Digital Commons Network^™

Randomized Study Of The Safety, Pharmacokinetics, And Bronchodilatory Efficacy Of A Proprietary Glycopyrronium Metered-Dose Inhaler In Study Patients With Chronic Obstructive Pulmonary Disease, Stephen I. Rennard, Charles Fogarty, Colin Reisner, Carlos Fernandez, Tracy Fischer, Michael Golden, Earl St Rose, Patrick Darken, Gregory Tardie, Chadwick Orevillo

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Bronchodilator medications are central to the symptomatic management of chronic obstructive pulmonary disease (COPD). Metered-dose inhalers (MDIs) are the most commonly used devices to deliver treatment to patients with COPD and asthma, comprising approximately 70% of bronchodilator prescriptions. Proprietary porous-particle technology permits the formulation of long-acting muscarinic antagonists, long-acting β2-agonists, and a combination of both in hydrofluoroalkane (HFA) MDIs, providing a solution to formulation challenges inherent to the development of HFA MDIs, which have contributed to the development of dry-powder inhalers.

METHODS: In this randomized, double-blind, 4-period, 6-treatment, placebo- and active-controlled, multicenter, crossover study, 4 ascending single doses of …

Detection Of Temporal Lobe Epilepsy Using Support Vector Machines In Multi-Parametric Quantitative Mr Imaging., Diego Cantor-Rivera, Ali R Khan, Maged Goubran, Seyed M Mirsattari, Terry M Peters

Robarts Imaging Publications

The detection of MRI abnormalities that can be associated to seizures in the study of temporal lobe epilepsy (TLE) is a challenging task. In many cases, patients with a record of epileptic activity do not present any discernible MRI findings. In this domain, we propose a method that combines quantitative relaxometry and diffusion tensor imaging (DTI) with support vector machines (SVM) aiming to improve TLE detection. The main contribution of this work is two-fold: on one hand, the feature selection process, principal component analysis (PCA) transformations of the feature space, and SVM parameterization are analyzed as factors constituting a classification …

Rule-Based Category Learning In Children: The Role Of Age And Executive Functioning., Rahel Rabi, John Paul Minda

Brain and Mind Institute Researchers' Publications

Rule-based category learning was examined in 4-11 year-olds and adults. Participants were asked to learn a set of novel perceptual categories in a classification learning task. Categorization performance improved with age, with younger children showing the strongest rule-based deficit relative to older children and adults. Model-based analyses provided insight regarding the type of strategy being used to solve the categorization task, demonstrating that the use of the task appropriate strategy increased with age. When children and adults who identified the correct categorization rule were compared, the performance deficit was no longer evident. Executive functions were also measured. While both working …

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.

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 …

Hyperglycemia-Induced Diaphragm Weakness Is Mediated By Oxidative Stress, Leigh Ann Callahan, Gerald S. Supinski

Internal Medicine Faculty Publications

INTRODUCTION: A major consequence of ICU-acquired weakness (ICUAW) is diaphragm weakness, which prolongs the duration of mechanical ventilation. Hyperglycemia (HG) is a risk factor for ICUAW. However, the mechanisms underlying HG-induced respiratory muscle weakness are not known. Excessive reactive oxygen species (ROS) injure multiple tissues during HG, but only one study suggests that excessive ROS generation may be linked to HG-induced diaphragm weakness. We hypothesized that HG-induced diaphragm dysfunction is mediated by excessive superoxide generation and that administration of a specific superoxide scavenger, polyethylene glycol superoxide dismutase (PEG-SOD), would ameliorate these effects.

METHODS: HG was induced in rats using streptozotocin …

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 …

Induction Of A Type I Interferon Signature In Normal Human Monocytes By Gadolinium-Based Contrast Agents: Comparison Of Linear And Macrocyclic Agents., Peter J. Wermuth, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

The gadolinium-based contrast agent (GdBCA) Omniscan activates human macrophages through Toll-like receptor (TLR)-4 and TLR-7 signalling. To explore the mechanisms responsible we compared the ability of linear and macrocyclic GdBCA to induce a type I interferon signature and a proinflammatory/profibrotic phenotype in normal human monocytes in vitro. Expression of genes associated with type I interferon signalling and inflammation and production of their corresponding proteins were determined. Both linear and macrocyclic GdBCA stimulated expression of multiple type I interferon-regulated genes and the expression of numerous chemokines, cytokines and growth factors in normal human peripheral blood monocytes. There was no correlation between …

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.

Identity And Cultural Competency : Critical Race And Postmodern Perspective, Nathan N. Orians

Theses, Dissertations, and Projects

This theoretical thesis explores how racism is unavoidable in social work because of the weight of systemic influences. It looks at how the use of cultural competency could be unethical, by using both critical race and postmodern theory. The use of critical race theory in thinking about cultural competency seems to allow for a passive acceptance of a system which has continued to be un-critical of its racist origins and assumptions. Furthermore the enacting of cultural competency through a postmodern view could at times be considered a micro aggression and as such unethical. This paper hopes that by acknowledging that …

Planning-Related Motor Processes Underlie Mental Practice And Imitation Learning., Patric Bach, Bassem Khalaf Allami, Mike Tucker, Rob Ellis

School of Psychology

It is still controversial whether mental practice-the internal rehearsal of movements to improve later performance-relies on processes engaged during physical motor performance and, if so, which processes these are. We report data from 5 experiments, in which participants mentally practiced complex rhythms with either feet or hands while using the same or different body parts to respond to unrelated sounds. We found that responses were impaired for those body parts that were concurrently used in mental practice, suggesting a binding of body-part-specific motor processes to action plans. This result was found when participants mentally trained to memorize the rhythms, to …

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 …

English-Learning One- To Two-Year-Olds Do Not Show A Consonant Bias In Word Learning., Caroline Floccia, Thierry Nazzi, Luche C Delle, Silvana Poltrock, Jeremy Goslin

School of Psychology

Following the proposal that consonants are more involved than vowels in coding the lexicon (Nespor, Peña & Mehler, 2003), an early lexical consonant bias was found from age 1;2 in French but an equal sensitivity to consonants and vowels from 1;0 to 2;0 in English. As different tasks were used in French and English, we sought to clarify this ambiguity by using an interactive word-learning study similar to that used in French, with British-English-learning toddlers aged 1;4 and 1;11. Children were taught two CVC labels differing on either a consonant or vowel and tested on their pairing of a third …

Evaluating The Application Of Research-Based Guidance To The Design Of An Emergency Preparedness Leaflet., E. Hellier, J. Edworthy, L. Newbold, K. Titchener, M. Tucker, E. Gabe-Thomas

School of Psychology

UNLABELLED: Guidelines for the design of emergency communications were derived from primary research and interrogation of the literature. The guidelines were used to re-design a nuclear emergency preparedness leaflet routinely distributed to households in the local area. Pre-test measures of memory for, and self-reported understanding of, nuclear safety information were collected. The findings revealed high levels of non-receipt of the leaflet, and among those who did receive it, memory for safety advice was poor. Subjective evaluations of the trial leaflet suggested that it was preferred and judged easier to understand than the original. Objective measures of memory for the two …

A Biological, Latent Variable Model Of Health (Earlybird 68)., Michael E. Hyland, Alison N. Jeffery, Terence J. Wilkin

School of Psychology

OBJECTIVE: To determine whether factor analysis of a set of health-related biomarkers provides evidence of an underlying common dimension of variation, and to explore the relationship between this dimension of variation with positive and negative affect. METHOD: Twelve health-related metabolic, immune and body-composition biomarkers at ages 5, 7, 9, 11, 14 and 16years were obtained from the EarlyBird longitudinal cohort of 347 children and supplemented by positive affect (PA) and negative affect (NA) measured at age 16years. RESULTS: At each age, principal factor analysis revealed that nine of the 12 biomarkers consistently loaded on the first extracted factor, accounting for …

Meiotic Drive Impacts Expression And Evolution Of X-Linked Genes In Stalk-Eyed Flies, Josephine A. Reinhardt, Cara L. Brand, Kimberly A. Paczolt, Philip M. Johns, Richard H. Baker, Gerald S. Wilkinson

Biology

Although sex chromosome meiotic drive has been observed in a variety of species for over 50 years, the genes causing drive are only known in a few cases, and none of these cases cause distorted sex-ratios in nature. In stalk-eyed flies (Teleopsis dalmanni), driving X chromosomes are commonly found at frequencies approaching 30% in the wild, but the genetic basis of drive has remained elusive due to reduced recombination between driving and non-driving X chromosomes. Here, we used RNAseq to identify transcripts that are differentially expressed between males carrying either a driving X (X SR ) or a standard X …

E5501: Phase Ii Study Of Topotecan Sequenced With Etoposide/Cisplatin, And Irinotecan/Cisplatin Sequenced With Etoposide For Extensive-Stage Small-Cell Lung Cancer., Taofeek K. Owonikoko, Joseph Aisner, Xin Victoria Wang, Suzanne E. Dahlberg, Eric H. Rubin, Suresh S. Ramalingam, Murugesan Gounder, Paul Gregory Rausch, Rita S. Axelrod, Md, Joan H. Schiller

Department of Medical Oncology Faculty Papers

PURPOSE: Sequence-dependent improved efficacy of topoisomerase I followed by topoisomerase 2 inhibitors was assessed in a randomized phase II study in extensive-stage small-cell lung cancer (SCLC).

METHODS: Patients with previously untreated extensive-stage SCLC with measurable disease, ECOG performance status of 0-3 and stable brain metastases were eligible. Arm A consisted of topotecan (0.75 mg/m(2)) on days 1, 2 and 3, etoposide (70 mg/m(2)) and cisplatin (20 mg/m(2)) (PET) on days 8, 9 and 10 in a 3-week cycle. Arm B consisted of irinotecan (50 mg/m(2)) and cisplatin (20 mg/m(2)) on days 1 and 8 followed by etoposide (85 mg/m(2) PO …

Using Forced Choice To Test Belief Bias In Syllogistic Reasoning., Dries Trippas, Michael F. Verde, Simon J. Handley

School of Psychology

In deductive reasoning, believable conclusions are more likely to be accepted regardless of their validity. Although many theories argue that this belief bias reflects a change in the quality of reasoning, distinguishing qualitative changes from simple response biases can be difficult (Dube, Rotello, & Heit, 2010). We introduced a novel procedure that controls for response bias. In Experiments 1 and 2, the task required judging which of two simultaneously presented syllogisms was valid. Surprisingly, there was no evidence for belief bias with this forced choice procedure. In Experiment 3, the procedure was modified so that only one set of premises …

Mediofrontal Event-Related Potentials In Response To Positive, Negative And Unsigned Prediction Errors., Thomas D. Sambrook, Jeremy Goslin

School of Psychology

Reinforcement learning models make use of reward prediction errors (RPEs), the difference between an expected and obtained reward. There is evidence that the brain computes RPEs, but an outstanding question is whether positive RPEs ("better than expected") and negative RPEs ("worse than expected") are represented in a single integrated system. An electrophysiological component, feedback related negativity, has been claimed to encode an RPE but its relative sensitivity to the utility of positive and negative RPEs remains unclear. This study explored the question by varying the utility of positive and negative RPEs in a design that controlled for other closely related …

Learning To Pronounce First Words In Three Languages: An Investigation Of Caregiver And Infant Behavior Using A Computational Model Of An Infant., Ian S. Howard, Piers Messum

School of Engineering, Computing and Mathematics

Words are made up of speech sounds. Almost all accounts of child speech development assume that children learn the pronunciation of first language (L1) speech sounds by imitation, most claiming that the child performs some kind of auditory matching to the elements of ambient speech. However, there is evidence to support an alternative account and we investigate the non-imitative child behavior and well-attested caregiver behavior that this account posits using Elija, a computational model of an infant. Through unsupervised active learning, Elija began by discovering motor patterns, which produced sounds. In separate interaction experiments, native speakers of English, French and …

Contourlet Textual Features: Improving The Diagnosis Of Solitary Pulmonary Nodules In Two Dimensional Ct Images, Jingjing Wang, Tao Sun, Ni Gao, Desmond D. Menon, Yanxia Luo, Qi Gao, Xia Li, Wei Wang, Huiping Zhu, Pingxin Lv, Zhigang Liang, Lixin Tao, Xiangtong Liu, Xiuhua Guo

Research outputs 2014 to 2021

Materials and Methods: A total of 6,299 CT images were acquired from 336 patients, with 1,454 benign pulmonary nodule images from 84 patients (50 male, 34 female) and 4,845 malignant from 252 patients (150 male, 102 female). Further to this, nineteen patient information categories, which included seven demographic parameters and twelve morphological features, were also collected. A contourlet was used to extract fourteen types of textural features. These were then used to establish three support vector machine models. One comprised a database constructed of nineteen collected patient information categories, another included contourlet textural features and the third one contained both …

Predictors Of Grandparental Investment Decisions In Contemporary Europe: Biological Relatedness And Beyond, David A. Coall, Sonja Hilbrand, Ralph Hertwig

Research outputs 2014 to 2021

Across human cultures, grandparents make a valued contribution to the health of their families and communities. Moreover, evidence is gathering that grandparents have a positive impact on the development of grandchildren in contemporary industrialized societies. A broad range of factors that influence the likelihood grandparents will invest in their grandchildren has been explored by disciplines as diverse as sociology, economics, psychology and evolutionary biology. To progress toward an encompassing framework, this study will include biological relatedness between grandparents and grandchildren, a factor central to some discipline's theoretical frameworks (e.g., evolutionary biology), next to a wide range of other factors in …

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 …

An Anemia Of Alzheimer's Disease, N G. Faux, A Rembach, J Wiley, K A. Ellis, D Ames, C J. Fowler, Ralph N. Martins, K K. Pertile, R L. Rumble, B Trounson, C L. Masters, A I. Bush

Research outputs 2014 to 2021

Lower hemoglobin is associated with cognitive impairment and Alzheimer's disease (AD). Since brain iron homeostasis is perturbed in AD, we investigated whether this is peripherally reflected in the hematological and related blood chemistry values from the Australian Imaging Biomarker and Lifestyle (AIBL) study (a community-based, cross-sectional cohort comprising 768 healthy controls (HC), 133 participants with mild cognitive impairment (MCI) and 211 participants with AD). We found that individuals with AD had significantly lower hemoglobin, mean cell hemoglobin concentrations, packed cell volume and higher erythrocyte sedimentation rates (adjusted for age, gender, APOE-ε4 and site). In AD, plasma iron, transferrin, transferrin saturation …

A Comparison Of Aphasia Therapy Outcomes Before And After A Very Early Rehabilitation Programme Following Stroke, Erin Godecke, Natalie A. Ciccone, Andrew S. Granger, Tapan Rai, Deborah West, Angela Cream, Jade Cartwright, Graeme J. Hankey

Research outputs 2014 to 2021

Background Very early aphasia rehabilitation studies have shown mixed results. Differences in therapy intensity and therapy type contribute significantly to the equivocal results. Aims To compare a standardized, prescribed very early aphasia therapy regimen with a historical usual care control group at therapy completion (4-5 weeks post-stroke) and again at follow-up (6 months). Methods & Procedures This study compared two cohorts from successive studies conducted in four Australian acute/sub-acute hospitals. The studies had near identical recruitment, blinded assessment and data-collection protocols. The Very Early Rehabilitation (VER) cohort (N = 20) had mild-severe aphasia and received up to 20 1-h sessions …

The Reliability Of An Adolescent Dietary Pattern Identified Using Reduced-Rank Regression: Comparison Of A Ffq And 3 D Food Record, Geeta Appannah, Gerda K. Pot, Therese A. O'Sullivan, Wendy H. Oddy, Susan A. Jebb, Gina L. Ambrosini

Research outputs 2014 to 2021

Despite the increasing use of dietary patterns (DP) to study diet and health outcomes, relatively few studies have examined the reliability of DP using different dietary assessment methods. Reduced-rank regression (RRR) is an emerging statistical method that incorporates a priori information to characterise DP related to specific outcomes of interest. The aim of the present study was to compare DP identified using the RRR method in a FFQ with those in a 3 d food record (FR). Participants were 783 adolescents from the Western Australian Pregnancy (Raine) Cohort Study who completed both a FFQ and FR at 14 years of …

Joint Effect Of Multiple Common Snps Predicts Melanoma Susceptibility, Shenying Fang, Jiali Han, Mingfeng Zhang, Li-E Wang, Qingyi Wei, Christopher I. Amos, Jeffrey E. Lee

Dartmouth Scholarship

Single genetic variants discovered so far have been only weakly associated with melanoma. This study aims to use multiple single nucleotide polymorphisms (SNPs) jointly to obtain a larger genetic effect and to improve the predictive value of a conventional phenotypic model. We analyzed 11 SNPs that were associated with melanoma risk in previous studies and were genotyped in MD Anderson Cancer Center (MDACC) and Harvard Medical School investigations. Participants with ≥15 risk alleles were 5-fold more likely to have melanoma compared to those carrying ≤6. Compared to a model using the most significant single variant rs12913832, the increase in predictive …

Contrast Negation Differentiates Visual Pathways Underlying Dynamic And Invariant Facial Processing, Pamela M. Pallett, Ming Meng

Dartmouth Scholarship

Abstract Bruce and Young (1986) proposed a model for face processing that begins with structural encoding, followed by a split into two processing streams: one for the dynamic aspects of the face (e.g., facial expressions of emotion) and the other for the invariant aspects of the face (e.g., gender, identity). Yet how this is accomplished remains unclear. Here, we took a psychophysical approach using contrast negation to test the Bruce and Young model. Previous research suggests that contrast negation impairs processing of invariant features (e.g., gender) but not dynamic features (e.g., expression). In our first experiment, participants discriminated differences in …

Adiponectin Inhibits Oxidative/Nitrative Stress During Myocardial Ischemia And Reperfusion Via Pka Signaling., Yanqing Zhang, Xiao-Liang Wang, Jianli Zhao, Ya-Jing Wang, Wayne Bond Lau, Yue-Xing Yuan, Er-He Gao, Walter J. Koch, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

The cardioprotective effects of adiponectin (APN) against myocardial ischemia/reperfusion (MI/R) injury are well known. However, comprehension of the mechanisms mediating intracellular APN signaling remains incomplete. We recently demonstrate the antioxidant/antinitrative effects of APN are not dependent on AMPK. Protein kinase A (PKA) has been previously shown to be activated by APN, with uncertain relevance to APN cardiac protection. The current study determined whether the antioxidative/antinitrative effect of APN is mediated by PKA. Administration of APN (2 μg/g) 10 min before reperfusion significantly enhanced cardiac PKA activity, reduced oxidative stress, and decreased infarct size. Knockdown of cardiac PKA expression (PKA-KD) by …

Targeting Inflammation Using Salsalate In Patients With Type 2 Diabetes: Effects On Flow-Mediated Dilation (Tinsal-Fmd)., Allison B Goldfine, J Stewart Buck, Cyrus Desouza, Vivian Fonseca, Yii-Der Ida Chen, Steven E Shoelson, Kathleen A. Jablonski, Mark A Creager, The Tinsal-Fmd Team

GW Biostatistics Center

OBJECTIVE: To test whether inhibiting inflammation with salsalate improves endothelial function in patients with type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS: We conducted an ancillary study to the National Institutes of Health-sponsored, multicenter, randomized, double-masked, placebo-controlled trial evaluating the safety and efficacy of salsalate in targeting inflammation to improve glycemia in patients with T2D. Flow-mediated, endothelium-dependent dilation (FMD) and endothelium-independent, nitroglycerin-mediated dilation (NMD) of the brachial artery were assessed at baseline and 3 and 6 months following randomization to either salsalate 3.5 g/day or placebo. The primary end point was change in FMD at 6 months.

RESULTS: A total …