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Showing papers by "McMaster University published in 2012"



Journal ArticleDOI
TL;DR: Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter- and intraspecific variation.
Abstract: Six DNA regions were evaluated as potential DNA barcodes for Fungi, the second largest kingdom of eukaryotic life, by a multinational, multilaboratory consortium. The region of the mitochondrial cytochrome c oxidase subunit 1 used as the animal barcode was excluded as a potential marker, because it is difficult to amplify in fungi, often includes large introns, and can be insufficiently variable. Three subunits from the nuclear ribosomal RNA cistron were compared together with regions of three representative protein-coding genes (largest subunit of RNA polymerase II, second largest subunit of RNA polymerase II, and minichromosome maintenance protein). Although the protein-coding gene regions often had a higher percent of correct identification compared with ribosomal markers, low PCR amplification and sequencing success eliminated them as candidates for a universal fungal barcode. Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter- and intraspecific variation. The nuclear ribosomal large subunit, a popular phylogenetic marker in certain groups, had superior species resolution in some taxonomic groups, such as the early diverging lineages and the ascomycete yeasts, but was otherwise slightly inferior to the ITS. The nuclear ribosomal small subunit has poor species-level resolution in fungi. ITS will be formally proposed for adoption as the primary fungal barcode marker to the Consortium for the Barcode of Life, with the possibility that supplementary barcodes may be developed for particular narrowly circumscribed taxonomic groups.

4,116 citations



Journal ArticleDOI
TL;DR: To update the American College of Rheumatology (ACR) 2000 recommendations for hip and knee osteoarthritis (OA) and develop new recommendations for hand OA.
Abstract: Objective To update the American College of Rheumatology (ACR) 2000 recommendations for hip and knee osteoarthritis (OA) and develop new recommendations for hand OA. Methods A list of pharmacologic and nonpharmacologic modalities commonly used to manage knee, hip, and hand OA as well as clinical scenarios representing patients with symptomatic hand, hip, and knee OA were generated. Systematic evidence-based literature reviews were conducted by a working group at the Institute of Population Health, University of Ottawa, and updated by ACR staff to include additions to bibliographic databases through December 31, 2010. The Grading of Recommendations Assessment, Development and Evaluation approach, a formal process to rate scientific evidence and to develop recommendations that are as evidence based as possible, was used by a Technical Expert Panel comprised of various stakeholders to formulate the recommendations for the use of nonpharmacologic and pharmacologic modalities for OA of the hand, hip, and knee. Results Both “strong” and “conditional” recommendations were made for OA management. Modalities conditionally recommended for the management of hand OA include instruction in joint protection techniques, provision of assistive devices, use of thermal modalities and trapeziometacarpal joint splints, and use of oral and topical nonsteroidal antiinflammatory drugs (NSAIDs), tramadol, and topical capsaicin. Nonpharmacologic modalities strongly recommended for the management of knee OA were aerobic, aquatic, and/or resistance exercises as well as weight loss for overweight patients. Nonpharmacologic modalities conditionally recommended for knee OA included medial wedge insoles for valgus knee OA, subtalar strapped lateral insoles for varus knee OA, medially directed patellar taping, manual therapy, walking aids, thermal agents, tai chi, self-management programs, and psychosocial interventions. Pharmacologic modalities conditionally recommended for the initial management of patients with knee OA included acetaminophen, oral and topical NSAIDs, tramadol, and intraarticular corticosteroid injections; intraarticular hyaluronate injections, duloxetine, and opioids were conditionally recommended in patients who had an inadequate response to initial therapy. Opioid analgesics were strongly recommended in patients who were either not willing to undergo or had contraindications for total joint arthroplasty after having failed medical therapy. Recommendations for hip OA were similar to those for the management of knee OA. Conclusion These recommendations are based on the consensus judgment of clinical experts from a wide range of disciplines, informed by available evidence, balancing the benefits and harms of both nonpharmacologic and pharmacologic modalities, and incorporating their preferences and values. It is hoped that these recommendations will be utilized by health care providers involved in the management of patients with OA.

2,615 citations


Journal ArticleDOI
01 Feb 2012-Chest
TL;DR: In this article, the authors focus on optimal prophylaxis to reduce postoperative pulmonary embolism and DVT following major orthopedic surgery, and suggest the use of low-molecular-weight heparin in preference to the other agents we have recommended as alternatives.

2,516 citations


Journal ArticleDOI
TL;DR: There is a substantial (if incomplete) evidence base to guide choice of knowledge translation activities targeting healthcare professionals and consumers and there are a profusion of innovative approaches that warrant further evaluation.
Abstract: One of the most consistent findings from clinical and health services research is the failure to translate research into practice and policy. As a result of these evidence-practice and policy gaps, patients fail to benefit optimally from advances in healthcare and are exposed to unnecessary risks of iatrogenic harms, and healthcare systems are exposed to unnecessary expenditure resulting in significant opportunity costs. Over the last decade, there has been increasing international policy and research attention on how to reduce the evidence-practice and policy gap. In this paper, we summarise the current concepts and evidence to guide knowledge translation activities, defined as T2 research (the translation of new clinical knowledge into improved health). We structure the article around five key questions: what should be transferred; to whom should research knowledge be transferred; by whom should research knowledge be transferred; how should research knowledge be transferred; and, with what effect should research knowledge be transferred? We suggest that the basic unit of knowledge translation should usually be up-to-date systematic reviews or other syntheses of research findings. Knowledge translators need to identify the key messages for different target audiences and to fashion these in language and knowledge translation products that are easily assimilated by different audiences. The relative importance of knowledge translation to different target audiences will vary by the type of research and appropriate endpoints of knowledge translation may vary across different stakeholder groups. There are a large number of planned knowledge translation models, derived from different disciplinary, contextual (i.e., setting), and target audience viewpoints. Most of these suggest that planned knowledge translation for healthcare professionals and consumers is more likely to be successful if the choice of knowledge translation strategy is informed by an assessment of the likely barriers and facilitators. Although our evidence on the likely effectiveness of different strategies to overcome specific barriers remains incomplete, there is a range of informative systematic reviews of interventions aimed at healthcare professionals and consumers (i.e., patients, family members, and informal carers) and of factors important to research use by policy makers. There is a substantial (if incomplete) evidence base to guide choice of knowledge translation activities targeting healthcare professionals and consumers. The evidence base on the effects of different knowledge translation approaches targeting healthcare policy makers and senior managers is much weaker but there are a profusion of innovative approaches that warrant further evaluation.

1,796 citations


Journal ArticleDOI
TL;DR: Subclinical atrial tachyarrhythmias, without clinical atrial fibrillation, occurred frequently in patients with pacemakers and were associated with a significantly increased risk of ischemic stroke or systemic embolism.
Abstract: One quarter of strokes are of unknown cause, and subclinical atrial fibrillation may be a common etiologic factor. Pacemakers can detect subclinical episodes of rapid atrial rate, which correlate with electrocardiographically documented atrial fibrillation. We evaluated whether subclinical episodes of rapid atrial rate detected by implanted devices were associated with an increased risk of ischemic stroke in patients who did not have other evidence of atrial fibrillation. Methods We enrolled 2580 patients, 65 years of age or older, with hypertension and no history of atrial fibrillation, in whom a pacemaker or defibrillator had recently been implanted. We monitored the patients for 3 months to detect subclinical atrial tachyarrhythmias (episodes of atrial rate >190 beats per minute for more than 6 minutes) and followed them for a mean of 2.5 years for the primary outcome of ischemic stroke or systemic embolism. Patients with pacemakers were randomly assigned to receive or not to receive continuous atrial overdrive pacing. Results By 3 months, subclinical atrial tachyarrhythmias detected by implanted devices had occurred in 261 patients (10.1%). Subclinical atrial tachyarrhythmias were associated with an increased risk of clinical atrial fibrillation (hazard ratio, 5.56; 95% confidence interval [CI], 3.78 to 8.17; P<0.001) and of ischemic stroke or systemic embolism (hazard ratio, 2.49; 95% CI, 1.28 to 4.85; P = 0.007). Of 51 patients who had a primary outcome event, 11 had had subclinical atrial tachyarrhythmias detected by 3 months, and none had had clinical atrial fibrillation by 3 months. The population attributable risk of stroke or systemic embolism associated with subclinical atrial tachyarrhythmias was 13%. Subclinical atrial tachyarrhythmias remained predictive of the primary outcome after adjustment for predictors of stroke (hazard ratio, 2.50; 95% CI, 1.28 to 4.89; P = 0.008). Continuous atrial overdrive pacing did not prevent atrial fibrillation. Conclusions Subclinical atrial tachyarrhythmias, without clinical atrial fibrillation, occurred frequently in patients with pacemakers and were associated with a significantly increased risk of ischemic stroke or systemic embolism. (Funded by St. Jude Medical; ASSERT ClinicalTrials.gov number, NCT00256152.)

1,651 citations


Journal ArticleDOI
01 Feb 2012-Chest
TL;DR: The eighth iteration of the American College of Chest Physicians Antithrombotic Guidelines presented, in a paper version, a narrative evidence summary and rationale for the recommendations, a small number of evidence profiles summarizing bodies of evidence, and some articles with quite extensive summary tables of primary studies.

1,423 citations


Journal ArticleDOI
01 Feb 2012-Chest
TL;DR: In this article, the authors present a perioperative anticoagulation management for patients with thromboembolism and bleeding, which is based on risk assessment for risk assessment.

1,393 citations


Journal ArticleDOI
TL;DR: Some of the mechanisms responsible for improved skeletal muscle metabolic control and changes in cardiovascular function in response to low‐ volume HIT are reviewed and insight is provided on the utility of low‐volume HIT for improving performance in athletes.
Abstract: Exercise training is a clinically proven, cost-effective, primary intervention that delays and in many cases prevents the health burdens associated with many chronic diseases. However, the precise type and dose of exercise needed to accrue health benefits is a contentious issue with no clear consensus recommendations for the prevention of inactivity-related disorders and chronic diseases. A growing body of evidence demonstrates that high-intensity interval training (HIT)canserveasaneffectivealternatetotraditionalendurance-basedtraining,inducingsimilar or even superior physiological adaptations in healthy individuals and diseased populations, at least when compared on a matched-work basis. While less well studied, low-volume HIT can also stimulate physiological remodelling comparable to moderate-intensity continuous training despite a substantially lower time commitment and reduced total exercise volume. Such findings areimportantgiventhat'lackoftime'remainsthemostcommonlycitedbarriertoregularexercise participation. Here we review some of the mechanisms responsible for improved skeletal muscle metabolic control and changes in cardiovascular function in response to low-volume HIT. We also consider the limited evidence regarding the potential application of HIT to people with, or at risk for, cardiometabolic disorders including type 2 diabetes. Finally, we provide insight on the utility of low-volume HIT for improving performance in athletes and highlight suggestions for future research.

1,362 citations


Journal ArticleDOI
TL;DR: How this extended communication system might influence a broad spectrum of diseases, including irritable bowel syndrome, psychiatric disorders and demyelinating conditions such as multiple sclerosis is reviewed.
Abstract: A bidirectional neurohumoral communication system known as the gut–brain axis integrates the activities of the intestine and the brain. In this Progress article, Collins, Surette and Bercik describe recent evidence suggesting that the intestinal microbiota is intimately connected with the gut–brain axis and can influence animal behaviour, development and health. The intestinal microbiota consists of a vast bacterial community that resides primarily in the lower gut and lives in a symbiotic relationship with the host. A bidirectional neurohumoral communication system, known as the gut–brain axis, integrates the host gut and brain activities. Here, we describe the recent advances in our understanding of how the intestinal microbiota communicates with the brain via this axis to influence brain development and behaviour. We also review how this extended communication system might influence a broad spectrum of diseases, including irritable bowel syndrome, psychiatric disorders and demyelinating conditions such as multiple sclerosis.

Journal ArticleDOI
TL;DR: This study provides a global estimate of the burden of asthma in adults, and suggests that asthma continues to be a major public health concern worldwide.
Abstract: Asthma is a major cause of disability, health resource utilization and poor quality of life world-wide. We set out to generate estimates of the global burden of asthma in adults, which may inform the development of strategies to address this common disease. The World Health Survey (WHS) was developed and implemented by the World Health Organization in 2002-2003. A total of 178,215 individuals from 70 countries aged 18 to 45 years responded to questions related to asthma and related symptoms. The prevalence of asthma was based on responses to questions relating to self-reported doctor diagnosed asthma, clinical/treated asthma, and wheezing in the last 12 months. The global prevalence rates of doctor diagnosed asthma, clinical/treated asthma and wheezing in adults were 4.3%, 4.5%, and 8.6% respectively, and varied by as much as 21-fold amongst the 70 countries. Australia reported the highest rate of doctor diagnosed, clinical/treated asthma, and wheezing (21.0%, 21.5%, and 27.4%). Amongst those with clinical/treated asthma, almost 24% were current smokers, half reported wheezing, and 20% had never been treated for asthma. This study provides a global estimate of the burden of asthma in adults, and suggests that asthma continues to be a major public health concern worldwide. The high prevalence of smoking remains a major barrier to combating the global burden of asthma. While the highest prevalence rates were observed in resource-rich countries, resource-poor nations were also significantly affected, posing a barrier to development as it stretches further the demands of non-communicable diseases.

Journal ArticleDOI
01 Feb 2012-Chest
TL;DR: The evidence supporting most recommendations for antithrombotic therapy in neonates and children remains weak and Studies addressing appropriate drug target ranges and monitoring requirements are urgently required in addition to site- and clinical situation-specific thrombosis management strategies.

Book
24 May 2012
TL;DR: Downregulation of intracortical inhibition induced by damage to the cochlea or to auditory projection pathways highlights neural processes that underlie the sensation of phantom sound.
Abstract: Tinnitus is an auditory phantom sensation (ringing of the ears) experienced when no external sound is present. Most but not all cases are associated with hearing loss induced by noise exposure or aging. Neuroscience research has begun to reveal how tinnitus is generated by the brain when hearing loss occurs, and to suggest new avenues for management and prevention of tinnitus following hearing injuries. Downregulation of intracortical inhibition induced by damage to the cochlea or to auditory projection pathways highlights neural processes that underlie the sensation of phantom sound.

Journal ArticleDOI
01 Feb 2012-Chest
TL;DR: In this article, the authors focused on the management of VTE and thrombophilia as well as the use of antithrombotic agents during pregnancy. But they did not consider the risk of pregnancy complications.

Journal ArticleDOI
01 Feb 2012-Chest
TL;DR: In this article, the authors focus on the common important management questions for which, at a minimum, low-quality published evidence is available to guide best practices and provide guidance for many common anticoagulation-related management problems.


Journal ArticleDOI
TL;DR: In this paper, the authors review the literature on sustainable supply chains during the last decade; 2000-2010; and provide frameworks for sustainable supply chain management and performance measures, and also provide a case study to illustrate the experience of a utility supply chain in setting performance indicators.

Journal ArticleDOI
TL;DR: Assessment of the prevalence, persistence, and sociodemographic correlates of commonly occurring DSM-IV disorders among adolescents in the National Comorbidity Survey Replication Adolescent Supplement suggests that disorder persistence is due more to episode recurrence than to chronicity of child-adolescent onset disorders.
Abstract: Context:Communityepidemiologicaldataontheprevalence and correlates of adolescent mental disorders are needed for policy planning purposes. Only limited data of this sort are available. Objective: To present estimates of 12-month and 30day prevalence, persistence (12-month prevalence among lifetime cases and 30-day prevalence among 12-month cases),andsociodemographiccorrelatesofcommonlyoccurring DSM-IV disorders among adolescents in the NationalComorbiditySurveyReplicationAdolescentSupplement.

Journal ArticleDOI
TL;DR: 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.
Abstract: Background 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. Objectives 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. Search methods 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. Selection criteria 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. Data collection and analysis 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. Main results 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. Authors' conclusions 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.

Journal ArticleDOI
01 Feb 2012-Chest
TL;DR: This article suggests that platelet count monitoring should be performed every 2 or 3 days for patients receiving heparin in whom clinicians consider the risk of HIT to be > 1%, and suggests the use of argatroban or lepirudin or danaparoid over other nonheparin anticoagulants.

Journal ArticleDOI
TL;DR: This megastudy presents age-of-acquisition ratings for 30,121 English content words (nouns, verbs, and adjectives) using the Web-based crowdsourcing technology offered by the Amazon Mechanical Turk to indicate that the ratings collected are as valid and reliable as those collected in laboratory conditions.
Abstract: We present age-of-acquisition (AoA) ratings for 30,121 English content words (nouns, verbs, and adjectives). For data collection, this megastudy used the Web-based crowdsourcing technology offered by the Amazon Mechanical Turk. Our data indicate that the ratings collected in this way are as valid and reliable as those collected in laboratory conditions (the correlation between our ratings and those collected in the lab from U.S. students reached .93 for a subsample of 2,500 monosyllabic words). We also show that our AoA ratings explain a substantial percentage of the variance in the lexical-decision data of the English Lexicon Project, over and above the effects of log frequency, word length, and similarity to other words. This is true not only for the lemmas used in our rating study, but also for their inflected forms. We further discuss the relationships of AoA with other predictors of word recognition and illustrate the utility of AoA ratings for research on vocabulary growth.

Journal ArticleDOI
TL;DR: This paper will attempt to explain the technique and theory behind western blot, and offer some ways to troubleshoot.
Abstract: Western blotting is an important technique used in cell and molecular biology. By using a western blot, researchers are able to identify specific proteins from a complex mixture of proteins extracted from cells. The technique uses three elements to accomplish this task: (1) separation by size, (2) transfer to a solid support, and (3) marking target protein using a proper primary and secondary antibody to visualize. This paper will attempt to explain the technique and theory behind western blot, and offer some ways to troubleshoot.

Journal ArticleDOI
01 Feb 2012-Chest
TL;DR: Three additional parenteral direct thrombin inhibitors and danaparoid are approved as alternatives to heparin in patients with HIT, and fondaparinux-associated HIT or osteoporosis is unlikely to occur.

Journal ArticleDOI
TL;DR: In critically ill patients, intensive glucose control leads to moderate and severe hypoglycemia, both of which are associated with an increased risk of death, and the association exhibits a dose-response relationship and is strongest for death from distributive shock.
Abstract: Background: Whether hypoglycemia leads to death in critically ill patients is unclear. Methods: We examined the associations between moderate and severe hypoglycemia (blood glucose, 41 to 70 mg per deciliter [2.3 to 3.9 mmol per liter] and ≤40 mg per deciliter [2.2 mmol per liter], respectively) and death among 6026 critically ill patients in intensive care units (ICUs). Patients were randomly assigned to intensive or conventional glucose control. We used Cox regression analysis with adjustment for treatment assignment and for baseline and postrandomization covariates. Results: Follow-up data were available for 6026 patients: 2714 (45.0%) had moderate hypoglycemia, 2237 of whom (82.4%) were in the intensive-control group (i.e., 74.2% of the 3013 patients in the group), and 223 patients (3.7%) had severe hypoglycemia, 208 of whom (93.3%) were in the intensive-control group (i.e., 6.9% of the patients in this group). Of the 3089 patients who did not have hypoglycemia, 726 (23.5%) died, as compared with 774 of the 2714 with moderate hypoglycemia (28.5%) and 79 of the 223 with severe hypoglycemia (35.4%). The adjusted hazard ratios for death among patients with moderate or severe hypoglycemia, as compared with those without hypoglycemia, were 1.41 (95% confidence interval [CI], 1.21 to 1.62; P 1 day vs. 1 day, P=0.01), those who died from distributive (vasodilated) shock (P<0.001), and those who had severe hypoglycemia in the absence of insulin treatment (hazard ratio, 3.84; 95% CI, 2.37 to 6.23; P<0.001). Conclusions: In critically ill patients, intensive glucose control leads to moderate and severe hypoglycemia, both of which are associated with an increased risk of death. The association exhibits a dose-response relationship and is strongest for death from distributive shock. However, these data cannot prove a causal relationship. (Funded by the Australian National Health and Medical Research Council and others; NICE-SUGAR ClinicalTrials.gov number, NCT00220987.).

Journal ArticleDOI
TL;DR: In this article, a multidimensional measure of knowledge hiding was developed and investigated, and the results of three studies suggest that knowledge hiding is comprised of three related factors: evasive hiding, rationalized hiding, and playing dumb.
Abstract: Summary Despite the efforts to enhance knowledge transfer in organizations, success has been elusive. It is becoming clear that in many instances employees are unwilling to share their knowledge even when organizational practices are designed to facilitate transfer. Consequently, this paper develops and investigates a novel construct, knowledge hiding. We establish that knowledge hiding exists, we distinguish knowledge hiding from related concepts (knowledge hoarding and knowledge sharing), and we develop a multidimensional measure of this construct. We also identify several predictors of knowledge hiding in organizations. The results of three studies, using different methods, suggest that knowledge hiding is comprised of three related factors: evasive hiding, rationalized hiding, and playing dumb. Each of these hiding behaviors is predicted by distrust, yet each also has a different set of interpersonal and organizational predictors. We draw implications for future research on knowledge management. Copyright © 2010 John Wiley & Sons, Ltd.

Journal ArticleDOI
Anna Kata1
28 May 2012-Vaccine
TL;DR: This overview examines the types of rhetoric individuals may encounter online in order to better understand why the anti-vaccination movement can be convincing, despite lacking scientific support for their claims.

Journal ArticleDOI
TL;DR: Daily supplementation with 1 g of n-3 fatty acids did not reduce the rate of cardiovascular events in patients at high risk for cardiovascular events.
Abstract: BACKGROUND: The use of n-3 fatty acids may prevent cardiovascular events in patients with recent myocardial infarction or heart failure. Their effects in patients with (or at risk for) type 2 diabe ...

Journal ArticleDOI
Paul A. Northcott1, Paul A. Northcott2, David Shih2, John Peacock2, Livia Garzia2, A. Sorana Morrissy2, Thomas Zichner, Adrian M. Stütz, Andrey Korshunov1, Jüri Reimand2, Steven E. Schumacher3, Rameen Beroukhim4, Rameen Beroukhim3, David W. Ellison, Christian R. Marshall2, Anath C. Lionel2, Stephen C. Mack2, Adrian M. Dubuc2, Yuan Yao2, Vijay Ramaswamy2, Betty Luu2, Adi Rolider2, Florence M.G. Cavalli2, Xin Wang2, Marc Remke2, Xiaochong Wu2, Readman Chiu5, Andy Chu5, Eric Chuah5, Richard Corbett5, Gemma Hoad5, Shaun D. Jackman5, Yisu Li5, Allan Lo5, Karen Mungall5, Ka Ming Nip5, Jenny Q. Qian5, Anthony Raymond5, Nina Thiessen5, Richard Varhol5, Inanc Birol5, Richard A. Moore5, Andrew J. Mungall5, Robert A. Holt5, Daisuke Kawauchi, Martine F. Roussel, Marcel Kool1, David T.W. Jones1, Hendrick Witt6, Africa Fernandez-L7, Anna Kenney8, Robert J. Wechsler-Reya9, Peter B. Dirks2, Tzvi Aviv2, Wiesława Grajkowska, Marta Perek-Polnik, Christine Haberler10, Olivier Delattre11, Stéphanie Reynaud11, François Doz11, Sarah S. Pernet-Fattet12, Byung Kyu Cho13, Seung-Ki Kim13, Kyu-Chang Wang13, Wolfram Scheurlen, Charles G. Eberhart14, Michelle Fèvre-Montange15, Anne Jouvet15, Ian F. Pollack16, Xing Fan17, Karin M. Muraszko17, G. Yancey Gillespie18, Concezio Di Rocco19, Luca Massimi19, Erna M.C. Michiels20, Nanne K. Kloosterhof20, Pim J. French20, Johan M. Kros20, James M. Olson21, Richard G. Ellenbogen22, Karel Zitterbart23, Leos Kren23, Reid C. Thompson8, Michael K. Cooper8, Boleslaw Lach24, Boleslaw Lach25, Roger E. McLendon26, Darell D. Bigner26, Adam M. Fontebasso27, Steffen Albrecht27, Steffen Albrecht28, Nada Jabado27, Janet C. Lindsey29, Simon Bailey29, Nalin Gupta30, William A. Weiss30, László Bognár31, Almos Klekner31, Timothy E. Van Meter, Toshihiro Kumabe32, Teiji Tominaga32, Samer K. Elbabaa33, Jeffrey R. Leonard34, Joshua B. Rubin34, Linda M. Liau35, Erwin G. Van Meir36, Maryam Fouladi37, Hideo Nakamura38, Giuseppe Cinalli, Miklós Garami39, Peter Hauser39, Ali G. Saad40, Achille Iolascon41, Shin Jung42, Carlos Gilberto Carlotti43, Rajeev Vibhakar44, Young Shin Ra45, Shenandoah Robinson, Massimo Zollo41, Claudia C. Faria2, Jennifer A. Chan46, Michael J. Levy21, Poul H. Sorensen5, Matthew Meyerson3, Scott L. Pomeroy3, Yoon Jae Cho47, Gary D. Bader2, Uri Tabori2, Cynthia Hawkins2, Eric Bouffet2, Stephen W. Scherer2, James T. Rutka2, David Malkin2, Steven C. Clifford29, Steven J.M. Jones5, Jan O. Korbel, Stefan M. Pfister1, Stefan M. Pfister6, Marco A. Marra5, Michael D. Taylor2 
02 Aug 2012-Nature
TL;DR: Somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas are reported, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Groups 4, which suggest future avenues for rational, targeted therapy.
Abstract: Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy.

Journal ArticleDOI
TL;DR: This article is the first of a series providing guidance for the use of the GRADE system of rating quality of evidence and grading strength of recommendations in systematic reviews, health technology assessments, and clinical practice guidelines addressing alternative management options.