Identification of damage within a structure requires extraction of damage-sensitive features and recognition of patterns in the collected information. In recent years, deep learning-based methods, particularly Convolutional Neural Networks (CNNs) have proved to be remarkable tools in finding the underlying patterns in raw data and establishing accurate mapping between the data and various damage indicators. This study examines the performance of CNNs when the time-frequency information obtained from Continuous Wavelet Transformation (CWT) is employed as input data for prediction of the presence and location of damage in a beam-like structure. The CWT data from the acceleration reflect the variations in the modal properties of the structure and the characteristics of external excitations and measurement noise over time. This can help the network to distinguish different damage cases. For verification of the proposed approach, the acceleration data obtained from finite element dynamic analyses of a simply supported beam under random excitation are utilized where damage is induced in the form of loss in the flexural stiffness of elements. The input to the CNN architecture is a 3D block of CWT data of multiple accelerometers and the network is trained to output the presence and location of damage across the beam. By considering different levels of damage and number of measurement points, it is demonstrated that high detection accuracy can be achieved. Also, robustness of the technique against noisy data is investigated where the acceleration data are intentionally corrupted by added random noise to simulate actual conditions.
Concrete-filled fibre-reinforced polymer (FRP) tubes are used as hybrid structural elements in the form of piles, columns, and girders. The concrete-filled FRP tube (CFFT) utilizes the best characteristics of both the FRP and the concrete. Several experimental, analytical, and numerical investigations have been conducted to develop models that can predict the confining effect of the FRP tubes. Although the available numerical investigations are reported capable of modeling the confinement with high accuracy, none of them is able to predict the failure mechanism of the CFFT. In this paper, a new numerical model is developed, employing the commercial finite element software ABAQUS, to investigate performance and failure of CFFTs under axial compression. In the CFFT system investigated, the FRP tube is modeled as a 3D object with its two components—the matrix and the fibres—modeled separately. The fibres are modeled as wires embedded in the matrix. This helps to properly model the damage that occurs in the matrix as the CFFT fails. The new model uses concrete damage plasticity (CDP) while assuming brittle fracture of the FRP. Results of a previous series of tests on CFFT specimens with different dimensions are used to verify the numerical model. It is shown that the new model is capable of predicting the stress–strain curve of the CFFT as well as its failure mechanism. Utilization of this model can help understand the confinement effects on the concrete in more detail and eliminate the arduous efforts to build and test physical models experimentally.
Design of the connections in bridges is always of great importance to bridge engineers. Since the use of double-headed studs is proven to be more efficient than conventional reinforcement such as stirrups and rebars, using them as the slab-to-girder connector was never investigated. Therefore, a set of experiments were performed at the University of Calgary in order to investigate the effectiveness of steel double-headed studs under shear force. Four large-scale slab-on-beam specimens were cast and loaded up to failure under static loading. The specimens were made up of prestressed concrete beams connected to reinforced concrete slab using double-headed studs. All the specimens had the same dimensions and properties while they had different arrangements of the studs in order to inspect the effects of studs’ inclination and spacing on their performance. A set of 36 mechanical slip gauges were installed on each slab-on-beam specimen to measure the slip that happens in each case. The tests showed that the double-headed studs, if used with sufficient spacing, can transfer the loads from the slab to the girder properly and make these two members act and deflect together. Also, it was shown that the inclination of the studs significantly improves the performance of the specimens under static loading. Based on the results, the double-headed studs can be used as a replacement for conventional reinforcement used for connecting the slab and the girders in bridge structures.
Alterations in brain/gut/microbiota axis are linked to Irritable Bowel Syndrome (IBS) physiopathology. Upon gastrointestinal infection, chronic abdominal pain and anxio-depressive comorbidities may persist despite pathogen clearance leading to Post-Infectious IBS (PI-IBS). This study assesses the influence of tryptophan metabolism, and particularly the microbiota-induced AhR expression, on intestinal homeostasis disturbance following gastroenteritis resolution, and evaluates the efficacy of IL-22 cytokine vectorization on PI-IBS symptoms. The Citrobacter rodentium infection model in C57BL6/J mice was used to mimic Enterobacteria gastroenteritis. Intestinal homeostasis was evaluated as low-grade inflammation, permeability, mucosa-associated microbiota composition, and colonic sensitivity. Cognitive performances and emotional state of animals were assessed using several tests. Tryptophan metabolism was analyzed by targeted metabolomics. AhR activity was evaluated using a luciferase reporter assay method. One Lactococcus lactis strain carrying an eukaryotic expression plasmid for murine IL-22 (L. lactisIL-22) was used to induce IL-22 production in mouse colonic mucosa. C. rodentium-infected mice exhibited persistent colonic hypersensitivity and cognitive impairments and anxiety-like behaviors after pathogen clearance. These post-infectious disorders were associated with low-grade inflammation, increased intestinal permeability, decrease of Lactobacillaceae abundance associated with the colonic layer, and increase of short-chain fatty acids (SCFAs). During post-infection period, the indole pathway and AhR activity were decreased due to a reduction of tryptophol production. Treatment with L. lactisIL-22 restored gut permeability and normalized colonic sensitivity, restored cognitive performances and decreased anxiety-like behaviors. Data from the video-tracking system suggested an upgrade of welfare for mice receiving the L.lactisIL-22 strain. Our findings revealed that AhR/IL-22 signaling pathway is altered in a preclinical PI-IBS model. IL-22 delivering alleviate PI-IBS symptoms as colonic hypersensitivity, cognitive impairments, and anxiety-like behaviors by acting on intestinal mucosa integrity. Thus, therapeutic strategies targeting this pathway could be developed to treat IBS patients suffering from chronic abdominal pain and associated well-being disorders.
Recent rodent microbiome experiments suggest that besides Akkermansia, Parasutterella sp. are important in type 2 diabetes and obesity development. In the present translational human study, we aimed to characterize Parasutterella in our European cross-sectional FoCus cohort (n = 1,544) followed by validation of the major results in an independent Canadian cohort (n = 438). In addition, we examined Parasutterella abundance in response to a weight loss intervention (n = 55). Parasutterella was positively associated with BMI and type 2 diabetes independently of the reduced microbiome α/β diversity and low-grade inflammation commonly found in obesity. Nutritional analysis revealed a positive association with the dietary intake of carbohydrates but not with fat or protein consumption. Out of 126 serum metabolites differentially detectable by untargeted HPLC-based MS-metabolomics, L-cysteine showed the strongest reduction in subjects with high Parasutterella abundance. This is of interest, since Parasutterella is a known high L-cysteine consumer and L-cysteine is known to improve blood glucose levels in rodents. Furthermore, metabolic network enrichment analysis identified an association of high Parasutterella abundance with the activation of the human fatty acid biosynthesis pathway suggesting a mechanism for body weight gain. This is supported by a significant reduction of the Parasutterella abundance during our weight loss intervention. Together, these data indicate a role for Parasutterella in human type 2 diabetes and obesity, whereby the link to L-cysteine might be relevant in type 2 diabetes development and the link to the fatty acid biosynthesis pathway for body weight gain in response to a carbohydrate-rich diet in obesity development.
The small intestinal epithelial barrier inputs signals from the gut microbiota in order to balance physiological inflammation and tolerance, and to promote homeostasis. Understanding the dynamic relationship between microbes and intestinal epithelial cells has been a challenge given the cellular heterogeneity associated with the epithelium and the inherent difficulty of isolating and identifying individual cell types. Here, we used single-cell RNA sequencing of small intestinal epithelial cells from germ-free and specific pathogen-free mice to study microbe-epithelium crosstalk at the single-cell resolution. The presence of microbiota did not impact overall cellular composition of the epithelium, except for an increase in Paneth cell numbers. Contrary to expectations, pattern recognition receptors and their adaptors were not induced by the microbiota but showed concentrated expression in a small proportion of epithelial cell subsets. The presence of the microbiota induced the expression of host defense- and glycosylation-associated genes in distinct epithelial cell compartments. Moreover, the microbiota altered the metabolic gene expression profile of epithelial cells, consequently inducing mTOR signaling thereby suggesting microbe-derived metabolites directly activate and regulate mTOR signaling. Altogether, these findings present a resource of the homeostatic transcriptional and cellular impact of the microbiota on the small intestinal epithelium.
Background Whether the fundamental hematological and cardiac variables determining cardiorespiratory fitness and their intrinsic relationships are modulated by major constitutional factors, such as sex and age remains unresolved. Methods Transthoracic echocardiography, central hemodynamics and pulmonary oxygen (O 2 ) uptake were assessed in controlled conditions during submaximal and peak exercise (cycle ergometry) in 85 healthy young (20–44 year) and older (50–77) women and men matched by age-status and moderate-to-vigorous physical activity (MVPA) levels. Main outcomes such as peak left ventricular end-diastolic volume (LVEDV peak ), stroke volume (SV peak ), cardiac output ( Q peak ) and O 2 uptake (VO 2peak ), as well as blood volume (BV), BV–LVEDV peak and LVEDV peak –SV peak relationships were determined with established methods. Results All individuals were non-smokers and non-obese, and MVPA levels were similar between sex and age groups ( P ≥ 0.140). BV per kg of body weight did not differ between sexes ( P ≥ 0.118), but was reduced with older age in men ( P = 0.018). Key cardiac parameters normalized by body size (LVEDV peak , SV peak , Q peak ) were decreased in women compared with men irrespective of age ( P ≤ 0.046). Older age per se curtailed Q peak ( P ≤ 0.022) due to lower heart rate ( P < 0.001). In parallel, VO 2peak was reduced with older age in both sexes ( P < 0.001). The analysis of fundamental circulatory relationships revealed that older women require a higher BV for a given LVEDV peak than older men ( P = 0.024). Conclusions Sex and age interact on the crucial circulatory relationship between total circulating BV and peak cardiac filling, with older women necessitating more BV to fill the exercising heart than age- and physical activity-matched men.
Background Despite the growing utility of cardiovascular magnetic resonance (CMR) for cardiac morphology and function, sex and age-specific normal reference values derived from large, multi-ethnic data sets are lacking. Furthermore, most available studies use a simplified tracing methodology. Using a large cohort of participants without history of cardiovascular disease (CVD) or risk factors from the Canadian Alliance for Healthy Heart and Minds, we sought to establish a robust set of reference values for ventricular and atrial parameters using an anatomically correct contouring method, and to determine the influence of age and sex on ventricular parameters. Methods and results Participants (n = 3206, 65% females; age 55.2 ± 8.4 years for females and 55.1 ± 8.8 years for men) underwent CMR using standard methods for quantitative measurements of cardiac parameters. Normal ventricular and atrial reference values are provided: (1) for males and females, (2) stratified by four age categories, and (3) for different races/ethnicities. Values are reported as absolute, indexed to body surface area, or height. Ventricular volumes and mass were significantly larger for males than females (p < 0.001). Ventricular ejection fraction was significantly diminished in males as compared to females (p < 0.001). Indexed left ventricular (LV) end-systolic, end-diastolic volumes, mass and right ventricular (RV) parameters significantly decreased as age increased for both sexes (p < 0.001). For females, but not men, mean LV and RVEF significantly increased with age (p < 0.001). Conclusion Using anatomically correct contouring methodology, we provide accurate sex and age-specific normal reference values for CMR parameters derived from the largest, multi-ethnic population free of CVD to date. Clinical trial registration ClinicalTrials.gov, NCT02220582. Registered 20 August 2014—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02220582 .
Background Although prior reports have evaluated the clinical and cost impacts of cardiovascular magnetic resonance (CMR) for low-to-intermediate-risk patients with suspected significant coronary artery disease (CAD), the cost-effectiveness of CMR compared to relevant comparators remains poorly understood. We aimed to summarize the cost-effectiveness literature on CMR for CAD and create a cost-effectiveness calculator, useable worldwide, to approximate the cost-per-quality-adjusted-life-year (QALY) of CMR and relevant comparators with context-specific patient-level and system-level inputs. Methods We searched the Tufts Cost-Effectiveness Analysis Registry and PubMed for cost-per-QALY or cost-per-life-year-saved studies of CMR to detect significant CAD. We also developed a linear regression meta-model (CMR Cost-Effectiveness Calculator) based on a larger CMR cost-effectiveness simulation model that can approximate CMR lifetime discount cost, QALY, and cost effectiveness compared to relevant comparators [such as single-photon emission computed tomography (SPECT), coronary computed tomography angiography (CCTA)] or invasive coronary angiography. Results CMR was cost-effective for evaluation of significant CAD (either health-improving and cost saving or having a cost-per-QALY or cost-per-life-year result lower than the cost-effectiveness threshold) versus its relevant comparator in 10 out of 15 studies, with 3 studies reporting uncertain cost effectiveness, and 2 studies showing CCTA was optimal. Our cost-effectiveness calculator showed that CCTA was not cost-effective in the US compared to CMR when the most recent publications on imaging performance were included in the model. Conclusions Based on current world-wide evidence in the literature, CMR usually represents a cost-effective option compared to relevant comparators to assess for significant CAD.
Background Most North American temperate forests are plantation or regrowth forests, which are actively managed. These forests are in different stages of their growth cycles and their ability to sequester atmospheric carbon is affected by extreme weather events. In this study, the impact of heat and drought events on carbon sequestration in an age-sequence (80, 45, and 17 years as of 2019) of eastern white pine ( Pinus strobus L.) forests in southern Ontario, Canada was examined using eddy covariance flux measurements from 2003 to 2019. Results Over the 17-year study period, the mean annual values of net ecosystem productivity (NEP) were 180 ± 96, 538 ± 177 and 64 ± 165 g C m –2 yr –1 in the 80-, 45- and 17-year-old stands, respectively, with the highest annual carbon sequestration rate observed in the 45-year-old stand. We found that air temperature (Ta) was the dominant control on NEP in all three different-aged stands and drought, which was a limiting factor for both gross ecosystem productivity (GEP) and ecosystems respiration (RE), had a smaller impact on NEP. However, the simultaneous occurrence of heat and drought events during the early growing seasons or over the consecutive years had a significant negative impact on annual NEP in all three forests. We observed a similar trend of NEP decline in all three stands over three consecutive years that experienced extreme weather events, with 2016 being a hot and dry, 2017 being a dry, and 2018 being a hot year. The youngest stand became a net source of carbon for all three of these years and the oldest stand became a small source of carbon for the first time in 2018 since observations started in 2003. However, in 2019, all three stands reverted to annual net carbon sinks. Conclusions Our study results indicate that the timing, frequency and concurrent or consecutive occurrence of extreme weather events may have significant implications for carbon sequestration in temperate conifer forests in Eastern North America. This study is one of few globally available to provide long-term observational data on carbon exchanges in different-aged temperate plantation forests. It highlights interannual variability in carbon fluxes and enhances our understanding of the responses of these forest ecosystems to extreme weather events. Study results will help in developing climate resilient and sustainable forestry practices to offset atmospheric greenhouse gas emissions and improving simulation of carbon exchange processes in terrestrial ecosystem models.
Canada was the first country in the world to establish multiculturalism as its official policy for the governance of diversity. Canadian multiculturalism has gained much popularity in political and public discourses in the past 50 years, and it has also received no less criticism as to its effectiveness in addressing issues of racism. There have also been ambiguities over the meaning and intention of multiculturalism, leading to divergent understandings of multiculturalism as an ideal of inclusion and equity, on the one hand, and a mere political rhetoric, on the other. On the occasion of celebrating the 50 th anniversary of Canada’s official multiculturalism policy, this article re-visits Canada’s multiculturalism by reviewing its history and ethos and critically examining its actual effects as manifested during the Covid-19 pandemic in Canada. The rise of anti-Asian racism, anti-Black racism, and anti-Indigenous racism incidents in the pandemic reveals that multiculturalism has in effect, sustained a racist and unequal society of Canada with racism entrenched in its history and ingrained in every aspect of its social structure. Multiculturalism tolerates cultural difference but does not challenge an unjust society premised on white supremacy. The anti-racism movement mobilized by racialized communities in Canada indicates that multiculturalism has failed to respond to racialized communities’ pressing demand for social change and action for social justice. The article concludes with a proposed alternative framework to multiculturalism, that is, pandemic anti-racism education model, to centre the issue of race and racism in an action-oriented, inclusive, and empowering approach toward a future of a just society.
Valosin-containing protein (VCP) associated multisystem proteinopathy (MSP) is a rare inherited disorder that may result in multisystem involvement of varying phenotypes including inclusion body myopathy, Paget’s disease of bone (PDB), frontotemporal dementia (FTD), parkinsonism, and amyotrophic lateral sclerosis (ALS), among others. An international multidisciplinary consortium of 40+ experts in neuromuscular disease, dementia, movement disorders, psychology, cardiology, pulmonology, physical therapy, occupational therapy, speech and language pathology, nutrition, genetics, integrative medicine, and endocrinology were convened by the patient advocacy organization, Cure VCP Disease, in December 2020 to develop a standard of care for this heterogeneous and under-diagnosed disease. To achieve this goal, working groups collaborated to generate expert consensus recommendations in 10 key areas: genetic diagnosis, myopathy, FTD, PDB, ALS, Charcot Marie Tooth disease (CMT), parkinsonism, cardiomyopathy, pulmonology, supportive therapies, nutrition and supplements, and mental health. In April 2021, facilitated discussion of each working group’s conclusions with consensus building techniques enabled final agreement on the proposed standard of care for VCP patients. Timely referral to a specialty neuromuscular center is recommended to aid in efficient diagnosis of VCP MSP via single-gene testing in the case of a known familial VCP variant, or multi-gene panel sequencing in undifferentiated cases. Additionally, regular and ongoing multidisciplinary team follow up is essential for proactive screening and management of secondary complications. The goal of our consortium is to raise awareness of VCP MSP, expedite the time to accurate diagnosis, define gaps and inequities in patient care, initiate appropriate pharmacotherapies and supportive therapies for optimal management, and elevate the recommended best practices guidelines for multidisciplinary care internationally.
Background The Coronavirus Disease-2019 (COVID-19) pandemic has created a spectrum of adversities that have affected older adults disproportionately. This paper examines older adults with multimorbidity using longitudinal data to ascertain why some of these vulnerable individuals coped with pandemic-induced risk and stressors better than others – termed multimorbidity resilience. We investigate pre-pandemic levels of functional, social and psychological forms of resilience among this sub-population of at-risk individuals on two outcomes – self-reported comprehensive pandemic impact and personal worry. Methods This study was conducted using Follow-up 1 data from the Canadian Longitudinal Study on Aging (CLSA), and the Baseline and Exit COVID-19 study, conducted between April and December in 2020. A final sub-group of 9211 older adults with two or more chronic health conditions were selected for analyses. Logistic regression and Generalized Linear Mixed Models were employed to test hypotheses between a multimorbidity resilience index and its three sub-indices measured using pre-pandemic Follow-up 1 data and the outcomes, including covariates. Results The multimorbidity resilience index was inversely associated with pandemic comprehensive impact at both COVID-19 Baseline wave (OR = 0.83, p < 0.001, 95% CI: [0.80,0.86]), and Exit wave (OR = 0.84, p < 0.001, 95% CI: [0.81,0.87]); and for personal worry at Exit (OR = 0.89, p < 0.001, 95% CI: [0.86,0.93]), in the final models with all covariates. The full index was also associated with comprehensive impact between the COVID waves (estimate = − 0.19, p < 0.001, 95% CI: [− 0.22, − 0.16]). Only the psychological resilience sub-index was inversely associated with comprehensive impact at both Baseline (OR = 0.89, p < 0.001, 95% CI: [0.87,0.91]) and Exit waves (OR = 0.89, p < 0.001, 95% CI: [0.87,0.91]), in the final model; and between these COVID waves (estimate = − 0.11, p < 0.001, 95% CI: [− 0.13, − 0.10]). The social resilience sub-index exhibited a weak positive association (OR = 1.04, p < 0.05, 95% CI: [1.01,1.07]) with personal worry, and the functional resilience measure was not associated with either outcome. Conclusions The findings show that psychological resilience is most pronounced in protecting against pandemic comprehensive impact and personal worry. In addition, several covariates were also associated with the outcomes. The findings are discussed in terms of developing or retrofitting innovative approaches to proactive coping among multimorbid older adults during both pre-pandemic and peri-pandemic periods.
Background The diagnostic journey for many rare disease patients remains challenging despite use of latest genetic technological advancements. We hypothesize that some patients remain undiagnosed due to more complex diagnostic scenarios that are currently not considered in genome analysis pipelines. To better understand this, we characterized the rare disorder (RD) spectrum using various bioinformatics resources (e.g., Orphanet/Orphadata, Human Phenotype Ontology, Reactome pathways) combined with custom-made R scripts. Results Our in silico characterization led to identification of 145 borderline-common, 412 rare and 2967 ultra-rare disorders. Based on these findings and point prevalence, we would expect that approximately 6.53%, 0.34%, and 0.30% of individuals in a randomly selected population have a borderline-common, rare, and ultra-rare disorder, respectively (equaling to 1 RD patient in 14 people). Importantly, our analyses revealed that (1) a higher proportion of borderline-common disorders were caused by multiple gene defects and/or other factors compared with the rare and ultra-rare disorders, (2) the phenotypic expressivity was more variable for the borderline-common disorders than for the rarer disorders, and (3) unique clinical characteristics were observed across the disorder categories forming the spectrum. Conclusions Recognizing that RD patients who remain unsolved even after genome sequencing might belong to the more common end of the RD spectrum support the usage of computational pipelines that account for more complex genetic and phenotypic scenarios.
The multifunctional soft sensor developed here is capable of simultaneously sensing six stimuli, including pressure, bending strain, temperature, proximity, UV light, and humidity, with high accuracy and without interference among the respective built-in components. The sensor is fabricated via a facile, scalable, and cost-effective supersonic cold-spraying method using silver nanowires (AgNWs), carbon nanotubes (CNTs), zinc oxide (ZnO), and conducting polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS). A mask and laser cutter are used in conjunction with the supersonic cold-spraying method to produce miniaturized multifunctional sensors that can be readily installed on various substrates; for example, the production of gloves capable of multifunctional sensing. In particular, the proximity sensor of the multifunctional glove sensor can produce a three-dimensional (3D) image of a scanned object, showing high potential for use in military, medical, and industrial applications.
Aim We undertook this systematic review to determine the efficacy and safety of cannabis-based medicine as a treatment for behavioral, psychological, and motor symptoms associated with neurocognitive disorders. Methods We conducted a PRISMA-guided systematic review to identify studies using cannabis-based medicine to treat behavioral, psychological, and motor symptoms among individuals with Alzheimer's disease (AD) dementia, Parkinson’s disease (PD), and Huntington’s disease (HD). We considered English-language articles providing original data on three or more participants, regardless of design. Findings We identified 25 studies spanning 1991 to 2021 comprised of 14 controlled trials, 5 pilot studies, 5 observational studies, and 1 case series. In most cases, the cannabinoids tested were dronabinol, whole cannabis, and cannabidiol, and the diagnoses included AD ( n = 11), PD ( n = 11), and HD ( n = 3). Primary outcomes were motor symptoms (e.g., dyskinesia), sleep disturbance, cognition, balance, body weight, and the occurrence of treatment-emergent adverse events. Conclusions A narrative summary of the findings from the limited number of studies in the area highlights an apparent association between cannabidiol-based products and relief from motor symptoms in HD and PD and an apparent association between synthetic cannabinoids and relief from behavioral and psychological symptoms of dementia across AD, PD, and HD. These preliminary conclusions could guide using plant-based versus synthetic cannabinoids as safe, alternative treatments for managing neuropsychiatric symptoms in neurocognitive vulnerable patient populations.
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