bluuebunny/crossref_metadata_2025 huggingface dataset:
2356 The nasopharyngeal microbiome is perturbed and associated with increased clinical severity during acute respiratory viral infection
Authors: Dinwiddie Darrell , Bradley Ashlee K. , Denson Jesse L. , Kennedy Joshua L. , Dehority Walter N. , Schwalm Kurt C. , Young Stephen A.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: We sought to investigate the role of the host microbiome during severe, acute respiratory infection (ARI) to understand the drivers of both acute clinical pathogenesis. METHODS/STUDY POPULATION: Nasopharyngeal swabs comprised of mixed cell populations at the active site of infection were collected from 192 hospitalized pediatric patients with ARI. We combined comprehensive respiratory virus detection and virus genome sequencing with 16S rRNA gene sequencing to evaluate the microbial content of the airway during ARI. This data was coupled with 11 clinical parameters, which were compiled to create a clinical severity score. The microbiome profiles were assessed to determine if clinical severity of infection, and/or specific virus was associated with increased clinical severity. RESULTS/ANTICIPATED RESULTS: We identified 8 major microbiome profiles classified by dominant bacterial genus, Moraxella, Corynebacterium, Staphylococcus, Haemophilus, Streptococcus, Alloiococcus, Schlegelella, and Diverse. Increased clinical severity was significantly associated with microbiome profiles dominated by Haemophilus, Streptococcus, and Schlegelella, whereas Corynebacterium and Alloiococcus were more prevalent in children with less severe disease. Independent of the microbial community, more than 60% of patients with the highest clinical severity were infected with either respiratory syncytial virus or rhinovirus. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate that individually and in combination, both virus and microbial composition may drive clinical severity during acute respiratory viral infections. It is still unclear how the complex interplay between virus, bacterial community, and the host response influence long-term respiratory impacts, such as the development of asthma. Nonetheless, during ARIs therapeutic interventions such as antibiotics and probiotics may be warranted in a subset of patients that are identified to have both a virus and microbiome profile that is associated with increased pathogenesis to limit both acute and long-term phenotypes.
2371 Validation of a novel PD-L1 assay for bladder cancer circulating tumor cells
Authors: Seranio Nicolas , Aguarin Louise , Dorsey Jay F. , Christodouleas John P. , Kao Gary D.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Bladder cancer patients being considered for immune checkpoint blockade are often judged on immunohistochemical staining for the checkpoint target protein PD-L1 in the original surgery or biopsy sample. However, sampling error or the clinical evolution of most patients’ cancer can render the original PD-L1 assessment no longer accurate. In contrast, circulating tumor cells (CTCs) allow serial noninvasive sampling of the current tumor status throughout a patient’s clinical course including those with the highest metastatic potential. We therefore sought to develop a method for quantifying PD-L1 expression in CTCs towards addressing inherent limitations of current UC management. METHODS/STUDY POPULATION: This work utilizes both cancer cell lines as well as patient samples. Positive and negative control cancer cell lines were assessed via “industry standard” antibodies for PD-L1 expression via Western blots and immunofluorescence, and a threshold-based method was developed for reliable quantification. PDL-1 expression was additionally verified via interferon-mediated up-regulation. CTCs isolated from bladder cancer patient samples via a density centrifugation method were then assessed for PD-L1 via the same antibodies. RESULTS/ANTICIPATED RESULTS: We will show preliminary preclinical and clinical data that validates the sensitivity and specificity of our assay. A case study will be presented that illustrate the potential useful of the novel approach we describe and which should be complementary to current clinical practices. In a patient with metastatic bladder cancer, this method effectively detected the PD-L1 expression in CTCs taken at a time coincident to when the patient derived an excellent response to the PD-L1 checkpoint inhibitor Pembrolizumab. DISCUSSION/SIGNIFICANCE OF IMPACT: This work highlights the potential utility of CTCs in the management of bladder cancer. It may be the case that this assay in conjunction with current methods of patient selection for immunotherapy may allow for better response prediction than either method alone.
2294 Do patient comorbidities impact the effectiveness of a COPD self-management program?
Authors: Thurber Emilia Galli , Aboumatar Hanan
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Chronic obstructive pulmonary disease (COPD) is a leading cause of both hospitalizations and readmissions in the United States, and about 1 in 5 hospitalized patients with COPD will be readmitted within 30 days. COPD-focused self-management programs are frequently used to help patients better manage their symptoms and prevent hospitalization. However, while the majority of patients with COPD have at least one comorbidity, most trials of COPD self-management programs either excluded patients with significant comorbidities or did not analyze the impact of comorbidities on patient outcomes. Using data from the BREATHE trial of a COPD self-management program, this study aims to determine if patient post-intervention outcomes differ based on the intensity and type of patient comorbidities. METHODS/STUDY POPULATION: In total, 240 patients hospitalized for COPD were randomly assigned to either a comprehensive self-management intervention or usual transitional care. Primary outcomes for this trial were the number of COPD-related hospitalizations and emergency department visits at 6 months and changes in COPD-specific quality of life. To determine whether patient comorbidities modify the effect of the self-management intervention on readmission and quality of life outcomes, we will compare patient outcomes across groups stratified by comorbidity burden (Charlson Comorbidity Index) and type (baseline diagnosis of congestive heart failure, diabetes, and depression). In addition, we will use regression analysis with interaction terms to test for interaction between comorbidity burden/type and intervention assignment. RESULTS/ANTICIPATED RESULTS: We hypothesize that the effect of the self-management intervention will differ in patients with greater comorbidity burden due to competing medical demands for patients with multimorbidity. DISCUSSION/SIGNIFICANCE OF IMPACT: The results of this study will help clinicians better target disease-specific self-management programs to the groups of patients with COPD who are likely to receive the greatest benefit from this type of intervention.
2326 Prognostic value of left ventricular mitral annular longitudinal displacement measured by tissue Doppler imaging in patients with acute coronary syndrome
Authors: Lassen Mats , Skaarup Kristoffer G. , Iversen Allan Z. , Jørgensen Peter G. , Olsen Flemming J. , Jensen Jan S. , Biering-Sørensen Tor
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: To investigate the prognostic value of left ventricular mitral annular longitudinal displacement (LD) measured with color tissue Doppler imaging (TDI) in a large population suffering from acute coronary syndrome (ACS). METHODS/STUDY POPULATION: In total, 501 ACS patients underwent an echocardiography within 9 days after a percutaneous coronary intervention. Regional LD was obtained from the 6 mitral annular regions with TDI and GLD was calculated as an average. RESULTS/ANTICIPATED RESULTS: During a median follow-up time of 4.4 years 46 ACS patients suffered CVD. Mean value of GLD in the population was 8.11mm (±2.4). GLD and LD obtained from the inferior wall remained significant independent predictors after multivariate adjustment for clinical parameters, GLD (HR: 1.43, 95% CI: 1.12–1.82, p=0.014, per 1mm decrease), inferior LD (HR: 1.38, 95% CI: 1.14–1.66, p=0.001). Furthermore, inferior wall LD was the primary source of prognostic information in GLD since only inferior LD remained significant when both measures were included in the same model: GLD (HR: 0.95, 95% CI: 0.64–1.40, p=0.781); inferior LD (HR: 1.60, 95% CI: 1.15–2.22, p=0.005). Of all walls, only inferior wall LD remained as an independent predictor after multivariate adjustment. DISCUSSION/SIGNIFICANCE OF IMPACT: GLD provides independent prognostic information in ACS patients over and beyond all conventional echocardiographic measures. Regional inferior LD was the primary source of prognostic information gained from GLD. GLD proved to be a better predictor of cardiovascular events than conventional echocardiographic measures. This could lead to better risk stratification in the clinical setting and open up for earlier intervention in high-risk individuals.
2562 Racial/ethnic variation in the relationship between metabolic syndrome components and cardiovascular disease and the role of uric acid among population with metabolic syndrome
Authors: Shaheen Magda
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: To examine the racial/ethnic variation in the relation between metabolic syndrome (MetS) components and cardiovascular disease (CVD) as well as examine the role of uric acid as a predictor of CVD among population with MetS. METHODS/STUDY POPULATION: We analyzed National Health and Nutrition Examination Surveys data (1999–2010) for adults aged >20 years with MetS. Using the ATP III clinical criteria for diagnosing MetS, subjects were classified as having MetS if they had ≥3 of the following: waist circumference ≥40 inches for men or ≥35 inches for women, triglyceride ≥150 mg/dL, HDL-C for men ≤40 mg/dL; women ≤50 mg/dL, pre-hypertension, or fasting glucose ≥110 mg/dL. We used multiple logistic regression in STATA 14 survey module to examine the relation between MetS components and CVD adjusting for age, gender, race/ethnicity, education, smoking, alcohol, albuminuria, glomerular filtration rate, C-reactive protein, uric acid and white blood count. To assess the racial/ethnic variation, we examined the same model in each race/ethnic group. RESULTS/ANTICIPATED RESULTS: Of the 3212 subjects, 78% were Whites, 10% were Blacks, and 15% had CVD. MetS components, CVD, and uric acid varied significantly by race/ethnicity (p<0.05). In the multivariate model, HDL-C level [odds ratio (OR)=1.5; 95% confidence interval (CI)=1.1–2.0], triglyceride level (OR=2.0; CI=1.4–2.9), and elevated uric acid (OR=1.4; CI=1.1–1.9) were independently related to CVD (p<0.05). While CVD was independently related to HDL-C, triglyceride, and elevated uric acid in Whites (p<0.05), it was associated with pre-hypertension and triglyceride in Blacks (p<0.05) and no predictors in Hispanics (p>0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: Elevated uric acid, HDL-C, and triglyceride levels are significant independent predictors of CVD among population with MetS. These predictors varied by race/ethnicity. Health care providers should be vigilant in the management of MetS components and control of uric acid level in each racial/ethnic group to prevent the CVD risk among the population with MetS.
2513 Evaluation of the current status of urologic training programs in the delivery of transgender care
Authors: Schoenfeld Daniel , Drzewiecki Beth
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Transgender individuals remain an underserved population with a unique set of healthcare needs. Given the recent increase in demand for gender affirmation surgery, there is a need to train urologists in the various aspects of surgical management of transgender patients. It is unclear how many urologic residency programs are participating in transgender care. In this study, we sought to determine the current status of urologic training programs in the delivery of transgender care and the sentiments regarding the current and future need to train urologists. METHODS/STUDY POPULATION: Between June and August 2017, a 22 item cross-sectional survey was emailed to all 138 program directors (PDs) as listed by the ACGME. Participation was voluntary and responses were anonymous. Statistical analysis was performed using SAS version 9.4. RESULTS/ANTICIPATED RESULTS: In total, 48 PDs completed the survey (36% of US PDs) and 1 declined to participate. All AUA regions had at least 25% representation, except the Western region (13%). In total, 42% of urology programs that responded participate in institutional transgender health programs; 76% of PDs believe there is a current or future need to train urology residents in the surgical care of transgender patients. PDs were significantly more likely to endorse a need for transgender training if their institution has a transgender health program (95% vs. 58%, p<0.005). Similarly, expressed interest in transgender care by trainees was associated with increased belief among PDs in the need for transgender training (95% vs. 58%, p<0.005). There was also an association between the presence of a transgender health program and trainee interest in transgender care (64% vs. 33%, p=0.04). Need for resident training in the following procedures was cited most often by PDs: complicated catheter placement (91%), orchiectomy (89%), urethral fistula repair (82%), penile/testicle prosthesis insertion (77%), phalloplasty (69%), vaginoplasty (66%), and metoidioplasty/urethral lengthening (54%). Despite the overall consensus that residents should be trained in transgender care, 83% of PDs responded that urologic transgender surgery should be trained in fellowship rather. DISCUSSION/SIGNIFICANCE OF IMPACT: There is an increased demand for surgeons competent in providing gender affirmation surgery. The majority of urology residency PDs believe in the need to train residents in the surgical care of transgender patients. A formalized curriculum for the urologic management of transgender patients should be instituted across residency programs to ensure adequate exposure and competency.
2442 Listening for empathy: Audio narratives in DPT curriculum as a model for interprofessional education
Authors: Farroni Jeffrey S. , Farroni Laura W. , Russell Rebecca
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: (1) Evaluate the auditory narrative process as a learning experience for interviewer, editor, and interviewee. (2) Discuss methodologies for developing or selecting audio narratives and suggest how to effectively integrate them into the DPT curriculum, or thread into individual coursework. (3) Experience and appraise podcast components developed for a DPT psychosocial aspects of disability course. METHODS/STUDY POPULATION: Students were provided preassessment and postassessment on empathy. Other methodologies include conducting interviews, developing story boards, and editing audio narratives. RESULTS/ANTICIPATED RESULTS: Learner feedback indicated that course material was experienced in a way that deepens one’s understanding of the complex and challenging issues facing patient, caregivers, and themselves as they embark on their profession. DISCUSSION/SIGNIFICANCE OF IMPACT: The utility of integrating different modalities within coursework is to enrich learner experience to encourage self-reflection and awareness of not only their identity but that of multidisciplinary collaborators.
2475 The leveling of clinical research competencies
Authors: Jones Carolynn T. , Brouwer Rebecca N. , Aldinger Carmen E. , Kolb Robert , Gluck William , Bierer Barbara , Sonstein Stephen A.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Objectives/goals: Describe the process used to develop leveled competencies and associated examples. Discuss the final leveled competencies and their potential use in clinical research professional workforce initiatives. METHODS/STUDY POPULATION: The revised JTFCTC Framework 2.0 has 51 competency statements, representing 8 domains. Each competency statement has now been refined to delineate fundamental, skilled or advanced levels of knowledge and capability. Typically, the fundamental level describes the competency for a professional that requires some coaching and oversight, but is able to understand and identify basic concepts. The skilled level of the competency reflects the professional’s solid understanding of the competency and use of the information to take action independently in most situations. The advanced level embodies high level thinking, problem solving, and the ability to guide others in the competency. The process for developing both the three levels and examples involved 5 workgroups, each chaired by a content expert and comprising of national/international clinical research experts, including representatives from research sites, professional associations, government, and industry and academic sponsors. RESULTS/ANTICIPATED RESULTS: The committee developed 51 specific competencies arrayed across 3 levels and examples of each to demonstrate an appropriate application of the competency. The competencies and examples, and potential utilization, will be described. DISCUSSION/SIGNIFICANCE OF IMPACT: The use of competencies in the context of workforce development and training initiatives is helping to create standards for the clinical research profession. These leveled competencies allow for an important refinement to the standards that can be used to enhance the quality and safety of the clinical research enterprise and guide workforce development.
2376 Efficacy of a 4-part program on brain development
Authors: Silver Emily , Michael Nancy
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: (1) Provide basic brain knowledge about development and resiliency. (2) Develop an understanding of how a mother can impact a child’s brain development. (3) Foster a sense of agency to increase the likelihood that a mother will enact positive changes. (4) Develop the ability to recognize a connection between one’s own behaviors and a child’s development and behaviors. METHODS/STUDY POPULATION: Tested the efficacy of a 4-week intervention program on neurodevelopment for homeless mothers. Mothers (n=4) residing at the Center for the Homeless in South Bend, IN were recruited. Used community partner feedback, weekly surveys, and pre/post tests to look at changes in basic content knowledge, behavioral change, and self-efficacy. RESULTS/ANTICIPATED RESULTS: Preliminary results indicate an increase in knowledge about neurodevelopment, although results on behavioral changes are inconclusive. The program is anticipated to run a second time with a new group of parents residing in the Center for the Homeless to increase sample size. DISCUSSION/SIGNIFICANCE OF IMPACT: Anticipated that the results will add to the existing literature concerning effective interventions in strengthening parenting and neuroscience knowledge in vulnerable populations.
2218 An application of the payback framework to evaluate the outcomes of pilot projects supported by the Georgia Clinical and Translational Science Alliance from 2007 to 2014
Authors: Rollins Latrice , Llewellyn Nicole , Nehl Eric , Sosa Astrid
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: We will use a structured evaluation framework, the payback framework, to document the outcomes of 15 case studies of pilot projects supported by Georgia CTSA from 2007 to 2014. METHODS/STUDY POPULATION: We will use a case study approach including bibliometric analyses of publications associated with the selected projects, document review (e.g., investigator curriculum vitae, biannual project reports) and investigator interviews. RESULTS/ANTICIPATED RESULTS: We will document outcomes in 5 “payback categories”: (1) knowledge, (2) research targeting, capacity building, and absorption, (3) policy and product development, (4) health benefits, and (5) broader economic benefits. DISCUSSION/SIGNIFICANCE OF IMPACT: This study will aid in characterizing the returns resulting from this research funding and identify its strengths and weaknesses. This study will inform our understanding of the diversity and breadth of outcomes resulting from Georgia CTSA-supported research, and the value pilot projects provide to clinical and translational science and the broader community.
2443 Attitudes and preferences for return of results from next-generation sequencing
Authors: Neu Matthew , Richards Jaimie , Knight Sara J.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Objectives: Decreasing costs and increasing evidence for clinical utility have contributed to whole genome sequencing (WGS) becoming a clinical reality. While previous studies have surveyed the attitudes of patients and community members towards specific gene tests, an emerging literature has begun to describe the preferences of diverse recipients for WGS results. In this study, we sought to identify and synthesize the quantitative evidence on preferences for results from WGS using a systematic review of the literature. METHODS/STUDY POPULATION: We conducted a search of articles on PubMed including subject index terms WGS, whole exome sequencing, genome sequencing, secondary findings, incidental findings, attitudes, preferences, choices, utilities, stated-preferences, discrete choice experiment, and willingness-to-pay. We conducted 11 formal searches to refine the strategy and conducted a final search in December 2017. Duplicates were eliminated and a title and abstract review was conducted to select articles meeting inclusion criteria. RESULTS/ANTICIPATED RESULTS: Our search strategy identified 79 publications meeting initial search criteria with 30 manuscripts meeting inclusion criteria. Of these, most studies were conducted with patient-participants enrolled in existing sequencing studies, while few engaged members of the general public. Of the studies conducted on patients, most were on the medical setting of cancer and related syndromes. The earliest publication date of a manuscript meeting our inclusion criteria was in 2012, yet the majority were published in 2015 or later. DISCUSSION/SIGNIFICANCE OF IMPACT: Between 2012 and 2015, we saw an increasing focus in the medical literature on understanding public and patient preferences for return of results from WGS and WES. Both public and patient populations participating in surveys expressed preferences for receiving results from next-generation sequencing, even if the results are secondary or incidental findings unrelated to the primary indication for sequencing. A primary factor related to patient interest in incidental or secondary findings is the extent to which these results can inform medical intervention. Few studies surveyed representative population-based samples, and this may be an area for future investigation.
2108 Factors associated with dual use of VA and civilian healthcare among U.S. National Guard and Reserve soldiers
Authors: Vest Bonnie M. , Kulak Jessica A. , Homish D. Lynn , Homish Gregory G.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Approximately 25%–45% of veterans are dual users of VA and civilian healthcare. In order to maximize patient outcomes, understanding factors related to dual use is important. This study examined mental and physical health factors related to dual use of VA and civilian healthcare among U.S. National Guard and Reserve (NG/R) soldiers. METHODS/STUDY POPULATION: NG/R soldiers and their partners (n=411 couples) participated in an electronic survey assessing health and health behaviors. Logistic regression models were used to examine the relationship between mental health (anxiety, depression, PTSD, anger), general health, and VA disability status at baseline, with usage of both VA and civilian healthcare among male soldiers (n=109) at the second year follow-up, controlling for age and race. RESULTS/ANTICIPATED RESULTS: In the final adjusted models, of the mental health conditions, only anxiety was related to dual use (OR: 1.08, 1.01–1.16, p<0.05). Having a VA disability rating (OR: 4.00, 1.22–13.18; p<0.05) was also related to being a dual user. General health was not related to dual use. DISCUSSION/SIGNIFICANCE OF IMPACT: While research has identified demographic characteristics (e.g., rurality, race, income) related to dual healthcare use, our results indicate that mental health, particularly anxiety, may also be related to dual use. Further study is needed to tease out the prime drivers of dual use to identify future care delivery mechanisms that will maximize treatment outcomes and minimize duplicative care.
2340 A robust spatial normalization pipeline for individuals with focal cortical lesions
Authors: DeMarco Andrew , Turkeltaub Peter
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: To develop a robust spatial normalization pipeline for brains of individuals with focal cortical lesions. METHODS/STUDY POPULATION: Individuals with chronic focal cortical lesions from stroke. RESULTS/ANTICIPATED RESULTS: We have developed a robust spatial normalization pipeline for brains of individuals with focal cortical lesions, and demonstrate how the pipeline overcomes obfuscated neuroanatomy to yield both consistent and excellent results. DISCUSSION/SIGNIFICANCE OF IMPACT: Our robust normalization pipeline will enable group analyses of individuals with cortical lesions with greater spatial precision. This greater spatial precision will improve answers to questions about functional localization in the brain, and ultimately allow translation of findings from neuroimaging studies in individuals with cortical lesions to the clinic.
2167 Beyond diagnosis: Using ultrasound to affect tumor vasculature for hepatocellular carcinoma (HCC) therapy
Authors: D’Souza Julia , Sultan Laith , Carlin Sean , Gade Terence , Hunt Stephen , Sehgal Chandra
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Preliminary animal studies showed that low-intensity ultrasound (US) coincident with intravascularly administered microbubbles locally disrupts tumor vasculature. This study translates the novel therapy of antivascular ultrasound (AVUS) into an autochthonous model of hepatocellular carcinoma (HCC). The differential effects produced by AVUS at low and high doses are evaluated. METHODS/STUDY POPULATION: HCC was induced in 12 Wistar rats by ingestion of 0.01% diethylnitrosamine in drinking water for 12 weeks. Rats received AVUS treatment at low and high doses. Low dose group (n=6) received 1 W/cm2 US for 1 minute with 0.2 mL microbubbles injected IV. High dose group (n=6) received 2 W/cm2 for 2 minute with 0.7 mL microbubbles IV. Perfusion was measured before and after AVUS with contrast-enhanced ultrasound (CE-US) and power Doppler (PD-US). Peak enhancement (PE) and perfusion index (PI) were measured from each US mode. Histology after sacrifice or natural death was compared to pre/post US. Analysis of H&E and trichrome sections was evaluated for percent area of hemorrhage and findings of tissue injury and repair including inflammation, necrosis, and fibrosis. RESULTS/ANTICIPATED RESULTS: After high dose AVUS, PE, and PI of CE-US decreased from baseline by an average of 33.3% and 29.7%, respectively. Histology showed extensive tissue injury (hemorrhage, necrosis, fibrosis) in 58% of tumor cross-sectional area. Conversely, low dose AVUS increased PE and PI of CE-US by an average of 39.3% and 67.8%, respectively. Histology showed smaller areas of microhemorrhage Versus large pools of hemorrhage (only 17% area). PD-US changes were similar to CE-US. DISCUSSION/SIGNIFICANCE OF IMPACT: In summary, the opposing effects of AVUS observed at 2 doses allows for multiple roles in tumor therapy. Enhanced perfusion at a low dose may improve drug delivery or radiation therapy. Whereas, vascular disruption at high doses of AVUS may allow noninvasive ischemic therapy. Furthermore, AVUS is ripe for translation given the use its component parts clinically: low-intensity long-tone burst for physiotherapy and microbubbles as an US contrast agent. Thus, AVUS should be evaluated for translation of its differential effects into noninvasive therapies for HCC and other tumors.
2433 Community forums as a channel for communicating with the public and to influence perceptions of cancer clinical trials
Authors: Flood-Grady Elizabeth , James Vaughan , Krieger Janice L.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Cancer clinical trials (CCTs) are vital tools in the advancement of cancer prevention and treatment. Yet, only 3%–5% of eligible patients enroll in CCTs. Low participation can be attributed, in part, to poor communication as well as a lack of awareness and understanding about CCTs. In order to increase participation in trials, interventions should foster meaningful communication about cancer prevention and CCTs, especially between medical professionals and members of the community. Community forums provide a channel to communicate about cancer with members public and to educate prospective participants about CCTs. Thus, our goal was to evaluate the efficacy of hosting community forums about cancer in order to educate the public and influence perceptions of CCT participation. METHODS/STUDY POPULATION: During the Spring of 2016, participants (n=51) who attended a community forum about CCTs completed a pretest and post-test survey assessing their understanding and perceptions of CCTs. RESULTS/ANTICIPATED RESULTS: Results from the pretest to post-test survey revealed a significant positive increase (p=0.01) in participants’ attitudes toward cancer clinical research as well as marginally significant increases in participants’ perceived subjective norms (p=0.06) about participating in CCTs and the perceived personal relevance (p=0.06) of clinical research participation pretest and post-test. DISCUSSION/SIGNIFICANCE OF IMPACT: Findings suggest that community forums about cancer and CCTs could lead to an increased awareness and understanding of CCTs among members of the population and could be useful channels for cancer interventions.
2564 Designing for dissemination: Characteristics of Clinical and Translational Science Award (CTSA) hubs as adopters of clinical and translational science innovation
Authors: Morrato Elaine H. , Lennox Lindsay , Schuster Anne
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: The Clinical and Translational Science Award (CTSA) program is a national consortium of 50+ academic medical research centers charged with accelerating the translation of clinical research. In 2017, the NIH National Center for Advancing Translational Sciences anticipates total CTSA program funding of over $500M. The consortium’s hub-and-spoke structure makes it a natural dissemination network, and the newest funding announcement makes dissemination of innovation across the consortium an explicit goal, but characteristics of CTSA hubs as adopters and transmitters of innovation are unknown. METHODS/STUDY POPULATION: A content analysis was conducted using data from CTSA hub Web sites (n=64) and a structured coding taxonomy based on 6 constructs drawn from literature about diffusion of innovation in service organizations (Greenhalgh et al., 2004): dissemination priority, institutional complexity, communication infrastructure, support for dissemination/implementation functions, cross-institutional collaboration/networking, and leadership composition. RESULTS/ANTICIPATED RESULTS: In total, 52% of hubs will renew under the new PAR in the next few years, providing an incentive to demonstrate dissemination capacity (although hubs will likely lag in operationalizing these activities until they are funded). A third of hubs (34%) represent more than one academic/research institution, and almost 80% of hubs have more than one clinical affiliate. To accommodate these different levels of institutional complexity, broad diffusion will require multi-modal, locally adapted dissemination efforts. Only 25% of hubs have capacity to undertake additional dissemination activities, and only 27% provide formal D&I support, suggesting that additional capacity/support will be needed to operationalize the CTSA dissemination mission. In total, 30% of hubs participate in cross-institutional collaboration/networking, so many may not have existing norms/tools supporting inter-institutional collaboration, but 77% include leadership from outside the School of Medicine, facilitating effective intrainstitutional dissemination. DISCUSSION/SIGNIFICANCE OF IMPACT: Understanding more about CTSA hubs as both adopters and transmitters of innovation can facilitate strategic use of these sites as a built-in dissemination network to amplify the reach and impact of clinical innovation and improve population health. Based on this initial analysis, the CTSA network does not appear to be fully primed for broad, rapid dissemination of innovation across its sites. In-depth interviews are being conducted to investigate CTSA hubs’ perceptions of their dissemination capacity and roles as adopters and transmitters of innovation.
2038 Effects of bilateral frontal transcranial direct current stimulation (tDCS) on the working memory network: An fMRI-tDCS study in healthy older adults
Authors: Nissim Nicole R. , O’Shea Andrew , Richards Lindsey , Telles Rachel , Porges Eric , Cohen Ronald , Woods Adam J.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: The study aimed to determine the effects of bilateral frontal active transcranial direct current stimulation (tDCS) at 2 mA for 12 minute Versus sham stimulation on functional connectivity of the working memory network during an fMRI N-Back task. METHODS/STUDY POPULATION: Stimulation was delivered over bilateral frontal dorsolateral prefrontal cortex via and MRI-compatible tDCS device during an fMRI working memory task in healthy older adults in a within-subject design. RESULTS/ANTICIPATED RESULTS: Active stimulation compared with sham resulted in significant increases in functional connectivity in working memory related brain regions during the N-Back task. DISCUSSION/SIGNIFICANCE OF IMPACT: Older adults typically have reduced functional connectivity compared with young adults. Our findings demonstrate that a single session of tDCS can increase functional connectivity of the working memory network in older adults. Based on this mechanism of effect, tDCS may serve as an adjunctive method for interventions aiming to enhance cognitive processes in older adults.
2338 Identifying the genetic determinants of human brown adipose tissue
Authors: Becher Tobias , Cohen Paul , Wibmer Andreas , Kramer Daniel J.
Published: November 2018

OBJECTIVES/SPECIFIC AIMS: Brown adipose tissue (BAT) increases energy expenditure by dissipating chemical energy as heat. The combustion of glucose and lipids produces beneficial metabolic effects and renders BAT an attractive target to battle obesity and associated diseases. The majority of adults do not display active BAT on positron emission tomography (PET) without prior cold exposure. Interestingly, a fraction of individuals with BAT positive PET scans exhibits excessive BAT (eBAT) activity, indicating a possible underlying genetic contributor. We aim to identify genetic determinants of BAT activity by studying individuals with eBAT activity using next-generation sequencing. A cellular model will be used to validate variants and perform in-depth pathway analysis. METHODS/STUDY POPULATION: We performed a retrospective review of PET scans over a period of 12 months in patients presenting with suspected or diagnosed cancer (n=20,348). The distribution of BAT positive individuals (n=1251) was used to implement a threshold to define eBAT activity. Samples from prospectively recruited individuals with BAT activity above the threshold will undergo whole exome sequencing. Variants associated with eBAT activity will be engineered into an immortalized BAT cell line using CRISPR to validate results and perform in-depth pathway analysis. RESULTS/ANTICIPATED RESULTS: We expect to identify genetic variants associated with eBAT. Studying the effects of these variants on thermogenesis followed by in-depth pathway analysis in genetically engineered cellular and mouse models may enable us to find new regulators of BAT activity. These findings may eventually contribute to the development of new drugs targeting obesity and its sequelae. DISCUSSION/SIGNIFICANCE OF IMPACT: The contribution of genetic factors to individual BAT activity is currently unknown. Identifying individuals with eBAT on PET scans and studying the underlying genetic determinants may provide the foundation for the discovery of new pathways for BAT activation.
Infection prevention in long-term care: re-evaluating the system using a human factors engineering approach
Authors: Katz Morgan Jane , Gurses Ayse P
Published: November 2018

The emergence and spread of extensively multidrug-resistant organisms is a public health crisis, and long-term care settings have been identified as a reservoir for the cultivation of these organisms. Long-term care settings are now taking on increasingly ill residents with complicated medical problems, indwelling devices, and significant healthcare exposure, all of which are considered risk factors selecting for resistant organisms. Despite this, guidelines addressing infection prevention procedures in long-term care remain vague, and implementation of these guidelines is challenging, largely due to staff turnover, limited resources, knowledge gaps, and lack of organizational support. Human factors engineering approaches have emerged as an important innovation to address patient safety issues and develop interventions in the healthcare work system (ie, tools and technologies, tasks, organization, physical environment) that support human performance, which, in turn, lead to improvements in processes (eg, compliance with infection prevention guidelines) and outcomes (eg, reduced infection rates). We propose the concept of using the methods and approaches from the scientific field of human factors engineering to address the unique challenges of implementing infection prevention in the long-term care setting.
Sensitivity of high-speed boundary-layer stability to base-flow distortion
Authors: Park J. , Zaki T. A.
Published: November 2018

The linear stability of high-speed boundary layers can be altered by distortions to the base velocity and temperature profiles. An analytic expression for the sensitivity is derived for parallel and spatially developing boundary layers, the latter using linear parabolized stability equations and their adjoint. Both the slow mode, S, and the fast mode, F, are investigated at Mach number 4.5. The mode S is more sensitive with respect to distortion in base velocity than in base temperature. The sensitivity is largest within the boundary layer away from the wall. Near the critical layer, where the phase speed of the mode equals the base streamwise velocity, the sensitivity to the base streamwise velocity is negative. For the mode F, there is a discontinuous jump in the sensitivity when the phase speed is below unity, and a critical layer is established. The sensitivity of the two modes increases with the Reynolds number, but there is a sudden drop and a jump in the sensitivities of the modes S and F, respectively, near the synchronization point where the phase speeds of the two modes are equal. Furthermore, the maximum uncertainty bounds are obtained for the distorted base state that maximizes the destabilization or stabilization of the modes by solving the Lagrangian optimization problem for the sensitivity. The sensitivity of the flow stability to surface heating is then studied, and changes in growth rate and the$N$-factor are evaluated. The formulation provides a clear physical interpretation of these changes, and establishes uncertainty bounds for stability predictions for a given level of uncertainty in wall temperature.
A comprehensive model for predicting droplet freezing features on a cold substrate
Authors: Tembely Moussa , Dolatabadi Ali
Published: November 2018

Water droplet freezing affects many aspects of our daily lives, although there is no comprehensive model which retrieves all of the experimentally observed features when a liquid water droplet deposited on a cold substrate turns to ice. In this paper, we present general governing equations to describe water droplet freezing on a solid substrate by accounting for the physical properties of each phase present, namely the liquid and ice, in addition to the solid substrate. The approach, which takes advantage of the full mean curvature expression of both the droplet–air and liquid–ice interfaces, disjoining pressure, the Gibbs–Thomson effect, natural convection and the substrate thermal and physico-chemical properties, enables us to model a more realistic frozen droplet shape, without a prior assumption for the freezing growth angle. In addition to correctly predicting the freezing time, we capture both qualitatively and quantitatively the key experimentally observed features during water droplet freezing such as volume expansion, concave ice front and the cusp singularity. Furthermore, the proposed equation for the tip angle seems to explain its experimentally observed variability.
When elites polarize over polarization: Framing the polarization debate in Turkey
Authors: Aydın-Düzgit Senem , Balta Evren
Published: November 2018

This article aims to explore the views of the Turkish elite on the state of polarization in Turkey. By identifying four political frames—namely, harmony, continuity/decline, conspiracy, and conflict—that selected Turkish political and civil society elites use in discussing the phenomenon of polarization in the country through their contributions to a workshop and in-depth qualitative interviews, the article finds that there is a considerable degree of polarization among the Turkish elite regarding their views on the presence of polarization in Turkey. Moreover, this overlaps with the divide between the government and the opposition in the country. An analysis of the justificatory arguments employed in constituting the aforementioned frames shows that, while those elites who deny the existence of polarization seek its absence in essentialist characteristics of society, in reductionist comparisons with history, or in internal/external enemies, those who acknowledge polarization’s presence look for its roots in political and institutional factors and processes. The article highlights how, given the denial of polarization by the pro-government elite and the substantial gap between the two camps’ justificatory narratives, the currently reported high rates of polarization in Turkey can, at best, be expected to remain as is in the near future, barring a radical change in political constellations.
Risk of non-affective psychotic disorder or bipolar disorder in autism spectrum disorder: a longitudinal register-based study in the Netherlands
Authors: Schalbroeck R. , Termorshuizen F. , Visser E. , van Amelsvoort T. , Selten J. P.
Published: November 2018

Background

Individuals with autism spectrum disorder (ASD) appear to be at increased risk of non-affective psychotic disorder (NAPD) and bipolar disorder (BD). However, most previous studies examined the co-occurrence of ASD and NAPD or BD, ignoring possible diagnostic bias and selection bias. We used longitudinal data from Dutch psychiatric case registers to assess the risk of NAPD or BD among individuals with ASD, and compared the results to those obtained for the Dutch population in earlier studies.

Methods

Individuals with ASD (n = 17 234) were followed up between 16 and 35 years of age. Kaplan–Meier estimates were used to calculate the risk of NAPD or BD. We conducted separate analyses to reduce possible bias, including an analysis among individuals diagnosed with ASD before age 16 years (n = 8337).

Results

Of the individuals with ASD, 23.50% (95% confidence interval 21.87–25.22) were diagnosed with NAPD and 3.79% (3.06–4.69) with BD before age 35 years. The corresponding figures for the general population were 0.91% (0.63–1.28) and 0.13% (0.08–0.20). Risk estimates were substantially lower, but still higher than general population estimates, when we restricted our analyses to individuals diagnosed with ASD before age 16, with 1.87% (1.33–2.61) being diagnosed with NAPD and 0.57% (0.21–1.53) with BD before age 25 years. The corresponding figures for the general population were 0.63% (0.44–0.86) and 0.08% (0.05–0.12).

Conclusions

Individuals with ASD are at increased risk of NAPD or BD. This is likely not the result of diagnostic or selection bias.
A review of learning planning action models
Authors: Arora Ankuj , Fiorino Humbert , Pellier Damien , Métivier Marc , Pesty Sylvie
Published: November 2018

Automated planning has been a continuous field of study since the 1960s, since the notion of accomplishing a task using an ordered set of actions resonates with almost every known activity domain. However, as we move from toy domains closer to the complex real world, these actions become increasingly difficult to codify. The reasons range from intense laborious effort, to intricacies so barely identifiable, that programming them is a challenge that presents itself much later in the process. In such domains, planners now leverage recent advancements in machine learning to learn action models, that is, blueprints of all the actions whose execution effectuates transitions in the system. This learning provides an opportunity for the evolution of the model toward a version more consistent and adapted to its environment, augmenting the probability of success of the plans. It is also a conscious effort to decrease laborious manual coding and increase quality. This paper presents a survey of the machine learning techniques applied for learning planning action models. It first describes the characteristics of learning systems. It then details the learning techniques that have been used in the literature during the past decades, and finally presents some open issues.
Liberal Justice: Kant, Rawls and Human Rights
Authors: O’Neill Onora
Published: November 2018

Kant’s practical philosophy, Rawls’s theory of justice and contemporary human rights thinking are landmarks in liberal discussions of justice. Each forms part of a powerful tradition of political thought, and although their substantive accounts of justice diverge at many points, they also overlap in substantial ways. This article focuses not on their substantive claims about justice, or about other ethical standards, but on their differing views of thequestionsto be addressed, on their proposedjustificationsfor standards of justice, and on a limited range of questions aboutinterpretingandinstitutionalizingthose standards.
Time-domain analysis of a CRLH coupled-line coupler using the CN-FDTD method
Authors: Gholami Mayani Mahdieh , Asadi Shahrooz , Karimian Shokrollah
Published: November 2018

In this study, the implicit Crank–Nicolson finite-difference time-domain (CN-FDTD) method is applied to discretize the governing telegrapher's equations of a composite right-/left-handed (CRLH) coupled-line coupler. The unconditionally stable CN-FDTD is compared with the conventional leap-frog (LF) FDTD method. The results obtained from the CN-FDTD scheme show up to 10 times increase in the temporal step size, reflecting in a dramatic decrease in processing time; in addition to having a good agreement with the LF method and the measurements.