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Objective: The primary objective of our study was to establish the prevalence of anxiety and depressive symptoms among professional football (ie, soccer; hereinafter “football”) players during the COVID-19 emergency period, drawing comparisons with players assessed before exposure to the COVID-19 emergency period. Design: Observational comparative cross-sectional study by means of electronic questionnaire. Setting: Professional football. Participants: A total of 468 female (mean age: 22.8 years) and 1134 male (mean age: 26.0 years) players participated. The non-COVID-19 comparison group consisted of 132 female (mean age: 23.1 years) and 175 male (mean age: 24.8 years) professional footballers. Intervention: N/A. Main Outcome Measures: Anxiety symptoms were measured with the validated Generalized Anxiety Disorder 7 and depressive symptoms with the validated Patient Health Questionnaire 9. Both instruments have been widely used in both clinical and research settings among different populations, showing excellent psychometric properties. Results: During the COVID-19 emergency period, the 2-week prevalence of symptoms consistent with a diagnosis of generalized anxiety disorder and depression was 18.2% and 21.6%, respectively, among female professional footballers and 15.5% and 12.9%, respectively, among male players. The 2-week prevalence of anxiety and depressive symptoms among professional footballers was significantly higher during the COVID-19 emergency period than before the global pandemic (P< 0.01). Differences were most pronounced for those worried about the playing future. Conclusions: The COVID-19 emergency period is associated with increased symptoms of anxiety and depression in professional footballers, especially among those worried about their future as players.

Summary Cancer is a substantial health burden for Inuit populations, an Indigenous peoples who primarily inhabit the circumpolar regions of Alaska, Canada, Greenland, and Russia. Access to radiotherapy is lacking or absent in many of these regions, despite it being an essential component of cancer treatment. This Review presents an overview of factors influencing radiotherapy delivery in each of the four circumpolar Inuit regions, which include population and geography, health-systems infrastructure, and cancer epidemiology. This Review also provides insight into the complex patient pathways needed to access radiotherapy, and on radiotherapy use. The unique challenges in delivering radiotherapy to circumpolar Inuit populations are discussed, which, notably, include geographical and cultural barriers. Recommendations include models of care that have successfully addressed these barriers, and highlight the need for increased collaboration between circumpolar referral centres in Alaska, Canada, Greenland, and Russia to ultimately allow for better delivery of cancer treatment.

Authors of systematic reviews that include patient-reported outcomes (PROs) should have a good understanding of how patient-reported outcome measures (PROMs) are developed, including the constructs they are intended to measure, their reliability, validity and responsiveness. This chapter describes the category of outcomes known as PROs and their importance for healthcare decision making, and illustrates the key issues related to reliability, validity and responsiveness that systematic review authors should consider when including PROs. It also addresses the structure and content of PROs and provides guidance for combining information from different PROs. The chapter outlines a step-by-step approach to addressing each of these elements in the systematic review process. The focus is on the use of PROs in randomized trials, and what is crucial in this context when selecting PROs to include in a meta-analysis. The chapter describes PROMs in more detail and discusses some issues to consider when deciding which PROMs to address in a review.

Abstract Purpose The quality of stereotactic body radiation therapy (SBRT) treatment plans for early stage lung cancer are unknown outside of peer-reviewed publications. Thus, a study was conducted to crowdsource and analyze a variety of lung SBRT treatment plans from around the world. Methods and Materials This study had 2 parts, planning and contouring, and each was facilitated by a web-based technology platform. For planning, lung SBRT planners were invited to design, score, and submit their treatment plans (prescription of 11 Gy × 5) for a centralized stage I lung cancer case using standardized images and predefined contours. Each plan was scored with 20 weighted metrics adapted from currently recruiting phase 3 lung SBRT trials. For contouring, a separate image set was used to evaluate organ-at-risk contour accuracy using Dice coefficients and a StructSure score. Results For planning 227 plans were submitted in total with 7 different treatment planning systems and 7 different delivery methods represented. Variability was primarily user driven and not associated with the treatment planning system, delivery modality, total monitor units, or estimated beam-on time. Many of the highest-quality plans required the shortest amount of time to deliver, independent of the delivery technique. For contouring, organ-at-risk contours were frequently over- or undercontoured and often included only the luminal air of the trachea, proximal bronchial tree, and esophagus, even when the mucosal linings were within a few centimeters of the target tumor. Conclusions These findings demonstrate the importance of quality assurance to help improve planning and contouring and the value of peer review and comparison. More readily accessible quality evaluation software solutions, such as the one used herein, may help meet this growing need.

Avital, Michel. "Digital "x": In Need of New Theories or Do Prior Theories Suffice?" Proceedings - Academy of Management. 2019.1 (2019): 1-1. Web.

Objectives To compare the prognostic value of the World Health Organization (WHO) 1973 and 2004 classification systems for grade in T1 bladder cancer (T1-BC), as both are currently recommended in international guidelines. Patients and methods Three uro-pathologists re-revised slides of 601 primary (first diagnosis) T1-BCs, initially managed conservatively (bacille Calmette-Guerin) in four hospitals. Grade was defined according to WHO1973 (Grade 1-3) and WHO2004 (low-grade [LG] and high-grade [HG]). This resulted in a lack of Grade 1 tumours, 188 (31%) Grade 2, and 413 (69%) Grade 3 tumours. There were 47 LG (8%) vs 554 (92%) HG tumours. We determined the prognostic value for progression-free survival (PFS) and cancer-specific survival (CSS) in Cox-regression models and corrected for age, sex, multiplicity, size and concomitant carcinoma in situ. Results At a median follow-up of 5.9 years, 148 patients showed progression and 94 died from BC. The WHO1973 Grade 3 was negatively associated with PFS (hazard ratio [HR] 2.1) and CSS (HR 3.4), whilst WHO2004 grade was not prognostic. On multivariable analysis, WHO1973 grade was the only prognostic factor for progression (HR 2.0). Grade 3 tumours (HR 3.0), older age (HR 1.03) and tumour size >3 cm (HR 1.8) were all independently associated with worse CSS. Conclusion The WHO1973 classification system for grade has strong prognostic value in T1-BC, compared to the WHO2004 system. Our present results suggest that WHO1973 grade cannot be replaced by the WHO2004 classification in non-muscle-invasive BC guidelines.

Alzheimer's disease (AD) is linked to the abnormal accumulation of amyloid ? peptide (A?) aggregates in the brain. Silybin B, a natural compound extracted from milk thistle (Silybum marianum), has been shown to significantly inhibit A? aggregation in vitro and to exert neuroprotective properties in vivo. However, further explorations of silybin B's clinical potential are currently limited by three main factors: (a) poor solubility, (b) instability in blood serum, and (c) only partial knowledge of silybin's mechanism of action. Here, we address these three limitations. We demonstrate that conjugation of a trehalose moiety to silybin significantly increases both water solubility and stability in blood serum without significantly compromising its antiaggregation properties. Furthermore, using a combination of biophysical techniques with different spatial resolution, that is, TEM, ThT fluorescence, CD, and NMR spectroscopy, we profile the interactions of the trehalose conjugate with both A? monomers and oligomers and evidence that silybin may shield the "toxic" surfaces formed by the N-terminal and central hydrophobic regions of A?. Finally, comparative analysis with silybin A, a less active diastereoisomer of silybin B, revealed how even subtle differences in chemical structure may entail different effects on amyloid inhibition. The resulting insight on the mechanism of action of silybins as aggregation inhibitors is anticipated to facilitate the future investigation of silybin's therapeutic potential.

AbstractThis research communication describes a genome-wide association study for Italian buffalo mammary gland morphology. Three single nucleotide polymorphisms (AX-85117983, AX-8509475 and AX-85117518) were identified to be significantly associated with buffalo anterior teat length, posterior teat length and distance between anterior and posterior teat, respectively. Two significant signals for buffalo mammary gland morphology were observed in two genomic regions on the chromosome 10, and chromosome 20. One of the regions located on the chromosome 10 has the most likely candidate genes ACTC1 and GJD2, both of which have putative roles in the regulation of mammary gland development. This study provides new insights into the genetic variants of buffalo mammary gland morphology and may be beneficial for understanding of the genetic regulation of mammary growth.

SLC35A2-CDG is caused by mutations in the X-linked SLC35A2 gene encoding the UDP-galactose transporter. SLC35A2 mutations lead to hypogalactosylation of N-glycans. SLC35A2-CDG is characterized by severe neurological symptoms and, in many patients, early-onset epileptic encephalopathy. In view of the diagnostic challenges, we studied the clinical, neuroradiological, and biochemical features of 15 patients (11 females and 4 males) with SLC35A2-CDG from various centers. We describe nine novel pathogenic variations in SLC35A2. All affected individuals presented with a global developmental delay, and hypotonia, while 70% were nonambulatory. Epilepsy was present in 80% of the patients, and in EEG hypsarrhythmia and findings consistent with epileptic encephalopathy were frequently seen. The most common brain MRI abnormality was cerebral atrophy with delayed myelination and multifocal inhomogeneous abnormal patchy white matter hyperintensities, which seemed to be nonprogressive. Thin corpus callosum was also common, and all the patients had a corpus callosum shorter than normal for their age. Variable dysmorphic features and growth deficiency were noted. Biochemically, normal mucin type O-glycosylation and lipid glycosylation were found, while transferrin mass spectrometry was found to be more specific in the identification of SLC35A2-CDG, as compared to routine screening tests. Although normal glycosylation studies together with clinical variability and genetic results complicate the diagnosis of SLC35A2-CDG, our data indicate that the combination of these three elements can support the pathogenicity of mutations in SLC35A2.

Aim. - This study explores the changes in glucose-lowering drug (GLD) use before and after cancer diagnosis among patients with diabetes. Methods. - New GLD users (1998-2011) living in the Dutch ECR-PHARMO catchment area were selected from the PHARMO Database Network (n = 52,228). Those with a primary cancer diagnosis were considered cases (n = 3281) and matched with eligible controls (n = 12,891) without cancer during follow-up. Conditional logistic regression analysis was used to assess changes in GLD use, such as treatment add-ons, treatments drops and initiation of insulin, for cases compared with controls associated with specific cancer types in four time windows (6-3 and 0-3 months before cancer diagnosis; 0-3 and 3-6 months after cancer diagnosis). Results. - In the 3 months before cancer diagnosis, patients with upper gastrointestinal (GI) cancers (oesophageal, stomach, pancreatic, liver cancers) had higher odds of initiating insulin (OR: 9.3; 95% CI: 3.6-24.1); to a lesser extent, this was also observed in the 3 months prior to that (at 6 months, OR: 3.9; 95% CI: 1.31-2.1). Diagnosis of colorectal (OR: 3.4; 95% CI: 1.4-8.4), pulmonary (OR: 2.5; 95% CI: 1.1-5.4) and upper GI (OR: 13.6; 95% CI: 5.0-36.9) cancers was associated with increased odds of initiating insulin in the 3 months after cancer diagnosis. During all study time windows, the odds of treatment drops were higher for patients with upper GI cancers whereas, for most other cancers, these odds were higher only after a diagnosis of cancer. Conclusion. - The greater odds of initiating insulin during the 6 months prior to diagnosis of upper GI cancers suggest reverse causation. After cancer diagnosis, drops in use of GLDs was commonly seen. (C) 2017 Elsevier Masson SAS. All rights reserved.