Digital Commons Network^™

What Is Biomedical Informatics?, Elmer V Bernstam, Jack W Smith, Todd R Johnson

Faculty, Staff and Student Publications

Biomedical informatics lacks a clear and theoretically-grounded definition. Many proposed definitions focus on data, information, and knowledge, but do not provide an adequate definition of these terms. Leveraging insights from the philosophy of information, we define informatics as the science of information, where information is data plus meaning. Biomedical informatics is the science of information as applied to or studied in the context of biomedicine. Defining the object of study of informatics as data plus meaning clearly distinguishes the field from related fields, such as computer science, statistics and biomedicine, which have different objects of study. The emphasis on data …

Partial And Transitional Atrioventricular Septal Defect Outcomes., L Luann Minich, Andrew M. Atz, Steven D. Colan, Lynn A. Sleeper, Seema Mital, James Jaggers, Renee Margossian, Ashwin Prakash, Jennifer S. Li, Meryl S. Cohen, Ronald V. Lacro, Gloria L. Klein, John A. Hawkins, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Surgical and perioperative improvements permit earlier repair of partial and transitional atrioventricular septal defects (AVSD). We sought to describe contemporary outcomes in a multicenter cohort.

METHODS: We studied 87 patients undergoing primary biventricular repair of partial or transitional AVSD between June 2004 and February 2006 across seven North American centers. One-month and 6-month postoperative data included weight-for-age z-scores, left atrioventricular valve regurgitation (LAVVR) grade, residual shunts, and left ventricular ejection fraction. Paired methods were used to assess 6-month change.

RESULTS: Median age at surgery was 1.8 years; median weight z-score was -0.88. Median days for ventilation were 1, intensive …

Progressive Changes In Microglia And Macrophages In Spinal Cord And Peripheral Nerve In The Transgenic Rat Model Of Amyotrophic Lateral Sclerosis, David J. Graber, William F. Hickey, Brent T. Harris

Dartmouth Scholarship

The role of neuroinflammation in motor neuron death of amyotrophic lateral sclerosis (ALS) is unclear. The human mutant superoxide dismutase-1 (hmSOD1)-expressing murine transgenic model of ALS has provided some insight into changes in microglia activity during disease progression. The purpose of this study was to gain further knowledge by characterizing the immunological changes during disease progression in the spinal cord and peripheral nerve using the more recently developed hmSOD1 rat transgenic model of ALS. Using immunohistochemistry, the extent and intensity of tissue CD11b expression in spinal cord, lumbar nerve roots, and sciatic nerve were evaluated in hmSOD1 rats that were …

Proliferation Of Aneuploid Human Cells Is Limited By A P53-Dependent Mechanism, Sarah L. Thompson, Duane A. Compton

Dartmouth Scholarship

Most solid tumors are aneuploid, and it has been proposed that aneuploidy is the consequence of an elevated rate of chromosome missegregation in a process called chromosomal instability (CIN). However, the relationship of aneuploidy and CIN is unclear because the proliferation of cultured diploid cells is compromised by chromosome missegregation. The mechanism for this intolerance of nondiploid genomes is unknown. In this study, we show that in otherwise diploid human cells, chromosome missegregation causes a cell cycle delay with nuclear accumulation of the tumor suppressor p53 and the cyclin kinase inhibitor p21. Deletion of the p53 gene permits the accumulation …

Eosinophilic Cholangitis And Cholangiopathy: A Sheep In Wolves Clothing, Catherine Nashed, Sujit Vijay Sakpal, Victoria Shusharina, Ronald Scott Chamberlain

Department of Surgery

BACKGROUND: Eosinophilic cholangitis (EC) is a rare benign disorder of the biliary tract which can cause biliary obstruction. Similar to other disease processes involving the bile ducts, this disorder can pose a difficult diagnostic challenge as it can mimic cholangiocarcinoma.

METHODS: A systematic search of the scientific literature was carried out using PubMed to access all publications related to EC. Search keywords that were utilized included "eosinophilic cholangitis," "etiology," "treatment," and "obstructive jaundice." Results. Twenty-three cases of EC have been reported. Nineteen patients (82.6%) who presented with EC remain disease-free; 15 of these 19 patients (78.9%) with followup time remain …

Myosin Light Chain Kinase Mediates Transcellular Intravasation Of Breast Cancer Cells Through The Underlying Endothelial Cells: A Three-Dimensional Fret Study, S. Khuon, L. Liang, R. W. Dettman, P. H. S. Sporn, R. B. Wysolmerski, T.-L. Chew

Faculty & Staff Scholarship

No abstract provided.

Recent Diarrhea Is Associated With Elevated Salivary Igg Responses To Cryptosporidium In Residents Of An Eastern Massachusetts Community, A. I. Egorov, L. M. Montuori Trimble, L. Ascolillo, H. D. Ward, Deborah A. Levy, R. D. Morris, E. N. Naumova, J. K. Griffiths

Journal Articles: Epidemiology

BACKGROUND: Serological data suggest that Cryptosporidium infections are common but underreported. The invasiveness of blood sampling limits the application of serology in epidemiological surveillance. We pilot-tested a non-invasive salivary anti-Cryptosporidium antibody assay in a community survey involving children and adults.

MATERIALS AND METHODS: Families with children were recruited in a Massachusetts community in July; symptoms data were collected at 3 monthly follow-up mail surveys. One saliva sample per person (n = 349) was collected via mail, with the last survey in October. Samples were analyzed for IgG and IgA responses to a recombinant C. hominis gp15 sporozoite protein using a …

The Most Important Medical Source: Aunt Mabel Knows Best., Lawrence Parish, Joseph A Witkowski

Department of Dermatology and Cutaneous Biology Faculty Papers

Not so long ago, one of us was consulted by a middle-aged woman with rosacea. For many years, she had had periodic flares of red papules and pustules on her nose and the adjoining areas. The confluent telangiectasia on her cheeks gave a permanent appearance of well-applied rouge. She had seen several dermatologists and had received a wide variety of medications, all of which seemed appropriate except to her as would be subsequently revealed. She wanted a new approach, but there were limitations placed upon her request: no pills or capsules; nothing odiferous; no agent that might bleach clothing; and …

A New Design For A Turing Test For Bots, Philip Hingston

Research outputs pre 2011

Interesting, human-like opponents add to the entertainment value of a video game, and creating such opponents is a difficult challenge for programmers. Can artificial intelligence and computational intelligence provide the means to convincingly simulate a human opponent? Or are simple programming tricks and deceptions more effective? To answer these questions, the author designed and organised a game bot programming competition, the BotPrize, in which competitors submit bots that try to pass a “Turing Test for Bots”. In this paper, we describe a new design for the competition, which will make it simpler to run, and, we hope, open up new …

The Transition From Medical Student To Junior Doctor: Today's Experiences Of Tomorrow's Doctors., Nicola Brennan, Oonagh Corrigan, Jon Allard, Julian Archer, Rebecca Barnes, Alan Bleakley, Tracey Collett, Bere Sr De

Peninsula Medical School

CONTEXT Medical education in the UK has recently undergone radical reform. Tomorrow's Doctors has prescribed undergraduate curriculum change and the Foundation Programme has overhauled postgraduate education. OBJECTIVES This study explored the experiences of junior doctors during their first year of clinical practice. In particular, the study sought to gain an understanding of how junior doctors experienced the transition from the role of student to that of practising doctor and how well their medical school education had prepared them for this. METHODS The study used qualitative methods comprising of semi-structured interviews and audio diary recordings with newly qualified doctors based at …

Bio-Informatics Analysis Of A Gene Co-Expression Module In Adipose Tissue Containing The Diet-Responsive Gene Nnat., X Li.X, Pa Thomason, Dj Withers, J Scott

Peninsula Medical School

Obesity causes insulin resistance in target tissues - skeletal muscle, adipose tissue, liver and the brain. Insulin resistance predisposes to type-2 diabetes (T2D) and cardiovascular disease (CVD). Adipose tissue inflammation is an essential characteristic of obesity and insulin resistance. Neuronatin (Nnat) expression has been found to be altered in a number of conditions related to inflammatory or metabolic disturbance, but its physiological roles and regulatory mechanisms in adipose tissue, brain, pancreatic islets and other tissues are not understood.

Temporal Distance And Person Memory: Thinking About The Future Changes Memory For The Past., Na Wyer, Tj Perfect, S Pahl

School of Psychology

Psychological distance has been shown to influence how people construe an event such that greater distance produces high-level construal (characterized by global or holistic processing) and lesser distance produces low-level construal (characterized by detailed or feature-based processing). The present research tested the hypothesis that construal level has carryover effects on how information about an event is retrieved from memory. Two experiments manipulated temporal distance and found that greater distance (high-level construal) improves face recognition and increases retrieval of the abstract features of an event, whereas lesser distance (low-level construal) impairs face recognition and increases retrieval of the concrete details of …

Neuronal Network Pharmacodynamics Of Gabaergic Modulation In The Human Cortex Determined Using Pharmaco-Magnetoencephalography., Stephen D. Hall, Gareth R. Barnes, Paul L. Furlong, Stefano Seri, Arjan Hillebrand

School of Psychology

Neuronal network oscillations are a unifying phenomenon in neuroscience research, with comparable measurements across scales and species. Cortical oscillations are of central importance in the characterization of neuronal network function in health and disease and are influential in effective drug development. Whilst animal in vitro and in vivo electrophysiology is able to characterize pharmacologically induced modulations in neuronal activity, present human counterparts have spatial and temporal limitations. Consequently, the potential applications for a human equivalent are extensive. Here, we demonstrate a novel implementation of contemporary neuroimaging methods called pharmaco-magnetoencephalography. This approach determines the spatial profile of neuronal network oscillatory power …

A Review Of Human Factors Principles For The Design And Implementation Of Medication Safety Alerts In Clinical Information Systems., Shobha Phansalkar, Judy Edworthy, Elizabeth Hellier, Diane L. Seger, Angela Schedlbauer, Anthony J. Avery, David W. Bates

School of Psychology

The objective of this review is to describe the implementation of human factors principles for the design of alerts in clinical information systems. First, we conduct a review of alarm systems to identify human factors principles that are employed in the design and implementation of alerts. Second, we review the medical informatics literature to provide examples of the implementation of human factors principles in current clinical information systems using alerts to provide medication decision support. Last, we suggest actionable recommendations for delivering effective clinical decision support using alerts. A review of studies from the medical informatics literature suggests that many …

Event-Related Potentials Dissociate Effects Of Salience And Space In Biased Competition For Visual Representation, Matthew R. Hilimire, Jeffrey R.W. Mounts, Nathan A. Parks, Paul M. Corballis

Psychology

Background: Selective visual attention is the process by which the visual system enhances behaviorally relevant stimuli and filters out others. Visual attention is thought to operate through a cortical mechanism known as biased competition. Representations of stimuli within cortical visual areas compete such that they mutually suppress each others' neural response. Competition increases with stimulus proximity and can be biased in favor of one stimulus (over another) as a function of stimulus significance, salience, or expectancy. Though there is considerable evidence of biased competition within the human visual system, the dynamics of the process remain unknown. Methodology/Principal Findings: Here, we …

Differential Gene Expression Profile Of Retinoblastoma Compared To Normal Retina., Arupa Ganguly, Carol L Shields

Wills Eye Hospital Papers

PURPOSE: The retinoblastoma gene (RB1) is a tumor suppressor gene that was first discovered in a rare ocular pediatric tumor called retinoblastoma (RB). The RB1 gene is essential for normal progression through the cell cycle and exerts part of its function through the family of transcription factors (E2F) and many other intermediaries. In the absence of normal RB1, genomic instability and chromosomal aberrations accumulate, leading to tumor initiation, progression, and ultimately metastasis. The purpose of this report was to identify the molecular pathways that are deregulated in retinoblastoma.

METHODS: We compared gene expression signatures of matched normal retinal tissue and …

Fdg-Pet Staging And Importance Of Lymph Node Suv In Head And Neck Cancer., Gregory J Kubicek, Collin Champ, Shannon Fogh, Fen Wang, Eashwer Reddy, Charles Intenzo, Reginald W Dusing, Mitchell Machtay

Department of Radiation Oncology Faculty Papers

OBJECTIVES: The role of positron emission tomography (PET) with fluoro-deoxy-glucose (FDG) in the staging of head and neck cancer (HNC) is unclear. The NCCN guidelines do not recommend FDG-PET as a part of standard workup. The purpose of this report is to examine the role of FDG-PET imaging in altering management and providing prognostic information for HNC.

METHODS: Retrospective review of HNC patients who had a staging FDG-PET scan performed at either Thomas Jefferson University or University of Kansas Medical Center between the years 2001 and 2007. A total of 212 PET scans were performed in patients who went on …

Social Support In An Internet Weight Loss Community, Kevin O Hwang, Allison J Ottenbacher, Angela P Green, M Roseann Cannon-Diehl, Oneka Richardson, Elmer V Bernstam, Eric J Thomas

Faculty, Staff and Student Publications

Purpose: To describe social support for weight loss shared by members of a large Internet weight loss community.

Methods: We conducted a mixed-methods study with surveys (n=193) and interviews (n=13) of community members along with a content analysis of discussion forum messages (n=1924 messages). Qualitative data were analyzed for social support themes.

Results: Survey respondents were primarily white (91.4%) and female (93.8%) with mean age 37.3 years and mean body mass index 30.9. They used forums frequently, with 56.8% reading messages, 36.1% replying to messages, and 18.5% posting messages to start a discussion related to weight loss on a daily …

Impaired Immune Tolerance To Porphyromonas Gingivalis Lipopolysaccharide Promotes Neutrophil Migration And Decreased Apoptosis., S Zaric, C Shelburne, R Darveau, Dj Quinn, S Weldon, Cc Taggart, Wa Coulter

Peninsula Dental School

Periodontitis, a chronic inflammatory disease of the tissues supporting the teeth, is characterized by an exaggerated host immune and inflammatory response to periopathogenic bacteria. Toll-like receptor activation, cytokine network induction, and accumulation of neutrophils at the site of inflammation are important in the host defense against infection. At the same time, induction of immune tolerance and the clearance of neutrophils from the site of infection are essential in the control of the immune response, resolution of inflammation, and prevention of tissue destruction. Using a human monocytic cell line, we demonstrate that Porphyromonas gingivalis lipopolysaccharide (LPS), which is a major etiological …

The Role Of Stereotactic Radiosurgery In The Management Of Patients With Newly Diagnosed Brain Metastases: A Systematic Review And Evidence-Based Clinical Practice Guideline., Mark E Linskey, David W Andrews, Anthony L Asher, Stuart H Burri, Douglas Kondziolka, Paula D Robinson, Mario Ammirati, Charles S Cobbs, Laurie E Gaspar, Jay S Loeffler, Michael Mcdermott, Minesh P Mehta, Tom Mikkelsen, Jeffrey J Olson, Nina A Paleologos, Roy A Patchell, Timothy C Ryken, Steven N Kalkanis

Department of Neurosurgery Faculty Papers

QUESTION: Should patients with newly-diagnosed metastatic brain tumors undergo stereotactic radiosurgery (SRS) compared with other treatment modalities? Target population These recommendations apply to adults with newly diagnosed solid brain metastases amenable to SRS; lesions amenable to SRS are typically defined as measuring less than 3 cm in maximum diameter and producing minimal (less than 1 cm of midline shift) mass effect. Recommendations SRS plus WBRT vs. WBRT alone Level 1 Single-dose SRS along with WBRT leads to significantly longer patient survival compared with WBRT alone for patients with single metastatic brain tumors who have a KPS > or = 70.Level 1 …

Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets With Alopecia Resulting From A Novel Missense Mutation In The Dna-Binding Domain Of The Vitamin D Receptor., Peter J. Malloy, Jining Wang, Tarak Srivastava, David Feldman

Manuscripts, Articles, Book Chapters and Other Papers

The rare genetic recessive disease, hereditary vitamin D resistant rickets (HVDRR), is caused by mutations in the vitamin D receptor (VDR) that result in resistance to the active hormone 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3) or calcitriol). In this study, we examined the VDR from a young boy with clinical features of HVDRR including severe rickets, hypocalcemia, hypophosphatemia and partial alopecia. The pattern of alopecia was very unusual with areas of total baldness, adjacent to normal hair and regions of scant hair. The child failed to improve on oral calcium and vitamin D therapy but his abnormal chemistries and his bone X-rays normalized …

Fagerstrom Test For Nicotine Dependence Vs Heavy Smoking Index In A General Population Survey, M. Pérez-Ríos, M. I. Santiago-Pérez, B. Alonso, A. Malvar, X. Hervada, Jose De Leon

Psychiatry Faculty Publications

BACKGROUND: The Fagerström Test for Nicotine Dependence (FTND) is used for assessing nicotine dependence. A shorter test derived from the FTND used for the general population is the Heavy Smoking Index (HSI) (six questions vs. two). The objective of this study is to compare the validity of the HSI versus the FTND.

METHODS: A survey of tobacco use in the general population was carried out in the northern Spanish region of Galicia using both the FTND and the HSI to study a representative sample of 1655 daily smokers. The HSI was compared with the FTND, considered the gold standard. Measures …

The Principled Control Of False Positives In Neuroimaging, Craig M. Bennett, George L. Wolford, Michael B. Miller

Dartmouth Scholarship

An incredible amount of data is generated in the course of a functional neuroimaging experiment. The quantity of data gives us improved temporal and spatial resolution with which to evaluate our results. It also creates a staggering multiple testing problem. A number of methods have been created that address the multiple testing problem in neuroimaging in a principled fashion. These methods place limits on either the familywise error rate (FWER) or the false discovery rate (FDR) of the results. These principled approaches are well established in the literature and are known to properly limit the amount of false positives across …

Hla-Dpb1 And Dpb2 Are Genetic Loci For Systemic Sclerosis: A Genome-Wide Association Study In Koreans With Replication In North Americans, Xiaodong Zhou, Jong Eun Lee, Frank C Arnett, Momiao Xiong, Min Young Park, Yeon Kyeong Yoo, Eun Soon Shin, John D Reveille, Maureen D Mayes, Jin Hyun Kim, Ran Song, Ji Yong Choi, Ji Ah Park, Yun Jong Lee, Eun Young Lee, Yeong Wook Song, Eun Bong Lee

Faculty, Staff and Student Publications

OBJECTIVE: To identify systemic sclerosis (SSc) susceptibility loci via a genome-wide association study.

METHODS: A genome-wide association study was performed in 137 patients with SSc and 564 controls from Korea using the Affymetrix Human SNP Array 5.0. After fine-mapping studies, the results were replicated in 1,107 SSc patients and 2,747 controls from a US Caucasian population.

RESULTS: The single-nucleotide polymorphisms (SNPs) (rs3128930, rs7763822, rs7764491, rs3117230, and rs3128965) of HLA-DPB1 and DPB2 on chromosome 6 formed a distinctive peak with log P values for association with SSc susceptibility (P=8.16x10(-13)). Subtyping analysis of HLA-DPB1 showed that DPB1*1301 (P=7.61x10(-8)) and DPB1*0901 (P=2.55x10(-5)) were …

Apolipoprotein E But Not B Is Required For The Formation Of Infectious Hepatitis C Virus Particles, Jieyun Jiang, Guangxiang Luo

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Our previous studies have found that hepatitis C virus (HCV) particles are enriched in apolipoprotein E (apoE) and that apoE is required for HCV infectivity and production. Studies by others, however, suggested that both microsomal transfer protein (MTP) and apoB are important for HCV production. To define the roles of apoB and apoE in the HCV life cycle, we developed a single-cycle HCV growth assay to determine the correlation of HCV assembly with apoB and apoE expression, as well as the influence of MTP inhibitors on the formation of HCV particles. The small interfering RNA (siRNA)-mediated knockdown of apoE expression …

Tb Research At Ut-Houston – A Review Of Cord Factor: New Approaches To Drugs, Vaccines And The Pathogenesis Of Tuberculosis, Robert L Hunter, Lisa Armitige, Chinnaswamy Jagannath, Jeffrey K Actor

Faculty, Staff and Student Publications

Tuberculosis remains a major threat as drug resistance continues to increase. Pulmonary tuberculosis in adults is responsible for 80% of clinical cases and nearly 100% of transmission of infection. Unfortunately, since we have no animal models of adult type pulmonary tuberculosis, the most important type of disease remains largely out of reach of modern science and many fundamental questions remain unanswered. This paper reviews research dating back to the 1950's providing compelling evidence that cord factor (trehalose 6,6 dimycolate [TDM]) is essential for understanding tuberculosis. However, the original papers by Bloch and Noll were too far ahead of their time …

Face Gender And Emotion Expression: Are Angry Women More Like Men?, Ursula Hess, Reginald B. Adams, Karl Grammer, Robert E. Kleck

Dartmouth Scholarship

Certain features of facial appearance perceptually resemble expressive cues related to facial displays of emotion. We hypothesized that because expressive markers of anger (such as lowered eyebrows) overlap with perceptual markers of male sex, perceivers would identify androgynous angry faces as more likely to be a man than a woman (Study 1) and would be slower to classify an angry woman as a woman than an angry man as a man (Study 2). Conversely, we hypothesized that because perceptual features of fear (raised eyebrows) and happiness (a rounded smiling face) overlap with female sex markers, perceivers would be more likely …

A Functional Role For The Ventrolateral Prefrontal Cortex In Non-Spatial Auditory Cognition, Y. E. Cohen, B. E. Russ, S. J. Davis, A. E. Baker, A. L. Ackelson, R. Niteck

Dartmouth Scholarship

Spatial and non-spatial sensory information is hypothesized to be evaluated in parallel pathways. In this study, we tested the spatial and non-spatial sensitivity of auditory neurons in the ventrolateral prefrontal cortex (vPFC), a cortical area in the non-spatial pathway. Activity was tested while non-human primates reported changes in an auditory stimulus' spatial or non-spatial features. We found that vPFC neurons were reliably modulated during a non-spatial auditory task but were not modulated during a spatial auditory task. The degree of modulation during the non-spatial task correlated positively with the monkeys' behavioral performance. These results are consistent with the hypotheses that …

Brazilian Adolescents Infected By Hiv: Epidemiologic Characteristics And Adherence To Treatment, Julia K. C. Machado, Maria J. C. Sant'anna, Veronica Coates, Flavia J. Almeida, Eitan N. Berezin, Hatim A. Omar

Pediatrics Faculty Publications

Over the last 3 decades since the first AIDS cases appeared, we have witnessed great progress in therapeutic methodologies that have transformed the evolution of the disease from debilitating and fatal, into chronic and controllable. HIV-infected children are arriving at adolescence and bringing specific challenges, not only to themselves, but also to their families and caregivers. This retrospective study sets forth epidemiological and treatment characteristics of 46 HIV-infected adolescents followed in a specialized university service relating said characteristics to therapy adherence assessed through a combination of three indirect methods. Therapy adherence did not reveal any association with either epidemiologic characteristics …

Suppression Of Erbb-2 In Androgen-Independent Human Prostate Cancer Cells Enhances Cytotoxic Effect By Gemcitabine In An Androgen-Reduced Environment., Li Zhang, Jeffrey S. Davis, Stanislav Zelivianski, Fen-Fen Lin, Rachel Schutte, Thomas L. Davis, Ralph Hauke, Surinder K. Batra, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

We examined the efficacy of combination treatments utilizing cytotoxic drugs plus inhibitors to members of the ErbB-ERK signal pathway in human prostate cancer (PCa) LNCaP C-81 cells. Under an androgen-reduced condition, 50nM gemcitabine caused about 40% growth suppression on C-81 cells. Simultaneous treatment of gemcitabine plus 10microM AG825 produced 60% suppression (p