Reconnu comme l’une des principales causes d’invalidité, le traumatisme crânio-cérébral (TCC) est une condition chronique pouvant occasionner des déficits physiques, cognitifs, émotionnels et comportementaux. Ces déficits interfèrent avec la capacité de la personne à s’engager dans ses activités quotidiennes, incluant des activités complexes comme la préparation de repas. Afin de soutenir cette population lors de la préparation de repas, une technologie d’assistance à la cognition (TAC) nommée Cognitive Orthosis for coOKing (COOK) a été développée en partenariat avec une résidence alternative pour des personnes ayant des incapacités graves à la suite d’un TCC. Suivant l’installation de COOK, trois résidents ont été en mesure de préparer des repas de façon sécuritaire et autonome. Toutefois, rien n’est connu sur la façon avec laquelle COOK pourrait répondre aux besoins des personnes ayant eu un TCC et vivant dans la communauté, ni comment cette technologie pourrait offrir de l’assistance personnalisée, minimale et contextualisée pour soutenir cette population. Cette thèse vise donc à développer des connaissances pour soutenir le développement d’une version bonifiée de COOK qui correspondrait aux besoins variés de ces utilisateurs, en répondant à trois objectifs : 1) définir les besoins d’assistance verbale des personnes ayant eu un TCC modéré à grave afin d’améliorer les capacités de personnalisation de COOK; 2) évaluer son utilisabilité et expérience utilisateur en laboratoire et en milieu réel; et 3) identifier les facilitateurs et obstacles pouvant influencer l’implantation de COOK auprès de personnes ayant eu un TCC et vivant dans la communauté. Suivant une démarche de conception centrée sur l’utilisateur, quatre études ont été réalisées : (1) une étude mixte avec transformation des données et analyse d’enregistrements vidéo pour documenter l’assistance verbale offerte à 45 participants ayant un TCC lors de la préparation d’un repas; (2) une étude d’utilisabilité mixte pendant laquelle 10 participants ayant un TCC ont testé COOK en laboratoire; (3) une étude mixte à sujet unique pour évaluer l’utilisabilité de COOK au domicile d’une personne ayant eu un TCC grave; et (4) une étude qualitative descriptive impliquant des personnes ayant eu un TCC, des personnes proches aidantes et des intervenants, pour explorer leurs perceptions quant aux facilitateurs et obstacles à l’implantation de COOK dans leur milieu respectif. La première étude a permis d’identifier neuf types d’assistance cognitive et un type d’assistance motivationnelle, et de documenter les difficultés pour lesquelles les ergothérapeutes offraient de l’assistance. Des enjeux d’utilisabilité ont ensuite été documentés pendant les essais en laboratoire (étude 2) et en milieu réel (étude 3), particulièrement au niveau du système de sécurité autonome. Plusieurs besoins de bonifications technologiques ont aussi été identifiés par les participants (études 2, 3 et 4). Enfin, la quatrième étude a identifié divers facilitateurs (p.ex. les fonctionnalités disponibles dans COOK) et obstacles (p.ex. la logistique entourant l’installation, l’apprentissage et le soutien) à l’implantation de TAC comme COOK pour soutenir les personnes vivant dans la communauté avec un TCC grave. Ultimement, ces connaissances cliniques pourront soutenir le développement continu et l’implantation de TAC comme COOK pour qu’elles répondent aux besoins d’une plus grande population. / Defined as one of the main causes of disability, traumatic brain injury (TBI) is a chronic condition that can cause physical, cognitive, emotional, and behavioral deficits. These deficits may interfere with the person's ability to engage in daily activities, including complex activities such as meal preparation. To support this population during meal preparation, an assistive technology for cognition (ATC) called Cognitive Orthosis for coOKing (COOK) was recently developed in collaboration with an alternative residence for people with severe TBI. Following the installation of COOK, three residents were able to prepare meals safely and independently within their home. However, little is known about how COOK could meet the needs of people with TBI living in the community, or how it could provide personalized, minimal and contextualised assistance to support this population. This thesis aimed to develop a knowledge base to support the development of an improved version of COOK that would meet the varied needs of this new population, by meeting three objectives: 1) define the verbal assistance needs of people with moderate to severe TBI to enhance COOK's customization possibilities; 2) evaluate the usability and user experience of COOK in a laboratory setting and in a real-world environment; and 3) identify the facilitators and obstacles that may influence the implementation of COOK within the homes of people with TBI and in clinical settings. Integrated in a user-centered design process, four studies were conducted: (1) a study using conversion mixed design and video data analysis to document the verbal assistance provided to 45 participants with TBI during a meal preparation task; (2) a usability mixed-methods study during which 10 participants with TBI tested COOK in a laboratory setting; (3) a mixed-methods single-case study to assess the usability of COOK with a man with severe TBI living in the community; and (4) a qualitative descriptive study involving people with TBI, caregivers and healthcare professionals, to explore their perceptions of the facilitators and obstacles to the potential implementation of COOK in their respective settings. The first study identified nine types of cognitive assistance and one type of motivational assistance that were provided by occupational therapists to support people with TBI, and documented the difficulties for which these assistances were provided. Several usability issues were also documented when testing COOK in a laboratory setting (study 2) and in a real-world environment (study 3), particularly with the self-monitoring security system. Modification needs were also identified by the participants (studies 2, 3, and 4) to improve COOK. Finally, the fourth study highlighted many facilitators (e.g., the functionalities available in COOK) and obstacles (e.g., the logistics surrounding installation, learning and support of COOK) to consider before implementing ATCs like COOK. Ultimately, this knowledge base will support the continued development and the implementations of ATCs such as COOK to meets the needs of a larger population.

Les traumatismes craniocérébraux (TCC) sont des perturbations des fonctions cérébrales causées par une force extérieure, dont la gravité et les conséquences varient. Après la phase aiguë, l'agitation survient souvent chez les patients victimes d'un TCC admis en unité de soins intensifs (USI), interférant avec les soins habituels, affectant la sécurité des patients ou retardant la réadaptation. Ces comportements, considérés comme un sous-type de délirium pendant l'amnésie post-traumatique, comprennent l'agression et la labilité émotionnelle, et posent des problèmes aux patients, aux familles et aux professionnels de la santé. Actuellement, il n'existe pas de directives standardisées pour la prise en charge de l'agitation chez les patients souffrant d'un TCC en USI, ce qui entraîne des approches variées et des risques potentiels. Cette thèse vise à (1) identifier et comprendre la gestion de l'agitation associée au TCC en explorant les attitudes, les croyances, les expériences et les perceptions des professionnels de santé dans les environnements de soins intensifs et à (2) explorer une utilisation potentielle de l'actigraphie pour surveiller l'agitation. Pour atteindre le premier objectif, nous avons conçu deux études qui nous permettent de comprendre comment les professionnels perçoivent l'agitation à travers leurs pratiques et leurs croyances. Tout d'abord, nous avons conçu une enquête électronique autoadministrée pour les médecins travaillant dans les unités de soins intensifs des centres de traumatologie de niveau 1 au Canada. Notre objectif était de décrire les croyances des médecins et l'importance qu'ils accordent à l'agitation associée au TCC chez les patients gravement malades. L'agitation associée au TCC est perçue comme un problème important par la plupart des médecins des services de soins intensifs. Bien qu'il y ait un consensus parmi les médecins concernant les différentes approches de gestion de cette agitation, il y a eu une variation dans l'accord sur l'épidémiologie et les facteurs de risque associés à cette agitation. Deuxièmement, une étude qualitative par entretiens a été conçue pour explorer les expériences et les perceptions des infirmières. Des infirmières de soins intensifs travaillant dans deux centres de traumatologie de niveau 1 à Montréal ont été interrogées. Cette étude a examiné les perspectives et les pratiques des infirmières dans la gestion de l'agitation chez les patients 6 souffrant d'un TCC, et a exploré les facteurs contextuels qui influencent leurs approches. Elle a pris en compte l'impact de l'environnement de l'unité de soins intensifs sur l'agitation et a identifié les domaines susceptibles d'être améliorés dans la gestion de l'agitation associée aux traumatismes crâniens dans les environnements de soins intensifs. Cette thèse contient une troisième étude évaluant l'utilisation potentielle de l'actigraphie pour surveiller l'agitation et comparant l'enregistrement des données actigraphiques entre les patients agités et non agités. Cette étude pilote a prouvé l'utilité de l'actigraphie pour la surveillance continue de l'agitation chez les patients souffrant d'un TCC. Cette thèse améliore la compréhension de l'agitation à la suite d'un TCC, de sa gestion et de son suivi. Bien que des recherches supplémentaires soient nécessaires, l'amalgame des résultats de ces études offre des perspectives précieuses sur les aspects complexes de l'agitation associée aux TCC. Il souligne l'importance d'adopter une approche holistique, fondée sur des données probantes, pour comprendre et traiter l'agitation dans le cadre des soins intensifs. Les résultats de cette thèse fournissent une vision à 360° de la gestion de l'agitation, permettant une base solide pour soutenir les études futures de diverses disciplines cliniques et/ou organisationnelles. / Traumatic brain injury (TBI) is a disruption in brain function caused by external force, resulting in varied severity and consequences. After the acute phase, agitation often occurs in TBI patients admitted in the intensive care unit (ICU), interfering in usual care, affecting patients’ safety, or delaying rehabilitation. These behaviors, considered a subtype of delirium during post-traumatic amnesia, include aggression and emotional lability, pose challenges for patients, families, and healthcare professionals. Currently, no standardized guidelines exist for managing agitation in ICU TBI patients, leading to varied approaches and potential risks. This thesis seeks to (1) identify and understand TBI-associated agitation management by exploring healthcare professionals' attitudes, beliefs, experiences, and perceptions in critical care settings and to (2) explore the use of actigraphy to monitor agitation. To achieve the first goal, we designed two studies that allow us to understand how professionals perceive agitation through their practices and beliefs. First, we designed an electronic, self-administered survey for physicians working in ICU at Level-1 trauma centers in Canada. We aimed to describe physicians’ beliefs and perceived importance of TBI-associated agitation in critically ill patients. TBI-associated agitation was perceived as an important issue for most ICU physicians. While there was a consensus among physicians regarding various approaches to managing this agitation, there existed a variation in agreement on epidemiology and risk factors associated with it. Secondly, a qualitative study was designed to explore experiences and perceptions of nurses. ICU-nurses working in two Level-1 trauma centers in Montreal. This study examined nurses' perspectives and practices in the management of agitation in TBI patients and explored contextual factors that influence their approaches. It considered the impact of ICU environment on agitation and identified areas for potential improvement in management of TBI-associated agitation in critical care settings. This thesis contains a third study assessing the potential use of actigraphy monitoring agitation and comparing actigraphy data registration between agitated and non-agitated critically ill TBI 4 patients. This pilot study proved the usefulness of actigraphy to continuously monitor agitation in TBI patients admitted in the ICU and compared agitated patients and non-agitated patients’ activity levels. Agitated patients showed higher activity rates, validating the potential of actigraphy as an objective tool to monitor agitation. This thesis enhances comprehension regarding agitation following TBI and its subsequent management and monitoring. Although additional research is necessary, amalgam of findings from these studies offer valuable perspectives of complex aspects of TBI-associated agitation, emphasizing the importance of adopting a holistic, evidence-based approach for both understanding and addressing agitation within critical care settings. Results of this thesis provide a 360º view on the management of agitation, allowing a solid base to support future studies from various clinical and/or organizational disciplines.

Die Höhe des optimalen zerebralen Perfusionsdruckes nach schwerem Schädel-Hirn-Trauma wird kontrovers diskutiert. Während im sogenannten Lund-Konzept ein niedriger Perfusionsdruck angestrebt und die Gabe von Katecholaminen aufgrund potentieller zerebraler vasokonstringierender und weiterer Nebeneffekte vermieden wird, befürwortet das CPP-Konzept nach Rosner eine Anhebung des zerebralen Perfusionsdruckes, wenn notwendig unter intravenöser Gabe von Katecholaminen. Vor diesem Hintergrund galt es, in einem experimentellen Schädel-Hirn-Trauma- Modell der Ratte (Controlled Cortical Impact Injury) den Bereich des optimalen zerebralen Perfusionsdruckes nach traumatischer Hirnkontusion zu ermitteln und den Effekt von Katecholaminen auf den posttraumatischen zerebralen Blutfluss und die Entwicklung des sekundären Hirnschadens zu untersuchen. Die wesentlichen Ergebnisse dieser Arbeit lassen sich wie folgt zusammenfassen: In der Akutphase nach Hirnkontusion liegt der Bereich des zerebralen Perfusionsdruckes, welcher die Entwicklung des Kontusionsvolumens nicht beeinflusst, zwischen 70 und 105 mm Hg. Eine Senkung des Perfusionsdruckes unterhalb bzw. Anhebung oberhalb dieser Schwellenwerte vergrößert das Kontusionsvolumen. Die Anhebung des Blutdruckes mittels intravenöser Infusion von Dopamin oder Noradrenalin führt sowohl in der Frühphase als auch in der Spätphase nach Trauma (4 Stunden bzw. 24 Stunden nach kortikaler Kontusion) zu einem signifikanten Anstieg im kortikalen perikontusionellen Blutfluss und in der Hirngewebe-Oxygenierung. Die durch Anhebung des zerebralen Perfusionsdruckes auf über 70 mm Hg induzierte Verbesserung des posttraumatischen zerebralen Blutflusses bewirkte jedoch keine Reduzierung der Hirnschwellung. Für eine Katecholamin-induzierte zerebrale Vasokonstriktion nach kortikaler Kontusion gibt es keinen Anhalt. Um die Entwicklung des sekundären Hirnschadens nach kortikaler Kontusion zu minimieren, sollte der zerebrale Perfusionsdruck nach traumatischem Hirnschaden nicht unterhalb 70 mm Hg liegen. Eine Anhebung des Perfusionsdruckes auf über 70 mm Hg erscheint nicht notwendig oder vorteilhaft zu sein. Wenn notwendig, kann sowohl in der Früh- als auch Spätphase nach Trauma der zerebrale Perfusionsdruck mittels intravenöser Gabe von Katecholaminen angehoben werden. / The optimum cerebral perfusion pressure after severe traumatic brain injury remains to be controversial. In the Lund concept a relatively low cerebral perfusion pressure is preferred, and administration of catecholamines is avoided due to potential catecholamine-mediated cerebral vasoconstriction and other side effects. In contrast, the CPP concept of Rosner recommends elevation of cerebral perfusion pressure, if needed by intravenous administration of catecholamines. Based on this, in an experimental model of traumatic brain injury of the rat (Controlled Cortical Impact Injury) the optimum range of cerebral perfusion pressure after traumatic brain contusion and the effects of catecholamines on posttraumatic cerebral perfusion and development of secondary brain injury were investigated. The most significant results can be summarized as follows: In the acute phase after brain contusion the range of cerebral perfusion pressure that does not affect the development of posttraumatic contusion volume was found to be between 70 and 105 mm Hg. Reduction of the cerebral perfusion pressure below or elevation above these thresholds increases contusion volume. Elevation of blood pressure by intravenous infusion of dopamine or norepinephrine during the early (4 hours) as well as late (24 hours) phase after trauma results in a significant increase in pericontusional blood flow and brain tissue oxygenation. The increase in cerebral blood flow by elevating cerebral perfusion pressure above 70 mm Hg did not decrease cerebral edema formation. There was no evidence of a catecholamine-induced cerebral vasoconstriction after cortical contusion. In order to minimize secondary brain injury after cortical contusion, cerebral perfusion pressure should not fall bellow 70 mm Hg. However, a further active elevation of cerebral perfusion pressure does not appear necessary or beneficial. If needed cerebral perfusion pressure can be elevated by administration of catecholamines in the early as well late phase after trauma.

This thesis examines how military members and veterans with Operational Stress Injuries are treated by Canadian justice systems. It suggests a correlation between mental injuries sustained on operations by military personnel and propensities for military and societal misconduct. By comparing civilian and military processes with American justice counterparts, a plan to improve the existing Canadian legal landscape is proposed. Using an analysis of the underlying philosophy and purpose of military justice, a problem solving diversionary court is recommended, along with legislative and policy amendments. The use of a consent-based “Treatment Standing Court Martial” would place military justice officials parallel to civilian justice alternative measures programs, and in a better position to break the cycle of recidivism among veterans by addressing root causes. Education to reduce stigma along with military-civilian partnerships are also advocated to enhance the detection of mental illness and to foster early treatment for military personnel and veterans. The overall goals of the work include: reducing recidivism, improving operational efficiency and taking care of military members, veterans and their families.

Mitt masterprojekt är en bok som syftar till att stötta anhöriga till personer med förvärvad hjärnskada, där jag använder mig själv och min egen rehabilitering efter en smitningsolycka som fallstudie. / My master project is a book that aims to support relatives of people with aquired brain injuries, where I use myself and my own rehabilitetion after a hit-and-run accident as a case study.

The aim of this project has been to investigate whether there are correlations to be found between gut microbes and serum metabolites, which could be involved in the development of epilepsy. To do so, metabolomics data containing metabolites and metagenomics data containing bacteria have been integrated and used in a pipeline utilizing the software package DIABLO in R Studio. DIABLO stands for Data Integration Analysis for Biomarker discovery using Latent cOmponents and utilizes multi-block pls-da to integrate multiple omics data sets to find potential biomarkers. The results in this project are mainly divided into two groups, the first group being from taking samples at an early time point, where subjects have not yet developed symptoms of epilepsy and the second group being from taking samples at a late time point, where the subjects have developed epilepsy. To find biomarkers in the data used for the integration, two subgroups are of highest interest, namely subgroup PTE, which is the group that develops epilepsy symptoms after an induced trauma to the brain, as well as subgroup TBI which do not develop epilepsy symptoms after an induced trauma to the brain. Results from the early time point suggests that bacteria such as those from Phelethenecus, Christenselellales, Ventrimonas, Ruminococcaceae and Acetatifactor, as well as metabolites such as LPC 17:0, Indole and Indole-3-carboxyaldehyde might be of interest in finding biomarkers previous to the development of epilepsy after induced brain trauma.  Results from the late time point suggests that bacteria such as those from Muribaculaceae and Avidehalobacter, as well as metabolites such as Dioctyl sulfosuccinate, Canrenone, LPC 18:0, Uric acid, Arjunolic acid and Pseudouridine might be of interest in finding underlying mechanisms behind the existing condition of epilepsy. The hope is that findings in this paper might aid in future development of knowledge behind this disease as well as its underlying mechanisms.

Traumatic brain injury (TBI) is a leading cause of disability worldwide. Annually, 150 to 200/1,000,000 people become disabled as a result of brain trauma. Axonal degeneration is a critical, early event following TBI of all severities but whether axon degeneration is a driver of TBI remains unclear. Molecular pathways underlying the pathology of TBI have not been defined and there is no efficacious treatment for TBI. Despite this significant societal impact, surprisingly little is known about the molecular mechanisms that actively drive axon degeneration in any context and particularly following TBI. Although severe brain injury may cause immediate disruption of axons (primary axotomy), it is now recognized that the most frequent form of traumatic axonal injury (TAI) is mediated by a cascade of events that ultimately result in secondary axonal disconnection (secondary axotomy) within hours to days. Proposed mechanisms include immediate post-traumatic cytoskeletal destabilization as a direct result of mechanical breakage of microtubules, as well as catastrophic local calcium dysregulation resulting in microtubule depolymerization, impaired axonal transport, unmitigated accumulation of cargoes, local axonal swelling, and finally disconnection. The portion of the axon that is distal to the axotomy site remains initially morphologically intact. However, it undergoes sudden rapid fragmentation along its full distal length ~72 h after the original axotomy, a process termed Wallerian degeneration. Remarkably, mice mutant for the Wallerian degeneration slow (Wlds) protein exhibit ~tenfold (for 2–3 weeks) suppressed Wallerian degeneration. Yet, pharmacological replication of the Wlds mechanism has proven difficult. Further, no one has studied whether Wlds protects from TAI. Lastly, owing to Wlds presumed gain-of-function and its absence in wild-type animals, direct evidence in support of a putative endogenous axon death signaling pathway is lacking, which is critical to identify original treatment targets and the development of viable therapeutic approaches. Novel insight into the pathophysiology of Wallerian degeneration was gained by the discovery that mutant Drosophila flies lacking dSarm (sterile a/Armadillo/Toll-Interleukin receptor homology domain protein) cell-autonomously recapitulated the Wlds phenotype. The pro-degenerative function of the dSarm gene (and its mouse homolog Sarm1) is widespread in mammals as shown by in vitro protection of superior cervical ganglion, dorsal root ganglion, and cortical neuron axons, as well as remarkable in-vivo long-term survival (>2 weeks) of transected sciatic mouse Sarm1 null axons. Although the molecular mechanism of function remains to be clarified, its discovery provides direct evidence that Sarm1 is the first endogenous gene required for Wallerian degeneration, driving a highly conserved genetic axon death program. The central goals of this thesis were to determine (1) whether post-traumatic axonal integrity is preserved in mice lacking Sarm1, and (2) whether loss of Sarm1 is associated with improved functional outcome after TBI. I show that mice lacking the mouse Toll receptor adaptor Sarm1 gene demonstrate multiple improved TBI-associated phenotypes after injury in a closed-head mild TBI model. Sarm1-/- mice developed fewer beta amyloid precursor protein (βAPP) aggregates in axons of the corpus callosum after TBI as compared to Sarm1+/+ mice. Furthermore, mice lacking Sarm1 had reduced plasma concentrations of the phosphorylated axonal neurofilament subunit H, indicating that axonal integrity is maintained after TBI. Strikingly, whereas wild type mice exhibited a number of behavioral deficits after TBI, I observed a strong, early preservation of neurological function in Sarm1-/- animals. Finally, using in vivo proton magnetic resonance spectroscopy, I found tissue signatures consistent with substantially preserved neuronal energy metabolism in Sarm1-/- mice compared to controls immediately following TBI. My results indicate that the Sarm1-mediated prodegenerative pathway promotes pathogenesis in TBI and suggest that anti-Sarm1 therapeutics are a viable approach for preserving neurological function after TBI.