bluuebunny/crossref_metadata_2025 huggingface dataset:
2264 Early findings from a real-world RCT: Acceptance and commitment therapy (ACT) for persistent pain in an integrated primary care setting
Authors: Kanzler Kathryn E. , Robinson Patricia , Munante Mariana , McGeary Donald , Potter Jennifer , Lopez Eliot , Mintz Jim , Kilpela Lisa , Hale Willie , Dougherty Donald , Velligan Dawn
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: This study seeks to test the feasibility and effectiveness of a brief Acceptance and commitment therapy (ACT) treatment for patients with persistent pain in a patient-centered medical home. METHODS/STUDY POPULATION: Participants are recruited via secure messaging, clinic advertisements and clinician referral. Primary care patients age 18 and older with at least 1 pain condition for 12 weeks or more in duration are stratified based on pain severity ratings and randomized into (a) ACT intervention or (b) control group [Enhanced Treatment as Usual (E-TAU)]. Participants in the ACT arm attend 1 individual visit with an integrated behavioral health provider, followed by 3 weekly ACT classes and a booster class 2 months later. E-TAU participants will receive usual care plus patient education handouts informed by cognitive behavioral science. Currently, 17% of our overall goal of 60 patients have completed ACT or enhanced treatment as usual. Average participant age is 49 years old, 70% female, and 70% Hispanic/Latino. Most report multisite pain conditions (e.g., musculoskeletal, fibromyalgia) and 30% are taking opioid medications. Data analysis in this presentation will include early correlational findings from baseline assessments. Upon study completion, we will analyze data using a general linear mixed regression model with repeated measures. RESULTS/ANTICIPATED RESULTS: The overall hypothesis is that brief ACT treatment reduces physical disability in patients with persistent pain when delivered by an integrated behavioral health provider in primary care. By examining a subset of patients on opioid medications, we also anticipate a reduction in opioid misuse behaviors. Additionally, it is anticipated that improvements in patient functioning will be mediated by patient change in pain acceptance and patient engagement in values-consistent behaviors. DISCUSSION/SIGNIFICANCE OF IMPACT: This pilot study will establish preliminary data about the feasibility and effectiveness of addressing persistent pain in a generalizable, “real-world” integrated primary care setting. Data will help support a larger trial in the future. If effective, findings could improve treatment methods and quality of life for patients with persistent pain using a scalable approach.
2163 Polypharmacy and patterns of prescription medication use among cancer survivors
Authors: Murphy Caitlin , Fullington Hannah , Alvarez Carlos , Lee Simon C. , Betts Andrea , Haggstrom David , Halm Ethan
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: The population of cancer survivors is rapidly growing in the United States. Long term and late effects of cancer, combined with ongoing management of other chronic conditions, make cancer survivors particularly vulnerable to polypharmacy and its adverse effects. We examined patterns of prescription medication use and polypharmacy in a population-based sample of cancer survivors. METHODS/STUDY POPULATION: Using data from the Medical Expenditure Panel Survey (MEPS), we matched cancer survivors (n=5216) to noncancer controls (n=19,588) by age, sex, and survey year. We defined polypharmacy as using 5 or more unique medications. We also estimated proportion of respondents prescribed specific medications within therapeutic classes and total prescription expenditures. RESULTS/ANTICIPATED RESULTS: A higher proportion of cancer survivors were prescribed 5 or more unique medications (64.0%, 95% CI 62.3%–65.8%) compared with noncancer controls (51.5%, 95% CI 50.4%–52.6%), including drugs with abuse potential. Across all therapeutic classes, a higher proportion of newly (≤1 year since diagnosis) and previously (>1 years since diagnosis) diagnosed survivors were prescribed medications compared to controls, with large differences in central nervous system agents (65.8% vs. 57.4% vs. 46.2%), psychotherapeutic agents (25.4% vs. 26.8% vs. 18.3%), and gastrointestinal agents (31.9% vs. 29.6% vs. 22.0%). Specifically, nearly 10% of cancer survivors were prescribed benzodiazepines and/or opioids compared to about 5% of controls. Survivors had more than double prescription expenditures (median $1633 vs. $784 among noncancer controls). Findings persisted similarly across categories of age and comorbidity. DISCUSSION/SIGNIFICANCE OF IMPACT: Cancer survivors were frequently prescribed a higher number of unique medications and inappropriate medications or drugs with abuse potential, increasing risk of adverse drug events, financial toxicity, poor adherence, and drug-drug interactions. Adolescent and young adult survivors appear at increased risk of polypharmacy.
2110 Prenatal near roadway air pollution exposure and early neurodevelopment in young Mexican-American children: Findings from the CHAMACOS prospective birth cohort study
Authors: Coe William H. , Feinberg Jason , Grunier Robert , Eskenazi Brenda , Volk Heather
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Previous studies suggest that prenatal exposure to environmental pollutants can have an adverse effect on brain development. We examine the association between prenatal near roadway air pollution (NRAP) exposure and early neurodevelopment. METHODS/STUDY POPULATION: The Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) Study is a prospective birth cohort that began in 1999 with 605 mother-child pairs of primarily Mexican-American descent. Maternal residence during pregnancy was geocoded using ArcGIS and prenatal NRAP exposure was assigned using the CALINE4 line source dispersion model. We used composite Bayley Scale scores for cognitive and motor development, and created separate linear regression models at 6, 12, and 24 months of age. RESULTS/ANTICIPATED RESULTS: After adjusting for relevant maternal and child characteristics, preliminary estimates suggest that prenatal NRAP exposure is associated with a nonsignificant increase in Bayley Scale scores at 6 and 24 months (cognitive: β=0.13, p-value=0.20 and motor: β=0.08, p-value=0.58 at 6 months; cognitive: β=0.16, p-value=0.42 and motor: β=0.20, p-value=0.25 at 24 months) and a nonsignificant decrease at 12 months (cognitive: β=−0.07, p-value=0.64 and motor: β=−0.12, p-value=0.56). DISCUSSION/SIGNIFICANCE OF IMPACT: Our preliminary findings do not suggest that prenatal NRAP exposure is associated with early cognitive development. Additional exploration of co-exposures known to effect neurodevelopment should be examined in this rural population.
2082 Profile of pediatric potentially avoidable transfers
Authors: Rosenthal Jennifer , Marcin James , Lieng Monica , Romano Patrick
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: While hospital-hospital transfers of pediatric patients is often necessary, some pediatric transfers are potentially avoidable. Pediatric potentially avoidable transfers (PAT) represent a process with high costs and safety risks but few, if any, benefits. To better understand this issue, we described pediatric inter-facility transfers with early discharges. METHODS/STUDY POPULATION: We conducted a descriptive study using electronic medical record data at a single-center over a 12-month period to examine characteristics of pediatric patients with a transfer admission source and early discharge. Among patients with early discharges, we performed descriptive statistics for PAT defined as patient transfers with a discharge home within 24 hours without receiving any specialized tests, interventions, consultations, or diagnoses. RESULTS/ANTICIPATED RESULTS: Of the 2414 pediatric transfers 31.2% were discharged home within 24 hours. Among transferred patients with early discharges, 348 patients (14.4% of total patient transfers) received no specialized tests, interventions, consultations, or diagnoses. Direct admissions were categorized as PAT 2.2-fold more frequently than transfers arriving to the emergency department. Among transferred direct admissions, PAT proportions to the neonatal intensive care unit (ICU), pediatric ICU, and non-ICU were 5.8%, 17.4%, and 27.3%, respectively. Respiratory infections, asthma, and fractures were the most common PAT diagnoses. DISCUSSION/SIGNIFICANCE OF IMPACT: Early discharges and PAT are relatively common among transferred pediatric patients. Further studies are needed to identify the etiologies and clinical impacts of PAT, with a focus on direct admissions given the high frequency of PAT among direct admissions to both the pediatric ICU and non-ICU.
2228 The association of gastrointestinal symptoms and hypertension in persons living with HIV on HAART
Authors: Butler Kierra R. , Harrell Faye , Henderson Wendy A.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: The advent of Highly Active Antiretroviral Treatments (HAART) has allowed HIV-positive individuals to live longer in recent years. This has resulted in a higher incidence of mortalities occurring in these individuals due to cardiovascular pathologies, as opposed to deaths due to HIV. Even with long-term HAART, persons living with HIV (PLWHIV) still exhibit inflammation, which is associated with deleterious cardiovascular outcomes. PLWHIV on HAART have a higher prevalence of hypertension, which is associated with an increased risk of cardiovascular events. Moreover, chronic inflammation has been shown to be related to the translocation of microbes and endotoxins across the gastrointestinal tract. Such microbial translocation (MT) is increased in individuals with digestive disorders and their associated symptoms (e.g., diarrhea, abdominal pain, and nausea). This study aims to explore the pathologies common to both MT-induced inflammation and cardiovascular symptoms by examining the associations between gastrointestinal symptoms and hypertension in PLWHIV on HAART. METHODS/STUDY POPULATION: The sample included 351 PLWHIV on HAART. Pre-existing de-identified data were analyzed. Sample demographics included 56.98 % African Americans, 41.31% Caucasians, ages 20–66 years (mean age=43.65years), 21% female, 89% male, HIV viral load, CD4 counts. Self-reported data from the Symptom Co-Morbidity Questionnaire and Socio-demographic questionnaire were analyzed with SPSS v.24. RESULTS/ANTICIPATED RESULTS: In total, 86 PLWHIV (24.50%) stated that they have hypertension; 39 subjects (45.3%) reported having diarrhea, 30 subjects (34.8%) reported nausea, and 12 (13.9%) reported constipation and vomiting. Among ethnicities with hypertension and gastrointestinal symptoms, African Americans compared with Caucasians had a higher percentage of diarrhea (28% vs. 17%), nausea (21% vs. 11%), constipation (11% vs. 2%), and vomiting (8% vs. 5%). Women compared with men reported a higher percentage of nausea (28% vs. 24%) and constipation (8% vs. 6%). Men compared with women reported a higher percentage of diarrhea (38% vs. 7%) and vomiting (8% vs. 5%). DISCUSSION/SIGNIFICANCE OF IMPACT: These data support the need for targeted screening to include both blood pressure and associated gastrointestinal symptoms. Further studies supporting these results may assist practitioners to target treatments that may prevent cardiovascular comorbidities.
2192 The association of preoperative functional capacity and outcomes for head and neck cancer patients undergoing definitive surgical treatment
Authors: Sindhar Sampat , Kallogjeri Dorina , Wildes Troy S. , Avidan Michael S. , Piccirillo Jay
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: To study the role functional capacity plays in surgical outcomes for head and neck cancers. METHODS/STUDY POPULATION: In this single-institution cohort study, we combined preoperative anesthesia assessment information with oncology registry data for newly-diagnosed patients with squamous cell carcinoma of the oral cavity, pharynx, and larynx (HNSCC) treated with definitive surgery at Siteman Cancer Center from 2012 to 2016. Patient-reported exercise capacity was assessed as metabolic equivalents. Metabolic equivalents<4 was defined as poor functional capacity. The primary outcome measure was overall survival (OS). Kaplan-Meir survival analysis was used to compare the survival of patients with poor functional capacity (PFC) and patients with normal functional capacity (NFC). Cox proportional hazard regression was used to explore the independent prognostic role of functional capacity on overall survival after controlling for other factors. RESULTS/ANTICIPATED RESULTS: A total of 671 patients underwent surgical treatment for HNSCC. The average age was 62 years (range: 19–94 years). Majority of the patients were male (n=481; 72%), White race (n=589; 88%), and smokers (n=528; 79%). Of 671 patients, 22% (n=146) had PFC. Two-year OS rate in PFC patients was 70% compared with 85% in NFC patients (15% difference; 95% CI: 7%–23%). Unadjusted Cox proportional hazard analysis showed that PFC patients had 2.2 times higher risk of death (95% CI: 1.5–3.2) than NFC patients. After adjustment for age at surgery, BMI, preoperative weight loss, comorbidity score, tumor site, and TNM stage the magnitude of the association between functional capacity and OS decreased (aHR=1.3; 95% CI: 0.88–1.98). DISCUSSION/SIGNIFICANCE OF IMPACT: Poor functional capacity is associated with decreased overall survival, but the magnitude of the association, while clinically meaningful, decreases after controlling for other important patient and tumor factors. Nevertheless, we believe preoperative functional capacity status is an important patient factor to consider when discussing prognosis and attempting risk stratification. We also believe that functional capacity may be associated with 30-day unplanned readmissions and 90-day complications and are currently performing chart review to ascertain this information.
2456 Cutaneous lupus erythematosus patients have increased circulating myeloid-derived suppressor cells with immunosuppressive properties
Authors: Florez-Pollack Stephanie , Tseng Lin-chiang , Kobayashi Masato , Chong Benjamin F. , Ariizumi Kiyoshi
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: MDSCs are potent suppressors of T cell function, and have been recently found to be implicated in skin diseases driven by T cell dysregulation. However, the function of MDSCs in CLE is poorly understood. We sought to characterize the MDSC population in the peripheral blood of DLE patients and evaluate their ability to suppress autologous T cells. METHODS/STUDY POPULATION: All patients were recruited through the UT Southwestern Cutaneous Lupus Registry. PBMCs from 32 CLE patients and 16 age-matched and gender-matched controls were analyzed using flow cytometry. Monocytic MDSCs were identified by the phenotype of CD14+ HLA-DR neg/low. Furthermore, autologous MDSCs and T cells were purified from CLE PBMCs (n=4) and co-cultured at different ratios of these cells. T cell function was measured by secretion of IFN-γ by ELISA. RESULTS/ANTICIPATED RESULTS: Monocytic MDSCs in CLE PBMCs (median: 2.04%, IQR: 0.67%–5.07%) were significantly higher compared with healthy control PBMCs (median: 0.5%, IQR: 0.1%–1.07%, p=0.002). Although not significant on subset analysis, patients with CLE limited to the head and neck had the highest levels of MDSCs. CLE MDSCs (n=4) were found to suppress autologous activated T-cells in a dose-dependent manner. DISCUSSION/SIGNIFICANCE OF IMPACT: In this cross-sectional study of patients of the UT Southwestern Cutaneous Lupus Registry, we observed differences in the levels of MDSCs among PBMCs of CLE patients Versus healthy controls. CLE patients had significantly higher levels of MDSCs, which could be explained by the presence of an inflammatory state in this group. Furthermore, CLE MDSCs were able to suppress autologous T cells, showing that these cells are functionally patent in CLE blood. Their up-regulation in CLE blood may represent the body’s response to limiting disease severity, since most patients had mild disease activity.
2042 CYP2C19*2 and PON1 Q192R polymorphisms are associated with platelet reactivity to clopidogrel in Puerto Rican Hispanics with cardiovascular disease
Authors: Suarez Dagmar F. H. , Botton Mariana R. , Scott Stuart A. , Tomey Matthew I. , Melin Kyle , Lopez-Candales Angel , Renta Jessicca Y. , Duconge Jorge
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: High on-treatment platelet reactivity (HTPR) with clopidogrel imparts an increased risk for ischemic events in adults with coronary artery disease. Although more potent antiplatelet agents are available, clopidogrel remains the most commonly used P2Y12 inhibitor in Puerto Rico. Platelet reactivity varies with ethnicity and is influenced by both clinical and genetic variables; however, no clopidogrel pharmacogenetic studies with Puerto Rican patients have been reported. Therefore, we sought to identify clinical and genetic determinants of on-treatment platelet reactivity in a cohort of Puerto Rican patients with cardiovascular disease. METHODS/STUDY POPULATION: We performed a retrospective study of 111 Puerto Rican patients on 75 mg/day maintenance dose of clopidogrel. Patients were allocated into 2 groups: Group I, without HTPR; and Group II, with HTPR. Clinical data was obtained from the medical record. Platelet function was measured ex vivo using the VerifyNow® P2Y12 assay and HTPR was defined as P2Y12 reaction units (PRU)≥230. Genotyping of CYP2C19, ABCB1, PON1, PY2R12, B4GALT2, CES1, and PEAR1 was performed using Taqman® Genotyping Assays. RESULTS/ANTICIPATED RESULTS: The mean PRU across the cohort was 203±61 PRU (range, 8–324), and 42 (38%) patients had HTPR. One in four individuals carried at least 1 copy of the CYP2C19*2 variant allele. Hematocrit and PON1 p.Q192R variant were inversely correlated with platelet reactivity (p<0.05). Multiple logistic regression showed that 27% of the total variation in PRU was explained by a history of diabetes mellitus, hematocrit, CYP2C19*2, and PON1 p.Q192R. Body mass index (OR=1.15; CI: 1.03–1.27), diabetes mellitus (OR=3.46; CI: 1.05–11.43), hematocrit (OR=0.75; CI: 0.65–0.87), and CYP2C19*2 (OR=4.44; CI: 1.21–16.20) were the only independent predictors of HTPR. DISCUSSION/SIGNIFICANCE OF IMPACT: In a representative sample of Puerto Rican patients with cardiovascular disease, diabetes mellitus, hematocrit, CYP2C19*2, and PON1 p.Q192R were associated with on-treatment platelet reactivity. These factors may identify a subset of patients at higher risk for adverse events on clopidogrel in the Hispanic population.
2269 Day-to-day association between alcohol use and physical activity in university students
Authors: Graupensperger Scott , Evans Michael B.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: The goal of the present study was to advance our understanding of how alcohol use may contribute to physical inactivity among university students by investigating this association at a day-to-day level. METHODS/STUDY POPULATION: In total, 57 university students (Mage=20.27; 54% male) completed daily diary questionnaires using a cellphone application, which prompted them each evening to report minutes of moderate/vigorous physical activity engaged in, and number of alcoholic drinks consumed, as well as intended minutes of physical activity for the following day. Longitudinal mixed-level modeling was used to disentangle within person and between-person effects of alcohol use on physical activity behavior and intentions. Separate models were run to investigate lagged effects of previous day alcohol use. We controlled for sex and age in all models. RESULTS/ANTICIPATED RESULTS: Results indicated that participants’ usual alcohol use (between-person) was not associated with physical activity behavior or intentions. At the within-person level, day-to-day variance in alcohol use was negatively associated with both physical activity behavior (γ=−0.34, p=0.003) and intentions to engage in physical activity the following day (γ=−0.70, p<0.001). The lagged model indicated that previous day alcohol use negatively predicted PA behavior (γ=−0.33, p=0.004). DISCUSSION/SIGNIFICANCE OF IMPACT: Previous studies have largely been constrained to cross-sectional designs, and have surmised that there exists a positive association between alcohol use and physical activity due to trait-level differences between university students. We advance this literature by using ecological momentary assessment to investigate the within-person effects of alcohol use on physical activity at a day-to-day level while controlling for between-person variance. Contrary to existing literature, we found that on days when students consumed relatively more alcohol than they typically report, they: (a) report fewer minutes of physical activity on the same day, (b) plan to engage in relatively less physical activity on the subsequent day, and (c) engage in less physical activity on the subsequent day. By advancing our understanding of how alcohol use may curtail other health behaviors such as physical activity, we inform interventions that aim to target these behaviors in conjunction, or as part of a multiple behavior change intervention.
2525 Development of human cell-based screening assays to detect subject-specific drug-response variability
Authors: Stillitano Francesca , Mayourian Joshua , Dave Jaydev , Hulot Jean-Sébastien , Hajjar Roger J.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: The goals of this study are to develop a human-based screening assay for testing individual drug reactions and investigate the mechanism underlying susceptibility to develop diLQT. METHODS/STUDY POPULATION: We derived iPSC-CMs from 10 subjects with a high sensitivity to Sotalol (high-S group) and 10 subjects with no changes in QT interval after administration of the same drug (low-S group). Multielectrode array (MEA) was used to measure field potential duration, a surrogate to the QT interval in the electrocardiogram, in iPSC-CMs under basal conditions and in response to increasing concentrations of Sotalol. Transcriptomic profiling of iPSC-CMs from high-S Versus low-S groups was performed using RNA-sequencing. A parameter sensitivity analysis was performed on the Paci et al. iPSC-CM mathematical model to further support the lead hits identified via RNA-sequencing. RESULTS/ANTICIPATED RESULTS: Cardiac differentiation resulted in the generation of iPSC-CMs with appropriate cardiac channel expression and response to a hERG blocker E4031. MEA recordings showed a significantly higher response to Sotalol in iPSC-CMs from high-S compared with low-S subjects. Transcriptomic profiling identified upregulation or downregulation of genes (DLG2, KCNE4, PTRF, HTR2C, CAMKV) involved in downstream regulation of cardiac repolarization and calcium handling machinery as underlying high sensitivity to Sotalol. In silico parameter sensitivity analysis corroborated transcriptomic profiling of select genes; upregulated KCNE4 and downregulated CAMKV were predicted to positively and negatively correlate with iPSC-CM action potential duration when exposed to Sotalol, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings suggest subject-specific iPSCs can be used to model functional abnormalities observed in diLQTS and offer novel insights into iPSC-based screening assays for toxic drug reactions. Success of this study may help identify key components underlying diLQT susceptibility to ultimately develop novel therapeutic agents.
2028 Discovery and evaluation of FOXP3 dimerization inhibitors
Authors: Thompson Ravyn , Coleman Cara , Dolloff Nathan G.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Immuno-oncology (IO) strategies are promising new approaches for the treatment of a variety of malignancies, including multiple myeloma (MM). Regulatory T cells (Tregs), which suppress effector T cell function, are a limitation to durable IO responses. The transcription factor FOXP3 is critical for the mature Treg phenotype. FOXP3 homodimerization is required for DNA binding and transcriptional activity, and mutations mapping to the dimerization region are associated with IPEX syndrome, resulting in dysfunctional Tregs in humans. We therefore hypothesize that inhibitors of FOXP3 dimerization will repress Treg suppression and enhance the anti-MM activity of IO. METHODS/STUDY POPULATION: To discover FOXP3 dimerization inhibitors, we are modeling FOXP3 homodimerization in vitro. Currently, we are optimizing an ALPHA screen and an ELISA-based dimerization assay using recombinant full length and truncated versions of FOXP3 to discover peptidomimetics that inhibit homodimerization. Induced Tregs expanded from human PBMCs will be treated with lead biologics and functional assays will be performed. RESULTS/ANTICIPATED RESULTS: Here we demonstrate Treg suppression of T cell proliferation and IFN-γ secretion after 5 days of co-culture under basal conditions. Additionally, we developed a MM/T cell co-culture system to measure anti-MM T cell responses and show decreased anti-MM T cell activity in the presence of Tregs. We expect to exploit the assays outlined here to demonstrate defective Treg suppression when FOXP3 dimerization is inhibited. DISCUSSION/SIGNIFICANCE OF IMPACT: These studies support drug discovery efforts that will ultimately improve IO therapies for patients with MM.
2510 Disparities in navigation to health research among Floridians
Authors: Cottler Linda B. , Varma Deepthi S. , Vaddiparti Krishna , Striley Catherine
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: The analyses explore socio-demographic characteristics of community members who are navigated and enrolled in health research through HealthStreet—the CTSA community engagement initiative at University of Florida. METHODS/STUDY POPULATION: HealthStreet utilizes the Community Health Worker model to reach the community, conduct health assessments, provide referrals to medical/social services and link people to health research. We compared never navigated, navigated and not enrolled, navigated and enrolled on demographics, access to care, common health conditions and drug use among this community dwelling population. RESULTS/ANTICIPATED RESULTS: Among the 9581 community members, 51% were navigated to a study; 41% were screened eligible and enrolled (n=2024) for an overall enrollment yield of 21%. Disparities were found for all variables; never navigated Versus the others were more likely to be African American, never married, reporting less education and less access to care. The navigated and enrolled Versus others were older females who reported more education, food insecurity, more access to care, and higher rates of hypertension, depression, and prescription opioid and marijuana use. DISCUSSION/SIGNIFICANCE OF IMPACT: Our unique and comprehensive data can assist investigators to tailor recruitment efforts that reduce disparities in health research.
2178 Drug development core facilitates institutional collaboration and translational science innovation
Authors: Morse Gene , Puzanov Igor , Gudkov Andrei , DiFrancesco Robin , Jusko William , Ernstoff Marc , Mohler James , Murphy Timothy , Bies Robert
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Drug development is a common research pursuit for basic and clinical scientists that interfaces diagnostic/therapeutic challenges with funding agencies, pharmaceutical industry, regulatory systems, and education. The University at Buffalo Clinical and Translational Science Institute (CTSI) has implemented a Drug Development Core (DDC) with goals that foster team science and collaboration, optimize laboratory use, and networks investigators. Our goals are to foster collaborations within the region and with other CTSAs. METHODS/STUDY POPULATION: The DDC met with 300 potential investigators from 14 departments and several local companies. There were 35 portal requests from 15 departments and 7 companies; 8 were from training programs. For 28 requests, a reviewer provided consultation, while 7 required discussions and review of data. DDC assisted with 15 grant applications (outcomes pending), 10 industry-related new drug development requests and 1 regulatory review. Curriculum reviews noted overlap and gaps. Cross-institute opportunities for M.D.-Ph.D. research mentoring were identified. RESULTS/ANTICIPATED RESULTS: The DDC met with 300 potential investigators from 14 departments and several local companies. There were 35 portal requests from 15 departments and 7 companies; 8 were from training programs. For 28 requests, a reviewer provided consultation, while 7 required discussions and review of data. DDC assisted with 15 grant applications (outcomes pending), 10 industry-related new drug development requests and 1 regulatory review. Curriculum reviews noted overlap and gaps. Cross-institute opportunities for M.D.-Ph.D. research mentoring were identified. DISCUSSION/SIGNIFICANCE OF IMPACT: The CTSI DDC was well received by investigators. The request process fosters collaboration among researchers with similar interests and identifies core laboratory resources that add innovation to ongoing research, funding applications, education, and interinstitutional planning.
2095 Drug screening and hit identification for night blindness with zebrafish
Authors: Ganzen Logan , Leung Yuk Fai
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Retinitis pigmentosa (RP), also known as night blindness, is an incurable disease which affects ~1 in 4000 individuals globally. Since there are no effective treatment options for RP, the goal of this project is to identify novel drug treatments that can prevent or slow the disease progression. To this end, we optimized a behavioral assay, visual-motor-response (VMR) assay, to investigate rod function (Ganzen et al., ARVO, 2017; Ganzen et al., IJMS, 2017). This was done utilizing a transgenic zebrafish RP model expressing human rhodopsin with the Q344X mutation. In this study, we used this model to perform a proof-of-concept screen for drugs which may improve the vision of the larvae. METHODS/STUDY POPULATION: To screen for beneficial drugs, the SCREEN-WELL® REDOX library was chosen for screening. This library was selected to identify a compound that may alleviate any excessive oxidative stress in the diseased retina. The Q344X zebrafish line suffers from significant rod degeneration by 7 days postfertilization (dpf) and displayed deficits in VMR under scotopic conditions (Ganzen et al., ARVO, 2017). The Q344X larvae were drug treated beginning at 5 dpf at 10 μM. Compounds that were toxic at this concentration were retested at 1 μM. The 5 dpf stage was chosen as most of the rods are intact, and these concentrations were chosen to optimize the drug effect based on similar studies. Hits were identified by assays that provided a robust and reproducible enhancement in the Q344X VMR. The retinae of any drug hits were dissected from larvae crossed with a rod EGFP reporter line and whole-mounted to analyze rod survival via fluorescence. To determine if drug effects were exerted through the retina, eyeless chokh mutant zebrafish were exposed to the drug and tested with the same assay. RESULTS/ANTICIPATED RESULTS: Of the 84 compounds tested, we identified 1 drug that ameliorated the VMR of the Q344X scotopic VMR. Eyeless chokh mutant zebrafish larvae did not exhibit the same VMR when treated with the same drug. Histological analysis suggested increased rod survival in the drug-treated retina of Q344X mutants. DISCUSSION/SIGNIFICANCE OF IMPACT: These results indicate that the vision of the Q344X zebrafish was improved via this beneficial drug treatment. Since eyeless chokh larvae did not respond to the same treatment, the drug likely mediated its positive effects through the Q344X retina, likely by improving rod survival. Together, our results have identified a beneficial drug that may treat RP.
2116 Exploring Müller cell-cone interactions in human fovea using 3-dimensional volume electron microscopy (EM)
Authors: Singireddy Ramya , Sloan Kenneth R. , Lichtman Jeff W. , Curcio Christine A. , Dacey Dennis M.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Müller cells, radial glial cells of the retina, are the principal repository of xanthophyll pigment (lutein, zeaxanthin, meso-zeaxanthin), which are modifiable by diet and visible clinically by autofluorescence imaging. To understand the structural basis of xanthophyll visualization in vivo, we used 3-dimensional electron microscopic reconstruction of Müller cells surrounding one cone in a healthy human fovea. METHODS/STUDY POPULATION: From a 21-year-old male organ donor, dissected retinas were rejuvenated by oxygenated Ames medium then fixed in 4% glutaraldehyde. A tissue block 3.5 mm2 centered on the fovea was prepared for Automated Tape Ultramicrotomy (Kasthuri et al., Cell 162: 648–661, 2015). From 1462 serial 65 nm horizontal sections, an area ~250×250 μm was imaged at 6 nm xy resolution. Images were stitched and aligned. TrackEM software on a pen display was used to trace, reconstruct, and display cone #5 (of 186) and its contacting Müller cells. RESULTS/ANTICIPATED RESULTS: Cone 5 is ensheathed by 2 types of Müller cells, outer and inner (Dacey, ARVO, 2016). The outer cell is first seen at the external limiting membrane (ELM) between cones 5 and 17. Moving inward from the ELM, it tightly wraps around cone 5’s fiber in a C-shape profile for 78 µm. This Müller cell also intermittently projects to neighboring cones, 2 of which were close to cone 5 at the ELM. As cone 5’s axon approaches the pedicle, it contorts into a corkscrew. The outer cell fluidly molds to this changing shape. At this level, this Müller cell doubles in volume to encompass not only cone 5, but also cone 17 and another Müller cell. In the final 17 µm of the block the Müller cell’s volume quickly dissipates as it sends a small projection towards the internal limiting membrane, eventually encasing an OFF midget bipolar cell also associated with cone 5. In contrast to this outer cell, an inner Müller cell adjoining cone 5 spans only 19 µm, interacting directly with cone 5 and the outer cell for 3.9 µm. DISCUSSION/SIGNIFICANCE OF IMPACT: Neural-glial relationships in a human fovea are visible through 3-dimensional volume EM. The volume of Müller cells in the fovea was impressive, consistent with a pivotal role in the health of cone photoreceptors and xanthophyll homeostasis. It is possible that individual glia also ensheath the post-receptoral neurons in a cone-driven circuit, supporting the concept that xanthophylls contribute to neural efficiency in vision.
2408 Genital microbiomes of women with recurrent bacterial vaginosis and their regular male sexual partner
Authors: Muzny Christina A. , Van Der Pol William J. , Lefkowitz Elliot J. , Ghosh Arindam , Li Mei , Redden David , Cui Xiangqin , Schwebke Jane
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Epidemiologic data suggest that BV is sexually transmitted with male partners colonized or infected with the responsible organism(s). The objective of this study was to compare the genital microbiota of women with recurrent BV and their regular male sexual partner using 16S rRNA gene sequencing and quantitative PCR targeting BV-candidate bacteria (Gardnerella vaginalis, Atopobium vaginae, BVAB1-3, Sneathia, Leptotrichia, and Megasphaera type I). METHODS/STUDY POPULATION: Women with recurrent BV (≥3 prior episodes, including a current episode) and their regular male partner participating in a BV treatment trial and providing genital specimens (women: vaginal; men: urethral, coronal sulcus, urine) at enrollment were included. Male specimens for each participant were pooled. 250 bp 16S rRNA V4 region PCR amplicons were sequenced and analyzed using the QIIME pipeline. Taxonomy was assigned using the RDP Classifier against a modified Greengenes database with additional vaginal taxonomies added. An average relative abundance cutoff of 0.5% was used for analysis. qPCR was also performed for specific BV-candidate bacteria. Spearman correlation coefficients were used to investigate associations between all genital bacteria in addition to BV-candidate bacteria between partnerships. To determine positive associations between partnerships, the Wilcoxon signed-rank test was used. RESULTS/ANTICIPATED RESULTS: In total, 45 partnerships were included. Mean partnership age was 31.3 (SD=7.9), 91.1% partnerships were African-American. The majority of partnerships (70.0%) reported condomless sex during the past 3 months. Regarding 16S data, 37 genital bacteria had an average relative abundance of ≥0.5%. The average Spearman correlation across all 45 partnerships was 0.28 (SD=0.27) (median=0.27, minimum=−0.21, maximum=0.84). Overall, a positive association of all genital bacteria existed across the partnerships (p<0.0001). However, regarding specific BV-candidate bacteria, Spearman correlation tests for G. vaginalis, A. vaginae, Prevotella bivia, Megasphaera type I, BVAB1, and BVAB2 were nonsignificant. In contrast, Sneathia spp. were positively correlated between partnerships (r=0.37, p=0.01). With regards to qPCR results, RNA Cq analyses provided significant evidence for a linear association between male and females for only A. vaginae (r=0.52, p=0.006). DISCUSSION/SIGNIFICANCE OF IMPACT: In monogamous heterosexual couples in which the female has BV, the vaginal microbiota of women and the penile/urine microbiota of men were significantly correlated, particularly with regards to Sneathia spp. and A. vaginae, supporting the hypothesis that BV-associated bacteria are exchanged during sex.
2012 Multivariate air pollutant exposure prediction in South Carolina
Authors: Boaz Ray , Lawson Andrew , Pearce John
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: The objective of this project is the application of complex fusion models, which combine observed and modeled data, to areas with sparse monitoring networks with multiple chemical components is under-developed. Such models could provide improved accuracy and coverage for air quality measurement predictions, an area greatly limited by the amount of missing data. METHODS/STUDY POPULATION: This project focuses on the development of methods for improved estimation of pollutant concentrations when only sparse monitor networks are found. Sparse monitoring networks are defined as areas where fewer than three criteria air pollutants (based on EPA standards) are monitored. Particularly, a multivariate air pollutant statistical model to predict spatio-temporally resolved concentration fields for multiple pollutants simultaneously is developed and evaluated. The multivariate predictions allow monitored pollutants to inform the prediction of nonmonitored pollutants in sparse networks. RESULTS/ANTICIPATED RESULTS: Daily, ZIP code level pollutant concentration estimates will be provided for 8 pollutants across South Carolina, and goodness of fit metrics for model variants and previously established methods will be compared. DISCUSSION/SIGNIFICANCE OF IMPACT: These methods utilize only widely available data resources, meaning that the improved predictive accuracy of sparsely monitored pollutant concentrations can benefit future studies in any US area by improving estimation of health effects and saving resources needed for supplemental air pollutant monitoring campaigns. Our method for estimation attempts to improve predictive accuracy and data availability for sparsely monitored pollutants and areas.
14C Release from TRIGA irradiated graphite
Authors: Bucur C , Ichim C , Florea I
Published: November 2018

Leaching tests were carried out in aerobic and anaerobic conditions to assess the 14C released from TRIGA irradiated graphite. Both total 14C and inorganic and organic fractions in the leachant solutions were measured. The experimental results obtained from the leaching tests confirm the low 14C release rate in alkaline environment. Less than 2% of the total 14C inventory in the specimens subject to the leaching tests was released as dissolved species. Both inorganic and organic 14C species are released in alkaline conditions, with more inorganic 14C release under aerobic conditions (around 68% of the total 14C released was released as inorganic dissolved species), and more organic 14C species in anaerobic conditions (around 65% of the total 14C released was released as organic dissolved species). Both for anaerobic and aerobic conditions, the leaching rates are high in the first days of immersion and decrease after that, indicating a two stage process: an initial quick release (less than 9 × 10–02 % of inventory/day for the first 48 days) followed by a slower release rate (around 4 × 10–03 % of inventory/day).
The representation of women in Ghanaian radio commercials: Sustaining or challenging gender stereotypes?
Authors: Diabah Grace
Published: November 2018

The relationship between gender and advertising has been discussed extensively. Scholarly works have often emanated from the West and have principally centred on visual advertisements, rather than radio (which plays a critical role in the lives of many Africans). Most of these studies have centred on how women are represented in traditionally stereotyped ways. However, recent studies have shown decreases in these stereotypes as ways of responding to changes in gender roles. But do gender-related adverts from Africa reflect the changing statuses and roles of African women (some of which challenge traditional gender stereotypes)? This article investigates how women are represented in Ghanaian radio commercials and indicates whether such representations reproduce, reinforce, or challenge feminine practices. An analysis of thirty-seven gender-related adverts reveals that, although women are rarely represented as challenging gender stereotypes, they are sometimes represented as using certain traditionally stereotyped roles as sources of ‘power’ to challenge other stereotypes. (Advertising, gender stereotypes, women, radio, Ghana, ideals of femininity)*
Trends in leaf traits, litter dynamics and associated nutrient cycling along a secondary successional chronosequence of semi-evergreen tropical forest in South-Eastern Mexico
Authors: Sánchez-Silva Sarai , De Jong Bernardus H.J. , Aryal Deb R. , Huerta-Lwanga Esperanza , Mendoza-Vega Jorge
Published: November 2018

Trends in structural and chemical leaf traits along a chronosequence of semi-evergreen tropical forest and their correlation with litter production and decomposition and associated carbon (C) and nitrogen (N) fluxes were assessed. Leaves of 15 dominant species in each plot were collected to measure leaf area, specific leaf area (SLA), C and N concentration and C:N ratio. Litterfall was measured and litter decomposition experiments were set up in 16 experimental plots in a chronosequence of secondary and mature forest. All five leaf traits combined discriminated the secondary forests from mature forest. SLA, N and C:N were significantly correlated to litter decomposition rates. Litter decomposition was significantly slower in mature forest compared with secondary forests. The N concentration of litter was lowest during the dry season, when litterfall was highest. N concentration in fresh leaves was higher than in litter, indicating that N is re-absorbed before leaf abscission. Leaf dynamics and associated nutrient cycling differ significantly between secondary forests and mature forest. Ecosystem-level leaf structural and chemical traits are good predictors of the stage of the forest and explain well the differences in decomposition rates between secondary and primary forests.
Habitat use by a mixed feeder: impalaAepyceros melampusin a heterogeneous protected area
Authors: Mandinyenya Bob , Monks Norman , Mundy Peter J. , Sebata Allan , Chirima Albert
Published: November 2018

Although large herbivore habitat use has been extensively studied, more information is still required on the use of heterogeneous vegetation types. Over 3 y we carried out monthly road transects in the Zambezi National Park (ZNP), Zimbabwe, to determine the impala density in each of five vegetation types. In addition we determined grass and browse chemical composition to test if at the time the impala switches from grass to browse, grass nutritive quality had declined below that of browse. Furthermore, grass height was measured in the five vegetation types. The impala used mixed, acacia and terminalia vegetation types, which constituted 37% of the protected area and avoided grassland and the predominant Zambezi teak (60% of ZNP) vegetation types. At the time of the diet switch by the impala from grass to browse, woody plant leaf nutritive quality was higher than grass in terms of nitrogen, calcium and acid detergent fibre content. The three vegetation types used by the impala had short to medium grass height. We concluded that when the impala switched from grass to browse the grass nutritive quality was lower than that of the browse.
War and Peace inThe Law of Peoples: Rawls, Kant and the Use of Force
Authors: Roberts Peri
Published: November 2018

Where Rawls’sThe Law of Peoplesaddresses war and the use of force then his position has often been identified closely with Walzer’s restatement of just war theory, as both positions appear to take nation-states, and the conflicts between them, to be the bedrock of the international system. On the other hand, Kant’s notion of a peaceful federation of states presents us with the notion of a world without war and where the international system is transformed. This article argues that Rawls’s account of the use of force is better understood if we read it with an eye to its resonances with Kant rather than with Walzer. Doing so rewards us with a clearer understanding of central aspects of Rawls’s account of just war and vision of international politics.
Atom Probe Reconstruction With a Locally Varying Emitter Shape
Authors: Beinke Daniel , Schmitz Guido
Published: November 2018

An improved reconstruction method for atom probe tomography is presented. In this approach, the curvature of the field emitter is variable, in contrast to the conventional reconstruction technique. The information about the tip shape at different stages of the reconstruction is directly extracted from the local density of events on the detector. To this end, the detector and the tip surface are split into different segments. According to the density distribution of events observed on the detector, the size of the corresponding segment on the tip surface is calculated, yielding an emitter profile which is not necessarily spherical. The new approach is demonstrated for emitter structures with radial symmetry that contain a spherical precipitate with a substantially lower or higher evaporation field compared to the surrounding matrix. A comparison to the conventional point projection approach is made.
Variability for grain protein content among germplasm accessions and advanced breeding lines in dolichos bean (Lablab purpureus L. Sweet var. Lignosus Prain)
Authors: Pranesh  , Ramesh S.
Published: November 2018

Protein energy malnutrition (PEM) is prevalent in south-east Asian countries including India. Breeding and introduction of grain protein-rich varieties of legumes such as dolichos bean is considered as cost-effective approach to combat PEM. Exploitation of genetic variability within germplasm accessions (GAs) and/or breeding populations is the short-term strategy for identification and delivery of protein-rich dolichos bean cultivars to cater to the immediate needs of the farmers and target population. A set of 118 dolichos bean genotypes consisting of 96 GAs and 20 advanced breeding lines (ABLs) and two released varieties (RVs) was field evaluated in augmented deign for dry grain yield per plant and their grain protein contents were estimated. The grain protein content among the genotypes ranged from 18.82 to 24.5% with a mean of 21.73%. The magnitude of estimates of absolute range, standardized range, and phenotypic coefficient of variation (PCV) for grain protein content was higher among GAs than those among ABLs + RVs. However, average grain protein contents of GAs were comparable to those of ABLs + RVs. Nearly 50% of the genotypes (mostly GAs) had significantly higher grain protein content than those of RVs, HA 3 and HA 4. The grain protein contents of the genotypes were poorly correlated with grain yield per plant. These results are discussed in relation to strategies to breed grain protein-rich dolichos bean cultivars.