Western University

BACKGROUND: Glioblastoma, the most common primary brain tumor in adults, is usually rapidly fatal. The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy plus temozolomide, given concomitantly with and after radiotherapy, in terms of efficacy and safety. 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. CONCLUSIONS: The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity.

This third edition of Braun and Murdoch's bestselling textbook now includes discussion of the use and design principles of the tidyverse packages in R, including expanded coverage of ggplot2, and R Markdown. The expanded simulation chapter introduces the Box–Muller and Metropolis–Hastings algorithms. New examples and exercises have been added throughout. This is the only introduction you'll need to start programming in R, the computing standard for analyzing data. This book comes with real R code that teaches the standards of the language. Unlike other introductory books on the R system, this book emphasizes portable programming skills that apply to most computing languages and techniques used to develop more complex projects. Solutions, datasets, and any errata are available from www.statprogr.science. Worked examples - from real applications - hundreds of exercises, and downloadable code, datasets, and solutions make a complete package for anyone working in or learning practical data science.

A new method for automatic indexing and retrieval is described. The approach is to take advantage of implicit higher-order structure in the association of terms with documents (“semantic structure”) in order to improve the detection of relevant documents on the basis of terms found in queries. The particular technique used is singular-value decomposition, in which a large term by document matrix is decomposed into a set of ca. 100 orthogonal factors from which the original matrix can be approximated by linear combination. Documents are represented by ca. 100 item vectors of factor weights. Queries are represented as pseudo-document vectors formed from weighted combinations of terms, and documents with supra-threshold cosine values are returned. Initial tests find this completely automatic method for retrieval to be promising. © 1990 John Wiley & Sons, Inc.

Organizational commitment has been conceptualized and measured in various ways. The two studies reported here were conducted to test aspects of a three‐component model of commitment which integrates these various conceptualizations. The affective component of organizational commitment, proposed by the model, refers to employees' emotional attachment to, identification with, and involvement in, the organization. The continuance component refers to commitment based on the costs that employees associate with leaving the organization. Finally, the normative component refers to employees' feelings of obligation to remain with the organization. In Study 1, scales were developed to measure these components. Relationships among the components of commitment and with variables considered their antecedents were examined in Study 2. Results of a canonical correlation analysis suggested that, as predicted by the model, the affective and continuance components of organizational commitment are empirically distinguishable constructs with different correlates. The affective and normative components, although distinguishable, appear to be somewhat related. The importance of differentiating the components of commitment, both in research and practice, is discussed.

Probiotics are widely regarded as live microorganisms that, when administered in sufficient amounts, confer a health benefit, but guidance is needed on the most appropriate use of the term. This Consensus Statement outlines recommendations for the scope and definition of the term 'probiotic' as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics in October 2013. An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic—“live microorganisms which when administered in adequate amounts confer a health benefit on the host”—was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.

Within the context of a double blind randomized controlled parallel trial of 2 nonsteroidal antiinflammatory drugs, we validated WOMAC, a new multidimensional, self-administered health status instrument for patients with osteoarthritis of the hip or knee. The pain, stiffness and physical function subscales fulfil conventional criteria for face, content and construct validity, reliability, responsiveness and relative efficiency. WOMAC is a disease-specific purpose built high performance instrument for evaluative research in osteoarthritis clinical trials.

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. METHODS: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). FINDINGS: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6-58·8) of global deaths and 41·2% (39·8-42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. INTERPRETATION: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. FUNDING: Bill & Melinda Gates Foundation.

Abstract The Astropy Project supports and fosters the development of open-source and openly developed Python packages that provide commonly needed functionality to the astronomical community. A key element of the Astropy Project is the core package astropy , which serves as the foundation for more specialized projects and packages. In this article, we provide an overview of the organization of the Astropy project and summarize key features in the core package, as of the recent major release, version 2.0. We then describe the project infrastructure designed to facilitate and support development for a broader ecosystem of interoperable packages. We conclude with a future outlook of planned new features and directions for the broader Astropy Project.

Microbiology Society journals contain high-quality research papers and topical review articles. We are a not-for-profit publisher and we support and invest in the microbiology community, to the benefit of everyone. This supports our principal goal to develop, expand and strengthen the networks available to our members so that they can generate new knowledge about microbes and ensure that it is shared with other communities.

Advances in causal modeling techniques have made it possible for researchers to simultaneously examine theory and measures. However, researchers must use these new techniques appropriately. In addition to dealing with the methodological concerns associated with more traditional methods of analysis, researchers using causal modeling approaches must understand their underlying assumptions and limitations. Most researchers are well equipped with a basic understanding of LISREL-type models. In contrast, current familiarity with PLS in the strategic management area is low. The current paper reviews four recent studies in the strategic management area which use PLS. The review notes that the technique has been applied inconsistently, and at times inappropriately, and suggests standards for evaluating future PLS applications. Copyright © 1999 John Wiley & Sons, Ltd.

This paper discusses the role of individuals’ beliefs about their abilities to competently use computers (computer self-efficacy) in the determination of computer use. A survey of Canadian managers and professionals was conducted to develop and validate a measure of computer self-efficacy and to assess both its impacts and antecedents. Computer self-efficacy was found to exert a significant influence on individuals’ expectations of the outcomes of using computers, their emotional reactions to computers (affect and anxiety), as well as their actual computer use. An individual’s self-efficacy and outcome expectations were found to be positively influenced by the encouragement of others in their work group, as well as others’ use of computers. Thus, self-efficacy represents an important individual trait, which moderates organizational influences (such as encouragement and support) on an individual’s decision to use computers. Understanding self-efficacy, then, is important to the successful implementation of systems in organizations. The existence of a reliable and valid measure of self-efficacy makes assessment possible and should have implications for organizational support, training, and implementation.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

he authors tested the generalizability of J. P. Meyer and N. J. Allen's (1991) 3-component model of organizational commitment to the domain of occupational commitment. Measures of affective, continuance, and normative commitment to occupation were developed and used to test hypotheses concerning their differential relations with antecedent and consequence variables. Confirmatory factor analyses conducted on data collected from samples of student and registered nurses revealed that the 3 component measures of occupational commitment were distinguishable from one another and from measures of the 3 components of organizational commitment

BACKGROUND: Evidence from animal and human studies suggests a protective effect of higher water intake on kidney function and cardiovascular disease (CVD). Here the associations between water intake, chronic kidney disease (CKD) and CVD were examined in the general population. METHODS: We conducted a cross-sectional analysis of the 2005-2006 National Health and Nutrition Examination Survey. Non-pregnant adults with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m(2) who were not taking diuretics were included. Total water intake from foods and beverages was categorized as low (<2.0 l/day), moderate (2.0-4.3 l/day) and high (>4.3 l/day). We examined associations between low total water intake and CKD (eGFR 30-60 ml/min/1.73 m(2)) and self-reported CVD. RESULTS: Of 3,427 adults (mean age 46 (range 20-84); mean eGFR 95 ml/min/1.73 m(2) (range 30-161)), 13% had CKD and 18% had CVD. CKD was higher among those with the lowest (<2.0 l/day) vs. highest total water intake (>4.3 l/day) (adjusted odds ratio (OR) 2.52; 95% confidence interval (CI) 0.91-6.96). When stratified by intake of (1) plain water and (2) other beverages, CKD was associated with low intake of plain water: adjusted OR 2.36 (95% CI 1.10-5.06), but not other beverages: adjusted OR 0.87 (95% CI 0.30-2.50). There was no association between low water intake and CVD (adjusted OR 0.76; 95% CI 0.37-1.59). CONCLUSIONS: Our results provide additional evidence suggesting a potentially protective effect of higher total water intake, particularly plain water, on the kidney.

With the continued interest in the role of the gut microbiota in health, attention has now turned to how to harness the microbiota for the benefit of the host. This Consensus Statement outlines the definition and scope of the term 'prebiotic' as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics in December 2016. In December 2016, a panel of experts in microbiology, nutrition and clinical research was convened by the International Scientific Association for Probiotics and Prebiotics to review the definition and scope of prebiotics. Consistent with the original embodiment of prebiotics, but aware of the latest scientific and clinical developments, the panel updated the definition of a prebiotic: a substrate that is selectively utilized by host microorganisms conferring a health benefit. This definition expands the concept of prebiotics to possibly include non-carbohydrate substances, applications to body sites other than the gastrointestinal tract, and diverse categories other than food. The requirement for selective microbiota-mediated mechanisms was retained. Beneficial health effects must be documented for a substance to be considered a prebiotic. The consensus definition applies also to prebiotics for use by animals, in which microbiota-focused strategies to maintain health and prevent disease is as relevant as for humans. Ultimately, the goal of this Consensus Statement is to engender appropriate use of the term 'prebiotic' by relevant stakeholders so that consistency and clarity can be achieved in research reports, product marketing and regulatory oversight of the category. To this end, we have reviewed several aspects of prebiotic science including its development, health benefits and legislation.

Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, 'possible' behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). 'Probable' behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia 'with definite frontotemporal lobar degeneration' requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer's disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met 'possible' criteria, and 104 (76%) met criteria for 'probable' behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with 'possible' and 'probable' criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines.

BACKGROUND: To determine whether a restrictive strategy of red-cell transfusion and a liberal strategy produced equivalent results in critically ill patients, we compared the rates of death from all causes at 30 days and the severity of organ dysfunction. METHODS: We enrolled 838 critically ill patients with euvolemia after initial treatment who had hemoglobin concentrations of less than 9.0 g per deciliter within 72 hours after admission to the intensive care unit and randomly assigned 418 patients to a restrictive strategy of transfusion, in which red cells were transfused if the hemoglobin concentration dropped below 7.0 g per deciliter and hemoglobin concentrations were maintained at 7.0 to 9.0 g per deciliter, and 420 patients to a liberal strategy, in which transfusions were given when the hemoglobin concentration fell below 10.0 g per deciliter and hemoglobin concentrations were maintained at 10.0 to 12.0 g per deciliter. RESULTS: Overall, 30-day mortality was similar in the two groups (18.7 percent vs. 23.3 percent, P= 0.11). However, the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill -- those with an Acute Physiology and Chronic Health Evaluation II score of < or =20 (8.7 percent in the restrictive-strategy group and 16.1 percent in the liberal-strategy group; P=0.03) -- and among patients who were less than 55 years of age (5.7 percent and 13.0 percent, respectively; P=0.02), but not among patients with clinically significant cardiac disease (20.5 percent and 22.9 percent, respectively; P=0.69). The mortality rate during hospitalization was significantly lower in the restrictive-strategy group (22.3 percent vs. 28.1 percent, P=0.05). CONCLUSIONS: A restrictive strategy of red-cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction and unstable angina.

After [15], [31], [19], [8], [25], [5], minimum cut/maximum flow algorithms on graphs emerged as an increasingly useful tool for exact or approximate energy minimization in low-level vision. The combinatorial optimization literature provides many min-cut/max-flow algorithms with different polynomial time complexity. Their practical efficiency, however, has to date been studied mainly outside the scope of computer vision. The goal of this paper is to provide an experimental comparison of the efficiency of min-cut/max flow algorithms for applications in vision. We compare the running times of several standard algorithms, as well as a new algorithm that we have recently developed. The algorithms we study include both Goldberg-Tarjan style "push-relabel" methods and algorithms based on Ford-Fulkerson style "augmenting paths." We benchmark these algorithms on a number of typical graphs in the contexts of image restoration, stereo, and segmentation. In many cases, our new algorithm works several times faster than any of the other methods, making near real-time performance possible. An implementation of our max-flow/min-cut algorithm is available upon request for research purposes.

Abstract When surrounded by a transparent emission region, black holes are expected to reveal a dark shadow caused by gravitational light bending and photon capture at the event horizon. To image and study this phenomenon, we have assembled the Event Horizon Telescope, a global very long baseline interferometry array observing at a wavelength of 1.3 mm. This allows us to reconstruct event-horizon-scale images of the supermassive black hole candidate in the center of the giant elliptical galaxy M87. We have resolved the central compact radio source as an asymmetric bright emission ring with a diameter of 42 ± 3 μ as, which is circular and encompasses a central depression in brightness with a flux ratio ≳10:1. The emission ring is recovered using different calibration and imaging schemes, with its diameter and width remaining stable over four different observations carried out in different days. Overall, the observed image is consistent with expectations for the shadow of a Kerr black hole as predicted by general relativity. The asymmetry in brightness in the ring can be explained in terms of relativistic beaming of the emission from a plasma rotating close to the speed of light around a black hole. We compare our images to an extensive library of ray-traced general-relativistic magnetohydrodynamic simulations of black holes and derive a central mass of M = (6.5 ± 0.7) × 10 9 M ⊙ . Our radio-wave observations thus provide powerful evidence for the presence of supermassive black holes in centers of galaxies and as the central engines of active galactic nuclei. They also present a new tool to explore gravity in its most extreme limit and on a mass scale that was so far not accessible.

Cross‐study differences in the contributions of work attitudes to the turnover process led us to (a) estimate the six relations among job satisfaction, organizational commitment, turnover intention/withdrawal cognitions, and turnover using meta‐analysis; (b) assess the effects of several psychometric moderators on those relations; and (c) compare the influences of satisfaction and commitment in the turnover process by applying path analysis to the meta‐analytic correlations. Based on aggregations involving a total of 178 independent samples from 155 studies, results showed that (a) satisfaction and commitment each contribute independently to the prediction of intention/cognitions; (b) intention/cognitions are predicted more strongly by satisfaction than by commitment; (c) intention/cognitions mediate nearly all of the attitu‐dinal linkage with turnover; and (d) attitudinal contributions to the turnover process vary with the use of single‐ versus multi‐item scales, the 9‐ versus 15‐item version of the Organizational Commitment Questionnaire, and turnover intention versus withdrawal cognition scales.