Showing papers by "University of Calgary published in 2005"
TL;DR: The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity.
Abstract: methods Patients with newly diagnosed, histologically confirmed glioblastoma were randomly assigned to receive radiotherapy alone (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival. results A total of 573 patients from 85 centers underwent randomization. The median age was 56 years, and 84 percent of patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone. The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P<0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologic toxic effects in 7 percent of patients.
16,653 citations
TL;DR: A multistep process to develop ICD-10 coding algorithms to define Charlson and Elixhauser comorbidities in administrative data and assess the performance of the resulting algorithms found these newly developed algorithms produce similar estimates ofComorbidity prevalence in administrativeData, and may outperform existing I CD-9-CM coding algorithms.
Abstract: Objectives:Implementation of the International Statistical Classification of Disease and Related Health Problems, 10th Revision (ICD-10) coding system presents challenges for using administrative data. Recognizing this, we conducted a multistep process to develop ICD-10 coding algorithms to define C
8,020 citations
TL;DR: Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylation of theMGMT promoter did notHave such a benefit and were assigned to only radiotherapy.
Abstract: background Epigenetic silencing of the MGMT (O 6 -methylguanine–DNA methyltransferase) DNArepair gene by promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma who receive alkylating agents. methods We tested the relationship between MGMT silencing in the tumor and the survival of patients who were enrolled in a randomized trial comparing radiotherapy alone with radiotherapy combined with concomitant and adjuvant treatment with temozolomide. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis. results The MGMT promoter was methylated in 45 percent of 206 assessable cases. Irrespective of treatment, MGMT promoter methylation was an independent favorable prognostic factor (P<0.001 by the log-rank test; hazard ratio, 0.45; 95 percent confidence interval, 0.32 to 0.61). Among patients whose tumor contained a methylated MGMT promoter, a survival benefit was observed in patients treated with temozolomide and radiotherapy; their median survival was 21.7 months (95 percent confidence interval, 17.4 to 30.4), as compared with 15.3 months (95 percent confidence interval, 13.0 to 20.9) among those who were assigned to only radiotherapy (P=0.007 by the log-rank test). In the absence of methylation of the MGMT promoter, there was a smaller and statistically insignificant difference in survival between the treatment groups. conclusions Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit.
6,018 citations
TL;DR: These functional CB2 receptors in the brainstem were activated by a CB2 receptor agonist, 2-arachidonoylglycerol, and by elevated endogenous levels of endocannabinoids, which also act at CB1 receptors.
Abstract: The presence and function of CB2 receptors in central nervous system (CNS) neurons are controversial. We report the expression of CB2 receptor messenger RNA and protein localization on brainstem neurons. These functional CB2 receptors in the brainstem were activated by a CB2 receptor agonist, 2-arachidonoylglycerol, and by elevated endogenous levels of endocannabinoids, which also act at CB1 receptors. CB2 receptors represent an alternative site of action of endocannabinoids that opens the possibility of nonpsychotropic therapeutic interventions using enhanced endocannabinoid levels in localized brain areas.
1,466 citations
TL;DR: It is proposed that mRNA released from disassembled polysomes is sorted and remodeled at SGs, from which selected transcripts are delivered to PBs for degradation, an interaction that is promoted by the related mRNA decay factors TTP and BRF1.
Abstract: Stress granules (SGs) are cytoplasmic aggregates of stalled translational preinitiation complexes that accumulate during stress. GW bodies/processing bodies (PBs) are distinct cytoplasmic sites of mRNA degradation. In this study, we show that SGs and PBs are spatially, compositionally, and functionally linked. SGs and PBs are induced by stress, but SG assembly requires eIF2alpha phosphorylation, whereas PB assembly does not. They are also dispersed by inhibitors of translational elongation and share several protein components, including Fas-activated serine/threonine phosphoprotein, XRN1, eIF4E, and tristetraprolin (TTP). In contrast, eIF3, G3BP, eIF4G, and PABP-1 are restricted to SGs, whereas DCP1a and 2 are confined to PBs. SGs and PBs also can harbor the same species of mRNA and physically associate with one another in vivo, an interaction that is promoted by the related mRNA decay factors TTP and BRF1. We propose that mRNA released from disassembled polysomes is sorted and remodeled at SGs, from which selected transcripts are delivered to PBs for degradation.
1,366 citations
TL;DR: In this article, the authors assessed the depth of online learning, with a focus on the nature of online interaction in four distance education course designs, and found that structure and leadership were crucial for online learners to take a deep and meaningful approach to learning.
Abstract: This study assessed the depth of online learning, with a focus on the nature of online interaction in four distance education course designs. The Study Process Questionnaire was used to measure the shift in students' approach to learning from the beginning to the end of the courses. Design had a significant impact on the nature of the interaction and whether students approached learning in a deep and meaningful manner. Structure and leadership were found to be crucial for online learners to take a deep and meaningful approach to learning.
1,305 citations
TL;DR: Inhaled ultrafine titanium dioxide particles were found on the luminal side of airways and alveoli, in all major lung tissue compartments and cells, and within capillaries, while particle uptake in vitro did not occur by any of the expected endocytic processes, but rather by diffusion or adhesive interactions.
Abstract: High concentrations of airborne particles have been associated with increased pulmonary and cardiovascular mortality, with indications of a specific toxicologic role for ultrafine particles (UFPs; particles < 0.1 microm). Within hours after the respiratory system is exposed to UFPs, the UFPs may appear in many compartments of the body, including the liver, heart, and nervous system. To date, the mechanisms by which UFPs penetrate boundary membranes and the distribution of UFPs within tissue compartments of their primary and secondary target organs are largely unknown. We combined different experimental approaches to study the distribution of UFPs in lungs and their uptake by cells. In the in vivo experiments, rats inhaled an ultrafine titanium dioxide aerosol of 22 nm count median diameter. The intrapulmonary distribution of particles was analyzed 1 hr or 24 hr after the end of exposure, using energy-filtering transmission electron microscopy for elemental microanalysis of individual particles. In an in vitro study, we exposed pulmonary macrophages and red blood cells to fluorescent polystyrene microspheres (1, 0.2, and 0.078 microm) and assessed particle uptake by confocal laser scanning microscopy. Inhaled ultrafine titanium dioxide particles were found on the luminal side of airways and alveoli, in all major lung tissue compartments and cells, and within capillaries. Particle uptake in vitro into cells did not occur by any of the expected endocytic processes, but rather by diffusion or adhesive interactions. Particles within cells are not membrane bound and hence have direct access to intracellular proteins, organelles, and DNA, which may greatly enhance their toxic potential.
1,259 citations
University of Florida1, Duke University2, Harvard University3, University of Cincinnati4, University of Michigan5, Johns Hopkins University6, University of North Carolina at Chapel Hill7, University of California, Los Angeles8, University of Texas Southwestern Medical Center9, University of Minnesota10, Mayo Clinic11, Ohio State University12, Northwestern University13, University of Calgary14, University of Kentucky15, Cleveland Clinic16, Vanderbilt University17, University of Alabama18, Case Western Reserve University19, University of Washington20, University of California, San Francisco21, University of Wisconsin-Madison22
TL;DR: Therapy to reduce volume overload during hospitalization for heart failure led to marked improvement in signs and symptoms of elevated filling pressures with or without the PAC, which reached significance for the time trade-off at all time points after randomization.
Abstract: Context Pulmonary artery catheters (PACs) have been used to guide therapy in multiple settings, but recent studies have raised concerns that PACs may lead to increased mortality in hospitalized patients. Objective To determine whether PAC use is safe and improves clinical outcomes in patients hospitalized with severe symptomatic and recurrent heart failure. Design, setting, and participants The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) was a randomized controlled trial of 433 patients at 26 sites conducted from January 18, 2000, to November 17, 2003. Patients were assigned to receive therapy guided by clinical assessment and a PAC or clinical assessment alone. The target in both groups was resolution of clinical congestion, with additional PAC targets of a pulmonary capillary wedge pressure of 15 mm Hg and a right atrial pressure of 8 mm Hg. Medications were not specified, but inotrope use was explicitly discouraged. Main outcome measures The primary end point was days alive out of the hospital during the first 6 months, with secondary end points of exercise, quality of life, biochemical, and echocardiographic changes. Results Severity of illness was reflected by the following values: average left ventricular ejection fraction, 19%; systolic blood pressure, 106 mm Hg; sodium level, 137 mEq/L; urea nitrogen, 35 mg/dL (12.40 mmol/L); and creatinine, 1.5 mg/dL (132.6 micromol/L). Therapy in both groups led to substantial reduction in symptoms, jugular venous pressure, and edema. Use of the PAC did not significantly affect the primary end point of days alive and out of the hospital during the first 6 months (133 days vs 135 days; hazard ratio [HR], 1.00 [95% confidence interval {CI}, 0.82-1.21]; P = .99), mortality (43 patients [10%] vs 38 patients [9%]; odds ratio [OR], 1.26 [95% CI, 0.78-2.03]; P = .35), or the number of days hospitalized (8.7 vs 8.3; HR, 1.04 [95% CI, 0.86-1.27]; P = .67). In-hospital adverse events were more common among patients in the PAC group (47 [21.9%] vs 25 [11.5%]; P = .04). There were no deaths related to PAC use, and no difference for in-hospital plus 30-day mortality (10 [4.7%] vs 11 [5.0%]; OR, 0.97 [95% CI, 0.38-2.22]; P = .97). Exercise and quality of life end points improved in both groups with a trend toward greater improvement with the PAC, which reached significance for the time trade-off at all time points after randomization. Conclusions Therapy to reduce volume overload during hospitalization for heart failure led to marked improvement in signs and symptoms of elevated filling pressures with or without the PAC. Addition of the PAC to careful clinical assessment increased anticipated adverse events, but did not affect overall mortality and hospitalization. Future trials should test noninvasive assessments with specific treatment strategies that could be used to better tailor therapy for both survival time and survival quality as valued by patients.
1,229 citations
TL;DR: In this paper, a review of important trends in the strategic management approach to studying family firms is provided, including convergence in definitions, accumulating evidence that family involvement may affect performance, and the emergence of agency theory and the resource-based view of the firm as the leading theoretical perspectives.
Abstract: This article provides a review of important trends in the strategic management approach to studying family firms: convergence in definitions, accumulating evidence that family involvement may affect performance, and the emergence of agency theory and the resourcebased view of the firm as the leading theoretical perspectives. We conclude by discussing directions for future research and other promising approaches to inform the inquiry concerning family business.
1,180 citations
TL;DR: A systematic review of the effectiveness and costs of different guideline development, dissemination, and implementation strategies was taken and a framework for deciding when it is efficient to develop and introduce clinical guidelines was developed.
Abstract: Objectives: A systematic review of the
effectiveness and costs of different guideline development,
dissemination, and implementation strategies wasundertaken. The resource
implications of these strategies was estimated, and a framework for
deciding when it is efficient to develop and introduce clinical
guidelines was developed.
1,079 citations
TL;DR: Intravenous desmoteplase administered 3 to 9 hours after acute ischemic stroke in patients selected with perfusion/diffusion mismatch is associated with a higher rate of reperfusion and better clinical outcome compared with placebo.
Abstract: Background and Purpose— Most acute ischemic stroke patients arrive after the 3-hour time window for recombinant tissue plasminogen activator (rtPA) administration. The Desmoteplase In Acute Ischemic Stroke trial (DIAS) was a dose-finding randomized trial designed to evaluate the safety and efficacy of intravenous desmoteplase, a highly fibrin-specific and nonneurotoxic thrombolytic agent, administered within 3 to 9 hours of ischemic stroke onset in patients with perfusion/diffusion mismatch on MRI. Methods— DIAS was a placebo-controlled, double-blind, randomized, dose-finding phase II trial. Patients with National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch were eligible. Of 104 patients, the first 47 (referred to as Part 1) were randomized to fixed doses of desmoteplase (25 mg, 37.5 mg, or 50 mg) or placebo. Because of an excessive rate of symptomatic intracranial hemorrhage (sICH), lower weight-adjusted doses escalating through 62.5 μg/kg, ...
TL;DR: A novel multiplex PCR assay allowing for concomitant detection of the methicillin resistance (mecA gene) to facilitate detection and classification of all currently described SCCmec types and subtypes I, II, III, IVa, b, c, d, and V is demonstrated.
Abstract: Staphylococcal cassette chromosome mec (SCCmec) typing is essential for understanding the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA). SCCmec elements are currently classified into types I to V based on the nature of the mec and ccr gene complexes, and are further classified into subtypes according to their junkyard region DNA segments. Previously described traditional SCCmec PCR typing schemes require multiple primer sets and PCR experiments, while a previously published multiplex PCR assay is limited in its ability to detect recently discovered types and subtypes such as SCCmec type V and subtypes IVa, b, c, and d. We designed new sets of SCCmec type- and subtype-unique and specific primers and developed a novel multiplex PCR assay allowing for concomitant detection of the methicillin resistance (mecA gene) (also serving as an internal control) to facilitate detection and classification of all currently described SCCmec types and subtypes I, II, III, IVa, b, c, d, and V. Our assay demonstrated 100% sensitivity and specificity in accurately characterizing 54 MRSA strains belonging to the various known SCCmec types and subtypes, when compared with previously described typing methods. Further application of our assay in 453 randomly selected local clinical isolates confirmed its feasibility and practicality. This novel assay offers a rapid, simple, and feasible method for SCCmec typing of MRSA, and may serve as a useful tool for clinicians and epidemiologists in their efforts to prevent and control infections caused by this organism.
TL;DR: Results showed that applicant attraction outcomes were predicted by job-organization characteristics, recruiter behaviors, perceptions of the recruiting process, perceived fit, and hiring expectancies, but not recruiter demographics or perceived alternatives.
Abstract: Attracting high-performing applicants is a critical component of personnel selection and overall organizational success. In this study, the authors meta-analyzed 667 coefficients from 71 studies examining relationships between various predictors with job-organization attraction, job pursuit intentions, acceptance intentions, and job choice. The moderating effects of applicant gender, race, and applicant versus nonapplicant status were also examined. Results showed that applicant attraction outcomes were predicted by job-organization characteristics, recruiter behaviors, perceptions of the recruiting process, perceived fit, and hiring expectancies, but not recruiter demographics or perceived alternatives. Path analyses showed that applicant attitudes and intentions mediated the predictor-job choice relationships. The authors discuss the implications of these findings for recruiting theory, research, and practice.
TL;DR: It is found that the magnitude of pollen limitation observed in natural populations depends on both historical constraints and contemporary ecological factors.
Abstract: ▪ Abstract Quantifying the extent to which seed production is limited by the availability of pollen has been an area of intensive empirical study over the past few decades. Whereas theory predicts that pollen augmentation should not increase seed production, numerous empirical studies report significant and strong pollen limitation. Here, we use a variety of approaches to examine the correlates of pollen limitation in an effort to understand its occurrence and importance in plant evolutionary ecology. In particular, we examine the role of recent ecological perturbations in influencing pollen limitation and discuss the relation between pollen limitation and plant traits. We find that the magnitude of pollen limitation observed in natural populations depends on both historical constraints and contemporary ecological factors.
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01 Jan 2005TL;DR: In this paper, the authors identify the Construct Links between Constructs Construct Cleanliness Single versus Multiple Constructs and Single versus multiple Constructs Summary and Next Step Problems and Exercises Designing and Writing Items Empirical, Theoretical, and Rational Approaches to Item Empirically, theoretical and rational approaches to item literature Search Subject Matter Experts How Many Items?
Abstract: Preface The Assessment of Individuals: The Critical Role and Fundamentals of Measurement Measurement in the Physical Sciences Measurement in the Social Sciences Historical Highlights of Measurement Statistics Background The First Step: Identifying the Construct Links Between Constructs Construct Cleanliness Single versus Multiple Constructs Summary and Next Step Problems and Exercises Designing and Writing Items Empirical, Theoretical and Rational Approaches to Item Empirical, Theoretical and Rational Approaches to Item Literature Search Subject Matter Experts How Many Items? Attitudinal Items: Early Work in Item Generation Assessing Behaviors Pilot Testing Summary and Next Step Problems and Exercises Designing and Scoring Responses Open-Ended Responses Closed-Ended Questions Example 1: Proportional Differences for a Single Variable Example 2: Proportional Differences for Two Variables Dichotomous Responses Multiple Choice Tests Continuous Responses Ipsative versus Normative Scales Difference and Change Scores Summary and Next Step Problems and Exercises Collecting Data: Sampling and Screening Probability Sampling Non-Probability Sampling Sample Sizes Missing Data Preparing to Analyze Your Data Summary and Next Step Problems and Exercises Classical Test Theory: Assumptions, Equations, Limitations and Item Analyses Classical Test Theory Theory of True and Error Scores: Description and Assumptions Ramifications and Limitations of Classical Test Theory Assumptions Item Analysis within CTT: Approaches, Statistical Analyses, and Interpretation Descriptive Statistics Summary Problems and Exercises Modern Test Theory: Assumptions, Equations, Limitations and Item Analyses Modern Test Theory Models One-Parameter Logistic Model Two-Parameter Logistic Model Three-Parameter Logistic Model Multiple-response IRT Models Parameter Estimation Scoring Respondents Model Fit Assumptions Ramifications of the Assumptions of Modern Test Theory Practical Advantages of Modern Test Theory Limitations of Modern Test Theory Computer Programs Practical Considerations Summary Next Steps Problems and Exercises Reliability of Test Scores and Test Items Test-retest Reliability Alternative Forms Reliability Measures of Internal Consistency Setting Confidence Intervals Reliability of a Composite Difference Scores - A Reliability Concern Practical Questions Summary and Next Steps Problems and Exercises Reliability of Raters Inter-Rater Reliability Indices Reliability Generalization Modern Test Theory Approaches to Reliability Summary and Next Steps Problems and Exercises Assessing Validity Using Content and Criterion Methods Asking the Test Takers Asking the Subject Matter Experts Assessments Using Correlation and Regression: Criterion-Related Studies Classification Approaches to Test Score Validation Group Differences and Test Bias Extending the Inferences of Criterion-Related Validity Studies Summary Problems and Exercises Assessing Validity Via Item Internal Structure Principal Components Analysis Common Factor Analysis Common Factor Analysis using Analysis of Covariance Structures Some Other Issues in Factor Analysis Practical Issues Concluding Comments on Internal Structure and Validity Threats to the Validity of Scores Multitrait-Multimethod Assessment Closing Comments on Test Score Validity Summary Problems and Exercises Ethics and Professional Issues in Testing Professional Standards and Guidelines Ethical Procedures and Protocols Test Administration Integrity Testing Computerized Testing Coaching, Testwiseness, and Re-takes Testing Legislation Test Item Bias and Adverse Impact Translation Issues Electronic Presentation and Capture Summary Problems and Exercises Brief Reviews of Some Selected Tests and Concluding Comments Information about Existing Tests Some Intelligence Tests Academic Achievement Tests Structured Personality Tests Career Interest/Guidance Instruments Chapter Summary A Quick Book Review Concluding Comments Problems and Exercises Appendices References Index
TL;DR: A centralized routing protocol called base-station controlled dynamic clustering protocol (BCDCP), which distributes the energy dissipation evenly among all sensor nodes to improve network lifetime and average energy savings and is compared to clustering-based schemes.
Abstract: Wireless sensor networks consist of small battery powered devices with limited energy resources. Once deployed, the small sensor nodes are usually inaccessible to the user, and thus replacement of the energy source is not feasible. Hence, energy efficiency is a key design issue that needs to be enhanced in order to improve the life span of the network. Several network layer protocols have been proposed to improve the effective lifetime of a network with a limited energy supply. In this article we propose a centralized routing protocol called base-station controlled dynamic clustering protocol (BCDCP), which distributes the energy dissipation evenly among all sensor nodes to improve network lifetime and average energy savings. The performance of BCDCP is then compared to clustering-based schemes such as low-energy adaptive clustering hierarchy (LEACH), LEACH-centralized (LEACH-C), and power-efficient gathering in sensor information systems (PEGASIS). Simulation results show that BCDCP reduces overall energy consumption and improves network lifetime over its comparatives.
TL;DR: Although there is substantial variation in outcome definition and methodology among the studies, consistent patterns of results emerge for various surgical interventions after adjusting for sources of heterogeneity.
Abstract: Summary Assessment of long-term outcomes is essential in brain surgery for epilepsy, which is an irreversible intervention for a chronic condition. Excellent short-term results of resective epilepsy surgery have been established, but less is known about long-term outcomes. We performed a systematic review and meta-analysis of the evidence on this topic. To provide evidence-based estimates of longterm results of various types of epilepsy surgery and to identify sources of variation in results of published studies, we searched Medline, Index Medicus, the Cochrane database, bibliographies of reviews, original articles and book chapters to identify articles published since 1991 that contained >20 patients of any age, undergoing resective or non-resective epilepsy surgery, and followed for a mean/median of >5 years. Two reviewers independently assessed study eligibility and extracted data, resolving disagreements through discussion. Seventy-six articles fulfilled our eligibility criteria, of which 71 reported on resective surgery (93%) and five (7%) on non-resective surgery. There were no randomized trials and only six studies had a control group. Some articles contributed more than one study, yielding 83 studies of which 78 dealt with resective surgery and five with non-resective surgery. Forty studies (51%) of resective surgery referred to temporal lobe surgery, 25 (32%) to grouped temporal and extratemporal surgery, seven (9%) to frontal surgery, two (3%) to grouped extratemporal surgery, two (3%) to hemispherectomy, and one (1%) each to parietal and occipital surgery. In the non-resective category, three studies reported outcomes after callosotomy and two after multiple subpial transections. The median proportion of long-term seizure-free patients was 66% with temporal lobe resections, 46% with occipital and parietal resections, and 27% with frontal lobe resections. In the long term, only 35% of patients with callosotomy were free of most disabling seizures, and 16% with multiple subpial transections remained free of all seizures. The year of operation, duration of follow-up and outcome classification system were most strongly associated with outcomes. Almost all long-term outcome studies describe patient cohorts without controls. Although there is substantial variation in outcome definition and methodology among the studies, consistent patterns of results emerge for various surgical interventions after adjusting for sources of heterogeneity. The long-term (>5 years) seizure free rate following temporal lobe resective surgery was similar to that reported in short-term controlled studies. On the other hand, long-term seizure freedom was consistently lower after extratemporal surgery and palliative procedures.
TL;DR: The role of adipose tissue in the development of obesity-linked insulin resistance, metabolic syndrome, and diabetes will be reviewed, including an examination of the molecular links between obesity and atherosclerosis, namely, the effects of fat-derived adipokines.
Abstract: Atherosclerotic disease remains the leading cause of death in industrialized nations despite major advances in its diagnosis, treatment, and prevention. The increasing epidemic of obesity, insulin resistance, and diabetes will likely add to this burden. Increasingly, it is becoming apparent that adipose tissue is an active endocrine and paracrine organ that releases several bioactive mediators that influence not only body weight homeostasis but also inflammation, coagulation, fibrinolysis, insulin resistance, diabetes, and atherosclerosis. The cellular mechanisms linking obesity and atherosclerosis are complex and have not been fully elucidated. This review summarizes the experimental and clinical evidence on how excess body fat influences cardiovascular health through multiple yet converging pathways. The role of adipose tissue in the development of obesity-linked insulin resistance, metabolic syndrome, and diabetes will be reviewed, including an examination of the molecular links between obesity and atherosclerosis, namely, the effects of fat-derived adipokines. Finally, we will discuss how these new insights may provide us with innovative therapeutic strategies to improve cardiovascular health.
Mayo Clinic1, Lille University of Science and Technology2, University of British Columbia3, University of Western Ontario4, University of Chicago5, University of Western Australia6, University of Calgary7, University of Kiel8, Cedars-Sinai Medical Center9, University of Amsterdam10, Élan11, Katholieke Universiteit Leuven12
TL;DR: Induction therapy with natalizumab for Crohn's disease resulted in small, nonsignificant improvements in response and remission rates, which will need to be weighed against the risk of serious adverse events.
Abstract: BackgroundNatalizumab, a humanized monoclonal antibody against α4 integrin, inhibits leukocyte adhesion and migration into inflamed tissue. MethodsWe conducted two controlled trials to evaluate natalizumab as induction and maintenance therapy in patients with active Crohn's disease. In the first trial, 905 patients were randomly assigned to receive 300 mg of natalizumab or placebo at weeks 0, 4, and 8. The primary outcome was response, defined by a decrease in the Crohn's Disease Activity Index (CDAI) score of at least 70 points, at week 10. In the second trial, 339 patients who had a response to natalizumab in the first trial were randomly reassigned to receive 300 mg of natalizumab or placebo every four weeks through week 56. The primary outcome was a sustained response through week 36. A secondary outcome in both trials was disease remission (a CDAI score of less than 150). ResultsIn the first trial, the natalizumab and placebo groups had similar rates of response (56 percent and 49 percent, respective...
TL;DR: In this paper, the authors review the conceptual and theoretical underpinnings of destination branding as conveyed by leading authors in the marketing field, and propose to refine and enhance the definition of destination brand to more fully represent the complexities of the tourism product.
Abstract: Although the concept of branding has been applied extensively to products and services, tourism destination branding is a relatively recent phenomenon. In particular, destination branding remains narrowly defined to many practitioners in destination management organizations (DMOs) and is not well represented in the tourism literature. Consequently, this study has three goals. First, it attempts to review the conceptual and theoretical underpinnings of branding as conveyed by leading authors in the marketing field. Second, it seeks to refine and enhance the definition of destination branding (acceptable to and understood by tourism destination managers) to more fully represent the complexities of the tourism product. Third, and most importantly, it seeks to improve our understanding of current destination branding practices among DMOs. The findings indicate that although DMO executives generally understand the concept of destination branding, respondents are implementing only selective aspects of this conc...
TL;DR: The meta-analysis documented that self-report instruments greatly overestimate the prevalence of every PD, and consistent differences that emerge between ED groups are high constraint and persistence and low novelty seeking in AN and high impulsivity, sensation seeking, novelty seeking, and traits associated with borderline PD in BN.
TL;DR: A new proposed classification system for thoracolumbar (TL) spine injuries, including injury severity assessment, designed to assist in clinical management and to facilitate clinical decision-making as a practical alternative to cumbersome classification systems already in use is devised.
Abstract: Study design A new proposed classification system for thoracolumbar (TL) spine injuries, including injury severity assessment, designed to assist in clinical management. Objective To devise a practical, yet comprehensive, classification system for TL injuries that assists in clinical decision-making in terms of the need for operative versus nonoperative care and surgical treatment approach in unstable injury patterns. Summary of background data The most appropriate classification of traumatic TL spine injuries remains controversial. Systems currently in use can be cumbersome and difficult to apply. None of the published classification schemata is constructed to aid with decisions in clinical management. Methods Clinical spine trauma specialists from a variety of institutions around the world were canvassed with respect to information they deemed pivotal in the communication of TL spine trauma and the clinical decision-making process. Traditional injury patterns were reviewed and reconsidered in light of these essential characteristics. An initial validation process to determine the reliability and validity of an earlier version of this system was also undertaken. Results A new classification system called the Thoracolumbar Injury Classification and Severity Score (TLICS) was devised based on three injury characteristics: 1) morphology of injury determined by radiographic appearance, 2) integrity of the posterior ligamentous complex, and 3) neurologic status of the patient. A composite injury severity score was calculated from these characteristics stratifying patients into surgical and nonsurgical treatment groups. Finally, a methodology was developed to determine the optimum operative approach for surgical injury patterns. Conclusions Although there will always be limitations to any cataloging system, the TLICS reflects accepted features cited in the literature important in predicting spinal stability, future deformity, and progressive neurologic compromise. This classification system is intended to be easy to apply and to facilitate clinical decision-making as a practical alternative to cumbersome classification systems already in use. The TLICS may improve communication between spine trauma physicians and the education of residents and fellows. Further studies are underway to determine the reliability and validity of this tool.
TL;DR: A combined CMR approach using T2-weighted imaging, early and late gadolinium enhancement, provides a high diagnostic accuracy and is a useful tool in the diagnosis and assessment of patients with suspected acute myocarditis.
TL;DR: In this paper, the authors investigated the relation of the three Dark Triad personality traits (psychopathy, Machiavellianism, and Narcissism) with the variables of the Five-Factor Model and the HEXACO model of personality structure.
University of Western Ontario1, University of California, San Francisco2, Columbia University3, University of British Columbia4, University of Calgary5, Providence Portland Medical Center6, University of Colorado Denver7, University of Saskatchewan8, Oregon Health & Science University9, University of Manitoba10
TL;DR: There is as yet no evidence that the antifracture efficacy of PTH will be superior to the bisphosphonates, whereas cost-utility estimates suggest that teriparatide is significantly more expensive.
Abstract: All therapies currently recommended for the management of osteoporosis act mainly to inhibit bone resorption and reduce bone remodeling. PTH and its analog, teriparatide [recombinant human PTH(1-34)], represent a new class of anabolic therapies for the treatment of severe osteoporosis, having the potential to improve skeletal microarchitecture. Significant reductions in both vertebral and appendicular fracture rates have been demonstrated in the phase III trial of teriparatide, involving elderly women with at least one prevalent vertebral fracture before the onset of therapy. However, there is as yet no evidence that the antifracture efficacy of PTH will be superior to the bisphosphonates, whereas cost-utility estimates suggest that teriparatide is significantly more expensive. Teriparatide should be considered as treatment for postmenopausal women and men with severe osteoporosis, as well as for patients with established glucocorticoid-induced osteoporosis who require long-term steroid treatment. Teriparatide should also be considered for the management of individuals at particularly high risk for fractures, including subjects who are younger than age 65 and who have particularly low bone mineral density measurements (T scores < or = 3.5). Teriparatide therapy is not recommended for more than 2 yr, based, in part, on the induction of osteosarcoma in a rat model of carcinogenicity. Total daily calcium intake from both supplements and dietary sources should be limited to 1500 mg together with adequate vitamin D intake (< or =1000 U/d). Monitoring of serum calcium may be safely limited to measurement after 1 month of treatment; mild hypercalcemia may be treated by withdrawing dietary calcium supplements, reducing the dosing frequency of PTH, or both. At present, concurrent therapy with antiresorptive therapy, particularly bisphosphonates, should be avoided, although sequential therapy with such agents may consolidate the beneficial effects upon the skeleton after PTH is discontinued.
TL;DR: Passive surveillance using administrative data are a useful tool for identifying stroke and its risk factors using both ICD-9 and I CD-10.
Abstract: Background and Purpose— Surveillance is necessary to understand and meet the future demands stroke will place on health care. Administrative data are the most accessible data source for stroke surveillance in Canada. The International Classification of Diseases, 10th revision (ICD-10) coding system has potential improvements over ICD-9 for stroke classification. Our purpose was to compare hospital discharge abstract coding using ICD-9 and ICD-10 for stroke and its risk factors. Methods— We took advantage of a switch in coding systems from ICD-9 to ICD-10 to independently review stroke patient charts. From time periods April 2000 to March 2001, 717 charts, and from April 2002 to March 2003, 249 charts were randomly selected for review. Using a before-and-after time period design, the accuracy of hospital coding of stroke (part I) and stroke risk factors (part II) using ICD-9 and ICD-10 was compared. We used careful definitions of stroke and its types based on ICD-9 using the fourth and fifth digit modifier...
TL;DR: More than two-thirds of students have heard of incidents of cyber-harassment, about one quarter (21%) have been harassed several times, and a few students (3%) admitted engaging in this form of harassment as mentioned in this paper.
Abstract: A total of 432 students from grades 7–9 in Canadian schools reported their experiences of cyber-harassment, which is a form of harassment that occurs through the use of electronic communications such as e-mail and cell phones. More than two-thirds of students (69%) have heard of incidents of cyber-harassment, about one quarter (21%) have been harassed several times, and a few students (3%) admitted engaging in this form of harassment. In addition, victims of cyber-harassment reported a variety of negative consequences, especially anger and sadness, and had experienced other forms of harassment. These results suggest several avenues of research needed to explain how and why adolescents use technological advances to harass their peers.
TL;DR: Although the majority of patients with sARF will die, most survivors will become independent from renal replacement therapy within a year and males, older patients, and those with underlying medical conditions are at greatest risk.
Abstract: Severe acute renal failure (sARF) is associated with considerable morbidity, mortality and use of healthcare resources; however, its precise epidemiology and long-term outcomes have not been well described in a non-specified population. Population-based surveillance was conducted among all adult residents of the Calgary Health Region (population 1 million) admitted to multidisciplinary and cardiovascular surgical intensive care units between May 1 1999 and April 30 2002. Clinical records were reviewed and outcome at 1 year was assessed. sARF occurred in 240 patients (11.0 per 100,000 population/year). Rates were highest in males and older patients (≥65 years of age). Risk factors for development of sARF included previous heart disease, stroke, pulmonary disease, diabetes mellitus, cancer, connective tissue disease, chronic renal dysfunction, and alcoholism. The annual mortality rate was 7.3 per 100,000 population with rates highest in males and those ≥65 years. The 28-day, 90-day, and 1-year case-fatality rates were 51%, 60%, and 64%, respectively. Increased Charlson co-morbidity index, presence of liver disease, higher APACHE II score, septic shock, and need for continuous renal replacement therapy were independently associated with death at 1 year. Renal recovery occurred in 78% (68/87) of survivors at 1 year. sARF is common and males, older patients, and those with underlying medical conditions are at greatest risk. Although the majority of patients with sARF will die, most survivors will become independent from renal replacement therapy within a year.
TL;DR: Overall sleep disturbance was significantly reduced and participants reported that their sleep quality had improved and the implications for improving quality of life of cancer patients are discussed.
Abstract: Sleep disturbance is a very common problem for cancer patients that has largely not been addressed in the clinical intervention literature. Mindfulness meditation has demonstrated clinical benefits for a variety of patient populations in other areas of functioning. This study examined the effects of an 8-week Mindfulness-Based Stress Reduction (MBSR) program on the sleep quality of a heterogeneous sample of 63 cancer patients. Overall sleep disturbance was significantly reduced (p < .001) and participants reported that their sleep quality had improved (p < .001). There was also a significant reduction in stress (p < .001), mood disturbance (p = .001), and fatigue (p < .001). The associations among these changes and implications for improving quality of life of cancer patients are discussed.
TL;DR: The authors show how institutionalist scholarship can pay greater attention to ideational processes without abandoning its core assumptions about the structuring impact of political institutions and policy legacies on welfare state development.
Abstract: Since the beginning of the 1980s, historical institutionalism has emerged as one of the most influential theoretical perspectives in social policy studies. Although their work is insightful, most institutionalist scholars tend to relegate policy ideas to the back of their theoretical constructions dealing with welfare state development. The objective of this paper is to show how institutionalist scholarship can pay greater attention to ideational processes without abandoning its core assumptions about the structuring impact of political institutions and policy legacies on welfare state development. If institutions truly influence policy-making, policy ideas matter in and beyond the agenda-setting process. Related to existing policy legacies, perceived problems mesh with policy alternatives grounded in a specific paradigm. When stressing the need to reform, and promoting new alternatives, policy entrepreneurs draw on existing ideological repertoires to frame these alternatives. The ability to successfully frame policy alternatives can become a decisive aspect of the policy process. A discussion of recent European and North American policy debates illustrates these claims.