Medicine and Health Sciences Commons^™

Technical Desiderata For The Integration Of Genomic Data Into Electronic Health Records., Daniel R Masys, Gail P Jarvik, Neil F Abernethy, Nicholas R Anderson, George J Papanicolaou, Dina N Paltoo, Mark A Hoffman, Isaac S Kohane, Howard P Levy

Manuscripts, Articles, Book Chapters and Other Papers

The era of "Personalized Medicine," guided by individual molecular variation in DNA, RNA, expressed proteins and other forms of high volume molecular data brings new requirements and challenges to the design and implementation of Electronic Health Records (EHRs). In this article we describe the characteristics of biomolecular data that differentiate it from other classes of data commonly found in EHRs, enumerate a set of technical desiderata for its management in healthcare settings, and offer a candidate technical approach to its compact and efficient representation in operational systems.

Perspectives On: Sgp Symposium On Mitochondrial Physiology And Medicine: Mitochondria Take Center Stage., Shey-Shing Sheu, Robert T Dirksen, Edward N Pugh

Center for Translational Medicine Faculty Papers

No abstract provided.

Perspectives On: Sgp Symposium On Mitochondrial Physiology And Medicine: Molecular Identities Of Mitochondrial Ca2+ Influx Mechanism: Updated Passwords For Accessing Mitochondrial Ca2+-Linked Health And Disease., Jin O-Uchi, Shi Pan, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

No abstract provided.

Management Of Hyperglycemia In Type 2 Diabetes: A Patient-Centered Approach: Position Statement Of The American Diabetes Association (Ada) And The European Association For The Study Of Diabetes (Easd)., Silvio E Inzucchi, Richard M Bergenstal, John B Buse, Michaela Diamant, Ele Ferrannini, Michael Nauck, Anne L Peters, Apostolos Tsapas, Richard Wender, David R. Matthews

Department of Family & Community Medicine Faculty Papers

No abstract provided.

The Quest For The Perfect Prostate Biopsy Continues, Leonard G. Gomella

Kimmel Cancer Center Faculty Papers

No abstract provided.

Acceptability Of Narratives To Promote Colorectal Cancer Screening In An Online Community, Kevin O Hwang, Amber W Trickey, Amanda L Graham, Eric J Thomas, Richard L Street, Jennifer L Kraschnewski, Sally W Vernon

Faculty, Staff and Student Publications

OBJECTIVE: To assess the acceptability of narratives to promote colorectal cancer (CRC) screening among members of an online weight loss community.

METHOD: Members of online weight loss community completed an Internet survey in 2010. Multiple logistic regression models examined demographic and attitudinal correlates of interest in sharing and receiving CRC screening narratives.

RESULTS: Participants (n=2386) were 92% female with mean (SD) age 58 (6) years; 68% were up-to-date with CRC screening. Among those who were up-to-date, 39% were interested in sharing their narratives with other members. African-Americans were more likely than other racial groups to be interested in sharing narratives …

Does The Load-Sharing Classification Predict Ligamentous Injury, Neurological Injury, And The Need For Surgery In Patients With Thoracolumbar Burst Fractures?: Clinical Article., Kristen Radcliff, Christopher K Kepler, Todd A Rubin, Motasem Maaieh, Alan S Hilibrand, James Harrop, Jeffrey A Rihn, Todd J Albert, Alexander R Vaccaro

Department of Orthopaedic Surgery Faculty Papers

OBJECT: The load-sharing score (LSS) of vertebral body comminution is predictive of results after short-segment posterior instrumentation of thoracolumbar burst fractures. Some authors have posited that an LSS > 6 is predictive of neurological injury, ligamentous injury, and the need for surgical intervention. However, the authors of the present study hypothesized that the LSS does not predict ligamentous or neurological injury.

METHODS: The prospectively collected spinal cord injury database from a single institution was queried for thoracolumbar burst fractures. Study inclusion criteria were acute (< 24 hours) burst fractures between T-10 and L-2 with preoperative CT and MRI. Flexion-distraction injuries and pathological fractures were excluded. Four experienced spine surgeons determined the LSS and posterior ligamentous complex (PLC) integrity. Neurological status was assessed from a review of the medical records.

RESULTS: Forty-four patients were included in the study. There were 4 patients for whom all observers …

Does Initial Shunt Type For The Norwood Procedure Affect Echocardiographic Measures Of Cardiac Size And Function During Infancy?: The Single Vventricle Reconstruction Trial., Peter C. Frommelt, Lin T. Guey, L Luann Minich, Majeed Bhat, Tim J. Bradley, Steve D. Colan, Greg Ensing, Jessica Gorentz, Haleh Heydarian, J Blaine John, Wyman W. Lai, Jami C. Levine, William T. Mahle, Stephen G. Miller, Richard G. Ohye, Gail D. Pearson, Girish S. Shirali, Pierre C. Wong, Meryl S. Cohen, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The Pediatric Heart Network trial comparing outcomes in 549 infants with single right ventricle undergoing a Norwood procedure randomized to modified Blalock-Taussig shunt or right ventricle-pulmonary artery shunt (RVPAS) found better 1-year transplant-free survival in those who received RVPAS. We sought to compare the impact of shunt type on echocardiographic indices of cardiac size and function up to 14 months of age.

METHODS AND RESULTS: A core laboratory measured indices of cardiac size and function from protocol exams: early after Norwood procedure (age 22.5 ± 13.4 days), before stage II procedure (age 4.8 ± 1.8 months), and at 14 …

Process Evaluation Of A Positive Youth Development Program In Hong Kong Based On Different Cohorts, Ben M. F. Law, Daniel T. L. Shek

Pediatrics Faculty Publications

There are only a few process evaluation studies on positive youth development programs, particularly in the Chinese context. This study aims to examine the quality of implementation of a positive youth development program (the Project P.A.T.H.S.: Positive Adolescent Training through Holistic Social Programmes) and investigate the relationships among program adherence, process factors, implementation quality, and perceived program success. Process evaluation of 97 classroom-based teaching units was conducted in 62 schools from 2005 to 2009. Findings based on different cohorts generally showed that there were high overall program adherence and implementation quality. Program adherence and implementation process were highly correlated with …

Interim Evaluation Of The Project P.A.T.H.S.: Findings Based On Different Datasets, Daniel T. L. Shek, Lu Yu

Pediatrics Faculty Publications

Interim evaluation studies were carried out in order to examine the implementation details of the Tier 1 Program of the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) in Hong Kong. Quantitative results of the interim evaluation findings based on eight datasets collected from 2006 to 2009 are reported in this paper. Three hundred and seventy-eight schools were randomly selected to provide information on the implementation details of the program via face-to-face interviews, telephone interviews, and self-completed questionnaires. Results showed that a majority of the workers perceived that the students had positive responses to the program and the program …

Qualitative Evaluation Of Project P.A.T.H.S.: An Integration Of Findings Based On Program Participants, Daniel T. L. Shek, Rachel C. F. Sun

Pediatrics Faculty Publications

An integration of the qualitative evaluation findings collected in different cohorts of students who participated in Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) (n = 252 students in 29 focus groups) was carried out. With specific focus on how the informants described the program, results showed that the descriptions were mainly positive in nature, suggesting that the program was well received by the program participants. When the informants were invited to name three metaphors that could stand for the program, positive metaphors were commonly used. Beneficial effects of the program in different psychosocial domains were also voiced by …

Interleukin-1Β Mediates Metalloproteinase-Dependent Renal Cell Carcinoma Tumor Cell Invasion Through The Activation Of Ccaat Enhancer Binding Protein Β, Brenda L. Petrella, Matthew P. P. Vincenti

Dartmouth Scholarship

Effective treatment of metastatic renal cell carcinoma (RCC) remains a major medical concern, as these tumors are refractory to standard therapies and prognosis is poor. Although molecularly targeted therapies have shown some promise in the treatment of this disease, advanced RCC tumors often develop resistance to these drugs. Dissecting the molecular mechanisms underlying the progression to advanced disease is necessary to design alternative and improved treatment strategies. Tumor-associated macrophages (TAMs) found in aggressive RCC tumors produce a variety of inflammatory cytokines, including interleukin-1 b (IL-1b). Moreover, the presence of TAMs and high serum levels of IL-1b in RCC patients correlate …

Deciphering Mechanisms Of Staphylococcal Biofilm Evasion Of Host Immunity., Mark L. Hanke, Tammy Kielian

Journal Articles: Pathology and Microbiology

Biofilms are adherent communities of bacteria contained within a complex matrix. Although host immune responses to planktonic staphylococcal species have been relatively well-characterized, less is known regarding immunity to staphylococcal biofilms and how they modulate anti-bacterial effector mechanisms when organized in this protective milieu. Previously, staphylococcal biofilms were thought to escape immune recognition on the basis of their chronic and indolent nature. Instead, we have proposed that staphylococcal biofilms skew the host immune response away from a proinflammatory bactericidal phenotype toward an anti-inflammatory, pro-fibrotic response that favors bacterial persistence. This possibility is supported by recent studies from our laboratory using …

Dna Methylation Arrays As Surrogate Measures Of Cell Mixture Distribution, Eugene Houseman, William P. Accomando, Devin C. Koestler, Brock C. Christensen, Carmen J. Marsit

Dartmouth Scholarship

There has been a long-standing need in biomedical research for a method that quantifies the normally mixed composition of leukocytes beyond what is possible by simple histological or flow cytometric assessments. The latter is restricted by the labile nature of protein epitopes, requirements for cell processing, and timely cell analysis. In a diverse array of diseases and following numerous immune-toxic exposures, leukocyte composition will critically inform the underlying immuno-biology to most chronic medical conditions. Emerging research demonstrates that DNA methylation is responsible for cellular differentiation, and when measured in whole peripheral blood, serves to distinguish cancer cases from controls.

Improved Tumor Contrast Achieved By Single Time Point Dual-Reporter Fluorescence Imaging, Kenneth M. Tichauer, Kimberley S. Samkoe, Kristian J. Sexton, Jason R. Gunn, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

In this study, we demonstrate a method to quantify biomarker expression that uses an exogenous dual-reporter imaging approach to improve tumor signal detection. The uptake of two fluorophores, one nonspecific and one targeted to the epidermal growth factor receptor (EGFR), were imaged at 1 h in three types of xenograft tumors spanning a range of EGFR expression levels (n  =  6 in each group). Using this dual-reporter imaging methodology, tumor contrast-to-noise ratio was amplified by >6 times at 1 h postinjection and >2 times at 24 h. Furthermore, by as early as 20 min postinjection, the dual-reporter imaging signal …

Factor Structure Of A Multidimensional Gender Identity Scale In A Sample Of Chinese Elementary School Children, Lu Yu, Dong Xie, Daniel T. L. Shek

Pediatrics Faculty Publications

This study examined the factor structure of a scale based on the four-dimensional gender identity model (Egan and Perry, 2001) in 726 Chinese elementary school students. Exploratory factor analyses suggested a three-factor model, two of which corresponded to "Felt Pressure" and "Intergroup Bias" in the original model. The third factor "Gender Compatibility" appeared to be a combination of "Gender Typicality" and "Gender Contentment" in the original model. Follow-up confirmatory factor analysis (CFA) indicated that, relative to the initial four-factor structure, the three-factor model fits the current Chinese sample better. These results are discussed in light of cross-cultural similarities and differences …

Pv1 Down-Regulation Via Shrna Inhibits The Growth Of Pancreatic Adenocarcinoma Xenografts, Sophie J. Deharvengt, Dan Tse, Olga Sideleva, Caitlin Mcgarry, Jason R. Gunn, Daniel S. Longnecker, Catherine Carriere, Radu V. Stan

Dartmouth Scholarship

PV1 is an endothelial-specific protein with structural roles in the formation of diaphragms in endothelial cells of normal vessels. PV1 is also highly expressed on endothelial cells of many solid tumours. On the basis of in vitro data, PV1 is thought to actively participate in angiogenesis. To test whether or not PV1 has a function in tumour angiogenesis and in tumour growth in vivo, we have treated pancreatic tumour-bearing mice by single-dose intratumoural delivery of lentiviruses encoding for two different shRNAs targeting murine PV1. We find that PV1 down-regulation by shRNAs inhibits the growth of established tumours derived from two …

The Meaning Of Parenteral Hydration To Family Caregivers And Patients With Advanced Cancer Receiving Hospice Care., Marlene Z. Cohen, Isabel Torres-Vigil, Beth E. Burbach, Allison De La Rosa, Eduardo Bruera

Journal Articles: College of Nursing

CONTEXT: In the U.S., patients with advanced cancer who are dehydrated or have decreased oral intake almost always receive parenteral hydration in acute care facilities but rarely in the hospice setting.

OBJECTIVES: To describe the meaning of hydration for terminally ill cancer patients in home hospice care and for their primary caregivers.

METHODS: Phenomenological interviews were conducted at two time points with 85 patients and 84 caregivers enrolled in a randomized, double-blind, controlled trial examining the efficacy of parenteral hydration in patients with advanced cancer receiving hospice care in the southern U.S. Transcripts were analyzed hermeneutically by the interdisciplinary research …

Prevention Of Stone Migration With The Accordion During Endoscopic Ureteral Lithotripsy., Christopher J Pagnani, Magdy El Akkad, Demetrius H Bagley

Department of Urology Faculty Papers

BACKGROUND AND PURPOSE: Endoscopic lithotripsy is often prolonged secondary to the retrograde migration of calculous fragments. Various balloons, baskets, and other devices have been used to prevent this migration. Our purpose is to analyze the effect of the Accordion(®) on stone migration and overall efficiency during lithotripsy.

PATIENTS AND METHODS: We prospectively evaluated 21 patients with a total of 23 distal ureteral stones. Patients underwent lithotripsy using an endoscopic impact lithotriptor. The Accordion was randomly used in 11 of these 21 patients. Data were collected regarding stone migration, stone size, stone ablation, ureteral clearing, and lengths of time for various …

Program Implementers' Evaluation Of The Project P.A.T.H.S.: Findings Based On Different Datasets Over Time, Daniel T. L. Shek, Cecilia M. S. Ma

Pediatrics Faculty Publications

This paper integrates the evaluation findings based on program implementers in nine datasets collected from 2005 to 2009 (244 schools and 7,926 implementers). Using consolidated data with schools as the unit of analysis, results showed that program implementers generally had positive perceptions of the program, themselves, and benefits of the program, with more than four-fifths of the implementers regarding the program as beneficial to the program participants. The subjective outcome evaluation instrument was found to be internally consistent. Multiple regression analyses revealed that perceived qualities of the program and program implementers predicted perceived effectiveness of the program. In conjunction with …

Recognition For Positive Behavior As A Critical Youth Development Construct: Conceptual Bases And Implications On Youth Service Development, Ben M. F. Law, Andrew M. H. Siu, Daniel T. L. Shek

Pediatrics Faculty Publications

Recognition for positive behavior is an appropriate response of the social environment to elicit desirable external behavior among the youth. Such positive responses, rendered from various social systems, include tangible and intangible reinforcements. The following theories are used to explain the importance of recognizing positive behavior: operational conditioning, observational learning, self-determination, and humanistic perspective. In the current work, culturally and socially desirable behaviors are discussed in detail with reference to Chinese adolescents. Positive behavior recognition is especially important to adolescent development because it promotes identity formation as well as cultivates moral reasoning and social perspective thinking from various social systems. …

Novel Napi-Iic Mutations Causing Hhrh And Idiopathic Hypercalciuria In Several Unrelated Families: Long-Term Follow-Up In One Kindred., Y Yu, S R. Sanderson, M Reyes, A Sharma, N Dunbar, Tarak Srivastava, H Jüppner, C Bergwitz

Manuscripts, Articles, Book Chapters and Other Papers

Homozygous and compound heterozygous mutations in SLC34A3, the gene encoding the sodium-dependent co-transporter NaPi-IIc, cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate-wasting resulting in hypophosphatemia, elevated 1,25(OH)(2) vitamin D levels, hypercalciuria, rickets/osteomalacia, and frequently kidney stones or nephrocalcinosis. Similar albeit less severe biochemical changes are also observed in heterozygous carriers, which are furthermore indistinguishable from those encountered in idiopathic hypercalciuria (IH). We now searched for SLC34A3 mutations (exons and introns) in two previously not reported HHRH kindreds, which resulted in the identification of three novel mutations. The affected members of kindred A were compound heterozygous …

Relative Telomere Length: A Novel Non-Invasive Biomarker For The Risk Of Non-Cirrhotic Hepatocellular Carcinoma In Patients With Chronic Hepatitis B Infection., Xiaoying Fu, Shaogui Wan, Hie-Won Hann, Md, Ronald E Myers, Phd, Richard S Hann, Jennifer Au, Bicui Chen, Jinliang Xing, Hushan Yang

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND AND AIMS: Telomere length has emerged as a promising risk predictor of various cancers including hepatocellular carcinoma (HCC). However, the majority of studies in this area measured telomere length in hepatocytes and one in lymphocytes with conflicting results. Moreover, no studies have been reported on using circulating DNA telomere length as a non-invasive HCC biomarker.

METHODS: We conducted a nested case-control study to determine the relative telomere length (RTL) in serum DNA from 140 hepatitis B virus (HBV)-related HCC cases and 280 frequency-matched cancer-free HBV controls.

RESULTS: Cases had a significantly longer RTL (median, 0.31; range, 0.02-2.31) than controls …

Nitrous Oxide Myelopathy Posing As Spinal Cord Injury., George M. Ghobrial, Md, Richard Dalyai, Md, Adam Flanders, Md, James Harrop, Md

Department of Neurosurgery Faculty Papers

The authors describe a patient who presented with acute tetraparesis and a proposed acute traumatic spinal cord injury that was the result of nitrous oxide myelopathy. This 19-year-old man sustained a traumatic fall off a 6-ft high wall. His examination was consistent with a central cord syndrome with the addition of dorsal column impairment. Cervical MRI demonstrated an isolated dorsal column signal that was suggestive of a nontraumatic etiology. The patient's symptoms resolved entirely over the course of 48 hours. Nitrous oxide abuse is increasing in prevalence. Its toxic side effects can mask vitamin B12 and folate deficiency and central …

Adult Ecmo And Gastrointestinal Bleeding From Small Bowel Arteriovenous Malformations: A Novel Treatment Using Spiral Enteroscopy., Konrad Sarosiek, Hitoshi Hirose, Harrison T Pitcher, Nicholas C. Cavarocchi

Department of Surgery Faculty Papers

Hemorrhagic complications on extracorporeal membrane oxygenation (ECMO) are common because of the need for anticoagulation to maintain the oxygenator and circuitry. Gastrointestinal bleeding (GIB) is reported to occur in 3-6% of ECMO patients, ¹ requiring frequent transfusions as well as multiple diagnostic and therapeutic interventions. Multiple transfusions can result in volume overload, coagulopathies and infections leading to significant morbidity and mortality. We present the first published case of GIB from an arteriovenous malformation (AVM) treated with a novel therapy termed spiral enteroscopy while the patient remained on venoarterial (VA) ECMO.

Early Developmental Outcome In Children With Hypoplastic Left Heart Syndrome And Related Anomalies: The Single Ventricle Reconstruction Trial., Jane W. Newburger, Lynn A. Sleeper, David C. Bellinger, Caren S. Goldberg, Sarah Tabbutt, Minmin Lu, Kathleen A. Mussatto, Ismee A. Williams, Kathryn E. Gustafson, Seema Mital, Nancy Pike, Erica Sood, William T. Mahle, David S. Cooper, Carolyn Dunbar-Masterson, Catherine Dent Krawczeski, Alan Lewis, Shaji C. Menon, Victoria L. Pemberton, Chitra Ravishankar, Teresa W. Atz, Richard G. Ohye, J William Gaynor, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Survivors of the Norwood procedure may experience neurodevelopmental impairment. Clinical trials to improve outcomes have focused primarily on methods of vital organ support during cardiopulmonary bypass.

METHODS AND RESULTS: In the Single Ventricle Reconstruction trial of the Norwood procedure with modified Blalock-Taussig shunt versus right-ventricle-to-pulmonary-artery shunt, 14-month neurodevelopmental outcome was assessed by use of the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Development-II. We used multivariable regression to identify risk factors for adverse outcome. Among 373 transplant-free survivors, 321 (86%) returned at age 14.3 ± 1.1 (mean ± SD) months. Mean …

A Two-Stage Cluster Sampling Method Using Gridded Population Data, A Gis, And Google Earth(Tm) Imagery In A Population-Based Mortality Survey In Iraq, Lp Galway, Nathaniel Bell, Al Shatari Sae, Amy Hagopian, Gilbert Burnham, Abraham Flaxman, Wiliam M. Weiss, Julie Rajaratnam, Tim K. Takaro

Faculty Publications

BACKGROUND:

Mortality estimates can measure and monitor the impacts of conflict on a population, guide humanitarian efforts, and help to better understand the public health impacts of conflict. Vital statistics registration and surveillance systems are rarely functional in conflict settings, posing a challenge of estimating mortality using retrospective population-based surveys.

RESULTS:

We present a two-stage cluster sampling method for application in population-based mortality surveys. The sampling method utilizes gridded population data and a geographic information system (GIS) to select clusters in the first sampling stage and Google Earth TM imagery and sampling grids to select households in the second sampling …

Nicotine, Ifn-Γ And Retinoic Acid Mediated Induction Of Muc4 In Pancreatic Cancer Requires E2f1 And Stat-1 Transcription Factors And Utilize Different Signaling Cascades., Sateesh Kunigal, Moorthy P. Ponnusamy, Navneet Momi, Surinder K. Batra, Srikumar P. Chellappan

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: The membrane-bound mucins are thought to play an important biological role in cell-cell and cell-matrix interactions, in cell signaling and in modulating biological properties of cancer cell. MUC4, a transmembrane mucin is overexpressed in pancreatic tumors, while remaining undetectable in the normal pancreas, thus indicating a potential role in pancreatic cancer pathogenesis. The molecular mechanisms involved in the regulation of MUC4 gene are not yet fully understood. Smoking is strongly correlated with pancreatic cancer and in the present study; we elucidate the molecular mechanisms by which nicotine as well as agents like retinoic acid (RA) and interferon-γ (IFN-γ) induce …

Uterine Epithelial Cells Specifically Induce Interferon-Stimulated Genes In Response To Polyinosinic-Polycytidylic Acid Independently Of Estradiol, Mickey V. Patel, Mimi Ghosh, John V. Fahey, Charles R. Wira

Dartmouth Scholarship

Interferon β (IFNβ) is an antiviral cytokine secreted in response to pathogenic exposure that creates a restrictive intracellular environment through the action of downstream interferon-stimulated genes (ISG). The objective of this study was to examine the expression of IFNβ and ISG in both human uterine epithelial cells (UEC) and the ECC-1 uterine epithelial cell line and determine if expression changes with TLR stimulation and hormone exposure. Stimulation of primary uterine epithelial cells and ECC-1 cells with the TLR3 agonist poly (I∶C) induced the mRNA expression of IFNβ, MxA, OAS2 and PKR. Other TLR agonists including imiquimod and CpG had no …

Spirituality As A Positive Youth Development Construct: A Conceptual Review, Daniel T. L. Shek

Pediatrics Faculty Publications

The concept of spirituality as a positive youth development construct is reviewed in this paper. Both broad and narrow definitions of spirituality are examined and a working definition of spirituality is proposed. Regarding theories of spirituality, different models pertinent to spiritual development and the relationship between spirituality and positive youth development are highlighted. Different ecological factors, particularly family and peer influences, were found to influence spirituality. Research on the influence of spirituality on adolescent developmental outcomes is examined. Finally, ways to promote adolescent spirituality are discussed.