OBJECTIVES/SPECIFIC AIMS: This research examined 3 aims to address the need to understand and quantify exertion in infants. Aim 1: Develop a schema to identify and code exertional behaviors in infants during treadmill stepping. Aim 2: Establish feasibility for the schema’s use with clinical populations. Aim 3: Pilot the schema in a study designed to induce infant exertion. METHODS/STUDY POPULATION: Aims 1 and 2 were achieved using existing treadmill stepping data. The data used in Aim 1 included eight typically-developing infants (age 7-10 months) who were able to sit independently, but not walk. The data used in Aim 2 came from two separate data sets from infants who took more than 10 steps in a 30-second trial: Data set A included six typically-developing infants (age 2-5 months) who were unable to sit independently (developmentally comparable to atypical populations who might receive treadmill interventions). Data set B included six infants with Spina Bifida (age 3-10 months). Aim 3 was addressed with a prospective study using an exertion model. Pre-walking, typically developing infants (age 8-10 months) underwent five total stepping trials. Trial 1 determined the infant’s individualized maximum stepping speed; trials 2-5 were each 60 seconds and alternated between a baseline stepping speed of.20 m/s and the infant’s maximum stepping speed determined in trial 1. All video data were coded for step type, step frequency, and exertional behavior. RESULTS/ANTICIPATED RESULTS: Aim 1: Two behaviors were identified and determined to capture infant exertion: foot dragging and leg crossing. Aim 2: The feasibility of capturing exertion with these two behaviors was established for young infants and infants with neuromotor delays, with exertional behaviors increasing with stepping exposure (p< 0.05). Aim 3: Total exertion (foot dragging + leg crossing) was higher in the maximum speed trials compared to baseline trials (p = 0.005). DISCUSSION/SIGNIFICANCE OF IMPACT: Exertion in infants can be quantified. The exertion schema developed with this study will support the development of dosing guidelines for infant treadmill intervention. The next step in this line of research is to examine the correlation between infant exertion and heart rate, in effort to move from behaviorally-informed protocols to more precise, individualized protocols based on the physiological response of the infant.

OBJECTIVES/SPECIFIC AIMS: Glaucoma is a leading cause of irreversible blindness worldwide; in the United States alone, over 2.7 million individuals are affected. Various risk factors for glaucoma are known and include age, race/ethnicity, genetics, and ocular measures. Despite numerous studies, molecular and environmental factors that contribute to glaucoma remain elusive. Our objective was to conduct a genome-wide association for glaucoma among black and white HRS respondents, and to determine the feasibility for future analyses examining shared genetic markers between glaucoma and other comorbidities, behaviors, and environmental risk factors. METHODS/STUDY POPULATION: The University of Michigan Health and Retirement Study (HRS) is a longitudinal survey of a representative sample of Americans over the age of 50. Supported by the National Institute on Aging and the Social Security Administration, the HRS is designed to provide reliable data on the decisions, choices, and behaviors of people as they age and respond to changes in public policy, the economy, and health. The study obtains information every two years about income and wealth, health and use of health services, work and retirement, and family connections. Through its unique and in-depth interviews, the HRS provides an invaluable and growing body of multidisciplinary data that researchers can use to address important questions about the challenges and opportunities of aging. Because of its innovation and importance, the HRS has become the model and hub for a growing network of harmonized longitudinal aging studies around the world. Saliva was collected on half of the HRS sample each wave starting in 2006 and respondents were genotyped on the Illumina Human Omni2.5-Quad (Omni2.5) BeadChip at the NIH Center for Inherited Disease Research. We accessed survey results to evaluate prevalence of glaucoma in this dataset and performed a genome-wide association study (GWAS) adjusting for age, sex, and significant Principal Components and stratifying by self-reported race (White / Black). RESULTS/ANTICIPATED RESULTS: Of 8179 respondents passing quality filters, 6409 (78.40%) were white and 985 (12.05%) were black. Self-reported glaucoma prevalence was 7.85% and 16.34% in white and black respondents, respectively. White respondents had a mean age of 76.97 (SD 7.53) and were 57.25% female. Black respondents had a similar mean age of 74.96 (SD 7.27) and were 62.54% female. More than 87% of both groups were assessed in 2012. Preliminary GWAS analyses did not replicate known glaucoma loci and no variants attained genome-wide significance. A suggestive variant (p<1e-05) in the black population was within 10kb of a known locus, rs1196998. Future analyses will evaluate genetic association with combinations of glaucoma and comorbidities. DISCUSSION/SIGNIFICANCE OF IMPACT: Glaucoma risk is higher in minority groups than in whites, and the majority of reported genetic studies of glaucoma have been performed in individuals of European descent. It is imperative to better understand the role of genetics, environment, and health behavior in glaucoma risk. Further, understanding common mechanisms underlying diseases that co-occur with glaucoma could illuminate novel disease mechanisms that can be targeted for early intervention and/or treatment.

OBJECTIVES/SPECIFIC AIMS: The prevalence of BPH, coupled with associated disability ranging from quality of life impairments to hospitalization, has spurred decades of research into its pathophysiology, diagnosis, treatment, and outcomes. For these reasons, we conducted a study to characterize the current landscape of BPH literature, including the most commonly cited articles impacting the field. METHODS/STUDY POPULATION: We used the Web of ScienceTM databases to conduct a bibliometric analysis of the top 100 leading BPH articles. Bibliometric analyses are quantitative approaches examining the impact of academic literature. We used the following search terms: ‘benign prostatic hyperplasia’ and ‘benign prostatic enlargement.’ We identified and characterized the 100 most-cited BPH articles including their citations, journal, author, year, and country through September 2018. RESULTS/ANTICIPATED RESULTS: The top 100 BPH articles were published between 1978 and 2012. The number of citations ranged from 143 to 2,158 across 26 different journals, including 9 urology-specific journals. The Journal of Urology (5-year impact factor: 4.91) was the most published journal with 26 articles, followed by European Urology (5-year impact factor: 15.66) with 16, and Urology (5-year impact factor: 2.39) with 13. The oldest 10 articles in the top 100 mainly focused on BPH etiology/pathogenesis, while the newest 10 articles mainly focused on medical treatment. The 1990’s was the most productive decade accounting for nearly half of the top 100 articles (n=46). Eight authors had two or more first author publications, and 8 institutions had five or more publications in the top 100. Thirteen different countries were represented in the top 100 articles, with the US (n = 64), Italy (n=7), and Germany (n=5) being the most common. The articles were published in the following Web of Science Categories: Urology & Nephrology (n=68), Medicine, General & Internal (n=15), and Endocrinology & Metabolism (n=7). DISCUSSION/SIGNIFICANCE OF IMPACT: This study represents the first bibliometric analysis of the leading 100 BPH articles impacting the academic literature. The literature focus has evolved from BPH pathogenesis/etiology to treatment, and was primarily published in 3 specialty journals. Our findings highlight the most impactful BPH literature, and may be used to guide research and funding priorities for this increasingly common condition.

OBJECTIVES/SPECIFIC AIMS: This study aims to identify genetic biomarkers of GDM and facilitate the understanding of its molecular underpinnings. METHODS/STUDY POPULATION: We identified a cohort of mothers diagnosed with GDM in our longitudinal birth study by mining Electronic Health Records of participants utilizing PheCode map with ICD-9 and ICD-10 codes. We verified each case using ACOG’s GDM diagnosis criteria. RESULTS/ANTICIPATED RESULTS: Whole genome sequencing (WGS) data were available for 111 confirmed cases (out of 205) and 706 controls (out of 1,429) from different ancestries (412 EUR, 256 AMR, 56 EAS, 26 SAS and 18 AFR; 49 OTHER). SAS had the highest incidence of GDM at 38.46% and EUR had the lowest at 6.55%. We performed logistic regression using computed ancestry, age and BMI as covariates to determine if any variants are associated with GDM. The top variant (rs139014401) was found in an intron of DFFB gene, which is p53-bound and regulates DNA fragmentation during apoptosis. We will investigate the robustness of 49 identified variants and will separate the cohort by ancestry to detect population-specific differences in the top loci. DISCUSSION/SIGNIFICANCE OF IMPACT: Identification of molecular biomarkers in GDM across different ancestral backgrounds will address a gap in current GDM research. Findings may enhance screening and enable clinicians to identify those at risk for developing GDM earlier in the pregnancy. Early management of mothers at risk may lead to better health outcomes for mother and baby.

OBJECTIVES/SPECIFIC AIMS: I would like to make clinicians aware about prescription opioid use and glycemic control among patients with diabetes. This is a quality of care issue that increases the disease burden for two conditions opioid dependence and diabetic complications. Big data analytics can bring out this quality of care issue and help in changing clinical practice through precision medicine METHODS/STUDY POPULATION: This is a population health study of patients on prescription opioid pain medications in Erie county medical center and local out patient clinic. The electronic data from the hospital records and Outpatient were collected, merged and de identified. The database was saved in a protected environment and made accessible to researchers through a secure login. The data was queried for the number of patients with diabetes. The glycohemoglobin levels were collected and then the analysis was made RESULTS/ANTICIPATED RESULTS: It was found that only 63 of the 89 patients with DPN and 156 of the 570 patients without DPN had any measurement of HbA1c in our data. It was found that 86 out of 156 patients without DPN had suboptimal glycemic control with a glycohemoglobin level > 7% while 36 out of 63 patients with DPN had a glycohemoglobin > 6.7%. The odds of patients with DPN having poor glycemic control is 0.57 while the odds of having poor glycemic control without DPN is.55. The relative risk being 1.03. DISCUSSION/SIGNIFICANCE OF IMPACT: Our population study revealed suboptimal glycemic control among a large set of patients in Western New York with a diagnosis of diabetes mellitus and a concurrent prescription for an opioid pain medication. A significant percentage of patients in our study population with a diagnosis of DPN might benefit in terms of decreased painful symptoms of neuropathy from monitoring and attempting to improve glycemic control. Additionally, in our patient population, there were no patients with diabetic peripheral neuropathy prescribed pregabalin or duloxetine, the first-line FDA-approved medications for painful DPN, Based on our population study, the quality of care for diabetic patients with DPN who are prescribed opioid pain medications should be monitored closely. First-line, FDA approved anticonvulsants and antidepressants should be considered for the treatment of painful symptoms when necessary. Attention should be directed towards monitoring and improving glycemic control in patients without DPN receiving opioid pain medications to attempt to prevent or delay the microvascular complications of diabetes, including the onset of painful peripheral neuropathy.

OBJECTIVES/SPECIFIC AIMS: The objective of this study is to identify and categorize non-invasive measurement methods for autonomic nervous system (ANS) symptoms that develop in hypoglycemic episodes. METHODS/STUDY POPULATION: We first reviewed literature for hypoglycemia symptomology. We then performed a selective literature review of Google Scholar, PubMed and Scopus for an ANS symptom and/or synonyms and the words ‘sensor’ or ‘detection’, e.g. ‘sweat sensor’ and ‘tremor detection’, studies utilizing non-invasive measurements in DM, and datasets of non-invasive measurements in DM. Measurement methods were then organized based on the ANS symptoms and existing metadata models for harmonizing sensors and surveys. RESULTS/ANTICIPATED RESULTS: We identified several measurement methods to for ANS symptoms during hypoglycemic events: thermometer, accelerometer, electrocardiogram (ECG), galvanic skin response (GSR), image processing, infrared imaging, thermal actuator, and ecological momentary assessment (EMA). The stage of implementation varied across the measurement methods from under development, to use in research and clinical settings, and even commercially available consumer products. Measurement methods that could be worn as wrist-band wearables or as film-based epidermal sensors would be capable of automatically gathering data with little to no effort required of the person wearing the device. Image-based methods would require the individual to actively engage in generating a photograph for analysis. In the case of EMA’s, a message containing a question is sent to the individual, often via text message, soliciting short and immediate responses. It is anticipated that one sensor alone would not be sufficient to measure ANS responses to hypoglycemia, but rather several data points would be required. For example, if the GSR was the only signal, sweat in response to vigorous exercise or a warm environment would inject noise into the signal. Including the accelerometer data would allow for the identification of body movement which would indicate exercise, while an ECG signal could confirm the exercise. DISCUSSION/SIGNIFICANCE OF IMPACT: Impaired awareness of hypoglycemia (IAH) is a complication that develops in about 30% of type 1 DM and 10% type 2 DM populations. In individuals with intact awareness of hypoglycemia, the ANS leads to symptoms which includes: shaking, trembling, anxiety, nervousness, palpitation (i.e. change in heart rate and/or function), clamminess, sweating, dry mouth, hunger, pallor (i.e. drop in blood flow and/or skin-surface temperature), and pupil dilation. IAH is defined as the onset of hypoglycemia before the appearance of autonomic warning symptoms. IAH is caused by repeated exposures to low blood glucose levels, which reduces the body’s ability to sense hypoglycemia, and therefore it is difficult for patients to recognize and self-treat. Individuals with IAH are six times more likely to experience severe hypoglycemia, an emergent condition which can lead to unconsciousness, seizure, coma, and death. Clinical investigators are developing interventions that aim to improve awareness of hypoglycemia. Surveys, observations by clinicians, and laboratory tests, often carried out in highly controlled in-patient settings, are currently used to assess the severity of IAH and the ANS’s ability to respond to hypoglycemia. In other disease states, for example heart disease and Parkinson’s disease, electrocardiograms and accelerometers have been used to assess heart function and tremor, respectively. However, there is currently a barrier to examining the efficacy of IAH interventions in real world settings as there are no established objective and non-invasive means to measure ANS symptoms due to hypoglycemia. This work encompasses the first important step necessary to direct translational researchers interested in testing the efficacy of IAH interventions and developing diagnostic tools for IAH in real-world studies outside the clinic. Next steps include evaluating these sensors and specifying EMA surveys, designing studies, and integration and assimilation of these data streams to identify true events of IAH by leveraging informatics platform such as the Utah PRISMS Informatics Ecosystem. Investigators would then be able to conduct studies that aim to develop and validate models that take sensor and EMA data as the input to detect and assess the severity of IAH.

OBJECTIVES/SPECIFIC AIMS: Patients are increasingly using online materials to learn about gynecologic cancer. Recent studies demonstrate that 85-96% of patients with a gynecologic malignancy utilize the Internet as a health resource. Providers can refer patients to educational materials produced by major medical associations available on their websites. However, patient educational materials (PEMs) published by professional organizations from other surgical specialties have been shown to be difficult to read for the average American. The NIH and AMA recommend that PEMs be written between a sixth and eighth grade reading level. In this study, we assess the readability of online PEMs on gynecologic cancer published by major medical associations. METHODS/STUDY POPULATION: Seven national medical association websites with PEMs on gynecologic malignancy were surveyed: American College of Obstetricians and Gynecologists, Center for Disease Control, Foundation for Women’s Cancer, National Cancer Institute, National Cervical Cancer Coalition, National Ovarian Cancer Coalition, and Society of Gynecologic Oncology. Online PEMs were identified and analyzed using five validated readability indices. One-way ANOVA and Tukey’s test were performed to detect differences in readability between publishers. RESULTS/ANTICIPATED RESULTS: Two hundred and thirty PEMs were included in this analysis. Mean readability grade levels with standard deviation were: 11.3 (2.8) for Coleman-Liau index; 11.8 (3.2) for Flesch-Kincaid; 11.1 (1.2) for FORCAST formula; 12.5 (2.7) for Gunning FOG formula; 12.1 (2.6) for New Dale-Chall formula; and 13.5 (2.5) for SMOG formula. Overall, PEMs were written at a mean 12th grade reading level. Only 4.3% of articles were written at an 8th grade reading level or below. ANOVA demonstrated a significant difference in readability between publishing associations (p<0.01). PEMs from the Center for Disease Control had a mean 10th grade reading level and were significantly lower than all other organizations. PEMs from The Foundation for Women’s Cancer had a mean 13th grade reading level and were significantly higher than most other organizations. DISCUSSION/SIGNIFICANCE OF IMPACT: Gynecologic oncology PEMs available from major medical association are written well above the recommended sixth to eight grade reading level. Simplifying PEMs may improve patient understanding of their disease and facilitate physician-patient communication.

OBJECTIVES/SPECIFIC AIMS: More than half a million adult patients nationally undergo cardiac surgery each year. Reintubation following cardiac surgery is common and associated with higher short- and long-term mortality, increased cost, and longer lengths of stay. The reintubation incidence is estimated at 5-10%. Patients undergoing cardiac surgery are increasing in age and comorbidity burden, and receive increasingly complex cardiac surgical procedures, complicating decision making around when to extubate postoperative patients. Compounding this complexity are financial pressures to maintain high throughput and maximize ICU bed availability. Providers are often compelled to extubate high-risk patients earlier, despite the potential for an increased risk of reintubation. Understanding the risk factors for reintubation after cardiac surgery and identifying effective interventions to reduce these reintubations is of critical importance to optimize patient outcomes. High-flow nasal cannula (HFNC) provides up to 60 liters per minute of 100% oxygen, dead space washout, and humidification to improve secretion clearance, and has shown some benefits in improving hypoxia and reducing reintubation in select populations. However, its benefit in high-risk patients undergoing cardiac surgical procedures is not known and therefore clinicians may still be reluctant to extubate these patients early and introduce HFNC, despite the known risks of prolonged intubation. To address this important issue, we aim to develop and validate a model to predict postoperative reintubation after cardiac surgery using data readily available from the electronic health record (EHR) and use this data to complete a pilot randomized controlled trial (RCT) of post-extubation HFNC to prevent reintubation in cardiac surgery patients identified as at high risk for reintubation. METHODS/STUDY POPULATION: Based on retrospective data demonstrating a 4.7% reintubation incidence within 48 hours in our CVICU, we estimate that there will be 340 reintubations available for analysis of the risk factors for reintubation to develop our predictive model from November 2, 2017 (our EHR go-live). We require 15 events per predictive variable to avoid overfitting the model, giving us at least 22 variables for analysis and inclusion in the model. Model validation and calibration will be performed using a bootstrapped validation cohort. Next, we will prospectively study 120 patients with a greater than 10% predicted risk of reintubation (double the baseline risk of the overall population) and randomly assign them to either HFNC or usual care, to test the hypothesis that HFNC decreases the rate of reintubation in high-risk patients. RESULTS/ANTICIPATED RESULTS: In addition to developing a predictive model, refining it, and validating its ability to predict the primary outcome of reintubation within 48 hours, I will further assess whether HFNC reduces total duration of mechanical ventilation, hospital length of stay, and ICU length of stay in this high-risk population. I will use these data to establish the feasibility of EHR-integrated predictive modeling and randomization, as well as to guide a future multicenter clinical trial that will pragmatically leverage the EHR for patient selection, enrollment, randomization, and data collection. DISCUSSION/SIGNIFICANCE OF IMPACT: Assuming HFNC decreases reintubation rates by 50%, at a 1:1 ratio of cases to controls, we will require 435 patients in each group (970 total), to have an 80% power and alpha of 0.05 to detect a difference. As this will require a multicenter study, we will instead focus on using data from this pilot study to: 1) refine our sample size estimates. 2) demonstrate the feasibility of our novel EHR-integrated pragmatic trial design. 3) identify and screen collaborators at other institutions, including obtaining important regulatory and legal approval. 4) establish a data safety monitoring board for the trial. 5) refine the data collection infrastructure, leveraging commercially available resources in one of the largest enterprise EHR systems (Epic) and associated resource-sharing products, such as Epic’s App Orchard.

OBJECTIVES/SPECIFIC AIMS: Characterize microbiome metadata describing specimens collected, genomic pipelines and microbiome results, and incorporate them into a data integration platform for enabling harmonization, integration and assimilation of microbial genomics with exposures as spatiotemporal events. METHODS/STUDY POPULATION: We followed similar methods utilized in previous efforts in charactering and developing metadata models for describing microbiome metadata. Due to the heterogeneity in microbiome and exposome data, we aligned them along a conceptual representation of different data used in translational research; microbiomes being biospecimen-derived, and exposomes being a combination of sensor measurements, surveys and computationally modelled data. We performed a review of literature describing microbiome data, metadata, and semantics [4–15], along with existing datasets [16] and developed an initial metadata model. We reviewed the model with microbiome domain experts for its accuracy and completeness, and with translational researchers for its utility in different studies, and iteratively refined it. We then incorporated the logical model into OpenFurther’s metadata repository MDR [17,18] for harmonization of different microbiome datasets, as well as integration and assimilation of microbiome-exposome events utilizing the UPIE. RESULTS/ANTICIPATED RESULTS: Our model for describing the microbiome currently includes three domains (1) the specimen collected for analysis, (2) the microbial genomics pipelines, and (3) details of the microbiome genomics. For (1), we utilized biospecimen data model that harmonizes the data structures of caTissue, OpenSpecimen and other commonly available specimen management platform. (3) includes details about the organisms, isolate, host specifics, sequencing methodology, genomic sequences and annotations, microbiome phenotype, genomic data and storage, genomic copies and associated times stamps. We then incorporated this logical model into the MDR as assets and associations that UPIE utilizes to harmonize different microbiome datasets, followed by integration and assimilation of microbiome-exposome events. Details of (2) are ongoing. DISCUSSION/SIGNIFICANCE OF IMPACT: The role of the microbiome and co-influences from environmental exposures in etio-pathology of various pulmonary conditions isn’t well understood [19–24]. This metadata model for the microbiome provides a systematic approach for integrating microbial genomics with sensor-based environmental and physiological data, and clinical data that are present in varying spatial and temporal granularities and require complex methods for integration, assimilation and analysis. Incorporation of this microbiome model will advance the performance of sensor-based exposure studies of the (UPIE) to support novel research paradigms that will improve our understanding of the role of microbiome in promoting and preventing airway inflammation by performing a range of hypothesis-driven microbiome-exposome pediatric asthma studies across the translational spectrum.

OBJECTIVES/SPECIFIC AIMS: The goals of this retrospective cohort study is threefold: 1) to assess how many pregnant women at Boston Medical Center from 2012 to 2017 have had their vitamin D status checked prior to and during pregnancy, 2) determine associations between vitamin D levels, birth outcomes and demographics and 3) assess how many of those found to have lower than satisfactory vitamin D levels (<30ng/mL) received interventions, including receiving vitamin D supplementation and/or being referred to an appropriate specialist such as an endocrinologist or a nutritionist. METHODS/STUDY POPULATION: Our study population is mothers over age 18 who received care at Boston Medical Center during their pregnancy from 2012 to 2017. Our primary outcomes are vitamin D utilization rates and associations between vitamin D levels with clinical outcomes during pregnancy and at birth. Secondary outcomes are demographic predictors of mothers who receive vitamin D testing and those who have complications associated with low vitamin D. We will conduct multiple linear regressions to check for associations between vitamin D levels, birth outcomes and demographic variables. We will adjust vitamin D levels with maternal BMI. De-identified clinical data was gathered from Boston University Medical Center’s (BUMC) Clinical Data Warehouse. This retrospective study was approved with a HIPAA waiver by the BUMC Institutional Data Warehouse. All statistical analysis was completed using SAS version 9.4 and was primarily done by the student PI and reviewed by Dr. Hossein, the co-investigator who is trained as a statistician and geneticist. The team also utilized Boston University’s Biostatistics, Epidemiology & Research Design (BERD) team to check the feasibility of the statistical methods. RESULTS/ANTICIPATED RESULTS: We anticipate that our descriptive demographic data will reflect the medical center’s predominantly black/Hispanic and low-income profile. Based on previous literature, we expect low vitamin D levels to have positive associations with gestational diabetes, pre-eclampsia, and preterm birth. Analyses are currently actively in progress and we expect to have results before the ACTS conference date in March, 2019. DISCUSSION/SIGNIFICANCE OF IMPACT: Vitamin D is an essential part of the human body system. It is well documented in current literature that vitamin D is correlated with bone health, mental health and maternal health. Moreover, there is evidence that maternal vitamin D supplementation prevents vitamin D deficiency in newborns. Previous literature suggests that low vitamin D may be associated with gestational diabetes, pre-eclampsia, and pre-term births. Boston Medical Center is Massachusetts’ largest urban medical center and acts as its only safety-net hospital, serving predominantly low-income and socially marginalized patient populations. There is limited existing research on assessment of maternal vitamin D in urban hospital settings. Pregnant women rarely receive vitamin D screenings as part of their prenatal checkups as current national and regional guidelines do not require pregnant women to be screened for vitamin D deficiency or insufficiency. The results will demonstrate the potential effects vitamin D supplementation, or lack thereof, in expectant mothers living in urban, safety net communities. We hope to inform prenatal care practices and attitudes of vitamin D supplementation in maternal health with the results of our study.

OBJECTIVES/SPECIFIC AIMS: The development of new anti-cancer agents for children requires an inherently longer timeline than in adults. The 3+3 study design for Phase 1 dose escalation trials is commonly used to estimate the maximum tolerated dose and assess safety. The Rolling 6 study design was developed to shorten the study conduct timeline. METHODS/STUDY POPULATION: This study compares twenty Phase 1 COG Pilot and Phase 1 Consortium trials that employed the Rolling 6 design with hypothetical results under the assumption that a 3+3 design had been executed. The number of evaluable patients required to complete the study, number of DLTs, number of inevaluable patients, overall study duration, time suspended to enrollment (i.e., waiting for DLT evaluation), and DLT risk are compared between study designs using Wilcoxon’s signed rank test. RESULTS/ANTICIPATED RESULTS: The Rolling 6 study design required less time to complete the studies compared with 3+3 design (median 273 vs. 297 days, P = 0.01). In general, the Rolling 6 study design required more patients, had more inevaluable patients, and there were more dose limiting toxicity (DLT) events. However, there was no significant difference in DLT risk (median 0.15 vs. 0.17, P = 0.72). DISCUSSION/SIGNIFICANCE OF IMPACT: The Rolling 6 study design effectively shortens the study conduct timeline compared with the traditional 3+3 design for Phase 1 COG Pilot and Phase 1 Consortium trials without increasing the risk of toxicity.

OBJECTIVES/SPECIFIC AIMS: Opioids are the first-line treatment for moderate to severe cancer-related pain. Increased awareness of opioid prescription misuse and adverse outcomes has prompted statements on their use from multiple national medical groups. In this study we characterize national-level opioid prescription patterns among gynecologic oncologists treating Medicare beneficiaries. METHODS/STUDY POPULATION: The Centers for Medicare and Medicaid Services (CMS) database was used to access Medicare Part D beneficiary data (2016). All available opioid claims prescribed by gynecologic oncologists were identified. Medication type, prescription length and other prescribing factors were recorded. Physician demographics were obtained from departmental websites and accrediting bodies. Physicians with <10 opioid claims are not included in the CMS database. Bivariate statistical analysis including chi-squared, Fisher’s exact test and Wilcoxon rank-sum test were performed to compare variables with threshold for significance set at p<0.05. Linear regression modeling was also performed to examine association of gender with number of opioids prescribed. RESULTS/ANTICIPATED RESULTS: A total of 494 board-certified gynecologic oncologists were included in this analysis. In 2016, gynecologic oncologists wrote 23,584 opioid prescriptions for 267,824 days of treatment (average of 9.24 prescribed days per claim). The most commonly prescribed opioid was oxycodone/acetaminophen (41%). Male physicians had significantly more opioid prescription claims than females (p<0.01) including after adjusting for differences in years of experience. The majority of physicians had 11-50 opioid prescription claims (68%). A minority were high prescribing physicians with >100 opioid claims (11%). Of these, the overwhelming majority were male (82%) and late career (46%, >15 years since board certification). Physicians in the South had the greatest number of opioid prescription claims and significantly more than physicians in the Northeast, who had the fewest (p<0.01). Mean number of opioid claims increased with increasing years of experience (p<0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: Among gynecologic oncologists, there were gender-based, regional and experience-related variations in opioid prescribing in the Medicare population in 2016. Further longitudinal studies are required to elucidate secular trends in opioid prescription practice.

OBJECTIVES/SPECIFIC AIMS: Objectives and goals of this study are to (i) determine whether IBS-D patients randomized to either rifaximin or low FODMAP diet show improvement in IBS-related symptoms; and (2) identify using longitudinal analyses how SIBO status and fecal microbiota features associate with response to either rifaximin or low FODMAP dietary intervention. METHODS/STUDY POPULATION: 42 patients ≥ 18 years of age who meet Rome IV criteria for IBS-D will be randomized to receive either rifaximin or low FODMAP diet intervention. The primary outcome will be the proportion of responders to intervention which is defined as ≥ 30% reduction in mean daily abdominal pain or bloating by visual analog scale compared with baseline. Exclusion criteria will include: (a) history of microscopic colitis, inflammatory bowel disease, celiac disease, or other organic disease that could explain symptoms, (b) prior gastrointestinal surgery, other than appendectomy or cholecystectomy > 6 months prior to study initiation, (c) prior use of rifaximin or formal dietary interventions for IBS-D, (d) use of antibiotics within the past 3 months, or (e) use of probiotics within 1 month of study entry. Glucose hydrogen breath tests will be performed at the beginning and end of the trial to evaluate for SIBO. Fecal samples will be collected at 0, 2, and 6 weeks to determine changes in fecal microbial composition and structure. RESULTS/ANTICIPATED RESULTS: This study seeks to examine whether longitudinal analyses of small intestinal and colonic microbiota can subtype IBS-D subjects into clinically relevant phenotypes. A total of 18 subjects have been enrolled into the study. Clinical variables, hydrogen breath test results, and fecal microbiota data are being collected for ongoing analysis. DISCUSSION/SIGNIFICANCE OF IMPACT: Results from this study may help move treatment of IBS from a purely symptom based approach to a more individualized approach by stratifying IBS-D patients into distinct clinical phenotypes which are amenable to targeted therapeutic approaches.

OBJECTIVES/SPECIFIC AIMS: Our objective was to compare the proteomics of HDL between youth with T1DM and healthy controls (HC). METHODS/STUDY POPULATION: We did chromatography-based HDL purification and SWATH-MS-based proteomic quantitation. Proteomic alterations of HDL fractions and their association with glycemic control was examined. Study population: 26 patients with T1DM and 13 HC. RESULTS/ANTICIPATED RESULTS: We quantified 78 proteins in isolated HDL, using mass spectrometry and label-free SWATH quantification. Youth with T1DM had significantly higher protein levels of A1BG (P = 0.008), A2AP (P = 0.0448), APOA4 (P = 0.0366), CFAH (P = 0.0476), FHR2 (P = 0.0005), ITIH4(P = 0.01), PGRP2 (P = 0.0167) and lower levels of ALBU (P = 0.0164) and CO3 (P = 0.019) compared to HC. A1BG (r=0.541, P<0.001) and ITIH4 (r=0.357, P = 0.026) were significantly positively correlated with HbA1c. DISCUSSION/SIGNIFICANCE OF IMPACT: Youth with T1DM have proteomic alterations of their HDL compared to HC, despite similar concentration of HDL cholesterol, that might affect the cardioprotective mechanisms of HDL. Future efforts should focus on investigating the role of these HDL associated proteins in regard to HDL function and their role in CVD risk in patients with T1DM.

OBJECTIVES/SPECIFIC AIMS: Industry payments to physicians can present a conflict of interest. The Physician Payments Sunshine Act mandates the disclosure of these financial relationships to increase transparency. Recent studies in other surgical specialties have shown that research productivity is associated with greater industry funding. In this study, we characterize the relationship between academic influence and industry funding among academic gynecologic oncologists. METHODS/STUDY POPULATION: Departmental websites were used to identify academic gynecologist oncologists and their demographic information. The Hirsch index (h-index) relates an author’s number of publications to number of times referenced by other publications, a validated measure of an author’s academic influence. This was obtained from the Scopus database. The Center for Medicaid and Medicare Services Open Payments online database was searched for all industry payments in 2017. The NIH Reporter online database was searched for active grants. Goodness of fit testing showed that all variables followed nonparametric distributions. Medians were compared using Mann-Whitney U tests and Kruskal-Wallis analysis of variance with post-hoc Dunn’s test. RESULTS/ANTICIPATED RESULTS: Four hundred and sixty-six academic gynecologic oncologists were included in the analysis. In 2017, 89.7% of this group received industry funding totaling $41.4 million. Median industry funding was $453 [IQR $67-19684] and median h-index was 14 [IQR 8-26]. Only 8.1% of gynecologic oncologists were NIH grant recipients and they received significantly higher industry payments ($357 vs. 11,168, P<0.01). Gender and academic rank were not associated with industry funding. Gynecologic oncologists in the highest decile of industry funding received a median payment of $447,651[N=46, IQR $285,770 – 896,310] totaling $36.5 million. The median h-index for this top-earning decile was 23 [N=46, IQR 16.5-30.3]. When stratified by payment amount, median h index increased but only reached statistical significance in the highest cohort receiving >$100,000 (N = 63, P<0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: The majority of academic gynecologic oncologists receive industry funding although there are large variations in payments. Those receiving the largest payments are more likely to hold NIH grants and have greater academic influence.

OBJECTIVES/SPECIFIC AIMS: The main aim of this study was to investigate the relationship between measures of adiposity and FGF-23 in a sample of patients with CKD stages 3-4. METHODS/STUDY POPULATION: This study was a clinic-based cross-sectional investigation of 71 CKD patients who underwent body composition and anthropometric assessments as part of the relationship of insulin sensitivity in kidney disease and vascular health (RISKD) study. Dual energy x-ray absorptiometry (DEXA) scans were used to measure total fat mass and body mass index (BMI) was computed using baseline weight and height measurements. Biomarkers included serum FGF-23 (C-terminal), serum leptin, high sensitivity C-reactive protein (hsCRP), serum triglycerides, high density lipoprotein (HDL) cholesterol and total cholesterol. Creatinine-based estimated glomerular filtration rate (eGFR) was computed using the CKD-EPI equation. Multiple linear regression with robust standard errors was used to investigate the relationship between FGF2-3 and measures of adiposity (BMI, total fat mass and serum leptin). Log-transformation was performed for variables (FGF-23, hsCRP and serum lipids) with considerable skewness. RESULTS/ANTICIPATED RESULTS: The median age of the study participants was 68 (IQR: 60, 73) years; 26% were female and 23% were African-American. Median eGFR was 46.9 ml/min/1.73m2 (IQR: 41.9, 52.8), median BMI was 31 kg/m2 (IQR: 27, 35). Log FGF-23 had a significant positive correlation with BMI (r = 0.27, p = 0.02), total fat mass (r = 0.30, p = 0.01) and serum leptin (r = 0.43, p < 0.0001). After full adjustment for age, sex, race, eGFR, log hsCRP, log HDL and log triglycerides, a 50% increase in FGF-23 was associated with a 1 kg/m2 [95% CI: 0.1, 1.9; p = 0.03] increase in BMI, a 2.5 kg [95% CI: 0.2, 4.8; p = 0.03] increase in total fat mass and a 6.7 ng/mL [95% CI: 1.0, 12.4; p = 0.02] increase in serum leptin. DISCUSSION/SIGNIFICANCE OF IMPACT: In this sample of patients with moderate-to-severe CKD, we found a significant independent association between higher FGF-23 levels and higher adiposity (BMI, total fat mass and the pro-atherogenic adipocytokine, leptin). The underlying causes and the implications of these associations − particularly in bone and vascular health − need to be further investigated.

OBJECTIVES/SPECIFIC AIMS: Lead (Pb) exposure can seriously affect nervous system and kidney. Young children are vulnerable to Pb exposure. However, the role of low-level Pb exposure in asthma in children and the age and racial disparity is not well studied. The objectives are to examine the relation between Pb level and asthma status and to determine the age and racial/ethnic differences in this relation. METHODS/STUDY POPULATION: We analyzed data from National Health and Nutrition Examination Survey 1999-2016 for 22,885 children 1-15 years old. Asthma information was collected by questionnaire. Blood lead level was measured using mass spectrometry. The association between blood Pb level and asthma status was assessed by logistic regression after adjusting for children’ age, gender, race/ethnicity, insurance status, and source of care; household poverty, mother’s age and smoking status. Data were analyzed using Stata 14 considering design and sample weight and p<0.05 is statistically significant. RESULTS/ANTICIPATED RESULTS: Pb level was associated with asthma status (Adjusted Odds Ratio (AOR)=1.4, 95% Confidence Interval (CI) = 1.2-1.7, p < 0.001). Stratified analysis by age showed that blood Pb level is related to asthma only in children 1-5 years old (AOR = 1.3, 95% CI = 1.1-1.5, p = 0.004). There was no racial/ethnic difference in this association. DISCUSSION/SIGNIFICANCE OF IMPACT: Pb level is associated with asthma status in children especially young children. Health risk of low Pb is a concern. Preventive measures by reducing potential sources of Pb should be introduced early.

OBJECTIVES/SPECIFIC AIMS: In a randomized controlled trial in participants with HIV infection, recombinant human growth hormone (rhGH) reduced visceral adipose tissue (VAT); addition of rosiglitazone to rhGH prevented the accompanying decline in insulin sensitivity (SI). Within this parent RCT, we sought to determine the effect of rosiglitazone and rhGH intervention on alpha-1-acid glycoprotein (AGP), a biomarker of inflammation. We also investigated AGP as an independent risk factor for SI and VAT changes along with any potential effect modification by AGP of the intervention. METHODS/STUDY POPULATION: Participants with HIV-infection (n = 72) with abdominal adiposity and insulin resistance were randomized to rosiglitazone, rhGH, combination, or placebo for 12 weeks (NCT00130286). SI was determined by frequently sampled intravenous glucose tolerance test, and VAT by whole body MRI. AGP concentrations were determined by immunoturbidimetric assay in available serum samples at baseline (time 0), 4, and 12 weeks (n = 41 participants with samples at all 3 time points). A linear mixed model was used to assess the impact of intervention over time on AGP concentrations. General linear models were used to assess baseline AGP concentrations as an independent predictor of SI and VAT changes by treatment group with the model initially including age quartile, gender, race, ethnicity, BMI, HIV RNA <400 copies/mL, antiretroviral regimen, CD4 count, Stavudine use, and zidovudine use with step-by-step removal of least significant predictors. Effect modification was assessed by adding an interaction term between AGP and assigned intervention. RESULTS/ANTICIPATED RESULTS: AGP did not differ among treatment groups at baseline; overall median (Q1, Q3): 0.608 (.526,.727) g/L, P = 0.92. Treatment with rosiglitazone, rhGH, or the combination significantly reduced AGP concentrations from baseline to week 12, compared to placebo (time by treatment interaction, P = 0.0038). Baseline AGP was not a significant predictor or effect modifier of SI change in response to treatment (P ≥ 0.50). Baseline AGP (g/L) was an independent predictor of VAT change (L) (β = 1.91, SE = 0.89, P = 0.038) in addition to a treatment effect (P < 0.001) and age quartile effect (P < 0.001). No other predictors or interactions were significant, including effect modification of AGP (AGP by treatment interaction P = 0.50). DISCUSSION/SIGNIFICANCE OF IMPACT: It is known that immune and metabolic pathways are highly integrated, and biomarkers of inflammation have predictive abilities for cardiovascular and metabolic disease outcomes. This analysis provides data showing that treatment with rosiglitazone or rhGH in the context of HIV reduces AGP concentrations, indicating efficacy in reducing systemic inflammation. Baseline AGP was an independent risk factor for VAT changes as those with lower AGP at baseline showed a greater reduction in VAT in response to treatment. Biomarkers of inflammation may provide prognostic information for individualized patient outcomes to help guide treatment and follow-up.

OBJECTIVES/SPECIFIC AIMS: Clostridium Difficile Infection (CDI), a prevalent cause of diarrhea, is the most notorious hospital-acquired infection, resulting in an alarming mortality and health care utilization rates. Herein, we investigate the impact of cannabis use, which is gaining significant legalization for recreational use, on the risk of CDI. METHODS/STUDY POPULATION: We selected adult records (age ≥ 18 years) from the Nationwide Inpatient Sample 2014, and identified cannabis users and other clinical conditions using ICD-9-CM codes. With multivariate logistic modeling, we generated propensity scores for cannabis users and matched them to non-users in a 1:1 ratio (104,936:104,936). We then estimated the adjusted relative risk (aRR) for having CDI using conditional Possion regression models with generalized estimating equations [SAS 9.4]. RESULTS/ANTICIPATED RESULTS: Among the matched hospitalizations (n=209,872), cannabis usage was associated with a reduced incidence of CDI (505.8[464.7-550.6] vs. 694.9[645.8-747.70] per 100,000 hospitalizations), resulting in a 27% reduced risk of CDI (aRR:0.73[0.65-0.81]; p-value:<0.0001). Non-dependent and dependent cannabis users respectively had 22% and 78% reduced likelihood of CDI when compared to non-cannabis users (0.78[0.69-0.90] & 0.22[0.12-0.40]). Furthermore, dependent users had less risk of CDI compared to non-dependent users (0.28[0.16-0.51]). Comparatively, abusive use of other substances like alcohol and tobacco was associated with increased risk for CDI (1.30[1.13-1.49] & 1.24[1.10-1.40]) DISCUSSION/SIGNIFICANCE OF IMPACT: Unlike alcohol and tobacco abuse which are associated with elevated risk for CDI, cannabis use, is related to a decreased risk of CDI amongst hospitalized patients. Further prospective and molecular mechanistic studies are required to elucidate how cannabis impacts CDI.

OBJECTIVES/SPECIFIC AIMS: Previous research suggests that weight loss during early TB treatment (first two months of anti-TB therapy) is a predictor of poor tuberculosis (TB) treatment outcomes among HIV-negative populations, but the relationship has not been well studied in the context of HIV. We examined the association between HIV and weight change during the first two months of anti-tuberculosis treatment, and also assessed the effects of HIV and early weight change on tuberculosis (TB) treatment outcomes. METHODS/STUDY POPULATION: Adults with culture-confirmed, drug-susceptible, pulmonary TB, regardless of HIV status, were enrolled into the Regional Prospective Observational Research for Tuberculosis (RePORT)-Brazil cohort and followed on standard anti-TB therapy. For the primary analysis, we compared weight change in persons living with HIV (PLWH) and HIV-negative patients between baseline and two months using multivariable bootstrapped quantile regression and modified Poisson regression. For secondary analysis, we examined the separate effects of HIV and weight change on poor TB treatment outcome (treatment failure, TB recurrence, or death) using Cox proportional hazards regression. RESULTS/ANTICIPATED RESULTS: Among 323 participants, 45 (14%) were HIV-positive. On average, PLWH lost 0.7% (interquartile range (IQR): −5.1%, 4.4%) of their baseline body weight between baseline and two months; those without HIV gained 3.5% (IQR: 0.8%, 6.7%). After adjusting for age, sex, and baseline BMI, PLWH lost 4.1% (95% confidence interval (CI): −6.5%, −1.6%) more weight during the first two months of anti-TB treatment than HIV-negative individuals. HIV infection was associated with weight loss ≥5% (adjusted odds ratio = 9.3; 95% CI: 4.2-20.6). Regarding the secondary analysis, 14 patients had a poor TB treatment outcome: 2 treatment failures, 4 cases of recurrent TB, and 8 deaths. PLWH and patients who lost ≥5% weight had significantly increased risk of poor TB treatment outcome with hazard ratios of 8.77 (95% CI: 2.96-25.94) and 4.09 (95% CI: 1.11-15.14), respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results suggest that HIV is associated with weight loss during early TB treatment, and both HIV and early weight loss were associated with poor treatment outcome. Future research should examine the potential etiologies of these findings and identify the types of interventions that would best promote weight gain during TB treatment, especially among PLWH, in order to prevent poor TB treatment outcomes.