SACM - Canada
Permanent URI for this collectionhttps://drepo.sdl.edu.sa/handle/20.500.14154/9651
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Item Restricted The effect of corticosteroids on sinus microbiota in chronic rhinosinusitis patients with nasal polyposis(McGill University, 2019) Alammar, Yousif; Rousseau, Simon; Tewfik, Marc; Rousseau, Simon; Tewfik, MarcBackground: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a multifactorial disease with no known single cause, but it is thought that bacteria play a role in the disease process. The short-term response of bacterial communities to corticosteroid therapy has been found to be unpredictable. As a result, this pilot study aims to assess the long-term effect of corticosteroid therapy on sinus microbiota in chronic rhinosinusitis patients with nasal polyposis (CRSwNP). Methods: A longitudinal prospective case-control study was done on patients with CRSwNP and on healthy subjects. Patients with CRSwNP were randomly allocated to a maximal medical therapy (corticosteroids and antibiotics) treatment group or a corticosteroid-only treatment group. Data was collected at 3 time points (before treatment, 1 and 3 months after treatment): A guarded sinus swab was collected from the middle meatus; the SNOT-22 questionnaire was used to assess clinical symptoms. Specimens were cultured and Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry (MS) was used as a bacterial detection method. The raw data produced was analyzed to characterize the sample and to assess the response to each medical treatment. Results: Data from 29 patients with CRSwNP (16 maximal medical therapy; 13 corticosteroids only) was compared to 15 healthy subjects. Patients reported significant symptoms improvement initially (1- month), but not on the long-term (3-months). This result was found as a response to both treatment groups, whether or not antibiotics was used. There was no significant difference in the sinus microbiota prevalence between CRSwNP patients and normal subjects. After three months from treatment, Corynebacterium genera tended to increase in the maximal medical therapy group, while Staphylococcus and gram-negative genera (Pseudomonas) tended to increase after corticosteroid treatment. Smoking, aspirin sensitivity and previous endoscopic sinus surgery were found to be co-factors significantly associated with the response to systemic corticosteroid therapy. Conclusion: In this pilot study both treatment options were effective on the short-term, but not on the long-term with no clear sinus microbiota response linked. As a result, this study agrees with previous reports that discourage the use of systemic antibiotics without evidence of active infection.14 0Item Restricted Exploring Physiologic Markers for the Identification of Vasovagal Syncope(University of Calgary, 2024) Robert S Sheldon, Mohammed Alsaleh; Sheldon, Robert SBackground: Vasovagal Syncope (VVS) is a common cardiovascular disorder, with at least 40% of individuals experiencing at least one episode in their life and about 20% of adults experiencing recurrent episodes. Traditional diagnostic methods such as the Head-Up Tilt (HUT) test and Implantable Cardiac Monitors (ICM) have significant limitations, including limited availability, high costs, and intensive resource requirements. A novel wearable, beat-to-beat blood pressure (BP) monitor is being developed to address these issues. This device, worn on the ear, samples BP at 50 Hz, stores and streams data, and features a rechargeable battery lasting up to 30 hours. This innovative solution will offer a cost-effective, user-friendly alternative for VVS management, potentially improving diagnostic accuracy and patient outcomes. Aims: We aimed to investigate the potential of a wearable beat-to-beat BP monitor in diagnosing vasovagal syncope. The thesis is structured around the following objectives: Objective 1: Provide a detailed narrative review of vasovagal syncope physiology, the BezoldJarisch reflex, and the need for a wearable beat-to-beat BP monitor. Objective 2: Validate the short-term blood pressure fluctuations during scripted physiological changes with a wearable beat-to-beat BP monitor. Methods: The narrative review explores physiological mechanisms underlying VVS, highlighting serotonin's role. For Objective 2 data were collected from 14 participants during activities such as rhythmic breathing and hand grips to validate the ear BP monitor. Spectral and coherence analyses assessed synchronization between the ear monitor and the Modelflow system, with non-parametric methods evaluating statistical differences. ii Results: The narrative review identified key markers for monitoring VVS. The narrative review identified key markers for monitoring vasovagal syncope (VVS), which guided the validation of the ear BP monitor. Data was successfully collected from 14 out of 20 participants, comprising 47% male and 53% female subjects, with an average age of 24.29 ± 5.61 years. The device demonstrated high coherence values (>0.95) across all activities, indicating strong synchronization with the Modelflow system. No significant differences were observed in systolic BP measurements, with p-values of 0.37 for low-frequency components and 0.18 for high-frequency components, confirming the ear BP monitor's ability to capture BP fluctuations during dynamic physiological changes accurately. Further analysis identified the fundamental heartbeat frequency as 1.4 Hz, with harmonics at 2.8 Hz, 4.2 Hz, and beyond. The coherence of these harmonics highlighted the consistency of the heartbeat-induced waveform shapes, indicating that the arterial blood pressure measurements from the Modelflow and EarBP devices were stable and reliable. Coherence across frequencies revealed comparable signal synchronization between the two devices, with significant coherence observed at the fundamental frequency and its harmonics. Coherence values were tightly clustered near the median across all conditions, with the Valsalva maneuver showing slightly more significant variability due to lower coherence values in some participants. These results collectively validate the ear BP monitor as a reliable tool for arterial pressure measurement and synchronized waveform analysis. Conclusion: This thesis advances the understanding of vasovagal syncope (VVS) physiology and validates using a novel ear-based blood pressure monitor. The narrative review identified key physiological markers and mechanisms, including the Bezold-Jarisch reflex and serotonin signaling, central to VVS episodes. The validation study demonstrated high accuracy and synchronization of the ear BP monitor with established standards, offering a non-invasive, iii wearable alternative for real-time blood pressure monitoring. While promising, further research is required to expand its validation across diverse populations and address potential limitations such as motion artifacts. These findings support the use of an ear BP monitor as an innovative tool with the potential to diagnose vasovagal syncope2 0Item Restricted THE NEUROPHYSIOLGY OF SELECTIVE ATTENTION IN HUMAN SUBCORTICAL MOTOR NUCLEI(University of Toronto, 2025) Alanazi, Frhan; William, HutchisonSelective attention and working memory are fundamental cognitive processes traditionally attributed to cortical regions. Emerging evidence suggests that subcortical motor nuclei, such as the thalamus and basal ganglia, also play crucial roles in these functions, but the mechanism is still unclear. This thesis aimed to examine the neurophysiological mechanisms of selective attention and working memory in subcortical motor nuclei through intraoperative single-unit and local field potential (LFP) recordings in humans. In the first study, neuronal activity was recorded from the ventral intermediate nucleus (Vim) and ventral oral anterior/posterior nuclei of the motor thalamus in 25 patients with parkinsonian and non-parkinsonian tremors during an auditory oddball task. Results showed a significant decrease in neuronal firing rates and in beta-band (13–35 Hz) oscillations to the deviant tones, indicating the involvement of Vim in auditory selective attention. Parkinson’s disease (PD) patients off medication exhibited increased beta power but reduced modulation to attended tones, suggesting dopamine's role in modulating thalamic beta oscillations for selective attention. The second study focused on the centromedian nucleus (CM) of the thalamus in 11 epilepsy patients performing a similar auditory attention task. CM neurons demonstrated selective, multiphasic firing and beta/low gamma (13–45 Hz) modulations to deviant tones in 81% of neurons tested. These findings highlight the CM's participation in cognitive function, supporting its role under top-down control and implicating beta and gamma oscillatory activities in cognitive processing. The third study investigated neuronal activity in the subthalamic nucleus (STN) and Vim during a visual 1-back task in 16 patients with PD or essential tremor. Both nuclei exhibited selective firing rate changes and beta desynchronization in response to target stimuli. Vim beta desynchronization occurred earlier than in the STN, even preceding the stimulus, suggesting a role in stimulus prediction. Collectively, these studies provide evidence that subcortical motor nuclei are actively involved in selective attention and working memory and have significant implications for understanding the neural circuitry underlying cognitive functions and the pathophysiology of neurological disorders like Parkinson’s disease and epilepsy. Furthermore, they offer potential insights for developing deep brain stimulation therapies targeting cognitive symptoms associated with these conditions.12 0Item Restricted A Security Risk Assessment Framework for IoT Systems(University of Regina, 2024-08) Waqdan, Mofareh Abdullah; MouhoubThe emergence and growth of the Internet of Things (IoT) have changed how we live and interact with technology. The seamless integration of connected devices, from household to industrial equipment, has brought about a new era of interconnectedness. However, this rapid expansion of the IoT also introduces new security concerns that need to be assessed. Assessing the security risks associated with deploying and using this technology is crucial. Consequently, organizations need a risk assessment framework that helps identify, evaluate, and manage the risks of IoT, including data privacy and confidentiality, system integrity, availability, and performance. The state-of-the-art has been given significant attention to security risk assessment in traditional cybersecurity with powerful computer systems, but the challenges of deploying IoT devices and their associated vulnerabilities have been overlooked. In this thesis, we first present a novel IoT security risk assessment framework for the healthcare environment, in which we have improved upon existing methodologies. The proposed framework dynamically calculates the risk score for different device profiles, considering their population and other parameters, such as network protocols, device heterogeneity, device security updates, device physical security status, device history status, layer history status, and device criticality. Second, we present a customizable framework for assessing the security risk of deploying and utilizing IoT devices in various environments. We dynamically calculate risk scores for different devices, considering their importance to the system and their vulnerabilities, among other parameters. The customizable framework considers the important parameters of the devices, their vulnerabilities, and how they impact the overall risk assessment. The importance of these devices and the severity of vulnerabilities are incorporated in the framework using the well-known Multi-Attribute Decision Making (MADM) methods, namely, Simple Additive Weighting (SAW) and Weighting Product (WP). Finally, the risk is assessed on a setup comprised of IoT devices widely deployed in healthcare systems, such as emergency rooms.8 0Item Restricted Modulation of Aryl Hydrocarbon Receptor-Regulated Genes by Methylmercury(University of Alberta, 2024) Alqahtani, Mohammed Ali; Ayman, ElKadiEnvironmental pollution poses a significant threat to public health, with various contaminants contributing to a wide range of adverse health effects. Among these contaminants, ؤ (MeHg) and the aryl hydrocarbon receptor (AHR) ligand 2,3,7,8-tetrachlorodibenzodioxin (TCDD) are particularly concerning due to their persistence in the environment and potent biological activities. Both compounds have been extensively studied for their individual effects, but the potential health risks associated with their combined exposure are less understood. The primary objective of this work was to investigate the individual and combined effects of MeHg and TCDD on AHR-regulated enzymes. This investigation was conducted using the murine hepatoma Hepa-1c1c7 cell line and extended to mouse hepatic and extrahepatic tissues. The effects of MeHg on Ahr-regulated gene expression were examined in the absence and presence of TCDD, along with evaluations of protein expression and enzymatic catalytic activity. In hepatic tissue, both MeHg and Hg2+ inhibited the TCDD-mediated induction of Cyp1a1/1a2 mRNA levels. However, only Hg2+ inhibited the TCDD-mediated induction of CYP1A1/1A2 protein and catalytic activity at posttranscriptional levels, indicating differential modulation by Hg2+ and MeHg. Additionally, the inhibitory role of HO-1 (heme oxygenase-1) on CYP1A activity induced by TCDD was investigated in vitro using the HO-1 competitive inhibitor tin-mesoporphyrin, which partially restored the MeHg-mediated decrease in CYP1A1 activity. In extrahepatic tissues, MeHg exhibited mainly inhibitory effects, particularly decreasing the basal level of Cyp1a1 and Cyp1a2 mRNA and protein, which was more evident at the 24-hour time point in kidneys, followed by hearts. Similarly, when mice were co-exposed, MeHg reduced the TCDD-induced Cyp1a1 and Cyp1a2 expression. However, MeHg potentiated kidney Cyp1b1 mRNA expression, opposing the observed change in its protein level. Exposure to MeHg induces several antioxidant enzymes, including NAD(P)H:quinone oxidoreductase (NQO1), whose expression is regulated by both AHR and nuclear factor erythroid 2-related factor-2 (NRF2). This co-regulation prompted an investigation into which transcription factor primarily orchestrates NQO1 expression upon MeHg exposure. Our findings demonstrate that NQO1 induction by MeHg is, at least in part, mediated by NRF2. In conclusion, the findings of this work reveal an intricate interplay between MeHg and TCDD on AHR-regulated CYP1 enzymes, with notable inhibitory effects that might be significant for procarcinogen metabolism. Varied responses across tissues highlight the potential implications for environmental health.7 0Item Restricted Sociocultural Determinants of Children’s Oral Health Among Immigrants: Developing and Testing a Conceptual Model(university of alberta, 2024) Dahlan, Rana; Amin, MaryamBackground: The Canadian Collaboration for Immigration and Refugee Health highlights oral health diseases among the top 11 health challenges for immigrants and refugees. Foreign-born individuals face higher vulnerability due to migration-related disruptions and limited dental access. Cultural shifts, known as "acculturation," impact immigrants' health, varying in degree. Understanding this requires considering post-migration socio-cultural context. Social connections change post-migration, affecting oral health, well-being, and quality of life. Recognizing these shifts is crucial for stakeholders: dentists, community workers, and researchers. Social support is vital for new immigrants, aiding adaptation, and healthcare access. Both parental acculturation and support shape children's oral health. Their combined impact on oral health remains underexplored in existing literature. Objective: The overarching objective of this research was to construct and assess a conceptual model aimed at predicting oral health behaviors and caries experience of immigrants’ children. The goal was to develop a model that explains the sociocultural factors influencing children’s oral health among immigrants, using Structural Equation Modeling (SEM). Methods: This study unfolded in three phases, beginning with ethics approval from the University of Alberta Research Ethics Board (Protocol # Pro00072345). The first phase encompassed two systematic reviews: one focused on acculturation's impact on oral health among immigrants and ethnic minorities, while the other explored social support's influence on oral health in these groups. The second phase, a cross-sectional study, investigated how parental acculturation and perceived social support affected their children's oral health behaviors and caries experience. Participants included first-generation immigrant parents residing in Canada for two or more years, with children aged 2–12 years. Data collection took place in convenient community settings through multilingual community workers using non-probability snowball sampling. Parents provided demographic, perceived social support, acculturation, and children's oral health behavior data. Trained dentists conducted dental exams and used the DMFT/dmft index to assess caries experience. Oral health behaviors were measured with an eight-item questionnaire. The main independent variables were parents' perceived social support (PSS),measured using the validated Personal Resource Questionnaire (PRQ2000) and parents' acculturation and strategies were evaluated with the Asian American Multidimensional Acculturation Scale (AAMAS). The data collected in the second phase informed the creation of a conceptual model in the third phase, aimed at predicting immigrant children’s oral health behaviors and caries experience through Structural Equation Modeling (SEM), examining parental acculturation and perceived social support's influences. Results: A total of 336 parent/child pairs participated in the study. The average parental acculturation level was 10.46, and the average perceived social support (PSS) score was 63.27. Factors like length of residency, parents' education, and household income significantly predicted acculturation level. Parents with higher Canadian cultural knowledge reported more frequent children's toothbrushing. Parents of children consuming >1 sugary item/day had higher acculturation levels, English language proficiency, and Canadian food adoption. Parents of recent dental visitors reported higher assimilation and lower separation scores, while those visiting due to problems had higher marginalization scores. Parental acculturation wasn't significantly linked to children's dental decay (DMFT/dmft). Household income predicted parental PSS (B = -5.69). Children of parents with higher PSS brushed teeth ≥2/day. Parental education predicted social integration and nurturance; income predicted social integration, worth, and assistance. Parents with more intimacy and social integration were more aware of children's oral health. Parental social integration scores were higher when children consumed ≥1 sugary snack/day. All domain scores were higher when children brushed teeth ≥2/day. Structural Equation Modeling (SEM) indicated 77% of DMFT/dmft variance was explained by parental PSS, acculturation, predisposing/enabling factors, and children's oral health (OH) behaviors. Parental PSS had a direct effect on reduced dental caries and sugar consumption. Parental acculturation mediated by positive OH behaviors increased caries risk. Conclusions: The SEM analysis found significant variance in immigrants’ children's caries experience. Findings highlight parental acculturation and PSS levels predicting oral health behaviors and caries. Recognizing sociocultural factors is vital for stakeholders—dentists, community workers, and researchers. Immigrants' vulnerability to oral health issues underscores the need for deeper exploration and expanding the model.1 0Item Restricted Exposure to Allergens and Proinflammatory Mediators Modulate Airway Epithelial Cell Innate Responses, Metabolism, and Physiology(University of Alberta, 2024) Alzahrani, Khadija Rashed; Vliagoftis, HarissiosLungs and airways health and protection depend on the integrity of airway epithelium. Insulin is a growth hormone that through activation of several signaling pathways play a central role to maintain cellular growth and activate metabolism. Airway epithelium is in constant exposure to inhaled agents like pathogens, allergens, pollutants, and particular matters. Airborne allergens like cockroach or house dust mite (HDM) contain proteases that can interact with airway epithelium and initiate immune responses through activation of airway epithelial cells and innate immune cells. Airway epithelium cytokines and innate immune cells promote activation of adaptive immune cells like Th2 lymphocytes that produce proinflammatory mediators like interleukin-4 (IL-4), IL-13, and IL-5. T helper 2 (Th2) cytokines amplify the immune responses and stimulate airway epithelial cells to release CCL chemotactic factors/eotaxins that attract eosinophils to the site of inflammation. Airway epithelium exposure to inhaled irritants and excessive inflammatory responses is known to disrupt epithelium integrity and exacerbate inflammatory responses. Th2 inflammation in asthma is associated with epithelial injury, epithelial remodeling, and metabolic alterations. Increased expression of inflammatory mediators tumor necrosis factor (TNF) and IL-6 in metabolically active tissues have been associated with cellular damage and insulin resistance. Inducible AECs local inflammation was shown to trigger systemic inflammation, insulin resistance, and impaired glucose metabolism, and the severity of inflammation correlated with impaired glucose metabolism. Several studies showed that insulin resistance increased the risk of aeroallergen sensitization and developing asthma-like symptoms. In this project we hypothesized that exposure of airway epithelial cells (AECs) to allergens and proinflammatory mediators may modulate Th2 immune cell responses, induce insulin resistance and metabolic shifts. First, we examined the effect of cockroach and house dust mite on IL-13 and IL-4-induced inflammatory responses. AECs were cultured and stimulated with cockroach or house dust mite, IL-13, IL-4, or a combination of an allergen and IL-13 or IL-4. IL-13 and IL-4 induced effects were measured. Then, we tested the effect of cockroach, house dust mite, TNF or IL-6-induced inflammatory responses on physiological epithelial changes and insulin-induced effects. Epithelial proliferation, resistance, energetic phenotype changes, and insulin induced activation of PI3K/Akt were examined. We showed that serine proteases of cockroach extract prevented IL-13-induced expression of eosinophil chemokine CCL26 from AECs. Depletion of CCL26 was previously shown to delay resolution of airway allergic inflammation which may result in prolonged eosinophilia. Prolonged inflammation was linked to altered metabolism and insulin action in several studies. We showed for the first time that house duct mite and TNF modulated insulin effects in AECs. TNF and HDM changed insulin-induced ATP production in AECs. Additionally, TNF reduced insulin-induced Akt phosphorylation, reduced epithelial barrier function and recovery after injury. Our data suggest that cockroach serine proteases and TNF may interfere with the Th2-mediated proinflammatory effects, regulate AECs energetic phenotype, and induce insulin resistance. These inflammatory and metabolic changes exacerbate the pathogenesis of asthma which may alter immune cell responses.5 0Item Restricted A Comparative Case Study: Exploring Health System Governance in Canada and Saudi Arabia(Western University, 2024) Almalki, Fawziah; Oudshoorn, Abe; Tryphonopoulos, Panagiota; Smith, Maxwell; Muntaner, CarlesHealth systems and health system outcomes are incredibly complex. To understand how they function, researchers explore individual components of the system, in the study herein the component is ‘governance’. Research to date has demonstrated a positive relationship between governance and population health outcomes. Governance, therefore, may be a concept that assists in understanding differential health outcomes of seemingly comparable countries. This study aims to explore macro-level governance, particularly the two sub-concepts of ‘government effectiveness’ and ‘perceived corruption’, in two countries: Saudi Arabia and Canada. Government effectiveness reflects the quality of public health policy development and implementation, and how much the government adheres to these policies. These comparator countries are selected as they share similarities on three levels, economy, population size, and free basic healthcare; yet differ significantly in governance models. A case study methodology as described by Stake (1995), guided this study. This study is particularly a comparative case study design with a focus on qualitative data. The data will be used to understand in-depth nuances of governance in health systems. Two overarching questions guided this study, one for each of the sub-concepts: 1) How the government effectiveness process, in terms of health policy development and implementation, unfolds within the health system in Saudi Arabia and Canada. 2) How corruption, as an aspect of governance, is present within health systems. This work is framed within a critical theoretical perspective. Concerns about good governance and corruption that guide this work is to the purpose of seeking the best health outcomes for all people. Governance as a whole, and sub-concepts of government effectiveness and corruption, are all amenable to change and improvement. To engage with system complexity, multiple data sources were utilized within this case study. Primary data consisted of interviewing 32 participants (15 in Canada and 17 in Saudi Arabia) who work in the health system in service provision, research, policy, management, or education. Secondary data included government documents about health system structure and strategies at the macro level. Data collection was conducted through two phases. Phase one of data collection involved in-depth interviews with experts across the health systems. The interviews were conducted in both English and Arabic. Documents for analysis were collected and accessed through official websites of governments or Ministries of health, and healthcare organizations, and scientific databases. These documents were analyzed via Critical Discourse Analysis (CDA) as outlined by Van Dijk (1993) and Mullet (2018). The findings are divided into three foci as three chapters: 1) a methodological piece on conducting bilingual research; 2) the nature of government effectiveness; and 3) the nature of corruption in health systems. Conducting research in a language not spoken by all the research team members is relatively common, yet addressing the nuanced details of implementing bilingual work has limited guidance within extant literature. This includes consideration of promising practices for concept development, translation, data analysis, and presenting the findings. This chapter is an exploration of the strengths and limitations of doing bilingual research, and recommendations regarding these aforementioned issues from our own experiences. Ultimately, it is proposed that via bilingual research, the accumulation of knowledge pertaining to qualitative research concepts, translation, analysis, and dissemination of comprehensive frameworks can be enacted, ultimately enhancing the rigour of qualitative research and increasing confidence in applying knowledge created in the chosen language of participants. Findings on government effectiveness in health systems in both Canada and Saudi Arabia are presented in four themes. These four themes are: 1) Health is Political, 2) Health System Privatization, 3) An Outdated System vs. A System that is Catching Up, and 4) Social Determinants of Health (SDoH) and Cross-Sectoral Collaboration. Recommendations are provided on how to better identify elements of government effectiveness and integrate them with the SDoH in order to enhance system effectiveness and improve the health of populations. For the chapter on corruption, it is noted that Governance is a complex theoretical concept that includes the sub-concept of ‘corruption’. A very ‘loaded’ term, this study sought to understand how corruption is present in health systems, often in very subtle ways. Findings illustrate how corruption is still a relevant concept in advanced health systems and can include both subtle and even overt forms within Canadian and Saudi health systems. This is explained in three themes: 1) Corruption in Wealthy Nations: Subtle Opportunism; 2) Nepotism and Professional Courtesy; and 3) A Strict System vs A Relaxed System. This analysis uncovers nuanced forms of potential personal gain within Canadian and Saudi health systems that make the concept of corruption still a timely concern. Addressing these risks must be seen as a collective obligation, where healthcare providers identify and report cases of potential corruption, managers prevent and address opportunities for personal gain, and researchers study how to develop policies and processes that are most immune to corruption. Ultimately, this study continues to unpack the complex ways that health systems are actualized, looking particularly at the concept of governance, and selected sub-concepts of government effectiveness and corruption.29 0Item Restricted SMART AUTHENTICATION MECHANISMS: UTILIZING BIG DATA FOR DYNAMIC AND PERSONALIZED SECURITY SOLUTIONS(The University of Western Ontario, 2024-08-25) Abu Sulayman, Iman; Ouda, AbdelkaderThe exponential growth of digital data is revolutionizing information security and reshaping defense strategies against unknown threats. Organizations are amassing vast amounts of personal data, collectively termed ”Big Data,” from various sources like social media, online transactions, and GPS signals. This surge in data presents new research challenges in information security, prompting organizations to leverage big data analytics for valuable insights within secure environments. As a result, organizations are redesigning network security protocols to effectively manage the characteristics of big data. While traditional research focuses on authenticating users to protect big data environments, an alternative perspective emerges: utilizing big data to raise a new generation of authentication mechanisms to safeguard other environments. To this end, we developed novel security solutions that harness big data analytics to generate unique patterns of users’ dynamic behaviors, enabling the design of smart knowledge-based authentication mechanisms to fulfill the requirements of the new era of the digital world. These solutions include three main modules. ”Data Security-based Analytics (DSA),” the first module, develops an innovative data transformation model. The model adapts big data’s characteristics to relevant human dynamic measures. The second module, known as ”Big Data Driven Authentication (BDA),” includes the Security User Profiles (SUP) creation model, which is responsible for identifying patterns in DSA’s output and then uses said patterns to detect legitimate but anomalous activity from the user and assemble a security profile about the user. BDA also includes another model, known as Just-in-time Human Dynamics-Based Authentication Engine (JitHDA), which uses the user’s security profiles to dynamically create secure challenge questions in real-time that derive from the user’s recent behavior. The third module describes the development of a novel “Big Data-Driven Authentication as a Service (AUTHaaS)” model. AUTHaaS is an authentication mechanism that is powered by SUP and JitHDA technologies to offer authentication services on the cloud. Another model in AUTHaaS is ”iAuth,” which is an integration framework for authentication services. We developed this model to offer a unified interface that enables collaboration and interoperability among various AUTHaaS service providers. Additionally, we have developed an algorithm-based data generation (ADG) engine that is capable of processing synthetic user data. We designed ADG to accommodate dual-mode user behavioral data, encompassing both normal and abnormal instances. More importantly, the engine does not necessitate an initial dataset or data distribution and serves as the dataset source for the DSA model as it generates data from five different application domains.7 0Item Restricted Advancing Oncolytic Virotherapy: The Role of Chemical Sensitizers in Enhancing Viral Oncolysis in Resistant Cancers(University of Ottawa, 2024-07-28) Alwithenani, Akram; Diallo, Jean-SimonOncolytic virotherapy, leveraging viruses to target cancer selectively, has shown promise with the FDA-approved oncolytic herpes simplex virus-1 (HSV-1) for melanoma treatment. However, the efficacy of oncolytic viruses (OVs) varies across cancer types, highlighting the need for strategies to sensitize resistant tumors. This thesis investigates the potential of Dimethyl fumarate (DMF), its analog Tepilamide Fumarate (TPF), and novel synthetic small molecules identified from a high-throughput screen to enhance OV effectiveness in cancer therapy. DMF, approved for multiple sclerosis and psoriasis, and TPF, under trial for psoriasis, were evaluated for their ability to boost HSV-1 and vesicular stomatitis virus (VSVΔ51) activity against cancer cells. Our findings reveal that pre-treatment with DMF or TPF significantly increases HSV-1 and VSVΔ51 replication in various cancer cell lines, including melanoma, and improves viral oncolysis. Notably, both DMF and TPF enhance OV infection in mouse-derived tumor cores and human tumor samples, while TPF exhibits a remarkable capacity to heighten VSVΔ51 infection and cell killing, outperforming DMF in vitro. Both compounds achieve these effects by downregulating the interferon (IFN) pathway, rendering cancer cells more susceptible to viral infection. Additionally, we demonstrate the ability of DMF and TPF to boost gene therapy vectors' transduction efficiency, which points to the broader utility of these drugs in gene therapy. Further exploration through a high-throughput screen identified several small molecules that sensitize human renal carcinoma cells to HSV-1 and VSVΔ51, highlighting potential new avenues for overcoming tumor resistance to OVs. These compounds enhance viral replication and oncolysis, presenting a promising path for future oncolytic virotherapy research and development. The synergistic potential of combining approved therapies like DMF with OVs, the promising effects of TPF, and newly identified small molecule sensitizers underscore the feasibility of enhancing OV efficacy in resistant cancers. This study not only broadens our understanding of how small molecules can potentiate oncolytic virotherapy but also sets the stage for clinical evaluation and the development of more effective, personalized cancer treatment strategies. Collectively, these findings advocate for further investigation into DMF, TPF, and other sensitizing compounds to unlock their full therapeutic potential in oncolytic virotherapy.14 0