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The University of Western Ontario , which is commonly referred to among Canadian universities as Western or Western University, is a public research university located in London, Ontario, Canada. The university was founded on 7 March 1878 by Bishop Isaac Hellmuth of the Anglican Diocese of Huron as "The Western University of London Ontario." It incorporated Huron University College, which had been founded in 1863. The first four faculties were Arts, Divinity, Law and Medicine. The Western University of London was eventually made non-denominational in 1908.According to the 2012 Academic Ranking of World Universities rankings, the university ranked 201–300 in the world and top 10 in Canada. The 2011 QS World University Rankings ranked the university 157th in the world, making it seventh in Canada. Several of Western's programs were also ranked in individual rankings. Social science at Western was ranked 96th in the world in the 2010 QS World University Rankings, and Western's Ivey Business School was ranked 1st in the World in the Global MBA Category of Bloomberg Businessweek.Western's Co-educational Student body of over 24,000 represents 107 countries around the world and Western scholars have established research and education collaborations and partnerships on every continent. There are more than 306,000 alumni who are active internationally, living and working around the globe. Notable alumni include government officials, academics, business leaders, Nobel Laureates, Rhodes Scholars, and distinguished fellows.Western's varsity teams, known as the Western Mustangs, compete in the Ontario University Athletics conference of the Canadian Interuniversity Sport. Wikipedia.


Vankoughnett M.R.,University of Western Ontario | Grogan P.,Queens University
Biogeochemistry | Year: 2014

Deciduous shrub density and landcover are increasing across many areas of the Arctic. Shrub growth may be promoted by a snow-shrub feedback whereby relatively tall shrubs accumulate deeper snow, raising winter soil temperature minima, increasing microbial activity, and enhancing soil solution nitrogen (N). Although there is good evidence for the above components of the hypothesis, it has not yet been determined if shrubs can access the elevated N pool generated by deepened snow. We added isotopic N tracer (15N) in late summer to control and snowfenced low birch hummock tundra to test the influence of deepened snow on N cycling. Furthermore, tracer was added to tall birch tundra to compare N cycling in low and tall shrub ecosystems that have the same species composition. Experimentally deepened snow in low birch tundra did not significantly affect 15N uptake by shrubs or any other species 2 years after the tracer addition. However, there were strong differences between the low and tall birch ecosystems, with the deciduous shrubs and graminoids accumulating more 15N than the evergreen shrubs in the relatively productive tall shrub site, and vice versa in the relatively infertile low birch site. The greater 15N acquisition by birch in the more fertile site, together with the absence of a deepened snow effect on 15N acquisition by any species in the low birch hummock ecosystem, suggest that climate-change induced increases in birch shrub growth and expansion across the landscape will tend to occur most rapidly in and around existing tall birch shrub patches. © 2013 Springer Science+Business Media Dordrecht.


Xu S.X.,University of Western Ontario
Frontiers in cellular and infection microbiology | Year: 2012

Superantigens (SAgs) are a family of potent immunostimulatory exotoxins known to be produced by only a few bacterial pathogens, including Staphylococcus aureus. More than 20 distinct SAgs have been characterized from different S. aureus strains and at least 80% of clinical strains harbor at least one SAg gene, although most strains encode many. SAgs have been classically associated with food poisoning and toxic shock syndrome (TSS), for which these toxins are the causative agent. TSS is a potentially fatal disease whereby SAg-mediated activation of T cells results in overproduction of cytokines and results in systemic inflammation and shock. Numerous studies have also shown a possible role for SAgs in other diseases such as Kawasaki disease (KD), atopic dermatitis (AD), and chronic rhinosinusitis (CRS). There is also now a rich understanding of the mechanisms of action of SAgs, as well as their structures and function. However, we have yet to discover what purpose SAgs play in the life cycle of S. aureus, and why such a wide array of these toxins exists. This review will focus on recent developments within the SAg field in terms of the molecular biology of these toxins and their role in both colonization and disease.


Determining sediment transport direction in ancient mudrocks is difficult. In order to determine both process and direction of mud transport, a portion of a well-mapped Cretaceous delta system was studied. Oriented samples from outcrop represent prodelta environments from ca 10 to 120 km offshore. Oriented thin sections of mudstone, cut in three planes, allowed bed microstructure and palaeoflow directions to be determined. Clay mineral platelets are packaged in equant, face-face aggregates 2 to 5 μm in diameter that have a random orientation; these aggregates may have formed through flocculation in fluid mud. Cohesive mud was eroded by storms to make intraclastic aggregates 5 to 20 μm in diameter. Mudstone beds are millimetre-scale, and four microfacies are recognized: Well-sorted siltstone forms millimetre-scale combined-flow ripples overlying scoured surfaces; deposition was from turbulent combined flow. Silt-streaked claystone comprises parallel, sub-millimetre laminae of siliceous silt and clay aggregates sorted by shear in the boundary layer beneath a wave-supported gravity flow of fluid mud. Silty claystone comprises fine siliceous silt grains floating in a matrix of clay and was deposited by vertical settling as fluid mud gelled under minimal current shear. Homogeneous clay-rich mudstone has little silt and may represent late-stage settling of fluid mud, or settling from wave-dissipated fluid mud. It is difficult or impossible to correlate millimetre-scale beds between thin sections from the same sample, spaced only ca 20 mm apart, due to lateral facies change and localized scour and fill. Combined-flow ripples in siltstone show strong preferred migration directly down the regional prodelta slope, estimated at ca 1 : 1000. Ripple migration was effected by drag exerted by an overlying layer of downslope-flowing, wave-supported fluid mud. In the upper part of the studied section, centimetre-scale interbeds of very fine to fine-grained sandstone show wave ripple crests trending shore normal, whereas combined-flow ripples migrated obliquely alongshore and offshore. Storm winds blowing from the north-east drove shore-oblique geostrophic sand transport whereas simultaneously, wave-supported flows of fluid mud travelled downslope under the influence of gravity. Effective wave base for sand, estimated at ca 40 m, intersected the prodelta surface ca 80 km offshore whereas wave base for mud was at ca 70 m and lay ca 120 km offshore. Small-scale bioturbation of mud beds co-occurs with interbedded sandstone but stratigraphically lower, sand-free mudstone has few or no signs of benthic fauna. It is likely that a combination of soupground substrate, frequent storm emplacement of fluid mud, low nutrient availability and possibly reduced bottom-water oxygen content collectively inhibited benthic fauna in the distal prodelta. © 2013 International Association of Sedimentologists.


Ganel T.,Ben - Gurion University of the Negev | Goodale M.A.,University of Western Ontario
Experimental Brain Research | Year: 2014

Garner's speeded classification task has been used as an effective tool to probe holistic processing of object shape. This is achieved by comparing classification performance of a given object dimension between two experimental conditions. Worse performance in a "filtering" condition in which a second, irrelevant dimension of the same object varies on a trial-to-trial basis, compared to a "baseline" condition in which the irrelevant dimension is held constant, is labeled Garner interference, and indicates that the two dimensions are processed in a holistic manner. About a decade ago, we used Garner's task to provide evidence for different frames of processing mediating action and perception. Unlike perceptual estimations, visually guided grasping showed no Garner interference when subjects were asked to reach out and grasp an object along a given dimension. In other words, slower reaction times were observed in the filtering compared to the baseline condition only for perceptual estimates but not for grasping. In two experiments, we extend these findings to kinematic measures beyond simple reaction times. The results showed that Garner interference is also expressed in the variability of the response, with more variable within-subject performance in the filtering compared to the baseline condition for perceptual estimates but not for grasping. These findings provide converging evidence for the idea that, unlike perception, which processes objects holistically, visually guided action is performed in an analytic manner. © 2014 Springer-Verlag.


The gap junctions (GJs) formed by Cx40 and Cx43 provide a low resistance passage allowing for rapid propagation of action potentials. Sporadic somatic mutations in GJA5 (encoding Cx40) have been identified in lone atrial fibrillation (AF) patients. More recently germline autosomal dominantly inherited mutations in GJA5 have been found in early onset lone AF patients in several families over generations. Characterizations of these AF-linked Cx40 mutants in model cells and in patient tissues revealed that some of the mutants reduced GJ channel function due to an impaired trafficking or channel formation. While others showed a gain-of-function in hemichannels. These functional alterations in GJs or hemichannel may play an important role in the pathogenesis of AF in the mutant carriers. © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


The semi-exponential basis set of radial functions [A.M. Frolov, Phys. Lett. A 374, 2361 (2010)] is used for variational computations of bound states in three-electron atomic systems. It appears that the semi-exponential basis set has a substantially greater potential for accurate variational computations of bound states in three-electron atomic systems than was originally anticipated. In particular, the 40-term Larson's wave function improved with the use of semi-exponential radial basis functions now produces the total energy -7.4780581457 a.u. for the ground 1 2S-state in the ∞ Li atom (only one spin function χ 1=αβ α -.αβ α was used in these calculations). This variational energy is very close to the exact ground state energy of the ∞ atom and is substantially lower than the total energy obtained with the original Larson's 40-term wave function (-7.477944869 a.u.). © 2011 EDP Sciences, SIF, Springer-Verlag Berlin Heidelberg.


Guaiana G.,University of Western Ontario
Cochrane database of systematic reviews (Online) | Year: 2010

Generalised anxiety disorder (GAD) is a common chronic long-term psychiatric disorder, particularly frequent in primary care. There are several treatment options available, both non-pharmacological (i.e. cognitive behavioral therapy) and pharmacological. Among the pharmacological interventions, antidepressants, buspirone and benzodiazepines (BDZs) have been studied in GAD. Hydroxyzine is an anti-histamine medication which has been used in the treatment of anxiety. 1. To determine the efficacy of hydroxyzine in comparison with placebo or any other active agent in alleviating the acute symptoms of GAD. 2. To review acceptability of treatment with hydroxyzine in comparison with placebo or any other active agent. 3. To investigate the adverse effects of hydroxyzine in comparison with other active agents. The Cochrane Depression, Anxiety and Neurosis Group's controlled trial registers (CCDANCTR-Studies and CCDANCTR-References) were searched on 1 March 2010. The author team ran complementary searches on MEDLINE, CINAHL and PsycINFO and checked reference lists of included studies, previous systematic reviews and major textbooks of anxiety disorders. Personal communication with pharmaceutical companies and experts in the field was also undertaken. Randomised controlled trials allocating patients with GAD to hydroxyzine versus placebo and/or any other anxiolytic agent. Two authors independently extracted data. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (such as the number of patients who responded to treatment or remitted), acceptability (the number of patients who failed to complete the study) and tolerability (side effect profile). The search yielded 39 studies. We included five studies in the review with a total of 884 participants. We excluded 31 studies and designated three as awaiting assessment. The data from the included studies provide some evidence that hydroxyzine is more effective than placebo for GAD (odds ratio (OR) 0.30, 95% CI 0.15 to 0.58) and that it is also acceptable/tolerable (OR 1.00, 95% CI 0.63 to 1.58) (OR 1.49, 95% CI 0.92 to 2.40). Compared to other anxiolytic agents (benzodiazepines and buspirone), hydroxyzine was equivalent in terms of efficacy, acceptability and tolerability (hydroxyzine vs chloridiazepoxide: OR 0.75, 95% CI 0.35 to 1.62; hydroxyzine vs buspirone efficacy OR 0.76, 95% CI 0.40 to 1.42). In terms of side effects, hydroxyzine was associated with a higher rate of sleepiness/drowsiness than the active comparators (OR 1.74, 95% CI 0.86 to 3.53). There was, however, a high risk of bias in the included studies. The included studies did not report on all the outcomes that were pre-specified in the protocol for this review. Even though more effective than placebo, due to the high risk of bias of the included studies, the small number of studies and the overall small sample size, it is not possible to recommend hydroxyzine as a reliable first-line treatment in GAD.


The self-induced dermatoses (such as trichotillomania, pathologic skin picking or neurotic excoriations, dermatitis artefacta, onychophagia and onychotillomania), which are caused as a result of excessive manipulation of the skin, hair, and nails by the patient, can contribute to significant morbidity and can even complicate the course of a primary dermatologic condition such as acne (eg, in acne excoriée) and some pruritic dermatoses. Reports on the self-induced dermatoses in the past decade have tended to focus upon the specific motor behaviors involved in self-inducing the lesions (ie, skin picking or hair pulling) rather than address the common psychopathologic factors underlying the self-injurious behaviors. In the current psychiatric nosology (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) the self-induced dermatoses are classified as Impulse Control Disorders and Stereotypic Movement Disorders, and this classification does not adequately consider the fact that in most patients with self-induced dermatoses, the frequency and severity of the self-injurious behaviors are directly related to acute or chronic problems with emotional regulation and dissociation. This may be part of the reason that there is a relative paucity of effective treatments for these disorders. The skin and its appendages are well innervated with a dense network of afferent sensory nerves and efferent autonomic nerves, and the integumentary system is frequently the focus of tension-reducing and emotion-regulating behaviors, especially during states of autonomic nervous system hyperarousal. This factor is important in the pathogenesis of the self-induced dermatoses. Mood-stabilizing agents, such as lithium carbonate, that are used to treat disorders of emotional regulation have not been adequately studied in the management of the self-induced dermatoses and may prove to be very helpful in the management of these disorders. © 2013 Elsevier Inc.


Veksler O.,University of Western Ontario
Proceedings of the IEEE Computer Society Conference on Computer Vision and Pattern Recognition | Year: 2015

Potts energy frequently occurs in computer vision applications. We present an efficient parallel method for optimizing Potts energy based on the extension of hierarchical fusion algorithm. Unlike previous parallel graph-cut based optimization algorithms, our approach has optimality bounds even after a single iteration over all labels, i.e. after solving only k-1 max-flow problems, where k is the number of labels. This is perhaps the minimum number of max-flow problems one has to solve to obtain a solution with optimality guarantees. Our approximation factor is O(log2k). Although this is not as good as the factor of 2 approximation of the well known expansion algorithm, we achieve very good results in practice. In particular, we found that the results of our algorithm after one iteration are always better than the results after one iteration of the expansion algorithm. We demonstrate experimentally the computational advantages of our parallel implementation on the problem of stereo correspondence, achieving a factor of 1.5 to 2.6 speedup compared to the serial implementation. These results were obtained with a small number of processors. The expected speedups with a larger number of processors are greater. © 2015 IEEE.


Myrvold W.C.,University of Western Ontario
Studies in History and Philosophy of Science Part B - Studies in History and Philosophy of Modern Physics | Year: 2011

One finds, in Maxwell's writings on thermodynamics and statistical physics, a conception of the nature of these subjects that differs in interesting ways from the way they are usually conceived. In particular, though-in agreement with the currently accepted view-Maxwell maintains that the second law of thermodynamics, as originally conceived, cannot be strictly true, the replacement he proposes is different from the version accepted by most physicists today. The modification of the second law accepted by most physicists is a probabilistic one: although statistical fluctuations will result in occasional spontaneous differences in temperature or pressure, there is no way to predictably and reliably harness these to produce large violations of the original version of the second law. Maxwell advocates a version of the second law that is strictly weaker; the validity of even this probabilistic version is of limited scope, limited to situations in which we are dealing with large numbers of molecules en masse and have no ability to manipulate individual molecules. Connected with this is his conception of the thermodynamic concepts of heat, work, and entropy; on the Maxwellian view, these are concept that must be relativized to the means we have available for gathering information about and manipulating physical systems. The Maxwellian view is one that deserves serious consideration in discussions of the foundation of statistical mechanics. It has relevance for the project of recovering thermodynamics from statistical mechanics because, in such a project, it matters which version of the second law we are trying to recover. © 2011 Elsevier Ltd.


Bernards M.A.,University of Western Ontario
Canadian Journal of Zoology | Year: 2010

Over the course of evolution, plants have adapted various structural and chemical mechanisms to protect themselves and interact with their environment. The chemical mechanisms are largely based on the secondary metabolites or natural products. Although plant natural products are generally divided into three main categories (terpenoids, alkaloids, and phenylpropanoids) that are based on structural type and biosynthetic origin, there are many other smaller categories of unique compounds. Many important in planta biological functions can be attributed to plant natural products, in large part, owing to their tremendous structural diversity. To understand the functional roles of plant natural products, both as protective compounds and interorganismal signals, it is important to know how they are formed in plants. This minireview provides a general background about the three main categories of plant natural products, their biosynthetic origins, and their structural diversity.


Leong-Sit P.,University of Western Ontario
Current Opinion in Cardiology | Year: 2015

PURPOSE OF REVIEW: Heart failure and atrial fibrillation are both common cardiac conditions that share multiple risk factors. Heart failure is a risk for atrial fibrillation and atrial fibrillation is a risk for heart failure. The need to understand the interplay between these two cardiac conditions and the effectiveness of management options becomes increasingly relevant.RECENT FINDINGS: Recent studies have focused on the prognostic nature of atrial fibrillation and heart failure, the questionable utility of digoxin and beta-blocker therapy when heart failure and atrial fibrillation coexist, and the efficacy of cardiac ablation and resynchronization therapy with concomitant heart failure and atrial fibrillation.SUMMARY: The predominant questions that require further attention with respect to atrial fibrillation and heart failure are whether catheter ablation and rhythm control offers benefit in a high-risk heart failure population with respect to mortality or heart failure reduction, and whether cardiac resynchronization therapy implantation truly benefits the subgroup of candidate patients with permanent atrial fibrillation. Large randomized multicentre studies are currently ongoing to address these important questions. © 2015 Wolters Kluwer Health | Lippincott Williams & Wilkins


Leask A.,University of Western Ontario
Journal of Cell Communication and Signaling | Year: 2013

It is well-established that the expression of CCN family of matricellular proteins is altered in essentially all cancers and, hence, targeting these proteins may be a novel therapeutic approach to treating these diseases. For example, CCN6 (WISP3) is downregulated in aggressive breast cancers, and this phenomenon appears to result in the tumor survival by promoting Akt phosphorylation. In a recent report by Pal et al. (Cancer Res 72(18):4818-4828, 2012), CCN6 knockdown was shown to promote BMP4-mediated activation of the Smad-independent TAK1 and p38 kinases. CCN6 expression was inversely associated with BMP4 and phospho-p38 levels in 69 % of invasive breast carcinomas. TAK1 inhibition has been previously shown to decrease tumor progression in preclinical models of TAK1-dependent cancers. These data are consistent with the idea that CCN6 may represent a novel therapeutic approach, as compared to attacking TAK1 directly, to selectively target breast cancers. © 2013 The International CCN Society.


Hunter G.K.,University of Western Ontario
Calcified Tissue International | Year: 2013

The presence of osteopontin (OPN) at high levels in both mineralized tissues such as bone and ectopic calcifications such as atherosclerotic plaque presents a conundrum: is OPN a promoter or inhibitor of hydroxyapatite (HA) formation? In vitro studies show that OPN adsorbs tightly to HA and is a potent inhibitor of crystal growth. Although the mechanism of the OPN-HA interaction is not fully understood, it is probably electrostatic in nature. Phosphorylation enhances OPN's ability to adsorb to and inhibit the growth of HA crystals, although other anionic groups also contribute to these properties. Recent findings suggest that OPN is an intrinsically unordered protein and that its lack of folded structure facilitates the protein's adsorption by allowing multiple binding geometries and the sequential formation of ionic bonds with Ca2+ ions of the crystal surface. By analogy with other biominerals, it is likely that adsorption of OPN to HA results in "pinning" of growth steps. The abundance of OPN at sites of ectopic calcification reflects upregulation of the protein in response to crystal formation or even in response to elevated phosphate levels. Therefore, it appears that OPN is one of a group of proteins that function to prevent crystal formation in soft tissues. The role of OPN in bone mineralization, if any, is less clear. However, it is possible that it modulates HA formation, either by preventing crystal growth in "inappropriate" areas such as the osteoid seam or by regulating crystal growth habit (size and shape). © 2013 Springer Science+Business Media New York.


Read E.A.,University of Western Ontario
Journal of advanced nursing | Year: 2014

AIM: To report an analysis of the concept of nurses' workplace social capital.BACKGROUND: Workplace social capital is an emerging concept in nursing with potential to illuminate the value of social relationships at work. A common definition is needed.DESIGN: Concept analysis.DATA SOURCES: The Cumulative Index to Nursing and Allied Health Literature, PubMed, PsychINFO and ProQuest Nursing.REVIEW METHODS: Databases were systematically searched using the keywords: workplace social capital, employee social capital, work environment, social capital and nursing. Sources published between January 1937-November 2012 in English that described or studied social capital of nurses at work were included. A total of 668 resources were found. After removing 241 duplicates, literature was screened in two phases: (1) titles and abstracts were reviewed (n = 427); and (2) remaining data sources were retrieved and read (n = 70). Eight sources were included in the final analysis.RESULTS: Attributes of nurses' workplace social capital included networks of social relationships at work, shared assets and shared ways of knowing and being. Antecedents were communication, trust and positive leadership practices. Nurses' workplace social capital was associated with positive consequences for nurses, their patients and healthcare organizations.CONCLUSION: Nurses' workplace social capital is defined as nurses' shared assets and ways of being and knowing that are evident in, and available through, nurses' networks of social relationships at work. Future studies should examine and test relationships between antecedents and consequences of nurses' workplace social capital to understand this important aspect of healthy professional practice environments better. © 2013 John Wiley & Sons Ltd.


LaDonna K.A.,University of Western Ontario
Journal of Neuroscience Nursing | Year: 2011

Although most neuromuscular disease research articles reflect traditional quantitative approaches, qualitative methods are becoming more prevalent in the neuromuscular literature. Arguably, qualitative research provides rich data that may be used to generate patient-centered outcome measures or influence current standards of care. The purpose of this article is to explore the qualitative literature pertaining to individuals and families living with chronic neuromuscular disease in order to suggest implications for practice. Fifty-six qualitative articles addressing seven research themes including Illness Experience; Work, Recreation, and Services; Assisted Ventilation; Caregiving; Genetics; Communication and Information Seeking; and Palliative Care were identified. © 2011 American Association of Neuroscience Nurses.


Singh G.,Dayanand Medical College | Singh G.,University College London | Burneo J.G.,University of Western Ontario | Sander J.W.,Dayanand Medical College
Epilepsia | Year: 2013

Summary Neurocysticercosis (NCC) is the main risk factor for late-onset seizures in many Taenia solium endemic countries and is also increasingly recognized in high income countries, where it was once thought to have been eliminated. The course and outcome of NCC-associated seizures and epilepsy are poorly understood. Substrates underlying NCC-associated seizures and epilepsy are unknown. Another unknown is if there is an association between NCC and hippocampal sclerosis (HS) and if it leads to intractable epilepsy. We review evidence regarding the structural basis of seizures and epilepsy in NCC and its association with HS. There are only a limited number of prospective studies of NCC-associated seizures and epilepsy. From these, it can be inferred that the risk of seizure recurrence is high following a first seizure, even though seizures are well-controlled with antiepileptic drugs. The single most important risk factor for ongoing or recurrent seizures is the persistence of either degenerating or residual calcified cysticercus cysts in the brain parenchyma on follow-up imaging studies. Medically intractable epilepsy requiring surgical treatment appears to be rare in people with NCC. In few cases that have been operated, gliosis around the cysticerci is the principal pathologic finding. Reports of the association between NCC and HS might be categorized into those in which the calcified cysticercus is located within the hippocampus and those in which the calcified cysticercus is located remote from the hippocampus. The former are convincing cases of medically intractable epilepsy with good seizure control following hippocampal resection. In the remaining, it is unclear whether a dual pathology relationship exists between HS and the calcified cysticercus. Carefully planned, follow-up studies incorporating high-resolution and quantitative imaging are desirable in order to clarify the outcome, the structural basis of NCC-associated epilepsy, and also its association with HS. © Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.


Gupta M.A.,University of Western Ontario
International Review of Psychiatry | Year: 2013

Post-traumatic stress disorder (PTSD) is associated with both (1) 'ill-defined' or 'medically unexplained' somatic syndromes, e.g. unexplained dizziness, tinnitus and blurry vision, and syndromes that can be classified as somatoform disorders (DSM-IV-TR); and (2) a range of medical conditions, with a preponderance of cardiovascular, respiratory, musculoskeletal, neurological, and gastrointestinal disorders, diabetes, chronic pain, sleep disorders and other immune-mediated disorders in various studies. Frequently reported medical co-morbidities with PTSD across various studies include cardiovascular disease, especially hypertension, and immune-mediated disorders. PTSD is associated with limbic instability and alterations in both the hypothalamic- pituitary-adrenal and sympatho-adrenal medullary axes, which affect neuroendocrine and immune functions, have central nervous system effects resulting in pseudo-neurological symptoms and disorders of sleep-wake regulation, and result in autonomic nervous system dysregulation. Hypervigilance, a central feature of PTSD, can lead to 'local sleep' or regional arousal states, when the patient is partially asleep and partially awake, and manifests as complex motor and/or verbal behaviours in a partially conscious state. The few studies of the effects of standard PTSD treatments (medications, CBT) on PTSD-associated somatic syndromes report a reduction in the severity of ill-defined and autonomically mediated somatic symptoms, self-reported physical health problems, and some chronic pain syndromes. © 2013 Institute of Psychiatry.


Rubin V.L.,University of Western Ontario
Information Processing and Management | Year: 2010

This article introduces a type of uncertainty that resides in textual information and requires epistemic interpretation on the information seeker's part. Epistemic modality, as defined in linguistics and natural language processing, is a writer's estimation of the validity of propositional content in texts. It is an evaluation of chances that a certain hypothetical state of affairs is true, e.g., definitely true or possibly true. This research shifts attention from the uncertainty-certainty dichotomy to a gradient epistemic continuum of absolute, high, moderate, low certainty, and uncertainty. An analysis of a New York Times dataset showed that epistemically modalized statements are pervasive in news discourse and they occur at a significantly higher rate in editorials than in news reports. Four independent annotators were able to recognize a gradation on the continuum but individual perceptions of the boundaries between levels were highly subjective. Stricter annotation instructions and longer coder training improved intercoder agreement results. This paper offers an interdisciplinary bridge between research in linguistics, natural language processing, and information seeking with potential benefits to design and implementation of information systems for situations where large amounts of textual information are screened manually on a regular basis, for instance, by professional intelligence or business analysts. © 2010 Elsevier Ltd. All rights reserved.


Gray D.F.,University of Western Ontario
Astronomical Journal | Year: 2014

Projected rotation rates of five early A-type slowly rotating stars are measured spectroscopically to a precision of 0.2 km s-1. A detailed Fourier analysis is done, as well as a comparison of profiles directly. Macroturbulence is needed in addition to rotation to reproduce the profile shapes. An upper limit of ≲2 km s-1 is placed on the microturbulence dispersion. Small unexplained differences between the models and the observations are seen in the sidelobe structure of the transforms. The v sin i results are: α Dra, 26.2; θ Leo, 22.5; α CMa A, 16.7; γ Gem A, 10.7; o Peg, 6.0 km s-1. These stars are suitable as standards for measuring rotation using less fundamental methods. © 2014. The American Astronomical Society. All rights reserved.


Chande N.,University of Western Ontario
Inflammatory Bowel Diseases | Year: 2013

Venous thromboembolism is a relatively common and potentially serious complication in inpatients with inflammatory bowel disease (IBD). There are a number of pathophysiologic mechanisms for venous thromboembolism that are specific to patients with IBD that may be active. The use of anticoagulants for prophylaxis against venous thromboembolism in hospitalized patients with IBD needs to be balanced against the potential for worsening of rectal bleeding. Evidence from randomized trials suggests that heparin and low-molecular weight heparin are generally safe to use in patients with active IBD, and a number of guidelines support their use for thromboprophylaxis in this patient population. Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.


Fenton M.B.,University of Western Ontario
Animal Behaviour | Year: 2013

In their 1960 paper about bats using echolocation to find and track flying insects, Donald R. Griffin, Fredric A. Webster and Charles R. Michael (Animal Behaviour, 8, 141-154) changed the face of research on this behaviour. They moved the field of echolocation from documenting that this animal or that one could echolocate to demonstrating an adaptive value of echolocation. They used experiments with captive bats, fruit flies, mosquitoes and crane flies to illustrate how bats used a 'feeding buzz' as they closed with their prey. The topic remains current today, and one of the first papers in Nature in 2013 (Jacobsen et al., 493, 93-96) presented more information about feeding buzzes building on the platform that Griffin et al. had established. In the intervening period, literally thousands of papers have been published about echolocation, demonstrating how curious minds, technological advances and basic information about natural history can result in diversification of a field of research. We have learned that bats can use echolocation to recognize water surfaces and to find insect prey on spider webs. The continuum between orientation and social functions of echolocation means that this behaviour not only influences foraging and negotiating obstacle paths, but is also a cue that brings individuals together. Acoustic wars between bats and potential insect prey have further enriched the discipline by identifying acoustic measures and countermeasures used by the players. Parallel studies with toothed whales have provided further examples of the enrichment that echolocation brings to the lives of animals and those who study them. © 2013 The Association for the Study of Animal Behaviour.


Neff B.D.,University of Western Ontario
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2013

Many species in the animal kingdom are characterized by alternative mating tactics (AMTs) within a sex. In males, such tactics include mate guarding versus sneaking behaviours, or territorial versus female mimicry. Although AMTs can occur in either sex, they have been most commonly described in males. This sex bias may, in part, reflect the increased opportunity for sexual selection that typically exists in males, which can result in a higher probability that AMTs evolve in that sex. Consequently, females and polyandry can play a pivotal role in governing the reproductive success associated with male AMTs and in the evolutionary dynamics of the tactics. In this review, we discuss polyandry and the evolution of AMTs. First, we define AMTs and review game theoretical and quantitative genetic approaches used to model their evolution. Second, we review several examples of AMTs, highlighting the roles that genes and environment play in phenotype expression and development of the tactics, as well as empirical approaches to differentiating among the mechanisms. Third, ecological and genetic constraints to the evolution of AMTs are discussed. Fourth, we speculate on why female AMTs are less reported on in the literature than male tactics. Fifth, we examine the effects of AMTs on breeding outcomes and female fitness, and as a source, and possibly also a consequence, of sexual conflict. We conclude by suggesting a new model for the evolution of AMTs that incorporates both environmental and genetic effects, and discuss some future avenues of research.


Williamson P.C.,University of Western Ontario | Allman J.M.,California Institute of Technology
Frontiers in Human Neuroscience | Year: 2012

Some promising genetic correlates of schizophrenia have emerged in recent years but none explain more than a small fraction of cases. The challenge of our time is to characterize the neuronal networks underlying schizophrenia and other neuropsychiatric illnesses. Early models of schizophrenia have been limited by the ability to readily evaluate large-scale networks in living patients. With the development of resting state and advanced structural magnetic resonance imaging, it has become possible to do this. While we are at an early stage, a number of models of intrinsic brain networks have been developed to account for schizophrenia and other neuropsychiatric disorders. This paper reviews the recent voxel-based morphometry (VBM), diffusion tensor imaging (DTI), and resting functional magnetic resonance imaging literature in light of the proposed networks underlying these disorders. It is suggested that there is support for recently proposed models that suggest a pivotal role for the salience network. However, the interactions of this network with the default mode network and executive control networks are not sufficient to explain schizophrenic symptoms or distinguish them from other neuropsychiatric disorders. Alternatively, it is proposed that schizophrenia arises from a uniquely human brain network associated with directed effort including the dorsal anterior and posterior cingulate cortex (PCC), auditory cortex, and hippocampus while mood disorders arise from a different brain network associated with emotional encoding including the ventral anterior cingulate cortex (ACC), orbital frontal cortex, and amygdala. Both interact with the dorsolateral prefrontal cortex and a representation network including the frontal and temporal poles and the fronto-insular cortex, allowing the representation of the thoughts, feelings, and actions of self and others across time. © 2012 Williamson and Allman.


McBean G.A.,University of Western Ontario
Current Opinion in Environmental Sustainability | Year: 2012

Our planet is under stress from the impacts of hazards, like earthquakes, floods and storms. These have major impacts on vulnerable, generally less-developed societies and make achieving sustainable development exceedingly difficult. A relatively new international research program, Integrated Research on Disaster Risk is now underway towards meeting its legacy of an enhanced capacity around the world to address hazards and make informed decisions on actions to reduce their impacts leading to societies shifting their focus from response-recovery towards prevention-mitigation, building resilience and reducing risks, learning from experience and avoiding past mistakes. © 2012 Elsevier B.V.


Annweiler C.,University of Angers | Annweiler C.,University of Western Ontario | Llewellyn D.J.,University of Exeter | Beauchet O.,University of Angers
Journal of Alzheimer's Disease | Year: 2013

Vitamin D has been investigated in association with cognitive function in older adults. It is unclear whether hypovitaminosis D could be associated with Alzheimer's disease (AD). Our objective was to systematically review and quantitatively synthesize the association of low serum 25-hydroxyvitamin D (25OHD) concentrations with AD in adults. A Medline and PsycINFO® search was conducted on May 2012, with no limit of date, using the MeSH terms 'Vitamin D' OR 'Hydroxycholecalciferols' combined with the MeSH terms 'Alzheimer disease' OR 'Dementia' OR 'Cognition' OR 'Cognition disorders' OR 'Memory' OR 'Memory Disorders' OR 'Executive Function' OR 'Attention' OR 'Neuropsychological Tests'. Of the 284 selected studies, 10 observational studies (including 9 case-controls and 1 cohort study) met the selection criteria. All were of good quality. The number of AD cases ranged from 20 to 211 (40%-100% female). Finally, 7 case-control studies were eligible for fixed and random-effects meta-analyses of bias-corrected effect size of the difference in serum 25OHD concentrations between AD cases and controls using an inverse-variance method. The pooled effect size in random-effects meta-analysis was 1.40 (95% CI: 0.26;2.54), a 'large' effect size that indicates that serum 25OHD concentrations were 1.4 standard deviation units lower in AD cases compared to cognitively healthy controls (p = 0.016). In conclusion, AD cases had lower serum vitamin D concentrations than matched controls. This reinforces the conceptualization of vitamin D as a 'neurosteroid hormone' and as a potential biomarker of AD. © 2013 - IOS Press and the authors. All rights reserved.


Leask A.,University of Western Ontario
Journal of Cell Communication and Signaling | Year: 2012

There is no therapy for chronic fibroproliferative diseases, in spite of the fact that current health statistics suggest that these (which include cardiovascular disease, pulmonary fibrosis, diabetic nephropathy, liver cirrhosis and systemic sclerosis) have been estimated to cause approximately 45% of the deaths in the developed world. Recently, many studies have shown that mitogen activated protein kinases (MAPKs) are activated in response to fibrogenic agents and contribute to the formation and function of the myofibroblast, the critical cell type responsible for excessive scarring. A recent report by Madala and colleagues (Am J Respir Cell Mol Biol, 2011) has provided a proof-of-concept study showing that the specific MEK inhibitor ARRY-142886 (ARRY) can both suppress the progression of fibrosis and reverse an animal model of lung fibrosis. Thus MEK inhibition could be a valuable method to treat lung fibrosis. © The International CCN Society 2011.


Doey T.,University of Western Ontario
Journal of Affective Disorders | Year: 2012

Background: Aripiprazole is an atypical antipsychotic with unique pharmacological properties, used for a variety of indications, including psychotic and mood disorders in youth. Existing literature was reviewed to summarize experience with this agent in that population. Methods: A review of relevant literature using the key words aripiprazole, children, pediatric, all child, schizophrenia, bipolar disorder, and atypical antipsychotics was conducted. Results: A total of 140 articles and book chapters were identified, of which 7 reported double-blind controlled trials with aripiprazole, 5 were meta-analyses of pooled data, 11 were open label trials, 10 were chart reviews, and 17 were case reports or case series. Limitations: Although every effort was made to locate all available data, some information from posters or researchers was not available. Publication bias tends to report positive outcomes with a treatment, while negative studies are less likely to be reported. Most trials are of short duration. Conclusions: Treatment with aripiprazole is associated with significant reduction of the Positive and Negative Symptom Scale (PANSS) scores in youth with schizophrenia, and reductions in items in the negative symptom scores at higher doses (30 mg/day). Significant reductions in the Young Mania Rating Scale (YMRS) have been demonstrated in youth with bipolar disorder. In mixed populations, reductions in the Clinical Global Impressions Scale (CGI-S) have also been demonstrated when compared with treatment with placebo. Head-to-head comparisons are fewer in number, and overall aripiprazole compares favorably with other atypical antipsychotics (ATAs) in the populations studied. Treatment with aripiprazole is reported to have a lower incidence of weight gain, and less elevation of prolactin. At higher doses, it appears more likely to result in extrapyramidal symptoms (EPS) and tremor. © 2012 Elsevier B.V. All rights reserved.


Kudoh T.,Japan National Astronomical Observatory | Basu S.,University of Western Ontario
Astrophysical Journal | Year: 2011

We employ three-dimensional magnetohydrodynamic simulations including ambipolar diffusion to study the gravitationally driven fragmentation of subcritical molecular clouds, in which the gravitational fragmentation is stabilized as long as magnetic flux-freezing applies. The simulations show that the cores in an initially subcritical cloud generally develop gradually over an ambipolar diffusion time, which is about a few ×107yr in a typical molecular cloud. On the other hand, the formation of collapsing cores in subcritical clouds is accelerated by supersonic nonlinear flows. Our parameter study demonstrates that core formation occurs faster as the strength of the initial flow speed in the cloud increases. We found that the core formation time is roughly proportional to the inverse of the square root of the enhanced density created by the supersonic nonlinear flows. The density dependence is similar to that derived in quasistatically contracting magnetically supported clouds, although the core formation conditions are created by the nonlinear flows in our simulations. We have also found that the accelerated formation time is not strongly dependent on the initial strength of the magnetic field if the cloud is highly subcritical. Our simulation shows that the core formation time in our model subcritical clouds is several ×106 yr due to the presence of large-scale supersonic flows (∼3 times sound speed). Once a collapsing core forms, the density, velocity, and magnetic field structure of the core do not strongly depend on the initial strength of the velocity fluctuation. The infall velocities of the cores are subsonic and the magnetic field lines show weak hourglass shapes. © 2011. The American Astronomical Society. All rights reserved. Printedin the U.S.A.


Christou A.A.,College Hill | Wiegert P.,University of Western Ontario
Icarus | Year: 2012

We have carried out a search for Main Belt Asteroids (MBAs) co-orbiting with the large MBA Vesta and the dwarf planet Ceres. Through improving the search criteria used in Christou (Christou, A.A. [2000b]. Astron. Astrophys. 356, L71-L74) and numerical integrations of candidate coorbitals, we have identified approximately 51 (44) objects currently in co-orbital libration with Ceres (Vesta). We show that these form part of a larger population of transient coorbitals; 129 (94) MBAs undergo episodes of co-orbital libration with Ceres (Vesta) within a 2Myr interval centred on the present. The lifetime in the resonance is typically a few times ~105yr but can exceed 2×106yr. The variational properties of the orbits of several co-orbitals were examined. It was found that their present states with respect to the secondary are well determined but knowledge of it is lost typically after ~2×105yr. Objects initially deeper into the coorbital region maintain their coorbital state for longer. Using the model of Namouni et al. (Namouni, F., Christou, A.A., Murray, C.D. [1999]. Phys. Rev. Lett. 83, 2506-2509) we show that their dynamics are similar to those of temporary coorbital NEAs of the Earth and Venus. As in that case, the lifetime of resonant libration is dictated by planetary secular perturbations, the inherent chaoticity of the orbits and close encounters with massive objects other than the secondary. In particular we present evidence that, while in the coorbital state, close encounters with the secondary are generally avoided and that Ceres affects the stability of tadpole librators of Vesta. Finally we demonstrate the existence of Quasi-Satellite orbiters of both Ceres and Vesta and conclude that decametre-sized objects detected in the vicinity of Vesta by the DAWN mission may, in fact, belong to this dynamical class rather than be bona-fide (i.e. Keplerian) satellites of Vesta. © 2011 Elsevier Inc.


Tan J.,University of Western Ontario | Berg M.,Uppsala University
Journal of the American Academy of Dermatology | Year: 2013

Case definitions are critical in epidemiologic research. However, modern disease indicators must now consider complex data from gene-based research along with traditional clinical parameters. Rosacea is a skin disorder with multiple signs and symptoms. In individuals, these features may be multiple or one may predominate. While studies on the epidemiology of rosacea have previously been sparse, there has been a recent increase in research activity. A broader body of epidemiological information that includes a greater variety of countries beyond Northern Europe and general population-based demographics is needed. As there are operational issues in current case definitions of rosacea subtypes - rationalization and standardization - universal consistent applications in future research is also imperative. Further improvement in disease definition combining new research information along with clinical pragmatism should increase the accuracy of rosacea case ascertainment and facilitate further epidemiological research. © 2013 by the American Academy of Dermatology, Inc.


Zhou W.,University of Western Ontario
Journal of Infrastructure Systems | Year: 2012

A methodology is developed to evaluate the annual failure probabilities of a pressurized pipeline at an active metal-loss corrosion defect. The methodology takes into account three different failure modes at the defect (i.e., small leak, large leak, and rupture) and the time dependency of the pipe's internal pressure by modeling the pressure as a simple stochastic process consisting of a sequence of independent and identically distributed random variables, each occupying a period of one year. The impact of periodic maintenance actions on the failure probabilities is incorporated in the methodology. Two numerical examples are used to illustrate the methodology. The sensitivity of the calculated failure probabilities with respect to the time dependency of the internal pressure is also investigated. © 2011 American Society of Civil Engineers.


Vanderloo L.M.,University of Western Ontario
BMC Pediatrics | Year: 2014

Background: Screen-viewing is one of the most common sedentary behaviors among preschoolers. Despite the high prevalence of sedentary behaviors in childcare, little research exists on the context and/or type of activities that account for these particular behaviors. Accordingly, if the amount of screen-viewing accumulated by preschoolers in childcare is not considered, researchers may be underestimating total screen time among this population, as only a portion of their day is being captured (i.e., the home environment). This systematic review provides a synthesis of research on the levels of screen-viewing among preschool-aged children (2.5-5 years) attending childcare (i.e., centre- and home-based childcare). This review also examined the correlates of screen-viewing among preschoolers in this setting. To provide additional contextual information, availability of screen activities was used to help ameliorate the understanding of preschoolers' screen-viewing behaviors in childcare.Methods: Twelve electronic databases were searched to retrieve relevant articles for inclusion (dating from 2000 onwards). Additional studies were identified via manual searching techniques (i.e., hand searching and citation tracking). Only English, published peer-reviewed articles that examined preschoolers' screen-viewing behaviors in childcare (i.e., rates of screen-viewing and access to/opportunities for related activities) were included. No restrictions to study design were applied.Results: Seventeen international studies (4 experimental; 12 cross-sectional; 1 mixed-methods) published between 2004 and 2014 were examined. Of those, eight studies reported rates of screen-viewing and found that preschoolers spent approximately 0.1 to 1.3 hrs/day and 1.8 to 2.4 hrs/day engaged in this behavior in center- and home-based childcare, respectively. High staff education (negative association) and type of childcare arrangement (notably, home-based childcare in comparison to center-based childcare; positive association) were identified as two correlates in relation to preschoolers' screen-viewing in childcare. Nine studies spoke to the availability of screen-viewing activities in childcare, and found the childcare environment to be conducive to this behavior.Conclusions: Despite some variability, preschoolers appear to engage in somewhat high levels of screen-viewing while in childcare, particularly within home-based facilities. This paper also highlighted the conduciveness of the childcare environment with regard to screen-viewing among preschoolers. Additional exploration into the correlates of screen-viewing in childcare is required. (PROSPORO registration: CRD42013005552). © 2014 Vanderloo; licensee BioMed Central Ltd.


Savundranayagam M.Y.,University of Western Ontario
International Journal of Geriatric Psychiatry | Year: 2014

Objective There is a growing body of literature on the rewards associated with caregiving and the utility of these rewards on buffering the negative consequences of caring for a family member with Alzheimer's disease. Many psychoeducational interventions aim to empower caregivers to seek and obtain help from their social support network, with the expectation that help will enable them to cope more effectively. Methods This study investigated the impact of changes in help and changes in satisfaction with help on positive aspects of caregiving for both spouse (N = 254) and adult-child (N = 208) caregivers who attended a psychoeducational intervention. Results Analyses using structural equation modeling revealed that increases in amount of help and satisfaction with help were significantly linked with increases in caregiver rewards for adult-children. However, only increases in satisfaction with help were significantly related to increases in caregiver rewards for spouses. Conclusions These group differences suggest that the quality of support is critical for spouses, whereas both quality and receiving extra help are useful for adult-child caregivers. These findings are discussed in terms of the importance of understanding the differential needs of spouse and adult-child caregivers in practice. Copyright © 2013 John Wiley & Sons, Ltd.


Staples J.F.,University of Western Ontario
Journal of Experimental Biology | Year: 2014

Hibernation evolved in some small mammals that live in cold environments, presumably to conserve energy when food supplies are low. Throughout the winter, hibernators cycle spontaneously between torpor, with low metabolism and near-freezing body temperatures, and euthermia, with high metabolism and body temperatures near 37° C. Understanding the mechanisms underlying this natural model of extreme metabolic plasticity is important for fundamental and applied science. During entrance into torpor, reductions in metabolic rate begin before body temperatures fall, even when thermogenesis is not active, suggesting active mechanisms of metabolic suppression, rather than passive thermal effects. Mitochondrial respiration is suppressed during torpor, especially when measured in liver mitochondria fuelled with succinate at 37° C in vitro. This suppression of mitochondrial metabolism appears to be invoked quickly during entrance into torpor when body temperature is high, but is reversed slowly during arousal when body temperature is low. This pattern may reflect body temperaturesensitive, enzyme-mediated post-translational modifications of oxidative phosphorylation complexes, for instance by phosphorylation © 2014. Published by The Company of Biologists Ltd.


Baines K.M.,University of Western Ontario
Chemical Communications | Year: 2013

In 1981, Adrian G. Brook published his seminal work on the synthesis and characterization of the first solid, stable silene. This viewpoint summarizes the work leading up to the publication of the article and explores the significant impact it had on the field. © 2013 The Royal Society of Chemistry.


Song Y.,Tongji University | Zou X.,University of Western Ontario
Computers and Mathematics with Applications | Year: 2014

Spatiotemporal dynamics in a ratio-dependent predator-prey model with diffusion is studied by analytical methods. Normal forms associated with codimension-two Hopf-Turing bifurcation are derived, which can be used to understand and classify the spatiotemporal dynamics of the model for values of parameters close to the Hopf-Turing bifurcation point. In the vicinity of this degenerate point, a wealth of complex spatiotemporal dynamics are observed. Our theoretical results are confirmed by numerical simulations. © 2014 Elsevier Ltd. All rights reserved.


In more than 4 Ga of geological evolution, the Earth has twice gone through extreme climatic perturbations, when extensive glaciations occurred, together with alternating warm periods which were accompanied by atmospheric oxygenation. The younger of these two episodes of climatic oscillation preceded the Cambrian "explosion" of metazoan life forms, but similar extreme climatic conditions existed between about 2.4 and 2.2 Ga. Over long time periods, changing solar luminosity and mantle temperatures have played important roles in regulating Earth's climate but both periods of climatic upheaval are associated with supercontinents. Enhanced weathering on the orogenically and thermally buoyed supercontinents would have stripped CO2 from the atmosphere, initiating a cooling trend that resulted in continental glaciation. Ice cover prevented weathering so that CO2 built up once more, causing collapse of the ice sheets and ushering in a warm climatic episode. This negative feedback loop provides a plausible explanation for multiple glaciations of the Early and Late Proterozoic, and their intimate association with sedimentary rocks formed in warm climates. Between each glacial cycle nutrients were flushed into world oceans, stimulating photosynthetic activity and causing oxygenation of the atmosphere. Accommodation for many ancient glacial deposits was provided by rifting but escape from the climatic cycle was predicated on break-up of the supercontinent, when flooded continental margins had a moderating influence on weathering. The geochemistry of Neoproterozoic cap carbonates carries a strong hydrothermal signal, suggesting that they precipitated from deep sea waters, overturned and spilled onto continental shelves at the termination of glaciations. Paleoproterozoic (Huronian) carbonates of the Espanola Formation were probably formed as a result of ponding and evaporation in a hydrothermally influenced, restricted rift setting. Why did metazoan evolution not take off after the Great Oxidation Event of the Paleoproterozoic? The answer may lie in the huge scar left by the ∼2023 Ma Vredefort impact in South Africa, and in the worldwide organic carbon-rich deposits of the Shunga Event, attesting to the near-extirpation of life and possible radical alteration of the course of Earth history. © 2013, China University of Geosciences (Beijing) and Peking University. Production and hosting by Elsevier B.V. All rights reserved.


Gladman D.D.,University of Western Ontario
Rheumatic Disease Clinics of North America | Year: 2012

Psoriatic arthritis is an inflammatory musculoskeletal disease associated with psoriasis that is usually seronegative for rheumatoid factor. Psoriatic arthritis affects men and women equally, usually during the fourth decade, although it may affect children and octogenarians. Psoriatic arthritis may lead to deformities, joint damage, reduced quality of life and function. Early detection and treatment may prevent untoward outcomes. © 2012 Elsevier Inc.


Song Y.,University of Western Ontario
Physical Chemistry Chemical Physics | Year: 2013

In addressing the global demand for clean and renewable energy, hydrogen stands out as the most suitable candidate for many fuel applications that require practical and efficient storage of hydrogen. Supplementary to the traditional hydrogen storage methods and materials, the high-pressure technique has emerged as a novel and unique approach to developing new potential hydrogen storage materials. Static compression of materials may result in significant changes in the structures, properties and performance that are important for hydrogen storage applications, and often lead to the formation of unprecedented phases or complexes that have profound implications for hydrogen storage. In this perspective article, 22 types of representative potential hydrogen storage materials that belong to four major classes - simple hydride, complex hydride, chemical hydride and hydrogen containing materials - were reviewed. In particular, their structures, stabilities, and pressure-induced transformations, which were reported in recent experimental works together with supporting theoretical studies, were provided. The important contextual aspects pertinent to hydrogen storage associated with novel structures and transitions were discussed. Finally, the summary of the recent advances reviewed and the insight into the future research in this direction were given. This journal is © the Owner Societies 2013.


Roberts W.A.,University of Western Ontario
Journal of Experimental Psychology: Animal Behavior Processes | Year: 2010

Number discrimination experiments with humans and monkeys have revealed distance and magnitude effects. When required to choose the more frequently occurring stimulus between two stimuli presented repeatedly in sequence, accuracy improves as the distance between number increases (distance effect) and decreases as distance is held constant and the size of the numbers increases (magnitude effect). These effects were shown in three experiments reported with pigeons as subjects. It was shown that a single model based on discrimination between noisy numerical representations could account for both the primate and bird findings. To model the pigeon data, an additional decay parameter was necessary to account for strong recency effects found for the influence on choice of terminal stimuli presented in a sequence. © 2010 American Psychological Association.


Leask A.,University of Western Ontario
Journal of Cell Communication and Signaling | Year: 2012

Scleroderma, an autoimmune disorder characterized by skin and organ fibrosis, has no treatment. Although over the past decade valuable insights into the molecular mechanisms underlying scleroderma have been generated, results in clinical trials have been disappointing. This issue is likely to arise due to the heterogeneity of scleroderma. Molecular insights into the heterogeneity of this disease have been provided by genome-wide expression profiling. In a recent paper, Bhattacharyya and colleagues (PLOS One 6:e23082, 2011b) to show that the overexpression of a range of "fibroproliferative" genes in diffuse cutaneous scleroderma patients are likely to be caused by the overexpression of transcription factor Early growth response (Egr)-1. Only a minority of Egr-1-regulated genes were also found to be regulated by TGF-β. Moreover, Greenblatt and colleagues (Am J Pathol., 2012) have shown that the over-expression of "inflammatory" genes overexpressed in "localized" scleroderma and a small subset of limited and diffuse scleroderma patients is likely to be due to the activity of interleukin-13 (IL-13). Intriguingly, at a gene expression level, murine sclerodermatous graft-versus-host disease (sclGVHD) approximates this inflammatory subset of scleroderma. These data suggest that targeting Egr-1 expression/activity might be a novel therapeutic strategy to control fibrosis in a subset of diffuse scleroderma patients, and further emphasize that notion that elevated canonical TGFβ signaling is insufficient to explain the fibrosis observed in scleroderma. Moreover, targeting IL-13 expression/activity might be a novel therapeutic strategy to target the inflammation leading to "localized" scleroderma. © The International CCN Society 2012.


Ware W.R.,University of Western Ontario
Dermato-Endocrinology | Year: 2010

There is growing evidence that vitamin D deficiency significantly increases the risk of adverse cardiovascular events and that a vitamin D status representing sufficiency or optimum is protective. Unfortunately, in clinical trials that address interventions for reducing risk of adverse cardiovascular events, vitamin D status is not generally measured. Failure to do this has now assumed greater importance with the report of a study that found rosuvastatin at doses at the level used in a recent large randomized lipid lowering trial (JUPITER) had a large and significant impact on vitamin D levels as measured by the metabolite 25-hydroxyvitamin D. The statin alone appears to have increased this marker such that the participants on average went from deficient to sufficient in two months. The difference in cardiovascular risk between those deficient and sufficient in vitamin D in observational studies was similar to the risk reduction found in JUPITER. Thus it appears that this pleiotropic effect of rosuvastatin may be responsible for part of its unusual effectiveness in reducing the risk of various cardiovascular endpoints found in JUPITER and calls into question the interpretation based only on LDL cholesterol and CRP changes. In addition, vitamin D status is a cardiovascular risk factor which up until now has not been considered in adjusting study results or in multivariate analysis, and even statistical analysis using only baseline values may be inadequate. © 2010 Landes Bioscience.


Leask A.,University of Western Ontario
Fibrogenesis and Tissue Repair | Year: 2010

Background: In response to normal tissue injury, fibroblasts migrate into the wound where they synthesize and remodel new extracellular matrix. The fibroblast responsible for this process is called the myofibroblast, which expresses the highly contractile protein α-smooth muscle actin (α-SMA). In normal tissue repair, the myofibroblast disappears. Conversely, abnormal myofibroblast persistence is a key feature of fibrotic dieases, including scleroderma (systemic sclerosis, SSc). Myofibroblasts can be derived from differentiation of local resident fibroblasts or by recruitment of microvascular pericytes.Clinical problem addressed: Controlling myofibroblast differentiation and persistence is crucial for developing anti-fibrotic therapies targeting SSc.Basic science advances: Insights have been recently generated into how the proteins transforming growth factor β (TGFβ), endothelin-1 (ET-1), connective tissue growth factor (CCN2/CTGF) and platelet derived growth factor (PDGF) contribute to myofibroblast differentiation and pericyte recruitment in general and to the persistent myofibroblast phenotype of lesional SSc fibroblast, specifically.Relevance to clinical care: This minireview summarizes recent findings pertinent to the origin of myofibroblasts in SSc and how this knowledge might be used to control the fibrosis in this disease.Conclusions: TGFβ, ET-1, CCN2 and PDGF are likely to cooperate in driving tissue repair and fibrogenic responses in fibroblasts. TGFβ, ET-1 and CCN2 appear to contribute to myofibroblast differentiation; PDGF appears to be involved with pericyte recruitment. Thus, different therapeutic strategies may exist for targeting the multisystem fibrotic disorder SSc. © 2010 Leask; licensee BioMed Central Ltd.


McGavin M.J.,University of Western Ontario
Frontiers in cellular and infection microbiology | Year: 2012

Staphylococcus aureus clonal complex CC30 has caused infectious epidemics for more than 60 years, and, therefore, provides a model system to evaluate how evolution has influenced the disease potential of closely related strains. In previous multiple genome comparisons, phylogenetic analyses established three major branches that evolved from a common ancestor. Clade 1, comprised of historic pandemic phage type 80/81 methicillin susceptible S. aureus (MSSA), and Clade 2 comprised of contemporary community acquired methicillin resistant S. aureus (CA-MRSA) were hyper-virulent in murine infection models. Conversely, Clade 3 strains comprised of contemporary hospital associated MRSA (HA-MRSA) and clinical MSSA exhibited attenuated virulence, due to common single nucleotide polymorphisms (SNP's) that abrogate production of α-hemolysin Hla, and interfere with signaling of the accessory gene regulator agr. We have now completed additional in silico genome comparisons of 15 additional CC30 genomes in the public domain, to assess the hypothesis that Clade 3 has evolved to favor niche adaptation. In addition to SNP's that influence agr and hla, other common traits of Clade 3 include tryptophan auxotrophy due to a di-nucleotide deletion within trpD, a premature stop codon within isdH encoding an immunogenic cell surface protein involved in iron acquisition, loss of a genomic toxin-antitoxin (TA) addiction module, acquisition of S. aureus pathogenicity islands SaPI4, and SaPI2 encoding toxic shock syndrome toxin tst, and increased copy number of insertion sequence ISSau2, which appears to target transcription terminators. Compared to other Clade 3 MSSA, S. aureus MN8, which is associated with Staphylococcal toxic shock syndrome, exhibited a unique ISSau2 insertion, and enhanced production of toxic shock syndrome toxin encoded by SaPI2. Cumulatively, our data support the notion that Clade 3 strains are following an evolutionary blueprint toward niche-adaptation.


Classen S.,University of Western Ontario
Occupational Therapy in Health Care | Year: 2014

Parkinson's disease (PD) is a complex neurodegenerative disorder leading to motor and non-motor impairments, all of which can affect fitness to drive. The literature suggest that on-road and simulated driving performances are impaired in people with PD, as compared to healthy control drivers. Clear associations exist between impaired driving performance and contrast sensitivity, visual processing speed, and psychomotor speed. Prior to this review and expert panel process, no evidence-based guidelines have existed to help occupational therapy practitioners determining fitness to drive in those with PD. Three consensus statements are presented in this work to enable occupational therapy practitioners and other driver rehabilitation specialists to make fitness to drive determinations in people with PD. © 2014 Informa Healthcare USA, Inc.


With the advent of new oral anticoagulants, the place of warfarin for stroke prevention in patients with atrial fibrillation needs re-evaluation. Warfarin is difficult to use, because of large individual differences in response and metabolism, many significant interactions with drugs and foods, and fluctuations in vitamin K absorption. It requires frequent blood testing and dose adjustments, so with good reason patients and physicians are eager for the newer agents that are easier to use. However, the purchase price of the new anticoagulants is so high that warfarin will remain in widespread use. It is important therefore for physicians to know how to use it well. Anticoagulants work much better for stroke prevention in atrial fibrillation than do antiplatelet agents; physicians need to understand the concept of red thrombus (for which anticoagulants are required) versus white thrombus - platelet aggregates - which are the target of antiplatelet agents. Stroke from atrial fibrillation increases steeply with age, and the elderly benefit disproportionately from anticoagulation. It is still necessary for physicians to know how to use warfarin, and to use it better than it has been used in the past. © 2013 Springer-Verlag Wien.


Adams P.C.,University of Western Ontario
International Journal of Laboratory Hematology | Year: 2015

Hemochromatosis is the most common genetic disease in northern European populations. Body iron stores progressively increase in most patients, which can lead to cirrhosis of the liver, hepatocellular carcinoma, heart failure, arthritis, and pigmentation. Simple blood tests such as the serum ferritin and transferrin saturation are useful to suggest the diagnosis which can be confirmed in most cases with a simple genetic test for the C282Y mutation of the HFE gene. However, these blood tests are often misinterpreted and there are rare patients with iron overload without HFE mutations. A diagnostic approach is presented based on a large referral practice and a population-based study (HEIRS) which screened for iron overload in 101 168 participants. © 2015 John Wiley & Sons Ltd.


Ciuffi A.,University of Lausanne | Barr S.D.,University of Western Ontario
Methods | Year: 2011

The integration of the Human Immunodeficiency Virus (HIV) genetic information into the host genome is fundamental for its replication and long-term persistence in the host. Isolating and characterizing the integration sites can be useful for obtaining data such as identifying the specific genomic location of integration or understanding the forces dictating HIV integration site selection. The methods outlined in this article describe a highly efficient and precise technique for identifying HIV integration sites in the host genome on a small scale using molecular cloning techniques and standard sequencing or on a massive scale using 454 pyrosequencing. © 2010 Elsevier Inc.


Leask A.,University of Western Ontario
Seminars in Immunopathology | Year: 2015

Systemic sclerosis (SSc, scleroderma) is an often-fatal disease characterized by connective tissue fibrosis of skin and internal organs. In scleroderma, there is an excessive production and accumulation of extracellular matrix (ECM) components resulting from an increase in collagen synthesis and matrix stability. Understanding how this how excessive ECM is produced and remodeled may represent a novel therapeutic approach. In this review, the transcription factors and collagen-modifying enzymes underlying collagen overexpression and enhancing stability in SSc are discussed. Moreover, the role of matrix stiffness in promoting fibrosis via a feed-forward mechanism is discussed. Indeed, the emerging evidence is that enhanced ECM remodeling resulting in increased ECM stiffness may be sufficient in itself to sustain persistence fibrosis in SSc. © 2015, Springer-Verlag Berlin Heidelberg.


Bansal P.,University of Western Ontario | Knox-Hayes J.,Georgia Institute of Technology
Organization and Environment | Year: 2013

In this article, we argue that prior organizations research has contributed to the erosion of the natural environment by failing to discriminate physical materiality from sociomateriality. The time-space attributes of physical materiality are more immutable than sociomateriality, so the compression of time and space in and by organizations is disrupting the cycles of the natural environment. We illustrate this point through the example of carbon markets. The development of futures and other financial derivatives contributes to the compression of time, whereas the movement of capital worldwide contributes to the compression of space. This time-space compression disembodies financial instruments from their physical target, namely, carbon, leading to the distortion of the instrument's "real" value and hampering carbon emissions reductions. We call for organizational theories that more fully account for physical materiality. © 2013 SAGE Publications.


The Health Assessment Questionnaire (HAQ) is a validated physical function measure. It is predictive for disability and mortality. The objective of this study was to determine the comparative efficacy of biologic agents in improving HAQ in patients with established RA who failed DMARDs or anti- TNF agents and in early RA (ERA). We performed random effects meta-analyses of published randomised, placebo-controlled trials. Outcome was the mean difference in change in HAQ for biologic agents compared to controls (ΔHAQB-ΔHAQC). Indirect comparisons of the different biologic drugs were conducted using the Q-test based on analysis of variance. Meta-regression was performed using the method of moments. Twenty-eight trials were included: 19 with DMARD-failures; 4 with anti-TNF-failures and 5 ERA. The following biologics were represented: abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab and tocilizumab. Efficacy of biologics at reducing HAQ was significantly different based on prior treatment (p=0.001). In RA patients with DMARD failures, ΔHAQB-ΔHAQC was -0.22; 95%CI: -0.24, -0.20 (I2=55%). Infliximab, abatacept and tocilizumab had lower ΔHAQB-ΔHAQC compared to other biologics (p<0.02). In anti-TNF-failures, ΔHAQB-ΔHAQC was -0.36; 95%CI: -0.42, -0.30 (I2=0%). In ERA, methotrexate-naïve trials, ΔHAQB-ΔHAQC was -0.19; 95% CI: -0.26, -0.13 (I2=0%). There were no significant differences in the efficacy of different biologics for anti-TNF failures and ERA. Biologic agents were efficacious at lowering HAQ in RA. Differences between agents in RA with DMARD failures were less than the minimally clinically important difference for HAQ; therefore, the clinical significance of these differences is unclear.


MacDougall-Shackleton S.A.,University of Western Ontario
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2011

The term levels of analysis has been used in several ways: to distinguish between ultimate and proximate levels, to categorize different kinds of research questions and to differentiate levels of reductionism. Because questions regarding ultimate function and proximate mechanisms are logically distinct, I suggest that distinguishing between these two levels is the best use of the term. Integrating across levels in research has potential risks, but many benefits. Consideration at one level can help generate novel hypotheses at the other, define categories of behaviour and set criteria that must be addressed. Taking an adaptationist stance thus strengthens research on proximate mechanisms. Similarly, it is critical for researchers studying adaptation and function to have detailed knowledge of proximate mechanisms that may constrain or modulate evolutionary processes. Despite the benefits of integrating across ultimate and proximate levels, failure to clearly identify levels of analysis, and whether or not hypotheses are exclusive alternatives, can create false debates. Such non-alternative hypotheses may occur between or within levels, and are not limited to integrative approaches. In this review, I survey different uses of the term levels of analysis and the benefits of integration, and highlight examples of false debate within and between levels. The best integrative biology reciprocally uses ultimate and proximate hypotheses to generate a more complete understanding of behaviour. © 2011 The Royal Society.


Moharana A.,University of Western Ontario | Dash P.K.,Siksha O' Anusandhan University
IEEE Transactions on Power Delivery | Year: 2010

This paper presents a robust nonlinear controller for VSC-HVDC transmission link using inputoutput linearization and sliding mode-control strategy. The feedback linearization is used to cancel nonlinearities and the sliding mode control offers invariant stability to modeling uncertainties due to converter parameter changes, changes in system frequency, and exogenous inputs. Comprehensive computer simulations are carried out to verify the proposed control scheme under several system disturbances, such as changes in short-circuit ratio, converter parametric changes, and faults on the converter and inverter buses. Based upon the time-domain simulations in the MATLAB/SIMULINK environment, the proposed controller is tested. © 2010 IEEE.


Bailey D.G.,London Health Sciences Center | Bailey D.G.,University of Western Ontario
British Journal of Clinical Pharmacology | Year: 2010

A new type of interaction in which fruit juices diminish oral drug bioavailability through inhibition of uptake transport is the focus of this review. The discovery was based on an opposite to anticipated finding when assessing the possibility of grapefruit juice increasing oral fexofenadine bioavailability in humans through inhibition of intestinal MDR1-mediated efflux transport. In follow-up investigations, grapefruit or orange juice at low concentrations potentially and selectively inhibited in vitro OATP1A2-mediated uptake compared with MDR1-caused efflux substrate transport. These juices at high volume dramatically depressed oral fexofenadine bioavailability. Grapefruit was the representative juice to characterize the interaction subsequently. A volume-effect relationship study using a normal juice amount halved average fexofenadine absorption. Individual variability and reproducibility data indicated the clinical interaction involved direct inhibition of intestinal OATP1A2. Naringin was a major causal component suggesting that other flavonoids in fruits and vegetables might also produce the effect. Duration of juice clinical inhibition of fexofenadine absorption lasted more than 2 h but less than 4 h indicating the interaction was avoidable with appropriate interval of time between juice and drug consumption. Grapefruit juice lowered the oral bioavailability of several medications transported by OATP1A2 (acebutolol, celiprolol, fexofenadine, talinolol, L-thyroxine) while orange juice did the same for others (atenolol, celiprolol, ciprofloxacin, fexofenadine). Juice clinical inhibition of OATP2B1 was unresolved while that of OATP1B1 seemed unlikely. The interaction between grapefruit juice and etoposide also seemed relevant. Knowledge of both affected uptake transporter and drug hydrophilicity assisted prediction of the clinical interaction with grapefruit or orange juice. © 2010 The Author British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.


Kuboki T.,University of Western Ontario
Journal of Cellular Plastics | Year: 2014

This paper investigates the effects of cellulose content and processing conditions on the mechanical properties and foaming behavior of injection molded cellulose fiber reinforced polypropylene composite foams. Composite foams were injection molded using an advanced structural foam molding machine with N2 as a physical blowing agent. Foamed specimens were prepared at different injection speeds and void fractions. The mechanical properties and foam morphologies of the specimens were evaluated. The results suggested that the specific flexural modulus was increased and the specific flexural strength and Izod impact strength were maintained by foaming, and that the strength, modulus, and notched Izod impact strength increased with the increase of cellulose content. Additionally, the results suggested that the cell morphology of the composite foams was improved by the increase of void fraction and the addition of cellulose fiber. © 2013 The Author(s).


Kuboki T.,University of Western Ontario
Journal of Cellular Plastics | Year: 2014

This paper investigates the effect of polypropylene type and cellulose content on the foaming behavior of cellulose fiber-reinforced polypropylene composites in extrusion. Two types of polypropylene (linear and branched structures) were used as a polymer matrix. The thermal properties of the composites were characterized by a differential scanning calorimeter, and the viscosity of the composites was evaluated by a rotational rheometer. The foaming behavior of the composites was examined using an extrusion foaming system, in which carbon dioxide was used as a physical blowing agent for foams. The results suggested that the cell density increased with the increase of cellulose content. On the other hand, the void fraction decreased with the addition of cellulose, but the void fraction at the 40 wt% cellulose was higher than that at the 20 wt% cellulose. The results also indicated that the two types of polypropylene had a minimal effect on the foaming behaviors of the cellulose fiber composites. © 2013 The Author(s).


Kwok T.,University of Western Ontario | Pope J.E.,St. Josephs Health Care London
Journal of Rheumatology | Year: 2010

Objective. To determine the minimally important difference (MID) for the Health Assessment Questionnaire-Disability Index (HAQ-DI), pain, fatigue, sleep, and global visual analog scale (VAS; 0-100 mm) in patients with psoriatic arthritis (PsA) using a patient-reported overall health status anchor. Patient-reported outcomes are often used to gauge the effect of PsA in clinical trials. There is currently no knowledge about the MID for patient-reported outcomes in PsA. Methods. Patients with a diagnosis of PsA who had answered questions about outcomes at 2 consecutive visits and an overall health status question ("How would you describe your overall status since your last visit: much better, better, the same, worse, much worse?") were included. MID was calculated as the mean change between visits for those who rated their disease as "better" or "worse." Results. Two hundred patients met inclusion criteria, of whom 17.5% rated their status as "better" and 25.0% rated their status as "worse" than the previous visit. MID estimates for improvement/ worsening (SD) respectively were -0.131 (0.411)/0.131 (0.309) for HAQ-DI, -9.37 (24.37)/13.96 (22.05) for pain VAS, -8.15 (23.52)/3.63 (27.62) for fatigue VAS, -10.97 (29.74)/13.81 (27.32) for sleep VAS, and -8.41 (21.17)/11.53 (21.03) for global VAS. Spearman's ρ correlation coefficients between the anchor and mean change were 0.374 (HAQ-DI), 0.448 (pain VAS), 0.239 (fatigue VAS), 0.326 (sleep VAS), 0.490 (global VAS); p < 0.01. Conclusion. This is the first study investigating MID of patient-reported outcomes in PsA. MID for HAQ-DI, pain, and global VAS were shown to be the best predictors for a patient's perception of overall changes in disease status. The Journal of Rheumatology Copyright © 2010. All rights reserved.


Laird D.W.,University of Western Ontario
Trends in Cell Biology | Year: 2010

In recent years our understanding of connexins has advanced from viewing them simply as proteins with a surprisingly short lifespan that form gap junction channels. Connexins are now known to be multifaceted proteins at the core of many multiprotein complexes that link to structural junctional complexes and cytoskeletal elements, and also to the cellular machinery that facilitates their transport, assembly, function and internalization. Collectively, these connexin-binding proteins can be termed the 'gap junction proteome'. The mechanistic understanding of the gap junction proteome with regards to the dynamic life cycle of connexins has grown further in importance in light of the large number of human diseases attributed to connexin gene mutations and regulatory changes in connexin spatial localization and expression levels. © 2009 Elsevier Ltd. All rights reserved.


House A.A.,University of Western Ontario
Clinical Journal of the American Society of Nephrology | Year: 2013

Cardiorenal syndromes (CRSs) with bidirectional heart-kidney signaling are increasingly being recognized for their association with increased morbidity and mortality. In acute CRS, recognition of the importance of worsening kidney function complicating management of acute decompensated heart failure has led to the examination of this specific outcome in the context of acute heart failure clinical trials. In particular, the role of fluid overload and venous congestion has focused interest in the most effective use of diuretic therapy to relieve symptoms of heart failure while at the same time preserving kidney function. Additionally, many novel vasoactive therapies have been studied in recent years with the hopes of augmenting cardiac function, improving symptoms and patient outcomes, while maintaining or improving kidney function. Similarly, recent advances in our understanding of the pathophysiology of chronic CRS have led to reanalysis of kidney outcomes in pivotal trials in chronic congestive heart failure, and newer trials are including changes in kidney function as well as kidney injury biomarkers as prospectively monitored and adjudicated outcomes. This paper provides an overview of some new developments in the pharmacologic management of acute and chronic CRS, examines several reports that illustrate a key management principle for each subtype, and discusses opportunities for future research. © 2013 by the American Society of Nephrology.


Hubinette M.M.,University of Western Ontario
Academic Medicine | Year: 2016

Health advocacy is a prominent component of health professionals’ training internationally and is frequently discussed in the medical education literature. Despite this, it continues to be a problematic and challenging topic for medical educators, health professionals, and trainees alike. Borrowing from the field of systems engineering, the authors suggest a need to reconceptualize health advocacy using a systems mind-set rather than a physician-centric perspective. Conceptualizing health advocacy as a systemic, collective effort requires educators, practitioners, and trainees to challenge the assumption that the role of a competent physician health advocate can be fully defined without regard to the larger system or collective within which physicians function. Further, this implies a substantially more dynamic understanding of physicians’ and other participants’ parts in the collective activity.Of course, this new way of conceptualizing physicians’ practices is not limited to health advocacy. The current education paradigm trains physicians for individual competency but expects them to practice collectively. Defining physician competencies, or the competencies of any health care provider, in isolation from the particular system of which that individual is an integral part implicitly places that health care provider as the central focus of that system. Thus, academic medicine needs to move its educational and research efforts forward in a manner that recognizes that a systems engineering approach to health improvement will allow the various players to maximize their individual efforts to more effectively support the collective activity. © 2016 by the Association of American Medical Colleges


Hassan M.M.,Amec Foster Wheeler | El Damatty A.A.,University of Western Ontario
Engineering Structures | Year: 2012

Modern cable-stayed bridges can be economically designed by applying optimum post-tensioning cable forces to achieve a minimum deflection and a uniform bending moment distribution in the bridge deck under the effect of dead loads. The determination of the optimum distribution of post-tensioning cable forces is an important task that affects the overall design of the bridge. In this study, a novel approach, combining finite element analysis, B-spline curves, and an optimization technique is presented to determine the optimum post-tensioning cable forces under dead load corresponding to the final configuration of the bridge. The new approach is based on using the B-spline curves to model the post-tensioning functions along the bridge. The Genetic Algorithm (GA), as a global search technique, is utilized to optimize shapes of post-tensioning functions to achieve minimum vertical deflections along the bridge deck. Optimizing shapes of post-tensioning functions instead of the cable forces decreases the number of the design variables. This reduction improves the convergence speed, the accuracy of final solutions, and the performance of the optimization technique. Another advantage of the proposed method is that it minimizes the vertical defection of the deck and the horizontal deflection of the pylon, simultaneously. The validity of this proposed method is checked by applying it to a bridge with geometry similar to an existing cable-stayed bridge. © 2012 Elsevier Ltd.


Dufault B.,University of Manitoba | Klar N.,University of Western Ontario
American Journal of Epidemiology | Year: 2011

The ecologic study design is routinely used by epidemiologists in spite of its limitations. It is presently unknown how well the challenges of the design are dealt with in epidemiologic research. The purpose of this bibliometric review was to critically evaluate the characteristics, statistical methods, and reporting of results of modern cross-sectional ecologic papers. A search through 6 major epidemiology journals identified all cross-sectional ecologic studies published since January 1, 2000. A total of 125 articles met the inclusion requirements and were assessed via common evaluative criteria. It was found that a considerable number of cross-sectional ecologic studies use unreliable methods or contain statistical oversights; most investigators who adjusted their outcomes for age or sex did so improperly (64%), statistical validity was a potential issue for 20% of regression models, and simple linear regression was the most common analytic approach (31%). Many authors omitted important information when discussing the ecologic nature of their study (31%), the choice of study design (58%), and the susceptibility of their research to the ecological fallacy (49%). These results suggest that there is a need for an international set of guidelines that standardizes reporting on ecologic studies. Additionally, greater attention should be given to the relevant biostatistical literature. © 2011 The Author.


Hackam D.G.,University of Western Ontario
Stroke | Year: 2015

Background and Purpose: An increasing number of case reports link cannabis consumption to cerebrovascular events. Yet these case reports have not been scrutinized using criteria for causal inference. Methods: All case reports on cannabis and cerebrovascular events were retrieved. Four causality criteria were addressed: temporality, adequacy of stroke work-up, effects of rechallenge, and concomitant risk factors that could account for the cerebrovascular event. Results: There were 34 case reports on 64 patients. Most cases (81%) exhibited a temporal relationship between cannabis exposure and the index event. In 70%, the evaluation was sufficiently comprehensive to exclude other sources for stroke. About a quarter (22%) of patients had another stroke after subsequent re-exposure to cannabis. Finally, half of patients (50%) had concomitant stroke risk factors, most commonly tobacco (34%) and alcohol (11%) consumption. Conclusions: Many case reports support a causal link between cannabis and cerebrovascular events. This accords well with epidemiological and mechanistic research on the cerebrovascular effects of cannabis. © 2015 American Heart Association, Inc.


Cruse D.,University of Western Ontario
Neurology | Year: 2012

Functional neuroimaging has shown that the absence of externally observable signs of consciousness and cognition in severely brain-injured patients does not necessarily indicate the true absence of such abilities. However, relative to traumatic brain injury, nontraumatic injury is known to be associated with a reduced likelihood of regaining overtly measurable levels of consciousness. We investigated the relationships between etiology and both overt and covert cognitive abilities in a group of patients in the minimally conscious state (MCS). Twenty-three MCS patients (15 traumatic and 8 nontraumatic) completed a motor imagery EEG task in which they were required to imagine movements of their right-hand and toes to command. When successfully performed, these imagined movements appear as distinct sensorimotor modulations, which can be used to determine the presence of reliable command-following. The utility of this task has been demonstrated previously in a group of vegetative state patients. Consistent and robust responses to command were observed in the EEG of 22% of the MCS patients (5 of 23). Etiology had a significant impact on the ability to successfully complete this task, with 33% of traumatic patients (5 of 15) returning positive EEG outcomes compared with none of the nontraumatic patients (0 of 8). The overt behavioral signs of awareness (measured with the Coma Recovery Scale-Revised) exhibited by nontraumatic MCS patients appear to be an accurate reflection of their covert cognitive abilities. In contrast, one-third of a group of traumatically injured patients in the MCS possess a range of high-level cognitive faculties that are not evident from their overt behavior.


Fletcher G.J.O.,Victoria University of Wellington | Simpson J.A.,University of Minnesota | Campbell L.,University of Western Ontario | Overall N.C.,University of Auckland
Perspectives on Psychological Science | Year: 2015

This article evaluates a thesis containing three interconnected propositions. First, romantic love is a “commitment device” for motivating pair-bonding in humans. Second, pair-bonding facilitated the idiosyncratic life history of hominins, helping to provide the massive investment required to rear children. Third, managing long-term pair bonds (along with family relationships) facilitated the evolution of social intelligence and cooperative skills. We evaluate this thesis by integrating evidence from a broad range of scientific disciplines. First, consistent with the claim that romantic love is an evolved commitment device, our review suggests that it is universal; suppresses mate-search mechanisms; has specific behavioral, hormonal, and neuropsychological signatures; and is linked to better health and survival. Second, we consider challenges to this thesis posed by the existence of arranged marriage, polygyny, divorce, and infidelity. Third, we show how the intimate relationship mind seems to be built to regulate and monitor relationships. Fourth, we review comparative evidence concerning links among mating systems, reproductive biology, and brain size. Finally, we discuss evidence regarding the evolutionary timing of shifts to pair-bonding in hominins. We conclude there is interdisciplinary support for the claim that romantic love and pair-bonding, along with alloparenting, played critical roles in the evolution of Homo sapiens. © The Author(s) 2014.


Zhou W.,University of Western Ontario
International Journal of Pressure Vessels and Piping | Year: 2010

A methodology is presented in this paper to evaluate the time-dependent system reliability of a pipeline segment that contains multiple active corrosion defects and is subjected to stochastic internal pressure loading. The pipeline segment is modeled as a series system with three distinctive failure modes due to corrosion, namely small leak, large leak and rupture. The internal pressure is characterized as a simple discrete stochastic process that consists of a sequence of independent and identically distributed random variables each acting over a period of one year. The magnitude of a given sequence follows the annual maximum pressure distribution. The methodology is illustrated through a hypothetical example. Furthermore, the impact of the spatial variability of the pressure loading and pipe resistances associated with different defects on the system reliability is investigated. The analysis results suggest that the spatial variability of pipe properties has a negligible impact on the system reliability. On the other hand, the spatial variability of the internal pressure, initial defect sizes and defect growth rates can have a significant impact on the system reliability. © 2010 Elsevier Ltd.


Mara T.G.,University of Western Ontario
Journal of Structural Engineering | Year: 2010

High-rise construction projects commonly use a tower crane attached to the building by braced connections along its height. The presence of the tower crane modifies the aerodynamic cross section of the building and can alter the expected wind loading characteristics. Wind tunnel tests were carried out to examine the impact of the solidity ratio, and location of the tower crane, on the wind loading for the overall building-crane system. Tower cranes of two solidity ratios, 20 and 100%, were tested. A tower crane having one of the two solidity ratios tested was placed at one of three locations along the building face in order to define a quantitative range of increased wind loads. Increases in mean and fluctuating loading were observed for particular wind directions, and were more pronounced for the greater solidity ratio. The increase was the most significant for the torsion base moment. The impact of the tower crane was reduced as its location neared the center of the building face. Recommendations are made for the choice of tower crane location. © 2010 ASCE.


Leask A.,University of Western Ontario
Journal of Investigative Dermatology | Year: 2012

There is no universally agreed-upon treatment for the fibrosis of scleroderma. Recently, much information has been generated relating to the fundamental mechanisms underlying this disease. Partly based on these observations, both anti-inflammatory and anti-fibrotic agents have been considered as possible therapies. However, this information has not been successfully translated into clinical practice. In this issue, Pendergrass et al. use genome-wide expression profiling to provide valuable insights into scleroderma. Previously, the authors showed that morphea and limited scleroderma patients and a small subset of diffuse scleroderma (dSSc) patients express an inflammatory profile, whereas the majority of dSSc patients express a fibroproliferative profile. In the current study, the investigators show that the gene expression profile of these patients is fixed over time; i.e., in contrast to a previously held belief, the inflammatory patients do not go on to become fibrotic, and vice versa. These data suggest that expression profiling might be used to design clinical trials for scleroderma. The inflammatory patients might be treated with anti-inflammatory agents, whereas fibroproliferative patients might be treated with antifibrotic agents. © 2012 The Society for Investigative Dermatology.


Fisher W.A.,University of Western Ontario
Vaccine | Year: 2013

Barriers to human papillomavirus (HPV) vaccine acceptability in Israel include Israel's relatively low incidence of cervical cancer; the religiously-based 80% circumcision rate in Israel, which is regarded as contributing to the lower incidence of HPV infection in the country; the fact that HPV vaccine provides immunity against only few virus types; the vaccine's high cost; and the perception that HPV transmission is associated with unacceptable sexual relations. A recent survey has demonstrated that, following media two campaigns, Israeli's level of awareness of the vaccine increased but the actual vaccination rate remained low, at approximately 10%. Survey findings also indicated that an enduring barrier to HPV vaccination is the vaccine's high cost. Recent research on a convenience sample of Israeli undergraduate women 21 to 24 years of age showed that intentions to receive HPV vaccination in the coming year were a function of women's attitudes towards getting vaccinated and their perceptions of social support for doing so. Undergraduate women who intended to be vaccinated perceived the prevention of cervical cancer, avoidance of personal health threat, and avoidance of HPV infection per se to be the advantages of undergoing HPV vaccination. Disadvantages of getting vaccinated included fear of vaccine side effects, cost of the vaccine, and newness of the vaccine, doubts about vaccines, time required to undergo multiple vaccinations, and dislike of injections. Friends', mothers' and physicians' recommendations influenced women's intentions to be vaccinated in the coming year as well. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in Israel" Vaccine Volume 31, Supplement 8, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. Copyright © 2013 Elsevier Ltd. All rights reserved.


Beier F.,University of Western Ontario | Loeser R.F.,Wake forest University
Journal of Cellular Biochemistry | Year: 2010

Chondrocytes provide the framework for the developing skeleton and regulate long-bone growth through the activity of the growth plate. Chondrocytes in the articular cartilage, found at the ends of bones in diarthroidial joints, are responsible for maintenance of the tissue through synthesis and degradation of the extracellular matrix. The processes of growth, differentiation, cell death and matrix remodeling are regulated by a network of cell signaling pathways in response to a variety of extracellular stimuli. These stimuli consist of soluble ligands, including growth factors and cytokines, extracellular matrix proteins, and mechanical factors that act in concert to regulate chondrocyte function through a variety of canonical and non-canonical signaling pathways. Key chondrocyte signaling pathways include, but are not limited to, the p38, JNK and ERK MAP kinases, the PI-3 kinase-Akt pathway, the Jak-STAT pathway, Rho GTPases and Wnt-β-catenin and Smad pathways. Modulation of the activity of any of these pathways has been associated with various pathological states in cartilage. This review focuses on the Rho GTPases, the PI-3 kinase-Akt pathway, and some selected aspects of MAP kinase signaling. Most studies to date have examined these pathways in isolation but it is becoming clear that there is significant cross-talk among the pathways and that the overall effects on chondrocyte function depend on the balance in activity of multiple signaling proteins. © 2010 Wiley-Liss, Inc.


Naus C.C.,University of British Columbia | Laird D.W.,University of Western Ontario
Nature Reviews Cancer | Year: 2010

The idea that the gap junction family of proteins, connexins, are tumour suppressors has been widely supported through numerous cancer models. However, the paradigm that connexins and enhanced gap junctional intercellular communication is of universal benefit by restricting tumour growth has been challenged by more recent evidence that suggests a role for connexins in facilitating tumour progression and metastasis. Therefore, connexins might be better classified as conditional tumour suppressors that modulate cell proliferation, as well as adhesion and migration. © 2010 Macmillan Publishers Limited. All rights reserved.


Goss P.E.,Harvard University | Chambers A.F.,University of Western Ontario
Nature Reviews Cancer | Year: 2010

The increasing number of cancer survivors is cause for celebration, but this expanding population has highlighted the problem of tumour dormancy, which can lead to relapse. As we start to understand more about the biology of dormant cancer cells, we can begin to address how best to treat this form of disease. Preclinical models and initial clinical trials, as exemplified in patients with breast cancer, are paving the way to address how best to treat long-term cancer survivors to minimize the risk of cancer recurrence. © 2010 Macmillan Publishers Limited. All rights reserved.


Price E.R.,University of Western Ontario
Comparative Biochemistry and Physiology - A Molecular and Integrative Physiology | Year: 2010

Birds rely substantially on fat to fuel migratory flights. The importance of the composition of those fat stores to flight performance is a field of recent interest. Here I review the evidence that dietary lipid fat composition affects exercise in birds. Seasonal changes in adipose composition and diet choice experiments have yet to provide strong evidence that fatty acid composition can affect flight performance. Direct manipulations of dietary fat, however, have been demonstrated to affect exercise performance in both avian and non-avian species. I also describe the major hypotheses for the mechanisms by which dietary fat affects exercise, focusing on the role of fatty acids as oxidative substrates and as structural components of membranes. Evidence is accumulating that fatty acids that are shorter or have more double bonds increase peak performance due to their higher transport rates en route to oxidation. Endurance and efficiency of flight may or may not be affected in similar ways. Other mechanisms requiring further investigation include membrane composition, peroxisome proliferator-activated receptors, and eicosanoid-mediated inflammation. Finally, I develop a theoretical framework for studying the composition of fat stores in migrants, focusing on the tradeoffs between fatty acid transport rates, energy storage, and assimilation during stopover refueling. © 2010 Elsevier Inc.


Colinet H.,CNRS Ecosystems, Biodiversity, and Evolution Laboratory | Sinclair B.J.,University of Western Ontario | Vernon P.,CNRS Ecosystems, Biodiversity, and Evolution Laboratory | Renault D.,CNRS Ecosystems, Biodiversity, and Evolution Laboratory
Annual Review of Entomology | Year: 2015

All climate change scenarios predict an increase in both global temperature means and the magnitude of seasonal and diel temperature variation. The nonlinear relationship between temperature and biological processes means that fluctuating temperatures lead to physiological, life history, and ecological consequences for ectothermic insects that diverge from those predicted from constant temperatures. Fluctuating temperatures that remain within permissive temperature ranges generally improve performance. By contrast, those which extend to stressful temperatures may have either positive impacts, allowing repair of damage accrued during exposure to thermal extremes, or negative impacts from cumulative damage during successive exposures. We discuss the mechanisms underlying these differing effects. Fluctuating temperatures could be used to enhance or weaken insects in applied rearing programs, and any prediction of insect performance in the field-including models of climate change or population performance-must account for the effect of fluctuating temperatures. © 2015 by Annual Reviews. All rights reserved.


Hutchison R.M.,Harvard University | Morton J.B.,University of Western Ontario
Journal of Neuroscience | Year: 2015

The transition from childhood to adulthood is marked by pronounced functional and structural brain transformations that impact cognition and behavior. Here, we use a functional imaging approach to reveal dynamic changes in coupling strength between networks and the expression of discrete brain configurations over human development during rest and a cognitive control task. Although the brain’s repertoire of functional states was generally preserved across ages, state-specific temporal features, such as the frequency of expression and the amount of time spent in select states, varied by age in ways that were dependent on condition. Increasing age was associated with greater variability of connection strengths across time at rest, while there was a selective inversion of this effect in higher-order networks during implementation of cognitive control. The results suggest that development is characterized by the modification of dynamic coupling to both maximize and constrain functional variability in response to ongoing cognitive and behavioral requirements. © 2015 the authors.


Hughson R.L.,University of Waterloo | Shoemaker J.K.,University of Western Ontario
Autonomic Neuroscience: Basic and Clinical | Year: 2015

Experimental models of physical inactivity associated with a sedentary lifestyle or extreme forms of inactivity with bed rest or spaceflight affect the balance between parasympathetic and sympathetic nervous system regulation of the cardiovascular system. Deconditioning effects are rapidly seen in the regulation of heart rate to compensate for physical modifications in blood volume and cardiac function. Reflex regulation of cardiovascular control during exercise by metaboreflex and baroreflex is altered by bed rest and spaceflight. These models of extreme inactivity provide a reference to guide physical activity requirements for optimal cardiovascular health. © 2014 Elsevier B.V.


Wong V.W.-S.,Chinese University of Hong Kong | Janssen H.L.A.,University of Western Ontario | Janssen H.L.A.,Erasmus Medical Center
Journal of Hepatology | Year: 2015

Summary Chronic hepatitis B is one of the leading causes of hepatocellular carcinoma (HCC) worldwide. Accurate prediction of HCC risk is important for decisions on antiviral therapy and HCC surveillance. In the last few years, a number of Asian groups have derived and validated several HCC risk scores based on well-known risk factors such as cirrhosis, age, male sex and high viral load. Overall, these scores have high negative predictive values of over 95% in excluding HCC development in 3 to 10 years. The REACH-B score was derived from a community cohort of non-cirrhotic patients and is better applied in the primary care setting. In contrast, the GAG-HCC and CU-HCC scores were derived from hospital cohorts and include cirrhosis as a major integral component. While the latter scores may be more applicable to patients at specialist clinics, the diagnosis of cirrhosis based on routine imaging and clinical parameters can be inaccurate. To this end, recent developments in non-invasive tests of liver fibrosis may further refine the risk prediction. The application of HCC risk scores in patients on antiviral therapy and in other ethnic groups should be evaluated in future studies. © 2015 European Association for the Study of the Liver.


Huang K.,London Health Sciences Center | Palma D.A.,London Health Sciences Center | Palma D.A.,University of Western Ontario
Journal of Thoracic Oncology | Year: 2015

Background: The use of stereotactic ablative radiotherapy (SABR) as primary treatment for early stage non-small-cell lung cancer, or for ablation of metastases, has increased rapidly in the past decade. With local recurrence rates reported at approximately 10%, and a patient population that is becoming increasingly fit and amenable to salvage treatment, appropriate multidisciplinary follow-up care is critical. Appropriate follow-up will allow for detection and management of radiation-related toxicity, early detection of recurrent disease and differentiation of recurrence from radiation-induced lung injury. Methods: This narrative review summarizes issues surrounding follow-up of patients treated with SABR in the context of a multidisciplinary perspective. We summarize treatment-related toxicities including radiation pneumonitis, chest wall pain, rib fracture, and fatal toxicity, and highlight the challenges of early and accurate detection of local recurrence, while avoiding unnecessary biopsy or treatment of benign radiation-induced fibrotic lung damage. Results: Follow-up recommendations based on the current evidence and available guidelines are summarized. Imaging follow-up recommendations include serial computed tomography (CT) imaging at 3-6 months posttreatment for the initial year, then every 6-12 months for an additional 3 years, and annually thereafter. With suspicion of progressive disease, recommendations include a multidisciplinary team discussion, the use of high-risk CT features for accurate detection of local recurrence, and positron emission tomography/CT SUVmax cutoffs to prompt further investigation. Biopsy and/or surgical or nonsurgical salvage therapy can be considered if safe and when investigations are nonreassuring. Conclusions: The appropriate follow-up of patients after SABR requires collaborative input from nearly all members of the thoracic multidisciplinary team, and evidence is available to guide treatment decisions. Further research is required to develop better predictors of toxicity and recurrence. © 2014 by the International Association for the Study of Lung Cancer.


Neff B.D.,University of Western Ontario | Svensson E.I.,Lund University
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2013

Many species in the animal kingdom are characterized by alternative mating tactics (AMTs) within a sex. In males, such tactics include mate guarding versus sneaking behaviours, or territorial versus female mimicry. Although AMTs can occur in either sex, they have been most commonly described in males. This sex bias may, in part, reflect the increased opportunity for sexual selection that typically exists in males, which can result in a higher probability that AMTs evolve in that sex. Consequently, females and polyandry can play a pivotal role in governing the reproductive success associated with male AMTs and in the evolutionary dynamics of the tactics. In this review, we discuss polyandry and the evolution of AMTs. First, we define AMTs and review game theoretical and quantitative genetic approaches used to model their evolution. Second, we review several examples of AMTs, highlighting the roles that genes and environment play in phenotype expression and development of the tactics, as well as empirical approaches to differentiating among the mechanisms. Third, ecological and genetic constraints to the evolution of AMTs are discussed. Fourth, we speculate on why female AMTs are less reported on in the literature than male tactics. Fifth, we examine the effects of AMTs on breeding outcomes and female fitness, and as a source, and possibly also a consequence, of sexual conflict. We conclude by suggesting a new model for the evolution of AMTs that incorporates both environmental and genetic effects, and discuss some future avenues of research. © 2013 The Author(s) Published by the Royal Society. All rights reserved.


Doty D.,University of Western Ontario
SIAM Journal on Computing | Year: 2010

Working in Winfree's abstract tile assembly model, we show that a constant-sized tile assembly system can be programmed through relative tile concentrations to build an n × n square with high probability for any sufficiently large n. This answers an open question of Kao and Schweller [Automata, Languages and Programming, Lecture Notes in Comput. Sci. 5125, Springer, Berlin, 2008, pp. 370-384], who showed how to build an approximately n × n square using tile concentration programming and asked whether the approximation could be made exact with high probability. We show how this technique can be modified to answer another question of Kao and Schweller by showing that a constant-sized tile assembly system can be programmed through tile concentrations to assemble arbitrary finite scaled shapes, which are shapes modified by replacing each point with a c × c block of points for some integer c. Furthermore, we exhibit a smooth trade-off between specifying bits of n via tile concentrations versus specifying them via hard-coded tile types, which allows tile concentration programming to be employed for specifying a fraction of the bits of "input" to a tile assembly system, under the constraint that concentrations can be specified to only a limited precision. Finally, to account for some unrealistic aspects of the tile concentration programming model, we show how to modify the construction to use only concentrations that are arbitrarily close to uniform. © 2010 Society for Industrial and Applied Mathematics.


Zou G.Y.,University of Western Ontario
Statistics in Medicine | Year: 2012

The number of subjects required to estimate the intraclass correlation coefficient in a reliability study has usually been determined on the basis of the expected width of a confidence interval. However, this approach fails to explicitly consider the probability of achieving the desired interval width and may thus provide sample sizes that are too small to have adequate chance of achieving the desired precision. In this paper, we present a method that explicitly incorporates a prespecified probability of achieving the prespecified width or lower limit of a confidence interval. The resultant closed-form formulas are shown to be very accurate. © 2012 John Wiley & Sons, Ltd.


Lindo Z.,University of Western Ontario | Nilsson M.-C.,Swedish University of Agricultural Sciences | Gundale M.J.,Swedish University of Agricultural Sciences
Global Change Biology | Year: 2013

Ecosystems in the far north, including arctic and boreal biomes, are a globally significant pool of carbon (C). Global change is proposed to influence both C uptake and release in these ecosystems, thereby potentially affecting whether they act as C sources or sinks. Bryophytes (i.e., mosses) serve a variety of key functions in these systems, including their association with nitrogen (N2)-fixing cyanobacteria, as thermal insulators of the soil, and producers of recalcitrant litter, which have implications for both net primary productivity (NPP) and heterotrophic respiration. While ground-cover bryophytes typically make up a small proportion of the total biomass in northern systems, their combined physical structure and N2-fixing capabilities facilitate a disproportionally large impact on key processes that control ecosystem C and N cycles. As such, the response of bryophyte-cyanobacteria associations to global change may influence whether and how ecosystem C balances are influenced by global change. Here, we review what is known about their occurrence and N2-fixing activity, and how bryophyte systems will respond to several key global change factors. We explore the implications these responses may have in determining how global change influences C balances in high northern latitudes. © 2013 Blackwell Publishing Ltd.


Rieder M.J.,University of Western Ontario | Carleton B.,University of British Columbia
Frontiers in Genetics | Year: 2014

Adverse drug reactions are a common and important complication of drug therapy in children. Over the past decade it has become increasingly apparent that genetically controlled variations in drug disposition and response are important determinants of adverse events for many important adverse events associated with drug therapy in children. While this research has been difficult to conduct over the past decade technical and ethical evolution has greatly facilitated the ability of investigators to conduct pharmacogenomic studies in children. Some of this research has already resulted in changes in public policy and clinical practice, for example in the case of codeine use by mothers and children. It is likely that the use of pharmacogenomics to enhance drug safety will first be realized among selected groups of children with high rates of drug use such as children with cancer, but it also likely that this research will be extended to other groups of children who have high rates of drug utilization and as well as providing insights into the mechanisms and pathophysiology of adverse drug reactions in children. © 2014 Rieder and Carleton.


Titantah J.T.,University of Western Ontario | Karttunen M.,University of Waterloo
Journal of the American Chemical Society | Year: 2012

The physical mechanisms behind hydrophobic hydration have been debated for over 65 years. Spectroscopic techniques have the ability to probe the dynamics of water in increasing detail, but many fundamental issues remain controversial. We have performed systematic first-principles ab initio Car-Parrinello molecular dynamics simulations over a broad temperature range and provide a detailed microscopic view on the dynamics of hydration water around a hydrophobic molecule, tetramethylurea. Our simulations provide a unifying view and resolve some of the controversies concerning femtosecond-infrared, THz-GHz dielectric relaxation, and nuclear magnetic resonance experiments and classical molecular dynamics simulations. Our computational results are in good quantitative agreement with experiments, and we provide a physical picture of the long-debated "iceberg" model; we show that the slow, long-time component is present within the hydration shell and that molecular jumps and over-coordination play important roles. We show that the structure and dynamics of hydration water around an organic molecule are non-uniform. © 2012 American Chemical Society.


Kermani M.R.,University of Western Ontario
IEEE Transactions on Control Systems Technology | Year: 2010

In this paper, the effect of an actuator on the natural frequencies and mode shapes of a cantilever Timoshenko beam is studied. In this regard, the equations of motion of a cantilever Tim-oshenko beam are considered. In order to incorporate the effect of the actuator in these equations, it is assumed that the beam is comprised of three uniform Timoshenko beams connected to one another at their boundaries. The continuity and equilibrium conditions are then utilized to find the sub-boundary conditions for each sub-beam. The effect of the actuator is considered as an external torque on the sub-boundary conditions. This leads to a set of partial differential equations for each sub-beam with coupled non-homogenous boundary conditions. A solution for the resulting equations is obtained and a state-space model of the beam strengthened with the actuator is derived. To evaluate the accuracy of the model, simulation and experimental results are presented. © 2009 IEEE.


Leask A.,University of Western Ontario
Journal of Cell Communication and Signaling | Year: 2011

CCN2 (formerly known as connective tissue growth factor) was identified by several different laboratories approximately 20 years ago. Almost since its identification as a factor induced in normal fibroblasts by transforming growth factor β and overexpressed in fibrotic disease, CCN2 has been hypothesized to be not only a marker but also a central mediator of fibrosis in vivo. Finally, in vivo data are emerging to validate this key hypothesis. For example, a neutralizing anti-CCN2 antibody was found to attenuate fibrogenesis in three separate animal models (Wang et al. in Fibrogenesis Tissue Repair 4:1-4, 2011). This commentary addresses recent data indicating that CCN2 appears to represent a key central mediator of fibrosis and a good target for anti-fibrotic drug intervention. © 2011 The International CCN Society.


Leask A.,University of Western Ontario
Journal of Cell Communication and Signaling | Year: 2011

Members of CCN family of matricellular proteins are being increasingly recognized by the translational research community as representing excellent targets for drug intervention. Although much effort has been expended in outlining the mechanisms involved in pancreatic carcinogenesis, the precise molecular pathways involved remain incompletely understood, and appropriate targets for drug intervention remain elusive. A recent exciting report by Haque and colleagues (Mol Cancer. 2011 Jan 13;10:8) provides strong evidence that CCN1 (cyr61) is a potential therapeutic target in pancreatic cancer. © 2011 The International CCN Society.


Chandok N.,University of Western Ontario | Watt K.D.,Mayo Medical School
Liver Transplantation | Year: 2012

Recipients of liver transplantation (LT) have a higher overall risk (2-3 times on average) of developing de novo malignancies than the general population, with standardized incidence ratios ranging from 1.0 for breast and prostate cancers to 3-4 for colon cancer and up to 12 for esophageal and oropharyngeal cancers. Aside from immunosuppression, other identified risk factors for de novo malignancies include the patient's age, a history of alcoholic liver disease or primary sclerosing cholangitis, smoking, and viral infections with oncogenic potential. Despite outcome studies showing that de novo malignancies are major causes of mortality and morbidity after LT, there are no guidelines for cancer surveillance protocols or immunosuppression protocols to lower the incidence of de novo cancers. Patient education, particularly for smoking cessation and excess sun avoidance, and regular clinical follow-up remain the standard of care. Further research in epidemiology, risk factors, and the effectiveness of screening and management protocols is needed to develop evidence-based guidelines for the prevention and treatment of de novo malignancies. © 2012 AASLD.


Sheldon J.R.,University of Western Ontario
Frontiers in cellular and infection microbiology | Year: 2012

Lipoproteins fulfill diverse roles in antibiotic resistance, adhesion, protein secretion, signaling and sensing, and many also serve as the substrate binding protein (SBP) partner to ABC transporters for the acquisition of a diverse array of nutrients including peptides, sugars, and scarcely abundant metals. In the staphylococci, the iron-regulated SBPs are significantly upregulated during iron starvation and function to sequester and deliver iron into the bacterial cell, enabling staphylococci to circumvent iron restriction imposed by the host environment. Accordingly, this subset of lipoproteins has been implicated in staphylococcal pathogenesis and virulence. Lipoproteins also activate the host innate immune response, triggered through Toll-like receptor-2 (TLR2) and, notably, the iron-regulated subset of lipoproteins are particularly immunogenic. In this review, we discuss the iron-regulated staphylococcal lipoproteins with regard to their biogenesis, substrate specificity, and impact on the host innate immune response.


Rowland J.W.,University of Western Ontario
Stem cells and development | Year: 2011

Neural stem cell-based approaches to repair damaged white matter in the central nervous system have shown great promise; however, the optimal cell population to employ in these therapies remains undetermined. A default mechanism of neural induction may function during development, and in embryonic stem cells (ESCs) neural differentiation is elicited in the absence of any extrinsic signaling in minimal, serum-free culture conditions. The default mechanism can be used to derive clonal neurosphere-forming populations of neural stem cells that have been termed leukemia inhibitory factor-dependent primitive neural stem cells (pNSCs), which subsequently give rise to fibroblast growth factor 2-dependent definitive NSCs (dNSCs). Here we characterized the neural differentiation pattern of these two cell types in vitro and in vivo when transplanted into the dysmyelinated spinal cords of shiverer mice. We compared the differentiation pattern to that observed for neural stem/progenitor cells derived from the adult forebrain subependymal zone [adult neural precursor cells (aNPCs)]. dNSCs produced a differentiation pattern similar to that of aNPCs in vitro and in the shiverer model in vivo, where both cell types produced terminally differentiated oligodendrocytes that associated with host axons and expressed myelin basic protein. This is the first demonstration of the in vivo differentiation of NSCs, derived from ESCs through the default mechanism, into the oligodendrocyte lineage. We conclude that dNSCs derived through the default pathway of neural induction are a similar cell population to aNPCs and that the default mechanism is a promising approach to generate NSCs from pluripotent cell populations for use in cell therapy or other research applications.


Ginsburg S.,University of Toronto | Lingard L.,University of Western Ontario
Medical Education | Year: 2011

Objectives: Context has been recognised as a key variable in studies of medical student professionalism, yet the effect of students' stage of training has not been well explored, despite growing recognition that medical students begin to form their professional ethos from their earliest medical school experiences. The purpose of this study, which builds on previous research involving clinical clerks, was to explore the decision-making processes of pre-clerkship medical students in the face of standardised professional dilemmas. Methods: Structured interviews were conducted with 30 pre-clerkship (Years1 and 2) medical students at one institution. During the interviews, students were asked to respond to five videotaped scenarios, each of which depicted a student facing a professional dilemma. Transcripts were analysed using an existing theoretical framework based on a constructivist grounded theory approach. Results: Pre-clerkship students' approaches to professional dilemmas were largely similar to those of clerks, despite their limited clinical experience, with several notable exceptions. For example, reliance on instincts and emotions was not as pervasive, but concerns with systems-associated issues were more recurrent. These findings were explored in the context of theory on professional identity formation. Conclusions: As the novice student constructs a professional identity, he or she may feel the need to take on the role of doctor and shed that of student, a process that involves the suppressing of emotions, but this may be misguided. Educators should be aware of these stages of identity formation and tailor their teaching and evaluation of professionalism accordingly. © Blackwell Publishing Ltd 2011.


Thompson J.L.,University of Nevada, Las Vegas | Nelson A.J.,University of Western Ontario
Human Nature | Year: 2011

The evolution of modern human life history has involved substantial changes in the overall length of the subadult period, the introduction of a novel early childhood stage, and many changes in the initiation, termination, and character of the other stages. The fossil record is explored for evidence of this evolutionary process, with a special emphasis on middle childhood, which many argue is equivalent to the juvenile stage of African apes. Although the "juvenile" and "middle childhood" stages appear to be the same from a broad comparative perspective, in that they begin with the eruption of the first molar and the achievement of the majority of adult brain size and end with sexual maturity, the detailed differences in the expression of these two stages, and how they relate to the preceding and following stages, suggest that a distinction should be maintained between them to avoid blurring subtle, but important, differences. © 2011 Springer Science + Business Media, LLC.


Cleary K.,Georgetown University | Peters T.M.,University of Western Ontario
Annual Review of Biomedical Engineering | Year: 2010

Image-guided interventions are medical procedures that use computer-based systems to provide virtual image overlays to help the physician precisely visualize and target the surgical site. This field has been greatly expanded by the advances in medical imaging and computing power over the past 20 years. This review begins with a historical overview and then describes the component technologies of tracking, registration, visualization, and software. Clinical applications in neurosurgery, orthopedics, and the cardiac and thoracoabdominal areas are discussed, together with a description of an evolving technology named Natural Orifice Transluminal Endoscopic Surgery (NOTES). As the trend toward minimally invasive procedures continues, image-guided interventions will play an important role in enabling new procedures, while improving the accuracy and success of existing approaches. Despite this promise, the role of image-guided systems must be validated by clinical trials facilitated by partnerships between scientists and physicians if this field is to reach its full potential. © 2010 by Annual Reviews. All rights reserved.


Bae E.,University of Bergen | Yuan J.,University of Western Ontario | Tai X.-C.,University of Bergen | Tai X.-C.,Nanyang Technological University
International Journal of Computer Vision | Year: 2011

This paper is devoted to the optimization problem of continuous multi-partitioning, or multi-labeling, which is based on a convex relaxation of the continuous Potts model. In contrast to previous efforts, which are tackling the optimal labeling problem in a direct manner, we first propose a novel dual model and then build up a corresponding duality-based approach. By analyzing the dual formulation, sufficient conditions are derived which show that the relaxation is often exact, i.e. there exists optimal solutions that are also globally optimal to the original nonconvex Potts model. In order to deal with the nonsmooth dual problem, we develop a smoothing method based on the log-sum exponential function and indicate that such a smoothing approach leads to a novel smoothed primal-dual model and suggests labelings with maximum entropy. Such a smoothing method for the dual model also yields a new thresholding scheme to obtain approximate solutions. An expectation maximization like algorithm is proposed based on the smoothed formulation which is shown to be superior in efficiency compared to earlier approaches from continuous optimization. Numerical experiments also show that our method outperforms several competitive approaches in various aspects, such as lower energies and better visual quality. © The Author(s) 2010. This article is published with open access at Springerlink.com.


The paper argues the position for retaining a monotypic Mespilus, i.e., in the sense of M. germanica, the medlar. Recent cladistic papers lend support for Mespilus being sister to Crataegus, and there is a clear morphological distinction from Crataegus, emphasized by adaptation to carnivore frugivory. Mespilus secured, the paper then treats each of the known hybrids between Mespilus and Crataegus, making the new combination Crataemespilus ×canescens (J.B. Phipps) J.B. Phipps. © 2016 Magnolia Press.


Basu S.,University of Western Ontario | Vorobyov E.I.,University of Vienna | Vorobyov E.I.,Southern Federal University
Astrophysical Journal | Year: 2012

We present a calculation of protostellar disk formation and evolution in which gaseous clumps (essentially, the first Larson cores formed via disk fragmentation) are ejected from the disk during the early stage of evolution. This is a universal process related to the phenomenon of ejection in multiple systems of point masses. However, it occurs in our model entirely due to the interaction of compact, gravitationally bound gaseous clumps and is free from the smoothing-length uncertainty that is characteristic of models using sink particles. Clumps that survive ejection span a mass range of 0.08-0.35 M, and have ejection velocities 0.8 ± 0.35kms-1, which are several times greater than the escape speed. We suggest that, upon contraction, these clumps can form substellar or low-mass stellar objects with notable disks, or even close-separation very low mass binaries. In this hybrid scenario, allowing for ejection of clumps rather than finished protostars/proto-brown-dwarfs, disk formation and the low velocity dispersion of low-mass objects are naturally explained, while it is also consistent with the observation of isolated low-mass clumps that are ejection products. We conclude that clump ejection and the formation of isolated low-mass stellar and substellar objects is a common occurrence, with important implications for understanding the initial mass function, the brown dwarf desert, and the formation of stars in all environments and epochs. © 2012. The American Astronomical Society. All rights reserved.


Serino C.A.,Boston University | Tiampo K.F.,University of Western Ontario | Klein W.,Boston University
Physical Review Letters | Year: 2011

We introduce a new model for an earthquake fault system that is composed of noninteracting simple lattice models with different levels of damage denoted by q. The undamaged lattice models (q=0) have Gutenberg-Richter scaling with a cumulative exponent β=1/2, whereas the damaged models do not have well defined scaling. However, if we consider the "fault system" consisting of all models, damaged and undamaged, we get excellent scaling with the exponent depending on the relative frequency with which faults with a particular amount of damage occur in the fault system. This paradigm combines the idea that Gutenberg-Richter scaling is associated with an underlying critical point with the notion that the structure of a fault system also affects the statistical distribution of earthquakes. In addition, it provides a framework in which the variation, from one tectonic region to another, of the scaling exponent, or b value, can be understood. © © 2011 American Physical Society.


Ward A.D.,University of Western Ontario | Hamarneh G.,Simon Fraser University
IEEE Transactions on Pattern Analysis and Machine Intelligence | Year: 2010

Medial representations of shapes are useful due to their use of an object-centered coordinate system that directly captures intuitive notions of shape such as thickness, bending, and elongation. However, it is well known that an object's medial axis transform (MAT) is unstable with respect to small perturbations of its boundary. This instability results in additional, unwanted branches in the skeletons, which must be pruned in order to recover the portions of the skeletons arising purely from the uncorrupted shape information. Almost all approaches to skeleton pruning compute a significance measure for each branch according to some heuristic criteria, and then prune the least significant branches first. Current approaches to branch significance computation can be classified as either local, solely using information from a neighborhood surrounding each branch, or global, using information about the shape as a whole. In this paper, we propose a third, groupwise approach to branch significance computation. We develop a groupwise skeletonization framework that yields a fuzzy significance measure for each branch, derived from information provided by the group of shapes. We call this framework the Groupwise Medial Axis Transform (G-MAT). We propose and evaluate four groupwise methods for computing branch significance and report superior performance compared to a recent, leading method. We measure the performance of each pruning algorithm using denoising, classification, and within-class skeleton similarity measures. This research has several applications, including object retrieval and shape analysis. © 2006 IEEE.


Heritable genomic variation and natural selection have long been acknowledged as striking parallels between evolution and cancer. The logical conclusion, that cancer really is a form of speciation, has seldom been expounded directly. My purpose is to reexamine the "cancer as species" thesis in the light of current attitudes to asexual speciation, and modern analyses of species definitions. The chief obstacles to accepting this thesis have been the asexual nature of cancer cell reproduction, the instability of the malignant genotype and phenotype, and our conditioning that speciation is an extremely rare and imperceptibly gradualistic process. However, these are not absolute barriers to the acceptance of cancers as bona fide species. Furthermore, although ongoing clonal evolution of extant cancers also results in a series of secondary speciation events, the initial emergence of a cancer requires a level of taxonomic reclassification even beyond the concept of speciation (i.e., phylogenation), and which is almost certain to provide a rich source of novel drug targets. The implications of the "cancer as species" idea may be as important for biology as for oncology, providing as it does an endless supply of observable if accelerated examples of a phenomenon once regarded as rare. From the perspective of cancer treatment, speciation guarantees the existence of causal molecular mechanisms which may have been neglected as exploitable targets for rational therapy; in particular, the mediators of metazoan life seem to have substantial overlap with components commonly deranged in cancer cells. However, the intractability of the drug resistance problem, residing as it does in the inherent plasticity of the genome, is traceable back to, and inseparable from, the very origins and nature of life. © 2010 The Author(s). Journal compilation © 2010 The Society for the Study of Evolution.


Ma S.,University of Western Ontario
Bulletin of the Seismological Society of America | Year: 2010

There are three usable regional depth phases, sPg, sPmP, and sPn, and their corresponding reference phases, Pg, PmP, and Pn. The differential time between each depth phase and its reference phase can be used to estimate earthquake focal depth. We have developed a method to determine focal depth for moderate and small earthquakes by using a regional depth-phase modeling (RDPM) method. We used a default focal mechanism to generate the differential times for all earthquakes. To estimate the reliability of the modeled focal depths, we compared our solutions with those obtained by other methods and found the consistency is good. Because the focal depths estimated by RDPM are model dependent, we tested the extent of the dependency and found that a 10% error in the crustal model may generate a 10%-15% error in the modeled depth. The absolute error is determined by the error in the crustal model and the focal depth itself. We found that earthquake location errors have only a small effect on the modeled focal depths. By analyzing synthetic and observed waveforms, we found a distance window within which sPmP and PmP are well developed, and, within the window, the P portion of the waveform is relatively simple and sPmP and PmP are easy to identify. We also demonstrated that the assumptions of sPmP and PmP are correct, that regional depth phases are not developed or not discernible in some regions, and that regional depth phases have special features that can be used to identify those phases.


Kurepin L.V.,University of Western Ontario | Pharis R.P.,University of Calgary
Plant Science | Year: 2014

Shoot growth of dicot plants is rigorously controlled by the interactions of environmental cues with several groups of phytohormones. The signaling effects of light on shoot growth are of special interest, as both light irradiance and light quality change rapidly throughout the day, causing profound changes in stem elongation and leaf area growth. Among the several dicot species examined, we have focused on sunflower ( Helianthus annuus L.) because its shoots are robust and their growth is highly plastic. Sunflower shoots thus constitute an ideal tissue for assessing responses to both light irradiance and light quality signals. Herein, we discuss the possible roles of gibberellins, auxin, ethylene, cytokinins and brassinosteroids in mediating the stem elongation and leaf area growth that is induced by shade light. To do this we uncoupled the plant's responses to changes in the red to far-red [R/FR] light ratio from its responses to changes in irradiance of photosynthetically active radiation [PAR]. Reducing each of R/FR light ratio and PAR irradiance results in increased sunflower stem elongation. However, the plant's response for leaf area growth differs considerably, with a low R/FR ratio generally promoting leaf area growth, whereas low irradiance PAR inhibits it. The increased stem elongation that occurs in response to lowering R/FR ratio and PAR irradiance is accomplished at the expense of leaf area growth. In effect, the low PAR irradiance signal overrides the low R/FR ratio signal in shade light's control of leaf growth and development. Three hormone groups, gibberellins, auxin and ethylene are directly involved in regulating these light-mediated shoot growth changes. Gibberellins and auxin function as growth promoters, with auxin likely acting as an up-regulator of gibberellin biosynthesis. Ethylene functions as a growth-inhibitor and probably interacts with gibberellins in regulating both stem and leaf growth of the sunflower shoot. © 2014.


Goda K.,University of Bristol | Atkinson G.M.,University of Western Ontario
Bulletin of the Seismological Society of America | Year: 2010

Spatial correlation of intraevent peak ground-motion amplitudes at different sites is an important issue for seismic hazard and risk assessment of spatially distributed buildings and infrastructure. Correlated seismic effects cause acute concentration and accumulation of seismic losses, potentially resulting in a catastrophic event. We investigate the adequacy of the existing spatial correlation model of Goda and Atkinson (2009b) for Japanese earthquakes in light of strong ground motion data obtained from the SK-net database, which achieves greater spatial density of recording stations in the Kanto region. The SK-net dataset is suitable for filling in gaps in the Go da-Atkinson dataset at short separation distances where data coverage is sparse. Spatial correlations based on the SK-net data decrease gradually with increasing inter station separation distance. At short separation distances, the estimated spatial correlation data points show large variability around the average trend. Sensitivity to the manner of estimating intra event standard deviation is significant, as positive correlations among residuals occur due to the dense spatial coverage of recording stations. The developed spatial correlation model fits the observed data reasonably well and is consistent with the Go da-Atkinson model. At short separation distances (less than 1 km), wherein empirical data are limited and estimates are uncertain, discretion is required in adopting such models for seismic hazard and risk assessment of spatially distributed structures.


Song Y.,Tongji University | Zou X.,University of Western Ontario
Nonlinear Dynamics | Year: 2014

In this paper, a ratio-dependent predator–prey model with diffusion is considered. The stability of the positive constant equilibrium, Turing instability, and the existence of Hopf and steady state bifurcations are studied. Necessary and sufficient conditions for the stability of the positive constant equilibrium are explicitly obtained. Spatially heterogeneous steady states with different spatial patterns are determined. By calculating the normal form on the center manifold, the formulas determining the direction and the stability of Hopf bifurcations are explicitly derived. For the steady state bifurcation, the normal form shows the possibility of pitchfork bifurcation and can be used to determine the stability of spatially inhomogeneous steady states. Some numerical simulations are carried out to illustrate and expand our theoretical results, in which, both spatially homogeneous and heterogeneous periodic solutions are observed. The numerical simulations also show the coexistence of two spatially inhomogeneous steady states, confirming the theoretical prediction. © 2014, Springer Science+Business Media Dordrecht.


Leyshon R.,University of Western Ontario
Work (Reading, Mass.) | Year: 2010

INTRODUCTION: Ergonomic interventions designed for office and computer work have become widely available and heavily marketed but there is little evidence to support their use with workers who already have a musculoskeletal disorder (MSD). The purpose of any ergonomic intervention can be to improve worker comfort, safety and/or productivity. The ergonomic research in secondary prevention typically focuses outcomes on improved worker comfort but less if any emphasis has been put on productivity and safety. The purpose of this study was to determine the level and quality of evidence supporting ergonomic interventions to improve the comfort, safety and/or productivity of office workers with symptoms of MSDs. METHOD: A search of the ergonomic intervention literature based on MSDs of four body areas (low back, upper limb, eye and neck) was employed. The studies underwent two levels of analysis for inclusion in a best-evidence synthesis approach, which included a priori evaluation of specific interventions relative to outcomes of comfort, safety and/or productivity. RESULTS: Twenty-seven out of 202 articles were synthesized based on relevance, quality and significant results. Only 8 articles were determined high quality and no strong levels of evidence were identified. Levels of evidence for specific ergonomic interventions ranged from insufficient to moderate. Generally outcomes were focused mostly on improved comfort of workers. CONCLUSIONS: There is still limited quality research that addresses ergonomic interventions designed for secondary prevention. Further high quality studies are needed to support evidence-based ergonomic interventions in practice. For all stakeholders to fully evaluate the usefulness of the ergonomic intervention studies need to attend to outcomes not only of worker comfort but also to productivity and safety.


Perlas A.,University of Western Ontario
Regional anesthesia and pain medicine | Year: 2010

GOALS: To summarize the existing evidence behind the role of ultrasonography in neuraxial anesthesia techniques. METHODS: A literature search of the MEDLINE, PubMed, ACP Journal Club databases, and the Cochrane Database of Systematic Reviews was performed using the term ultrasonography combined with each of the following: spinal, intrathecal, epidural, and lumbar puncture. Only studies related to regional anesthesia or acute pain practice were included. Case reports and letters to the editor were excluded. Seventeen relevant studies were identified and included in this review. RESULTS: Neuraxial ultrasonography is a recent development in regional anesthesia practice. Most clinical studies to date come from a limited number of centers and have been performed by very few and highly experienced operators. The existing evidence may be classified in 2 main content areas: (a) ultrasound-assisted neuraxial techniques and (b) real-time ultrasound-guided neuraxial techniques. CONCLUSIONS: Neuraxial ultrasonography has been recently introduced to regional anesthesia practice. The limited data available to date suggest that it is a useful adjunct to physical examination, allowing for a highly precise identification of regional landmarks and a precise estimation of epidural space depth, thus facilitating epidural catheter insertion. Further research is needed to conclusively establish its impact on procedure success and safety profile, particularly in the adult nonobstetric population.


Van De Wiel M.J.,University of Western Ontario | Coulthard T.J.,University of Hull
Geology | Year: 2010

For many years researchers have linked increases in sediment and bedload from drainage basins to external factors such as increased rainfall. However, natural systems have always shown a high degree of scatter or nonlinearity in this response, which has made prediction of sediment yields difficult. We identify and describe a mechanism for self-organized criticality in the bedload sediment output from a simple drainage basin evolution model. This implies that identical floods will give considerably different sediment yields, which effectively renders the system unpredictable. Therefore, existing empirical methods for estimating sediment yields may need to be radically reevaluated. Furthermore, sedimentary records used to infer past climate or environmental conditions could simply reflect the internal system dynamics instead of external drivers. © 2010 Geological Society of America.


Sandre M.K.,McMaster University | Rohekar S.,University of Western Ontario
Seminars in Arthritis and Rheumatism | Year: 2015

Objective: Psoriatic arthritis (PsA) has a diverse range of clinical manifestations, both articular and extra-articular. Although the association of PsA with skin changes is well established, the relationship of PsA with psoriatic nail changes remains relatively unexplored. Methods: This report reviews the current literature surrounding the association of PsA with nail changes. A review of the literature was completed using PubMed, MEDLINE, and EMBASE in September 2013, encompassing years 1964-2012. Results: A total of 21 articles were reviewed. On average, 66% [standard deviation (SD) 17.7] of PsA patients had nail changes. The type of nail changes and their associations varied widely between studies. Conclusions: Studies of nail changes in PsA are highly variable with a wide range of results. Given the variability of results that were observed in this review, our recommendations are that further large studies on nail changes in patients with PsA should be conducted. © 2014 Elsevier Inc.


Paivio A.,University of Western Ontario
Journal of Experimental Psychology: General | Year: 2013

Kousta, Vigliocco, Del Campo, Vinson, and Andrews (2011) questioned the adequacy of dual coding theory and the context availability model as explanations of representational and processing differences between concrete and abstract words. They proposed an alternative approach that focuses on the role of emotional content in the processing of abstract concepts. Their dual coding critique is, however, based on impoverished and, in some respects, incorrect interpretations of the theory and its implications. This response corrects those gaps and misinterpretations and summarizes research findings that show predicted variations in the effects of dual coding variables in different tasks and contexts. Especially emphasized is an empirically supported dual coding theory of emotion that goes beyond the Kousta et al. emphasis on emotion in abstract semantics. © 2013 American Psychological Association.


Stan Leung L.,University of Western Ontario
Journal of Neuroscience | Year: 2011

A hippocampal place cell fires at an increasingly earlier phase in relation to the extracellular theta rhythm as a rodent moves through the place field. The present report presents a compartment model of a CA1 pyramidal cell that explains the increase in amplitude and the phase precession of intracellular theta oscillations, with the assumption that the cell receives an asymmetric ramp depolarization (<10 mV) in the place field and rhythmic inhibitory and/or excitatory synaptic driving. Intracellular subthreshold membrane potential oscillations (MPOs) increase in amplitude and frequency, and show phase precession within the place field. Theta phase precession and MPO power and frequency increase in the place field are caused by a shift in excitatory-inhibitory response, intrinsic theta-frequency resonance, and intrinsic oscillations that depend on voltage-dependent persistent Na+ and slowly inactivating K+ currents, but not on Ih. Phase precession is diminished when theta-frequency resonance is decreased. Simulated spikes fire near the peak ofMPOsand precess similarly as the MPOs. The phase of the MPOs/spikes codes for distance in a one-dimensional place field, and phase precession is only weakly dependent on firing rate, running speed, or the duration needed to cross the place field. In addition, phase precession within the place field resumes quickly after disruption by maximal afferent pulse stimulation. © 2011 the authors.


Thompson G.J.,University of Western Ontario
Biology letters | Year: 2013

William D. Hamilton postulated the existence of 'genes underlying altruism', under the rubric of inclusive fitness theory, a half-century ago. Such genes are now poised for discovery. In this article, we develop a set of intuitive criteria for the recognition and analysis of genes for altruism and describe the first candidate genes affecting altruism from social insects and humans. We also provide evidence from a human population for genetically based trade-offs, underlain by oxytocin-system polymorphisms, between alleles for altruism and alleles for non-social cognition. Such trade-offs between self-oriented and altruistic behaviour may influence the evolution of phenotypic diversity across all social animals.


De Bruyn J.R.,University of Western Ontario
Journal of Fluid Mechanics | Year: 2012

A flowing granular material can behave like a collection of individual interacting grains or like a continuum fluid, depending in large part on the energy imparted to the grains. As yet, however, we have no general understanding of how or under what conditions the fluid limit is reached. Marston, Li & Thoroddsen (J. Fluid Mech., this issue, vol. 704, 2012, pp. 5-36) use high-speed imaging to investigate the ejection of grains from a granular bed due to the impact of a spherical projectile. Their high temporal resolution allows them to study the very fast processes that take place immediately following the impact. They demonstrate that for very fine grains and high impact energies, the dynamics of the ejecta is both qualitatively and quantitatively similar to what is seen in analogous experiments with fluid targets. © 2012 Cambridge University Press.


Active membrane transporters are dynamic molecular machines that catalyse transport across a membrane by coupling solute movement to a source of energy such as ATP or a secondary ion gradient. A central question for many active transporters concerns the mechanism by which transport is coupled to a source of energy. The transport process and associated energetic coupling involve conformational changes in the transporter. For efficient transport, the conformational changes must be tightly regulated and they must link energy use to movement of the substrate across the membrane. The present review discusses active transport using the well-established energetic framework for enzyme-mediated catalysis. In particular, membrane transport systems can be viewed as ensembles consisting of low-energy and high-energy conformations. The transport process involves binding interactions that selectively stabilize the higher energy conformations, and in this way promote conformational changes in the system that are coupled to decreases in free energy and substrate translocation. The major facilitator superfamily of secondary active transporters is used to illustrate these ideas, which are then be expanded to primary active transport mediated by ABC (ATP-binding cassette) import systems, with a focus on the well-studied maltose transporter. © The Authors Journal compilation © 2015 Biochemical Society.


Murli C.,University of Western Ontario | Song Y.,Bhabha Atomic Research Center
Journal of Physical Chemistry B | Year: 2010

We report here the first in-situ Raman spectroscopic study of pressure-induced structural and polymeric transformations of acrylic acid. Two crystalline phases (I and II) were observed upon compression to ∼0.3 and ∼2.7 GPa. Phase I can be characterized with a single s-cis molecular conformation with possibly a similar structure to the low-temperature phase, while phase II suggests significantly enhanced molecular interactions toward polymerization and structural disordering. Beyond ∼8 GPa, spectroscopic features indicate the onset of polymerization. The high-pressure polymeric phase together with the pressure-quenched materials was examined and compared with two commercial acrylic acid polymers using Raman spectroscopy. The characteristics of polymeric acrylic acid and their transformation mechanisms as well as the implications of hydrogen-bonding interactions are discussed. © 2010 American Chemical Society.


Smith D.R.,University of Western Ontario | Lee R.W.,Dalhousie University
Plant Physiology | Year: 2014

Polytomella spp. are free-living, nonphotosynthetic green algae closely related to the model organism Chlamydomonas reinhardtii. Although colorless, Polytomella spp. have a plastid, but it is still unknown whether they harbor a plastid genome. We took a next generation sequencing approach, along with transcriptome sequencing, to search for a plastid genome and an associated gene expression system in Polytomella spp. Illumina sequencing of total DNA from four Polytomella spp. did not produce any recognizable plastid-derived reads but did generate a large number of mitochondrial DNA sequences. Transcriptomic analysis of Polytomella parva uncovered hundreds of putative nuclear-encoded, plastid-targeted proteins, which support the presence of plastid-based metabolic functions, similar to those observed in the plastids of other nonphotosynthetic algae. Conspicuously absent, however, were any plastid-targeted proteins involved in the expression, replication, or repair of plastid DNA. Based on these findings and earlier findings, we argue that the Polytomella genus represents the first wellsupported example, to our knowledge, of a primary plastid-bearing lineage without a plastid genome. © 2014 American Society of Plant Biologists. All Rights Reserved.


Winterhager E.,University of Duisburg - Essen | Kidder G.M.,University of Western Ontario
Human Reproduction Update | Year: 2015

Background: Connexins comprise a family of ~20 proteins that form intercellular membrane channels (gap junction channels) providing a direct route for metabolites and signalling molecules to pass between cells. This reviewprovides a critical analysis of the evidence for essential roles of individual connexins in female reproductive function, highlighting implications for women's reproductive health. Methods: No systematic review has been carried out. Published literature from the past 35 years was surveyed for research related to connexin involvement in development and function of the female reproductive system. Because of the demonstrated utility of genetic manipulation for elucidating connexin functions in various organs,muchof the cited information comes fromresearch with genetically modified mice. Insomecases, a distinction is drawn between connexin functions clearly related to the formation of gap junction channels and those possibly linked to nonchannel roles. Results and conclusions: Based on work with mice, several connexins are known to be required for female reproductive functions. Loss of connexin43 (CX43) causes an oocyte deficiency, and follicles lacking or expressing less CX43 in granulosa cells exhibit reduced growth, impairing fertility. CX43 is also expressed in human cumulus cells and, in the context of IVF, has been correlated with pregnancy outcome, suggesting that this connexin may be a determinant of oocyte and embryo quality in women. Loss of CX37, which exclusively connects oocytes with granulosa cells in the mouse, caused oocytes to cease growing without acquiring meiotic competence. Blocking of CX26 channels in the uterine epithelium disrupted implantation whereas loss or reduction of CX43 expression in the uterine stroma impaired decidualization and vascularization in mouse and human. Several connexins are important in placentation and, in the human, CX43 is a key regulator of the fusogenic pathway from the cytotrophoblast to the syncytiotrophoblast, ensuring placental growth. CX40, which characterizes the extravillous trophoblast (EVT), supports proliferation of the proximal EVTs while preventing them from differentiating into the invasive pathway. Furthermore, women with recurrent early pregnancy loss as well as those with endometriosis exhibit reduced levels of CX43 in their decidua. The antimalaria drug mefloquine, which blocks gap junction function, is responsible for increased risk of early pregnancy loss and stillbirth, probably due to inhibition of intercellular communication in the decidua or between trophoblast layers followed by an impairment of placental growth. Gap junctions also play a critical role in regulating uterine blood flow, contributing to the adaptive response to pregnancy. Given that reproductive impairment can result from connexin mutations in mice, it is advised that women suffering from somatic disease symptoms associated with connexin gene mutations be additionally tested for impacts on reproductive function. Better knowledge of these essential connexin functions in human female reproductive organs is important for safeguarding women's reproductive health. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Reliability analysis of structures requires statistical models of multi-variate random data that are nonlinearly interrelated. The current reliability methods that use the Nataf transformation and the linear correlation matrix may encounter difficulties in dealing with such situations. A copula approach can offer a general and flexible way of describing nonlinear dependence among multi-variate data in isolation from their marginal probability distributions, and serves as a powerful tool for modeling and simulating nonlinearly-interrelated data. In this study, an introduction as well as illustrative application of the copula theory is given in the context of structural reliability. The numerical example deals with the performance evaluation of existing structures subjected to earthquake loading in terms of both peak and residual displacement demands. The joint probability distribution modeling of peak and residual displacement seismic demands based on the copula theory is demonstrated, and the developed statistical models are used to examine the effects of nonlinear dependence on seismic reliability assessment. © 2009 Elsevier Ltd. All rights reserved.


Siegers G.M.,University of Western Ontario | Lamb L.S.,University of Alabama at Birmingham
Molecular Therapy | Year: 2014

Exploration of cancer immunotherapy strategies that incorporate γδ T cells as primary mediators of antitumor immunity are just beginning to be explored and with a primary focus on the use of manufactured phosphoantigen-stimulated Vγ9Vδ2 T cells. Increasing evidence, however, supports a critical role for Vδ1+ γδ T cells, a minor subset in peripheral blood with distinct innate recognition properties that possess powerful tumoricidal activity. They are activated by a host of ligands including stress-induced self-antigens, glycolipids presented by CD1c/d, and potentially many others that currently remain unidentified. In contrast to Vγ9Vδ2 T cells, tumor-reactive Vδ1+ T cells are not as susceptible to activation-induced cell death and can persist in the circulation for many years, potentially offering durable immunity to some cancers. In addition, specific populations of Vδ1+ T cells can also exhibit immunosuppressive and regulatory properties, a function that can also be exploited for therapeutic purposes. This review explores the biology, function, manufacturing strategies, and potential therapeutic role of Vδ1+ T cells. We also discuss clinical experience with Vδ1+ T cells in the setting of cancer, as well as the potential of and barriers to the development of Vδ1+ T cell-based adoptive cell therapy strategies. © The American Society of Gene & Cell Therapy.


Di Cresce C.,University of Western Ontario
Current cancer drug targets | Year: 2010

Antisense reagents and technology have developed as extraordinarily useful tools for analysis of gene function. The capacity of antisense to reduce expression of RNA (including protein-encoding mRNA and non-coding RNA) important in a multitude of diseases (including cancer) has led to the concept of using antisense molecules as drugs to treat those diseases. Both antisense RNA (RNAi) and antisense oligonucleotides (ASOs) are being developed for this purpose, with ASOs currently the most advanced in clinical testing. ASOs inhibit translation or induce degradation of complementary target RNA, and both Phase I and Phase II trials are either completed or in progress for a number of diseases. In this review, we focus on antisense approaches to treatment of two cancers (melanoma and hormone-resistant prostate cancer) where the early application of ASOs has provided important information revealing both potential for success and lessons for future preclinical and clinical investigation of ASOs as anti-cancer drugs. The progress of clinical application of two ASOs showing promise in treatment of human cancers--Oblimersen (G3139), targeting BCL2 for the treatment of metastatic melanoma, and Custirsen (OGX-11), targeting clusterin for the treatment of hormone refractory prostate cancer (HRPC)--is examined.


Gupta M.A.,University of Western Ontario
Current psychiatry reports | Year: 2014

Several diagnoses in the new DSM-5 chapter on 'Obsessive-Compulsive and Related Disorders' directly relate to psychodermatology. The new excoriation (skin-picking) disorder (SPD) and trichotillomania (TTM) both manifest as recurrent body-focused repetitive behaviors that have compulsive and dissociative features, the latter being more prevalent in TTM than SPD. The DSM-5 refers to SPD and TTM occurring without full awareness or preceding tension, however does not specifically mention the possible role of dissociation. This has important treatment implications, as patients with high dissociative symptoms are not likely to respond to the standard treatments for obsessive-compulsive disorder. Body dysmorphic disorder (BDD), which is frequently associated with cutaneous body image (CBI) dissatisfaction, is present in 9%-15% of dermatology patients. Treatment guidelines in dermatology are increasingly considering the psychosocial morbidity related to CBI in their treatment outcome measures. The presence of BDD, if unrecognized, may therefore directly affect the dermatologic treatment regimens offered to the patient.


Adamiak K.,University of Western Ontario
Journal of Electrostatics | Year: 2013

This paper attempts to review the most important works on numerical simulation of processes in electrostatic precipitators published so far. Only the wire-plate configuration is considered, although the discharge electrode may have different geometries: smooth cylinder, barbed wire of different shape or helical electrode. Different mathematical models and numerical algorithms for gas flow, electric field, corona discharge and particle transport have been compared. The discussion is focused on coupling between different phenomena. A continuous progress has been shown from early works published about 30 years ago, which dealt with much idealized models of the problem, to recent publications, where the numerical predictions show close agreement with the experimental data. © 2013 Elsevier B.V.


Nehdi M.L.,University of Western Ontario
Construction and Building Materials | Year: 2014

Limitations in guidelines and standards on the amount of clay in sand and coarse aggregate micro-fines and the influence of such micro-fines on fresh and hardened concrete properties is often ambiguous for practitioners and quality control professionals. This is compounded by conflicting related data in the open literature and the inadequacy of some standard test procedures for capturing the real problems associated with the presence of clays in cement-based materials. This paper examines the various types of clay, limitations on clays in aggregates in various standards, and the test methods used to assess the presence of clays in aggregates. A critical overview of literature on the possible effects of clay in cement-based materials is provided, including effects on water demand, workability, mechanical strength, dimensional stability and chemical admixtures dosage. The problem of dimensional stability of aggregates bearing clay minerals is examined. Possible chemical treatment of clays to mitigate their detrimental effects in concrete is also outlined. Finally, emerging research on using nano-clays in cement-based materials is highlighted and recommendations to resolve ambiguity related to the presence of clays in cement-based materials are proposed. © 2013 Elsevier Ltd. All rights reserved.


Manchanda R.,University of Western Ontario
Canadian journal of psychiatry. Revue canadienne de psychiatrie | Year: 2013

To review the evidence for the role of long-acting injectable (LAI) antipsychotics (APs), especially the second-generation AP (SGA) LAIs, in the treatment of schizophrenia and to discuss the use rates of LAIs in Canada. A search of online medical databases was conducted of the published literature (1995-2012) of the effects of LAIs on the domains of remission, adherence, relapse, and hospitalization. Results obtained from randomized controlled trials (RCTs), systematic reviews, meta-analyses, and large-scale observational studies were included. Expert consensus data were also solicited on LAI use within a Canadian context. While the efficacy of LAIs, compared with placebo, is well established, the evidence from RCTs is equivocal for any specific advantage for SGA LAIs, compared with oral medications, probably owing to challenges in conducting such RCTs. Evidence from methodologically less rigorous studies and from clinical practice suggests some advantages in achieving and maintaining remission, risk of relapse, and hospitalization. The rate of LAI (first-generation AP and SGA) use from published outpatient studies is low at 6.3% in Canada, compared with 15% to 80% worldwide. However, there is a relatively high rate of use in specific early psychosis programs and in conjunction with community treatment orders in Canada. LAIs are at least as effective as oral APs in the treatment of psychotic disorders. The former may have specific advantages for patients who demonstrate covert nonadherence. The underuse of LAIs in Canada needs to be better understood and addressed.


Guaiana G.,University of Western Ontario
The Cochrane database of systematic reviews | Year: 2013

Major depressive disorder (MDD), or depression, is a syndrome characterised by a number of behavioural, cognitive and emotional features. It is most commonly associated with a sad or depressed mood, a reduced capacity to feel pleasure, feelings of hopelessness, loss of selective serotonin reuptake inhibitors (SSRIs), namely paroxetine, fluoxetine, sertraline, escitalopram, and to the serotonin-norepinephrine reuptake inhibitor (SNRI), venlafaxine. Participants were followed up for six to 12 weeks. Agomelatine did not show any advantage or disadvantage over the other antidepressants for our primary outcome, response to treatment (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.95 to 1.08, P value 0.75 compared to SSRIs, and RR 1.06; 95% CI 0.98 to 1.16, P value 0.16 compared to venlafaxine). Also, agomelatine showed no advantage or disadvantage over other antidepressants for remission (RR 0.83; 95% CI 0.68 to 1.01, P value 0.07 compared to SSRIs, and RR 1.08; 95% CI 0.94 to 1.24, P value 0.73 compared to venlafaxine). Overall, agomelatine appeared to be better tolerated than venlafaxine in terms of lower rates of drop outs (RR 0.40; 95% CI 0.24 to 0.67, P value 0.0005), and showed the same level of tolerability as SSRIs (RR 0.95; 95% CI 0.83 to 1.09, P value 0.44). Agomelatine induced a lower rate of dizziness than venlafaxine (RR 0.19, 95% CI 0.06 to 0.64, P value 0.007).With regard to the quality of the body of evidence, there was a moderate risk of bias for all outcomes, due to the number of included unpublished studies. There was some heterogeneity, particularly between published and unpublished studies. The included studies were conducted in inpatient and outpatient settings, thus limiting the generalisability of the results to primary care settings. With regard to precision, the efficacy outcomes were precise, but the tolerability outcomes were mostly imprecise. Publication bias was variable and depended on the outcome of the trial. Our review included unpublished studies, and we think that this reduced the impact of publication bias. The overall methodological quality of the studies was not very good. Almost all of the studies were sponsored by the pharmaceutical company that manufactures agomelatine (Servier), and some of these were unpublished. Attempts to contact the pharmaceutical company Servier for additional information on all unpublished studies were unsuccessful. Agomelatine did not seem to provide a significant advantage in efficacy over other antidepressive agents for the acute-phase treatment of major depression. Agomelatine was better tolerated than paroxetine and venlafaxine in terms of overall side effects, and fewer participants treated with agomelatine dropped out of the trials due to side effects compared to sertraline and venlafaxine, but data were limited because the number of included studies was small. We found evidence that compared agomelatine with only a small number of other active antidepressive agents, and there were only a few trials for each comparison, which limits the generalisability of the results. Moreover, the overall methodological quality of the studies was low, and, therefore, no firm conclusions can be drawn concerning the efficacy and tolerability of agomelatine.


Avison W.R.,University of Western Ontario
Journal of Health and Social Behavior | Year: 2010

Emerging themes in demography, developmental medicine, and psychiatry suggest that a comprehensive understanding of mental health across the life course requires that we incorporate the lives of children into our research. If we can learn more about the ways in which the stress process unfolds for children, we will gain important insights into the factors that influence initial set points of trajectories of mental health over the life course. This will simultaneously extend the scope of the stress process paradigm and elaborate the life course perspective on mental health. Incorporating children's lives into the sociology of mental health will also extend the intellectual influence of the discipline on sociomedical and biomedical research on mental illness. I contend that sociology's greatest promise in understanding trajectories of mental health across the life course lies in a systematic analysis of the social and social-psychological conditions of children, the stressful experiences that arise out of these conditions, and the processes that mediate and moderate the stress process in childhood. In this regard, there are three major issues that sociologists could begin to address: (1) the identification of structural and institutional factors that pattern children's exposure to stress; (2) the construction of a stress universe for children; and (3) the identification of key elements of the life course perspective that may set or alter trajectories of mental health in childhood and adolescence. © American Sociological Association 2010.


Cianci A.M.,Drexel University | Klein H.J.,Ohio State University | Seijts G.H.,University of Western Ontario
Journal of Applied Psychology | Year: 2010

The purpose of this experiment was to examine the interplay of goal content, conscientiousness, and tension on performance following negative feedback. Undergraduate students were assigned either a learning or performance goal and then were provided with false feedback indicating very poor performance on the task they performed. After assessing tension, participants performed the task again with the same learning or performance goal. A mediated moderation model was tested, and results were supportive of our hypotheses. Specifically, individuals assigned a learning goal experienced less tension and performed better following negative feedback than individuals assigned a performance goal. Individuals high in conscientiousness experienced greater tension than individuals low in conscientiousness. Conscientiousness and goal content interacted in relating to both tension and performance, with tension as a mediator, such that high conscientiousness amplified the detrimental effect of a performance goal on tension following negative feedback leading to lower performance. High conscientiousness facilitated performance for participants with a learning goal. © 2010 American Psychological Association.


Rocks are heterogeneous materials. Deformation structures and fabrics in the ductile lithosphere can result from the history of the three dimensional flow field, or the progressive deformation of some rheologically distinct elements embedded in the 3D flow field, or a combination of both. The flow and progressive deformation of a rheologically distinct element is generally non-steady even if the hosting 3D flow field is steady. Vorticity decomposition is the key to following the progressive history of the deformation of specific elements. A general theoretical background to the problem is presented. Flow and progressive deformation of surface (and layer-like) elements in 3D homogeneous flows are investigated specifically. Analytical procedures to calculate the sectional vorticity number and the sectional dilatancy number on a general section in a 3D flow field are introduced. The theoretical analysis is applied to various examples of sectional flow embedded in different types of 3D homogeneous and steady flow fields. Implications of this investigation for kinematic analysis of natural rock deformation are discussed. All types of material line histories are expected in sectional flows of layer-like elements. Shortened boudins can be formed in a single progressive deformation. In sequences of rocks with a well-developed transposition foliation common in large scale high-strain zones, each layer unit may have undergone a unique deformation history during its rotation to the final, shear zone boundary parallel orientation. In kinematic analysis of such areas, it is important to ascribe the correct kinematic significance to structural associations and fabrics. © 2010 Elsevier B.V.


Atkinson G.M.,University of Western Ontario
Bulletin of the Seismological Society of America | Year: 2010

Ground-motion prediction equations (GMPEs) for Hawaii are developed using the referenced empirical approach. The technique is based on the use of residual analysis that models discrepancies between ground-motion observations for Hawaii and a reference GMPE, in this case the GMPE of Boore and Atkinson (2008) for shallow crustal earthquakes in active tectonic regions. The referenced empirical approach provides GMPEs for Hawaii that are in agreement with regional ground-motion observations, while being constrained to follow the overall scaling behavior of ground motion that is observed in better-instrumented regions. GMPEs are developed for both shallow (depth < 20 km) and deep (35 to 40 km) earthquakes in Hawaii.


Samsonov S.,Institute of Geological & Nuclear Sciences | Samsonov S.,University of Western Ontario
IEEE Transactions on Geoscience and Remote Sensing | Year: 2010

L-band synthetic aperture radar (SAR) interferometry is very successful for mapping ground deformation in densely vegetated regions. However, due to its larger wavelength, the capacity to detect slow deformation over a short period of time is limited. Stacking and small baseline subset (SBAS) techniques are routinely used to produce time series of deformation and average deformation rates by reducing the contribution of topographic and atmospheric noise. For large sets of images that are presently available from C-band European Remote Sensing Satellites (ERS-1/2) and Environmental Satellite (ENVISAT), the standard stacking and SBAS algorithms are accurate. However, the same algorithms are often inaccurate when used for processing of interferograms from L-band Advanced Land Observing Satellite Phased Array type L-band SAR (ALOS PALSAR). This happens because only a limited number of interferograms is acquired and also because of large spatial baselines often correlated with the time of acquisition. In this paper two techniques are suggested that can be used for removing the residual topographic component from stacking and SBAS results, thereby increasing their accuracy. © 2006 IEEE.


Krayenhoff E.S.,University of British Columbia | Voogt J.A.,University of Western Ontario
Journal of Applied Meteorology and Climatology | Year: 2010

The authors combine urban and soil-vegetation surface parameterization schemes with one-dimensional (1D) boundary layer mixing and radiation parameterizations to estimate the maximum impact of increased surface albedo on urban air temperatures. The combined model is evaluated with measurements from an urban neighborhood in Basel, Switzerland, and the importance of surface-atmosphere model coupling is demonstrated. Impacts of extensive albedo increases in two Chicago, Illinois, neighborhoods are modeled. Clear-sky summertime reductions of diurnal maximum air temperature for the residential neighborhood (λp = 0.33) are -1.1°, -1.5°, and -3.6°C for uniform roof albedo increases of 0.19, 0.26, and 0.59, respectively; reductions are about 40% larger for the downtown core (λp = 0.53). Realistic impacts will be smaller because the 1D modeling approach ignores advection; a lake-breeze scenario is modeled and temperature reductions decline by 80%. Assuming no advection, the analysis is extended to seasonal and annual time scales in the residential neighborhood. Yearly average temperature decreases for a 0.59 roof albedo increase are about -1°C, with summer (winter) reductions about 60% larger (smaller). Annual cooling degree-day decreases are approximately offset by heating degree-day increases and the frequency of very hot days is reduced. Despite the variability of modeling approaches and scenarios in the literature, a consistent range of air temperature sensitivity to albedo is emerging; a 0.10 average increase in neighborhood albedo (a 0.40 roof albedo increase for λp = 0.25) generates a diurnal maximum air temperature reduction of approximately 0.5°C for "ideal" conditions, that is, a typical clear-sky midlatitude summer day. © 2010 American Meteorological Society.


Fernando Capretz L.,University of Western Ontario
IEEE Software | Year: 2014

The human aspects involved in the software development process are vital to a successful completion of a software project. The author advocates for human factor topics to be part of mainstream software engineering education in order to elevate job satisfaction, improve performance, and increase productivity of software engineers. Emphasis should be on providing a practical overview of software engineering processes from a human perspective, offering alternative viewpoints within technically saturated curricula. © 1984-2012 IEEE.


Atkinson G.M.,University of Western Ontario
Bulletin of the Seismological Society of America | Year: 2015

The evaluation of seismic hazard from induced seismicity requires the development of ground-motion prediction equations (GMPEs) that are tuned to the key magnitude-distance range for such applications. I use events of M 3-6 at hypocentral distances less than 40 km, drawn from the Next Generation Attenuation-West 2 (NGA-West 2) database, to develop a GMPE that accounts correctly for point-source scaling in both magnitude and distance space for such events. The developed GMPE is in demonstrable agreement with the NGA-West 2 database and with the predictions of a stochastic point-source simulation model. The database is sparse at close distances, implying epistemic uncertainty of as much as a factor of 2 in ground-motion amplitudes within 10 km of the hypocenter. An important conclusion from this study is that the ground-motion amplitudes for moderate induced events could be much larger near the epicenter than predicted by most of the NGA-West 2 GMPEs. The potential for large motions is a consequence of the shallow depth of induced events, which places the earthquake fault only a short distance beneath the epicenter. © 2015, Bulletin of the Seismological Society of America. All rights reserved.


Tabari M.,University of Western Ontario | Yazdani A.,Ryerson University
IEEE Transactions on Smart Grid | Year: 2014

This paper proposes a method for enhancing the stability of a dc distribution system that integrates plug-in hybrid electric vehicles (PHEVs) with an ac power grid. The dc distribution system is interfaced with the host ac grid via a voltage-sourced converter and can also embed photovoltaic (PV) modules. Thus, bidirectional dc-dc electronic power converters act as battery chargers and interface the PHEVs with the dc distribution system, while PV modules are interfaced with the dc distribution system via unidirectional dc-dc converters. The dc distribution system is expected to be more efficient and economical than a system of ac-dc battery chargers directly interfaced with an ac grid, but it is prone to instabilities due to the constant-power property of the dc-dc converters. Using a nonlinear control strategy, the proposed stability enhancement method mitigates the issue of instability by altering the power setpoints of the battery chargers, bidirectional dc-dc converters, without a need for changing system parameters or hardware. The paper presents mathematical models for the original and modified systems and demonstrates that the proposed technique expands the stable operating region of the dc distribution system. Simulation results demonstrate the effectiveness of the proposed method for a study system in the PSCAD/EMTDC software environment. © 2014 IEEE.


Semenikhin O.A.,University of Western Ontario
Annual Reports on the Progress of Chemistry - Section C | Year: 2010

The experimental evidence of the inhomogeneity of conducting and semiconducting organic π-conjugated polymers is reviewed. A special attention is paid to the mesoscopic inhomogeneity, which originates from variability in the interactions between the molecules that constitute these materials. First, the effects of inhomogeneity on selected macroscopic parameters of the organic materials such as conductivity, charge mobility and electrochemical responses are analysed. Next, the microscopic evidence of inhomogeneity obtained with the help of various microscopic and scanning probe techniques is reviewed. In conclusion, possible mechanisms of the emergence of the energetic and structural inhomogeneity and the domain structure of conducting and semiconducting polymers and related materials are discussed. © The Royal Society of Chemistry 2010.


Elkasabgy M.,Amec Foster Wheeler | El Naggar M.H.,University of Western Ontario
Canadian Geotechnical Journal | Year: 2013

The dynamic performance of helical piles is of significant interest because such piles can offer an efficient alternative to conventional piling systems in many applications where the foundation is subjected to dynamic loads. This paper presents the results of full-scale dynamic vertical load tests on a 9.0 m double-helix, large-capacity helical pile and a driven steel pile of the same length and shaft geometry. Comparing the results is considered necessary to evaluate, qualitatively and quantitatively, the dynamic performance characteristics of large-capacity helical piles. The test piles were closed-ended steel shafts with an outer diameter of 324 mm. The piles were subjected to harmonic (quadratic) loading of different force intensities acting within a frequency range that covered the resonant frequencies of the tested pile-soil-cap systems. The dynamic and static properties of the subsurface soil adjacent to the test piles were determined using the seismic cone penetration technique and the conventional soil boring and testing methods. In addition, field observations are compared with calculated responses using the program DYNA 6 to better understand the pile-soil interaction for the case of helical piles. The effects of soil nonlinearity and pile-soil separation were accounted for in the analysis by employing a weak boundary zone around the piles in the analytical model. The experimental results show that the dynamic behavior of helical piles is essentially the same as that of driven steel piles with the same geometric properties (without the helix plates). In addition, it was demonstrated that the program DYNA 6 can accurately simulate the behavior of both helical and driven piles.


Striemer C.L.,University of Western Ontario | Danckert J.A.,University of Waterloo
Trends in Cognitive Sciences | Year: 2010

Many studies have demonstrated that prism adaptation can reduce several symptoms of visual neglect: a disorder in which patients fail to respond to information in contralesional space. The dominant framework to explain these effects proposes that prisms influence higher order visuospatial processes by acting on brain circuits that control spatial attention and perception. However, studies that have directly examined the influence of prisms on perceptual biases inherent to neglect have revealed very few beneficial effects. We propose an alternative explanation whereby many of the beneficial effects of prisms arise via the influence of adaptation on circuits in the dorsal visual stream controlling attention and visuomotor behaviors. We further argue that prisms have little influence on the pervasive perceptual biases that characterize neglect. © 2010.


Veksler O.,University of Western Ontario
International Journal of Computer Vision | Year: 2012

Optimization with graph cuts became very popular in recent years. While exact optimization is possible in a few cases, many useful energy functions are NP hard to optimize. One approach to approximate optimization is the so-called move making algorithms. At each iteration, a move-making algorithm makes a proposal (move) for a pixel p to either keep its old label or switch to a new label. Two move-making algorithms based on graph cuts are in wide use, namely the swap and expansion. Both of these moves are binary in nature, that is they give each pixel a choice of only two labels. An evaluation of optimization techniques shows that the expansion and swap algorithms perform very well for energies where the underlying MRF has the Potts prior. However for more general priors, the swap and expansion algorithms do not perform as well. The main contribution of this paper is to develop multi-label moves. A multi-label move, unlike expansion and swap, gives each pixel has a choice of more than two labels to switch to. In particular, we develop several multi-label moves for truncated convex priors. We evaluate our moves on image restoration, inpainting, and stereo correspondence. We get better results than expansion and swap algorithms, both in terms of the energy value and accuracy. © 2011 Springer Science+Business Media, LLC.


Hill H.,University of Western Ontario
Library and Information Science Research | Year: 2013

The library profession is a strong and vocal proponent of increased information access for people with disabilities. With the discipline's longstanding interest in the subject of services to people with disabilities, questions arise about how the profession perceives the phenomenon. How is library and information science (LIS), as a discipline, conceptualizing disability and accessibility? A content analysis of the LIS literature was conducted to examine this question. The literature provides a fertile ground for study as it reflects the profession's approaches to, and perceptions of, a topic. This research identifies the major issues and trends in the research about accessibility and disability in the LIS literature throughout a 10-year period, 2000-2010. The strongest theme in the literature is accessibility as it relates to web, database, and software, while the prevailing disability of focus is visual disabilities. The overall environment emphasizes technology more than attitudinal aspects associated with disabilities. The research could benefit from increased direct participation of people with disabilities. © 2013 Elsevier Inc.


Kalsi-Ryan S.,University of Western Ontario
Spine | Year: 2013

Narrative review. To identify suitable outcome measures that can be used to quantify neurological and functional impairment in the management of cervical spondylotic myelopathy (CSM). CSM is the leading cause of acquired spinal cord disability, causing varying degrees of neurological impairment which impact on independence and quality of life. Because this impairment can have a heterogeneous presentation, a single outcome measure cannot define the broad range of deficits seen in this population. Therefore, it is necessary to define outcome measures that characterize the deficits with greater validity and sensitivity. This review was conducted in 3 stages. Stage I: To evaluate the current use of outcome measures in CSM, PubMed was searched using the name of the outcome measure and the common abbreviation combined with "CSM" or "myelopathy." Stage II: Having identified a lack of appropriate outcome measures, we constructed criteria by which measures appropriate for assessing the various aspects of CSM could be identified. Stage III: A second literature search was then conducted looking at specified outcomes that met these criteria. All literature was reviewed to determine specificity and psychometric properties of outcomes for CSM. Nurick grade, modified Japanese Orthopaedic Association Scale, visual analogue scale (VAS) for pain, Short Form (36) Health Survey (SF-36), and Neck Disability Index were the most commonly cited measures. The Short-Form 36 Health Survey and Myelopathy Disability Index have been validated in the CSM population with multiple studies, whereas the modified Japanese Orthopaedic Association Scale score, Nurick grade, and European Myelopathy Scale each had only one study assessing psychometric characteristics. No validity, reliability, or responsiveness studies were found for the VAS or Neck Disability Index in the CSM population. We recommend that the modified Japanese Orthopaedic Association Scale, Nurick grade, Myelopathy Disability Index, Neck Disability Index, and 30-Meter Walk Test are most appropriate for the assessment of CSM. However, 6 additional outcome measures (QuickDASH, Berg Balance Scale, Graded Redefined Assessment of Strength Sensibility and Prehension, Grip Dynamometer, and GAITRite Analysis) were identified, which provide complementary assessments for CSM. SUMMARY STATEMENTS: There does not exist a single or composite of outcome instruments that measures myelopathy impairment, function/disability, and participation that have also demonstrated reliability, validity, and responsiveness in a CSM population. More work in the development and psychometric evaluation of new or existing measures is necessary to identify the ideal composite of measures to be used in the clinical and research settings. The mJOA, Nurick grade, NDI, MDI, and 30MWT should be adopted in any clinical practice that treats CSM both for screening and clinical follow-up. We propose that clinicians and researchers consider using the ancillary measures identified, such as the QuickDASH, Berg Balance Scale, GRASSP version 1.0, Grip Strength, and GAITRite Analysis. It is highly recommended that baseline and follow-up measurements should be performed in patients with CSM.


Dick F.A.,University of Western Ontario | Rubin S.M.,University of California at Santa Cruz
Nature Reviews Molecular Cell Biology | Year: 2013

Inactivation of the RB protein is one of the most fundamental events in cancer. Coming to a molecular understanding of its function in normal cells and how it impedes cancer development has been challenging. Historically, the ability of RB to regulate the cell cycle placed it in a central role in proliferative control, and research focused on RB regulation of the E2F family of transcription factors. Remarkably, several recent studies have found additional tumour-suppressor functions of RB, including alternative roles in the cell cycle, maintenance of genome stability and apoptosis. These advances and new structural studies are combining to define the multifunctionality of RB. © 2013 Macmillan Publishers Limited. All rights reserved.


Dechene D.J.,IBM | Shami A.,University of Western Ontario
IEEE Transactions on Mobile Computing | Year: 2014

In this paper, we propose a framework for energy efficient resource allocation in multiuser localized SC-FDMA with synchronous HARQ constraints. Resource allocation is formulated as a two-stage problem where resources are allocated in both time and frequency. The impact of retransmissions on the time-frequency problem segmentation is handled through the use of a novel block scheduling interval specifically designed for synchronous HARQ to ensure uplink users do not experience ARQ blocking. Using this framework, we formulate the optimal margin adaptive allocation problem, and based on its structure, we propose two suboptimal approaches to minimize average power allocation required for resource allocation while attempting to reduce complexity. Results are presented for computational complexity and average power allocation relative to system complexity and data rate, and comparisons are made between the proposed optimal and suboptimal approaches. © 2014 IEEE.


Karmazyn M.,University of Western Ontario
Journal of Molecular and Cellular Cardiology | Year: 2013

The concept of NaH exchange (NHE) involvement in cardiac pathology has been espoused for decades and supported by a plethora of experimental studies demonstrating salutary effects of NHE inhibition in protecting the myocardium against ischemic and reperfusion injury as well as attenuating myocardial remodelling and heart failure. NHE is actually a family of sodium and proton transporting proteins of which 10 isoforms have been identified. Myocardial NHE is represented primarily by the ubiquitous NHE-1 subtype which is expressed in most tissues. The robust positive results seen with NHE-1 inhibitors in experimental studies have led to relatively rapid development of these pharmacological agents for clinical assessment especially as potential cardioprotective therapies. Yet clinical studies have revealed, at best, inconsistent results as evidenced by poor efficacy and serious side effects, the latter revealed with the use of the NHE-1 inhibitor cariporide in high-risk patients undergoing coronary artery bypass grafting and evidenced by an increased incidence of cerebrovascular events of thromboembolic origin. The lack of success in clinical trials coupled with potential for toxicity has had a negative impact on development of cardiac therapeutic agents which have been developed based on the concept of NHE-1 inhibition. Whether this response is justified is open for discussion although a close scrutiny of clinical trial outcomes suggests that it may not be and that NHE-1 inhibition, if applied appropriately continues to represent an effective, if not the most effective approach for myocardial salvage following ischemic insult. Moreover, in addition to its cardioprotective effects, emerging evidence further suggests that NHE-1 inhibition is an effective strategy to minimize myocardial remodelling as well as a potentially effective strategy to improve efficacy of resuscitation following cardiac arrest. Thus, NHE-1 inhibition continues to represent a potentially highly effective therapeutic approach for the treatment of heart disease. This article is part of a Special Issue entitled "Na+ Regulation in Cardiac Myocytes". © 2013 Elsevier Ltd.


Moores J.E.,University of Western Ontario | Schuerger A.C.,University of Florida
Journal of Geophysical Research E: Planets | Year: 2012

Reanalysis of the Viking Lander results on Mars has suggested a surface reservoir of organic carbon at the ppm level. The size of this putative reservoir could be explained if the source of carbon on Mars is meteoritic in origin and is destroyed primarily by UV irradiation, yielding methane. By combining a numerical UV model for the surface of Mars with published laboratory measurements of organic UV photolysis, the times required to completely convert the carbon within individual particles to methane may be calculated. For interplanetary dust particles (IDPs) initially containing 10 wt% carbon, lifetimes of organics range from 3.9 years for a 0.2 m diameter particle at equatorial latitudes to 4900 years for a 200 m diameter particle at polar latitudes, and implies a median time for IDP organics by UV photolysis of 320 years at equatorial latitudes and 1500 years at polar latitudes. Assuming no redistribution of organics over the surface, the IDP organic reservoir at the surface would range from 1.1 × 10 -6 kg m -2 at equatorial latitudes to 6.6 × 10 -6 kg m -2 at polar latitudes. If accreted carbon is evenly mixed with the soil, up to 3.4 ppm of organic carbon at the VL1 landing site can be explained from a meteoritic origin and up to 4.9 ppm at the VL2 landing site. Derived from the IDP organic reservoir, small fluctuations in methane would exist due to variations in UV irradiation with latitude and L S. Production of methane is expected to range up to 0.35 pptv sol -1. © 2012. American Geophysical Union. All Rights Reserved.


Fung K.,University of Western Ontario
Laryngoscope | Year: 2015

Objectives/Hypothesis: Medical students graduate with the knowledge and skills to be undifferentiated general physicians. Otolaryngology-head and neck surgery (OtoHNS) is an essential component of primary healthcare, but is disproportionately under-represented in undergraduate medical education (UME). Advances and innovations in educational technology may represent an exciting and creative solution to this important problem. Failure to meet this educational need will result in substantial downstream effects in primary healthcare delivery. The objectives of this study were to 1) demonstrate current deficits in OtoHNS teaching at the UME level; 2) develop, validate, and critically appraise educational innovations that may enrich OtoHNS teaching in medical school curricula; and 3) propose a process for standardization of learning objectives for OtoHNS in UME as it relates to development and deployment of such educational tools. Study Design: A white paper, prepared as a Triological Society thesis, which consolidates a prospective 10-year investigation of the problem of and potential solutions for under-representation of OtoHNS in UME. Cited datasets include multicenter surveys, cohort studies, and prospective, randomized controlled trials. Methods: A series of published and unpublished data were synthesized that addresses the following: 1) the current state of OtoHNS teaching at the UME level with respect to content, volume, structure, and methods; and 2) educational innovations including e-learning and simulation with emphasis on validity and learning effectiveness. Educational innovations specific to postgraduate (residency) training were excluded. Results: Data support the observation that there is uniformly disproportionate under-representation of OtoHNS within UME curricula. Medical school graduates, especially those pursuing primary care specialties, report poor overall comfort levels in managing OtoHNS problems. A series of novel teaching methods were developed and validated using e-learning and simulation. Selected technologies may have a role in medical student teaching. It has been shown that e-learning has limited value in teaching complex spatial anatomy to novice learners, but good value in teaching basic clinical knowledge and selected technical skills. The role of simulation as it pertains to the novice learner is evolving. Important factors to consider during development of these tools include: 1) knowledge base and learning style of the learner, 2) complexity and nature of the learning objectives, 3) understanding the features and limitations of different technological genres, and 4) a team approach to module development. There remains a role for traditional teaching paradigms such as lectures, labs, and standardized patients; however, the choice of instructional genre should be fundamentally tailored to the nature of the learning outcomes. Conclusions: Enriching OtoHNS teaching in medical school is essential optimize primary care delivered to patients. Although e-learning and simulation are broadly accepted and desirable by today's medical students, these technologies should be woven into the fabric of UME pedagogical principles judiciously, and only after empiric assessment. Foundational to the development and implementation of these technologies is the framework of standardized competency-based learning objectives, common to all graduating medical students. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.


Hong H.P.,University of Western Ontario
Reliability Engineering and System Safety | Year: 2013

Fitting the extreme value distributions to samples is needed in many reliability analysis problems. The ordinary, weighted and generalized least-squares methods (OL, WL and GL method) are used to fit extreme value distributions based on the moments of order statistics and adopted plotting positions. An analyst may consider the observed ordered sample or the reduced variate as the regressand. The choice of the regressand for the least-squares methods and their corresponding relative accuracy are not always clear. Simulation results are presented in this study to rank the performance of the OL, WL and GL methods in combination with the choice of the regressands to estimate the distribution parameters, quantiles and nonexceedance probability. Analysis results for the OL method are also presented by adopting different plotting positions. The results indicate that the use of the ordered sample as the regressand is preferred. In such a case, the GL method outperforms the OL and WL methods for small sample size; the performance of the OL, WL and GL methods are similar for the sample size greater than about 20. The application of the OL method can be of value, if the adopted plotting position approximates well the mean of order statistics. © 2013 Elsevier Ltd.


Cancer viewed as a programmed, evolutionarily conserved life-form, rather than just a random series of disease-causing mutations, answers the rarely asked question of what the cancer cell is for, provides meaning for its otherwise mysterious suite of attributes, and encourages a different type of thinking about treatment. The broad but consistent spectrum of traits, well-recognized in all aggressive cancers, group naturally into three categories: taxonomy ("phylogenation"), atavism ("re-primitivization") and robustness ("adaptive resilience"). The parsimonious explanation is not convergent evolution, but the release of an highly conserved survival program, honed by the exigencies of the Pre-Cambrian, to which the cancer cell seems better adapted; and which is recreated within, and at great cost to, its host. Central to this program is the Warburg Effect, whose malign influence permeates well beyond aerobic glycolysis to include biomass interconversion and genomic heuristics. Warburg-type metabolism and genomic instability are targets whose therapeutic disablement is a major priority. © 2012 WILEY Periodicals, Inc.


Zubkov M.A.,University of Western Ontario
Annals of Physics | Year: 2015

We consider massive SU(. N) gauge theory with fermions. Gauge bosons become massive due to the interaction with the scalar field, whose vacuum average provides the spontaneous breakdown of gauge symmetry. We investigate Dyson-Schwinger equation for the fermion propagator written in ladder approximation and in Landau gauge. Our analysis demonstrates that the chiral symmetry breaking in the considered theory is the strong coupling phenomenon. There are the indications that there appears the second order phase transition between chirally broken and symmetric phases of the theory at the value of coupling constant αc=(1+γ)×π3×12C2(F), where 0. <. γ. <. 1, and γ depends on the scale, at which the fluctuations of the scalar field destroy the gauge boson mass. In the broken phase near the critical value of α the Dyson-Schwinger equation is approximated well by the gap equation of the effective Nambu-Jona-Lasinio model with the value of cutoff around gauge boson mass M and the effective four-fermion coupling constant 4παM2×2C2(F)N. The dynamical fermion mass m may be essentially smaller than M. © 2014 Elsevier Inc.


Gray D.F.,University of Western Ontario
Astronomical Journal | Year: 2010

New high-resolution spectroscopic observations of the supergiant γ Cyg (F8 Iab) taken between 2000 and 2008 consistently show strongly reversed-C-shaped bisectors for all unblended spectral lines. Small-amplitude variations in radial velocity and line shapes occur in an irregular manner with time scales ∼100 days and longer. The radial velocities occasionally show changes as large as 2 km s-1, but much smaller changes are going on continuously. Differential line bisectors show shape changes and Doppler displacement characteristic of radial expansion and contraction. These might arise from non-periodic radial pulsation-like motions or from the appearance of giant convection cells that occupy most of the visible hemisphere of the star. Line-depth ratios are correlated with the line shifts on a seasonal basis and indicate temperature changes ranging up to ∼15 K, with larger temperature occurring during times of most rapid contraction. © 2010. The American Astronomical Society. All rights reserved.


Guo F.,CAS Xishuangbanna Tropical Botanical Garden | Fang Z.,CAS Xishuangbanna Tropical Botanical Garden | Xu C.C.,University of Western Ontario | Smith Jr. R.L.,Tohoku University
Progress in Energy and Combustion Science | Year: 2012

Solid acid catalysts, which have favorable characteristics such as efficient activity, high selectivity, long catalyst life and ease in recovery and reuse, have great potential for efficiently transforming lignocellulosic biomass into biofuels and can replace many conventional liquid acids for hydrolysis and pretreatment. This work briefly introduces conventional biomass pretreatment and hydrolysis techniques, and reviews in detail the characteristics of biomass hydrolysis for five types of solid acid catalysts grouped as H-form zeolites, transition-metal oxides, cation-exchange resins, supported solid acids and heteropoly compounds. Carbonaceous solid acid (CSA) catalysts are considered as the most promising catalyst for cellulose hydrolysis, since they provide good access of reactants to the acidic sites of SO 3H groups. High glucose yields of up to 75% with 80% selectivity have been achieved at 150 °C for 24 h with CSA. However, separation of CSA from un-hydrolyzed cellulose residues after hydrolysis needs further research since these catalysts have similar physical and chemical properties to the residues. Use of functionalized CSA catalysts that contain paramagnetic groups is one method to improve CSA separation and reuse. Suggestions are given for promoting catalytic efficiency for each kind of solid acid catalysts. Methods to promote reactions or increase selectivities such as microwave, ultrasonication and nanotechnology are introduced. Finally, we highlight a recent strategy that exploits acid-functionalized paramagnetic nanoparticles suitable for cellulose hydrolysis, and address new opportunities for the use of solid acid catalysts. © 2012 Elsevier Ltd. All rights reserved.


Goodale M.A.,University of Western Ontario
Proceedings of the Royal Society B: Biological Sciences | Year: 2014

Vision not only provides us with detailed knowledge of the world beyond our bodies, but it also guides our actions with respect to objects and events in that world. The computations required for vision-for-perception are quite different from those required for vision-for-action. The former uses relational metrics and scene-based frames of reference while the latter uses absolute metrics and effector-based frames of reference. These competing demands on vision have shaped the organization of the visual pathways in the primate brain, particularly within the visual areas of the cerebral cortex. The ventral 'perceptual' stream, projecting from early visual areas to inferior temporal cortex, helps to construct the rich and detailed visual representations of the world that allow us to identify objects and events, attach meaning and significance to them and establish their causal relations. By contrast, the dorsal 'action' stream, projecting from early visual areas to the posterior parietal cortex, plays a critical role in the real-time control of action, transforming information about the location and disposition of goal objects into the coordinate frames of the effectors being used to performthe action. The idea of two visual systems in a single brain might seeminitially counterintuitive. Our visual experience of the world is so compelling that it is hard to believe that some other quite independent visual signal-one that we are unaware of-is guiding our movements. But evidence from a broad range of studies from neuropsychology to neuroimaging has shown that the visual signals that give us our experience of objects and events in the world are not the same ones that control our actions. © 2014 The Author(s) Published by the Royal Society. All rights reserved.


Goodale M.A.,University of Western Ontario
Developmental Medicine and Child Neurology | Year: 2013

The visual control of skilled goal-directed movements requires transformations of incoming visual information that are quite different from those required for visual perception. These differences in the required computations have led to the emergence of dedicated visuomotor modules in the dorsal visual stream of the cerebral cortex that are quite separate from the networks in the ventral visual stream that mediate our conscious perception of the world. Although the identification and selection of goal objects and an appropriate course of action depends on the perceptual machinery of the ventral stream and associated cognitive modules in the temporal and frontal lobes, the execution of the subsequent goal-directed action is mediated by dedicated online control systems in the dorsal stream and associated motor areas. This functional distinction can provide a useful framework for interpreting the range of perceptual and visuomotor deficits observed in children with cortical visual impairment. © 2013 Mac Keith Press.


Cristancho S.,University of Western Ontario | Moussa F.,University of Toronto | Dubrowski A.,University of Toronto
Surgery (United States) | Year: 2012

Background: Simulation-based programs allow trainees to be progressively challenged in a systematic, learner-centered and patient-focused fashion. The design of these programs requires an understanding of the individual steps that comprise the entire surgical procedure and our ability to assess the progress of the learner. We present the results of the design and validation of performance assessment checklists for a progressive simulation-based program in cardiac surgery. Methodology: Using a case study design, we videotaped 10 off-pump coronary artery bypass procedures and applied a new methodological framework to deconstruct the procedure into teachable components for which 6 simulation scenarios were developed. Individual checklists were designed and validated using the Delphi technique. An expert panel of 11 cardiac surgeons rated each checklist item by using a 5-point Likert-type scale and provided comments on the rating choice. The consistency of the experts' ratings were interpreted as consensus achieved when 70% of experts rated 3.5 or greater on the 5-point Likert-type scale for each assessment item. Results: An in vivo workflow diagram was developed, and 6 simulation modules with progressive difficulty were selected to design an off-pump coronary artery bypass simulation-based program. The corresponding 6 assessment checklists were designed and validated. After 2 Delphi rounds, the overall average score across all checklists was 4.0, and all items were greater 3.5. The final checklists comprise between 12 and 23 items. Conclusion: We have demonstrated the feasibility of designing simulation-based program for complex operative procedures in a progressive fashion. The complexity at each level was given by the predefined training objectives and assessment checklists were designed and validated as content-specific assessment tools for each simulation scenario. © 2012 Mosby, Inc. All rights reserved.


Rotondi M.A.,York University | Donner A.,University of Western Ontario
Journal of Clinical Epidemiology | Year: 2012

Objective: Studies measuring interobserver agreement (reliability) are common in clinical practice, yet discussion of appropriate sample size estimation techniques is minimal as compared with clinical trials. The authors propose a sample size estimation technique to achieve a prespecified lower and upper limit for a confidence interval for the κ coefficient in studies of interobserver agreement. Study Design and Setting: The proposed technique can be used to design a study measuring interobserver agreement with any number of outcomes and any number of raters. Potential application areas include: pathology, psychiatry, dentistry, and physical therapy. Results: This technique is illustrated using two examples. The first considers a pilot study in oral radiology, whose authors studied the reliability of the mandibular cortical index as measured by three dental professionals. The second example examines the level of interobserver agreement among four nurses with respect to five triage levels used in the Canadian Triage and Acuity Scale. Conclusion: This method should be useful in the planning stages of an interobserver agreement study in which the investigator would like to obtain a prespecified level of precision in the estimation of κ. An R software package (R Foundation for Statistical Computing, Vienna, Austria), kappaSize is also provided that implements this method. © 2012 Elsevier Inc. All rights reserved.


Moehring A.J.,University of Western Ontario
Evolution | Year: 2011

In general, heterozygosity is considered to be advantageous, primarily because it masks the effects of deleterious recessive alleles. However, there is usually a reduction in fitness in individuals that are heterozygous due to the pairing of two species (heterospecific). Because the parental alleles arose along separate evolutionary paths, they may not function properly when brought together within an individual. The formation of these unfit interspecies hybrids is one of the mechanisms that maintains species isolation. Interestingly, it has been observed that later-generation individuals resulting from a backcross to one parent are more often sterile than those resulting from a backcross to the other parent, but the mechanism underlying this trend is unknown. Here, I show that one direction of backcross produces offspring with more heterospecific genome, and that this is correlated with the directionality seen in backcross hybrid sterility. Therefore, the directionality in sterility is likely due to the different amounts of heterospecific genome present in the two backcrosses. Surprisingly, in spite of the potential fitness consequences, I also find that interspecies laboratory backcrosses in general yield an excess of heterospecific individuals, and that this trend is consistent across multiple taxa. © 2011 The Author(s). Evolution © 2011 The Society for the Study of Evolution.


Leask A.,University of Western Ontario
Open Rheumatology Journal | Year: 2012

There is no treatment for the fibrosis observed in scleroderma (systemic sclerosis, SSc). Although genomewide expression profiling has suggested that differences in gene expression patters between non-lesional and lesional skin are minimal, phenotypically these areas of tissue are quite different. In fact, lesional areas of scleroderma patients can be distinguished by the presence of a differentiated form of fibroblast, termed the myofibroblast. This cell type expresses the highly contractile protein α-smooth muscle actin (α-SMA). Fibroblasts isolated from SSc lesions excessively synthesize, adhere to and contract extracellular matrix (ECM) and display activated adhesive signaling pathways. Strategies aimed at blocking myofibroblast differentiation, persistence and activity are therefore likely to be useful in alleviating the fibrosis in scleroderma. © Andrew Leask; Licensee Bentham Open.


Fosang A.J.,University of Melbourne | Beier F.,University of Western Ontario
Best Practice and Research: Clinical Rheumatology | Year: 2011

Articular cartilage is a uniquely ordered tissue that is designed to resist compression and redistribute load, but is poorly equipped for self-repair. The chondrocyte is the only resident cell type, responsible for maintaining a specialised and extensive matrix that is avascular and lacks innervation. These attributes, as well as the slow turnover rate of aggrecan and type II collagen in mature articular cartilage, present a considerable challenge to the tissue engineer. Similarly, those attempting to halt the progression of cartilage erosion must contend with these unusual characteristics. This review explores the gaps in our knowledge of cartilage biology and pathology, including what is known about the relative contribution of collagenases and aggrecanases to cartilage degradation, the need to regulate the chondrocytic phenotype and the putative role of chondrocyte hypertrophy in the pathogenesis of degenerative and rheumatic joint disease. Recent advances in cartilage tissue engineering are also reviewed. © 2011 Elsevier Ltd. All rights reserved.


Chandok N.,University of Western Ontario
Annals of Hepatology | Year: 2012

Polycystic liver disease rarely occurs in isolation as part of autosomal dominant polycystic liver disease, but more commonly, it exists as an extra-renal manifestation of autosomal dominant polycystic kidney di-sease. The pathogenesis of polycystic liver disease involves defects in the primary cilium of the cholangio-cyte, with genetic mutations that impair key proteins integral to the complex functioning of cilia. While most patients are asymptomatic and require no intervention aside from reassurance and genetic counse-ling, in a minority of patients, polycystic liver disease creates a myriad of symptoms from the compressive effects of enlarged cysts, and can even cause malnutrition and liver decompensation in the severest of ca-ses. In patients with symptomatic disease, a variety of interventional radiology or surgical techniques can be considered, including aspiration with sclerotherapy of a dominant cyst, fenestration, segmental hepatic resection, and even liver transplantation. Although there are no curative medical options for polycystic li-ver disease, somatostatin analogs hold promise and have shown minimal efficacy in human studies. Howe-ver, further research is needed to develop more efficacious medical treatments.


Geballe M.T.,OpenEye Scientific Software | Guthrie J.P.,University of Western Ontario
Journal of Computer-Aided Molecular Design | Year: 2012

Prediction of the free energy of solvation of a small molecule, or its transfer energy, is a necessary step along the path towards calculating the interactions between molecules that occur in an aqueous environment. A set of these transfer energies were gathered from the literature for series of chlorinated molecules with varying numbers of chlorines based on ethane, biphenyl, and dibenzo-p-dioxin. This focused set of molecules were then provided as a blinded challenge to assess the ability of current computational solvation methods to accurately model the interactions between water and increasingly chlorinated compounds. This was presented as part of the SAMPL3 challenge, which represented the fourth iterative blind prediction challenge involving transfer energies. The results of this exercise demonstrate that the field in general has difficulty predicting the transfer energies of more highly chlorinated compounds, and that methods seem to be erring in the same direction. © Springer Science+Business Media B.V. 2012.


Cadotte D.W.,University of Toronto | Fehlings M.G.,University of Toronto | Fehlings M.G.,University of Western Ontario
Clinical Orthopaedics and Related Research | Year: 2011

Background: Spinal cord injury (SCI) is a devastating event often resulting in permanent neurologic deficit. Research has revealed an understanding of mechanisms that occur after the primary injury and contribute to functional loss. By targeting these secondary mechanisms of injury, clinicians may be able to offer improved recovery after SCI. Questions/purposes: In this review, we highlight advances in the field of SCI by framing three questions: (1) What is the preclinical evidence for the neuroprotective agent riluzole that has allowed this agent to move into clinical trials? (2) What is the preclinical evidence for Rho antagonists that have allowed this group of compounds to move into clinical trials? (3) What is the evidence for early surgical decompression after SCI? Methods: We conducted a systematic review of MEDLINE and EMBASE-cited articles related to SCI to address these questions. Results: As a result of an improved understanding of the secondary mechanisms of SCI, specific clinical strategies have been established. We highlight three strategies that have made their way from bench to bedside: the sodiumglutamate antagonist riluzole, the Rho inhibitor Cethrin, and early surgical decompression. Each of these modalities is under clinical investigation. We highlight the fundamental science that led to this development. Conclusions: As our understanding of the fundamental mechanisms of SCI improves, we must keep abreast of these discoveries to translate them into therapies that will hopefully benefit patients. We summarize this process of bench to bedside with regard to SCI. © The Association of Bone and Joint Surgeons® 2010.


Speechley M.,University of Western Ontario
Canadian Journal on Aging | Year: 2011

PubMed lists over 6,000 references (700 reviews) on unintentional falls in older adults. This article traces key methodological milestones in the application of epidemiologic methods since the earliest publications in the late 1940s. Within the context of advances in case definition, sampling, measurement, research design, and statistical analysis, the article reviews estimates of frequency of occurrence, risk factor associations, morbidity and mortality consequences, demonstration of the multiple risk factor theory of falls using fall prevention interventions, and the challenges of fall risk prediction models. Methodological explanations are provided for observed heterogeneities, and the case is presented for moving beyond undifferentiated lists of risk factors by focusing on balance and gait as the factors through which the mechanistic effects of distal risk factors can be understood. Moreover, the case is made to advance our statistical analyses by looking at interactions among intrinsic risk factors and between intrinsic, extrinsic, and environmental factors. Copyright © 2011 Canadian Association on Gerontology.


Lingard L.,University of Western Ontario
Medical Education | Year: 2013

Objectives This paper considers the state of the science regarding language matters in medical education, with particular attention to two informal language practices: silence and humour. Silence and humour pervade clinical training settings, although we rarely attend explicitly to them. Methods This paper considers the treatment of these topics in our field to date and introduces a selection of the scholarship on silence and humour from other fields, including philosophy, sociology, anthropology, linguistics and rhetoric. Particular attention is paid to distilling the theoretical and methodological possibilities for an elaborated research agenda around silence and humour in medical education. Results These two language practices assume a variety of forms and serve a range of social functions. Episodes of silence and humour are intimately tied to their relational and institutional contexts. Power often figures centrally, although not predictably. Conclusions A rich theoretical and methodological basis exists on which to elaborate a research agenda around silence and humour in medical education. Such research promises to reveal more fully the contributions of silence and humour to socialisation in clinical training settings. © 2013 Blackwell Publishing Ltd.


Biggar K.K.,University of Western Ontario | Storey K.B.,Carleton University
Journal of Experimental Biology | Year: 2015

Living animals are constantly faced with various environmental stresses that challenge normal life, including: oxygen limitation, very low or high temperature, as well as restriction of water and food. It has been well established that in response to these stresses, tolerant organisms regularly respond with a distinct suite of cellular modifications that involve transcriptional, translational and posttranslational modification. In recent years, a new mechanism of rapid and reversible transcriptome regulation, via the action of noncoding RNA molecules, has emerged into post-transcriptional regulation and has since been shown to be part of the survival response. However, these RNA-based mechanisms by which tolerant organisms respond to stressed conditions are not well understood. Recent studies have begun to show that non-coding RNAs control gene expression and translation of mRNA to protein, and can also have regulatory influence over major cellular processes. For example, select microRNAs have been shown to have regulatory influence over the cell cycle, apoptosis, signal transduction, muscle atrophy and fatty acid metabolism during periods of environmental stress. As we are on the verge of dissecting the roles of non-coding RNA in environmental stress adaptation, this Commentary summarizes the hallmark alterations in microRNA expression that facilitate stress survival. © 2015. Published by The Company of Biologists Ltd.


Brotchie J.,University of Western Ontario | Jenner P.,Kings College London
International Review of Neurobiology | Year: 2011

L-DOPA-induced dyskinesia (LID) is a major complication of the treatment of Parkinson's disease (PD). LID comprises two major components, the priming process responsible for its onset and the expression of involuntary movements that underlies its clinical manifestation. The mechanisms responsible for these components are partially understood and their biochemical basis is being unraveled but avoidance and treatment remain an issue. In this chapter, we review what is known about the involvement of dopaminergic systems in LID and the way in which dopaminergic therapy can be used to avoid the onset of LID or to reverse or suppress involuntary movements once these have been established. The involvement of specific dopamine receptor subtypes, continuous dopaminergic stimulation (CDS) and continuous drug delivery (CDD) is reviewed. However, a major role is emerging in the avoidance and suppression of LID through the use of nondopaminergic mechanisms and we consider the present and future use of glutamatergic drugs, serotoninergic agents, adenosine antagonists and others as a means of improving therapy. There is compelling basic science supporting a role for nondopaminergic approaches to LID but at the moment the translational benefit to PD is not being achieved as predicted. There needs to be further consideration of why this is the case and how in future, both experimental models of dyskinesia and clinical trial design can be optimized to ensure success. © 2011 Elsevier Inc.


Paulson W.D.,University of Georgia | Moist L.,University of Western Ontario | Lok C.E.,Toronto General Hospital
Kidney International | Year: 2012

Hemodialysis vascular access surveillance continues to be widely recommended despite ongoing controversy as to its benefit in prolonging access patency compared with clinical monitoring alone. The most common screening tests are access blood flow and dialysis venous pressure measurements. When surveillance test results cross a predetermined threshold, accesses are referred for intervention with correction of stenosis to reduce future thrombosis and prolong access survival. Current surveillance strategies have four components: (1) underlying condition; (2) screening test; (3) intervention; and (4) outcomes. However, limitations exist within each component that may prevent achieving the desired outcomes. This review discusses these limitations and their consequences. To date, randomized controlled trials have not consistently shown that surveillance improves outcomes in grafts, and there is limited evidence that surveillance reduces thrombosis without prolonging the life of native fistulae. In conclusion, current evidence does not support the concept that all accesses should undergo routine surveillance with intervention. © 2012 International Society of Nephrology.


Elueze I.N.,University of Western Ontario
Health Information and Libraries Journal | Year: 2015

Objective: The aim of this study was to identify the effectiveness of knowledge brokering as a knowledge translation (KT) strategy used in promoting evidence-based decision-making, evidence-based practice or collaboration between researchers, health practitioners and policymakers. Methods: A systematised review of literature was performed using MEDLINE (through ProQuest® Dialog), PubMed and Scopus electronic databases. A search strategy was developed to identify primary studies indexed in these databases on knowledge translation that reported the implementation of knowledge brokering. Sixty-two titles related to knowledge brokering were identified from the search after the removal of duplicates, and 24 articles met the eligibility criteria following the review of the full text documents. The findings were then synthesised using a narrative approach. Results: It was found that knowledge brokering has been an effective strategy for knowledge translation. Conclusion: Although this review shows that knowledge brokering has been an effective strategy for KT, it advocates for more empirical studies to compare the effectiveness of specific knowledge brokering approaches with others. It also calls for empirical studies to explicate the role of library and information science professionals in knowledge brokering. © 2015 Health Libraries Group.


House A.A.,University of Western Ontario | House A.A.,London Health Sciences Center
Seminars in Nephrology | Year: 2012

Cardiovascular diseases such as coronary artery disease, congestive heart failure, arrhythmia, and sudden cardiac death represent the leading causes of morbidity and mortality in patients with CKD, increasing sharply as patients approach end-stage renal disease. The pathogenesis includes a complex, bidirectional interaction between the heart and kidneys that encompasses traditional and nontraditional risk factors, and has been termed cardio-renal syndrome type 4. In this review, an overview of the epidemiology and scope of this problem is provided, some suggested mechanisms for the pathophysiology of this disorder are discussed, and some of the key treatment strategies are described, with particular focus on recent clinical trials, both negative and positive. © 2012 Elsevier Inc.


Greason W.D.,University of Western Ontario
Journal of Electrostatics | Year: 2010

The effect of charge injection due to CDM ESD in capacitive MEMS structures is analyzed. The results show that as feature size is reduced, ESD injected charge produces a change for the stiction effect which is inversely proportional to the square of the plate area and a change in the dielectric layer breakdown which is inversely proportional to the plate area. An electric field model is developed to examine charge and voltage modes in MEMS. A charge injection test method is proposed to determine the susceptibility of MEMS to CDM ESD. © 2010 Elsevier B.V. All rights reserved.


Owen A.M.,University of Western Ontario
Handbook of Clinical Neurology | Year: 2015

In recent years, rapid technological developments in the field of neuroimaging have provided new methods for revealing thoughts, actions, and intentions based solely on the pattern of activity that is observed in the brain. In specialized centres, these methods are now being employed routinely in the assessment of patients diagnosed with so-called "disorders of consciousness," mapping patterns of residual function and dysfunction and helping to reduce diagnostic errors between related conditions such as the vegetative and minimally conscious states. Both functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) have now been shown to be effective tools for detecting covert awareness in behaviorally nonresponsive patients when standard clinical approaches have been unable to provide that information. Indeed, in some patients, communication with the outside world via simple "yes" and "no" questions has been achieved, even in cases where no possibility for behavioral interaction exists. These studies have profound implications for clinical care, diagnosis, prognosis and medical-legal decision making relating to the prolongation, or otherwise, of life after severe brain injury. Moreover, the results suggest an urgent need for a re-evaluation of the existing diagnostic guidelines for behaviorally nonresponsive patients to include information derived from functional neuroimaging. © 2015 Elsevier B.V.


Hicks D.J.,University of Western Ontario
Studies in History and Philosophy of Science Part C :Studies in History and Philosophy of Biological and Biomedical Sciences | Year: 2015

This paper examines the scientific controversy over the yields of genetically modified [GM] crops as a case study in epistemologically deep disagreements. Appeals to "the evidence" are inadequate to resolve such disagreements; not because the interlocutors have radically different metaphysical views (as in cases of incommensurability), but instead because they assume rival epistemological frameworks and so have incompatible views about what kinds of research methods and claims count as evidence. Specifically, I show that, in the yield debate, proponents and opponents of GM crops cite two different sets of claims as evidence, which correspond to two rival epistemological frameworks, classical experimental epistemology and Nancy Cartwright's evidence for use. I go on to argue that, even if both sides of the debate accepted Cartwright's view, they might still disagree over what counts as evidence, because evidence for use ties standards of evidence to what is sometimes called the "context of application. © 2015 Elsevier Ltd.


Bainbridge D.,London Health Sciences Center | Martin J.,University of Western Ontario | Arango M.,London Health Sciences Center | Cheng D.,London Health Sciences Center
The Lancet | Year: 2012

Background The magnitude of risk of death related to surgery and anaesthesia is not well understood. We aimed to assess whether the risk of perioperative and anaesthetic-related mortality has decreased over the past five decades and whether rates of decline have been comparable in developed and developing countries. Methods We did a systematic review to identify all studies published up to February, 2011, in any language, with a sample size of over 3000 that reported perioperative mortality across a mixed surgical population who had undergone general anaesthesia. Using standard forms, two authors independently identified studies for inclusion and extracted information on rates of anaesthetic-related mortality, perioperative mortality, cardiac arrest, American Society of Anesthesiologists (ASA) physical status, geographic location, human development index (HDI), and year. The primary outcome was anaesthetic sole mortality. Secondary outcomes were anaesthetic contributory mortality, total perioperative mortality, and cardiac arrest. Meta-regression was done to ascertain weighted event rates for the outcomes. Findings 87 studies met the inclusion criteria, within which there were more than 21 4 million anaesthetic administrations given to patients undergoing general anaesthesia for surgery. Mortality solely attributable to anaesthesia declined over time, from 357 per million (95% CI 324-394) before the 1970s to 52 per million (42-64) in the 1970s-80s, and 34 per million (29-39) in the 1990s-2000s (p<0 00001). Total perioperative mortality decreased over time, from 10 603 per million (95% CI 10 423-10 784) before the 1970s, to 4533 per million (4405-4664) in the 1970s-80s, and 1176 per million (1148-1205) in the 1990s-2000s (p<0 · 0001). Meta-regression showed a significant relation between risk of perioperative and anaesthetic-related mortality and HDI (all p<0 · 00001). Baseline risk status of patients who presented for surgery as shown by the ASA score increased over the decades (p<0 · 0001). Interpretation Despite increasing patient baseline risk, perioperative mortality has declined significantly over the past 50 years, with the greatest decline in developed countries. Global priority should be given to reducing total perioperative and anaesthetic-related mortality by evidence-based best practice in developing countries.


Atkinson G.,University of Western Ontario
Seismological Research Letters | Year: 2013

Horizontal-component response spectra data for ground motions recorded on hard-rock sites in eastern North America (ENA) are used to explore the aleatory and epistemic uncertainty in ground-motion prediction equations (GMPEs). An all-station sigma, expressing the total calculated scatter of values about a GMPE, ranges from 0.25 to 0:29 log10 unit. Single-station sigmas, in which the scatter is evaluated station by station relative to a regional GMPE, average in the range of 0.23-0.28. The scatter of observations about site-specific GMPEs (GMPEs developed from multiple events recorded at a single station), which comes the closest to measuring the actual aleatory variability, has average values of 0.22-0.26. Overall, aleatory variability of ground motions in ENA is no larger than that for California, at least for moderate events recorded on hard-rock sites. Epistemic uncertainty is considered by looking at the standard deviation of GMPEs developed separately for each station (i.e., the scatter of predictions rather than the scatter of observations). This exercise suggests that the overall epistemic uncertainty in ENA GMPEs should be at least 0.15 log unit (as a standard deviation of the median GMPEs) in the magnitude-distance range in which the prediction equations can be anchored by empirical data (magnitude <5:5, distances >50 km). It should be larger than 0.15 unit at large magnitudes and close distances.


Vorobyov E.I.,Saint Marys University, Halifax | Vorobyov E.I.,Southern Federal University | Basu S.,University of Western Ontario
Astrophysical Journal Letters | Year: 2010

Motivated by the recent discovery of massive planets on wide orbits, we present a mechanism for the formation of such planets via disk fragmentation in the embedded phase of star formation. In this phase, the forming disk intensively accretes matter from the natal cloud core and undergoes several fragmentation episodes. However, most fragments are either destroyed or driven into the innermost regions (and probably onto the star) due to angular momentum exchange with spiral arms, leading to multiple FU-Ori-like bursts and disk expansion. Fragments that are sufficiently massive and form in the late embedded phase (when the disk conditions are less extreme) may open a gap and evolve into giant planets on typical orbits of several tens to several hundreds of AU. For this mechanism to work, the natal cloud core must have sufficient mass and angular momentum to trigger the burst mode and also form extended disks of the order of several hundreds of AU. When mass loading from the natal cloud core diminishes and the main fragmentation phase ends, such extended disks undergo a transient episode of contraction and density increase, during which they may give birth to a last and survivable set of giant planets on wide and relatively stable orbits. © 2010 The American Astronomical Society.


Tuttle M.P.,M. Tuttle and Associates | Atkinson G.M.,University of Western Ontario
Seismological Research Letters | Year: 2010

Earthquake-induced liquefaction features have been found in Holocene and Late Wisconsin sediments exposed along three rivers in the Charlevoix seismic zone. On the basis of their stratigraphic position and radiocarbon age constraints, the liquefaction features are thought to have formed during three or more earthquake episodes centered in Charlevoix during the past 10,000 years, including at least two prehistoric episodes approximately 5,000 and 10,000 years ago. The spatial distribution of liquefaction features coupled with liquefaction potential analysis suggests that the Charlevoix earthquakes were of moment magnitude (M) ≥ 6.2. Liquefaction features have not been found in similar sediments exposed along eight rivers in the Quebec City-Trois Rivieres area, 70 to 150 km from Charlevoix in the St. Lawrence River Valley. The apparent absence of liquefaction features in the Quebec City-Trois Rivieres area suggests that few, if any, large earthquakes have occurred here during the same time period. The geologic record of earthquakes may be incomplete in both areas due to fluctuations in Holocene sea level. Nevertheless, the rate of large earthquakes has apparently been much higher in the Charlevoix seismic zone than in adjacent areas of the St. Lawrence for thousands of years. These findings suggest that seismicity is localized in Charlevoix and that the presence of Iapetan rift faults that underlie the St. Lawrence Valley of southeastern Canada may not, in itself, indicate earthquake potential. These results may have important implications for other Iapetan rift faults in the eastern United States, as well as seismic source zone characterization and hazard assessment throughout eastern North America.


Cechetto D.F.,University of Western Ontario
Experimental Physiology | Year: 2014

New Findings: What is the topic of this review? The pathways in the brain by which visceral information, in particular cardiopulmonary afferents, ascend to the cerebral cortex have been delineated in animal models. Studies using functional magnetic resonance imaging in humans have confirmed what was known from the animal studies and established the critical sites in the cerebral cortex of humans for autonomic control and the significance of these sites for cognitive emotional function. What advances does it highlight? Stimulation of cardiopulmonary afferents in humans has consistently resulted in activation in the insular cortex and the anterior cingulate cortex. It has been shown that individuals who are characterized as cardiovascular responders to mental stress have a different pattern of activity in the cortex related to the cardiac changes. A number of animal studies in the rat and cat have been particularly useful for determining the pathways and the sites in the forebrain and cortex that are responsible for autonomic control. For example, these experiments have demonstrated that there is a viscerotopically organized pathway, with the first site of termination in the nucleus of the solitary tract and with subsequent relays in the parabrachial nucleus and the ventroposterior parvocellular nucleus of the thalamus before final visceral afferent inputs in the insular cortex. Several neuroimaging studies in humans, using cardiopulmonary manipulations, have confirmed the importance of the insular cortex as a site of for visceral afferent inputs. The anterior cingulate cortex has also been implicated in cardiopulmonary control. Both the insular cortex and the infralimbic cortex have been shown to be involved in descending control of the cardiovascular system. Neuroimaging with functional magnetic resonance imaging has demonstrated that the cortical autonomic control pathways are different in individuals who are characterized as cardiovascular reactors to mental stress. There is evidence that this alteration in pathways in the cortex may be due to past experiences, including childhood trauma. © 2013 The Author. Experimental Physiology © 2013 The Physiological Society.


Charland L.C.,University of Western Ontario
Current Opinion in Psychiatry | Year: 2013

Purpose of review: This review considers the literature on ethical and conceptual issues in eating disorders from the last 18 months. Some reference to earlier work is necessary in order to provide context for the recent findings from research that is ongoing. Recent findings: Empirical ethics research on anorexia nervosa includes novel ethical and conceptual findings on the role of authenticity and personal identity in individuals' reports of their experience, as well as new evidence on the role of affective states and values in decision making at later stages of the illness. Evidence points to the hypothesis that anorexia nervosa may be a distinct affective syndrome that organizes feelings and emotions in accordance with a fixed idea. Summary: There has been impressive progress in empirical ethics research on anorexia nervosa, with important implications for ethical and conceptual issues that surround decision-making capacity and our understanding of the illness. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Nalamachu S.,International Clinical Research Institute Inc. | Morley-Forster P.,University of Western Ontario
Drugs and Aging | Year: 2012

Postherpetic neuralgia (PHN) represents a potentially debilitating and often undertreated form of neuropathic pain that disproportionately affects vulnerable populations, including the elderly and the immunocompromised. Varicella zoster infection is almost universally prevalent, making prevention of acute herpes zoster (AHZ) infection and prompt diagnosis and aggressive management of PHN of critical importance. Despite the recent development of a herpes zoster vaccine, prevention of AHZ is not yet widespread or discussed in PHN treatment guidelines. Diagnosis of PHN requires consideration of recognized PHN signs and known risk factors, including advanced age, severe prodromal pain, severe rash, and AHZ location on the trigeminal dermatomes or brachial plexus. PHN pain is typically localized, unilateral and chronic, but may be constant, intermittent, spontaneous and/or evoked. PHN is likely to interfere with sleep and daily activities. First-line therapies for PHN include tricyclic antidepressants, gabapentin and pregabalin, and the lidocaine 5 % patch. Second-line therapies include strong and weak opioids and topical capsaicin cream or 8 % patch. Tricyclic antidepressants, gabapentinoids and strong opioids are effective but are also associated with systemic adverse events that may limit their use in many patients, most notably those with significant medical comorbidities or advanced age. Of the topical therapies, the topical lidocaine 5 % patch has proven more effective than capsaicin cream or 8 % patch and has a more rapid onset of action than the other first-line therapies or capsaicin. Given the low systemic drug exposure, adverse events with topical therapies are generally limited to application-site reactions, which are typically mild and transient with lidocaine 5 % patch, but may involve treatment-limiting discomfort with capsaicin cream or 8 % patch. Based on available clinical data, clinicians should consider administering the herpes zoster vaccine to all patients aged 60 years and older. Clinicians treating patients with PHN may consider a trial of lidocaine 5 % patch monotherapy before resorting to a systemic therapy, or alternatively, may consider administering the lidocaine 5 % patch in combination with a tricyclic antidepressant or a gabapentinoid to provide more rapid analgesic response and lower the dose requirement of systemic therapies. © 2012 The Author(s).


Grahn J.A.,University of Western Ontario
Topics in Cognitive Science | Year: 2012

Perception of temporal patterns is fundamental to normal hearing, speech, motor control, and music. Certain types of pattern understanding are unique to humans, such as musical rhythm. Although human responses to musical rhythm are universal, there is much we do not understand about how rhythm is processed in the brain. Here, I consider findings from research into basic timing mechanisms and models through to the neuroscience of rhythm and meter. A network of neural areas, including motor regions, is regularly implicated in basic timing as well as processing of musical rhythm. However, fractionating the specific roles of individual areas in this network has remained a challenge. Distinctions in activity patterns appear between "automatic" and "cognitively controlled" timing processes, but the perception of musical rhythm requires features of both automatic and controlled processes. In addition, many experimental manipulations rely on participants directing their attention toward or away from certain stimulus features, and measuring corresponding differences in neural activity. Many temporal features, however, are implicitly processed whether attended to or not, making it difficult to create controlled baseline conditions for experimental comparisons. The variety of stimuli, paradigms, and definitions can further complicate comparisons across domains or methodologies. Despite these challenges, the high level of interest and multitude of methodological approaches from different cognitive domains (including music, language, and motor learning) have yielded new insights and hold promise for future progress. © 2012 Cognitive Science Society, Inc.


Ho Y.Y.,McGill University | Lagares D.,Harvard University | Tager A.M.,Harvard University | Kapoor M.,University of Western Ontario
Nature Reviews Rheumatology | Year: 2014

Fibrosis is a pathological process characterized by excessive accumulation of connective tissue components in an organ or tissue. Fibrosis is produced by deregulated wound healing in response to chronic tissue injury or chronic inflammation, the hallmarks of rheumatic diseases. Progressive fibrosis, which distorts tissue architecture and results in progressive loss of organ function, is now recognized to be one of the major causes of morbidity and mortality in individuals with one of the most lethal rheumatic disease, systemic sclerosis (SSc). In this Review, we discuss the pathological role of fibrosis in SSc. We discuss the involvement of endothelium and pericyte activation, aberrant immune responses, endoplasmic reticulum stress and chronic tissue injury in the initiation of fibrosis in SSc. We then discuss fibroblast activation and myofibroblast differentiation that occurs in response to these initiating processes and is responsible for excessive accumulation of extracellular matrix. Finally, we discuss the chemical and mechanical signals that drive fibroblast activation and myofibroblast differentiation, which could serve as targets for new therapies for fibrosis in SSc. © 2014 Macmillan Publishers Limited.


Harris D.,University of Western Ontario
Omega: Journal of Death and Dying | Year: 2010

Bereaved individuals often experience profound social pressure to conform to societal norms that constrict the experience of grief rather than support it. This article explores grief in Western society1 through an analysis of the underlying structures and values that are a part of this social system, utilizing the lens of critical theory. Critical theory examines social norms and conditions in order to identify and expose oppression in various contexts. This article examines the social rules that govern the expression of grief, the role of attachment, social pain, and shame as potent forces that promote compliance with social rules, and the ways that the underlying assumptions and values in Western society shape how bereaved individuals are expected to react. Implications for clinicians who work with terminally ill or bereaved individuals are then reviewed.


Leask A.,University of Western Ontario
Journal of Cell Communication and Signaling | Year: 2011

Osteoarthritis (OA), or degenerative arthritis, is characterized by mechanical stress-induced changes in cartilage and bone. OA is a leading cause of chronic disability in North America and Europe. A recent study written by Blom and colleagues (Arthritis and Rheumatism 2009; 60:501-12) showed that elevated wnt signaling was observed in experimental OA as well as in patient samples. The authors found that the known wnt target WISP-1 (CCN4) was also overexpressed; CCN4 was sufficient to recapitulate an OA phenotype in vitro and in vivo, suggesting that CCN4 may be a novel target for drug intervention in OA. This commentary summarizes these exciting findings. © 2010 The International CCN Society.


Van Tasell D.J.,IntriCon | Folkeard P.,University of Western Ontario
Otology and Neurotology | Year: 2013

OBJECTIVE: To evaluate the reliability and accuracy of a method for measuring pure tone air conduction thresholds in which the user adjusts test tones to threshold, using an iPad, automated instructions, and minimal supervision. STUDY DESIGN: Prospective nonrandomized validation study. SETTING: University hearing research laboratories and audiology clinics. PATIENTS: Fifty-five adults with hearing loss in at least 1 ear ranging from mild to severe. INTERVENTION: Automated measurement of pure tone air conduction thresholds using the following: a software-controlled adaptive method, and a user-controlled method of adjustment, both implemented on a calibrated iPad and using standard audiometry earphones. MAIN OUTCOME MEASURE: Test-retest reliability of both methods, comparison of thresholds measured with automated techniques to thresholds measured using manual audiometry. RESULTS: For both iPad methods, test-retest differences were smaller than those reported in other studies for manual audiometry. Average automated versus manual threshold differences were within the range of expected variance of manual audiometry. Subjects preferred the adjustment method. CONCLUSION: Both iPad self-test methods yield accurate and reliable pure tone air conduction thresholds. Copyright © 2012 Otology &Neurotology, Inc.


Pyatkovskiy P.K.,University of Western Ontario
Physical Review B - Condensed Matter and Materials Physics | Year: 2013

Edge states in biased bilayer graphene in a magnetic field are studied within the four-band continuum model. The analysis is done for the semi-infinite graphene plane and for the graphene ribbon of a finite width, in the cases of zigzag and armchair edges. Exact dispersion equations for the edge states and analytic expressions for their wave functions are written in terms of the parabolic cylinder functions. The spectrum of edge states for each type of the boundary conditions is found by numerically solving the corresponding dispersion equations. The low-energy modes localized at zigzag edges are explored in detail. © 2013 American Physical Society.


Hemsworth J.C.,University of Western Ontario
Gut microbes | Year: 2012

The Human Immunodeficiency Virus has devastating effects worldwide. The burden is less pronounced, but still present in Canada where approximately 64,000 men and women are HIV positive. The virus and the life-saving antiretroviral therapies often contribute to diarrhea and other gastrointestinal disturbances. Certain probiotic organisms, such as Lactobacillus rhamnosus GR-1, have been shown to alleviate diarrhea as well as delay the decline of CD4 lymphocytes in some subjects. In addition, micronutrient formulae have been used extensively among HIV positive persons as a cost-effective method for improving quality of life and immune function. The objective of the present study was to combine probiotics and micronutrients into an affordable and highly palatable nutritional supplement and assess outcomes in 21 HIV-positive participants receiving highly active antiretroviral therapy in London, Ontario, Canada. The design was a randomized, double blind, three-period, cross-over controlled trial with three different formulations of supplemented yogurt; micronutrient and probiotic (A), micronutrient alone (B) and probiotic alone (C). The period of intake for each of the types was 30 days with a 14 day wash-out period between the intervention types. The mean increase in CD4 was greatest with B (41 cells/μL, SD 221). Supplement A showed a mean change of +19 cells/μL (SD 142) and supplement C a mean change of - 7 cells/μL (SD 154). All yogurt types caused an increase in subjective energy and ability to perform daily activity scores. According to the safety measures taken to assess the tolerance of the yogurt, there were no adverse events and the yogurt was well-tolerated. These preliminary findings suggest that micronutrient supplemented probiotic yogurt may support immune function among people living with HIV.


Koren G.,University of Western Ontario
Journal of Population Therapeutics and Clinical Pharmacology | Year: 2011

In pharmacokinetics drug absorption, distribution, clearance, and bioequivalence are usually considered, but during pregnancy the most important variable is adherence or compliance. Pharmacokinetic changes during pregnancy that may lead to changes in maternal drug use are described through presentation of cases highlighting the relevance of these changes. Non-invasive methods of pharmacokinetic analysis, such as determining concentrations of drug in hair, are now being tested and used. Pharmacokinetics are important, but one needs to consider the entire pregnant state and its circumstances when treating women. One treats people, not a "volume of distribution" or a drug level. Therapy should be individualized as much as possible, addressing kinetic changes in the context of dynamic alterations and the effects of underlying medical conditions. To ensure that women are not orphaned from advances in drug therapy, much more research is needed into the determinants of pharmacokinetic and pharmacodynamic changes in pregnancy. © 2011 Canadian Society of Pharmacology and Therapeutics.


Davies E.G.R.,University of Alberta | Simonovic S.P.,University of Western Ontario
Advances in Water Resources | Year: 2011

Awareness of increasing water scarcity has driven efforts to model global water resources for improved insight into water resources infrastructure and management strategies. Most water resources models focus explicitly on water systems and represent socio-economic and environmental change as external drivers. In contrast, the system dynamics-based integrated assessment model employed here, ANEMI, incorporates dynamic representations of these systems, so that their broader changes affect and are affected by water resources systems through feedbacks. Sectors in ANEMI therefore include the global climate system, carbon cycle, economy, population, land use and agriculture, and novel versions of the hydrological cycle, global water use and water quality. Since the model focus is on their interconnections through explicit nonlinear feedbacks, simulations with ANEMI provide insight into the nature and structure of connections between water resources and socio-economic and environmental change. Of particular interest to water resources researchers and modelers will be the simulated effects of a new water stress definition that incorporates both water quality and water quantity effects into the measurement of water scarcity. Five simulation runs demonstrate the value of wastewater treatment and reuse programs and the feedback-effects of irrigated agriculture and greater consumption of animal products. © 2011 Elsevier Ltd.


Nehdi M.L.,University of Western Ontario
Construction and Building Materials | Year: 2013

The world's tallest skyscrapers are taking concrete to ever higher altitudes. Indeed, high-strength flowable concrete has become a material of choice for the construction of tall buildings. However, technological challenges associated with using concrete in super-tall buildings are daunting. For instance, Dubai's Burj Khalifa, the world's tallest building completed in 2010 standing 828-m tall with 163 floors, had plans to take concrete higher abandoned somewhere around an altitude of 580-m due to pumping challenges. In 2012, the Holy City of Makah's Royal Clock Tower became the world's second tallest building, standing 601-m tall. This building also experienced the dares of pumping concrete beyond 520-m in height. The City of Jeddah's Kingdom Tower is expected to exceed one kilometer in height upon completion and will take concrete higher than ever before in stringent hot weather conditions. This article discusses the experience with flowable and self-consolidating concrete in skyscrapers, examines the opportunities and technical challenges facing SCC construction in super-tall buildings and highlights needed innovations and technological breakthroughs. © 2013 Elsevier Ltd. All rights reserved.


Csiernik R.,University of Western Ontario
Journal of Workplace Behavioral Health | Year: 2011

Five electronic databases were searched using the key words Employee Assistance, research, and evaluation for articles published from 2000 to 2009 along with a manual search of the two prominent journals in the Employee Assistance field. Forty-two evaluations were found that were categorized using Macdonald's structure into four groups: needs assessments (n = 2), program development (case study) (n = 21), outcome (n = 10), and process (n = 9). Although the majority of evaluations were conducted in the United States (n = 29), there was a distinct international component with studies from Australia (n = 1), Canada (n = 5), Israel (n = 1), Japan (n = 1), South Africa (n = 2), South Korea (n = 1), and the United Kingdom (n = 2) also being published during the first 10 years of the new millennium. Evaluations were conducted upon programs delivered across the entire helping continuum: by peers, professionals working for the organization, and external providers as well as joint internal-external service delivery models. A broad range of methodologies were employed that demonstrated in general that the Employee Assistance Programs (EAPs) that were reviewed produced positive outcomes including saving organizations money as well as in producing positive change in those who sought counseling through their auspices. However, as well as describing new initiatives, program evolution, and offering insights into how specific programs could be further enhanced, broader themes were also examined such as who is and is not availing themselves of EAP services and the stigma that some still feel in seeking help through EAPs. © 2011 Copyright Taylor and Francis Group, LLC.


McIntyre C.W.,University of Western Ontario | Goldsmith D.J.,Kings College
Kidney International | Year: 2015

Abnormalities of cognitive function and high levels of depression incidence are characteristic of hemodialysis patients. Although previously attributed to the humoral effects of uremia, it is becoming increasingly appreciated that many elements of the overall disease state in CKD patients contribute to functional disturbances and physical brain injury. These factors range from those associated with the underlying primary diseases (cardiovascular, diabetes etc.) to those specifically associated with the requirement for dialysis (including consequences of the hemodialysis process itself). They are, however, predominantly ischemic threats to the integrity of brain tissue. These evolving insights are starting to allow nephrologists to appreciate the potential biological basis of dependency and depression in our patients, as well as develop and test new therapeutic approaches to this increasingly prevalent and important issue. This review aims to summarize the current understanding of brain injury in this setting, as well as examine recent advances being made in the modification of dialysis-associated brain injury. © 2015 International Society of Nephrology.


Atkinson G.M.,University of Western Ontario | Boore D.M.,U.S. Geological Survey
Bulletin of the Seismological Society of America | Year: 2014

We develop an empirical model of the decay of Fourier amplitudes for earthquakes of M 3-6 recorded on rock sites in eastern North America and discuss its implications for source parameters. Attenuation at distances from 10 to 500 km may be adequately described using a bilinear model with a geometric spreading of 1/R1.3 to a transition distance of 50 km, with a geometric spreading of 1/R0.5 at greater distances. For low frequencies and distances less than 50 km, the effective geometric spreading given by the model is perturbed using a frequency and hypocentral depth-dependent factor defined in such a way as to increase amplitudes at lower frequencies near the epicenter but leave the 1 km source amplitudes unchanged. The associated anelastic attenuation is determined for each event, with an average value being given by a regional quality factor of Q = 525f0.45. This model provides a match, on average, between the known seismic moment of events and the inferred low-frequency spectral amplitudes at R = 1 km (obtained by correcting for the attenuation model). The inferred Brune stress parameters from the high-frequency source terms are about 600 bars (60 MPa), on average, for events of M > 4.5.


Fang H.,Sun Yat Sen University | Beier F.,University of Western Ontario
Nature Reviews Rheumatology | Year: 2014

Osteoarthritis (OA) is a prevalent musculoskeletal disease that results in pain and low quality of life for patients, as well as enormous medical and socioeconomic burdens. The molecular mechanisms responsible for the initiation and progression of OA are still poorly understood. As such, mouse models of the disease are having increasingly important roles in OA research owing to the advancements of microsurgical techniques and the use of genetically modified mice, as well as the development of novel assessment tools. In this Review, we discuss available mouse models of OA and applicable assessment tools in studies of experimental OA. © 2014 Macmillan Publishers Limited.


Kothari A.,University of Western Ontario | Armstrong R.,University of Melbourne
Implementation Science | Year: 2011

Background: Knowledge translation is an interactive process of knowledge exchange between health researchers and knowledge users. Given that the health system is broad in scope, it is important to reflect on how definitions and applications of knowledge translation might differ by setting and focus. Community-based organizations and their practitioners share common characteristics related to their setting, the evidence used in this setting, and anticipated outcomes that are not, in our experience, satisfactorily reflected in current knowledge translation approaches, frameworks, or tools.Discussion: Community-based organizations face a distinctive set of challenges and concerns related to engaging in the knowledge translation process, suggesting a unique perspective on knowledge translation in these settings. Specifically, community-based organizations tend to value the process of working in collaboration with multi-sector stakeholders in order to achieve an outcome. A feature of such community-based collaborations is the way in which 'evidence' is conceptualized or defined by these partners, which may in turn influence the degree to which generalizable research evidence in particular is relevant and useful when balanced against more contextually-informed knowledge, such as tacit knowledge. Related to the issues of evidence and context is the desire for local information. For knowledge translation researchers, developing processes to assist community-based organizations to adapt research findings to local circumstances may be the most helpful way to advance decision making in this area. A final characteristic shared by community-based organizations is involvement in advocacy activities, a function that has been virtually ignored in traditional knowledge translation approaches.Summary: This commentary is intended to stimulate further discussion in the area of community-based knowledge translation. Knowledge translation, and exchange, between communities, community-based organizations, decision makers, and researchers is likely to be beneficial when ensuring that 'evidence' meets the needs of all end users and that decisions are based on both relevant research and community requirements. Further exploratory work is needed to identify alternative methods for evaluating these strategies when applied within community-based settings. © 2011 Kothari and Armstrong; licensee BioMed Central Ltd.


Sivak J.M.,University of Western Ontario | Sivak J.M.,University of Toronto
Investigative Ophthalmology and Visual Science | Year: 2013

Alzheimer's disease (AD) is a common, incurable, and progressive dementia, characterized by loss of learning and memory and the neuropathologic accumulation of amyloid plaques and neurofibrillary tangles in the brain. A number of similarities between AD pathology and several distinct retinal degenerations have been described, particularly with respect to either glaucoma or age-related macular degeneration (AMD), each a leading cause of vision loss and blindness worldwide. Although comparisons between these diseases may provide important new insights into their pathogenic mechanisms, glaucoma and AMD result in markedly different degenerations. Therefore, analyses of the differences and the similarities between these conditions may prove equally productive. Common mechanisms that appear to underlie all three diseases are explored here, as well as potential use of the retina as a biomarker for AD diagnosis and progression. Based on this comparison, past and current efforts to transfer therapeutic strategies between diseases are discussed. © 2013 The Association for Research in Vision and Ophthalmology, Inc.


Seifu D.G.,Laval University | Purnama A.,Laval University | Mequanint K.,University of Western Ontario | Mantovani D.,Laval University
Nature Reviews Cardiology | Year: 2013

Vascular occlusion remains the leading cause of death in Western countries, despite advances made in balloon angioplasty and conventional surgical intervention. Vascular surgery, such as CABG surgery, arteriovenous shunts, and the treatment of congenital anomalies of the coronary artery and pulmonary tracts, requires biologically responsive vascular substitutes. Autografts, particularly saphenous vein and internal mammary artery, are the gold-standard grafts used to treat vascular occlusions. Prosthetic grafts have been developed as alternatives to autografts, but their low patency owing to short-term and intermediate-term thrombosis still limits their clinical application. Advances in vascular tissue engineering technology-such as self-assembling cell sheets, as well as scaffold-guided and decellularized-matrix approaches-promise to produce responsive, living conduits with properties similar to those of native tissue. Over the past decade, vascular tissue engineering has become one of the fastest-growing areas of research, and is now showing some success in the clinic. © 2013 Macmillan Publishers Limited.


Sibbald R.W.,University of Western Ontario
Healthcare quarterly (Toronto, Ont.) | Year: 2011

Despite improvements in communication, errors in end-of-life care continue to be made. For example, healthcare professionals may take direction from the wrong substitute decision-maker, or from family members when the patient is capable; permit families to propose treatment plans; conflate values and beliefs with prior expressed wishes or fail to inquire about prior expressed wishes. Sometimes healthcare professionals know what prior expressed wishes are but do not respect them; others do not believe they have enough time to have an end-of-life discussion or lack the confidence, willingness and skills to manage one. As has been shown in initiatives to improve in surgical safety, the use of a checklist presents opportunities to potentially minimize common mistakes and errors. When engaging in end-of-life care, a checklist can help focus on what needs to be communicated rather than how it needs to be communicated. We propose a checklist to support healthcare professionals in meeting their ethical and legal obligations to patients at the end of life. The checklist should minimize common mistakes, and in situations where irreconcilable conflict is unavoidable, it will ensure that both healthcare teams and family members are informed and prepared.


Hora M.,Georgia Institute of Technology | Klassen R.D.,University of Western Ontario
Journal of Operations Management | Year: 2013

Risks arising from operations are increasingly being highlighted by managers, customers, and the popular press, particularly related to large-scale (and usually low-frequency) losses. If poorly managed, the resulting disruptions in customer service and environmental problems incur enormous recovery costs, prompt large legal liabilities, and damage customer goodwill and brand equity. Yet, despite conventional wisdom that firms should improve their own operations by observing problems that occur in others' processes, significant operational risks appear to be ignored and similar losses recur. Using a randomized vignette-based field experiment, we tested the influence of organization-level factors on knowledge acquisition. Two organization-level factors, namely perceived operational similarity, and to a lesser extent, market leadership, significantly influenced the risk manager's likelihood of acquiring knowledge about possible causes that triggered another firm's operational loss. These findings suggest that senior managers need to develop organizational systems and training to expand the screening by risk managers to enhance knowledge acquisition. Moreover, industry and trade organizations may have a role in fostering the transfer of knowledge and potential learning from operational losses of firms. © 2012 Elsevier B.V. All rights reserved.


Soros P.,London Health Sciences Center | Whitehead S.,University of Western Ontario | Spence J.D.,Robarts Research Institute | Hachinski V.,London Health Sciences Center
Nature Reviews Neurology | Year: 2013

Hypertension is a highly prevalent risk factor for stroke and dementia, and is the greatest risk factor for small-vessel disease - a frequent cause of lacunar infarction and intracerebral haemorrhage. Lacunar and cortical strokes contribute to the development of dementia in patients with, and in those without, Alzheimer disease pathology; this relationship between stroke and dementia is probably mediated by ischaemia-induced neuroinflammation. Antihypertensive treatment can reduce the risk of stroke and dementia, but requires optimal blood pressure targets to be established for individual patients. Although the rate of treatment and control of hypertension has improved markedly over the past two decades, many physicians remain reluctant to prescribe antihypertensive medication to elderly patients owing to potential adverse events such as cardiovascular morbidity and postural hypotension. In this article we argue that, in patients of all ages, not treating hypertension is a missed opportunity to prevent some of the most prevalent brain diseases. Copyright © 2013 Macmillan Publishers Limited.


This paper examines the relationship between Mespilus (medlar) and Crataegus (hawthorn) in both academic and folk taxonomy. Academic taxonomy since Linnaeus has mostly kept Mespilus and Crataegus distinct but not always for correct or adequate reasons. On the other hand, the study of folk-names, explored across 22 European and Near-Eastern modern languages, finds medlar always different from hawthorn, which, from such a large sample, underlines the cultural distinctness of medlar, and supports its taxonomic distinctness. Looking at the earliest recorded usage of the two generic names, in ancient Greece, the Greek names as found in Theophrastus have debatable applications, though this may be due to a corrupt text. The findings of the present paper thus lend support to those in a companion paper by the author clarifying the morphological distinction between the Mespilus and Crataegus, and arguing for the retention of a monotypic Mespilus, which distinction receives support from recent cladistic work. © 2016 Magnolia Press.


Perret L.,CNRS Laboratory for Hydrodynamics, Energetics & Atmospheric Environment | Savory E.,University of Western Ontario
Boundary-Layer Meteorology | Year: 2013

An analysis of the dynamics of the flow over a street canyon immersed in an atmospheric boundary layer is presented, using particle image velocimetry measurements in a wind tunnel. Care was taken to generate a 1:200 model scale urban type boundary layer that is correctly scaled to the size of the canyon buildings. Using proper orthogonal decomposition (POD) of the velocity field and conditional averaging techniques, it is first shown that the flow above the opening of the canyon consists of a shear layer separating from the upstream obstacle, animated by a coherent flapping motion and generating large-scale vortical structures. These structures are alternately injected into the canyon or shed off the obstacle into the outer flow. It is shown that unsteady fluid exchanges between the canyon and the outer flow are mainly driven by the shear layer. Finally, using POD, the non-linear interaction between the large-scale structures of the oncoming atmospheric boundary layer and the flow over the canyon is demonstrated. © 2013 Springer Science+Business Media Dordrecht.


Young R.,University of Western Ontario
Oxford Review of Economic Policy | Year: 2014

This article demonstrates that the costs incurred in the process of a region becoming a sovereign state can be large enough to outweigh the long-term material benefits of independence. Transition costs consist of transaction costs, fiscal costs, and the cost of uncertainty. Their size depends crucially on whether the politics of the transition are cooperative. Game theory, however, shows that there are incentives for threats of non-cooperation and for the exercise of such threats. These considerations are applied, briefly, to the debate about Scottish independence. This includes a short analysis of how transition costs can be reduced. A final section inquires about possible transition benefits, which can consist of solidarity. © The Author 2014. Published by Oxford University Press.


Objectives: The purpose of this paper was to systematically appraise youths' perceptions of tobacco-cigarette-related addiction and health risks. Methods: Five electronic databases were searched for articles relating to youth, smoking, and risk perception, and the references of relevant articles were hand searched resulting in 10 studies with over 2500 participants meeting the inclusion/exclusion criteria. Articles were systematically appraised based on risk perception according to susceptibility, severity, barriers, and benefits. Perceptions of health risks and addiction were categorized as optimistic among smoking youth, pessimistic among non-smoking youth, and realistic among a portion of older smoking youth. Results: Smoking youth were optimistic and held self-exempting beliefs regarding likelihood of addiction, ability to quit, mortality, and tobacco-related diseases. Youth rationalized smoking by perceiving barriers to quitting as more relevant than the benefits of quitting, with this balance shifting when youth decided to attempt cessation. Conclusions: Implications of these findings are widespread and offer insight for researchers, educators, and cessation interventionists, as awareness of self-exempting beliefs held by smoking youth creates a vantage point to facilitate behaviour change. © 2013 Informa UK Ltd. All rights reserved.


Southen J.M.,University of Western Ontario | Rowe R.K.,Queens University
Geosynthetics International | Year: 2011

A fully coupled model is used to simulate the results of large-scale laboratory tests that investigated the non-isothermal behaviour of geosynthetic clay liners in landfill basal liner applications. Results of numerical simulations of the laboratory tests in terms of water content, capillary pressure, temperature and stress distributions are presented, and encouraging agreement between the numerical and experimental results is achieved. Under the conditions examined, a 25°C/m temperature gradient led to the development of tensile stresses within the GCL, increasing the resultant likelihood of cracking. A Poisson's ratio of 0.25 resulted in predicted horizontal tensile stresses supporting qualitative observation of desiccation cracking in the GCLs. One important implication of the work reported herein is that elevated temperatures need not occur for extended periods to create the risk of desiccation. © 2011 Thomas Telford Ltd.


Leask A.,University of Western Ontario
Journal of Cell Communication and Signaling | Year: 2011

There are no approved drugs for treating the fibrosis in scleroderma (systemic sclerosis, SSc). Myfibroblasts within connective tissue express the highly contractile protein α-smooth muscle actin (α-SMA) and are responsible for the excessive synthesis and remodeling of extracellular matrix (ECM) characterizing SSc. Drugs targeting myofibroblast differentiation, recruitment and activity are currently under consideration as anti-fibrotic treatments in SSc but thus far have principally focused on the transforming growth factor β (TGFβ), endothelin-1 (ET-1), connective tissue growth factor (CCN2/CTGF) and platelet derived growth factor (PDGF) pathways, which display substantial signaling crosstalk. Moreover, peroxisome proliferator-activated receptor (PPAR)γ also appears to act by intervening in TGFβ signaling. This review discusses these potential candidates for antifibrotic therapy in SSc. © 2011 The International CCN Society.


Tyml K.,Lawson Health Research Institute | Tyml K.,University of Western Ontario
Microcirculation | Year: 2011

Sepsis is a complex multifaceted response to a local infectious insult. One important facet is the circulatory system dysfunction, which includes capillary bed plugging. This review addresses the mechanisms of capillary plugging and highlights our recent discoveries on the roles of NO, ROS, and activated coagulation in platelet adhesion and blood flow stoppage in septic mouse capillaries. We show that sepsis increases platelet adhesion, fibrin deposition and flow stoppage in capillaries, and that NADPH oxidase-derived ROS, rather than NO, play a detrimental role in this adhesion/stoppage. P-selectin and activated coagulation are required for adhesion/stoppage. Further, platelet adhesion in capillaries (i) strongly predicts capillary flow stoppage, and (ii) may explain why severe sepsis is associated with a drop in platelet count in systemic blood. Significantly, we also show that a single bolus of the antioxidant ascorbate (injected intravenously at clinically relevant dose of 10mg/kg) inhibits adhesion/stoppage. Our data suggest that eNOS-derived NO at the platelet-endothelial interface is anti-adhesive and required for the inhibitory effect of ascorbate. Because of the critical role of ROS in capillary plugging, ascorbate bolus administration may be beneficial to septic patients whose survival depends on restoring microvascular perfusion. © 2011 John Wiley & Sons Ltd.


Kreyling J.,University of Bayreuth | Henry H.A.L.,University of Western Ontario
Climate Research | Year: 2011

Current climate models are effective at projecting trends in mean winter temperature; however, other ecologically relevant parameters - such as snow cover and soil frost dynamics - are less well investigated. Changes in these parameters are expected to have strong ecological implications, especially in the temperate zone, where it is uncertain whether snow and soil frost will occur with regularity in the future. We explored trends in days with snow on the ground (snowdays), minimum soil temperature (MST), and number of soil freeze/thaw cycles (FTCs, i.e. changes in sign from negative to positive in any pair of consecutive soil temperature records at 5 cm depth) at 177 German weather stations for 1950-2000. Future trends were explored by statistical modelling based on climatic and topographic predictors. Snowdays decreased uniformly at a rate of 0.5 d yr-1 in the recent past. This trend is projected to continue to a point where significant parts of Germany will no longer regularly experience snow cover. MST has increased, and is projected to do so in the future, mainly in southern Germany. FTCs have been decreasing uniformly in the recent past. No evidence for increased FTCs or decreased MST with decreasing insulation due to missing snow cover was found. FTCs are projected to decrease disproportionately in northeastern Germany, where past frequencies were higher. Ecological implications of the significant decrease in the occurrence and magnitude of the climate parameters studied include changes in nutrient cycling, productivity and survival of organisms over wintering at the soil surface. Ecological research is needed, as the effects of diminished winters on ecosystems are not well understood. © Inter-Research 2011.


Valvano M.A.,University of Western Ontario
Biochemistry (Moscow) | Year: 2011

The biosynthesis of glycoconjugates is remarkably conserved in all types of cells since the biochemical reactions involved exhibit similar characteristics, which can be summarized as follows: (a) the saccharide moiety is formed as a lipidlinked, membrane-associated glycan; (b) the lipid component in most cases is a polyisoprenoid phosphate; (c) the assembly of the lipid-linked saccharide intermediate depends on reactions taking place at both sides of the cell membrane, which requires the obligatory transmembrane movement of amphipathic molecules across the lipid bilayer. These general characteristics are present in the biosynthesis of the O-antigen component of the bacterial lipopolysaccharide, which serves as a model system to investigate the molecular and mechanistic basis of glycoconjugate synthesis, as summarized in this minireview. © 2011 Pleiades Publishing, Ltd.


Guaiana G.,University of Western Ontario
Clinical Practice and Epidemiology in Mental Health | Year: 2011

Anti-depressant (AD) prescribing rose in several countries worldwide over the last 20 years. Some concerns have been raised over the fact that AD use, mainly Selective Serotonin Reuptake Inhibitors (SSRI) may increase the risk of suicide. AD consumption and suicide rates data in Emilia-Romagna region, Italy have been extracted from regional government databases on AD prescribing and suicide rates, from 1999 to 2008. A statistical model using ordinary least squares linear regression was employed. The overall suicide rates decreased during the period under examination, in spite of the observed exponential increase in use of ADs. Despite the doubling in prescribing of SSRI and newer ADs in recent years, there continues to be no negative impact on suicide rates in Emilia Romagna. © Giuseppe Guaiana et al.


Kleinstiver B.P.,University of Western Ontario
G3 (Bethesda, Md.) | Year: 2014

Precise genome editing in complex genomes is enabled by engineered nucleases that can be programmed to cleave in a site-specific manner. Here, we fused the small, sequence-tolerant monomeric nuclease domain from the homing endonuclease I-TevI to transcription-like activator effectors (TALEs) to create monomeric Tev-TALE nucleases (Tev-mTALENs). Using the PthXo1 TALE scaffold to optimize the Tev-mTALEN architecture, we found that choice of the N-terminal fusion point on the TALE greatly influenced activity in yeast-based assays, and that the length of the linker used affected the optimal spacing of the TALE binding site from the I-TevI cleavage site, specified by the motif 5'-CNNNG-3'. By assaying activity on all 64 possible sequence variants of this motif, we discovered that in the Tev-mTALEN context, I-TevI prefers A/T-rich triplets over G/C-rich ones at the cleavage site. Profiling of nucleotide requirements in the DNA spacer that separates the CNNNG motif from the TALE binding site revealed substantial, but not complete, tolerance to sequence variation. Tev-mTALENs showed robust mutagenic activity on an episomal target in HEK 293T cells consistent with specific cleavage followed by nonhomologous end-joining repair. Our data substantiate the applicability of Tev-mTALENs as genome-editing tools but highlight DNA spacer and cleavage site nucleotide preferences that, while enhancing specificity, do confer moderate targeting constraints. Copyright © 2014 B. P. Kleinstiver et al.


Buckingham G.,University of Western Ontario
Journal of vision | Year: 2011

Vision provides many reliable cues about the likely weight of an object, allowing individuals to predict how heavy it will be. The forces used to lift an object for the first time reflect these predictions. This, however, leads to inevitable errors during lifts of objects that weigh unexpected amounts. Fortunately, these errors are rarely made twice in a row-lifters have the impressive ability to detect and correct large or small misapplications of fingertip forces, even while experiencing weight illusions. Although it has been assumed that we detect and correct these errors exclusively with our sense of touch, recent evidence has demonstrated a role for vision in this fingertip force scaling. Here, we demonstrate that even when stimulus set size, delay, and modality are controlled for, individuals are unable to skillfully scale their grip and load force rates over repeated lifts without vision. However, eliminating only the task-relevant visual information, while maintaining the rest of the visual world, shifts participants back into the normal, skilled mode of control. These findings clarify the role of visual information in the ostensibly haptic task of lifting objects, suggesting individuals use priors under conditions where uncertainty is high.


Das S.,University of Western Ontario | Singh Sidhu T.,University of Ontario Institute of Technology
IEEE Transactions on Industrial Informatics | Year: 2014

In this paper, areas of power system synchrophasor data communication which can be improved by compressive sampling (CS) theory are identified. CS reduces the network bandwidth requirements of Wide Area Measurement Systems (WAMS). It is shown that CS can reconstruct synchrophasors at higher rates while satisfying the accuracy requirements of IEEE standard C37.118.1-2011. Different steady state and dynamic power system scenarios are considered here using mathematical models of C37.118.1-2011. Synchrophasors of lower reporting rates are exempted from satisfying the accuracy requirements of C37.118.1-2011 during system dynamics. In this work, synchrophasors are accurately reconstructed from above and below Nyquist rates. Missing data often pose challenges to the WAMS applications. It is shown that missing and bad data can be reconstructed satisfactorily using CS. Performance of CS is found to be better than the existing interpolation techniques for WAMS communication. © 2005-2012 IEEE.


We previously established that COX-2 overexpression promotes breast cancer progression and metastasis. As long-term use of COX-2 inhibitors (COX-2i) can promote thrombo-embolic events, we tested an alternative target, prostaglandin E2 receptor EP4 subtype (EP4), downstream of COX-2. Here we used the highly metastatic syngeneic murine C3L5 breast cancer model to test the role of EP4-expressing macrophages in vascular endothelial growth factor (VEGF)-C/D production, angiogenesis, and lymphangiogenesis in situ, the role of EP4 in stem-like cell (SLC) functions of tumor cells, and therapeutic effects of an EP4 antagonist RQ-15986 (EP4A). C3L5 cells expressed all EP receptors, produced VEGF-C/D, and showed high clonogenic tumorsphere forming ability in vitro, functions inhibited with COX-2i or EP4A. Treating murine macrophage RAW 264.7 cell line with COX-2i celecoxib and EP4A significantly reduced VEGF-A/C/D production in vitro, measured with quantitative PCR and Western blots. Orthotopic implants of C3L5 cells in C3H/HeJ mice showed rapid tumor growth, angiogenesis, lymphangiogenesis (CD31/LYVE-1 and CD31/PROX1 immunostaining), and metastasis to lymph nodes and lungs. Tumors revealed high incidence of EP4-expressing, VEGF-C/D producing macrophages identified with dual immunostaining of F4/80 and EP4 or VEGF-C/D. Celecoxib or EP4A therapy at non-toxic doses abrogated tumor growth, lymphangiogenesis, and metastasis to lymph nodes and lungs. Residual tumors in treated mice revealed markedly reduced VEGF-A/C/D and phosphorylated Akt/ERK proteins, VEGF-C/D positive macrophage infiltration, and proliferative/apoptotic cell ratios. Knocking down COX-2 or EP4 in C3L5 cells or treating cells in vitro with celecoxib or EP4A and treating tumor-bearing mice in vivo with the same drug reduced SLC properties of tumor cells including preferential co-expression of COX-2 and SLC markers ALDH1A, CD44, OCT-3/4, β-catenin, and SOX-2. Thus, EP4 is an excellent therapeutic target to block stem-like properties, angiogenesis, and lymphangiogenesis induced by VEGF-A/C/D secreted by cancer cells and tumor infiltrating macrophages. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.


Way D.A.,Duke University | Way D.A.,University of Western Ontario | Pearcy R.W.,University of California at Davis
Tree Physiology | Year: 2012

Sunflecks are brief, intermittent periods of high photon flux density (PFD) that can significantly improve carbon gain in shaded forest understories and lower canopies of trees. In this review, we discuss the physiological basis of leaf-level responses to sunflecks and the mechanisms plants use to tolerate sudden changes in PFD and leaf temperature induced by sunflecks. We also examine the potential effects of climate change stresses (including elevated temperatures, rising CO2 concentrations and drought) on the ability of tree species to use sunflecks, and advocate more research to improve our predictions of seedling and tree carbon gain in future climates. Lastly, while we have the ability to model realistic responses of photosynthesis to fluctuating PFD, dynamic responses of photosynthesis to sunflecks are not accounted for in current models of canopy carbon uptake, which can lead to substantial overestimates of forest carbon fixation. Since sunflecks are a critical component of seasonal carbon gain for shaded leaves, sunfleck regimes and physiological responses to sunflecks should be incorporated into models to more accurately capture forest carbon dynamics. © 2012 The Author.


Gujral N.,University of Alberta | Freeman H.J.,University of British Columbia | Thomson A.B.R.,University of Western Ontario
World Journal of Gastroenterology | Year: 2012

Celiac disease (CD) is one of the most common diseases, resulting from both environmental (gluten) and genetic factors [human leukocyte antigen (HLA) and non- HLA genes]. The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world. However, the population with diabetes, autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD, at least in part, because of shared HLA typing. Gliadin gains access to the basal surface of the epithelium, and interact directly with the immune system, via both trans- and para-cellular routes. From a diagnostic perspective, symptoms may be viewed as either "typical" or "atypical". In both positive serological screening results suggestive of CD, should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet (GFD) to confirm the diagnosis. Positive anti-tissue transglutaminase antibody or antiendomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy. Currently, the only treatment available for CD individuals is a strict life-long GFD. A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide, prevent toxic gliadin peptide absorption, blockage of selective deamidation of specific glutamine residues by tissue, restore immune tolerance towards gluten, modulation of immune response to dietary gliadin, and restoration of intestinal architecture. © 2012 Baishideng. All rights reserved.


Sadrekarimi A.,University of Western Ontario
Soils and Foundations | Year: 2016

As a result of the difficulties related to obtaining undisturbed samples of cohesionless soils, CPT-based empirical correlations, often developed from calibration chamber experiments, are widely used for determining many soil parameters for geotechnical investigation. This paper describes the application of 19 reduced-scale calibration chamber cone penetration tests to evaluate empirical correlations for predicting the relative density, the unit weight, the constrained modulus, and the soil identification of loose to medium-dense sands. A subtraction cone, 6. mm in diameter with an apex angle of 60° and a net area ratio of 0.75, is used in the laboratory tests. Due to the fine gradation of the quartz sand used in the experiments, some of the CPT results are located within the silty sand range of the soil identification charts. An extensive evaluation is also presented for the stress normalization process of the CPT data. It is determined that a relative density-based overburden stress normalization method provided the best estimates for correcting the cone tip resistance for effective overburden stress. © 2016 Japanese Geotechnical Society.


Braimoh J.,McMaster University | Davies L.,University of Western Ontario
Social Science and Medicine | Year: 2014

In this paper, we focus on the initial experiences of breastfeeding among mothers to examine the ways that infant-feeding is socially constructed in the hospital. Data comes from 51 in-depth interviews with 17 first-time mothers in Ontario, Canada. Analysis reveals 52 magnified moments that we categorize as Successful, Ultimately Successful and Unsuccessful. For mothers who describe Successful and Ultimately Successful moments, breastfeeding is understood as physiologically natural, and as something they must learn to do. Unsuccessful moments reveal that when health care providers interpret breastfeeding as not working, the breastfeeding discourse frequently shifts to one that incorporates formula as the means to achieve optimal infant health. In other words, in the hospital 'breast is best' holds true when breast 'works', otherwise mothers are often directed to give their babies formula. While formula appears to be compulsory in these moments, it is not typically understood as a "good or best" infant-feeding practice. For mothers in this situation, the shift from breast to formula is experienced as failures or evidence of inadequacy in their mothering. Paradoxically, our results suggest that formula may not, in and of itself, pose a threat to mothers' overall continued practice of breastfeeding. It appears that Successful and Ultimately Successful moments coincide with the current dominant 'breast is best' understanding. Unsuccessful moments, conversely, are insightful because they reveal when and how hospital practices disrupt mothers' understanding of their bodies and their role in providing the 'best' form of infant food. The implications for policy and practice are discussed. © 2014.


Myrskyla M.,The London School of Economics and Political Science | Myrskyla M.,University of Helsinki | Margolis R.,University of Western Ontario
Demography | Year: 2014

Understanding how having children influences parents’ subjective well-being (“happiness”) has great potential to explain fertility behavior. We study parental happiness trajectories before and after the birth of a child, using large British and German longitudinal data sets. We account for unobserved parental characteristics using fixed-effects models and study how sociodemographic factors modify the parental happiness trajectories. Consistent with existing work, we find that happiness increases in the years around the birth of a first child and then decreases to before-child levels. Moreover, happiness increases before birth, suggesting that the trajectories may capture not only the effect of the birth but also the broader process of childbearing, which may include partnership formation and quality. Sociodemographic factors strongly modify this pattern. Those who have children at older ages or who have more education have a particularly positive happiness response to a first birth; and although having the first two children increases happiness, having a third child does not. The results, which are similar in Britain and Germany, suggest that having up to two children increases happiness, and mostly for those who have postponed childbearing. This pattern is consistent with the fertility behavior that emerged during the second demographic transition and provides new insights into low and late fertility. © 2014, Population Association of America.


Chouinard P.A.,University of Western Ontario | Paus T.,Rotman Research Institute
Frontiers in Human Neuroscience | Year: 2010

The purpose of this paper is twofold. First, we will review different approaches that one can use with transcranial magnetic stimulation (TMS) to study both its effects on motor behavior and on neural connections in the human brain. Second, we will present evidence obtained in TMS-based studies showing that the dorsal premotor area (PMd), the ventral premotor area (PMv), the supplementary motor area (SMA), and the pre-supplementary motor area (pre-SMA) each have different roles to play in motor behavior. We highlight the importance of the PMd in response selection based on arbitrary cues and in the control of arm movements, the PMv in grasping and in the discrimination of bodily actions, the SMA in movement sequencing and in bimanual coordination, and the pre-SMA in cognitive control. We will also discuss ways in which TMS can be used to chart true cerebral reorganization in clinical populations and how TMS might be used as a therapeutic tool to facilitate motor recovery after stroke. We will end our review by discussing some of the methodological challenges and future directions for using this tool in basic and clinical neuroscience. © 2010 Chouinard and Paus.


Lother A.,Albert Ludwigs University of Freiburg | Moser M.,Albert Ludwigs University of Freiburg | Bode C.,Albert Ludwigs University of Freiburg | Feldman R.D.,University of Western Ontario | Hein L.,Albert Ludwigs University of Freiburg
Annual Review of Pharmacology and Toxicology | Year: 2015

The mineralocorticoid aldosterone is a key regulator of water and electrolyte homeostasis. Numerous recent developments have advanced the field of mineralocorticoid pharmacology-namely, clinical trials have shown the beneficial effects of aldosterone antagonists in chronic heart failure and post-myocardial infarction treatment. Experimental studies using cell type-specific gene targeting of the mineralocorticoid receptor (MR) gene in mice have revealed the importance of extrarenal aldosterone signaling in cardiac myocytes, endothelial cells, vascular smooth cells, and macrophages. In addition, several molecular pathways involving signal transduction via the classical MR as well as the G protein-coupled receptor GPER mediate the diverse spectrum of effects of aldosterone on cells. This knowledge has initiated the development of new pharmacological ligands to specifically interfere with targets on different levels of aldosterone signaling. For example, aldosterone synthase inhibitors such as LCI699 and the novel nonsteroidal MR antagonist BAY 94-8862 have been tested in clinical trials. Interference with the interaction between MR and its coregulators seems to be a promising strategy toward the development of selective MR modulators. ©2015 by Annual Reviews. All rights reserved.


Bai D.,University of Western Ontario
Seminars in Cell and Developmental Biology | Year: 2016

A gap junction (GJ) channel is formed by docking of two GJ hemichannels and each of these hemichannels is a hexamer of connexins. All connexin genes have been identified in human, mouse, and rat genomes and their homologous genes in many other vertebrates are available in public databases. The protein sequences of these connexins align well with high sequence identity in the same connexin across different species. Domains in closely related connexins and several residues in all known connexins are also well-conserved. These conserved residues form signatures (also known as sequence logos) in these domains and are likely to play important biological functions. In this review, the sequence logos of individual connexins, groups of connexins with common ancestors, and all connexins are analyzed to visualize natural evolutionary variations and the hot spots for human disease-linked mutations. Several gap junction domains are homologous, likely forming similar structures essential for their function. The availability of a high resolution Cx26 GJ structure and the subsequently-derived homology structure models for other connexin GJ channels elevated our understanding of sequence logos at the three-dimensional GJ structure level, thus facilitating the understanding of how disease-linked connexin mutants might impair GJ structure and function. This knowledge will enable the design of complementary variants to rescue disease-linked mutants. © 2015 Elsevier Ltd.


Veiseh M.,Lawrence Berkeley National Laboratory | Turley E.A.,University of Western Ontario
Integrative Biology | Year: 2011

Clinical and experimental evidence increasingly support the concept of cancer as a disease that emulates a component of wound healing, in particular abnormal stromal extracellular matrix remodeling. Here we review the biology and function of one remodeling process, hyaluronan (HA) metabolism, which is essential for wound resolution but closely linked to breast cancer (BCA) progression. Components of the HA metabolic cycle (HAS2, SPAM1 and HA receptors CD44, RHAMM/HMMR and TLR2) are discussed in terms of their known functions in wound healing and in breast cancer progression. Finally, we discuss recent advances in the use of HA-based platforms for developing nanoprobes to image areas of active HA metabolism and for therapeutics in breast cancer. © The Royal Society of Chemistry.


Ye Q.-Z.,University of Western Ontario | Hui M.-T.,Nhut Thung Pau Observatory
Astrophysical Journal | Year: 2014

The dynamically new comet, C/2013 A1 (Siding Spring), is to make a close approach to Mars on 2014 October 19 at 18:30 UT at a distance of 40 ± 1 Martian radii. Such an extremely rare event offers a precious opportunity for the spacecrafts on Mars to closely study a dynamically new comet itself as well as the planet-comet interaction. Meanwhile, the high-speed meteoroids released from C/Siding Spring also pose a threat to physically damage the spacecrafts. Here we present our observations and modeling results of C/Siding Spring to characterize the comet and assess the risk posed to the spacecrafts on Mars. We find that the optical tail of C/Siding Spring is dominated by larger particles at the time of the observation. Synchrone simulation suggests that the comet was already active in late 2012 when it was more than 7 AU from the Sun. By parameterizing the dust activity with a semi-analytic model, we find that the ejection speed of C/Siding Spring is comparable to comets such as the target of the Rosetta mission, 67P/Churyumov-Gerasimenko. Under a nominal situation, the simulated dust cone will miss the planet by about 20 Martian radii. At the extreme ends of uncertainties, the simulated dust cone will engulf Mars, but the meteoric influx at Mars is still comparable to the nominal sporadic influx, seemly indicating that an intense and enduring meteoroid bombardment due to C/Siding Spring is unlikely. Further simulation also suggests that gravitational disruption of the dust tail may be significant enough to be observable at Earth. © 2014. The American Astronomical Society. All rights reserved..


Su N.,University of Western Ontario
MIS Quarterly: Management Information Systems | Year: 2013

With China emerging as a new frontier of global IT outsourcing, many Chinese IT service suppliers are actively expanding in three major markets: Asia, especially Japan, the West, especially the United States, and the Chinese domestic market. Compared to multinational suppliers and established Indian suppliers, Chinese IT service firms are at a relatively early, but rapidly growing stage, which offers a unique opportunity to explore an understudied topic in the information systems literature: internationalization strategies of IT service suppliers from emerging economies. Through a three-part qualitative case study of 13 China-based IT service firms, including almost all of the Chinese suppliers recognized globally, this study elaborates the internationalization behavior and decision rationale of these suppliers. The findings show that these major Chinese suppliers include both firms that incrementally internationalize and firms that are "born global." For both types of firms, the entry and growth in different markets is a highly dynamic activity combining a strategically planned, resource-seeking process and a flexible, opportunistic bricolage process based on existing operation capabilities and client relationships. The suppliers dynamically oscillate between these processes to exploit and create opportunities while expanding in multiple markets. Copyright © 2013 by the Management Information Systems Research Center (MISRC) of the University of Minnesota.


Wang Y.,Acadia University | Meister D.B.,University of Western Ontario | Gray P.H.,University of Virginia
MIS Quarterly: Management Information Systems | Year: 2013

Theory suggests that coworkers may influence individuals' technology use behaviors, but there is limited research in the technology diffusion literature that explicates how such social influence processes operate after initial adoption. We investigate how two key social influence mechanisms (identification and internalization) may explain the growth over time in individuals' use of knowledge management systems (KMS)-a technology that because of its publicly visible use provides a rich context for investigating social influence. We test our hypotheses using longitudinal KMS usage data on over 80,000 employees of a management consulting firm. Our approach infers the presence of identification and internalization from associations between actual system use behaviors by a focal individual and prior system use by a range of reference groups. Evidence of these kinds of associations between system use behaviors helps construct a more complete picture of social influence mechanisms, and is to our knowledge novel to the technology diffusion literature. Our results confirm the utility of this approach for understanding social influence effects and reveal a fine-grained pattern of influence across different social groups: we found strong support for bottom-up social influence across hierarchical levels, limited support for peer-level influence within levels, and no support for top-down influence. Copyright © 2013 by the Management Information Systems Research Center (MISRC) of the University of Minnesota.


Sasanian S.,Air Worldwide Corporation | Newson T.A.,University of Western Ontario
Soils and Foundations | Year: 2014

Although extensive research has been conducted on the mechanical behaviour of Portland cement-treated soft clays, there has been less emphasis on the correlation of the observed behaviour with clay mineralogy. In this study, experimental results from the authors have been combined with the data found in the literature to investigate the effect of parameters such as curing time, cement content, moisture content, liquidity index, and mineralogy on the mechanical properties of cement-treated clays. The findings show that undrained shear strength and sensitivity of cemented clays still continue to increase after relatively long curing times; expressions are proposed to predict the strength and sensitivity with time. This parametric study also indicates the relative importance of the activity of the soil, as well as the water-cement ratio, to the mechanical properties of cementitious admixtures. Two new empirical parameters are introduced herein. Based on the results of unconfined compression, undrained triaxial, and oedometer tests on cement-enhanced clays, expressions that use these parameters to predict undrained shear strength, yield stress, and the slope of the compression line are proposed. The observed variations in the mechanical behaviour with respect to mineralogy and the important effect of curing time are explained in terms of the pozzolanic reactions. The possible limitations of applying Abrams' law to cement-admixed clays are also discussed. © 2014 The Japanese Geotechnical Society.


Yan X.,University of Western Ontario | Zhao H.,Purdue University
Operations Research | Year: 2011

We study the information asymmetry issues in a decentralized inventory-sharing system consisting of a manufacturer and two independent retailers, who privately hold demand information, noncooperatively place their orders, but cooperatively share inventories with each other. We find that although the manufacturer needs retailers' mean demand and standard deviation for her wholesale price decision, each retailer only needs to know the other retailer's demand standard deviation for his order quantity decision. However, an incentive compatibility analysis shows that retailers have incentives to share their demand information untruthfully. Although a truth-inducing scheme can be developed for a system with symmetric retailers who share information between themselves, no such scheme can be developed to ensure truth-telling to the manufacturer. Further, we develop a coordination mechanism (CIS) for the decentralized inventory-sharing system, considering information asymmetry. We show that CIS coordinates the manufacturer-retailers system and leads to an all-win situation under complete information. More importantly, CIS minimizes the value of information such that each party can obtain expected profits very close to their first-best profits even under asymmetric information and hence indirectly solves the information asymmetry problem. To our knowledge, this work is the first to study decentralized inventory sharing and its coordination considering asymmetric information. © 2011 INFORMS.


Vasan A.,Birla Institute of Technology and Science | Simonovic S.P.,University of Western Ontario
Journal of Water Resources Planning and Management | Year: 2010

The paper describes the development of a DENET computer model that involves the application of an evolutionary optimization technique, differential evolution, linked to the hydraulic simulation solver, EPANET, for optimal design of water distribution networks. A model is formulated with the objective of minimizing cost and this formulation is applied to two benchmark water distribution system optimization problems-New York water supply system and Hanoi water distribution network. The study yielded promising results as compared with earlier studies in the literature and encouraged to reformulate the model for a new objective of maximizing network resilience. The results of the analysis demonstrate that DENET can be considered as a potential alternative tool for economical and reliable water distribution network planning and management. © 2010 ASCE.


Huey L.,University of Western Ontario
Theoretical Criminology | Year: 2011

Scholars have noted an ever-increasing growth in the number of crime-themed leisure and tourism venues. Within this article I examine one such site: the Vienna Kriminalmuseum. An analysis of this site provides an opportunity to explore how the 'sublime in crime' is presented to the Museum's visitors in ways that intentionally merge the macabre with the educational. This presentation says much, I suggest, not only about the Museum's goals, but about its intended audience, an audience seeking to be exposed to elements of the darkest side of humanity, now sanitized for wider public consumption through the union of educational and entertainment strategies. © The Author(s) 2011.


Timoshenko A.V.,University of Western Ontario
Cellular and Molecular Life Sciences | Year: 2015

Galectins, a family of soluble β-galactoside-binding proteins, serve as mediators of fundamental biological processes, such as cell growth, differentiation, adhesion, migration, survival, and death. The purpose of this review is to summarize the current knowledge regarding the ways in which the expression of individual galectins differs in normal and transformed human cells exposed to various stimuli mimicking physiological and pathological microenvironmental stress conditions. A conceptual point is being made and grounded that the modulation of galectin expression profiles is a key aspect of cellular stress responses. Moreover, this modulation might be precisely regulated at transcriptional and post-transcriptional levels in the context of non-overlapping transcription factors and miRNAs specific to galectins. © 2015 Springer Basel.


Johnson C.A.,University of Western Ontario
Library and Information Science Research | Year: 2012

In this qualitative study exploring the content of social interactions between library staff and patrons, interviews were held with 15 library staff members in three neighborhood branch libraries in a large American midwestern city. An analysis of the interviews suggests that public libraries may contribute to social capital through the relationships and interactions that occur between staff and patrons. Some of the ways in which these relationships and interactions may contribute to social capital include: building patrons' trust in the library and its staff, connecting people to both community and library resources, providing social support for patrons, reducing social isolation, helping patrons gain skills to function in an increasingly online world, and providing a positive place for neighborhood residents to gather. The kinds of social interactions occurring in libraries that may help to build social capital are highlighted. © 2011 Elsevier Inc.


Laliberte Rudman D.,University of Western Ontario
Journal of Aging Studies | Year: 2015

Within contemporary Western contexts, positive aging discourses are a key aspect of structured mandates for how to think about and act toward aging bodies. This study adds to previous work on embodiment that has situated how aging bodies are managed by focusing on the body as an aspect of retirement preparation, and critically considering how the imperative to govern the aging body in ways consistent with being a 'good' neoliberal citizen circulated through positive aging discourses is negotiated by aging individuals. Utilizing narrative data from a study addressing the discursive re-shaping and narrative negotiation of retirement within the Canadian context conducted with 30 informants aged 45 to 83, this paper draws upon a governmentality perspective to critically analyze ways informants talked about their aging bodies as part of preparing for and moving into retirement. Overall, the findings illustrate how informants embodied positive aging discourses and, in turn, embodied neoliberal rationality particularly in taking up the call to attend to the body as part of the broadening of retirement planning within a neoliberal context in which health, social, financial and other responsibilities are increasingly shifted toward individuals. Although informants described realizing some of the promises offered up with positive aging discourses, such as a sense of youthfulness and bodily control, their narratives also point to detrimental individual and social implications that can arise out of the limits of bodily practices, the need for perpetual risk management, an aversion to oldness, and attributions of failure. As such, this study raises concerns about the implications of the intersections of positive aging discourses and the neoliberal agenda of activation, responsibilization and individualization. © 2015 .


Hayes K.C.,University of Western Ontario
Neuropsychiatric Disease and Treatment | Year: 2011

Dalfampridine extended release (ER) 10 mg is an oral tablet form of the potassium (K+) channel-blocking compounded dalfampridine, also known as fampridine, and chemically 4-aminopyridine or 4-AP, which received regulatory approval in the United States for the treatment of walking in patients with multiple sclerosis (MS) in January 2010. Two pivotal Phase 3 clinical trials demonstrated significant improvements in walking in patients with the four primary forms of MS following administration of dalfampridine ER tablets 10 mg twice daily. The drug is thought to act by restoring conduction in focally demyelinated axons and by enhancing neurotransmission, thereby leading to improved neurological function. This review describes how dalfampridine represents a new pharmacotherapeutic approach to the clinical management of mobility impairment. It describes the mechanism of action and chemistry of dalfampridine ER, its pharmacokinetics, tolerability, and side effects, and the outcomes of multicenter trials showing its efficacy in improving walking speed. Clinician and patient global assessments, as well as patient self-assessment of the impact of MS on their gait disability, confirm clinically relevant benefit from the therapy. Patients tolerate the drug well and their improvement in terms of household and community ambulation, inferred from analysis of pooled data from several studies, is likely to translate into benefits in the performance of instrumental activities of daily living and a reduction in the neuropsychiatric burden of disease. © 2011 Bowden.


Gupta M.B.,University of Western Ontario
Journal of Cell Communication and Signaling | Year: 2015

Fetal growth restriction (FGR) increases the risk of perinatal complications and predisposes the infant to developing metabolic, cardiovascular, and neurological diseases in childhood and adulthood. The pathophysiology underlying FGR remains poorly understood and there is no specific treatment available. Biomarkers for early detection are also lacking. The insulin-like growth factor (IGF) system is an important regulator of fetal growth. IGF-I is the primary regulator of fetal growth, and fetal circulating levels of IGF-I are decreased in FGR. IGF-I activity is influenced by a family of IGF binding proteins (IGFBPs), which bind to IGF-I and decrease its bioavailability. During fetal development the predominant IGF-I binding protein in fetal circulation is IGFBP-1, which is primarily secreted by the fetal liver. IGFBP-1 binds IGF-I and thereby inhibits its bioactivity. Fetal circulating levels of IGF-I are decreased and concentrations of IGFBP-1 are increased in FGR. Phosphorylation of human IGFBP-1 at specific sites markedly increases its binding affinity for IGF-I, further limiting IGF-I bioactivity. Recent experimental evidence suggests that IGFBP-1 phosphorylation is markedly increased in the circulation of FGR fetuses suggesting an important role of IGFBP-1 phosphorylation in the regulation of fetal growth. Understanding of the significance of site-specific IGFBP-1 phosphorylation and how it is regulated to contribute to fetal growth will be an important step in designing strategies for preventing, managing, and/or treating FGR. Furthermore, IGFBP-1 hyperphosphorylation at unique sites may serve as a valuable biomarker for FGR. © 2015, The International CCN Society.