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Analyzing Networks Of Phenotypes In Complex Diseases: Methodology And Applications In Copd, Jen-Hwa Chu, Craig P. Hersh, Peter J. Castaldi, Michael H. Cho, Benjamin A. Raby, Nan Laird, Russell Bowler, Stephen I. Rennard, Joseph Loscalzo, John Quackenbush, Edwin K. Silverman Jan 2014

Analyzing Networks Of Phenotypes In Complex Diseases: Methodology And Applications In Copd, Jen-Hwa Chu, Craig P. Hersh, Peter J. Castaldi, Michael H. Cho, Benjamin A. Raby, Nan Laird, Russell Bowler, Stephen I. Rennard, Joseph Loscalzo, John Quackenbush, Edwin K. Silverman

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: The investigation of complex disease heterogeneity has been challenging. Here, we introduce a network-based approach, using partial correlations, that analyzes the relationships among multiple disease-related phenotypes.

RESULTS: We applied this method to two large, well-characterized studies of chronic obstructive pulmonary disease (COPD). We also examined the associations between these COPD phenotypic networks and other factors, including case-control status, disease severity, and genetic variants. Using these phenotypic networks, we have detected novel relationships between phenotypes that would not have been observed using traditional epidemiological approaches.

CONCLUSION: Phenotypic network analysis of complex diseases could provide novel insights into disease susceptibility, disease …


Clinical And Computed Tomographic Predictors Of Chronic Bronchitis In Copd: A Cross Sectional Analysis Of The Copdgene Study, Victor Kim, Adam Davey, Alejandro P. Comellas, Meilan K. Han, George Washko, Carlos H. Martinez, David Lynch, Jin Hwa Lee, Edwin K. Silverman, James D. Crapo, Barry J. Make, Gerard J. Criner, The Copdgene® Investigators Jan 2014

Clinical And Computed Tomographic Predictors Of Chronic Bronchitis In Copd: A Cross Sectional Analysis Of The Copdgene Study, Victor Kim, Adam Davey, Alejandro P. Comellas, Meilan K. Han, George Washko, Carlos H. Martinez, David Lynch, Jin Hwa Lee, Edwin K. Silverman, James D. Crapo, Barry J. Make, Gerard J. Criner, The Copdgene® Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic bronchitis (CB) has been related to poor outcomes in Chronic Obstructive Pulmonary Disease (COPD). From a clinical standpoint, we have shown that subjects with CB in a group with moderate to severe airflow obstruction were younger, more likely to be current smokers, male, Caucasian, had worse health related quality of life, more dyspnea, and increased exacerbation history compared to those without CB. We sought to further refine our clinical characterization of chronic bronchitics in a larger cohort and analyze the CT correlates of CB in COPD subjects. We hypothesized that COPD patients with CB would have thicker airways …


Dnah5 Is Associated With Total Lung Capacity In Chronic Obstructive Pulmonary Disease, Jin Hwa Lee, Merry-Lynn N Mcdonald, Michael H. Cho, Emily S. Wan, Peter J. Castaldi, Gary M. Hunninghake, Nathaniel Marchetti, David A. Lynch, James D. Crapo, David A. Lomas, Harvey O. Coxson, Per S. Bakke, Edwin K. Silverman, Craig P. Hersh, The Copdgene And Eclipse Investigators Jan 2014

Dnah5 Is Associated With Total Lung Capacity In Chronic Obstructive Pulmonary Disease, Jin Hwa Lee, Merry-Lynn N Mcdonald, Michael H. Cho, Emily S. Wan, Peter J. Castaldi, Gary M. Hunninghake, Nathaniel Marchetti, David A. Lynch, James D. Crapo, David A. Lomas, Harvey O. Coxson, Per S. Bakke, Edwin K. Silverman, Craig P. Hersh, The Copdgene And Eclipse Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction. The aim of our study was to identify genetic variants associated with TLC in COPD.

METHODS: We performed genome-wide association studies (GWASs) in white subjects from three cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway). All subjects were current or ex-smokers …


Broad And Direct Interaction Between Tlr And Siglec Families Of Pattern Recognition Receptors And Its Regulation By Neu1., Guo-Yun Chen, Nicholas K. Brown, Wei Wu, Zahra Khedri, Hai Yu, Xi Chen, Diantha Van De Vlekkert, Alessandra D'Azzo, Pan Zheng, Yang Liu Jan 2014

Broad And Direct Interaction Between Tlr And Siglec Families Of Pattern Recognition Receptors And Its Regulation By Neu1., Guo-Yun Chen, Nicholas K. Brown, Wei Wu, Zahra Khedri, Hai Yu, Xi Chen, Diantha Van De Vlekkert, Alessandra D'Azzo, Pan Zheng, Yang Liu

Pediatrics Faculty Publications

Both pathogen- and tissue damage-associated molecular patterns induce inflammation through toll-like receptors (TLRs), while sialic acid-binding immunoglobulin superfamily lectin receptors (Siglecs) provide negative regulation. Here we report extensive and direct interactions between these pattern recognition receptors. The promiscuous TLR binders were human SIGLEC-5/9 and mouse Siglec-3/E/F. Mouse Siglec-G did not show appreciable binding to any TLRs tested. Correspondingly, Siglece deletion enhanced dendritic cell responses to all microbial TLR ligands tested, while Siglecg deletion did not affect the responses to these ligands. TLR4 activation triggers Neu1 translocation to cell surface to disrupt TLR4:Siglec-E interaction. Conversely, sialidase inhibitor Neu5Gc2en prevented TLR4 ligand-induced …


Influence Of Diet And Obesity On Copd Development And Outcomes, Corrine K. Hanson, Erica P. Rutten, Emiel F.M. Wouters, Stephen I. Rennard Jan 2014

Influence Of Diet And Obesity On Copd Development And Outcomes, Corrine K. Hanson, Erica P. Rutten, Emiel F.M. Wouters, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

The global increase in the prevalence and incidence of obesity has called serious attention to this issue as a major public health concern. Obesity is associated with many chronic diseases, including cardiovascular disease and diabetes, and recently the role of overweight and obesity in lung disease has received new interest. Independently of obesity, diet also plays a role as a risk factor for many chronic diseases, and evidence is accumulating to support a role for diet in the prevention and management of several lung diseases. Chronic obstructive lung disease is the third-leading cause of death globally, and both obesity and …


Roflumilast And Dyspnea In Patients With Moderate To Very Severe Chronic Obstructive Pulmonary Disease: A Pooled Analysis Of Four Clinical Trials, Stephen I. Rennard, Shawn X. Sun, Stavros Tourkodimitris, Paul Rowe, Udo M. Goehring, Dirk Bredenbröker, Peter M.A. Calverley Jan 2014

Roflumilast And Dyspnea In Patients With Moderate To Very Severe Chronic Obstructive Pulmonary Disease: A Pooled Analysis Of Four Clinical Trials, Stephen I. Rennard, Shawn X. Sun, Stavros Tourkodimitris, Paul Rowe, Udo M. Goehring, Dirk Bredenbröker, Peter M.A. Calverley

Journal Articles: Pulmonary & Critical Care Med

PURPOSE: Breathlessness is a predominant symptom of chronic obstructive pulmonary disease (COPD), making it a valuable outcome in addition to lung function to assess treatment benefit. The phosphodiesterase-4 inhibitor roflumilast has been shown to provide small but significant improvements in dyspnea, as measured by the transition dyspnea index (TDI), in two 1-year studies in patients with severe to very severe COPD.

PATIENTS AND METHODS: To provide a more comprehensive assessment of the impact of roflumilast on dyspnea, post hoc analyses of four 1-year roflumilast studies (M2-111, M2-112, M2-124, and M2-125) in patients with moderate to very severe COPD were conducted. …


The Impact Of Multisensory Integration Deficits On Speech Perception In Children With Autism Spectrum Disorders., Ryan A Stevenson, Magali Segers, Susanne Ferber, Morgan D Barense, Mark T Wallace Jan 2014

The Impact Of Multisensory Integration Deficits On Speech Perception In Children With Autism Spectrum Disorders., Ryan A Stevenson, Magali Segers, Susanne Ferber, Morgan D Barense, Mark T Wallace

Brain and Mind Institute Researchers' Publications

Speech perception is an inherently multisensory process. When having a face-to-face conversation, a listener not only hears what a speaker is saying, but also sees the articulatory gestures that accompany those sounds. Speech signals in visual and auditory modalities provide complementary information to the listener (Kavanagh and Mattingly, 1974), and when both are perceived in unison, behavioral gains in in speech perception are observed (Sumby and Pollack, 1954). Notably, this benefit is accentuated when speech is perceived in a noisy environment (Sumby and Pollack, 1954). To achieve a behavioral gain from multisensory processing of speech, however, the auditory and visual …


There Are Laterality Effects In Memory Functioning In Children/Adolescents With Focal Epilepsy., Michelle Y Kibby, Morris J Cohen, Sylvia E Lee, Lisa Stanford, Yong D Park, Suzanne M Strickland Jan 2014

There Are Laterality Effects In Memory Functioning In Children/Adolescents With Focal Epilepsy., Michelle Y Kibby, Morris J Cohen, Sylvia E Lee, Lisa Stanford, Yong D Park, Suzanne M Strickland

Publications

In a sample of individuals with childhood focal epilepsy, children/adolescents with left hemisphere foci outperformed those with right foci on both measures of nonverbal learning. Participants with left foci performed worse than controls on paired associate delayed recall and semantic memory, and they had greater laterality effects in IQ. Participants with right foci performed worse than controls on delayed facial recognition. Both groups displayed reduced focused attention and poor passage retention over time. Although participants with bilateral foci displayed poor learning and lower IQ than controls, they did not have worse impairment than those with a unilateral focus.


Analysis Of Schizophrenia Data Using A Nonlinear Threshold Index Logistic Model., Zhenyu Jiang, Chengan Du, Assen Jablensky, Hua Liang, Zudi Lu, Yang Ma, Kok Lay Teo Jan 2014

Analysis Of Schizophrenia Data Using A Nonlinear Threshold Index Logistic Model., Zhenyu Jiang, Chengan Du, Assen Jablensky, Hua Liang, Zudi Lu, Yang Ma, Kok Lay Teo

GW Biostatistics Center

Genetic information, such as single nucleotide polymorphism (SNP) data, has been widely recognized as useful in prediction of disease risk. However, how to model the genetic data that is often categorical in disease class prediction is complex and challenging. In this paper, we propose a novel class of nonlinear threshold index logistic models to deal with the complex, nonlinear effects of categorical/discrete SNP covariates for Schizophrenia class prediction. A maximum likelihood methodology is suggested to estimate the unknown parameters in the models. Simulation studies demonstrate that the proposed methodology works viably well for moderate-size samples. The suggested approach is therefore …


Differential Expression Of The Nuclear-Encoded Mitochondrial Transcriptome In Pediatric Septic Shock., Scott L Weiss, Natalie Z Cvijanovich, Geoffrey L Allen, Neal J Thomas, Robert J. Freishtat, Nick Anas, +11 Additional Authors Jan 2014

Differential Expression Of The Nuclear-Encoded Mitochondrial Transcriptome In Pediatric Septic Shock., Scott L Weiss, Natalie Z Cvijanovich, Geoffrey L Allen, Neal J Thomas, Robert J. Freishtat, Nick Anas, +11 Additional Authors

Pediatrics Faculty Publications

INTRODUCTION: Increasing evidence supports a role for mitochondrial dysfunction in organ injury and immune dysregulation in sepsis. Although differential expression of mitochondrial genes in blood cells has been reported for several diseases in which bioenergetic failure is a postulated mechanism, there are no data about the blood cell mitochondrial transcriptome in pediatric sepsis.

METHODS: We conducted a focused analysis using a multicenter genome-wide expression database of 180 children ≤ 10 years of age with septic shock and 53 healthy controls. Using total RNA isolated from whole blood within 24 hours of PICU admission for septic shock, we evaluated 296 nuclear-encoded …


Hiv Testing Implementation In Two Urban Cities: Practice, Policy, And Perceived Barriers., Camden J Hallmark, Jennifer Skillicorn, Thomas P Giordano, Jessica A Davila, Marlene Mcneese, Nestor Rocha, Avemaria Smith, Stacey Cooper, Amanda D. Castel Jan 2014

Hiv Testing Implementation In Two Urban Cities: Practice, Policy, And Perceived Barriers., Camden J Hallmark, Jennifer Skillicorn, Thomas P Giordano, Jessica A Davila, Marlene Mcneese, Nestor Rocha, Avemaria Smith, Stacey Cooper, Amanda D. Castel

Epidemiology Faculty Publications

BACKGROUND: Although funding has supported the scale up of routine, opt-out HIV testing in the US, variance in implementation mechanisms and barriers in high-burden jurisdictions remains unknown.

METHODS: We conducted a survey of health care organizations in Washington, DC and Houston/Harris County to determine number of HIV tests completed in 2011, policy and practices associated with HIV testing, funding mechanisms, and reported barriers to testing in each jurisdiction and to compare results between jurisdictions.

RESULTS: In 2012, 43 Houston and 35 DC HIV-testing organizations participated in the survey. Participants represented 85% of Department of Health-supported testers in DC and 90% …


Primary Microrna Processing Assay Reconstituted Using Recombinant Drosha And Dgcr8., Ian Barr, Feng Guo Jan 2014

Primary Microrna Processing Assay Reconstituted Using Recombinant Drosha And Dgcr8., Ian Barr, Feng Guo

Natural Sciences and Mathematics | Faculty Scholarship

In animals, the Microprocessor complex cleaves primary transcripts of microRNAs (pri-miRNAs) to produce precursor microRNAs in the nucleus. The core components of Microprocessor include the Drosha ribonuclease and its RNA-binding partner protein DiGeorge critical region 8 (DGCR8). DGCR8 has been shown to tightly bind an Fe(III) heme cofactor, which activates its pri-miRNA processing activity. Here we describe how to reconstitute pri-miRNA processing using recombinant human Drosha and DGCR8 proteins. In particular, we present the procedures for expressing and purifying DGCR8 as an Fe(III) heme-bound dimer, the most active form of this protein, and for estimating its heme content.


Efficacy And Safety Of Fixed-Dose Combinations Of Aclidinium Bromide/Formoterol Fumarate: The 24-Week, Randomized, Placebo-Controlled Augment Copd Study, Anthony D. D'Urzo, Stephen I. Rennard, Edward M. Kerwin, Victor Mergel, Anne R. Leselbaum, Cynthia F. Caracta, Augment Copd Study Investigators Jan 2014

Efficacy And Safety Of Fixed-Dose Combinations Of Aclidinium Bromide/Formoterol Fumarate: The 24-Week, Randomized, Placebo-Controlled Augment Copd Study, Anthony D. D'Urzo, Stephen I. Rennard, Edward M. Kerwin, Victor Mergel, Anne R. Leselbaum, Cynthia F. Caracta, Augment Copd Study Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone. The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.

METHODS: In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, …


Factors Associated With Diabetes-Related Distress: Implications For Diabetes Self-Management., Jana L. Wardian Phd, Fei Sun Jan 2014

Factors Associated With Diabetes-Related Distress: Implications For Diabetes Self-Management., Jana L. Wardian Phd, Fei Sun

Journal Articles: Hospital Medicine

As 7.8% of the U.S. population is affected by diabetes, health care providers are tasked with providing resources to assist patients toward self-management. Psychosocial issues have an effect on diabetes self-care. Diabetes-related distress is associated with self-management and lower A1C. This cross-sectional study seeks to understand how demographic factors, psychological orientations, support, and diabetes management behaviors predict diabetes-related distress. This study uses data from 267 adults with Type 2 diabetes. The Diabetes Distress Scale (DDS) is a 17-item scale measuring diabetes-related distress including emotional distress, physician-related distress, regimen distress, and interpersonal distress. Hierarchical regression was conducted in four stages. The …


Isprm Discussion Paper: Proposing A Conceptual Description Of Health-Related Rehabilitation Services., Thorsten Meyer, Christoph Gutenbrunner, Carlotte Kiekens, Dimitrios Skempes, John L Melvin, Kuno Schedler, Marta Imamura, Gerold Stucki Jan 2014

Isprm Discussion Paper: Proposing A Conceptual Description Of Health-Related Rehabilitation Services., Thorsten Meyer, Christoph Gutenbrunner, Carlotte Kiekens, Dimitrios Skempes, John L Melvin, Kuno Schedler, Marta Imamura, Gerold Stucki

Department of Rehabilitation Medicine Faculty Papers

There is a need for a comprehensive classification system of health-related rehabilitation services. For conceptual clarity our aim is to provide a health-related conceptual description of the term "rehabilitation service". First, we introduce a common understanding of the term "rehabilitation", based on the current definition in the World Health Organization's World Report on Disability, and a conceptual description of rehabilitation agreed upon by international Physical and Rehabilitation Medicine organizations. From a health perspective, rehabilitation can be regarded as a general health strategy with the aim of enabling persons with health conditions experiencing or likely to experience disability to achieve and …


Health Care Avoidance Among Rural Populations: Results From A Nationally Representative Survey, Angela M. Spleen, Eugene J. Lengerich, Fabian T. Camacho, Robin C. Vanderpool Jan 2014

Health Care Avoidance Among Rural Populations: Results From A Nationally Representative Survey, Angela M. Spleen, Eugene J. Lengerich, Fabian T. Camacho, Robin C. Vanderpool

Health, Behavior & Society Faculty Publications

BACKGROUND: Previous research suggests that certain populations, including rural residents, exhibit health care avoidant behaviors more frequently than other groups. Additionally, health care avoidance is related to sociodemographics, attitudes, social expectations, ability to pay for care, and prior experiences with providers. However, previous studies have been limited to specific geographic areas, particular health conditions, or by analytic methods.

METHODS: The 2008 Health Information Trends Survey (HINTS) was used to estimate the magnitude of health care avoidance nationally and, while controlling for confounding factors, identify groups of people in the United States who are more likely to avoid health care. Chi-square …


The Role Of Positive Alcohol Expectancies In Underage Binge Drinking Among College Students, Nicole M Mcbride, Blake Barrett, Kathleen A. Moore, Lawrence Schonfeld Jan 2014

The Role Of Positive Alcohol Expectancies In Underage Binge Drinking Among College Students, Nicole M Mcbride, Blake Barrett, Kathleen A. Moore, Lawrence Schonfeld

Mental Health Law & Policy Faculty Publications

Objective: This study explored associations between positive alcohol expectancies, and demographics, as well as academic status and binge drinking among underage college students. Participants: A sample of 1,553 underage college students at 3 public universities and 1 college in the Southeast who completed the Core Alcohol and Drug Survey in the Spring 2013 semester. Methods: A series of bivariate analyses and logistic regression models were used to examine associations between demographic and academic status variables as well as positive alcohol expectancies with self-reported binge drinking. Positive alcohol expectancies were examined in multivariable models via 2 factors derived from principal component …


Identification Of Threshold Concepts For Biochemistry, Jennifer Loertscher, David Green, Jennifer E. Lewis, Sara Lin, Vicky Minderhout Jan 2014

Identification Of Threshold Concepts For Biochemistry, Jennifer Loertscher, David Green, Jennifer E. Lewis, Sara Lin, Vicky Minderhout

Chemistry Faculty Publications

Threshold concepts (TCs) are concepts that, when mastered, represent a transformed understanding of a discipline without which the learner cannot progress. We have undertaken a process involving more than 75 faculty members and 50 undergraduate students to identify a working list of TCs for biochemistry. The process of identifying TCs for biochemistry was modeled on extensive work related to TCs across a range of disciplines and included faculty workshops and student interviews. Using an iterative process, we prioritized five concepts on which to focus future development of instructional materials. Broadly defined, the concepts are steady state, biochemical pathway dynamics and …


Potential Role Of Orexin And Sleep Modulation In The Pathogenesis Of Alzheimer's Disease, Jee Hoon Roh, Hong Jiang, Mary Beth Finn, Floy R. Stewart, Thomas E. Mahan, John R. Cirrito, Ashish Heda, B. Joy Snider, Mingjie Li, Masashi Yanagisawa, Luis De Lecea, David M. Holtzman Jan 2014

Potential Role Of Orexin And Sleep Modulation In The Pathogenesis Of Alzheimer's Disease, Jee Hoon Roh, Hong Jiang, Mary Beth Finn, Floy R. Stewart, Thomas E. Mahan, John R. Cirrito, Ashish Heda, B. Joy Snider, Mingjie Li, Masashi Yanagisawa, Luis De Lecea, David M. Holtzman

Open Access Publications

Age-related aggregation of amyloid-β (Aβ) is an upstream pathological event in Alzheimer's disease (AD) pathogenesis, and it disrupts the sleep-wake cycle. The amount of sleep declines with aging and to a greater extent in AD. Poor sleep quality and insufficient amounts of sleep have been noted in humans with preclinical evidence of AD. However, how the amount and quality of sleep affects Aβ aggregation is not yet well understood. Orexins (hypocretins) initiate and maintain wakefulness, and loss of orexin-producing neurons causes narcolepsy. We tried to determine whether orexin release or secondary changes in sleep via orexin modulation affect Aβ pathology. …


Differential Responding By Rhesus Monkeys (Macaca Mulatta) And Humans (Homo Sapiens) To Variable Outcomes In The Assurance Game, Audrey E. Parrish, Sarah F. Brosnan, Bart J. Wilson, Michael J. Beran Jan 2014

Differential Responding By Rhesus Monkeys (Macaca Mulatta) And Humans (Homo Sapiens) To Variable Outcomes In The Assurance Game, Audrey E. Parrish, Sarah F. Brosnan, Bart J. Wilson, Michael J. Beran

Economics Faculty Articles and Research

Behavioral flexibility in how one responds to variable partner play can be examined using economic coordination games in which subjects play against a variety of partners and therefore may need to alter their behavior to produce the highest payoff. But how do we study this behavioral flexibility once players have settled on a response? Here, we investigated how responding by rhesus monkeys (Macaca mulatta) and humans (Homo sapiens) playing a computerized single-player version of a coordination game, the Assurance game, changed as a function of the variable responses (Stag/Hare) generated by multiple simulations (SIMs). We were interested in whether individuals …


Plagiarism Of Ideas. Benjamin Rush And Charles Caldwell--A Student-Mentor Dispute, Charles T. Ambrose Jan 2014

Plagiarism Of Ideas. Benjamin Rush And Charles Caldwell--A Student-Mentor Dispute, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.


A Simplified Score To Quantify Comorbidity In Copd, Nirupama Putcha, Milo A. Puhan, M. Bradley Drummond, Meilan K. Han, Elizabeth A. Regan, Nicola A. Hanania, Carlos H. Martinez, Marilyn Foreman, Surya P. Bhatt, Barry Make, Joe Ramsdell, Dawn L. Demeo, R. Graham Barr, Stephen I. Rennard, Fernando Martinez, Edwin K. Silverman, James Crapo, Robert A. Wise, Nadia N. Hansel Jan 2014

A Simplified Score To Quantify Comorbidity In Copd, Nirupama Putcha, Milo A. Puhan, M. Bradley Drummond, Meilan K. Han, Elizabeth A. Regan, Nicola A. Hanania, Carlos H. Martinez, Marilyn Foreman, Surya P. Bhatt, Barry Make, Joe Ramsdell, Dawn L. Demeo, R. Graham Barr, Stephen I. Rennard, Fernando Martinez, Edwin K. Silverman, James Crapo, Robert A. Wise, Nadia N. Hansel

Journal Articles: Pulmonary & Critical Care Med

IMPORTANCE: Comorbidities are common in COPD, but quantifying their burden is difficult. Currently there is a COPD-specific comorbidity index to predict mortality and another to predict general quality of life. We sought to develop and validate a COPD-specific comorbidity score that reflects comorbidity burden on patient-centered outcomes.

MATERIALS AND METHODS: Using the COPDGene study (GOLD II-IV COPD), we developed comorbidity scores to describe patient-centered outcomes employing three techniques: 1) simple count, 2) weighted score, and 3) weighted score based upon statistical selection procedure. We tested associations, area under the Curve (AUC) and calibration statistics to validate scores internally with outcomes …


A Divisive Shuffling Approach (Vista) For Gene Expression Analysis To Identify Subtypes In Chronic Obstructive Pulmonary Disease, Jörg Menche, Amitabh Sharma, Michael H. Cho, Ruth J. Mayer, Stephen I. Rennard, Bartolome Celli, Bruce E. Miller, Nick Locantore, Ruth Tal-Singer, Soumitra Ghosh, Chris Larminie, Glyn Bradley, John H. Riley, Alvar Agusti, Edwin K. Silverman, Albert-László Barabási Jan 2014

A Divisive Shuffling Approach (Vista) For Gene Expression Analysis To Identify Subtypes In Chronic Obstructive Pulmonary Disease, Jörg Menche, Amitabh Sharma, Michael H. Cho, Ruth J. Mayer, Stephen I. Rennard, Bartolome Celli, Bruce E. Miller, Nick Locantore, Ruth Tal-Singer, Soumitra Ghosh, Chris Larminie, Glyn Bradley, John H. Riley, Alvar Agusti, Edwin K. Silverman, Albert-László Barabási

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: An important step toward understanding the biological mechanisms underlying a complex disease is a refined understanding of its clinical heterogeneity. Relating clinical and molecular differences may allow us to define more specific subtypes of patients that respond differently to therapeutic interventions.

RESULTS: We developed a novel unbiased method called diVIsive Shuffling Approach (VIStA) that identifies subgroups of patients by maximizing the difference in their gene expression patterns. We tested our algorithm on 140 subjects with Chronic Obstructive Pulmonary Disease (COPD) and found four distinct, biologically and clinically meaningful combinations of clinical characteristics that are associated with large gene expression …


Improving Sexual Health In Men With Prostate Cancer: Randomised Controlled Trial Of Exercise And Psychosexual Therapies, Prue Cormie, Suzanne K. Chambers, Robert U. Newton, Robert A. Gardiner, Nigel Spry, Dennis R. Taaffe, David Joseph, M Akhlil Hamid, Peter Chong, David Hughes, Kyra Hamilton, Daniel A. Galvão Jan 2014

Improving Sexual Health In Men With Prostate Cancer: Randomised Controlled Trial Of Exercise And Psychosexual Therapies, Prue Cormie, Suzanne K. Chambers, Robert U. Newton, Robert A. Gardiner, Nigel Spry, Dennis R. Taaffe, David Joseph, M Akhlil Hamid, Peter Chong, David Hughes, Kyra Hamilton, Daniel A. Galvão

Research outputs 2014 to 2021

Background: Despite being a critical survivorship care issue, there is a clear gap in current knowledge of the optimal treatment of sexual dysfunction in men with prostate cancer. There is sound theoretical rationale and emerging evidence that exercise may be an innovative therapy to counteract sexual dysfunction in men with prostate cancer. Furthermore, despite the multidimensional aetiology of sexual dysfunction, there is a paucity of research investigating the efficacy of integrated treatment models. Therefore, the purpose of this study is to: 1) examine the efficacy of exercise as a therapy to aid in the management of sexual dysfunction in men …


Heat-Killed Probiotic Bacteria Differentially Regulate Colonic Epithelial Cell Production Of Human Β-Defensin-2: Dependence On Inflammatory Cytokines., N. Habil, W. Abate, J. Beal, A. D. Foey Jan 2014

Heat-Killed Probiotic Bacteria Differentially Regulate Colonic Epithelial Cell Production Of Human Β-Defensin-2: Dependence On Inflammatory Cytokines., N. Habil, W. Abate, J. Beal, A. D. Foey

School of Biomedical Sciences

The inducible antimicrobial peptide human β-defensin-2 (hBD-2) stimulated by pro-inflammatory cytokines and bacterial products is essential to antipathogen responses of gut epithelial cells. Commensal and probiotic bacteria can augment such mucosal defences. Probiotic use in the treatment of inflammatory bowel disease, however, may have adverse effects, boosting inflammatory responses. The aim of this investigation was to determine the effect of selected probiotic strains on hBD-2 production by epithelial cells induced by pathologically relevant pro-inflammatory cytokines and the role of cytokine modulators in controlling hBD-2. Caco-2 colonic intestinal epithelial cells were pre-incubated with heat-killed probiotics, i.e. Lactobacillus casei strain Shirota (LcS) …


Self-Regulating Smoking And Snacking Through Physical Activity., Hwajung Oh, Adrian H. Taylor Jan 2014

Self-Regulating Smoking And Snacking Through Physical Activity., Hwajung Oh, Adrian H. Taylor

Peninsula Medical School

OBJECTIVE: Emotional snacking contributes to weight gain after smoking cessation. Exercise acutely reduces cravings for cigarettes and snack food. This study examined if different exercise intensities acutely reduces snack and cigarette cravings and attentional bias (AB) to video clips of snacks and cigarettes among abstinent smokers. METHODS: Abstinent smokers (and snackers; N = 23) randomly did 15 mins of moderate and vigorous cycling and a passive control in a cross-over design. Visual initial AB (IAB) and maintained AB (MAB) were assessed pre- and after treatment while watching paired snacking/neutral or smoking/neutral video clips. Desire to snack and smoke were assessed …


The Bacterial Skin Microbiome In Psoriatic Arthritis, An Unexplored Link In Pathogenesis: Challenges And Opportunities Offered By Recent Technological Advances., Madhura Castelino, Stephen Eyre, Mathew Upton, Pauline Ho, Anne Barton Jan 2014

The Bacterial Skin Microbiome In Psoriatic Arthritis, An Unexplored Link In Pathogenesis: Challenges And Opportunities Offered By Recent Technological Advances., Madhura Castelino, Stephen Eyre, Mathew Upton, Pauline Ho, Anne Barton

School of Biomedical Sciences

The resident microbial community, harboured by humans in sites such as the skin and gastrointestinal tract, is enormous, representing a candidate environmental factor affecting susceptibility to complex diseases, where both genetic and environmental risk factors are important. The potential of microorganisms to influence the human immune system is considerable, given their ubiquity. The impact of the host-gene-microbe interaction on the maintenance of health and the development of disease has not yet been assessed robustly in chronic inflammatory conditions. PsA represents a model inflammatory disease to explore the role of the microbiome because skin involvement and overlap with IBD implicates both …


Galleria Mellonella Infection Model Demonstrates High Lethality Of St69 And St127 Uropathogenic E. Coli., Majed F. Alghoribi, Tarek M. Gibreel, Andrew R. Dodgson, Scott A. Beatson, Mathew Upton Jan 2014

Galleria Mellonella Infection Model Demonstrates High Lethality Of St69 And St127 Uropathogenic E. Coli., Majed F. Alghoribi, Tarek M. Gibreel, Andrew R. Dodgson, Scott A. Beatson, Mathew Upton

School of Biomedical Sciences

Galleria mellonella larvae are an alternative in vivo model for investigating bacterial pathogenicity. Here, we examined the pathogenicity of 71 isolates from five leading uropathogenic E. coli (UPEC) lineages using G. mellonella larvae. Larvae were challenged with a range of inoculum doses to determine the 50% lethal dose (LD50) and for analysis of survival outcome using Kaplan-Meier plots. Virulence was correlated with carriage of a panel of 29 virulence factors (VF). Larvae inoculated with ST69 and ST127 isolates (10(4) colony-forming units/larvae) showed significantly higher mortality rates than those infected with ST73, ST95 and ST131 isolates, killing 50% of the larvae …


The Complete Genome Sequence Of Escherichia Coli Ec958: A High Quality Reference Sequence For The Globally Disseminated Multidrug Resistant E. Coli O25b:H4-St131 Clone., Brian M. Forde, Zakour Nl Ben, Mitchell Stanton-Cook, Minh Duy Phan, Makrina Totsika, Kate M. Peters, Kok Gan Chan, Mark A. Schembri, Mathew Upton, Scott A. Beatson Jan 2014

The Complete Genome Sequence Of Escherichia Coli Ec958: A High Quality Reference Sequence For The Globally Disseminated Multidrug Resistant E. Coli O25b:H4-St131 Clone., Brian M. Forde, Zakour Nl Ben, Mitchell Stanton-Cook, Minh Duy Phan, Makrina Totsika, Kate M. Peters, Kok Gan Chan, Mark A. Schembri, Mathew Upton, Scott A. Beatson

School of Biomedical Sciences

Escherichia coli ST131 is now recognised as a leading contributor to urinary tract and bloodstream infections in both community and clinical settings. Here we present the complete, annotated genome of E. coli EC958, which was isolated from the urine of a patient presenting with a urinary tract infection in the Northwest region of England and represents the most well characterised ST131 strain. Sequencing was carried out using the Pacific Biosciences platform, which provided sufficient depth and read-length to produce a complete genome without the need for other technologies. The discovery of spurious contigs within the assembly that correspond to site-specific …


Qualified Doctor And Medical Students' Use Of Resources For Accessing Information: What Is Used And Why?, Nicola Brennan, Sarah Edwards, Narcie Kelly, Alice Miller, Lucy Harrower, Karen Mattick Jan 2014

Qualified Doctor And Medical Students' Use Of Resources For Accessing Information: What Is Used And Why?, Nicola Brennan, Sarah Edwards, Narcie Kelly, Alice Miller, Lucy Harrower, Karen Mattick

Peninsula Medical School

BACKGROUND: Learning to access information using resources such as books and search engines is an important and fast changing challenge for doctors and medical students. Many resources exist to support evidence-based clinical decision-making, but a wide range of factors influences their use. OBJECTIVE: To explore qualified doctor and medical students' use of resources for accessing information and to determine what is used and why. METHODS: A stratified sample of 46 participants was recruited in Devon, UK. Participants kept a self-report diary of resources used over a week. The diaries were then used to stimulate recall within a semi-structured interview. Diary …