Showing papers by "University of Western Ontario published in 2002"

Initial sequencing and comparative analysis of the mouse genome.

Abstract: The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.

Dissemination and growth of cancer cells in metastatic sites

Abstract: Metastases, rather than primary tumours, are responsible for most cancer deaths. To prevent these deaths, improved ways to treat metastatic disease are needed. Blood flow and other mechanical factors influence the delivery of cancer cells to specific organs, whereas molecular interactions between the cancer cells and the new organ influence the probability that the cells will grow there. Inhibition of the growth of metastases in secondary sites offers a promising approach for cancer therapy.

A Randomized Trial of Arthroscopic Surgery for Osteoarthritis of the Knee

Abstract: Background The efficacy of arthroscopic surgery for the treatment of osteoarthritis of the knee is unknown. Methods We conducted a single-center, randomized, controlled trial of arthroscopic surgery in patients with moderate-to-severe osteoarthritis of the knee. Patients were randomly assigned to surgical lavage and arthroscopic debridement together with optimized physical and medical therapy or to treatment with physical and medical therapy alone. The primary outcome was the total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (range, 0 to 2400; higher scores indicate more severe symptoms) at 2 years of follow-up. Secondary outcomes included the Short Form-36 (SF-36) Physical Component Summary score (range, 0 to 100; higher scores indicate better quality of life). Results Of the 92 patients assigned to surgery, 6 did not undergo surgery. Of the 86 patients assigned to control treatment, all received only physical and medical therapy. After 2 years, the mean (±SD) WOMAC score for the surgery group was 874±624, as compared with 897±583 for the control group (absolute difference [surgery-group score minus control-group score], −23±605; 95% confidence interval [CI], −208 to 161; P = 0.22 after adjustment for baseline score and grade of severity). The SF-36 Physical Component Summary scores were 37.0±11.4 and 37.2±10.6, respectively (absolute difference, −0.2±11.1; 95% CI, −3.6 to 3.2; P = 0.93). Analyses of WOMAC scores at interim visits and other secondary outcomes also failed to show superiority of surgery.

Organizational citizenship behavior and workplace deviance: the role of affect and cognitions

Abstract: To investigate the role of affect and cognitions in predicting organizational citizenship behavior (OCB) and workplace deviance behavior (WDB), data were collected from 149 registered nurses and their coworkers. Job affect was associated more strongly than were job cognitions with OCB directed at individuals, whereas job cognitions correlated more strongly than did job affect with OCB directed at the organization. With respect to WDB, job cognitions played a more important role in prediction when job affect was represented by 2 general mood variables (positive and negative affect). When discrete emotions were used to represent job affect, however, job affect played as important a role as job cognition variables, strongly suggesting the importance of considering discrete emotions in job affect research.

Commitment to organizational change: extension of a three-component model.

Abstract: Three studies were conducted to test the application of a three-component model of workplace commitment (J. P. Meyer & N. J. Allen, 1991: J. P. Meyer & L. Herscovitch, 2001) in the context of employee commitment to organizational change. Study 1, conducted with 224 university students, provided preliminary evidence for the validity of newly developed Affective, Continuance, and Normative Commitment to Change Scales. Studies 2 and 3, conducted with hospital nurses (N = 157 and 108, respectively), provided further support for the validity of the three Commitment to Change Scales, and demonstrated that (a) commitment to a change is a better predictor of behavioral support for a change than is organizational commitment, (b) affective and normative commitment to a change are associated with higher levels of support than is continuance commitment, and (c) the components of commitment combine to predict behavior.

Toward a Theory of Entrepreneurial Cognition: Rethinking the People Side of Entrepreneurship Research:

Abstract: The failure of past “entrepreneurial personality”—based research to clearly distinguish the unique contributions to the entrepreneurial process of entrepreneurs as people, has created a vacuum with...

Managing An Organizational Learning System By Aligning Stocks and Flows

Abstract: This paper considers the relationship between the stocks and flows of learning across levels in an overall organizational learning system. A survey instrument based on the Strategic Learning Assessment Map (SLAM) was administered to 15 individuals representing senior-, middle- and non-management levels from each of 32 organizations, resulting in a total sample of 480 respondents. This research supports the premise that there is a positive relationship between the stocks of learning at all levels and business performance. Furthermore, the proposition that the misalignment of stocks and flows in an overall organizational learning system is negatively associated with business performance is also supported.

Believe it or not: Factors influencing credibility on the Web

Abstract: This article reviews selected literature related to the credibility of information, including (1) the general markers of credibility, and how different source, message and receiver characteristics affect people's perceptions of information; (2) the impact of information medium on the assessment of credibility; and (3) the assessment of credibility in the context of information presented on the Internet. The objective of the literature review is to synthesize the current state of knowledge in this area, develop new ways to think about how people interact with information presented via the Internet, and suggest next steps for research and practical applications. The review examines empirical evidence, key reviews, and descriptive material related to credibility in general, and in terms of on-line media. A general discussion of credibility and persuasion and a description of recent work on the credibility and persuasiveness of computer-based applications is presented. Finally, the article synthesizes what we have learned from various fields, and proposes a model as a framework for much-needed future research in this area.

Multicolor and Electron Microscopic Imaging of Connexin Trafficking

Abstract: Recombinant proteins containing tetracysteine tags can be successively labeled in living cells with different colors of biarsenical fluorophores so that older and younger protein molecules can be sharply distinguished by both fluorescence and electron microscopy. Here we used this approach to show that newly synthesized connexin43 was transported predominantly in 100- to 150-nanometer vesicles to the plasma membrane and incorporated at the periphery of existing gap junctions, whereas older connexins were removed from the center of the plaques into pleiomorphic vesicles of widely varying sizes. Selective imaging by correlated optical and electron microscopy of protein molecules of known ages will clarify fundamental processes of protein trafficking in situ.

Ventricular pacing or dual-chamber pacing for sinus-node dysfunction

Abstract: Background Dual-chamber (atrioventricular) and single-chamber (ventricular) pacing are alternative treatment approaches for sinus-node dysfunction that causes clinically significant bradycardia. However, it is unknown which type of pacing results in the better outcome. Methods We randomly assigned a total of 2010 patients with sinus-node dysfunction to dual-chamber pacing (1014 patients) or ventricular pacing (996 patients) and followed them for a median of 33.1 months. The primary end point was death from any cause or nonfatal stroke. Secondary end points included the composite of death, stroke, or hospitalization for heart failure; atrial fibrillation; heart-failure score; the pacemaker syndrome; and the quality of life. Results The incidence of the primary end point did not differ significantly between the dual-chamber group (21.5 percent) and the ventricular-paced group (23.0 percent, P=0.48). In patients assigned to dual-chamber pacing, the risk of atrial fibrillation was lower (hazard ratio, 0.79; 9...

PatternHunter: faster and more sensitive homology search

Abstract: Motivation: Genomics and proteomics studies routinely depend on homology searches based on the strategy of finding short seed matches which are then extended. The exploding genomic data growth presents a dilemma for DNA homology search techniques: increasing seed size decreases sensitivity whereas decreasing seed size slows down computation. Results: We present a new homology search algorithm ‘PatternHunter’ that uses a novel seed model for increased sensitivity and new hit-processing techniques for significantly increased speed. At Blast levels of sensitivity, PatternHunter is able to find homologies between sequences as large as human chromosomes, in mere hours on a desktop. Availability: PatternHunter is available at http://www. bioinformaticssolutions.com, as a commercial package. It runs on all platforms that support Java. PatternHunter technology is being patented; commercial use requires a license from BSI, while non-commercial use will be free.

Aging of the human neuromuscular system.

Abstract: Loss of cells from the motor system occurs during the normal aging process, leading to reduction in the complement of motor neurons and muscle fibers. The latter age-related decrease in muscle mass has been termed “sarcopenia” and is often combined with the detrimental effects of a sedentary lifestyle in older adults, leading to a significant reduction in reserve capacity of the neuromuscular system, which is the primary subject of this review. Clear evidence of this aging effect is seen when voluntary or stimulated muscle strength is compared across the adult lifespan, with a steady decline of ∼1–2% per year occurring after the sixth decade. Interestingly, when compared with isometric contractions, the effect of aging is more pronounced for concentric movements and less for eccentric movements (i.e., muscle shortening versus lengthening). This phenomenon appears to be linked to the stiffer muscle structures and prolonged myosin crossbridge cycles of aged muscles. It is encouraging that the capability of physiological adaptations in the motor pathways remains into very old age — when an appropriate exercise stimulus is given — and long-term prevention strategies are advocated to avoid excessive physical impairments and activity restrictions in this age group. © 2002 John Wiley & Sons, Inc. Muscle Nerve 25: 17–25, 2002

Glossary of descriptive terminology for ictal semiology: report of the ILAE task force on classification and terminology.

Abstract: INTRODUCTION PRINCIPLES FOR TERMS AND DEFINITIONS DATA SOURCES I GENERAL TERMS 1.0 SEMIOLOGY 2.0 EPILEPTIC SEIZURE 3.0 ICTUS 4.0 EPILEPSY 5.0 FOCAL 6.0 GENERALIZED 7.0 CONVULSION II TERMS DESCRIBING EPILEPTIC SEIZURE SEMIOLOGY 1.0 MOTOR 1.1 ELEMENTARY MOTOR 1.1.1 TONIC 1.1.1.1 EPILEPTIC SPASM 1.1.1.2 POSTURAL 1.1.1.2.1 VERSIVE 1.1.1.2.2 DYSTONIC 1.1.2 MYOCLONIC 1.1.2.1 NEGATIVE MYOCLONIC 1.1.2.2 CLONIC 1.1.2.2.1 JACKSONIAN MARCH 1.1.3 TONIC-CLONIC 1.1.3.1 GENERALIZED TONIC-CLONIC SEIZURE 1.1.4 ATONIC 1.1.5 ASTATIC 1.1.6 SYNCHRONOUS 1.2 AUTOMATISM 1.2.1 OROALIMENTARY 1.2.2 MIMETIC 1.2.3 MANUAL OR PEDAL 1.2.4 GESTURAL 1.2.5 HYPERKINETIC 1.2.6 HYPOKINETIC 1.2.7 DYSPHASIC 1.2.8 DYSPRAXIC 1.2.9 GELASTIC 1.2.10 DACRYSTIC 1.2.11 VOCAL 1.2.12 VERBAL 1.2.13 SPONTANEOUS 1.2.14 INTERACTIVE 2.0 NON-MOTOR 2.1 AURA 2.2 SENSORY 2.2.1 ELEMENTARY 2.2.1.1 SOMATOSENSORY 2.2.1.2 VISUAL 2.2.1.3 AUDITORY 2.2.1.4 OLFACTORY 2.2.1.5 GUSTATORY 2.2.1.6 EPIGASTRIC 2.2.1.7 CEPHALIC 2.2.1.8 AUTONOMIC 2.2.2 EXPERIENTIAL 2.2.2.1 AFFECTIVE 2.2.2.2 MNEMONIC 2.2.2.3 HALLUCINATORY 2.2.2.4 ILLUSORY 2.3 DYSCOGNITIVE 3.0 AUTONOMIC EVENTS 3.1 AUTONOMIC AURA 3.2 AUTONOMIC SEIZURE 4.0 SOMATOTOPIC MODIFIERS 4.1 LATERALITY 4.1.1 UNILATERAL 4.1.1.1 HEMI4.1.2 GENERALIZED (syn. “bilateral”) 4.1.2.1 ASYMMETRICAL 4.1.2.2 SYMMETRICAL 4.2 BODY PART 4.3 CENTRICITY 4.3.1 AXIAL Epilepsia, 42(9):1212–1218, 2001 Blackwell Science, Inc. © International League Against Epilepsy

The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist.

Abstract: THE purpose of this review is to evaluate recent developments in our understanding of the inflammatory response to cardiac surgery. Scientific knowledge in this field is continually expanding, potentially significant advances are regularly reported, and this area constitutes a major interface of clinical and basic scientific research. The review is divided into four major sections. The first section describes the pathophysiology of the inflammatory response to cardiac surgery. Factors that influence the extent of the inflammatory response, including the immunomodulatory effects of drugs commonly administered perioperatively, are discussed in the second section. The third section examines the evidence that the inflammatory response contributes to adverse perioperative events, in particular organ dysfunction, while the final section evaluates potential therapeutic strategies to control this response. The review concludes with a summary of potential future research directions and key deficiencies in our knowledge regarding the inflammatory response to cardiac surgery.

Centers of excellence in multinational corporations

Abstract: This paper seeks to understand the conditions under which ‘centers of excellence’ emerge in foreign subsidiaries of multinational firms. We define a center of excellence as an organizational unit that embodies a set of capabilities that has been explicitly recognized by the firm as an important source of value creation, with the intention that these capabilities be leveraged by and/or disseminated to other parts of the firm. Drawing on overlapping research in international business and strategic management, we argue that the formation of centers of excellence is shaped by conditions in the subsidiary's local environment as well as by various aspects of the subsidiary's relationship with other parts of the multinational firm. Based on a survey of 99 foreign units in Canada, our results highlight the fundamental role played by parent firm investment as well as the role of internal and external organizations in the development of subsidiary capabilities. Performance implications of the center of excellence phenomenon are also explored. Copyright © 2002 John Wiley & Sons, Ltd.

Survival and Profitability: The Roles of Experience and Intangible Assets in Foreign Subsidiary Performance

Abstract: This study integrates research on the financial performance of multinational firms with research on foreign subsidiary survival. We examined the influences a firm's intangible assets and its experience have on foreign subsidiary survival and profitability using a sample of 3,080 subsidiaries of 641 Japanese firms. The results show survival and profitability have different antecedents. Host country experience has a direct effect on survival but a contingent relationship with profitability. The entry mode moderated the nature of these relationships.

Compositions of the Apatite-Group Minerals: Substitution Mechanisms and Controlling Factors

Abstract: The apatite-group minerals of the general formula, M10(ZO4)6X2 (M = Ca, Sr, Pb, Na…, Z = P, As, Si, V…, and X = F, OH, Cl…), are remarkably tolerant to structural distortion and chemical substitution, and consequently are extremely diverse in composition (e.g., Kreidler and Hummel 1970; McConnell 1973; Roy et al. 1978; Elliott 1994). Of particular interest is that a number of important geological, environmental/paleoenvironmental, and technological applications of the apatite-group minerals are directly linked to their chemical compositions. It is therefore fundamentally important to understand the substitution mechanisms and other intrinsic and external factors that control the compositional variation in apatites. The minerals of the apatite group are listed in Table 1⇓, and representative compositions of selected apatite-group minerals are given in Table 2⇓. Also, more than 100 compounds with the apatite structure have been synthesized (Table 3⇓). Phosphate apatites, particularly fluorapatite and hydroxylapatite, are by far the most common in nature and are often synonymous with “apatite(s)”. For example, fluorapatite is a ubiquitous accessory phase in igneous, metamorphic, and sedimentary rocks and a major constituent in phosphorites and certain carbonatites and anorthosites (McConnell 1973; Dymek and Owens 2001). Of particular importance in biological systems, hydroxylapatite and fluorapatite (and their carbonate-bearing varieties) are important mineral components of bones, teeth and fossils (McConnell 1973; Wright et al. 1984; Grandjean-Lecuyer et al. 1993; Elliott 1994; Wilson et al. 1999; Suetsugu et al. 2000; Ivanova et al. 2001). View this table: Table 1. Summary of the apatite-group minerals View this table: Table 2. Representative compositions and unit-cell parameters of selected apatite-group minerals. View this table: Table 3. Formulas of selected synthetic compounds with the apatite structure. Following Fleischer and Mandarino (1995), Table 1⇑ also includes melanocerite-(Ce), tritomite-(Ce), and tritomite-(Y), the compositions …

Cohesion and performance in sport: a meta analysis.

Abstract: The main purpose of this study was to conduct a meta-analytic summary of the cohesion-performance relationship in sport. A secondary purpose was to examine the influence of a number of potential moderator variables. Another secondary purpose was to examine the cohesion–performance relationship reported in studies using the Group Environment Questionnaire (GEQ). Standard literature searches produced 46 studies containing a total of 164 effect sizes. Overall, a significant moderate to large relationship was found between cohesion and performance. A moderate effect was found in studies that used the GEQ. A larger cohesion–performance effect was found in refereed publications (vs. nonpublished sources) and for female teams. These results have implications for practitioners in terms of the importance of team building to enhance team cohesion, the nature of those team-building programs (e.g., both task- or social-oriented programs should be beneficial), and their target group (e.g., both interdependent and coac...

Why can't we just get along? Interpersonal biases and interracial distrust.

Abstract: The authors review a series of studies that illustrate how one form of contemporary racial bias of Whites, aversive racism, can shape different perspectives of Blacks and Whites in ways that can undermine race relations. This research demonstrates that contemporary racism among Whites is subtle, often unintentional, and unconscious but that its effects are systematically damaging to race relations by fostering miscommunication and distrust. In particular, the authors examine the effects of aversive racism on outcomes for Blacks (e.g., in selection decisions), on the ways that Whites behave in interracial interactions, in the impressions that Whites and Blacks form of each other in these interactions, and on the task efficiency of interracial dyads.

Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine.

Abstract: Objectives Our objective was to examine the effect of different fruits and their constituents on P-glycoprotein and organic anion transporting polypeptide (OATP) activities in vitro and on drug disposition in humans. Methods P-glycoprotein–mediated digoxin or vinblastine efflux was determined in polarized epithelial cell monolayers. OATP-mediated fexofenadine uptake was measured in a transfected cell line. The oral pharmacokinetics of 120 mg fexofenadine was assessed with water, 25%-strength grapefruit juice, or normal-strength grapefruit, orange, or apple juices (1.2 L over 3 hours) in a randomized 5-way crossover study in 10 healthy subjects. Results Grapefruit juice and segments and apple juice at 5% of normal strength did not alter P-glycoprotein activity. Grapefruit extract reduced transport. 6′,7′-Dihydroxybergamottin had modest inhibitory activity (50% inhibitory concentration [IC50], 33 μmol/L). In contrast, grapefruit, orange, and apple juices at 5% of normal strength markedly reduced human OATP and rat oatp activity. 6′,7′-Dihydroxybergamottin potently inhibited rat oatp3 and oatp1 (IC50, 0.28 μmol/L). Other furanocoumarins and bioflavonoids also reduced rat oatp3 activity. Grapefruit, orange, and apple juices decreased the fexofenadine area under the plasma concentration–time curve (AUC), the peak plasma drug concentration (Cmax), and the urinary excretion values to 30% to 40% of those with water, with no change in the time to reach Cmax, elimination half-life, renal clearance, or urine volume in humans. Change in fexofenadine AUC with juice was variable among individuals and inversely dependent on value with water. Conclusions Fruit juices and constituents are more potent inhibitors of OATPs than P-glycoprotein activities, which can reduce oral drug bioavailability. Results support a new model of intestinal drug absorption and mechanism of food-drug interaction. Clinical Pharmacology & Therapeutics (2002) 71, 11–20; doi: 10.1067/mcp.2002.121152

Carotid Plaque Area A Tool for Targeting and Evaluating Vascular Preventive Therapy

Abstract: Background and Purpose—Carotid plaque area measured by ultrasound (cross-sectional area of longitudinal views of all plaques seen) was studied as a way of identifying patients at increased risk of stroke, myocardial infarction, and vascular death. Methods—Patients from an atherosclerosis prevention clinic were followed up annually for up to 5 years (mean, 2.51.3 years) with baseline and follow-up measurements recorded. Plaque area progression (or regression) was defined as an increase (or decrease) of 0.05 cm 2 from baseline. Results—Carotid plaque areas from 1686 patients were categorized into 4 quartile ranges: 0.00 to 0.11 cm 2 (n422), 0.12 to 0.45 cm 2 (n424), 0.46 to 1.18 cm 2 (n421), and 1.19 to 6.73 cm 2 (n419). The combined 5-year risk of stroke, myocardial infarction, and vascular death increased by quartile of plaque area: 5.6%, 10.7%, 13.9%, and 19.5%, respectively (P0.001) after adjustment for all baseline patient characteristics. A total of 1085 patients had 1 annual carotid plaque area measurements: 685 (63.1%) had carotid plaque progression, 306 (28.2%) had plaque regression, and 176 (16.2%) had no change in carotid plaque area over the period of follow-up. The 5-year adjusted risk of combined outcome was 9.4%, 7.6%, and 15.7% for patients with carotid plaque area regression, no change, and progression, respectively (P0.003). Conclusions—Carotid plaque area and progression of plaque identified high-risk patients. Plaque measurement may be useful for targeting preventive therapy and evaluating new treatments and response to therapy and may improve cost-effectiveness of secondary preventive treatment. (Stroke. 2002;33:2916-2922.)

Issues in the meta-analysis of cluster randomized trials

Abstract: Meta-analyses involving the synthesis of evidence from cluster randomization trials are being increasingly reported. These analyses raise challenging methodologic issues beyond those raised by meta-analyses which include only individually randomized trials. In this paper we review and comment on a selected number of these issues, including problems of study heterogeneity, difficulties in estimating design effects from individual trials and the choice of statistical methods.

Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome)

Abstract: Andersen syndrome (AS) is a rare, inherited disorder characterized by periodic paralysis, long QT (LQT) with ventricular arrhythmias, and skeletal developmental abnormalities. We recently established that AS is caused by mutations in KCNJ2, which encodes the inward rectifier K(+) channel Kir2.1. In this report, we characterized the functional consequences of three novel and seven previously described KCNJ2 mutations using a two-microelectrode voltage-clamp technique and correlated the findings with the clinical phenotype. All mutations resulted in loss of function and dominant-negative suppression of Kir2.1 channel function. In mutation carriers, the frequency of periodic paralysis was 64% and dysmorphic features 78%. LQT was the primary cardiac manifestation, present in 71% of KCNJ2 mutation carriers, with ventricular arrhythmias present in 64%. While arrhythmias were common, none of our subjects suffered sudden cardiac death. To gain insight into the mechanism of arrhythmia susceptibility, we simulated the effect of reduced Kir2.1 using a ventricular myocyte model. A reduction in Kir2.1 prolonged the terminal phase of the cardiac action potential, and in the setting of reduced extracellular K(+), induced Na(+)/Ca(2+) exchanger-dependent delayed afterdepolarizations and spontaneous arrhythmias. These findings suggest that the substrate for arrhythmia susceptibility in AS is distinct from the other forms of inherited LQT syndrome.