Although a number of cytoskeletal derangements have been described in the setting of traumatic axonal injury (TAI), little is known of early structural changes that may serve to initiate a cascade of further axonal degeneration. Recent work by the authors has examined conformational changes in cytoskeletal constituents of neuronal axons undergoing traumatic axonal injury (TAI) following focal compression through confocal imaging data taken in vitro and in situ. The present study uses electron microscopy to understand and quantify in vitro alterations in the ultrastructural composition of microtubules and neurofilaments within neuronal axons of rats following focal compression. Standard transmission electron microscopy processing methods are used to identify microtubules, while neurofilament identification is performed using antibody labeling through gold nanoparticles. The number, density, and spacing of microtubules and neurofilaments are quantified for specimens in sham Control and Crushed groups with fixation at <1min following load. Our results indicate that the axon caliber dependency known to exist for microtubule and neurofilament metrics extends to axons undergoing TAI, with the exception of neurofilament spacing, which appears to remain constant across all Crushed axon diameters. Confidence interval comparisons between Control and Crushed cytoskeletal measures suggests early changes in the neurofilament spatial distributions within axons undergoing TAI may precede microtubule changes in response to applied loads. This may serve as a trigger for further secondary damage to the axon, representing a key insight into the temporal aspects of cytoskeletal degeneration at the component level, and suggests the rapid removal of neurofilament sidearms as one possible mechanism.
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The ACLeeve is a portable and easy to use electromyography (EMG) device to be used during ACL injury recovery to aid in the rehabilitation process. The ACLeeve is wrapped around the user's leg using a knee sleeve and electrodes, and then wirelessly transfers data to the user's phone or laptop. To achieve this, the ACLeeve must be small and lightweight, with electronics and software capable of detecting EMG readings and then transmitting them over a secure wireless connection. As well, the ACLeeve must be safe for the user and conform to all relevant standards. ACLeeve will monitor the user's movements of both quadriceps using surface EMGs (SEMGs) and Strain Sensors. These devices will be actively transmitting the collected data to a microprocessor, which will then process and send the data to an external device for further software analysis. The ACLeeve will provide real-time feedback to the user (audio or visual) regarding the performance of their movements, which will allow the user to physically adjust in order to achieve better long-term results.Our software will perform long-term analyses which will evaluate the progress of obtaining the goal of 80-90% asymmetry between the user's ACL-injured quadricep and their other healthy quadricep.
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L’objectif de cette thèse était la validation de l’existence ainsi que la découverte de nouveaux sous-types au sein de la maladie d’Alzheimer, première cause de démence au monde. Afin d’explorer son hétérogénéité, nous avons employé des méthodes d’apprentissage profond appliquées à une modalité de neuroimagerie, l’imagerie par résonance magnétique structurelle.Cependant, la découverte de biais méthodologiques importants dans de nombreuses études de notre domaine, ainsi que l’absence de consensus de la communauté sur la manière d’interpréter les résultats des méthodes d’apprentissage profond a fait en partie dévier la thèse de son objectif principal pour s’orienter d’avantage vers des problématiques de validation, de robustesse et d’interprétabilité de l’apprentissage profond. Ainsi, trois études expérimentales ont été menées pour s’assurer de la capacité des réseaux profonds de correctement détecter la maladie. La première est une étude expérimentale de méthodes d’apprentissage profond pour la classification de la maladie d’Alzheimer et a permis d’établir une juste comparaison des méthodes. La seconde étude a permis de constater un manque de robustesse de la classification avec l’apprentissage profond en termes de motifs d’atrophie découverts à l’aide de méthodes d’interprétabilité. Enfin, la dernière étude propose une méthode de découverte de sous-types aidée par l’augmentation de données. Bien que fonctionnant sur des données synthétiques, celle-ci ne généralise pas aux données réelles.Une contribution majeure de la thèse est la librairie ClinicaDL, grâce à laquelle les résultats expérimentaux de la thèse ont été produits de manière à être reproductibles. The goal of this PhD was the validation of the existence and the discovery of new subtypes of Alzheimer’s disease, the first cause of dementia worldwide. Indeed, despite its discovery more than a century ago, this disease is still not well defined and existing treatments are only weakly effective, possibly because several phenotypes exist within the disease. In order to explore its heterogeneity, we employed deep learning methods applied to a neuroimaging modality, structural magnetic resonance imaging.However, the discovery of important methodological biases in many studies in our field, as well as the lack of consensus regarding deep learning interpretability, partly changed the main objective of the PhD to focus more on issues of validation, robustness and interpretability of deep learning. Then, to correctly assess the ability of deep learning to detect Alzheimer’s disease, three experimental studies were conducted. The first one is a study of deep learning methods for Alzheimer’s classification and allowed a fair comparison of the methods. The second study found a lack of robustness of classification with deep learning in terms of atrophy patterns discovered using interpretability methods. Finally, the last study proposed a subtype discovery method aided by data augmentation. Although it works on synthetic data, it does not generalize to real data.Experimental results of this PhD were obtained thanks to ClinicaDL, one major contribution of this PhD. It is an open source Python library that was used to improve the reproducibility of deep learning experiments.
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Low health literacy (HL) increases the risk of adverse stroke-related health outcomes. The aim of this review was to identify 1. what the quality and what the limitations to educational materials used to improve HL in stroke patients are 2. what the levels of HL among stroke patients and stroke survivors are, and 3. how HL and stroke literacy levels affect health-related behaviours and outcomes of stroke patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. 6 computerized databases and gray literature sources were searched: MEDLINE, OVID, EMBSE, CINAHL, Cochrane library, Web of Science, and Health and Psychosocial Instruments, and Google Scholar. Papers published in English between January 01, 2000 and August 01, 2020 were included. Five themes were identified across the 26 studies regarding the education and measurement of stroke with relevance to HL. This review concludes that current instruments used to improve HL in stroke are inadequate as they fail to provide a holistic assessment of health literacy, especially concerning stroke patients and stroke literacy. This review identified a paucity of literature on HL in relation to stroke management and outcomes. Therefore, the authors are in strong favour of future research prioritizing the development of effective tools to assess HL and develop best-practice guidelines for stroke education materials.
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New role of glutamate as an immunoregulator via glutamate receptors and transporters.
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Our MRI scanner is an innovative solution to provide tissue and bone imaging. Designed to be cost effective and portable, our MRI scanner will provide greater access to MRI scans and allow for remote imaging. Our proposed design uses the rotation of the magnet’s inhomogeneous field and a projection-based imaging technique to reconstruct the spatial location and frequency of detected signals. Our design relaxes the homogeneity constraints and removes the need for heavy gradient coils, thereby allowing our scanner to be cost-effective and lightweight.
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handle: 10294/7092
The long and complex network of roads leading to a better understanding of Autism Spectrum Disorder is a little less tangled thanks to a collaborative research project between the University of Regina and Stanford University in California. Staff no
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The development of a translational research path has traditionally been a haphazard approach, filtering technologies so that the ‘best of breed’ may ultimately succeed. The conversion ratio of brilliant ideas to useful devices remains suboptimal, as many ‘fail to progress’. The reality of developing biotechnology transfer and Knowledge Transfer (KT) generally, is that the ability of multidisciplinary teams (MDT) to assimilate and then act upon information is becoming the rate limiting step for the building of complex projects. The model proposed here considers both the biological aspects of Life Sciences (LS) and the establishment of Technology Readiness for its implementation.
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Dynamic processes, such as intracellular calcium signaling, are hallmark of cellular biology. As real-time imaging modalities become widespread, a need for analytical tools to reliably characterize time-series data without prior knowledge of the nature of the recordings becomes more pressing. The goal of this study is to develop a signal-processing algorithm for MATLAB that autonomously computes the parameters characterizing prominent single transient responses (TR) and/or multi-peaks responses (MPR). The algorithm corrects for signal contamination and decomposes experimental recordings into contributions from drift, TRs, and MPRs. It subsequently provides numerical estimates for the following parameters: time of onset after stimulus application, activation time (time for signal to increase from 10 to 90% of peak), and amplitude of response. It also provides characterization of the (i) TRs by quantifying their area under the curve (AUC), response duration (time between 1/2 amplitude on ascent and descent of the transient), and decay constant of the exponential decay region of the deactivation phase of the response, and (ii) MPRs by quantifying the number of peaks, mean peak magnitude, mean periodicity, standard deviation of periodicity, oscillatory persistence (time between first and last discernable peak), and duty cycle (fraction of period during which system is active) for all the peaks in the signal, as well as coherent oscillations (i.e., deterministic spikes). We demonstrate that the signal detection performance of this algorithm is in agreement with user-mediated detection and that parameter estimates obtained manually and algorithmically are correlated. We then apply this algorithm to study how metabolic acidosis affects purinergic (P2) receptor-mediated calcium signaling in osteoclast precursor cells. Our results reveal that acidosis significantly attenuates the amplitude and AUC calcium responses at high ATP concentrations. Collectively, our data validated this algorithm as a general framework for comprehensively analyzing dynamic time-series.
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Although a number of cytoskeletal derangements have been described in the setting of traumatic axonal injury (TAI), little is known of early structural changes that may serve to initiate a cascade of further axonal degeneration. Recent work by the authors has examined conformational changes in cytoskeletal constituents of neuronal axons undergoing traumatic axonal injury (TAI) following focal compression through confocal imaging data taken in vitro and in situ. The present study uses electron microscopy to understand and quantify in vitro alterations in the ultrastructural composition of microtubules and neurofilaments within neuronal axons of rats following focal compression. Standard transmission electron microscopy processing methods are used to identify microtubules, while neurofilament identification is performed using antibody labeling through gold nanoparticles. The number, density, and spacing of microtubules and neurofilaments are quantified for specimens in sham Control and Crushed groups with fixation at <1min following load. Our results indicate that the axon caliber dependency known to exist for microtubule and neurofilament metrics extends to axons undergoing TAI, with the exception of neurofilament spacing, which appears to remain constant across all Crushed axon diameters. Confidence interval comparisons between Control and Crushed cytoskeletal measures suggests early changes in the neurofilament spatial distributions within axons undergoing TAI may precede microtubule changes in response to applied loads. This may serve as a trigger for further secondary damage to the axon, representing a key insight into the temporal aspects of cytoskeletal degeneration at the component level, and suggests the rapid removal of neurofilament sidearms as one possible mechanism.
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The ACLeeve is a portable and easy to use electromyography (EMG) device to be used during ACL injury recovery to aid in the rehabilitation process. The ACLeeve is wrapped around the user's leg using a knee sleeve and electrodes, and then wirelessly transfers data to the user's phone or laptop. To achieve this, the ACLeeve must be small and lightweight, with electronics and software capable of detecting EMG readings and then transmitting them over a secure wireless connection. As well, the ACLeeve must be safe for the user and conform to all relevant standards. ACLeeve will monitor the user's movements of both quadriceps using surface EMGs (SEMGs) and Strain Sensors. These devices will be actively transmitting the collected data to a microprocessor, which will then process and send the data to an external device for further software analysis. The ACLeeve will provide real-time feedback to the user (audio or visual) regarding the performance of their movements, which will allow the user to physically adjust in order to achieve better long-term results.Our software will perform long-term analyses which will evaluate the progress of obtaining the goal of 80-90% asymmetry between the user's ACL-injured quadricep and their other healthy quadricep.
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L’objectif de cette thèse était la validation de l’existence ainsi que la découverte de nouveaux sous-types au sein de la maladie d’Alzheimer, première cause de démence au monde. Afin d’explorer son hétérogénéité, nous avons employé des méthodes d’apprentissage profond appliquées à une modalité de neuroimagerie, l’imagerie par résonance magnétique structurelle.Cependant, la découverte de biais méthodologiques importants dans de nombreuses études de notre domaine, ainsi que l’absence de consensus de la communauté sur la manière d’interpréter les résultats des méthodes d’apprentissage profond a fait en partie dévier la thèse de son objectif principal pour s’orienter d’avantage vers des problématiques de validation, de robustesse et d’interprétabilité de l’apprentissage profond. Ainsi, trois études expérimentales ont été menées pour s’assurer de la capacité des réseaux profonds de correctement détecter la maladie. La première est une étude expérimentale de méthodes d’apprentissage profond pour la classification de la maladie d’Alzheimer et a permis d’établir une juste comparaison des méthodes. La seconde étude a permis de constater un manque de robustesse de la classification avec l’apprentissage profond en termes de motifs d’atrophie découverts à l’aide de méthodes d’interprétabilité. Enfin, la dernière étude propose une méthode de découverte de sous-types aidée par l’augmentation de données. Bien que fonctionnant sur des données synthétiques, celle-ci ne généralise pas aux données réelles.Une contribution majeure de la thèse est la librairie ClinicaDL, grâce à laquelle les résultats expérimentaux de la thèse ont été produits de manière à être reproductibles. The goal of this PhD was the validation of the existence and the discovery of new subtypes of Alzheimer’s disease, the first cause of dementia worldwide. Indeed, despite its discovery more than a century ago, this disease is still not well defined and existing treatments are only weakly effective, possibly because several phenotypes exist within the disease. In order to explore its heterogeneity, we employed deep learning methods applied to a neuroimaging modality, structural magnetic resonance imaging.However, the discovery of important methodological biases in many studies in our field, as well as the lack of consensus regarding deep learning interpretability, partly changed the main objective of the PhD to focus more on issues of validation, robustness and interpretability of deep learning. Then, to correctly assess the ability of deep learning to detect Alzheimer’s disease, three experimental studies were conducted. The first one is a study of deep learning methods for Alzheimer’s classification and allowed a fair comparison of the methods. The second study found a lack of robustness of classification with deep learning in terms of atrophy patterns discovered using interpretability methods. Finally, the last study proposed a subtype discovery method aided by data augmentation. Although it works on synthetic data, it does not generalize to real data.Experimental results of this PhD were obtained thanks to ClinicaDL, one major contribution of this PhD. It is an open source Python library that was used to improve the reproducibility of deep learning experiments.
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Low health literacy (HL) increases the risk of adverse stroke-related health outcomes. The aim of this review was to identify 1. what the quality and what the limitations to educational materials used to improve HL in stroke patients are 2. what the levels of HL among stroke patients and stroke survivors are, and 3. how HL and stroke literacy levels affect health-related behaviours and outcomes of stroke patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. 6 computerized databases and gray literature sources were searched: MEDLINE, OVID, EMBSE, CINAHL, Cochrane library, Web of Science, and Health and Psychosocial Instruments, and Google Scholar. Papers published in English between January 01, 2000 and August 01, 2020 were included. Five themes were identified across the 26 studies regarding the education and measurement of stroke with relevance to HL. This review concludes that current instruments used to improve HL in stroke are inadequate as they fail to provide a holistic assessment of health literacy, especially concerning stroke patients and stroke literacy. This review identified a paucity of literature on HL in relation to stroke management and outcomes. Therefore, the authors are in strong favour of future research prioritizing the development of effective tools to assess HL and develop best-practice guidelines for stroke education materials.
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New role of glutamate as an immunoregulator via glutamate receptors and transporters.
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Our MRI scanner is an innovative solution to provide tissue and bone imaging. Designed to be cost effective and portable, our MRI scanner will provide greater access to MRI scans and allow for remote imaging. Our proposed design uses the rotation of the magnet’s inhomogeneous field and a projection-based imaging technique to reconstruct the spatial location and frequency of detected signals. Our design relaxes the homogeneity constraints and removes the need for heavy gradient coils, thereby allowing our scanner to be cost-effective and lightweight.
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