Anatomy Commons^™

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

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 …

Acoustic Divergence In The Rut Vocalizations Of Persian And European Fallow Deer, J. B. Stachowicz, E. Vannoni, B. J. Pitcher, Elodie F. Briefer, E. Geffen, A. G. Mcelligott

Veterinary Science and Medicine Collection

We conducted a study of the male rut vocalizations (groans) of two closely related species, Persian and European fallow deer. Persian fallow deer are endangered, restricted to Iran and Israel, and their rut vocalizations have never been studied. By contrast, European fallow deer are one of the most common deer species in the world, and have been the subject of numerous detailed studies. Persian bucks are approximately 16% larger than European bucks, and this can have important implications for vocalizations. Persian bucks were recorded in Israel, and European bucks were recorded in the UK and Ireland. We measured temporal, fundamental …

Comparison Of Serum, Edta Plasma And P100 Plasma For Luminex-Based Biomarker Multiplex Assays In Patients With Chronic Obstructive Pulmonary Disease In The Spiromics Study, Wanda K. O'Neal, Wayne Anderson, Patricia V. Basta, Elizabeth E. Carretta, Claire M. Doerschuk, R. Graham Barr, Eugene R. Bleecker, Stephanie A. Christenson, Jeffrey L. Curtis, Meilan K. Han, Nadia N. Hansel, Richard E. Kanner, Eric C. Kleerup, Fernando J. Martinez, Bruce E. Miller, Stephen P. Peters, Stephen I. Rennard, Mary Beth Scholand, Ruth Tal-Singer, Prescott G. Woodruff, David J. Couper, Sonia M. Davis, Spiromics Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: As a part of the longitudinal Chronic Obstructive Pulmonary Disease (COPD) study, Subpopulations and Intermediate Outcome Measures in COPD study (SPIROMICS), blood samples are being collected from 3200 subjects with the goal of identifying blood biomarkers for sub-phenotyping patients and predicting disease progression. To determine the most reliable sample type for measuring specific blood analytes in the cohort, a pilot study was performed from a subset of 24 subjects comparing serum, Ethylenediaminetetraacetic acid (EDTA) plasma, and EDTA plasma with proteinase inhibitors (P100).

METHODS: 105 analytes, chosen for potential relevance to COPD, arranged in 12 multiplex and one simplex platform …

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 …

The Helminthological Society Of Washington 2013 Anniversary Award: Larry S. Roberts, Sherman S. Hendrix

Center for Brain, Biology, and Behavior: Faculty Publications

Dr. Roberts was born in the great state of Texas, and much of his early life is murky, but snakes are often mentioned. Larry received his Bachelor’s degree at Southern Methodist University; his Master of Science at the University of Illinois; and his Doctorate in the Department of Pathobiology at the Johns Hopkins School of Hygiene and Public Health. Larry’s doctoral research, published in Experimental Parasitology, documented the early development and crowding effect of the tapeworm, Hymenolepis diminuta, in the rat small intestine. His publication on this subject opened the door to the golden age of cestode physiology and biochemistry …

Can Helmet Design Reduce The Risk Of Concussion In Football?, Steven Rowson, Stefan M. Duma, Richard M. Greenwald, Jonathan Beckwith, Jeffrey J. Chu, Kevin M. Guskiewicz, Jason P. Mihalik, Joe Crisco, Bethany J. Wilcox, Thomas W. Mcallister, Arthur C. Maerlender, Steven P. Broglio, Brock Schnebel, Scott Anderson, P. Gunnar Brolinson

Center for Brain, Biology, and Behavior: Faculty Publications

Of all sports, football accounts for the highest incidence of concussion in the US due to the large number of athletes participating and the nature of the sport. While there is general agreement that concussion incidence can be reduced through rule changes and teaching proper tackling technique, there remains debate as to whether helmet design may also reduce the incidence of concussion. A retrospective analysis was performed of head impact data collected from 1833 collegiate football players who were instrumented with helmet-mounted accelerometer arrays for games and practices. Data were collected between 2005 and 2010 from 8 collegiate football teams: …

Winning And Losing: Differences In Reward And Punishment Sensitivity Between Smokers And Nonsmokers, Laura E. Martin, Lisa S. Cox, William M. Brooks, Cary R. Savage

Center for Brain, Biology, and Behavior: Faculty Publications

Background: Smokers show increased brain activation in reward processing regions in response to smoking-related cues, yet few studies have examined secondary rewards not associated with smoking (i.e., money). Inconsistencies exist in the studies that do examine secondary rewards with some studies showing increased brain activation in reward processing brain regions, while others show decreased activation or no difference in activation between smokers and nonsmokers. Aims: The goal of the current study is to see if smokers process the evaluation and delivery of equally salient real world rewards similarly or differently than nonsmokers. Methods: The current study employed functional magnetic resonance …

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

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. …

A Mitochondrial Rnai Screen Defines Cellular Bioenergetic Determinants And Identifies An Adenylate Kinase As A Key Regulator Of Atp Levels, Nathan J. Lanning, Brendan D. Looyenga, Audra L. Kauffman, Natalie M. Niemi

University Faculty Publications and Creative Works

Altered cellular bioenergetics and mitochondrial function are major features of several diseases, including cancer, diabetes, and neurodegenerative disorders. Given this important link to human health, we sought to define proteins within mitochondria that are critical for maintaining homeostatic ATP levels. We screened an RNAi library targeting >1,000 nuclear-encoded genes whose protein products localize to the mitochondria in multiple metabolic conditions in order to examine their effects on cellular ATP levels. We identified a mechanism by which electron transport chain (ETC) perturbation under glycolytic conditions increased ATP production through enhanced glycolytic flux, thereby highlighting the cellular potential for metabolic plasticity. Additionally, …

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, …

Posterior Mediastinal Branchial Cleft Cyst: An Unusual Site, Abdul Rashid, Vaqas Ahmad, Saqib Qazi, Abdul Gaffar Billoo, Sajida Rashid, Ali Faisal Saleem

Department of Paediatrics and Child Health

A two and a half year old Kenyan girl presented with recurrent chest infections and difficulty in swallowing. Her clinical and laboratory workup was suggestive of lower respiratory tract infection for which she received a course of antibiotics; however, she remains symptomatic after the management of her suspected diagnosis. Therefore, further radiological workup including a chest CT scan and barium study were performed. This showed a homogeneous mass surrounded by ascending and descending aorta in the posterior mediastinum that was compressing the middle esophagus. She had a posterolateral thoracotomy which revealed a cystic mass with smooth surfaces (5x5 cm) in …

Early Recovery In Post Varicella Transverse Myelitis, Prem Chand, Shahnaz Brahim, Syed Sohail Zaidi, Nida Amjad

Department of Paediatrics and Child Health

A two and a half year old Kenyan girl presented with recurrent chest infections and difficulty in swallowing. Her clinical and laboratory workup was suggestive of lower respiratory tract infection for which she received a course of antibiotics; however, she remains symptomatic after the management of her suspected diagnosis. Therefore, further radiological workup including a chest CT scan and barium study were performed. This showed a homogeneous mass surrounded by ascending and descending aorta in the posterior mediastinum that was compressing the middle esophagus. She had a posterolateral thoracotomy which revealed a cystic mass with smooth surfaces (5 x 5 …

The Bivariate Erlang And Its Application In Modeling Recurrence Times Of Kidney Dialysis Data, Norou Diawara, S.H. Sathish Indika, Melva Grant, Edgard M. Maboudou-Tchao

Mathematics & Statistics Faculty Publications

Recent advances in computer modeling allows us to find closer fits to data. Our emphasis is on the interdependence between occurrence at kidney dialysis. The interdependence between kidney dialysis occurrences is modelled by a bivariate exponential that we propose in this article. The application is shown on the McGilchrist and Aisbett kidney data set with the use of the exponential distribution. The proposed bivariate exponential model has exponential marginal densities, correlated via a latent random variables and with finite probability of simultaneous occurrence. Extension of the model to a bivariate Erlang type distribution with same shape parameter is presented.

Leptin Regulates Cd16 Expression On Human Monocytes In A Sex-Specific Manner, Joseph G. Cannon, Gyanendra Sharma, Gloria Sloan, Christiana Dimitropoulou, R. Randall Baker, Andrew Mazzoli, Barbara Kraj, Anthony Mulloy, Miriam Cortez-Cooper

School of Medical Diagnostics & Translational Sciences Publications

Fat mass is linked mechanistically to the cardiovascular system through leptin, a 16 kDa protein produced primarily by adipocytes. In addition to increasing blood pressure via hypothalamic-sympathetic pathways, leptin stimulates monocyte migration, cytokine secretion, and other functions that contribute to atherosclerotic plaque development. These functions are also characteristics of CD16-positive monocytes that have been implicated in the clinical progression of atherosclerosis. This investigation sought to determine if leptin promoted the development of such CD16-positive monocytes. Cells from 45 healthy men and women with age ranging from 20 to 59 years were analyzed. Circulating numbers of CD14++16++ monocytes, which are primary …

Osteoarthritis And Articular Cartilage: Biomechanics And Novel Treatment Paradigms, Ray Marks

Publications and Research

Background: Osteoarthritis is a widespread highly painful disabling age-related disease with no known cure. Although novel strategies for ameliorating osteoarthritic damage abound, it is likely that none will be successful over time if the entire spectrum of the disease and the effects of joint biomechanics on joint tissues are not carefully considered.

Objectives: 1) To detail the structure of healthy articular cartilage, the key tissue affected by osteoarthritis. 2) To detail what aspects of cartilage damage best characterize osteoarthritis. 3) To consider the role of biomechanical factors in developing solutions to treat osteoarthritic joint damage. Methods: Literature sources from 1980 …

Delivery Of Interleukin-15 To B16 Melanoma By Electroporation Leads To Tumor Regression And Long-Term Survival, Bernadette Marrero, Shawna Shirley, Richard Heller

Bioelectrics Publications

Electroporation (EP) is a method used to physically deliver therapeutic molecules such as plasmid DNA directly to tissues. It has been used safely and successfully in clinical studies and preclinical cancer models to deliver genes to a variety of tissues. In cancer research cytokine therapy is emerging as a promising tool that can be used to boost the host response to tumor antigens. The delivery of cytokines as recombinant proteins can result in toxicity and other adverse effects; however the delivery of cytokine genes using EP has been shown to be safe and effective. Interleukin 15 (IL-15) is a cytokine …

Temporal Modulation Of Plasma Species In Atmospheric Dielectric Barrier Discharges, Aijun Yang, Xiaohua Wang, Dingxin Liu, Mingzhe Rong, Michael G. Kong

Bioelectrics Publications

The atmospheric pressure dielectric barrier discharge in helium is a pulsed discharge in nature and the moment of maximum species densities is almost consistent with peak discharge current density. In this paper, a one-dimensional fluid model is used to investigate the temporal structure of plasma species in an atmospheric He-N₂ dielectric barrier discharge (DBD). It is demonstrated that there exist microsecond delays of the moments of the maximum electron and ion densities from the peak of discharge current density. These time delays are caused by a competition between the electron impact and Penning ionizations, modulated by the N_{2 …}

Pain Assessment And Possible Mechanism Of Delayed Onset Muscle Soreness, Wing Yin Lau

Theses: Doctorates and Masters

Muscle pain is felt during exercise or daily activities for several days after performing unaccustomed exercise, which is referred to as delayed onset muscle soreness (DOMS). Many people experience DOMS, but its underlying mechanisms are not fully understood. One of the challenges in the investigation of DOMS is its subjective nature, which makes the assessment ambiguous, thus establishing a standardised protocol is necessary. The present thesis scrutinised muscle pain assessments (Study 1, Study 2), developed a new assessment of muscle pain focusing on muscle fascia (Study 3), and investigated why DOMS is reduced after the second than the first bout …