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Showing papers by "University of Western Ontario published in 2013"


Journal ArticleDOI
Gad Getz1, Stacey Gabriel1, Kristian Cibulskis1, Eric S. Lander1  +280 moreInstitutions (31)
02 May 2013-Nature
TL;DR: In this paper, the authors performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array-and-sequencing-based technologies, and classified them into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy number high.
Abstract: We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

3,719 citations


Journal ArticleDOI
TL;DR: This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).
Abstract: Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).

3,691 citations



Journal ArticleDOI
TL;DR: Abiraterone improved radiographic progression-free survival, showed a trend toward improved overall survival, and significantly delayed clinical decline and initiation of chemotherapy in patients with metastatic castration-resistant prostate cancer.
Abstract: A b s t r ac t Background Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after chemotherapy. We evaluated this agent in patients who had not received previous chemotherapy. Methods In this double-blind study, we randomly assigned 1088 patients to receive abiraterone acetate (1000 mg) plus prednisone (5 mg twice daily) or placebo plus prednisone. The coprimary end points were radiographic progression-free survival and overall survival. Results The study was unblinded after a planned interim analysis that was performed after 43% of the expected deaths had occurred. The median radiographic progressionfree survival was 16.5 months with abiraterone–prednisone and 8.3 months with prednisone alone (hazard ratio for abiraterone–prednisone vs. prednisone alone, 0.53; 95% confidence interval [CI], 0.45 to 0.62; P<0.001). Over a median follow-up period of 22.2 months, overall survival was improved with abiraterone–prednisone (median not reached, vs. 27.2 months for prednisone alone; hazard ratio, 0.75; 95% CI, 0.61 to 0.93; P = 0.01) but did not cross the efficacy boundary. Abiraterone–predni sone showed superiority over prednisone alone with respect to time to initiation of cytotoxic chemotherapy, opiate use for cancer-related pain, prostate-specific antigen progression, and decline in performance status. Grade 3 or 4 mineralocorticoid-related adverse events and abnormalities on liver-function testing were more common with abiraterone–prednisone. Conclusions Abiraterone improved radiographic progression-free survival, showed a trend toward improved overall survival, and significantly delayed clinical decline and initiation of chemotherapy in patients with metastatic castration-resistant prostate cancer. (Funded by Janssen Research and Development, formerly Cougar Biotechnology; ClinicalTrials.gov number, NCT00887198.)

2,315 citations


Journal ArticleDOI
TL;DR: Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis and the frequency of adverse events was similar in the vedolIZumab and placebo groups.
Abstract: We conducted two integrated randomized, double-blind, placebo-controlled trials of vedolizumab in patients with active disease. In the trial of induction therapy, 374 pa tients (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to vedolizumab at week 6 were randomly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active disease) of at least 3 points and a de crease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. Results Response rates at week 6 were 47.1% and 25.5% among patients in the vedolizumab group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95% confidence interval [CI], 11.6 to 31.7; P 1), as compared with 15.9% of pa tients who switched to placebo (adjusted difference, 26.1 percentage points for vedoliz umab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P<0.001] and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [95% CI, 17.9 to 40.4; P<0.001]). The frequency of adverse events was similar in the vedolizumab and placebo groups. Conclusions Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis. (Funded by Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.)

2,071 citations


Journal ArticleDOI
TL;DR: Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive vedolIZumab (rather than switching to placebo) were morelikely to be in remission at week 52.
Abstract: BackgroundUstekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. MethodsWe randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 w...

2,059 citations


Journal ArticleDOI
TL;DR: There is an urgent worldwide need for diagnostic screening together with early and aggressive treatment of this extremely high-risk condition, familial hypercholesterolaemia.
Abstract: Aims The first aim was to critically evaluate the extent to which familial hypercholesterolaemia (FH) is underdiagnosed and undertreated. The second aim was to provide guidance for screening and treatment of FH, in order to prevent coronary heart disease (CHD). Methods and results Of the theoretical estimated prevalence of 1/500 for heterozygous FH, <1% are diagnosed in most countries. Recently, direct screening in a Northern European general population diagnosed approximately 1/200 with heterozygous FH. All reported studies document failure to achieve recommended LDL cholesterol targets in a large proportion of individuals with FH, and up to 13-fold increased risk of CHD. Based on prevalences between 1/500 and 1/200, between 14 and 34 million individuals worldwide have FH. We recommend that children, adults, and families should be screened for FH if a person or family member presents with FH, a plasma cholesterol level in an adult ≥8 mmol/L(≥310 mg/dL) or a child ≥6 mmol/L(≥230 mg/dL), premature CHD, tendon xanthomas, or sudden premature cardiac death. In FH, low-density lipoprotein cholesterol targets are <3.5 mmol/L(<135 mg/dL) for children, <2.5 mmol/L(<100 mg/dL) for adults, and <1.8 mmol/L(<70 mg/dL) for adults with known CHD or diabetes. In addition to lifestyle and dietary counselling, treatment priorities are (i) in children, statins, ezetimibe, and bile acid binding resins, and (ii) in adults, maximal potent statin dose, ezetimibe, and bile acid binding resins. Lipoprotein apheresis can be offered in homozygotes and in treatment-resistant heterozygotes with CHD. Conclusion Owing to severe underdiagnosis and undertreatment of FH, there is an urgent worldwide need for diagnostic screening together with early and aggressive treatment of this extremely high-risk condition.

2,039 citations


Journal ArticleDOI
TL;DR: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria and should allow for more patients to be classified correctly as having the disease.
Abstract: Objective The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. Methods Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by (1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and (2) validating against the combined view of a group of experts on a set of cases with or without SSc. Results It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, seven additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud9s phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. Conclusions The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.

1,899 citations


Journal ArticleDOI
TL;DR: This updated review includes 15 studies that measured the effectiveness of IPE interventions compared to no educational intervention and found that seven studies indicated that IPE produced positive outcomes in the following areas: diabetes care, emergency department culture and patient satisfaction.
Abstract: BACKGROUND: The delivery of effective, high-quality patient care is a complex activity. It demands health and social care professionals collaborate in an effective manner. Research continues to suggest that collaboration between these professionals can be problematic. Interprofessional education (IPE) offers a possible way to improve interprofessional collaboration and patient care. OBJECTIVES: To assess the effectiveness of IPE interventions compared to separate, profession-specific education interventions; and to assess the effectiveness of IPE interventions compared to no education intervention. SEARCH METHODS: For this update we searched the Cochrane Effective Practice and Organisation of Care Group specialised register, MEDLINE and CINAHL, for the years 2006 to 2011. We also handsearched the Journal of Interprofessional Care (2006 to 2011), reference lists of all included studies, the proceedings of leading IPE conferences, and websites of IPE organisations. SELECTION CRITERIA: Randomised controlled trials (RCTs), controlled before and after (CBA) studies and interrupted time series (ITS) studies of IPE interventions that reported objectively measured or self reported (validated instrument) patient/client or healthcare process outcomes. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed the eligibility of potentially relevant studies. For included studies, at least two review authors extracted data and assessed study quality. A meta-analysis of study outcomes was not possible due to heterogeneity in study designs and outcome measures. Consequently, the results are presented in a narrative format. MAIN RESULTS: This update located nine new studies, which were added to the six studies from our last update in 2008. This review now includes 15 studies (eight RCTs, five CBA and two ITS studies). All of these studies measured the effectiveness of IPE interventions compared to no educational intervention. Seven studies indicated that IPE produced positive outcomes in the following areas: diabetes care, emergency department culture and patient satisfaction; collaborative team behaviour and reduction of clinical error rates for emergency department teams; collaborative team behaviour in operating rooms; management of care delivered in cases of domestic violence; and mental health practitioner competencies related to the delivery of patient care. In addition, four of the studies reported mixed outcomes (positive and neutral) and four studies reported that the IPE interventions had no impact on either professional practice or patient care. AUTHORS' CONCLUSIONS: This updated review reports on 15 studies that met the inclusion criteria (nine studies from this update and six studies from the 2008 update). Although these studies reported some positive outcomes, due to the small number of studies and the heterogeneity of interventions and outcome measures, it is not possible to draw generalisable inferences about the key elements of IPE and its effectiveness. To improve the quality of evidence relating to IPE and patient outcomes or healthcare process outcomes, the following three gaps will need to be filled: first, studies that assess the effectiveness of IPE interventions compared to separate, profession-specific interventions; second, RCT, CBA or ITS studies with qualitative strands examining processes relating to the IPE and practice changes; third, cost-benefit analyses.

1,666 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: Clinical CBD phenotypes and features were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies.
Abstract: Current criteria for the clinical diagnosis of pathologically confirmed corticobasal degeneration (CBD) no longer reflect the expanding understanding of this disease and its clinicopathologic correlations. An international consortium of behavioral neurology, neuropsychology, and movement disorders specialists developed new criteria based on consensus and a systematic literature review. Clinical diagnoses (early or late) were identified for 267 nonoverlapping pathologically confirmed CBD cases from published reports and brain banks. Combined with consensus, 4 CBD phenotypes emerged: corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS). Clinical features of CBD cases were extracted from descriptions of 209 brain bank and published patients, providing a comprehensive description of CBD and correcting common misconceptions. Clinical CBD phenotypes and features were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies. Probable CBD criteria require insidious onset and gradual progression for at least 1 year, age at onset ≥50 years, no similar family history or known tau mutations, and a clinical phenotype of probable CBS or either FBS or naPPA with at least 1 CBS feature. The possible CBD category uses similar criteria but has no restrictions on age or family history, allows tau mutations, permits less rigorous phenotype fulfillment, and includes a PSPS phenotype. Future validation and refinement of the proposed criteria are needed.

Journal ArticleDOI
TL;DR: Even short durations of an intraoperative mean arterial pressure less than 55 mmHg are associated with AKI and myocardial injury, and Randomized trials are required to determine whether outcomes improve with interventions that maintain an intraoper MAP of at least 55mmHg.
Abstract: Background:Intraoperative hypotension may contribute to postoperative acute kidney injury (AKI) and myocardial injury, but what blood pressures are unsafe is unclear. The authors evaluated the association between the intraoperative mean arterial pressure (MAP) and the risk of AKI and myocardial inju

Journal ArticleDOI
TL;DR: In this paper, the authors examine whether shareholders are sensitive to corporations' environmental footprint and find that companies reported to behave responsibly toward the environment experience a significant stock price increase, whereas firms that behave irresponsibly face a significant decrease.
Abstract: This study examines whether shareholders are sensitive to corporations' environmental footprint. Specifically, I conduct an event study around the announcement of corporate news related to environment for all US publicly traded companies from 1980 to 2009. In keeping with the view that environmental corporate social responsibility (CSR) generates new and competitive resources for firms, I find that companies reported to behave responsibly toward the environment experience a significant stock price increase, whereas firms that behave irresponsibly face a significant decrease. Extending this view of “environment-as-a-resource,” I posit that the value of environmental CSR depends on external and internal moderators. First, I argue that external pressure to behave responsibly towards the environment―which has increased dramatically over recent decades―exacerbates the punishment for eco-harmful behavior and reduces the reward for eco-friendly initiatives. This argument is supported by the data: over time, the ...

Journal ArticleDOI
TL;DR: This comprehensive article reviews these adverse events of systemic corticosteroid therapy and provides practical recommendations for their prevention and management based on both current literature and the clinical experience of the authors.
Abstract: Systemic corticosteroids play an integral role in the management of many inflammatory and immunologic conditions, but these agents are also associated with serious risks. Osteoporosis, adrenal suppression, hyperglycemia, dyslipidemia, cardiovascular disease, Cushing’s syndrome, psychiatric disturbances and immunosuppression are among the more serious side effects noted with systemic corticosteroid therapy, particularly when used at high doses for prolonged periods. This comprehensive article reviews these adverse events and provides practical recommendations for their prevention and management based on both current literature and the clinical experience of the authors.

Journal ArticleDOI
TL;DR: The Database Consortium model is now externally validated and can be applied to stratify patients by risk in clinical trials and to counsel patients about prognosis.
Abstract: Summary Background The International Metastatic Renal-Cell Carcinoma Database Consortium model offers prognostic information for patients with metastatic renal-cell carcinoma. We tested the accuracy of the model in an external population and compared it with other prognostic models. Methods We included patients with metastatic renal-cell carcinoma who were treated with first-line VEGF-targeted treatment at 13 international cancer centres and who were registered in the Consortium's database but had not contributed to the initial development of the Consortium Database model. The primary endpoint was overall survival. We compared the Database Consortium model with the Cleveland Clinic Foundation (CCF) model, the International Kidney Cancer Working Group (IKCWG) model, the French model, and the Memorial Sloan-Kettering Cancer Center (MSKCC) model by concordance indices and other measures of model fit. Findings Overall, 1028 patients were included in this study, of whom 849 had complete data to assess the Database Consortium model. Median overall survival was 18·8 months (95% 17·6–21·4). The predefined Database Consortium risk factors (anaemia, thrombocytosis, neutrophilia, hypercalcaemia, Karnofsky performance status Interpretation The Database Consortium model is now externally validated and can be applied to stratify patients by risk in clinical trials and to counsel patients about prognosis. Funding None.

Journal ArticleDOI
TL;DR: The use of nano zero valent iron (nZVI) for groundwater remediation has been investigated for its potential to reduce subsurface contaminants such as PCBs, chlorinated solvents, and heavy metals.

Journal ArticleDOI
TL;DR: In this paper, the atomic layer deposition (ALD) technique was used to synthesize single Pt atoms anchored to graphene nanosheet using the ALD technique, and the single-atom catalysts exhibit significantly improved catalytic activity (up to 10 times) over that of the state-of-the-art commercial Pt/C catalyst.
Abstract: Platinum-nanoparticle-based catalysts are widely used in many important chemical processes and automobile industries. Downsizing catalyst nanoparticles to single atoms is highly desirable to maximize their use efficiency, however, very challenging. Here we report a practical synthesis for isolated single Pt atoms anchored to graphene nanosheet using the atomic layer deposition (ALD) technique. ALD offers the capability of precise control of catalyst size span from single atom, subnanometer cluster to nanoparticle. The single-atom catalysts exhibit significantly improved catalytic activity (up to 10 times) over that of the state-of-the-art commercial Pt/C catalyst. X-ray absorption fine structure (XAFS) analyses reveal that the low-coordination and partially unoccupied densities of states of 5d orbital of Pt atoms are responsible for the excellent performance. This work is anticipated to form the basis for the exploration of a next generation of highly efficient single-atom catalysts for various applications.

Journal ArticleDOI
TL;DR: The Canadian Hypertension Education Program reviews the hypertension literature annually and provides detailed recommendations regarding hypertension diagnosis, assessment, prevention, and treatment, and 4 new recommendations were added and 2 existing recommendations were modified this year.

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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


Journal ArticleDOI
TL;DR: The Poisson regression model using a sandwich variance estimator has become a viable alternative to the logistic regression model for the analysis of prospective studies with independent binary outcomes and is extended to studies with correlated binary outcomes as arise in longitudinal or cluster randomization studies.
Abstract: The Poisson regression model using a sandwich variance estimator has become a viable alternative to the logistic regression model for the analysis of prospective studies with independent binary outcomes. The primary advantage of this approach is that it readily provides covariate-adjusted risk ratios and associated standard errors. In this article, the model is extended to studies with correlated binary outcomes as arise in longitudinal or cluster randomization studies. The key step involves a cluster-level grouping strategy for the computation of the middle term in the sandwich estimator. For a single binary exposure variable without covariate adjustment, this approach results in risk ratio estimates and standard errors that are identical to those found in the survey sampling literature. Simulation results suggest that it is reliable for studies with correlated binary data, provided the total number of clusters is at least 50. Data from observational and cluster randomized studies are used to illustrate the methods.

Journal ArticleDOI
TL;DR: Numerical results show that for both AF and DF protocols, the intercept probability performance of proposed optimal relay selection is strictly better than that of the traditional relay selection and multiple relay combining methods.
Abstract: In this paper, we explore the physical-layer security in cooperative wireless networks with multiple relays where both amplify-and-forward (AF) and decode-and-forward (DF) protocols are considered. We propose the AF and DF based optimal relay selection (i.e., AFbORS and DFbORS) schemes to improve the wireless security against eavesdropping attack. For the purpose of comparison, we examine the traditional AFbORS and DFbORS schemes, denoted by T-AFbORS and T-DFbORS, respectively. We also investigate a so-called multiple relay combining (MRC) framework and present the traditional AF and DF based MRC schemes, called T-AFbMRC and T-DFbMRC, where multiple relays participate in forwarding the source signal to destination which then combines its received signals from the multiple relays. We derive closed-form intercept probability expressions of the proposed AFbORS and DFbORS (i.e., P-AFbORS and P-DFbORS) as well as the T-AFbORS, T-DFbORS, T-AFbMRC and T-DFbMRC schemes in the presence of eavesdropping attack. We further conduct an asymptotic intercept probability analysis to evaluate the diversity order performance of relay selection schemes and show that no matter which relaying protocol is considered (i.e., AF and DF), the traditional and proposed optimal relay selection approaches both achieve the diversity order M where M represents the number of relays. In addition, numerical results show that for both AF and DF protocols, the intercept probability performance of proposed optimal relay selection is strictly better than that of the traditional relay selection and multiple relay combining methods.

Journal ArticleDOI
TL;DR: Electrospray ionization generates intact gas-phase ions from analytes in solution for mass spectrometric investigations and has been proposed for disordered polymers.
Abstract: Electrospray ionization (ESI) generates intact gas-phase ions from analytes in solution for mass spectrometric investigations. ESI can proceed via different mechanisms. Low molecular weight analyte...

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TL;DR: This article presents a critical review, focusing on various microalgae species that consume CO2 and nutrients from wastewater, and provide high quality biofuel.
Abstract: Algae have recently received growing attention given its prospects as a source of renewable energy and its potential for CO2 capture. Algae culture is of increasing value given that: (i) algae can be cultivated on non-agricultural land using wastewater, (ii) algae can provide a high yield on a per unit of light irradiated area, (iii) algae growth requires CO2 and nutrients that can be obtained from wastewater and fossil fuel combustion and (iv) algae contains high oil and starch making possible the production of high quality biodiesel. Thus, algae culture can contribute to CO2 fixation, wastewater treatment and can be a source of bioenergy. This article presents a critical review, focusing on various microalgae species that consume CO2 and nutrients from wastewater, and provide high quality biofuel. In this respect, a number of relevant topics are discussed in this review: (a) the media for algae culture, (b) the photobioreactor, (c) the associated wastewater treatment processes, (d) the CO2 capture mechanism and (e) microalgal harvesting. This review also considers various aspects of the biomass processing such as (a) lipid extraction, (b) thermodynamics of the produced biomass conversion, (c) biomass gasification, (d) biodiesel production, (e) catalysts, (f) reaction pathways/mechanisms and (g) reaction kinetics.

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TL;DR: A few neuroimaging studies revealed that brain activation during number comparison correlates with children's mathematics achievement level, but the consistency of such relationships for symbolic and non-symbolic processing is unclear.

Journal ArticleDOI
02 Jul 2013-PLOS ONE
TL;DR: ALDEx, an ANOVA-like differential expression procedure, is developed to identify genes with greater between- to within-condition differences and it is shown that the presence of differential expression and the magnitude of these comparative differences can be reasonably estimated with even very small sample sizes.
Abstract: Experimental variance is a major challenge when dealing with high-throughput sequencing data. This variance has several sources: sampling replication, technical replication, variability within biological conditions, and variability between biological conditions. The high per-sample cost of RNA-Seq often precludes the large number of experiments needed to partition observed variance into these categories as per standard ANOVA models. We show that the partitioning of within-condition to between-condition variation cannot reasonably be ignored, whether in single-organism RNA-Seq or in Meta-RNA-Seq experiments, and further find that commonly-used RNA-Seq analysis tools, as described in the literature, do not enforce the constraint that the sum of relative expression levels must be one, and thus report expression levels that are systematically distorted. These two factors lead to misleading inferences if not properly accommodated. As it is usually only the biological between-condition and within-condition differences that are of interest, we developed ALDEx, an ANOVA-like differential expression procedure, to identify genes with greater between- to within-condition differences. We show that the presence of differential expression and the magnitude of these comparative differences can be reasonably estimated with even very small sample sizes.

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TL;DR: Several treatment-related risk factors predict the development of symptomatic pneumonitis, and elderly patients who undergo CCRT with carboplatin-paclitaxel chemotherapy are at highest risk.
Abstract: Background Radiation pneumonitis is a dose-limiting toxicity for patients undergoing concurrent chemoradiation therapy (CCRT) for non-small cell lung cancer (NSCLC). We performed an individual patient data meta-analysis to determine factors predictive of clinically significant pneumonitis. Methods and Materials After a systematic review of the literature, data were obtained on 836 patients who underwent CCRT in Europe, North America, and Asia. Patients were randomly divided into training and validation sets (two-thirds vs one-third of patients). Factors predictive of symptomatic pneumonitis (grade ≥2 by 1 of several scoring systems) or fatal pneumonitis were evaluated using logistic regression. Recursive partitioning analysis (RPA) was used to define risk groups. Results The median radiation therapy dose was 60 Gy, and the median follow-up time was 2.3 years. Most patients received concurrent cisplatin/etoposide (38%) or carboplatin/paclitaxel (26%). The overall rate of symptomatic pneumonitis was 29.8% (n=249), with fatal pneumonitis in 1.9% (n=16). In the training set, factors predictive of symptomatic pneumonitis were lung volume receiving ≥20 Gy (V 20 ) (odds ratio [OR] 1.03 per 1% increase, P =.008), and carboplatin/paclitaxel chemotherapy (OR 3.33, P P =.09); the model remained predictive in the validation set with good discrimination in both datasets (c-statistic >0.65). On RPA, the highest risk of pneumonitis (>50%) was in patients >65 years of age receiving carboplatin/paclitaxel. Predictors of fatal pneumonitis were daily dose >2 Gy, V 20 , and lower-lobe tumor location. Conclusions Several treatment-related risk factors predict the development of symptomatic pneumonitis, and elderly patients who undergo CCRT with carboplatin-paclitaxel chemotherapy are at highest risk. Fatal pneumonitis, although uncommon, is related to dosimetric factors and tumor location.

Journal ArticleDOI
TL;DR: Several recent studies have found additional tumour-suppressor functions of RB, including alternative roles in the cell cycle, maintenance of genome stability and apoptosis, and are combining to define the multifunctionality of RB.
Abstract: Inactivation of the RB protein is one of the most fundamental events in cancer. Coming to a molecular understanding of its function in normal cells and how it impedes cancer development has been challenging. Historically, the ability of RB to regulate the cell cycle placed it in a central role in proliferative control, and research focused on RB regulation of the E2F family of transcription factors. Remarkably, several recent studies have found additional tumour-suppressor functions of RB, including alternative roles in the cell cycle, maintenance of genome stability and apoptosis. These advances and new structural studies are combining to define the multifunctionality of RB.

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TL;DR: The results suggest that the more managers are seen as authentic, by emphasizing transparency, balanced processing, self-awareness and high ethical standards, the more nurses perceive they have access to workplace empowerment structures, are satisfied with their work, and report higher performance.
Abstract: Aim To report a study conducted to test a model linking authentic leadership of managers with nurses' perceptions of structural empowerment, performance, and job satisfaction. Background Authentic leadership has been proposed as the root element of effective leadership needed to build healthier work environments because there is special attention to the development of empowering leader–follower relationships. Although the influence of leadership style and empowerment on job satisfaction is well documented, there are few studies examining the influence of authentic leadership on nurses' empowerment and work outcomes. Design A non-experimental, predictive survey. Method In 2008, a random sample of 600 Registered Nurses working in acute care hospitals across Ontario in Canada was surveyed. The final sample consisted of 280 (48% response rate) nurses. Variables were measured using the Authentic Leadership Questionnaire, Conditions of Work Effectiveness Questionnaire, Global Job Satisfaction Survey, and General Performance scale. The theoretical model was tested using structural equation modelling. Results/outcomes The final model fit the data acceptably. Authentic leadership significantly and positively influenced staff nurses' structural empowerment, which in turn increased job satisfaction and self-rated performance. Conclusion The results suggest that the more managers are seen as authentic, by emphasizing transparency, balanced processing, self-awareness and high ethical standards, the more nurses perceive they have access to workplace empowerment structures, are satisfied with their work, and report higher performance.

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TL;DR: The current research applied Jacoby's (1991) process dissociation procedure to independently quantify the strength of deontological and utilitarian inclinations within individuals, providing evidence for the independent contributions of de ontological andilitarian inclinations to moral judgments.
Abstract: Dual-process theories of moral judgment suggest that responses to moral dilemmas are guided by two moral principles: the principle of deontology states that the morality of an action depends on the intrinsic nature of the action (e.g., harming others is wrong regardless of its consequences); the principle of utilitarianism implies that the morality of an action is determined by its consequences (e.g., harming others is acceptable if it increases the well-being of a greater number of people). Despite the proposed independence of the moral inclinations reflecting these principles, previous work has relied on operationalizations in which stronger inclinations of one kind imply weaker inclinations of the other kind. The current research applied Jacoby's (1991) process dissociation procedure to independently quantify the strength of deontological and utilitarian inclinations within individuals. Study 1 confirmed the usefulness of process dissociation for capturing individual differences in deontological and utilitarian inclinations, revealing positive correlations of both inclinations to moral identity. Moreover, deontological inclinations were uniquely related to empathic concern, perspective-taking, and religiosity, whereas utilitarian inclinations were uniquely related to need for cognition. Study 2 demonstrated that cognitive load selectively reduced utilitarian inclinations, with deontological inclinations being unaffected. In Study 3, a manipulation designed to enhance empathy increased deontological inclinations, with utilitarian inclinations being unaffected. These findings provide evidence for the independent contributions of deontological and utilitarian inclinations to moral judgments, resolving many theoretical ambiguities implied by previous research.