OBJECTIVES/SPECIFIC AIMS: Childhood obesity has become an issue of some concern worldwide. Some reviews and a recent study in adults have indicated that obesity-related inflammatory responses produce brain damage. However, studies exploring associations between inflammation and executive functions in children are overlooked. Therefore, the objective of this cross-sectional study is to determine whether difficulties in executive functions and emotional processing are associated with obesity and inflammation. METHODS/STUDY POPULATION: We have recruited 12 of a total of 60 children aged 6–8 years old. They have completed the NIH Toolbox Cognition Battery and the NEPSY II Affect Recognition tests. Samples of plasma and saliva were collected to quantify inflammatory biomarkers cytokines (IL-6 and TNF-α) assay by Luminex procedure. We performed descriptive analysis and Mann-Whitney U test to compare obese Versus nonobese groups. RESULTS/ANTICIPATED RESULTS: Obese children have lower scores in measures of affect recognition than healthy weight children. They also showed higher median scores in both salivary and plasma IL-6 and TNF-α. DISCUSSION/SIGNIFICANCE OF IMPACT: Although no statistical differences were found among groups in either measurement, these preliminary data based on the initial recruitment suggest that children with higher body mass index may have difficulties in emotional processing. More data will be available after completing recruitment to determine if the association between obesity and affect recognition is significant and if it is mediated by inflammation.

OBJECTIVES/SPECIFIC AIMS: Peripheral neuropathy is the dose limiting toxicity of paclitaxel treatment. Paclitaxel pharmacokinetics (PK), specifically the Cmax and amount of time the concentration remains above 0.05 µM (Tc>0.05), have been associated with occurrence of severe, clinician-documented neuropathy. The objective of this study was to confirm that paclitaxel PK predicts progression of patient-reported neuropathy. METHODS/STUDY POPULATION: This observational trial enrolled breast cancer patients receiving weekly 1-hour paclitaxel infusions (80 mg/m2×12 cycles) at the University of Michigan Comprehensive Cancer Center. Paclitaxel concentration was measured via LC/MS in plasma samples collected at the end of (Cmax) and 16–24 hours after (Tc>0.05) first infusion. Patient-reported neuropathy was collected (EORTC CIPN20) at baseline and each cycle. The rate of neuropathy severity increase per treatment cycle is being modeled for each patient. Cmax and Tc>0.05 values will be introduced into the model to confirm that PK independently contributes to neuropathy progression. RESULTS/ANTICIPATED RESULTS: PK and neuropathy data have been collected from 60 patients for ongoing analysis. Our initial model will characterize the expected severity of neuropathy after each cycle of paclitaxel treatment. The PK-neuropathy model will include either PK parameter to validate their contribution to the progression of neuropathy severity during treatment. We anticipate, based on our preliminary analysis of the first 16 patients, that both PK parameters will significantly contribute to the model but Tc>0.05 will be more strongly associated with neuropathy progression. DISCUSSION/SIGNIFICANCE OF IMPACT: This project will generate a model that can be used to predict a patient’s neuropathy severity throughout treatment using a single, conveniently collected and easily measured PK sample during their first cycle. The next steps of this project include identifying genetic and metabolomic biomarkers that predict which patients experienced more severe neuropathy than would be anticipated based on their paclitaxel PK, and a planned interventional trial of personalized paclitaxel dosing to enhance efficacy and/or prevent neuropathy.

OBJECTIVES/SPECIFIC AIMS: Recent data suggest that fecal microbiota and intraluminal organic acids may play an important role in irritable bowel syndrome (IBS) pathogenesis through effects on intestinal secretion and motility. Understanding their contribution will be critical in developing diagnostic and treatment strategies. Objectives and goals of this study will be to: (1) compare fecal microbiota and fecal organic acids in IBS patients and controls and (2) investigate the association between colonic transit and fecal microbiota in IBS patients and controls. METHODS/STUDY POPULATION: We propose a prospective investigation of fecal organic acids, colonic transit and fecal microbiota in 36 IBS patients and 18 healthy controls. The target population will be adults ages 18–65 years meeting Rome IV criteria for IBS (both diarrhea predominant and constipation-predominant, IBS-D, and IBS-C) and asymptomatic controls. Exclusion criteria are: (a) history of microscopic colitis, inflammatory bowel disease, celiac disease, cancer, chronic infectious disease, immunodeficiency, uncontrolled thyroid disease, liver disease, or elevated AST/ALT>2.0x the upper limit of normal, (b) prior radiation therapy of the abdomen or abdominal surgeries with the exception of appendectomy or cholecystectomy>6 months before study initiation, (c) ingestion of prescription, over the counter, or herbal medications affecting gastrointestinal transit or study interpretation within 6 months of study initiation for controls or within 2 days before study initiation for IBS patients, (d) pregnant females, (e) antibiotic usage within 3 months prior to study participation, (f) prebiotic or probiotic usage within the 2 weeks prior to study initiation, (g) tobacco users. Primary outcomes will be fecal bile acid excretion and profile, short-chain fatty acid (SCFA) excretion and profile, colonic transit, and fecal microbiota. Secondary outcomes will be stool characteristics based on responses to validated bowel diaries. Stool samples will be collected from participants during the last 2 days of a 4-day 100-g fat diet and split into 3 samples for fecal microbiota, SCFA, and bile acid analysis and frozen. Frozen aliquots will be shipped to the Metabolite Profiling Facility at Purdue University and the Mayo Clinic Department of Laboratory Medicine and Pathology for SCFA and bile acid measurements, respectively. Analysis of fecal microbiota will be performed in the research laboratory of Dr. David Nelson in collaboration with bioinformatics expertise affiliated with the Nelson lab. Colonic transit time will be measured with the previously validated method using radio-opaque markers. Generalized linear models will be used as the analysis framework for comparing study endpoints among groups. RESULTS/ANTICIPATED RESULTS: This study seeks to examine the innovative concept that specific microbial signatures are associated with increased fecal excretion of organic acids to provide unique insights on a potential mechanistic link between altered intraluminal organic acids and fecal microbiota. DISCUSSION/SIGNIFICANCE OF IMPACT: Results may lead to development of targets for novel therapies and diagnostic biomarkers for IBS, emphasizing the role of the fecal metabolome.

OBJECTIVES/SPECIFIC AIMS: To describe the use of primary debulking surgery and neoadjuvant chemotherapy in advanced-stage ovarian cancer patients treated at Memorial Sloan Kettering Cancer Center (MSKCC) over the period of 1 year. Specifically, identify a subset of patients that are medically eligible to be considered for surgery. Examine the ultimate treatment designation for those patients, assessing the application of the MSKCC resectability algorithm and its utility in guiding treatment choice. METHODS/STUDY POPULATION: Using the prospectively maintained Ovarian Cancer Database at MSKCC, we queried patients who presented for initial management of ovarian cancer from July 1, 2015 to June 30, 2016. All patients with stage IIIB-IV disease who received their primary treatment at MSKCC were included in our study. Patients needed to have pathology-confirmed ovarian cancer and all histological subtypes were included. Data were collected and analyzed in Excel. RESULTS/ANTICIPATED RESULTS: There were a total of 173 patients treated for stage IIIB-IVB ovarian cancer at MSKCC during the study period. Of those 98 patients received PDS, whereas 75 were directed to NACT, making MSKCC’s overall NACT rate 43.4% for the year we studied. Of the patients who received NACT, 19 met full Aletti Criteria at diagnosis, precluding them from being considered for surgery. In addition, 21 patients had medical contraindications to surgery, meaning that a total of 40 patients who were given NACT were not able to be considered for PDS. If we then take into account only the patients who were medically eligible for PDS, the rate of NACT at MSKCC drops to 23.1%, almost half of the original value. These medically eligible patients are the population that should be receiving an MSKCC resectability score. Of the 98 patients who underwent PDS, 73.5% had a preoperative resectability score calculated. Based on the algorithm, 81.3% of those patients were deemed to be “low risk” and 15.2% were deemed to be “high risk” of a suboptimal debulking. The algorithm dictates that all “high risk” patients who go on to PDS should undergo a laparoscopy first to assess for resectability and potentially avoid an unnecessary open procedure. Hundered percent of the “high risk” cases that were taken to the OR had an initial laparoscopy before proceeding with PDS. Overall, 93.1% of patients that underwent PDS had an optimal cytoreduction, or ≤1 cm residual disease at the conclusion of surgery. Of the 6 patients throughout the year that had a suboptimal outcome, or >1 cm residual disease, 3 were initially scored as “low risk,” 1 was scored as “high risk,” and 2 did not receive an MSKCC resectability score prior to their procedure. Of note, 3 of the suboptimal cases had unresectable disease in an anatomical location not accounted for in the resectability algorithm. DISCUSSION/SIGNIFICANCE OF IMPACT: The rates of PDS Versus NACT vary widely between institutions, and it is not always clear how calculations are made. High-volume centers likely see a higher percentage of sicker patients with more advanced disease, which could increase their rates of NACT as many of these patients are not eligible for surgery. It is important to standardize the way our field quotes NACT rates, and to understand how treatment decisions are being made at a given institution. PDS has a demonstrated survival benefit, and while we would ideally use this modality for all of our patients, there will always be a baseline percentage of patients who cannot be considered for the surgery. Since we will never be able to offer those patients PDS, our objective should be to identify patients who can be considered for the procedure and to work toward optimizing their outcomes. In this study we identified the population of patients who are truly the PDS Versus NACT cohort as they were eligible for both modalities. We then examined the application and utility of the MSKCC resectability algorithm in an attempt to further optimize treatment allocation. This scoring system was implemented at our hospital over the past year with the goal that 100% patients going on to PDS would receive a preoperative score. Unfortunately, 26.5% of PDS patients were not scored prior to their procedure. This makes it more difficult to evaluate the efficacy of the scoring system, especially considering 1/3 of the suboptimal cases were not scored. Had these patients received a score, they might have been deemed “high risk” and could have avoided a lengthy operation with a significant chance of a suboptimal outcome. In addition, it is important to note that 3 of the suboptimal PDS outcomes were initially scored as “low risk,” and 3 of the suboptimal outcomes were due to disease locations not accounted for in the original resectability algorithm. We will continue logging disease locations of suboptimal cases, it is possible that a certain disease location not in the scoring system is responsible for a significant portion of suboptimal outcomes. The resectability score model had an overall predictive accuracy of 0.756 when it was initially published, and we must continue tracking scores and outcomes to determine its validity when applied prospectively in our population. In order to accurately do so however, an emphasis should be made to ensure 100% of patients being considered for PDS receive a score going forward.

OBJECTIVES/SPECIFIC AIMS: Falls are a major source of morbidity and disability in the aging population. Twenty to thirty percent of older adults who fall suffer moderate to severe injuries such as lacerations, hip fractures, and head traumas. A serious component of falling often overlooked is the fear of falling. The fear of falling is part of a debilitating spiral that leads to decreased activity and muscle weakness. The goal of this investigation was to determine if a novel 2-phase rehabilitation program designed to reduce the fear of falling and increase muscle strength could improve postural control during falls in older adults with balance impairments. METHODS/STUDY POPULATION: Four older adults participated in 8 cognitive restructuring workshops entitled A Matter of Balance (AMOB): 2 hours/week, total of 16 hours, designed to restructure thought patterns relative to falls and reduce the fear of falling. Within 1–2 weeks of completion, participants enrolled in Phase II: a standardized 10-week lower-extremity strengthening program. Participants performed high-intensity concentric resistance exercise on a modified seated ergometer (Eccentron, BTE Technologies) twice per week for up to 20 minutes per session. Fear of falling was assessed using the Activities-Specific Balance Confidence (ABC) scale. Postural control was assessed during reproducible falls at 3 phases: baseline (T0), after Phase I AMOB (T1), and after Phase II strengthening (T2). Falls were induced by treadmill perturbations (VGait system, MotekForce Link) occurring at slow and fast belt accelerations. A 3×3 ANOVA was conducted on postural control outcomes with phase and stepping cycle as independent factors. Pairwise comparisons were analyzed with the Bonferroni correction. RESULTS/ANTICIPATED RESULTS: Statistically significant main effects were found for phase and stepping cycle (p=0.003, p=0.00). No statistically significant interaction effects were found. However, a trend toward increasing Center of Pressure-Center of Mass (COP-COM) distance occurred after each intervention phase (T1 and T2) during fast treadmill perturbations. The greatest increase in COP-COM distance was found at 100% of the stepping cycle during fast perturbations following 10 weeks of resistance training compared with baseline (p=0.006). No significant differences were found in fear of falling between phases (p=0.682). DISCUSSION/SIGNIFICANCE OF IMPACT: A large COP-COM distance suggests the individual is able to allow straying of the COM outside of the functional base while recovering balance. Meanwhile, a small COP-COM distance represents a conservative approach to postural tasks, in that the performer does not feel stable enough to allow separation of the COP and COM. These pilot data suggest that a 2-phase rehabilitation program can improve specific components of postural control during recovery from falls. Rehabilitation interventions aimed at reducing falls in older adults should consider adding a component of cognitive restructuring in conjunction with standard of care resistance training.

OBJECTIVES/SPECIFIC AIMS: (1) Evaluate safety of a novel influenza vaccination strategy in patients with plasma cell disorders. (2) Measure laboratory-confirmed influenza infection rates following a novel influenza vaccination strategy in patients with plasma cell disorders. (3) Evaluate clinical correlates of response following a novel influenza vaccination strategy in patients with plasma cell disorders. METHODS/STUDY POPULATION: We conducted a double-blind, randomized study over the 2015–16 flu season, comparing 2 doses of Fluzone® High-Dose influenza vaccination (separated by 30 d) to the current standard of care influenza vaccination. Patients were allocated to the experimental arm in 2:1 ratio compared with standard of care arm. Standard of care influenza vaccination was considered single age-based vaccination (standard dose for those <65 y and high dosefor those ≥65 y) and patients in this arm received a saline placebo injection at 30 days to assist in blinding. Eligibility criteria allowed any patient with a PCD and no contraindication to trivalent inactivated influenza vaccine. The primary endpoint was laboratory-confirmed flu infection rate. Protocol-driven surveillance screened patients for flu-like illnesses and performed laboratory testing for influenza until the end of the flu season in May 2016. Secondary endpoints include HAI titer serologic response rates, clinical correlates of protection from influenza infection, and exploratory studies of cell-mediated immunity through characterization of T cell subpopulations, cytokine profiles, and flu-specific T-cell responsiveness. RESULTS/ANTICIPATED RESULTS: In total, 122 plasma cell disorder patients were enrolled (97 with disease requiring therapy and 25 with asymptomatic gammopathy). Of those 48 patients received a single standard of care influenza vaccination and 74 patients received 2 doses of Fluzone® high-dose vaccine. Median age was 67 years (range 42–90). This 2-dose vaccination strategy was safely tolerated in all patients with no grade 2 adverse events attributed to vaccine. With close clinical follow-up, only 4% of patients receiving 2 vaccine doses developed laboratory confirmed influenza Versus 8.3% of those receiving single vaccine. When compared to the expected CDC influenza infection rate of 10%–15%, 1 sample, 2-tailed binomial testing revealed patients receiving 2 vaccines experienced a significantly lower rate of infection than the expected rate (p<0.05) whereas those receiving single vaccine showed no significant difference (p=0.38). DISCUSSION/SIGNIFICANCE OF IMPACT: This randomized study demonstrates that the 2 dose strategy of Fluzone® high-dose influenza vaccine is safely tolerated in patients with plasma cell disorders and associated with significantly less than expected laboratory-confirmed influenza infections. The results suggest that this novel vaccination strategy may have a clinical benefit in reducing influenza infections in plasma cell disorder patients and thus may have practice changing implications. Final analyses of serologic responses, clinical correlates of response, and cell-mediated immune correlates may provide valuable insights into in vivo “immune-competence” in patients with plasma cell disorders.

OBJECTIVES/SPECIFIC AIMS: The objective of this study is the pharmacology of sublingual Buprenorphine in Hispanics/Latino men and women. Specifically we plan to: (1) Administer sublingual buprenorphine to Hispanic/Latino men and women volunteers, and measure the circulating amounts of the drug in the bloodstream as a function of time; that is, pharmacokinetics of buprenorphine. The goal of the proposed study is to evidence that there are gender and ethnic differences in the pharmacokinetics of sublingual buprenorphine between not only Hispanics/Latinos and non-Hispanics/Latinos (Caucasian), but also within Hispanic/Latino men and women. METHODS/STUDY POPULATION: We are proposing a phase 1 of buprenorphine using 12 healthy volunteers. To test for differences in pharmacokinetics between Hispanic/Latino men and women, 6 Hispanic/Latino men, and 6 Hispanic/Latino women 21 years of age and older will be recruited. The volunteers should be living in Puerto Rico, and must have both parents born in Puerto Rico. Sublingual buprenorphine will be administered using a low dose of 16 mg one time only. Blood samples will be collected from each volunteer at t=0, 1, 2, 4, 6, 8, 12, and 24 hours after administration. The amount of circulating drug in the bloodstream of the volunteers will be measured using liquid chromatography combined with mass spectrometry. Pharmacokinetic obtained parameters will be maximal plasma concentration, minimal plasma concentration, predose concentration, 24 hour post predose concentration, the time for maximum concentration. The area under the curve will be determined by the trapezoidal rule. Male Versus female data will be compared using 2-tailed t-test. RESULTS/ANTICIPATED RESULTS: We anticipate that: (1) Hispanic/Latino women will have longer circulating times of the drug in the bloodstream and higher maximum concentrations, compared with men. (2) Hispanic/Latino men and women will have higher amounts of the circulating drug, compared with already reported pharmacokinetic data of non-Hispanic Caucasian men. DISCUSSION/SIGNIFICANCE OF IMPACT: Gender differences have been elucidated in the prevalence rates of substance abuse, health service utilization, treatment outcomes, and physiological consequences of drug consumption in the United States. It is known that in general, women progress from drug use to dependence must faster than men; women also suffer more severe physical and emotional consequences than men, yet women seek treatment for drug addiction in lower rates compared with men. Women also show lower pharmacological treatment effectiveness as they are less likely to feel satisfied upon entering a substance abuse treatment and they show higher cravings. Sublingual buprenorphine is a very popular and relatively new medication used primarily for opiate addiction since 2002. Gender differences have been elucidated in the pharmacology of buprenorphine sublingual tablets used for the treatment of opioid addiction. One study showed that women had higher concentrations of circulating parent drug and it is metabolites compared with men. One metabolite in particular norbuprenorphine was found in almost double the plasma concentration in women. Interestingly, gender differences were not pursued at all by the Pharmaceutical Company sponsoring the approval of the sublingual Buprenorphine by the FDA. The cytochrome enzyme CYP 3A4 responsible for the metabolism of Buprenorphine has higher activity in Caucasian/African American women compared with men. However these studies failed to design and recruit significant amount of patients with Hispanic ethnicity to adequately elucidate the gender differences within this ethnic group. Higher plasma concentrations and longer circulation times of a drug may result not only in lower efficacy outcomes but also higher toxicity and undesired effects. Unfortunately, the lack of pharmacological effectiveness and lack of satisfaction in women undergoing drug treatment programs has not been adequately studied to understand the gender difference in pharmacological treatment outcomes between Hispanic/Latino men and women. Due to the under-representation of Hispanic/Latino men but most importantly women in s studying the pharmacology of sublingual Buprenorphine, and considering the well-established gender difference of the principal enzyme (CYP 3A4) responsible for the pharmacology of Buprenorphine, we are proposing a pilot study of the pharmacology of sublingual Buprenorphine in Hispanic/Latino volunteers living in Puerto Rico with equal number of male and female patients. We expect our research to clinically and scientifically elucidate the gender differences of sublingual buprenorphine for opioid addiction in Hispanics/Latinos. The outcome of such research will be the foundation of subsequent clinical studies that aim in updating the current standard of care for Hispanic/Latino men and women that require therapy for opioid addiction.

OBJECTIVES/SPECIFIC AIMS: To date, only 1 documented case of an individual cured of HIV has been reported. He received an allogeneic bone marrow transplant with cells harboring an HIV-resistant genotype. To mimic this result, we have initiated a Phase I to evaluate the safety of an autologous stem cell gene therapy bone marrow transplant in HIV-related lymphoma patients. METHODS/STUDY POPULATION: The first cohort of patients will receive a 1:1 ratio of unmanipulated CD34 hematopoietic stem cells (HSC) and lentivector modified CD34 HSC expressing a combination of HIV-resistant genes and a selectable marker for cell sorting prior to transplantation. Safety of the HIV-resistant stem cells will be assessed by evaluating engraftment, expression of the anti-HIV genes, and the stability and sequence of the vector. RESULTS/ANTICIPATED RESULTS: One patient has been enrolled and transplanted with the HIV-resistant stem cells. After 1 and 2 months post-transplant, patient blood samples were received, processed for genomic DNA, analyzed by quantitative PCR (qPCR), and displayed successful engraftment of 16 and 12 vector copies per 100 cells, respectively. Expression of all anti-HIV genes was confirmed by qPCR. PCR on genomic DNA confirmed the correct sizes and sequences of the integrated vector and confirmed the successful engraftment of our gene modified cells. Currently, we are enrolling more patients into the trial. DISCUSSION/SIGNIFICANCE OF IMPACT: If successful, this therapy has the potential to change HIV treatment.

OBJECTIVES/SPECIFIC AIMS: Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of ~16 months. Novel methods to improve local control are needed. Nab-paclitaxel (abraxane) has shown efficacy in pancreatic cancer and is FDA approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced disease. METHODS/STUDY POPULATION: We performed a phase 1 study using a 3+3 dose-escalation strategy to determine the safety and tolerability of dose escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with 2 cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy. RESULTS/ANTICIPATED RESULTS: Nine patients received nab-paclitaxel at a dose level of either 100 mg/m2 (n=3) or 125 mg/m2 (n=6). One DLT (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab-paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%), and neutropenia (11%). No grade 4 toxicities were observed. With a median follow-up of 8 months (range 5–28 months), median survival was 19 months and median progression-free survival was 10 months. Following chemoradiation, 3 patients underwent surgical resection, all with negative margins and limited tumor viability. Of the 3 patients, 2 initially had borderline resectable tumors and 1 had an unresectable tumor. Tumor (SMAD-4, Caveolin-1) and peripheral (circulating tumor cells and microvesicles) biomarkers were collected and are being analyzed. DISCUSSION/SIGNIFICANCE OF IMPACT: The combination of fractionated radiation and weekly nab-paclitaxel was safe and well tolerated. This regimen represents a potentially promising therapy for patients with unresectable and borderline resectable pancreatic cancer and warrants further investigation.

OBJECTIVES/SPECIFIC AIMS: Sleep disturbance is a common problem following military deployment. Insomnia is associated with other adverse psychiatric and medical health outcomes. There are specialized cognitive behavioral therapies that can effectively treat insomnia; however, these tend to emphasize dysfunctional beliefs about sleep rather than nocturnal vigilance. Deployment to a threatening environment can engender nocturnal vigilance, which appears to be a salient feature of sleep disturbance in formerly deployed veterans. The purpose of this analysis is to characterize sleep-interfering thoughts and behaviors observed in an ongoing pilot study of a novel 2-session intervention incorporating various cognitive techniques to improve sleep in veterans. METHODS/STUDY POPULATION: To date, 10 formerly deployed US veterans with disturbed sleep have been recruited from the greater DC area. Participants are assessed at baseline, receive 2 intervention sessions, and are again assessed in 3 months. Sleep-interfering thoughts and behaviors are evaluated via self-report forms including the Fear of Sleep Inventory (FoSI), interviews, and prospective diaries. A portion of both intervention sessions addresses vigilant behaviors and sleep-interfering thoughts by teaching participants 1 of 4 techniques that target nocturnal vigilance: cognitive defusion, body scan, self-guided pleasant imagery, and dream rescripting. RESULTS/ANTICIPATED RESULTS: All of the first 10 participants endorsed sleep-interfering thoughts on the Fear of Sleep Index (FOSI) at a severity level of at least “a few times per month” (rating of ≥1), including several regarding previous trauma (#5) and nightmares (#10 and #16). Other elicited thoughts included thoughts about their environment (n=6), sleep (n=5), social or occupational concerns (n=8), nightmares (n=5), and health (n=4). All of the first 10 participants endorsed vigilant behaviors, including being over-attentive to their environment (n=7), checking behaviors (n=6), and being “on-guard” (n=8). Cognitive technique was selected by the participant in collaboration with the facilitator. Customized recommendations were given as to the timing and duration of practice, but all participants were instructed to practice at least once daily. Three participants (n=3) were fully compliant with their cognitive technique recommendations (choosing a body scan or imagery), 5 were partially compliant, and 2 were not compliant (both chose cognitive defusion). There was a significant reduction in sleep onset latency and wake after sleep onset from baseline to post-treatment (p<0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: The preliminary data suggests that veterans exhibit cognitive and behavioral patterns that involve vigilance and interfere with sleep and demonstrates the need for an intervention targeting the link between nocturnal vigilance and sleep disturbance. More veteran participants and feedback are needed to optimize the efficacy and effectiveness of this sleep training.

OBJECTIVES/SPECIFIC AIMS: The current study examined hangover following IV alcohol self-administration (IV-ASA) using the Computer-Assisted Infusion System. The goal of the study was to identify predictors of hangover, including drinking history, alcohol sensitivity, family history, expectancies, and sex differences in nondependent drinkers. METHODS/STUDY POPULATION: The study sample included 89 healthy, nondependent drinkers aged 21–45 years. After a screening to exclude any medical illness or psychiatric disorders, participants completed an IV-ASA session. Each session consisted of a 25-minute priming phase, during which participants were prompted to press a button to receive individually standardized alcohol infusions, followed by a 2-hour “open bar” phase, during which they were instructed to recreate a typical drinking experience. Results from the IV-ASA included peak and average BrAC. Drinking patterns were assessed using the Alcohol Use Disorders Identification Test, which provided 3 subscales: consumption (AUDIT-C), dependence (AUDIT-D), and harmful drinking (AUDIT-H). Subjective response to alcohol was measured using the Drug Effects Questionnaire (DEQ). The Alcohol Hangover Scale (AHS) was used to assess hangover for the period between participants’ departure from the study unit and 10 am the next morning. The Alcohol Effects Questionnaire (AEFQ) is a measure which includes 40 true/false statements about how alcohol typically makes respondents feel, and was used to measure alcohol expectancies. RESULTS/ANTICIPATED RESULTS: Results showed that 78% of participants endorsed having at least 1 hangover symptom following IV-ASA. The most commonly reported items were tired, thirsty, headache, and hangover. There was no association between hangover scores and the AUDIT-C or IV-ASA. Because alcohol consumption was not related to hangover symptoms, risky drinking behavior was examined. Results indicated that participants endorsing 4 or more items on the AUDIT-D plus AUDIT-H subscales showed significantly higher average hangover scores. Linear regression analyses indicated that alcohol hangover scores were associated with DEQ items feel, high, and intoxicated. Ongoing analyses are examining additional predictors of hangover including family history, alcohol expectancies, sex differences, and other alcohol sensitivity measures. DISCUSSION/SIGNIFICANCE OF IMPACT: The results indicated that risky drinking patterns and alcohol response measures were positively associated with hangover symptoms in non-dependent drinks, while no correlation between consumption and hangover symptoms were found. Since previous research has shown than greater subjective response is associated with heavy drinking and predictive of alcohol use disorder, it is possible that hangover symptoms is a marker of this relationship. Since the role of hangover in the transition from heavy drinking to disorder still remains unclear, it will be important to characterize this relationship between alcohol sensitivity and hangover as a function of drinking patterns. This understanding may help to prevent this transition from at-risk drinking to alcohol dependent drinking.

OBJECTIVES/SPECIFIC AIMS: Engagement in risky behaviors is not uncommon among adolescents. Two factors associated with risk taking are difficulty regulating emotions and impulsivity. Moreover, youth who exhibit higher scores on impulsivity-like personality traits (ie, negative urgency, positive urgency, sensation seeking, lack of premeditation, and lack of perseverance) are at even heightened risk. An effective intervention decreasing risk-taking behavior among adolescent populations in clinical settings is Dialectical Behavioral Therapy for Adolescents (DBT-A), which teaches skills on emotion regulation, distress tolerance, and mindfulness. However, DBT-A has yet to be tested as an intervention for youth in a nonclinical setting. The current study aimed to fill this gap in the literature. METHODS/STUDY POPULATION: A 9-week DBT-A skills group was implemented in a public high school classroom (7th-8th graders; N=41) and an alternative high school for at risk youth (7th-12th graders; n=21). Of the 41 youth from the public high school classroom participated, with preintervention and postintervention data provided by 30 participants (retention of 73%). RESULTS/ANTICIPATED RESULTS: Results found a significant increase in mindfulness skills and marginally significant increase in emotion regulation skills. Although there was not an overall change in risky behavior among participants, those who were higher on lack of premeditation and positive urgency showed steeper improvements on the skills. The second study at the alternative high school is currently underway, with no current results to report. DISCUSSION/SIGNIFICANCE OF IMPACT: This study will demonstrate that DBT-A skills training is feasible in a school-based setting and shows promising preliminary evidence of decreasing risk of engagement in risky health behaviors among adolescents, particularly among high-risk youth.

OBJECTIVES/SPECIFIC AIMS: Impulsivity is a significant predictor of alcohol use and drinking behavior, and has been shown to be a critical trait in those with alcohol use disorder. Suggestibility, or susceptibility to social influence, has been shown to correlate with impulsivity, with highly suggestible individuals being more likely to make impulsive decisions influenced by peer groups. However, the relationship between social influence and drinking behavior is unclear. Our objective was to describe the relationship between social influence and impulsivity traits using the social delayed discounting task and potential differences in intravenous alcohol self-administration (IV-ASA) behavior. METHODS/STUDY POPULATION: Healthy, non-dependent drinkers (n=20) completed a CAIS session, which consisted of an initial 25-minute priming phase, where subjects were prompted to push a button to receive individually standardized IV alcohol infusions, followed by a 125-minute phase during which they could push the button for additional infusions. IV-ASA measures included the peak (PEAK) and average (AVG) BrAC and Number of Button Presses (NBP). Participants completed a social delayed discounting task (SDDT), where participants were presented with the choice of a small, sooner (SS) reward or a large, later (LL) reward. Before starting the task, participants chose peers who selected either the impulsive (SI) or non-impulsive choice (S). Intermittently, the peers’ choice was not shown (X) or different choices (D) were selected. Participants also completed the MISS, the Barratt Impulsiveness Scale (BIS-11), UPPS-P Impulsive Behavior Scale, and the NEO personality inventory. RESULTS/ANTICIPATED RESULTS: Participants with higher suggestibility scores had greater NBP, AVG, and PEAK BrAC in the early phase of the IV-ASA session. Higher scores on the MISS were also correlated with higher impulsivity scores including the NEO Neuroticism (N-factor) measure, BIS-11, and UPPS-P. Results also showed that the MISS score was inversely correlated with the percent of impulsive choices in the SDDT, but that this was independent of peers’ impulsive or nonimpulsive choices. DISCUSSION/SIGNIFICANCE OF IMPACT: These results indicate that non-dependent drinkers that were more susceptible to social influence had heavier drinking patterns, higher IV-ASA, and higher scores on impulsivity measures. In addition, individuals that were more susceptible to social influence made more impulsive choices in general, but those choices were not affected by peer decisions during the task. As such, susceptibility to social influence may be an important determinant of impulsive choices, particularly in relation to alcohol consumption.

OBJECTIVES/SPECIFIC AIMS: To explore the racial differences in rotational thromboelastometry findings using whole blood and plasma samples from healthy volunteers. METHODS/STUDY POPULATION: We studied a cohort of patients at Tulane University Hospitals who came into the pre-op clinic to get blood drawn for labs. The cohort included a total of 44 patients who were otherwise healthy adult volunteers with no history of cardiovascular nor thromboembolic events, 30 African Americans and 14 Caucasians. Patients who required lab work for their upcoming surgery were asked to participate in the study by giving a sample of blood collecting in a light blue-top sodium citrate tube. We excluded patients who were currently on any anticoagulation or antiplatelet medications. We also excluded those with current or previous history of cancer, those with known bleeding disorder, and those who were on chronic transfusion protocol, or had received a blood transfusion within the last 21 days. Data collection was carried out after informed consent was obtained; we collected citrated whole-blood (WB) samples. WB samples were processed within 3 hours of phlebotomy. Platelet free plasma, obtained after centrifugation at 2500 cGy of whole blood for 20 minutes, was kept frozen at −70°C. Frozen plasma was thawed at 37°C for 5 minutes before testing. Samples were recalcified with star-tem reagent, and then the in-tem reagent was added. The latter contains an optimized concentration of ellagic acid and partial thromboplastin phospholipid from rabbit brain. Thromboelastometry (ROTEM) parameters including clotting time, clot formation time, alpha angle, maximum clot firmness, and Lysis Index after 30 and 45 minutes were determined. Data was then retrieved from the ROTEM database and put into an Excel sheet to be analyzed. RESULTS/ANTICIPATED RESULTS: Our results showed that the CFT was higher in both the plasma and the WB of Caucasians when compared with African Americans with a difference between means 137.5±233.7 (p=0.56) and 11±7.85 (p=0.168), respectively; while MCF was increased in the WB and plasma of AA with a difference between means of 1.719±1.974 (p=0.38) and 5.37±2.49 (p=0.037), respectively. In other words, the plasma of Caucasians did seem to take longer to reach the maximum firmness (however not statistically significant p>0.05), while the maximum clot firmness was significantly higher in plasma of AA. In summary and compatibly with the previously published data, our results showed significantly increased prothrombotic profile in the plasma of African Americans when compared with Caucasians. DISCUSSION/SIGNIFICANCE OF IMPACT: This reinforces the role of the whole vascular system and the interaction between its different components in the pathophysiology of thromboembolic events. In one case control study, African ethnicity was associated with increased risk of DVT in parallel with significantly increased peak thrombin on thrombin generation when compared with Caucasians. With our preliminary results, we confirm these data using another tool for the assessment of the plasma in addition to comparing WB samples too. More prospective studies, with higher number of subjects evaluating the value of the results in predicting the risk of development of thromboembolic events in different ethnicities, are needed for better understanding of this disease. In addition, thromboelastometry might require adjustment for ethnicity in studies evaluating ethnically diverse populations.

OBJECTIVES/SPECIFIC AIMS: To identify brain regions with the highest and least variable rate of multiple sclerosis (MS)-specific atrophy using an agnostic approach, and to perform simulation-based sample size calculations for Phase II s using these regions as primary endpoint. METHODS/STUDY POPULATION: In total, 601 subjects (2638 MRI scans) were analyzed; 520 subjects with relapsing forms of MS across the spectrum of disease severity and duration were followed in a single-center prospective cohort study at an academic MS Center between 2005 and 2010 with annual 3 T MRIs and clinical visits for 5 years, including standardized 1 mm3 3D T1-weighted images (3DT1s; 2483 MRIs). Separately, a convenience sample of 81 healthy controls (HC) was recruited from the same center and scanned longitudinally using the same MRI scanner and protocol (155 MRIs). 3DT1s were processed using FreeSurfer’s longitudinal pipeline (software version 5.3). Rates of change in all cortical and subcortical regions (n=119 brain regions) were estimated in MS patients and HC with linear mixed effects models. An effect size was calculated for each region as the difference in change over time between MS patients and HC divided by the standard error of the difference [d=β(MS×time)/SE β(MS×time)]. Regions were ranked according to absolute effect size, and the top regions were chosen for simulation-based sample size calculations to estimate the number of subjects needed to achieve 80% power to detect a slowing of MS atrophy down to normal aging, assuming significance levels of 5% and 10%. Ten percent was included because some have advocated for a more relaxed alpha in Phase II s. RESULTS/ANTICIPATED RESULTS: Four regions (putamen, subcortical grey matter, caudate, and thalamus) yielded the smallest sample sizes. At 80% power, ~50 subjects per arm would be needed with putamen or subcortical grey matter volume, or ~80–85 subjects per arm with caudate or thalamic volume as primary endpoint. For the remaining regions, >140 subjects per arm would be needed. A 20%–30% increase in sample size was observed when α=5% was used. DISCUSSION/SIGNIFICANCE OF IMPACT: Using an agnostic approach considering all brain regions and simulation-based sample size calculations specifically designed for longitudinal studies, putaminal, subcortical grey, caudate, and thalamic volumes are sensitive to change over time and yield feasible sample sizes for Phase II studies in MS. Because the effect size estimates incorporate normal aging, these regions represent the most sensitive outcomes for testing therapeutic interventions that target irreversible, MS-specific brain atrophy. The clinical relevance of these regions is our next focus to help inform which of these regions should be favored as primary endpoint.

OBJECTIVES/SPECIFIC AIMS: Cardiac complications are common after hospital admission for sepsis, and elevated troponin has been associated with increased all-cause mortality. However, little is known about clinical or imaging factors that predict these cardiac events. Coronary artery calcification (CAC) is an easily identifiable imaging finding, even on nongated CT scans. The goal of this study is to identify if CAC predicts all cause mortality and acute myocardial infarction. METHODS/STUDY POPULATION: This is a single center, nonconcurrent cohort study including 899 patients who were admitted for sepsis and had a detectable TnI level from January 2013 to December 2013. Patients with a CT scan of the chest or abdomen done for other clinical indications within 6 months of this admission were reviewed for the presence or absence of CAC. Medical records were individually reviewed for mortality and type I acute myocardial infarctions at 1 year. RESULTS/ANTICIPATED RESULTS: In total, 144 patients (mean age 57±14.8 years, 48% female) were included in the analysis. CAC was seen in 59% of these scans. Compared to those without detectable CAC, the CAC group had similar APACHE score (18 vs. 16.6, p=0.259), peak TnI (3.64 vs. 2.11 mg/dL, p=0.363), aspirin (63% vs. 51%, p=0.144), and β blocker use (90% vs. 85%, p=0.357) and had higher statin use (48% vs. 27%, p=0.013). CAC was associated with increased all-cause mortality (59.5% vs. 38.9%, p=0.016) and type I myocardial infarctions (10.6% vs. 1.7%, p=0.039) compared with those without CAC. DISCUSSION/SIGNIFICANCE OF IMPACT: Coronary artery calcification is often seen when patients present with a noncardiac acute illness, such as sepsis, often making a new diagnosis for these patients. Mortality and acute MI after sepsis can be predicted by coronary calcification, and identify patients who should be targeted for therapy and close follow-up.

OBJECTIVES/SPECIFIC AIMS: Alcohol craving, particularly in response to stress and alcohol cues, can lead to relapse in alcohol-dependent individuals. Hypothalamus-pituitary-adrenal (HPA) axis markers such as the cortisol to corticotrophin (CORT:ACTH) ratio have been shown to be a significant predictor of alcohol relapse. Our objective was to evaluate the influence of HPA-axis measures on intravenous alcohol self-administration (IV-ASA) in binge and nonbinge drinkers. METHODS/STUDY POPULATION: Healthy, non-dependent binge drinkers (n=14) and nonbinge drinkers (n=11) participated in this study. They underwent 3 personalized imagery sessions, where they heard 5-minute personalized audio scripts designed to trigger stress, alcohol craving, and neutral-relaxation states. Immediately following these cues, participants were given access to alcohol using a novel IV-ASA paradigm for 120 minutes. Serial blood samples were collected for cortisol and ACTH levels. Subjective measures were collected serially using the Subjective Units of Distress Scale (SUDS), Drug Effects Questionnaire (DEQ), and Alcohol Urge Questionnaire (AUQ). Analyses were conducted using linear regression. RESULTS/ANTICIPATED RESULTS: Results showed that peak and average ACTH levels as well as the CORT:ACTH ratio during the early phase of the IV-ASA session following the stress and alcohol cues were significantly higher than the neutral script; this effect was seen primarily in binge drinkers. After script administration, a greater change from baseline for ACTH predicted time to peak BrAC during IV-ASA. Gender and binge group predicted AUQ MAX (peak alcohol craving over the entire study session) and WANT MAX (peak “want more alcohol” scores over the session). There was a significant correlation between IV-ASA and increased ACTH peak and average values in binge drinkers. The DEQ and AUQ measures were positively correlated with ACTH peak and ACTH change from baseline. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings, to our knowledge, are the first demonstration that exposure to both stress and alcohol cues lead to an increase in ACTH during cue-induced IV-ASA, particularly in binge drinkers. These results suggest that changes in HPA-axis reactivity following stress and alcohol may be important determinants of alcohol consumption in non-dependent binge drinkers.

OBJECTIVES/SPECIFIC AIMS: Clostridium difficile is the most common cause of infectious antibiotic associated diarrhea. It is often refractory to antimicrobial therapy and fecal microbiota transplantation (FMT) is emerging as a therapeutic option. The objective is to characterize the direct effects of FMT on the gut microbiota. METHODS/STUDY POPULATION: Fecal specimens were obtained from a cohort of 29 subjects with recurrent C. difficile infection who received FMTs from 1 of 4 healthy donors as part of a phase 2 trial (Rebiotix). Fecal specimens were collected from the subject before FMT and up to 6 months post FMT. 16S rRNA sequencing and whole-genome shotgun sequencing were used to assess microbial community composition as compared by weighted Unifrac. RESULTS/ANTICIPATED RESULTS: Before treatment, the microbial community of subjects with C. difficile infection was highly distinct from the composition of the healthy donors in terms of metabolic profile. Quantification of phylogenetic community distance from donor by weighted Unifrac distance showed a significant decrease within the 1st week (Wilcoxon rank sum, p<0.01). This metric was predictive of both treatment failures and antibiotic resistance gene count (LR=22.45, p<0.0001). DISCUSSION/SIGNIFICANCE OF IMPACT: We conclude that distance from donor is a useful metric to quantify FMT success and that FMTs are a promising treatment for otherwise untreatable carriage of antibiotic resistance genes and organisms.

OBJECTIVES/SPECIFIC AIMS: Congenital heart disease (CHD) is the most frequently occurring birth defect in the United States affecting about 40,000 infants born every year. Despite significant advances in postsurgical survival, developmental outcomes remain disproportionately poor. Therapeutic hypothermia has been used for neuroprotection during cardiac surgery since the 1950s. Infants undergoing cardiac surgery are typically cooled to 28–33°C during the operation and then rapidly rewarmed to normothermia following surgery at a rate of 1°C every 3–5 minutes to minimize concerns surrounding the risks associated with prolonged bypass exposure. However, emerging evidence from animal models has shown rapid temperature changes following surgery may diminish or even negate the neuroprotective effect of intraoperative hypothermia. No prospective studies have assessed the safety or impact of alternative approaches to postoperative temperature management on the outcome of infants with CHD undergoing cardiac surgery. Therefore, we conducted a pilot study to examine the safety of a novel application of a temperature-regulating device to slowly rewarm infants with congenital heart disease over the 12 hours following cardiac surgery. METHODS/STUDY POPULATION: From November 2014 to July 2016, infants with CHD requiring surgery with cardiopulmonary bypass before the age of 12 months were prospectively recruited. Infants were randomized in blocks of 3 with 1 allocated to standard of care and 2 to the experimental protocol. Infants assigned to the standard of care were rewarmed in the operating room while on bypass at a rate of 1°C every 3–5 minutes back to a temperature of 37°C. Infants assigned to the experimental intervention, were rewarmed on bypass to 35°C and then over the subsequent 12 hours following surgery, gradually rewarmed using an FDA approved “cooling blanket” to increase temperature by 0.3°C every 2 hours for 6 hours and then by 0.2°C every 2 hours for 6 hours until the goal temperature of 36.5°C was achieved. Frequency of serious, moderate and other adverse events were tracked. Detailed vital sign data was collected hourly for the first 12 hours after surgery and then every 6 hours for the next 36 hours and included temperature, highest and lowest heart rate, highest and lowest systolic blood pressure, and highest and lowest diastolic blood pressure. Presence or absence of abnormal cardiac rhythms was recorded per 24-hour interval. Chest tube output was recorded in cc/kg/8 hours for as long as the chest tube was in place. Laboratory data points included serum creatinine level, serum glucose level, liver function tests (AST and ALT), platelet count, hematocrit level, PTT, INR, fibrinogen, white blood cell count and lactate. Blood samples for biomarkers of brain injury (s100b and NSE) were obtained on all infants at the following 4 intervals; the preoperative setting for baseline, postoperatively after bypass, on postoperative day 1, and on postoperative day 2. For this safety study, the primary outcome measure was a composite outcome of the frequency of serious adverse events as well as the frequency of any adverse events and was compared among treatment groups. Data were analyzed using an intent to treat analysis. The study was approved by the Maine Medical Center Institutional Review Board. RESULTS/ANTICIPATED RESULTS: Seven infants were randomized to the standard of care group and 9 were randomized to the experimental group. There were 2 exclusions after randomization in the standard of care group with 1 death in the operating room and 1 unsuccessful attempt to wean from bypass. The mean temperature upon arrival to the PICU for the experimental infants was 35.2°C (range 34–36°C) and for the standard of care infants was 37.5°C (range 36.9–38.9°C). For the first 8 hours after surgery, infants in the standard of care group had mean temperatures over 37.0°C. There were no significant differences in the frequency of serious, moderate, or other adverse events between the standard of care group and experimental group. No infant in either group had need for cardiopulmonary resuscitation or exploratory surgery within 48 hours following surgery nor did any infant experience any clinically appreciated adverse neurological events such as stroke or seizure. No infant in either group experienced clinically significant bradycardia of less than 100 beats per minute or sustained tachycardia of greater than 160 beats per minute. There was a trend toward lower heart rates in the experimental group. Junctional Ectopic tachycardia (JET) occurred in 2 patients in the experimental group and 1 in the standard of care group. The mean highest INR in both groups was 1.4 (range 1.2–1.6). The mean lowest recorded platelet level in the first 48 hours was 128.8 (range 87–160) in the standard of care group and 123.8 (range 49–229) in the experimental group. Infants in the experimental group had lower chest tube output overall than the standard of care infants. The mean days of intubation for standard of care infants was 5 days (range 1–15 days) and for experimental infants the mean was 3.7 days (range 0–16 d). The PICU length of stay was shorter for the experimental infants (6.9 vs. 12 d for standard of care). The total length of stay was also shorter for experimental infants (12.4 vs. 16.4 d for standard of care). Serum biomarkers of brain injury (s100b and Neuron specific enolase) were elevated in the immediate postoperative period for infants in the standard of care group compared with the experimental group but normalized more quickly for standard of care. DISCUSSION/SIGNIFICANCE OF IMPACT: This small pilot study suggests that mild hypothermia following congenital heart surgery in infants under the age of 12 months is safe as there was no increase in the rate of severe, moderate, or other adverse outcomes in infants who received the experimental treatment of delayed rewarming. This study provides evidence for the efficacy of the cooling blanket in regulating the temperature of infants after surgery. Trends toward lower chest tube output, shorter intubation and decreased length of stay are possibly the result of improved hemodynamic stability in the absence of postoperative fever. Future studies will need to assess the effect of mild hypothermia compared with a normothemic control group.

OBJECTIVES/SPECIFIC AIMS: The objective of this analysis was to characterize the impact of stress, both early life and chronic, on intravenous alcohol self-administration (IV-ASA) in healthy non-dependent drinkers using the Computer-Assisted Infusion System (CAIS). Personality measures also have shown to impact drinking behavior, particularly impulsivity. Few studies have assessed the impact of stress and impulsivity on drinking behaviors in a non-dependent population. METHODS/STUDY POPULATION: Healthy non-dependent drinkers (n=28) completed a CAIS session, where they push a button adlib to self-administer standardized IV alcohol infusions. Participants completed the Cumulative Chronic Stress interview and the Early Life Stress Questionnaire (ELSQ) for stress measures. The Cumulative Chronic Stress interview was broken up into 4 sections: major life events, life traumas, recent life events, and chronic stressors. The number of endorsed events was added up to create 4 separate scores. Subjective response and craving measures were collected serially using the Drug Effects Questionnaire (DEQ) and Alcohol Urge Questionnaire (AUQ). The Impaired Control Scale (ICS) assessed failed control over recent drinking in the past 6 months. Impulsivity was assessed using the NEO personality inventory, which included the N-impulsive sub-facet, as well as the UPPS-P Impulsive Behavior Scale. RESULTS/ANTICIPATED RESULTS: Results showed early life stress events (ELSQ) are related to more chronic stressors in the cumulative chronic stress interview (p=0.005). Participants with higher chronic stress scores showed lower subjective effects, as measured by the DEQ, following the priming exposure (p=0.036) but had more craving for alcohol as measured by the AUQ (p=0.009). A regression analysis showed the number of chronic stressful events predicted ICS failed attempts to control drinking (p=0.034), after covarying for sex. Participants with more chronic stressful events showed more impulsivity on the N-impulsivity measure (p=0.034) and the UPPS-P positive urgency measure (p=0.005). DISCUSSION/SIGNIFICANCE OF IMPACT: Non-dependent drinkers with more early life stress tend to have a higher number of chronic stressful events. More chronically stressful events were associated with feeling less effects of alcohol and higher craving for alcohol. Participants with more chronically stressful events also appear to have more failed attempts at controlling their drinking. Future analysis will assess for mediation and moderation of these factors. Chronically stressful events and impulsive behaviors could serve as important areas for intervention for better treatment outcomes for alcohol use disorders.