OBJECTIVES/SPECIFIC AIMS: In patients with recurrent glioblastoma (GBM) who undergo a second surgery following standard chemoradiotherapy, histopathologic examination of the resected tissue often reveals a combination of viable tumor and treatment-related inflammatory changes. However, it remains unclear whether the degree of viable tumor Versus “treatment effect” in these specimens impacts prognosis. We sought to determine whether the percentage of viable tumor Versus “treatment effect” in recurrent GBM surgical samples, as assessed by a trained neuropathologist and quantified on a continuous scale, is associated with overall survival. METHODS/STUDY POPULATION: We reviewed the records of 47 patients with histopathologically confirmed GBM who underwent surgical resection as the first therapeutic modality for suspected radiographic progression following standard radiation therapy and temozolomide. The percentage of viable tumor Versus “treatment effect” in each specimen was estimated by one neuropathologist who was blinded to patient outcomes. RESULTS/ANTICIPATED RESULTS: After adjusting for other known prognostic factors in a multivariate Cox proportional hazards model, there was no association between the degree of viable tumor and overall survival (HR 0.83; 95% CI, 0.20–3.4; p=0.20). DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that, in patients who undergo resection for recurrent GBM following standard first-line chemoradiotherapy, histopathologic quantification of the degree of viable tumor Versus “treatment effect” present in the surgical specimen has limited prognostic influence and clinical utility.

OBJECTIVES/SPECIFIC AIMS: MicroRNAs are small, non-coding RNAs that control gene expression by inhibiting protein translation. Preclinical studies in rodent stroke models suggest that changes in microRNA expression contribute to neural repair mechanisms. To our knowledge, no one has previously assessed microRNA changes during the recovery phase of human stroke. Our goal was to determine whether patients with significant upper limb recovery following stroke have alteration of neural repair-related microRNA expression when compared to those with poor recovery. METHODS/STUDY POPULATION: Plasma was collected at 19 days post-stroke from 27 participants with mild-moderate upper extremity impairment enrolled in the Critical Periods After Stroke Study. MicroRNA expression was assessed using TaqMan microRNA assays (Thermo Fisher Scientific). Good recovery was defined as ≥6 point change in the Action Research Arm Test (ARAT) score from baseline to 6 months. Bioinformatics analysis compared the plasma microRNA expression profiles of participants with good Versus poor recovery. Candidate biomarkers were identified after correcting for multiple comparisons using a false discovery rate <0.05. RESULTS/ANTICIPATED RESULTS: Eleven microRNAs had significantly altered expression in the good (n=22) Versus poor (n=5) recovery groups, with 2 showing increased expression—miR-371-3p and miR-520g, and 9 showing decreased expression—miR-449b, miR-519b, miR-581, miR-616, miR-892b, miR-941, miR-1179, miR-1292, and miR1296. Three of these could be implicated in neural repair mechanisms. Elevated miR-371-3p levels increase the likelihood that pluripotent stem cells will differentiate into neural progenitors. MiR-892b decreases levels of amyloid precursor protein, which has been implicated as a regulator of synapse formation. Finally miR-941, the only known human-specific microRNA, downregulates the CSPα protein which is involved in neurotransmitter release. DISCUSSION/SIGNIFICANCE OF IMPACT: This preliminary study suggests that circulating microRNAs in the plasma may help serve as biomarkers of neural repair and aid in understanding human neural repair mechanisms. If validated in larger studies with appropriate controls, these markers could aid in timing rehabilitation therapy or designing recovery-based therapeutics.

OBJECTIVES/SPECIFIC AIMS: The purpose of the present secondary data analysis was to examine the effect of moderate-severe disturbed sleep before the start of radiation therapy (RT) on subsequent RT-induced pain. METHODS/STUDY POPULATION: Analyses were performed on 676 RT-naïve breast cancer patients (mean age 58, 100% female) scheduled to receive RT from a previously completed nationwide, multicenter, phase II randomized controlled trial examining the efficacy of oral curcumin on radiation dermatitis severity. The trial was conducted at 21 community oncology practices throughout the US affiliated with the University of Rochester Cancer Center NCI’s Community Oncology Research Program (URCC NCORP) Research Base. Sleep disturbance was assessed using a single item question from the modified MD Anderson Symptom Inventory (SI) on a 0–10 scale, with higher scores indicating greater sleep disturbance. Total subjective pain as well as the subdomains of pain (sensory, affective, and perceived) were assessed by the short-form McGill Pain Questionnaire. Pain at treatment site (pain-Tx) was also assessed using a single item question from the SI. These assessments were included for pre-RT (baseline) and post-RT. For the present analyses, patients were dichotomized into 2 groups: those who had moderate-severe disturbed sleep at baseline (score≥4 on the SI; n=101) Versus those who had mild or no disturbed sleep (control group; score=0–3 on the SI; n=575). RESULTS/ANTICIPATED RESULTS: Prior to the start of RT, breast cancer patients with moderate-severe disturbed sleep at baseline were younger, less likely to have had lumpectomy or partial mastectomy while more likely to have had total mastectomy and chemotherapy, more likely to be on sleep, anti-anxiety/depression, and prescription pain medications, and more likely to suffer from depression or anxiety disorder than the control group (all p’s≤0.02). Spearman rank correlations showed that changes in sleep disturbance from baseline to post-RT were significantly correlated with concurrent changes in total pain (r=0.38; p<0.001), sensory pain (r=0.35; p<0.001), affective pain (r=0.21; p<0.001), perceived pain intensity (r=0.37; p<0.001), and pain-Tx (r=0.35; p<0.001). In total, 92% of patients with moderate-severe disturbed sleep at baseline reported post-RT total pain compared with 79% of patients in the control group (p=0.006). Generalized linear estimating equations, after controlling for baseline pain and other covariates (baseline fatigue and distress, age, sleep medications, anti-anxiety/depression medications, prescription pain medications, and depression or anxiety disorder), showed that patients with moderate-severe disturbed sleep at baseline had significantly higher mean values of post-RT total pain (by 39%; p=0.033), post-RT sensory pain (by 41%; p=0.046), and post-RT affective pain (by 55%; p=0.035) than the control group. Perceived pain intensity (p=0.066) and pain-Tx (p=0.086) at post-RT were not significantly different between the 2 groups. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that moderate-severe disturbed sleep prior to RT is an important predictor for worsening of pain at post-RT in breast cancer patients. There could be several plausible reasons for this. Sleep disturbance, such as sleep loss and sleep continuity disturbance, could result in impaired sleep related recovery and repair of tissue damage associated with cancer and its treatment; thus, resulting in the amplification of pain. Sleep disturbance may also reduce pain tolerance threshold through increased sensitization of the central nervous system. In addition, pain and sleep disturbance may share common neuroimmunological pathways. Sleep disturbance may modulate inflammation, which in turn may contribute to increased pain. Further research is needed to confirm these findings and whether interventions targeting sleep disturbance in early phase could be potential alternate approaches to reduce pain after RT.

OBJECTIVES/SPECIFIC AIMS: To investigate the prognostic value of left ventricular mitral annular longitudinal displacement (LD) measured with color tissue Doppler imaging (TDI) in a large population suffering from acute coronary syndrome (ACS). METHODS/STUDY POPULATION: In total, 501 ACS patients underwent an echocardiography within 9 days after a percutaneous coronary intervention. Regional LD was obtained from the 6 mitral annular regions with TDI and GLD was calculated as an average. RESULTS/ANTICIPATED RESULTS: During a median follow-up time of 4.4 years 46 ACS patients suffered CVD. Mean value of GLD in the population was 8.11mm (±2.4). GLD and LD obtained from the inferior wall remained significant independent predictors after multivariate adjustment for clinical parameters, GLD (HR: 1.43, 95% CI: 1.12–1.82, p=0.014, per 1mm decrease), inferior LD (HR: 1.38, 95% CI: 1.14–1.66, p=0.001). Furthermore, inferior wall LD was the primary source of prognostic information in GLD since only inferior LD remained significant when both measures were included in the same model: GLD (HR: 0.95, 95% CI: 0.64–1.40, p=0.781); inferior LD (HR: 1.60, 95% CI: 1.15–2.22, p=0.005). Of all walls, only inferior wall LD remained as an independent predictor after multivariate adjustment. DISCUSSION/SIGNIFICANCE OF IMPACT: GLD provides independent prognostic information in ACS patients over and beyond all conventional echocardiographic measures. Regional inferior LD was the primary source of prognostic information gained from GLD. GLD proved to be a better predictor of cardiovascular events than conventional echocardiographic measures. This could lead to better risk stratification in the clinical setting and open up for earlier intervention in high-risk individuals.

OBJECTIVES/SPECIFIC AIMS: A course of oral broad-spectrum antibiotics frequently has a positive effect on morbidity and mortality in severe acute malnutrition (SAM), but the actual mechanism for this effect is unknown. This mechanism is especially important to find and quantify because of the possibility that using antibiotics prophylactically may accelerate the danger from antibiotic resistant infections. This study aims to answer (1) how antibiotic therapy improves the nutritional recovery and (2) how much it affects the prevalence of resistance genes in the microbiome. METHODS/STUDY POPULATION: Stool samples were collected from children with SAM between 6 and 60 weeks of age who received either one week of amoxicillin or placebo (n=164). The children were followed for 12 weeks with longitudinal sampling, and a subset were followed out to 2 years. All samples were frozen at −80°C and prepared for metagenome shotgun sequencing via the Illumina Nextera platform. RESULTS/ANTICIPATED RESULTS: Antibiotic treatment at the start of the nutritional program is associated with significant improvements in weight gain, mid-upper-arm circumference, and graduation from the treatment program. It is also associated with qualitative decreases in early-life fermenter Lactobacillus and known enteropathogen Campylobacter. Two years after the use of amoxicillin, the Shannon diversity index is significantly higher than that of malnourished children (effect size 0.507, 95% CI: 0.204–0.630, p=0.0007), while children who received placebo are not distinguishable from malnourished children by the same metric (effect size 0.147, 95% CI: −0.311, 0.630, p=0.5878). Sustained antibiotic resistance gene enrichment within the microbiota did not occur, as the enrichment effects disappears by week 4 of follow-up. DISCUSSION/SIGNIFICANCE OF IMPACT: The use of amoxicillin to treat uncomplicated SAM has therapeutic benefits visible by anthropometry and by content of the gut microbiota. The main concern with the use of prophylactic antibiotics for this purpose is the effect on antibiotic resistance gene enrichment in the children’s microbiota. This concern was not supported here. The benefit/cost ratio for the use of prophylactic antibiotics for individuals in this cohort is positive when weighing effects on anthropometry, microbiome, and antibiotic resistance. The results of this study impact the treatment of millions of children each year at nutritional therapy clinics around the world.

OBJECTIVES/SPECIFIC AIMS: To examine the racial/ethnic variation in the relation between metabolic syndrome (MetS) components and cardiovascular disease (CVD) as well as examine the role of uric acid as a predictor of CVD among population with MetS. METHODS/STUDY POPULATION: We analyzed National Health and Nutrition Examination Surveys data (1999–2010) for adults aged >20 years with MetS. Using the ATP III clinical criteria for diagnosing MetS, subjects were classified as having MetS if they had ≥3 of the following: waist circumference ≥40 inches for men or ≥35 inches for women, triglyceride ≥150 mg/dL, HDL-C for men ≤40 mg/dL; women ≤50 mg/dL, pre-hypertension, or fasting glucose ≥110 mg/dL. We used multiple logistic regression in STATA 14 survey module to examine the relation between MetS components and CVD adjusting for age, gender, race/ethnicity, education, smoking, alcohol, albuminuria, glomerular filtration rate, C-reactive protein, uric acid and white blood count. To assess the racial/ethnic variation, we examined the same model in each race/ethnic group. RESULTS/ANTICIPATED RESULTS: Of the 3212 subjects, 78% were Whites, 10% were Blacks, and 15% had CVD. MetS components, CVD, and uric acid varied significantly by race/ethnicity (p<0.05). In the multivariate model, HDL-C level [odds ratio (OR)=1.5; 95% confidence interval (CI)=1.1–2.0], triglyceride level (OR=2.0; CI=1.4–2.9), and elevated uric acid (OR=1.4; CI=1.1–1.9) were independently related to CVD (p<0.05). While CVD was independently related to HDL-C, triglyceride, and elevated uric acid in Whites (p<0.05), it was associated with pre-hypertension and triglyceride in Blacks (p<0.05) and no predictors in Hispanics (p>0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: Elevated uric acid, HDL-C, and triglyceride levels are significant independent predictors of CVD among population with MetS. These predictors varied by race/ethnicity. Health care providers should be vigilant in the management of MetS components and control of uric acid level in each racial/ethnic group to prevent the CVD risk among the population with MetS.

OBJECTIVES/SPECIFIC AIMS: Central neuropathic pain is a severely disabling consequence of conditions that cause tissue damage in the central nervous system (CNS) such as multiple sclerosis (MS) and neuromyelitis optica (NMO). It impacts mood, mobility and quality of life, but is often refractory to common treatments. Scrambler Therapy is an emerging non-invasive pain modifying technique that utilizes transcutaneous electrical stimulation of nociceptive fibers with the intent of re-organizing maladaptive signaling pathways. It has been examined for treatment of peripheral neuropathy with favorable safety and efficacy outcomes, but its use in central neuropathic pain has not been reported. We aim to explore acceptability and safety of Scrambler Therapy through a Phase II sham-controlled trial in NMO, and describe its use to date in central neuropathic pain. METHODS/STUDY POPULATION: Two patients with longstanding central neuropathic pain who failed multiple drug trials were treated as proof-of-concept, supporting the recent launch of a Phase II randomized controlled trial in NMO where patients receive 10 daily Scrambler treatments versus sham. Safety and acceptability from those recruited to date will be reported. Acceptability is measured by adherence and responses to patient surveys. RESULTS/ANTICIPATED RESULTS: We plan to recruit 22 patients, randomized 1:1 into experimental and sham arms. We will present acceptability and safety data for Scrambler use in patients with NMO who have been recruited by the time of this conference, as well as effectiveness data from two cases that have been completed outside of the trial. One case involved a 65-year-old woman with a 4-year history of central neuropathic pain following a C3-C5 TM. Her numerical rating scale (NRS) pain score was reduced to 0/10 from a baseline score of 5/10. The second case involved a 52-year-old woman with a 13-year history of pain following a medullary cavernoma bleed. Her baseline NRS pain score was 9/10, which was reduced to 0.5/10 post-treatment. No adverse events were reported. Pain relief was sustained at 30 days’ post-treatment. DISCUSSION/SIGNIFICANCE OF IMPACT: We are investigating the acceptability and efficacy of Scrambler Therapy for central neuropathic pain treatment in NMO. Proof-of-concept was supported by two patients whose pain scores improved considerably more in response to this treatment than with previous pharmacologic and non-pharmacologic interventions. Results from this trial may support future investigation in other disorders that cause damage in the CNS, including MS and TM.

OBJECTIVES/SPECIFIC AIMS: Emotional processing theory and some observations suggest that activation of subjective and physiological distress during therapeutic exposure and habituation across exposure sessions are key to improvement. This study sought to determine whether initial subjective and physiological activation and between-session habituation would predict PTSD symptom reduction after a series of written trauma narrative exposure sessions. METHODS/STUDY POPULATION: In total, 29 urban-residing African-American participants with PTSD participated in four 30-minute writing sessions. Writing sessions 1 and 2 were 12 hours apart and session 3 and 4 were performed 1 week later, also 12 hours apart. PTSD symptoms were measured at baseline, after session 2, and 1 week after all 4 writing sessions with the Clinician Administered PTSD Scale. During each session, Subjective Units of Distress Scores (SUDS) were assessed 4 times and heart rate was measured continuously. RESULTS/ANTICIPATED RESULTS: Participants exhibited PTSD symptom improvement and habituation of subjective distress, but not physiological arousal, across writing sessions. First session baseline-corrected SUDS maximum and SUDS decrease from the initial to the final writing session were both positively associated with symptom improvement. DISCUSSION/SIGNIFICANCE OF IMPACT: Increased subjective, but not physiological, distress in the first exposure session and diminished subjective distress across sessions may be a helpful marker of emotional processing for clinicians and predictor of symptom improvement after written trauma narrative exposure.

OBJECTIVES/SPECIFIC AIMS: Peer groups are one of the strongest determinants of alcohol use and misuse. Furthermore, social influence plays a significant role in alcohol use across the lifespan. One of the factors that most consistently predicts successful treatment outcomes for alcohol use disorders is one’s ability to change their social network. However, the concept of social influence as defined by suggestibility or susceptibility to social influence has not yet been studied as it relates to drinking behavior and acute subjective response to alcohol. Our objective was to examine the relationship between suggestibility and alcohol consumption and responses, using an intravenous alcohol self-administration (IV-ASA) paradigm in social drinkers. METHODS/STUDY POPULATION: Healthy, social drinkers (n=20) completed a human laboratory session in which they underwent the IV-ASA paradigm. This consisted of an initial 25-minute priming phase, where participants 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 and average breath alcohol concentration (BrAC) and number of button presses. Subjective responses were assessed using the Drug Effects Questionnaire (DEQ) and Alcohol Urge Questionnaire (AUQ) collected serially during the session. Participants completed the Multidimensional Iowa Suggestibility Scale (MISS) to assess suggestibility. The Alcohol Effects Questionnaire (AEFQ) was used to assess alcohol expectancies and the Timeline Followback questionnaire measured recent drinking history. RESULTS/ANTICIPATED RESULTS: After controlling for drinking history, greater suggestibility significantly predicted greater average BrAC, greater peak BrAC, and a greater number of button presses (p=0.03, p=0.02, p=0.04, respectively) during the early open bar phase. Suggestibility significantly predicted subjective alcohol effects following the priming phase which included “Feel,” “Want,” “High,” and “Intoxicated” and was trending for “Like” (p=0.02, p=0.03, p=0.01, p=0.03, p=0.054, respectively) as well as AUQ (p=0.03). After controlling for drinking history, suggestibility significantly predicted “Feel,” “Like,” “High,” and “Intoxicated” peak scores during the open bar phase (p=0.03, p=0.009, p=0.03, p=0.03, respectively). There was no association between suggestibility and “Want More” alcohol. Suggestibility was positively associated with three positive expectancies (global positive; p=0.04, social expressiveness; p=0.005, relaxation; p=0.03), and one negative expectancy (cognitive and physical impairment; p=0.02). DISCUSSION/SIGNIFICANCE OF IMPACT: These results indicate that social drinkers that were more suggestible had higher alcohol consumption, greater acute subjective response to alcohol, and more positive alcohol expectancies. As such, susceptibility to social influence may be an important determinant of alcohol consumption, and may provide insight into harmful drinking behavior such as binge drinking. Future analyses should examine the impact of suggestibility on alcohol-related phenotypes across the spectrum of drinking from social to binge and heavy drinking patterns.

OBJECTIVES/SPECIFIC AIMS: Synthetic cannabinoids (SC) are widely available and are associated with acute psychosis. Our recent study indicated that SC using psychiatric inpatients admitted in 2014 had more psychotic symptoms, aggression, and agitation compared with cannabis [marijuana (MJ)] using patients. The current study will review more charts and will characterize the demographics and presentations of current SC Versus MJ using patients. METHODS/STUDY POPULATION: A chart review was conducted of patients admitted to a New York City inpatient dual diagnosis psychiatric unit from 2014 to 2016. Inclusion criteria were self-reported current SC use or MJ use, or urine toxicology (+) for MJ. RESULTS/ANTICIPATED RESULTS: In total, 585 charts met inclusion criteria, 168 reported current SC use (40 f, 128 m SC users; 122 f, 295 m MJ users). SC using patients were younger (p=0.050), more likely to be Black (p=0.003), and homeless or living in a shelter (p=0.001). SC users were also more likely to be agitated (OR: 2.26) and aggressive (OR: 2.04) and have psychotic symptoms (OR: 3.03) compared with MJ users. SC users received more PRN medication (p<0.001) and had longer lengths of stay (p=0.001). DISCUSSION/SIGNIFICANCE OF IMPACT: Results demonstrate that current SC users had a different demographic profile compared with current MJ users. Our results also support our previous findings: SC using patients were more likely to be agitated and aggressive and were more likely to demonstrate positive psychotic symptoms.

OBJECTIVES/SPECIFIC AIMS: The objective of the study is to test the effect of oral inorganic nitrate on the primary outcomes of exercise capacity and quality of life in patients who have undergone TAVR for severe aortic stenosis. We will also test the effect of the study drug on various physiology endpoints, including systemic vasodilator response to exercise, LV diastolic function and myocardial strain, late systolic LV load and pulsatile arterial wave reflections. METHODS/STUDY POPULATION: This is a randomized double-blind crossover clinical trial, in which 24 subjects who underwent TAVR for severe AS 3 or more months before enrollment will receive the following 2 interventions, in randomized order: (1) Potassium nitrate (KNO3), at a dose of 12–18 mmol/day by mouth for ~4 weeks, or (2) Potassium chloride (KCl), at a dose of 12–18 mmol/day by mouth for ~4 weeks. A 1-week washout period will be introduced between the 2 interventions. RESULTS/ANTICIPATED RESULTS: We hypothesize that sustained oral administration of potassium nitrate will lead to improvement of exercise capacity and quality of life in this population.DISCUSSION/SIGNIFICANCE OF IMPACT: His study will have a significant impact on assessment and management of patients after TAVR. We will gain a better understanding of physiologic abnormalities leading to exercise intolerance after TAVR. In addition, there are currently no proven therapies that improve exercise capacity in this population.

OBJECTIVES/SPECIFIC AIMS: Screening the general population for prostate cancer with prostate specific antigen (PSA) continues to be controversial. Patients with advanced heart failure undergoing evaluation for suitability for cardiac transplantation are often requested to undergo prostate cancer screening, with guiding evidence generated from the general population. The objective of this study is to determine the clinical implications of a positive prostate cancer screen result in this patient population. METHODS/STUDY POPULATION: A retrospective cohort study was performed on all men that were referred to a tertiary care cardiac transplant center between January 2000 and December 2015. Patients were classified as having either a “positive screen” (PSA≥4 ng/mL) or a “negative screen” (PSA<4 ng/mL) at the point of evaluation. The primary outcome of time to listing for cardiac transplant (days) was calculated from the date of referral to the date of listing. A multivariable Cox proportional hazards model was developed to assess the association between a positive prostate cancer test result and listing for cardiac transplantation. RESULTS/ANTICIPATED RESULTS: Among the 704 patients included in this study, 66 men (9.4%) had a positive prostate cancer screen result. Men with a positive prostate cancer screen were approximately 4 year older (mean 58.5 vs. 54.1 years), more likely to have a diagnosis of Ischemic Cardiomyopathy (74% vs. 53%) and require continuous mechanical support (61% vs. 16%) at the point of transplant evaluation. The median time for listing for cardiac transplant was greater in patients with a positive PSA (119 vs. 48 days, p<0.05). After adjusting for age, renal function, clinical status at evaluation, history of COPD, and year of referral, patients with a positive prostate cancer screen had a reduced hazards ratio (HR) for progressing to cardiac transplant listing compared with those with a negative screen (HR 0.58, 95%CI: 0.38–0.91). DISCUSSION/SIGNIFICANCE OF IMPACT: Screening patients undergoing cardiac transplant evaluation for prostate cancer with PSA has a low diagnostic yield. An individual’s PSA value is influenced by their age and clinical status at the time of screening, with a positive screen being associated with a reduced likelihood for progressing to listing for cardiac transplant.

OBJECTIVES/SPECIFIC AIMS: This study aims to assess the safety, feasibility, clinical benefits and pharmacodynamics of adding allopurinol to standard maintenance therapy that includes 6-mecaptopurine (6-MP) in pediatric patients with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma. Our goal is to investigate if allopurinol improves hepatotoxicity and GI toxicity, if it safely decreases acute neutrophil count (ANC), if it reduces the 6-MP dose required during chemotherapy, and if it works through our hypothesized mechanism by lowering the levels of the toxic metabolite, 6-methylmecaptopurine (6-MMP) and by raising the levels of the active metabolite, 6-thioguanine (6-TGN). METHODS/STUDY POPULATION: This is a single arm, nonblinded pilot study of patients under age 30 years who were being treated in the maintenance phase of therapy for ALL or lymphoblastic lymphoma, and had adverse effects such as high 6-MMP:6-TGN ratio, high ANC, and high liver enzymes. Patients enrolled were started with allopurinol in addition to ongoing oral chemotherapy. Data from beginning maintenance to end of chemotherapy was collected in the electronic medical record, EPIC for the 13 patients enrolled at Johns Hopkins, and data analysis was conducted using STATA and Excel. RESULTS/ANTICIPATED RESULTS: Initial data analysis reveals that the required dose of 6-MP after addition of allopurinol to the chemotherapy regimen was significantly lower compared with that before the addition of allopurinol in 11 out of the 12 patients assessed (p<0.05). Among the 10 patients that were assessed for 6MMP:6TG ratio, all had lower average 6MMP:6TGN ratios after allopurinol compared to before allopurinol; the percentage of weeks that goal 6MMP:6TGN ratio (<40) were maintained were statistically significant in 6 patients (p<0.05) and close to significance in 2 other patients (p=0.057). The percentage of weeks that patients maintained alanine aminotransferase levels below 120 was significantly greater after addition of allopurinol compared to before the addition of allopurinol in 9 out of 13 patients assessed, suggesting that allopurinol may be associated with reduced hepatotoxicity. Further data analysis is ongoing to assess the percentage of weeks that patients maintained goal total bilirubin, direct bilirubin, and ANC, as well as average number of admissions for infections and average number of therapy holds after allopurinol addition compared to before allopurinol addition. DISCUSSION/SIGNIFICANCE OF IMPACT: Allopurinol is associated with reduction in required 6-MP dose, decrease in the percentage of weeks that patients have hepatotoxicity, and reduction in the ratio of toxic metabolite to active anti-leukemic metabolite in several patients. We hope that the results of this study can be used for further research and for guiding clinical practice since there are no established guidelines in pediatric oncology regarding addressing side effects of oral chemotherapy using 6-MP. If allopurinol indeed is safe and effective, adding it to the standard chemotherapy regimen can lead to better tolerance and compliance to oral maintenance chemotherapy, and hopefully improved outcomes for children with ALL and lymphoblastic leukemia.

OBJECTIVES/SPECIFIC AIMS: Our study seeks to answer the following questions: (1) To determine whether higher numbers of gravidity and parity are associated with a decreased risk of mild cognitive impairment or dementia; (2) To determine whether higher numbers of gravidity and parity are associated with a decreased risk of amyloid deposition by PET MRI. METHODS/STUDY POPULATION: Our study population includes all female study participants in the Atherosclerosis Risk in Communities (ARIC) study who did not have a diagnosis of dementia before enrollment. Participants were also required to have been evaluated for cognitive impairment in the ARIC-NCS ancillary study, or to have received an MRI PET scan of their brain as part of the ARIC-PET ancillary study. Baseline information on the gravidity and parity of all the women was recorded at initial enrollment. We use statistical analyses and epidemiological measures to explore our study questions. For our first question, we use logistic regression to evaluate the association of gravidity and parity as two separate ordinal variables using adjudicated mild cognitive impairment (MCI) and dementia. For our second question, we use logistic regression to evaluate the association of gravidity and parity (again as ordinal variables) with amyloid positivity. We use STATA for our statistical analyses. RESULTS/ANTICIPATED RESULTS: We hypothesize that increased gravidity and parity will have either no effect or a protective effect against MCI, dementia, and amyloid deposition. Our preliminary analyses show that older age of a woman at first pregnancy and at first live birth are both positively correlated with increased incidence of cognitive impairment. No relationship was found between these surrogates of lifetime estrogen exposure and cerebral amyloid deposition. DISCUSSION/SIGNIFICANCE OF IMPACT: Multiple basic science and clinical research studies have shown that estrogen exposure has an effect on cognitive function, likely through a complex interplay of multiple physiologic systems. Our study expands the research in this area by using a large, established epidemiologic cohort to examine gravidity and parity as important factors in lifetime estrogen exposure as they relate to cognitive impairment and amyloid plaque deposition.

OBJECTIVES/SPECIFIC AIMS: Abnormal eating behavior is a core and distinguishing diagnostic feature of behavioral variant frontotemporal dementia (bvFTD) that differentiates it from other neurodegenerative disorders and late-life psychiatric conditions. Though it has been proposed that hyperphagia in bvFTD results from cognitive dysfunction, the observation of altered sweet preferences and food foraging indicate that bvFTD is accompanied by fundamental dietary changes associated with hypothalamic and insular atrophy. In the current study, we examined how cognitive dysfunction contributes to abnormal feeding behavior in bvFTD. METHODS/STUDY POPULATION: We analyzed first-visit eating and neuropsychological data from the National Alzheimer’s Coordinating Center database (7 centers; September 2017 data freeze) in a subset of bvFTD patients with clinician-rated characterization of disturbed feeding severity. Group differences in cognitive domains of attention, processing speed, language, memory, and executive functioning were examined between patients with abnormal eating behavior (n=59) and a demographically-matched sample of patients with normal feeding behavior (n=60). Group differences in informant-reported empathy, behavioral inhibition, and depressive symptoms were also examined. RESULTS/ANTICIPATED RESULTS: Cognitive profiles in bvFTD patients did not vary as a function of disturbed feeding behavior. In a subset of cases pathologically-confirmed at autopsy, processing speed was better in cases with abnormal feeding behavior. No significant group differences were found for behavioral indices. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that cognitive dysfunction is not the sole driver of abnormal eating behavior in bvFTD. Future studies with comprehensive characterization of feeding behavior, cognition and physiological/neuroimaging indices are warranted.

OBJECTIVES/SPECIFIC AIMS: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects one in 68 children. Children with ASD have 2 core areas of difficulty: social communication skills and restricted and repetitive interests and patterns of behavior. Children with social skills deficits are at higher risk of developing mental health problems, and underdeveloped social skills predict poorer quality of life in adulthood. Therapies have been developed to help people with ASD improve social abilities in childhood, often involving a clinician directly teaching social skills lessons, either one-on-one or in a group setting. However, children with ASD can become anxious when interacting with other people and have an intrinsic motivation to interact with technology. To capitalize on this interest, this research team developed a robot, the socially animated machine (SAM) to teach social skills to children with ASD. Previous research found that this intervention was feasible and enjoyable for children with ASD and average cognitive ability, and participants improved in complex emotion recognition following intervention. The purpose of this study was to determine whether participants of all IQ levels were motivated by the SAM intervention, and whether they improved on emotion identification, facial recognition, social skills, and adaptive behavior. METHODS/STUDY POPULATION: This study recruited 20 children with ASD ages 5–14. Children completed tasks measuring ASD symptoms, IQ, receptive language, facial recognition, and emotion identification and were assigned to the control group (nonemotion dance games with SAM robot) or the intervention group (emotion games with SAM robot). Parents and teachers completed questionnaires about the child’s social skills. Following the robot intervention, facial recognition, emotion identification, and social skills were measured again, and parents and children rated participant enjoyment during the robot interaction. RESULTS/ANTICIPATED RESULTS: Overall, parents and children in both groups rated the robot interaction as highly enjoyable and motivating (parent ratings: M=26.4 out of 30, child ratings: M=17.5 out of 20). There were no differences between groups on post-test measures when controlling for pre-test scores (all p>0.05). Both groups improved over time on emotion identification accuracy (intervention: M=13.0% improvement, t=2.57, p<0.05; control: M=10.2% improvement, t=2.38, p<0.05) and parent-rated social skills (intervention: pre-test M=113.8, post-test M=100.6, t=−3.37, p=0.01; Control: pre-test M=107.9, post-test M=89.0, t=−2.83, p<0.05; decrease in scores indicates improvement). Teachers saw a decrease in problem behaviors for the intervention group (pre-test M=127.4, post-test M=119.6, t=−3.79, p<0.01, decrease in scores indicates improvement). DISCUSSION/SIGNIFICANCE OF IMPACT: This study shows that children with ASD and all levels of cognitive ability enjoyed and were motivated by the SAM robot intervention. This is particularly important for children with ASD who often have difficulty with attention and motivation. Children who are intrinsically motivated by the learning process will be more likely to benefit from it; therefore, continuing to pursue the methodology of robot-based interventions with this population is a worthwhile endeavor.

OBJECTIVES/SPECIFIC AIMS: Afebrile septic patients are twice as likely to die and develop nosocomial infections as compared with those with fever; the reason for these differences is unknown. One hypothesis is that elevated temperatures directly boost immunity and inhibit microorganism growth. However, there is little data examining the clinical effects of warming septic patients. The goal of this study was to determine whether warming afebrile septic patients to fever-range hyperthermia with noninvasive forced air warmers is feasible and safe. METHODS/STUDY POPULATION: This is an ongoing randomized trial on afebrile mechanically ventilated patients with severe sepsis. The intervention consisted of 48 hours of external warming with a forced air warming device to a goal core temperature of 1.5°C higher than the lowest recorded temperature within the 24 hours preceding enrollment. Efficacy of the intervention and adverse event data (i.e., increases in heart rate and vasopressor doses) were collected. Clinical outcomes included 28-day mortality and acquisition of secondary infections. RESULTS/ANTICIPATED RESULTS: In total, 18 patients were randomized to the control and warming groups, respectively. Baseline characteristics (including demographics, comorbidities, and illness severity scores) were similar among the 2 groups, except the control group had more males (61% vs. 28%, p=0.04). Median (IQR) body temperature averaged over the 48-hour intervention period was higher in the warming group [38.2 (37.6, 38.6) vs. 37.1 (36.4, 37.4) °C, p<0.001). Patients in the warming group achieved core temperatures above their goal for a median of 37 (IQR 11, 45) hours during the 48-hour intervention period. There were no differences in heart rate or vasopressor dose changes or acquisition of secondary infections between the groups. Eight (44.4%) control patients and 3 (16.7%) warmed patients died by day 28 (p=0.07). DISCUSSION/SIGNIFICANCE OF IMPACT: Externally warming severe septic patients with forced air warming devices effectively raises core body temperature and is safe. Additional research will focus on cellular and immunological changes seen in warmed Versus control patients.

OBJECTIVES/SPECIFIC AIMS: Although parent involvement is recognized as an integral autism intervention component, and two-thirds of children are currently raised in 2-parent families, the majority of ASD parent research to date has focused on mother-implemented interventions, and fathers have been largely overlooked. However, fathers use interaction styles and language models that are different from mothers and may benefit children with ASD in unique ways. Thus there is a critical need in the field to expand our understanding of the potential contributions of various caregivers to communication outcomes. This investigation aimed to address this void in the research literature and contribute to clinical practice by including fathers in parent-implemented intervention, and adapting parent-implemented autism intervention to fit paternal interaction and communication styles. Specifically, this pilot study investigated the effects of a father-mediated intervention on parent use of responsive verbal and play strategies. Distal effects on child communication and pre-post changes in parental stress levels were also investigated. METHODS/STUDY POPULATION: A single subject, multiple baselines across strategies experiment was conducted with one dyad (i.e., father, child with ASD). In-home father coaching sessions were delivered weekly, targeting 4 responsive strategies (i.e., follow-in comments, follow-in directives, symbolic object play, rough-tumble play). Single subject designs are particularly suitable for autism interventions, as they allow for experimental control with participants who are from heterogeneous populations (McReynolds and Kearn, 1983). Child participant was 3 years, 1 month at the start of intervention and had previously received a received community diagnosis of ASD by a psychologist. Throughout the duration of the study, the child participant attended part-day community-based day care and received 20 hours per week of Applied Behavioral Analysis intervention both in-home and community daycare, as well as occupational therapy and speech-language therapy for 1 hour per week. The participating father was a biological parent who resided with the child continuously since birth. In addition, the father had no other formal parent training in communication intervention before participating. RESULTS/ANTICIPATED RESULTS: The results of the father-implemented intervention program yielded positive results for both father and child participant. The father quickly achieved a high level of competency using 3 of the 4 targeted strategies (i.e., follow-in comments, follow-in directives, and rough-and-tumble/physical play). Follow-in comments were used more frequently than follow-in directives and rough-and-tumble play strategies were used more frequently than symbolic play. Child use of single words increased over baseline and beginning use of multiword utterances was documented. Pre-post changes in parental stress for participating father and his spouse were not significant, however patterns of change across Parental Stress Index subscales scores were noted. DISCUSSION/SIGNIFICANCE OF IMPACT: This pilot investigation provided information regarding the treatment efficacy of a clinically relevant instructional program designed to enhance fathers’ ability to use responsive strategies to increase communicative acts or children with ASD. The results of this investigation advance clinical practice in the ASD field by providing intervention data relating to the efficacy of father-implemented instructional programs on child communication goals.

OBJECTIVES/SPECIFIC AIMS: Patients with gynecologic cancer are known to have an increased risk of venous thromboembolism (VTE) in the postoperative period secondary to hypercoagulability from both malignancy and pelvic surgery. Recent literature suggests that chemotherapy itself may be thrombogenic and prophylaxis may be beneficial in ambulatory patients receiving chemotherapy. Although extended VTE prophylaxis is commonly given after surgical staging, administration of prophylactic anticoagulation during chemotherapy or radiation treatment is not routinely performed. This study seeks to characterize risk factors and timing of VTE in a cohort of women diagnosed with uterine serous carcinoma (USC). METHODS/STUDY POPULATION: After institutional review board approval, a cross-sectional study was performed of all women diagnosed with USC between January 1999 and January 2016 at Albert Einstein College of Medicine. Data analysis was performed using Stata version 14.2 (Stata Statistical Software: Release 14, 2015. College Station, TX: StataCorp LP). Baseline clinical data was analyzed to calculate descriptive statistics. Normality of continuous variables was visually assessed and if no substantial violations were noted, data was reported as means±standard deviations. Otherwise, they were reported as medians with interquartile ranges. Categorical data was presented as number of patients with percentages. Bivariate analysis was performed to assess the association between clinical variables and diagnosis of VTE. Continuous variables (age, body mass index, number of risk factors for VTE) were visually assessed for normality. Levene’s test was used to assess for equal variance among groups. If no substantial violations were noted, means and standard deviations were calculated using 2 sample t-test for equal variance. Variables violating normality assumptions were analyzed using the Mann-Whitney U-test, calculating medians and interquartile ranges. Categorical and dichotomous variables (VTE risk factors, race, stage) were examined using the χ2 test or Fisher’s exact test (if expected values for more than 20% of cells were less than 5). Odds ratios were reported with 95% confidence intervals. Using a backwards stepwise elimination approach, a multivariable logistic regression model was fit to accurately examine association of risk factors with VTE, adjusting for other covariates. The resulting model was assessed for calibration and discrimination using Hosmer-Lemeshow test for goodness of fit, classification table, and ROC curve. Regression diagnostics were run in order to identify potentially influential covariate patterns in the model. First-order interactions were assessed for using product interaction terms (interaction defined as p-value for the likelihood ratio test <0.05). The resulting model was assessed for calibration and discrimination using Hosmer-Lemeshow test for goodness of fit, classification table, and ROC curve. A Cox proportional hazards model was also fit in order to examine the association between individual covariates and time to clot development. Log-rank testing was performed to compare survivorship experience by groups and survivorship curves were generated using the Kaplan-Meier method. Assumptions of the proportional hazards model was confirmed visually using log-log plots and goodness of fit assessment. RESULTS/ANTICIPATED RESULTS: A total of 413 patients were identified for inclusion in the study. The majority of patients (83%) were of non-White race. Bivariate analysis revealed no significant associations between age, BMI, or race with diagnosis of VTE (p=0.75, 0.49, and 0.28, respectively). Patients who had more than 2 risk factors for VTE had a significantly increased likelihood of VTE diagnosis (p=0.02). There was a highly significant association between stage of USC and diagnosis of VTE (p=0.005). Patients with stage III and stage IV cancer were 2.4 and 3.5 times more likely to develop VTE than patients with stage I cancer (95% CI: 1.09–5.30, 1.74–6.83, respectively). Of the 70 patients who were diagnosed with VTE, most were not postoperative (64.3%) and a large proportion developed clots while receiving chemotherapy (35.7%). Patients who developed VTE while on chemotherapy had a median Khorana score of 1 (IQR: 1, 2). In logistic regression modeling examining association of VTE with potential risk factors, covariates selected as significant for inclusion at the p<0.25 level included cancer stage, composite number of risk factors, diabetes, hypertension, cardiovascular disease (CVD), and COPD. Composite risk score was identified to be a potential confounder of the relationship between individual risk factors and development of clot and was therefore left in the model for adjustment. After adjusting for other covariates, only stage 4 disease (OR: 2.66, 95% CI: 1.53, −4.64) and hypertension (OR: 2.90, 95% CI: 1.14–7.36) were associated with development of VTE and were included in the final model. No concerning violation of assumptions of logistic regression or interaction was identified. The Hosmer-Lemeshow goodness of fit test identified that the model was well-fit using 10 groupings (p=0.35) and receiver operator characteristic testing showed that the model had acceptable discrimination with a ROC value of 0.7. The final model was found to classify 83.1% of participants correctly. Regression diagnostics identified 4 potentially influential covariate patterns. These patterns were eliminated from the model and no meaningful differences were noted. Patients contributed a total of 16,414 person months of analysis time in study follow-up. A negative, linear association was noted between stage of cancer and time to clot development. Long-rank testing revealed a significant difference in failure by stage of disease (p<0.001) and presence of hypertension (p=0.03). Cox proportional hazard modeling revealed that after adjustment for other covariates, only cancer stage and the presence of cardiovascular disease were significantly associated with time to failure. Patients with cardiovascular disease had a 2.02-fold increased risk of CVD compared to those without CVD (95% CI: 1.16–3.47). Those with stage 3 and 4 cancer were 3.19 (95% CI: 1.53-6.64) and 8.05 (95% CI: 4.11–15.78) fold more likely to develop VTE compared to those with stage 1 disease, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study demonstrated that patients with USC are at high risk of developing VTE at all time points after their disease diagnosis, not just those who have undergone recent surgery. This risk is highest for women with hypertension, CVD, and stages III and IV disease. The fact that patients who developed clots on chemotherapy had an average Khorana score of 1, suggesting that they would not have been successfully risk stratified using previously published tools. To the best of our knowledge, this is the first study to report a high hazard for VTE in patients with serious endometrial cancer even several months after surgical staging. Although this is a retrospective study and cannot make inferences about VTE incidence, it generates the hypothesis that extended VTE prophylaxis may be beneficial in this cohort of patients regardless of their latency from surgical staging. Large randomized studies are needed to test this hypothesis.

OBJECTIVES/SPECIFIC AIMS: Acute care research is a unique area of clinical research that demands specialized skills, knowledge, and talents from empathetic professionals working in the field. Building off existing competencies for clinical research professionals, the Cincinnati Acute Care Research Council (ACRC) developed additional areas of competency for professionals working in the acute care research discipline. METHODS/STUDY POPULATION: Qualitative data obtained from job shadowing, clinical observations, and interviews were analyzed to understand the educational needs and desires of the acute care research workforce. We then utilized Bloom’s Taxonomy to build acute care research competencies that are measurable for job performance and build off of foundational clinical research professionals’ domains and competencies developed by the Joint Task Force of Clinical Trial Competency. RESULTS/ANTICIPATED RESULTS: Results suggest 35 special interest competencies for acute care clinical research professionals under 8 common domains set by the Joint Task Force of Clinical Trial Competency. Additionally an approved ACRC tactic, from actionable learnings through community assessments throughout 2017, is the creation of a Task Force made up of acute care research Principal Investigators and Clinical Research Directors to focus on the identified training and professional development obstacles in the clinical research enterprise. DISCUSSION/SIGNIFICANCE OF IMPACT: The competencies developed for acute care research should serve as guidelines for training a workforce prepared for the challenges of conducting research with each acute audience, as its own vulnerable population. These competencies will guide development of a multi-pronged program of professional development that will include new hire onboarding, new hire on-job training, and ongoing on-job training.