Digital Commons Network^™

Venn, A Tool For Titrating Sequence Conservation Onto Protein Structures, Jay Vyas, Michael R. Gryk, Martin R. Schiller

Life Sciences Faculty Research

Residue conservation is an important, established method for inferring protein function, modularity and specificity. It is important to recognize that it is the 3D spatial orientation of residues that drives sequence conservation. Considering this, we have built a new computational tool, VENN that allows researchers to interactively and graphically titrate sequence homology onto surface representations of protein structures. Our proposed titration strategies reveal critical details that are not readily identified using other existing tools. Analyses of a bZIP transcription factor and receptor recognition of Fibroblast Growth Factor using VENN revealed key specificity determinants. Weblink: http://sbtools.uchc.edu/venn/.

The Effects Of Shoe Traction And Obstacle Height On Lower Extremity Coordination Dynamics During Walking., Leslie Decker, Jeremy J. Houser, John M. Noble, Gregory M. Karst, Nicholas Stergiou

Journal Articles: Physical Therapy

This study aims to investigate the effects of shoe traction and obstacle height on lower extremity relative phase dynamics (analysis of intralimb coordination) during walking to better understand the mechanisms employed to avoid slippage following obstacle clearance. Ten participants walked at a self-selected pace during eight conditions: four obstacle heights (0%, 10%, 20%, and 40% of limb length) while wearing two pairs of shoes (low and high traction). A coordination analysis was used and phasing relationships between lower extremity segments were examined. The results demonstrated that significant behavioral changes were elicited under varied obstacle heights and frictional conditions. Both decreasing …

Clinical Decision Support Capabilities Of Commercially-Available Clinical Information Systems, Adam Wright, Dean F Sittig, Joan S Ash, Sapna Sharma, Justine E Pang, Blackford Middleton

Faculty, Staff and Student Publications

BACKGROUND: The most effective decision support systems are integrated with clinical information systems, such as inpatient and outpatient electronic health records (EHRs) and computerized provider order entry (CPOE) systems. Purpose The goal of this project was to describe and quantify the results of a study of decision support capabilities in Certification Commission for Health Information Technology (CCHIT) certified electronic health record systems.

METHODS: The authors conducted a series of interviews with representatives of nine commercially available clinical information systems, evaluating their capabilities against 42 different clinical decision support features.

RESULTS: Six of the nine reviewed systems offered all the applicable …

Advances In Progenitor Cell Therapy Using Scaffolding Constructs For Central Nervous System Injury, Peter A Walker, Kevin R Aroom, Fernando Jimenez, Shinil K Shah, Matthew T Harting, Brijesh S Gill, Charles S Cox

Faculty, Staff and Student Publications

Traumatic brain injury (TBI) is a major cause of morbidity and mortality in the United States. Current clinical therapy is focused on optimization of the acute/subacute intracerebral milieu, minimizing continued cell death, and subsequent intense rehabilitation to ameliorate the prolonged physical, cognitive, and psychosocial deficits that result from TBI. Adult progenitor (stem) cell therapies have shown promise in pre-clinical studies and remain a focus of intense scientific investigation. One of the fundamental challenges to successful translation of the large body of pre-clinical work is the delivery of progenitor cells to the target location/organ. Classically used vehicles such as intravenous and …

Wireless Networks: Spert: A Stateless Protocol For Energy-Sensitive Real-Time Routing For Wireless Sensor Network, Sohail Jabbar, Abid Ali Minhas, Raja Adeel Akhtar

International Conference on Information and Communication Technologies

Putting constraints on performance of a system in the temporal domain, some times turns right into wrong and update into outdate. These are the scenarios where apposite value of time inveterate in the reality. But such timing precision not only requires tightly scheduled performance constraints but also requires optimal design and operation of all system components. Any malfunctioning at any relevant aspect may causes a serious disaster and even loss of human lives. Managing and interacting with such real-time system becomes much intricate when the resources are limited as in wireless sensor nodes. A wireless sensor node is typically comprises …

Intra-Tumor Heterogeneity Of Mlh1 Promoter Methylation Revealed By Deep Single Molecule Bisulfite Sequencing., Katherine E Varley, David G Mutch, Tina B Edmonston, Paul J Goodfellow, Robi D Mitra

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A single tumor may contain cells with different somatic mutations. By characterizing this genetic heterogeneity within tumors, advances have been made in the prognosis, treatment and understanding of tumorigenesis. In contrast, the extent of epigenetic intra-tumor heterogeneity and how it influences tumor biology is under-explored. We have characterized epigenetic heterogeneity within individual tumors using next-generation sequencing. We used deep single molecule bisulfite sequencing and sample-specific DNA barcodes to determine the spectrum of MLH1 promoter methylation across an average of 1000 molecules in each of 33 individual samples in parallel, including endometrial cancer, matched blood and normal endometrium. This first glimpse, …

Improving Clinical Quality Indicators Through Electronic Health Records: It Takes More Than Just A Reminder, Dean F Sittig, Jonathan M Teich, Jerome A Osheroff, Hardeep Singh

Faculty, Staff and Student Publications

No abstract provided.

The Role Of Demography And Markets In Determining Deforestation Rates Near Ranomafana National Park, Madagascar., Christopher P. Brooks, Christopher Holmes, Karen Kramer, Barry Barnett, Timothy H. Keitt

CAS Publications

The highland forests of Madagascar are home to some of the world's most unique and diverse flora and fauna and to some of its poorest people. This juxtaposition of poverty and biodiversity is continually reinforced by rapid population growth, which results in increasing pressure on the remaining forest habitat in the highland region, and the biodiversity therein. Here we derive a mathematical expression for the subsistence of households to assess the role of markets and household demography on deforestation near Ranomafana National Park. In villages closest to urban rice markets, households were likely to clear less land than our model …

Failure To Replicate A Genetic Association May Provide Important Clues About Genetic Architecture, Casey S. Greene, Nadia M. Penrod, Scott M. Williams, Jason H. Moore

Dartmouth Scholarship

Replication has become the gold standard for assessing statistical results from genome-wide association studies. Unfortunately this replication requirement may cause real genetic effects to be missed. A real result can fail to replicate for numerous reasons including inadequate sample size or variability in phenotype definitions across independent samples. In genome-wide association studies the allele frequencies of polymorphisms may differ due to sampling error or population differences. We hypothesize that some statistically significant independent genetic effects may fail to replicate in an independent dataset when allele frequencies differ and the functional polymorphism interacts with one or more other functional polymorphisms. To …

How Tagging Helps Bridge The Gap Between Social And Technical Aspects In Software Development, Christoph Treude, Margaret-Anne Storey

Research Collection School Of Computing and Information Systems

Empirical research on collaborative software development practices indicates that technical and social aspects of software development are often intertwined. The processes followed are tacit and constantly evolving, thus not all of them are amenable to formal tool support. In this paper, we explore how ldquotaggingrdquo, a lightweight social computing mechanism, is used to bridge the gap between technical and social aspects of managing work items. We present the results from an empirical study on how tagging has been adopted and adapted over the past two years of a large project with 175 developers. Our research shows that the tagging mechanism …

Automated Identification Of Tumor Microscopic Morphology Based On Macroscopically Measured Scatter Signatures, Pilar Beatriz Garcia-Allende, Venkataramanan Krishnaswamy, P Jack Hoopes, Kimberley S. Samkoe, Olga M. Conde, Brian W. Pogue

Dartmouth Scholarship

An automated algorithm and methodology is presented to identify tumor-tissue morphologies based on broadband scatter data measured by raster scan imaging of the samples. A quasi-confocal reflectance imaging system was used to directly measure the tissue scatter reflectance in situ, and the spectrum was used to identify the scattering power, amplitude, and total wavelength-integrated intensity. Pancreatic tumor and normal samples were characterized using the instrument, and subtle changes in the scatter signal were encountered within regions of each sample. Discrimination between normal versus tumor tissue was readily performed using a K-nearest neighbor classifier algorithm. A similar approach worked …

Efficacy Of Formal Screening For Depression In Pediatric Type 1 Diabetes Clinic, Jeffrey Winer

Yale Medicine Thesis Digital Library

This study was undertaken to examine the efficacy of screening for depression in a pediatric diabetes clinic and how the yield of such screening compares with established screening protocols aimed at identifying early microvascular complications and associated autoimmune diseases. Two-hundred-fifteen children and adolescents 8-18 years old in the Yale Pediatric Diabetes Center were screened for depression using the Children's Depression Inventory (CDI), with information including gender, age, duration of diabetes, HbA1C, and results of other screening protocols compiled. A total of 8.4% of our cohort had CDI scores ≥13 indicative of clinically-significant depressive symptoms, with a range of 0-34. Depression …

Characterization Of Conserved Properties Of Hemagglutinin Of H5n1 And Human Influenza Viruses: Possible Consequences For Therapy And Infection Control, Veljko Veljkovic, Nevena Veljkovic, Claude P. Muller, Sybille Müller, Sanja Glisic, Vladimir Perovic, Heinz Köhler

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: Epidemics caused by highly pathogenic avian influenza virus (HPAIV) are a continuing threat to human health and to the world's economy. The development of approaches, which help to understand the significance of structural changes resulting from the alarming mutational propensity for human-to-human transmission of HPAIV, is of particularly interest. Here we compare informational and structural properties of the hemagglutinin (HA) of H5N1 virus and human influenza virus subtypes, which are important for the receptor/virus interaction.

RESULTS: Presented results revealed that HA proteins encode highly conserved information that differ between influenza virus subtypes H5N1, H1N1, H3N2, H7N7 and defined an …

Smoking Enhances Risk For New External Genital Warts In Men, Dorothy J. Wiley, David Elashoff, Emmanuel V. Masongsong, Diane M. Harper

Dartmouth Scholarship

Repeat episodes of HPV-related external genital warts reflect recurring or new infections. No study before has been sufficiently powered to delineate how tobacco use, prior history of EGWs and HIV infection affect the risk for new EGWs. Behavioral, laboratory and examination data for 2,835 Multicenter AIDS Cohort Study participants examined at 21,519 semi-annual visits were evaluated. Fourteen percent (391/2835) of men reported or were diagnosed with EGWs at 3% (675/21,519) of study visits. Multivariate analyses showed smoking, prior episodes of EGWs, HIV infection and CD4+ T-lymphocyte count among the infected, each differentially influenced the risk for new EGWs.

Lymphocyte Proliferation To Mycobacterial Antigens Is Detectable Across A Spectrum Of Hiv-Associated Tuberculosis, Timothy Lahey, Mecky Matee, Lillian Mtei, Muhammad Bakari, Kisali Pallangyo, C Fordham Von Reyn

Dartmouth Scholarship

Background:

Identifying novel TB diagnostics is a major public health priority. We explored the diagnostic characteristics of antimycobacterial lymphocyte proliferation assays (LPA) in HIV-infected subjects with latent or active TB.

Methods:

HIV-infected subjects with bacille Calmette Guérin (BCG) scars and CD4 counts ≥ 200 cells/mm³ entering a TB booster vaccine trial in Tanzania had baseline in vivo and in vitro immune tests performed: tuberculin skin tests (TST), LPA and five day assays of interferon gamma (IFN-γ) release. Assay antigens were early secreted antigenic target 6 (ESAT-6), antigen 85 (Ag85), and Mycobacterium tuberculosis whole cell lysate (WCL). Subjects were screened …

Iatrogenic Bile Duct Injury Associated With Anomalies Of The Right Hepatic Sectoral Ducts: A Misunderstood And Underappreciated Problem, Nitin Babel, Sujit Vijay Sakpal, Prakash Paragi, Jason Wellen, Stephen Feldman, Ronald Scott Chamberlain

Department of Surgery

Although laparoscopic cholecystectomy (LC) has been widely accepted as the standard of care, it continues to have a higher complication rate than open cholecystectomy. Bile duct injury with LC has often been attributed to surgical inexperience, but it is also clear that aberrant bile ducts are present in a significant number of patients who sustain biliary injuries during these procedures. We present three cases of right sectoral hepatic duct injuries which occurred during LC and provide a discussion of the conditions which are likely to lead to these injuries, as part of a strategy to prevent them.

Improving Follow-Up Of Abnormal Cancer Screens Using Electronic Health Records: Trust But Verify Test Result Communication, Hardeep Singh, Lindsey Wilson, Laura A Petersen, Mona K Sawhney, Brian Reis, Donna Espadas, Dean F Sittig

Faculty, Staff and Student Publications

BACKGROUND: Early detection of colorectal cancer through timely follow-up of positive Fecal Occult Blood Tests (FOBTs) remains a challenge. In our previous work, we found 40% of positive FOBT results eligible for colonoscopy had no documented response by a treating clinician at two weeks despite procedures for electronic result notification. We determined if technical and/or workflow-related aspects of automated communication in the electronic health record could lead to the lack of response.

METHODS: Using both qualitative and quantitative methods, we evaluated positive FOBT communication in the electronic health record of a large, urban facility between May 2008 and March 2009. …

The Root Of Dental Anatomy: A Case For Naming Eustachius The "Father Of Dental Anatomy"., Gregory W. Bennett

Journal Articles: College of Dentistry

When one considers the names of those whose affect on dentistry reached far beyond their lifetimes, one may think of Fauchard, Wells, Morton and Black. One name that deserves to be called among the pantheon of the greats is Bartholomaeus Eustachius. Eustachius was not the first to study the anatomy of the teeth and jaws, having been preceded by Da Vinci; however, he was the first to publish a treatise devoted entirely to this subject, Libellus de Dentibus, in 1563. As Sir William Osler, the father of modern medicine, stated: "In Science, the credit goes to the man who convinces …

Taxonomy Development And Knowledge Representation Of Nurses' Personal Cognitive Artifacts, Sharon Mclane, James P Turley

Faculty, Staff and Student Publications

Nurses prepare knowledge representations, or summaries of patient clinical data, each shift. These knowledge representations serve multiple purposes, including support of working memory, workload organization and prioritization, critical thinking, and reflection. This summary is integral to internal knowledge representations, working memory, and decision-making. Study of this nurse knowledge representation resulted in development of a taxonomy of knowledge representations necessary to nursing practice.This paper describes the methods used to elicit the knowledge representations and structures necessary for the work of clinical nurses, described the development of a taxonomy of this knowledge representation, and discusses translation of this methodology to the cognitive …

Extended Kalman Filter For Estimation Of Parameters In Nonlinear State-Space Models Of Biochemical Networks, Xiaodian Sun, Li Jin, Momiao Xiong

Faculty, Staff and Student Publications

It is system dynamics that determines the function of cells, tissues and organisms. to develop mathematical models and estimate their parameters are an essential issue for studying dynamic behaviors of biological systems which include metabolic networks, genetic regulatory networks and signal transduction pathways, under perturbation of external stimuli. In general, biological dynamic systems are partially observed. Therefore, a natural way to model dynamic biological systems is to employ nonlinear state-space equations. Although statistical methods for parameter estimation of linear models in biological dynamic systems have been developed intensively in the recent years, the estimation of both states and parameters of …

Memory Functioning In Children With Reading Disabilities And/Or Attention Deficit/Hyperactivity Disorder: A Clinical Investigation Of Their Working Memory And Long-Term Memory Functioning., Michelle Y. Kibby, Morris J. Cohen

Publications

We examined memory functioning in children with reading disabilities (RD), Attention deficit/hyperactivity disorder (ADHD), and RD/ADHD using a clinic sample with a clinical instrument: the Children's Memory Scale, enhancing its generalizability. Participants included 23 children with RD, 30 with ADHD, 30 with RD/ADHD, and 30 controls. Children with RD presented with reduced verbal short-term memory (STM) but intact visual STM, central executive (CE), and long-term memory (LTM) functioning. Their deficit in STM appeared specific to tasks requiring phonetic coding of material. Children with ADHD displayed intact CE and LTM functioning but reduced visual-spatial STM, especially when off stimulant medication. Children …

Focus On Rna Isolation: Obtaining Rna For Microrna (Mirna) Expression Profiling Analyses Of Neural Tissue, Wang-Xia Wang, Bernard R. Wilfred, Donald A. Baldwin, R. Benjamin Isett, Na Ren, Arnold J. Stromberg, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are present in all known plant and animal tissues and appear to be somewhat concentrated in the mammalian nervous system. Many different miRNA expression profiling platforms have been described. However, relatively little research has been published to establish the importance of 'upstream' variables in RNA isolation for neural miRNA expression profiling. We tested whether apparent changes in miRNA expression profiles may be associated with tissue processing, RNA isolation techniques, or different cell types in the sample. RNA isolation was performed on a single brain sample using eight different RNA isolation methods, and results were correlated using a conventional …

Sustained Attention In Children With Two Etiologies Of Early Hydrocephalus, Maegan D. Swartwout, Paul T. Cirino, Amy W. Hampson, Jack M. Fletcher, Michael E. Brandt, Maureen Dennis

Faculty, Staff and Student Publications

Several studies have shown that children with spina bifida meningomyelocele (SBM) and hydrocephalus have attention problems on parent ratings and difficulties in stimulus orienting associated with a posterior brain attention system. Less is known about response control and inhibition associated with an anterior brain attention system. Using the Gordon Vigilance Task (Gordon, 1983), we studied error rate, reaction time, and performance over time for sustained attention, a key anterior attention function, in 101 children with SBM, 17 with aqueductal stenosis (AS; another condition involving congenital hydrocephalus), and 40 typically developing controls (NC). In SBM, we investigated the relation between cognitive …

Effect Of Progressive Mandibular Advancement On Pharyngeal Airway Size In Anesthetized Adults, Samuel T Kuna, Lee C Woodson, Daneshvari R Solanki, Oliver Esch, Donald E Frantz, Mali Mathru

Faculty, Staff and Student Publications

BACKGROUND: General anesthesia in adult humans is associated with narrowing or complete closure of the pharyngeal airway. The purpose of this study was to determine the effect of progressive mandibular advancement on pharyngeal airway size in normal adults during intravenous infusion of propofol for anesthesia.

METHODS: Magnetic resonance imaging was performed in nine normal adults during wakefulness and during propofol anesthesia. A commercially available intraoral appliance was used to manually advance the mandible. Images were obtained during wakefulness without the appliance and during anesthesia with the participants wearing the appliance under three conditions: without mandibular advancement, advancement to 50% maximum …

Molecular And Macromolecular Alterations Of Recombinant Adenoviral Vectors Do Not Resolve Changes In Hepatic Drug Metabolism During Infection, Shellie M Callahan, Piyanuch Wonganan, Maria A Croyle

Faculty, Staff and Student Publications

In this report we test the hypothesis that long-term virus-induced alterations in CYP occur from changes initiated by the virus that may not be related to the immune response. Enzyme activity, protein expression and mRNA of CYP3A2, a correlate of human CYP3A4, and CYP2C11, responsive to inflammatory mediators, were assessed 0.25, 1, 4, and 14 days after administration of several different recombinant adenoviruses at a dose of 5.7 x 1012 virus particles (vp)/kg to male Sprague Dawley rats. Wild type adenovirus, containing all viral genes, suppressed CYP3A2 and 2C11 activity by 37% and 39%, respectively within six hours. Levels fell …

Generalized Fuzzy Clustering For Segmentation Of Multi-Spectral Magnetic Resonance Images, Renjie He, Sushmita Datta, Balasrinivasa Rao Sajja, Ponnada A Narayana

Faculty, Staff and Student Publications

An integrated approach for multi-spectral segmentation of MR images is presented. This method is based on the fuzzy c-means (FCM) and includes bias field correction and contextual constraints over spatial intensity distribution and accounts for the non-spherical cluster's shape in the feature space. The bias field is modeled as a linear combination of smooth polynomial basis functions for fast computation in the clustering iterations. Regularization terms for the neighborhood continuity of intensity are added into the FCM cost functions. To reduce the computational complexity, the contextual regularizations are separated from the clustering iterations. Since the feature space is not isotropic, …

Caffeine Use: Association With Nicotine Use, Aggression, And Other Psychopathology In Psychiatric And Pediatric Outpatient Adolescents, Catherine A. Martin, Circe Cook, John H. Woodring, Gretchen Burkhardt, Greg Guenthner, Hatim A. Omar, Tom H. Kelly

Psychiatry Faculty Publications

The objective of this study was to evaluate the relationship between caffeine use, other drug use, and psychopathology in adolescents, using self-report measures. The study group consisted of 132 adolescents (average age 14.01 ± 2.06 years, 52% female, 19% African American, 5% other categories, 76% Caucasian). Most (47%) were recruited from a child psychiatry clinic with emphasis on youth with disruptive disorders, with 35% from an adolescent pediatric clinic with emphasis on prevention of risk-taking behavior and 18% from a pediatric clinic for families with limited resources. Subjects were consecutively recruited before or after regular clinic visits. Consent was obtained …

Surveillance Of Cirrhosis For Hepatocellular Carcinoma: A Cost-Utility Analysis., Coon J Thompson, G. Rogers, P. Hewson, D. Wright, R. Anderson, S. Jackson, S. Ryder, M. Cramp, K. Stein

Peninsula Medical School

Using a decision-analytic model, we evaluated the effectiveness and cost-effectiveness of surveillance for hepatocellular carcinoma (HCC) in individuals with cirrhosis. Separate cohorts with cirrhosis due to alcoholic liver disease, hepatitis B and hepatitis C were simulated. Results were also combined to approximate a mixed aetiology population. Comparisons were made between a variety of surveillance algorithms using alpha-foetoprotein (AFP) assay and/or ultrasound at 6- and 12-monthly intervals. Parameter estimates were obtained from comprehensive literature reviews. Uncertainty was explored using one-way and probabilistic sensitivity analyses. In the mixed aetiology cohort, 6-monthly AFP+ultrasound was predicted to be the most effective strategy. The model …

Abstracts In High Profile Journals Often Fail To Report Harm, Enrique Bernal-Delgado, Elliot S. Fisher

Dartmouth Scholarship

To describe how frequently harm is reported in the abstract of high impact factor medical journals. We carried out a blinded structured review of a random sample of 363 Randomised Controlled Trials (RCTs) carried out on human beings, and published in high impact factor medical journals in 2003. Main endpoint: 1) Proportion of articles reporting harm in the abstract; and 2) Proportion of articles that reported harm in the abstract when harm was reported in the main body of the article. Analysis: Corrected Prevalence Ratio (cPR) and its exact confidence interval were calculated. Non-conditional logistic regression was used.

The Acute Effects Of Elevated Blood Lipid Levels On Endothelial Function, Alexander Nissen

Yale Medicine Thesis Digital Library

The association between prolonged elevation of blood lipid levels and coronary artery disease is well established. Research focusing on the acute effects of hyperlipidemia is not as abundant, and often looks only at large-sized arteries. The purpose of our study was to measure the acute effects of elevated blood lipid levels on microvascular endothelial function, non-invasively, by means of laser Doppler flowmetry and the administration of vasoactive challenges. With IRB approval, six healthy subjects were recruited for a three-session study in which they were given isocaloric meals with variable fat content (non-fat meal = NM; fatty meal = FM; or …