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Primary Sponsor Madison M. Berl, PhD Assistant Professor, Psychiatry & Behavioral Sciences Dept. of Neuropsychology, CNMC 111 Michigan Avenue, NW Washington, DC 20010 Office Phone: (202) 476-2545; Fax: (301) 765-5497 [email protected] Secondary Sponsor William Davis Gaillard MD/ Plasticity Of Language and Epilepsy Research (POLER) lab Professor, Pediatrics & Neurology Dept. of Neurology, CNMC same as above Office Phone: 202-476-5224; Fax: (202) 476-5226 [email protected] Name of proposed project: Functional and structural connectivity of cognition (language and working memory) in children with epilepsy. Sponsor research focus: The focus of our research is to characterize the functional, structural, and neuropsychological differences in pediatric epilepsy patients as compared to healthy volunteers with regard to neuropsychological performance, specifically language and working memory. Background and overall design of the research project (please indicate if this is a new project or a part of a larger and/or existing research effort): As part of a larger research project, this individual project will look specifically at the functional role and structural organization of the language neural network, particularly the frontal lobes. DTI may be used to identify structural abnormalities associated with functional differences and cognitive dysfunction, particularly when traditional MRI studies are within normal limits. DTI measures the degree to which the direction of the diffusion is affected by the macromolecular and tissue structure providing a mechanism for determining the architecture of tissue in vivo especially white matter. This is a cross-sectional design looking at 15 normal controls compared to 15 epilepsy patients in how they compare on variables generated from DTI analysis specifically, anisotropy (or diffusivity). It is hypothesized that patients will have frontal areas of increased diffusivity. If there is time, the student may want to correlate these values with neuropsychological performance and/or activation from functional MRI studies. There are several analysis methods and the student will utilize one method that has not yet been conducted by this lab. 1

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Primary SponsorMadison M. Berl, PhDAssistant Professor, Psychiatry & Behavioral SciencesDept. of Neuropsychology, CNMC111 Michigan Avenue, NW Washington, DC 20010Office Phone: (202) 476-2545; Fax:(301) [email protected]

Secondary SponsorWilliam Davis Gaillard MD/ Plasticity Of Language and Epilepsy Research (POLER) labProfessor, Pediatrics & NeurologyDept. of Neurology, CNMCsame as aboveOffice Phone: 202-476-5224; Fax: (202) [email protected]

Name of proposed project:Functional and structural connectivity of cognition (language and working memory) in children with epilepsy.

Sponsor research focus:The focus of our research is to characterize the functional, structural, and neuropsychological differences in pediatric epilepsy patients as compared to healthy volunteers with regard to neuropsychological performance, specifically language and working memory.

Background and overall design of the research project (please indicate if this is a new project or a part of a larger and/or existing research effort):As part of a larger research project, this individual project will look specifically at the functional role and structural organization of the language neural network, particularly the frontal lobes. DTI may be used to identify structural abnormalities associated with functional differences and cognitive dysfunction, particularly when traditional MRI studies are within normal limits. DTI measures the degree to which the direction of the diffusion is affected by the macromolecular and tissue structure providing a mechanism for determining the architecture of tissue in vivo especially white matter. This is a cross-sectional design looking at 15 normal controls compared to 15 epilepsy patients in how they compare on variables generated from DTI analysis specifically, anisotropy (or diffusivity). It is hypothesized that patients will have frontal areas of increased diffusivity. If there is time, the student may want to correlate these values with neuropsychological performance and/or activation from functional MRI studies. There are several analysis methods and the student will utilize one method that has not yet been conducted by this lab.

Student’s role in the proposed project:1. Learn and integrate principles of neuroimaging (fMRI and DTI), pediatric epilepsy, and

neuropsychology.2. Analyze data on Linux work station following instruction on Linux platform using specialized

software for DTI and functional connectivity analyses. Results will involve calculation of diffusivity values, correlation values, and ability to make a 3D reconstruction of white matter tracts.

3. Compile data within a database to run statistical analyses to determine if group differences between controls and patients are significant.

There must be sufficient support throughout the proposed project period. What is the source of financial support for this project? For what period of time is this project supported?We will be present at the initiation and for the duration of the research, and will be present at any presentations. We will provide instruction in computer analysis of neuroimaging data. We will also provide an educational packet, consisting of relevant articles from the imaging, epilepsy, and neuropsychological literature to provide a basic foundation for this neuroscience research examining the neural basis of language functioning. These papers will be reviewed on a weekly basis with the student fellow. There will also be opportunities to see clinical application of such work.

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Blatt IPrimary SponsorBenjamin Blatt, MDCLASS Clinical Skills Center900 23 St NWOffice Phone: 202 994 2664 [email protected]

Title of proposed project: CREATING A CERTIFICATE PROGRAM IN TEACHING FOR MEDICAL STUDENTS

Sponsor research focus: Medical Education

Provide background and overall design of the research project: GW was one of the first medical schools to initiate a medical students-as-teachers program. Called TALKS, it has been offered as an elective for senior medical students for the past 15 years and has been elected by 35-80 students per year. It consists of 6 workshops and a practicum, in which participating medical students serve as peer teachers for first and second year medical students in physical diagnosis. TALKS students also serve as standardized-patient feedback givers for M1s and M2s during their fall performance-based examinations.

The purpose of this project is to expand the TALKS program to be a requirement for all students. TALKS would be divided into TALKS BASIC and TALKS Certificate programs as outlined below:1. TALKS will be offered in 2 forms: TALKS basic and TALKS certificate2. TALKS basic—required of all med students:

Didactic: - 4th year: 3.5 hour workshop: Adult learning, Feedback, Teaching a Skill(alternative: present the program on every clerkship during rotation 6 on student day) to be co-taught with Ed Track students-2 hours: SP training by SP educatorsPracticum:--Teach year 1/2 physical examination--serve as SP-feedback giver for year 1 and 2Incentives:--mention in Dean’s letter

3. TALKS certificateDidactic-4th year: 6 workshops (to include new workshops on Small Group Facilitation., Teaching Patients); 14 BMJ articles on education;

Feedback/ Evaluation-Video submission: sample of teaching-Knowledge MCQ exam based on manual and BMJ readings-3/4 Project

Practicum--Teach year 1/2 physical examination--serve as SP-feedback giver for year 1 and 2--Serve as standardized learners for faculty development sessions--Options to serve as curriculum developers or small group facilitators

Incentives-Certificate—ideally could be applied for credit toward Master of education--4 weeks vacation

Describe student’s role in the proposed project to maximize the student’s learning experience:The student would work closely with the TALKS faculty (Drs Blatt, Greenberg and others from the Master Teachers Program) to develop the TALKS Certificate Program. The work would include developing new

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Blatt Iworkshops and a new didactic framework and establishing links with the Master Teacher’s Program, the Medical Education Track and other elements involved in medical education. The student would have the opportunity to help design an evaluation for the new program and co-present and co-author presentations and papers which evolve from the program. This project is ideal for a student interested in teaching and/or academic medicine. It will provide a wonderful chance to develop skills in curriculum development, teaching and evaluation

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Blatt IIPrimary SponsorBenjamin Blatt, MDDirector, CLASS clinical skills center6th floor hospital Office Phone: 202 994 2664 [email protected]

Secondary SponsorMargaret Plack, PhDChair, Health Sciences and Physical Therapy program

Title of proposed project: Teaching and Learning with Students From Other Professions: Developing an Interprofessional Peer Assisted Learning Program

Sponsor research focus: Medical Education

Provide background and overall design of the research project: GW has pioneered programs to teach students to be skilled teachers. The medical school developed the award-winning TALKS teaching senior students to be teachers program about 15 years ago; the Physical Therapy and Physician Assistant Programs have an extremely sophisticated programs to teach their students teaching skills.

The purpose of this proposal is to coordinate the 3 programs, developing a common curriculum and developing novel interprofessional ventures in peer teaching. Possibilities include developing team exercises for end of life care and serving as standardized patients for students from different professional schools.

Describe student’s role in the proposed project to maximize the student’s learning experience:The student could choose roles in several areas: curriculum development, development of team exercises, and program evaluation. The student could develop a project in one of these areas and work with faculty to develop it into publishable scholarship. This is an exciting opportunity to get involved in a really hot area—interprofessional education.

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Blatt IIIPrimary SponsorBenjamin Blatt, MDDirector, CLASS clinical skills center6th floor Hospital Office Phone: 202 994 2664 [email protected]

Secondary SponsorChristina Puchalski MDDirector, George Washington Institute on Spirituality and Health

Title of proposed project: The Foundational Science of Communicating Compassionate Presence

Sponsor research focus: doctor-patient communication - Medical Education

Provide background and overall design of the research project: GW has pioneered programs to teach doctor-patient communication and spirituality in health care. The purpose of this proposal is to understand in behavioral terms a power communication method called compassionate presence. The principle investigators will make videos of expert clinicians communicating compassionate presence and analyze them for teachable behavioral components. Based on this analysis they will develop an approach to teaching compassionate presence to doctors-in-training.

Describe student’s role in the proposed project to maximize the student’s learning experience:The student would participate actively in all aspects of the project including the research involved in assessing the project.

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Primary SponsorSusan Ceryak, PhDAssociate Research Professor of Pharmacology and PhysiologyThe George Washington University Medical Center2300 I Street, NW, Room 650 Ross Hall, Washington, DC 20037Office Phone: 202 994 3896 [email protected]

Title of proposed project: The role of mitochondria in death resistance

Sponsor research focus: Cellular death resistance is thought to be the foundation of neoplastic evolution. Our overarching goal is to understand cellular and molecular mechanisms of early stages of carcinogenesis after initial exposure to a genotoxin. Our recent discoveries have led to the intriguing hypothesis that survival after genotoxic insult may involve the selection of cells with intrinsic or induced mitochondrial dysregulation, leading to death resistance. The results of our proposed studies will identify molecular mechanism(s) that can confer a growth advantage to cells after genotoxic insult, and thus add new insights to our understanding of early oncogenesis.

Provide background and overall design of the research project: Our early studies focused on a unique model developed in our laboratory of hexavalent chromium [Cr(VI)]-induced death-resistant, telomerase-immortalized cells. In collaboration with Dr. Orian Shiriai, Boston University and Dr. Eric Kaldjian, Trangenomics, Inc., we have uncovered a novel role for mitochondrial survival signaling in the death resistant phenotype of these cells. These collaborators have renowned expertise in state-of-the-art determination of mitochondrial respirometry and mitochondrial DNA damage assessment, respectively. Our recent studies have uncovered a novel mechanism by which death resistant cells limit their mitochondrial respiratory activity, producing less reactive oxygen species, and leading to less mtDNA damage. Consequently, the death resistant cells were found to have a greater respiratory "reserve" if they were pushed to maximize their respiratory output under the condition of genotoxic stress. These novel findings hearken to the hypothesis of Otto Warburg, over 50 years ago, that cancer cells originated from non-neoplastic cells via acquisition of a permanent respiratory defect, which is still a subject of debate. Taken together, our data lead us to postulate that the repair/recovery process of normal cells after a single genotoxic insult may involve the selection of cells with intrinsic or induced mitochondrial dysregulation leading to death resistance, a hallmark of tumorigenesis.

Study of oxidative stress response in control and death-resistant cell lines: We will first analyze the ability of the death resistant cells to produce reactive oxygen species (ROS), in particular total ROS, and mitochondrially-derived superoxide. We will use the death-resistant cell lines and the control cell lines (parental and clonogenic), and our studies will be carried out under basal conditions, and after exposure to genotoxic stress. in a time-and dose-dependent fashion. We will determine whether the mitochondria from the death-resistant cells express more superoxide dismutase, and whether the activity of this enzyme is also up regulated. We already have extensive experience in this type of analysis.

Study of the role of mitochondrial DNA repair in death-resistance: We will study mitochondrial DNA damage response pathways in the context of cellular death-resistance. We will study AP1 activity and expression, as well as the production of AP1-repsonsive mitochondrial DNA lesions. This now routine technique is currently being successfully implemented in our lab.This project is part of a larger research effort as defined by the indicated research grant proposal.

Describe student’s role in the proposed project to maximize the student’s learning experience:The laboratory training plan is designed to give the Gil fellow specific experience in (i) using relevant human cell culture models, (ii) cell biology, focusing on analysis of key parameters of mitochondrial function and cell survival (iii) and molecular biology, focusing on gene knockdown. These approaches represent a cross-section of state-of-the-art approaches to molecular oncology. It is anticipated that the fellow will submit an abstract to and attend the annual American Association for Cancer Research meeting as a result of this research. I will supervise all aspects of the project, and will conduct weekly meetings with the fellow. In addition, the fellow will participate in a weekly group meeting where all lab members present their current results. I will be involved in data collection and interpretation and will provide oversight in

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Ceryak Page 2manuscript preparation. I plan to be present for the duration of the project as well as for subsequent student research presentations.

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Primary SponsorTaeun Chang, M.D.Director, Neonatal NeurologyCo-Director, Perinatal Brain Injury ClinicChildren’s National Medical Center (CNMC)Dept of Neurology111 Michigan Avenue, N.W.Washington, D.C. 20010Office Phone: 202-476-2120Fax: [email protected]

Secondary SponsorKarin Nelson, M.D.Scientist EmeritusNINDS, NIHChildren’s National Medical Center (CNMC)Dept of Neurology111 Michigan Avenue, N.W.Washington, D.C. 20010Office Phone: 202-476-2120Fax: [email protected]

Proposed Project: Placental pathology findings in infants presenting with neonatal encephalopathy for therapeutic hypothermia

Sponsor Research Focus: To determine the antecedents for neonatal encephalopathy / birth asphyxia / hypoxic ischemic encephalopathy so as to prevent and/or minimize subsequent brain injury.Dr. Chang has been studying a prospective cohort of patients referred to CNMC for therapeutic hypothermia for neonatal encephalopathy for the past 4 years. We have cooled 124 infants to date. The clinical history, hospital course, EEG findings, MRI findings, placental pathology and developmental outcome are being prospectively collected and entered into a Microsoft Office Access database designed by the sponsor.

Background and Overall Research Design: Background: Placental pathology can be useful in determining the underlying mechanisms leading to complications in pregnancy/delivery and thereby for guiding future investigations and interventions for the newborn. It can predict persistent neurological impairment in newborns. However, few studies have examined the placenta to determine the antecedents for birth asphyxia or neonatal encephalopathy.

Specific Aim: To examine whether the examination of the placenta can provide information concerning the pathophysiology of neonatal encephalopathy (NE) in term and near-term infants. Methods: CNMC has been cooling since May 2005 using a modified protocol for whole-body cooling {Shanakaran et al. NEJM 2005]. Infants at least 36 weeks of gestation, 1800g and within 6 hrs of presumed hypoxic-ischemic insult as indicated by physiologic signs of acidosis (pH ≤ 7.0 or base deficit ≥ 16) and/or a sentinel event and neurologic exam of moderate to severe encephalopathy or seizures were transferred to our institution for therapeutic hypothermia. Cooling was initiated within 6 hours of life to an esophageal temperature of 33.4°C for 72 hours and then gradually rewarmed 0.5°C every 60 minutesover 7 hours to a baseline temperature of 36.5°C. 124 patients were cooled between May 2005 and October 2009. 100 placental pathology reports were available for review. Each report was reviewed by a perinatal pathologist for standardized features and categorized as having vascular, inflammatory, and/or chronic/developmental findings. In addition, each finding was identified as either acute, subacute or chronic features. Patient cases were classified based on birth history as either “sentinel” or “non-sentinel” cases. Sentinel events were defined as uterine rupture, placental abruption, cord-related disorders (prolapsed cord, true cord knot, cord tear or transaction), tight nuchal cord, and maternal shock/trauma/demise. Placental weights were examined when available in the reports [Naeye 1987 Human Pathology] [Swanson & Bewtra 2008]. Abnormal placental weight was defined as less than 5% or greater

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Chang Page 2than 95% of normative weights for gestational age using normative values [Boyd et al 1999]. Abnormal fetal/placental ratio (F/P) was defined as less than 5% or greater than 95% of normative values for gestational age. Placental pathology findings will be examined between sentinel versus non-sentinel events, compared to presence of EEG-confirmed seizures, MRI location & pattern of injury, and NICU outcomes (death, days of assisted ventilation, achievement of oral feeding, abnormal neuromotor evaluation, length of hospitalization). Subtypes of neonatal encephalopathy will be identified and characterized.

Student’s Role: The student may choose to compose their own question or examine one of the questions raised above. He/she will have the opportunity to learn about the clinical and pathological aspects of neonatal encephalopathy, to retrieve and examine data from a clinical database, and summarize their findings into abstract form for submission to a national meeting. If the abstract is accepted, then the student will be allowed to follow through and put together a presentation (poster or platform) for a national meeting. The student will be working directly with the sponsor and co-sponsor. Mentorship will be provided by both long this research process.

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Primary SponsorKatherine Chretien, MD, FACPAssistant Professor of MedicineDC Veterans Affairs Medical Center50 Irving Street, NW, Washington, DC 20422Office Phone: 202-745-8393 [email protected]

Secondary SponsorTerry Kind, MD, MPHAssociate Professor of Pediatrics, Director of Pediatrics Medical EducationChildren’s National Medical CenterChildren’s Health Center at Martin Luther King, 3029 Martin Luther King, Jr, Ave, SE, Washington, DC 20032Office Phone: [email protected]

Title of proposed project: Physicians on Twitter

Sponsor research focus: Dr. Chretien’s research focus revolves around medical education, professionalism, and the use of Web 2.0 technologies (such as blogs and social networking sites) in medicine. Dr. Chretien has published work on using blogs as tools in medical education, and along with Dr. Kind, has published research on U.S. Deans’ views on medical student online professionalism. Current research projects involve exploring the medical student and faculty perspective with regards to online professionalism.

Provide background and overall design of the research project: Web 2.0 technologies are changing the interface between medicine and the public; this will have enormous impact on how doctors and patients communicate and get health information. Web 2.0 also has blurred the intersection between doctors’ personal and professional lives.

Twitter, a social networking and micro-blogging tool, has been growing in popularity as a way for information exchange and communication. Hospitals, public health departments, and other medical institutions have started to use Twitter as a way to disseminate health information, as well as for marketing purposes. It is unclear how individual physicians are using Twitter: what are physicians on Twitter posting about?

This project will involve content analysis of Twitter updates published by Twitters users who identify themselves as physicians. We will develop a standardized search strategy to identify these users and collect data for a specified period of time.

Describe student’s role in the proposed project to maximize the student’s learning experience:The student will be involved in planning, data collection, and be guided through the qualitative analysis. The student will also be mentored in preparing data for presentation, assist in manuscript preparation, and hopefully have the opportunity to present this research in abstract form at a medical meeting.

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Primary SponsorAisha Barber Davis, MDAssistant Professor of Pediatrics, Attending Physician, Hospitalist DivisionChair, CNMC Bronchiolitis Clinical Practice Guideline TeamCo-chair, Hospitalist Division Education CommitteeChildren’s National Medical CenterHospitalist Office Suite 4800, 111 Michigan Ave, NW, Washington, DC 20010Office Phone: [email protected]

Title of proposed project: Effects of reduced oxygen saturation threshold for supplemental oxygen on acute outcomes in hospitalized patients with bronchiolitis.

Sponsor research focus: Two of my primary responsibilities are pediatric clinical inpatient education of pediatric residents and students and the care of hospitalized patients with bronchiolitis.

As the Chairperson of the interprofessional team dedicated to standardizing and improving bronchiolitis care at CNMC, I have worked with a team to revise the bronchiolitis clinical practice guideline which guides the care of bronchiolitis patients. The revisions have been implemented over the past year and are based upon the 2006 American Academy of Pediatrics recommendations. This study aims to evaluate the effect of the implemented changes on provider behavior and patient care outcomes.

Background: Bronchiolitis is a respiratory illness which predominantly affects infants and young children. Admission rates and healthcare costs have risen over the past decades and bronchiolitis is responsible for nearly 20% of all infant hospitalizations exclusive of birth. Due to respiratory distress and/ or hypoxemia, progression to respiratory failure is feared and patients may be hospitalized. There were 149,000 hospitalizations for bronchiolitis in the US in 2002 and a total cost of $543 million during that year. Hospitalization rates were 2.4 times higher for bronchiolitis in 1996 than 1980. Despite these increases in hospitalizations and cost, the mortality rate remains unchanged and relatively low, between 250 and 500 children per year in the US. The mainstay of treatment for bronchiolitis remains supportive care with good evidence that most treatments are ineffective. However, hospitalizations and health care costs associated continue to be significant. It has been suggested that this may be attributable partially to the ease of measuring oxygen saturation and its influence on the decision to admit.

Previous studies have noted the significant influence which oxygen saturation (SpO2) threshold can have on admission rate. However the arterial partial pressure of oxygen (PaO2) is the true measurement of interest. Small differences in pulse oximetry measurements when the SpO2 is around 90% are unlikely to have a significant impact on PaO2 in a patient with the normal oxyhemoglobin dissociation curve that is likely to apply to mild to moderately ill bronchiolitis patients.

The Knowledge Gap: The original CNMC inpatient bronchiolitis practice guideline specified maintenance of SpO2 ≥ 92% for patients meeting inclusion criteria for the pathway. A 2006 American Academy of Pediatrics guideline regarding diagnosis and management of bronchiolitis recommend maintaining oxygen saturation ≥ 90% for patients with bronchiolitis who are without risk factors for shifted oxyhemoglobin dissociation curves. Literature search reveals no objective clinical evidence for or against this change in threshold and, despite widespread adoption, there were no studies found which evaluated the impact of this change on short or long-term clinical outcomes.

Our revised bronchiolitis pathway features a goal oxygen saturation of ≥ 90% in the absence of other signs concerning for decompensation for patients who meet inclusion criteria for the practice guideline. This threshold is used to guide admission and supplemental oxygen provision. The pathway also features the added safety features of increased respiratory assessment frequency for higher risk patients and identification of populations at risk for clinical worsening so they may be more closely monitored. These revisions were implemented during November 2009.

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Davis Page 2

We will evaluate whether this change influences safety outcomes including critical care transfer rates, readmission rate, and rapid responses and cost-effectiveness outcomes such as length of stay, medication utilization, and length of oxygen therapy in our hospitalized bronchiolitis patients.

The Significance: Bronchiolitis admissions occur predominantly during the winter months during which time hospitals are often at capacity with many ill patients awaiting bed space. If bronchiolitis hospitalizations could be expedited safely then wait times, resource utilization, healthcare costs, and nosocomial infections could be improved and resources focused on the sickest patients. SpO2 measurements have been shown to impact the decisions physicians make regarding admission and discharge. If this threshold can be safely decreased, then hospital days and cost of care may also decrease.

Study Design:

Study type: Retrospective case-controlControl Group (Goal SpO2 ≥ 92%) = Discharge dates 11/1/2008 – 4/1/2009Case Group (Goal SpO2 ≥ 90%) = Discharge dates 11/1/2009 – 4/1/2010

1. The Trend Star database will be searched for patients discharged with primary diagnoses of bronchiolitis in the case and control group time periods. This administrative database will also be queried for other patient care data.

2. Chart review of patients identified above to collect data including: date and time of admission, date and time of discharge, date and time of oxygen therapy start, date and time of last recording of oxygen therapy. Decompensations as documented by rapid response team and code team calls for bronchiolitis patients will also be evaluated for the case and control time periods.

3. Statistical analysis will include t-tests to compare the length of oxygen therapy, number of adjunctive treatments, and length of stay between the case and control groups. Chi-square will be used to evaluate readmissions and rapid responses/ PICU transfers.

Describe student’s role in the proposed project to maximize the student’s learning experience:

The student will be involved in evaluation of a clinical practice guideline through patient care outcomes, primarily. In addition, this data will be used to evaluate an educational intervention aimed at implementation of this guideline. The primary role of the student will be data collection through review of the electronic medical record. Through this data collection, the student will learn about appropriate documentation, quality and process improvement, and implementation of clinical practice guidelines.

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Primary SponsorRoberta L. DeBiasi, MDAssociate Professor of Pediatrics; Acting Chief, Pediatric Infectious DiseasesChildren’s National Med Ctr/GWU/ Children’s Research InstitutePediatric Infectious DiseasesAddress: 11 Michigan Ave NW, West Wing 3.5, Wash DC 20010Office Phone: 202-476-5052Email: [email protected]

Title of proposed project: Clinical Impact Analysis following Implementation of an Evidence Based Clinical Management Algorithm for Complicated Pediatric Pneumonia

Sponsor research focus: Dr. DeBiasi is an experienced clinician, bench science and clinical researcher in the area of Pediatric Infectious Diseases. Her grant-funded basic laboratory work centers on the pathogenesis of viral myocarditis. In addition to clinical research related to antiviral therapy for severe viral infections, her clinical research focus has focused on the epidemiology, diagnosis and treatment of Complicated Pneumonia in the pediatric population, including pleural effusion, pleural empyema, and lung abscess.

Dr. DeBiasi has successfully mentored 5 students in her basic science laboratory. She has alsosuccessfully mentored 2 GWU students in the School for Public Health and the School of Medicine, aswell as a CNMC Pulmonary Fellow in clinical research projects in the area of complicated pediatricpneumonia, which have resulted in poster presentations at Children’s National Medical CenterResearch Day, abstract submission to the Pediatric Academic Societies National Meeting, andsubmission of an original research manuscript for publication in a peer-reviewed medical journal. Dr.DeBiasi is also Associate Program Director of the Pediatric Infectious Diseases Fellowship TrainingProgram at CNMC, with direct responsibility and oversight of educational curriculum and researchendeavors of the Pediatric ID division and its fellows in training.

Provide background and overall design of the research project: Bacterial pneumonia is an important cause of hospitalization in children, occurring either as uncomplicated, or with complications such as pleural effusion/empyema or lung abscess. Routine administration of pneumococcal conjugate vaccine (PCV7) since 2000 has led to reductions in invasive pneumococcal disease (bacteremia, meningitis, pneumonia). However, non-vaccine-serotype pneumococci and other bacterial species, including methicillin-resistant staphylococcus aureus (MRSA) may also cause uncomplicated and complicated pneumonia. We have completed a descriptive epidemiologic characterization of pediatric bacterial pneumonia at CNMC and nationwide from 2002 to 2007 utilizing the Pediatric Health Information System (PHIS) database. Despite routine childhood PCV-7 vaccination, pleural effusion/empyema rates in the pediatric population have not significantly changed at CNMC or nationwide over this period and remain a common cause of hospitalization.

Despite the importance of this clinical problem, there is great variability in strategies for thediagnosis and treatment of children who develop complications of bacterial pneumonia, including pleuraleffusion, empyema, necrotizing pneumonia and lung abscess. At CNMC, a 280 bed free-standing tertiarypediatric hospital, a group of providers sought to optimize the diagnosis and care of patients withcomplicated pneumonia. In order to develop a consensus for management, a multidisciplinary committee(Complicated Pneumonia Committee, CPC) was formed, consisting of physician representatives from theHospitalist, Infectious Diseases, Pulmonary Medicine, Radiology, Surgery and Emergency MedicineDivisions at CNMC. This CPC developed consensus clinical management algorithm incorporating the bestavailable evidence to achieve the following goals: (1) minimize morbidity and mortality, (2) maximize quality of patient care in the acute and chronic setting, (3) decrease radiation exposure, (4) limit unnecessary antibiotic use, (5) decrease hospital length of stay, (5) improve communication between sub-specialists and hospitalists, (6) work within existing hospital structures and systems, and (7) provide adequate postdischarge follow-up care with the appropriate care providers. Additionally, our goal was to design the management algorithm in such a way that it would provide the framework for future quality improvement studies related to diagnosis and treatment of pediatric patients with complicated pneumonia.In November 2008, the resulting clinical management algorithm for complicated pneumonia wasformatted as a user-friendly flow chart and posted on the hospital intranet, along with an evidence-based

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DeBaisi Page 2treatment guidelines document, to facilitate immediate access to all caregivers. To maximize utilization ofthe algorithm and suggested approaches, the algorithm was formally introduced to resident and attendingphysicians at a dedicated educational conference, in conjunction with a Grand Rounds focusing onmanagement of complicated pneumonia.

One year post-implementation of this algorithm, we now plan to assess the impact ofimplementation of this algorithm on several clinical parameters, such as utilization of radiation-intensive(Computed tomography) vs. radiation-sparing (ultrasound) diagnostic procedures. Using a retrospectivecohort study design, we plan to assess impact by comparing two cohorts of patients with complicatedpneumonia: Cohort 1 will consist of patients in the 1-2 year period immediately prior to implementation ofthe consensus algorithm. Cohort 2 will consist of patients in the 1 year period following implementation ofthe consensus management algorithm. Patients with complicated pneumonia in both cohorts have beenidentified from CNMC electronic medical records by ICD-9 codes for pleural effusion, pleural empyema, and lung abscess. Approximately 50 patients in each cohort have been identified using this methodology. Using a previously designed, validated and IRB -approved clinical data extraction tool, we will extract relevant clinical data from identified medical records and analyze differences between the two study cohorts, including formal statistical analysis.

Describe student’s role in the proposed project to maximize the student’s learning experience:The student will be involved in all aspects of this study. Specifically, it is envisioned that the studentinvolved in this project will:

a. Assist in identifying relevant clinical endpoints for analysisb. Develop hypotheses relevant to identified clinical endpoints of interest.c. Perform data extraction from systematic review of electronic medical recordsof identified patients in both cohorts using a previously validated and IRB -approved data extraction tool.d. Work with a biostatistical consultant to analyze data for trends/statistical significance.e. Write an abstract and begin a manuscript describing research findingsf. Submit and present a research abstract at national meeting

The student will be closely supervised throughout the research period and mentored at each stage of datacollection, analysis, summary, and presentation. As noted above, Dr. DeBiasi has already performed preliminary case identification for the defined study period (pre and post-algorithm implementation), which will save the student significant time and effort. This project can easily be completed in the summer term with the abstract and manuscript preparation being continued by the research team VII. There must be sufficient support throughout the proposed project period. Please answer the following questions:What is the source of financial support for this project? No financial support is necessary for this project.Access to CNMC medical record for review of identified medical records is already secured. Biostatisticalconsultation is available from Dr. DeBiasi’s appointment within Children’s Research Institute.

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Primary SponsorKate Douglass, MD, MPHFellowship Director, International Emergency Medicine,Assistant Professor of Emergency Medicine,Adjunct Assistant Professor of Global HealthRonald Reagan Institute of Emergency MedicineMedical Faculty AssociatesThe George Washington University2150 Pennsylvania Ave NW, Suite 2B, Washington, DC 20037Office Phone: 202 741 [email protected]

Secondary SponsorSteven M Andescavage, DO, MPHFellow, International Emergency MedicineAdjunct Assistant Professor of Global HealthRonald Reagan Institute of Emergency MedicineMedical Faculty AssociatesThe George Washington University2150 Pennsylvania Ave NW, Suite 2B, Washington, DC 20037Office Phone: 202 741 2954Email: [email protected] or [email protected]

Title of proposed project: Updated Assessment of International Emergency Medicine and GlobalHealth Fellowships in the United States

Sponsor research focus: Our aim is to gather, analyze, and present the most current status ofInternational Emergency Medicine Fellowships and Global Health programs in the United States. Severalliterature searches produce similar studies as recent as 2005. During the time from 2005 to present, therehas roughly been a doubling of the number of Emergency Residency sponsored International/GlobalHealth Fellowships. The scope of each fellowship is variable, ranging from programs focusing on facultydevelopment to humanitarian aid. By compiling the most recent data, this will enable prospective fellowsto invesigate each program, and aid in selecting the most appropriate fellowship for their interests. It willalso provide further evidence that there is a growing demand and interest in International EmergencyMedicine and Global Health in Emergency Medicine-trained physicians. Provide background and overall design of the research project: This study is simply anobservational, data collection study. ACGME (American Council of Graduate Medical Education) andAOA (American Osteopathic Association) approved Emergency Medicine residency programs will becontacted via email or phone if no response. On-line surveys will be distributed to each program director.According to the ACGME, there are 149 Emergency Medicine residency programs in the US, andaccording to the AOA (American Osteopathic Association), there are 43 residency programs. Efforts toachieve 100% response will be made. Data will be collected via email and analyzed through SPSSsoftware. Very basic statistical analysis will be conducted, such as percent of programs responded to thesurvery, percent of programs sponsoring a fellowship, percent of programs offering graduate degrees, aswell as reporting of other data points (length of fellowship, number of faculty and focused interests.Additional data analysis will be conducted, such as length of fellowship, number of faculty and focusedinterests. An effort to contact all Emergency Medicine residency programs will be made, and several listsare available on the web such as ACGME.org, SAEM.org (Society of Academic Emergency Medicine),and ACEP.org (American College of Emergency Physicians). For completeness, we would like to have aresponse from all approved Emergency Medicine residency programs. Similar studies in the past haveachieved 100% response rate.

Describe student’s role in the proposed project to maximize the student’s learning experience:Research assistants will be expected to participate in all facets of the project; from study design, datacollection, analysis, and manuscript preparation. Our aim is to publish in either the Society of AmericanEmergency Physicians journal or the Annals of Emergency Medicine (the American College ofEmergency Medicine’s journal). Additionally, there is potential for poster or oral presentation of the

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Douglas Page 2project at one of several national or regional meetings upon acceptance. The assistants will have anexcellent opportunity to develop skills involving medical academic research. It will also offer anopportunity to network with Emergency Medicine physicians and faculty at the Medical FacultyAssociates involved with International medical work. We hope to attract applicants with interests inPublic Health, Medical Education, Research, Emergency Medicine, or International Medical EmergencyMedicine. Students will have direct mentorship from Drs. Andescavage and Douglass at the MFA(Medical Faculty Associates). Interested applicants are encouraged to contact Dr. Andescavage via emailfor questions: [email protected]

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Primary SponsorMalika Fair, MD, MPHInstructor of Emergency MedicineMedical Faculty Associates Department of Emergency Medicine/ Prince George’s Hospital Center Department of Emergency Medicine2150 Pennsylvania Avenue, NW, Suite 2B-417 Washington, DC 20037Office Phone: 202-741-2939 [email protected]

Secondary SponsorPeter Shin, Ph.D., MPHAssociate Research Professor in School of Public Health and Health SciencesDepartment of Health Policy2021 K st, NW, Suite 800, Washington, DC 20006Office Phone: 202-994-4144 [email protected]

Title of proposed project: Strengthening the safety net: An evaluation and intervention to improve access to primary care among emergency department patients.

Sponsor research focus: Dr. Fair’s research interests surround access to care issues for the medically vulnerable emergency department population.

Provide background and overall design of the research project: A large number of patients are discharged from emergency departments (ED) each day without the certainty of appropriate follow-up with a primary care physician. This is common among the low-income population. Access to regular primary care may significantly improve health status and reduce avoidable ED visits.

We intent to create a new prospective study to identify patients without a primary medical physician discharged from the Prince George’s Emergency Department. The first part of the study would track the percentage of patients without a primary medical physician based on insurance status. The second part of the study would provide patients with a list of available providers to contact and assistance with scheduling the appointments.

Specifically we hope to 1) access the rate of patients who have a primary care provider based on insurance status 2) to evaluate barriers to obtaining a new primary care physician upon discharge and 3) measure the effectiveness of a dedicated appointment scheduler.

Describe student’s role in the proposed project to maximize the student’s learning experience:Students would assist with data collection on patient’s current health status, insurance coverage, and assess their relationship with a primary care physician. They would also act as “case managers” for the intervention group and schedule appointments with local providers. Lastly, they would conduct phone interviews to assess barriers to obtaining primary care for both the control and intervention group.

Students would be involved in all parts of the study including publication generation and presentation at national meetings.

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Primary SponsorJulia B. FrankDirector of Medical Student Education in PsychiatryGWU MFA2150 Pennsylvania Ave NW, Washington, DC 20037Office Phone: 202-741-2865 [email protected]

Secondary SponsorLinda RaphaelAssociate Clinical Professor of Psychiatry and Behavioral Sciences; Director of Medical HumanitiesGWUMC, 900 23rd St, NW, Suite 6205 Washington DC 20037Office Phone: 202 994 1034 [email protected]

Title of proposed projects: Effects Professional Education on Trainee Attitudes Towards the Chronically Mentally Ill

Sponsor research focus: Dr. Frank is a senior member of the medical school faculty, responsible for curriculum in psychiatry and behavioral science. She has presented on educational topics to various educational meetings including the Association for Behavioral Sciences in Medical Education, the Association of Directors of Medical Student Education in Psychiatry, and the American Psychiatric Association. She has also collaborated on multi-site education studies, including a study of student interactions with pharmaceutical companies that was published in JAMA and another study of educational accountability currently under consideration by Academic Psychiatry. She has long been concerned about the ways in which medical students’ attitudes toward the mentally ill develop during their professional training, the focus of the current proposed studies. Her collaborator, Dr. Raphael, is a central figure in the medical humanities program. Her main interest has been the effects of in using narratives in to enhance professional development.

Background: Developing medical manpower to deliver mental health care to patients seen in and outside of psychiatric settings remains an unsolved challenge. Stigma against the mentally ill is one of many factors contributing to the problem of residency recruitment in psychiatry. Stigma also impedes the process of helping students develop commitment to and comfort with providing good mental health care outside of psychiatry. The impact of different forms of professional education on either reducing or inducing stigma in psychiatric patients has received little systematic study, though parallel efforts dealing with intellectually impaired or developmentally disabled people are progressing.

Dr. Frank would like to recruit a student to help develop two separate studies in this area, one involving the specialty choice of students in the clinical years and one on the effect of different methods of instruction on pre-clinical students and clerkship students. Regarding the first study, one educational strategy often proposed for increasing the capacity of the health care system to care for the mentally ill has been to integrate psychiatry with either neurology or primary care during undergraduate clinical training. These proposals imply two radically different ideas about the relationship between psychiatry and other specialties, each of which conceals assumptions about student attitudes toward the mentally ill. Increasing the integration with neurology assumes that students need a more thorough foundation for understanding the neurological substrates of behavioral disorders and greater application of the biomedical model to psychiatry. Allying psychiatry with primary care is thought to foster interest in providing psychiatric care in students who seek a specialty based on commitment to serve a population in need and on the desire for fulfilling, long term relationships with patients. However, few studies provide useful insight into what actually draws students to or away from providing psychiatric services.

Overall Design: With a Gil student, I would like to design a de-identified survey of the third and fourth year classes, finding some measure of attitudes toward psychiatry and psychiatric patients and correlating this with a rank ordering of their possibly choices of residency. This will likely involve adaptation of the Implicit Attitudes Test used in studying attitudes toward the disabled. I would then like to compare students

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Frank Page 2who rank psychiatry among their top three choices with those who rank it in the lowest three. Such data would clarify whether their view of psychiatry actually correlates with their attitudes toward the mentally ill and also whether their other top or bottom choices include neurology or a primary care specialty or are more random. The role of the Gil student would be to help find the appropriate measurements and choose a platform for administering the study, and then helping in writing up a protocol (with appropriate statistics) for IRB approval. I would anticipate data collection to be done in the fall and data analysis in the spring, with the student’s continued involvement if desired.

The second study of preclinical students would be done in conjunction with Dr. Raphael, comparing real and indirect exposure to psychiatric patients in their possible impact on student attitudes toward the mentally ill. Background: A very limited amount of data suggests that of the three factors known to change stigma, involvement with anti-stigma advocacy is least effective, education is somewhat effective, and direct contact with stigmatized people is most effective. Whether indirect contact via narrative has any effect needs further study. Overall Design: As with the previous study, I propose to use a measure of medical students’ attitudes toward the mentally ill. In this case, I would like to compare students in two conditions: those who participate in a medical humanities seminar which includes some narratives related to psychiatry and those who participate in a seminar that involves discussion of some direct, videotaped interviews with real patients. A second wave of data collection before and after all the students see examples of real patient interviews in the psychopathology course would also be of interest, allowing for the comparison of attitudes in students who are not self selected for their interest in humanities. In addition to helping with protocol development and IRB submission, the Gil student could help me to make the appropriate tapes.

I believe the proposed work is feasible within the expected time frame of 20 hours per week for six weeks and that there would be a concrete outcome of two approved protocols by the beginning of September, 2010.

Describe student’s role in the proposed project to maximize the student’s learning experience: The student will be involved in developing the projects from the beginning, from literature review to choice of measures and means of statistical analysis. After taking CITI training, he or she will help write up the proposals for IRB review. For the second project, the student will also be involved in obtaining consent from the patients and in making the videotapes. During the school year, 2010-11, the student will have the opportunity to participate in data analysis and preparation of research reports.

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Primary SponsorWilliam Davis Gaillard, M.D./Plasticity of Language and Epilepsy Project (POLER)Professor, NeurologistChildren’s National Medical Center/NIH, NINDS/GWU Medical Center/Georgetown111 Michigan Avenue NW, Washington, DC 20010Office Phone: 202-476-5224 Email: [email protected]

Secondary SponsorMadison M. Berl, Ph.D./POLERAssistant Professor, NeuropsychologistChildren’s National Medical Center/GWU Medical Centersame as aboveOffice Phone: 202-476-2545 [email protected]

Title of proposed project: Neuroimaging of Language Organization in Epilepsy Patients Compared to Normal Controls Using Functional MRI (fMRI)

Sponsor research focus: The focus of our research is to characterize the functional differences in epilepsy patients as compared to healthy volunteers with consideration of epilepsy factors (e.g., seizure location, seizure frequency, medications) and neuropsychological performance in predicting outcomes.

Provide background and overall design of the research project: The proposed research is part of an ongoing investigation of the cerebral organization underlying cognitive processes in patients with epilepsy. Functional MRI can be used to map neural networks responsible for cognitive activity. With this technique, we have performed several fMRI language studies in children and adults. We have previously demonstrated that fMRI can identify hemispheric language dominance (non-invasively) in patients with intractable epilepsy being considered for epilepsy surgery. This project is designed to test the hypotheses that there is inter-hemispheric reorganization of activation patterns in patients with a left hemisphere seizures focus compared to a normal population and those with a right hemisphere focus. Furthermore we expect an effect on the representation of atypical language based on location of seizure focus --that expressive language networks are more malleable than temporal networks based on normal developmental functional imaging data. All subjects undergo a panel of language fMRI tasks targeted at different aspects of language. The primary tasks to be analyzed are reading and listening comprehension. Data will be analyzed using SPM 5, in normalized space using a region of interest approach (Wake Forrest Pick Atlas, Broca’s area (inferior frontal gyrus), mid frontal gyrus, Wernicke’s area, and cerebellum) and a bootstrap algorithm. Laterality indices will be calculated LI=(L-R)/L+R), with AI < 0.20 considered atypical for each region. Further analysis that measures the functional connectivity across regions will be conducted, if time allows.

Describe student’s role in the proposed project to maximize the student’s learning experience:The plan of the project is to perform fMRI and analyze data from patients who will be evaluated over the summer as well as identifying data (previously collected) on 150 patients with localization related epilepsy (75 left focus, 75 right focus; 30 normal volunteers). We hypothesize that patients with right focus and left language will not differ individually from normal controls, that patients with left focus but left language will exhibit evidence for inter hemispheric re-organization of language. We also expect to see an effect of lobar location of seizure focus. (That a temporal lobe focus will be associated with atypical language in temporal and frontal regions, but that a frontal focus will only be associated with atypical language in frontal, not temporal, regions). Other epilepsy factors will be considered as time allows. Specific tasks for the student includes:1. Interview and screen patient volunteers for the fMRI study.2. Perform fMRI studies (supervised by WDG and neuroradiology staff).3. Analyze data on Linux work station (after extensive instruction on use of work station and MRI

analysis programs, will involve 3D automated reconstruction and threshold determination, region of interest analysis on extent and magnitude of activation)

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Gaillard Page 24. Compile and analyze data to examine group (patient vs. normal) and focus related differences in

regional activation patterns. Madison Berl PhD will help supervise statistical handling of data.5. There will be an educational series of talks and tutorials covering cerebral organization of language,

imaging techniques (especially brain mapping), data analysis. There will be discussion regarding how this work is pertinent to epilepsy research. A syllabus of relevant articles for brain mapping, neuroimaging, and epilepsy will be given to the student and will provide the basis for directed reading and education. The student may join me in epilepsy clinic and the neuroradiologists during reading rounds.

6. An abstract will be submitted to for GWU poster day with the further aim of submission to American Epilepsy Society meeting and development of a manuscript.

We will be present at the initiation and for the duration of the research, and will be present at any presentations. We will provide instruction in computer analysis of neuroimaging data. We will also provide an educational packet, consisting of relevant articles from the imaging, epilepsy, and neuropsychological literature to provide a basic foundation for this neuroscience research examining the neural basis of language functioning. These papers will be reviewed on a weekly basis with the student fellow. There will also be opportunities to see clinical application of such work.

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Primary SponsorPenny Glass, Ph.D.Associate Professor of Pediatrics (GWU School of Medicine & Health Sciences)Director, Child Development ProgramDept of Psychiatry & Behavioral ScienceDivision of Neuroscience & Behavioral MedicineChildren’s National Medical Center111 Michigan Ave NW Washington DC 20010Office Phone: 202-476-2132 [email protected]

Secondary SponsorTara Brennan, Psy.D.Staff Psychologist, Child Development ProgramChildren’s National Medical Center111 Michigan Ave NW Washington DC 20010Office Phone: 202-476-3640 [email protected]

Title of proposed project: Neurodevelopmental Deficits in Infants and Toddlers with Sickle Cell Disease

Sponsor research focus: to characterize the prevalence of developmental delays in children with SCD under the age of 4 years and to examine the moderating effects of sickle cell phenotype and hematologic variables on developmental outcome.

Provide background and overall design of the research project: This year two of a 4-year mixed cross-sectional longitudinal study of early neurodevelopmental status in children younger than 4 years with SCD. The study aims are to (1) characterize the prevalence and nature of the developmental deficits in infants and toddlers while controlling for SES; (2) examine the moderating effects of sickle cell phenotype, hematologic severity, and parent characteristics on developmental outcome; (3) improve patient outcomes by including routine parent education about normal development and behavior during each patient visit at the SCD Clinic. To accomplish these primary aims the study has two components: a Neurodevelopmental Evaluation Component and a Parent Education. The Neurodevelopmental Evaluation component will determine the prevalence of developmental deficits among young children with SCD at specific age levels (9, 15, 21, 30, and 40 months). We plan a minimum of 45 assessments at each of the 5 age levels (225 assessments). The Parent Education component is a recurrent, SCD clinic-based intervention intended to impact patient outcomes. Medical data is obtained from the patient’s outpatient clinic chart or inpatient medical record if they have been hospitalized.

Describe student’s role in the proposed project to maximize the student’s learning experience:This study presents important challenges and opportunities to better understand and address complex interactions between biological factors basis of developmental delays and socioeconomic/environmental factors that impede normal childhood development. The student’s time will be split between the Child Development Clinic and the Hematology/Oncology Clinic, allowing the student the opportunity to interact with families of children with SCD to gain an understanding of the stress and concerns that arise when raising a child with SCD. Additionally, the student will be able to observe medical providers during physical examination, review of laboratory results, assist with administration of Transcutaneous Doppler procedure, and attend the discussions of disease management. As a result, the student will learn about not only potential developmental concerns, but also medical conditions related to SCD and therapeutic approaches to their disease. The summer student will obtain and enter medical data into the database concerning patient genotype and markers of disease severity. They will be able to observe first hand neurodevelopmental assessment and types of developmental deficits across different age groups. The student will learn basic statistical analyses, compile data from the patients’ TCD (transcutaneous Doppler) procedure and produce a research paper.

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Primary SponsorLarrie Greenberg, M.D.Internal consultant, Faculty DevelopmentGWU, 900 23d street NWOffice Phone: 202-994-9302 [email protected]

Title of proposed project: Does empathy in medical students change over time?

Sponsor research focus: We will be examining medical student empathy skills from the first week of medical school until the completion of their clerkships using a standardized and validated instrument called the Interpersonal Reactivity Index (IRI). The Institute of Medicine and others have questioned the communication that occurs between doctors and patients, including the empathic skills of medical students as they traverse the medical school curriculum. No one has used the IRI over time in medical students to determine if scores on this instrument change and in what direction.

Provide background and overall design of the research project: We will be administering this instrument to first year medical students as they begin their matriculation, will follow that with the same instrument the end of their second year, and then upon completion of the clerkships. The idea is to determine, as the literature suggests, that there is a waning of empathy as students matriculate through medical school. We would hypothesize that much of this attrition will occur in the clinical year because of negative role-modeling by residents and faculty. Therefore, we would predict that the results in years 1 & 2 will be similar and will change negatively by the end of the junior year.

There is no problem with the completion of the project as it is self-limited and should be easy to administer in years 1-3 to the cohort class of 2014.

Describe student’s role in the proposed project to maximize the student’s learning experience : The student will learn about how empathy is measured and will have responsibility in helping to administer the test in the first year and thereafter, if possible. The student will have access to other studies we have done on empathy in the CLASS center and will be encouraged to be an active participant in the project. The student will enter data on the IRI the summer of 2010 and potentially in the future. Based on the student’s initiative we would envision including him/her on subsequent abstracts and/or publications.

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Primary SponsorAndrea Gropman, M.D.Associate Professor, Dept. of NeurologyChildren’s National Medical Center111 Michigan Avenue, N.W, Washington, D.C., 20010Office Phone: 202-476-3511 [email protected]

Title of proposed project: Alterations of white matter integrity in major fiber bundles in children with Ornithine transcarbamylase deficiency

Sponsor research focus: My research uses non invasive measures (advanced MRI technologies and neurocognitive testing) to measure brain injury in patients with inborn errors of metabolism in the urea cycle. A recent expansion of the research involves the use of 13C MRS with allows measure of brain neurotransmitter flux and turnover in real time. In our first phase of funding we identified biomarkers of neurological injury in adults with ornithine transcarbamylase deficiency. We are now focusing on children and markers of intellectual impairment in this condition.

Provide background and overall design of the research project: Urea cycle disorders represent a group of rare inborn errors of metabolism that lead to accumulation of ammonia, a toxic product of protein metabolism. Individuals with urea cycle disorders cannot metabolize the ammonia that accumulates due to enzyme deficiency. The symptoms of these disorders may present at birth, childhood or adulthood (milder deficiencies). There are currently eight enzyme deficiencies that constitute the range of inborn errors of ureagenesis. This project will focus on the most common enzyme disorder of the urea cycle, ornithine transcarbamylase deficiency, inherited as an X-linked trait. OTCD, an X-linked disorder, is the most common of the urea cycle disorders. Neonatal onset disease is associated with uniformly poor outcome. Males with late onset OTCD show deficits in executive function, motor planning and working memory. A broad phenotype is observed in heterozygous females. A specific neurobehavioral phenotype associated with white matter dysfunction and impaired attention and working memory has been described. Autopsy and neuroimaging studies are consistent with white matter damage. The extent to which the deficits involve specific pathways in the brain is unknown. We used Diffusion tensor imaging (DTI) and found changes in white matter associated with the cingulate cortex in adults. This is an important structure that subserves pathways involved in attention and working memory. We are now going to expand this project to pediatric patients and look at changes in white matter using a volumetrics approach and neurocognitive testing in which we will validate a computerized testing modality that can be used to follow patients over time. Because of the importance of the corpus callosum (the major white matter bundle connecting the two hemispheres) we are planning a detailed analysis to look at fiber integrity of the corpus callosum in patients with the most severe deficits and relate this to their cognitive functioning.

Describe student’s role in the proposed project to maximize the student’s learning experience:A student who undertakes a project in the laboratory will learn several valuable skills such as clinical neurology and molecular genetics and will have the opportunity to interact with patients with inborn errors of metabolism. He/she will also learn the theory and hands on skills related to magnetic resonance imaging spectroscopy, data analysis using several custom and automated analyses packages and will have the opportunity to participate in a urea cycle research consortium meeting held in Washington, D.C.

The student will learn and be involved in all aspects of this clinical translational study including subject recruitment, performing neuroimaging studies after completing scanner training, and data analysis. In addition, there is the opportunity to learn and administer neurocognitive testing protocols. The opportunity to attend the National Urea cycle disease family meeting in Boston, and attend scientific and family conferences will round out this experience.

The student will work with me as well as other members of the imaging laboratory which is housed at Georgetown University center for Functional and molecular imaging.

I will mentor the student in the following:a. Formation of research hypothesis and selection of the studyb. Analysis of the data using statistical software

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c. Review initial data for interesting / important trendsd. Write an abstract and begin manuscript on findings, prepared poster for GW student research daye. Present abstract at national meeting or local medical meeting

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Primary SponsorJeanne A. JordanProfessor-Epidemiology and Biostatistics, and Co-director of the GWU-APHL International Institute for Public Health Lab ManagementThe George Washington University, SPHHS2300 Eye St., NW, 231 Ross Hall, Washington, DC 20037Office Phone: 202-994-7062 [email protected]

Secondary SponsorRalph TimperiSenior Director Laboratory Practice & Management-APHL and Co-director of the GWU-APHL International Institute for Public Health Lab ManagementAssociation for Public Health LaboratoriesGeorgia Avenue, Silver Spring, MD 20901Office Phone: 240-485-2782 [email protected]

Title of proposed project: Validation of a simple and cost-effective nucleic acid test for HIV Detection

Sponsor research focus: A long-term focus for Dr. Jordan is her interest and expertise is designing and evaluating molecular diagnostics for infectious diseases that impact maternal and infant health. She has 20 years of experience in this area with funding through NIH NICHD, NIH NIAID, CDC NHANES and industry-funded clinical trial opportunities.

Provide background and overall design of the research project: By the end of 2007, an estimated 33.2 million people globally were living with HIV/AIDS, including 15.4 million women and 2.5 million children1. At that same time, there were ~2.5 million new HIV infections and 2.1 million deaths due to HIV/AIDS. Sub-Saharan African remains the region most affected from HIV/AIDS. During 2007 there were 22.5 million people living with HIV/AIDS, 1.7 million new infections and 1.6 million deaths occurred due to HIV; it is here where more than two thirds of all HIV-infected people live and where more than three quarters of all AIDS deaths in 2007 occurred1. Unlike other regions of the world, the majority of people living with HIV are women.

Because of the existence of circulating maternal antibodies, standard HIV antibody tests cannot be used to reliably identify HIV infected infants before they are 18 months of age. This fact increases the chance that the infant will be lost to follow, or a delay in care and treatment, which increases the infant’s risk of morbidity/mortality. Half of all HIV-infected infants will die before their second birthday if treatment has not been initiated by then.

Fortunately, nucleic acid amplification testing (NAAT) for HIV can be performed sooner than antibody-based testing to identify HIV infected infants, which allows for earlier care and treatment and improved outcome. To that end, rural sites have been trained to collect dried blood spot (DBS) specimens on infants that need testing. Unlike whole blood or plasma, DBS specimens are stable at ambient temperatures for transport to central labs. However, HIV NAAT is performed at a limited number of centralized labs, and the testing is highly complex and requires specialized equipment and highly trained personnel.

The other problem to this approach is the lengthy turn-around-time (TAT) for DBS NAAT; it takes weeks to months for rural clinic sites to receive the testing results back from the central lab. The goal of this project is to identify and validate a simpler, NAAT-based approached that could be implemented into provincial-level laboratories to decrease the TAT for identifying which infants need care and treatment.

Jordan Page 2

1 HIV/AIDS Epidemiological Surveillance Report for the WHO African Region 2007 Update

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The research test we are evaluating in this study is the helicase-dependent assay (HDA) being developed by Biohelix (Waltham, MA). The HDA assay is a qualitative isothermal amplification-based assay that can amplify both RNA and DNA targets of HIV using a simple water bath or heat block. The amplified product is performed at room temperature using a simple lateral flow cassette, which requires no additional steps or reagents. This simpler approach would allow less highly trained technologists to perform the testing at a provincial level laboratory.

We have an active IRB (GW IRB # 040907) that enables us to obtained blood specimens from consent HIV-infected subjects from the MFA Infectious Disease Clinic. It also allows us access to the subject’s HIV RNA viral load and CD4 counts, information that will be used to compare to determine the level of detection for the HDA assay.

If the HDA test is found to consistently detect levels of HIV at 10,000 copies/ml, we will begin piloting the test in one or two provincial labs within Mozambique through our collaborations with the Global division of APHL (Ralph Timperi), the Maputo, Mozambique office of the Elizabeth Glaser Pediatric AIDS Foundation (Caroline De Schacht) and the head of research at the Ministry of Health in Maputo, Mozambique (Ilesch Jani).

Piloting the HDA test in one or two sites will allow us to compare the analytical performance of the HDA test performed at the provincial lab with the gold standard test (HIV DNA PCR) performed at the central lab, as well as the HDA test result performed at the central lab. In addition, we will document the average length of time that it takes for rural health clinic to receive the HIV DNA PCR results from the central lab and compare that to a theoretical amount of time if the rural health clinic could receive HIV HDA results from the provincial lab.

Describe student’s role in the proposed project to maximize the student’s learning experience: The student will be trained to extract nucleic acid from DBS specimens, and to perform the HDA testing. The laboratory work will be performed in Dr. Jordan’s laboratory (231 Ross Hall). Once the student is found to be proficient in these protocols, s/he will assess the HDA test’s ability to recognize non-B subtypes that are uncommon to the US, but quite common to Sub-Saharan Africa. Non-B subtype testing will be accomplished using a commercially available international HIV subtype challenge panel. Evaluating whether the current primers used in the HDA assay can recognize non-B subtypes is critical to knowing whether the assay could be considered for international use. Lastly, the student will have the opportunity to assist in creating educational materials for the Mozambican provincial labs, including detailed standard operating procedures, which when completed will be translated into Portuguese.

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Primary Sponsor Rebecca Katz, PhD, MPH Assistant Professor of Health Policy and Emergency Medicine The George Washington University, School of Public Health and Health Service 2021 K Street, NW, Suite 800, Washington, DC 20006 Office Phone: 202-994-4179 [email protected]

Title of proposed project: Implementing the International Health Regulations (2005) through Core Capacity Development

Sponsor research focus: Dr. Katz’s research is focused on public health preparedness and the intersection of infectious diseases and national security. Her current research, and the focus of this project, looks at the Revised International Health Regulations (IHR (2005)), how they are being implemented, their role in global governance of disease, and capacity building to meet IHR (2005) obligations. Dr. Katz has been studying IHR (2005) implementation challenges at both the domestic and international level for the past three years and has just begun a project with the Stimson Center to try to determine what defines core capacity for public health surveillance and how much that costs to implement in a variety of nations.

Provide background and overall design of the research project: In response, the United States and the other 193 member states of the World Health Organization (WHO) agreed to a long-debated legal framework for national and international responses to public health crises. The revised International Health Regulations [IHR (2005)], which entered into force in 2007, require state parties to develop the core capacity to detect, report, and respond rapidly and effectively to “public health emergencies of international concern” in return for improved information sharing and technical assistance. Technical assistance and resources will be critical to achieving truly global disease surveillance and response capabilities, as many countries need a great deal of work to meet these core capacities. However, the costs of achieving IHR (2005) compliance at the country level remain largely conjectural, creating a barrier to marshalling donor assistance effectively. In addition, the regime remains poorly understood within many governments – including the U.S. – beyond the health authorities at the focal point of implementation.

Phase I The project will develop a flexible IHR (2005) compliance costing model that could be adapted for use by national authorities as well as international donors. This output will be accomplished in two steps: 1. Conducting strategic interviews and convening a task force of technical experts in disease surveillance, diagnostic laboratory practice and management, and other relevant fields of public health to construct a detailed matrix of the infrastructure, skills, tools, and resources critical to achieving core capacity for rapid disease detection, assessment, and reporting as mandated by the IHR (2005). 2. Developing a template for assessing the cost of achieving these core capacities by selecting model countries and/or region to represent each of the IHR 2005 compliance strategies outline above and applying the “requirements matrix” described above to actual costs within those nations.

Phase II Over the last decade, the U.S. government has launched a profusion of domestic and global health security programs, primarily organized around specific diseases or threats. As the Obama Administration seeks overarching strategies to guide U.S. public health preparedness and global health engagement, the IHR (2005) offer an obvious tool for eliminating unhelpfully duplicative disease detection and reporting efforts. In addition, U.S. foreign assistance for health has focused increasingly on moving from “combating” a single disease to strengthening public health capacities more generally in vulnerable nations – a trend complicated by the lack of metrics to evaluate progress. As all nations are required to meet specific core capabilities in disease detection and response under the IHR (2005), these metrics might be used as a standard for evaluating recipient nation progress toward health systems strengthening. In addition to a series of conferences, meetings and website development, we will produce a series of manuscripts and issue briefs to help decision makers better understand the IHRs, the U.S. obligations under these regulations, and the means by which the U.S. can assist in implementation efforts globally.

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Katz Page 2Describe student’s role in the proposed project to maximize the student’s learning experience: The student will be involved in all parts of the study, fully participating in data analysis and writing of publications for the website, policy makers and journals. It is anticipated that the student will be involved in drafting at least one paper for publication and assisting with conference presentations.

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Primary SponsorMatthew W. Kay, DSc. Assistant Professor Dept of Electrical & Comp. Engineering and Dept of Pharmacology & Physiology 2300 Eye Street NW, Ross Hall 456, Washington DC, 20037 Office Phone: 4-2898, Lab Phone: 4-0621, Fax:4-2870 [email protected]

Secondary Sponsor: Narine Sarvazyan, PhD. Associate Professor Dept of Pharmacology & Physiology 2300 Eye Street NW, Ross Hall 640, Washington DC, 20037 Office Phone: 4-0626, Fax:4-2870 [email protected]

Title of proposed project: Low flow reperfusion after acute myocardial ischemia.

Sponsor research focus: Dr. Kay’s research is focused upon understanding the effect of transient ischemia and reperfusion on regional cardiac metabolism and resulting disturbances in electrical activity. A better understanding of the relationship between metabolism and arrhythmias may lead to new therapies for sudden cardiac death, a major unmet medical need. A main goal is to conduct studies in living tissue to identify arrhythmia mechanisms using state-of-the-art fluorescence imaging techniques. A primary experimental approach is to simultaneously measure combinations of fluorescence signals, such as NADH fluorescence, transmembrane potentials, calcium transients and intracellular pH.

Provide background and overall design of the research project: In United States almost 6.5 million people are living with coronary heart disease. During episodes of unstable angina, the affected myocardial tissue experiences transient episodes of acute ischemia followed by reperfusion, often at reduced flow rates. Our lab studies mechanisms of ischemia and reperfusion arrhythmias from a new perspective: that of connecting local changes in tissue metabolism caused by perturbations in coronary flow to the resulting disturbances in electrical activity. Despite a clear causative link between cardiac muscle metabolism and its electrical activity, surprisingly few studies have attempted to study them together in working heart preparations using fluorescence imaging. Our recent work has been to enhance the capabilities of our existing dual imaging system by incorporating 1) a high resolution camera for fast imaging of NADH fluorescence, 2) pulsed ultraviolet light illumination that is gated to the ECG, and 3) hardware and software for a third fluorescence imaging camera. Our plan is to use multi-mode fluorescence imaging to study specific pathologic conditions in working heart preparations of acute ischemic injury and subsequent reperfusion. These conditions include: rapid pacing, fibrillation, low-flow reperfusion, and ischemic preconditioning. These studies will provide major advances in the methodology required to conduct studies at the intersection of the research fields of coronary flow, cardiac metabolism, and cardiac electrophysiology while also providing the potential to gain improved understanding of the physiology that causes lethal arrhythmias during unstable coronary flow. Ultimately, this will provide new insights into possible therapeutic interventions to prevent sudden cardiac death.

Describe student’s role in the proposed project to maximize the student’s learning experience: The role of the student will be to participate in experimental procedures, data collection, conduction velocity assessment and image analysis. Studies will be performed using ex-vivo perfused rat hearts. The student will be supported in all aspects of the project by working side-by-side with Dr. Kay and Luther Swift, a graduate student. Dr. Sarvazyan will also play a large role in mentoring the student and guiding the direction of the project. In the past, Dr. Kay has supervised two Gill’s fellows (Brian Martell and Craig Forleiter). Both students ranked their summer experiences very high. These students also produced a sufficient amount work to be included as authors in four abstracts and two peer-reviewed publications.

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Primary Sponsor Susan Knoblach, PhDAssociate Professor Dept. of Integrative Systems Biology, George Washington Univ. School of Medicine and Research Center for Genetic Medicine, CNMC 111 Michigan Ave NW, Washington DC 20010 Office Phone: 202-476-6094 [email protected]

Secondary Sponsor Eric P. Hoffman, PhD Chairman and Director Dept. of Integrative Systems Biology, George Washington Univ. School of Medicine and Research Center for Genetic Medicine, CNMC 111 Michigan Ave NW, Washington DC 20010 Office Phone:202-476-6011 [email protected]

Title of proposed project: Development of Novel Steroids as Neuroprotective Agents for Spinal Cord Injury Sponsor research focus: Chronic neurodegenerative disease and acute CNS trauma/injury are among the most debilitating of all human afflictions. Significant challenges remain with respect to the early and accurate diagnosis of these illnesses, as well as treatment. Recent advances in genomics, proteomics and bioinformatics allow comprehensive and novel ways to answer research questions, and have the potential to rapidly move neurodegeneration research forward, and offer new options for recovery of function. Our laboratory uses these methods together with novel drug design approaches to identify, characterize and ultimately reverse neuronal cell death in chronic neurodegenerative disease and/or acute central nervous system injury. Background:Few treatments offer effective neuroprotection against the secondary injury mechanisms that result in paralysis after spinal cord injury (SCI). Surgical decompression and/or treatment with methylprednisolone (MP) remain the current standard of care for such injuries. MP has shown multipotent activity against important SCI-induced secondary injury mechanisms (inflammation, lipid peroxidation, blood-brain barrier breakdown), but the efficacy and negative side effects of MP are increasingly questioned. Problems with MP may, in part, be related to its activation of glucocorticoid receptors, as well as non-specific effects due to the relatively high dosages needed for neuroprotection. We recently developed novel C 21 steroids that lack the glucocorticoid receptor binding activity that is associated with MP, yet they still act as potent inhibitors of inflammation. In addition, because their steroid structure retains some similarities to MP, they may also have the potential to limit lipid peroxidation and blood-barrier breakdown induced by SCI. Some of these novel drugs were neuroprotective at picomolar concentrations against several different types of in vitro neuronal insults, including neurodegeneration induced by rotenone, glutamate or oxidant stress. Overall Design: 1) Conduct proof-of-principle studies to determine whether novel C21 steroids improve chronic functional outcome in a translational rodent model of traumatic SCI, and 2) Determine whether novel C21 steroids reduce acute secondary inflammation, lipid peroxidation, and increases in blood-brain barrier permeability.

Describe student’s role in the proposed project to maximize the student’s learning experience: Student’s Role: The student will: 1)learn the rat spinal cord injury model 2) test the efficacy of 2 novel steroid drugs in this model; 3) learn and use neurobehavioral tests to determine the neurological status of the rats as they recover from the injury; 4) learn biochemical assays (ELISA, enzyme activity assay) to evaluate inflammation, lipid peroxidation and blood-brain barrer permeability in injured spinal cord tissue and determine whether the novel drugs have any effect on these injury components; 5) learn how and why

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Knoblach Page 2to apply the analysis and statistical methods that are relevant to each outcome; 6) learn how to prepare data for publication, and write a research report and/or poster presentation. The student will participate fully, and be able to work independently (after training) in all phases of the studies as detailed above. The student is also strongly encouraged to present the data at relevant research meetings and submit any resultant manuscripts for publication. Environment: All the equipment needed to carry out the studies is already in place. The mentor has extensive experience with all the methods and will train the students directly. The laboratory is part of a large, convivial center that is home to students, residents and both clinical and research faculty of all levels.

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Primary SponsorYiju Teresa Liu, MD, RDMSAssistant Professor, Department of Emergency MedicineThe George Washington University2150 Pennsylvania Ave, 2B-408, Washington, DC, 20037Office Phone: 202-741-2911 [email protected]

Secondary SponsorKeith Boniface, MD, RDMSAssociate Professor, Department of Emergency MedicineThe George Washington University2150 Pennsylvania Ave, 2B-408, Washington, DC, 20037Office Phone: [email protected]

Title of proposed project: Point-of-care (POC) ultrasound diagnosis of biliary and obstetric/gynecological pathology in the emergency department

Sponsor research focus: Dr. Liu’s research is focused on the utilization of point-of-care ultrasoundin the evaluation of patients in the acute care and critical care settings.

Provide background and overall design of the research project: Studies have shown that there is widely varying availability of point-of-care (POC) ultrasound (US) in the emergency departments (ED) in the United States. One study attempted to discern the actual utilization of POC US through a search of the 1997 Medicare Part D database, revealing emergency physicians performed only 1,551 (0.7%) of the 234,820 ultrasound studies performed in ED. This data was subject to documentation/billing bias and likely does not represent current utilization. New research is needed to evaluate current practice patterns, the result of which will have implications in training for and implementation of POC US.

This is a multi-center retrospective chart review study. Individual medical records for biliary andpregnancy related cases are identified through a search of ICD-9 codes. These records are reviewed forthe type of imaging studies performed to support the ED diagnosis. We will then analyze the pattern ofimaging studies ordered during the patient stay in the ED. We aim to analyze the data to determine thedegree that POC ultrasound exams are utilized in the evaluation and management of ED patients. We willthen compare the characteristics of the different participating clinical sites to determine the barriers toutilizing point-of-care ultrasound in the ED.

Describe student’s role in the proposed project to maximize the student’s learning experience:The successful Gill scholar will be involved with all parts of the study. At minimum, the student isexpected to complete data collection and assist with data analysis in the summer term. Depending uponthe student’s interest, the student may attend weekly ultrasound image review sessions and shadowsponsor faculty during clinical shifts. Through these activities, the student will learn basic POC US examsand understand the importance of incorporating POC US in patient evaluation. The student will receivementorship from the sponsor faculty as well as the research faculty in the department of emergencymedicine in research study design, implementation, and abstract/manuscript preparation.

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Primary SponsorRobert McCarterDirector of Biostatistics and Informatics Children’s National Medical CenterRm M7654, 111 Michigan Avenue NW Washington, DC 20010Office Phone: 202-476--3140 Email: [email protected]

Title of proposed project: Effects of Differential Glycation on Diabetes Complications

Sponsor research focus: We wish to show that diabetic patients with the same mean blood glucose level will have differential hemoglobin A1c levels and that these differences will be important predictors of risk of complications including retinopathy, nephropathy and perhaps bouts of hypoglycemia. This research will lead to at least one manuscript and the participating student will share authorship.

Provide background and overall design of the research project: The research will make use of existing data from the Diabetes Control and Complications Trial (DCCT) which includes repeated blood glucose tests per day, periodic HbA1c results, and recorded complications developing in an average of more than 7 years of follow-up.

Describe student’s role in the proposed project to maximize the student’s learning experience : The student will become part of a research team participating in discussions related to evidence of differential glycation in several settings, development of specific aims and complementary analysis plans. The student will learn to develop linear and logistic regression models, to interpret results of such models, and to draw inferences from them to construct at least one manuscript.

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Primary SponsorDr. Rita Manfredi Assistant Clinical Professor, Emergency MedicineMilliken Fellow, George Washington Institute for Spirituality and HealthDept of Emergency Medicine, GWU2150 Pennsylvania Ave, NWOffice Phone: 703-999-5570 [email protected]

Secondary SponsorDr. Christina PuchalskiExecutive Director, GWISH, Professor, Internal MedicineGeorge Washington Institute for Spirituality and Health2300 K St. NW, Warwick Building, Suite 313, Washington, DC, 20037Office Phone: 202-994-6220 [email protected]

Title of proposed project: Attitudes of Emergency Medicine Patients concerning Spirituality in the Emergency Department Sponsor research focus: This research attempts to identify whether spirituality is important to emergency medicine patients and whether these patients would like their health care provider to discuss any spiritual beliefs that will affect the patient’s stay in the emergency department. We will also look at the specific instances/disease processes/situations in which the patient would like to have a discussion.

Provide background and overall design of the research project: Much has been written about patients’ attitudes concerning spirituality in the medical environment. Many studies demonstrate that patients would like their doctors to talk about spiritual matters in a variety of situations: 95% if dealing with end-of-life matters or a diagnosis of a serious illness or a hospital admission or chronic pain. Sixty percent of patients would like their spiritual issues addressed in the context of a new history and physical exam. It is well documented that patients benefit medically if the spiritual portion of the patient’s history is pursued and discussed. In 1994 McCord and colleagues published in the Annals of Family Medicine a study to determine if family practice patients desired physician inquiry about their spirituality. Of those who wanted to discuss their beliefs, 87% wanted their physician to understand how their beliefs influenced how they dealt with their illness, 85% wanted their physician to understand them better as a person, and 83% wanted their physician to understand their decision making. Overall 5% of patients wanted spirituality discussed for minor problems, 43% for medical histories, and 77% during death and dying situations.

As noted from the above study, the majority of patients would like their spirituality addressed when they are in serious medical situations similar to the ones faced by the majority of patients in the emergency department. Yet, little research has been done in the emergency department setting to determine if patients, during a heightened time of stress in their lives, want emergency physicians and staff to talk about their spirituality with them. This study is a survey tool that looks at the attitudes of emergency medicine patients concerning spirituality in a relatively high stress situation such as the emergency department.

The survey has 77 questions and is currently being piloted for feasibility in Prince George’s Hospital Emergency Department. In the project planned for the medical student a greater number of patients will be surveyed at Prince George’s Hospital as well as at GWU and the VA hospitals. Patients will be given informed consent sheets to sign and those agreeing to be part of the study will then be interviewed by a research assistant who will administer the questionnaire to emergency medicine patients in the waiting room or in patient care areas while patients are waiting for test results, x-rays, etc. There is no risk to the patient and there will be no identifying data on the survey sheet that links the patient’s name with his/her responses.

This survey will be conducted in conjunction with Dr. Christina Puchalski, Executive Director of George Washington Institute for Spirituality and Healing at George Washington University. Dr. Puchalski is

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Manfredi Page 2Professor of Medicine at the medical school and has written extensively about patients and spirituality, conducted many research projects as lead PI, as well as being an expert in palliative care.

Describe student’s role in the proposed project to maximize the student’s learning experience: The student will play a vital role in this project as a research assistant and survey administrator. Each student will interact directly with patients in the emergency department as well as in the waiting room. He/she will be exposed to the controlled chaos of emergency medicine and experience first hand what patients experience when they are in crisis. In addition to interviewing the patient, the student will input the data and participate in data analysis once the surveys are completed. Thus the student will learn survey interviewing techniques and data analysis. Also, these interactions between patient and student will contribute to the development of the student’s future “bedside manner” as well as help to train the student to listen directly or mindfully while interacting with the patient. The student will be asked to keep a narrative journal of his/her experience during the summer as part of a reflective practice that is taught in medical school.

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Primary SponsorDave Mathison, MDDepartment of Emergency MedicineChildren's National Medical Center

Project description for summer students: I am conducting a pilot project using intranasal ketamine to sedate children for burn debridement in the ED.

This type of sedation has never been studied in a pediatric ED. This would not in any way be a full-time commitment, but if there were students in the hospital that were interested in participating when patients come in, it could be interesting for them and helpful for enrollment. It could be a nice complement to a less interactive (computer or chart review) type of project. I can provide more information if need be.

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Primary SponsorLarissa May, MD, MSPHAssistant Professor of Emergency Medicine, Microbiology, Immunology and Tropical Medicine, and Epidemiology and BiostatisticsAssociate Director of Clinical Research, Department of Emergency MedicineThe George Washington University Department of Emergency Medicine2150 Pennsylvania Avenue, Suite 2B, Washington, DC 20037Office Phone: 2027412920 [email protected], [email protected] (preferred)

Secondary SponsorKabir Yadav, MDAssistant Professor of Emergency MedicineThe George Washington University Department of Emergency Medicine2150 Pennsylvania Avenue, Suite 2B, Washington, DC 20037Office Phone: 2027412920 Email: [email protected]

Title of proposed project: Practice patterns, epidemiologic factors, and clinical outcomes for purulent skin and soft tissue infections in the emergency department (GW IRB Number 030927)

Sponsor research focus: Dr. May’s principal research interests are in emerging infectious diseases, acute infectious disease epidemiology, and clinical emergency medicine practice patterns related to infectious diseases

Provide background and overall design of the research project:

Background: CA-MRSA and Skin and Soft Tissue Infections:Over the last decade the incidence of skin and soft tissue infections due for the most part to Community-acquired MRSA (ca-MRSA) has significantly increased and physicians are seeing an increased number of abscesses presenting to the emergency department due to this bacterium. Recommendations for treatment of abscesses are vague. Most sources recommend incision and drainage as adequate for abscesses without cellulitis or systemic symptoms, however given the concerns re MRSA, providers may be prescribing antibiotics for abscesses alone, even though in most cases incision and drainage alone may be sufficient.Practice patterns with regard to incision and drainage may vary in terms of technique, including use of sterile precautions, extent of incision, and use of packing. No studies were found comparing I and D techniques and clinical outcomes in patients with MRSA-related abscesses in the emergency department, and there is limited data for microbial susceptibilities for abscesses at our institution and in the DC area.

Objective: This pilot study aims to examine the epidemiologic risk factors and pathogens associated with purulent skin and soft tissue infections (SSTI) in a single, urban emergency department for a the period from July 2009 to August 2010 or until enough subjects have been enrolled. We plan to enroll up to 1000 patients for this study.

Specific Aims:

Our study purpose is two-fold:

1. To describe clinical practice patterns for abscess/purulent infection management and determine best practices for incision and drainage and empiric antibiotic selection. Our measured outcome for this aim will be clinical improvement at 2-7 days. We will collect data on Incision and Drainage technique, abscess characteristics, antibiotic selection, and patient comorbidities to control for confounders and stratify by infection type and severity.

2. To study the epidemiology and perceptions of abscesses and purulent infections in the DC area, of which little is known, as measured by our urban ED population. The study will provide descriptive epidemiology on abscesses in patients with comorbidities and by zip code.

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May Page 2Describe student’s role in the proposed project to maximize the student’s learning experience:The selected student will gain experience in enrolling and consenting emergency department patients for the study, assisting with data analysis and result interpretation, and drafting of the manuscript for publication.

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Primary SponsorSharon Maynard, MDAssistant Professor of MedicineGeorge Washington University School of Medicine2150 Pennsylvania Ave NWOffice Phone: 202-741-2283 [email protected]

Title of proposed project: Focus On Mom: A Novel Recruitment Approach to Identify Hypertensive Women after Preeclampsia

Sponsor research focus: Clinical research in preeclampsia

Provide background and overall design of the research project: Women who have had preeclampsia have an increased risk of subsequent chronic hypertension, cardiovascular disease, stroke, and chronic kidney disease. Unrecognized, untreated, and uncontrolled hypertension among these women represents a potentially modifiable risk factor for these outcomes, but the incidence of untreated hypertension after preeclampsia is unknown. For this pilot study, we test the feasibility of a screening program for hypertension after preeclampsia based at the pediatrician’s office. Women will be recruited at their child’s regular pediatricians office visit based on a prior history of preeclampsia, and we will compare rates of hypertension, hypertension awareness, treatment, and control in women with and without prior preeclampsia. We will also pilot a referral intervention for women found to have uncontrolled hypertension.

Describe student’s role in the proposed project to maximize the student’s learning experience:

Ideally, the student will be involved in all aspects of the study, including:1. Literature review and formulation of hypotheses2. Finalization of study design and IRB approval3. Recruitment and enrollment of study subjects4. Coordination of study visits and collection of study data, including blood pressure measurement5. Interpretation of results and preparation of abstract for presentation at a national meeting.

It is expected that the major study activities will be completed in the time leading up to and including the summer period, but the student will be encouraged to continue to work on data analysis, interpretation, and abstract preparation after the completion of the summer fellowship if needed.

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Primary SponsorAndrew C Meltzer, MD FAAEMAssistant Professor of Emergency MedicineGeorge Washington University School of MedicineDepartment of Emergency Medicine2150 Pennsylvania Avenue, Suite 2B-417Office Phone: 202 741-2917 Fax: 202 [email protected]

Name of proposed project: A Phase III Randomized Multicenter Clinical Trial Of High-Dose Human Albumin Therapy For Neuroprotection In Acute Ischemic Stroke (ALIAS.)

Sponsor research focus: Dr. Meltzer’s area of research focus is the acute care of the stroke patient. Stroke is the third leading cause of death in the U.S. The only proven therapy for acute stroke must be started within the first 3 hours of symptom onset. This reality has thrust the emergency department into the forefront of developing cutting edge therapy for acute stroke. In the quest to develop new therapies for acute stroke to limit the high morbidity and high mortality of this disease, researchers are focusing on therapies given in the period immediately after symptom onset. The limited time frame makes research and development of new therapies especially challenging. New multi-center emergency room networks allow research that beforehand was not possible and may change the way we treat acute stroke. George Washington University is a spoke on one of these national networks.

Background and overall design of the research project: There is no clinically approved neuroprotectant for acute ischemic stroke. In preclinical studies, moderate- to high-dose human serum albumin therapy has been shown to be markedly neuroprotective in models of focal cerebral ischemia, global ischemia, and acute brain trauma. We view the multiple unique physiochemical properties of albumin as being integral to its neuroprotective effect: specifically, its binding and transport of plasma fatty acids; its major role as a plasma antioxidant and free-radical scavenger; and its salutary actions on vascular endothelium.

A Phase I pilot clinical clinical trial was designed to establish the safety of administering moderate-dose human serum albumin intravenously (in a multiple-tier, dose-escalation design) to patients with acute ischemic stroke. The study was structured as a two-center, open-label, non-randomized trial. NIH Stroke Scale (NIHSS) is assessed sequentially until discharge; NIHSS, Rankin, and Barthel are assessed at 1 and 3 months. Now that the safety of albumin has been established, the phase 3 trial has been designed to show whether albumin improves clinical outcomes when given soon after symptom onset for patients with acute ischemic stroke.

Student’s role in the proposed project: The student will be involved in all parts of the study. As Dr. Meltzer and the neurology (Dr. Burger) collaborators are well versed with acute stroke care, we know the potential advantages and pitfalls of this trial. The student will be stationed in the ER and will observe the triage of acute stroke patients as they present to the ER. Student will need to be familiar with details of the study protocol, especially the inclusion and exclusion criteria. When potential stroke patients present to the ER, an overhead alert to the “Brain Attack Team” will sound. The student will be expected to respond with the rest of the brain attack team to the patient.

Student will learn details of a multi-center NIH funded study. The student will participate in all levels of performing a randomized control trial which will likely lead to an important national publication and international abstract presentation. Students will also be expected to learn how to assess an NIHSS, Rankin and Barthel score on stroke patients. This project will be extremely valuable to a student who plans on doing clinical research in the future, especially federally funded research.

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Primary SponsorAndrew C Meltzer, MD FAAEMAssistant Professor of Emergency MedicineGeorge Washington University School of MedicineDepartment of Emergency Medicine2150 Pennsylvania Avenue, Suite 2B-417Office Phone: 202 741-2917 Fax: 202 [email protected]

Name of proposed project: Video Capsule Endoscopy in the Emergency Room

Sponsor research focus: Dr. Meltzer’s area of research focus is the use of video capsule endoscopy to diagnose and treat acute gastrointestinal hemorrhage in the emergency department. The ability of VCE to rapidly inspect the gastrointestinal tract without the need for sedation enables the emergency room physician to rapidly diagnose and treat the patient’s affecting lesion. Early identification of the source and nature of the bleeding may improve the emergency physician’s ability to coordinate rapid intervention and hospital admission as needed. We aim to show that VCE can assist in the management of patients who present to the ED with suspected UGIH and to show that the ED physician can utilize the VCE to independently guide his consultation with the gastroenterologist.

Background and overall design of the research project: Acute upper gastrointestinal hemorrhage (UGIH) may present as a life-threatening condition for patients in the emergency department. The investigation of UGIH has always represented a diagnostic challenge for emergency physicians. With existing methodology, the emergency physician is unable to visualize the lesion that is causing the bleeding. Conventional techniques of endoscopy are limited by the need for a gastrointestinal specialist, the need for procedural sedation and the invasive nature of the technique.

We aim to determine the feasibility and efficacy of the VCE for UGIH in the ED. All patients with suspected UGIH who are older than 18 years will be eligible for the study. Suspected UGIH will be classified as presenting with actual or reported hematemesis or melena. The primary data end-points that will be collected for all subjects will answer whether the VCE can detect acute UGIH. We will specifically be asking whether the VCE can detect blood in the UGI tract and/or active bleeding.

This is a new, stand-alone project utilizing a relatively novel diagnostic technique that has never been studied in the ER population. Dr. Meltzer has received special training in the administration and interpretation of video capsule endoscopy. The student will work in the ER and attempt to identify patients who might be suitable candidates for VCE. Student must learn the signs and symptoms of UGIH and must be well-versed in inclusion and exclusion criteria of the study. For potential study subjects, the student will work with a research coordinator to contact the on-call attending and facilitate consent and performance of the VCE. The student will record demographic data and baseline labs. In addition, student will be responsible for archiving images from the procedure into a secure database. Since all enrolled patients must be followed for a minimum of 24 hours, the student will collect additional clinical parameters and EGD results. Finally, data analysis, including calculation of interobserver reliability and significance testing will be calculated. Data analysis will be performed in conjunction with colleagues in department of biostatistics. At the end of enrollment, student will be involved in abstract presentation at a national meeting and ultimately manuscript submission.

Student’s role in the proposed project:The student will be involved in all parts of the study. As Dr. Meltzer and the gastroenterology collaborators are well versed with VCE, we know the potential advantages and pitfalls of this procedure and the subsequent data analysis. As this is a proof of principle project with low target enrollment, this project can be completed in the summer term with the abstract and manuscript preparation being continued by the research team.

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Moon IPrimary SponsorRachel Y. Moon, M.D.Associate Professor of PediatricsChildren’s National Medical Center111 Michigan Avenue NW, Washington DC 20010Office Phone: 202-476-5476 [email protected]

Title of proposed project: Changes in sleep patterns and stress in infants entering child care: Implications for SIDS

Sponsor research focus: Dr. Moon is a general pediatrician and a SIDS researcher. Her area of research focus is on SIDS epidemiology and risk factors, particularly in high-risk groups, such as African-American infants and infants attending child care. She has authored or co-authored more than 40 peer-reviewed articles pertaining to SIDS. Dr. Moon’s studies have shown that 20% of SIDS occurs in child care settings. A large proportion of these deaths occur during the first week – and often on the first day – that the infant attends child care. This study will investigate specific factors that may increase SIDS risk in infants at the time of transition to child care. The central goal of this study is to describe the changes in sleep patterns and markers of infant stress levels and circadian rhythm associated with child care entry.

Background: Sudden infant death syndrome (SIDS) is the most common cause of death in infants 1 month-1 year of age, with approximately 2300 infants dying each year in the US. Surprisingly, 16-20% of all SIDS deaths occur in child care settings, and many of these deaths occur during the first week. Since 75% of US infants are in some form of child care, it is critical to identify factors contributing to this heightened risk of SIDS. No single factor accounts for all SIDS cases, but changes in routine are common. The altered routine may either cause or be the result of changes in sleep pattern. Anecdotal observations suggest that infants newly introduced to child care have altered sleep patterns, but no published data describe these changes. Since many of the deaths in child care occur within the first week there, infant stress level may also be a critical factor and may be associated with the first extended separation from caregivers, parental stress, the presence of other infants, and changes in the timing and quality of environmental response to basic care needs. Increased levels of stress can also create sleep disruption. The risk of SIDS may also be related to a disruption in the normal maturation of the infant circadian rhythm. For instance, environmental changes, such as exposure to ambient light, can cause changes in the normal rhythm development and may explain the seasonal variation seen in SIDS rates (more common in winter months).

Design: Prospective cohort study.

Methods: The study will be a prospective investigation of two cohorts of infants, one entering child care and the other remaining in home care. Infants will be compared with themselves (before and after entering child care) and with infants in the other group (child care vs. home groups). Healthy infants will be recruited before the age of 3 months. An initial screening survey to determine eligibility and cohort assignment will be conducted. Evaluations will be scheduled for each infant as follows (day 0 indicates the day when the infant will enter child care for the child care cohort; home babies will be age-matched to the child care babies):

1) Continuous actigraphy (a device that looks like a wristwatch that calculates sleep and awake cycles by measuring movement): Day -14 through Day +14

2) Infant care practices interview to assess typical home practices with regards to type of feeding, sleep location, environmental risk factors for SIDS: upon study entry

3) Sleep and feeding diary that indicates type and timing of feedings; sleep location, position, and timing: Day -14 through Day +14

4) Urine collection for cortisol and melatonin (urine will be collected by parents using urine collection pads): Days -14, -7, -1, 0, +1, +7, +14

A staff member will visit each family’s home once a week during the course of the study to download actigraphy data and collect forms and urine samples from the previous week. Visits will be pre-arranged with the family so that the time of the visit will be convenient for all.

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Moon I Page 2Describe student’s role in the proposed project to maximize the student’s learning experience:The student will recruit families for the study and maintain contact with participants to facilitate data and specimen collection. In addition, the student will actively participate in actigraphy data download and analysis. The student will learn about experimental procedures and data analysis.

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Moon IIPrimary SponsorRachel Y. Moon, M.D.Associate Professor of PediatricsChildren’s National Medical Center111 Michigan Avenue NW, Washington DC 20010Office Phone: 202-476-5476 [email protected]

Title of proposed project: Sociocultural influences on parental decisions that are relevant to SIDS risk

Sponsor research focus: Dr. Moon is a general pediatrician and a SIDS researcher. Her area of research focus is on SIDS epidemiology and risk factors, particularly in high-risk groups, such as African-American infants and infants attending child care. She has authored or co-authored more than 30 peer-reviewed articles pertaining to SIDS. Epidemiologic studies have demonstrated what behaviors increase the risk for SIDS, and that behavioral differences may explain much of the black-white disparity seen in SIDS. However, it is less clear why parents make decisions with regards to sleep position, sleep location, pacifier use, bedding, etc. that may increase their infants’ risk for SIDS. This study aims to better understand the sociocultural milieu and the influences that impact on parental decisions.

Provide background and overall design of the research project: Background: Studies have consistently demonstrated a racial disparity in SIDS. Although there may be genetic factors that contribute to this disparity, behavioral differences are also important. For instance, African American infants are twice as likely to sleep prone and to bed share than Caucasian infants. Both of these behaviors are associated with an increased risk for SIDS. Very little is known about the reasons why African-American parents choose prone position, bed sharing, and other SIDS relevant behaviors more often than other racial/ethnic groups.

Design: Cross-sectional multi-modal study that uses both quantitative and qualitative techniques.

Methods: Parents of infants 0-6 months of age are recruited to participate. An initial 5-10 minute survey is conducted to assess knowledge, attitudes, and practice regarding SIDS-relevant behaviors. A subset of parents will then be asked to participate in either a focus group or extensive individual interview to discuss knowledge, beliefs, practices, and influences on practices.

Describe student’s role in the proposed project to maximize the student’s learning experience: The student will participate in conducting parent surveys. In addition, s/he will attend focus groups. S/he will read transcripts of past focus groups and, after discussion with the sponsor, analyze focus group data on a specific area of interest. Possibilities include but are not limited to pacifier use, breastfeeding, and bedding. It is hoped that the student will actively participate in the project by helping to refine focus group questions that may help the student on his/her individual project. The student’s efforts will be facilitated by closely working with the research staff and with the sponsor, including meetings with the sponsor on a weekly basis.

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Primary Sponsor Evan Paul Nadler, MD Director, Bariatric Surgery Program, The Joseph E. Robert, Jr. Center for Surgical Care; Co-Director, Obesity Institute Children’s National Medical Center, Children’s National Medical Center, Div. of General and Thoracic Surgery 111 Michigan Avenue, NW, Washington, DC 20010 Office Phone: 202 476-5000 [email protected]

Secondary Sponsor Stephen Teach, MD, MPH Associate Chief, Emergency Medicine and Trauma Center; Associate Director, Children's Research Institute (CRI), Center for Clinical and Community Research (CCCR); Professor, Pediatrics, Emergency Medicine Children’s National Medical Center; George Washington University School of Medicine and Health Sciences Children’s National Medical Center, Division of Emergency Medicine 111 Michigan Avenue, NW, Washington, DC 20010 Office Phone: 202 476-5000 [email protected]

Title of proposed project: The effect of an asthma intervention on growth and weight status in young asthmatic children

Sponsor research focus: Dr. Nadler's basic science research focuses on liver fibrosis associated with biliary atresia. His clinical and translational science investigates the systems biology of obesity surgery, and the safety and effectiveness of various weight loss procedures in adolescents. As co-director of the Obesity Institute at Children’s National, Evan is reshaping multidisciplinary research efforts in both clinical and pre-clinical investigations to lead toward a better understanding of how clinical care and community efforts can prevent overweight and produce better health outcomes for patients who are overweight and obese.

Dr. Teach’s primary academic focus is on the disparities evident in the care of inner-city children with asthma, including their over-reliance on urban emergency departments for episodic asthma care. He is principal investigator and medical director of “Improving Pediatric Asthma Care in the District of Columbia,” IMPACT DC, an asthma surveillance, research, clinical care, and advocacy program in Washington. Although Children’s National has participated in multi-site studies, the proposed project is the first initiated by Children’s to examine how different intensities of asthma care may effect body weight deposition in young children who reside in the District of Columbia. Prevention of overweight and obesity in young asthmatic children is especially important for increasing the likelihood that patients will respond to conventional treatment, reduce emergent care visits, and successfully manage their disease as they approach adolescence.

Background and overall design of the research project: The project will utilize an existing database from a prior study that Dr. Teach compiled including data for n=124 asthmatic children aged 1 to 12 years who received an asthma intervention. The student will extend the analysis to investigate growth rate of these children and whether greater intensity of care produced better weight status. This effort will require the student to retrieve growth measures from medical records in order to supplement the existing database so that growth rate prior to and after the baseline visit can be calculated, and so that weight status six months post-baseline visit can be determined.

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Nadler Page 2Describe student’s role in the proposed project to maximize the student’s learning experience:Under the guidance and supervision of the Sponsors, the student will be responsible for the bulk of the work in this study. The student will be required to complete The Collaborative Institutional Training Initiative (CITI) training prior to accessing protected health information. Dr. Teach and his research team have previously analyzed and summarized the findings derived from the database. Dr. Nadler has the necessary expertise to guide and supervise the student’s efforts. The proposed project can be completed within the minimum 8-week summer timeframe as a practicum-type experience. Catherine Klein, PhD, RD will serve as site-preceptor to facilitate and coordinate the student’s activities. Dr. Klein has supervised the development and successful conduct of several GW graduate student research projects at Children’s. The Sponsors realize the Gill award student may be presenting a ppt-supported talk of the project in fall 2010 and a poster on the summer experience at the Medical Center’s Research Day in the spring of 2011 and can provide feedback to the student on the content of the draft communications prior to presentation. The specific learning activities under the supervision of the Primary Sponsors include:

1. Gaining an understanding of proactive asthma management and the impact of pediatric asthma programs on the co-morbid condition of obesity. 2. Extracting previously collected data of asthmatic children and organizing data for statistical

analysis; creating additional variables as needed, i.e., generating BMI percentiles from CDC automated program to categorize weight status

3. Conducting an analysis in SPSS to determine growth rate and weight status of children at entry into the Asthma program and the changes in weight status between those who received follow-up reminders and those who did not.

4. Reviewing published literature and interpreting research results in the context of previously published evidence.

5. Summarizing results in a research brief (up to 2,000 words and a maximum of two tables and/or figures).

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Primary SponsorMary C. Ottolini MD, MPHVice Chair of EducationChildren’s National Medical Center111 Michigan Ave NW, Washington DC 20010Office Phone: 202-476-3938 [email protected]

Secondary SponsorChristine Sheehy PhDDirector of Nursing EducationChildren’s National Medical Center111 Michigan Ave NWWashington DC, 20010Office Phone: [email protected]

Title of proposed project: Virtual Pediatric Sedation: Using Second Life to Create a Moderate Sedation Simulation Module

Sponsor research focus: Pediatric Medical Education- Simulation in Learning:

Provide background and overall design of the research project: This is an interdisciplinary proposal about clinical teaching effectiveness. Education and training are important components of Children’s National mission.

1. SPECIFIC AIMSThe primary purpose of the proposed project is to design and evaluate a virtual learning environment to be used in training clinicians involved in clinically managing moderate sedation in hospitalized Pediatric patients.

The specific aims of the project are to:

1. Design a virtual learning environment in a modality known as ‘SecondLife®’, to be used in training clinicians who administer and/or monitor moderate sedation in hospitalized Pediatric patients.

2. Evaluate the acceptability and usability of this virtual learning environment among clinicians involved in clinically managing moderate sedation in hospitalized Pediatric patients.

3. Determine whether exposure to this virtual learning environment suggests a trend for enhanced educational effectiveness.

4. Assess the implementation of this modality for wider application in education and training.

2. SIGNIFICANCE

Multiple challenges surround the current education and training needs of health care clinicians. Advances in understanding of clinical phenomena, including evidence based practices (EBPs), are published regularly and information about these must be added to already substantial curricula. At the same time, length of most training programs has remained the same while student clinical experiences have decreased. Further, knowledge is only one part of the learning process. Technical skills and critical reasoning abilities are also essential to mastery of accurate and safe patient care. These develop gradually and are perfected by repeated practice and application.

Physician and nurses in training have historically practiced under an apprenticeship model in which one waits for an opportunity to perform a particular skill under the guidance of a senior clinician or faculty member. This approach is time and labor intensive, requiring one-to-one supervision and evaluation of learning. This can result in far fewer practice occasions than desirable to achieve competence. It also may

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Ottolini Page 2result in unnecessary discomfort for patients while students perform procedures when one is not adept in a skill. Anecdotally, parents witnessing a student clinician ‘learning’ on their child risk losing confidence. Although there is considerable evidence that practice makes perfect, the approach to clinical training has changed little to compensate for the challenges. Only one technology has been widely used to strengthen clinical learning and expertise for physicians and nurses: Simulation Learning Centers (SLCs). Fortunately, we at Children’s National have the advantage of a SLC to augment our training programs, including practice in communication and team dynamics. Both of the latter are clearly associated with providing safe care. However, there is much more that can be done to provide technological innovation in clinical education. That observation has been recently emphasized in articulation of our strategic goals for education.

Virtual learning environments can provide an important supplement to the need for “deliberate practice” and feedback. Virtual worlds offer an immersive environment that enable collaborative team training and 3D context sensitive interaction with virtual objects within a realistic environment. There are many different types of virtual or immersive worlds – single and multiplayer video games, simulators and stimulators such as flight simulators, Cave Automatic Virtual Environment (CAVE), and social networking worlds such as SecondLife®.

We chose sedation training to be the focus of this project because being able to offer appropriate sedation and analgesia 24/7 is crucial to our institution’s efforts to eliminate painful experiences for children at Children’s National. Inappropriate sedation and analgesia can have life-threatening consequences. A large number of physicians and nurses must be well trained to be able to provide sedation and analgesia in a safe and effective manner whenever it is needed. This proposed project is an important step in our effort to make greater use of technology to reinforce clinical learning and reasoning. In addition to being state-of-the-art for student and new graduate education, the technology potentially also has broad application to credentialing and re-credentialing of clinicians in the overall quality program. In the future we hope to be able to design additional studies that will capture clinical outcome measures including understanding about the relationship between virtual teaching environments and prevention of adverse events.

3. RESEARCH DESIGN AND METHODS

Design

The proposed project is an experimental design in which participants will be randomly assigned to one of two interventions: 1) a traditional learning method available and currently in use in the CHEX online learning system; or 2) a SecondLife® virtual model learning modality.

Design of the SecondLife ® virtual model

Aim #1 - Design a virtual learning environment in a modality known as ‘SecondLife®’, to be used in training clinicians who administer and/or monitor moderate in hospitalized Pediatric patients.

For this study we will be creating a virtual hospital room or procedure room in SecondLife® on the SRA Island in which residents and nurses will work through clinical scenarios about team training, problem solving, managing, communicating, and appropriately to situations involving moderate sedation. An ‘island’ is simply the term used to denote a virtual space in which the training scenarios are placed and housed. The overall goal is to determine whether the virtual world is an effective modality when compared to standard training practices.

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Ottolini Page 3SRA Center of Excellence for Learning and Performance Excellence (SRA CELPE) has a team of experts that specializes in developing virtual, 3-D mediums for use in desktop simulation, intelligent tutoring systems, on-the-job training, collaboration and team training. The Centers for Disease Control and Prevention, the USAF School of Aerospace Medicine, the National Library of Medicine, the Environmental Protection Agency, the Red Cross and the U.S. Army are examples of customers for whom SRA has developed immersive training or education in SecondLife®.

Describe student’s role in the proposed project to maximize the student’s learning experience:The student will learn how to apply adult learning principles in creating simulated learning environments. Specifically the student will learn to develop a series of pediatric sedation simulation cases. By participating in this research project the student will learn how/when to use virtual world simulation in education. He/she will also learn about indications for pediatric sedation, common medications used, safe monitoring procedures; anticipating and managing common complications.

The student will assist in many aspects of project design from creation of scenarios, to development of virtual environments and pilot testing aspects of the simulations.

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Primary SponsorDiego Preciado, MD, PhD, FAAPAssistant Professor of Otolaryngology and PediatricsChildren’s National Medical CenterDiv. of Otolaryngology, CNMC111 Michigan Avenue, NW, Washington, DC 20010Office Phone: 202 476-3852 Fax: 202 [email protected]

Title of proposed project: Bacterial antigen induction of mucin glycoproteins in middle ear cells.

Sponsor research focus: Dr. Preciado spends 50% of his time performing basic science research in otolaryngology, focusing specifically on molecular mechanisms of oitis media pathophysiology. He has published an article recently demonstrating that dissolved cigarette smoke products lead to increased mucin gene expression in otitis media cell models. He has previously mentored 4 Gill Fellows, experiences resulting in authorship in otolaryngology manuscripts published in peer reviewed journals.

Provide background and overall design of the research project: Otitis media (OM) is a ubiquitous condition of early childhood accounting for 16 million physician office visits a year [1] at a national cost of $3 to $6 billion[2]. Acute OM (AOM) is defined as acute onset of middle ear effusion along with signs and symptoms of middle ear inflammation and infection. OM with Effusion (OME) is thought to result as a response to chronic inflammation in the middle ear, and is characterized by persistence of mucoid middle ear effusion. In the first year of life, >50% of children will experience OME, increasing to >60% by 2 years. OME is associated with hearing loss, delayed speech development, and the potential for permanent middle ear damage. The transition from AOM to OME is marked by middle ear epithelial goblet cell metaplasia [3, 4] and mucus hypersecretion. Currently there are no medical treatments available that work adequately either to prevent or resolve middle ear effusions in the setting of inflammation.

As part normal epithelial defense mechanisms, mucin glycoproteins act as physiological barriers to contaminants and bacteria by forming mucous, a viscoelastic gel. However, mucin over-production and the resulting mucous obstruction or stagnation clearly contributes to pathologic disease state of OME [5]. A number of stimuli, including bacterial products and pro-inflammatory cytokines have been shown to lead to middle ear mucosal metaplasia and mucus hypersecretion [6-9].

Despite the strong casual OM data with infectious, inflammatory and environmental stimuli, direct genetic regulatory mechanisms of whereby mucoid middle ear secretory effusions form are under-investigated. Parallels, however, can be drawn relatively more advanced studies of pulmonary diseases. Mechanisms whereby some of these agents induce mucin gene upregulation and overproduction in lung epithelial cells have been investigated. The current paradigm is that bacterial products, pro-inflammatory cytokines, and cigarette smoke signal through membrane bound receptors activating transcription factors, which ultimately increase secreted mucin gene transcription in respiratory epithelial cells [9, 10].Whether parallel effects are exerted in OM disease models is the subject of our proposed investigations. Collaborators from my previous lab at the University of Minnesota, have shown in animal models of OM that injection of bacterial products into rat middle ears induces mucoid effusions reliably [11], a process that closely mimics the human disease condition.

We recently found that in vitro stimulation of murine middle epithelial cells with dissolved cigarette smoke particulate matter leads to induction of the ubiquitous, pro-inflammatory transcription factor NF-κB and with subsequent increased transcription of Muc5b[12], the most prominent secretory mucin identified in human otitis media [13], and in a time and dose dependent cytokine response. The overriding aims of our proposal are first to investigate whether mucin genes are similarly upregulated at the promoter level in middle ear cells by specific transcription factors, predominantly NF-κB, in differentiated middle ear cell models after stimulation other pathologically relevant agents such as non-typeable Hemophilus Influenza(NHTi) and the pro-inflammatory cytokines TNF-α and IL-5. This will be the main component of the project that the medical student Gill Fellow will be involved with.

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Preciado Page 2Secondly is to determine whether transcription factor inhibition strategies can be utilized to minimize formation of mucoid middle ear effusion in the face of inflammatory stimulation in rat models of OM. Essential to the accomplishment of this second aim is to have the capability of measuring effects on hearing secondary to the effusion and/or the treatment. This is done by measuring evoked auditory brainstem responses (ABR) with special equipment we are requesting funds for.

Specific Aim 1. Determine whether cultured middle ear cells exposed to pathologically relevant bacterial lysate stimuli upregulate MUC5AC and/or MUC5B genes mRNA abundance and cytokines through cis-interaction of NF-kappaB to the 5’ flanking regulatory sequences of these genes.

Specific Aim 2. Animals treated with transcription factor inhibitors will have a marked reduction in the development of otitis media effusions and improvement in hearing thresholds upon bacterial middle ear inoculation.

Specific Aim 3. Determine whether treatment of OME patients with a relevant, low side effect NF-κB drug results in clinical resolution of middle ear effusions, reversal of conductive hearing loss and ultimately decreased need for surgical intervention.

Describe student’s role in the proposed project to maximize the student’s learning experience:

Specifically, the student will work on elucidation of Aim 1 listed above. Specifically, he/she will be responsible for performing the following:

1) RT-PCR for Muc5b and Muc5ac mRNA levels after time and dose dependent simulation of middle ear cells.

2) Western blots on human and mouse middle ear cell supernatants and patient middle ear effusion samples for identification of secreted MUC5B and MUC5AC proteins after bacterial lysate exposure.

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Primary SponsorClaudia Ranniger, MD, PhDMedical Director, Simulation CenterOffice of Interdisciplinary Medical EducationRm 6200, CLASS Center, 6th Floor, GWU Hospital, 900 23rd St, NWOffice Phone: [email protected]

Secondary SponsorBenjamin Blatt, MDMedical Director, Clinical Skills CenterOffice of Interdisciplinary Medical EducationRm 6216, CLASS Center, 6th Floor, GWU Hospital, 900 23rd St, NWOffice Phone: [email protected]

Faculty/Lab Sponsor name: Frank Slaby, PhDCourse Director, Gross AnatomyDepartment of Anatomy and Regenerative BiologyRoss Hall 212, 2300 I Street, NWOffice Phone: [email protected]

Title of proposed project: Clinical Correlation in the Anatomy Lab: Connecting Anatomy withClinical Practice

Sponsor research focus: Curriculum Development and Educational Research. Dr. Ranniger‘sresearch focus is on the integration of simulation and technology into medical education, and theeducational outcomes that can be achieved by vertically integrating examination and procedural skills intothe medical school curriculum. Dr. Blatt’s educational interests include the integration of clinical andbasic sciences in a longitudinal curriculum (practice of medicine), the education of students as teachers,and communications skills. Dr. Slaby directs the Gross Anatomy course, and has completed GW’s MasterTeacher program.

Provide background and overall design of the research project: During the last two years Drs Ranniger, Blatt and Slaby have created clinical correlation exercises for first year medical students which support the transfer of anatomic knowledge to clinical skills, in the context of Gross Anatomy. Preclinical students traditionally have limited contact with the clinical environment, and thus often fail to identify and internalize the relationship between the human body’s external landmarks and internal organs / structures. The goal of the clinical exercises is to enhance anatomic learning by explicitly linking anatomic structures with clinical examination or procedural skills within the anatomy lab curriculum.

Successful pilot project ‘modules’ have included clinical anatomy in the context of cardiopulmonaryresuscitation (CPR), cricothyrotomy, and placement of intraosseous vascular access lines. These moduleshave been well received, and exam questions results and voluntary post-course surveys indicate thatstudent performance is enhanced. However, no full evaluation via comprehensive anatomic and clinicalskills examination, or subjective survey has been completed. In addition, further correlation exercises thatleverage the unique opportunities of the anatomy lab should be developed.

The overall project goals are 1) to further enhance the Gross Anatomy course’s clinical correlation sectionwith additional modules, and 2) to demonstrate educational benefit of these modules both via objectivemeasures and comprehensive student ratings. The end product will be a ‘clinical correlations in anatomy’curriculum that has validated educational outcomes, and is publishable and/or presentable at a nationalconference.

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Ranniger 2The anatomy class is taught solely in the fall semester. Course development occurs in the spring andsummer, and final evaluation of the modules occurs at the end of the fall semester. Identifiable steps inthe process include:1) Identification of potential modules via evaluation of anatomy curricular materials2) Skill evaluation in the anatomy lab to ensure that the hands-on module is clinically relevant anddo-able3) Development of the module content and learning objectives4) Development of the lab handout and other materials required to perform the exercise5) Session planning (teaching modality, educator recruitment, date selection, etc)6) Training of faculty clinicians and/or anatomists in the educational goals and clinical procedure7) Development of surveys and examination tools8) Implementation of the modules and post-module evaluation process9) Data analysis and publication

Describe student’s role in the proposed project to maximize the student’s learning experience:The potential student fellow would have the opportunity to participate in the development of one or morecurricular modules, inclusive of all steps. The bulk of the development work (module, skillsdemonstration in lab, survey and examination tools) will be performed during the summer (May-August).By the time class starts in August, modules for the first half of the course should be near completion, andmodules for the last half should be identified and validated in the lab. Implementation and coursedelivery (during the fall semester) is less time intensive, and the fellow may elect to participate in anafternoon lab session related to their module during the school year. The fellow will also have the optionof participating in the post course data analysis and publication process in the spring of the following year.The fellow will be mentored jointly by the sponsors.

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Primary SponsorMary C. Rose, Ph.DProfessor, Departments of Integrative Systems Biology, Pediatrics, Biochemistry & Molecular

BiologyGeorge Washington University School of Medicine and Health Sciences/CNMCCtr for Genetic Medicine Research, Rm 5726/5R, CNMC, Washington D.C. 20010Office Phone: 202 476 [email protected]; [email protected]

Secondary Sponsor (on chronic rhinosinusitis projects)Maria T. Pena, M.D.Associate Professor, Department of Surgery and of PediatricsGWU Division of Otolarnygology, CNMCOffice Phone: 202 476 3837, [email protected]

Title of proposed project: Mucus Obstruction in Lower and Upper Respiratory Tract Diseases

Sponsor research focus: Diseases of the respiratory tract are a major medical burden in the western world. Mucus obstruction and overproduction of mucin glycoproteins (mucins) is a major contributor to morbidity and mortality in chronic diseases and is a major characteristic of asthma, cystic fibrosis (CF), and chronic rhinosinusitis (CRS). The etiology of mucus obstruction/hypersecretion is different for each of these diseases and can include mucin gene upregulation by inflammatory/immune response mediators, goblet cell hyperplasia and submucosal glandular hyperplasia. The goal of this laboratory is to investigate the biological processes that lead to goblet cell hyperplasia, submucosal gland hyperplasia, and mucin gene regulation. Dr. Rose’s research focuses primarily on the lower respiratory tract while Dr. Pena’s focuses on the sinus mucosa in the upper respiratory tract.

Provide background and overall design of the research project: Research Project: Mucin genes are upregulated by inflammatory mediators present in the bronchial secretions of patients with lung diseases and are repressed by glucocorticoids and macrolides. We are investigating how glucocorticoid-induced chromatin remodeling leads to repression of MUC5AC, a major lung mucin gene. This project is supported by an NIH RO1 grant, years 22-25. Student Projects: (a) Compare the efficacy of various glucocorticoids on mucin gene repression. (b) Characterize potential co-repressors recruited to the MUC5AC promoter by glucocoticoids.

Research Project. Hyperplasia of submucosal glands is a major contributor to mucus obstruction in CRS and cystic fibrosis (CF). An in vitro glandular acinar model system established in the lab is being used to investigate glandular acinar differentiation of human bronchial, nasal, and sinus epithelial cells and to determine whether specific inflammatory mediators activate this process. Student Project: Perform functional studies of candidate genes for glandular development, which gene products were identified by Affymetrix expression array analyses and validated by RT-PCR.

Research Project. Candidate master genes that mediate the IL13-induced goblet cell metaplasia in murine models of asthma have been identified by Affymetrix arrays. Two of these candidate genes have now been validated in vitro in differentiated mouse tracheal cells and are being functionally evaluated. Student Project: Clone the promoters of candidate genes into luciferase reporter plasmids and perform transfection and promoter assays.

Describe student’s role in the proposed project to maximize the student’s learning experience:The student’s learning experience would be in a basic research laboratory that focuses on lung biology and would be at both the intellectual and technical level. The precise role of the student would depend on the particular project the student selected after discussion with Dr. Rose and on the student’s level of laboratory experience. It would involve training of the student in the necessary techniques by graduate students or postdoctoral fellows or Visiting Scientists in the lab. The student would be expected to present the experimental approach to the project at lab meeting at the beginning and progress made at the end of the rotation.

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Primary SponsorCharles P. Samenow, MD, MPHAssistant ProfessorDepartment of Psychiatry and Behavioral Sciences/MFA 2150 Pennsylvania Ave, NW Washington, DC 20036Office Phone: 202-741-2875 [email protected]

Secondary SponsorNancy Gaba, MDAssociate Professor of Obstetrics and GynecologyDept. of OB/GYN/MFA2150 Pennsylvania Ave, NW Washington, DC 20036Office Phone: (202) 741-2553 [email protected]

Title of proposed project: Using Medical Student’s ERAS Application to Predict Unprofessional Conduct in Residency

Sponsor research focus: Dr. Samenow’s predominant area of research is in physician health and wellness. He has authored articles and presented internationally on disruptive physician behavior and physicians involved in sexual boundary violations. Specifically, he has conducted an evaluation of the impact of a CME course on physician behavior and is currently researching how childhood family functioning may impact physician behavior later in life. He has also developed curriculum for medical students and residents focused on professionalism, impairment and communication skills. He currently chairs the George Washington University Faculty/Physician Wellness Committee.

Dr. Gaba is the Associate Dean for Graduate Medical Education, and the residency Program Director for the obstetrics and gynecology Residency Program. She has authored articles and given many peer-reviewed presentations in the area of resident education and resident selection. Dr. Gaba's areas of interest include research on Mentorship and curricular innovations to improve resident evaluation. She has been recognized with national teaching awards, such as the Parker Palmer Courage to Teach Award, and serves on the faculty of several educational groups designed to improve resident education in ob/gyn. Dr. Gaba serves on the Medical School's Committee on the Learning Environment as well as the Faculty/Physician Wellness Committee.

Provide background and overall design of the research project: It is known that past misconduct in medical school clerkships is the most predictive variable for future physician disciplinary action. However, little research has been done on how incidents of misconduct in medical school are communicated to residency training program directors. This study aims to use both quantitative and qualitative methods to analyze the medical school files (ERAS, including Dean’s Letters, Letters of Recommendation, USMLE scores, and Clerkship Grades) of a cohort of residents disciplined for unprofessional behavior in their residencies compared to a matched control group. The goal is to see if there are any indicators in medical students’ applications to residency that may predict problems later on during graduate medical education or practice.

Describe student’s role in the proposed project to maximize the student’s learning experience:Medical students will be given the opportunity to engage in an original research project under the guidance of Drs. Samenow and Gaba with the goal of publication in a medical journal such as Academic Medicine, Medical Teacher or Academic Psychiatry or presentation at a national conference such as the Federation of Physician Health Programs or AMA International Conference on Physician Health. Students will be responsible for assisting with:

a) IRB approval -- The project will involve residents from a variety of institutions across the country. Students will help develop a research protocol that protects subject identity and minimizes confidentiality risks. Students will be expected to complete the CITI program for research medical ethics.

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Samenow Page 2b) Background Information – Drs. Samenow and Gaba will supervise students in performing a

literature review on professional behaviors in research.

c) Research Design -- The primary design is a chart review comparing a cohort of disciplined physicians to those who are a control. Students will help in recruiting participants from residency programs around the country.

d) Data Collection and Analysis – Students will help with the chart review to identify important variables that may be correlated with professional behavior. Students will use qualitative and quantitative methods to find predictive value. Where applicable, statistical analysis with be used.

e) Write-Up/Presentation – Students will assist in manuscript and poster production.

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Primary SponsorNarine Sarvazyan, PhD. Associate Professor Dept of Pharmacology & Physiology 2300 Eye Street NW, Ross Hall 640Washington DC, 20037 Office Phone: 4-0626, Fax: 4-2870 [email protected]

Secondary SponsorZaruhi Karabekian, PhD. Research Assistant Professor,Dept of Pharmacology & Physiology 2300 Eye Street NW, Ross Hall 640Washington DC, 20037 Office Phone: 4-2028, Fax: 4-2870 [email protected]

Title of proposed project: Making non-immunogenic embryonic stem cell derived cardiomyocytes.

Sponsor research focus: My scientific interests involve two topics. The first one is the mechanisms behind ectopic arrhythmias that can cause sudden cardiac arrest. The second topic is repair of injured myocardium using stem cell based approaches.

Provide background and overall design of the research project: To prevent allogeneic and even more so xenogeneic rejection of any graft, generally it is the host that is undergoing immunosuppressive treatment. However “it takes two to tango” and if the donor antigens responsible for inducing an immune response are down-regulated, then rejection should not occur. The latter approach allows one to avoid complications arriving from systemic immunosuppressive treatment of the host. We propose to develop a method that can produce a large amount of allo- and xeno- immunocompatible cardiomyocytes from embryonic stem cells. To produce cardiomyocytes we will use mouse embryonic stem cells in which antibiotic resistance gene is driven by cardiac-specific promoter. To diminish immunogenicity we will down-regulate Major Histocompatibility Complex class I and/or II molecules (MHC I & MHC II) expression. This will be achieved by lentiviral RNA interference (shRNA) technology that leads to down-regulation of MHC I and/or II. The derived cells will be terminally differentiated (thus will not bear risks of teratoma formation) and will be “immunoneutral” (thus immunosuppression of a host will not be required). The starting point for our experiments will be commercially available mouse embryonic stem cells (called αPIG44 ESC cells) in which puromycin resistance gene is linked to an alpha-myosin heavy chain promoter. The approach allows one to produce large amounts of 99.5% pure cardiac myocytes. The Natural Killer or T-lymphocytes are two major players of graft rejection in allo- and xenogeneic hosts. Natural Killer attack cells with very low MHC I levels (part of innate response). T-lymphocytes destroy cells that express foreign MHC (part of acquired response). It is important to note that differentiated α-PIG44 cells have been shown to be resistant to Natural Killer (NK) cells despite their low MHC I levels. Yet even low MHC I levels can elicit a robust T-lymphocyte response in non-syngeneic host. Notably, under inflammatory conditions, such as post-infracted myocardium, MHC I expression on α-PIG44 cells is likely to be further increased, amplifying the risk of immune rejection.

HYPOTHESIS: By stripping MHC class I molecules from differentiated α-PIG44 cells we expect to create a population of cells which will be RESISTANT to both Natural Killer and T-lymphocytes mediated cell lysis. If proven to be successful, this strategy can be further refined and generalized to produce a universal donor cells from embryonic step cells.

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Sarvazyan Page 2The project will be conducted using the following experiments: STEP 1. To determine background levels of MHC class I, Fas ligand and co-stimulatory molecules throughout differentiation process of αPIG44 ESC cells. To test if exposure of αPIG44 ESC to proinflammatory cytokines, which mimics environment of the infracted heart, elevates MHC I presence and/or affects the amount or quality of differentiated cells. STEP 2. To permanently inhibit MHC class I expression by RNA interference in differentiated αPIG44 ESC. To test whether MHC-I deletion affects the amount or quality of differentiated cells. STEP 3. To test immunogenicity of MHC-depleted αPIG44 ESC derived cardiomyocytes by a) in vitro approach using Cytotoxic T Lymphocyte assay and Lymphocytes proliferation assay; b) in vivo approach using a delayed type hypersensitivity assay in allogeneic mice and xenogeneic rats.

Describe student’s role in the proposed project to maximize the student’s learning experience: The role of the student will be to fully participate in experimental procedures and data collection. In the summer of 2010 studies are expected to be conducted mainly using in vitro approaches. The student will be supported in all aspects of the project by working side-by-side with Drs. Sarvazyan and Karabekian. In the past, Dr. Sarvazyan co-supervised two Gill’s fellows (Brian Martell and Craig Forleiter). Both students ranked their summer experiences very high. They also produced a sufficient amount work to be included as authors in four abstracts and two peer-reviewed publications.

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Primary SponsorReuven Schore, MDAttending Physician, Center for Cancer and Blood DisordersLeukemia & Lymphoma Program, Division of OncologyChildren’s National Medical Center111 Michigan Avenue NWWashington, DC 20010Office Phone: [email protected]

Title of proposed project: Effect of frequency of lab collection on anti-metabolite dosage and infectious outcomes in Acute Lymphoblasic Leukemia (ALL) patients on maintenance chemotherapy

Sponsor research focus: Dr Schore’s research focuses on improving therapies in the treatment of leukemia. Two sub foci are the use of new combinations of agents in leukemia treatment and improved supportive care of leukemia patients. Dr Schore is a study vice chair of a nationwide trial looking into the use of a novel formulation of asparaginase in newly diagnosed leukemia patients. He is also working on several projects to optimize the prevention of infections in the susceptible patients using antibiotic and antifungal prophylaxis.

Provide background and overall design of the research project: Acute Lymphoblastic Leukemia (ALL) is the most common type of childhood cancer. Tremendous progress has been made in the treatment and cure of ALL over the past years by carefully building on past clinical trials and application of pharmacologic knowledge. The overall cure rate for children with acute lymphoblastic leukemia has improved from 0% to 80% in the last sixty years. Based on previous research, patients are now generally treated for two and a half to three and a half years, during which time they receive various cycles of chemotherapy. These cycles include induction, consolidation, interim maintenance, delayed intensification, and, finally, maintenance.

Maintenance therapy typically consists primarily of regular doses of oral chemotherapy (mercaptopurineand methotrexate) with intermittent IV chemotherapy (Vincristine) and periodic oral steroids.Mercaptopurine is taken daily for the duration of maintenance, while methotrexate is commonly givenweekly. Doses of these medicines are routinely adjusted based on the patient’s white blood cell andabsolute neutrophil counts to maintain optimal dose intensity while minimizing infectious complications.This leads to dose adjustments and, occasionally, to the holding of chemotherapy in order to allow countsto recover when they are low.

Historically, different approaches exist as to the frequency of monitoring blood counts in patients onmaintenance therapy. Before a single co-operative group Children’s Oncology Group (COG) was formedfrom the merger of the Pediatric Oncology Group (POG) and Cancer in Children Group (CCG), each ofthese had their own protocol of monitoring patients on maintenance chemotherapy. The POG groupprotocol monitored them every 2 weeks and the CCG every 4 weeks. Merging of these 2 groups broughtabout consensus in many aspects of treatment, but many former POG institutions continue to monitorpatients on a bi-weekly basis, even though 4 weeks has been recommended by the COG. No informationthat we know of has looked at the effect of frequency of monitoring. It is hypothesized that too frequentmonitoring may cause patients to be held off medication more often as ANC and WBC counts often varyfor benign reasons. Another hypothesis indicates that monitoring less frequently may cause moreinfectious complications as we detect neutropenia when more severe prior to holding chemotherapy. Thereare studies that have shown patients who take more chemotherapy have better outcomes.This study aims to look at historical data on patients monitored at different time intervals and determine ifan optimal time interval for patients to be monitored exists, so as to minimize infectious complications anddays held off of chemotherapy due to lab values and optimize cumulative dosages of 6-MP andmethotrexate received. We aim to learn from this that frequency may or may not matter. In either case, anoptimal standard for monitoring may be reached to avoid interruption of chemotherapy and optimize thepatients’ quality of life.

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Schore Page 2Describe student’s role in the proposed project to maximize the student’s learning experience:The student’s role in this project would be to retrospectively review charts of patients who had beentreated for ALL at the two sites (DC and Fairfax, VA) to determine the frequency of blood counts beingobtained, cumulative dose of chemotherapy and infectious complications. Adequate mentoring andsupervision would be provided to allow the project to be completed in the allotted time. The project database has already been developed, and the data collection process is beginning. The project can be completed in the summer term, and, after data collection is complete, we will proceed with data analysis and abstract and manuscript preparation, which will be continued by the research team. There will also be opportunity for the student to enhance their literature search and writing abilities.

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Primary SponsorAmeet Singh, MDAssistant Professor of Surgery (Otolaryngology) and NeurosurgeryGeorge Washington University Medical CenterDivision of Otolaryngology2021 K Street, Suite 206, Washington DC 20037Office Phone: 202 741 3437 Fax: 202 741 [email protected]

Secondary SponsorFabio Roberti, MDAssistant Professor of Neurosurgery and SurgeryGeorge Washington University Medical CenterDepartment of Neurosurgery2150 NW Pennsylvania Avenue, 7th Floor, Washington DC 20037Office Phone: 202 741 Fax: 202 741 [email protected]

Title of proposed project: Skull base reconstruction in endoscopic skull base surgery

Sponsor research focus: Drs. Singh (otolaryngologist) and Roberti (neurosurgeon) are performing minimally invasive approaches for the surgical management of anterior skull base pathology. Traditionally, anterior skull base tumors have been approached through a combination of transcranial and transfacial approaches. Although these techniques are sound and time-tested, they result in dyscosmesis, brain retraction, and usually require a lengthy hospitalization and recovery. Endoscopic endonasal surgical techniques are being increasingly used to address a variety of anterior skull base pathology such as pituitary adenomas, cranipharyngiomas, Rathke’s cleft cysts, meningiomas, encephaloceles and cerebrospinal fluid leaks. These techniques offer improved visualization, magnification, and capability of looking around corners, thereby promising to improve outcomes for resection, neurovascular and sinonasal preservation. Endoscopic skull base surgery is a burgeoning field promising to offer significant advances in addressing anterior skull base pathology. The field also offers young investigators significant opportunities for clinical research.

Background: One of the challenges in endoscopic skull base surgery has been post-operative cerebrospinal fluid leaks, which may increase the risk of meningitis and pneumocephalus. Although a number of methods for endoscopic skull base reconstruction have been utilized, a greater repertoire of skull base reconstruction techniques is required. Drs Singh and Roberti have a special interest in endoscopic skull base reconstruction and have been accumulating a wealth of clinical experience in this area. Vascularized flaps have been utilized recently as one of the methods of skull base reconstruction. However, surgical dimensions, vascular supply, tensile strength, and clinical utility of these reconstruction techniques remains to be elucidated.

Aims:1. Understand endoscopic skull base anatomy through cadaveric dissection including transphenoidal,

transcribriform, transethmoidal, and transpterygoid approaches. Study the surgical dimensions, surgical coverage, vascular supply, strength, pliability and clinical utility of several vascularized endoscopic pedicled flaps.

2. Study the clinical database of endoscopic skull base cases performed by Drs. Singh and Roberti with specific interest in endoscopic skull base reconstruction techniques used. This would include mining data for types of grafts utilized, reconstruction techniques (multilayered, extended multilayered, gasket, vascularized pedicle), rate of post-operative cerebrospinal fluid leaks, and a number of other variables. Although, this is a suggested clinical project, the student will also be encouraged to review and literature and identify other areas in the database that may be retrospectively studied.

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Singh Page 2Student’s role in the proposed project to maximize student’s learning experience:The student will be involved in all aspects of the endoscopic skull base team work. The student with pursue cadaveric dissections under the guidance of Drs. Singh and Roberti, with an emphasis on gaining anatomical knowledge as well as elucidating the anatomical details and clinical utility of vascularized pedicled flaps. The student will also be encouraged to observe all endoscopic skull base cases as part of the Otolaryngology and Neurosurgery services. Finally, the student will be supported to complete a clinical paper regarding our series of endoscopic skull base surgery with a special emphasis on skull base reconstruction.

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Primary SponsorFrank Slaby, Ph.D. Professor Department of Anatomy & Regenerative Biology 212 Ross HallOffice Phone: 202-994-8813 Email: [email protected]

Title of proposed project: Surface Anatomy of the Chest and Abdomen

Sponsor research focus: Frank Slaby’s educational interests have focused on developing (1) student exercises which provide clinical application of gross anatomy knowledge and (2) curricular processes which promote integration of the curriculum. Provide background and overall design of the research project: The overall design of the project is for a rising Year II medical student to sequentially photograph the chest and abdomen of a male cadaver as the regions are dissected from the anterior chest and abdominal walls to the posterior chest and abdominal walls. Markers will be placed at the points of the shoulders (the points of the shoulders overlie the acromion processes of the scapulae) and the pubic symphysis so that the photographs can be sized to overlie each other exactly. The photographs and drawings made from them will be incorporated into a Flash shockwave file that will be used in the gross anatomy course to help medical and physician assistant students learn better the surface anatomy of the chest and abdomen. The program will also be displayed on the monitors in gross lab to assist medical students in their dissection of the chest and abdomen. I do not know of any publication or educational program that offers this perspective on thoracic and abdominal anatomy.

Describe student’s role in the proposed project to maximize the student’s learning experience: The student will dissect and photograph the cadaver under the sponsor’s direction. The sponsor will also instruct the student on how to use Flash MX to produce a software program that can display three views of the cadaver at every dissection level: (1) a photographic view of the cadaver at the dissection level, (2) a drawing of the viscera visible at the dissection level, and (3) the anterior surface projection of key structures. The student will learn how to construct buttons that enable a student to study view 1 alone, view alone, or a semi-transparent image of view 3 overlying either view 1 or view 2.

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Primary SponsorRandi Streisand, Ph.D., CDEAssociate Professor of Psychiatry and PediatricsChildren’s National Medical CenterDepartment of Psychology, CNMC111 Michigan Avenue, NW, Washington, DC 20010Office Phone: 202 476-3425 Fax: 202 [email protected]

Name of proposed projects: Family Teamwork ProjectYoung Child Project

Sponsor research focus: Dr. Streisand is currently the Principal Investigator on an NIDDK funded multi-site project within Type 1 diabetes, and she serves as the Site-Investigator for another NIDDK funded project. Her work focuses on adherence to diabetes management, parent and child adjustment, and managing diabetes in young children. She also serves as Director of Psychosocial Services for the Diabetes Team.

Background and overall design of the research projectFamily TeamworkThe Teamwork Project is an ongoing NIH funded intervention for adolescents with Type 1 diabetes and their parents designed to promote communication, problem solving skills, and parental involvement in adolescent’s diabetes management. Data collection includes recall interviews with parents/children, self-report questionnaires, parent-report questionnaires, and program satisfaction measures.

Young Child ProjectThe Young Child project is an ongoing NIH funded intervention for parents of young children (ages 1 to 6) with type 1 diabetes designed to provide parenting support and diabetes education and to address specific challenges related to parenting a young child with diabetes. Data collection is ongoing and includes parent-completed questionnaires related to diabetes management, child behavior, and parent emotional functioning, and recall interviews with parents. Blood glucose variability and metabolic control are also obtained.

Student’s role in the proposed projects : Family Teamwork-Given that baseline data collection will be complete by start of summer 2010, the Fellow will have the opportunity to examine data that he/she is interested in, and work together with our team on putting together a deliverable such as poster presentation by summer’s end, with the longer term goal of serving as a co-author on a paper stemming from such a project. In addition to working on his/her own smaller project, the fellow will have the opportunity to participate in all areas of research activities including administration of interviews to parents/children, data entry, and medical record reviews. The fellow will also participate in research lab meetings. Potential projects for the fellow include examining: blood glucose variability in teens and how this relates to metabolic control and measure of behavioral adherence; the relationship among nutrition, physical activity, and metabolic control; parenting behaviors and how they relate to teen’s self-care for diabetes management. Other topics related to diabetes, teenagers, and parenting are also possible.

Young Child Project-Similar to the Teamwork Project, the fellow on the Young Child project will have an opportunity to gain experience with ongoing research methodology and activities and will be trained to administer parent interviews, enter data, and obtain medical data via medical record review. The fellow will identify one specific area of interest given possible measures from baseline assessment and will work towards a deliverable by the end of fellowship such as a poster/paper presentation and/or submission of journal article. The fellow will be encouraged to choose a project of interest and may include such topics as glycemic variability in young children, social support and parenting behaviors, sleep in parent/child. Other topics are also possible.

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Primary Sponsor Lillian Su, MDAttending, Pediatric Critical Care MedicineChildren’s National Medical Center111 Michigan Avenue NW, Washington, DC 20010Office Phone: 202.476.5246, Fax: [email protected]

Secondary Sponsors John Berger, MDMedical Director, Cardiac Intensive CareChildren’s National Medical Center111 Michigan Avenue NW, Washington, DC 20010Office Phone: 202.476.6817Fax: [email protected]

Naomi Luban, MDDivision Chief, Laboratory MedicineChildren’s National Medical Center111 Michigan Avenue NW, Washington, DC 20010Office Phone: 202. 476.5000, Fax: 202.476.5724

Title of proposed project: Di(2-ethylhexl) phthalate (DEHP) and Bisphenol A (BPA) Exposure in Pediatric Cardiac Surgery Patients

Sponsor Research Focus: The FDA (Federal Drug Administration) has awarded Dr. Su and Children’s National Medical Center to study the levels of DEHP and BPA in the pediatric population. DEHP and BPA have received a lot of recent media attention in recent articles and news segments on NPR and the Washington Post. DEHP and BPA are substances found in everyday plastics that impart flexibility. There has been some suggestion backed by animal data and emerging human data that these substances may have effects on the reproductive, cardiovascular, and endocrine systems. Although deemed to be safe initially by the FDA, enough public pressure has emerged to have the FDA look again. This is an exciting project with a lot of potential implications not only for the medical field but everyday life.

Background and overall design of the research project:Specific Aims:

1. Determine the pharmacokinetics of the production of urinary metabolites of DEHP and BPA after cardiopulmonary bypass in children.2. In a pilot study, quantify the exposure of children to DEHP and BPA while undergoing cardiopulmonary bypass (CPB) as compared to critically ill children without cardiac surgery and healthy controls.

Hypotheses: 1) Levels of DEHP and BPA are higher in children after CPB as compared to other critically ill children or control patients with congenital heart disease.

Student’s role in the proposed project: This is a unique opportunity for a student interested in pediatric cardiology, pediatric cardiovascular surgery, pediatric intensive care, pediatric cardiac intensive care, toxicology, or environmental health and exposures to have an active role in this FDA funded research project. The student will work closely with the above faculty to collect data, analyze data and to report main findings. The student will have opportunities to observe bypass patients while in the OR and be exposed to the world of congenital heart surgery. Depending on the student’s interest, her/his role can be tailored. Children’s National Medical Center has a busy and active pediatric cardiovascular surgery program and there will be many opportunities for the student to interact with the cardiology, critical care and cardiovascular surgery faculty. There will also be opportunities to interact with the FDA if the student is more interested in toxicology/environmental exposures.

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Primary SponsorStephen Teach, MD, MPHAssociate Director, Center for Clinical and Community ResearchChildren’s National Medical CenterCenter for Clinical and Community Research, CNMC111 Michigan Avenue, NW, Washington, DC 20010Office Phone: 202 476-5134 Fax: 202 [email protected]

Title of proposed project: IMPACT DC (Improving Pediatric Asthma Care in the District of Columbia)

Sponsor research focus: Dr. Teach’s primary academic focus is on the disparities evident in the care of inner-city children with asthma, including their over-reliance on urban emergency departments forepisodic asthma care. He is principal investigator and medical director of “Improving Pediatric Asthma Care in the District of Columbia,” IMPACT DC, an asthma surveillance, research, clinical care, and advocacy program in Washington.

Background and overall design of the research project: Under the direction of Dr. Teach and IMPACT DC, there are a number of approved and pending protocols. Research initiatives include: Trends in acuity of asthma presentations to the Emergency Department Primary Care Provider follow-up after Emergency Department visits for acuterespiratory illness Access barriers to asthma care Evaluation of school-based asthma education intervention Pilot of electronic transfer of medical information from IMPACT DC to PrimaryCare Providers

Describe student’s role in the proposed project to maximize the student’s learning experience:The student will be involved in data collection and analysis, and will also assist theresearch team in designing and implementing new studies as appropriate.Mentoring: The student will be supported in all aspects of his or her involvement inIMPACT DC projects under the supervision of the Research Coordinator, with theguidance of Project Director Deborah Quint, MPH as well as Dr. Teach. IMPACT DC hasa significant history of demonstrating commitment to the education and mentorship ofmedical students. There will be ample opportunities to interact with other researchfaculty and investigators in the Children’s Research Institute in addition to opportunitiesto shadow Dr. Teach in his role as Associate Chief of Emergency Medicine and TraumaCenter.

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Primary SponsorLaura Tosi MDDirector, Bone Health Program, Division of Orthopaedics and Sports MedicineChildren’s National Medical Center (CNMC)111 Michigan Avenue, NW Washington, DC 20010Office Phone: 202 476 [email protected]

Secondary SponsorEric Hoffman PhD(1) and Joseph Devaney (PhD)Director, Research Center for Genetic MedicineDirector of SNP Discovery, Research Center for Genetic MedicineChildren’s National Medical Center111 Michigan Avenue, NW Washington, DC 20010Office Phone: 202 [email protected] and [email protected]

Project Title: Fine Mapping of Genetic Loci That Influence Bone Morphometry

Sponsor research focus: Dr. Laura Tosi is an Orthopaedic Surgeon at Children’s National Medical Center and the Director of the Bone Health Program. Her research focuses on the study of genetic influences on bone morphometry. She has partnered with Eric Hoffman PhD, Director of the Research Center for Genetic Medicine and Joseph Devaney, PhD, Director of SNP Discovery, at CNMC for over five years on a project which seeks to analyze genetic contributions to bone strength. In particular, she has used anthropomorphic data and DNA samples from Dr. Hoffman’s R0-1 funded project “Functional Polymorphism Associated with Human Muscle Size and Strength (FMS)” to identify genes which may influence bone size and shape using whole genome analysis.

Provide background and overall design of the research project: While bone health, and its antithesis, osteoporosis, are influenced by age, weight, exercise and nutrition, genetics are felt to determine ~70% of an individual’s bone mineral density (BMD) and its major outcome, fracture risk. Identifying and characterizing specific genes that lead to low BMD might eventually allow physicians to have better strategies for diagnosing, preventing, and treating osteoporosis and subsequent fractures. In addition, recent research, has demonstrated that bone strength is not dependent solely on BMD. Bone integrity is the result of multiple factors including structure (size or mass), geometry (distribution of mass or shape), and material composition. This more comprehensive notion of bone quality, or more specifically the physiologic processes that impact bone strength and maintain it during aging, offers a broad array of researchopportunities. The Bone Health Program research program focuses on the discovery of genes that influencebone size. .Using data and samples from the FMS study and the Affymetrix 1-million SNP chip, we have performed agenome-wide analysis to identify genes that might influence bone size. We have identified genetic regions that may contain genes that contribute to bone phenotypes. We now wish to refine our search and identify functional SNPs within these different genomic regions that drive bone “quality” phenotypes such as total bone volume, cortical volume, medullary volume, moments of inertia, etc.

We will accept up to two students. We will assign each student one of the newly identified regions and teach them how to fine map their assigned regions using SNPs from the dbSNP database in an effort to discover functional variants driving the different bone phenotypes. Our long term goal is to discover genes that have not yet been recognized that influence bone quality. The role of the students will be to help us refine the results of the genome-wide scan by testing for genetic associations between the SNP’s of the newly identified genes and measures of bone quality in our study population using allelic discrimination assays.

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Tosi Page 2Describe student’s role in the proposed project to maximize the student’s learning experience:The students will learn laboratory skills such as genotyping, single nucleotide polymorphism (SNP) discovery, and techniques for measuring bone, muscle and fat volume on MRI. The students will be encouraged to attend all research conferences held in the Research Center for Genetic Medicine. In addition, the students will be required to attend our weekly Orthopaedic Bone Health Clinic so that they develop a better appreciation of the clinical impact of skeletal health and disease. Finally the students will have the opportunity to observe in the Orthopaedic Operating Room from time to time should they desire!Dr. Tosi will meet with the students almost daily. However, realistically, Dr. Tosi is a practicing surgeon.Therefore, the students will be supervised daily by Joe Devaney, PhD, Director of SNP Discovery, who will provide supervision and training in the laboratory. In addition we have a terrific bioinformatics staff, which will assist with data analysis as needed.

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Primary SponsorAmy Weiss, MDFellow, Division of Adolescent and Young Adult MedicineChildren’s National Medical Center111 Michigan Avenue NW, Washington, DC 20010Office Phone: 202-476-3145Email: [email protected]

Secondary SponsorAlexandra Rucker, MDAttending Physician, Division of Emergency Medicine and Trauma ServicesChildren’s National Medical Center111 Michigan Avenue NW, Washington, DC 20010Office Phone: 202-476-5522Email: [email protected]

Title of proposed project: Why do adolescents seek care for non-urgent medical problems at the emergency department instead of at their primary care physician’s office?

Sponsor research focus: Dr. Weiss is currently an Adolescent Medicine fellow at Children’s National Medical Center, and this research project is part of her scholarly work for fellowship. She became interested in this topic when she was working as an associate in the Children’s National Emergency Department last year and repeatedly cared for children and adolescents with non-urgent medical conditions who would have been better served by their primary care physicians. The area of appropriate health care utilization and the concept of a medical home are especially timely now with the current ongoing debate over health care reform. Dr. Rucker is acting as Dr. Weiss’s primary faculty advisor for this research project.

Provide background and overall design of the research project: Overcrowding has become increasingly prevalent in emergency departments (EDs) in the United States over the past 15 years. EDs are experiencing higher numbers of patient visits, a large portion of which are for non-urgent conditions which could and should be addressed in a primary care setting. While studies have examined reasons for non-urgent ED visits in adults and young children, none have looked specifically at adolescents’ reasons for use of the ED instead of their primary care provider (PCP). In this study, we seek to characterize the population of teenagers presenting to an urban children’s hospital emergency department and determine the reasons why teens present to the ED instead of to their PCP (such as convenience, characteristics of the PCP and the medical office, or the relationship of the teen to the PCP). We will approach teenagers and their parents or guardians in the waiting room of Children’s National Emergency Department and invite them to participate in the study. If they choose to participate, consent and assent will be obtained, and they will complete a brief on-line survey using a laptop computer. Once enough surveys have been collected, the data will be analyzed and a manuscript reporting the findings will be written. We also hope to prepare an abstract and submit it for presentation at a national meeting.

Describe student’s role in the proposed project to maximize the student’s learning experience:The student will be involved in all aspects, from data collection to data analysis, as well as assisting with preparation of the abstract and manuscript. There will be a greater focus on data collection and analysis during the summer time period, but the student can remain involved with the later stages of the project. Because data collection will be in a clinical setting rather than in a laboratory, this project may be more attractive for someone interested in clinical medicine rather than bench research. The student will be working closely with Dr. Weiss and Dr. Rucker, and thus can receive direct mentorship from two female pediatric subspecialty physicians. Another benefit of participating in the project will be gaining experience and confidence speaking to teenagers and parents about health care and related subjects in a clinical setting.

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Weidermann IPrimary SponsorBernhard L. Wiedermann, MD, MAProfessor of Pediatrics, Attending in Infectious Diseases; Director, Continuing MedicalEducation and Educational TechnologyGWU, Children’s National Medical Center111 Michigan Avenue, NW, Suite W 3.5-100Office Phone: [email protected]

Secondary SponsorJoseph Campos, PhDDirector, Microbiology Laboratory, Molecular Diagnostics Laboratory, and LaboratoryInformatics; Professor of Pediatrics, Pathology, and Microbiology/Immunology/Tropical MedicineGWU, Children’s National Medical Center111 Michigan Avenue, NWOffice Phone: [email protected]

Title of proposed project: Clinical features associated with Human Metapneumovirus (HMPV) inpediatric patients

Sponsor research focus: Pediatric infectious diseases, clinical microbiology, antimicrobial therapy,medical information, medical informatics

Provide background and overall design of the research project: This is a new study designed toelaborate on clinical features associated with HMPV infection in pediatric patients. Currently, the clinicalspectrum in HMPV disease in children is expanding, with increasing discovery of more severe respiratorydisease. Testing for this pathogen is not routinely available, but in December 2009 Children’s Hospitalbegan including HMPV PCR testing on respiratory specimens. By the summer of 2010, sufficient resultswill have accumulated in the laboratory and clinical electronic databases to permit analysis. Thisproposed study is designed to compare clinical features of children with and without HMPV in respiratorysamples, in an attempt to identify whether characteristic or novel features may be present.

Describe student’s role in the proposed project to maximize the student’s learning experience: Thestudent’s role in the project will be as primary data extractor and interpreter, performing medical recordreviews with a standardized form to extract relevant clinical data from cases and controls. He/she willcomplete standard training in research methodology and study design, including the IRBsubmission/approval process, learn to use electronic databases, and learn basic statistical approaches toanalyze results. Depending on the time period the student is able to spend on the study, he/she mayparticipate in the initial study design and IRB submission as well as in writing up the results. The projectis structured to have data collection and analysis completed over a summer’s time period of 2-3 months,and the student can expect to be an author on any presentation or publication resulting from the study.

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Weidermann IIPrimary SponsorBernhard L. Wiedermann, MD, MAProfessor of Pediatrics, Attending in Infectious Diseases; Director, Continuing MedicalEducation and Educational TechnologyGWU, Children’s National Medical Center111 Michigan Avenue, NW, Suite W 3.5-100Office Phone: [email protected]

Secondary SponsorJoseph Campos, PhDDirector, Microbiology Laboratory, Molecular Diagnostics Laboratory, and LaboratoryInformatics; Professor of Pediatrics, Pathology, and Microbiology/Immunology/Tropical MedicineGWU, Children’s National Medical Center111 Michigan Avenue, NWOffice Phone: [email protected]

Title of proposed project: Clinical features associated with Aeromonas sp. isolation from stools inpediatric patients

Sponsor research focus: Pediatric infectious diseases, clinical microbiology, antimicrobial therapy,medical information, medical informatics

Provide background and overall design of the research project: This is a new study designed toelaborate on clinical features associated with presumptive Aeromonas gastroenteritis in pediatric patients.Currently, the role for Aeromonas as a cause of diarrhea in humans is uncertain. Although there is strongevidence suggesting that this organism is a pathogen in the human GI tract, Koch’s postulates have notbeen fulfilled, and there have been no clear outbreaks of disease due to this organism. At Children’sNational Medical Center for over 15 years, all stool cultures have been evaluated for presence ofAeromonas sp. in addition to the traditionally-accepted bacterial stool pathogens. Now, a large electronicdatabase of these results is available, and the study is designed to compare clinical features of childrenwith and without Aeromonas in stool cultures, in an attempt to identify whether characteristic featuresmay be present

Describe student’s role in the proposed project to maximize the student’s learning experience: Thestudent’s role in the project will be as primary data extractor and interpreter, performing medical recordreviews with a standardized form to extract relevant clinical data from cases and controls. He/she willcomplete standard training in research methodology and study design, including the IRBsubmission/approval process, learn to use electronic databases, and learn basic statistical approaches toanalyze results. Depending on the time period the student is able to spend on the study, he/she mayparticipate in the initial study design and IRB submission as well as in writing up the results. The projectis structured to have data collection and analysis completed over a summer’s time period of 2-3 months,and the student can expect to be an author on any presentation or publication resulting from the study.

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Yadav IPrimary SponsorKabir YadavAssistant Professor, Emergency MedicineGeorge Washington University Department of Emergency Medicine2150 Pennsylvania Ave NW, Suite 2B-408Office Phone: (202) [email protected]

Title of proposed project: Pain Management for Older Adults in the Emergency Department Setting

Sponsor research focus: ED Crowding, Medical Informatics Provide background and overall design of the research project: Pain management, which has been identified as an issue for quality of care improvement in older adults, serves as a useful model to explore ED care in the geriatric population. The quality of geriatric pain care in the ED setting has not been extensively explored and studies to date have yielded conflicting information. Health care initiatives to improve the quality of pain management and processes involved with pain care across medical settings have gradually increased clinical staff awareness of the need to address pain. It is also not well known how these changes may have translated into improvements in pain care management and outcomes for older adults. The medical complexity of older adults who are unfamiliar to ED staff upon presentation, combined with the surging pressure of ED crowding and its potentially negative effects on the delivery of patient care, may be impeding progress in pain management practice.

The hypotheses of this project are as follows:1. Are there disparities for older adults with pain management (assessment and treatment) in the EDsetting?Hypothesis 1: Greater age and other patient-related characteristics (e.g., greater comorbidities,polypharmacy, cognitive impairment) of older adults are associated with poorer pain management.2. Do conditions in the ED, such as crowding, exacerbate the quality of pain management for olderadults?Hypothesis 2: ED crowding (as measured by environmental factors such as ED census, number ofadmitted patients awaiting beds, staffing levels) is associated with poorer pain management forolder adults.This is a multicenter, retrospective cohort review of adult patients >= 18 years age seen in the EDs of theEmergency Medicine Research Group Investigative Consortium (EMRGINC) (Mount Sinai, Mount SinaiQueens, University of Colorado Health Sciences Center, Oregon Health and Sciences University, andGeorge Washington University,) with a chief complaint (CC) of a painful condition AND a final EDdiagnosis of a painful condition will be eligible for review. Based upon our experience gathering datafrom previous projects, we will focus on painful conditions likely to occur in older adults: falls, hip,abdomen and extremity pain. IRB exemption has been granted at all participating sites.

Describe student’s role in the proposed project to maximize the student’s learning experience:The student will have the opportunity to function at various levels in this research project depending upontheir interest. At minimum, the student will play an invaluable role in this project as a research assistant,which will include formal training in the fundamentals of biomedical research. Primary responsibility willbe in performing data extraction and abstraction using our department’s electronic medical record. If thestudent is interested, opportunities for training and participation in statistical analysis and manuscriptpreparation will be available. The student will receive acknowledgement in publications stemming fromthis research, up to and including authorship if their level of participation is substantial. In addition todirect participation in clinical research, the student will have opportunities to work closely with facultyand residents of the Department of Emergency Medicine, with opportunities for career advice and lettersof support if requested.

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Yadav IIPrimary SponsorKabir YadavAssistant Professor, Emergency MedicineGeorge Washington University Department of Emergency Medicine2150 Pennsylvania Ave NW, Suite 2B-408Office Phone: (202) [email protected]

Title of proposed project: Antibiotic Prophylaxis for Prevention of Infection in EmergencyDepartment Patients with Simple Hand Lacerations

Sponsor research focus: Evidenced-Based Medicine

Provide background and overall design of the research project: Simple hand lacerations are commonly seen in emergency departments (EDs) across the world. These injuries can have significant impact on the functional status of patients as they take quite some time to heal and can limit the ability of patients to go back to work. Some clinicians recommend using prophylactic antibiotics to prevent wound infection in all hand lacerations due to the risk of disability from prolonged infections. The harm of giving antibiotics includes developing resistance, adverse effects, allergies, as well as cost. It has already been shown that prophylactic antibiotics are beneficial in patients with open fractures, crush injuries and animal bites. There is some data that shows that antibiotic prophylaxis is not required in simple lacerations. The rate of infection has been defined as anywhere from 1% to 10%. But the sizes of these trials have limited power to determine whether there is a true difference between control and treatment groups. Furthermore, a few trials used antibiotics that are not commonly used in the U.S. and used intra-muscular administration of antibiotics that is not used today. A recent evidence-based medicine review identified only 3 trials with inclusion/exclusion criteria similar to the proposed study. However, all 3 studies were underpowered and suffered from major methodological flaws such as violations of randomization and concealment.Due to the limitations of the previous studies done on hand lacerations, we believe there is a need for aprospective, blinded, placebo controlled trial to determine whether antibiotics not only prevent infectionbut also improve cosmetic appearance of the injured hand. We hypothesize that antibiotics will notprovide a statistical or clinical benefit to patients. It probably will not have an impact on cosmetic resultseither. We will design our study in such a way to avoid the weaknesses that affected the previous trialsdone regarding antibiotics and hand lacerations. The first phase of our project will be to assess the currentpractice of healthcare providers in the George Washington University Hospital emergency department,including patient expectations and reported compliance with treatment.

Describe student’s role in the proposed project to maximize the student’s learning experience:The student will have the opportunity to function at various levels in this research project depending upontheir interest. At minimum, the student will play an invaluable role in this project as a research assistant,which will include formal training in the fundamentals of biomedical research. The student will interactdirectly with patients and practitioners to administer surveys, getting firsthand exposure to the challengesof caring for patients in the emergency department. Additional responsibilities will include data entry fromsurvey data as well as phone follow-ups of patients. If the student is interested, opportunities for trainingand participation in statistical analysis and manuscript preparation will be available. The student willreceive acknowledgement in publications stemming from this research, up to and including authorship iftheir level of participation is substantial as well as presentation of findings at regional or nationalconferences. In addition to direct participation in clinical research, the student will have opportunities towork closely with faculty and residents of the Department of Emergency Medicine, with opportunities forcareer advice and letters of support if requested.

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Yadav IIIPrimary SponsorKabir YadavAssistant Professor, Emergency MedicineGeorge Washington University Department of Emergency Medicine2150 Pennsylvania Ave NW, Suite 2B-408Office Phone: (202) [email protected]

Title of proposed project: Selective Orbital Computed Tomography in Blunt Trauma

Sponsor research focus: Clinical Decision Rules, Medical Informatics Provide background and overall design of the research project: United States emergency departments (EDs) annually treat approximately 2.6 million patients for eye and face injuries, of which nearly 195,000 (7.5%) are diagnosed with orbital fractures. Plain x-ray and computed tomography (CT) are the most common imaging methods used for the evaluation of orbital trauma, with over 550,000 patients undergoing x-rays and over 300,000 patients undergoing CT imaging for their diagnosis. Clearly, many patients without orbital fractures are undergoing radiographic imaging, subjecting them to increased healthcare costs, increased time in the ED, and unnecessary exposure to ionizing radiation. Furthermore, it is unclear whether most patients diagnosed with orbital fractures have fractures of clinical importance (e.g. requiring emergent intervention). They may in fact have radiographic imaging either deferred to a setting where imaging is more readily available, or forgone altogether. Clinical decision rules are sets of clinical signs and symptoms (clinical predictors) that effectively rule out a suspected diagnosis without using a particular resource. To reduce unnecessary utilization of radiographic testing, clinical decision rules have been derived and validated for the selective use of ankle films, knee films, cervical spine films, and head CT for blunt head trauma. These rules have been widely accepted into the clinical practice of emergency and primary care physicians, and studies have demonstrated decreased resource utilization without compromising patient safety. To date, no rule has been derived and validated for diagnosing traumatic orbital fractures. The proposed research is designed to derive, validate, and implement a CDR to determine clinical predictors for the presence of orbital fractures in blunt orbital trauma patients, utilizing health IT tofacilitate data collection and point-of-care decision support. We hypothesize that such a rule can bederived providing nearly 100% sensitivity for determining the presence of orbital fractures.To date, we have completed data collection for a 2-year derivation study from outside emergencydepartments. Present work is focused on statistical analysis of the derivation study as well as developing avalidation study at the George Washington University Medical Center.

Describe student’s role in the proposed project to maximize the student’s learning experience:The student will have the opportunity to function at various levels in this research project depending upontheir interest. At minimum, the student will play an invaluable role in this project as a research assistant,which will include formal training in the fundamentals of biomedical research. Primary responsibility willbe in performing data abstraction of an existing data set of electronic surveys and radiology reports. If thestudent is interested, development of focus groups using advanced qualitative research methods will alsobe underway, as well as opportunities for training and participation in statistical analysis and manuscriptpreparation. The student will receive acknowledgement in publications stemming from this research, up toand including authorship if their level of participation is substantial as well as presentation of findings atregional or national conferences. In addition to direct participation in clinical research, the student willhave opportunities to work closely with faculty and residents of the Department of Emergency Medicine,with opportunities for career advice and letters of support if requested.

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Zeichner IPrimary SponsorSteven Zeichner, MD, PhDProfessor of Pediatrics and Microbiology, Immunology, and Tropical Medicine; Senior Investigator, Children’s Research Institute, Children’s National Medical CenterChildren’s National Medical Center111 Michigan Ave NW, Washington, DC 20010Office Phone: 202-476-6131 [email protected]

Title of proposed project: Activation of HIV replication via selective targeting of host cell genes.

Sponsor research focus: Molecular virology

Provide background and overall design of the research project: The main barrier to a cure for HIV infection is the existence of long-lived reservoirs of cells latently infected with HIV. Considerable interest has focused on finding new, non-toxic ways to activate HIV because activating HIV within a patient while maintaining highly effective combination antiretroviral therapy to block new infections may offer a way to attack and deplete the reservoir of HIV latently infected cells. We are investigating a variety of approaches aimed at identifying and targeting cellular gene products that can lead

Describe student’s role in the proposed project to maximize the student’s learning experience: Working with lab personnel, the student will be exposed to a variety of techniques in molecular virology, including cell culture, siRNA design and transfection, realtime PCR, immunoblotting, and ELISA assays.

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Zeichner IIPrimary SponsorSteven Zeichner, MD, PhDProfessor of Pediatrics and Microbiology, Immunology, and Tropical Medicine; Senior Investigator, Children’s Research Institute, Children’s National Medical CenterChildren’s National Medical Center111 Michigan Ave NW, Washington, DC 20010Office Phone: 202-476-6131 [email protected]

Title of proposed project: Identification of novel antigens that induce anti-HIV broadly neutralizing immune responses.

Sponsor research focus: Molecular virology

Provide background and overall design of the research project: Using a variety of technologies, including synthetic biology, the development of DNA barcodes, and high throughput sequencing/specialized microarray technologies the project seeks to develop a new, in vivo, highly parallel, high throughput technology to identify potential immunogens that may be used to induce a broadly neutralizing anti-HIV immune response.

Describe student’s role in the proposed project to maximize the student’s learning experience: Working with other members of the lab, the student will be exposed to a variety of approaches, such as bacteriology, molecular cloning, in silico and in vitro molecular biology, contemporary DNA analysis technologies such as microarrays and high throughput sequencing, and small animal work.

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Zeichner IIIPrimary SponsorSteven Zeichner, MD, PhDProfessor of Pediatrics and Microbiology, Immunology, and Tropical Medicine; Senior Investigator, Children’s Research Institute, Children’s National Medical CenterChildren’s National Medical Center111 Michigan Ave NW, Washington, DC 20010Office Phone: 202-476-6131 [email protected]

Title of proposed project: Alternative replication programs of Kaposi’s sarcoma-associated herpesvirus.

Sponsor research focus: Molecular virology Provide background and overall design of the research project: Kaposi’s sarcoma associated herpesvirus (KSHV), like other herpesviruses, replicates via a clear and carefully order gene expression program. However, we have recently found that KSHV employs a very different replication program when the health its host cell is threatened. The student will be involved in describing this alternate replication program, and the mechanisms that trigger and control it.

Describe student’s role in the proposed project to maximize the student’s learning experience: Working with laboratory staff and dependent on the stage of the project during the summer, the student will be exposed to a variety of molecular biological techniques that will be used to define and characterize the alternative KSHV replication program, including cell culture, DNA and RNA isolation, realtime PCR and RT-PCR, immunoblotting, and flow cytometry.

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