In this study, the self-healing behavior of fiber-reinforced mortars incorporating crystalline additives under various temperatures and relative humidities was investigated. Optical microscopy, scanning electron microscopy with energy dispersive X-ray (SEM–EDS) analysis, were conducted to evaluate and characterize the self-healing. Pre-cracked reference specimens were cured underwater, while identical specimens were subjected to cyclic temperature and relative humidity. Results show that specimens incorporating crystalline additives exhibited more significant crack-healing after water submersion compared to that of the control specimens. In contrast, no considerable crack self-healing occurred in both control and specimens incorporating crystalline additives when exposed to cyclic temperature and relative humidity. SEM–EDS analysis confirmed that the main self-healing compound was calcium carbonate. It was found that the exposure environments of specimens played an essential role in crack self-healing.
Differential settlement could be triggered by many factors within the soil strata, including frost heave, seismic activities, collapse of sinkholes, poorly compacted soil, or adjacent excavation activities. Such activities result in an uneven relaxation within the soil, forming undesirable settlements and imposing stress conditions, which are unaccounted for in the design process. Ground settlements can inflict serious, and in some cases, irreparable damage to pre-existing structures. Understanding the impact such settlements could have on structural systems is vital in developing effective preventative measures that would help mitigate such effects. Hence, this study investigates the effects of the differential settlement on a reinforced concrete framed structure by examining the structural behaviour considering different spans and heights. The nonlinear behaviour of the structure is simulated through two-dimensional (2D) frame finite element simulations. The propagation of mechanical damage within the structural members and the plastic hinge formation with respect to the induced settlements are then analyzed. The affect of ductility on the frame’s behaviour is demonstrated, and comparisons with settlement tolerances proposed in literature are drawn to assess the effectiveness of these limits.
The Middle Road Bridge, constructed in 1909 on present-day Sherway Drive to span Etobicoke Creek between Toronto and Mississauga, was recognized as a CSCE Civil Engineering Historic Site in 2009. The official CSCE plaque for this structure will be unveiled at the 2021 Annual Conference and subsequently installed on site. The Toronto firm Barber & Young designed the bridge, the first reinforced-concrete tied-arch-truss (or “rainbow”) bridge built in North America. The paper describes some of the design and construction innovations in the structure and the professional lives of James Franklin Barber (1875–1945) and Clarence Richard Young (1869–1964), who left the partnership in 1911 to become Professor of Civil Engineering at the University of Toronto and, subsequently, Dean of the Faculty of Applied Science and Engineering from 1941 to 1949.
Ingestion of amatoxin-containing mushrooms can lead to fulminant hepatotoxicity and death. Despite recent interest in therapeutic options for amatoxin-exposed patients, there is no single, recommended treatment for amatoxin poisoning. Alpha-amanitin, the principal toxin in amatoxin-containing mushrooms, requires entry into hepatocytes via organic anion transporting polypeptide (OATP) 1B3 before the cascade of cellular events occurs leading to hepatocyte necrosis, liver failure, and in severe cases liver transplantation or death. Three patients managed through a single poison centre with confirmed amatoxin-containing mushrooms ingestions were treated with intravenous cyclosporine, a known potent OATP1B3 inhibitor, along with supportive care. All patients presented with classic delayed symptoms of nausea, vomiting and diarrhea. No patient progressed to fulminant hepatic failure, although two patients developed a transient rise in liver transaminases. All recovered and were discharged from hospital. No patient had an adverse effect from cyclosporine. In addition, we performed an in-vitro study of the role of cyclosporine in cultured HEK293T cells and human hepatoma Huh7 cells. Cyclosporine effectively inhibited OATP1B3-mediated uptake of alpha-amanitin, and improved cell viability of alpha-amanitin exposed cultured Huh7 cells. We conclude that IV cyclosporine, a drug readily available in most hospitals, may be useful to reduce hepatotoxicity from amatoxin poisoning.
High-fidelity translation was considered a requirement for living cells. The frozen accident theory suggested that any deviation from the standard genetic code should result in the production of so much mis-made and non-functional proteins that cells cannot remain viable. Studies in bacterial, yeast, and mammalian cells show that significant levels of mistranslation (1-10% per codon) can be tolerated or even beneficial under conditions of oxidative stress. Single tRNA mutants, which occur naturally in the human population, can lead to amino acid mis-incorporation at a codon or set of codons. The rate or level of mistranslation can be difficult or impossible to measure in live cells. We developed a novel red fluorescent protein reporter that is sensitive to serine (Ser) mis-incorporation at proline (Pro) codons. The mCherry Ser151Pro mutant is efficiently produced in Escherichia coli but non-fluorescent. We demonstrated in cells and with purified mCherry protein that the fluorescence of mCherry Ser151Pro is rescued by two different tRNASer gene variants that were mutated to contain the Pro (UGG) anticodon. Ser mis-incorporation was confirmed by mass spectrometry. Remarkably, E. coli tolerated mistranslation rates of ~10% per codon with negligible reduction in growth rate. Conformational sampling simulations revealed that the Ser151Pro mutant leads to significant changes in the conformational freedom of the chromophore precursor, which is indicative of a defect in chromophore maturation. Together our data suggest that the mCherry Ser151 mutants may be used to report Ser mis-incorporation at multiple other codons, further expanding the ability to measure mistranslation in living cells.
Background: Systemic oppression, particularly towards sexual minorities, continues to be deeply rooted in the bedrock of many societies globally. Experiences with minority stressors (e.g. discrimination, hate-crimes, internalized homonegativity, rejection sensitivity, and microaggressions or everyday indignities) have been consistently linked to adverse mental health outcomes. Elucidating the neural adaptations associated with minority stress exposure will be critical for furthering our understanding of how sexual minorities become disproportionately affected by mental health burdens. Methods: Following PRISMA-guidelines, we systematically reviewed published neuroimaging studies that compared neural dynamics among sexual minority and heterosexual populations, aggregating information pertaining to any measurement of minority stress and relevant clinical phenomena. Results: Only 1 of 13 studies eligible for inclusion examined minority stress directly, where all other studies focused on investigating the neurobiological basis of sexual orientation. In our narrative synthesis, we highlight important themes that suggest minority stress exposure may be associated with decreased activation and functional connectivity within the default-mode network (related to the sense-of-self and social cognition), and summarize preliminary evidence related to aberrant neural dynamics within the salience network (involved in threat detection and fear processing) and the central executive network (involved in executive functioning and emotion regulation). Importantly, this parallels neural adaptations commonly observed among individuals with posttraumatic stress disorder (PTSD) in the aftermath of trauma and supports the inclusion of insidious forms of trauma related to minority stress within models of PTSD. Conclusions: Taken together, minority stress may have several shared neuropsychological pathways with PTSD and stress-related disorders. Here, we outline a detailed research agenda that provides an overview of literature linking sexual minority stress to PTSD and insidious trauma, moral affect (including shame and guilt), and mental health risk/resiliency, in addition to racial, ethnic, and gender related minority stress. Finally, we propose a novel minority mosaic framework designed to inform future directions of minority stress neuroimaging research from an intersectional lens.
Background Clinical endpoints for upcoming therapeutic trials in frontotemporal dementia (FTD) are increasingly urgent. Cognitive composite scores are often used as endpoints but are lacking in genetic FTD. We aimed to create cognitive composite scores for genetic frontotemporal dementia (FTD) as well as recommendations for recruitment and duration in clinical trial design. Methods A standardized neuropsychological test battery covering six cognitive domains was completed by 69 C9orf72 , 41 GRN , and 28 MAPT mutation carriers with CDR® plus NACC-FTLD ≥ 0.5 and 275 controls. Logistic regression was used to identify the combination of tests that distinguished best between each mutation carrier group and controls. The composite scores were calculated from the weighted averages of test scores in the models based on the regression coefficients. Sample size estimates were calculated for individual cognitive tests and composites in a theoretical trial aimed at preventing progression from a prodromal stage (CDR® plus NACC-FTLD 0.5) to a fully symptomatic stage (CDR® plus NACC-FTLD ≥ 1). Time-to-event analysis was performed to determine how quickly mutation carriers progressed from CDR® plus NACC-FTLD = 0.5 to ≥ 1 (and therefore how long a trial would need to be). Results The results from the logistic regression analyses resulted in different composite scores for each mutation carrier group (i.e. C9orf72 , GRN , and MAPT ). The estimated sample size to detect a treatment effect was lower for composite scores than for most individual tests. A Kaplan-Meier curve showed that after 3 years, ~ 50% of individuals had converted from CDR® plus NACC-FTLD 0.5 to ≥ 1, which means that the estimated effect size needs to be halved in sample size calculations as only half of the mutation carriers would be expected to progress from CDR® plus NACC FTLD 0.5 to ≥ 1 without treatment over that time period. Discussion We created gene-specific cognitive composite scores for C9orf72 , GRN , and MAPT mutation carriers, which resulted in substantially lower estimated sample sizes to detect a treatment effect than the individual cognitive tests. The GENFI-Cog composites have potential as cognitive endpoints for upcoming clinical trials. The results from this study provide recommendations for estimating sample size and trial duration.
Background Food Protein-Induced Enterocolitis Syndrome (FPIES) is a non-IgE mediated food allergy most commonly presenting in infants. The most common food triggers include soy, cow’s milk and grains. Symptoms may include intractable vomiting, diarrhea, lethargy, pallor, abdominal distention, hypotension and/or shock. Oral food challenges (OFCs) given at food protein dose of 0.06–0.6 g/kg in 3 equivalent doses administered over a few hours are recommended in guidelines to confirm a diagnosis. Case presentation The patient is a 6-month-old girl with a history of severe FPIES symptoms to egg. In our clinic, we perform OFC with 1/100 serving dose on visit 1 and then increase the dose monthly. The patient takes the tolerated dose daily at home between visits. An OFC to baked egg at 1/100 of a serving was performed and was well-tolerated on her initial visit. The patient remained on the same dose upon returning home. Within 1-week, she developed FPIES symptoms including watery diarrhea and severe emesis requiring ondansetron. She required an Emergency Department visit for one of the reactions. Conclusions Our patient had severe FPIES symptoms with a small amount of egg. We believe that administration of three large food challenge doses on one clinic visit, as guidelines currently suggest, does not allow adequate time for symptoms to appear. Our patient likely would have suffered a severe reaction. Also, this guidelines protocol does not allow for monitoring of more delayed or chronic FPIES. We propose a modified protocol to OFCs with cautious up-dosing to allow for safer OFCs and monitoring of chronic FPIES. We have implemented an OFC approach where only one food challenge dose (starting with 1/100 of final dose) is given at each visit. The up-titration of the dose is completed every 4-weeks with one dose only. When the serving sized dose is reached and tolerated, the food can be maintained in the diet.
Background: The aim of this study was to evaluate speech outcomes following surgical intervention for velopharyngeal dysfunction (VPD). Perceptual speech outcome data were subsequently analyzed in conjunction with patient factors such as congenital abnormalities, presence of cleft lip and/or palate, and age of repair. We hope to aid in the eventual creation of treatment algorithms for VPD, allowing practitioners to tailor surgical technique selection to patient factors. Methods: A retrospective analysis was performed for all patients who underwent surgical correction of VPD at London Health Sciences Centre between the years 2005 and 2018. Two hundred and two consecutive VPD patients (median age 10.6 years) were followed for an average of 20.2 months after having undergone a superiorly based pharyngeal flap (121), Furlow palatoplasty (72), or sphincteroplasty (9). Speech outcomes were measured via the American Cleft Palate-Craniofacial Association (ACPA) perceptual speech assessment, and MacKay-Kummer Simplified Nasometric Assessment Procedures Revised (SNAP-R) was used to measure nasalence. Comparisons of mean preoperative and postoperative outcomes were made, as well as analyses regarding surgical procedure, syndrome, cleft status, and age. Results: Mean perceptual scores improved significantly postoperatively (p < .0001), and successful perceptual resonance was identified in 86.1% patients (n = 174). Postoperative perceptual speech scores for three ACPA domains were superior with pharyngeal flap compared to both Furlow palatoplasty and sphincteroplasty ([hypernasality: p < .001, p < .02], [audible nasal emissions: p < .002, p < .05], [velopharyngeal function: p < .001, p < .05]). Success rate was higher in pharyngeal flap (94.2%) than in Furlow palatoplasty (75.0%, p < .001) or sphincter pharyngoplasty (66.7%, p < .001). No significant difference was identified in success rate based on syndrome or cleft status. Conclusion: Operative management of VPD is highly effective in improving perceptual speech outcomes. Given proper patient selection, all three procedures are viable treatment options for VPD. For those patients identified as appropriate to undergo a pharyngeal flap, robust improvements in speech outcomes were observed.
Background In the era of COVID-19, utilization of telemedicine has dramatically increased. In addition to reduced travel times, patient expenses, and work or school days missed, telemedicine allows clinicians to provide continued care while minimizing face-to-face interactions, maintaining social distancing, and limiting potential COVID-19 exposures. Clinical Immunology and Allergy (CIA), like many specialties, has adapted to incorporate telemedicine into practice. Previous studies have demonstrated similar patient satisfaction between virtual and in-person visits. However, evidence from fully publicly funded health care systems such as Canada has been limited. Methods We performed a quality improvement (QI) initiative to assess the feasibility of telemedicine. Between 1 March and 30 September 2020, patient encounters of two academic allergists at a single institution in London, Ontario, Canada were analyzed. Assessments were categorized into in-person or telemedicine appointments. A random sample of patients assessed virtually completed a voluntary patient satisfaction survey. Qualitative analysis was performed on survey comments. Results In total 3342 patients were seen. The majority were adults (n = 2162, or 64.7%) and female (n = 1872, or 56%). 1543 (46.2%) assessments were virtual and 1799 (53.8%) assessments were in-person. 67 of 100 random patient surveys sent to those in the virtual assessment group were completed. 89.6% (n = 60) agreed or strongly agreed when asked if they were satisfied with their telemedicine visit. 64.2% (n = 43) felt they received the same level of care compared to in-person assessments and 91% (n = 61) stated they would attend another virtual appointment. 95.4% (n = 62) of patients reported saving time with virtual assessment, the majority (n = 42, 62.7%) estimating between 1–4 h saved. Reported shortcomings included technical difficulties, “feeling rushed”, and missing in-person interactions. Conclusions Our quality improvement initiative demonstrated high patient satisfaction and time savings with virtual assessment in a publicly funded health care system. Studies suggest that CIA may be uniquely situated to benefit from permanent integration of virtual care into regular practice for both new and follow-up appointments. We anticipate continued increased utilization of telemedicine, signifying a lasting beneficial change in the delivery of healthcare.
Anaplastic thyroid cancer (ATC) is a rare, aggressive form of undifferentiated thyroid cancer, which exhibits rapid progression and is almost universally fatal. At least a subset of ATC is thought to arise from pre-existing well-differentiated thyroid cancer, most frequently papillary thyroid cancer (PTC). While PIK3CA mutations are rare in PTC, they are common in ATC and tend to co-occur with BRAF mutations. This provided the rationale for our study to identify the potential role of PIK3CA mutations in the progression from well-differentiated to undifferentiated thyroid cancer. We introduced PIK3CA E545K into the LAM1 PTC cell line, which carries a BRAF V600E mutation. In culture, the engineered cell line (LAM1: PIK3CA E545K ) proliferated faster and demonstrated increased clonogenic potential relative to the parental line carrying an empty vector (LAM1 EV ). Both the LAM1 EV and LAM1: PIK3CA E545K edited lines were implanted into hind flanks of athymic nude mice for in vivo determination of disease progression. While tumour weights and volumes were not significantly higher in LAM1: PIK3CA E545K mice, there was a decrease in expression of thyroid differentiation markers TTF-1, thyroglobulin, PAX8 and B-catenin, suggesting that introduction of PIK3CA E545K led to dedifferentiation in vivo. Collectively, this study provides evidence of a role for PIK3CA E545K in driving disease progression from a well-differentiated to an undifferentiated thyroid cancer; however, over-expression was not a determinant of an accelerated growth phenotype in ATC. Graphical Abstract
Recently, in Winnipeg, the implementation of new bus rapid transit (BRT) system in the middle of the COVID-19 pandemic has raised many concerns, challenging the rationale behind the untimely release. However, the new BRT service can benefit low-income, socio-economically vulnerable, and transit captive passengers who must travel to essential services and work opportunities during the pandemic. This study evaluates whether the new BRT system has positive impacts on accessibility to such essential services during the pandemic. Isochrones with different time budgets as well as times of a day are generated based on high-resolution public transit network via the General Transit Feed Specification (GTFS) data and used for evaluating accessibility benefits before and after the BRT construction. The new BRT service in Winnipeg demonstrates varying accessibility impacts across different parts of the BRT corridor. Areas near dedicated lane-section show a significant increase, whereas areas near non-dedicated lane sections show a decrease in accessibility. Nevertheless, across the whole BRT corridor, the new BRT service presents an overall increase in accessibility to essential services. This demonstrates the positive accessibility benefits of the new BRT service to residents seeking essential services during the COVID-19 pandemic. A decrease in accessibility along some parts suggests the necessity of using local transit improvement strategies (e.g., dedicated lanes) to improve service speed when planning BRT services within urban areas.
Purpose This systematic review and meta-analysis aimed to study surgical site infection of wound closure using staples versus sutures in elective knee and hip arthroplasties. Methods A systematic literature review was performed to search for randomized controlled trials that compared surgical site infection after wound closure using staples versus sutures in elective knee and hip arthroplasties. The primary outcome was surgical site infection. The risk of bias was assessed with the Cochrane risk of bias assessment tool. The relative risk and 95% confidence interval with a random-effects model were assessed. Results Eight studies were included in this study, including 2 studies with a low risk of bias, 4 studies having ‘some concerns’, and 2 studies with high risk of bias. Significant difference was not found in the risk of SSI for patients with staples (n = 557) versus sutures (n = 573) (RR: 1.70, 95% CI: 0.94–3.08, I ² = 16%). The results were similar after excluding the studies with a high risk of bias (RR: 1.67, 95% CI: 0.91–3.07, I ² = 32%). Analysis of studies with low risk of bias revealed a significantly higher risk of surgical site infection in patients with staples ( n = 331) compared to sutures ( n = 331) (RR: 2.56, 95% CI: 1.20–5.44, I ² = 0%). There was no difference between continuous and interrupted sutures ( P > 0.05). In hip arthroplasty, stapling carried a significantly higher risk of surgical site infection than suturing (RR: 2.51, 95% CI: 1.15–5.50, I ² = 0%), but there was no significant difference in knee arthroplasty (RR: 0.87, 95% CI: 0.33–2.25, I ² = 22%; P > 0.05). Conclusions Stapling might carry a higher risk of surgical site infection than suturing in elective knee and hip arthroplasties, especially in hip arthroplasty.
The COVID-19 pandemic necessitated school closures globally, resulting in an abrupt move to online/distance teaching or emergency remote teaching (ERT). Teachers and students pivoted from face-to-face engagement to online environments, thus impacting curriculum, pedagogy, and student outcomes across a variety of disciplines. In this paper, the authors focus on science/STEM teachers’ experiences with online teaching and learning in a Canadian context during the pandemic. Qualitative and quantitative data were collected through an online questionnaire administered to 75 Grade 1–12 science/STEM teachers in a Canadian province in May–July 2020. Through the TPACK framework and self-efficacy theory, the authors explore i) curriculum planning and implementation in online settings, ii) assessment practices and their effectiveness, and iii) student outcomes, as observed by the teachers. Results indicate that teachers used a variety of platforms, and choice of platform was mainly due to user-friendliness and interactivity, or administrative decision making. Despite teachers organizing online lessons during ERT, gaps were identified in teachers’ TPACK framework and self-efficacy, thus impacting their curriculum development, pedagogical approaches, and assessment practices. In general, teaching strategies included pre-recorded videos and self-directed learning in which teachers assigned specific tasks for students to perform independently. Teachers prioritized subject content and covering curriculum objectives over creative and student-centered pedagogical approaches. Assessment techniques employed were viewed by teachers as unauthentic and generally ineffective. Moreover, teachers reported difficulties addressing student needs and abilities, resulting in challenges providing equitable and inclusive online teaching. Finally, online teaching was viewed negatively by most teachers, in terms of student engagement and outcomes.
Stainless steel ASTM 316 L is often used in the food industry as contact material with protein-rich dairy products. It has to be welded at some locations for many of these contact materials. This study aimed at i) determining any combined effects of the presence of whey protein (WP) and welding-induced weaknesses on corrosion and metal release, and ii) determining the appropriate welding procedure and filler metal (316 L, 309 L, 312). All weld metals (WMs) showed a higher pitting corrosion susceptibility as compared to the base metal (BM). Under induced friction (stirring), WP significantly enhanced the metal release from all materials, which was accelerated between 1 and 3 days of exposure. Post-imaging indicated pits. 312-WM released significantly higher amounts of metals as compared to the BM and the other WMs. This study indicated that the presence of WP, friction, and weldment-induced corrosion susceptibilities could synergistically cause metal release and corrosion of food contact materials.
Computational semantics, a branch of computational linguistics, involves automated meaning analysis that relies on how words occur together in natural language. This offers a promising tool to study schizophrenia. At present, we do not know if these word-level choices in speech are sensitive to the illness stage (i.e., acute untreated vs. stable established state), track cognitive deficits in major domains (e.g., cognitive control, processing speed) or relate to established dimensions of formal thought disorder. In this study, we collected samples of descriptive discourse in patients experiencing an untreated first episode of schizophrenia and healthy control subjects (246 samples of 1-minute speech; n = 82, FES = 46, HC = 36) and used a co-occurrence based vector embedding of words to quantify semantic similarity in speech. We obtained six-month follow-up data in a subsample (99 speech samples, n = 33, FES = 20, HC = 13). At baseline, semantic similarity was evidently higher in patients compared to healthy individuals, especially when social functioning was impaired; but this was not related to the severity of clinically ascertained thought disorder in patients. Across the study sample, higher semantic similarity at baseline was related to poorer Stroop performance and processing speed. Over time, while semantic similarity was stable in healthy subjects, it increased in patients, especially when they had an increasing burden of negative symptoms. Disruptions in word-level choices made by patients with schizophrenia during short 1-min descriptions are sensitive to interindividual differences in cognitive and social functioning at first presentation and persist over the early course of the illness.
Precisely reducing the size of metal-organic frameworks (MOFs) derivatives is an effective strategy to manipulate their phase engineering owing to size-dependent oxidation; however, the underlying relationship between the size of derivatives and phase engineering has not been clarified so far. Herein, a spatial confined growth strategy is proposed to encapsulate small-size MOFs derivatives into hollow carbon nanocages. It realizes that the hollow cavity shows a significant spatial confinement effect on the size of confined MOFs crystals and subsequently affects the dielectric polarization due to the phase hybridization with tunable coherent interfaces and heterojunctions owing to size-dependent oxidation motion, yielding to satisfied microwave attenuation with an optimal reflection loss of −50.6 dB and effective bandwidth of 6.6 GHz. Meanwhile, the effect of phase hybridization on dielectric polarization is deeply visualized, and the simulated calculation and electron holograms demonstrate that dielectric polarization is shown to be dominant dissipation mechanism in determining microwave absorption. This spatial confined growth strategy provides a versatile methodology for manipulating the size of MOFs derivatives and the understanding of size-dependent oxidation-induced phase hybridization offers a precise inspiration in optimizing dielectric polarization and microwave attenuation in theory.
One of the most important and common criteria for evaluating the emergency medical systems is the response time, which is a function of the availability of an ambulance at the time of the request and the time that it takes for the ambulance to arrive at the call location. In this study, an optimization model is proposed to deal with the problem of the emergency medical service stations’ location and ambulance allocation. In order to capture the impacts of uncertainty in the network and obtain more realistic results, it is assumed that medical aid demands from any location in the city at any time slot of the day have a probabilistic distribution. In addition, to consider the traffic fluctuations in the modeling process, it is assumed that the arrival time to the request location is a time dependent variable. To deal with the complexity of the proposed approach and find optimal solutions in a reasonable execution time, some heuristic algorithms are suggested to solve the ambulance routing problem and the proposed non-linear integer model. To show the applicability of proposed models and algorithms in large-scale networks, the models and algorithms have been applied to the emergency medical system of the city of Isfahan, Iran. Three different scenarios are defined to improve the performance of the emergency medical services in Isfahan. The results show that relocating emergency medical service stations and reallocating ambulances will lead to significant improvements in both response time and coverage area in Isfahan.
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