Showing papers by "University of Ottawa published in 2011"
TL;DR: This article introduces a 20-part series providing guidance for the use of GRADE methodology that will appear in the Journal of Clinical Epidemiology.
1,975 citations
Heribert Schunkert1, Inke R. König1, Sekar Kathiresan2, Muredach P. Reilly3 +163 more•Institutions (59)
TL;DR: This paper performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals.
Abstract: We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 - 10'8 and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
1,705 citations
TL;DR: In comparison with no intervention, technology-enhanced simulation training in health professions education is consistently associated with large effects for outcomes of knowledge, skills, and behaviors and moderate effects for patient-related outcomes.
Abstract: Context Although technology-enhanced simulation has widespread appeal, its effectiveness remains uncertain. A comprehensive synthesis of evidence may inform the use of simulation in health professions education. Objective To summarize the outcomes of technology-enhanced simulation training for health professions learners in comparison with no intervention. Data Source Systematic search of MEDLINE, EMBASE, CINAHL, ERIC, PsychINFO, Scopus, key journals, and previous review bibliographies through May 2011. Study Selection Original research in any language evaluating simulation compared with no intervention for training practicing and student physicians, nurses, dentists, and other health care professionals. Data Extraction Reviewers working in duplicate evaluated quality and abstracted information on learners, instructional design (curricular integration, distributing training over multiple days, feedback, mastery learning, and repetitive practice), and outcomes. We coded skills (performance in a test setting) separately for time, process, and product measures, and similarly classified patient care behaviors. Data Synthesis From a pool of 10 903 articles, we identified 609 eligible studies enrolling 35 226 trainees. Of these, 137 were randomized studies, 67 were nonrandomized studies with 2 or more groups, and 405 used a single-group pretest-posttest design. We pooled effect sizes using random effects. Heterogeneity was large (I2>50%) in all main analyses. In comparison with no intervention, pooled effect sizes were 1.20 (95% CI, 1.04-1.35) for knowledge outcomes (n = 118 studies), 1.14 (95% CI, 1.03-1.25) for time skills (n = 210), 1.09 (95% CI, 1.03-1.16) for process skills (n = 426), 1.18 (95% CI, 0.98-1.37) for product skills (n = 54), 0.79 (95% CI, 0.47-1.10) for time behaviors (n = 20), 0.81 (95% CI, 0.66-0.96) for other behaviors (n = 50), and 0.50 (95% CI, 0.34-0.66) for direct effects on patients (n = 32). Subgroup analyses revealed no consistent statistically significant interactions between simulation training and instructional design features or study quality. Conclusion In comparison with no intervention, technology-enhanced simulation training in health professions education is consistently associated with large effects for outcomes of knowledge, skills, and behaviors and moderate effects for patient-related outcomes.
1,420 citations
University of Auckland1, Union for International Cancer Control2, Pan American Health Organization3, Imperial College London4, Commonwealth Secretariat5, International Union Against Tuberculosis and Lung Disease6, Massey University7, Organisation for Economic Co-operation and Development8, International Diabetes Federation9, World Bank10, Brigham and Women's Hospital11, University of Ottawa12, University of London13, University of Sydney14, National Heart Forum15, University of Melbourne16, World Heart Federation17, Public Health Foundation of India18, University of Southampton19, Harvard University20, Yonsei University21
TL;DR: The Lancet NCD Action Group and the NCD Alliance propose five overarching priority actions for the response to the crisis and the delivery of five priority interventions--tobacco control, salt reduction, improved diets and physical activity, reduction in hazardous alcohol intake, and essential drugs and technologies.
1,418 citations
University of Manchester1, Boston University2, Medical University of Vienna3, University of Ottawa4, VU University Amsterdam5, Leiden University6, Johns Hopkins University7, Columbia University8, University of Pisa9, University of Melbourne10, University of York11, University of Florence12, University of Paris13, University of Leeds14, University of California, Los Angeles15, University of Santiago de Compostela16, University of Toronto17, University of Bristol18, Maastricht University19, University of Nebraska Medical Center20, Autonomous University of Madrid21, New York University22, Food and Drug Administration23, Genentech24, Stanford University25, University of Basel26, MedImmune27, University of Kansas28
TL;DR: It is proposed that a patient's RA can be defined as being in remission based on one of two definitions: (1) when scores on the tender joint count, swollen joint counts, CRP level, and patient global assessment are all ≤1, or (2) when the score on the Simplified Disease Activity Index is ≤3.
Abstract: Objective Remission in rheumatoid arthritis (RA) is an increasingly attainable goal, but there is no widely used defi nition of remission that is stringent but achievable and could be applied uniformly as an outcome measure in clinical trials. This work was undertaken to develop such a defi nition. Methods A committee consisting of members of the American College of Rheumatology, the European League Against Rheumatism, and the Outcome Measures in Rheumatology Initiative met to guide the process and review prespecifi ed analyses from RA clinical trials. The committee requested a stringent defi nition (little, if any, active disease) and decided to use core set measures including, as a minimum, joint counts and levels of an acute-phase reactant to defi ne remission. Members were surveyed to select the level of each core set measure that would be consistent with remission. Candidate defi nitions of remission were tested, including those that constituted a number of individual measures of remission (Boolean approach) as well as defi nitions using disease activity indexes. To select a defi nition of remission, trial data were analysed to examine the added contribution of patient-reported outcomes and the ability of candidate measures to predict later good radiographic and functional outcomes. Results Survey results for the defi nition of remission suggested indexes at published thresholds and a count of core set measures, with each measure scored as 1 or less (eg, tender and swollen joint counts, C reactive protein (CRP) level, and global assessments on a 0–10 scale). Analyses suggested the need to include a patientreported measure. Examination of 2-year follow-up data suggested that many candidate defi nitions performed comparably in terms of predicting later good radiographic and functional outcomes, although 28-joint Disease Activity Score–based measures of remission did not
1,273 citations
Mayo Clinic1, New York University2, University of Hamburg3, Children's National Medical Center4, University of Girona5, Johns Hopkins University6, St George's, University of London7, Harvard University8, University of Ottawa9, University of Toronto10, University of Miami11, University of Paris12, University College London13, University of Münster14, University of Sydney15, Cincinnati Children's Hospital Medical Center16, University of Oxford17, University of Amsterdam18, Indiana University19
TL;DR: This dissertation aims to provide a history of modern medicine and some of the techniques and practices used in modern medicine, as well as some new approaches, that were introduced in the field of medicine more than 40 years ago.
1,254 citations
TL;DR: The Canadian Society for Exercise Physiology, in cooperation with ParticipACTION and other stakeholders, and with support from the Public Health Agency of Canada, has developed the new Canadian Physical Activity Guidelines.
Abstract: The Canadian Society for Exercise Physiology (CSEP), in cooperation with ParticipACTION and other stake- holders, and with support from the Public Health Agency of Canada (PHAC), has developed the new Canadian Physical Activity Guidelines for Children (aged 5-11 years), Youth (aged 12-17 years), Adults (aged 18-64 years), and Older Adults (aged ‡65 years). The new guidelines include a preamble to provide context and specific guidelines for each age group. The entire guideline development process was guided by the Appraisal of Guidelines for Research Evaluation (AGREE) II instrument, which is the international standard for clinical practice guideline development. Thus, the guide- lines have gone through a rigorous and transparent developmental process; we based the recommendations herein on evi- dence from 3 systematic reviews, and the final guidelines benefitted from an extensive online and in-person consultation process with hundreds of stakeholders and key informants, both domestic and international. Since 2006, the products of our efforts resulted in the completion of 21 peer-reviewed journal articles (including 5 systematic reviews) that collectively guided this work. The process that Canadian researchers undertook to update the national physical activity guidelines rep- resents the most current synthesis, interpretation, and application of the scientific evidence to date.
1,168 citations
Mayo Clinic1, New York University2, University of Hamburg3, George Washington University4, University of Girona5, Johns Hopkins University6, St George's, University of London7, Harvard University8, University of Ottawa9, Hospital for Sick Children10, University of Miami11, Paris Descartes University12, University College London13, University of Sydney14, Cincinnati Children's Hospital Medical Center15, John Radcliffe Hospital16, University of Amsterdam17, Indiana University18
TL;DR: This international consensus statement provides the state of genetic testing for the channelopathy and cardiomyopathies and summarizes the opinion of the international writing group members based on their own experience and on a general review of the literature with respect to the use and role of geneticTesting for these potentially heritable cardiac conditions.
Abstract: This international consensus statement provides the state of genetic testing for the channelopathies and cardiomyopathies. It summarizes the opinion of the international writing group members based on their own experience and on a general review of the literature with respect to the use and role of genetic testing for these potentially heritable cardiac conditions. This document focuses primarily on the state of genetic testing for the 13 distinct entities detailed and the relative diagnostic, prognostic, and therapeutic impact of the genetic test result for each entity. It does not focus on the therapeutic management of the various channelopathies and cardiomyopathies. Treatment/management issues are only discussed for those diseases (i.e., LQTS, HCM, DCM + CCD, RCM) in which the genetic test result could potentially influence treatment considerations.
Writing recommendations for genetic diseases require adaptation of the methodology normally adopted to prepare guidelines for clinical practice. Documents produced by other scientific societies have acknowledged the need to define the criteria used to rank the strength of recommendation for genetic diseases.1
The most obvious difference is that randomized and/or blinded studies do not exist. Instead, most of the available data are derived from registries that have followed patients and recorded outcome information. The authors of this statement have therefore defined specific criteria for Class I, Class IIa or b, and Class III recommendations and have used the conventional language adopted by AHA/ACC/ESC Guidelines to express each class. All recommendations are level of evidence (LOE) C (i.e., based on experts' opinions).
A Class I recommendation ( “is recommended” ) was applied for genetic testing in index cases with a sound clinical suspicion for the presence of a channelopathy or a cardiomyopathy when the positive predictive value of a genetic test is high (likelihood of positive result >40% and signal/noise ratio >10; Table 3), AND/OR when …
1,147 citations
TL;DR: Findings link abnormalities in ubiquilin 2 to defects in the protein degradation pathway, abnormal protein aggregation and neurodegeneration, indicating a common pathogenic mechanism that can be exploited for therapeutic intervention.
Abstract: ing cases of familial ALS and of the vast majority of sporadic ALS are unknown. Despite extensive studies of previously identified ALS-causing genes, the pathogenic mechanism underlying motorneuron degeneration in ALS remains largely obscure. Dementia, usually of the frontotemporal lobar type, may occur in some ALS cases. It is unclear whether ALS and dementia share common aetiology and pathogenesis in ALS/dementia. Here we show that mutations in UBQLN2, which encodes the ubiquitin-like protein ubiquilin 2, cause dominantly inherited, chromosome-X-linked ALS and ALS/dementia. We describe novel ubiquilin 2 pathology in the spinal cords of ALS cases and in the brains of ALS/dementia cases with or without UBQLN2 mutations. Ubiquilin 2 is a member of the ubiquilin family, which regulates the degradation of ubiquitinated proteins. Functional analysis showed that mutations in UBQLN2 lead to an impairment of protein degradation. Therefore, our findings link abnormalities in ubiquilin 2 to defects in the protein degradation pathway, abnormal protein aggregation and neurodegeneration, indicating a common pathogenic mechanism that can be exploited for therapeutic intervention.
1,068 citations
TL;DR: Data from the head-to-head trials suggest an advantage of aprotinin over the lysine analogues TXA and EACA in terms of reducing perioperative blood loss, but the differences were small.
Abstract: BACKGROUND: Concerns regarding the safety of transfused blood have led to the development of a range of interventions to minimise blood loss during major surgery. Anti-fibrinolytic drugs are widely used, particularly in cardiac surgery, and previous reviews have found them to be effective in reducing blood loss, the need for transfusion, and the need for re-operation due to continued or recurrent bleeding. In the last few years questions have been raised regarding the comparative performance of the drugs. The safety of the most popular agent, aprotinin, has been challenged, and it was withdrawn from world markets in May 2008 because of concerns that it increased the risk of cardiovascular complications and death. OBJECTIVES: To assess the comparative effects of the anti-fibrinolytic drugs aprotinin, tranexamic acid (TXA), and epsilon aminocaproic acid (EACA) on blood loss during surgery, the need for red blood cell (RBC) transfusion, and adverse events, particularly vascular occlusion, renal dysfunction, and death. SEARCH STRATEGY: We searched: the Cochrane Injuries Group's Specialised Register (July 2010), Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 3), MEDLINE (Ovid SP) 1950 to July 2010, EMBASE (Ovid SP) 1980 to July 2010. References in identified trials and review articles were checked and trial authors were contacted to identify any additional studies. The searches were last updated in July 2010. SELECTION CRITERIA: Randomised controlled trials (RCTs) of anti-fibrinolytic drugs in adults scheduled for non-urgent surgery. Eligible trials compared anti-fibrinolytic drugs with placebo (or no treatment), or with each other. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. MAIN RESULTS: This review summarises data from 252 RCTs that recruited over 25,000 participants. Data from the head-to-head trials suggest an advantage of aprotinin over the lysine analogues TXA and EACA in terms of reducing perioperative blood loss, but the differences were small. Compared to control, aprotinin reduced the probability of requiring RBC transfusion by a relative 34% (relative risk [RR] 0.66, 95% confidence interval [CI] 0.60 to 0.72). The RR for RBC transfusion with TXA was 0.61 (95% CI 0.53 to 0.70) and was 0.81 (95% CI 0.67 to 0.99) with EACA. When the pooled estimates from the head-to-head trials of the two lysine analogues were combined and compared to aprotinin alone, aprotinin appeared more effective in reducing the need for RBC transfusion (RR 0.90; 95% CI 0.81 to 0.99).Aprotinin reduced the need for re-operation due to bleeding by a relative 54% (RR 0.46, 95% CI 0.34 to 0.62). This translates into an absolute risk reduction of 2% and a number needed-to-treat (NNT) of 50 (95% CI 33 to 100). A similar trend was seen with EACA (RR 0.32, 95% CI 0.11 to 0.99) but not TXA (RR 0.80, 95% CI 0.55 to 1.17). The blood transfusion data were heterogeneous and funnel plots indicate that trials of aprotinin and the lysine analogues may be subject to publication bias.When compared with no treatment aprotinin did not increase the risk of myocardial infarction (RR 0.87, 95% CI 0.69 to 1.11), stroke (RR 0.82, 95% CI 0.44 to 1.52), renal dysfunction (RR 1.10, 95% CI 0.79 to 1.54) or overall mortality (RR 0.81, 95% CI 0.63 to 1.06). Similar trends were seen with the lysine analogues, but data were sparse. These data conflict with the results of recently published non-randomised studies, which found increased risk of cardiovascular complications and death with aprotinin. There are concerns about the adequacy of reporting of uncommon events in the small clinical trials included in this review.When aprotinin was compared directly with either, or both, of the two lysine analogues it resulted in a significant increase in the risk of death (RR 1.39, 95% CI 1.02, 1.89), and a non-significant increase in the risk of myocardial infarction (RR 1.11 95% CI 0.82, 1.50). Most of the data contributing to this added risk came from a single study - the BART trial (2008). AUTHORS' CONCLUSIONS: Anti-fibrinolytic drugs provide worthwhile reductions in blood loss and the receipt of allogeneic red cell transfusion. Aprotinin appears to be slightly more effective than the lysine analogues in reducing blood loss and the receipt of blood transfusion. However, head to head comparisons show a lower risk of death with lysine analogues when compared with aprotinin. The lysine analogues are effective in reducing blood loss during and after surgery, and appear to be free of serious adverse effects.
1,042 citations
TL;DR: A systematic review of studies comparing adult chronic dialysis patients with kidney transplantation recipients for clinical outcomes found significantly lower mortality associated with transplantation, and the relative magnitude of the benefit seemed to increase over time.
TL;DR: The Update Committee noted the importance of continued symptom monitoring throughout therapy, and Clinicians underestimate the incidence of nausea, which is not as well controlled as emesis.
Abstract: Purpose To update the American Society of Clinical Oncology (ASCO) guideline for antiemetics in oncology. Methods A systematic review of the medical literature was completed to inform this update. MEDLINE, the Cochrane Collaboration Library, and meeting materials from ASCO and the Multinational Association for Supportive Care in Cancer were all searched. Primary outcomes of interest were complete response and rates of any vomiting or nausea. Results Thirty-seven trials met prespecified inclusion and exclusion criteria for this systematic review. Two systematic reviews from the Cochrane Collaboration were identified; one surveyed the pediatric literature. The other compared the relative efficacy of the 5-hydroxytryptamine-3 (5-HT3) receptor antagonists. Recommendations
TL;DR: Systematic inquiry into patients’ migration trajectory and subsequent follow-up on culturally appropriate indicators of social, vocational and family functioning over time will allow clinicians to recognize problems in adaptation and undertake mental health promotion, disease prevention or treatment interventions in a timely way.
Abstract: Background: Recognizing and appropriately treating mental health problems among new immigrants and refugees in primary care poses a challenge because of differences in language and culture and because of specific stressors associated with migration and resettlement. We aimed to identify risk factors and strategies in the approach to mental health assessment and to prevention and treatment of common mental health problems for immigrants in primary care. Methods: We searched and compiled literature on prevalence and risk factors for common mental health problems related to migration, the effect of cultural influences on health and illness, and clinical strategies to improve mental health care for immigrants and refugees. Publications were selected on the basis of relevance, use of recent data and quality in consultation with experts in immigrant and refugee mental health. Results: The migration trajectory can be divided into three components: premigration, migration and postmigration resettlement. Each phase is associated with specific risks and exposures. The prevalence of specific types of mental health problems is influenced by the nature of the migration experience, in terms of adversity experienced before, during and after resettlement. Specific challenges in migrant mental health include communication difficulties because of language and cultural differences; the effect of cultural shaping of symptoms and illness behaviour on diagnosis, coping and treatment; differences in family structure and process affecting adaptation, acculturation and intergenerational conflict; and aspects of acceptance by the receiving society that affect employment, social status and integration. These issues can be addressed through specific inquiry, the use of trained interpreters and culture brokers, meetings with families, and consultation with community organizations. Interpretation: Systematic inquiry into patients’ migration trajectory and subsequent follow-up on culturally appropriate indicators of social, vocational and family functioning over time will allow clinicians to recognize problems in adaptation and undertake mental health promotion, disease prevention or treatment interventions in a timely way.
TL;DR: Aerobics, weight bearing and resistance exercises are all effective in increasing the BMD of the spine in postmenopausal women and walking is also effective on the hip.
Abstract: Background
Osteoporosis is a condition resulting in an increased risk of skeletal fractures due to a reduction in the density of bone tissue. Treatment of osteoporosis typically involves the use of pharmacological agents. In general it is thought that disuse (prolonged periods of inactivity) and unloading of the skeleton promotes reduced bone mass, whereas mechanical loading through exercise increases bone mass.
Objectives
To examine the effectiveness of exercise interventions in preventing bone loss and fractures in postmenopausal women.
Search methods
During the update of this review we updated the original search strategy by searching up to December 2010 the following electronic databases: the Cochrane Musculoskeletal Group's Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2010 Issue 12); MEDLINE; EMBASE; HealthSTAR; Sports Discus; CINAHL; PEDro; Web of Science; Controlled Clinical Trials; and AMED. We attempted to identify other studies by contacting experts, searching reference lists and searching trial registers.
Selection criteria
All randomised controlled trials (RCTs) that met our predetermined inclusion criteria.
Data collection and analysis
Pairs of members of the review team extracted the data and assessed trial quality using predetermined forms. For dichotomous outcomes (fractures), we calculated risk ratios (RRs) using a fixed-effect model. For continuous data, we calculated mean differences (MDs) of the percentage change from baseline. Where heterogeneity existed (determined by the I2 statistic), we used a random-effects model.
Main results
Forty-three RCTs (27 new in this update) with 4320 participants met the inclusion criteria. The most effective type of exercise intervention on bone mineral density (BMD) for the neck of femur appears to be non-weight bearing high force exercise such as progressive resistance strength training for the lower limbs (MD 1.03; 95% confidence interval (CI) 0.24 to 1.82). The most effective intervention for BMD at the spine was combination exercise programmes (MD 3.22; 95% CI 1.80 to 4.64) compared with control groups. Fractures and falls were reported as adverse events in some studies. There was no effect on numbers of fractures (odds ratio (OR) 0.61; 95% CI 0.23 to 1.64). Overall, the quality of the reporting of studies in the meta-analyses was low, in particular in the areas of sequence generation, allocation concealment, blinding and loss to follow-up.
Authors' conclusions
Our results suggest a relatively small statistically significant, but possibly important, effect of exercise on bone density compared with control groups. Exercise has the potential to be a safe and effective way to avert bone loss in postmenopausal women.
TL;DR: Teriflunomide significantly reduced relapse rates, disability progression (at the higher dose), and MRI evidence of disease activity, as compared with placebo.
Abstract: Teriflunomide reduced the annualized relapse rate (0.54 for placebo vs. 0.37 for teri flunomide at either 7 or 14 mg), with relative risk reductions of 31.2% and 31.5%, respectively (P<0.001 for both comparisons with placebo). The proportion of patients with confirmed disability progression was 27.3% with placebo, 21.7% with teriflunomide at 7 mg (P = 0.08), and 20.2% with teriflunomide at 14 mg (P = 0.03). Both teriflunomide doses were superior to placebo on a range of end points measured by magnetic resonance imaging (MRI). Diarrhea, nausea, and hair thinning were more common with teriflunomide than with placebo. The incidence of elevated alanine aminotransferase levels (≥1 times the upper limit of the normal range) was higher with teriflunomide at 7 mg and 14 mg (54.0% and 57.3%, respectively) than with placebo (35.9%); the incidence of levels that were at least 3 times the upper limit of the normal range was similar in the lower- and higher-dose teriflunomide groups and the placebo group (6.3%, 6.7%, and 6.7%, respectively). Serious infections were reported in 1.6%, 2.5%, and 2.2% of patients in the three groups, respectively. No deaths occurred. Conclusions Teriflunomide significantly reduced relapse rates, disability progression (at the higher dose), and MRI evidence of disease activity, as compared with placebo. (Funded by Sanofi-Aventis; TEMSO ClinicalTrials.gov number, NCT00134563.)
TL;DR: A systematic review of research describing the epidemiology of childhood-onset inflammatory bowel disease (IBD) to assess changes in incidence rates over time and to evaluate international differences was conducted in this paper.
Abstract: Background:
Temporal trends in the incidence of pediatric-onset inflammatory bowel disease (IBD) are controversial and a wide range of estimates have been reported worldwide. We conducted a systematic review of research describing the epidemiology of childhood-onset IBD to assess changes in incidence rates over time and to evaluate international differences.
Methods:
The following electronic databases were searched for articles published 1950–2009: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane IBD/Functional Bowel Disorders Group Specialised Trial Register. All included studies reported incidence or prevalence of IBD, Crohn's disease (CD) or ulcerative colitis (UC). Two authors independently completed the data extraction form for each eligible study. Choropleth maps demonstrated the international incidence of IBD, CD, and UC. Incidence of CD and UC was graphed using data from studies reporting rates in multiple time periods.
Results:
The search yielded 2209 references and review resulted in 139 included studies from 32 countries. A wide range of incidence was reported internationally; however, rates of IBD were not described in most countries. Twenty-eight studies (20.1%) used statistical analysis to assess trends over time, and 77.8% reported statistically significantly increased incidence of pediatric IBD. Of studies calculating statistical trends in CD incidence, 60% reported significantly increased incidence. Of similar UC studies, 20% reported significantly increased incidence.
Conclusions:
Globally rising rates of pediatric IBD (due primarily to the rising incidence of CD) was demonstrated in both developed and developing nations; however, most countries lack accurate estimates. Analyzing incidence trends may help identify specific environmental and genetic risk factors for pediatric IBD. (Inflamm Bowel Dis 2011;)
TL;DR: Concerted metalation-deprotonation (CMD) is now proposed to be the turnover limiting step and DFT calculations conducted on this system agree with a stepwise C-N bond reductive elimination/N-O bond oxidative addition mechanism to afford the desired heterocycle.
Abstract: Directing groups that can act as internal oxidants have recently been shown to be beneficial in metal-catalyzed heterocycle syntheses that undergo C−H functionalization. Pursuant to the rhodium(III)-catalyzed redox-neutral isoquinolone synthesis that we recently reported, we present in this article the development of a more reactive internal oxidant/directing group that can promote the formation of a wide variety of isoquinolones at room temperature while employing low catalyst loadings (0.5 mol %). In contrast to previously reported oxidative rhodium(III)-catalyzed heterocycle syntheses, the new conditions allow for the first time the use of terminal alkynes. Also, it is shown that the use of alkenes, including ethylene, instead of alkynes leads to the room temperature formation of 3,4-dihydroisoquinolones. Mechanistic investigations of this new system point to a change in the turnover limiting step of the catalytic cycle relative to the previously reported conditions. Concerted metalation−deprotonation ...
TL;DR: The authors provides an overview of the key theoretical and empirical insights into the Porter Hypothesis, draws policy implications from these insights, and sketches out major research themes going forward, as well as highlights the major research topics going forward.
Abstract: Twenty years ago, Harvard Business School economist and strategy professor Michael Porter stood conventional wisdom about the impact of environmental regulation on business on its head by declaring that well-designed regulation could actually enhance competitiveness. The traditional view of environmental regulation held by virtually all economists until that time was that requiring firms to reduce an externality like pollution necessarily restricted their options and thus by definition reduced their profits. After all, if profitable opportunities existed to reduce pollution, profit-maximizing firms would already be taking advantage of those opportunities. Over the past 20 years, much has been written about what has since become known simply as the Porter Hypothesis (PH). Yet even today, we find conflicting evidence and alternative theories that might explain the PH, and oftentimes a misunderstanding of what the PH does and does not say. This paper provides an overview of the key theoretical and empirical insights into the PH to date, draws policy implications from these insights, and sketches out major research themes going forward.
TL;DR: A whole-brain based quantitative meta-analysis of recent fMRI studies of empathy found that the dACC-aMCC-SMA and bilateral anterior insula can be considered as forming a core network in empathy, and that cognitive-evaluative and affective-perceptual empathy can be distinguished at the level of regional activation.
TL;DR: The data suggest that the sense of self may result from a specific kind of interaction between resting state activity and stimulus-induced activity, i.e., rest-stimulus interaction, within the midline regions.
TL;DR: The Consort 2010 Statement as mentioned in this paper has been used worldwide to improve the reporting of randomised controlled trials and has been updated by Schulz et al. in 2010, based on new methodological evidence and accumulating experience.
TL;DR: The rate of serious adverse events, serious infections, lymphoma, and congestive heart failure were not statistically significantly different between biologics and control treatment, and direct comparisons revealed that abatacept and anakinra were associated with a significantly lower risk ofserious adverse events compared to most other biologicics.
Abstract: Background Biologics are used for the treatment of rheumatoid arthritis and many other conditions. While the efficacy of biologics has been established, there is uncertainty regarding the adverse effects of this treatment. Since serious risks such as tuberculosis (TB) reactivation, serious infections, and lymphomas may be common to the biologics but occur in small numbers across the various indications, we planned to combine the results from biologics used in many conditions to obtain the much needed risk estimates. Objectives To compare the adverse effects of tumor necrosis factor blocker (etanercept, adalimumab, infliximab, golimumab, certolizumab), interleukin (IL)-1 antagonist (anakinra), IL-6 antagonist (tocilizumab), anti-CD28 (abatacept), and anti-B cell (rituximab) therapy in patients with any disease condition except human immunodeficiency disease (HIV/AIDS). Methods Randomized controlled trials (RCTs), controlled clinical trials (CCTs) and open-label extension (OLE) studies that studied one of the nine biologics for use in any indication (with the exception of HIV/AIDS) and that reported our pre-specified adverse outcomes were considered for inclusion. We searched The Cochrane Library, MEDLINE, and EMBASE (to January 2010). Identifying search results and data extraction were performed independently and in duplicate. For the network meta-analysis, we performed mixed-effects logistic regression using an arm-based, random-effects model within an empirical Bayes framework. Main results We included 163 RCTs with 50,010 participants and 46 extension studies with 11,954 participants. The median duration of RCTs was six months and 13 months for OLEs. Data were limited for tuberculosis (TB) reactivation, lymphoma, and congestive heart failure. Adjusted for dose, biologics as a group were associated with a statistically significant higher rate of total adverse events (odds ratio (OR) 1.19, 95% CI 1.09 to 1.30; number needed to treat to harm (NNTH) = 30, 95% CI 21 to 60) and withdrawals due to adverse events (OR 1.32, 95% CI 1.06 to 1.64; NNTH = 37, 95% CI 19 to 190) and an increased risk of TB reactivation (OR 4.68, 95% CI 1.18 to 18.60; NNTH = 681, 95% CI 143 to 14706) compared to control.The rate of serious adverse events, serious infections, lymphoma, and congestive heart failure were not statistically significantly different between biologics and control treatment. Certolizumab pegol was associated with significantly higher risk of serious infections compared to control treatment (OR 3.51, 95% CI 1.59 to 7.79; NNTH = 17, 95% CI 7 to 68). Infliximab was associated with significantly higher risk of withdrawals due to adverse events compared to control (OR 2.04, 95% CI 1.43 to 2.91; NNTH = 12, 95% CI 8 to 28). Indirect comparisons revealed that abatacept and anakinra were associated with a significantly lower risk of serious adverse events compared to most other biologics. Although the overall numbers are relatively small, certolizumab pegol was associated with significantly higher odds of serious infections compared to etanercept, adalimumab, abatacept, anakinra, golimumab, infliximab, and rituximab; abatacept was significantly less likely than infliximab and tocilizumab to be associated with serious infections. Abatacept, adalimumab, etanercept and golimumab were significantly less likely than infliximab to result in withdrawals due to adverse events. Authors' conclusions Overall, in the short term biologics were associated with significantly higher rates of total adverse events, withdrawals due to adverse events and TB reactivation. Some biologics had a statistically higher association with certain adverse outcomes compared to control, but there was no consistency across the outcomes so caution is needed in interpreting these results.There is an urgent need for more research regarding the long-term safety of biologics and the comparative safety of different biologics. National and international registries and other types of large databases are relevant sources for providing complementary evidence regarding the short- and longer-term safety of biologics.
TL;DR: Among individuals without known CAD, nonobstructive and obstructive CAD by CCTA are associated with higher rates of mortality, with risk profiles differing for age and sex, and absence of CAD is associated with a very favorable prognosis.
TL;DR: Three study-level factors (teaching status of hospital, whether all diagnoses or only some were considered, and length of follow-up) were significantly associated with the proportion of admissions deemed to be avoidable and explained some, but not all, of the heterogeneity between the studies.
Abstract: Background Readmissions to hospital are increasingly being used as an indicator of quality of care. However, this approach is valid only when we know what proportion of readmissions are avoidable. We conducted a systematic review of studies that measured the proportion of readmissions deemed avoidable. We examined how such readmissions were measured and estimated their prevalence. Methods We searched the MEDLINE and EMBASE databases to identify all studies published from 1966 to July 2010 that reviewed hospital readmissions and that specified how many were classified as avoidable. Results Our search strategy identified 34 studies. Three of the studies used combinations of administrative diagnostic codes to determine whether readmissions were avoidable. Criteria used in the remaining studies were subjective. Most of the studies were conducted at single teaching hospitals, did not consider information from the community or treating physicians, and used only one reviewer to decide whether readmissions were avoidable. The median proportion of readmissions deemed avoidable was 27.1% but varied from 5% to 79%. Three study-level factors (teaching status of hospital, whether all diagnoses or only some were considered, and length of follow-up) were significantly associated with the proportion of admissions deemed to be avoidable and explained some, but not all, of the heterogeneity between the studies. Interpretation All but three of the studies used subjective criteria to determine whether readmissions were avoidable. Study methods had notable deficits and varied extensively, as did the proportion of readmissions deemed avoidable. The true proportion of hospital readmissions that are potentially avoidable remains unclear.
TL;DR: It is concluded that, in macrophage foam cells, lysosomal hydrolysis contributes to the mobilization of LD-associated cholesterol for reverse cholesterol transport.
TL;DR: The 2011 World Development report 2011: conflict, security, and development, by the World Bank, Washington DC, World Bank 2011, 325 pp., ISBN 978-0-8213-8429-8 (paperback) as discussed by the authors.
Abstract: World development report 2011: conflict, security, and development, by the World Bank, Washington DC, World Bank, 2011, 325 pp., ISBN 978-0-8213-8429-8 (paperback) This year's World Bank World Deve...
TL;DR: A taxonomy of the ad hoc routing protocols is created to uncover the requirements considered by the different protocols, the resource limitations under which they operate, and the design decisions made by the authors.
University of Oregon1, Macquarie University2, University of Bristol3, University of Wyoming4, University of the Algarve5, École Polytechnique Fédérale de Lausanne6, University of Ottawa7, University of Minnesota8, Centre national de la recherche scientifique9, University of Helsinki10, Tallinn University11, United States Geological Survey12, University of Wisconsin-Madison13, Chinese Academy of Sciences14
TL;DR: In this article, the mid-Holocene (MH, around 6 ka) and the Last Glacial Maximum (LGM, around 21 ka) were compared with palaeoclimate simulations currently being carried out as part of the fifth Assessment Report (AR5) of the Intergovernmental Panel on Climate Change.
Abstract: Subfossil pollen and plant macrofossil data derived from 14 C-dated sediment profiles can provide quantitative information on glacial and interglacial cli- mates. The data allow climate variables related to growing- season warmth, winter cold, and plant-available moisture to be reconstructed. Continental-scale reconstructions have been made for the mid-Holocene (MH, around 6 ka) and Last Glacial Maximum (LGM, around 21 ka), allowing comparison with palaeoclimate simulations currently being carried out as part of the fifth Assessment Report (AR5) of the Intergovernmental Panel on Climate Change. The synthesis of the available MH and LGM climate recon- structions and their uncertainties, obtained using modern- analogue, regression and model-inversion techniques, is presented for four temperature variables and two moisture variables. Reconstructions of the same variables based on
TL;DR: iHEM reduces the expenses of the consumers for each case, and packet delivery ratio, delay, and jitter of the WSHAN improve as the packet size of the monitoring applications, that also utilize theWSHAN, decreases.
Abstract: Wireless sensor networks (WSNs) will play a key role in the extension of the smart grid towards residential premises, and enable various demand and energy management applications. Efficient demand-supply balance and reducing electricity expenses and carbon emissions will be the immediate benefits of these applications. In this paper, we evaluate the performance of an in-home energy management (iHEM) application. The performance of iHEM is compared with an optimization-based residential energy management (OREM) scheme whose objective is to minimize the energy expenses of the consumers. We show that iHEM decreases energy expenses, reduces the contribution of the consumers to the peak load, reduces the carbon emissions of the household, and its savings are close to OREM. On the other hand, iHEM application is more flexible as it allows communication between the controller and the consumer utilizing the wireless sensor home area network (WSHAN). We evaluate the performance of iHEM under the presence of local energy generation capability, prioritized appliances, and for real-time pricing. We show that iHEM reduces the expenses of the consumers for each case. Furthermore, we show that packet delivery ratio, delay, and jitter of the WSHAN improve as the packet size of the monitoring applications, that also utilize the WSHAN, decreases.
TL;DR: The Dy(2) complex is an ideal candidate for the elucidation of slow relaxation of the magnetization mechanism seen in lanthanide systems.
Abstract: A family of five dinuclear lanthanide complexes has been synthesized with general formula [Ln(III)(2)(valdien)(2)(NO(3))(2)] where (H(2)valdien = N1,N3-bis(3-methoxysalicylidene)diethylenetriamine) and Ln(III) = Eu(III)1, Gd(III)2, Tb(III)3, Dy(III)4, and Ho(III)5. The magnetic investigations reveal that 4 exhibits single-molecule magnet (SMM) behavior with an anisotropic barrier U(eff) = 76 K. The step-like features in the hysteresis loops observed for 4 reveal an antiferromagnetic exchange coupling between the two dysprosium ions. Ab initio calculations confirm the weak antiferromagnetic interaction with an exchange constant J(Dy-Dy) = -0.21 cm(-1). The observed steps in the hysteresis loops correspond to a weakly coupled system similar to exchange-biased SMMs. The Dy(2) complex is an ideal candidate for the elucidation of slow relaxation of the magnetization mechanism seen in lanthanide systems.