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Showing papers by "Queen's University published in 2013"


Journal ArticleDOI
09 Jan 2013-BMJ
TL;DR: The SPIRIT 2013 Explanation and Elaboration paper provides important information to promote full understanding of the checklist recommendations and strongly recommends that this explanatory paper be used in conjunction with the SPIRit Statement.
Abstract: High quality protocols facilitate proper conduct, reporting, and external review of clinical trials. However, the completeness of trial protocols is often inadequate. To help improve the content and quality of protocols, an international group of stakeholders developed the SPIRIT 2013 Statement (Standard Protocol Items: Recommendations for Interventional Trials). The SPIRIT Statement provides guidance in the form of a checklist of recommended items to include in a clinical trial protocol. This SPIRIT 2013 Explanation and Elaboration paper provides important information to promote full understanding of the checklist recommendations. For each checklist item, we provide a rationale and detailed description; a model example from an actual protocol; and relevant references supporting its importance. We strongly recommend that this explanatory paper be used in conjunction with the SPIRIT Statement. A website of resources is also available (www.spirit-statement.org). The SPIRIT 2013 Explanation and Elaboration paper, together with the Statement, should help with the drafting of trial protocols. Complete documentation of key trial elements can facilitate transparency and protocol review for the benefit of all stakeholders.

3,108 citations


Journal ArticleDOI
TL;DR: The Canadian Network for Mood and Anxiety Treatments published guidelines for the management of bipolar disorder in 2005, with updates in 2007 and 2009, and this third update, in conjunction with the International Society for Bipolar Disorders, reviews new evidence and is designed to be used in conjunctionWith the previous publications.
Abstract: The Canadian Network for Mood and Anxiety Treatments published guidelines for the management of bipolar disorder in 2005, with updates in 2007 and 2009. This third update, in conjunction with the International Society for Bipolar Disorders, reviews new evidence and is designed to be used in conjunction with the previous publications.The recommendations for the management of acute mania remain largely unchanged. Lithium, valproate, and several atypical antipsychotic agents continue to be first-line treatments for acute mania. Monotherapy with asenapine, paliperidone extended release (ER), and divalproex ER, as well as adjunctive asenapine, have been added as first-line options.For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, as well as olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. Lurasidone monotherapy and the combination of lurasidone or lamotrigine plus lithium or divalproex have been added as a second-line options. Ziprasidone alone or as adjunctive therapy, and adjunctive levetiracetam have been added as not-recommended options for the treatment of bipolar depression. Lithium, lamotrigine, valproate, olanzapine, quetiapine, aripiprazole, risperidone long-acting injection, and adjunctive ziprasidone continue to be first-line options for maintenance treatment of bipolar disorder. Asenapine alone or as adjunctive therapy have been added as third-line options.

1,369 citations


Journal ArticleDOI
TL;DR: 37 guideline items address 14 subjects, including 15 recommendations (evidence grade A/B), to use testing for EGFR mutations and ALK fusions to guide patient selection for therapy with an epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitor in all patients with advanced-stage adenocarcinoma.

1,230 citations


Journal ArticleDOI
Masroor Hussain1, Dongmei Chen1, Angela Cheng1, Hui Wei, David Stanley 
TL;DR: This paper begins with a discussion of the traditionally pixel-based and (mostly) statistics-oriented change detection techniques which focus mainly on the spectral values and mostly ignore the spatial context, followed by a review of object-basedchange detection techniques.
Abstract: The appetite for up-to-date information about earth’s surface is ever increasing, as such information provides a base for a large number of applications, including local, regional and global resources monitoring, land-cover and land-use change monitoring, and environmental studies. The data from remote sensing satellites provide opportunities to acquire information about land at varying resolutions and has been widely used for change detection studies. A large number of change detection methodologies and techniques, utilizing remotely sensed data, have been developed, and newer techniques are still emerging. This paper begins with a discussion of the traditionally pixel-based and (mostly) statistics-oriented change detection techniques which focus mainly on the spectral values and mostly ignore the spatial context. This is succeeded by a review of object-based change detection techniques. Finally there is a brief discussion of spatial data mining techniques in image processing and change detection from remote sensing data. The merits and issues of different techniques are compared. The importance of the exponential increase in the image data volume and multiple sensors and associated challenges on the development of change detection techniques are highlighted. With the wide use of very-high-resolution (VHR) remotely sensed images, object-based methods and data mining techniques may have more potential in change detection.

1,159 citations


Journal ArticleDOI
Predrag Radivojac1, Wyatt T. Clark1, Tal Ronnen Oron2, Alexandra M. Schnoes3, Tobias Wittkop2, Artem Sokolov4, Artem Sokolov5, Kiley Graim4, Christopher S. Funk6, Karin Verspoor6, Asa Ben-Hur4, Gaurav Pandey7, Gaurav Pandey8, Jeffrey M. Yunes7, Ameet Talwalkar7, Susanna Repo9, Susanna Repo7, Michael L Souza7, Damiano Piovesan10, Rita Casadio10, Zheng Wang11, Jianlin Cheng11, Hai Fang, Julian Gough12, Patrik Koskinen13, Petri Törönen13, Jussi Nokso-Koivisto13, Liisa Holm13, Domenico Cozzetto14, Daniel W. A. Buchan14, Kevin Bryson14, David T. Jones14, Bhakti Limaye15, Harshal Inamdar15, Avik Datta15, Sunitha K Manjari15, Rajendra Joshi15, Meghana Chitale16, Daisuke Kihara16, Andreas Martin Lisewski17, Serkan Erdin17, Eric Venner17, Olivier Lichtarge17, Robert Rentzsch14, Haixuan Yang18, Alfonso E. Romero18, Prajwal Bhat18, Alberto Paccanaro18, Tobias Hamp19, Rebecca Kaßner19, Stefan Seemayer19, Esmeralda Vicedo19, Christian Schaefer19, Dominik Achten19, Florian Auer19, Ariane Boehm19, Tatjana Braun19, Maximilian Hecht19, Mark Heron19, Peter Hönigschmid19, Thomas A. Hopf19, Stefanie Kaufmann19, Michael Kiening19, Denis Krompass19, Cedric Landerer19, Yannick Mahlich19, Manfred Roos19, Jari Björne20, Tapio Salakoski20, Andrew Wong21, Hagit Shatkay21, Hagit Shatkay22, Fanny Gatzmann23, Ingolf Sommer23, Mark N. Wass24, Michael J.E. Sternberg24, Nives Škunca, Fran Supek, Matko Bošnjak, Panče Panov, Sašo Džeroski, Tomislav Šmuc, Yiannis A. I. Kourmpetis25, Yiannis A. I. Kourmpetis26, Aalt D. J. van Dijk26, Cajo J. F. ter Braak26, Yuanpeng Zhou27, Qingtian Gong27, Xinran Dong27, Weidong Tian27, Marco Falda28, Paolo Fontana, Enrico Lavezzo28, Barbara Di Camillo28, Stefano Toppo28, Liang Lan29, Nemanja Djuric29, Yuhong Guo29, Slobodan Vucetic29, Amos Marc Bairoch30, Amos Marc Bairoch31, Michal Linial32, Patricia C. Babbitt3, Steven E. Brenner7, Christine A. Orengo14, Burkhard Rost19, Sean D. Mooney2, Iddo Friedberg33 
TL;DR: Today's best protein function prediction algorithms substantially outperform widely used first-generation methods, with large gains on all types of targets, and there is considerable need for improvement of currently available tools.
Abstract: Automated annotation of protein function is challenging. As the number of sequenced genomes rapidly grows, the overwhelming majority of protein products can only be annotated computationally. If computational predictions are to be relied upon, it is crucial that the accuracy of these methods be high. Here we report the results from the first large-scale community-based critical assessment of protein function annotation (CAFA) experiment. Fifty-four methods representing the state of the art for protein function prediction were evaluated on a target set of 866 proteins from 11 organisms. Two findings stand out: (i) today's best protein function prediction algorithms substantially outperform widely used first-generation methods, with large gains on all types of targets; and (ii) although the top methods perform well enough to guide experiments, there is considerable need for improvement of currently available tools.

859 citations


Journal ArticleDOI
TL;DR: Alterations in mitochondrial dynamics underlie various human diseases, including cancer and neurologic and cardiovascular diseases, and defining the alterations may identify potential therapeutic targets.
Abstract: Mitochondria fuse and divide in response to cell demands and environment. Alterations in mitochondrial dynamics underlie various human diseases, including cancer and neurologic and cardiovascular diseases. Defining the alterations may identify potential therapeutic targets.

814 citations


Journal ArticleDOI
01 Jan 2013-Gut
TL;DR: A critical review of current hypotheses regarding the pathogenetic involvement of microbiota in FGID is provided and the results of microbiota-directed interventions are evaluated and clinical guidance on modulation of gut microbiota in IBS is provided.
Abstract: It is increasingly perceived that gut host–microbial interactions are important elements in the pathogenesis of functional gastrointestinal disorders (FGID) The most convincing evidence to date is the finding that functional dyspepsia and irritable bowel syndrome (IBS) may develop in predisposed individuals following a bout of infectious gastroenteritis There has been a great deal of interest in the potential clinical and therapeutic implications of small intestinal bacterial overgrowth in IBS However, this theory has generated much debate because the evidence is largely based on breath tests which have not been validated The introduction of culture-independent molecular techniques provides a major advancement in our understanding of the microbial community in FGID Results from 16S rRNA-based microbiota profiling approaches demonstrate both quantitative and qualitative changes of mucosal and faecal gut microbiota, particularly in IBS Investigators are also starting to measure host–microbial interactions in IBS The current working hypothesis is that abnormal microbiota activate mucosal innate immune responses which increase epithelial permeability, activate nociceptive sensory pathways and dysregulate the enteric nervous system While we await important insights in this field, the microbiota is already a therapeutic target Existing controlled trials of dietary manipulation, prebiotics, probiotics, synbiotics and non-absorbable antibiotics are promising, although most are limited by suboptimal design and small sample size In this article, the authors provide a critical review of current hypotheses regarding the pathogenetic involvement of microbiota in FGID and evaluate the results of microbiota-directed interventions The authors also provide clinical guidance on modulation of gut microbiota in IBS

774 citations


Journal ArticleDOI
TL;DR: Early provision of glutamine or antioxidants did not improve clinical outcomes, and glutamine was associated with an increase in mortality among critically ill patients with multiorgan failure.
Abstract: Methods In this blinded 2-by-2 factorial trial, we randomly assigned 1223 critically ill adults in 40 intensive care units (ICUs) in Canada, the United States, and Europe who had multiorgan failure and were receiving mechanical ventilation to receive supplements of glutamine, antioxidants, both, or placebo. Supplements were started within 24 hours after admission to the ICU and were provided both intravenously and enterally. The primary outcome was 28-day mortality. Because of the interim-analysis plan, a P value of less than 0.044 at the final analysis was considered to indicate statistical significance. Results There was a trend toward increased mortality at 28 days among patients who received glutamine as compared with those who did not receive glutamine (32.4% vs. 27.2%; adjusted odds ratio, 1.28; 95% confidence interval [CI], 1.00 to 1.64; P = 0.05). In-hospital mortality and mortality at 6 months were significantly higher among those who received glutamine than among those who did not. Glutamine had no effect on rates of organ failure or infectious complications. Antioxidants had no effect on 28-day mortality (30.8%, vs. 28.8% with no antioxidants; adjusted odds ratio, 1.09; 95% CI, 0.86 to 1.40; P = 0.48) or any other secondary end point. There were no differences among the groups with respect to serious adverse events (P = 0.83). Conclusions Early provision of glutamine or antioxidants did not improve clinical outcomes, and glutamine was associated with an increase in mortality among critically ill patients with multiorgan failure. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00133978.)

711 citations


Journal ArticleDOI
TL;DR: This proof-of-principle study demonstrates that a stool substitute mixture comprising a multi-species community of bacteria is capable of curing antibiotic-resistant C. difficile colitis.
Abstract: Fecal bacteriotherapy (‘stool transplant’) can be effective in treating recurrent Clostridium difficile infection, but concerns of donor infection transmission and patient acceptance limit its use. Here we describe the use of a stool substitute preparation, made from purified intestinal bacterial cultures derived from a single healthy donor, to treat recurrent C. difficile infection that had failed repeated standard antibiotics. Thirty-three isolates were recovered from a healthy donor stool sample. Two patients who had failed at least three courses of metronidazole or vancomycin underwent colonoscopy and the mixture was infused throughout the right and mid colon. Pre-treatment and post-treatment stool samples were analyzed by 16 S rRNA gene sequencing using the Ion Torrent platform. Both patients were infected with the hyper virulent C. difficile strain, ribotype 078. Following stool substitute treatment, each patient reverted to their normal bowel pattern within 2 to 3 days and remained symptom-free at 6 months. The analysis demonstrated that rRNA sequences found in the stool substitute were rare in the pre-treatment stool samples but constituted over 25% of the sequences up to 6 months after treatment. This proof-of-principle study demonstrates that a stool substitute mixture comprising a multi-species community of bacteria is capable of curing antibiotic-resistant C. difficile colitis. This benefit correlates with major changes in stool microbial profile and these changes reflect isolates from the synthetic mixture. Clinical trial registration number: CinicalTrials.gov NCT01372943

677 citations


Journal ArticleDOI
TL;DR: Evidence is provided that cognitive, behavioral, and mindfulness interventions are effective in reducing stress in university students and universities are encouraged to make such programs widely available to students.

662 citations


Journal ArticleDOI
TL;DR: In this article, a simple linear regression between log10 transformed mercury (Hg) concentration and stable nitrogen isotope values (δ15N), hereafter called trophic magnification slope (TMS), was used to represent the overall degree of Hg biomagnification.
Abstract: The slope of the simple linear regression between log10 transformed mercury (Hg) concentration and stable nitrogen isotope values (δ15N), hereafter called trophic magnification slope (TMS), from several trophic levels in a food web can represent the overall degree of Hg biomagnification. We compiled data from 69 studies that determined total Hg (THg) or methyl Hg (MeHg) TMS values in 205 aquatic food webs worldwide. Hg TMS values were compared against physicochemical and biological factors hypothesized to affect Hg biomagnification in aquatic systems. Food webs ranged across 1.7 ± 0.7 (mean ± SD) and 1.8 ± 0.8 trophic levels (calculated using δ15N from baseline to top predator) for THg and MeHg, respectively. The average trophic level (based on δ15N) of the upper-trophic-level organisms in the food web was 3.7 ± 0.8 and 3.8 ± 0.8 for THg and MeHg food webs, respectively. For MeHg, the mean TMS value was 0.24 ± 0.08 but varied from 0.08 to 0.53 and was, on average, 1.5 times higher than that for THg with a...

Journal ArticleDOI
TL;DR: The development of these minimum measurement standards is intended to promote the appropriate use of PRO measures to inform PCOR and CER, which in turn can improve the effectiveness and efficiency of healthcare delivery.
Abstract: Purpose An essential aspect of patient-centered outcomes research (PCOR) and comparative effectiveness research (CER) is the integration of patient perspectives and experiences with clinical data to evaluate interventions. Thus, PCOR and CER require capturing patient-reported outcome (PRO) data appropriately to inform research, healthcare delivery, and policy. This initiative’s goal was to identify minimum standards for the design and selection of a PRO measure for use in PCOR and CER.

Journal ArticleDOI
TL;DR: Few reports have aimed to describe the mediational effect of cognitive deficits on functional outcomes in major depressive disorder, and relatively few interventions are demonstrated to mitigate cognitive deficits in MDD.
Abstract: Background Few reports have aimed to describe the mediational effect of cognitive deficits on functional outcomes in major depressive disorder (MDD), and relatively few interventions are demonstrated to mitigate cognitive deficits in MDD. Methods Studies enrolling subjects between the ages of 18–65 were selected for review. Bibliographies from identified articles were reviewed to identify additional original reports aligned with our objectives. Results Cognitive deficits in MDD are consistent, replicable, nonspecific, and clinically significant. The aggregated estimated effect size of cognitive deficits in MDD is small to medium. Pronounced deficits in executive function (≥1 SD below the normative mean) are evident in ∼20–30% of individuals with MDD). Other replicated abnormalities are in the domains of working memory, attention, and psychomotor processing speed. Mediational studies indicate that cognitive deficits may account for the largest percentage of variance with respect to the link between psychosocial dysfunction (notably workforce performance) and MDD. No conventional antidepressant has been sufficiently studied and/or demonstrated robust procognitive effects in MDD. Conclusions Cognitive deficits in MDD are a principal mediator of psychosocial impairment, notably workforce performance. The hazards posed by cognitive deficits in MDD underscore the need to identify a consensus-based neurocognitive battery for research and clinical purposes. Interventions (pharmacological, behavioral, neuromodulatory) that engage multiple physiological systems implicated in cognitive deficits hold promise to reduce, reverse, and prevent cognitive deficits.

Journal ArticleDOI
TL;DR: In this article, a model that links environmentally-specific transformational leadership and leaders' workplace proenvironmental behaviors to employees' pro-environmental passion and behaviors was developed and tested.
Abstract: Summary Climate change is a serious global issue that poses many risks to environmental and human systems. Although human activity is cited as the main cause of climate change and organizations significantly contribute to climate change, research that investigates workplace pro-environmental behaviors remains scarce. We develop and test a model that links environmentally-specific transformational leadership and leaders’ workplace pro-environmental behaviors to employees’ pro-environmental passion and behaviors. Structural equation modeling on data from 139subordinate–leaderdyads(Mages=37.42and40.17years,respectively)showedthatleaders’environmental descriptive norms predicted their environmentally-specific transformational leadership and their workplace pro-environmental behaviors, both of which predicted employees’ harmonious environmental passion. In turn, employees’ own harmonious environmental passion and their leaders’ workplace pro-environmental behaviors predicted their workplace pro-environmental behaviors. These findings show that leaders’environmental descriptive norms and the leadership and pro-environmental behaviors they enact play an important role in the greening of organizations. Conceptual and practical implications are discussed. Copyright © 2012 John Wiley & Sons, Ltd.

Journal ArticleDOI
03 Jan 2013-Nature
TL;DR: Radial velocity measurements reveal that the satellites in this structure have the same sense of rotation about their host, and shows conclusively that substantial numbers of dwarf satellite galaxies share the same dynamical orbital properties and direction of angular momentum.
Abstract: Dwarf satellite galaxies are thought to be the remnants of the population of primordial structures that coalesced to form giant galaxies like the Milky Way. It has previously been suspected that dwarf galaxies may not be isotropically distributed around our Galaxy, because several are correlated with streams of H I emission, and may form coplanar groups. These suspicions are supported by recent analyses. It has been claimed that the apparently planar distribution of satellites is not predicted within standard cosmology, and cannot simply represent a memory of past coherent accretion. However, other studies dispute this conclusion. Here we report the existence of a planar subgroup of satellites in the Andromeda galaxy (M 31), comprising about half of the population. The structure is at least 400 kiloparsecs in diameter, but also extremely thin, with a perpendicular scatter of less than 14.1 kiloparsecs. Radial velocity measurements reveal that the satellites in this structure have the same sense of rotation about their host. This shows conclusively that substantial numbers of dwarf satellite galaxies share the same dynamical orbital properties and direction of angular momentum. Intriguingly, the plane we identify is approximately aligned with the pole of the Milky Way's disk and with the vector between the Milky Way and Andromeda.

Journal ArticleDOI
TL;DR: The findings indicate that “Just-In-Time Quality Assurance” may provide an effort-reducing way to focus on the most risky changes and thus reduce the costs of developing high-quality software.
Abstract: Defect prediction models are a well-known technique for identifying defect-prone files or packages such that practitioners can allocate their quality assurance efforts (e.g., testing and code reviews). However, once the critical files or packages have been identified, developers still need to spend considerable time drilling down to the functions or even code snippets that should be reviewed or tested. This makes the approach too time consuming and impractical for large software systems. Instead, we consider defect prediction models that focus on identifying defect-prone (“risky”) software changes instead of files or packages. We refer to this type of quality assurance activity as “Just-In-Time Quality Assurance,” because developers can review and test these risky changes while they are still fresh in their minds (i.e., at check-in time). To build a change risk model, we use a wide range of factors based on the characteristics of a software change, such as the number of added lines, and developer experience. A large-scale study of six open source and five commercial projects from multiple domains shows that our models can predict whether or not a change will lead to a defect with an average accuracy of 68 percent and an average recall of 64 percent. Furthermore, when considering the effort needed to review changes, we find that using only 20 percent of the effort it would take to inspect all changes, we can identify 35 percent of all defect-inducing changes. Our findings indicate that “Just-In-Time Quality Assurance” may provide an effort-reducing way to focus on the most risky changes and thus reduce the costs of developing high-quality software.

Journal ArticleDOI
TL;DR: There is sufficient evidence that exercise training is effective for improving both aerobic capacity and muscular strength among those with mild to moderate disability from MS and exercise may improve mobility, fatigue, and health-related quality of life.


Journal ArticleDOI
TL;DR: Dissection of the role of pulmonary inflammation in the initiation and promotion of PH has revealed a complex yet fascinating interplay with pulmonary vascular remodeling, promising to lead to novel therapeutics and diagnostics.

Journal ArticleDOI
TL;DR: In this paper, a blind analysis of 140.2 kg data taken between July 2007 and September 2008 revealed three WIMP-candidate events with a surface event background estimate of 0.41 and 0.08 events at the 90% confidence level, respectively.
Abstract: We report results of a search for weakly interacting massive particles (WIMPS) with the silicon detectors of the CDMS II experiment. This blind analysis of 140.2 kg day of data taken between July 2007 and September 2008 revealed three WIMP-candidate events with a surface-event background estimate of 0.41^(+0.20)_(−0.08)(stat)^(+0.28)_(−0.24)(syst). Other known backgrounds from neutrons and ^(206)Pb are limited to <0.13 and <0.08 events at the 90% confidence level, respectively. The exposure of this analysis is equivalent to 23.4 kg day for a recoil energy range of 7–100 keV for a WIMP of mass 10 GeV/c^2. The probability that the known backgrounds would produce three or more events in the signal region is 5.4%. A profile likelihood ratio test of the three events that includes the measured recoil energies gives a 0.19% probability for the known-background-only hypothesis when tested against the alternative WIMP+background hypothesis. The highest likelihood occurs for a WIMP mass of 8.6 GeV/c2 and WIMP-nucleon cross section of 1.9×10^(−41) cm^2.

Journal ArticleDOI
TL;DR: The results substantiate the possibility of OO from autism spectrum disorders and demonstrate an overall level of functioning within normal limits for this group.
Abstract: Background: Although autism spectrum disorders (ASDs) are generally considered lifelong disabilities, literature suggests that a minority of individuals with an ASD will lose the diagnosis. However, the existence of this phenomenon, as well as its frequency and interpretation, is still controversial: were they misdiagnosed initially, is this a rare event, did they lose the full diagnosis, but still suffer significant social and communication impairments or did they lose all symptoms of ASD and function socially within the normal range? Methods: The present study documents a group of these optimal outcome individuals (OO group, n = 34) by comparing their functioning on standardized measures to age, sex, and nonverbal IQ matched individuals with high-functioning autism (HFA group, n = 44) or typical development (TD group, n = 34). For this study, ‘optimal outcome’ requires losing all symptoms of ASD in addition to the diagnosis, and functioning within the nonautistic range of social interaction and communication. Domains explored include language, face recognition, socialization, communication, and autism symptoms. Results: Optimal outcome and TD groups’ mean scores did not differ on socialization, communication, face recognition, or most language subscales, although three OO individuals showed below-average scores on face recognition. Early in their development, the OO group displayed milder symptoms than the HFA group in the social domain, but had equally severe difficulties with communication and repetitive behaviors. Conclusions: Although possible deficits in more subtle aspects of social interaction or cognition are not ruled out, the results substantiate the possibility of OO from autism spectrum disorders and demonstrate an overall level of functioning within normal limits for this group. Keywords: Autism, outcome, optimal.

Journal ArticleDOI
TL;DR: It is demonstrated that high maternal cortisol in pregnancy and/or inhibition of HSD2 are associated with programmed outcomes in childhood including higher blood pressure, behavioural disorders as well as altered brain structure, and this may be altered in obesity.

Journal ArticleDOI
TL;DR: In this article, the authors explored the relationship between energy balance closure and landscape heterogeneity using MODIS products and GLOBEstat elevation data and found that landscape-level heterogeneity in vegetation and topography cannot be ignored as a contributor to incomplete energy balance closures at the surface-atmosphere exchange measurements.

Journal ArticleDOI
TL;DR: In this article, the authors argue that women-owned businesses are frequently described as underperforming in that the majority remain small and marginal and that such performance profiles reflect the constrained performance of most small firms.
Abstract: Purpose – Women‐owned businesses are frequently described as under‐performing in that the majority remain small and marginal. The authors dispute this description; within this paper, it is argued that such performance profiles reflect the constrained performance of most small firms. The assertion that women owned firms under‐perform reflects a gendered bias within the entrepreneurial discourse where femininity and deficit are deemed coterminous. In addition, women‐owned firms are expected to under‐perform given expectations of female weakness in the context of male normativity and superiority. Accordingly, the aim of this paper is to critically evaluate the association between gender and business performance suggesting that this critique has implications for the broader development of our understanding of entrepreneuring behaviours.Design/methodology/approach – This is a conceptual research note which explores the notion of performance and under‐performance in the context of gender.Findings – It is argued...

Journal ArticleDOI
B. Aharmim1, S. N. Ahmed2, A. E. Anthony3, N. Barros, E. W. Beier4, Alain Bellerive5, B. Beltran6, M. Bergevin7, M. Bergevin8, S. D. Biller9, K. Boudjemline2, K. Boudjemline5, Mark Guy Boulay2, Bei Cai2, Yuen-Dat Chan7, D. Chauhan1, M. L. Chen2, B. T. Cleveland9, G. A. Cox10, X. Dai9, X. Dai2, X. Dai5, H. Deng4, J. A. Detwiler7, M. DiMarco2, P. J. Doe10, G. Doucas9, P.-L. Drouin5, F. A. Duncan2, M. Dunford4, E. D. Earle2, Steven Elliott11, Steven Elliott10, Hal Evans2, G. T. Ewan2, J. Farine5, J. Farine1, H. Fergani9, F. Fleurot1, R. J. Ford2, Joseph A. Formaggio12, Joseph A. Formaggio10, N. Gagnon, J. Tm. Goon13, K. Graham5, K. Graham2, E. Guillian2, S. Habib6, R. L. Hahn14, A. L. Hallin6, E. D. Hallman1, P. J. Harvey2, Ryuta Hazama10, W. J. Heintzelman4, J. Heise11, J. Heise2, J. Heise15, R. L. Helmer16, A. Hime11, C. Howard, M. Huang, P. Jagam, B. Jamieson, N. A. Jelley, M. Jerkins, K. J. Keeter, J. R. Klein, L. L. Kormos, M. Kos, C. Kraus, C. B. Krauss, A. Krüger, T. Kutter, Christopher C. M. Kyba, R. Lange, J. Law, I. T. Lawson, K. T. Lesko, J. R. Leslie, J. C. Loach, R. MacLellan, S. Majerus, H. B. Mak, J. Maneira, R. D. Martin, N. McCauley, A. B. McDonald, S. McGee, M. L. Miller, Benjamin Monreal, Jocelyn Monroe, B. G. Nickel, A. J. Noble, H. M. O'Keeffe, N. S. Oblath, R. W. Ollerhead, G. D. Orebi Gann, S. M. Oser, R. A. Ott, S. J. M. Peeters, A. W. P. Poon, G. Prior, S. D. Reitzner, Keith Rielage, B. C. Robertson, R. G. H. Robertson, Rachel Rosten, M. H. Schwendener, J. A. Secrest, S. Seibert, Olivier Simard, J. J. Simpson, P. Skensved, T. Sonley, L. C. Stonehill, G. Tešić, N. Tolich, T. Tsui, R. Van Berg, B.A. VanDevender, C. J. Virtue, H. Wan Chan Tseung, D. L. Wark, Peter Watson, J. Wendland, N. West, J. F. Wilkerson, J. R. Wilson, J. M. Wouters, A. Wright, Minfang Yeh, F. Zhang, Kai Zuber 
TL;DR: In this paper, a combined analysis of solar neutrino data from all phases of the Sudbury Neutrino Observatory was presented, which showed that particle identification information obtained from the proportional counters installed during the third phase improved background rejection in that phase of the experiment.
Abstract: We report results from a combined analysis of solar neutrino data from all phases of the Sudbury Neutrino Observatory. By exploiting particle identification information obtained from the proportional counters installed during the third phase, this analysis improved background rejection in that phase of the experiment. The combined analysis resulted in a total flux of active neutrino flavors from 8B decays in the Sun of (5.25 \pm 0.16(stat.)+0.11-0.13(syst.))\times10^6 cm^{-2}s^{-1}. A two-flavor neutrino oscillation analysis yielded \Deltam^2_{21} = (5.6^{+1.9}_{-1.4})\times10^{-5} eV^2 and tan^2{\theta}_{12}= 0.427^{+0.033}_{-0.029}. A three-flavor neutrino oscillation analysis combining this result with results of all other solar neutrino experiments and the KamLAND experiment yielded \Deltam^2_{21} = (7.41^{+0.21}_{-0.19})\times10^{-5} eV^2, tan^2{\theta}_{12} = 0.446^{+0.030}_{-0.029}, and sin^2{\theta}_{13} =(2.5^{+1.8}_{-1.5})\times10^{-2}. This implied an upper bound of sin^2{\theta}_{13} < 0.053 at the 95% confidence level (C.L.).

Journal ArticleDOI
TL;DR: The findings dissociate morphine-induced hyperalgesia from tolerance and suggest the microglia-to-neuron P2X4-BDNF-KCC2 pathway as a therapeutic target for preventing hyperalGESia without affecting morphine analgesia.
Abstract: A major unresolved issue in treating pain is the paradoxical hyperalgesia produced by the gold-standard analgesic morphine and other opiates. We found that hyperalgesia-inducing treatment with morphine resulted in downregulation of the K(+)-Cl(-) co-transporter KCC2, impairing Cl(-) homeostasis in rat spinal lamina l neurons. Restoring the anion equilibrium potential reversed the morphine-induced hyperalgesia without affecting tolerance. The hyperalgesia was also reversed by ablating spinal microglia. Morphine hyperalgesia, but not tolerance, required μ opioid receptor-dependent expression of P2X4 receptors (P2X4Rs) in microglia and μ-independent gating of the release of brain-derived neurotrophic factor (BDNF) by P2X4Rs. Blocking BDNF-TrkB signaling preserved Cl(-) homeostasis and reversed the hyperalgesia. Gene-targeted mice in which Bdnf was deleted from microglia did not develop hyperalgesia to morphine. However, neither morphine antinociception nor tolerance was affected in these mice. Our findings dissociate morphine-induced hyperalgesia from tolerance and suggest the microglia-to-neuron P2X4-BDNF-KCC2 pathway as a therapeutic target for preventing hyperalgesia without affecting morphine analgesia.

Journal ArticleDOI
TL;DR: Sarcopenia is highly prevalent in the elderly population with traumatic injuries and represents a potential new predictor for mortality, discharge disposition, and ICU utilization, according to traditional measures of nutritional assessment.
Abstract: Introduction As the population ages, the number of injured elderly is increasing. We sought to determine if low skeletal muscle mass adversely affected outcome in elderly patients following trauma.

Vanessa Watts1
04 May 2013
TL;DR: In this article, the authors examine how agency is circulated through human and non-human worlds in the creation and maintenance of society from an Indigenous point of view, and argue that agency becomes exclusive to humans, thereby removing nonhuman agency out of what constitutes a society and that it is in this limited space of human-only thought and agency that colonial tactics of violence against Indigenous territory and Indigenous women are most ripe.
Abstract: This paper will examine how agency is circulated through human and non-human worlds in the creation and maintenance of society from an Indigenous point of view. Through processes of colonization, the corruption of essential categories of Indigenous conceptions of the world (the feminine and land) has led to a disconnect between how this agency is manifested in society. Through a comparison between the epistemological-ontological divide and an Indigenous conception of Place-Thought, this paper will argue that agency becomes exclusive to humans, thereby removing non-human agency out of what constitutes a society. It is in this limited space of human-only thought and agency that colonial tactics of violence against Indigenous territory and Indigenous women are most ripe. This is accomplished in part through mythologizing Indigenous origin stories and separating out communication, treaty-making, historical agreements that human beings held with the animal world, the sky world, the spirit world, etc. Thus, in order for colonialism to operationalize itself, it must attempt to make Indigenous peoples stand in disbelief of themselves and their histories. This paper will reaffirm this sacred connection between place, non-human and human in an effort to access the “pre-colonial mind”.


Journal ArticleDOI
TL;DR: A review of the current relevant pre-clinical and clinical data is presented and the rationale for dual inhibition of these pathways in the treatment of BC patients is discussed.