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

OBJECTIVES/GOALS: For patients suffering from respiratory failure there are limited options to support gas exchange aside from mechanical ventilation. Our goal is to design, investigate, and refine a novel device for extrapulmonary gas exchange via peritoneal perfusion with perfluorocarbons (PFC) in an animal model. METHODS/STUDY POPULATION: Hypoxic respiratory failure will be modeled using 50 kg swine mechanically ventilated with subatmospheric (10-12%) oxygen. Through a midline laparotomy, two cannulas, one for inflow and one for outflow, will be placed into the peritoneal space. After abdominal closure, the cannulas will be connected to a device capable of draining, oxygenating, regulating temperature, filtering, and pumping perfluorodecalin at a rate of 3-4 liters per minute. During induced hypoxia, the physiologic response to PFC circulation through the peritoneal space will be monitored with invasive (e.g. arterial and venous blood gases) and non-invasive measurements (e.g. pulse oximetry). RESULTS/ANTICIPATED RESULTS: We anticipate that the initiation of oxygenated perfluorocarbons perfusion through the peritoneal space during induced hypoxia will create an increase in hemoglobin oxygen saturation and partial pressure of oxygen in arterial blood. As we expect gas exchange to be occurring in the microvascular beds of the peritoneal membrane, we expect to observe an increase in the venous blood oxygen content sampled from the inferior vena cava. Using other invasive hemodynamic measures (e.g. cardiac output) and blood samples taken from multiple venous sites, a quantifiable rate of oxygen delivery will be calculable. DISCUSSION/SIGNIFICANCE: Peritoneal perfluorocarbon perfusion, if able to deliver significant amounts of oxygen, would provide a potentially lifesaving therapy for patients in respiratory failure who are unable to be supported with mechanical ventilation alone, and are not candidates for extracorporeal membrane oxygenation.

OBJECTIVES/SPECIFIC AIMS: This study aims to evaluate potentially traumatic events (PTEs) and its relationship with posttraumatic stress symptoms (PTSS), posttraumatic growth (PTG), and resilience in a sample of help-seeking individuals in Puerto Rico. METHODS/STUDY POPULATION: This is an analytic, cross sectional design. Adults receiving health services will participate in the study. Recruited participants will provide informed consent during a visit to a community mental health clinic or community hospital. They will complete a demographic document and four retrospective questionnaires about the variables of study. RESULTS/ANTICIPATED RESULTS: We expect that a high rate of potentially traumatic events (PTEs) is associated with an increased rate of posttraumatic stress symptoms (PTSS). We also expect that a high rate of PTSS is associated with an increased rate of posttraumatic growth (PTG). We expect that a high rate of resilience is associated with low rates of PTSS and PTG. DISCUSSION/SIGNIFICANCE OF IMPACT: This is a first step in the development of effective, clearly targeted interventions, specifically designed to treat negative effects, and also to facilitate positive change and resilience after PTE exposure.

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

Advancing the new field of translational science and developing innovative solutions to overcome translational roadblocks are key priorities of the Clinical and Translational Science Awards (CTSA) Program of the National Center for Advancing Translational Science (NCATS). However, interpreting this emerging concept of “translational science” (TS) as a field of inquiry distinct from “translational research” (TR) and developing real-world investigations in TS can be challenging. The goal of this paper is to share the obstacles the Einstein-Montefiore CTSA hub has faced in generating institutional interest and research in TS and to present potential strategies for addressing them. The aim is to stimulate dialog within the wider CTSA community and beyond about the need to systematically examine how TS should be efficiently and effectively pursued, that is, the science of translational science. The collective sharing of experiences and innovative approaches to overcoming TS challenges that arise at CTSA hubs is critical if the field is to grow and gain wider recognition and acceptance by the scientific and broader communities.

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/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.

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/SPECIFIC AIMS: This report describes the evolution of scientific culture since the NIH/translational science (TS) mandate. The transition of the conduct of science to an increasingly translational model involves 2 dimensions of change. The first dimension consists of change in the structure and process of scientific work, in terms of factors such as funding, administration, application of new knowledge, and so forth. The second dimension consists of change in culture of scientific work. The culture of science is the set of values, assumptions, meanings, and traditions that inform the conduct of science. As part of the comprehensive evaluation of TS at the University of Texas Medical Branch-Galveston, we have monitored the status of the culture of science there through a sociological framework. We focused on the ways the changing culture of science facilitates and/or inhibits creative and effective medical research. We argue that the long-term success of TS is dependent upon the evolution of assumptions, everyday practices, and taken-for-granted ways of conducting research. Culture also provides meanings for who its people are and helps us define who we are to ourselves (ie, self-concept). In terms of the scientific enterprise, self-identity provides the motivation to participate in group activities or to be content with being a “lone ranger” researcher; the orientation to be either a leader or a follower; the security to take creative chances with one’s work or to simply conduct “normal science”; and the sense of esteem for being the best or simply doing one’s job. TS requires a constant “reengineering” of its total enterprise. Consequently, we raised the following research questions: (1) What is the traditional culture of science at UTMB? (2) How has the culture of science at UTMB changed since the introduction of the Clinical and Translational Science Award project? (3) What has been the relationship between the culture of science and the conduct of science at UTMB since CTSA? (4) How have cultural influences on self-concept changed? METHODS/STUDY POPULATION: Data have been collected by means of ongoing 1-on-1 interviews with CTSA participants at all levels; observations of lab and classroom interaction; participation in organizational and planning committees; and other everyday organizational activities. RESULTS/ANTICIPATED RESULTS: Following the grounded theory method of qualitative analysis and discovery, we found 3 stages of cultural change. Stage 1 is Cultural Invasion of the existing culture at UTMB by the implementation of the CTSA project. Stage 2 is Cultural Accommodation by which internal responses to change follow the normal scientific paradigm. Stage 3 is Cultural Expansion by which the organizational and cultural platform for conducting science has expanded regionally, nationally and cross-disciplinarily. DISCUSSION/SIGNIFICANCE OF IMPACT: Whether a distinct fourth stage emerges depends on such factors as funding and programmatic directives from NIH; the tension between research and clinical demands for resources; and the emergence of junior investigators schooled on the principles of TS.

OBJECTIVES/GOALS: While mutant TP53 is an attractive therapeutic target in TNBC, attempts to target the mutant p53 protein directly have failed. Thus, we aim to identify pathways critical for the survival of TP53 mutant cells that can be targeted in TNBC. We have identified Kif11 as one such target and aim to further investigate its function in TP53 mutant TNBC. METHODS/STUDY POPULATION: We conducted a dual in silico/in vivo screen that identified Kif11 inhibition as preferentially inhibiting the growth of TP53 mutant TNBC. We obtained data on TP53 mutational status, KIF11 mRNA expression levels, and clinical characteristics from TCGA, METABRIC, and CCLE datasets. We treated breast cancer cell lines with the KIF11 inhibitor SB-743921. Cell counts were obtained through staining with DAPI or Hoechst and imaging on the ImageXPress PICO. We detected cell death by DRAQ7 staining and flow cytometry analysis following Annexin V-PI staining. To investigate mitotic spindle organization, we performed immunofluorescent staining with an anti-tubulin antibody and DAPI co-staining. Cell cycle analysis was performed through flow cytometry. RESULTS/ANTICIPATED RESULTS: KIF11 is highly expressed in TP53 mutant and TNBC clinical samples. High KIF11 expression is associated with poorer clinical outcomes. Kif11 inhibition suppresses growth of both TP53 mutant and wild-type breast cancer cells, but preferentially induces the death of TP53 mutant cells as detected by DRAQ7 and Annexin V/PI staining. Kif11 inhibition induces a G2-M block and growth inhibition in TP53 wild-type cells. On the other hand, following treatment with the Kif11 inhibitor SB-743921, TP53 mutant cells undergo mitotic spindle dysfunction leading to the formation of multinucleated cells and cell death. DISCUSSION/SIGNIFICANCE: These results demonstrate that Kif11 is a promising therapeutic target in aggressive, TP53 mutant TNBCs. Kif11 inhibitors, including SB-743921, have been tested in human trials, and are well tolerated, but it is unclear which patients would most benefit. Our studies show that Kif11 inhibitors may be most useful in patients with TP53 mutant TNBCs.

OBJECTIVES/SPECIFIC AIMS: Goal—broaden the academic offer to enhance clinical and translational research productivity and cost effectiveness. Objective—implement a distance learning program on conducting proficient research management. METHODS/STUDY POPULATION: Needs assessment attested students’ interest in enrolling and willingness to recruit graduates by the research industry and academia. A master of science in clinical research management and regulatory compliance (MS-CRMRC) was developed using the Core Competency Domains for Clinical Research Professional. Experts from research academia, pharmaceutical industry, composed a Proposal Development Committee. RESULTS/ANTICIPATED RESULTS: Access of a distance learning MS-CRMRC program for students with time constrains. Competent research professional graduates working side by side with the principal investigator on onsite teamwork management, to streamline research processes in compliance to regulations. DISCUSSION/SIGNIFICANCE OF IMPACT: Improvement of clinical and translational research productivity and efficient use of grants funds prevails as a generalized concern. The MS-CRMRC offers an accessible alternative to empower the research enterprise by developing knowledgeable skilled professionals to tackle this need.

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/SPECIFIC AIMS: Consequently, we have decided to evaluate the presence of single nucleotide polymorphism (SNP) previously associated with AF on a European-descent population in an attempt to first identify the most common loci present in the PRH population and then search for specific PRH SNP associated with AF. METHODS/STUDY POPULATION: A secondary analysis of a Puerto Rican population sample (n = 120) from The Pharmacogenetics of Warfarin in Puerto Ricans Study will be performed. We will implement data from the 1000 genome project to establish a control group of healthy PRH population. Will evaluate the presence of 111 known single nucleotide polymorphisms associated with AF in Europeans and determine the frequency in PRH population sample, and validate predictability of such SNPs. Using admixture informatic markers (AIM) analysis will determine the percentage of admixture by Yoruba, Native American and Iberic-European. Statistical analysis will include the use of the Pearson Product-Moment Coefficient correlation analysis and multivariate linear regression. For admixture will use Maximum Likelihood Estimation and Markov Chain Monte Carlo models. RESULTS/ANTICIPATED RESULTS: A higher frequency of AF associated European single nucleotide polymorphisms, and an overall higher percentage of European admixture will be associated with atrial fibrillation in Puerto Rican Hispanic patients. DISCUSSION/SIGNIFICANCE OF IMPACT: Our contributions here are expected to be the elucidation of European ancestry as a risk factor for AF. These contributions will be significant because it can provide a robust scientific basis for larger GWAS studies in the Puerto Rican community and further narrow down the mechanism specific to this population. Research in this subject could lead to early identification of patients with high risk of developing atrial fibrillation and further decrease incidence and disease burden in the PRH population. Puerto Rican Hispanics have an exclusive genetic admixture that makes for an appealing research subject that could deliver unique results.

OBJECTIVES/SPECIFIC AIMS: Clinical trials (CTs) play an important role in developing new treatments, expanding or refining treatments that are already available, and/or identifying behavioral changes that can prolong or improve the lives of subjects. CTs are also conducted to understand normal human physiology, pathophysiology, and factors associated with health outcomes. Results from CTs are then used to determine the safety and efficacy of medications or treatment. CT participants should reflect the diversity of those receiving the treatments because, exclusion of specific populations in CTs may potentially result in knowledge gaps for clinicians and regulators. Historically, women and geriatrics have been underrepresented as CT participants. For women, this is the result of Food and Drug Administration (FDA) action in 1977 which restricted women with childbearing potential from participating in phase I and early phase II CTs after thousands of birth defects resulted from thalidomide usage during pregnancy. While the U.S. Government Accountability Office’s 1992 and 2001 reports documented an increased female inclusion in later stages of CTs, earlier phases of CTs were still lacking. Likewise, older adults and geriatrics have been excluded in CTs arbitrarily or to avoid adverse events associated with drug-drug interactions and comorbidities. Over the past few decades, the FDA has worked to address this issue and increase diversity and transparency in CTs. In 2015, the FDA’s Action Plan for Food and Drug Administration Safety and Innovation Act (FDASIA) Section 907 called for improved CT inclusion and reporting of demographic subgroups (sex, age, race, and ethnicity), highlighting three priority areas: quality, participation, and transparency. This research examines the current state of female inclusion in phase I and II CTs (2016 to 2017) and geriatric inclusion in phase III CTs (2010 to 2017). METHODS/STUDY POPULATION: To assess female representation in phase I and II CTs, data from 2016 CTs was extracted from clinicaltrials.gov. The average percentage of male and female participation in trials recruiting for males and females was determined; CTs conducted in only males or females (due to sex specific disease states) were excluded. The data was further differentiated into investigator-initiated and industry-sponsored trials to determine any differences in sex representation. Data from 2017 CTs on clinicaltrials.gov will be extracted and analyzed as well as 2016 to 2017 data from FDA novel drug approvals. To assess geriatric representation in phase III CTs, geriatric subsections of drug labels from novel drug applications approved between 2010 to 2017 were assessed for geriatric-specific information based on four areas: 1) reporting of CT including geriatrics, 2) reporting of percentage of CT participants ages 75+, 3) providing geriatric dosage recommendations, 4) determining product safety and efficacy for geriatrics. RESULTS/ANTICIPATED RESULTS: It is mandatory that all US CTs are registered on clinicaltrials.gov with the exception of Phase I studies, and results posted within 1 year of CT completion. In 2016, 916 phase I and 713 phase II CTs were registered on clinicaltrials.gov. Of these registered CTs, 4% of phase I and 9% of phase II CTs posted results. Of these, phase I studies included more males than females. Of these, phase I studies showed higher percentage of males (58%) than females (42%). In phase I/II, phase II, and phase II/III CTs, females were represented at a higher levels than males by 8-20% (Table 1). Phase I industry-sponsored and investigator-initiated trials and phase II/III investigator-initiated trials included less females than males (Table 2); all other types of CTs had more female than male subjects (Table 2). Preliminary findings will be expanded to include 2017 CTs and a wider pool of clinical trials will include all those associated with FDA novel drugs approved in 2016 and 2017. Of the 250 labels of novel drugs approved from 2010 to 2017 assessed for geriatric inclusion, 74% reported a CT including geriatrics, and 55% reported including CT participants ages 75+. Further, 31% provided geriatric dosage recommendations and 62% indicated insufficient evidence to determine product safety/efficacy for geriatrics (Figure 1). There was no consistent increase following the 2015 implementation of FDASIA section 907 in any of the four areas examined (Figure 2). Labels providing geriatric dosage recommendations were consistently the least fulfilled area across all years analyzed (Figure 3). DISCUSSION/SIGNIFICANCE OF IMPACT: A lack of inclusion of specific populations in CTs can lead to serious complications. For example, in 2013, the FDA required a lower recommended dose for women for drugs containing the sedative-hypnotic zolpidem (i.e. Ambien) due to persisting next morning drowsiness; the FDA arbitrarily recommended the dosage be halved from 10 mg to 5 mg as it found that women appeared to eliminate zolpidem from their bodies more slowly than men. Additionally, $35.7 million is spent annually on hospitalization from adverse drug reactions in the elderly. And, although government acts and initiatives have called for greater inclusion of certain populations like females and geriatrics in CTs, there is no penalty for exclusion. Problems like these may be avoided if these specific populations are included in CTs so that drugs can be properly studied. It may be preliminary to make conclusions about female representation in phase I clinical trials because it is not mandatory to register all phase I trials on clinicaltrials.gov, but further investigation will be conducted into FDA summary reports. Preliminary findings indicate that efforts to include female subjects may be effective in the subset of studies that reported their results. As of 2017, 51.3% of the U.S. population over 18 years old is female (U.S. Census Bureau). Early clinical trials often help to establish safety and dosing for phase III trials. Thus, it is pertinent that the inclusion rate is reflective of the general population at all clinical trial stages, not just pivotal, phase III trials. It would be prudent to monitor this trend as more studies report their results. Given that the average US life expectancy is now 78 years and that elderly population is expected to double in coming decades (NIH, 2016), there is an urgent need to include this population in current and future clinical research. Geriatrics, particularly those age 75+, use more than a third of total prescription and over-the-counter medications sold in US (Merck Institute, 2014), but is severely underrepresented in CTs. The effects of polypharmacy and changes in drug metabolism with age increase the need for specific drug dosage recommendations for geriatrics. As there was no discernable difference in drug labels fulfilling areas examined before and after 2015, FDASIA implementation may not have impacted geriatric inclusion in CT for drugs approved between 2010 to 2017. As many of these CTs began prior to FDASIA 2012 signing and 2015 implementation, the legislation’s full impact may occur in future years. Nonetheless, inadequate language currently found in geriatric drug labels can create challenges for clinicians when prescribing these medications for geriatric patients, potentially contributing to adverse drug events.

OBJECTIVES/GOALS: To determine the utility of any standard, one must first evaluate whether or not the standard meets the needs of the use case it is meant to support. We aim to quantify data availability of the HL7 FHIR standard to support data collection for three state-based registries in a rural state and measure the potential effects on data quality and collection time. METHODS/STUDY POPULATION: FHIR mapping will be performed to assess the level of HL7 FHIR standard completeness (or data element coverage) in supporting data collection for the three registries. A systematic approach, previously developed and used by Garza and Zozus, will be used to map registry data elements to corresponding HL7 FHIR standard resources. FHIR coverage will be calculated as a percentage (total data elements “Available in FHIR” vs. total data elements overall) and will be observed across different domain areas (i.e., demographics vs. medications vs. vital signs, etc.) in order to identify the domains with the least and most coverage. RESULTS/ANTICIPATED RESULTS: Although there have been informatics solutions that relied on data exchange standards to improve data collection, none have actually evaluated the coverage of the standard for supporting the needs of clinical data registries. To address this gap, we aim to evaluate the availability of the HL7 FHIR standard to support data collection for three state-based registries. These results will provide insight into the generalizability of a FHIR-based solution to support data acquisition and processing across multiple registries and demonstrate the potential for seamless exchange of that data for secondary use in clinical and translational research. Quantifying the coverage will also be used to further advance its development in order to meet the data collection needs of state and national clinical data registries. DISCUSSION/SIGNIFICANCE: Registries often rely on manual abstraction of EHR data. These manual approaches have had a negative impact on data quality and cost, often due to the complexities associated with collection and mapping of the data to fit the registry model. HL7 FHIR has the potential to address these issues by automating part or all of the data collection process.

ABSTRACT IMPACT: This public health work contributes to the development and implementation of best practices for working with sex trafficked youth who experience placement instability and justice involvement. OBJECTIVES/GOALS: Youth removed from their home into foster care or a group home (i.e., placement instability) are vulnerable to sex trafficking. This study examines whether placement instability predicts mental health, behavioral and justice-related outcomes among sex-trafficked girls. METHODS/STUDY POPULATION: Placement instability occurs when children are temporarily or permanently removed from their home and placed in foster care or a group home. Domestic minor sex trafficking is exploitation and abuse of children for commercial sexual purposes in exchange for money or other goods/services. We hypothesize that sex trafficked girls who experience placement instability will report more mental health challenges, substance use, abuse history and justice involvement than those without placement instability. Data came from participant files in a specialty court program from 2012-2014 (N=184). Multiple sources contribute to the information contained court files; all data extracted by the research team come solely from the court files. Descriptive, bivariate, and logistic regression analyses were performed. RESULTS/ANTICIPATED RESULTS: All participants were (cis)female, 74% were African American, 96% US citizens, with average age of 16 years. Three-quarters of participants had a documented mental health challenge, such as depression and 88% reported substance use. Eighty-one percent of participants had been in a placement, with a group average of 4.5 placements. Girls with placement instability reported more mental health challenges (p<.001), substance use (p<.001), abuse (p<.001), running away (p<.001) and bench warrants (p<.001) than girls without placement instability. Logistic regression estimated housing instability was positively associated with mental health challenge, substance use, running away, number of bench warrants, and number of citations. DISCUSSION/SIGNIFICANCE OF FINDINGS: Among girls who have been trafficked, placement instability places them at greater risk for personal and behavioral challenges, including increased justice involvement. Comprehensive trauma-informed services should be provided to the family to help mitigate issues in the home.