Showing papers by "University of Western Ontario published in 2016"

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Abstract: 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 that there 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 complete process 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 increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most 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 many cases, 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 for reviewers 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 multiple assays 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 autophagy-related 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.

Platinum single-atom and cluster catalysis of the hydrogen evolution reaction

Abstract: Platinum-based catalysts have been considered the most effective electrocatalysts for the hydrogen evolution reaction in water splitting. However, platinum utilization in these electrocatalysts is extremely low, as the active sites are only located on the surface of the catalyst particles. Downsizing catalyst nanoparticles to single atoms is highly desirable to maximize their efficiency by utilizing nearly all platinum atoms. Here we report on a practical synthesis method to produce isolated single platinum atoms and clusters using the atomic layer deposition technique. The single platinum atom catalysts are investigated for the hydrogen evolution reaction, where they exhibit significantly enhanced catalytic activity (up to 37 times) and high stability in comparison with the state-of-the-art commercial platinum/carbon catalysts. The X-ray absorption fine structure and density functional theory analyses indicate that the partially unoccupied density of states of the platinum atoms’ 5d orbitals on the nitrogen-doped graphene are responsible for the excellent performance. Downsizing platinum based nanocatalysts has the twin advantages of lower platinum usage and increased activity per platinum atom. Here, the authors report an atomic layer deposition technique for single platinum atom catalyst fabrication and assess their hydrogen evolution activity.

A Survey on Wireless Security: Technical Challenges, Recent Advances, and Future Trends

Abstract: Due to the broadcast nature of radio propagation, the wireless air interface is open and accessible to both authorized and illegitimate users. This completely differs from a wired network, where communicating devices are physically connected through cables and a node without direct association is unable to access the network for illicit activities. The open communications environment makes wireless transmissions more vulnerable than wired communications to malicious attacks, including both the passive eavesdropping for data interception and the active jamming for disrupting legitimate transmissions. Therefore, this paper is motivated to examine the security vulnerabilities and threats imposed by the inherent open nature of wireless communications and to devise efficient defense mechanisms for improving the wireless network security. We first summarize the security requirements of wireless networks, including their authenticity, confidentiality, integrity, and availability issues. Next, a comprehensive overview of security attacks encountered in wireless networks is presented in view of the network protocol architecture, where the potential security threats are discussed at each protocol layer. We also provide a survey of the existing security protocols and algorithms that are adopted in the existing wireless network standards, such as the Bluetooth, Wi-Fi, WiMAX, and the long-term evolution (LTE) systems. Then, we discuss the state of the art in physical-layer security, which is an emerging technique of securing the open communications environment against eavesdropping attacks at the physical layer. Several physical-layer security techniques are reviewed and compared, including information-theoretic security, artificial-noise-aided security, security-oriented beamforming, diversity-assisted security, and physical-layer key generation approaches. Since a jammer emitting radio signals can readily interfere with the legitimate wireless users, we also introduce the family of various jamming attacks and their countermeasures, including the constant jammer, intermittent jammer, reactive jammer, adaptive jammer, and intelligent jammer. Additionally, we discuss the integration of physical-layer security into existing authentication and cryptography mechanisms for further securing wireless networks. Finally, some technical challenges which remain unresolved at the time of writing are summarized and the future trends in wireless security are discussed.

Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis

Abstract: Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD-abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions.

Pioglitazone after Ischemic Stroke or Transient Ischemic Attack

Abstract: BackgroundPatients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. MethodsIn this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. ResultsBy 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group...

General Equilibrium Computations of the Marginal Welfare Costs of Taxes in the United States

Abstract: In recent years, increasing attention has been paid by public finance economists to the marginal excess burden (MEB)1 per additional dollar of tax revenue. Estimates of MEBs stand in contrast to estimates of the welfare cost of taxes which are calculated by totally removing existing taxes and replacing them with equal yield lump sum taxes. Instead, an MEB estimate measures the incremental welfare costs of raising extra revenues from an already existing distorting tax. Earlier estimates of MEBs have either concentrated on particular portions of the tax system, or have employed partial equilibrium methods. Here, we examine the MEB of all major taxes in the United States, using a multisector, dynamic computational general equilibrium model. This allows us to calculate simultaneously the marginal welfare effects of individual income taxes, corporate taxes, payroll taxes, sales and excise taxes, and other smaller sources of revenue. We find that the marginal excess burden

Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma

Abstract: BackgroundGrade 2 gliomas occur most commonly in young adults and cause progressive neurologic deterioration and premature death. Early results of this trial showed that treatment with procarbazine, lomustine (also called CCNU), and vincristine after radiation therapy at the time of initial diagnosis resulted in longer progression-free survival, but not overall survival, than radiation therapy alone. We now report the long-term results. MethodsWe included patients with grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma who were younger than 40 years of age and had undergone subtotal resection or biopsy or who were 40 years of age or older and had undergone biopsy or resection of any of the tumor. Patients were stratified according to age, histologic findings, Karnofsky performance-status score, and presence or absence of contrast enhancement on preoperative images. Patients were randomly assigned to radiation therapy alone or to radiation therapy followed by six cycles of combination chemotherapy...

Recent Developments and Understanding of Novel Mixed Transition-Metal Oxides as Anodes in Lithium Ion Batteries

Abstract: Mixed transition-metal oxides (MTMOs), including stannates, ferrites, cobaltates, and nickelates, have attracted increased attention in the application of high performance lithium-ion batteries. Compared with traditional metal oxides, MTMOs exhibit enormous potential as electrode materials in lithium-ion batteries originating from higher reversible capacity, better structural stability, and high electronic conductivity. Recent advancements in the rational design of novel MTMO micro/nanostructures for lithium-ion battery anodes are summarized and their energy storage mechanism is compared to transition-metal oxide anodes. In particular, the significant effects of the MTMO morphology, micro/nanostructure, and crystallinity on battery performance are highlighted. Furthermore, the future trends and prospects, as well as potential problems, are presented to further develop advanced MTMO anodes for more promising and large-scale commercial applications of lithium-ion batteries.

Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study

Abstract: Summary Background Bortezomib with dexamethasone is a standard treatment option for relapsed or refractory multiple myeloma. Carfilzomib with dexamethasone has shown promising activity in patients in this disease setting. The aim of this study was to compare the combination of carfilzomib and dexamethasone with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Methods In this randomised, phase 3, open-label, multicentre study, patients with relapsed or refractory multiple myeloma who had one to three previous treatments were randomly assigned (1:1) using a blocked randomisation scheme (block size of four) to receive carfilzomib with dexamethasone (carfilzomib group) or bortezomib with dexamethasone (bortezomib group). Randomisation was stratified by previous proteasome inhibitor therapy, previous lines of treatment, International Staging System stage, and planned route of bortezomib administration if randomly assigned to bortezomib with dexamethasone. Patients received treatment until progression with carfilzomib (20 mg/m 2 on days 1 and 2 of cycle 1; 56 mg/m 2 thereafter; 30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or bortezomib (1·3 mg/m 2 ; intravenous bolus or subcutaneous injection) and dexamethasone (20 mg oral or intravenous infusion). The primary endpoint was progression-free survival in the intention-to-treat population. All participants who received at least one dose of study drug were included in the safety analyses. The study is ongoing but not enrolling participants; results for the interim analysis of the primary endpoint are presented. The trial is registered at ClinicalTrials.gov, number NCT01568866. Findings Between June 20, 2012, and June 30, 2014, 929 patients were randomly assigned (464 to the carfilzomib group; 465 to the bortezomib group). Median follow-up was 11·9 months (IQR 9·3–16·1) in the carfilzomib group and 11·1 months (8·2–14·3) in the bortezomib group. Median progression-free survival was 18·7 months (95% CI 15·6–not estimable) in the carfilzomib group versus 9·4 months (8·4–10·4) in the bortezomib group at a preplanned interim analysis (hazard ratio [HR] 0·53 [95% CI 0·44–0·65]; p vs 45 [10%] of 456 patients in the bortezomib group), hypertension (41 [9%] vs 12 [3%]), thrombocytopenia (39 [8%] vs 43 [9%]), and pneumonia (32 [7%] vs 36 [8%]). Interpretation For patients with relapsed or refractory multiple myeloma, carfilzomib with dexamethasone could be considered in cases in which bortezomib with dexamethasone is a potential treatment option. Funding Onyx Pharmaceuticals, Inc., an Amgen subsidiary.

International consensus guidance for management of myasthenia gravis: Executive summary

Abstract: Objective: To develop formal consensus-based guidance for the management of myasthenia gravis (MG). Methods: In October 2013, the Myasthenia Gravis Foundation of America appointed a Task Force to develop treatment guidance for MG, and a panel of 15 international experts was convened. The RAND/UCLA appropriateness methodology was used to develop consensus guidance statements. Definitions were developed for goals of treatment, minimal manifestations, remission, ocular MG, impending crisis, crisis, and refractory MG. An in-person panel meeting then determined 7 treatment topics to be addressed. Initial guidance statements were developed from literature summaries. Three rounds of anonymous e-mail votes were used to attain consensus on guidance statements modified on the basis of panel input. Results: Guidance statements were developed for symptomatic and immunosuppressive treatments, IV immunoglobulin and plasma exchange, management of impending and manifest myasthenic crisis, thymectomy, juvenile MG, MG associated with antibodies to muscle-specific tyrosine kinase, and MG in pregnancy. Conclusion: This is an international formal consensus of MG experts intended to be a guide for clinicians caring for patients with MG worldwide.

Can we predict ectotherm responses to climate change using thermal performance curves and body temperatures

Abstract: Thermal performance curves (TPCs), which quantify how an ectotherm's body temperature (Tb ) affects its performance or fitness, are often used in an attempt to predict organismal responses to climate change. Here, we examine the key - but often biologically unreasonable - assumptions underlying this approach; for example, that physiology and thermal regimes are invariant over ontogeny, space and time, and also that TPCs are independent of previously experienced Tb. We show how a critical consideration of these assumptions can lead to biologically useful hypotheses and experimental designs. For example, rather than assuming that TPCs are fixed during ontogeny, one can measure TPCs for each major life stage and incorporate these into stage-specific ecological models to reveal the life stage most likely to be vulnerable to climate change. Our overall goal is to explicitly examine the assumptions underlying the integration of TPCs with Tb , to develop a framework within which empiricists can place their work within these limitations, and to facilitate the application of thermal physiology to understanding the biological implications of climate change.

Azathioprine or 6-mercaptopurine for induction of remission in Crohn's disease.

Abstract: Objectives To determine the effectiveness of azathioprine and 6-mercaptopurine in inducing remission of active Crohn's disease. Search strategy Studies were selected using the MEDLINE data base (1966 - December 1997), abstracts from major gastrointestinal meetings and references from published articles and reviews. The Cochrane Controlled Trials Register and the Inflammatory Bowel Disease Review Group Trials Register was also searched. Selection criteria Eight randomized placebo controlled trials of azathioprine and 6-mercaptopurine therapy in adult patients were identified: five dealt with active disease and three had multiple therapeutic arms. Data collection and analysis Data were extracted by three independent observers based on the intention to treat principle. Each study was given a quality score based on predetermined criteria. Extracted data were converted to 2X2 tables (response versus no response and antimetabolite versus placebo) and then synthesized into a summary test statistic using the pooled odds ratio and 95% confidence intervals as described by Cochran and Mantel and Haenszel ('Odds Ratio' in MetaView). Main results The odds ratio of a response to azathioprine or 6-mercaptopurine therapy compared with placebo in active Crohn's disease was 2.36 (95% CI 1.57-3.53). This corresponded to a number needed to treat of about 5 to observe an effect of therapy in one patient. When the two trials using 6-mercaptopurine in active disease were excluded from the analysis, the odds ratio of response was 2.04 (CI 1.24 - 3.35). Treatment >/= 17 weeks increased the odds ratio of a response to 2.51 (CI 1.63-3. 88). A steroid sparing effect was seen with an odds ratio of 3.86 (CI 2.14 - 6.96), corresponding to a number needed to treat of about 3 to observe steroid sparing in one patient. Adverse events requiring withdrawal from a trial, principally allergy, leukopenia, pancreatitis, and nausea were increased on therapy with an odds ratio of 3.01 (CI 1.30 - 6.96). The number needed to treat to observe one adverse event in one patient treated with azathioprine or 6-mercaptopurine was 14. Reviewer's conclusions Azathioprine and 6-mercaptopurine are effective therapy for inducing remission in active Crohn's disease. The odds ratio of response increases after >/= 17 weeks of therapy, suggesting that there is a minimum length of time for a trial of azathioprine or 6-mercaptopurine therapy. Adverse events were more common among patients on therapy.

Current knowledge and perspectives of Paenibacillus : a review

Abstract: Isolated from a wide range of sources, the genus Paenibacillus comprises bacterial species relevant to humans, animals, plants, and the environment. Many Paenibacillus species can promote crop growth directly via biological nitrogen fixation, phosphate solubilization, production of the phytohormone indole-3-acetic acid (IAA), and release of siderophores that enable iron acquisition. They can also offer protection against insect herbivores and phytopathogens, including bacteria, fungi, nematodes, and viruses. This is accomplished by the production of a variety of antimicrobials and insecticides, and by triggering a hypersensitive defensive response of the plant, known as induced systemic resistance (ISR). Paenibacillus-derived antimicrobials also have applications in medicine, including polymyxins and fusaricidins, which are nonribosomal lipopeptides first isolated from strains of Paenibacillus polymyxa. Other useful molecules include exo-polysaccharides (EPS) and enzymes such as amylases, cellulases, hemicellulases, lipases, pectinases, oxygenases, dehydrogenases, lignin-modifying enzymes, and mutanases, which may have applications for detergents, food and feed, textiles, paper, biofuel, and healthcare. On the negative side, Paenibacillus larvae is the causative agent of American Foulbrood, a lethal disease of honeybees, while a variety of species are opportunistic infectors of humans, and others cause spoilage of pasteurized dairy products. This broad review summarizes the major positive and negative impacts of Paenibacillus: its realised and prospective contributions to agriculture, medicine, process manufacturing, and bioremediation, as well as its impacts due to pathogenicity and food spoilage. This review also includes detailed information in Additional files 1, 2, 3 for major known Paenibacillus species with their locations of isolation, genome sequencing projects, patents, and industrially significant compounds and enzymes. Paenibacillus will, over time, play increasingly important roles in sustainable agriculture and industrial biotechnology.

Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis

Abstract: Background Oral 5-aminosalicylic acid (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. Previously, it was found that 5-ASA drugs in doses of at least 2 g/day, were more effective than placebo but no more effective than SASP for inducing remission in ulcerative colitis. This updated review includes more recent studies and evaluates the efficacy and safety of 5-ASA preparations used for the treatment of mild to moderately active ulcerative colitis. Objectives The primary objectives were to assess the efficacy, dose-responsiveness and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators for induction of remission in active ulcerative colitis. A secondary objective of this systematic review was to compare the efficacy and safety of once daily dosing of oral 5-ASA with conventional (two or three times daily) dosing regimens. Search methods A computer-assisted literature search for relevant studies (inception to July 9, 2015) was performed using MEDLINE, EMBASE and the Cochrane Library. Review articles and conference proceedings were also searched to identify additional studies. Selection criteria Studies were accepted for analysis if they were randomized controlled clinical trials of parallel design, with a minimum treatment duration of four weeks. Studies of oral 5-ASA therapy for treatment of patients with active ulcerative colitis compared with placebo, SASP or other formulations of 5-ASA were considered for inclusion. Studies that compared once daily 5-ASA treatment with conventional dosing of 5-ASA (two or three times daily) and 5-ASA dose ranging studies were also considered for inclusion. Data collection and analysis The outcomes of interest were the failure to induce global/clinical remission, global/clinical improvement, endoscopic remission, endoscopic improvement, adherence, adverse events, withdrawals due to adverse events, and withdrawals or exclusions after entry. Trials were separated into five comparison groups: 5-ASA versus placebo, 5-ASA versus sulfasalazine, once daily dosing versus conventional dosing, 5-ASA versus comparator 5-ASA, and 5-ASA dose-ranging. Placebo-controlled trials were subgrouped by dosage. SASP-controlled trials were subgrouped by 5-ASA/SASP mass ratios. Once daily versus conventional dosing studies were subgrouped by formulation. 5-ASA-controlled trials were subgrouped by common 5-ASA comparators (e.g. Asacol, Claversal, Salofalk and Pentasa). Dose-ranging studies were subgrouped by 5-ASA formulation. We calculated the relative risk (RR) and 95% confidence intervals (95% CI) for each outcome. Data were analyzed on an intention-to-treat basis. Main results Fifty-three studies (8548 patients) were included. The majority of included studies were rated as low risk of bias. 5-ASA was significantly superior to placebo with regard to all measured outcome variables. Seventy-one per cent of 5-ASA patients failed to enter clinical remission compared to 83% of placebo patients (RR 0.86, 95% CI 0.82 to 0.89). A dose-response trend for 5-ASA was also observed. No statistically significant differences in efficacy were found between 5-ASA and SASP. Fifty-four per cent of 5-ASA patients failed to enter remission compared to 58% of SASP patients (RR 0.90, 95% CI 0.77 to 1.04). No statistically significant differences in efficacy or adherence were found between once daily and conventionally dosed 5-ASA. Forty-five per cent of once daily patients failed to enter clinical remission compared to 48% of conventionally dosed patients (RR 0.94, 95% CI 0.83 to 1.07). Eight per cent of patients dosed once daily failed to adhere to their medication regimen compared to 6% of conventionally dosed patients (RR 1.36, 95% CI 0.64 to 2.86). There does not appear to be any difference in efficacy among the various 5-ASA formulations. Fifty per cent of patients in the 5-ASA group failed to enter remission compared to 52% of patients in the 5-ASA comparator group (RR 0.94, 95% CI 0.86 to 1.02). A pooled analysis of 3 studies (n = 1459 patients) studies found no statistically significant difference in clinical improvement between Asacol 4.8 g/day and 2.4 g/day used for the treatment of moderately active ulcerative colitis. Thirty-seven per cent of patients in the 4.8 g/day group failed to improve clinically compared to 41% of patients in the 2.4 g/day group (RR 0.89; 95% CI 0.78 to 1.01). Subgroup analysis indicated that patients with moderate disease may benefit from the higher dose of 4.8 g/day. One study compared (n = 123 patients) Pentasa 4 g/day to 2.25 g/day in patients with moderate disease. Twenty-five per cent of patients in the 4 g/day group failed to improve clinically compared to 57% of patients in the 2.25 g/day group (RR 0.44; 95% CI 0.27 to 0.71). A pooled analysis of two studies comparing MMX mesalamine 4.8 g/day to 2.4 g/day found no statistically significant difference in efficacy (RR 1.03, 95% CI 0.82 to 1.29). There were no statistically significant differences in the incidence of adverse events between 5-ASA and placebo, once daily and conventionally dosed 5-ASA, 5-ASA and comparator 5-ASA formulation and 5-ASA dose ranging (high dose versus low dose) studies. Common adverse events included flatulence, abdominal pain, nausea, diarrhea, headache and worsening ulcerative colitis. SASP was not as well tolerated as 5-ASA. Twenty-nine percent of SASP patients experienced an adverse event compared to 15% of 5-ASA patients (RR 0.48, 95% CI 0.37 to 0.63). Authors' conclusions 5-ASA was superior to placebo and no more effective than SASP. Considering their relative costs, a clinical advantage to using oral 5-ASA in place of SASP appears unlikely. 5-ASA dosed once daily appears to be as efficacious and safe as conventionally dosed 5-ASA. Adherence does not appear to be enhanced by once daily dosing in the clinical trial setting. It is unknown if once daily dosing of 5-ASA improves adherence in a community-based setting. There do not appear to be any differences in efficacy or safety among the various 5-ASA formulations. A daily dosage of 2.4 g appears to be a safe and effective induction therapy for patients with mild to moderately active ulcerative colitis. Patients with moderate disease may benefit from an initial dose of 4.8 g/day.

The long-term benefits of organizational resilience through sustainable business practices

Abstract: Research summary: Prior work on the benefits of business sustainability often applies short-term causal logic and data analysis. In this article, we argue that the social and the environmental practices (SEPs) associated with business sustainability not only contribute to short-term outcomes, but also to organizational resilience, which we define as the firm's ability to sense and correct maladaptive tendencies and cope positively with unexpected situations. Because organizational resilience is a latent, path-dependent construct, we assess it through the long-term outcomes, including improved financial volatility, sales growth, and survival rates. We tested these hypotheses with data from 121 U.S.-based matched-pairs (242 individual firms) over a 15-year period. We also tested, but did not find support for, the relationship between SEPs and short-term financial performance. Managerial summary: Most managers look for short-term financial benefits to justify socially responsible or sustainable practices. In this article, we argue that such practices also help firms become more resilient, which helps them avoid crises and bounce back from shocks. However, it is difficult to measure the avoidance of shocks, so we analyzed long-term outcomes. We show that firms that adopt responsible social and environmental practices, relative to a carefully matched control group, have lower financial volatility, higher sales growth, and higher chances of survival over a 15-year period; yet, we were unable to find any differences in short-term profits. We hope this research provides good reasons for firms to practice sustainability beyond the pursuit of short-term profits. Copyright © 2015 John Wiley & Sons, Ltd.

Canadian stroke best practice recommendations: Stroke rehabilitation practice guidelines, update 2015

Abstract: Stroke rehabilitation is a progressive, dynamic, goal-orientated process aimed at enabling a person with impairment to reach their optimal physical, cognitive, emotional, communicative, social and/or functional activity level. After a stroke, patients often continue to require rehabilitation for persistent deficits related to spasticity, upper and lower extremity dysfunction, shoulder and central pain, mobility/gait, dysphagia, vision, and communication. Each year in Canada 62,000 people experience a stroke. Among stroke survivors, over 6500 individuals access in-patient stroke rehabilitation and stay a median of 30 days (inter-quartile range 19 to 45 days). The 2015 update of the Canadian Stroke Best Practice Recommendations: Stroke Rehabilitation Practice Guidelines is a comprehensive summary of current evidence-based recommendations for all members of multidisciplinary teams working in a range of settings, who provide care to patients following stroke. These recommendations have been developed to address both the organization of stroke rehabilitation within a system of care (i.e., Initial Rehabilitation Assessment; Stroke Rehabilitation Units; Stroke Rehabilitation Teams; Delivery; Outpatient and Community-Based Rehabilitation), and specific interventions and management in stroke recovery and direct clinical care (i.e., Upper Extremity Dysfunction; Lower Extremity Dysfunction; Dysphagia and Malnutrition; Visual-Perceptual Deficits; Central Pain; Communication; Life Roles). In addition, stroke happens at any age, and therefore a new section has been added to the 2015 update to highlight components of stroke rehabilitation for children who have experienced a stroke, either prenatally, as a newborn, or during childhood. All recommendations have been assigned a level of evidence which reflects the strength and quality of current research evidence available to support the recommendation. The updated Rehabilitation Clinical Practice Guidelines feature several additions that reflect new research areas and stronger evidence for already existing recommendations. It is anticipated that these guidelines will provide direction and standardization for patients, families/caregiver(s), and clinicians within Canada and internationally.

Fake News or Truth? Using Satirical Cues to Detect Potentially Misleading News.

Abstract: Satire is an attractive subject in deception detection research: it is a type of deception that intentionally incorporates cues revealing its own deceptiveness. Whereas other types of fabrications aim to instill a false sense of truth in the reader, a successful satirical hoax must eventually be exposed as a jest. This paper provides a conceptual overview of satire and humor, elaborating and illustrating the unique features of satirical news, which mimics the format and style of journalistic reporting. Satirical news stories were carefully matched and examined in contrast with their legitimate news counterparts in 12 contemporary news topics in 4 domains (civics, science, business, and “soft” news). Building on previous work in satire detection, we proposed an SVMbased algorithm, enriched with 5 predictive features (Absurdity, Humor, Grammar, Negative Affect, and Punctuation) and tested their combinations on 360 news articles. Our best predicting feature combination (Absurdity, Grammar and Punctuation) detects satirical news with a 90% precision and 84% recall (F-score=87%). Our work in algorithmically identifying satirical news pieces can aid in minimizing the potential deceptive impact of satire.

Oral 5‐aminosalicylic acid for maintenance of remission in ulcerative colitis

Abstract: Background Oral 5-aminosalicylic (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. Previously, it was found that 5-ASA drugs were more effective than placebo but had a statistically significant therapeutic inferiority relative to SASP. This updated review includes more recent studies and evaluates the effectiveness, dose-responsiveness, and safety of 5-ASA preparations used for maintenance of remission in quiescent ulcerative colitis. Objectives The primary objectives were to assess the efficacy, dose-responsiveness and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators for maintenance of remission in quiescent ulcerative colitis. A secondary objective was to compare the efficacy and safety of once daily dosing of oral 5-ASA with conventional (two or three times daily) dosing regimens. Search methods A literature search for relevant studies (inception to 9 July 2015) was performed using MEDLINE, EMBASE and the Cochrane Library. Review articles and conference proceedings were also searched to identify additional studies. Selection criteria Studies were accepted for analysis if they were randomized controlled trials with a minimum treatment duration of six months. Studies of oral 5-ASA therapy for treatment of patients with quiescent ulcerative colitis compared with placebo, SASP or other 5-ASA formulations were considered for inclusion. Studies that compared once daily 5-ASA treatment with conventional dosing of 5-ASA and 5-ASA dose ranging studies were also considered for inclusion. Data collection and analysis The primary outcome was the failure to maintain clinical or endoscopic remission. Secondary outcomes included adherence, adverse events, withdrawals due to adverse events, and withdrawals or exclusions after entry. Trials were separated into five comparison groups: 5-ASA versus placebo, 5-ASA versus sulfasalazine, once daily dosing versus conventional dosing, 5-ASA versus comparator 5-ASA formulation, and 5-ASA dose-ranging. Placebo-controlled trials were subgrouped by dosage. Once daily versus conventional dosing studies were subgrouped by formulation. 5-ASA-controlled trials were subgrouped by common 5-ASA comparators (e.g. Asacol and Salofalk). Dose-ranging studies were subgrouped by 5-ASA formulation. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for each outcome. Data were analyzed on an intention-to-treat basis. Main results Forty-one studies (8928 patients) were included. The majority of included studies were rated as low risk of bias. Ten studies were rated at high risk of bias. Seven of these studies were single-blind and three studies were open-label. However, two open-label studies and four of the single-blind studies utilized investigator performed endoscopy as an endpoint, which may protect against bias. 5-ASA was significantly superior to placebo for maintenance of clinical or endoscopic remission. Forty-one per cent of 5-ASA patients relapsed compared to 58% of placebo patients (7 studies, 1298 patients; RR 0.69, 95% CI 0.62 to 0.77). There was a trend towards greater efficacy with higher doses of 5-ASA with a statistically significant benefit for the 1 to 1.9 g/day (RR 0.65; 95% CI 0.56 to 0.76) and the > 2 g/day subgroups (RR 0.73, 95% CI 0.60 to 0.89). SASP was significantly superior to 5-ASA for maintenance of remission. Forty-eight per cent of 5-ASA patients relapsed compared to 43% of SASP patients (12 studies, 1655 patients; RR 1.14, 95% CI 1.03 to 1.27). A GRADE analysis indicated that the overall quality of the evidence for the primary outcome for the placebo and SASP-controlled studies was high. No statistically significant differences in efficacy or adherence were found between once daily and conventionally dosed 5-ASA. Twenty-nine per cent of once daily patients relapsed over 12 months compared to 31% of conventionally dosed patients (8 studies, 3127 patients; RR 0.91, 95% CI 0.82 to 1.01). Eleven per cent of patients in the once daily group failed to adhere to their medication regimen compared to 9% of patients in the conventional dosing group (6 studies, 1462 patients; RR 1.22, 95% CI 0.91 to 1.64). There does not appear to be any difference in efficacy among the various 5-ASA formulations. Forty-four per cent of patients in the 5-ASA group relapsed compared to 41% of patients in the 5-ASA comparator group (6 studies, 707 patients; RR 1.08, 95% CI 0.91 to 1.28). A pooled analysis of two studies showed no statistically significant difference in efficacy between Balsalazide 6 g and 3 g/day. Twenty-three per cent of patients in the 6 g/day group relapsed compared to 33% of patients in the 3 g/day group (216 patients; RR 0.76; 95% CI 0.45 to 2.79). One study found Balsalazide 4 g to be superior to 2 g/day. Thirty-seven per cent of patients in the 4 g/day Balsalazide group relapsed compared to 55% of patients in the 2 g/day group (133 patients; RR 0.66; 95% CI 0.45 to 0.97). One study found a statistically significant difference between Salofalk granules 3 g and 1.5 g/day. Twenty-five per cent of patients in the Salofalk 3 g/day group relapsed compared to 39% of patients in the 1.5 g/day group (429 patients; RR 0.65; 95% CI 0.49 to 0.86). Common adverse events included flatulence, abdominal pain, nausea, diarrhea, headache, dyspepsia, and nasopharyngitis. There were no statistically significant differences in the incidence of adverse events between 5-ASA and placebo, 5-ASA and SASP, once daily and conventionally dosed 5-ASA, 5-ASA and comparator 5-ASA formulations and 5-ASA dose ranging studies. The trials that compared 5-ASA and SASP may have been biased in favour of SASP because most trials enrolled patients known to be tolerant to SASP which may have minimized SASP-related adverse events. Authors' conclusions 5-ASA was superior to placebo for maintenance therapy in ulcerative colitis. However, 5-ASA had a statistically significant therapeutic inferiority relative to SASP. Oral 5-ASA administered once daily is as effective and safe as conventional dosing for maintenance of remission in quiescent ulcerative colitis. There does not appear to be any difference in efficacy or safety between the various formulations of 5-ASA. Patients with extensive ulcerative colitis or with frequent relapses may benefit from a higher dose of maintenance therapy. High dose therapy appears to be as safe as low dose and is not associated with a higher incidence of adverse events.

Construction of CuS Nanoflakes Vertically Aligned on Magnetically Decorated Graphene and Their Enhanced Microwave Absorption Properties

Abstract: Hybrid nanocomposites with enhanced microwave absorption properties have been designed by growing CuS nanoflakes on magnetically decorated graphene, and the effect of special nanostructures on microwave absorption properties has been investigated. The structure of the nanocomposites was characterized by Fourier transform infrared spectra (FTIR), X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscope (FESEM), transmission electron microscope (TEM), N2 adsorption–desorption, and vibrating sample magnetometer (VSM). The influence of cetyltrimethylammonium bromide (CTAB) on the morphology of CuS nanoflakes was also investigated. A possible formation process of the nanocomposites and the mechanism of microwave absorption were explained in detail. As an absorber, the nanocomposites with a filler loading of 20 wt % exhibited enhanced microwave absorption properties due to the special nanostructures, extra void space, and synergistic effect...

Azathioprine and 6‐mercaptopurine for maintenance of remission in ulcerative colitis

Abstract: Background Maintenance of remission is a major issue in inflammatory bowel disease. In ulcerative colitis, the evidence for the effectiveness of azathioprine and 6-mercaptopurine for the maintenance of remission is still controversial. Objectives To assess the effectiveness and safety of azathioprine and 6-mercaptopurine for maintaining remission of ulcerative colitis. Search methods The MEDLINE, EMBASE and Cochrane Library databases were searched from inception to 30 July 2015. Both full randomized controlled trials and associated abstracts were included. Selection criteria Randomized controlled trials of at least 12 months duration that compared azathioprine or 6-mercaptopurine with placebo or standard maintenance therapy (e.g. mesalazine) were included. Data collection and analysis Two authors independently extracted data using standard forms. Disagreements were solved by consensus including a third author. Study quality was assessed using the Cochrane risk of bias tool. The primary outcome was failure to maintain clinical or endoscopic remission. Secondary outcomes included adverse events and withdrawal due to adverse events. Analyses were performed separately by type of control (placebo, or active comparator). Pooled risk ratios were calculated based on the fixed-effect model unless heterogeneity was shown. The GRADE approach was used to assess the overall quality of evidence for pooled outcomes. Main results Seven studies including 302 patients with ulcerative colitis were included in the review. The risk of bias was high in three of the studies due to lack of blinding. Azathioprine was shown to be significantly superior to placebo for maintenance of remission. Fourty-four per cent (51/115) of azathioprine patients failed to maintain remission compared to 65% (76/117) of placebo patients (4 studies, 232 patients; RR 0.68, 95% CI 0.54 to 0.86). A GRADE analysis rated the overall quality of the evidence for this outcome as low due to risk of bias and imprecision (sparse data). Two trials that compared 6-mercaptopurine to mesalazine, or azathioprine to sulfasalazine showed significant heterogeneity and thus were not pooled. Fifty per cent (7/14) of 6-mercaptopurine patients failed to maintain remission compared to 100% (8/8) of mesalazine patients (1 study, 22 patients; RR 0.53, 95% CI 0.31 to 0.90). Fifty-eight per cent (7/12) of azathioprine patients failed to maintain remission compared to 38% (5/13) of sulfasalazine patients (1 study, 25 patients; RR 1.52, 95% CI 0.66 to 3.50). One small study found that 6-mercaptopurine was superior to methotrexate for maintenance of remission. In the study, 50% (7/14) of 6-mercaptopurine patients and 92% (11/12) of methotrexate patients failed to maintain remission (1 study, 26 patients; RR 0.55, 95% CI 0.31 to 0.95). One very small study compared azathioprine with cyclosporin and found that there was no significant difference between patients failing remission on azathioprine (50%, 4/8) or cyclosporin (62.5%, 5/8) (1 study, 16 patients, RR 0.80 95% CI 0.33 to 1.92). When placebo-controlled studies were pooled with aminosalicylate-comparator studies to assess adverse events, there was no statistically significant difference between azathioprine and control in the incidence of adverse events. Nine per cent (11/127) of azathioprine patients experienced at least one adverse event compared to 2% (3/130) of placebo patients (5 studies, 257 patients; RR 2.82, 95% CI 0.99 to 8.01). Patients receiving azathioprine were at significantly increased risk of withdrawing due to adverse events. Eight per cent (8/101) of azathioprine patients withdrew due to adverse events compared to 0% (0/98) of control patients (5 studies, 199 patients; RR 5.43, 95% CI 1.02 to 28.75). Adverse events related to study medication included acute pancreatitis (3 cases, plus 1 case on cyclosporin) and significant bone marrow suppression (5 cases). Deaths, opportunistic infection or neoplasia were not reported. Authors' conclusions Azathioprine therapy appears to be more effective than placebo for maintenance of remission in ulcerative colitis. Azathioprine or 6-mercaptopurine may be effective as maintenance therapy for patients who have failed or cannot tolerate mesalazine or sulfasalazine and for patients who require repeated courses of steroids. More research is needed to evaluate superiority over standard maintenance therapy, especially in the light of a potential for adverse events from azathioprine. This review updates the existing review of azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis which was published in the Cochrane Library (September 2012).