Showing papers by "University of Western Ontario published in 2021"

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma

Abstract: Background Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib ...

CHAPTER 5 – The Social Psychology of Humor

Abstract: According to recent theory, many of the interpersonal functions of humor derive from its inherently ambiguous nature due to the multiple concurrent meanings that it conveys. Because of this ambiguity, humor is a useful vehicle for communicating certain messages and dealing with situations that would be more difficult to handle using a more serious, unambiguous mode of communication. Importantly, a message communicated in a humorous manner can be retracted more easily than if it were expressed in the serious mode, allowing both the speaker and the listener to save face if the message is not well received. These insights concerning the ambiguity and face-saving potential of humor have been applied by theorists and researchers to account for a wide variety of social uses of humor, including self-disclosure and social probing, decommitment and conflict de-escalation, enforcing social norms and exerting social control, establishing and maintaining status, enhancing group cohesion and identity, discourse management, and social play. The multiple interpersonal functions of humor suggest that it may be viewed as a type of social skill or interpersonal competence. Employed in an adept manner, humor can be a very useful tool for achieving one's interpersonal goals.

Systematic and collaborative approach to problem solving using X-ray photoelectron spectroscopy

Abstract: The methodology presented within this work is a result of years of interactions between many junior and senior X-ray Photoelectron Spectroscopy (XPS) users operating within the CasaXPS spectral processing and interpretation program framework. In particular, discussions arising from a series of workshops have been a significant source for developing the overall XPS data processing concept and are the motivation for creating this work. These workshops organized by the Institut des Materiaux Jean Rouxel (IMN), Nantes gather both experienced and novice users of XPS for a week of discourse in conceptual experiment design and the resulting data processing. However, the framework constructed and utilized within these workshops encouraged the dissemination of knowledge beyond XPS data analysis and emphasized the importance of a multi-disciplinary collaborative approach to surface analysis problem-solving. The material presented here embodies data treatment originating from data made available to the first CNRS Thematic Workshop presented at Roscoff 2013. The methodology described here has evolved over the subsequent workshops in 2016 and 2019 and currently represents the philosophy used in CasaXPS spectral data processing paradigm.

Municipal solid waste management and landfilling technologies: a review

Abstract: The USA, China and India are the top three producers of municipal solid waste. The composition of solid wastes varies with income: low-to-middle-income population generates mainly organic wastes, whereas high-income population produces more waste paper, metals and glasses. Management of municipal solid waste includes recycling, incineration, waste-to-energy conversion, composting or landfilling. Landfilling for solid waste disposal is preferred in many municipalities globally. Landfill sites act as ecological reactors where wastes undergo physical, chemical and biological transformations. Hence, critical factors for sustainable landfilling are landfill liners, the thickness of the soil cover, leachate collection, landfill gas recovery and flaring facilities. Here, we review the impact of landfill conditions such as construction, geometry, weather, temperature, moisture, pH, biodegradable matter and hydrogeological parameters on the generation of landfill gases and leachate. Bioreactor landfills appear as the next-generation sanitary landfills, because they augment solid waste stabilization in a time-efficient manner, as a result of controlled recirculation of leachate and gases. We discuss volume reduction, resource recovery, valorization of dumped wastes, environmental protection and site reclamation toward urban development. We present the classifications and engineered iterations of landfills, operations, mechanisms and mining.

Improving reporting standards for polygenic scores in risk prediction studies

Abstract: Polygenic risk scores (PRSs), which often aggregate results from genome-wide association studies, can bridge the gap between initial discovery efforts and clinical applications for the estimation of disease risk using genetics. However, there is notable heterogeneity in the application and reporting of these risk scores, which hinders the translation of PRSs into clinical care. Here, in a collaboration between the Clinical Genome Resource (ClinGen) Complex Disease Working Group and the Polygenic Score (PGS) Catalog, we present the Polygenic Risk Score Reporting Standards (PRS-RS), in which we update the Genetic Risk Prediction Studies (GRIPS) Statement to reflect the present state of the field. Drawing on the input of experts in epidemiology, statistics, disease-specific applications, implementation and policy, this comprehensive reporting framework defines the minimal information that is needed to interpret and evaluate PRSs, especially with respect to downstream clinical applications. Items span detailed descriptions of study populations, statistical methods for the development and validation of PRSs and considerations for the potential limitations of these scores. In addition, we emphasize the need for data availability and transparency, and we encourage researchers to deposit and share PRSs through the PGS Catalog to facilitate reproducibility and comparative benchmarking. By providing these criteria in a structured format that builds on existing standards and ontologies, the use of this framework in publishing PRSs will facilitate translation into clinical care and progress towards defining best practice.

Mostly worse, occasionally better: impact of COVID-19 pandemic on the mental health of Canadian children and adolescents.

Abstract: This large cross-sectional study examined the impact of COVID-19 emergency measures on child/adolescent mental health for children/adolescents with and without pre-existing psychiatric diagnoses. Using adapted measures from the CRISIS questionnaire, parents of children aged 6–18 (N = 1013; 56% male; 62% pre-existing psychiatric diagnosis) and self-reporting children/adolescents aged 10–18 (N = 385) indicated changes in mental health across six domains: depression, anxiety, irritability, attention, hyperactivity, and obsessions/compulsions. Changes in anxiety, irritability, and hyperactivity were calculated for children aged 2–5 years using the Strengths and Difficulties Questionnaire. COVID-19 exposure, compliance with emergency measures, COVID-19 economic concerns, and stress from social isolation were measured with the CRISIS questionnaire. Prevalence of change in mental health status was estimated for each domain; multinomial logistic regression was used to determine variables associated with mental health status change in each domain. Depending on the age group, 67–70% of children/adolescents experienced deterioration in at least one mental health domain; however, 19–31% of children/adolescents experienced improvement in at least one domain. Children/adolescents without and with psychiatric diagnoses tended to experience deterioration during the first wave of COVID-19. Rates of deterioration were higher in those with a pre-exiting diagnosis. The rate of deterioration was variable across different age groups and pre-existing psychiatric diagnostic groups: depression 37–56%, anxiety 31–50%, irritability 40–66%, attention 40–56%, hyperactivity 23–56%, obsessions/compulsions 13–30%. Greater stress from social isolation was associated with deterioration in all mental health domains (all ORs 11.12–55.24). The impact of pre-existing psychiatric diagnosis was heterogenous, associated with deterioration in depression, irritability, hyperactivity, obsession/compulsions for some children (ORs 1.96–2.23) but also with improvement in depression, anxiety, and irritability for other children (ORs 2.13–3.12). Economic concerns were associated with improvement in anxiety, attention, and obsessions/compulsions (ORs 3.97–5.57). Children/adolescents with and without pre-existing psychiatric diagnoses reported deterioration. Deterioration was associated with increased stress from social isolation. Enhancing social interactions for children/adolescents will be an important mitigation strategy for current and future COVID-19 waves.

Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies-a consensus statement from the European Atherosclerosis Society

Abstract: Recent advances in human genetics, together with a large body of epidemiologic, preclinical, and clinical trial results, provide strong support for a causal association between triglycerides (TG), TG-rich lipoproteins (TRL), and TRL remnants, and increased risk of myocardial infarction, ischaemic stroke, and aortic valve stenosis. These data also indicate that TRL and their remnants may contribute significantly to residual cardiovascular risk in patients on optimized low-density lipoprotein (LDL)-lowering therapy. This statement critically appraises current understanding of the structure, function, and metabolism of TRL, and their pathophysiological role in atherosclerotic cardiovascular disease (ASCVD). Key points are (i) a working definition of normo- and hypertriglyceridaemic states and their relation to risk of ASCVD, (ii) a conceptual framework for the generation of remnants due to dysregulation of TRL production, lipolysis, and remodelling, as well as clearance of remnant lipoproteins from the circulation, (iii) the pleiotropic proatherogenic actions of TRL and remnants at the arterial wall, (iv) challenges in defining, quantitating, and assessing the atherogenic properties of remnant particles, and (v) exploration of the relative atherogenicity of TRL and remnants compared to LDL. Assessment of these issues provides a foundation for evaluating approaches to effectively reduce levels of TRL and remnants by targeting either production, lipolysis, or hepatic clearance, or a combination of these mechanisms. This consensus statement updates current understanding in an integrated manner, thereby providing a platform for new therapeutic paradigms targeting TRL and their remnants, with the aim of reducing the risk of ASCVD.

Countering Misinformation and Fake News Through Inoculation and Prebunking

Abstract: There has been increasing concern with the growing infusion of misinformation, or “fake news”, into public discourse and politics in many western democracies. Our article first briefly reviews the ...

Ozanimod as induction and maintenance therapy for ulcerative colitis.

Abstract: Background Ozanimod, a selective sphingosine-1-phosphate receptor modulator, is under investigation for the treatment of inflammatory bowel disease. Methods We conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial of ozanimod as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. In the 10-week induction period, patients in cohort 1 were assigned to receive oral ozanimod hydrochloride at a dose of 1 mg (equivalent to 0.92 mg of ozanimod) or placebo once daily in a double-blind manner, and patients in cohort 2 received open-label ozanimod at the same daily dose. At 10 weeks, patients with a clinical response to ozanimod in either cohort underwent randomization again to receive double-blind ozanimod or placebo for the maintenance period (through week 52). The primary end point for both periods was the percentage of patients with clinical remission, as assessed with the three-component Mayo score. Key secondary clinical, endoscopic, and histologic end points were evaluated with the use of ranked, hierarchical testing. Safety was also assessed. Results In the induction period, 645 patients were included in cohort 1 and 367 in cohort 2; a total of 457 patients were included in the maintenance period. The incidence of clinical remission was significantly higher among patients who received ozanimod than among those who received placebo during both induction (18.4% vs. 6.0%, P Conclusions Ozanimod was more effective than placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. (Funded by Bristol Myers Squibb; True North ClinicalTrials.gov number, NCT02435992.).

Recent advances and perspectives on thin electrolytes for high-energy-density solid-state lithium batteries

Abstract: Solid-state lithium batteries (SSLBs) are promising next-generation energy storage devices due to their potential for high energy density and improved safety. The properties and physical parameters of the solid-state electrolyte (SSE), as a critical component of the battery, have a significant effect on the electrochemical performance and energy density. In recent years, thick SSEs have been widely used in SSLBs but present several drawbacks in terms of increased internal resistance, additional inactive material content, low practical energy densities, and higher battery manufacturing costs. Reducing the thickness of SSEs and developing high-performance thin SSE-based SSLBs are essential for the commercialization of SSLBs. In this review, we comprehensively summarize the fabrication methods of thin SSEs, their rational design, and their manufacturing processes and applications in different SSLB systems. Moreover, advanced characterization techniques for understanding the Li+ transport kinetics and structural evolution of SSEs at the interface are introduced. Additionally, the gravimetric/volumetric energy densities for various SSLB pouch cells with SSEs less than 100 μm thick are evaluated. Lastly, other cell design parameters are tuned to achieve gravimetric/volumetric energy densities over 300 W h kg−1/500 W h L−1, and the future directions of thin SSEs in SSLBs are speculated upon.

Machine Learning Algorithms in Civil Structural Health Monitoring: A Systematic Review

Abstract: Applications of Machine Learning (ML) algorithms in Structural Health Monitoring (SHM) have become of great interest in recent years owing to their superior ability to detect damage and deficiencies in civil engineering structures. With the advent of the Internet of Things, big data and the colossal and complex backlog of aging civil infrastructure assets, such applications will increase very rapidly. ML can efficiently perform several analyses of clustering, regression and classification of damage in diverse structures, including bridges, buildings, dams, tunnels, wind turbines, etc. In this systematic review, the diverse ML algorithms used in this domain have been classified into two major subfields: vibration-based SHM and image-based SHM. The efficacy of deploying ML algorithms in SHM has been discussed and detailed critical analysis of ML applications in SHM has been provided. Accordingly, practical recommendations have been made and current knowledge gaps and future research needs have been outlined.

Thermochemical conversion of plastic waste to fuels: a review

Abstract: Plastics are common in our daily lifestyle, notably in the packaging of goods to reducing volume, enhancing transportation efficiency, keeping food fresh and preventing spoilage, manufacturing healthcare products, preserving drugs and insulating electrical components. Nonetheless, massive amounts of non-biodegradable plastic wastes are generated and end up in the environment, notably as microplastics. The worldwide industrial production of plastics has increased by nearly 80% since 2002. Based on the degree of recyclability, plastics are classified into seven major groups: polyethylene terephthalate, high-density polyethylene, polyvinyl chloride, low-density polyethylene, polypropylene, polystyrene and miscellaneous plastics. Recycling technologies can reduce the accumulation of plastic wastes, yet they also pollute the environment, consume energy, labor and capital cost. Here we review waste-to-energy technologies such as pyrolysis, liquefaction and gasification for transforming plastics into clean fuels and chemicals. We focus on thermochemical conversion technologies for the valorization of waste plastics. This technology reduces the diversion of plastics to landfills and oceans, reduces carbon footprints, and has high conversion efficiency and cost-effectiveness. Depending on the conversion method, plastics can be selectively converted either to bio-oil, bio-crude oil, synthesis gas, hydrogen or aromatic char. We discuss the influence of process parameters such as temperature, heating rate, feedstock concentration, reaction time, reactor type and catalysts. Reaction mechanisms, efficiency, merits and demerits of biological and thermochemical plastic conversion processes are also discussed.

Greenhouse-inspired supra-photothermal CO2 catalysis

Abstract: Converting carbon dioxide photocatalytically into fuels using solar energy is an attractive route to move away from a reliance on fossil fuels. Photothermal CO2 catalysis is one approach to achieve this, but improved materials that can more efficiently harvest and use solar energy are needed. Here, we report a supra-photothermal catalyst architecture—inspired by the greenhouse effect—that boosts the performance of a catalyst for CO2 hydrogenation compared to traditional photothermal catalyst designs. The catalyst consists of a nanoporous-silica-encapsulated nickel nanocrystal (Ni@p-SiO2), which is active for methanation and reverse water–gas shift reactions. Under illumination, the local temperatures achieved by Ni@p-SiO2 exceed those of Ni-based catalysts without the SiO2 shell. We suggest that the heat insulation and infrared shielding effects of the SiO2 sheath confine the photothermal energy of the nickel core, enabling a supra-photothermal effect. Catalyst sintering and coking is also lessened in Ni@p-SiO2, which may be due to spatial confinement effects. Light-driven catalytic conversion of CO2 to fuels and chemicals presents a way to reduce reliance on fossil fuels, but new strategies are needed to improve performance. Here the authors find that greenhouse effects can be exploited in photothermal catalysts to enhance their ability to produce methane and carbon monoxide.

Intersectionality in quantitative research: A systematic review of its emergence and applications of theory and methods.

Abstract: Background Intersectionality is a theoretical framework rooted in the premise that human experience is jointly shaped by multiple social positions (e.g. race, gender), and cannot be adequately understood by considering social positions independently. Used widely in qualitative studies, its uptake in quantitative research has been more recent. Objectives To characterize quantitative research applications of intersectionality from 1989 to mid-2020, to evaluate basic integration of theoretical frameworks, and to identify innovative methods that could be applied to health research. Methods Adhering to PRISMA guidelines, we conducted a systematic review of peer-reviewed articles indexed within Scopus, Medline, ProQuest Political Science and Public Administration, and PsycINFO. Original English-language quantitative or mixed-methods research or methods papers that explicitly applied intersectionality theoretical frameworks were included. Experimental studies on perception/stereotyping and measures development or validation studies were excluded. We extracted data related to publication, study design, quantitative methods, and application of intersectionality. Results 707 articles (671 applied studies, 25 methods-only papers, 11 methods plus application) met inclusion criteria. Articles were published in journals across a range of disciplines, most commonly psychology, sociology, and medical/life sciences; 40.8% studied a health-related outcome. Results supported concerns among intersectionality scholars that core theoretical tenets are often lost or misinterpreted in quantitative research; about one in four applied articles (26.9%) failed to define intersectionality, while one in six (17.5%) included intersectional position components not reflective of social power. Quantitative methods were simplistic (most often regression with interactions, cross-classified variables, or stratification) and were often misapplied or misinterpreted. Several novel methods were identified. Conclusions Intersectionality is frequently misunderstood when bridging theory into quantitative methodology. Further work is required to (1) ensure researchers understand key features that define quantitative intersectionality analyses, (2) improve reporting practices for intersectional analyses, and (3) develop and adapt quantitative methods.

All-solid-state lithium batteries enabled by sulfide electrolytes: from fundamental research to practical engineering design

Abstract: Sulfide electrolyte (SE)-based all-solid-state lithium batteries (ASSLBs) have gained worldwide attention because of their instrinsic safety and higher energy density over conventional lithium-ion batteries (LIBs). However, poor air stability of SEs, detrimental interfacial reactions, insufficient solid–solid ionic contact, and the large gap between fundamental study and practical engineering have impeded the commercialization of SE-based ASSLBs. This review aims to combine fundamental and engineering perspectives to rationally design practical SE-based ASSLBs with high energy density, covering SEs, interface, and practical all-solid-state pouch cells. First, the latest progress of typical pseudo-binary, pseudo-ternary, and pseudo-quaternary SEs is summarized, and effective strategies to improve ionic conductivity and chemical and electrochemical stability are highlighted. Moreover, challenges and strategies at the cathode and anode interfaces are reviewed separately. Furthermore, advanced in situ characterization techniques are examined to better understand the interface of ASSLBs. Encouraging demonstrations of SE-based all-solid-state lithium-ion and all-solid-state lithium–sulfur batteries are exemplified. Most importantly, energy-density-oriented all-solid-state pouch cells are designed using practical engineering parameters. The proposed design can serve as a quantitative framework to predict the practical energy density of SE-based all-solid-state pouch cells in future. Finally, future directions and our perspectives in SE-based ASSLBs are presented.

Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect

Abstract: The heart muscle diseases hypertrophic (HCM) and dilated (DCM) cardiomyopathies are leading causes of sudden death and heart failure in young, otherwise healthy, individuals. We conducted genome-wide association studies and multi-trait analyses in HCM (1,733 cases), DCM (5,521 cases) and nine left ventricular (LV) traits (19,260 UK Biobank participants with structurally normal hearts). We identified 16 loci associated with HCM, 13 with DCM and 23 with LV traits. We show strong genetic correlations between LV traits and cardiomyopathies, with opposing effects in HCM and DCM. Two-sample Mendelian randomization supports a causal association linking increased LV contractility with HCM risk. A polygenic risk score explains a significant portion of phenotypic variability in carriers of HCM-causing rare variants. Our findings thus provide evidence that polygenic risk score may account for variability in Mendelian diseases. More broadly, we provide insights into how genetic pathways may lead to distinct disorders through opposing genetic effects.

Guidelines for Reporting Trial Protocols and Completed Trials Modified Due to the COVID-19 Pandemic and Other Extenuating Circumstances: The CONSERVE 2021 Statement.

Abstract: Importance Extenuating circumstances can trigger unplanned changes to randomized trials and introduce methodological, ethical, feasibility, and analytical challenges that can potentially compromise the validity of findings. Numerous randomized trials have required changes in response to the COVID-19 pandemic, but guidance for reporting such modifications is incomplete. Objective As a joint extension for the CONSORT and SPIRIT reporting guidelines, CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstances) aims to improve reporting of trial protocols and completed trials that undergo important modifications in response to extenuating circumstances. Evidence A panel of 37 international trial investigators, patient representatives, methodologists and statisticians, ethicists, funders, regulators, and journal editors convened to develop the guideline. The panel developed CONSERVE following an accelerated, iterative process between June 2020 and February 2021 involving (1) a rapid literature review of multiple databases (OVID Medline, OVID EMBASE, and EBSCO CINAHL) and gray literature sources from 2003 to March 2021; (2) consensus-based panelist meetings using a modified Delphi process and surveys; and (3) a global survey of trial stakeholders. Findings The rapid review yielded 41 673 citations, of which 38 titles were relevant, including emerging guidance from regulatory and funding agencies for managing the effects of the COVID-19 pandemic on trials. However, no generalizable guidance for all circumstances in which trials and trial protocols might face unanticipated modifications were identified. The CONSERVE panel used these findings to develop a consensus reporting guidelines following 4 rounds of meetings and surveys. Responses were received from 198 professionals from 34 countries, of whom 90% (n = 178) indicated that they understood the concept definitions and 85.4% (n = 169) indicated that they understood and could use the implementation tool. Feedback from survey respondents was used to finalize the guideline and confirm that the guideline’s core concepts were applicable and had utility for the trial community. CONSERVE incorporates an implementation tool and checklists tailored to trial reports and trial protocols for which extenuating circumstances have resulted in important modifications to the intended study procedures. The checklists include 4 sections capturing extenuating circumstances, important modifications, responsible parties, and interim data analyses. Conclusions and Relevance CONSERVE offers an extension to CONSORT and SPIRIT that could improve the transparency, quality, and completeness of reporting important modifications to trials in extenuating circumstances such as COVID-19.