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Hamilton, Canada

McMaster University is a public research university located in Hamilton, Ontario, Canada. The main campus is located on 121 hectares of land in the residential neighbourhood of Westdale, adjacent to Hamilton's Royal Botanical Gardens. The university operates six academic faculties: the DeGroote School of Business, Engineering, Health science, Humanities, Social Science, and Science. It is a member of the U15, a group of research-intensive universities in Canada.The university bears the name of Honourable William McMaster, a prominent Canadian Senator and banker who bequeathed C$900,000 to the founding of the university. McMaster University was incorporated under the terms of an act of the Legislative Assembly of Ontario in 1887, merging the Toronto Baptist College with Woodstock College. It opened in Toronto in 1890. Inadequate facilities and the gift of land in Hamilton prompted the institution to relocate in 1930. McMaster was controlled by the Baptist Convention of Ontario and Quebec until it became a privately chartered, publicly funded non-denominational institution in 1957.The university is co-educational, and has over 24,500 undergraduate and nearly 4,000 post-graduate students. Alumni and former students of the university can be found all across Canada and in 140 countries around the world. Notable alumni include government officials, academics, business leaders and two Nobel laureates. The university ranked 4th among Canadian universities and 92nd in the world according to the 2013-2014 Times Higher Education World University Rankings, 4th among Canadian universities and 90th in the world according to the 2014 Academic Ranking of World Universities, and 6th among Canadian universities and 113th in the world according to the 2014 QS World University Rankings. In addition, the McMaster University Medical School was ranked 1st in Canada and 14th in the world for clinical medicine by Times Higher Education in 2013. The McMaster athletic teams are known as the Marauders, and are members of the Canadian Interuniversity Sport. Wikipedia.


Kim Y.,Pennsylvania State University | Kim Y.,McMaster University | Logan B.E.,Pennsylvania State University
Desalination | Year: 2013

Microbial desalination cells (MDCs) are a new, energy-sustainable method for using organic matter in wastewater as the energy source for desalination. The electric potential gradient created by exoelectrogenic bacteria desalinates water by driving ion transport through a series of ion-exchange membranes (IEMs). The specific MDC architecture and current conditions substantially affect the amount of wastewater needed to desalinate water. Other baseline conditions have varied among studies making comparisons of the effectiveness of different designs problematic. The extent of desalination is affected by water transport through IEMs by both osmosis and electroosmosis. Various methods have been used, such as electrolyte recirculation, to avoid low pH that can inhibit exoelectrogenic activity. The highest current density in an MDC to date is 8.4A/m2, which is lower than that produced in other bioelectrochemical systems. This implies that there is a room for substantial improvement in desalination rates and overall performance. We review here the state of the art in MDC design and performance, safety issues related to the use of MDCs with wastewater, and areas that need to be examined to achieve practical application of this new technology. © 2012 Elsevier B.V.


Harris G.L.H.,University of Waterloo | Poole G.B.,University of Melbourne | Harris W.E.,McMaster University
Monthly Notices of the Royal Astronomical Society | Year: 2014

We explore several correlations between various large-scale galaxy properties, particularly total globular cluster population (NGC), the central black hole mass (M•), velocity dispersion (nominally σe) and bulge mass (Mdyn). Our data sample of 49 galaxies, for which both NGC and M• are known, is larger than used in previous discussions of these two parameters and we employ the same sample to explore all pairs of correlations. Further, within this galaxy sample, we investigate the scatter in each quantity, with emphasis on the range of published values for σe and effective radius (Re) for any one galaxy. We find that these two quantities in particular are difficult to measure consistently and caution that precise intercomparison of galaxy properties involving Re and σe is particularly difficult. Using both conventional x2-minimization and Monte Carlo Markov Chain fitting techniques, we show that quoted observational uncertainties for all parameters are too small to represent the true scatter in the data. We find that the correlation between Mdyn and NGCis stronger than either the M•-σe or the M•-NGC relations. We suggest that this is because both the galaxy bulge population and NGC were fundamentally established at an early epoch during the same series of star-forming events. By contrast, although the seed for M• was likely formed at a similar epoch, its growth over time is less similar from galaxy to galaxy and thus less predictable. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.


Adams II T.A.,McMaster University | Barton P.I.,Massachusetts Institute of Technology
Fuel Processing Technology | Year: 2011

Several polygeneration process systems are presented which convert natural gas and coal to gasoline, diesel, methanol, and electricity. By using solid oxide fuel cells as the primary electricity generator, the presented systems improve upon a recently introduced concept by which natural gas is reformed inside the radiant cooler of a gasifier. Simulations and techno-economic analyses performed for a wide range of process configurations and market conditions show that this strategy results in significant efficiency and profitability improvements when CO2 capture and sequestration are employed. Market considerations for this analysis include variations in purchase prices of the coal and natural gas, sale prices of the products, and CO 2 emission tax rates. © 2011 Elsevier B.V. All rights reserved.


Moffat T.,McMaster University
Medical Anthropology Quarterly | Year: 2010

There has been a meteoric rise over the past two decades in the medical research and media coverage of the so-called global childhood obesity epidemic. Recently, in response to this phenomenon, there has been a spate of books and articles in the fields of critical sociology and cultural studies that have argued that this "epidemic" is socially constructed, what Natalie Boero (2007) dubs a "postmodern epidemic." As an anthropologist who has studied child nutrition and obesity in relation to poverty and the school environment, I am concerned about both the lack of reflexivity among medical researchers as well as critical scholars' treatment of the problem as entirely socially constructed. In this article I present both sides of this debate and then discuss how we can attempt to navigate a middle course that recognizes this health issue but also offers alternative approaches to those set by the biomedical agenda. © 2010 by the American Anthropological Association.


Negret A.,Horia Hulubei National Institute of Physics and Nuclear Engineering | Singh B.,McMaster University
Nuclear Data Sheets | Year: 2015

The experimental nuclear spectroscopic data for known nuclides of mass number 86 (Ga, Ge, As, Se, Br, Kr, Rb, Sr, Y, Zr, Nb, Mo, Tc) have been evaluated and presented together with Adopted properties for levels and γ rays. New high-spin data are available for 86Se, 86Br, 86Kr, 86Sr, 86Y, 86Zr and 86Mo; and lifetime data for high-spin states in 86Y and 86Zr. No significant new data since the 2001 NDS for A=86 have been reported for 86Rb and 86Nb. No data are yet available for excited states in 86Ga and 86As. The decay scheme of radioactive 86Ge is unknown, while those for 86Ga, 86As, 47.4 min isomer of 86Y, 86Nb and 86Tc are deemed as incomplete. Isomerism in 86Nb remains unconfirmed. This work supersedes the data presented in the previous NDS evaluation of A=86 published by 2001Si43. © 2014 Elsevier Inc.


This article responds to issues raised by Antilla et al. in the Journal of Clinical Epidemiology about the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group's approach to rating imprecision and GRADE's use of statistics. They argue that GRADE confuses statistical terms and should provide a stepwise rating of imprecision for making decisions. Here, a clarification of those perceptions is provided. GRADE's ratings of imprecision and other quality of evidence domains is an iterative process that may or may not consider people important thresholds of effects when systematic review authors rate imprecision. Regardless of ratings in systematic reviews, those suggesting decisions such as guideline panels, should consider if they agree or need to revise these suggested thresholds to make informed ratings about imprecision. Decision relevant thresholds are the result of a complex interplay between critical outcomes for a decision-making. The certainty in the evidence of one critical outcome and the resulting possible certainty range, which I conceptualize in this article, may influence ratings of other outcomes. To relieve systematic review authors of the often challenging burden of defining worthwhile or important effects for judging precision based on the optimal information size (OIS), a modified OIS or review information size (RIS) could be used to rate imprecision at the systematic review stage. The RIS focuses only on plausible rather plausible and worthwhile effects. The advantages of using the RIS include avoiding the reliance on statistical significance alone and the varying thresholds resulting from the importance and the baseline risk of the outcome on which the OIS relies. Finally, I argue that GRADE's certainty in the evidence is related to the statistical definition of accuracy but given GRADE's broad application to other ratings of certainty such as qualitative evidence, statistical accuracy does not serve as a definition for GRADE's quality or certainty in the evidence. © 2016 Elsevier Inc.


Gupta R.S.,McMaster University
Advances in Botanical Research | Year: 2013

Microbial genomes provide a rich resource for identifying molecular markers that can reliably distinguish different groups of photosynthetic organisms and provide insights into the origin and spread of photosynthesis. This review summarises work on molecular markers consisting of conserved signature indels (CSIs) and signature proteins that are specific for different phyla of photosynthetic bacteria and their major subclades. Based upon these markers and phylogenetic analyses, photosynthetic. Chloroflexi are divided into two suborders viz. Chloroflexineae and Roseiflexineae consistent with their biochemical, morphological and molecular characteristics. Within Cyanobacteria three major clades (referred to as Clade A, B and C) are distinguished at the highest phylogenetic/taxonomic levels. Phylogenetic analyses and several CSIs in key bacteriochlorophyll (BChl) biosynthesis proteins, BchL, BchN and BchB, provide evidence that their homologues in Proteobacteria have been acquired from Clade C Cyanobacteria, whereas those in the Chlorobi are derived from Chloroflexi by lateral gene transfers. Phylogenetic analyses and other CSIs in the sequentially duplicated proteins BchL, BchX and NifH provide evidence that the BchX homologues required for anoxygenic photosynthesis originated before the BchL homologues needed for oxygenic photosynthesis. Another CSI in the duplicated BchX-BchL proteins provides evidence that the BchL homologues of Heliobacteriaceae (Firmicutes phylum) are primitive in comparison to other photosynthetic bacteria. © 2013 Elsevier Ltd.


Dukas R.,McMaster University
Animal Behaviour | Year: 2013

All animals are highly plastic and rely on the modulation of gene action, physiology and behaviour to continuously modify their phenotypes. Compared to other types of plasticity, learning, defined as the internal representation of novel information, allows animals to better exploit environmental features unique to certain times and places. This distinctive property of learning gives it an enormous potential to promote evolution through increased robustness, innovation and speciation rate. First, learning can enhance robustness because it allows individuals to adopt new resources and avoid novel threats. Empirical examples include the modification of egg-laying timing and nesting site selection in birds and of egg-laying substrate choice in insects. Second, learning can lead to innovation because it often has an exploratory stage that can lead to the discovery and refinement through trial and error of new, fitness-enhancing features. The best examples are cases of social learning that lead to the exploitation of novel food sources followed by genetic changes that optimize use of the new diet. Finally, learning can increase the levels of assortative mating that lead to population divergence either when young imprint on their parents or when individuals restrict their mate choice criteria based on interactions with prospective mates. While the notion that learning can have strong effects on evolution is backed by theory and some data, we currently lack broad experimental evidence to support that claim. © 2013 The Association for the Study of Animal Behaviour.


Tarride J.E.,McMaster University
Arthritis and rheumatism | Year: 2012

Little is known about the burden of osteoarthritis (OA) in Canada. This study was undertaken to estimate the excess burden of OA in Ontario, the largest province in Canada. The records of Ontarian respondents to the Canadian Community Health Survey (CCHS) who provided consent to data linkage were linked to the Ontario Health Insurance Program physician claims database and the Discharge Abstract Database Inpatient and Day Procedure databases. Patients with OA (n = 1,474) were identified using CCHS 1.1 and the physician claims database. To determine the excess burden of OA, a control group matched by age, sex, and rural/urban status was created, with 3 controls per case (n = 4,422). Sociodemographic and medical characteristics, health-related quality of life, and 1-year physician, day (outpatient) procedure, and hospitalization costs were compared between the 2 groups. Regression analyses were performed to identify predictors of medical characteristics, health utility, and cost. The mean age of the OA patients and the control subjects was 66 years, and 74% of all study subjects were women. Several differences were observed between patients with OA and subjects without OA in terms of socioeconomic and medical characteristics. On a scale of 0-1, the mean utility value associated with OA was 0.68, compared to 0.84 for the control group (P < 0.0001), representing a utility decrement of 0.16. The 1-year physician, outpatient procedure, and hospitalization costs were significantly higher in the OA group than in the non-OA group ($2,233 Canadian versus $1,033 Canadian, respectively; P < 0.0001). These results indicate that the excess burden of OA in Ontario is considerable. Copyright © 2012 by the American College of Rheumatology.


Gonzalez A.,McMaster University
Paediatrics and Child Health (Canada) | Year: 2013

Childhood maltreatment represents a significant risk factor for the development of a number of mental and physical health outcomes. Converging evidence suggests that early adversity induces significant and persistent biological changes in individuals ('biological embedding'). The present review focuses on the impact of childhood maltreatment on the hypothalamic-pituitary- adrenal axis and immune system function in both children and adults. Research suggests that childhood maltreatment is associated with hypothalamic- pituitaryadrenal axis dysregulation and diurnal cortisol profiles, as well as stress reactivity. Furthermore, childhood maltreatment is associated with disruptions in various immune system markers including pro- and anti-inflammatory substances, and markers of cell-mediated immunity. The potential of interventions to reduce these negative biological effects in maltreated children is also discussed.


Resch B.,Medical University of Graz | Paes B.,McMaster University
Early Human Development | Year: 2011

Preterm infants are at increased risk of being rehospitalised during the first few months of life with severe respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) that usually manifests as apnea and hypoxemia. This occurs more commonly in preterm infants < 33. weeks gestational age (GA), but recent studies demonstrate that late preterm infants (those born between 34. weeks and 0. days to 36. weeks and 6. days GA) are equally susceptible to RSV LRTI as those with lower GA. Factors associated with severe LRTI include immaturity of both the humoral and cell-mediated immune system and interrupted lung development prior to 36. weeks GA which results in lower functional residual capacity, reduced compliance, diminished forced expiratory air flow and impaired gas exchange. Morbidity and mortality are significantly increased in late preterms compared to their term counterparts. Prophylaxis with palivizumab against RSV infection seems to be crucial. Due to the large number of infants in this age group, additional risk factors have been identified in order to tailor palivizumab prophylaxis effectively to those at highest risk for severe RSV LRTI. © 2011 Elsevier Ltd.


Ayeni O.,McMaster University
The journal of knee surgery | Year: 2012

A healthy meniscus is important for normal function of the knee. Numerous studies support that the repair of a torn meniscus is important to prevent degenerative changes in the knee. The ability to repair torn menisci is based on several factors including location, tear orientation, chronicity, and concomitant ligamentous knee injuries. In this systematic review, meniscal repair technology is evaluated. Specifically, the retear rates are compared between the arrow repair and the suture repair techniques. After searching three databases (PubMed, Cochrane Central Register of Controlled Trials, and Embase) and reviewing annual meeting abstracts from the American Orthopaedic Society for Sports Medicine (2005 to 2010), four studies (two observational and two randomized controlled trials) were selected for this systematic review. Due to the limited study number and variability between studies (study design, sample population, outcome measures, and surgical technique), a meta-analysis was not performed. The overall quality of the literature was poor and thus conclusions are limited. No clear superiority of one technique was determined by this review. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.


Ouellet C.,Brookhaven National Laboratory | Singh B.,McMaster University
Nuclear Data Sheets | Year: 2011

Nuclear spectroscopic information for experimentally investigated nuclides of mass 32 (Ne,Na,Mg,Al,Si, P,S,Cl,Ar) has been evaluated. The principal sources of the Adopted Levels presented for nuclides close to the stability line are Endt's evaluations (1990En08,1978En02). The data sets for reactions and decays, including all available gamma-ray data, are based mostly on the original literature. Except for the half-life of 32Ne decay, no other details about its decay characteristics are available. Structure data for 32Ne and 32Na are limited to only one excited state in each. The 32Mg nuclide is of central and prime relevance in the 'island of inversion' at or near N=20 semi-closed shell. The lifetime of only one excited state in 32Mg is known. The spin-parity assignments of several levels in this nucleus are not quite firm. The structure of 32Ar is limited to only one known state at low energy and two resonances in the giant-dipole excitation region. The 32P, 32S and 32Cl remain the most extensively studied nuclei through various reaction channels. © 2011 Elsevier Inc.


Khalaf A.A.,McMaster University
Acta Materialia | Year: 2016

Controlled diffusion solidification (CDS) is a novel process. It depends on mixing two precursor alloys that have different thermal masses to make another alloy, and then, the mixture is poured into a near net-shaped mold. The process changes the microstructure of the product to a non-dendritic structure. The mechanism of CDS depends on three considerations: mixing two precursor alloys, nucleation and growth. It has been found that the turbulence that occurs during the mixing blends the two precursor alloys and results in a mixture that has a matrix and morphologies. The matrix forms of the precursor alloy that has a higher mass (Alloy1), while the morphologies form of the alloy that has a lower mass (Alloy2). Nucleation occurs in the alloy that has the higher liquidus temperature near the boundary with the second alloy, thus forming the primary Al phase that grows away from the second alloy. The temperature of the second alloy strongly affects the stability of the solid-liquid interface. A two-dimension model was built using the heat, diffusion and Navier stokes equations to understand the probability of the nucleation, the growth rate and the stability of the solid-liquid interface. The results show that the solid-liquid interface is stable during the CDS process compared to during conventional casting processes. The numerical results were supported by experimental results and scanning electron microscopy (SEM). © 2015 Acta Materialia Inc.


Burke J.D.,University of Pittsburgh | Rowe R.,University of Sheffield | Boylan K.,McMaster University
Journal of Child Psychology and Psychiatry and Allied Disciplines | Year: 2014

Background Oppositional defiant disorder(ODD) is considered to be a disorder of childhood, yet evidence suggests that prevalence rates of the disorder are stable into late adolescence and trajectories of symptoms persist into young adulthood. Functional outcomes associated with ODD through childhood and adolescence include conflict within families, poor peer relationships, peer rejection, and academic difficulties. Little examination of functional outcomes in adulthood associated with ODD has been undertaken. Method Data for the present analyses come from a clinic referred sample of 177 boys aged 7-12 followed up annually to age 18 and again at age 24. Annual parental report of psychopathology through adolescence was used to predict self-reported functional outcomes at 24. Results Controlling for parent reported symptoms of attention deficit hyperactivity disorder (ADHD), Conduct disorder (CD), depression and anxiety, ODD symptoms from childhood through adolescence predicted poorer age 24 functioning with peers, poorer romantic relationships, a poorer paternal relationship, and having nobody who would provide a recommendation for a job. CD symptoms predicted workplace problems, poor maternal relationship, lower academic attainment, and violent injuries. Only parent reported ODD symptoms and child reported CD symptoms predicted a composite of poor adult outcomes. Conclusion Oppositional defiant disorder is a disorder that significantly interferes with functioning, particularly in social or interpersonal relationships. The persistence of impairment associated with ODD into young adulthood calls for a reconsideration of ODD as a disorder limited to childhood. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.


Burgessa C.P.,Perimeter Institute for Theoretical Physics | Van Nierop L.,McMaster University
Journal of High Energy Physics | Year: 2011

We compute the back-reaction of pairs of codimension-two branes within an explicit flux-stabilized compactification, to trace how its properties depend on the parameters that define the brane-bulk couplings. Both brane tension and magnetic couplings to the stabilizing flux play an important role in the resulting dynamics, with the magnetic coupling allowing some of the flux to be localized on the branes (thus changing the flux-quantization conditions). We find that back-reaction lifts the classical flat directions of the bulk supergravity, and we calculate both the scalar potential and changes to the extra-dimensional and on-brane geometries that result, as functions of the assumed brane couplings. When linearized about simple rugby-ball geometries the resulting solutions allow a systematic exploration of the system's response. Several of the systems we explore have remarkable properties. Among these are a propensity for the extra dimensions to stabilize at exponentially large sizes, providing a mechanism for generating extremely large volumes. In some circumstances the brane-dilaton coupling allows the bulk dilaton to adjust to suppress the on-brane curvature parametrically below the change in brane tension, potentially providing a mechanism for reducing the vacuum energy. We explore the stability of this suppression to quantum effects in the case where their strength is controlled by the value of the field along the classical flat direction, and find it can (but need not) be stable. © SISSA 2011.


Lee S.-S.,McMaster University | Lee S.-S.,Perimeter Institute for Theoretical Physics
Nuclear Physics B | Year: 2011

Based on the earlier work [S.-S. Lee, Nucl. Rev. B 832 (2010) 567], we derive a holographic dual for the D-dimensional U(N) lattice gauge theory from a first principle construction. The resulting theory is a lattice field theory of closed loops, dubbed as lattice loop field theory which is defined on a (D+1)-dimensional space. The lattice loop field theory is well defined non-perturbatively, and it becomes weakly coupled and local in the large N limit with a large 't Hooft coupling. © 2011 Elsevier B.V.


O'Donnell M.,McMaster University
European heart journal | Year: 2012

Cognitive impairment may increase the risk of all cardiovascular (CV) events. We prospectively evaluated the independent association between Mini-Mental State Examination (MMSE) score and myocardial infarction, stroke, hospital admission for heart failure and mortality, and their CV composite (major CV events), in a large high-risk CV population. Mini-Mental State Examination was recorded at baseline in 30 959 individuals enrolled into two large parallel trials of patients with prior cardiovascular disease or high-risk diabetes and followed for a median of 56 months. We used a Cox regression model to determine the association between MMSE score and incident CV events and non-CV mortality, adjusted for age, sex, education, history of vascular events, dietary factors, blood pressure, smoking, glucose, low-density lipoprotein, high-density lipoprotein, CV medications, exercise, alcohol intake pattern, depression, and psychosocial stress. Patients were categorized into four groups based on baseline MMSE; 30 (reference), 29-27, 26-24, and <24. Compared with patients with an MMSE of 30 (n = 9624), those with scores of 29-27 [n = 13 867; hazard ratio (HR) 1.08; 95% confidence intervals (CI) 1.01-1.16], 26-24 (n = 4764; HR: 1.15; 95% CI: 1.05-1.26) and <24 (n = 2704; HR: 1.35; 95% CI: 1.21-1.50) had a graded increase in the risk of major vascular events (P < 0.0001). Mini-Mental State Examination score was significantly associated with each of the individual components of the composite, except myocardial infarction. There was also no association between baseline MMSE and hospitalization for unstable or new angina. Within MMSE domains, impairments in orientation to place (HR: 1.52; 1.25-1.85), attention-calculation (HR: 1.10; 1.02-1.18), recall (HR: 1.10; 1.04-1.16), and design copy (HR: 1.15; 1.06-1.24) were the most predictive of major vascular events and mortality. The magnitude of increased risk of CV events associated with an MMSE <24 was similar to a previous history of stroke. In people at increased CV risk, impairments on baseline cognitive testing are associated with a graded increase in the risk of stroke, congestive heart failure, and CV death, but not coronary events. An MMSE score of <24 increased CV disease risk to the same extent as a previous stroke.


The predictive model based soft sensor technique has become increasingly important to provide reliable online measurements, facilitate advanced process control and optimization, and improve product quality in process industries. The conventional soft sensors are normally single-model based and thus may not be appropriate for processes with shifting operating phases or conditions and the underlying changing dynamics. In this study, a multiway Gaussian mixture model (MGMM) based adaptive kernel partial least-squares (AKPLS) method is proposed to handle online quality prediction of batch or semibatch processes with multiple operating phases. The three-dimensional measurement data are first preprocessed and unfolded into two-dimensional matrix. Then, the multiway Gaussian mixture model is estimated in order to identify and isolate different operating phases. Further, the process and quality measurements are separated into multiple segments corresponding to those identified phases, and the various localized kernel PLS models are built in the high-dimensional nonlinear feature space to characterize the shifting dynamics across different operating phases. Using Bayesian inference strategy, each process measurement sample of a new batch is classified into a particular phase with the maximal posterior probability, and thus, the local kernel PLS model representing the identical phase can be adaptively chosen for online quality variable prediction. The presented soft sensor modeling method is applied to a simulated multiphase penicillin fermentation process, and the computational results demonstrate that the proposed MGMM-AKPLS approach is superior to the conventional kernel PLS model in terms of prediction accuracy and model reliability. © 2012 American Chemical Society.


Gagliardi A.R.,A+ Network | Brouwers M.C.,McMaster University
BMJ Open | Year: 2015

Objective: Providers and patients are most likely to use and benefit from guidelines accompanied by implementation support. Guidelines published in 2007 and earlier assessed with the Appraisal of Guidelines, Research and Evaluation (AGREE) instrument scored poorly for applicability, which reflects the inclusion of implementation instructions or tools. The purpose of this study was to examine the applicability of guidelines published in 2008 or later and identify factors associated with applicability. Design: Systematic review of studies that used AGREE to assess guidelines published in 2008 or later. Data sources: MEDLINE and EMBASE were searched from 2008 to July 2014, and the reference lists of eligible items. Two individuals independently screened results for English language studies that reviewed guidelines using AGREE and reported all domain scores, and extracted data. Descriptive statistics were calculated across all domains. Multilevel regression analysis with a mixed effects model identified factors associated with applicability. Results: Of 245 search results, 53 were retrieved as potentially relevant and 20 studies were eligible for review. The mean and median domain scores for applicability across 137 guidelines published in 2008 or later were 43.6% and 42.0% (IQR 21.8-63.0%), respectively. Applicability scored lower than all other domains, and did not markedly improve compared with guidelines published in 2007 or earlier. Country (UK) and type of developer (disease-specific foundation, non-profit healthcare system) appeared to be associated with applicability when assessed with AGREE II (not original AGREE). Conclusions: Despite increasing recognition of the need for implementation tools, guidelines continue to lack such resources. To improve healthcare delivery and associated outcomes, further research is needed to establish the type of implementation tools needed and desired by healthcare providers and consumers, and methods for developing high-quality tools.


Chouinard V.,McMaster University
Health and Place | Year: 2012

This article aims to advance our understanding of women's and men's experiences of negotiating bipolar 'madness' in society and space. It addresses gaps in the clinical literature on life with bipolar and geographic accounts of 'madness' and psycho-emotional distress by considering altered ways of being in place that bipolar 'madness' entails and how narrative sense is made of these. Conceptually, I build on Cosgrove's (2000) approach to psycho-emotional distress and geographic insights about being 'mad' in place. Methodologically and empirically, I draw on thematic narrative analysis of autobiographies of living with bipolar. Key findings include altered paradoxically (dis)embodied ways of being-in-place, 'fractured' or 'whole' senses of self and ways of relating to people/places, 'straddling' 'real' and 'delusional' worlds and bipolar ways of negotiating places are not straightforwardly 'irrational'. While narrative accounts most often invoke dominant discourses about bipolar, sometimes these are challenged through 'rescripting' and 'revaluing mad' identities and ways of being in place. In conclusion, key findings and avenues for future geographical research are discussed. © 2011 Elsevier Ltd.


Kline K.A.,Nanyang Technological University | Bowdish D.M.E.,McMaster University
Current Opinion in Microbiology | Year: 2016

The global population is rapidly aging. Currently, 566 million people are ≥65 years old worldwide, with estimates of nearly 1.5 billion by 2050, particularly in developing countries. Infections constitute a third of mortality in people ≥65 years old. Moreover, lengthening life spans correlate with increased time in hospitals or long-term care facilities and exposure to drug-resistant pathogens. Indeed, the risk of nosocomial infections increases with age, independent of duration spent in healthcare facilities. In this review, we summarize our understanding of how the aging immune system relates to bacterial infections. We highlight the most prevalent infections affecting aging populations including pneumonia, urinary tract infections, and wound infections and make recommendations for future research into infection in aging populations. © 2015 Elsevier Ltd.


Harris W.E.,McMaster University
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2010

The ensemble of all star clusters in a galaxy constitutes its star cluster system. In this review, the focus of the discussion is on the ability of star clusters, particularly the systems of old massive globular clusters (GCs), to mark the early evolutionary history of galaxies. I review current themes and key findings in GC research, and highlight some of the outstanding questions that are emerging from recent work. © 2010 The Royal Society.


McPhee J.B.,Ryerson University | Schertzer J.D.,McMaster University
Clinical Science | Year: 2015

The bacteria that inhabit us have emerged as factors linking immunity and metabolism. Changes in our microbiota can modify obesity and the immune underpinnings of metabolic diseases such as Type 2 diabetes. Obesity coincides with a low-level systemic inflammation, which also manifests within metabolic tissues such as adipose tissue and liver. This metabolic inflammation can promote insulin resistance and dysglycaemia. However, the obesity and metabolic disease-related immune responses that are compartmentalized in the intestinal environment do not necessarily parallel the inflammatory status of metabolic tissues that control blood glucose. In fact, a permissive immune environment in the gut can exacerbate metabolic tissue inflammation. Unravelling these discordant immune responses in different parts of the body and establishing a connection between nutrients, immunity and the microbiota in the gut is a complex challenge. Recent evidence positions the relationship between host gut barrier function, intestinal T cell responses and specific microbes at the crossroads of obesity and inflammation in metabolic disease. A key problem to be addressed is understanding how metabolite, immune or bacterial signals from the gut are relayed and transferred into systemic or metabolic tissue inflammation that can impair insulin action preceding Type 2 diabetes. © 2015 Authors.


Cheng J.J.,McMaster University | Berry P.,Climate Change and Health Office
International Journal of Public Health | Year: 2013

Objectives: Many public health adaptation strategies have been identified in response to climate change. This report reviews current literature on health co-benefits and risks of these strategies to gain a better understanding of how they may affect health. Methods: A literature review was conducted electronically using English language literature from January 2000 to March 2012. Of 812 articles identified, 22 peer-reviewed articles that directly addressed health co-benefits or risks of adaptation were included in the review. Results: The co-benefits and risks identified in the literature most commonly relate to improvements in health associated with adaptation actions that affect social capital and urban design. Health co-benefits of improvements in social capital have positive influences on mental health, independently of other determinants. Risks included reinforcing existing misconceptions regarding health. Health co-benefits of urban design strategies included reduced obesity, cardiovascular disease and improved mental health through increased physical activity, cooling spaces (e.g., shaded areas), and social connectivity. Risks included pollen allergies with increased urban green space, and adverse health effects from heat events through the use of air conditioning. Conclusions: Due to the current limited understanding of the full impacts of the wide range of existing climate change adaptation strategies, further research should focus on both unintended positive and negative consequences of public health adaptation. © 2012 The Author(s).


Parnas D.L.,McMaster University
Communications of the ACM | Year: 2010

An illustration of the problems caused by a lack of discipline in software development and our failure to apply what is known in the field. © 2010 ACM.


Fiacconi C.M.,McMaster University
Experimental aging research | Year: 2013

BACKGROUND/STUDY CONTEXT: The perception of naturalistic events depends on the ability to integrate perceptual information from multiple sensory systems. Currently, little is known about how multisensory integration is affected by normal aging. The authors conducted two experiments to investigate audiovisual temporal processing in younger (18-29 years) and older (70+ years) adults. In both experiments, participants were presented with a brief visual stimulus and a brief auditory stimulus separated by various temporal offsets, and participants judged which stimulus was presented first. In Experiment 1, the auditory and visual stimuli were presented from the same perceived location, whereas in Experiment 2 they were presented from different locations. The authors found no effect of stimulus location, and no evidence of age-related declines in performance in either experiment. Older adults appear to retain the ability to discriminate the temporal order of audiovisual stimuli and can perform similarly to younger adults.


Plastic deformation of crystals and glasses produces internal strains (stresses), which change their energy and other thermodynamic properties. On annealing, these stresses decrease at a rate faster than the structure relaxes toward the equilibrium state. Mechanism of such relaxations in crystals differs from that in glasses and it also differs for glasses of different types. In all cases, the energy related properties decrease with time isothermally and on heating, resembling the structure relaxation of a stress-free glass. We consider these features and argue that kinetics of enthalpy loss with time yields the rate constants of the stress release and of the structure change, and not the viscosity determining α-relaxation time. Since thermal cycling does not recover the enthalpy from internal stresses, a glass with stresses has neither a glass-softening temperature, Tg, nor a fictive temperature, T f. Plastic deformation would not rejuvenate a physically aged glass to the properties of its un-aged state. The Prigogine-Defay ratio can be extended to all Tfs, and used to investigate the effect of distribution of relaxation times on its value, but it can not be defined for an internally stressed glass. After discussing the effects of annealing on the heat capacity and DSC scans, we conclude that on slow heating, glass with deformation-induced stresses would show two exothermic minima, and normal glass would show only one such minimum. Temperature-modulated scanning calorimetry would also distinguish an internally stressed glass from an equally high-enthalpy, stress-free glass. Enthalpy matching procedure would yield inaccurate Tf value of a plastically deformed glass, but not of a hyperquenched glass. Phenomenological analysis given here has consequences for interpretation of the calorimetric changes observed on heating the shear-amorphized, as well as pressure-collapsed states of crystals. © 2014 Elsevier B.V.


Crohn's disease is a chronic inflammatory condition of the gastrointestinal tract in which alterations to the bacterial community contribute to disease. Adherent-invasive Escherichia coli are associated with human Crohn's disease; however, their role in intestinal immunopathology is unclear because of the lack of an animal model compatible with chronic timescales. Here we establish chronic adherent-invasive Escherichia coli infection in streptomycin-treated conventional mice (CD1, DBA/2, C3H, 129e and C57BL/6), enabling the study of host response and immunopathology. Adherent-invasive Escherichia coli induces an active T-helper 17 response, heightened levels of proinflammatory cytokines and fibrotic growth factors, with transmural inflammation and fibrosis. Depletion of CD8+ T cells increases caecal bacterial load, pathology and intestinal fibrosis in C57BL/6 mice, suggesting a protective role. Our findings provide evidence that chronic adherent-invasive Escherichia coli infections result in immunopathology similar to that seen in Crohn's disease. With this model, research into the host and bacterial genetics associated with adherent-invasive Escherichia coli-induced disease becomes more widely accessible.


Agnelli G.,University of Perugia | Cohen A.,Kings College | Curto M.,Pfizer | Gallus A.S.,Flinders University | And 4 more authors.
New England Journal of Medicine | Year: 2013

BACKGROUND: Apixaban, an oral factor Xa inhibitor that can be administered in a simple, fixed-dose regimen, may be an option for the extended treatment of venous thromboembolism. METHODS: In this randomized, double-blind study, we compared two doses of apixaban (2.5 mg and 5 mg, twice daily) with placebo in patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy and for whom there was clinical equipoise regarding the continuation or cessation of anticoagulation therapy. The study drugs were administered for 12 months. RESULTS: A total of 2486 patients underwent randomization, of whom 2482 were included in the intention-to-treat analyses. Symptomatic recurrent venous thromboembolism or death from venous thromboembolism occurred in 73 of the 829 patients (8.8%) who were receiving placebo, as compared with 14 of the 840 patients (1.7%) who were receiving 2.5 mg of apixaban (a difference of 7.2 percentage points; 95% confidence interval [CI], 5.0 to 9.3) and 14 of the 813 patients (1.7%) who were receiving 5 mg of apixaban (a difference of 7.0 percentage points; 95% CI, 4.9 to 9.1) (P<0.001 for both comparisons). The rates of major bleeding were 0.5% in the placebo group, 0.2% in the 2.5-mg apixaban group, and 0.1% in the 5-mg apixaban group. The rates of clinically relevant nonmajor bleeding were 2.3% in the placebo group, 3.0% in the 2.5-mg apixaban group, and 4.2% in the 5-mg apixaban group. The rate of death from any cause was 1.7% in the placebo group, as compared with 0.8% in the 2.5-mg apixaban group and 0.5% in the 5-mg apixaban group. CONCLUSIONS: Extended anticoagulation with apixaban at either a treatment dose (5 mg) or a thromboprophylactic dose (2.5 mg) reduced the risk of recurrent venous thromboembolism without increasing the rate of major bleeding. (Funded by Bristol-Myers Squibb and Pfizer; AMPLIFY-EXT ClinicalTrials.gov number, NCT00633893.) Copyright © 2012 Massachusetts Medical Society.


Das S.,University of Lethbridge | Bhaduri R.K.,McMaster University
Classical and Quantum Gravity | Year: 2015

We show that dark matter consisting of bosons of mass of about 1 eV or less has a critical temperature exceeding the temperature of the Universe at all times, and hence would have formed a Bose-Einstein condensate at very early epochs. We also show that the wavefunction of this condensate, via the quantum potential it produces, gives rise to a cosmological constant that may account for the correct dark energy content of our Universe. We argue that massive gravitons or axions are viable candidates for these constituents. In the far future this condensate is all that remains of our Universe. © 2015 IOP Publishing Ltd.


Schwarcz H.P.,McMaster University
Seminars in Cell and Developmental Biology | Year: 2015

Mineral makes up more than half the volume of bone, but its spatial and structural relationship to collagen and other proteins is still a matter of debate. Due to the nanometer-size of bone crystals this matter can be resolved only with transmission electron microscope (TEM) images. Using sections cut with an ultramicrotome, previous investigators determined most mineral lies in the 40. nm wide gap zone in collagen fibrils. Using less invasive sectioning methods (ion milling and focused ion beam [FIB]) reveals that most mineral is extrafibrillar, occurring in the form of mineral lamellae, polycrystalline plates 300. nm or more long, packed around collagen fibrils in stacks of four or more lamellae <1. nm apart. While Ca and P also occur in the gap zone, they do not appear to be in the form of well-crystallized apatite. This new model for bone ultrastructure resolves outstanding problems presented by the previous model. © 2015 Elsevier Ltd.


Mills E.J.,Stanford University | Thorlund K.,Stanford University | Thorlund K.,McMaster University | Eapen S.,University of Ottawa | And 2 more authors.
Circulation | Year: 2014

BACKGROUND-: Stopping smoking is associated with many important improvements in health and quality of life. The use of cessation medications is recommended to increase the likelihood of quitting. However, there is historical and renewed concern that smoking cessation therapies may increase the risk of cardiovascular disease events associated within the quitting period. We aimed to examine whether the 3 licensed smoking cessation therapies-nicotine replacement therapy, bupropion, and varenicline-were associated with an increased risk of cardiovascular disease events using a network meta-analysis. METHODS AND RESULTS-: We searched 10 electronic databases, were in communication with authors of published randomized, clinical trials (RCTs), and accessed internal US Food and Drug Administration reports. We included any RCT of the 3 treatments that reported cardiovascular disease outcomes. Among 63 eligible RCTs involving 21 nicotine replacement therapy RCTs, 28 bupropion RCTs, and 18 varenicline RCTs, we found no increase in the risk of all cardiovascular disease events with bupropion (relative risk [RR], 0.98; 95% confidence interval [CI], 0.54-1.73) or varenicline (RR, 1.30; 95% CI, 0.79-2.23). There was an elevated risk associated with nicotine replacement therapy that was driven predominantly by less serious events (RR, 2.29; 95% CI, 1.39-3.82). When we examined major adverse cardiovascular events, we found a protective effect with bupropion (RR, 0.45; 95% CI, 0.21-0.85) and no clear evidence of harm with varenicline (RR, 1.34; 95% CI, 0.66-2.66) or nicotine replacement therapy (RR, 1.95; 95% CI, 0.26-4.30). CONCLUSION-: Smoking cessation therapies do not appear to raise the risk of serious cardiovascular disease events. © 2013 American Heart Association, Inc.


Chouinard V.,McMaster University
Antipode | Year: 2014

Most of what is known about disabled women's and men's lives is based on research conducted in the global North despite the fact that 80% of the world's one billion disabled people live in countries of the global South. This article addresses this gap in our understanding of disabled people's lives by examining impairment and disability as outcomes of processes of social embodiment that unfold in an unequal global capitalist order. Drawing on 87 interviews conducted with disabled women and men in Guyana, the article illustrates how colonial and neo-colonial relations of power and processes of development give rise to material conditions of life such as extreme poverty and male violence that contribute to impairment and disability. The article concludes by discussing the article's contributions, challenges in developing southern perspectives on impairment and disability, and the need to address socio-spatial injustices experienced by disabled people in the global South. © 2013 Antipode Foundation Ltd.


Jeffrey I.,McMaster University
Thrombosis and Haemostasis | Year: 2014

Acute coronary syndrome (ACS) is a medical emergency. Patients who survive the initial event remain at risk of recurrent cardiovascular events. In most cases, ACS is triggered by thrombosis after rupture of an atherosclerotic plaque. Key to thrombus formation at this site is the generation of thrombin, which not only converts fibrinogen to fibrin but also serves as a potent platelet agonist and induces platelet aggregation at the site of vascular injury. Although dual antiplatelet therapy is more effective for the prevention of recurrent events than aspirin alone after ACS, there remains an approximately 10 % risk of recurrent ischaemic events at one year. Recent studies have evaluated whether the addition of an anticoagulant to antiplatelet therapy reduces the risk of recurrent ischaemia after an ACS event. Rivaroxaban, an oral factor Xa inhibitor, attenuates thrombin generation. When used in conjunction with dual antiplatelet therapy in patients with stabilised ACS, rivaroxaban 2.5 mg twice daily significantly reduced the risk of the composite endpoint of cardiovascular death, myocardial infarction and stroke compared with placebo. Although it increased the risk of bleeding, rivaroxaban was associated with a reduction in mortality; a finding that supports the use of a dual-pathway approach that combines anticoagulant and antiplatelet therapy. This review explores the pathophysiology of ACS to provide perspective on the results of recent clinical trials with novel oral anticoagulants for ACS and to identify their potential role in this setting. © Schattauer 2014.


Paez A.,McMaster University
Journal of Transport Geography | Year: 2013

Exploratory Spatial Data Analysis of attitudinal variables can provide useful information about underlying behavioral processes. In this paper, elemental symbol mapping and spatial association analysis techniques are applied to travelers' attitudes. Attitudinal data, drawn from a recent travel survey conducted in McMaster University (Hamilton, Canada) among staff, students, and faculty, are analyzed. The place of residence of the respondents is geocoded in order to map the responses, and the spatial pattern of the qualitative/ordinal attitudinal variables is analyzed using the Q(m) statistic. Analysis of a selection of variables shows how some attitudes appear to develop independently from the local environments, whereas others are related to a preference towards certain types of local environments or social aspects of the local environment, which suggests underlying processes of self-selection or adaptation. © 2012 Elsevier Ltd.


Analyses of genome sequences, by some approaches, suggest that the widespread occurrence of horizontal gene transfers (HGTs) in prokaryotes disguises their evolutionary relationships and have led to questioning of the Darwinian model of evolution for prokaryotes. These inferences are critically examined in the light of comparative genome analysis, characteristic synapomorphies, phylogenetic trees and Darwin's views on examining evolutionary relationships. Genome sequences are enabling discovery of numerous molecular markers (synapomorphies) such as conserved signature indels (CSIs) and conserved signature proteins (CSPs), which are distinctive characteristics of different prokaryotic taxa. Based on these molecular markers, exhibiting high degree of specificity and predictive ability, numerous prokaryotic taxa of different ranks, currently identified based on the 16S rRNA gene trees, can now be reliably demarcated in molecular terms. Within all studied groups, multiple CSIs and CSPs have been identified for successive nested clades providing reliable information regarding their hierarchical relationships and these inferences are not affected by HGTs. These results strongly support Darwin's views on evolution and classification and supplement the current phylogenetic framework based on 16S rRNA in important respects. The identified molecular markers provide important means for developing novel diagnostics, therapeutics and for functional studies providing important insights regarding prokaryotic taxa. © FEMS 2016.


Szymanski T.H.,McMaster University
IEEE Communications Magazine | Year: 2016

A convergence is occurring in the networking world. Industrial networks currently provide deterministic services in robotic factories and aircraft, while the best effort Internet of Things provides best effort services for consumers. We argue that a convergence should occur, and that a future converged Industrial Internet of Things (IIoT) should support both best effort and deterministic services, with very low latency and jitter. This article presents the design of a deterministic IIoT core network consisting of many simple deterministic packet switches configured by an SDN control plane. The use of deterministic communications can reduce router buffer sizes by a factor of ≥ 1000, and can reduce end-to-end latencies to the speed of light in fiber. A speed-of-light deterministic core network can have a profound impact on virtually all consumer services such as multimedia distribution, e-Commerce, and cloud computing or gaming systems. Highly aggregated video streams can be delivered over a deterministic virtual network with very high link utilization (≤ 100 percent), very low packet jitter (≤ 10 μs), and zero congestion. In addition to improving consumer services, a converged deterministic IIoT core network can save billions of dollars per year as a result of significantly improved network utilization and energy efficiency. © 2016 IEEE.


Gupta R.S.,McMaster University
Antonie van Leeuwenhoek, International Journal of General and Molecular Microbiology | Year: 2011

The prokaryotic organisms can be divided into two main groups depending upon whether their cell envelopes contain one membrane (monoderms) or two membranes (diderms). It is important to understand how these and other variations that are observed in the cell envelopes of prokaryotic organisms have originated. In 2009, James Lake proposed that cells with two membranes (primarily Gram-negative bacteria) originated from an ancient endosymbiotic event involving an Actinobacteria and a Clostridia (Lake 2009). However, this Perspective argues that this proposal is based on a number of incorrect assumptions and the data presented in support of this model are also of questionable nature. Thus, there is no reliable evidence to support the endosymbiotic origin of double membrane bacteria. In contrast, many observations suggest that antibiotic selection pressure was an important selective force in prokaryotic evolution and that it likely played a central role in the evolution of diderm (Gram-negative) bacteria. Some bacterial phyla, such as Deinococcus-Thermus, which lack lipopolysaccharide (LPS) and yet contain some characteristics of the diderm bacteria, are postulated as evolutionary intermediates (simple diderms) in the transition between the monoderm bacterial taxa and the bacterial groups that have the archetypal LPS-containing outer cell membrane found in Gram-negative bacteria. It is possible to distinguish the two stages in the evolution of diderm-LPS cells (viz. monoderm bacteria → simple diderms lacking LPS → LPS containing archetypal diderm bacteria) by means of conserved inserts in the Hsp70 and Hsp60 proteins. The insert in the Hsp60 protein also distinguishes the traditional Gram-negative diderm bacterial phyla from atypical taxa of diderm bacteria (viz. Negativicutes, Fusobacteria, Synergistetes and Elusimicrobia). The Gram-negative bacterial phyla with an LPS-diderm cell envelope, as defined by the presence of the Hsp60 insert, are indicated to form a monophyletic clade and no loss of the outer membrane from any species from this group seems to have occurred. This argues against the origin of monoderm prokaryotes from diderm bacteria by loss of outer membrane. © 2011 The Author(s).


Nakamura I.,California Institute of Technology | Shi A.-C.,McMaster University | Wang Z.-G.,California Institute of Technology
Physical Review Letters | Year: 2012

Using field-theoretic techniques, we study the solvation of salt ions in liquid mixtures, accounting for the permanent and induced dipole moments, as well as the molecular volume of the species. With no adjustable parameters, we predict solvation energies in both single-component liquids and binary liquid mixtures that are in excellent agreement with experimental data. Our study shows that the solvation energy of an ion is largely determined by the local response of the permanent and induced dipoles, as well as the local solvent composition in the case of mixtures, and does not simply correlate with the bulk dielectric constant. In particular, we show that, in a binary mixture, it is possible for the component with the lower bulk dielectric constant but larger molecular polarizability to be enriched near the ion. © 2012 American Physical Society.


Andrews G.J.,McMaster University
Health and Place | Year: 2011

Recent research in the geography of health care moves beyond distributive concerns focusing more sensitively on the nature of health care settings. As part of this, a growing number of studies explore the importance of individuals' personal circumstances on their emplaced experiences and agency. Extending this line of inquiry, and drawing on ideas in emotional geographies, the current study illustrates how experiences and agency can be impacted profoundly by needle phobia. Interviews with 11 self-identifying sufferers explore the physical, emotional, behavioral and spatial manifestations of their condition. Specifically how their fear of, and reactions to, clinical objects and procedures (needles and their insertion by health professionals into the body) and health care settings (that possess the risk of encountering or host the encounters with, these objects and procedures), can combine as a single spatial affect. © 2011 Elsevier Ltd.


Zhang T.,Huazhong University of Science and Technology | Chen L.,Huazhong University of Science and Technology | Li X.,McMaster University
Optics Express | Year: 2013

Considering the dielectric permittivity of graphene can be tuned to be negative by external electric field, we propose to construct alternating graphene/dielectric multilayer based optical hyperlens for far-field subdiffraction imaging at mid-infrared frequencies. For such a scheme, hyperbolic dispersion curve can be achieved under the condition that the thickness of dielectric layer is made comparable to that of graphene layer, which is capable of supporting the propagation of evanescent wave with large wave vector. Simulation results by finite-element method demonstrate that two point sources with separation far below the diffraction limit can be magnified by the systems to the extent that conventional far-field optical microscopy can further manipulate. Such a hyperlens has the advantage of operating in a wideband region due to the tunability of graphene's dielectric permittivity as opposed to previous metal based hyperlens, enabling the potential applications in real-time super-resolution imaging, nanolithography, and sensing. ©2013 Optical Society of America.


Galef B.G.,McMaster University
Current Biology | Year: 2013

A recent study shows that subordinate rats reduce their rate of sniffing while dominants explore their faces thus delaying dominants' subsequent aggression. Sniffing not only facilitates acquisition of olfactory information, but unexpectedly, also serves as a medium for communication. © 2013 Elsevier Ltd.


Cuthbertson L.,University of Guelph | Cuthbertson L.,McMaster University | Kos V.,University of Guelph | Whitfield C.,University of Guelph
Microbiology and Molecular Biology Reviews | Year: 2010

Complex glycoconjugates play critical roles in the biology of microorganisms. Despite the remarkable diversity in glycan structures and the bacteria that produce them, conserved themes are evident in the biosynthesis-export pathways. One of the primary pathways involves representatives of the ATP-binding cassette (ABC) transporter superfamily. These proteins are responsible for the export of a wide variety of cell surface oligo- and polysaccharides in both Gram-positive and Gram-negative bacteria. Recent investigations of the structure and function of ABC transporters involved in the export of lipopolysaccharide O antigens have revealed two fundamentally different strategies for coupling glycan polymerization to export. These mechanisms are distinguished by the presence (or absence) of characteristic nonreducing terminal modifications on the export substrates, which serve as chain termination and/or export signals, and by the presence (or absence) of a discrete substrate-binding domain in the nucleotide-binding domain polypeptide of the ABC transporter. A bioinformatic survey examining ABC exporters from known oligo- and polysaccharide biosynthesis loci identifies conserved nucleotide-binding domain protein families that correlate well with themes in the structures and assembly of glycans. The familial relationships among the ABC exporters generate hypotheses concerning the biosynthesis of structurally diverse oligo- and polysaccharides, which play important roles in the biology of bacteria with different lifestyles. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Hutchison B.,McMaster University | Glazier R.,Institute for Clinical Evaluative science
Health Affairs | Year: 2013

Primary care in Ontario, Canada, has undergone a series of reforms designed to improve access to care, patient and provider satisfaction, care quality, and health system efficiency and sustainability. We highlight key features of the reforms, which included patient enrollment with a primary care provider; funding for interprofessional primary care organizations; and physician reimbursement based on varying blends of fee-for-service, capitation, and pay-for-performance. With nearly 75 percent of Ontario's population now enrolled in these new models, total payments to primary care physicians increased by 32 percent between 2006 and 2010, and the proportion of Ontario primary care physicians who reported overall satisfaction with the practice of medicine rose from 76 percent in 2009 to 84 percent in 2012. However, primary care in Ontario also faces challenges. There is no meaningful performance measurement system that tracks the impact of these innovations, for example. A better system of risk adjustment is also needed in capitated plans so that groups have the incentive to take on high-need patients. Ongoing investment in these models is required despite fiscal constraints. We recommend a clearly articulated policy road map to continue the transformation. © 2013 Project HOPE-The People-to-People Health Foundation, Inc.


Johnson N.J.J.,University of Victoria | Korinek A.,McMaster University | Dong C.,University of Victoria | Van Veggel F.C.J.M.,University of Victoria
Journal of the American Chemical Society | Year: 2012

We demonstrate a novel epitaxial layer-by-layer growth on upconverting NaYF 4 nanocrystals (NCs) utilizing Ostwald ripening dynamics tunable both in thickness and composition. Injection of small sacrificial NCs (SNCs) as shell precursors into larger core NCs results in the rapid dissolution of the SNCs and their deposition onto the larger core NCs to yield core-shell structured NCs. Exploiting this NC size dependent dissolution/growth, the shell thickness can be controlled either by manipulating the number of SNCs injected or by successive injection of SNCs. In either of these approaches, the NCs self-focus from an initial bimodal distribution to a unimodal distribution (σ <5%) of core-shell NCs. The successive injection approach facilitates layer-by-layer epitaxial growth without the need for tedious multiple reactions for generating tunable shell thickness, and does not require any control over the injection rate of the SNCs, as is the case for shell growth by precursor injection. © 2012 American Chemical Society.


Warkentin T.E.,McMaster University
Expert Opinion on Drug Safety | Year: 2014

Introduction: Devastating thromboses can complicate heparin-induced thrombocytopenia (HIT) and disseminated intravascular coagulation (DIC). In these disorders, acquired abnormalities of the partial thromboplastin time (PTT) and international normalized ratio (INR) can confound monitoring of PTT- and INR-Adjusted anticoagulant therapies, contributing to treatment failure. Areas covered: Illustrative patient cases of anticoagulant failure due to PTT and INR confounding are discussed. Four different scenarios of thrombosis progression associated with inappropriate anticoagulant interruption/underdosing, contributing to ischemic limb necrosis, are presented: i) PTT confounding of heparin therapy of warfarin-Associated microthrombosis complicating cancer hypercoagulability; ii) PTT confounding of direct thrombin inhibitor (DTI) therapy complicating HIT-Associated DIC; iii) INR confounding during argatroban-warfarin overlap of HIT-Associated deep-vein thrombosis; and iv) PTT confounding of anticoagulant therapy during acute DIC/hepatic necrosis-ischemic limb necrosis syndrome. Expert opinion: Abnormal coagulation test results at pre-Treatment baseline can provide an important clue regarding the risk of subsequent anticoagulant failure due to PTT or INR confounding. Greater awareness of the potential for anticoagulant failure due to PTT and INR confounding could assist clinicians in management of prothrombotic coagulopathies, for example, by choosing alternative anticoagulants (e.g., fondaparinux, danaparoid) that are not monitored by global coagulation assays, or by obtaining specific drug levels (anti-factor Xa levels, DTI levels). © Informa UK, Ltd.


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.


Saigal S.,McMaster University
Seminars in Fetal and Neonatal Medicine | Year: 2014

The outcomes of very low birth weight survivors born in the early post-neonatal intensive care era have now been reported to young adulthood in several longitudinal cohort studies, and more recently from large Scandinavian national databases. The latter reports corroborate the findings that despite disabilities, a significant majority of very low birth weight survivors are leading productive lives, and are functioning better than expected. This is reassuring, but there are still concerns about future psychopathology, cardiovascular and metabolic problems as they approach middle age. Although these findings may not be directly applicable to the current survivors of modern neonatal intensive care, they do provide a yardstick by which to project the outcomes of future survivors until more contemporaneous data are available. © 2013 Elsevier Ltd.


Giguere A.,McMaster University
Cochrane database of systematic reviews (Online) | Year: 2012

Printed educational materials are widely used passive dissemination strategies to improve the quality of clinical practice and patient outcomes. Traditionally they are presented in paper formats such as monographs, publication in peer-reviewed journals and clinical guidelines. To assess the effect of printed educational materials on the practice of healthcare professionals and patient health outcomes.To explore the influence of some of the characteristics of the printed educational materials (e.g. source, content, format) on their effect on professional practice and patient outcomes. For this update, search strategies were rewritten and substantially changed from those published in the original review in order to refocus the search from published material to printed material and to expand terminology describing printed materials. Given the significant changes, all databases were searched from start date to June 2011. We searched: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), HealthStar, CINAHL, ERIC, CAB Abstracts, Global Health, and the EPOC Register. We included randomised controlled trials (RCTs), quasi-randomised trials, controlled before and after studies (CBAs) and interrupted time series (ITS) analyses that evaluated the impact of printed educational materials (PEMs) on healthcare professionals' practice or patient outcomes, or both. We included three types of comparisons: (1) PEM versus no intervention, (2) PEM versus single intervention, (3) multifaceted intervention where PEM is included versus multifaceted intervention without PEM. There was no language restriction. Any objective measure of professional practice (e.g. number of tests ordered, prescriptions for a particular drug), or patient health outcomes (e.g. blood pressure) were included. Two review authors undertook data extraction independently, and any disagreement was resolved by discussion among the review authors. For analyses, the included studies were grouped according to study design, type of outcome (professional practice or patient outcome, continuous or dichotomous) and type of comparison. For controlled trials, we reported the median effect size for each outcome within each study, the median effect size across outcomes for each study and the median of these effect sizes across studies. Where the data were available, we re-analysed the ITS studies and reported median differences in slope and in level for each outcome, across outcomes for each study, and then across studies. We categorised each PEM according to potential effects modifiers related to the source of the PEMs, the channel used for their delivery, their content, and their format. The review includes 45 studies: 14 RCTs and 31 ITS studies. Almost all the included studies (44/45) compared the effectiveness of PEM to no intervention. One single study compared paper-based PEM to the same document delivered on CD-ROM. Based on seven RCTs and 54 outcomes, the median absolute risk difference in categorical practice outcomes was 0.02 when PEMs were compared to no intervention (range from 0 to +0.11). Based on three RCTs and eight outcomes, the median improvement in standardised mean difference for continuous profession practice outcomes was 0.13 when PEMs were compared to no intervention (range from -0.16 to +0.36). Only two RCTs and two ITS studies reported patient outcomes. In addition, we re-analysed 54 outcomes from 25 ITS studies, using time series regression and observed statistically significant improvement in level or in slope in 27 outcomes. From the ITS studies, we calculated improvements in professional practice outcomes across studies after PEM dissemination (standardised median change in level = 1.69). From the data gathered, we could not comment on which PEM characteristic influenced their effectiveness. The results of this review suggest that when used alone and compared to no intervention, PEMs may have a small beneficial effect on professional practice outcomes. There is insufficient information to reliably estimate the effect of PEMs on patient outcomes, and clinical significance of the observed effect sizes is not known. The effectiveness of PEMs compared to other interventions, or of PEMs as part of a multifaceted intervention, is uncertain.


Burrows L.L.,McMaster University
Structure | Year: 2014

The type II secretion system (T2SS) and the type IV pilus system (T4PS) are structurally related molecular machines that reversibly assemble helical fibers in an ATP-dependent manner. In this issue of Structure, Nivaskumar and colleagues provide support for a "spooling" model of T2SS pseudopilus assembly and suggest that the T2S - and by extension, T4P - system motors may operate in a rotary manner to assemble filaments. © 2014 Elsevier Ltd.


Gupta B.P.,McMaster University
WormBook : the online review of C. elegans biology | Year: 2012

The C. elegans hermaphrodite vulva is an established model system to study mechanisms of cell fate specification and tissue morphogenesis. The adult vulva is a tubular shaped organ composed of seven concentric toroids that arise from selective fusion between differentiated vulval progeny. The dorsal end of the vulval tubule is connected to the uterus via a multinucleate syncytium utse (uterine-seam) cell. The vulval tubule and utse are formed as a result of changes in morphogenetic processes such as cell polarity, adhesion, and invagination. A number of genes controlling these processes are conserved all the way up to human and function in similar developmental contexts. This makes it possible to extend the findings to other metazoan systems. Gene expression studies in the vulval and uterine cells have revealed the presence of regulatory networks specifying distinct cell fates. Thus, these two cell types serve as a good system to understand how gene networks confer unique cell identities both experimentally and computationally. This chapter focuses on morphogenetic processes during the formation of the vulva and its connection to uterus.


Weitz J.I.,McMaster University | Pollack C.V.,University of Pennsylvania
Thrombosis and Haemostasis | Year: 2015

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used in the prevention and treatment of venous thromboembolism and in the prevention of stroke in patients with non-valvular atrial fibrillation. In phase III clinical trials and meta-analyses, the NOACs were at least as effective as vitamin K antagonists (VKAs) and were associated with a similar or lower incidence of major bleeding, including consistent and significant decreases in intracranial bleeding, although with an increase in gastrointestinal bleeding for some agents compared with VKAs. Subsequent real-world evidence supports these outcomes. Despite this, physicians have concerns about serious bleeding or emergencies because there are no specific reversal agents for the NOACs. However, in clinical trials, patients receiving NOACs generally had similar or better outcomes after these events than those taking VKAs. As with any bleeding, anticoagulant-related bleeding should first be stratified according to severity and location; risk can be minimised by ongoing assessment. Management protocols for NOAC-related bleeding are similar to those for VKAs but should take into account the pharmacological profile of the specific drug. Because of their short half-lives, NOAC-related mild bleeding can often be controlled by temporarily withholding treatment. More severe bleeding requires standard escalating haemodynamic support measures, and non-specific reversal agents can be considered in lifethreatening situations, based on limited clinical data. Specific and rapid reversal agents are not currently available for any oral anti - coagulant and restoration of coagulation may not necessarily lead to better outcomes. Nevertheless, specific NOAC reversal agents are in development and show promise in healthy volunteers. © Schattauer 2015.


Yaghoobi M.,McMaster University
Clinical and Translational Gastroenterology | Year: 2015

Bone marrow-derived stem cells (BMSCs) are now believed to be the progenitors in the development of gastric cancer in patients with chronic infection with Helicobacter pylori. However, the mechanism of recruitment and malignant transformation of these cells has not been completely understood. Here I will discuss selected findings on how BMSCs compromise local immunity and skip local defense mechanisms in order to undergo malignant transformation. In addition, the role of C-X-C chemokine receptor type 4 through binding to its ligand stromal-derived factor in migration of BMSCs in mouse model of gastric cancer will be looked at. These findings are important in understanding the pathogenesis of H. pylori-associated gastric cancer and to develop new diagnostic and therapeutic modalities. © 2015 the American College of Gastroenterology. All rights reserved.


Verdu E.F.,McMaster University
American Journal of Gastroenterology | Year: 2012

Humans harbor complex microbial communities that cover the skin and the mucosal surfaces, including the gastrointestinal mucosa. The intestinal microbiota has coevolved with humans and has a key role in immune and functional gut maturation, maintenance of homeostasis as well as regulation of functions beyond the gastrointestinal tract. On the other hand it is becoming apparent that compositional, metabolic, or genetic changes in this ecosystem (dysbiosis) are associated with disease. The development of high-throughput approaches to analyze the intestinal microbiota has increased markedly our knowledge of the intestinal microbiome. Although distinct associations between gut microbial communities and inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and celiac disease (CD) have been identified in adult individuals, no direct causal link to disease has been established. The relationship between dysbiosis and gastrointestinal diseases remains, thus far, circumstantial. This emphasizes the importance of studying the composition, diversity, and metabolic capacity of the intestinal microbiota in the context of mechanisms of disease and clinical phenotypes. © 2012 by the American College of Gastroenterology.


Elit L.,McMaster University
Maturitas | Year: 2014

Objective To review the literature concerning the role of cervical screening in women 60 years and older.Methods Literature review was conducted using PubMed and the search terms cervical neoplasm, cancer, middle aged, elderly, aged, postmenopausal, cervical cytology and screening. To be included in the review, the article must have been in the English language. The search focused on publications from 2000 forward.Results The case control and modeling studies that addressed the role of cervical cytology screening in women 60 and older were reviewed. The outcomes of interest included: (1) the benefits of screening in terms of decrease rate of cervical cancer incidence (6 studies) and mortality (3 studies); (2) the duration of protection of the last screening test (4 studies); and (3) the harms of screening older women including false positive test results and cost.Conclusions Cervical cytology screening is beneficial for women over 60 years in terms of preventing the occurrence and death from cervical cancer. A negative cytology test appears to have 5 years of protection in this age group. Age of last screen with in an organized screening program may differ compared to the goals and wishes of individual women. © 2014 Elsevier Ireland Ltd. All rights reserved.


Dumitrescu S.,McMaster University
IEEE Transactions on Information Theory | Year: 2016

The general approach in a noisy channel scalar quantizer design is an iterative descent algorithm, which guarantees only a locally optimal solution. While sufficient conditions under which the local optimum becomes a global optimum are known in the noiseless channel case, such sufficient conditions were not derived for the noisy counterpart. Moreover, efficient globally optimal design techniques for general discrete distributions in the noiseless case exist; however, they seem not to extend to the noisy scenario when a fixed index assignment is assumed. Recently, the design of noisy channel scalar quantizer with random index assignment (RIA) was proposed using a locally optimal iterative algorithm. In this paper, we derive sufficient conditions for the uniqueness of a local optimum, which, thus, guarantee the global optimality of the solution. These sufficient conditions are satisfied for a log-concave probability density function which is, additionally, symmetric around its mean. Furthermore, we show that, assuming an RIA, the globally optimal design for general discrete sources can also be carried out efficiently. © 2015 IEEE.


Gunturkun U.,McMaster University
IEEE Journal of Oceanic Engineering | Year: 2010

In this paper, we propose a target signature search algorithm to address the radar scene analyzer in explicit terms for cognitive radar reception. A cognitive radar receiver encompasses two main blocks: the radar scene analyzer (RSA) and the Bayesian target tracker (BTT). The BTT needs to have prior knowledge of what it is looking for, such as terrain conditions, and the potential targets in that terrain. This information is provided by the RSA with the aid of other external resources. More formally, the statistical information about the environment and the target are central to the realization of the BTT. However, modeling the statistics of unknown target returns is a particularly challenging task. The objective of the proposed RSA structure is to tackle this challenge by extracting useful information about the target from the environment based on the texture modeling of sea clutter. Specifically, we formulate a weak target as an unknown input embedded in the sea surface, whose dynamics are closely coupled by those of the clutter. The mapping that governs the unknown system's dynamics is assumed to be smooth. The observables from the environment are then predicted one-step ahead with a bank of echo state networks (ESNs). The unknown target's signature is extracted from the ESN prediction error and then refined in two adaptive filtering stages. Performance of the resulting method is evaluated using the posterior Cramer-Rao lower bound (PCRB) on some controlled simulations. Finally, the intended application is presented on live recorded sea returns collected by the McMaster Intelligent PIXel Processing (IPIX) radar. Experiments show that the algorithm can accurately extract the target template from the environment. © 2010 IEEE.


Phillips S.M.,McMaster University
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2010

Purpose of review: Loss of skeletal muscle mass is a common feature of a number of clinical scenarios including limb casting, bed rest, and various disorders such as HIV-AIDS, sepsis, cancer cachexia, heart failure, and uremia. Commonly, muscle disuse (hypodynamia) is the sole reason, or a large part, of why muscle mass is lost. The reduction in strength, or dynapenia, that accompanies these conditions is also a function of the degree of hypodynamia and is related to muscle loss. Recent findings: The major and consistent finding in a number of human-based models of muscle wasting is a decline in the synthesis of new muscle proteins both in the postabsorptive and fed states. Thus, countermeasures are best suited to those that augment muscle protein synthesis and not those that attempt to counteract proteolysis. Our main thesis is that retention of muscle mass in wasting conditions will be achieved to the greatest extent by focussing on increased muscle use with moderate-to-high resistance loads as the primary countermeasure with a secondary countermeasure being to provide adequate nutritional support. Either intervention alone will alleviate some part of hypodynamia-induced muscle mass loss and dynapenia; however, together nutrition and muscular contraction will result in greater mitigation of muscle loss. Summary: Advances in our understanding of hypodynamia-induced muscle loss, a condition common to almost all syndromes of muscle wasting, has led to a focus on reduced basal and feeding-induced elevations in protein synthesis. Countermeasures for wasting should focus on stimulating anabolism rather than alleviating catabolism. © 2010 Wolters Kluwer Health. Lippincott Williams & Wilkins.


McKerlie M.,McMaster University
Nature communications | Year: 2011

Cyclin B-Cdk1 is a key mediator of mitotic entry; however, little is known about its role in the separation of sister chromatids. Here we report that upon mitotic entry, Cdk1 specifically phosphorylates threonine 371 of TRF1, a telomere binding protein implicated in the regulation of sister telomere cohesion. Such phosphorylation is removed in late mitosis when Cdk1 activity is inhibited, indicative of a tight regulation of T371 phosphorylation. We show that T371 phosphorylation by Cdk1 keeps TRF1 free of chromatin and this phosphorylation is associated with loss of telomere-bound TRF1 and TIN2, and a reduction in telomere heterochromatin. We find that a phosphomimic mutation at T371 of TRF1 induces telomere deprotection, resulting in telomere loss and the formation of telomere fusions, whereas a non-phosphorylatable substitution of T371 blocks sister telomere resolution, promotes micronuclei formation and impairs cell proliferation. Our work suggests that Cdk1 controls TRF1 association with telomeres to facilitate temporal telomere de-protection, which is essential for sister telomere resolution.


Tikhonov D.B.,RAS Sechenov Institute of Evolutionary Physiology and Biochemistry | Zhorov B.S.,McMaster University
Biochimica et Biophysica Acta - Biomembranes | Year: 2014

The inner pore of potassium channels is targeted by many ligands of intriguingly different chemical structures. Previous studies revealed common and diverse characteristics of action of ligands including cooperativity of ligand binding, voltage- and use-dependencies, and patterns of ligand-sensing residues. Not all these data are rationalized in published models of ligand-channel complexes. Here we have used energy calculations with experimentally defined constraints to dock flecainide, ICAGEN-4, benzocaine, vernakalant, and AVE0118 into the inner pore of Kv1.5 channel. We arrived at ligand-binding models that suggest possible explanations for different values of the Hill coefficient, different voltage dependencies of ligands action, and effects of mutations of residues in subunit interfaces. Two concepts were crucial to build the models. First, the inner-pore block of a potassium channel requires a cationic "blocking particle". A ligand, which lacks a positively charged group, blocks the channel in a complex with a permeant ion. Second, hydrophobic moieties of a flexible ligand have a tendency to bind in hydrophobic subunit interfaces. © 2013 Elsevier B.V.


Scarpignato C.,University of Parma | Hunt R.H.,McMaster University
Gastroenterology Clinics of North America | Year: 2010

Increasing life expectancy in developed countries has led to a growing prevalence of arthritic disorders, which has been accompanied by increasing prescriptions for nonsteroidal antiinflammatory drugs (NSAIDs). These are the most widely used agents for musculoskeletal and arthritic conditions. Although NSAIDs are effective, their use is associated with a broad spectrum of adverse reactions in the liver, kidney, cardiovascular system, skin, and gut. Gastrointestinal (GI) side effects are the most common. The dilemma for the physician prescribing NSAIDs is, therefore, to maintain the antiinflammatory and analgesic benefits, while reducing or preventing GI side effects. The challenge is to develop safer NSAIDs by shifting from a focus on GI toxicity to the increasingly more appreciated cardiovascular toxicity. © 2010 Elsevier Inc.


Sprague S.,McMaster University
Journal of injury & violence research | Year: 2013

Intimate partner violence (IPV) is an important health issue. Many medical students and residents have received training relating to IPV, but previous studies show that many students feel that their training has been inadequate. Our objective was to assess the knowledge, attitudes and perceptions about IPV among university medical students and surgical residents. We administered an online survey to a sample of Ontario medical students and surgical residents. The survey instrument was a modified version of the Provider Survey. Two hundred medical students and surgical residents participated in the survey (response rate: 29%). Misperceptions about IPV among respondents included the following: 1) victims must get something from the abusive relationships (18.2%), 2) physicians should not interfere with a couple's conflicts (21%), 3) asking about IPV risks offending patients (45%), 4) Victims choose to be victims (11.1%), 5) it usually takes 'two to tango' (18.3%), and 6) some patients' personalities cause them to be abused (41.1%). The majority of respondents (75.0%) believed identifying IPV was very relevant to clinical practice. The majority of medical students (91.2%) and surgical residents (96.9%) estimated the IPV prevalence in their intended practice to be 10% or less. Most of the medical students (84%) and surgical residents (60%) felt that their level of training on IPV was inadequate and over three quarters of respondents (77.2%) expressed a desire to receive additional education and training on IPV. There are misconceptions among Canadian medical students and surgical residents about intimate partner violence. These misconceptions may stem from lack of education and personal discomfort with the issue or from other factors such as gender. Curricula in medical schools and surgical training programs should appropriately emphasize educational opportunities in the area of IPV. © 2013 KUMS, All rights reserved.


Turak A.,McMaster University
RSC Advances | Year: 2013

After efficiency, lifetime is the second most important parameter for organic devices. Interfaces play a major role in that lifetime. This article reviews the current state of the art with regards to interfacial stability and control of electrode/active layer interfaces to understand the performance of organic optoelectronic devices. From examples relating to interfacial chemical reactions, interfacial morphological changes, and interfacial electronic level modification, a comprehensive picture of the role of the organic-electrode interfaces in device stability can be formed. The review begins with a brief overview of degradation in organic devices, including definitions and measurement approaches. It is then broken into two sections. The first focuses on the bottom contact (substrate) interface, specifically chemical reactions and dewetting, as the two main mechanisms of device degradation. The second section examines the top contact interface, which is prone to oxidation, interdiffusion, blistering and delamination, and inhomogeneous loss of performance (dark spots). For both sections, various approaches to overcoming device instabilities are given, with special attention to the various interlayers that have been introduced into devices for improved stability. Each section also includes examples where the main degradation mechanism is used advantageously to produce novel device architectures and surprising solutions to device degradation. © 2013 The Royal Society of Chemistry.


Elit L.M.,McMaster University
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society | Year: 2010

With the widespread implementation of screening programs internationally, there will be an increase in early stage cervical cancer cases. In response to this, the Ministry of Health in each country will need to plan strategies to provide care such as radical surgery or radiation for this potentially curable group of women. The Gynaecologic Oncologists of Canada created a teaching module to intensively train a small number of locally identified gynecologists to perform radical hysterectomy and pelvic lymphadenectomy. The process was based on adult learning principles; it involved a Canadian gynecologic oncologist working in the low- or middle-resource country with the gynecologists and problem-solving local issues in health care delivery. The teaching process included a pretest and a posttest on the basis of the objectives of the module. There were 7 modules including preoperative evaluation of the patient, cone biopsy, radical hysterectomy, pelvic lymphadenectomy, ureteric injury, vascular injury, and follow-up after surgery. Each module was divided into background information, techniques, and complications. There were video clips imbedded in the modules. After the educational modules had been reviewed, the learners were walked through the surgical procedures repeatedly including a detailed assessment of performance after each case. Participants had the opportunity to provide feedback on the training program. The module was reviewed in Mongolia and implemented in Kenya. In low- and middle-resource countries where there is an urgent need to provide a curative surgical option for the management of early cervical cancer, a focused high-intensity curriculum delivered by a trained surgeon can translate into immediate change in clinical and surgical practice.


Samaan M.C.,McMaster University
Diabetology and Metabolic Syndrome | Year: 2011

Obesity is a worldwide pandemic representing one of the major challenges that societies face around the globe. Identifying the mechanisms involved in its development and propagation will help the development of preventative and therapeutic strategies that may help control its rising rates. Obesity is associated with chronic low-grade inflammation, and this is believed to be one of the major contributors to the development of insulin resistance, which is an early event in obesity and leads to type 2 diabetes when the pancreas fails to keep up with increased demand for insulin. In this review, we discuss the role of macrophages in mediation of inflammation in obesity in metabolic organs including adipose tissue, skeletal muscle and liver. The presence of immune cells at the interface with metabolic organs modulates both metabolic function and inflammatory responses in these organs, and may provide a potential therapeutic target to modulate metabolic function in obesity. © 2011Samaan; licensee BioMed Central Ltd.


Cooper N.,Imperial College London | Arnold D.M.,McMaster University
British Journal of Haematology | Year: 2010

Depletion of B lymphocytes using the anti-CD20 monoclonal antibody rituximab has wide-spread use in the treatment of patients with autoimmune disorders. As haematopoietic progenitor cells and only a fraction of differentiated plasma express CD20, the effect of rituximab on immune function appears to be minimal. However, hypogammagobulinaemia can occur with repeated doses and emerging data from large studies suggest a subtle increase in the risk of infection. Reactivation of latent JC virus, resulting in progressive multifocal leucoencephalopathy, and hepatitis B virus, resulting in hepatoxicity, have been documented in patients receiving rituximab; although confounding effects of concomitant immunosuppressive therapies and immune dysregulation due to the underlying disease make causal associations of infections problematic. This review discusses the efficacy of B cell depletion therapy in the treatment of autoimmune diseases, the effect of B cell depletion on infection and immunity including the role of the B cell in autoimmunity, and identifies areas of controversy. © 2010 Blackwell Publishing Ltd.


Ganame J.,McMaster University
Current Pharmaceutical Design | Year: 2015

We have gained considerable insight and understanding about the etiology, embryogenesis of the myocardium, genetic background, diagnosis and outcome of left ventricular non-compaction (LVNC) over the last 2 decades. LVNC has a distinct morphological appearance with a thickened, two-layered myocardium consisting of an epicardial compacted and a thicker endocardial non-compacted layer. These features make the recognition with non-invasive imaging modalities highly feasible. We now recognize LVNC is a distinct phenotype of the myocardium with genetic heterogeneity. In several cases, LVNC shares a common genetic background with other forms of cardiomyopathy. Therefore, most likely it is not a distinct form of cardiomyopathy but rather a morphological expression of different diseases. LVNC can present as an isolated condition or associated with congenital heart disease, neuromuscular disease or genetic syndromes. It may be sporadic or a familial disease, with an autosomal dominant or X-linked mode of transmission. The clinical features associated with LVNC vary from asymptomatic individuals diagnosed during screening to symptomatic patients, with the potential for heart failure, arrhythmias, thromboembolic events, and sudden cardiac death. A comprehensive diagnostic approach includes clinical history, electrocardiogram, imaging (in many instances with more than one technique), genetic assessment, and screening of first-degree relatives. This increases the chances of instituting the most appropriate therapy. Therapy for the most part is very similar to the general heart failure population with the exception that anticoagulation is started at a lower threshold. © 2015 Bentham Science Publishers.


Pelinovsky D.,McMaster University
Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2012

We use the Cole-Hopf transformation and the Laplace method for the heat equation to justify the numerical results on enstrophy growth in the viscous Burgers equation on the unit circle.We show that the maximum enstrophy achieved in the time evolution is scaled as E3/2, where E is the large initial enstrophy, whereas the time needed for reaching the maximal enstrophy is scaled as E?1/2. These bounds are sharp for initial conditions given by odd C3 functions that are convex on half-period. © 2012 The Royal Society.


Barr R.D.,McMaster University
Pediatric Blood and Cancer | Year: 2010

Imatinib is an inhibitor of the BCR-ABL fusion gene product that characterizes chronic myeloid leukemia (CML), and of the related tyrosine kinases c-KIT and platelet-derived growth factor (PDGF) receptor. The drug is now included as front-line therapy for CML and Philadelphia chromosome-positive acute lymphoblastic leukemia in children and adolescents, though valid concerns about serious late sequelae remain unresolved and are important issues for further study. European and North American consortia have conducted phase I and II clinical trials of imatinib in children and adolescents with brain and other solid tumors that have provided little evidence of efficacy. © 2010 Wiley-Liss, Inc.


Weitz J.I.,McMaster University
Journal of Thrombosis and Thrombolysis | Year: 2015

Oral anticoagulants are a mainstay for the prevention and treatment of venous and arterial thrombosis. In 2015, the non-vitamin K oral anticoagulants (NOACs) are already replacing warfarin for many indications. Ongoing studies are focused on development of antidotes and specific reversal agents for the NOACs, and assessing their utility for prevention of cardiovascular events in patients with heart failure, coronary or peripheral artery disease, or embolic stroke of unknown source. This paper (a) lists the current indications for the NOACs; (b) reviews the current impact of the NOACs in each of these indications; (c) outlines future opportunities for the NOACs, and (e) provides perspective on new anticoagulant strategies that may be safer than the NOACs. © 2015, Springer Science+Business Media New York.


Cao J.,Illinois Institute of Technology | Cao J.,Chrysler Group LLC | Emadi A.,Illinois Institute of Technology | Emadi A.,McMaster University
IEEE Transactions on Power Electronics | Year: 2012

In this paper, a new battery/ultracapacitor hybrid energy storage system (HESS) is proposed for electric drive vehicles including electric, hybrid electric, and plug-in hybrid electric vehicles. Compared to the conventional HESS design, which uses a larger dc/dc converter to interface between the ultracapacitor and the battery/dc link to satisfy the real-time peak power demands, the proposed design uses a much smaller dc/dc converter working as a controlled energy pump to maintain the voltage of the ultracapacitor at a value higher than the battery voltage for the most city driving conditions. The battery will only provide power directly when the ultracapacitor voltage drops below the battery voltage. Therefore, a relatively constant load profile is created for the battery. In addition, the battery is not used to directly harvest energy from the regenerative braking; thus, the battery is isolated from frequent charges, which will increase the life of the battery. Simulation and experimental results are presented to verify the proposed system. © 2011 IEEE.


Woods D.R.,McMaster University
Chemical Engineering Education | Year: 2012

In this paper the focus is on what Barrows called authentic or original PBL where no lectures are given, students learn new knowledge, and all students in the group must learn the new knowledge. Institutions using this form of aPBL have found that, compared to traditional lectures, marks in subject knowledge are the same; clinical or troubleshooting skills are better; deep learning is promoted instead of surface learning; surveys of graduates and alumni are positive; student motivation is higher; student retention of the knowledge is higher, graduates have improved skill in gathering data, and there is improved efficiency in the graduation rates with fewer dropouts. In addition, the following career skills are developed: problem solving, teamwork, confidence, life-long learning, information gathering, interpersonal relations, and communication. To implement an aPBL learning environment, we need to decide whether tutored or tutorless groups will be used. For tutored groups, one tutor is needed for each group of five to eight students. For tutorless groups, the students have to be trained with the skills needed to function effectively without a tutor. Seven concerns include preparing students for aPBL, scaling back to the fundamentals, providing the literature and room facilities needed, using reflective journals, anticipating problems, investing the up-front work to set up aPBL, and creating the problems that will drive the learning. © Copyright ChE Division of ASEE 2012.


Andrews G.J.,McMaster University | Chen S.,Central East Community Care Access Center | Myers S.,Trent University
Social Science and Medicine | Year: 2014

For the last two decades health geography has focused on the dynamics between health and place. Although the social constructivist perspective of much research has provided many insights into the meanings of health and health care arguably, mirroring progress in the parent discipline of human geography, there could be a far more serious engagement with non-representational theory and the 'taking place' of health and health care. To showcase the importance and potential of this broadly, the idea of wellbeing is re-approached. The paper reflects on the ways wellbeing has been treated in research primarily as a meaningful and relatively prescribed state of life, to the neglect of process. Based on this critique, a qualitative study then illustrates the most immediate and everyday ways wellbeing might arise through 'affect'; the pre-personal mobile energies and intensities that result from physical encounters within assemblages of bodies and objects. Indeed, theoretically the findings support the proposition that, at one level, wellbeing might not be taken from environment but instead might emerge as the affective environment. They certainly raise awareness of how much in health might originate at the surface, prior to meaning, within life's infinite spatial doings, and thus they launch some final thoughts on the wider challenges and opportunities for non-representational health geographies. © 2014 Elsevier Ltd.


Beiko G.,McMaster University | Steinert R.,University of California at Irvine
Journal of Cataract and Refractive Surgery | Year: 2013

The original technique for scleral fixation of an intraocular lens using fibrin glue requires an assistant to grasp and hold an externalized haptic with forceps. We present a modification of the technique in which the externalized haptic is maintained by a silicone "tire" without the aid of an assistant. Financial Disclosure: Drs. Beiko and Steinert are consultants to Abbott Medical Optics, Inc., Milpitas, CA, USA. Neither has a financial or proprietary interest in any material or method mentioned. © 2012 ASCRS and ESCRS Published by Elsevier Inc.


Dowrick A.S.,Alfred Hospital | Bhandari M.,McMaster University
Journal of Bone and Joint Surgery - Series A | Year: 2012

The placebo effect is based on the expectations of the patient regarding the effectiveness of the treatment. The high levels of stress and rituals involved with surgery can lead to a strong placebo effect. However, the ethical principles of performing sham surgery to measure any placebo effect have been questioned, and sham-controlled surgical trials are rarely conducted. While there are a number of ethical principles that must be considered to justify the implementation of a sham-controlled surgical clinical trial, four areas deserve particular attention: equipoise, risk minimization, informed consent, and deception. Particularly in orthopaedics, where equipoise is common, sham-controlled trials may be important to ensure that inferior or ineffective treatments do not become standard practice. Copyright © 2012 by The Journal of Bone and Joint Surgery, Incorporated.


Larche M.,McMaster University
Annals of the American Thoracic Society | Year: 2014

Allergen immunotherapy with whole proteins is clinically efficacious but requires a protracted treatment period because of frequent allergic adverse events. A combination of duration of treatment and adverse events leads to poor compliance. Short synthetic peptides containing the major immunodominant T cell epitopes of allergenic proteins have been shown to reduce IgE cross-linking ability, thereby leading to fewer allergic adverse events following their administration to patients with allergies. Peptide immunotherapy has been shown to result in clinically meaningful ef fi cacy in several Phase II, randomized, double-blind, placebo-controlled clinical trials. Exactly how peptide immunotherapy achieves its efficacy remains incompletely understood, but the mechanisms are thought to include immune deviation and induction of regulatory T cells capable of suppressing allergen-specific immune responses. Limited data are available on the effects of peptide therapy on humoral immune responses. Induction of allergen-speci fic IgG has been observed after peptide therapy, but the levels of antibody induced were much lower than generally seen with the utilization of whole allergen approaches. Thus, the immunological mechanisms of peptide immunotherapy appear to overlap, although not completely, with those seen in whole allergen therapy. Further studies are required to fully elucidate mechanisms of action. Copyright © 2014 by the American Thoracic Society


Atkinson S.A.,McMaster University
American Journal of Clinical Nutrition | Year: 2011

The pioneering project of the harmonization of Dietary Reference Intakes (DRIs) for the United States and Canada resulted in the production of 13 reports from 1997 to 2006 that included 6 reports on specific nutrient groups, 3 reports in preparation for setting recommendations for fiber and antioxidants, 2 reports on applications of DRIs, a report of the synthesis of identified research gaps, and a summary report, Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. This bicountry collaborative effort to harmonize values of reference nutrient intakes has continued through meetings to evaluate the strengths and weaknesses of the first harmonized DRI process in North America and to refine the framework for future revisions of DRIs. © 2011 American Society for Nutrition.


Taylor E.,McMaster University | Randeria M.,Ohio State University
Physical Review Letters | Year: 2012

Recent experiments on a 2D Fermi gas find an undamped breathing mode at twice the trap frequency over a wide range of parameters. To understand this seemingly scale-invariant behavior in a system with a scale, we derive two exact results valid across the entire Bardeen-Cooper-Schrieffer-Bose-Einstein condensation (BCS-BEC) crossover at all temperatures. First, we relate the shift of the mode frequency from its scale-invariant value to γ d(1+2/d)P-ρ(P/ρ) s in d dimensions. Next, we relate γ d to dissipation via a new low-energy bulk viscosity sum rule. We argue that 2D is special, with its logarithmic dependence of the interaction on density, and thus γ 2 is small in both the BCS-BEC regimes, even though P-2ε/d, sensitive to the dimer binding energy that breaks scale invariance, is not. © 2012 American Physical Society.


Tasker E.J.,McMaster University | Tasker E.J.,University of Florida
Astrophysical Journal | Year: 2011

We investigate the effect of star formation and diffuse photoelectric heating on the properties of giant molecular clouds (GMCs) formed in high-resolution (≲10pc) global (∼20kpc) simulations of isolated Milky-Way-type galaxy disks. The clouds are formed through gravitational fragmentation, and structures with densities n H,c>100 cm -3 are identified as GMCs. Between 1000 and 1500 clouds are created in the simulations with masses M>105 M 1 and 180-240 with masses M>106 M ⊙ in agreement with estimates of the Milky Way's population. We find that the effect of photoelectric heating is to suppress the fragmentation of the interstellar medium, resulting in a filamentary structure in the warm gas surrounding clouds. This environment suppresses the formation of a retrograde rotating cloud population, with 88% of the clouds rotating prograde with respect to the galaxy after 300Myr. The diffuse heating also reduces the initial star formation rate (SFR), slowing the conversation of gas into stars. We therefore conclude that the interstellar environment plays an important role in the GMC evolution. Our clouds live between 0 and 20Myr with a high infant mortality (t′ < 3Myr) due to cloud mergers and star formation. Other properties, including distributions of mass, size, and surface density, agree well with observations. Collisions between our clouds are common, occurring at a rate of ∼ 1/4 of the orbital period. It is not clear whether such collisions trigger or suppress star formation at our current resolution. Our SFR is a factor of 10 higher than observations in local galaxies. This is likely due to the absence of localized feedback in our models. © 2011. The American Astronomical Society. All rights reserved.


Linkins L.-A.,McMaster University
Blood Reviews | Year: 2013

Vitamin K antagonists are widely used for the prevention of stroke due to atrial fibrillation, treatment and secondary prevention of venous thromboembolism, prevention of valvular thromboembolism in patients with prosthetic heart valves, and secondary prevention of acute myocardial infarction. The most common adverse event experienced by patients receiving anticoagulant therapy is major bleeding. The incidence of major bleeding in patients receiving long-term anticoagulation with a vitamin K antagonist in contemporary studies is 1-3% per year. To determine if the benefits of anticoagulant therapy outweigh the risk of bleeding in an individual patient, physicians must be aware of the risk factors associated with major bleeding. This narrative review will provide an overview of the incidence of major bleeding in patients receiving therapeutic anticoagulant therapy with vitamin K antagonists, discuss the risk factors for bleeding, and outline the most commonly used clinical prediction rules for bleeding. © 2013 Elsevier Ltd.


Eyink G.L.,Johns Hopkins University | Lazarian A.,University of Wisconsin - Madison | Vishniac E.T.,McMaster University
Astrophysical Journal | Year: 2011

Magnetic field lines in astrophysical plasmas are expected to be frozen-in at scales larger than the ion gyroradius. The rapid reconnection of magnetic-flux structures with dimensions vastly larger than the gyroradius requires a breakdown in the standard Alfvén flux-freezing law. We attribute this breakdown to ubiquitous MHD plasma turbulence with power-law scaling ranges of velocity and magnetic energy spectra. Lagrangian particle trajectories in such environments become "spontaneously stochastic," so that infinitely many magnetic field lines are advected to each point and must be averaged to obtain the resultant magnetic field. The relative distance between initial magnetic field lines which arrive at the same final point depends upon the properties of two-particle turbulent dispersion. We develop predictions based on the phenomenological Goldreich & Sridhar theory of strong MHD turbulence and on weak MHD turbulence theory. We recover the predictions of the Lazarian & Vishniac theory for the reconnection rate of large-scale magnetic structures. Lazarian & Vishniac also invoked "spontaneous stochasticity," but of the field lines rather than of the Lagrangian trajectories. More recent theories of fast magnetic reconnection appeal to microscopic plasma processes that lead to additional terms in the generalized Ohm's law, such as the collisionless Hall term. We estimate quantitatively the effect of such processes on the inertial-range turbulence dynamics and find them to be negligible in most astrophysical environments. For example, the predictions of the Lazarian & Vishniac theory are unchanged in Hall MHD turbulence with an extended inertial range, whenever the ion skin depth δi is much smaller than the turbulent integral length or injection-scale Li. © 2011. The American Astronomical Society. All rights reserved.


Wong A.,McMaster University
Canadian Journal of Anesthesia | Year: 2012

Purpose: Excellence in anesthesia education has been advocated to meet the future needs and direction of the specialty. The purpose of this article is twofold: first, to review the current medical education literature and theory in order to inform teaching and learning in anesthesia; and second, to advocate for excellence in anesthesia education. Source: This review considers the general education, educational psychology, and medical education literature based on a search of the MEDLINE and ERIC databases, educational Web sites, and library catalogues. Principal findings: Excellent teaching is considered that which facilitates and maximizes learning. A conceptual framework of learning as a convergence of teacher, learner, assessment, and context is proposed. The contribution of each component to learning is examined in order to enable anesthesia teachers to choose and adapt the most appropriate educational approaches for their particular contexts. The relationship of excellent teaching, scholarly teaching, and the scholarship of teaching is explored. Strategies for promoting excellence in anesthesia education are suggested. Conclusions: The call for excellence in anesthesia has become an important theme, particularly with respect to education. While excellent teaching is a goal to which all anesthesia faculty should aspire, scholarly teaching and scholarship in teaching should also be promoted in order to advance anesthesia education for the benefit of the profession and ultimately for patient care. © 2011 Canadian Anesthesiologists' Society.


Frazier T.W.,Cleveland Clinic | Georgiades S.,McMaster University | Bishop S.L.,Cornell College | Hardan A.Y.,Stanford University
Journal of the American Academy of Child and Adolescent Psychiatry | Year: 2014

Objective To examine differences in behavioral symptoms and cognitive functioning between males and females with autism spectrum disorder (ASD). Method We analyzed data from 2,418 probands with autism (304 females and 2,114 males) included in the Simons Simplex Collection. Sex differences were evaluated across measures of autism symptoms, cognitive and motor functioning, adaptive behavior, and associated behavior problems. Measurement bias was examined using latent variable models of symptoms. Unadjusted and propensity-adjusted analyses were computed to ensure that sex differences were not due to unbalanced sampling. Moderator and mediator analyses evaluated whether sex differences were modified by clinical characteristics or were driven by cognitive ability. Results Females with ASD had greater social communication impairment, lower levels of restricted interests, lower cognitive ability, weaker adaptive skills, and greater externalizing problems relative to males. Symptom differences could not be accounted for by measurement differences, indicating that diagnostic instruments captured autism similarly in males and females. IQ reductions mediated greater social impairment and reduced adaptive behavior in females with ASD, but did not mediate reductions in restricted interests or increases in irritability. Conclusions A specific female ASD phenotype is emerging that cannot be accounted for by differential symptom measurement. The present data suggest that the relatively low proportion of high-functioning females may reflect the effect of protective biological factors or may be due to under-identification. Additional carefully accrued samples are needed to confirm the present pattern and to evaluate whether observed sex ratios in high-functioning cases are reduced if female-specific indicators of restricted interests are included.


Embury D.,McMaster University | Bouaziz O.,ArcelorMittal | Bouaziz O.,French National Center for Scientific Research
Annual Review of Materials Research | Year: 2010

In this overview of steel-based composites, consideration is given to conventional metal-matrix composites, in which steel is combined with another metal, ceramic, or polymer. In addition, we define fully steel composites, in which both components of the structure are developed within the steel. These approaches are integrated by discussing a series of macroscopic, mesoscopic, and microscopic examples. This review provides an integrated view of steel composites and allows modeling of the mechanical response to be considered both at the continuum level and in terms of dislocation mechanisms depending on the length scale and the degree of mechanical contrast between the constituent phases. In the context of fully steel composites, consideration is given to static systems in which the volume fraction of the strengthening phase is constant and the length scale is varied by heat treatment or imposed plastic strain. Moreover, we discuss dynamic systems in which a phase transition occurs concomitantly with plastic strain, resulting in an increase in the density of planar barriers that control the plasticity. A discussion of classical works that describe materials such as Damascus steels is used as a template to consider a variety of ways of producing ultrahigh-strength steel composites. Examples of applications are cited and linked to the important issue of developing appropriate fabrication methods for the production of current and future steel composites. © 2010 by Annual Reviews. All rights reserved.


Boothe K.,McMaster University
Journal of Health Politics, Policy and Law | Year: 2012

When policy change is considered, what determines its success or failure? Why do plans for broad reforms often fall short, and why do certain types of change become more difficult over time? This article addresses these questions by examining health policy development in Canada, Australia, and the United Kingdom-specifically, why Canada alone failed to adopt nationwide, public pharmaceutical insurance. It demonstrates that the pace of change has significant implications for the scope of policy development. It provides new mechanisms to explain why incremental reforms stall based on the reciprocal relationship between elite ideas and public expectations and suggests that similar factors can explain how barriers to policy change develop and the conditions under which those barriers may be overcome. © 2012 by Duke University Press.


Rheinstadter M.C.,McMaster University | Rheinstadter M.C.,University of Southern Denmark | Mouritsen O.G.,National Research Council Canada
Current Opinion in Colloid and Interface Science | Year: 2013

Cholesterol is the single most abundant molecule in animal plasma membranes, in the range of 20-30. mol%, where it is known to modulate the lipid-bilayer component of the membrane and lead to increased mechanical stability, lower permeability, larger thickness, and a distinct lateral organization. The phase equilibria of membranes with cholesterol and the associated large- and small-scale structure have turned out to be a particularly elusive problem. With the proposal that lipid domains and so-called 'rafts', characterized by high local levels of cholesterol in a liquid-ordered phase, are important for a wide range of cellular functions, an understanding and a quantitative assessment of the nature of these cholesterol-induced structures and their types of ordering have become urgent. Recent progress in neutron diffraction studies of lipid-cholesterol model membranes has now revealed details of the lateral ordering, and combined with earlier molecular model studies a picture emerges of the membrane as a locally structured liquid with small ordered 'domains' of a highly dynamic nature. © 2013 Elsevier Ltd.


Khaleghi B.,University of Waterloo | Khamis A.,University of Waterloo | Karray F.O.,University of Waterloo | Razavi S.N.,McMaster University
Information Fusion | Year: 2013

There has been an ever-increasing interest in multi-disciplinary research on multisensor data fusion technology, driven by its versatility and diverse areas of application. Therefore, there seems to be a real need for an analytical review of recent developments in the data fusion domain. This paper proposes a comprehensive review of the data fusion state of the art, exploring its conceptualizations, benefits, and challenging aspects, as well as existing methodologies. In addition, several future directions of research in the data fusion community are highlighted and described. © 2011 Elsevier B.V. All rights reserved.


The temperature dependence of electrical resistivity (ER) in pure Mg poly and single crystals, and the commercial Mg alloys AZ31 and AZ80 have been studied during continuous heating from room temperature (RT) to 420 °C. Effects of chemistry, heating rate, grain size, cold deformation and artificial ageing on the behaviors of ER were researched. A complimentary application of differential scanning calorimetric (DSC) analysis gives additional data about the overall processes during continuous heating which explain in more detail the non-monotonic behaviors of ER in these materials. © 2009 Elsevier B.V. All rights reserved.


Huizinga J.D.,McMaster University | Chen J.-H.,Wuhan University
Current Gastroenterology Reports | Year: 2014

The basic science and clinical interest in the networks of interstitial cells of Cajal (ICC) keep growing, and here, research from 2010 to mid-2013 is highlighted. Highresolution gastrointestinal manometry and spatiotemporal mapping are bringing exciting new insights into motor patterns, their function and their myogenic and neurogenic origins, as well as the role of ICC. Critically important knowledge is emerging on the partaking of PDGFRa+ cells in ICC pacemaker networks. Evidence is emerging that ICC and PDGFRa+ cells have unique direct roles in muscle innervation. Chronic constipation is associated with loss and injury to ICC, which is stimulating extensive research into maintenance and repair of ICC after injury. In gastroparesis, high-resolution electrical and mechanical studies are beginning to elucidate the pathophysiological role of ICC and the pacemaker system in this condition. Receptors and ion channels that play a role in ICC function are being discovered and characterized, which paves the way for pharmacological interventions in gut motility disorders through ICC. © Springer Science+Business Media New York 2014.


Paluzzi J.P.V.,McMaster University
General and Comparative Endocrinology | Year: 2012

Insects have adapted to live in a wide variety of habitats and utilize an array of feeding strategies that present challenges to their ability to maintain osmotic balance. Regardless of the feeding strategy, water and ion levels within the haemolymph (insect blood) are maintained within a narrow range. This homeostasis involves the action of a variety of tissues, but is often chiefly regulated by the excretory system. Until recently, most research on the hormonal control of the excretory tissues has focused on factors known to have diuretic activities. In this mini-review, the current state of knowledge on anti-diuretic factors in insects will be discussed with a particular emphasis on the CAPA peptides in the blood-feeding Chagas' disease vector, Rhodnius prolixus. © 2011 Elsevier Inc.


Archer N.,McMaster University | Cocosila M.,Athabasca University
Journal of Medical Internet Research | Year: 2011

Background: There is a major campaign involving large expenditures of public money to increase the adoption rate of electronic health record (EHR) systems in Canada. To maximize the chances of success in this effort, physician views on EHRs must be addressed, since user perceptions are key to successful implementation of technology innovations. Objective: We propose a theoretical model comprising behavioral factors either favoring or against EHR adoption and use in Canadian medical practices, from the physicians' point of view. EHR perceptions of physicians already using EHR systems are compared with those not using one, through the lens of this model. Methods: We conducted an online cross-sectional survey in both English and French among medical practitioners across Canada. Data were collected both from physicians using EHRs and those not using EHRs, and analyzed with structural equation modeling (SEM) techniques. Results: We collected 119 responses from EHR users and 100 from nonusers, resulting in 2 valid samples of 102 and 83 participants, respectively. The theoretical adoption model explained 55.8% of the variance in behavioral intention to continue using EHRs for physicians already using them, and 66.8% of the variance in nonuser intention to adopt such systems. Perception of ease of use was found to be the strongest motivator for EHR users (total effect .525), while perceptions of usefulness and of ease of use were the key determinants for nonusers (total effect .538 and .519, respectively) to adopt the system. Users see perceived overall risk associated with EHR adoption as a major obstacle (total effect -.371), while nonusers perceive risk only as a weak indirect demotivator. Of the 13 paths of the SEM model, 5 showed significant differences between the 2 samples (at the .05 level): general doubts about using the system (P = .02), the necessity for the system to be relevant for their job (P < .001), and the necessity for the system to be useful (P = .049) are more important for EHR nonusers than for users, while perceptions of overall obstacles to adoption (P = .03) and system ease of use (P = .042) count more for EHR users than for nonusers. Conclusions: Relatively few differences in perceptions about EHR system adoption and use exist between physicians already using such systems and those not yet using the systems. To maximize the chances of success for new EHR implementations from a behavioral point of view, general doubts about the rationale for such systems must be mitigated through improving design, stressing how EHRs are relevant to physician jobs, and providing substantiating evidence that EHRs are easier to use and more effective than nonusers might expect.


Chain F.J.,McMaster University
BMC genomics | Year: 2011

Gene duplication is an important biological phenomenon associated with genomic redundancy, degeneration, specialization, innovation, and speciation. After duplication, both copies continue functioning when natural selection favors duplicated protein function or expression, or when mutations make them functionally distinct before one copy is silenced. Here we quantify the degree to which genetic parameters related to gene expression, molecular evolution, and gene structure in a diploid frog - Silurana tropicalis - influence the odds of functional persistence of orthologous duplicate genes in a closely related tetraploid species - Xenopus laevis. Using public databases and 454 pyrosequencing, we obtained genetic and expression data from S. tropicalis orthologs of 3,387 X. laevis paralogs and 4,746 X. laevis singletons - the most comprehensive dataset for African clawed frogs yet analyzed. Using logistic regression, we demonstrate that the most important predictors of the odds of duplicate gene persistence in the tetraploid species are the total gene expression level and evenness of expression across tissues and development in the diploid species. Slow protein evolution and information density (fewer exons, shorter introns) in the diploid are also positively correlated with duplicate gene persistence in the tetraploid. Our findings suggest that a combination of factors contribute to duplicate gene persistence following whole genome duplication, but that the total expression level and evenness of expression across tissues and through development before duplication are most important. We speculate that these parameters are useful predictors of duplicate gene longevity after whole genome duplication in other taxa. © 2011 Chain et al; licensee BioMed Central Ltd.


Schunemann H.J.,McMaster University
Current Allergy and Asthma Reports | Year: 2011

Decisions are like double-edged swords: they always come with benefits and downsides. That is, any decision in life bears desirable and undesirable consequences, even if the latter only involves the time it takes to make or think about the decision, which can be considered the harm of decision making. Therefore, it is impossible to adhere to the Hippocratic Oath's concept of "primum non nocere," which is frequently interpreted as "never do harm." The guiding principle for health care decision making should be to ensure that there is, in summary, more benefit than harm-in other words, "to do no net harm" ("primum non net nocere"). Practice guidelines support decision making and, as a consequence, would require the explicit consideration of both desirable and undesirable consequences, and assigning due considerations depending on the magnitude and importance of the consequences. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group ( http://www.gradeworkinggroup.org ) has made these considerations more explicit when developing health care recommendations. This article briefly summarizes the work of the GRADE working group based on examples of its application in the field of allergy and asthma, and provides an outlook for advances in the field of guideline development. These developments focus on funding of guidelines and handling conflict of interest, working with observational and diagnostic test accuracy studies, developing appropriate group processes, and the integration of values and preferences in the formulation of recommendations. © 2011 Springer Science+Business Media, LLC.


Lim W.,McMaster University
Current Opinion in Hematology | Year: 2011

Purpose of Review: The antiphospholipid antibody syndrome (APS) is characterized by arterial or venous thrombosis or pregnancy morbidity in patients with persistent antiphospholipid antibodies (aPL). Experimental data supporting activation of the complement cascade has provided critical insight into the underlying pathophysiology of aPL-induced pregnancy loss and thrombosis. Recent Findings: Although the mechanism by which pregnancy loss and thrombosis is incompletely elucidated, studies using mice deficient in complement components and specific inhibitors to complement have demonstrated that activation of complement contributes to fetal loss, growth restriction and thrombosis. Inhibition of complement activation can prevent these complications. Use of a specific complement inhibitor to C5 has been used successfully in a patient with catastrophic APS undergoing renal transplantation. Summary: Activation of complement plays an important role in the pathogenesis of aPL-induced pregnancy morbidity and thrombosis. This understanding has been advanced primarily using mouse models of APS and clinical studies in patients with APS are needed. Although there is currently no specific complement-targeted therapy approved for APS, developing and evaluating complement-targeted therapies in patients with APS are warranted. Complement inhibition may provide a novel upstream treatment option for patients with APS compared with the current standard treatment of anticoagulation. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Niewczas M.,McMaster University
Acta Materialia | Year: 2010

The correspondence of the dominant slip modes in parent and twin structures in hexagonal closed-packed crystals is considered within the framework of the theory of deformation twinning. The correspondence matrices, which provide a link between the parent and twin lattices, have been worked out for compound twinning modes and selected metals. Geometrical considerations suggest that in most cases deformation twins should inherit a harder dislocation substructure than that of the corresponding parent. Possible mechanisms of twin hardening are discussed. © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.


Turel O.,California State University, Fullerton | Serenko A.,Lakehead University | Bontis N.,McMaster University
Information and Management | Year: 2010

Hedonic digital artifacts have become prevalent in today's society. Their users typically pay for them, and in exchange are generally provided with benefits involving enjoyment. Today's research on technology adoption and use, though, has focused mostly on organizational or personal aids that provide efficiency and effectiveness and are free of charge for users. To bridge this gap, we identified several value drivers of hedonic digital artifacts and measured them in the context of mobile phone ringtones using the theory of consumption values. Hypothesis testing was performed using PLS on data collected from 422 ringtone users. Results confirmed that the overall value of hedonic digital artifacts is a third-order composite assessment, which successfully predicted behavioral usage and positive word-of-mouth intentions. Theoretical and practical implications were discussed. © 2009 Elsevier B.V. All rights reserved.


Rollo C.D.,McMaster University
Aging and Disease | Year: 2010

A temporal framework linking circadian rhythms and clocks to aging rates identifies a specific window of target of rapamycin (TOR) signaling associated with growth hormone (GH) and insulin-like growth factor (IGF-1) (largely exclusive of insulin) in early sleep. IGF-1 signaling is released by growth hormone secretory peaks and downregulation of IGF-1 binding protein-1 resulting in activation of the mitogen activated protein kinase/extracellular signal response kinase (MAPK/ERK) and phosphoinositide 3-kinase-protein kinase B (PI3K-PKB/Akt) signaling pathways. Phosphorylation of Akt activates TOR which mediates the protein synthesis and growth functions of the GH axis. TOR activity is also associated with downregulated stress resistance, faster aging and reduced lifespan. IGF-1 signaling is terminated by falling GH and upregulation of IGF-1 binding proteins mediated by somatostatin and rising corticosteroids in later sleep. This suppresses PI3K-Akt signaling, thus activating the forkhead transcription factors (FOXOs) and stress-resistance pathways involved in promoting longevity. Thus, sleep appears to encompass both pathways currently identified as most relevant to aging and they toggle successively on the phosphorylation status of Akt. I propose a modified version of Pearl's rate of living theory emphasizing the hard-wired antagonism of growth (TOR) and stress resistance (FOXO). The sleep association of TOR and FOXO in temporally separated windows and their sequential temporal deployment may change much of the way we think about aging and how to manipulate it.


Wallace J.L.,McMaster University
Antioxidants and Redox Signaling | Year: 2010

Like nitric oxide and carbon monoxide, hydrogen sulfide has historically been recognized as an industrial pollutant, but in recent years, it has been shown to be an important mediator of many physiological processes. Hydrogen sulfide contributes to the maintenance of gastrointestinal mucosal defense and repair. It also exerts many antiinflammatory effects, including inhibition of leukocyte adherence to the vascular endothelium and leukocyte migration to sites of inflammation. Conversely, inhibition of endogenous hydrogen sulfide synthesis leads to a loss of mucosal integrity and to an increase in mucosal inflammation. Hydrogen sulfide therefore appears to have overlapping actions with nitric oxide and prostaglandins in terms of modulating mucosal defense and resolution of inflammation. Recent evidence suggests that these properties of hydrogen sulfide can be exploited in the design of novel therapies for ulcerative and inflammatory diseases of the gastrointestinal tract. Antioxid. Redox Signal. 12, 0000-0000. © 2010, Mary Ann Liebert, Inc.


Wekerle C.,McMaster University | Wekerle C.,University of Toronto
Child Abuse and Neglect | Year: 2013

A human rights perspective places the care for children in the obligation sphere. The duty to protect from violence is an outcome of having a declaration confirming inalienable human rights. Nationally, rights may be reflected in constitutions, charters, and criminal codes. Transnationally, the United Nation's (UN) Convention on the Rights of the Child (CRC) prioritizes a child's basic human rights, given their dependent status. UN CRC signatory countries commit to implementing minimal standards of care for minors. Laws requiring professionals to report child maltreatment to authorities is one practical strategy to implement minimal child protection and service standards. Mandatory reporting laws officially affirm the wrong of maltreatment and the right of children. Mandatory reporting can be conceptualized as part of a resilience process, where the law sets the stage for child safety and well-being planning. Although widely enacted law, sizeable research gaps exist in terms of statistics on mandatory reporting compliance in key settings; obstacles and processes in mandatory reporting; the provision of evidence-based training to support the duty to report; and the training-reporting-child outcomes relationship, this latter area being virtually non-existent. The fact that mandatory reporting is not presently evidence-based cannot be separated from this lack of research activity in mandatory reporting. Reporting is an intervention that requires substantial inter-professional investment in research to guide best practices, with methodological expectations of any clinical intervention. Child abuse reporting is consistent with a clinician's other duties to report (i.e., suicidality, homicidality), practice-based skills (e.g., delivering " bad" news, giving assessment feedback), and the pervasive professional principle of best interests of the child. Resilience requires the presence of resources and, mandated reporting, is one such resource to the maltreated child. Practice strategies identified in the literature are discussed. © 2012 Elsevier Ltd.


Nikolova N.K.,McMaster University
IEEE Microwave Magazine | Year: 2011

Microwaves and millimeter waves have been used extensively to image dielectric bodies. The relatively long wavelengths (from a millimeter to a meter) allow for penetration into many optically opaque mediums such as living tissues, wood, ceramics, plastics, clothing, concrete, soil, fog, foliage, etc. While the public usually associates microwave radar with target detection and tracking, it has also been used for decades in remote sensing, i.e., for the imaging of weather patterns or the surface of remote planets, for underground surveillance, etc. More recently, microwave and millimeter-wave systems have been deployed for a variety of short-range applications, most notably in concealed weapon detection, through-the-wall imaging, and nondestructive testing for structural integrity. © 2011 IEEE.


Larche M.,McMaster University
Immunology and Allergy Clinics of North America | Year: 2011

Because of the need to standardize allergen immunotherapy and the desire to reduce allergic adverse events during therapy, a transition to recombinant/synthetic hypoallergenic approaches is inevitable. Evidence supports the notion that effective therapy can be delivered using a limited panel of allergens or even epitopes, weakening the argument that all allergens must be present for optimal efficacy. Moreover, standardized products will allow direct comparisons between studies and, for the first time, immunotherapy studies will be truly blinded, allowing an accurate assessment of the actual treatment effect that can be achieved with this form of intervention. © 2011 Elsevier Inc.


Wright G.D.,McMaster University
Chemistry and Biology | Year: 2012

Antibiotic resistance is one of the most significant challenges to the health care sector in the 21st century. A myriad of resistance mechanisms have emerged over the past decades and are widely disseminated worldwide through bacterial populations. At the same time there have been ever fewer new antibiotics brought to market, and the pharmaceutical industry increasingly sees antibiotics as a poor investment. Paradoxically, we are in a Golden Age of understanding how antibiotics work and where resistance comes from. This knowledge is fueling a renaissance of interest and innovation in antibiotic discovery, synthesis, and mechanism that is poised to inform drug discovery to address pressing clinical needs. © 2012 Elsevier Ltd All rights reserved.


Dobbins M.,McMaster University
Cochrane database of systematic reviews (Online) | Year: 2013

The World Health Organization (WHO) estimates that 1.9 million deaths worldwide are attributable to physical inactivity and at least 2.6 million deaths are a result of being overweight or obese. In addition, WHO estimates that physical inactivity causes 10% to 16% of cases each of breast cancer, colon, and rectal cancers as well as type 2 diabetes, and 22% of coronary heart disease and the burden of these and other chronic diseases has rapidly increased in recent decades. The purpose of this systematic review was to summarize the evidence of the effectiveness of school-based interventions in promoting physical activity and fitness in children and adolescents. The search strategy included searching several databases to October 2011. In addition, reference lists of included articles and background papers were reviewed for potentially relevant studies, as well as references from relevant Cochrane reviews. Primary authors of included studies were contacted as needed for additional information. To be included, the intervention had to be relevant to public health practice (focused on health promotion activities), not conducted by physicians, implemented, facilitated, or promoted by staff in local public health units, implemented in a school setting and aimed at increasing physical activity, included all school-attending children, and be implemented for a minimum of 12 weeks. In addition, the review was limited to randomized controlled trials and those that reported on outcomes for children and adolescents (aged 6 to 18 years). Primary outcomes included: rates of moderate to vigorous physical activity during the school day, time engaged in moderate to vigorous physical activity during the school day, and time spent watching television. Secondary outcomes related to physical health status measures including: systolic and diastolic blood pressure, blood cholesterol, body mass index (BMI), maximal oxygen uptake (VOmax), and pulse rate. Standardized tools were used by two independent reviewers to assess each study for relevance and for data extraction. In addition, each study was assessed for risk of bias as specified in the Cochrane Handbook for Systematic Reviews of Interventions. Where discrepancies existed, discussion occurred until consensus was reached. The results were summarized narratively due to wide variations in the populations, interventions evaluated, and outcomes measured. In the original review, 13,841 records were identified and screened, 302 studies were assessed for eligibility, and 26 studies were included in the review. There was some evidence that school-based physical activity interventions had a positive impact on four of the nine outcome measures. Specifically positive effects were observed for duration of physical activity, television viewing, VO max, and blood cholesterol. Generally, school-based interventions had little effect on physical activity rates, systolic and diastolic blood pressure, BMI, and pulse rate. At a minimum, a combination of printed educational materials and changes to the school curriculum that promote physical activity resulted in positive effects.In this update, given the addition of three new inclusion criteria (randomized design, all school-attending children invited to participate, minimum 12-week intervention) 12 of the original 26 studies were excluded. In addition, studies published between July 2007 and October 2011 evaluating the effectiveness of school-based physical interventions were identified and if relevant included. In total an additional 2378 titles were screened of which 285 unique studies were deemed potentially relevant. Of those 30 met all relevance criteria and have been included in this update. This update includes 44 studies and represents complete data for 36,593 study participants. Duration of interventions ranged from 12 weeks to six years.Generally, the majority of studies included in this update, despite being randomized controlled trials, are, at a minimum, at moderate risk of bias. The results therefore must be interpreted with caution. Few changes in outcomes were observed in this update with the exception of blood cholesterol and physical activity rates. For example blood cholesterol was no longer positively impacted upon by school-based physical activity interventions. However, there was some evidence to suggest that school-based physical activity interventions led to an improvement in the proportion of children who engaged in moderate to vigorous physical activity during school hours (odds ratio (OR) 2.74, 95% confidence interval (CI), 2.01 to 3.75). Improvements in physical activity rates were not observed in the original review. Children and adolescents exposed to the intervention also spent more time engaged in moderate to vigorous physical activity (with results across studies ranging from five to 45 min more), spent less time watching television (results range from five to 60 min less per day), and had improved VOmax (results across studies ranged from 1.6 to 3.7 mL/kg per min). However, the overall conclusions of this update do not differ significantly from those reported in the original review. The evidence suggests the ongoing implementation of school-based physical activity interventions at this time, given the positive effects on behavior and one physical health status measure. However, given these studies are at a minimum of moderate risk of bias, and the magnitude of effect is generally small, these results should be interpreted cautiously. Additional research on the long-term impact of these interventions is needed.


Hitchcock A.P.,McMaster University
Journal of Electron Spectroscopy and Related Phenomena | Year: 2015

Instrumentation and current capabilities of soft X-ray (50-2000 eV) spectromicroscopy are outlined with examples from recently published and some new work. Four common techniques are treated - transmission X-ray microscopy (TXM), scanning transmission X-ray microscopy (STXM), X-ray photoemission electron microscopy (XPEEM) and scanning photoemission microscopy (SPEM). I also present a fifth, emerging technique, that of soft X-ray spectro-ptychography which has significantly improved spatial resolution and provides new contrast mechanisms. Perspectives for near future (5-10 years) evolution of soft X-ray spectromicroscopy are outlined based on current trends and instrumentation under development. © 2015 Elsevier B.V. All rights reserved.


Arsenault K.A.,McMaster University
Cochrane database of systematic reviews (Online) | Year: 2013

Atrial fibrillation is a common post-operative complication of cardiac surgery and is associated with an increased risk of post-operative stroke, increased length of intensive care unit and hospital stays, healthcare costs and mortality. Numerous trials have evaluated various pharmacological and non-pharmacological prophylactic interventions for their efficacy in preventing post-operative atrial fibrillation. We conducted an update to a 2004 Cochrane systematic review and meta-analysis of the literature to gain a better understanding of the effectiveness of these interventions. The primary objective was to assess the effects of pharmacological and non-pharmacological interventions for preventing post-operative atrial fibrillation or supraventricular tachycardia after cardiac surgery. Secondary objectives were to determine the effects on post-operative stroke or cerebrovascular accident, mortality, cardiovascular mortality, length of hospital stay and cost of treatment during the hospital stay. We searched the Cochrane Central Register of ControlLed Trials (CENTRAL) (Issue 8, 2011), MEDLINE (from 1946 to July 2011), EMBASE (from 1974 to July 2011) and CINAHL (from 1981 to July 2011). We selected randomized controlled trials (RCTs) that included adult patients undergoing cardiac surgery who were allocated to pharmacological or non-pharmacological interventions for the prevention of post-operative atrial fibrillation or supraventricular tachycardia, except digoxin, potassium (K(+)), or steroids. Two review authors independently abstracted study data and assessed trial quality. One hundred and eighteen studies with 138 treatment groups and 17,364 participants were included in this review. Fifty-seven of these studies were included in the original version of this review while 61 were added, including 27 on interventions that were not considered in the original version. Interventions included amiodarone, beta-blockers, sotalol, magnesium, atrial pacing and posterior pericardiotomy. Each of the studied interventions significantly reduced the rate of post-operative atrial fibrillation after cardiac surgery compared with a control. Beta-blockers (odds ratio (OR) 0.33; 95% confidence interval) CI 0.26 to 0.43; I(2) = 55%) and sotalol (OR 0.34; 95% CI 0.26 to 0.43; I(2) = 3%) appear to have similar efficacy while magnesium's efficacy (OR 0.55; 95% CI 0.41 to 0.73; I(2) = 51%) may be slightly less. Amiodarone (OR 0.43; 95% CI 0.34 to 0.54; I(2) = 63%), atrial pacing (OR 0.47; 95% CI 0.36 to 0.61; I(2) = 50%) and posterior pericardiotomy (OR 0.35; 95% CI 0.18 to 0.67; I(2) = 66%) were all found to be effective. Prophylactic intervention decreased the hospital length of stay by approximately two-thirds of a day and decreased the cost of hospital treatment by roughly $1250 US. Intervention was also found to reduce the odds of post-operative stroke, though this reduction did not reach statistical significance (OR 0.69; 95% CI 0.47 to 1.01; I(2) = 0%). No significant effect on all-cause or cardiovascular mortality was demonstrated. Prophylaxis to prevent atrial fibrillation after cardiac surgery with any of the studied pharmacological or non-pharmacological interventions may be favored because of its reduction in the rate of atrial fibrillation, decrease in the length of stay and cost of hospital treatment and a possible decrease in the rate of stroke. However, this review is limited by the quality of the available data and heterogeneity between the included studies. Selection of appropriate interventions may depend on the individual patient situation and should take into consideration adverse effects and the cost associated with each approach.


Beake B.D.,Micro Materials Ltd | Fox-Rabinovich G.S.,McMaster University
Surface and Coatings Technology | Year: 2014

Frictional heating results in very high operating temperatures in high speed machining but the nanoindentation tests used to evaluate novel PVD coating systems for improved cutting performance are invariably performed at room temperature. If nanomechanical measurements are to be used reliably in the optimisation of coatings for high speed machining then it is much better that the measurements are performed at the relevant temperature. High temperature nanoindentation data are reviewed for a wide range of nitride-based hard coatings on cemented carbide and design rules suggested for coating optimisation for different machining applications. The importance of high temperature mechanical properties and microstructure on the adaptive and multifunctional behaviour in improving tool life is investigated. The coatings studied show large differences in how their hardness, modulus and H/. E vary with increasing temperature which have a significant influence on their behaviour in high temperature mechanical contact applications which have differing requirements in terms of hot hardness and plasticity. In continuous high-speed turning operations the high temperature hardness is paramount and coatings with high hot hardness display longer tool life. In interrupted cutting conditions toughness and plasticity are at least as important, and in end milling of hardened steels for example, high hot hardness should be combined with improved plasticity for longer tool life. Multilayer AlTiCrSiYN/AlTiCrN coatings have shown improved performance compared to the state of the art monolayer coatings. The reasons for this improved performance are discussed. Overall, the high temperature nanoindentation data show excellent correlation to coating life in high speed machining applications. © 2014 Elsevier B.V.


Elit L.,McMaster University
Maturitas | Year: 2014

Objectives (1) To understand whether women who are older when diagnosed with cervical cancer have a poorer survival compared to those younger, and if so, to determine the relative importance of patient, tumor and treatment factors. (2) To review whether older women are candidates for aggressive curative treatment for their cervical cancer and the age related effectiveness and toxicity. Methods A review of the published English literature from 1990 to 2014 using search terms related to cervical cancer and older age was conducted. Results A number of confounders may influence whether advanced age impacts survival such as patient comorbidities, stage, histology, grade, no or incomplete treatment, less radical surgery, palliative rather than curative treatment, lack of adjuvant radiation after surgery, lower rates of chemotherapy and others. When older women are treated as aggressively as their younger counterparts, survival is the same; however, especially where radiation or chemotherapy is used, toxicities may occur at the same or slightly higher rate. Conclusions The more recent population based studies have larger sample sizes and minimize the biases seen in single center studies. They have also corrected for confounders giving a more accurate answer concerning the outcomes of older women treated for cervical cancer. Performance status (or "frailty") and not chronologic age should define the optimal treatment strategy for older women with cervical cancer. Treatment related toxicities can be managed with treatment breaks or dose reductions. For those who receive curative treatment, the outcomes appear similar regardless of age. © 2014 Elsevier Ireland Ltd.


Bryant-Lukosius D.,McMaster University
Nursing leadership (Toronto, Ont.) | Year: 2010

The clinical nurse specialist (CNS) provides an important clinical leadership role for the nursing profession and broader healthcare system; yet the prominence and deployment of this role have fluctuated in Canada over the past 40 years. This paper draws on the results of a decision support synthesis examining advanced practice nursing roles in Canada. The synthesis included a scoping review of the Canadian and international literature and in-depth interviews with key informants including CNSs, nurse practitioners, other health providers, educators, healthcare administrators, nursing regulators and government policy makers. Key challenges to the full integration of CNSs in the Canadian healthcare system include the paucity of Canadian research to inform CNS role implementation, absence of a common vision for the CNS role in Canada, lack of a CNS credentialing mechanism and limited access to CNS-specific graduate education. Recommendations for maximizing the potential and long-term sustainability of the CNS role to achieve important patient, provider and health system outcomes in Canada are provided.


There is considerable unexplained heterogeneity in previous meta-analyses of randomized controlled trials (RCTs) evaluating the effects of patient decision aids on the accuracy of knowledge of outcome probabilities. The purpose of this review was to explore possible effect modification by three covariates: the type of control intervention, decision aid quality and patients' baseline knowledge of probabilities. A sub-analysis of studies previously identified in the 2011 Cochrane review on decision aids for people facing treatment and screening decisions was conducted. Additional unpublished data were requested from relevant study authors to maximize the number of eligible studies. RCTs (to 2009) comparing decision aids with standardized probability information to control interventions (lacking such information) and assessing the accuracy of patient knowledge of outcome probabilities were included. The proportions of patients with accurate knowledge of outcome probabilities in each group were converted into relative effect measures. Intervention quality was assessed using the International Patient Decision Aid Standards instrument (IPDASi) probabilities domain. A main effects analysis of 17 eligible studies confirmed that decision aids significantly improve the accuracy of patient knowledge of outcome probabilities (relative risk = 1.80 [1.51, 2.16]), with considerable heterogeneity (87%). The type of control did not modify effects. Meta-regression suggested that the IPDASi probabilities domain score (reflecting decision aid quality) is a potential effect modifier (P = 0.037), accounting for a quarter of the variability (R2 = 0.28). Meta-regression indicated the control event rate (reflecting baseline knowledge) is a significant effect modifier (P = 0.001), with over half the variability in ln(OR) explained by the linear relationship with log-odds for the control group (R2 = 0.52); this relationship was slightly strengthened after correcting for the statistical dependence of the effect measure on the control event rate. Patients' baseline level of knowledge of outcome probabilities is an important variable that explains the heterogeneity of effects of decision aids on improving accuracy of this knowledge. Greater relative effects are observed when the baseline proportion of patients with accurate knowledge is lower. This may indicate that decision aids are more effective in populations with lower knowledge.


Dal Bello-Haas V.,McMaster University
The Cochrane database of systematic reviews | Year: 2013

Despite the high incidence of muscle weakness in individuals with amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND), the effects of exercise in this population are not well understood. This is an update of a review first published in 2008. To systematically review randomised and quasi-randomised studies of exercise for people with ALS or MND. We searched The Cochrane Neuromuscular Disease Group Specialized Register (2 July 2012), CENTRAL (2012, Issue 6 in The Cochrane Library), MEDLINE (January 1966 to June 2012), EMBASE (January 1980 to June 2012), AMED (January 1985 to June 2012), CINAHL Plus (January 1938 to June 2012), LILACS (January 1982 to June 2012), Ovid HealthSTAR (January 1975 to December 2012). We also searched ProQuest Dissertations & Theses A&I (2007 to 2012), inspected the reference lists of all papers selected for review and contacted authors with expertise in the field. We included randomised or quasi-randomised controlled trials of people with a diagnosis of definite, probable, probable with laboratory support, or possible ALS, as defined by the El Escorial criteria. We included progressive resistance or strengthening exercise, and endurance or aerobic exercise. The control condition was no exercise or standard rehabilitation management. Our primary outcome measure was improvement in functional ability, decrease in disability or reduction in rate of decline as measured by a validated outcome tool at three months. Our secondary outcome measures were improvement in psychological status or quality of life, decrease in fatigue, increase in, or reduction in rate of decline of muscle strength (strengthening or resistance studies), increase in, or reduction in rate of decline of aerobic endurance (aerobic or endurance studies) at three months and frequency of adverse effects. We did not exclude studies on the basis of measurement of outcomes. Two review authors independently assessed trial quality and extracted the data. We collected adverse event data from included trials. The review authors contacted the authors of the included studies to obtain information not available in the published articles. We identified two randomised controlled trials that met our inclusion criteria, and we found no new trials when we updated the searches in 2012. The first, a study with overall unclear risk of bias, examined the effects of a twice-daily exercise program of moderate load endurance exercise versus "usual activities" in 25 people with ALS. The second, a study with overall low risk of bias, examined the effects of thrice weekly moderate load and moderate intensity resistance exercises compared to usual care (stretching exercises) in 27 people with ALS. After three months, when the results of the two trials were combined (43 participants), there was a significant mean improvement in the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) measure of function in favour of the exercise groups (mean difference 3.21, 95% confidence interval 0.46 to 5.96). No statistically significant differences in quality of life, fatigue or muscle strength were found. In both trials adverse effects, investigators reported no adverse effects such as increased muscle cramping, muscle soreness or fatigue The included studies were too small to determine to what extent strengthening exercises for people with ALS are beneficial, or whether exercise is harmful. There is a complete lack of randomised or quasi-randomised clinical trials examining aerobic exercise in this population. More research is needed.


Khan M.S.,Environment Canada | Coulibaly P.,McMaster University
Journal of Hydrometeorology | Year: 2010

A major challenge in assessing the hydrologic effect of climate change remains the estimation of uncertainties associated with different sources, such as the global climate models, emission scenarios, downscaling methods, and hydrologic models. There is a demand for an efficient and easy-to-use rainfall-runoff modeling tool that can capture the different sources of uncertainties to generate future flow simulations that can be used for decision making. To manage the large range of uncertainties in the climate change impact study on water resources, a neural network-based rainfall-runoff model-namely, Bayesian neural network (BNN)-is proposed. The BNN model is used with Canadian Centre for Climate Modelling and Analysis Coupled GCM, versions 1 and 2 (CGCM1 and CGCM2, respectively) with two emission scenarios, Intergovernmental Panel on Climate Change (IPCC) IS92a and Special Report on Emissions Scenarios (SRES) B2. One widely used statistical downscaling model (SDSM) is used in the analysis. The study is undertaken to simulate daily river flow and daily reservoir inflow in the Serpent and the Chute-du-Diable watersheds, respectively, in northeastern Canada. It is found that the uncertainty bands of the mean ensemble flow (i.e., flow simulated using the mean of the ensemble members of downscaled meteorological variables) is able to mostly encompass all other flows simulated with various individual downscaled meteorological ensemble members whichever CGCM or emission scenario is used. In addition, the uncertainty bands are also able to typically encompass most of the flows simulated with another rainfall-runoff model, namely, Hydrologiska Byråns Vattenbalansavdelning (HBV). The study results suggest that the BNN model could be used as an effective hydrological modeling tool in assessing the hydrologic effect of climate change with uncertainty estimates in the form of confidence intervals. It could be a good alternative method where resources are not available to implement the general multimodel ensembles approach. The BNN approach makes the climate change impact study on water resources with uncertainty estimate relatively simple, cost effective, and time efficient. © 2010 American Meteorological Society.


In the past decade, antithrombotic therapy research has focused on the development of new oral anticoagulant drugs to replace vitamin K antagonists for stroke prevention in patients with chronic atrial fibrillation, for preventing cardiovascular complications of acute coronary syndromes, and for the prevention and treatment of venous thromboembolism. The most anticipated studies relate to the use of new oral anticoagulants to replace vitamin K antagonists for the prevention of stroke in patients with atrial fibrillation. This review will focus on dabigatran, the first non-vitamin K anticoagulant approved for this clinical indication, and will assess the RE-LY trial (Randomized Evaluation of Long Term Anticoagulant Therapy) findings according to the level of anticoagulation control in warfarin-treated patients. The objectives of this review are: 1) to provide an overview of dabigatran, highlighting clinically relevant properties; 2) to provide a commentary on the study by Wallentin et al. within the context of how the quality of anticoagulation control affects warfarin efficacy and safety; and 3) to consider which patients with chronic atrial fibrillation should receive and which may not need to receive dabigatran. Copyright by Medycyna Praktyczna, Kraków 2011.


Phillips S.M.,McMaster University | van Loon L.J.C.,Maastricht University
Journal of Sports Sciences | Year: 2011

Opinion on the role of protein in promoting athletic performance is divided along the lines of how much aerobic-based versus resistance-based activity the athlete undertakes. Athletes seeking to gain muscle mass and strength are likely to consume higher amounts of dietary protein than their endurance-trained counterparts. The main belief behind the large quantities of dietary protein consumption in resistance-trained athletes is that it is needed to generate more muscle protein. Athletes may require protein for more than just alleviation of the risk for deficiency, inherent in the dietary guidelines, but also to aid in an elevated level of functioning and possibly adaptation to the exercise stimulus. It does appear, however, that there is a good rationale for recommending to athletes protein intakes that are higher than the RDA. Our consensus opinion is that leucine, and possibly the other branched-chain amino acids, occupy a position of prominence in stimulating muscle protein synthesis; that protein intakes in the range of 1.3-1.8 g · kg -1 · day -1 consumed as 3-4 isonitrogenous meals will maximize muscle protein synthesis. These recommendations may also be dependent on training status: experienced athletes would require less, while more protein should be consumed during periods of high frequency/intensity training. Elevated protein consumption, as high as 1.8-2.0 g · kg -1 · day -1 depending on the caloric deficit, may be advantageous in preventing lean mass losses during periods of energy restriction to promote fat loss. © 2011 Taylor and Francis Group, LLC.


Ofosu F.A.,McMaster University
Thrombosis and Haemostasis | Year: 2012

With the expiry or pending expiry of originator low-molecular-weight heparin (LMWH) patents, pharmaceutical companies have invested in developing non-proprietary versions of LMWHs. LMWHs are manufactured by depolymerising highly purified unfractionated heparin. In contrast to traditional synthetic drugs with well-defined chemical structures, LMWHs contain complex oligosaccharide mixtures and the different manufacturing processes for LMWHs add to the heterogeneity in their physicochemical properties such that the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) consider existing originator LMWHs to be distinct medicinal entities that are not clinically interchangeable. The FDA views LMWHs as drugs and has approved two non-proprietary (generic) LMWHs, using the Abbreviated New Drug Application pathway. In contrast, the World Health Organization and the EMA view LMWHs as biological medicines. Therefore, the EMA and also the Scientific and Standardization Subcommittee on Anticoagulation of the International Society on Thrombosis and Haemostasis and the South Asian Society of Atherosclerosis and Thrombosis have all published specific guidelines for assessing non-proprietary (biosimilar) LMWHs. This manuscript reviews why there are two distinct pathways for approving non-proprietary LMWHs. Available literature on non-proprietary LMWHs approved in some jurisdictions is also reviewed in order to assess whether they satisfy the requirements for LMWHs in the three guidance documents. The review also highlights some of the significant difficulties the two pathways pose for manufacturers and an urgent need to develop a consensus governing the manufacture and regulation of non-proprietary LMWHs to make them more widely available. © Schattauer 2012.


Background The transition process of vulnerable adolescents, including those with complex health conditions, occurs in all domains of their life. Systems of care are usually designed but also restricted within certain aspects of life, as addressed by health, education and social welfare. The need for a co-ordinated approach to support the transition process has been voiced before, but usually publications focus on one system of care, usually the healthcare system or the education system. Recent moves, especially in the UK, are trying to integrate these different systems allowing for a more integrated transition process. This article illustrates how these developments are represented within the framework of the International Classification of Functioning, Disability and Health (ICF) and provides arguments that favour a greater integration of systems of care. Methods Examples of systems of care from North America and the EU (Germany and the UK) are described. They were selected from a literature search using the terms 'systems of care', 'transition' and 'transitional care' in different combinations. Further supportive information derives from personal experience working in some of these systems in different countries. The systems were analysed according to the components of health they address within the ICF. Results In order to assist adolescents in transition of services, there is a consensus that the approach should be individualized. The overall goal of any intervention or service should be to achieve optimal functioning of the patients. In the framework of the ICF, this means that biomedical and contextual (psychosocial) issues need to be taken into consideration. This requires an exchange of information between the different systems or the integration of those systems involved with the patient. Conclusion To facilitate transition, it has been shown that close collaboration between agencies, a transdisciplinary approach of the professionals involved and the use of key workers are helpful. © 2011 Blackwell Publishing Ltd.


Testing for genetic effects on mean values of a quantitative trait has been a very successful strategy. However, most studies to date have not explored genetic effects on the variance of quantitative traits as a relevant consequence of genetic variation. In this report, we demonstrate that, under plausible scenarios of genetic interaction, the variance of a quantitative trait is expected to differ among the three possible genotypes of a biallelic SNP. Leveraging this observation with Levene's test of equality of variance, we propose a novel method to prioritize SNPs for subsequent gene-gene and gene-environment testing. This method has the advantageous characteristic that the interacting covariate need not be known or measured for a SNP to be prioritized. Using simulations, we show that this method has increased power over exhaustive search under certain conditions. We further investigate the utility of variance per genotype by examining data from the Women's Genome Health Study. Using this dataset, we identify new interactions between the LEPR SNP rs12753193 and body mass index in the prediction of C-reactive protein levels, between the ICAM1 SNP rs1799969 and smoking in the prediction of soluble ICAM-1 levels, and between the PNPLA3 SNP rs738409 and body mass index in the prediction of soluble ICAM-1 levels. These results demonstrate the utility of our approach and provide novel genetic insight into the relationship among obesity, smoking, and inflammation.


Guo P.,McMaster University
Acta Geotechnica | Year: 2010

This paper revisits the earth pressure coefficient at rest K0 of granular materials, with the focus being placed on the variation of K0 with the internal friction angle, density and compressibility of soils. Following laboratory tests that are carried out to determine K0 of two granular materials, the experimental data are interpreted using the original hypoplasticity model for sand proposed by von Wolffersdorff [49]. K0 is generally a function of void ratio, stress level and the critical state friction angle; it can be alternatively related to the compressibility of soil. The results show that Jáky's equation may still be considered as a reasonable representation of K0 for granular soils statistically, even though it may not be able to reproduce the experimental data of a specific soil. © 2010 Springer-Verlag.


Hoyt J.J.,McMaster University
Modelling and Simulation in Materials Science and Engineering | Year: 2014

In recent years, atomistic simulations have provided valuable insights into the thermodynamic and kinetic properties of grain and interphase boundaries. In this work, we provide a brief overview of kinetic processes occurring at migrating interfaces and survey various molecular dynamics techniques for extracting grain boundary mobilities. The advantages and disadvantages of fluctuation and applied driving force methods will be discussed. In addition, we review recent examples of simulations that have identified structural phase transformations at grain boundaries. Finally, simulations that have investigated the mobility and atomic mechanisms of growth of an fcc-bcc interphase boundary are summarized. © 2014 IOP Publishing Ltd.


Forsythe P.,McMaster University
Chest | Year: 2011

Increasing awareness of the role of intestinal commensal bacteria in the development and modulation of the immune system has led to great interest in the therapeutic potential of probiotics and other bacteria-based strategies for a range of immune-related disorders. Studies in animal models have identified strong immunomodulatory effects of many nonpathogenic bacteria and provided evidence that intestinal microbes can activate a common mucosal immune response and, thus, influence sites distant to the intestine, including the respiratory tract. Respiratory effects of probiotics in animal models have included attenuating allergic airway responses and protecting against respiratory pathogens. Dendritic cells appear central to directing the beneficial immune response to probiotic bacteria and in translating microbial signals from the innate to the adaptive immune system, whereas regulatory T cells are emerging as potentially key effectors of probiotic-mediated responses, particularly in the reduction of allergic inflammation. Despite progress in basic research, clinical trials of probiotics in allergy/asthma and respiratory infection have been highly variable at best, leading to an undermining of confidence in this potential therapeutic strategy. It is clear that there is still much to learn regarding the determinants of the diverse immune responses elicited by different bacterial strains. A deeper knowledge of the interactions between administered probiotics and the existing microbiota, together with an understanding of how the dialogue between microbes and the innate immune system is translated into beneficial/protective responses, will be required before we can achieve clinically effective bacteria-based strategies that maintain and promote respiratory health. © 2011 American College of Chest Physicians.


Kata A.,McMaster University
Vaccine | Year: 2010

The Internet plays a large role in disseminating anti-vaccination information. This paper builds upon previous research by analyzing the arguments proffered on anti-vaccination websites, determining the extent of misinformation present, and examining discourses used to support vaccine objections. Arguments around the themes of safety and effectiveness, alternative medicine, civil liberties, conspiracy theories, and morality were found on the majority of websites analyzed; misinformation was also prevalent. The most commonly proposed method of combating this misinformation is through better education, although this has proven ineffective. Education does not consider the discourses supporting vaccine rejection, such as those involving alternative explanatory models of health, interpretations of parental responsibility, and distrust of expertise. Anti-vaccination protestors make postmodern arguments that reject biomedical and scientific "facts" in favour of their own interpretations. Pro-vaccination advocates who focus on correcting misinformation reduce the controversy to merely an "educational" problem; rather, these postmodern discourses must be acknowledged in order to begin a dialogue. © 2009 Elsevier Ltd. All rights reserved.


Prince M.J.,Kings College London | Wu F.,Shanghai Institutes of Preventative Medicine | Guo Y.,U.S. Center for Disease Control and Prevention | Gutierrez Robledo L.M.,National Autonomous University of Mexico | And 3 more authors.
The Lancet | Year: 2015

23% of the total global burden of disease is attributable to disorders in people aged 60 years and older. Although the proportion of the burden arising from older people (≤60 years) is highest in high-income regions, disability-adjusted life years (DALYs) per head are 40% higher in low-income and middle-income regions, accounted for by the increased burden per head of population arising from cardiovascular diseases, and sensory, respiratory, and infectious disorders. The leading contributors to disease burden in older people are cardiovascular diseases (30·3% of the total burden in people aged 60 years and older), malignant neoplasms (15·1%), chronic respiratory diseases (9·5%), musculoskeletal diseases (7·5%), and neurological and mental disorders (6·6%). A substantial and increased proportion of morbidity and mortality due to chronic disease occurs in older people. Primary prevention in adults aged younger than 60 years will improve health in successive cohorts of older people, but much of the potential to reduce disease burden will come from more effective primary, secondary, and tertiary prevention targeting older people. Obstacles include misplaced global health priorities, ageism, the poor preparedness of health systems to deliver age-appropriate care for chronic diseases, and the complexity of integrating care for complex multimorbidities. Although population ageing is driving the worldwide epidemic of chronic diseases, substantial untapped potential exists to modify the relation between chronological age and health. This objective is especially important for the most age-dependent disorders (ie, dementia, stroke, chronic obstructive pulmonary disease, and vision impairment), for which the burden of disease arises more from disability than from mortality, and for which long-term care costs outweigh health expenditure. The societal cost of these disorders is enormous. © 2015 Elsevier Ltd.


Beiko G.H.H.,McMaster University
Journal of Cataract and Refractive Surgery | Year: 2013

Purpose: To compare near vision and quality of vision after controlling for pseudoaccommodation in patients with single-optic accommodating intraocular lenses (IOLs) or monofocal IOLs targeted for mini-monovision. Setting: Clinical practice. Design: Prospective randomized controlled clinical trial. Methods: Patients were randomized to bilateral implantation of the Crystalens HD silicone accommodating IOL, the Tetraflex acrylic accommodating IOL, or the Tecnis 1-piece monofocal (nonaccommodating) control IOL. The target refraction for the control group was mini-monovision (-0.25 diopter [D] and -0.75 D). In the accommodating IOL groups, manufacturer recommendations were followed; that is, a target refraction of mini-monovision (-0.25 D and -0.75 D) in the acrylic accommodating group and +0.25 D in the silicone accommodating group. Pupil size and anterior corneal spherical aberration were measured preoperatively. Main outcome measures were binocular target refraction corrected near vision and contrast sensitivity 3 months postoperatively. Results: There were no statistically significant differences between the 3 groups in age, photopic or mesopic pupil size, anterior corneal spherical aberration, corneal astigmatism, or the power of the IOLs implanted. Binocular distance visual acuity at 4 m was 20/20- in all groups, intermediate vision was approximately 20/25, and near vision was 20/40 to 20/50. There were no statistically significant differences between the 3 groups in visual acuity or contrast sensitivity. Conclusion: Single-optic accommodating IOLs did not offer a significant advantage in near visual acuity over mini-monovision with a monofocal (nonaccommodating) IOL. Financial Disclosure: Dr. Beiko received research support for this study from Abbott Medical Optics, Inc. and Lenstec, Inc. © 2013 ASCRS and ESCRS.


Pelton R.,McMaster University
Langmuir | Year: 2014

With the highest content of primary amine functional groups of any polymer, polyvinylamine (PVAm) is a potent tool for the modification of macroscopic and nanoparticle surfaces. Based on the free radical polymerization and subsequent hydrolysis of N-vinylformamide, PVAm is prepared as linear polymers (0.8 kDa to >1 MDa), microgels, macrogels, and copolymers. The amine groups serve as reaction sites for grafting PVAm to surfaces and for the preparation of derivatives. Coupling low-molecular-weight molecules and oligomers gives PVAm-X, where X includes hydrophobes, carbohydrate oligomers, proteins, TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy), phenylboronic acids, and fluorocarbons. This contribution highlights the use of PVAm and PVAm-X to modify solid surface properties. Where possible, the PVAm properties and applications as an interfacial agent are compared to those of linear polyethylenimine, polyallylamine, and chitosan. © 2014 American Chemical Society.


Goldhaber S.Z.,Harvard University | Leizorovicz A.,University of Lyon | Kakkar A.K.,University College London | Haas S.K.,TU Munich | And 3 more authors.
New England Journal of Medicine | Year: 2011

BACKGROUND: The efficacy and safety of prolonging prophylaxis for venous thromboembolism in medically ill patients beyond hospital discharge remain uncertain. We hypothesized that extended prophylaxis with apixaban would be safe and more effective than short-term prophylaxis with enoxaparin. METHODS: In this double-blind, double-dummy, placebo-controlled trial, we randomly assigned acutely ill patients who had congestive heart failure or respiratory failure or other medical disorders and at least one additional risk factor for venous thromboembolism and who were hospitalized with an expected stay of at least 3 days to receive apixaban, administered orally at a dose of 2.5 mg twice daily for 30 days, or enoxaparin, administered subcutaneously at a dose of 40 mg once daily for 6 to 14 days. The primary efficacy outcome was the 30-day composite of death related to venous thromboembolism, pulmonary embolism, symptomatic deep-vein thrombosis, or asymptomatic proximal-leg deep-vein thrombosis, as detected with the use of systematic bilateral compression ultrasonography on day 30. The primary safety outcome was bleeding. All efficacy and safety outcomes were independently adjudicated. RESULTS: A total of 6528 subjects underwent randomization, 4495 of whom could be evaluated for the primary efficacy outcome - 2211 in the apixaban group and 2284 in the enoxaparin group. Among the patients who could be evaluated, 2.71% in the apixaban group (60 patients) and 3.06% in the enoxaparin group (70 patients) met the criteria for the primary efficacy outcome (relative risk with apixaban, 0.87; 95% confidence interval [CI], 0.62 to 1.23; P = 0.44). By day 30, major bleeding had occurred in 0.47% of the patients in the apixaban group (15 of 3184 patients) and in 0.19% of the patients in the enoxaparin group (6 of 3217 patients) (relative risk, 2.58; 95% CI, 1.02 to 7.24; P = 0.04). CONCLUSIONS: In medically ill patients, an extended course of thromboprophylaxis with apixaban was not superior to a shorter course with enoxaparin. Apixaban was associated with significantly more major bleeding events than was enoxaparin. (Funded by Bristol- Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00457002.) Copyright © 2011 Massachusetts Medical Society.


Boden W.E.,State University of New York at Buffalo | Probstfield J.L.,University of Washington | Anderson T.,University of Calgary | Chaitman B.R.,Saint Louis University | And 5 more authors.
New England Journal of Medicine | Year: 2011

BACKGROUND: In patients with established cardiovascular disease, residual cardiovascular risk persists despite the achievement of target low-density lipoprotein (LDL) cholesterol levels with statin therapy. It is unclear whether extended-release niacin added to simvastatin to raise low levels of high-density lipoprotein (HDL) cholesterol is superior to simvastatin alone in reducing such residual risk. METHODS: We randomly assigned eligible patients to receive extended-release niacin, 1500 to 2000 mg per day, or matching placebo. All patients received simvastatin, 40 to 80 mg per day, plus ezetimibe, 10 mg per day, if needed, to maintain an LDL cholesterol level of 40 to 80 mg per deciliter (1.03 to 2.07 mmol per liter). The primary end point was the first event of the composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for an acute coronary syndrome, or symptom-driven coronary or cerebral revascularization. RESULTS: A total of 3414 patients were randomly assigned to receive niacin (1718) or placebo (1696). The trial was stopped after a mean follow-up period of 3 years owing to a lack of efficacy. At 2 years, niacin therapy had significantly increased the median HDL cholesterol level from 35 mg per deciliter (0.91 mmol per liter) to 42 mg per deciliter (1.08 mmol per liter), lowered the triglyceride level from 164 mg per deciliter (1.85 mmol per liter) to 122 mg per deciliter (1.38 mmol per liter), and lowered the LDL cholesterol level from 74 mg per deciliter (1.91 mmol per liter) to 62 mg per deciliter (1.60 mmol per liter). The primary end point occurred in 282 patients in the niacin group (16.4%) and in 274 patients in the placebo group (16.2%) (hazard ratio, 1.02; 95% confidence interval, 0.87 to 1.21; P = 0.79 by the log-rank test). CONCLUSIONS: Among patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of less than 70 mg per deciliter (1.81 mmol per liter), there was no incremental clinical benefit from the addition of niacin to statin therapy during a 36-month follow-up period, despite significant improvements in HDL cholesterol and triglyceride levels. (Funded by the National Heart, Lung, and Blood Institute and Abbott Laboratories; AIM-HIGH ClinicalTrials.gov number, NCT00120289.) Copyright © 2011 Massachusetts Medical Society. All rights reserved.


Woody E.Z.,University of Waterloo | Szechtman H.,McMaster University
Frontiers in Human Neuroscience | Year: 2013

Research indicates that there is a specially adapted, hard-wired brain circuit, the security motivation system, which evolved to manage potential threats, such as the possibility of contamination or predation. The existence of this system may have important implications for policy-making related to security. The system is sensitive to partial, uncertain cues of potential danger, detection of which activates a persistent, potent motivational state of wariness or anxiety. This state motivates behaviors to probe the potential danger, such as checking, and to correct for it, such as washing. Engagement in these behaviors serves as the terminating feedback for the activation of the system. Because security motivation theory makes predictions about what kinds of stimuli activate security motivation and what conditions terminate it, the theory may have applications both in understanding how policy-makers can best influence others, such as the public, and also in understanding the behavior of policy-makers themselves. © 2013 Woody and Szechtman.


Nair P.,Firestone Institute for Respiratory Health | Hargreave F.E.,McMaster University
Chest | Year: 2010

Airway inflammation is fundamental to the cause and persistence of asthma and other airway conditions. It contributes to symptoms, variable airflow limitation, airway hyperresponsiveness, and the structural changes (remodeling) associated with asthma. However, the presence and type of airway inflammation can be difficult to detect clinically, delaying the introduction of appropriate treatment. Cellular inflammation in the airway can be accurately and reliably assessed by examining spontaneous or, when not available, induced sputum. Induced sputum cell counts are relatively noninvasive, safe, and reliable. They can accurately discriminate eosinophilic airway inflammation from noneosinophilic airway inflammation and, thus, help to guide therapy. Eosinophilic airway inflammation is steroid responsive, whereas noneosinophilic (usually neutrophilic) inflammation generally is not. Monitoring of airway inflammation using sputum cell counts helps to identify the impending loss of asthma control and, thus, the need to adjust antiinflammatory medications in patients with a variety of airway diseases, such as asthma, smoker's COPD, and chronic cough. Other noninvasive, indirect measurements of airway inflammation, such as exhaled nitric oxide, do not help to identify the cellular nature of airway inflammation associated with exacerbations of airway diseases, particularly in patients who are already on corticosteroids. Thus, although they can be a predictor of steroid responsiveness, these measures do not help to reduce asthma exacerbations when used in clinical practice. The clinical usefulness of measurements in exhaled breath condensate has not yet been established. © 2010 American College of Chest Physicians.


Steinberg G.R.,McMaster University | Dandapani M.,University of Dundee | Hardie D.G.,University of Dundee
Trends in Endocrinology and Metabolism | Year: 2013

Salicylates are among the oldest medicinal compounds known to humans, and have been used to reduce fever, pain, and inflammation. The major oral salicylates are aspirin and salsalate, both of which are rapidly metabolized to salicylate in vivo. Owing to its acetyl group, aspirin irreversibly inhibits cyclo-oxygenases and thus blocks platelet aggregation, whereas salsalate has been used for treatment of inflammatory diseases such as rheumatoid arthritis. Recently, beneficial effects of salicylates in type 2 diabetes and cancer have been proposed. This has led to renewed interest in understanding how these simple molecules have such diverse and multifaceted effects. Here we discuss the idea that AMP-activated protein kinase (AMPK) might mediate some effects of salicylate-based drugs, particularly by modulating cellular metabolism. © 2013 Elsevier Ltd.


Wright G.D.,McMaster University
Canadian Journal of Microbiology | Year: 2014

Antibiotic discovery is in crisis. Despite a growing need for new drugs resulting from the increasing number of multiantibiotic- resistant pathogens, there have been only a handful of new antibiotics approved for clinical use in the past 2 decades. Faced with scientific, economic, and regulatory challenges, the pharmaceutical sector seems unable to respond to what has been called an "apocalyptic" threat. Natural products produced by bacteria and fungi are genetically encoded products of natural selection that have been the mainstay sources of the antibiotics in current clinical use. The pharmaceutical industry has largely abandoned these compounds in favor of large libraries of synthetic molecules because of difficulties in identifying new natural product antibiotics scaffolds. Advances in next-generation genome sequencing, bioinformatics, and analytical chemistry are combining to overcome barriers to natural products. Coupled with new strategies in antibiotic discovery, including inhibition of resistance, novel drug combinations, and new targets, natural products are poised for a renaissance to address what is a pressing health care crisis.


Mothersill C.E.,McMaster University
Radiation Research | Year: 2010

We examined bystander cell death produced in T98G cells by exposure to irradiated cell conditioned medium (ICCM) produced by high-energy 20 MeV electrons at a dose rate of 10 Gy min-1 and doses up to 20 Gy. ICCM induced a bystander response in T98G glioma cells, reducing recipient cell survival by more than 25 below controls at 5 and 10 Gy. Higher doses increased survival to near control levels. ICCM was analyzed for the presence of transforming growth factor α (TGF-α) and transforming growth factor β1 (TGF-β1). Monoclonal antibodies for TGF-α (mAb TGF-α) and TGF-β1 (mAb TGF-β1) were added to the ICCM to neutralize any potential effect of the cytokines. The results indicate that TGF-α was not present in the ICCM and addition of mAb TGF-α to the ICCM had no effect on bystander cell survival. No active TGF-β1 was present in the ICCM; however, addition of mAb TGF-β1 completely abolished bystander death of reporter cells at all doses. These results indicate that bystander cell death can be induced in T98G glioma if a large enough radiation stress is applied and that TGF-β1 plays a downstream role in this response. © 2010 by Radiation Research Society.


Weiner N.,New York University | Yavin I.,McMaster University | Yavin I.,Perimeter Institute for Theoretical Physics
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

Models that seek to produce a line at ∼130 GeV as possibly present in the Fermi data face a number of phenomenological hurdles, not the least of which is achieving the high cross section into γγ required. A simple explanation is a fermionic dark matter particle that couples to photons through loops of charged messengers. We study the size of the dimension-5 dipole (for a pseudo-Dirac state) and dimension-7 Rayleigh operators in such a model, including all higher order corrections in 1/Mmess. Such corrections tend to enhance the annihilation rates beyond the naive effective operators. We find that while freeze-out is generally dominated by the dipole, the present-day gamma-ray signatures are dominated by the Rayleigh operator, except at the most strongly coupled points, motivating a hybrid approach. With this, the magnetic inelastic dark matter scenario provides a successful explanation of the lines at only moderately strong coupling. We also consider the pure Majorana weakly interacting massive particle, where both freeze-out and the Fermi lines can be explained, but only at very strong coupling with light (∼200-300 GeV) messengers. In both cases there is no conflict with nonobservation of continuum photons. © 2013 American Physical Society.


Davis G.A.,Murdoch Childrens Research Institute | Purcell L.K.,McMaster University
British Journal of Sports Medicine | Year: 2014

Background: There are many reasons why concussion in children needs to be considered different from adults. The Zurich (2008) recommendations on the management of concussion in children are restricted to children less than to 10 years of age. It does not include recommendations for children aged 5-10 years. The aim of this study is to review the current literature on (1) concussion assessment at the sideline and during recovery stages, especially in the age group 5-15 years, and (2) the management of concussion in children and adolescents. Methods: A literature review using the MEDLINE database was undertaken. Articles were selected that included evaluation and/or management in children aged 5-15 years. Results: There are no sideline assessment tools validated for use in this age group. There are a number of different symptom scales that have been validated during different stages of the follow-up assessment in children. No single paediatric concussion assessment tool has been validated for use from sideline through to all stages of recovery. Reliability studies have been published on Balance Error Scoring System in children, but validity studies in this age group have not been published. The management of concussion includes withdrawal from play on the day and cognitive and physical rest. The priority of concussion management in children is to return to learn; while this is usually rapid, there are some children in whom a graduated return to school is required, which should include a number of accommodations. Conclusions: A young child is physically, cognitively and emotionally very different from adults, and requires the use of a different set of tools for the diagnosis, recoveryassessment and management of concussion. Age-specific, validated diagnostic tools are required, and management of concussion in children should focus attention on return to learn before considering return to play.


Dumitrescu S.,McMaster University
IEEE Transactions on Information Theory | Year: 2011

The design of optimal multi-resolution scalar quantizers using the generalized Lloyd method was proposed by Brunk and Farvardin for the case of squared error distortion. Since the algorithm details heavily rely on the quadratic expression of the error function, its extension to general error functions faces some challenges, especially at the encoder optimization step. In this work we show how these challenges can be overcome for any convex difference distortion measure, under the assumption that all quantizer cells are convex (i.e., intervals), and present an efficient algorithm for optimal encoder partition computation. The proposed algorithm is faster than the algorithm used by Brunk and Farvardin. Moreover, it can also be applied to channel-optimized and to multiple description scalar quantizer design with squared error distortion, and it outperforms in speed the previous encoder optimization algorithms proposed for these problems. © 2011 IEEE.


Verdijk L.B.,McMaster University
Medicine and Science in Sports and Exercise | Year: 2016

PURPOSE: Skeletal muscle capillarization plays a key role in oxygen and nutrient delivery to muscle. The loss of muscle mass with aging and the concept of anabolic resistance have been, at least partly, attributed to changes in skeletal muscle capillary structure and function. We aimed to compare skeletal muscle capillarization between young and older men, and evaluate whether resistance type exercise training increases muscle capillarization in older men. METHODS: Muscle biopsies were obtained from the vastus lateralis of healthy young (n=14, 26±2 y) and older (n=16, 72±1 y) adult men, with biopsies before and after 12 weeks of resistance type exercise training in the older subjects. Immunohistochemistry was used to assess skeletal muscle fiber size, capillary contacts per muscle fiber (CC), and the capillary-to-fiber perimeter exchange (CFPE) index in type I and II muscle fibers. RESULTS: Type II muscle fibers were smaller in old vs young (4507±268 vs 6084±497 μm, respectively, P=0.007). Type I and type II muscle fiber CC and CFPE index were smaller in old compared with young muscle (CC type I: 3.8±0.2 vs 5.0±0.3; CC type II: 3.2±0.2 vs 4.2±0.2, respectively; both P<0.001). Resistance type exercise training increased type II muscle fiber size only. In addition, CC and CFPE index increased in both the type I (26±9 and 27±8%) and type II muscle fibers (33±7 and 24±6%, respectively; all P≤0.001) following 12 weeks resistance training in older men. CONCLUSION: We conclude that resistance type exercise training can effectively augment skeletal muscle fiber capillarization in older males. The greater capillary supply may be an important prerequisite to reverse anabolic resistance and support muscle hypertrophy during lifestyle interventions aiming to support healthy aging. © 2016 American College of Sports Medicine


Gunturkun U.,McMaster University
Physica D: Nonlinear Phenomena | Year: 2010

This paper describes a functional analysis-based method for the estimation of driving-forces from nonlinear dynamic systems. The driving-forces account for the perturbation inputs induced by the external environment or the secular variations in the internal variables of the system. The proposed algorithm is applicable to the problems for which there is too little or no prior knowledge to build a rigorous mathematical model of the unknown dynamics. We derive the estimator conditioned on the differentiability of the unknown system's mapping, and smoothness of the driving-force. The proposed algorithm is an adaptive sequential realization of the blind prediction error method, where the basic idea is to predict the observables, and retrieve the driving-force from the prediction error. Our realization of this idea is embodied by predicting the observables one-step into the future using a bank of echo state networks (ESN) in an online fashion, and then extracting the raw estimates from the prediction error and smoothing these estimates in two adaptive filtering stages. The adaptive nature of the algorithm enables to retrieve both slowly and rapidly varying driving-forces accurately, which are illustrated by simulations. Logistic and Moran-Ricker maps are studied in controlled experiments, exemplifying chaotic state and stochastic measurement models. The algorithm is also applied to the estimation of a driving-force from another nonlinear dynamic system that is stochastic in both state and measurement equations. The results are judged by the posterior Cramer-Rao lower bounds. The method is finally put into test on a real-world application; extracting sun's magnetic flux from the sunspot time series. © 2010 Elsevier B.V. All rights reserved.


Treatment of venous thromboembolism (VTE) should be continued until the reduction of recurrent VTE that anticoagulation is expected to achieve no longer outweighs the increase in bleeding associated with therapy, or until the patient wants to stop treatment even if treatment is expected to be of benefit. Reversibility of risk factors for VTE is the most important factor that influences risk of recurrence and duration of therapy. VTE associated with a reversible risk factor (eg, surgery) is treated for 3 months; unprovoked VTE often benefits from indefinite therapy provided patients do not have risk factors for bleeding; and cancer-associated VTE is usually treated indefinitely. A systematic approach to managing warfarin therapy improves its efficacy, safety, and acceptability. © 2010 Elsevier Inc.


Bilgin B.,Illinois Institute of Technology | Emadi A.,McMaster University | Krishnamurthy M.,Illinois Institute of Technology
IEEE Transactions on Industrial Electronics | Year: 2012

Switched-reluctance-machine (SRM) technology is a potential candidate for the propulsion systems of hybrid and plug-in hybrid electric vehicles. They are robust in harsh operational conditions and have a wide constant power speed range. Conventional SRM configurations have a higher number of stator poles than rotor poles. This paper presents the advantages of a novel SRM configuration with the number of rotor poles greater than the number of stator poles. It also investigates different design challenges toward the traction applications. The proposed SRM configuration is based on a pole-design formula. Geometrical design equations and related challenges are introduced, and their applicability has been verified on a three-phase 6/10 SRM using finite-element-analysis simulations. © 2012 IEEE.


El Dib R.P.,McMaster University
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: Anderson-Fabry disease is an X-linked defect of glycosphingolipid metabolism. Progressive renal insufficiency is a major source of morbidity, additional complications result from cardio- and cerebro-vascular involvement. Survival is reduced among affected males and symptomatic female carriers. OBJECTIVES: To evaluate the effectiveness and safety of enzyme replacement therapy compared to other interventions, placebo or no interventions, for treating Anderson-Fabry disease. SEARCH STRATEGY: We searched 'Clinical Trials' on The Cochrane Library, MEDLINE, EMBASE, LILACS and the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register (date of the most recent search: 07 April 2010). SELECTION CRITERIA: Randomized controlled trials of agalsidase alfa or beta in participants diagnosed with Anderson-Fabry disease. DATA COLLECTION AND ANALYSIS: Two authors selected relevant trials, assessed methodological quality and extracted data. MAIN RESULTS: Five studies comparing either agalsidase alfa or beta in 187 participants fulfilled the selection criteria.Both trials comparing agalsidase alfa to placebo reported on globotriaosylceramide concentration in plasma and tissue; aggregate results were non-significant. One study reported pain scores, there was a statistically significant improvement for participants receiving treatment at up to three months, mean difference -2.10 (95% confidence interval (CI) -3.79 to -0.41); at up to five months, mean difference -1.90 (95% CI -3.65 to -0.15); and at up to six months, mean difference -2.00 (95% CI -3.66 to -0.34). There was a significant difference in pain-related quality of life at over five months and up to six months, mean difference -2.10 (95% CI -3.92 to -0.28) but not at other time-points. Neither study reported deaths.One of the three trials comparing agalsidase beta to placebo reported on globotriaosylceramide concentration in plasma and tissue and showed significant improvement: kidney, mean difference -1.70 (95% CI -2.09 to -1.31); heart, mean difference -0.90 (95% CI -1.18 to -0.62); and composite results (renal, cardiac, and cerebrovascular complications and death), mean difference -4.80 (95% CI -5.45 to -4.15). There was no significant difference between groups for death; no studies reported on pain. AUTHORS' CONCLUSIONS: Five small, poor quality randomised controlled trials provide no robust evidence for use of either agalsidase alfa and beta to treat Anderson-Fabry disease.


DiCenso A.,McMaster University
Nursing leadership (Toronto, Ont.) | Year: 2010

The objective of this decision support synthesis was to identify and review published and grey literature and to conduct stakeholder interviews to (1) describe the distinguishing characteristics of clinical nurse specialist (CNS) and nurse practitioner (NP) role definitions and competencies relevant to Canadian contexts, (2) identify the key barriers and facilitators for the effective development and utilization of CNS and NP roles and (3) inform the development of evidence-based recommendations for the individual, organizational and system supports required to better integrate CNS and NP roles into the Canadian healthcare system and advance the delivery of nursing and patient care services in Canada. Four types of advanced practice nurses (APNs) were the focus: CNSs, primary healthcare nurse practitioners (PHCNPs), acute care nurse practitioners (ACNPs) and a blended CNS/NP role. We worked with a multidisciplinary, multijurisdictional advisory board that helped identify documents and key informant interviewees, develop interview questions and formulate implications from our findings. We included 468 published and unpublished English- and French-language papers in a scoping review of the literature. We conducted interviews in English and French with 62 Canadian and international key informants (APNs, healthcare administrators, policy makers, nursing regulators, educators, physicians and other team members). We conducted four focus groups with a total of 19 APNs, educators, administrators and policy makers. A multidisciplinary roundtable convened by the Canadian Health Services Research Foundation formulated evidence-informed policy and practice recommendations based on the synthesis findings. This paper forms the foundation for this special issue, which contains 10 papers summarizing different dimensions of our synthesis. Here, we summarize the synthesis methods and the recommendations formulated at the roundtable.


BACKGROUND: Pediatric patients with health conditions requiring follow-up typically depend on a caregiver to mediate at least part of the necessary two-way communication with health care providers on their behalf. Health information technology (HIT) and its subset, information communication technology (ICT), are increasingly being applied to facilitate communication between health care provider and caregiver in these situations. Awareness of the extent and nature of published research involving HIT interventions used in this way is currently lacking. OBJECTIVE: This scoping review was designed to map the health literature about HIT used to facilitate communication involving health care providers and caregivers (who are usually family members) of pediatric patients with health conditions requiring follow-up. METHODS: Terms relating to care delivery, information technology, and pediatrics were combined to search MEDLINE, EMBASE, and CINAHL for the years 1996 to 2008. Eligible studies were selected after three rounds of duplicate screening in which all authors participated. Data regarding patient, caregiver, health care provider, HIT intervention, outcomes studied, and study design were extracted and maintained in a Microsoft Access database. Stage of research was categorized using the UK's Medical Research Council (MRC) framework for developing and evaluating complex interventions. Quantitative and qualitative descriptive summaries are presented. RESULTS: We included 104 eligible studies (112 articles) conducted in 17 different countries and representing 30 different health conditions. The most common conditions were asthma, type 1 diabetes, special needs, and psychiatric disorder. Most studies (88, 85%) included children 2 to 12 years of age, and 73 (71%) involved home care settings. Health care providers operated in hospital settings in 96 (92%) of the studies. Interventions featured 12 modes of communication (eg, Internet, intranets, telephone, video conferencing, email, short message service [SMS], and manual downloading of information) used to facilitate 15 categories of functions (eg, support, medication management, education, and monitoring). Numerous patient, caregiver, and health care relevant outcomes have been measured. Most outcomes concerned satisfaction, use, usability, feasibility, and resource use, although behavior changes and quality of life were also reported. Most studies (57 studies, 55%) were pilot phase, with a lesser proportion of development phase (24 studies, 23%) and evaluation phase (11 studies, 11%) studies. HIT interventions addressed several recurring themes in this review: establishing continuity of care, addressing time constraints, and bridging geographical barriers. CONCLUSIONS: HIT used in pediatric care involving caregivers has been implemented differently in a range of disease settings, with varying needs influencing the function, form and synchronicity of information transfer. Although some authors have followed a phased approach to development, evaluation and implementation, a greater emphasis on methodological standards such as the MRC guidance for complex interventions would produce more fruitful programs of development and more useful evaluations in the future. This review will be especially helpful to those deciding on areas where further development or research into HIT for this purpose may be warranted.


Norman G.,McMaster University
Medical Education | Year: 2011

Context Medical education research has been an academic pursuit for over 50years, tracing its roots back to the Office of Medical Education at the State University of New York at Buffalo, New York, with George Miller. As the field has matured, the nature of the questions posed and the disciplinary bases of its practitioners have evolved. Methods I identify three chronological 'generations' of academics who have contributed to the field, at intervals of roughly 10-15years. Results Members of the first generation came from diverse and unrelated academic backgrounds and essentially learned their craft on the job. A second generation, emerging in the 1980s and 1990s, consisted of individuals with PhD-level training in relevant fields such as psychology, psychometrics and sociology, who actively chose a career in health sciences education, often during graduate work. These individuals brought a strong disciplinary orientation to their research. Finally, the proliferation of graduate programmes in medical education means that we are now seeing the evolution of a new type of academic, often a health professional, whose only discipline is medical education. Conclusions I propose that we should strike a balance between seeking to create a separate specialty of medical education and continuing to actively recruit from other academic disciplines. I believe that the strong disciplinary roots of these individuals are a critical element in the continuing growth and progress of medical education research. © Blackwell Publishing Ltd 2011.


Britz-McKibbin P.,McMaster University
Methods in molecular biology (Clifton, N.J.) | Year: 2011

Metabolomics is a rapidly emerging field of functional genomics research whose aim is the comprehensive analysis of low molecular weight metabolites in a biological sample. Capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS) represents a promising hyphenated microseparation platform in metabolomics, since a majority of primary metabolites are intrinsically polar. CE-ESI-MS offers a convenient format for the separation of complex mixtures of cationic, anionic, and/or zwitterionic metabolites, as well as their isobaric/isomeric ions without complicated sample handling. Moreover, online sample preconcentration with desalting is readily integrated during separation prior to ionization, where the migration behavior and ionization response of metabolites can be predicted based on their fundamental physicochemical properties. Herein, we describe recent developments in CE-ESI-MS with emphasis on practical protocols necessary for realizing reliable analyses as applied to targeted metabolite profiling and untargeted metabolomic studies in various biological samples.


Kaasalainen S.,McMaster University
Nursing leadership (Toronto, Ont.) | Year: 2010

Advanced practice nursing has evolved over the years to become recognized today as an important and growing trend among healthcare systems worldwide. To understand the development and current status of advanced practice nursing within a Canadian context, it is important to explore its historical roots and influences. The purpose of this paper is to provide a historical overview of the major influences on the development of advanced practice nursing roles that exist in Canada today, those roles being the nurse practitioner and the clinical nurse specialist. Using a scoping review and qualitative interviews, data were summarized according to three distinct time periods related to the development of advanced practice nursing. They are the early beginnings; the first formal wave, between the mid 1960s and mid 1980s; and the second wave, beginning in the late 1980s and continuing to the present. This paper highlights how advanced practice nursing roles have evolved over the years to meet emerging needs within the Canadian healthcare system. A number of influential factors have both facilitated and hindered the development of the roles, despite strong evidence to support their effectiveness. Given the progress over the past few decades, the future of advanced practice nursing within the Canadian healthcare system is promising.


Nidorf S.M.,Heart Care Western Australia | Eikelboom J.W.,McMaster University | Budgeon C.A.,University of Western Australia | Thompson P.L.,Western Research Institute
Journal of the American College of Cardiology | Year: 2013

Objectives: The objective of this study was to determine whether colchicine 0.5 mg/day can reduce the risk of cardiovascular events in patients with clinically stable coronary disease. Background: The presence of activated neutrophils in culprit atherosclerotic plaques of patients with unstable coronary disease raises the possibility that inhibition of neutrophil function with colchicine may reduce the risk of plaque instability and thereby improve clinical outcomes in patients with stable coronary disease. Methods: In a clinical trial with a prospective, randomized, observer-blinded endpoint design, 532 patients with stable coronary disease receiving aspirin and/or clopidogrel (93%) and statins (95%) were randomly assigned colchicine 0.5 mg/day or no colchicine and followed for a median of 3 years. The primary outcome was the composite incidence of acute coronary syndrome, out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke. The primary analysis was by intention-to-treat. Results: The primary outcome occurred in 15 of 282 patients (5.3%) who received colchicine and 40 of 250 patients (16.0%) assigned no colchicine (hazard ratio: 0.33; 95% confidence interval [CI] 0.18 to 0.59; p < 0.001; number needed to treat: 11). In a pre-specified secondary on-treatment analysis that excluded 32 patients (11%) assigned to colchicine who withdrew within 30 days due to intestinal intolerance and a further 7 patients (2%) who did not start treatment, the primary outcome occurred in 4.5% versus 16.0% (hazard ratio: 0.29; 95% CI: 0.15 to 0.56; p < 0.001). Conclusions: Colchicine 0.5 mg/day administered in addition to statins and other standard secondary prevention therapies appeared effective for the prevention of cardiovascular events in patients with stable coronary disease. © 2013 American College of Cardiology Foundation.


Maurer D.,McMaster University | Hensch T.K.,Harvard University
Developmental Psychobiology | Year: 2012

In this introductory article, we summarize the evidence from humans and animal models on the shaping of postnatal visual development by focused binocular input. When balanced input is missing during a sensitive period, deficits emerge, including seemingly permanent impairments in visual acuity that are labeled amblyopia. Rodent models have identified neurochemical changes that control the onset of such sensitive periods and molecular and structural brakes that lead to the diminution of the plasticity thereafter. Both animal and human studies of amblyopia have recently identified exciting ways to remediate vision in adulthood that bear some similarity to the interventions that have proved successful in promoting recovery from stroke. © 2012 Wiley Periodicals, Inc.


Galef B.G.,McMaster University
Behavioural Brain Research | Year: 2012

Philip Teitelbaum's focus on detailed description of behavior, the interplay of analysis and synthesis in experimental investigations and the importance of converging lines of evidence in testing hypotheses has proven useful in fields distant from the physiological psychology that he studied throughout his career. Here we consider the social biasing of food choice in Norway rats as an instance of the application of Teitelbaum's principles of behavioral analysis and synthesis and the usefulness of convergent evidence as well as the contributions of detailed behavioral analysis of social influences on food choice to present understanding of both sensory processes and memory. © 2011 Elsevier B.V.


Li C.,McMaster University
Clinical Genetics | Year: 2011

The delivery of personalized genomic medicine (refer Table 1 for a comparison of genomic vs genetic medicine and box 1 for glossary) hinges on obtaining personal genomic data through genome-wide association studies (GWAS) or whole-genome sequencing. After the completion of the human genome project (see box 2 for human genome projects and its derivative projects) in 2003, there appeared to be a period of euphoric optimism that as soon as the cost of sequencing the whole human genome could be brought down to an affordable range, the promise of personalized medicine would become a reality. However, inasmuch as the miraculous technological advancements are making whole-genome data acquisition an inexpensive reality, we are also starting to appreciate that making sense of the enormous amount of genomic data is a far bigger hurdle. Issues, both scientific and ethico-legal, will have to be addressed as genomic data are been pushed for clinical and direct-to-consumer utilization. © 2011 John Wiley & Sons A/S.


Balakrishnan N.,McMaster University
Methods and Applications of Statistics in Clinical Trials | Year: 2014

Methods and Applications of Statistics in Clinical Trials, Volume 2: Planning, Analysis, and Inferential Methods includes updates of established literature from the Wiley Encyclopedia of Clinical Trials as well as original material based on the latest developments in clinical trials. Prepared by a leading expert, the second volume includes numerous contributions from current prominent experts in the field of medical research. In addition, the volume features: Multiple new articles exploring emerging topics, such as evaluation methods with threshold, empirical likelihood methods, nonparametric ROC analysis, over- and under-dispersed models, and multi-armed bandit problems. Up-to-date research on the Cox proportional hazard model, frailty models, trial reports, intrarater reliability, conditional power, and the kappa index. Key qualitative issues including cost-effectiveness analysis, publication bias, and regulatory issues, which are crucial to the planning and data management of clinical trials. © 2014 John Wiley & Sons, Inc. All rights reserved.


Lasowski F.,McMaster University
Optometry and Vision Science | Year: 2016

PURPOSE: Drug delivery to the anterior eye has a low compliance and results in significant drug losses. In pediatric patients, eye diseases such as myopia and retinoblastoma can potentially be treated pharmacologically, but the risk associated with high drug concentrations coupled with the need for regular dosing limits their effectiveness. The current study examined the feasibility of atropine and roscovitine delivery from model silicone hydrogel materials which could potentially be used to treat myopia and retinoblastoma, respectively. METHODS: Model silicone hydrogel materials that comprised TRIS and DMA were prepared with the drug incorporated during synthesis. Various materials properties, with and without incorporated drug, were investigated including water uptake, water contact angle, and light transmission. Drug release was evaluated under sink conditions into phosphate buffered saline. RESULTS: The results demonstrate that up to 2 wt% of the drugs can be incorporated into model silicone hydrogel materials without adversely affecting critical materials properties such as water uptake, light transmission, and surface hydrophilicity. Equilibrium water content ranged from 15 to 32% and transmission exceeded 89% for materials with at least 70% DMA. Extended release exceeding 14 days was possible with both drugs, with the total amount of drug released from the materials ranging from 16% to over 76%. Although a burst effect was noted, this was thought to be due to surface-bound drug, and therefore storage in an appropriate packaging solution could be used to overcome this if desired. CONCLUSIONS: Silicone hydrogel materials have the potential to deliver drugs for over 2 weeks without compromising lens properties. This could potentially overcome the need for regular drop instillation and allow for the maintenance of drug concentration in the tear film over the period of wear. This represents a potential option for treating a host of ophthalmic disorders in children including myopia and retinoblastoma. © 2016 American Academy of Optometry


Progress in the treatment of cancers in young people has resulted in an increasing success rate in curing the different forms of malignant diseases. The mission of the CPAC/C17 Task Force on Adolescents and Young Adults (AYA) with cancer is to ensure prompt, equitable access to the best care; establish research priorities to optimize health outcomes and health-related quality of life; and mitigate current disparities of care through advances in treatment, education, and research. Although these goals are important, the mission statement seems to ignore an important factor: "affordability, " or the ability to achieve these goals due to scarcity of resources. In this article, the role of economics in helping decision makers decide on resource allocation is discussed. Also described is the economic basis for the healthcare problem; the inability of the current methodology of cost-effectiveness to provide information that can help improve resource allocation in health; and how economics should be used to promote efficient use of healthcare resources. The author argued that "affordability" should be recognized in the mission statement. Recognizing "affordability" means recognizing the need to justify the transfer (or allocation) of additional resources to AYA cancer, which requires demonstration that the value of what is gained from the use of these resources in AYA cancer exceeds the value of what is forgone by using them elsewhere. This will also require making explicit the values or equity criteria to which society subscribes. Copyright © 2011 American Cancer Society.


Soares C.N.,Womens Health Concerns Clinic | Soares C.N.,McMaster University
Drugs and Aging | Year: 2013

Epidemiologic and clinic data have unequivocally supported the notion that women experience more psychiatric problems at some point in their lives compared with men, particularly mood and anxiety symptoms and sleep problems. It is also known that, for some women, such increased risk might be associated with reproductive cycle events such as the postpartum period or the menopausal transition. These periods are not only marked by substantial hormone variations but also quite often accompanied by stressful events and changes in personal, family and professional responsibilities. The complexity of these reproductive-related 'windows of vulnerability' poses a challenge to physicians and other professionals dedicated to women's health across the lifespan. The menopausal transition and early postmenopausal years constitute a characteristic example; during this period in life, dynamic changes in sex hormones and reproductive function co-occur with modifications in metabolism, sexuality, lifestyle behaviours and overall health, sometimes affecting a woman's quality of life and overall functioning. For most women, however, this transition has little or no significant impact on their mental wellness. A prior depressive episode - particularly if related to reproductive events - is the strongest predictor of mood symptoms or depression during menopausal years. Also, the presence and severity of vasomotor symptoms and other health-related issues appear to modulate the risk for depression in midlife women. Mechanistically, estrogen plays an important modulatory role in mood and cognitive regulation, hence the effects noted when midlife women are exposed to significant estrogen fluctuations or to estrogen-based therapies (use or withdrawal). Transdermal estradiol, as well as serotonergic and noradrenergic antidepressants, have shown efficacy in the management of depression in this population. Other evidence-based treatment options (hormonal, pharmacological, behavioural) are available to clinicians and health professionals who care for this population. © 2013 Springer International Publishing Switzerland.


Tarnopolsky M.A.,McMaster University
Annals of Nutrition and Metabolism | Year: 2010

Background/Aims: Caffeine and creatine are 2 of the most widely available and used compounds in sport. Although the use of either is not considered a doping infraction, the evidence does suggest ergogenic potential in certain sports. The purpose of this paper is to review the pharmacology and potential mechanism(s) of action of caffeine and creatine as they pertain to possible use as an ergogenic aid in sport. Methods: Previous review articles on caffeine and creatine use in sport were screened for relevant information and references, and studies for review and recent articles (2007 onwards) were obtained and reviewed using a PUBMED search with the terms 'caffeine AND exercise', 'creatine and creatine monohydrate AND exercise', and appropriate linked articles were evaluated. Results: Caffeine taken before (3-6 mg/kg) or during (1-2 mg/kg) endurance exercise enhances performance, through central nervous system and direct muscle effects. Creatine monohydrate supplementation at higher (approx. 20 g/day x 3-5 days) or lower (approx. 5 g/day x 30 days) doses increases skeletal muscle total and phosphocreatine by 10-20%. Creatine supplementation appears to minimally but significantly enhance high-intensity sport performance and the mass and possibly strength gains made during resistance exercise training over the first few months. Conclusions: Although caffeine and creatine appear to be ergogenic aids, they do so in a sport-specific context and there is no rationale for their simultaneous use in sport. Higher doses of caffeine can be toxic and appear to be ergolytic. There is no rationale for creatine doses in excess of the recommendations, and some athletes can get stomach upset, especially at higher creatine doses. Copyright © 2011 S. Karger AG.


Stockl H.,London School of Hygiene and Tropical Medicine | Devries K.,London School of Hygiene and Tropical Medicine | Rotstein A.,McMaster University | Abrahams N.,Gender and Health Research Unit | And 3 more authors.
The Lancet | Year: 2013

Background: Homicide is an important cause of premature mortality globally, but evidence for the magnitude of homicides by intimate partners is scarce and hampered by the large amount of missing information about the victim-offender relationship. The objective of the study was to estimate global and regional prevalence of intimate partner homicide. Methods: A systematic search of fi ve databases (Medline, Global Health, Embase, Social Policy, and Web of Science) yielded 2167 abstracts, and resulted in the inclusion of 118 full-text articles with 1122 estimates of the prevalence of intimate partner homicide after double-blind screening. All studies were included that reported the number or proportion of women or men who were murdered by an intimate partner in a country, province, or town, using an inclusive defi nition of an intimate partner. Additionally, a survey of offi cial sources of 169 countries provided a further 53 estimates. We selected one estimate per country-year using a quality assessment decision algorithm. The median prevalence of intimate partner homicide was calculated by country and region overall, and for women and men separately. Findings: Data were obtained for 66 countries. Overall 13.5% (IQR 9.2-18.2) of homicides were committed by an intimate partner, and this proportion was six times higher for female homicides than for male homicides (38.6%, 30.8-45.3, vs 6.3%, 3.1-6.3). Median percentages for all (male and female) and female intimate partner homicide were highest in high-income countries (all, 14.9%, 9.2-18.2; female homicide, 41.2%, 30.8-44.5) and in southeast Asia (18.8%, 11.3-18.8; 58.8%, 58.8-58.8). Adjustments to account for unknown victim-off ender relationships generally increased the prevalence, suggesting that results presented are conservative. Interpretation: At least one in seven homicides globally and more than a third of female homicides are perpetrated by an intimate partner. Such violence commonly represents the culmination of a long history of abuse. Strategies to reduce homicide risk include increased investment in intimate partner violence prevention, risk assessments at diff erent points of care, support for women experiencing intimate partner violence, and control of gun ownership for people with a history of violence. Improvements in country-level data collection and monitoring systems are also essential, because data availability and quality varied strongly across regions. Funding: WHO, Sigrid Rausing Trust, and the UK Economic and Social Research Council.


Surette M.G.,McMaster University
Annals of the American Thoracic Society | Year: 2014

The chronic colonization of the lower airways by bacterial pathogens is the leading cause of morbidity and mortality in patients with cystic fibrosis (CF). Pseudomonas aeruginosa is the most common CF pathogen, followed by Staphylococcus aureus. Improvements in airway clearance and more effective treatment of the conventional CF pathogens has led to the emergence of new airway pathogens such as Stenotrophomonas maltophilia, Mycobacterium abscessus, and Achromobacter. More recently, it has become appreciated that the lower airways in patients with CF are colonized by a more complex polymicrobial community composed primarily of bacteria found in the upper respiratory tract. This includes obligate anaerobes, most commonly Prevotella. Expanded culturing methods and culture-independent molecular methods are being used to characterize the composition and dynamics of these polymicrobial communities in patients with CF. The contribution of the CF microbiome to airway disease is actively being investigated and will present new opportunities for disease management in CF. However, there remain many challenges that must be overcome if microbiome profiling is going to inform clinical practice. Copyright © 2014 by the American Thoracic Society.


Forsythe P.,McMaster University
Annals of the American Thoracic Society | Year: 2014

There is increasing interest in the potential for microbe-based therapeutic approaches to asthma and respiratory infection. However, to date, clinical trials of probiotics in the treatment of respiratory disease have met with limited success. It is becoming clear that to identify the true therapeutic potential of microbes we must move away from a purely empirical approach to clinical trials and adopt knowledge-based selection of candidate probiotics strains, dose, and means of administration. Animal models have played a key role in the identification of mechanisms underlying the immunomodulatory capacity of specific bacteria. Microbe-induced changes in dendritic cell phenotype and function appear key to orchestrating the multiple pathways, involving inter alia, T cells, natural killer cells, and alveolar macrophages, associated with the protective effect of probiotics. Moving forward, the development of knowledge-based strategies for microbe-based therapeutics in respiratory disease will be aided by greater understanding of how specific bacterial structural motifs activate unique combinations of pattern recognition receptors on dendritic cells and thus direct desired immune responses. Copyright © 2014 by the American Thoracic Society.


Modabber M.,McMaster University | Kundu S.,Vein Institute of Toronto
CardioVascular and Interventional Radiology | Year: 2013

Central venous occlusive disease (CVD) is a common concern among the hemodialysis patient population, with the potential to cause significant morbidity. Endovascular management of CVD, comprising percutaneous balloon angioplasty and bare-metal stenting, has been established as a safe alternative to open surgical treatment. However, these available treatments have poor long-term patency, requiring close surveillance and multiple repeat interventions. Recently, covered stents have been proposed and their efficacy assessed for the treatment of recalcitrant central venous stenosis and obstruction. Moreover, newly proposed algorithms for the surgical management of CVD warrant consideration. Here, we seek to provide an updated review of the current literature on the various treatment modalities for CVD. © 2012 Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).


Cooper R.G.,McMaster University
Research Technology Management | Year: 2014

Overview: As the creator of the Stage-Gate® process, I am often asked, "What's next after stage-gate?" For years, I've not had an answer. Now, we're seeing new approaches emerging from progressive companies that represent a new generation of idea-to-launch processes. In some cases, it's an evolution of Stage-Gate to a better, faster model; in other firms, its closer to a revolution, moving to a very different system. But there is anything but unanimity as to what the next generation ideato-launch system should be. This article looks at what leading firms are doing to move beyond their current idea-to-launch methodology and tries to integrate these practices into a next-generation system. Copyright © 2014 Industrial Research Institute, Inc.


Leontiadis G.I.,McMaster University
American Journal of Gastroenterology | Year: 2013

A rigorously conducted cohort study published in this edition of the American Journal of Gastroenterology shows that the use of a proton-pump inhibitor is not associated with recurrent Clostridium difficile infection among hospitalized patients. This contradicts the findings of previous studies that, however, were at a high risk of bias. Where does the truth lie? Regardless of the answer, it is important that proton-pump inhibitors, not dissimilar to any other drug, are used appropriately.


Schulman S.,McMaster University
Current Opinion in Pulmonary Medicine | Year: 2012

PURPOSE OF REVIEW: The first study on the treatment of venous thromboembolism (VTE) with dabigatran (RE-COVER) was published in 2009. Three additional phase III trials on acute VTE therapy and extended treatment were recently presented. This article reviews the data and, where applicable, compares them with other novel oral anticoagulants, particularly rivaroxaban, for which all phase III trials have been published. RECENT FINDINGS: A twin study to RE-COVER (RE-COVER II) confirmed that dabigatran is not inferior to warfarin regarding efficacy and confers a lower risk for clinically relevant bleeding in the treatment of acute VTE for 6 months. Two studies on the extended treatment of VTE with dabigatran showed that the results for efficacy and safety can be extrapolated to another 16 months (mean) of treatment (RE-MEDY) and that dabigatran reduces the risk of recurrence by 90 compared with placebo (RE-SONATE). In the latter case, there is an increase of the risk for clinically relevant bleeding. SUMMARY: Dabigatran offers an alternative to warfarin for treatment of VTE without a need for coagulation monitoring or dose adjustments. Management of patients with VTE could thereby be simplified. Extended treatment might be considered more often for patients at higher risk of recurrence. Copyright © 2012 Lippincott Williams & Wilkins.


Isaacs S.,McMaster University
Primary health care research & development | Year: 2013

To explore how an organization's trust in the cultural competency of other service providers (competence trust) can influence the effectiveness of a services network in meeting the needs of recent immigrant families. Primary health care for recent immigrants arriving in Canada is delivered through a network of community-based services. To ensure the functioning of the network and its ability to facilitate access to needed services for new arrivals, network members need to be able to work together collaboratively. A case study involving services for an urban community in Atlantic Canada was undertaken in 2009 to explore how service organizations worked together to address the needs of recent immigrant families with young children. This paper focuses on provider perceptions of cultural competency among local service organizations and how this influenced trust and desire to work together for the benefit of families. The case study utilized both social network analysis and qualitative inquiry methodology. Twenty-one of 27 selected organizations responded to the online social network survey, and 14 key informant interviews were conducted. Social network measures and network mapping were used to demonstrate trusting relationships and associated interactions, while interview data were used to explain the relationships observed. Perceived cultural competency affected the degree of trust and collaboration within the services network when addressing the needs of recent immigrant families. Competence trust toward other providers increased the desire and commitment to work together, while lack of competence trust created avoidance. Non-government organizations were identified among the most culturally competent. The perceived positive and negative experiences of families with different providers influenced the level of trust among network members. The development of systemic cultural competences within a services network is needed in order to improve collaborations and access to services for immigrant families.


Oncolytic human herpes simplex virus type 1 (HSV-1) shows promising treatment efficacy in late-stage clinical trials. The anticancer activity of oncolytic viruses relies on deregulated pathways in cancer cells, which make them permissive to oncolysis. To identify pathways that restrict HSV-1 KM100-mediated oncolysis, this study used a pooled genome-wide short hairpin RNA library and found that depletion of the splicing factor arginine-rich splicing factor 2 (SRSF2) leads to enhanced cytotoxicity of breast cancer cells by KM100. Serine/arginine-rich (SR) proteins are a family of RNA-binding phosphoproteins that control both constitutive and alternative pre-mRNA splicing. Further characterization showed that KM100 infection of HS578T cells under conditions of low SRSF2 leads to pronounced apoptosis without a corresponding increase in virus replication. As DNA topoisomerase I inhibitors can limit the phosphorylation of SRSF2, we combined a topoisomerase I inhibitor chemotherapeutic with KM100 and observed synergistic anticancer effect in vitro and prolonged survival of tumor-bearing mice in vivo.Oncogene advance online publication, 10 August 2015; doi:10.1038/onc.2015.303. © 2015 Macmillan Publishers Limited


Spyropoulos A.C.,University of Rochester | Douketis J.D.,McMaster University
Blood | Year: 2012

The periprocedural management of patients receiving long-term oral anticoagulant therapy remains a common but difficult clinical problem, with a lack of highquality evidence to inform best practices. It is a patient's thromboembolic risk that drives the need for an aggressive periprocedural strategy, including the use of heparin bridging therapy, to minimize time off anticoagulant therapy, while the procedural bleed risk determines how and when postprocedural anticoagulant therapy should be resumed. Warfarin should be continued in patients undergoing selected minor procedures, whereas in major procedures that necessitate warfarin interruption, heparin bridging therapy should be considered in patients at high thromboembolic risk and in a minority of patients at moderate risk. Periprocedural data with the novel oral anticoagulants, such as dabigatran, rivaroxaban, and apixaban, are emerging, but their relatively short half-life, rapid onset of action, and predictable pharmacokinetics should simplify periprocedural use. This review aims to provide a practical, clinician-focused approach to periprocedural anticoagulant management. © 2012 by The American Society of Hematology.


Norman G.,McMaster University
Medical Education | Year: 2011

Context Recently several authors have drawn parallels between educational research and some theories of natural science, in particular complexity theory and chaos theory. The central claim is that both the natural science theories are useful metaphors for education research in that they deal with phenomena that involve many variables interacting in complex, non-linear and unstable ways, and leading to effects that are neither reproducible nor comprehensible. Methods This paper presents a counter-argument. I begin by carefully examining the concepts of uncertainty, complexity and chaos, as described in physical science. I distinguish carefully between systems that are, respectively, complex, chaotic and complicated. I demonstrate that complex and chaotic systems have highly specific characteristics that are unlikely to be present in education systems. I then suggest that, in fact, there is ample evidence that human learning can be understood adequately with conventional linear models. Conclusions The implications of these opposing world views are substantial. If education science has the properties of complex or chaotic systems, we should abandon any attempt at control or understanding. However, as I point out, to do so would ignore a number of recent developments in our understanding of learning that hold promise to yield substantial improvements in effectiveness and efficiency of learning. © Blackwell Publishing Ltd 2011.


Iorio A.,McMaster University | Puccetti P.,University of Perugia | Makris M.,University of Sheffield
Blood | Year: 2012

The development of alloantibodies or inhibitors is the most serious complication a patient with severe hemophilia can experience from treatment with clotting factor concentrates. Although common in previously untreated patients, inhibitor development is rare in multiply exposed, well-tolerized patients. There has been a nonevidence-based reluctance to change concentrate because of a perceived greater inhibitor risk after the switch, even though most patients are now likely to be using a concentrate on which they did not begin. Inhibitors in previously treated patients are observed in approximately 2 per 1000 patient/years, which makes it difficult to study and compare rates among different products. Because the baseline inhibitor risk in previously treated patients may vary over time, it is important to compare the risk in patients switching to a new product with that in a parallel control group of nonswitching patients or within a case-controlled study. The study designs imposed by regulators are suboptimal in detecting immunogenicity signals. The issue of immunogenicity of new products is likely to gain more relevance in the near future, with a call for effective postmarketing surveillance studies for all of the new engineered factor VIII concentrates with prolonged half-lives that are likely to enter clinical practice. © 2012 by The American Society of Hematology.


Nair P.,McMaster University
Canadian Respiratory Journal | Year: 2013

Airway inflammation is a central feature of many airway diseases such as asthma, chronic bronchitis, bronchiectasis and chronic cough; therefore, it is only logical that it is measured to optimize its treatment. However, most treatment recommendations, including the use of anti-inflammatory therapies such as corticosteroids, are based on assessments of only airflow and symptoms. Over the past 10 years, methods have been developed to assess airway inflammation relatively noninvasively. Quantitative cell counts in sputum and the fraction of exhaled nitric oxide are the most validated tests. Judicious use of currently available drugs, such as corticosteroids, bronchodilators and antibiotics, and other anti-inflammatory therapies guided by sputum eosinophil and neutrophil counts, have been demonstrated to decrease exacerbations of asthma and chronic obstructive pulmonary disease, ameliorate cough, improve quality of life in patients with these diseases and is cost effective compared with treatment strategies based on guidelines that do not incorporate these measurements. Thus, it is unfortunate that this is not used more widely in the management of airway diseases, particularly in patients with severe asthma and chronic obstructive pulmonary disease who experience frequent exacerbations. © 2013 Pulsus Group Inc.


Spyropoulos A.C.,McMaster University
Current Opinion in Hematology | Year: 2010

Purpose of review: Patients undergoing oral anticoagulation treatment with vitamin K antagonist (VKA) therapy are at a high risk of bleeding when undergoing an invasive surgery or procedure. Bridging therapy with parenteral heparin, usually at therapeutic doses, aims to protect these patients against thromboembolism during temporary periprocedural interruption of VKA therapy. Whether or not to interrupt VKA therapy and initiate bridging therapy is a difficult decision that is based upon both the patient's and the procedure's thromboembolic and bleeding risks. Recent findings: There are minor procedures that can safely be done without the need for VKA interruption. Patient groups that may benefit from bridging therapy during temporary VKA interruption for a procedure include those who are at moderate-to-high risk of thromboembolism. Procedural bleed risk should determine when to resume bridging and VKA therapies. Recent findings highlight that low-molecular-weight heparin, usually in the outpatient setting, is the preferred agent over intravenous unfractionated heparin for bridging therapy, which includes patients with prosthetic heart valve indications for VKA therapy. Summary: Large, recently initiated placebo-controlled trials in bridging therapy are discussed, as well as future alternatives to VKA therapy in oral anticoagulation during the periprocedural period. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Bhandari M.,McMaster University
The Journal of bone and joint surgery. American volume | Year: 2012

Despite the large number of fracture outcome studies, there remains variability in the definitions of fracture-healing. It is unclear how orthopaedic surgeons are diagnosing and managing delayed unions and nonunions in clinical practice. We aimed to explore the current opinions of orthopaedic surgeons with regard to defining, diagnosing, and treating delayed unions and nonunions in extremity fractures. We developed a survey using previous literature, key informants in the field of orthopaedic surgery, and a sample-to-redundancy strategy. Our final survey contained four sections and twenty-nine questions focusing on demographics and surgical experience, definitions of fracture union, prognostic factors for union, and the need for clinical trials. The Internet-based survey and follow-up e-mails were continued until our a priori sample size of a minimum of 320 completed and eligible responses were collected. Three hundred and thirty-five surgeons completed the survey. The typical respondent was a North American, male orthopaedic surgeon or consultant over the age of thirty years who had completed trauma fellowship training, worked in an academic practice, supervised residents, and had more than six years of experience in treating orthopaedic injuries. Most surgeons endorsed a lack of standardization in definitions for delayed unions (73%) and nonunions (55%); almost all agreed that defining a delayed union and nonunion should be done on the basis of both radiographic and clinical criteria (88%). Most respondents believed that the degree of soft-tissue injury (approximately 93%), smoking history (approximately 82%), and vascular disease (approximately 76%) increased the risk of healing complications. Surgeons use similar prognostic factors to define and assess delayed unions and nonunions, but there is a lack of consensus in the definitions of delayed union and nonunion. The need for standardization and future randomized trials was strongly endorsed.


Gewurtz R.E.,McMaster University
Psychiatric rehabilitation journal | Year: 2012

This article reports on the consequences of the revised policy for employment supports within the Ontario Disability Support Program, a disability benefit program administered by the provincial government in Ontario, Canada. The revised policy involves a change from a fee-for-service model to an outcome-based funding model. This revision has encouraged a shift from preemployment to job placement services, with a particular focus on rapid placement into available jobs. Using a qualitative case study approach, 25 key informant interviews were conducted with individuals involved in developing or implementing the policy, or delivering employment services for individuals living with mental illness under the policy. Policy documents were also reviewed in order to explore the intent of the policy. Analysis focused on exploring how the policy has been implemented in practice, and its impact on employment services for individuals living with mental illness. The findings highlight how employment support practices have evolved under the new policy. Although there is now an increased focus on employment rather than preemployment supports, the financial imperative to place individuals into jobs as quickly as possible has decreased attention to career development. Jobs are reported to be concentrated at the entry-level with low pay and little security or benefits. These findings raise questions about the quality of employment being achieved under the new policy, highlight problems with adopting selected components of evidence-based approaches, and begin to explicate the influence that funding structures can have on practice.


Hankey G.J.,Royal Perth Hospital | Eikelboom J.W.,McMaster University
The Lancet Neurology | Year: 2010

Aspirin is widely used for the prevention of recurrent stroke in patients with transient ischaemic attack (TIA) and ischaemic stroke of arterial origin, because it is effective and inexpensive. Clopidogrel and the combination of aspirin and extended-release dipyridamole are more effective than aspirin, but are also much more expensive. No other antithrombotic regimens provide significant advantages over aspirin, although cilostazol and the novel platelet protease activated receptor-1 antagonist, SCH 530348, are currently being evaluated. For patients with TIA and ischaemic stroke of cardiac origin due to atrial fibrillation, vitamin K antagonists (VKAs) are highly effective in preventing recurrent ischaemic stroke but have important limitations and are thus underused. Antiplatelet therapy is much less effective than VKAs. The direct thrombin inhibitor, dabigatran etexilate, has shown efficacy over warfarin in a recent trial. Other new anticoagulants, including the oral factor Xa inhibitors, rivaroxaban, apixaban, and edoxaban, the parenteral factor Xa inhibitor, idrabiotaparinux, and the novel VKA, tecarfarin, are currently being assessed. © 2010 Elsevier Ltd. All rights reserved.


Fallen R.S.,McMaster University
Skin therapy letter | Year: 2012

Rosacea is a common chronic skin disorder that has significant impact on the self-esteem and quality of life of affected individuals. Currently understood as an inflammatory condition that occurs in the context of an altered innate immune response, the available topical and systemic therapies function as immunomodulators to restore cutaneous homeostasis. The goals of therapy include reduction of papules, pustules, erythema and physical discomfort with improvement in quality of life. Standard topical treatments include metronidazole and azelaic acid, although many other agents and regimens have been presented. Subantimicrobial/antiinflammatory dose oral doxycycline was US FDA approved in 2006 for the management of rosacea, but Health Canada clearance was only recently granted for this indication. Furthermore, renewed research interest has led to the development of other emerging therapies including topical ivermectin, brimonidine and oxymetazoline that hold promise for patients suffering from this condition.


Mishra A.K.,Texas A&M University | Coulibaly P.,McMaster University
Journal of Hydrology | Year: 2010

In recent years, climate change impacts on water resources sectors have been extensively documented. Anticipated changes range from more severe storms to more frequent floods and drought at regional scale. Pressure on water resources and hence on the environment will probably increase with the need of quality data for sustainable design of water resources projects. Therefore, for an optimal network design, hydrometric networks are to be reviewed periodically based on the information needs of the various end users and the perspective for future water resources development. This paper evaluates hydrometric networks to identify essential streamflow stations and critical areas (highly poor network density) within major watersheds across the different provinces of Canada using entropy theory. The method is applied to daily streamflow data and information coefficients such as marginal entropy, joint entropy and transinformation index are used for the identification of important stations as well as critical areas in the basin. The analysis results show that almost all Canadian main watersheds contain deficient hydrometric networks. The most deficient streamflow networks are identified in Alberta (North Saskatchewan, Oldman, and Red Deer basins), Northern Ontario (Hudson Bay basin), and the Northwest Territories. The information might prove to be helpful for decision makers to undertake cost-benefit analyses for hydrometric network updating in each region. © 2009 Elsevier B.V. All rights reserved.


Johari G.P.,McMaster University
Journal of Chemical Physics | Year: 2013

By using the known formalism for the effect of an externally applied electric field, E, on thermodynamics of a dielectric material, we calculated the field-induced configurational entropy factor, ΔSconf E/E2, of 50 dipolar liquids, including those whose static permittivity, εs, decreases on cooling. The field induced change, ΔSconfE, is found to be experimentally detectable only when E is on the order of 105 V/cm, a value less than the dielectric breakdown field strength of some liquids but in the range of nonlinear dielectric response. We argue that the dielectric response is formally nonlinear already for E > 0, and then show that the difference between the Langevin-function and the extrapolated linear response is < 0.15% for E in the 105 V/cm range. Therefore, such high E values may be used to estimate ΔSconfE. We conclude that (i) for E in the 105 V/cm range, ΔSconfE is high enough to produce a measurable change in the viscosity and relaxation time of some ultraviscous liquids with prominent dipolar interactions, thereby changing their glass formation temperature, and (ii) application of E would reversibly transform, isothermally, some liquids to glass, and transform some glasses to liquid. Finally, we suggest that the effect of E can be used to determine the merits of the models for non-Arrhenius kinetics. © 2013 American Institute of Physics.


Coulibaly P.,McMaster University
Journal of Hydrology | Year: 2010

The use of echo state network (ESN) for dynamical system modeling is known as Reservoir Computing and has been shown to be effective for a number of applications, including signal processing, learning grammatical structure, time series prediction and motor/system control. However, the performance of Reservoir Computing approach on hydrological time series remains largely unexplored. This study investigates the potential of ESN or Reservoir Computing for long-term prediction of lake water levels. Great Lakes water levels from 1918 to 2005 are used to develop and evaluate the ESN models. The forecast performance of the ESN-based models is compared with the results obtained from two benchmark models, the conventional recurrent neural network (RNN) and the Bayesian neural network (BNN). The test results indicate a strong ability of ESN models to provide improved lake level forecasts up to 10-month ahead - suggesting that the inherent structure and innovative learning approach of the ESN is suitable for hydrological time series modeling. Another particular advantage of ESN learning approach is that it simplifies the network training complexity and avoids the limitations inherent to the gradient descent optimization method. Overall, it is shown that the ESN can be a good alternative method for improved lake level forecasting, performing better than both the RNN and the BNN on the four selected Great Lakes time series, namely, the Lakes Erie, Huron-Michigan, Ontario, and Superior. © 2009 Elsevier B.V. All rights reserved.


Wystrach A.,University of Sussex | Schwarz S.,McMaster University
Current Biology | Year: 2013

Insect navigation is a fruitful system for analysing the ingenious and economical mechanisms that can underlie complex behaviour [1]. Past work has highlighted unsuspected navigational abilities in ants and bees, such as accurate path integration, long distance route following or homing from novel locations [2]. Here we report that ants can deal with one of the greatest challenges for any navigator: uncontrolled passive displacements. Foraging ants were blown by a jet of air over 3 meters into a dark pit. When subsequently released at windless unfamiliar locations, ants headed in the compass direction opposite to the one they had been blown away, thus functionally increasing their chance of returning to familiar areas. Ants do not appear to collect directional information during the actual passive displacement, but beforehand, while clutching the ground to resist the wind. During that time window, ants compute and store the compass direction of the wind. This is achieved by integrating the egocentric perception of the wind direction relative to their current body-axis with celestial compass information from their eyes. © 2013 Elsevier Ltd.


Garcia D.,University of New Mexico | Barrett Y.C.,Bristol Myers Squibb | Ramacciotti E.,Bristol Myers Squibb | Weitz J.I.,McMaster University
Journal of Thrombosis and Haemostasis | Year: 2013

In contrast to vitamin K antagonists, which reduce the functional levels of several coagulation factors, the new oral anticoagulants specifically target either thrombin or factor Xa. These new agents have such predictable pharmacokinetics and pharmacodynamics that routine coagulation monitoring is unnecessary. However, there are still some situations in which measurement of anticoagulant effect may be required. The coagulation assays that are used to monitor heparin derivatives or vitamin K antagonists may not always accurately reflect the anticoagulant activity of the new oral anticoagulants, and specialized assays may be needed. In this article, we: (i) identify situations in which assessment of anticoagulant effect may aid treatment decisions; (ii) describe the effects of the new oral anticoagulants on the various coagulation tests; (iii) review the specialized coagulation assays that have been developed to measure the anticoagulant effects of the new oral anticoagulants; and (iv) provide a clinical perspective on the role of coagulation testing in the clinical management of patients treated with the new oral anticoagulants. © 2012 International Society on Thrombosis and Haemostasis.


Valliant J.F.,McMaster University
Journal of Nuclear Medicine | Year: 2010

The field of nuclear medicine will rely increasingly on the discovery, proper evaluation, and clinical use of molecular imaging probes and on collaborations. Collaborations will include new initiatives among experts already involved in the field and with researchers, technologists, and clinicians from different areas of science and medicine. This article serves to highlight some of the opportunities in which molecular imaging and nuclear medicine in conjunction with probe development, new imaging technologies, and multidisciplinary collaborations can have a significant impact on health care and basic science from the perspective of a person involved in probe development. The article emphasizes breast cancer, but the concepts are readily applied to other areas of medicine and medical research. Copyright © 2010 by the Society of Nuclear Medicine, Inc.


Wu X.,McMaster University | Zhai G.,Shanghai JiaoTong University
IEEE Signal Processing Magazine | Year: 2013

A new paradigm of information display, called temporal psychoviusal modulation (TPVM), which is conceived as an ingenious interplay of signal processing, optoelectronics, and psychophysics, is proposed. In TPVM, a high-speed display sequentially emits a set of atom frames. Unlike in time multiplexing, these atom frames are not completely formed images but rather constituent parts of images; these atom frames are amplitude modulated by display-synchronized shutter devices. TPVM can be implemented by a combination of a high-speed display and display synchronized active liquid crystal (LC) glasses. The signal processing operations performed optoelectronically via the display-glasses coupling and the resulting psychovisual effects of TPVM can be mathematically modeled. A defining and unique characteristic of the new TPVM display system is that the optoelectronic modulator is coupled with a biological demodulator.


Yu J.,McMaster University
Engineering Applications of Artificial Intelligence | Year: 2013

This paper presents a novel Bayesian inference based Gaussian mixture contribution (BIGMC) method to isolate and diagnose the faulty variables in chemical processes with multiple operating modes. The statistical confidence intervals of traditional principal component analysis (PCA) based T2 and SPE diagnostics rely upon the assumption that the operating data follow a multivariate Gaussian distribution approximately and therefore may not be able to determine the faulty variables in multimode non-Gaussian processes accurately. As an alternative solution, the proposed BIGMC method first identifies the multiple Gaussian modes corresponding to different operating conditions and then integrates the Mahalanobis distance based variable contributions across all the Gaussian clusters through Bayesian inference strategy. The derived BIGMC index is of probabilistic feature and includes all operation scenarios with posterior probabilities as weighting factors. The Tennessee Eastman process (TEP) is used to demonstrate the utility of the proposed BIGMC method for fault diagnosis of multimode processes. The comparison of the single-PCA and multi-PCA based contribution approaches shows that the BIGMC method can effectively identify the leading faulty variables with superior diagnosis capability. © 2012 Elsevier Ltd. All rights reserved.


Jobba M.,McMaster University | Mishra R.K.,General Motors | Niewczas M.,General Motors
International Journal of Plasticity | Year: 2015

Analysis of the flow stress and work hardening behaviour has been carried out in series of Al-Mg solid solutions between 4 K and 298 K. The results reveal that the yield stress decreases linearly with the temperature and increases approximately linearly with the Mg content in the solution. The thermomechanical and Portevin-Le Chatelier instabilities dominate the flow stress behaviour of alloys at 4 K and 298 K. Dynamics of these instabilities increases with the solute content. It is argued that neither PLC nor adiabatic instabilities contribute to the premature failure of the samples. The work-hardening can be reproduced by the Voce type scaling law in a broad range of temperatures. The mean slip distance obtained from the macroscopic model of work hardening is correlated to the scale of the referenced microstructure; Λmin is interpreted as a transition from cell-like to micro shear band microstructure. The failure is discussed in terms of a critical point in a transition form unsaturated to saturated with defects dislocation substructure. © 2014 Elsevier Ltd.


Dayes I.S.,McMaster University
Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2013

Because of its morbidity and chronicity, arm lymphedema remains a concerning complication of breast cancer treatment. Although massage-based decongestive therapy is often recommended, randomized trials have not consistently demonstrated benefit over more conservative measures. Women previously treated for breast cancer with lymphedema were enrolled from six institutions. Volumes were calculated from circumference measurements. Patients with a minimum of 10% volume difference between their arms were randomly assigned to either compression garments (control) or daily manual lymphatic drainage and bandaging followed by compression garments (experimental). The primary outcome was percent reduction in excess arm volume from baseline to 6 weeks. A total of 103 women were randomly assigned, and 95 were evaluable. Mean reduction of excess arm volume was 29.0% in the experimental group and 22.6% in the control group (difference, 6.4%; 95% CI, -6.8% to 20.5%; P = .34). Absolute volume loss was 250 mL and 143 mL in the experimental and control groups, respectively (difference, 107 mL; 95% CI, 13 to 203 mL; P = .03). There was no difference between groups in the proportion of patients losing 50% or greater excess arm volume. Quality of life (Short Form-36 Health Survey) and arm function were not different between groups. This trial was unable to demonstrate a significant improvement in lymphedema with decongestive therapy compared with a more conservative approach. The failure to detect a difference may have been a result of the relatively small size of our trial.


Yan F.,McMaster University | Wang J.,Ohio State University
Control Engineering Practice | Year: 2013

This paper presents a singular perturbation based method for controlling the dual-loop exhaust gas recirculation (DL-EGR) air-path systems on advanced diesel engines. A DL-EGR air-path system, consisting of a high-pressure loop EGR (HPL-EGR) and a low-pressure loop EGR (LPL-EGR), has significantly different time-scales (fast and slow) due to the inherent difference in the HPL-EGR's and LPL-EGR's corresponding control volumes. Such a feature of the DL-EGR systems makes the cooperative control of intake manifold gas conditions challenging. By considering the DL-EGR air-path system as a singularly perturbed system, a composite control law was devised to achieve systematic control of the air-path conditions including gas pressure, temperature, and oxygen fraction in the intake manifold. The effectiveness of the control method is experimentally evaluated on a medium-duty diesel engine. © 2013 Elsevier Ltd.


Nair P.,McMaster University
Current Opinion in Pulmonary Medicine | Year: 2011

Purpose of review: The present review examines the effects of early intervention with inhaled corticosteroids (ICSs) on clinical efficacy and natural history of asthma based on two recent clinical trials: the Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) and Prevention of Early Asthma in Kids (PEAK) trials, and a comparison of the effect of regular vs. intermittent therapy based on the Improving Asthma Control Trial (IMPACT). Recent findings: In most patients, both adults and children, who have a new diagnosis of asthma and whose symptoms are mild but persistent, treatment with ICS should be recommended as soon as the diagnosis is made. This is a cost-effective and well tolerated treatment. However, symptoms may recur and lung function may decline again if treatment is discontinued. Summary: ICS is the most cost-effective initial treatment for both adults and children with a new diagnosis of asthma. If patients are reluctant to use ICS daily for long periods, it would be reasonable to delay the onset of treatment with ICS. Initial therapy with leukotriene receptor antagonist is not likely to be as effective as initial therapy with ICS. Biomarkers of airway inflammation such as sputum cell counts and exhaled nitric oxide are probably not necessary to treat patients with mild intermittent asthma. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Sears M.R.,McMaster University
Current Opinion in Pulmonary Medicine | Year: 2011

Purpose of review: Although long-acting beta-agonists (LABAs) have been used for two decades, with many studies showing benefit versus increasing inhaled corticosteroid (ICS), controversy regarding safety has resulted in the United States Food and Drug Administration (FDA) recently mandating label changes restricting LABA use. This review addresses these safety concerns together with clinical studies and meta-analyses assessing the appropriate use of LABAs. Recent findings: Effective use of LABAs requires sufficient ICS to control inflammation. Underuse of ICS, which is often manifest by exacerbations, may reflect undue emphasis on alleged steroid-sparing effects of LABAs. The FDA meta-analysis found that LABA with mandatory ICS was not associated with increased risks of serious adverse events. The role of LABA with ICS as initial therapy in steroid-naïve patients is debated, as is LABA use in children, with data indicating less benefit than in adults. The FDA recommendation that LABA be withdrawn once control is achieved remains problematic, as greater ICS reduction can be achieved when LABA is continued. Summary: The safe use of LABAs, which are clearly effective in many patients with moderate to severe asthma, requires high compliance with ICS therapy, which is best assured if ICS and LABA are provided in a single inhaler. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Wekerle C.,McMaster University
Child Abuse and Neglect | Year: 2011

Childhood maltreatment captured medical attention almost 50 years ago. Reviews considering the evidence for published maltreatment prevention programming emerged about 20 years ago. In the second decade of the 21st century, evidence-based maltreatment prevention is a reality for at-risk groups; however, the research-to-practice and policy gap remains in most countries. This article considers the importance of personal financial health and how that is necessarily the building blocks of national health. It argues for the primacy of the goal of problem prevention-the prevention of childhood maltreatment. A twofold approach is suggested: (1) broad-scale adoption of evidence-based prevention and (2) and on-going commitment to refining the evidence base for effective, promising, and novel intervention. © 2011.


Lazo-Langner A.,University of Western Ontario | Lang E.S.,University of Calgary | Douketis J.,McMaster University
Critical Care | Year: 2013

New oral anticoagulants, including dabigatran, rivaroxaban, and apixaban, have been recently approved for primary and secondary prophylaxis of thromboembolic conditions. However, there is no clear strategy for managing and reversing their anticoagulant effects. We aimed to summarize the available evidence for clinical management and reversal of bleeding associated with new oral anticoagulants. Using a systematic review approach, we aimed to identify studies describing reversal strategies for dabigatran, rivaroxaban, and apixaban. The search was conducted using Medline, EMBASE, HealthSTAR, and grey literature. We included laboratory and human studies. We included 23 studies reported in 37 out of 106 potentially relevant references. Four studies were conducted in humans and the rest were in vitro and in vivo studies. The majority of the studies evaluated the use of prothrombinase complex concentrate (PCC), either activated or inactivated, and recombinant activated factor VII (rFVIIa). Other interventions were also identified. Laboratory studies suggest that hemostatic parameters and bleeding might be partially or completely corrected by PCC for rivaroxaban better than dabigatran. Studies in humans suggest that PCC might reverse the effects of rivaroxaban better than dabigatran assessed by hemostatic tests. We were not able to locate studies evaluating the clinical efficacy of these agents. The best available evidence suggests that PCC (activated or inactivated) might be the best option for reversing new anticoagulants. Evidence for rFVIIa is less compelling. There might be differences in the efficacy of reversing agents for different anticoagulants. Studies assessing the clinical efficacy of these reversal agents are urgently needed. © 2013 BioMed Central Ltd.


Suzuki H.,Keio University | Moayyedi P.,McMaster University
Nature Reviews Gastroenterology and Hepatology | Year: 2013

Functional dyspepsia is the most common reason for patients to experience chronic epigastric pain or discomfort. The causes of functional dyspepsia are multifactorial but Helicobacter pylori infection is one likely candidate. Infection with this bacterial pathogen clearly results in chronic mucosal inflammation in the stomach and duodenum, which, in turn, might lead to abnormalities in gastroduodenal motility and sensitivity. Chronic gastritis might also affect a variety of endocrine functions of the stomach including the production of the gastrointestinal hormones and neurotransmitters somatostatin, gastrin and ghrelin. Although these abnormalities might generate symptoms in some patients with functional dyspepsia, the clinical evidence needs to be critically evaluated before this hypothesis can be confirmed. A Cochrane review reported that eradication of H. pylori in these patients had a small but statistically significant long-term effect on symptom relief when compared with placebo, lasting at least 12 months after 1 week of eradication therapy. The efficacy of eradication therapy was seen in all symptom subtypes of functional dyspepsia, but was more marked in Asian than Western patients. This evidence has led to alterations in most of the major guidelines throughout the world, which now recommend H. pylori eradication in patients with functional dyspepsia if they test positive for this bacterium. © 2013 Macmillan Publishers Limited. All rights reserved.


Sweet M.,McMaster University
Urban Studies | Year: 2014

Traffic congestion alleviation has long been a common core transport policy objective, but it remains unclear under which conditions this universal byproduct of urban life also impedes the economy. Using panel data for 88 US metropolitan statistical areas, this study estimates congestion’s drag on employment growth (1993 to 2008) and productivity growth per worker (2001 to 2007). Using instrumental variables, results suggest that congestion slows job growth above thresholds of approximately 4.5 minutes of delay per one-way auto commute and 11,000 average daily traffic (ADT) per lane on average across the regional freeway network. While higher ADT per freeway lane appears to slow productivity growth, there is no evidence of congestion-induced travel delay impeding productivity growth. Results suggest that the strict policy focus on travel time savings may be misplaced and, instead, better outlooks for managing congestion’s economic drag lie in prioritising the economically most important trips (perhaps through road pricing) or in providing alternative travel capacity to enable access despite congestion. © 2013 Urban Studies Journal Limited.


Tikhonov D.B.,RAS Sechenov Institute of Evolutionary Physiology and Biochemistry | Zhorov B.S.,McMaster University
Molecular Pharmacology | Year: 2012

The X-ray structure of the bacterial sodium channel NavAb provides a new template for the study of sodium and calcium channels. Unlike potassium channels, NavAb contains P2 helices in the outer-pore region. Because the sequence similarity between eukaryotic and prokaryotic sodium channels in this region is poor, the structural similarity is unclear. We analyzed it by using experimental data on tetrodotoxin block of sodium channels. Key tetrodotoxin-binding residues are outer carboxylates in repeats I, II, and IV, three positions downstream from the selectivity-filter residues. In a NavAb-based model of Nav1 channels derived from the sequence alignment without insertions/deletions, the outer carboxylates did not face the pore and therefore did not interact with tetrodotoxin. The hypothesis that the evolutionary appearance of Nav1 channels involved point deletions in an ancestral channel between the selectivity filter and the outer carboxylates allowed building of a NavAb-based model with tetrodotoxin-channel contacts similar to those proposed previously. This hypothesis also allowed us to reproduce in Nav1 the folding-stabilizing contacts between long-side chain residues in P1 and P2, which are seen in NavAb. The NavAb-based inner-pore model of Nav1 preserved major features of our previous KcsA-based models, including the access pathway for ligands through the repeat III/IV interface and their interactions with specific residues. Thus, structural properties of eukaryotic voltage-gated sodium channels that are suggested by functional data were reproduced in the NavAb-based models built by using the unaltered template structure but with adjusted sequence alignment. Sequences of eukaryotic calcium channels aligned with NavAb without insertions/deletions, which suggests that NavAb is a promising basis for the modeling of calcium channels. Copyright © 2012 The American Society for Pharmacology and Experimental Therapeutics.


Streiner D.L.,McMaster University | Streiner D.L.,University of Toronto
American Journal of Clinical Nutrition | Year: 2015

Testing many null hypotheses in a single study results in an increased probability of detecting a significant finding just by chance (the problem of multiplicity). Debates have raged over many years with regard to whether to correct for multiplicity and, if so, how it should be done. This article first discusses how multiple tests lead to an inflation of the a level, then explores the following different contexts in which multiplicity arises: testing for baseline differences in various types of studies, having >1 outcome variable, conducting statistical tests that produce >1 P value, taking multiple "peeks" at the data, and unplanned, post hoc analyses (i.e., "data dredging," "fishing expeditions," or "P-hacking"). It then discusses some of the methods that have been proposed for correcting for multiplicity, including single-step procedures (e.g., Bonferroni); multistep procedures, such as those of Holm, Hochberg, and Šidák; false discovery rate control; and resampling approaches. Note that these various approaches describe different aspects and are not necessarily mutually exclusive. For example, resampling methods could be used to control the false discovery rate or the family-wise error rate (as defined later in this article). However, the use of one of these approaches presupposes that we should correct for multiplicity, which is not universally accepted, and the article presents the arguments for and against such "correction." The final section brings together these threads and presents suggestions with regard to when it makes sense to apply the corrections and how to do so. © 2015 American Society for Nutrition.


Kettridge N.,McMaster University | Binley A.,Lancaster University
Journal of Geophysical Research: Biogeosciences | Year: 2011

The structural arrangement of peat constituents controls the hydrological and thermal properties of peat. However, the importance of these structural characteristics on other physical processes within a peatland has not been fully assessed. Here, we evaluate the importance of peat structure on its ability to entrain biogenic gas bubbles and control ebullition, an important transport mechanism for methane. X-ray computed tomography (CT) was applied to characterize the structure of a range of peats at varying levels of decomposition. The structural properties of the peat were quantified from a vector representation of the CT images, and the potential of each sample to entrain biogenic gas bubbles was quantified using a rule-based Monte Carlo model that calculates the tortuosity of bubbles pathways through the peat. Sixty-six percent of the variability in the trapping potential of the peat results from porosity variations and 34% from structural variations between samples. A metric that represents this structural control was not identified for all peat types because of difficulties adequately representing some peats as a vector network. However, for S. magellanicum peat we were able to establish that the influence of peat structure on the entrainment of gas bubbles is characterized by L v, the average vector length of the stems and branches. Peat characterized by longer structural components (larger Lv) enhances the entrainment of gas bubbles. Our findings demonstrate the need to incorporate some representation of the peat structure in numerical models of biogenic gas transport in peat. Copyright 2011 by the American Geophysical Union.


Thorne R.,McMaster University
Hydrology and Earth System Sciences | Year: 2011

Like many high latitude areas, the mountainous region of subarctic Canada has experienced recent warming and is an area of large inter-annual temperature variations, most notably during the winter. Quantifying how climate tendencies affect streamflow, especially in the spring melt season, is critical not only to regional water resource management, but to understanding the influence of freshwater on the Arctic sea-ice cover and global climate system. The impact of projected atmospheric warming on the discharge of the Liard River is unclear. Here, uncertainty in climate projections associated with GCM structure (2 °C prescribed warming) and magnitude of increases in global mean air temperature (1 to 6 °C) on the river discharge are assessed using a well-tested, semi-distributed hydrological model. Analyses have shown that the hydrological impacts are highly dependant on the GCM scenario. Uncertainties between the GCM scenarios are driven by the inconsistencies in projected spatial variability and magnitude of precipitation, rather than warming temperatures. Despite these uncertainties, the entire scenario simulations project that the subarctic nival regime will be preserved in the future, but the magnitude of change in river discharge is highly uncertain. Generally, spring freshet will arrive earlier, autumn to spring discharge will increase whereas summer flow will decrease, leading to an overall increase in annual discharge. © Author(s) 2011.


There is a continuing effort to advance the skill of long-range hydrological forecasts to support water resources decision making. The present study investigates the potential of an extended Kalman filter approach to perform supervised training of a recurrent multilayer perceptron (RMLP) to forecast up to 12-month-ahead lake water levels and streamflows in Canada. The performance of the RMLP was compared with the conventional multilayer perceptron (MLP) using suites of diagnostic measures. The results of the forecasting experiment showed that the RMLP model was able to provide a robust modelling framework capable of describing complex dynamics of the hydrological processes, thereby yielding more accurate and realistic forecasts than the MLP model. The performance of the method in the present study is very promising; however, further investigation is required to ascertain the versatility of the approach in characterizing different water resources and environmental problems. © 2011 IAHS Press.


Warkentin T.E.,McMaster University | Basciano P.A.,Cornell University | Knopman J.,Weill Cornell Medical Center | Bernstein R.A.,Northwestern University
Blood | Year: 2014

The existence of spontaneous heparin-induced thrombocytopenia (HIT) syndrome (or autoimmune HIT), defined as a transient prothrombotic thrombocytopenic disorder without proximate heparin exposure serologically indistinguishable from HIT, is controversial. We describe 2 new cases presenting with thrombotic stroke/thrombocytopenia: one following shoulder hemi-arthroplasty (performed without heparin) and the other presenting to the emergency room without prior hospitalization, heparin exposure, or preceding infection. Both patients tested strongly positive for anti-platelet factor 4 (PF4)/heparin immunoglobulin (Ig)Gin 2 different immunoassays and in the platelet serotonin-release assay.Crucially, both patients' sera also caused strong (>80%) serotonin release in the absence of heparin, a serologic feature characteristic of delayed-onset HIT (ie, where heparin use precedes HIT but is not required for subsequent development or worsening of thrombocytopenia). We propose that a rigorous definition of spontaneous HIT syndrome should include otherwise unexplained thrombocytopenia/thrombosis without proximate heparin exposure and with anti-PF4/heparin IgG antibodies that cause strong in vitro platelet activation even in the absence of heparin. © 2014 by The American Society of Hematology.


Sweet M.N.,McMaster University
Journal of Transport Geography | Year: 2014

Much transport policy aims to use congestion relief measures to support economic activity, but planners know relatively little about how individual firms respond to traffic congestion. This study helps fill this gap by exploring individual firm location responses to traffic congestion within the Philadelphia metropolitan area between 2003 and 2007. This study tests whether existing, basic-industry firms flee congested areas to minimize exposure to the congestion externality. Relocation responses are estimated and compared for five separate industries (finance and insurance, health care, manufacturing, real estate and leasing, and wholesale trade) using firm-level data collected by InfoUSA and obtained from ESRI. Results suggest that congestion influences firm location decisions, but that the scale of congestion is important. While firms appear to relocate out of areas with high regionally-scaled congestion, areas with high local congestion are associated with a lower likelihood of relocating. In sum, while regional congestion appears to be a drag, local congestion appears to function as an amenity - implying that there is truth in the competing notions among engineers and economists of congestion as a diseconomy and among urban designers of congestion as an amenity. © 2014 Elsevier Ltd.


Papageorgiou Y.Y.,McMaster University
Journal of Regional Science | Year: 2014

The existing empirical literature about polycentric population density has focused on the urban scale, and the alternative models proposed in that context have been justified using heuristic arguments. This paper describes how polycentric density distributions can, in general, be endowed with a theoretical framework which differs from the existing literature with respect to the treatment of centers: instead of assuming that they represent places of work, it assumes they are places that provide goods and services to households. This imposes a hierarchical structure on the model, which allows replacing the set of distances to all centers (typically used in the existing literature as the same explanans irrespectively of location) with a smaller set of distances that corresponds to the number of levels in the hierarchy and varies with location. The central-place framework used also provides a direct link between a polycentric model and the Clark formula, in the sense that the latter can emerge through a smoothing procedure of the former. Finally, in the context of central places, the scope of related empirical investigations can be extended naturally from the urban to the regional scale. This is the scale of a simple test presented here, which has been specifically included to support the corresponding theoretical arguments about the structure of a polycentric density gradient. The paper concludes with some expected problems and advantages of applying these ideas to the urban scale. © 2014 Wiley Periodicals, Inc.


BACKGROUND:: Open fractures are an important source of morbidity and are associated with delayed union, nonunion, and infection. Preventing infection through meticulous irrigation and debridement is an important goal in management, and different lavage fluids and irrigation techniques (e.g., high- or low-pressure lavage) have been described for this purpose. However, there are a limited number of randomized trials comparing irrigating solutions or irrigating technique. We compared the use of castile soap versus normal saline and high- versus low-pressure pulsatile lavage on the rates of reoperations and complications in patients with open fracture wounds. METHODS:: We conducted a multicenter, blinded, randomized 2 × 2 factorial pilot trial of 111 patients in whom an open fracture wound was treated with either castile soap solution or normal saline and either high- or low-pressure pulsatile lavage. The primary composite outcome of reoperation, measured at 12 months after initial operative procedure, included infection, wound healing problems, and nonunion. Planned reoperations were not included. Secondary outcomes included all infection, all wound healing problems, and nonunion as well as functional outcomes scores (EuroQol-5 dimensions and short form-12). RESULTS:: Eighty-nine patients completed the 1-year follow-up. Among all patients, 13 (23%) in the castile soap group and 13 (24%) in the saline group had a primary outcome event (hazard ratio, 0.91, 95% confidence interval: 0.42-2.00, p = 0.52). Sixteen patients (28%) in the high-pressure group and 10 patients (19%) in the low-pressure group had a primary outcome event (hazard ratio 0.55, 95% confidence interval: 0.24-1.27, p = 0.17). Functional outcome scores showed no significant differences at any time point between groups. CONCLUSION:: The fluid lavage of open wounds pilot randomized controlled trial demonstrated the possibility that the use of low pressure may decrease the reoperation rate for infection, wound healing problems, or nonunion. We have demonstrated the desirability and feasibility of a definitive trial examining the effects of alternative irrigation approaches. Copyright © Lippincott Williams & Wilkins.


Reinisch W.,McMaster University | Smolen J.,Medical University of Vienna
Seminars in arthritis and rheumatism | Year: 2015

OBJECTIVES: This article provides insight into the guidelines issued by the European Medicines Agency (EMA) and the draft guidances issued by the US Food and Drug Administration (FDA) regarding potential safety considerations associated with the development and use of biosimilars.METHODS: EMA and FDA guidelines and the literature were reviewed to identify recommendations and experience of manufacturers regarding the safety of biosimilars.RESULTS: Recent results of phase 3 comparability clinical trials comparing biosimilars with their reference products, and the approval of a biosimilar infliximab by several regulatory agencies, demonstrate the growing importance of biosimilars in inflammatory diseases. The safety profiles of biosimilars developed according to regulatory guidelines appear to be highly similar to the reference product, and postmarketing pharmacovigilance programs are in place. Additional topics related to biosimilars, such as interchangeability, automatic substitution, and nomenclature, are discussed.CONCLUSIONS: Safety considerations in the development of biosimilars are an important focus of regulatory guidelines, although topics such as interchangeability, automatic substitution, and nomenclature are still being debated. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.


Santesso N.,McMaster University
The Cochrane database of systematic reviews | Year: 2014

Older people living in nursing care facilities or older adults living at home are at high risk of falling and a hip fracture may occur after a fall. Hip protectors have been advocated as a means to reduce the risk of hip fracture. Hip protectors are plastic shields (hard) or foam pads (soft), usually fitted in pockets in specially designed underwear.This is an update of a Cochrane review first published in 1999, and updated several times, most recently in 2010. To determine if the provision of external hip protectors (sometimes referred to as hip pads or hip protector pads) reduces the risk of fracturing the hip in older people. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (December 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 12), MEDLINE (1950 to week 3 November 2012), MEDLINE In-Process (18 December 2012), EMBASE (1988 to 2012 Week 50), CINAHL (1982 to December 2012), BioMed Central (January 2010), trial registers and reference lists of relevant articles. All randomised or quasi-randomised controlled trials comparing an intervention group provided with hip protectors with a control group not provided with hip protectors. Two review authors independently assessed risk of bias and extracted data. We sought additional information from trialists. Data were pooled using fixed-effect or random-effects models as appropriate. This review includes 19 studies, nine of which were cluster randomised. These included approximately 17,000 people (mean age range 78 to 86 years). Most studies were overall at low risk of bias for fracture outcomes. Trials tested hard or soft hip protectors enclosed in special underwear in 18 studies.Pooling of data from 14 studies (11,808 participants) conducted in nursing or residential care settings found moderate quality evidence for a small reduction in hip fracture risk (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.67 to 1.00); the absolute effect is 11 fewer people (95% CI, from 20 fewer to 0) per 1000 having a hip fracture when provided with hip protectors.There is moderate quality evidence when pooling data from five trials in the community (5614 participants) that shows little or no effect in hip fracture risk (RR 1.15, 95% CI 0.84 to 1.58); the absolute effect is two more people (95% CI 2 fewer to 6 more) per 1000 people having a hip fracture when provided with hip protectors.There is probably little to no effect on falls (rate ratio 1.02, 95% CI 0.9 to 1.16) or fractures other than of the hip or pelvis (rate ratio 0.87, 95% CI 0.71 to 1.07). However, the risk ratio for pelvic fractures is RR 1.27 (95% CI 0.78 to 2.08); this is an absolute effect of one more person (95% CI 1 fewer to 5 more) per 1000 having a pelvic fracture when provided with hip protectors.The incidence of adverse events while wearing hip protectors, including skin irritation, ranged from 0% to 5%. Adherence, particularly in the long term, was poor. Hip protectors probably reduce the risk of hip fractures if made available to older people in nursing care or residential care settings, without increasing the frequency of falls. However, hip protectors may slightly increase the small risk of pelvic fractures. Poor acceptance and adherence by older people offered hip protectors is a barrier to their use. Better understanding is needed of the personal and design factors that may influence acceptance and adherence.


Nonequilibrium molecular dynamics (NEMD) simulations are used to investigate pressure-driven water flow passing through carbon nanotube (CNT) membranes at low pressures (5.0 MPa) typical of real nanofiltration (NF) systems. The CNT membrane is modeled as a simplified NF membrane with smooth surfaces, and uniform straight pores of typical NF pore sizes. A NEMD simulation system is constructed to study the effects of the membrane structure (pores size and membrane thickness) on the pure water transport properties. All simulations are run under operating conditions (temperature and pressure difference) similar to a real NF processes. Simulation results are analyzed to obtain water flux, density, and velocity distributions along both the flow and radial directions. Results show that water flow through a CNT membrane under a pressure difference has the unique transport properties of very fast flow and a non-parabolic radial distribution of velocities which cannot be represented by the Hagen-Poiseuille or Navier-Stokes equations. Density distributions along radial and flow directions show that water molecules in the CNT form layers with an oscillatory density profile, and have a lower average density than in the bulk flow. The NEMD simulations provide direct access to dynamic aspects of water flow through a CNT membrane and give a view of the pressure-driven transport phenomena on a molecular scale.


McIvor R.A.,McMaster University
Annals of Allergy, Asthma and Immunology | Year: 2015

Objective Asthma is a chronic inflammatory disorder of the airways with increasing worldwide prevalence. Despite treatment according to guidelines, a considerable proportion of patients with asthma remain symptomatic. Different potential therapeutic options for the treatment of these patients are currently in development and undergoing clinical trials, and it is important to regularly review their status. Data Sources A search of ClinicalTrials.gov was performed and supported by a PubMed literature search and restricted to the previous 10 years to ensure currency of data. The results were manually filtered to identify relevant articles. Study Selections Emerging therapies that are currently in phase 2 and 3 development include anti-interleukin agents (benralizumab, reslizumab, dupilumab, brodalumab, lebrikizumab, and mepolizumab), a chemoattractant receptor-homologous molecule expressed on a T-helper type 2 lymphocyte antagonist (OC000459), a phosphodiesterase-4 inhibitor (roflumilast), and long-acting muscarinic antagonists (glycopyrronium bromide, umeclidinium bromide, and tiotropium bromide). Results The clinical trial program of the long-acting muscarinic antagonist tiotropium is currently the most advanced, with data available from different phase 2 and 3 studies. Results demonstrate that it is an efficacious add-on to at least inhaled corticosteroid maintenance therapy across severities of symptomatic asthma. Conclusion The results of ongoing and future studies will help to determine whether these emerging therapeutic options will help address the unmet need for improvement in asthma management. © 2015 American College of Allergy, Asthma and Immunology. Published by Elsevier Inc. All rights reserved.


Surette M.G.,McMaster University
Cell Host and Microbe | Year: 2016

In this issue of Cell Host & Microbe, Ismail et al. (2016) demonstrate that damaged epithelial cells release a signal that activates bacterial quorum sensing pathways, providing insight into the chemical interplay between hosts and their microbes. This activity represents a potential mechanism for host modulation of bacteria. © 2016 Elsevier Inc.


Kearon C.,McMaster University
Current Opinion in Hematology | Year: 2012

Purpose of review: Deficiency of antithrombin, protein C, and protein S increases the risk of a first venous thromboembolism (VTE) by at least 10-fold and is rare (i.e., <0.5% of population), whereas factor V Leiden and the prothrombin G20210A gene increase this risk by 2-5-fold and are common (2-5% of whites). Antiphospholipid antibodies are considered acquired thrombophilic states. Testing for these abnormalities is widespread. This review will consider if the results of testing should influence how patients with VTE are treated. Recent findings: There are no randomized trials that have compared testing for thrombophilia with no testing; consequently, current assessments of whether testing should influence treatment of VTE are based on indirect evidence. Observational studies indicate that anticoagulants are equally effective in patients with and without thrombophilia; therefore, the presence of thrombophilia should not influence the choice of anticoagulant or the intensity of therapy. A lupus anticoagulant, however, can complicate monitoring of vitamin K antagonist therapy. The risk of recurrent VTE after stopping anticoagulant therapy may be higher in patients with thrombophilia, but not enough to influence whether anticoagulants should be stopped at 3 months or continued indefinitely. Summary: Thrombophilia should rarely influence the treatment of VTE. Therefore, routine thrombophilia testing of patients with VTE is not indicated as a way to guide treatment decisions. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Devuyst O.,UCL Medical School | Margetts P.J.,McMaster University | Topley N.,University of Cardiff
Journal of the American Society of Nephrology | Year: 2010

The development of peritoneal dialysis (PD) as a successful therapy has and still depends on experimental models to test and understand critical pieces of pathophysiology. To date, the majority of studies performed in rat and rabbit models derive mechanistic insights primarily on the basis of interventional pharmacologic agents, blocking antibodies, or transient expression systems. Because body size no longer limits the performance of in vivo studies of PD, genetic mouse models are increasingly available to investigate the molecular and pathophysiologic mechanisms of the peritoneal membrane. We illustrate in this review how these investigations are catching up with other areas of biomedical research and provide direct evidence for understanding transport and ultrafiltration, responses to infection, and structural changes including fibrosis and angiogenesis. These studies are relevant to mechanisms responsible not only for the major complications of PD but also for endothelial biology, host defense, inflammation, and tissue repair processes. Copyright © 2010 by the American Society of Nephrology.


Riddle D.L.,Virginia Commonwealth University | Stratford P.W.,McMaster University
Arthritis Care and Research | Year: 2013

Objective To determine if a dose-response relationship exists between percentage changes in body weight in persons with symptomatic knee osteoarthritis (OA) and self-reported pain and function. Methods Data from persons in the Osteoarthritis Initiative (OAI) and the Multicenter Osteoarthritis (MOST) study data sets (n = 1,410) with symptomatic function-limiting knee OA were studied. For the OAI, we used baseline and 3-year followup data, while for the MOST study, baseline and 30-month data were used. Key outcome variables were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function and pain change scores. In addition to covariates, the predictor variable of interest was the extent of weight change over the study period divided into 5 categories representing different percentages of body weight change. Results A significant dose-response relationship (P < 0.003) was found between the extent of percentage change in body weight and the extent of change in WOMAC physical function and WOMAC pain scores. For example, persons who gained ≥10% of body weight had WOMAC physical function score changes of -5.4 (95% confidence interval -8.7, -2.00) points, indicating worsening physical function relative to the reference group of persons with weight changes between <5% weight gain and <5% weight reduction. Conclusion Our data suggest a dose-response relationship exists between changes in body weight and corresponding changes in pain and function. The threshold for this response gradient appears to be body weight shifts of ≥10%. Weight changes of ≥10% have the potential to lead to important changes in pain and function for patient groups as well as individual patients. Copyright © 2013 by the American College of Rheumatology.


Johari G.P.,McMaster University
Journal of Chemical Physics | Year: 2010

We use thermodynamics of lattice vacancies to test the merits of the view that (i) statistical entropy, kB ln Ω, vanishes on vitrification of a liquid and hence there is no residual entropy and (ii) k B ln Ω of a nonergodic state would increase with time t as its structure relaxes. We argue that this view conflicts with the precepts of the configurational entropy of a crystal, -R [x ln x+ (1-x) ln (1-x)], where x is the fractional population of vacancies, and with the observed decrease in x with t on structural relaxation. The issue of whether the entropy of a kinetically arrested crystal state is equal to kB ln Ω or equal to -R [x ln x+ (1-x) ln (1-x)] can be resolved by measuring the vapor pressure, the emf of an electrolytic cell, and by scanning calorimetry. We also consider how the energy landscapes of a crystal and liquid differ, and point out that since crystals are in a nonequilibrium state, their thermodynamic data are inappropriate for testing the validity of the third law. © 2010 American Institute of Physics.


Lysov Z.,McMaster University
Blood Coagulation and Fibrinolysis | Year: 2016

Lung cancer is the second leading type of cancer, with venous thromboembolism being the second leading cause of death. Studies have shown increased levels of microparticles and cell-free DNA (CFDNA) in cancer patients, which can activate coagulation through extrinsic and intrinsic pathways, respectively. However, the impact of lung cancer chemotherapy on microparticle and/or CFDNA generation is not completely understood. The aim of the study was to study the effects of platinum-based chemotherapeutic agents on generation of procoagulant microparticles and CFDNA in vitro and in vivo. Microparticles were isolated from chemotherapy-treated monocytes, human umbilical vein endothelial cells, or cancer cells. Tissue factor (TF) and phosphatidylserine levels were characterized and thrombin/factor Xa generation assays were used to determine microparticle procoagulant activity. CFDNA levels were isolated from cell supernatants and plasma. A murine xenograft model of human lung carcinoma was used to study the procoagulant effects of TF microparticles and CFDNA in vivo. In vitro, platinum-based chemotherapy induced TF/phosphatidylserine microparticle shedding from A549 and A427 lung cancers cells, which enhanced thrombin generation in plasma in a FVII-dependent manner. CFDNA levels were increased in supernatants of chemotherapy-treated neutrophils and plasma of chemotherapy-treated mice. TF microparticles were elevated in plasma of chemotherapy-treated tumour-bearing mice. Plasma CFDNA levels are increased in chemotherapy-treated tumour-free mice and correlate with increased thrombin generation. In tumour-bearing mice, chemotherapy increases plasma levels of CFDNA and TF/phosphatidylserine microparticles. Platinum-based chemotherapy induces the shedding of TF/phosphatidylserine microparticles from tumour cells and the release of CFDNA from host neutrophils. Copyright © 2016 YEAR Wolters Kluwer Health, Inc. All rights reserved.


O'Connor J.J.,McMaster University
Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior | Year: 2011

Sexual infidelity can be costly to members of both the extra-pair and the paired couple. Thus, detecting infidelity risk is potentially adaptive if it aids in avoiding cuckoldry or loss of parental and relationship investment. Among men, testosterone is inversely related to voice pitch, relationship and offspring investment, and is positively related to the pursuit of short-term relationships, including extra-pair sex. Among women, estrogen is positively related to voice pitch, attractiveness, and the likelihood of extra-pair involvement. Although prior work has demonstrated a positive relationship between men's testosterone levels and infidelity, this study is the first to investigate attributions of infidelity as a function of sexual dimorphism in male and female voices. We found that men attributed high infidelity risk to feminized women's voices, but not significantly more often than did women. Women attributed high infidelity risk to masculinized men's voices at significantly higher rates than did men. These data suggest that voice pitch is used as an indicator of sexual strategy in addition to underlying mate value. The aforementioned attributions may be adaptive if they prevent cuckoldry and/or loss of parental and relationship investment via avoidance of partners who may be more likely to be unfaithful.


Banerjee A.T.,McMaster University
Journal of pediatric oncology nursing : official journal of the Association of Pediatric Oncology Nurses | Year: 2011

The purpose of this study is to describe cultural beliefs and coping strategies related to dealing with childhood cancer identified through a qualitative study of the caregiving experiences of first-generation South Asian immigrant parents of children with cancer. A constructivist grounded theory approach was employed. Families with a child at least 6 months postdiagnosis were recruited from 5 Canadian pediatric oncology centers. In-depth semistructured interviews were conducted in English, Hindi, Punjabi, or Urdu with a sample of 25 South Asian parents. Analysis of interviews involved line-by-line coding and using the constant comparison method. The following 2 central themes related to culture and coping emerged: (a) cultural beliefs about childhood cancer being incurable, rare, unspeakable, and understood through religion and (b) parental coping strategies included gaining information about the child's cancer, practicing religious rituals and prayers, trusting the health care professionals, and obtaining mutual support from other South Asian parents. These cultural beliefs and coping strategies have important implications for health care providers to understand the variations in the perceptions of childhood cancer and coping in order to implement culturally sensitive health care services.


Phillips S.M.,McMaster University
Sports Medicine | Year: 2014

With regular practice, resistance exercise can lead to gains in skeletal muscle mass by means of hypertrophy. The process of skeletal muscle fiber hypertrophy comes about as a result of the confluence of positive muscle protein balance and satellite cell addition to muscle fibers. Positive muscle protein balance is achieved when the rate of new muscle protein synthesis (MPS) exceeds that of muscle protein breakdown (MPB). While resistance exercise and postprandial hyperaminoacidemia both stimulate MPS, it is through the synergistic effects of these two stimuli that a net gain in muscle proteins occurs and muscle fiber hypertrophy takes place. Current evidence favors the post-exercise period as a time when rapid hyperaminoacidemia promotes a marked rise in the rate of MPS. Dietary proteins with a full complement of essential amino acids and high leucine contents that are rapidly digested are more likely to be efficacious in this regard. Various other compounds have been added to complete proteins, including carbohydrate, arginine and glutamine, in an attempt to augment the effectiveness of the protein in stimulating MPS (or suppressing MPB), but none has proved particularly effective. Evidence points to a higher protein intake in combination with resistance exercise as being efficacious in allowing preservation, and on occasion increases, in skeletal muscle mass with dietary energy restriction aimed at the promotion of weight loss. The goal of this review is to examine practices of protein ingestion in combination with resistance exercise that have some evidence for efficacy and to highlight future areas for investigation. © The Author(s) 2014.


Fox J.,McMaster University | Carvalho M.S.,Escola Nacional de Saude Publica
Journal of Statistical Software | Year: 2012

The R Commander graphical user interface to R is extensible via plug-in packages, which integrate seamlessly with the R Commander's menu structure, data, and model handling. The paper describes the RcmdrPlugin.survival package, which makes many of the facilities of the survival package for R available through the R Commander, including Cox and parametric survival models. We explain the structure, capabilities, and limitations of this plug-in package and illustrate its use.


Cannulation techniques have been recognized to be important in causing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, considerable controversy exists about the usefulness of the guidewire-assisted cannulation technique for the prevention of PEP. To systematically review evidence from randomised controlled trials (RCTs) assessing the effectiveness and safety of the guidewire-assisted cannulation technique compared to the conventional contrast-assisted cannulation technique for the prevention of PEP. We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, and CINAHL databases and major conference proceedings, up to February 2012, using the Cochrane Upper Gastrointestinal and Pancreatic Diseases model with no language restrictions. RCTs comparing the guidewire-assisted cannulation technique versus the contrast-assisted cannulation technique in patients undergoing ERCP. Two review authors conducted study selection, data extraction and methodological quality assessment independently. Using intention-to-treat analysis with random-effects models, we combined dichotomous data to obtain risk ratios (RR) with 95% confidence intervals (CI). We assessed heterogeneity using the Chi2 test (P < 0.15) and I2 statistic (> 25%). To explore sources of heterogeneity, we conducted a priori subgroup analyses according to trial design, publication type, risk of bias, use of precut sphincterotomy, inadvertent guidewire insertion or contrast injection of the pancreatic duct (PD), use of a PD stent, cannulation device, and trainee involvement in cannulation. To assess the robustness of our results we carried out sensitivity analyses using different summary statistics (RR versus odds ratio (OR)) and meta-analytic models (fixed-effect versus random-effects), and per protocol analysis. Twelve RCTs comprising 3450 participants were included. There was statistical heterogeneity among trials for the outcome of PEP (P = 0.04, I2 = 45%). The guidewire-assisted cannulation technique significantly reduced PEP compared to the contrast-assisted cannulation technique (RR 0.51, 95% CI 0.32 to 0.82). In addition, the guidewire-assisted cannulation technique was associated with greater primary cannulation success (RR 1.07, 95% CI 1.00 to 1.15), less precut sphincterotomy (RR 0.75, 95% CI 0.60 to 0.95), and no increase in other ERCP-related complications. Subgroup analyses indicated that this significant risk reduction in PEP with the guidewire-assisted cannulation technique existed only in 'non-crossover' trials (RR 0.22, 95% CI 0.12 to 0.42). The results were robust in sensitivity analyses. Compared with the contrast-assisted cannulation technique, the guidewire-assisted cannulation technique increases the primary cannulation rate and reduces the risk of PEP, and it appears to be the most appropriate first-line cannulation technique.


Jovanovic M.,McMaster University
Social Science and Medicine | Year: 2014

Using a sociology of diagnosis approach, this paper discusses the implication of high cholesterol being promoted as a disease rather than a risk factor for cardiovascular diseases. Drawing on data collected during the spring/summer of 2012 from 49 in-depth interviews with women over the age of forty concerned with high cholesterol in Ontario, Canada, I explore participants' understanding of the issue of high cholesterol as a disease. More specifically, I examine where blame and responsibility for high cholesterol are placed and if they vary by women's class background. My findings reveal that all the participants believed in and internalized the diagnosis of high cholesterol. However, the disease is blamed on 'lifestyle choices', and individual responsibilities, while women's awareness of the social determinants of health varies by class. I argue the sense of urgency surrounding high cholesterol is worrisome and the sole focus on lifestyle choice as both the cause and solution to high cholesterol is problematic for three reasons: it assumes that individual responsibility is adequate; it minimizes the socioeconomic constraints women face on a daily basis; and it reinforces the idea that individuals can be blamed for their health problems. © 2013 Elsevier Ltd.


Aboriginal people living in Canada have a high prevalence of obesity, type 2 diabetes, and cardiovascular disease (CVD). To better understand the pre and postnatal influences on the development of adiposity and related cardio-metabolic factors in adult Aboriginal people, we will recruit and follow prospectively Aboriginal pregnant mothers and their children - the Aboriginal Birth Cohort (ABC) study. We aim to recruit 300 Aboriginal pregnant mothers and their newborns from the Six Nations Reserve, and follow them prospectively to age 3 years. Key details of environment and health including maternal nutrition, glucose tolerance, physical activity, and weight gain will be collected. At birth, cord blood and placenta samples will be collected, as well as newborn anthropometric measurements. Mothers and offspring will be followed annually with serial measurements of diet and physical activity, growth trajectory, and adiposity. There is an urgent need to understand maternal and child factors that underlie the early development of adiposity and type 2 diabetes in Aboriginal people. The information generated from this cohort will assist the Six Nations community in developing interventions to prevent early adiposity in Aboriginal children.


Potential impacts of genetically modified (GM) animals in natural environments are explored in a framework of regulatory evolution. Transgenic growth hormone animals express remarkable alterations and plasticity in development, physiology and behavior in response to environmental factors (nutrition, temperature, photoperiod), suggesting that standard laboratory assessments are likely to underestimate their evolutionary potential. Sexual selection is examined in the context of female self-referent appraisal of male fitness that reflects performance in the species-specific niche. Wild-type females may recognize and discriminate against GM males (the Transparent Genome Hypothesis) but if accepted as mates, pleiotropic disruption associated with GMs may reduce fitness of the natural population (the Trojan Gene Hypothesis). Alternatively, facilitation of regulatory evolution by sexual reproduction (recombination and segregation) may derive modifier selection, masking, integration, or niche shifts. Other aspects explored include mutation theory, purging, pleiotropy, epigenetics and plasticity, behavior and the Bruce effect, and mismatch of genetic or epigenetic background between GM stock and natural populations. © 2014 Springer Science+Business Media New York.


Wright G.D.,McMaster University
Current Opinion in Microbiology | Year: 2010

The emergence of resistance to all classes of antibiotics in previously susceptible bacterial pathogens is a major challenge to infectious disease medicine. The origin of the genes associated with resistance has long been a mystery. There is a growing body of evidence that is demonstrating that environmental microbes are highly drug resistant. The genes that make up this environmental resistome have the potential to be transferred to pathogens and indeed there is some evidence that at least some clinically relevant resistance genes have originated in environmental microbes. Understanding the extent of the environmental resistome and its mobilization into pathogenic bacteria is essential for the management and discovery of antibiotics. © 2010 Elsevier Ltd.


Chan T.M.,McMaster University | Rosenberg H.,University of Ottawa | Lin M.,University of California at San Francisco
Annals of Emergency Medicine | Year: 2014

From January 20 to 24, 2014, Annals continued a successful collaboration with an academic Web site, Academic Life in Emergency Medicine (ALiEM), to host another Global Emergency Medicine Journal Club session featuring the 2013 Journal of the American Medical Association article "Clinical Decision Rules to Rule Out Subarachnoid Hemorrhage for Acute Headache" by Perry et al. This online journal club used the power of rapid Twitter conversations, a live videocast with the authors, and more detailed discussions hosted on the ALiEM Web site's comment section. There were more than 1,431 individuals from 501 cities in 59 countries who viewed the blog post. During this 5-day event, 28 comments (average word count 153 words) and 206 tweets were made. This summary article details the community discussion, shared insights, and analytic data generated during this novel, multiplatform approach. © 2013 by the American College of Emergency Physicians.


Weitz J.I.,McMaster University
Thrombosis and Haemostasis | Year: 2010

Although currently available anticoagulants are effective for the prevention and treatment of thromboembolic disorders, they have several drawbacks. Low-molecular-weight heparins and fondaparinux produce a predictable level of anticoagulation that obviates the need for coagulation monitoring, but they must be given parenterally, which renders them inconvenient for long-term use. Vitamin K antagonists, such as warfarin, are administered orally, but produce a variable anticoagulant response because genetic polymorphisms, dietary vitamin K intake and multiple drug-drug interactions affect their metabolism. Consequently, coagulation monitoring and frequent dose adjustments are needed to ensure that a therapeutic level of anticoagulation is achieved. This is burdensome for patients and physicians, and costly for the healthcare system. These limitations have prompted the development of new oral anticoagulants that target thrombin or factor Xa and can be given in fixed doses without coagulation monitoring. This paper focuses on the new oral anticoagulants in the most advanced stages of development. © Schattauer 2010.


Potvin J.R.,McMaster University
International Journal of Industrial Ergonomics | Year: 2014

The purpose of this study was to perform a systematic and comprehensive comparison between the recommended weights of lift (RWL) from the revised NIOSH lifting equation, and the specific biomechanical, psychophysical and physiological criteria that were stated to be used in the equation's development. A composite acceptable load (CAL) table was developed for the 216 conditions presented in the female lifting table of Snook and Ciriello (1991). Each CAL value was calculated to correspond to the most conservative load of the three design criteria. The RWLs caused lumbar compression forces close to the biomechanical limit of 3400N for lifts below knuckle height, but resulted in compression forces that are much lower at higher lifting heights. At moderate lifting frequencies, the average RWL would be acceptable to more than 95% of female workers according to the psychophysical criterion. At the highest frequencies, the RWL was found to be an average of 63% of the CAL values based on the integration of the psychophysical and physiological criteria. It is recommended that ergonomists acknowledge the very conservative nature of the revised NIOSH lifting equation when using it to evaluate occupational lifting tasks. Relevance to industry: The results from this study provide insight into the conservative nature of the recommended loads from the revised NIOSH lifting equation, and suggest that more specific ergonomic tools should be used when designing to biomechanical, psychophysical and physiological criteria for lifting. © 2013 Elsevier B.V.


Hassini E.,McMaster University | Surti C.,University of Ontario Institute of Technology | Searcy C.,Ryerson University
International Journal of Production Economics | Year: 2012

We review the literature on sustainable supply chains during the last decade; 2000-2010. We analyze the literature from different perspectives. We then provide frameworks for sustainable supply chain management and performance measures. We also provide a case study to illustrate the experience of a utility supply chain in setting performance indicators. © 2012 Elsevier B.V. All rights reserved.


Phillips S.M.,McMaster University
Meat Science | Year: 2012

From a health perspective, an underappreciated consequence of the normal aging process is the impacts that the gradual loss of skeletal muscle mass, termed sarcopenia, has on health beyond an effect on locomotion. Sarcopenia, refers to the loss of muscle mass, and associated muscle weakness, which occurs in aging and is thought to proceed at a rate of approximately 1% loss per year. However, periods of inactivity due to illness or recovery from orthopedic procedures such as hip or knee replacement are times of accelerated sarcopenic muscle loss from which it may be more difficult for older persons to recover. Some of the consequences of age-related sarcopenia are easy to appreciate such as weakness and, eventually, reduced mobility; however, other lesser recognized consequences include, due to the metabolic role the skeletal muscle plays, an increased risk for poor glucose control and a predisposition toward weight gain. What we currently know is that two stimuli can counter this age related muscle loss and these are physical activity, specifically resistance exercise (weightlifting), and nutrition. The focus of this paper is on the types of dietary protein that people might reasonably consume to offset sarcopenic muscle loss. © 2012 Elsevier Ltd.


An R.,McMaster University
Journal of biomedical optics | Year: 2013

When using ultrafast laser ablation in some orthopedic applications where precise cutting/drilling is required with minimal damage to collateral tissue, it is challenging to produce large-sized and deep holes using a tightly focused laser beam. The feasibility of producing deep, millimeter-size structures under different ablation strategies is investigated. X-ray computed microtomography was employed to analyze the morphology of these structures. Our results demonstrated the feasibility of producing holes with sizes required in clinical applications using concentric and helical ablation protocols.


Muluye G.Y.,McMaster University
Journal of Hydroinformatics | Year: 2012

There are several statistical downscaling methods available for generating local-scale meteorological variables from large-scale model outputs. There is still no universal single method, or group of methods, that is clearly superior, particularly for downscaling daily precipitation. This paper compares different statistical methods for downscaling daily precipitation from numerical weather prediction model output. Three different methods are considered: (i) hybrids; (ii) neural networks; and (iii) nearest neighbor-based approaches. These methods are implemented in the Saguenay watershed in northeastern Canada. Suites of standard diagnostic measures are computed to evaluate and inter-compare the performances of the downscaling models. Although results of the downscaling experiment show mixed performances, clear patterns emerge with respect to the reproduction of variation in daily precipitation and skill values. Artificial neural network-logistic regression (ANN-Logst), partial least squares (PLS) regression and recurrent multilayer perceptron (RMLP) models yield greater skill values, and conditional resampling method (SDSM) and K-nearest neighbor (KNN)-based models show the potential to capture the variability in daily precipitation. © IWA Publishing 2012.


Wu X.,McMaster University
IEEE Transactions on Image Processing | Year: 2011

This paper proposes a novel algorithmic approach of image enhancement via optimal contrast-tone mapping. In a fundamental departure from the current practice of histogram equalization for contrast enhancement, the proposed approach maximizes expected contrast gain subject to an upper limit on tone distortion and optionally to other constraints that suppress artifacts. The underlying contrast-tone optimization problem can be solved efficiently by linear programming. This new constrained optimization approach for image enhancement is general, and the user can add and fine tune the constraints to achieve desired visual effects. Experimental results demonstrate clearly superior performance of the new approach over histogram equalization and its variants. © 2006 IEEE.


Hayward C.P.M.,McMaster University
Blood Reviews | Year: 2011

Platelet function disorders are inherited and acquired conditions that represent a common cause of bleeding. Their clinical findings are generally similar to von Willebrand disease. It is often challenging to diagnose common platelet function disorders due to heterogeneity in their features, uncertainties about their pathogenesis and genetic cause, variability in the procedures used to assess platelet function in diagnostic laboratories and the lack of diagnostic criterion. Some inherited platelet function disorders have been established to increase risks for bleeding and bleeding scores. However, bleeding history assessment tools are not validated for use in diagnosing platelet function disorders. Standardized tests that assess aggregation function, dense granule deficiency and dense granule secretion are useful for diagnosing common platelet function disorders, in addition to some rare conditions. Guidelines have emerged to improve and standardize the laboratory tests for diagnosing platelet function disorders, including how to interpret aggregometry findings. Nonetheless, there is need to further evaluate the features, pathogenesis and genetic cause of many platelet function disorders, including the inherited conditions that impair granule secretion. © 2011 Elsevier Ltd.


Venous thromboembolism (VTE) is the most common potentially preventable form of hospital-related mortality. It presents as a major healthcare burden, affecting both medical and surgical patients. The prevention of VTE has been identified as one of the most important in-hospital safety practices in the US. VTE guideline recommendations provide a framework for clinical practice and guide VTE prophylaxis policies. Guidelines produced by the American College of Chest Physicians (ACCP) are considered to be the 'gold standard' in VTE prevention, diagnosis and management, and have been updated. A number of differences exist between the new 2008 ACCP guidelines on VTE prevention and the previous version published in 2004. There are variations regarding VTE prevention, including new and stronger evidence-based recommendations for several indications and agents. The updated guidelines give a strong recommendation that every hospital develop a VTE prevention policy, which is particularly important given the current international drive to reduce the incidence of VTE. A formal hospital policy should help improve compliance with appropriate VTE prophylaxis strategies. The ACCP guidelines form a basis for improving patient safety at a time of public reporting of quality of care, hospital accreditation, national standards of care, and pay for performance initiatives. In this review, changes in recommendations for VTE prevention in the 2008 ACCP guidelines compared with the previous edition in 2004 are outlined. In addition, outstanding areas of debate are discussed and the role of the 2008 ACCP guidelines in the context of the new VTE performance measures analyzed. © 2010 Springer Science+Business Media, LLC.


Sparkes J.,McMaster University
Telemedicine journal and e-health : the official journal of the American Telemedicine Association | Year: 2012

This article reports on a usability study of remote noninvasive cardiac testing in homes. We studied the Vitaphone 3100BT (Bluetooth®) event loop recorder (Vitaphone GmbH, Mannheim, Germany) and paired BlackBerry® Curve™ 8520 smartphone (Research In Motion, Ltd., Waterloo, ON, Canada). This application requires independent device set-up by patients in their own homes following receipt by mail out of the kit (instructions plus the event loop recorder and smartphone). The case studies of five participants, each with varying experience with technology, were documented as they interacted with the devices. Participants were videotaped following written instructions as they performed a "think aloud" procedure while completing 20 device set-up tasks. Interviews provided insight into how the independent device set-up and processes could be improved. This study concluded that gender, age, and familiarity with technology seemed to influence the participants' abilities to successfully set up these devices and that sending the kit by mail appeared to be an acceptable strategy to provide remote noninvasive cardiac diagnostic services. This study provides a foundation for future research assessing usability of mobile healthcare technology.


Although estrogens help to prepare the uterus for blastocyst implantation, small elevations above optimal levels can prevent implantation. In diverse mammals, stressors including extreme temperatures, physical restraint, environment changes, and predator exposure can impede implantation. This can be mimicked by treating inseminated females with exogenous estrogens. Peri-implantation stressors can elevate estradiol levels, while exogenous estrogen antibodies can mitigate the influences of stress on implantation. Another stimulus that disrupts implantation is exposure to novel males (the "Bruce effect"). This effect, best known in mice, is mediated by chemical factors in male urine. Although a longstanding hypothesis relates the Bruce effect to the female's olfactory memory trace of the sire and reaction to odors of novel males, evidence increasingly supports an alternative hypothesis that implicates males' excreted estrogens. Male urine contains substantial amounts of unconjugated estradiol, and males actively deliver urine toward females which impinges on their nasal region. The Bruce effect can be diminished by drug treatment of males that reduces urinary estradiol, and by treatment of females with estrogen antibodies. Tritiated estradiol ( 3H-E 2) systemically delivered to male mice was evident in their urine. When 3H-E 2 was given intra-nasally to inseminate females, it was found in their circulation and in diverse tissues, with greatest radioactivity in the uterus. Accordingly, evidence indicates that males' excreted estradiol can arrive at the female reproductive tract, where it can disrupt implantation through known mechanisms. © 2011 Elsevier Ireland Ltd.


Clark D.A.,McMaster University
Journal of Reproductive Immunology | Year: 2010

Increased production of Th1 cytokines such as TNFα plus IFNγ compared to the Th2 cytokine IL-10 is linked to infertility and recurrent spontaneous abortion (RSA). In murine models, direct evidence of pathogenic mechanisms has been elucidated, and these have been validated where possible by correlation with human data. Although there are a number of potential targets that could be utilized for therapeutic benefit, TNFα is currently the most feasible and uncorrected abnormality. Two recently published observational cohort-controlled studies of the addition of anti-TNFα agents to treatment with heparin plus aspirin, with or without IVIG, in RSA and in infertile (repeat IVF failure) patients are reviewed with respect to methodological and biological rigor, and literature supporting the reliability, feasibility, and value of observational cohort-controlled trials compared to double-blind randomized controlled trials is outlined. For those who do not believe the existing data is sufficiently strong for adoption of anti-TNFα therapy, a hybrid approach is outlined for validation of efficacy in specific subsets of pregnancy failure patients. Potential side effects and key issues in informed consent are set out. Anti-TNFα drugs may offer a new safe and effective approach to treating patients with Th1-cytokine-dependent infertility and recurrent miscarriages. © 2010 Elsevier Ireland Ltd.