and concussion participants (FDR < 0.05). Within concussion participants, all 15 miRNAs trended back toward control levels by 30-60 days post injury. A regression algorithm employing 6 of the 15 miRNAs differentiated control and concussion participants with an area under the curve (AUC) of 0.78 in a training set (n = 244) and 0.84 in a naïve test set (n = 24). Similarly, 6 miRNAs were able to differentiate symptomatic (SCAT-5 symptom score > 7) and asymptomatic concussion participants with an AUC of 0.73 in a training set (n = 219) and 0.76 in a naïve test set (n = 44). Furthermore, 5 miRNAs showed significant (R > 0.3; FDR < 0.05) associations with subjective and/or objective measures of concussion-related symptoms. DISCUSSION/SIGNIFICANCE OF IMPACT: Saliva miRNAs levels are altered in children with concussion, and display predictable longitudinal trends following injury. Saliva miRNA measurement represents a non-invasive, objective tool that could be rapidly assessed to provide biologic evidence for clinicians managing pediatric concussion. CONFLICT OF INTEREST DESCRIPTION: I serve as a paid consultant and scientific advisory board member for Quadrant Biosciences, who has funded a portion of this work and licensed the findings from the Penn State College of Medicine.

OBJECTIVES/GOALS: Our purpose is to promote traffic toward the NJ ACTS Regulatory Cores recently launched website and increase investigator engagement through marketing strategies on LinkedIn. Landscaping to characterize the profiles of researchers on LinkedIn was also completed to estimate the feasibility of engaging with a target population on LinkedIn. METHODS/STUDY POPULATION: Insight gathering was performed to analyze what percentage of researchers possessed a LinkedIn profile and actively used their accounts. A sample population consisting of 284 NJ ACTS members were analyzed to summarize the type of researchers on LinkedIn, and their likelihood of responding to LinkedIn marketing campaigns. Efforts to launch a company LinkedIn page and collect followers were completed. Different methods of promotion were evaluated, including direct vs. mass email outreach to over 600+ researchers at Rutgers. Effectiveness of our platform was measured by comparing/overlaying Regulatory website traffic with LinkedIn traffic, as well as tracking the metrics of LinkedIn posts. RESULTS/ANTICIPATED RESULTS: Among 284 NJ ACTS members, 76% (n=215) possess a LinkedIn profile, but only 21% (n=59) are actively interacting with material on LinkedIn, such as creating, commenting, or sharing posts. Among the NJ ACTS LinkedIn users, 27% of individuals (n=57/215) responded to a direct outreach. Retention of the created organizational page was strong, as most users who visited the Regulatory Core page were likely to become followers. Massive email outreach to 600+ researchers within RBHS did not yield a strong LinkedIn following, however it did result in strong signals of website traffic during the days after the promotion was sent. Engagement with posts on LinkedIn can also be amplified and messaging proliferated when colleagues reshare Regulatory posts on their personal feeds. DISCUSSION/SIGNIFICANCE: 3/4 of academic researchers are likely to be on LinkedIn but may not be active users of the platform. The most effective outreach is through direct messaging as opposed to broader, less individualized tactics (including mass email outreach). Evidence suggests potential to utilize LinkedIn to proactively engage in regulatory-related activities.

OBJECTIVES/SPECIFIC AIMS: Community stakeholder engagement along the translational spectrum of biomedical research has been identified as a potentially crucial factor for encouraging participation among underrepresented groups, improving research relevance, and adoption of evidence into practice. Although we have developed various methods to improve communication between researchers and community stakeholders, we have not focused much attention on the manner by which community stakeholders choose to communicate with researchers in scientific feedback settings. In our PCORI funded study using Community Engagement Studios to elicit feedback on research from community stakeholders, we found that feedback from participants was frequently provided in the form of stories. This presentation aims to describe these narratives, examine their function in the feedback process and consider how a focus on these narratives enhances our understanding of community engagement for clinical and translational research. METHODS/STUDY POPULATION: The present study comes from a larger randomized, controlled methodological study. We randomized 20 investigators seeking input on their research to either a Community Engagement Studio (a panel of community members or patients) or a Translational Studio (a panel of researchers). Any faculty member or research trainee at Vanderbilt University or Meharry Medical College was eligible to participate. Each Studio panel was convened to provide project-specific input. The 153 stakeholders who participated in CE Studios were patients, caregivers, or patient advocates identified by health status, health condition, or demographic variables based on the project-based needs of the 20 researchers randomized in this project. Stakeholders include individuals with diabetes, heart failure, Parkinson’s disease, sickle cell disease, and ICU survivors. All stakeholders had experience as a partner or consultant on a research project or through serving on a research advisory board or committee. All Studios were recorded and transcribed, and experienced qualitative researchers analyzed the data. For this paper, we focus on the narrative feedback in the form of stories elicited in the CE Studios. Using qualitative methods, we coded the transcripts from the 20 CE Studios to identify stories and their functions in the feedback. Stories were defined as narratives with (a) at least one actor (b) action that unfolds over time, and (c) a realization, destination, or conflict resolution (i.e., a point of the story). For example, “I refilled my mother’s pillbox on Sunday and on Friday I found the pillbox still completely full” would be a story, however, “my mother doesn’t take her meds correctly” would not. We coded the stories for how they facilitated communication in the Studio using an open-coding style, that is we did not apply a specific theoretical framework of interaction or communication. It was possible for any given story to have more than one code applied to it; that is they were not classified in a mutually exclusive way. RESULTS/ANTICIPATED RESULTS: We found 5 major functions of stories in the Studios. Basic sender-receiver functions were noted, including responding to queries and seeking mutual understanding. The other functions served to move or add to the conversation, including adding expansion and depth, characterizing abstract concepts, and providing context, with the latter being the most frequent function of stories. Speakers provided context in a wide variety of dimensions, ranging from the context of the body to spatial and institutional contexts. These stories served to help others understand the speakers’ lived experiences. DISCUSSION/SIGNIFICANCE OF IMPACT: We often engage community members in research for their expertise with regards to their lived experiences as patients or community members, and for their experiences of healthcare and social determinants of health in particular community contexts. Yet we may expect them to share their expertise in a manner that is consistent with a scientific, explanatory framing and language. However, we know there is a difference in the way that professional researchers discuss research Versus how community members discuss research. In our PCORI study, we found that our Community Studio participants relied on storytelling as an important means to communicate their lived experiences. Their stories were often key to communicating the complex contexts of their experiences. We focus on examining these narrative practices and their functions in how community members engaged with and provided advice to researchers. This understanding may help us in: (1) Characterizing the contexts, processes, and meanings associated with community stakeholder experiences that are otherwise difficult to access. (2) Identifying community priorities relevant to research that are embedded in community narratives to better align research priorities with community needs and to improve patient outcomes. (3) Collecting insights for improving the design of community engagement activities in research. (4) Harnessing more fully the potential of community engagement in research.

OBJECTIVES/SPECIFIC AIMS: In an effort to elucidate the role of potentially cancer chemopreventive drugs, we leveraged the Mayo Clinic-Karolinska Institute collaboration to create a multidisciplinary team that included an epidemiologist, statisticians, and physicians. We performed a population-based cohort study to examine the association between low dose aspirin, non-aspirin NSAIDs, statins, metformin, other risk factors and the risk of biliary tract cancer (BTC), while assessing confounding by sex. METHODS/STUDY POPULATION: We conducted a nationwide Swedish population-based cohort study using the Swedish Prescribed Drug Registry, which virtually completely enumerates use of prescribed medications nationwide since 2005. BTC diagnosis (intrahepatic cholangiocarcinoma [iCCA], extrahepatic cholangiocarcinoma [eCCA] or gallbladder cancer [GBC]) was ascertained from the Swedish Cancer Registry. Age-scaled Cox models, with exposure as time-varying covariates, were used to calculate hazard ratios (HRs), separately for men and women. RESULTS/ANTICIPATED RESULTS: In the 5.7 million person cohort, the risk of iCCA was significantly lower in men using statins (HR 0.62,95%CI 0.39-1.00, p = 0.05), with a non-significant reduction in women. Statin use was associated with a significantly decreased risk of eCCA in both women (HR 0.60,0.38-0.94, p = 0.03) and men (HR 0.47,0.28-0.80, p = 0.01). Low dose aspirin (HR 0.76,0.60-0.97, p = 0.03) was associated with a lower risk of GBC only in women, while statins (HR 0.72,0.55-0.93, p = 0.01) showed a significantly decreased risk of GBC in women and a non-significant reduction in men. For all BTC subtypes, combined use of low dose aspirin and statins did not confer additional risk reductions beyond those achieved by statins alone. Male and female users of non-aspirin NSAIDs appeared to be at increased risk of BTC and its subtypes. Metformin did not significantly affect risk of BTC. DISCUSSION/SIGNIFICANCE OF IMPACT: Our collaborative efforts allowed us to develop the largest population-based cohort evaluating risk and protective factors for BTC. Our results provide strong evidence in favor of the chemopreventive roles of low dose aspirin and statins in a subtype- and sex-specific manner. Individual risk factors contribute to development of BTC subtypes in different magnitudes. The next steps to translate these findings into clinical practice require randomized clinical trials that validate our results and provide a more complete picture of the risk-benefit ratio.