title: Low dose radiation response in the lungs and spleen

contributor: Radiation Sciences (Medical Physics/Radiation Biology)

subject:
Radiation biology
Immunology
Low dose radiation
Critical care medicine
Lungs
Spleen
Animal model
Rats
X-rays
Respiratory mechanics

abstract:
Patients in the intensive and critical care unit frequently undergo diagnostic radiology procedures such as computed tomography (CT) and X-ray imaging. As these patients often require respiratory assistance and are vulnerable to infection, it is important to understand the potential acute effects of these procedures on the lungs and immune system. The aim of this study was to determine the acute effects of a single clinically relevant low-dose X-ray exposure in order to establish baseline responses in markers of lung injury and immune function in a rodent model.
Male Sprague-Dawley rats (200-250 g) were irradiated with 0, 2, 20 or 200 mGy whole-body X-rays in an XRAD 320 irradiator. Markers of lung injury and immune activation in the lungs and spleen were evaluated 0.5, 4, and 24 h post-irradiation to examine the acute stages of the physiological and immunological response. Intratrachaeal lipopolysaccharide (LPS) exposure was used as a positive control model of acute lung injury. Lung injury endpoints included respiratory mechanics, pulmonary oedema, arterial blood oxygenation, histological analysis, and cellular and proteinaceous infiltrate via bronchoalveolar lavage. Immunological measures in the spleen focused on splenocyte proliferation, using the MTS assay and differential cell counts before and after stimulation with LPS or concanavalin A (Con A), as compared to unstimulated cultures.
Splenocyte proliferation in response to Con A, but not LPS, was significantly decreased after 200 mGy in vivo X-irradiation (repeated measures two-way ANOVA with LSD post-hoc, p=0.024). There was a non-significant trend towards increased lung tissue resistance after 200 mGy, with no significant effect on pulmonary oedema, cellular or proteinaceous infiltrate, nor other aspects of respiratory mechanics (two-way ANOVA with LSD post-hoc, p>0.05).
A clear understanding of these immunological and physiological effects informs the responsible use of medical diagnostic procedures in modern medicine. Establishment of this model for the elucidation of acute immune effects of low-dose radiation will facilitate future work evaluating these parameters in disease models, mimicking patients in intensive care.

abstract: Thesis

abstract: Master of Science (MSc)

abstract:
Diagnostic procedures such as computed tomography (CT) and X-ray imaging are a common part of intensive and critical care medicine. Some physicians are concerned that this exposure to diagnostic radiation may negatively affect the health of their patients, who are prone to infection and who often need a machine to breathe for them. In order for doctors to make informed decisions, the possible effects of these levels of radiation must be understood. To improve this understanding, this study looked at the short-term effects of X-ray doses on key organs affected by critical illness, the lungs, and the spleen, which is an important organ of the immune system that helps fight infection.
Using an animal model, doses of X-rays in the range of diagnostic radiation (0-200 mGy) were examined and no significant effect on lung health was found. However, the highest dose of X-rays tested, which is greater than that expected for a single CT scan, did have an effect on cells from the spleen. Spleen cells are designed to multiply when they detect various types of infection, so that there are more immune cells to fight that infection. The cells from animals that were given the highest dose of X-rays didn’t multiply as much in response to infective stimulus as those from animals that received lower doses, or no X-rays at all.
Overall, it seems that diagnostic radiation doesn’t have an effect in the lungs, but very high diagnostic doses could slightly affect a patient’s ability to fight infection. It is important to remember that patients in critical care are very sick, so doctors have good reason to use diagnostic tools available to them. Missing a diagnosis has major and immediate consequences, which must be balanced against the potential small risks of using radiation to make that diagnosis.


title: XUROGRAPHIC MICROWIRE INTEGRATION TECHNIQUE FOR LAB ON CHIP APPLICATIONS

contributor:
Selvaganapathy, Ponnambalam
Mechanical Engineering

subject:
Lab on chip
Microelectrode
Microwire
xurography

abstract: Many functions in a lab-on-a-chip device such as heating, electrochemical sensing and electrophoresis require integration of microelectrodes. However, conventional techniques for microelectrode integration are either requiring expensive facilities, cleanroom environment or insufficient in resolution and microelectrode thickness. Microwires have also been integrated into LOC devices as microelectrodes. They are commercially available in a diversity of material. and diameter, with industrial production standard and mechanical strength comparable to bulk metal, which make them ideal candidate for microelectrode. Nonetheless a technique to integrate these microwires into complicated microelectrode patterns has not yet been developed. In this thesis, two microwire integration techniques based on xurography are developed for elastomer and rigid polymer. Copper, silver, platinum, carbon and Ni-Cr alloy microwires down to 15 µm with minimum spacing of 150 µm and controllable position in the height direction are successfully integrated. The microwire electrode can also be suspended in the middle of the microchannel with desired length and angle. Various applications are presented to demonstrate the versatility of the xurographic microwire integration process.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: The intestinal microbiome in inflammatory bowel disease and its response to therapy

contributor:
Surette, Michael
Biochemistry and Biomedical Sciences

abstract: Inflammatory bowel diseases, consisting of both Crohn’s disease (CD) and ulcerative colitis (UC), occur when a susceptible host mounts a chronic aberrant immune response to its commensal microbial community resulting in chronic inflammation. CD and UC may exhibit similar clinical manifestations that oscillate between active disease and remission, but these diseases are distinct, and are characterized by specific pathophysiology. The incidence and prevalence of IBD has been increasing over time, with the highest rates occurring in Europe and North America. Although many genome-wide association studies (GWAS) on CD and UC have found loci associated with these diseases, studies conducted on monozygotic twins show low concordance rates, suggesting environmental causes play an important role in the onset of IBD. Current therapies for treatment of IBD focus on suppressing the immune response, but remission rates remain low and relapses occur often. There is a dire need for new treatment options that involve suppressing the immune system stimuli – the commensal gut microbiota. The commensal microbiota triggers the mucosal immune system to drive chronic inflammation in IBD, and studies have shown that patients display a gut dysbiosis compared to healthy individuals. Modulation of the disease through modulation of the gut microbiome, has recently gained interest as a potential treatment option. Little is known about how the microbial community in IBD patients will respond to therapies that attempt to modulate the community. Thus, the overall goal of this thesis was to characterize the IBD microbiome in relation to disease status, severity, and response to therapy. Together these results, (a) provide an in-depth characterization of the intestinal microbiome in IBD, (b) demonstrate the response of the gut microbiome in UC patients to FMT, providing insight into the successful mechanism, and (c) provide evidence for inflammation related differences in CD giving insight into the mechanism of pathogenesis. These results not only further our understanding regarding dysbiosis in IBD, but also can be used to modify our current treatment protocols to increase efficacy.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: The Effect of Load Rate on the Axial Fracture Tolerance of the Isolated Tibia During Automotive and Military Impacts

title: Effect of Load Rate on the Fracture Tolerance of the Tibia

contributor:
Quenneville, Cheryl E
Mechanical Engineering

subject: biomechanics bone fracture

abstract:
Fractures of the lower leg are common during frontal automotive collisions and military blasts. These two scenarios cause injury via a similar axial loading mechanism. The majority of previous studies that have conducted axial impact tests to determine the injury limits of the lower leg have simulated automotive impacts; however, due to the viscoelastic nature of bone, it remains unclear whether limits from automotive experiments can be applied to higher-rate blasts. The purpose of this work was to study the effect of load rate on the fracture tolerance of the tibia during these two scenarios.
The instrumentation required to quantify impacts to lower leg specimens using a pneumatic impactor was developed, and included capturing synchronized load, acceleration, velocity, strain, and high-speed video data. Subsequently, impact testing was performed on twelve human cadaveric tibias. Velocities and impact durations were matched to literature values to simulate an automotive collision and a military blast. Force and impulse were found to significantly differ between the two conditions, while kinetic energy did not. Specimens impacted at higher rates required greater forces to achieve fracture, which suggests that load rate needs to be accounted for in future injury criteria. Two commonly used anthropomorphic test device lower legs were tested under similar loading conditions, and new thresholds were developed for these devices. Finally, a finite element model was tested for its ability to simulate loading of the tibia during varied impacts. This model can be used to assess injury risk and protective measures for the leg.
Understanding the effect of load rate on the tibia’s fracture tolerance is essential when developing injury thresholds that can be applied to impacts of various rates. The results of this work can be used in the future to design and evaluate improved protective systems to be implemented in vehicles.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract:
Fractures of the lower leg are common during frontal automotive collisions and military blasts. Due to the viscoelastic nature of bone, it remains unclear whether safety limits from automotive experiments can be applied to higher-rate blasts. The purpose of this work was to study the effect of load rate on the fracture tolerance of the tibia during these two scenarios.
Impact testing was performed on twelve human cadaveric tibias. Specimens impacted at higher rates required greater forces to achieve fracture, which suggests that load rate needs to be accounted for in future injury criteria. Two commonly used crash test dummy lower legs were tested under similar loading conditions, and a finite element model was developed and tested to simulate loading of the tibia during high-rate impacts.
The results of this work can be used to design and evaluate improved protective systems to be implemented in vehicles.


title: Soft Nanoparticle Flotation Collectors

contributor:
Pelton, Robert
Chemical Engineering

subject: Nanoparticle Flotation

abstract:
Flotation is arguably the most important mineral separation technique. It has been demonstrated that hydrophobic nanoparticles adsorbed onto hydrophilic mineral surfaces can facilitate mineral particles attachment to air bubbles in flotation process. This thesis explores the effects of nanoparticle adhesiveness, size and shape on the performance of nanoparticle flotation collectors. For this, a series of rigid polystyrene, soft shelled polystyrene-poly (n-butyl methacrylate) (PS-PB) and soft lobed polystyrene/poly (n-butyl methacrylate) (PS/PB) Janus nanoparticles were prepared and characterized.  Flotation experiments with glass beads, a model for mineral particles, revealed that soft-shelled particles were more effective collectors than were hard polystyrene particles. The small (92 nm) Janus particles were particularly good flotation collectors for glass beads.
The pull-off forces required to remove nanoparticles from glass were measured by AFM and the results were compared to the abilities of the nanoparticles to induce the flotation of hydrophilic glass beads.  Soft PS-PB particles were strongly adhering and were very effective nanoparticle flotation collectors.  By contrast, hard PS particles were weakly adhering and were poor flotation collectors.  These observations led to the hypothesis that weakly adhering nanoparticles were dislodged from the glass bead surfaces during flotation.  Experimental support for this hypothesis included: (1) the coverage of nanoparticle on glass bead surfaces decreased with increased conditioning time; (2) large nanoparticles aggregates were detected in flotation pulp as well as on bead surfaces; and, (3) dislodged soft-shelled PS-PB particles left polymeric patches, we call footprints, on the glass bead surfaces.  Indeed, the presence of the footprints, suggests that a nano-scale stamping process can be used to cover surfaces with hydrophobic polymer footprints.
Arguments are made that hydrodynamic forces alone were insufficient to detach the small nanoparticles from the glass bead surfaces in our experiments.  Instead, it is proposed that bead-bead collisions during conditioning and flotation caused weakly adhering particles to detach; a process is termed as “nano-scale ball milling”. Furthermore, geometric arguments show that during a bead-bead encounter, larger nanoparticles are more susceptible to removal than small particles which is consistent with the experimental data.
Although all experiments were performed with model glass beads and rather simple nanoparticles, this work has for the first time explained why larger polystyrene nanoparticles are ineffective flotation collectors.  The work highlights the need to consider nanoparticle/mineral adhesion when designing collectors for real mineral systems.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: It's Not in The Job Description: Post-Traumatic Stress Disorder as an Occupational Illness Among Paramedics

contributor:
Storey, Robert
Labour Studies

subject:
PTSD
Emergency First Responders
Paramedic
Occupational Health
Occupational Illness
Mental Health

abstract: Given that the rates of post-traumatic stress disorder (PTSD) are increasing in today’s society, it is important to gain a better understanding of how organizational factors shape the work experiences of those who have suffered or suffer from PTSD. Paramedics constantly face hazardous situations on the job and thus it is reasonable to argue that many of these situations may have lasting negative impacts on their mental health such as depression, anxiety, and alienation. The purpose of my research is to explore the understanding and experiences of workers in these professions who have experienced PTSD either directly or indirectly. I hypothesize that the supports that emergency first responders receive for PTSD are largely based on organizational factors that shape these professions. For example, the inherent masculine culture associated with this line of work, and the emotional and physical labour that is associated with the job. In exploring the aspects of support received by paramedics, a deeper understanding of why the workers in these professions are not talking about PTSD, seeking or offering support will be gained.  It will be shown that the support paramedics receive, whether it be through family, friends, doctors, and/or co-workers, determines how PTSD is addressed and viewed within these professions. It is hoped that through this research PTSD within emergency first response professions will be better understood as an occupational illness.

abstract: Thesis

abstract: Master of Arts (MA)


title: Carbon and Oxygen Isotope Effects in Synthesized Carbonates at 25 °C

contributor:
Kim, Sang-Tae
School of Geography and Geology

abstract: Carbonate minerals have been abundant throughout Earth’s geological history and the carbon and oxygen isotope ratios of carbonates can be used for paleoclimate reconstruction based upon the recognized stable isotopic relationship with the environmental factors. However, their accuracy is obscured by “non-equilibrium isotope effects” caused by physicochemical factors, such as solution chemistry, pH and precipitation rate. This study aimed to better understand these factors to improve the robustness of isotope-based paleotemperature proxy and assist in providing a reference frame for future research.  Carbonates were synthesized using passive CO2(g) degassing at two different pH levels (~8.2 and ~11.07) through the dissolution of 5, 15 and 25 mmolal sodium bicarbonate (NaHCO3) or sodium carbonate (NA2CO3) and calcium chloride dihydrate (CaCl2•2H2O) at 25 ± 0.1 oC. The 1000ln18α(CaCO3-H2O) and 1000ln13α(CaCO3-DIC) values were then compared with established isotopic equilibrium values for oxygen and carbon.  Samples were also synthesized in the presence of various concentrations of carbonic anhydrase (CA) and it was found that this enzyme may not influence kinetic isotope effects at higher precipitation rates.  A positive, concentration based trend was found for the mid-pH solutions between 1000ln13α(CaCO3-DIC) and 1000ln18α(CaCO3-H2O) values which began at the oxygen isotopic equilibrium value proposed by Kim and O’Neil (1997).  This trend deviated upwards towards that of Coplen (2007) due to the kinetic influence of precipitation rate and degassing caused by the production of CO2(aq) as a by-product of the aforementioned reaction.  The high pH solutions followed an opposite trend, with 1000ln13α(CaCO3-DIC) continuing the enrichment trend but 1000ln18α(CaCO3-H2O) values declining and may have been caused by CO2(aq) not being produced in the high pH reactions.  The DIC equilibration time at this pH took 7 days as shown by Kim et al. (2006) and not 45 days as discussed in Beck et al. (2005).

abstract: Thesis

abstract: Master of Science (MSc)


title: Preclinical evaluation of the antithrombotic potential of the most commonly prescribed antiplatelets

contributor: Medical Sciences (Blood and Cardiovascular)

abstract:
Myocardial infarctions and stroke are the leading causes of death in developed countries, and often result from arterial thrombus formation triggered by the rupture of an advanced atherosclerotic plaque. Plasma levels of cholesterol are correlated with risk of cardiovascular disease. In addition, platelets have a predominant role in the formation of arterial thrombi. Thus, lipid-lowering drugs, such as atorvastatin, are used in combination with antiplatelet agents, such as acetylsalicylic acid (ASA) and clopidogrel, to prevent and treat cardiovascular disease.
In the studies described in this thesis, we measured the antiplatelet effects of atorvastatin, ASA and clopidogrel in mice. We discovered that atorvastatin attenuates platelet activation via protease-activated receptor 4 (PAR4, thrombin receptor) signaling in a nitric oxide (NO)-independent manner. We evaluated the antiplatelet effects of all three medications in vitro. Furthermore, we measured the antithrombotic potential of these three medications in vivo in a murine arterial thrombosis model. We first demonstrated that the sensitivity of the laser injury thrombosis model is improved by measuring platelet activation markers (platelet aggregation, degranulation and phosphatidylserine (PS) exposure). Using this modified laser injury thrombosis model, we found that neither atorvastatin nor ASA reduces thrombus volume, however both delayed in vivo platelet activation. Moreover, we showed that in the context of co-administration with clopidogrel (which is the standard-of-care), ASA at 10 mg is more effective at reducing in vivo thrombosis than ASA at 40 mg. This supports the notion that high doses of ASA offset the partial inhibitory effect of P2Y12 antagonists by interfering with prostacyclin (PGI2) formation.
In conclusion, our results support PAR4 signaling as a target for developing new antiplatelets and advocate for ASA dose adjustment in standard-of-care therapeutic strategies that use both ASA and P2Y12 antagonists. Our findings will help guide and improve future pharmaceutical intervention strategies for arterial thrombosis patients.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Characterizing Cooperative and competitive interactions involving Streptococcus intermedius

contributor:
Surette, Michael G.
Biochemistry

subject:
Streptococcus intermedius
polymicrobial interactions

abstract:
The Streptococcus Anginosus/Milleri group (SMG) colonize mucosal surfaces in humans but are also associated with numerous respiratory and invasive infections. These infections are often polymicrobial in nature, with obligate anaerobes often being isolated. The group consists of three species, S. anginosus, S. constellatus and S. intermedius. SMG are considered to be lactic acid bacteria, producing acids such as lactate, formate and acetate as byproducts of their metabolism. Their genomes have been recently sequenced but little is known about their metabolism. Understanding the basis of their metabolism is beneficial in determining optimal growth conditions and mechanisms associated with their pathogenicity. The isolation of obligate anaerobes from SMG polymicrobial infections suggests that they have anoxic microenvironments. There is also some evidence for synergy between SMG species and anaerobes. While cooperation might be occurring with certain anaerobes, streptococci also produce inhibitors such as hydrogen peroxide and short peptides called bacteriocins. These give streptococci a competitive advantage in polymicrobial commensal communities such as the oral cavity. The Streptococcus invasion locus controls bacteriocin production in Group A streptococci and has been identified in SMG species as well. It is unknown if SMG have mechanisms to compete with closely related streptococci. The goal of my thesis is to characterize the cooperative and competitive interactions of S. intermedius with other species.
In chapter 2, we characterized the in vitro metabolism of S. intermedius under aerobic (5% CO2) and anaerobic conditions. Using a transcriptomic and metabolomic approach, we mapped the pathways involved in S. intermedius B196 metabolism. We found that there was a minimal upregulation of core pathways including carbohydrate metabolism under anaerobic conditions. Under aerobic conditions, oxidative stress genes were induced. An increased growth rate was also observed anaerobically.
In chapter 3, I demonstrated that Streptococcus strains, including S. intermedius, can deplete oxygen and create an anaerobic environment. Certain strains could support the viability of the obligate anaerobe Prevotella melaninogenica in broth cultures under hypoxic conditions, while others inhibited Prevotella by producing hydrogen peroxide. S. intermedius B196 has an alkylhydroperoxidase system (ahpCF), which is thought to endogenously detoxify peroxides. An S. intermedius ahpCF mutant produced hydrogen peroxide and inhibited P. melaninogenica in coculture.  Complementation in S. intermedius restored P. melaninogenica viability in coculture. I demonstrated that the ahpCF peroxide detoxification system directly protects S. intermedius from peroxides and indirectly affects a polymicrobial community.
In chapter 4, we used a subcutaneous abscess model in BALB/c mice to demonstrate that S. intermedius promotes P. melaninogenica survival during co-infection in comparison to a P. melaninogenica mono-infection. S. intermedius induced abscesses appeared to induce apoptosis, necrosis and NETosis in neutrophils that infiltrated the site of infection. Our results demonstrate the complexity of SMG infections.
In chapter 5, I demonstrated that S. intermedius B196 produces inhibitors of other SMG in response to stimulation with the pheromone peptide SilCR. This is the first case of S. intermedius inhibiting a closely related SMG strain. A bioinformatic analysis was done on the sil system in SMG.  The system is associated with a genetically heterogeneous bacteriocin cluster which can carry any combination of sixteen putative open reading frames, six of which are putative bacteriocins.
Together, my thesis outlines that S. intermedius has specific mechanisms of cooperation and competition. These allow it to cooperate with obligate anaerobes such as P. melaninogenica and inhibit other SMG species. Oxygen depletion, hydrogen peroxide production and bacteriocin production are only three factors addressed in this thesis. However, there are many factors involved in shaping a polymicrobial environment with SMG species. More research in SMG polymicrobial interactions is required to fully understand SMG pathogenicity.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: THE SOCIAL ORGANIZATION OF SCHOOL HEALTH SUPPORT SERVICES FOR CHILDREN WITH DIABETES IN ONTARIO SCHOOLS: AN INSTITUTIONAL ETHNOGRAPHY

contributor:
Sinding, Christina
Social Work

subject:
Institutional Ethnography
Children with diabetes
School health support services
Caregiving

abstract:
This thesis is an institutional ethnography (IE) examining the social organization of Community Care Access Centre School Health Support Services (CCAC SHSS) for children with diabetes in Ontario schools. More specifically, it explicates the social relations embedded in, and coordinating the work organization of mothering (parenting) and nursing in the school setting. The inquiry begins in my personal experience as a mother of a child with diabetes starting kindergarten, and the troubles I encountered in getting the care and attention needed to keep my child safe at school. Starting from experience, a place outside of theory and institutionalized categories and discourse, I set out on a journey to discover the social organization that coordinates my experience, and to seek answers to my query: how are school health supports put together in such a way that I, as a parent, am left feeling worried about my child’s safety when she is at school, have had to fight to secure the much needed ‘diabetes care’, and even then, am often called upon to provide voluntary supplementary healthcare work to ensure her safety at school?
I have structured this thesis into two main parts. The first part provides the set-up for this thesis. First, I orient readers to this distinctive way of doing an IE, directing their attention to how I used the core IE concepts in this research and calling upon them to read the remainder of the thesis taking up this distinctive theoretical and conceptual lens. Indeed, what we know and how we know it has much to do with how knowledge is socially organized. Then, I go on to examine the different ways of knowing about ‘diabetes care’, how these distinctive ways of knowing create a disjuncture for me as a parent and how this disjuncture is used to establish the research standpoint to begin and direct the explication. The last chapter in this part situates health supports for children with diabetes within the services provided by public-funded home care. I sketch three decades of the history of reform and organizational restructuring of home care in Ontario, in particular, the introduction of privatizing relations into the local practices of community nursing and the creation of CCACs. These relations of privatization reorganized the home care sector, the workforce, and the relation between the ‘state’ and its citizens. What went on before sets the groundwork for what can happen next, and it is under this context and conditions in which my inquiry is set.
The second part consists of four academic journal manuscripts. They are the descriptive analysis for this IE. These four chapters describe what I have learned and discovered in doing this research, and three of them in particular provide an empirical analysis showing how school health supports for children with diabetes are put together such that the troubles I experienced came into being. These four chapters are conventionally referred to as research ‘findings’ in traditional qualitative research methodology. Each of these chapters speaks to a particular way of knowing about ‘diabetes care’. One focuses on parents’ experiential ways of knowing based on the actualities of their daily and nightly everyday world to show the amount of work and knowledge required to care for and to keep their children with diabetes alive; while the other three underscore the CCACs’ institutional ways of knowing about ‘diabetes care’ in the school setting. I show how these objectified ways of knowing derived from institutional texts (Standardized CCAC Medial Orders, information technology software and the Diabetes Checklist for Independence) are used to determine a child’s eligibility to receive health supports at school. These objectified textual forms of knowing are removed from the actualities of people’s real life circumstances, and differ significantly with how and what parents know is needed for their children with diabetes to stay well and safe at school. It is precisely this form of text-mediated social coordination that leaves parents feeling worried and draws them in to doing voluntary healthcare work at school, without which the child’s safety and the continuity of care is not possible.
Tracing the institutional relations organizing how health support services for children with diabetes actually happen in the classroom, I show the kind of work expected of parents, and demonstrate that the CCAC SHSS policy and practices only ‘work’ as they should with the incorporation of parents’ ‘unauthorized’ knowledge and their ongoing voluntary complementary healthcare work. While it is in parents’ interests to ensure their children’s safety and well-being at school, there are differences between parents in how, and if, they can deliver their knowledge and resources.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Diabetes is a chronic health condition that requires individuals with diabetes or their families to maintain a daily well-coordinated and intensive diabetes self-care routine. Lapses in this complex daily regimen can have devastating immediate and long-term consequences. How children’s diabetes, that is children’s health and well-being, are cared for at school is of concern for parents. The inquiry begins in my personal experience as a mother of a child with diabetes starting kindergarten, and the troubles I encountered in getting the care needed to keep my child safe at school. Starting from experience, this thesis examines how the institutional context and routine practices of diabetes care in school affects the care children actually receive. Despite legislation that requires accommodations for students with disabilities, what I found in this study is that parental involvement (which is inequitably available) is essential to ensure diabetes care is adequate for children in schools.


title: Robustness to Estimation Errors  for Size-Aware Scheduling

contributor:
Down, Douglas
Computing and Software

abstract:
When scheduling size-aware single server systems, Shortest Remaining Processing Time (SRPT) has strong optimality properties - it minimizes the number of jobs at the server and as a consequence, the mean response time. A major caveat of SRPT is that it requires job sizes a priori. This thesis examines a scenario that is likely to occur in practice, where only estimates of job sizes are available. A single server model and a multi-server model using SRPT are compared to a Class-Based policy that is designed to increase robustness to estimation errors. In the single server model we observe from simulations that such robustness is crucial to achieve good performance. In contrast, we observe that a multi-server system is inherently more robust than a single server system. Both policies work well with the estimation errors in the
multi-server system.

abstract: Thesis

abstract: Master of Applied Science (MASc)


contributor:
Kramer, J.R.
Geology

abstract: Title: Formation of Ferric Phosphate Minerals and Adsorption of Phosphate on Amorphous Iron Oxide, Author: Norman D. Warry, Location: Thode

abstract:
A series of experiments was designed to investigate the
reaction of orthophosphate with amorphous iron oxide under conditions
approximating those encountered in lacustrine environments. A
dynamic physical sorption reaction explained the uptake of the ion
onto the solid. When total P was <200 μg/l and total Fe≥2.5 mg/l,
more than 95% of the dissolved orthophosphate was adsorbed onto the
Fe(OH)3 particles. When total Fe was = 0. 25 mg/l or less, no phosphate
was adsorbed. The sorption was a maximum in the pH range
between 4 and 7.5, as long as particulate Fe(OH)3 was present in the
solution. Outside of this pH range, the sorption of phosphate by the
solid decreased dramatically. The lower limit of Eh stability for the
P-Fe(OH)3 complex was found to be on the order of 200 mv, equivalent
to 1 mg/l D. O. Below this Eh value, the complex dissolved. No upper
limit of Eh stability was found.

The complex was capable of being altered to a crystalline
mineralogical phase if total orthophosphate was increased to > 10^-4M.
The structure of this phase was quite similar to that expected for a
mixture of the ferric phosphate minerals strengite and metastrengite. (ΣHPO4^-3 ≃1x10^-3M, Eh > 300 mv, pH≃7) of this solid with those necessary for the formation of strengite (Nriagu, 1972b) show a good correlation. Formation of these mineral phases in lacustrine sediments is not likely, however, because the requisite conditions are rarely satisfied in natural sedimentary environments.

abstract: Thesis

abstract: Master of Science (MS)


title: Design and Operation of Process Supply Chains under Uncertainty

contributor:
Swartz, Christopher L.E.
Chemical Engineering

subject:
Supply chain optimization
Supply chain planning
Supply chain system
Supply chain design
Robust Multistage MPC
Integrated SC planning
Model predictive control

abstract:
This thesis deals with the problems of design and operation of process supply chains. Process supply chains face many challenges due to volatile market conditions, production and transportation delays, and stiff market competition, which ultimately affect their profitability. Supply chain management (SCM) is the process of managing the flow of materials and information within supply chain to optimize the SC performance. SCM is carried out using a hierarchical decision-making framework, where the top most layer looks at network design and the bottom-most layer deals with scheduling day-to-day activities. In this research, the systems engineering principles are applied to devise an improved methodology for supply chain optimization (SCO).

First, we consider the design of supply chain in the presence of demand uncertainty. The representation of network topology plays an important role in deriving the optimal network design. In real practice, the shipping cost for transferring goods from one location to another is determined based on service time and quantity. More importantly, the cost associated with establishing a transportation linkage is relatively small for existing transportation infrastructure and can be changed if beneficial. The flexibility of changing the transportation routes is included in the network topology representation by the explicit inclusion of time limited transportation contract agreements. Further, the customer demand is volatile, and it is very difficult to predict accurately. To handle the demand uncertainty, a two-stage stochastic programming formulation is applied in the SC design approach.

Next, we consider the problem of handling uncertainty in SC planning by applying a system engineering control principle, robust model predictive control (MPC). The uncertainty in model parameters (yield) and demand are captured by stochastic programming. In this approach, the planning activities are represented by a hybrid model with decisions governed by logical conditions/rulesets. An MPC based rolling horizon control framework is used to schedule the planning activities, where the SC performance is expressed using a multi-criterion objective comprising customer service and economics. The uncertainty in demand and yield are propagated by two mechanisms - an open-loop approach, and an approximate closed-loop strategy.

Finally, we consider the problem of integration of SC planning and scheduling. Due to the use of different time scale models for planning and scheduling, the decision derived from the planning layer may result in infeasibility when those targets are implemented at the scheduling level, which ultimately affects the supply chain efficiency. To address this issue, we model tactical and operational planning activities using an integrated hybrid time modeling approach in which the first few planning periods are formulated using an operational planning model and the remaining time periods are modeled with a tactical planning model. The main rationale for formulating an integrated model is that customer demand forecast becomes less accurate for a future time, therefore making a detailed planning model unnecessary. A key benefit of using a hybrid modeling approach is that it avoids the problem of infeasibility encountered in the hierarchical decision framework, as well as the computational burden associated with the use of a detailed planning model over a long time horizon. We employ an MPC based rolling horizon framework as a tactical decision policy where the integrated model is used to predict the system behavior.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


contributor:
Hamielec, A.E.
Lu, W.K.
Chemical Engineering

abstract: Title: Thermal Diffusion in Kinetic and Equilibrium Measurements by Levitation Technique, Author: Malcolm Sunderland, Location: Thode

abstract:
An experimental investigation of thermal diffusion was carried out
using a levitated iron sample and, a binary gas mixture of hydrogen and hydrogen
sulphide . The iron was liquid and the moving gas stream was at room temperature. A range of drop temperatures, gas flow rates and compositions was studied.

The fluxes due to thermal diffusion were found to be significant in
this particular system. Interpretation of the rate data for the sulphurisation
and desulphurisation of the iron showed a pronounced effect of thermal diffusion
upon rate and equilibrium measurements.

An overall rate expression which accounts for thermal diffusion and
normal mass transfer in the gas phase has been developed. It is in agreement
with experiment. Equillibrium data in the literature have been corrected for
thermal diffusion error by means of this expression. These corrected equilibria
are in agreement with measurements made by crucible techniques.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: CULTURALLY TAILORED SELF-MANAGEMENT INTERVENTIONS FOR SOUTH ASIANS WITH TYPE 2 DIABETES: A SYSTEMATIC REVIEW

contributor:
Sherifali, Diana
Nursing

subject:
Type 2 diabetes
South Asian
Culture
Self-management

abstract: Introduction: As the prevalence of diabetes continues to rise in Canada, South Asians, as the largest visible minority group in Canada, are at higher risk for developing diabetes than the general population. Although diabetes self-management education (DSME) interventions for South Asians with type 2 diabetes (T2DM) have been researched, these interventions have not been assessed for their cultural congruency. Methods: This systematic review examined the effectiveness of DSME interventions for South Asians with T2DM. Electronic databases (MEDLINE, EMBASE, Cochrane CENTRAL and CINAHL) were searched since inception, along with relevant reviews and guidelines. Title and abstract and full text screening were conducted independently by two reviewers; data extraction was done by one reviewer and confirmed by another. Quality assessment of the included studies was completed using the Cochrane Risk of Bias tool; cultural congruency was assessed using Leininger’s Sunrise Model. All results were synthesized narratively. Results: A total of 1259 studies were found in the search, of which only four randomized controlled trials (RCT) met the inclusion criteria. All studies were consistent in showing a reduction in A1C following the intervention; however only one study reported statistically significant reductions in A1C. Interventions were conducted in person, with follow-up periods ranging from six months to two years, with the use of South Asian community link workers in most interventions. Bias was identified across all studies for sequence generation, allocation concealment and blinding. All studies had limited evidence of cultural congruency, particularly for gender roles and responsibilities. Conclusions: This review found limited effectiveness of culturally specific DSME interventions for South Asians with T2DM. Furthermore, the interventions were scant in their description of cultural congruency. Future research ought to begin with designing interventions for cultural congruency and improved methodologies for DSME research to improve internal and external validity.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: South Asians are the largest visible ethnic minority group in Canada and are at high risk of developing type 2 diabetes (T2DM). This research project aims to understand how diabetes self-management education (DSME) and support (DSMS) is delivered to South Asians with T2DM and how these practices are culturally tailored.  The scientific literature was searched using electronic databases to find 1259 research studies, of which four examined the effectiveness of DSME/DSMS provided to migrant South Asians with T2DM. Only one study showed significant improvements in blood glucose control. All of the four studies contained several DSME/DSMS components and they all failed to address differences in gender roles and responsibilities in relation to South Asian culture. Thus, there is a need for future studies to design DSME/DSMS interventions that are culturally tailored to improve blood glucose control and thus, improve the health and well-being of South Asians with T2DM.


title: Low Dose Effects of Gamma and Neutron Radiation on Peripheral Blood Lymphocytes

abstract:
This thesis examines the effects of radiation on human peripheral blood lymphocytes, with the goal of elucidating a biomarker of radiation quality.  The issues studied were (1) the effect of thermal and fast neutron exposure on chromosome aberrations, and (2) the effect of thermal neutron and gamma radiation on apoptosis and necrosis induction.  As a starting point, a literature review was performed to examine how neutron RBE values vary with neutron energy, reference radiation, anticoagulant status, irradiation container, and RBE calculation method.  The dicentric chromosome assay (DCA) was utilized for the microscope-based analysis of chromosome aberrations, whereas imaging flow cytometry was used to examine cell death.
Chromosome aberrations were induced following both low dose 252Cf and thermal neutron irradiations (doses ranged between 10 mGy – 108 mGy and 1.2 mGy – 13.4 mGy, respectively), with both radiations demonstrating a linear relationship between dose and aberration induction.  The results produced were compared to a pre-existing 137Cs dose response curve and indicated a RBE of 20.1 ± 2.9 for chromosome damage by 252Cf fast neutron radiation, and 26.1 ± 7.0 following low-dose thermal neutron exposure.  When damage is assessed in lymphocytes via the dicentric chromosome assay, these results indicate that 252Cf is approximately 20 times more damaging than 137Cs gamma radiation, and thermal neutron radiation is approximately 26 times more damaging than 137Cs gamma radiation.  In contrast, a RBE value could not be assigned to either apoptotic or necrotic induction following thermal neutron radiation, as no cell death dose-response was observed at doses between 0.2 mGy and 18.9 mGy.  However, 60Co gamma doses between 0.03 Gy and 2.5 Gy demonstrated a quadratic dose-dependent increase for both types of cell death.
Neither the chromosome aberration study nor the cell death study yielded a biomarker of radiation quality.  While non-Poisson chromosome aberration over-dispersion of radiation-induced DNA aberrations is normally the result of either high-LET radiation exposure or a partial body exposure, it was found that neither the 252Cf nor the thermal neutron exposures consistently induced over-dispersion.  As such, over-dispersion should not be used to differentiate high-and low-LET radiation exposures in lymphocytes.  Unfortunately, due to a late-breaking thermal neutron dose rate decrease, it was not possible to assess whether the percentage of apoptosis and/or necrosis could be used as a biomarker of radiation quality, as the very low doses of thermal neutron radiation failed to demonstrate a significant dose response.  That said, the 60Co cell death experiments demonstrated a linear-quadratic dose response for both apoptosis and necrosis at doses up to 2.5 Gy.  Additionally, these experiments established that donor variability had little effect on cell death induction.
This work contributes to our understanding of the biological effects of neutron and gamma radiation, and suggests that both thermal and fast neutron radiations induce chromosome aberrations in a dose-dependent manner.  In contrast, it was found that in surviving cells at 48 hours post-irradiation, apoptosis and necrosis induction are independent of thermal neutron dose, a phenomenon that deserves further investigation.  Additionally, since the low-dose 252Cf and thermal neutron DCA data failed to indicate consistent over-disperson typically characteristic of high-LET exposures, the results suggest that following accidental low-dose gamma exposures, estimates of dose, made using the DCA method, could be unreliable if the subject has a history of occupational exposures to neutrons.

abstract: Thesis

abstract: Master of Science (MSc)


title: Cognitive Deficits in Cardiac Rehabilitation: A Comparison of Post-Bypass and Post-Angioplasty Patients

contributor:
Strachan, Patricia
Nursing

subject:
cognitive deficits
cognitive impairment
cognitive function
cardiac rehabilitation
coronary revascularization
CABG
PCI
coronary artery bypass graft surgery
coronary angioplasty
cardiac surgery

abstract: Mild cognitive deficits that negatively impact self-management education-related outcomes may be present in a proportion of cardiac rehabilitation patients and the degree of impairment may vary by the type of coronary revascularization procedure. The purpose of this study was to compare cognitive function, as measured by the Montreal Cognitive Assessment (MoCA), between coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) patients, and to determine independent variables of MoCA score. In a cross-sectional study, 78 cardiac rehabilitation patients (CABG n = 38, PCI n = 40) completed the MoCA. Demographics were collected and disease burden was calculated using the age-adjusted Charlson Comorbidity Index (ACCI). Mild cognitive deficits (MoCA ≤26) were present in 55.3% CABG and 30.0% PCI patients. An independent Student’s t test showed that MoCA scores were significantly lower among CABG patients (mean = 24.5, SD = 3.3) compared to PCI patients (M = 26.7, SD = 2.7), t (76) = 3.15, p < 0.01. Descriptive analyses of cognitive domain scores indicated that deficits in short-term memory and language were present among CABG patients. Using a backward regression, coronary revascularization procedure (CABG vs. PCI) (p = 0.006) and disease burden (ACCI) (p = 0.015) remained significant, while heart failure diagnosis became non-significant and was removed from the model (F (2, 75) = 8.382, p < 0.001). The final model explained 16.1% of the total variance in MoCA score (adjusted R2 = 0.161). Results indicate that cognitive deficits were present in cardiac rehabilitation participants and associated with the type of coronary revascularization procedure, suggesting the need for formal cognitive screening and adaptation of education interventions in cardiac rehabilitation. A future prospective cohort study is required to establish temporality, and to measure education-related outcomes, such as health-related quality of life (HRQOL) and self-management.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Cardiac rehabilitation (CR) is a multifaceted program consisting of exercise and education that is essential to the care of post-coronary revascularization patients. While exercise has shown to improve health outcomes, education has demonstrated inconsistent effects. Since education has imposed cognitive demands, this discrepancy in outcomes may, in part, be due to cognitive deficits present in a proportion of program attendees: the degree of impairment may vary by type of coronary revascularization procedure prior to CR. This study compared cognitive function between two groups of coronary revascularization patients, post-coronary bypass surgery and post-coronary angioplasty, and determined independent variables for cognitive function. Results showed that coronary bypass surgery patients had significantly lower cognitive function than coronary angioplasty patients at program intake. Coronary bypass surgery and accumulated disease burden were weakly associated with decreased cognitive function. Cognitive screening and adapted education for patients with cognitive deficits should be considered to improve CR outcomes.


title: CUSUM Control Charts for Censored Gamma Distributed Quality Measurements

contributor:
Viveros-Aguilera, Román
Mathematics and Statistics

abstract: Many companies conduct life tests on their products to ascertain their quality. In some cases, the tests are performed under accelerated circumstances and very often under censoring. The gamma distribution is widely used as a viable model for the lifetimes. In this thesis, we develop likelihood ratio cumulative sum (CUSUM) control charts for Type I right-censored data to monitor the mean lifetime of a product. The primary focus of this research centers on monitoring changes in the scale parameter η of the gamma distribution while the shape parameter β is kept fixed. A simulation study was conducted to assess the effect of sample size and censoring rate on the chart’s average run length (ARL) to detect changes in the scale parameter. We use two methods to calculate the ARL of the chart: a simulation method and a Markov chain method. In the first method, we follow Dickinson et al. (2014) by simulating data repeatedly until the chart reaches an out-of-control state then take the average, whereas in the second method we follow Lucas and Saccucci (1990) and Runger and Prabhu (1996) and use a Markov chain method along with the empirical cumulative distribution function (ECDF). Finally, we assess the off-target performance by finding the distribution and the probability of false alarms following Huh (2010)’s work. From the simulation method and the Markov chain method, we found that the CUSUM charts detect a change quickly if we increase the sample size, and increase or decrease the scale parameter. While from the probability of false alarms, the CUSUM charts perform well for small transition times t.

abstract: Thesis

abstract: Master of Science (MSc)


title: Modelling the Impact of Anthropogenic Disturbance on Water Quality in the Coastal Zone of Eastern Georgian Bay, Lake Huron

contributor:
Chow-Fraser, Patricia
Biology

subject: Laurentian Great Lakes, Georgian Bay, nutrient model, coastal embayment, coastal wetland, anthropogenic disturbance

abstract: Though the water in eastern Georgian Bay is oligotrophic, some of the coastal embayments and wetlands have begun to show signs of water quality impairment that is thought to be related to human development along the shoreline. The primary objective of my thesis is to provide environmental agencies with the resources to effectively manage water quality in the coastal zone of eastern Georgian Bay. First, I evaluate the ability of the Lakeshore Capacity Model (LCM), developed for inland Precambrian Shield lakes, to predict the trophic status of coastal embayments. Finding that the LCM does not accurately predict trophic status, I develop the Anthro-geomorphic Model (AGM), which uses the level of human development and the degree of mixing between the embayment and open waters of Georgian Bay to predict embayment trophic status.  Second, I explore the spatial association between densities of building, dock and road development and Water Quality Index (WQI) scores, an index designed to evaluate wetland condition, for wetlands in the Township of Georgian Bay. I found an inverse relationship between WQI scores and the density of these stressor variables inside wetland catchments, which indicates that these stressors have a negative impact on wetland water quality. I then created a series of mapping products that present building, dock and road densities, along with WQI scores for 61 wetlands in the Township of Georgian Bay, to determine how wetland water quality is spatially associated with densities of these stressor variables. I found that regions with high densities of building, dock and road development were associated with wetlands of lower quality, whereas wetlands in areas that had low densities of development were of higher quality. I used this information to identify areas of conservation priority for management in the Township of Georgian Bay. The results from this thesis will provide environmental managers with resources to protect the valuable coastal waters of eastern Georgian Bay.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: A number of coastal embayments and wetlands of eastern Georgian Bay show signs of water quality impairment thought to be caused by cottage development. The objective of my thesis is to develop and evaluate models designed to measure the impact of human development on water quality in these coastal zones. First, finding that the Ontario Lakeshore Capacity Model, developed for Muskoka lakes, does not accurately predict trophic status in embayments, I develop the Anthro-geomorphic Model, which uses building density and basin morphometry to predict embayment trophic status. Second, I explore the appropriateness of using development densities (building, dock and road) to quantify anthropogenic stress in coastal wetlands. This thesis provides the scientific basis for choosing management practices to protect the coastal waters of Georgian Bay.


title: An Investigation of Social and Behavioural Factors Associated with Psychiatric Outcomes

contributor: Clinical Health Sciences (Health Research Methodology)

subject:
opioid use disorder
methadone maintenance treatment
suicidal behaviour
social factors

abstract:
Background: Social adversities are prevalent among those with psychiatric disorders and may be involved in poor outcomes among patients receiving treatment. Identification of social risk factors influencing outcomes will help provide targeted interventions for at-risk patients. This thesis explored the role of social and behavioural factors in relation to adverse psychiatric outcomes, specifically relapse to substance use and attempted suicide.
Methods: We used scoping study methodology to perform a comprehensive review to identify the gaps in the literature examining social functioning and MMT outcomes. This review informed our primary cohort study examining the association between social factors and continued opioid use in MMT. Lastly, we conducted a case-control study to identify risk factors for suicide attempts by comparing psychiatric patients with and without suicide attempt history (cases and controls, respectively). Multivariable logistic regression analyses were conducted in both primary studies to examine the association between predictors and outcomes.
Results: The review included 101 observational studies and determined the need for further research on social factors and MMT outcomes among a current sample of Canadian patients.  Our cohort study included 1043 participants (mean age=38.4 years, standard deviation [SD]=11.06); 45.8% women) to investigate this and found that unemployment, criminal activity and interpersonal conflict with friends significantly increased odds of illicit opioid use. In examining risk factors for suicide attempts, we recruited 146 cases (mean age=45.18 years, SD=14.70 years; 55% female) and 104 control participants (mean age=45.01 years, SD=14.23 years; 50% female). No sociodemographic differences existed between groups, however higher impulsivity and borderline personality symptoms significantly increased odds of attempted suicide.
Conclusions: Findings from these studies may indicate the need for structured monitoring of at-risk psychiatric patients. It may be important to develop tools to measure social and behavioural factors in clinical settings and promote further integration of social services in treatment settings.

abstract: Thesis

abstract: Master of Science (MSc)


title: SYSTEM-LEVEL SEISMIC PERFORMANCE QUANTIFICATION OF REINFORCED MASONRY BUILDINGS WITH BOUNDARY ELEMENTS

contributor:
El-Dakhakhni, Wael
Wiebe, Lydell
Civil Engineering

subject:
Boundary Elements
System-Level
Wall Confinement
Reinforced Masonry
Seismic Fragility
Resilience
Seismic Risk Assessment
Nonlinear Analysis
OpenSees
Backbone model
Hysteretic response
Collapse Risk Assessment

abstract:
The traditional construction practice used in masonry buildings throughout the world is limited to walls with rectangular cross sections that, when reinforced with steel bars, typically accommodate only single-leg horizontal ties and a single layer of vertical reinforcement. This arrangement provides no confinement at the wall toes, and it may lead to instability in critical wall zones and significant structural damage during seismic events. Conversely, the development of a new building system, constructed with reinforced masonry (RM) walls with boundary elements, allows closed ties to be used as confinement reinforcement, thus minimizing such instability and its negative consequences. Relative to traditional walls, walls with boundary elements have enhanced performance because they enable the compression reinforcement to remain effective up to much larger displacement demands, resulting in a damage tolerant system and eventually, more resilient buildings under extreme events.
Research on the system-level (complete building) performance of RM walls with boundary elements is, at the time of publication of this dissertation, nonexistent in open literature. What little research has been published on this innovative building system has focused only on investigating the component-level performance of RM walls with boundary elements under lateral loads. To address this knowledge gap, the dissertation presents a comprehensive research program that covered: component-level performance simulation; system-level (complete building) experimental testing; seismic risk assessment tools; and simplified analytical models to facilitate adoption of the developed new building system. In addition, and in order to effectively mobilize the knowledge generated through the research program to stakeholders, the work has been directly related to building codes in Canada and the USA (NBCC and ASCE-7) as well as other standards including FEMA P695 (FEMA 2009) (Chapter 2), TMS 402 and CSA S304 (Chapter 3), FEMA P58 (FEMA 2012) (Chapter 4), and ASCE-41 (Chapter 5). Chapter 1 of the dissertation highlights its objectives, focus, scope and general organization. The simulation in Chapter 2 is focused on evaluating the component-level overstrength, period-based ductility, and seismic collapse margin ratios under the maximum considered earthquakes. Whereas previous studies have shown that traditional RM walls might not meet the collapse risk criteria established by FEMA P695, the analysis presented in this chapter clearly shows that RM shear walls with boundary elements not only meet the collapse risk criteria, but also exceed it with a significant margin. Following the component-level simulation presented in Chapter 2, Chapter 3 focused on presenting the results of a complete two-story asymmetrical RM shear wall building with boundary elements, experimentally tested under simulated seismic loading. This effort was aimed at demonstrating the discrepancies between the way engineers design buildings (as individual components) and the way these buildings actually behave as an integrated system, comprised of these components. In addition, to evaluate the enhanced resilience of the new building system, the tested building was designed to have the same lateral resistance as previously tested building with traditional RM shear walls, thus facilitating direct comparison. The experimental results yielded two valuable findings: 1) it clearly demonstrated the overall performance enhancements of the new building system in addition to its reduced reinforcement cost; and 2) it highlighted the drawbacks of the building acting as a system compared to a simple summation of its individual components. In this respect, although the slab diaphragm-wall coupling enhanced the building lateral capacity, this enhancement also meant that other unpredictable and undesirable failure modes could become the weaker links, and therefore dominate the performance of the building system. Presentation of these findings has attracted much attention of codes and standards committees (CSA S304 and TMS 402/ACI 530/ASCE 5) in Canada and the USA, as it resulted in a paradigm shift on how the next-generation of building codes (NBCC and ASCE-7) should be developed to address system-levels performance aspects. Chapter 4 introduced an innovative system-level risk assessment methodology by integrating the simulation and experimental test results of Chapters 2 and 3. In this respect, the experimentally validated simulations were used to generate new system-level fragility curves that provide a realistic assessment of the overall building risk under different levels of seismic hazard. Although, within the scope of this dissertation, the methodology has been applied only on buildings constructed with RM walls with boundary elements, the developed new methodology is expected to be adopted by stakeholders of other new and existing building systems and to be further implemented in standards based on the current FEMA P58 risk quantification approaches. Finally, and in order to translate the dissertation findings into tools that can be readily used by stakeholders to design more resilient buildings in the face of extreme events, simplified backbone and hysteretic models were developed in Chapter 5 to simulate the nonlinear response of RM shear wall buildings with different configurations. These models can be adapted to perform the nonlinear static and dynamic procedures that are specified in the ASCE-41 standards for both existing and new building systems. The research in this chapter is expected to have a major positive impact, not only in terms of providing more realistic model parameters for exiting building systems, but also through the introduction of analytical models for new more resilient building systems to be directly implemented in future editions of the ASCE-41. This dissertation presents a cohesive body of work that is expected to influence a real change in terms of how we think about, design, and construct buildings as complex systems comprised of individual components. The dissertation’s overarching hypothesis is that previous disasters have not only exposed the vulnerability of traditional building systems, but have also demonstrated the failure of the current component-by-component design approaches to produce resilient building systems and safer communities under extreme events.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: MICRO/NANOSTRUCTURED SURFACES THROUGH THIN FILM STENCIL LIFT-OFF: APPLICATIONS TO PATTERNING AND SENSING

contributor:
Moran-Mirabal, Jose
Chemistry

subject:
Micro/nano- structured surfaces
Polymer stencil lift-off
Supported lipid bilayer
Micropatterning
Electrochemical sensing

abstract:
The rapid development of micro/nanofabrication techniques have enabled engineering of material interfacial properties. Micro/nanostructures with unique electrical, mechanical, thermal, magnetic, optical, and biological properties, have found applications in a wide range of fields such as electronics, photonics, biological/chemical sensing, tissue engineering, and diagnostics, etc. As such, numerous strategies have been developed for structuring materials into micro/nano- scale. However, the challenge still lies in the high cost, low throughput, complexity in fabrication, and difficulty in scaling up. This thesis aims to explore fabrication strategies for micro/nanostructured surfaces that are versatile, simple, and inexpensive. The thin film stencil lift-off technique with both Parylene and self-adhesive vinyl has been explored for this purpose. Further applications of the resulted micro/nanostructured surfaces are also presented in this thesis.
Through improved Parylene stencil fabrication process, both spontaneously phase-segregated and arbitrary binary supported lipid bilayer patterns have been achieved. Also, the microstructured Parylene surfaces have been ddemonstrated for patterning stacked SLBs that are either homogeneous or phase-segregated. Without any lithography technique involved, vinyl stencil lift-off offers as a facile and inexpensive benchtop method for patterning thin films such as metal and glassy films. Combining the thermal shrinking of shape memory polymer, the patterned feature sizes are further decreased by 60% in both x and y dimensions, pushing the patterning resolution to down to sub-100 μm range. In addition, the shrinking process induces micro/nanostructures onto the deposited thin film, and the structure sizes are easily tunable with film thickness deposited. Further applications of such patterned micro/nanostructured surfaces has also been explored. The structured gold films have served as high-surface-area electrodes for electrochemical sensing. By introducing photoresist as a sacrificial layer, the structured gold thin films can be lifted off and transferred onto elastomeric substrate, and serve stretchable and flexible sensors. Such sensing devices exhibit great stability and reproducibility even when working under external strain. Finally, the micro/nanostructured glassy surfaces have been employed as substrate for cell growth to study topographical effect on cell morphology. It has been concluded that rougher surfaces lead to cell elongation, and finer structures promote filopodia generation.
These results underscore the strength and suitability of thin film stencil lift-off as a powerful technique for creating micro- and nanostructured surfaces. These structured surfaces could find applications in many other areas, due to their great properties such as tunable structure size, high surface area, flexibility, and long-term stability.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Simultaneous Electromyography and Functional Magnetic Resonance Imaging of Skeletal Muscle

contributor:
Noseworthy, Michael
Biomedical Engineering

subject: EMG, fMRI, skeletal muscle, BOLD, simultaneous, exercise

abstract: Work focusing on the combination of EMG and fMRI in skeletal muscle.

abstract:
Two commonly used diagnostic techniques for examining muscle function in vivo are functional magnetic resonance imaging (fMRI) and electromyography (EMG). EMG allows for examination of the functional, electrical activity of muscle during force production. Comparatively, fMRI or more specifically blood oxygen level dependant imaging can be applied to visualize muscle activation and recovery post-exercise. It is a combination of oxygenation, metabolism, blood flow and blood volume. The proposed method combines both techniques in simultaneous data acquisition to provide greater muscle physiological information during exercise. Additionally, both techniques are non-invasive making repeated measurements feasible.

EMG hardware filtering was designed and constructed to facilitate EMG measurements alongside MRI scans during simultaneous acquisition. Next, a complex artifact subtraction method called fMRI artifact slice template removal (FASTR) was implemented. With custom scripts and small adaptations to FASTR, it was modified for use with EMG/fMRI, specifically, with a echo planar imaging (EPI) BOLD sequence. Several experiments were then performed to test it's capabilities improving the signal-to-noise ratio (SNR) of the EMG data from 2.8 to 46 in one case.

After EMG hardware and software were developed and implemented, a simple exercise protocol was developed to investigate changes in concurrent BOLD/EMG, recording before, during and following exercise. A linear correlation analyses was performed to compare EMG and BOLD results. A strong correlation between the EMG root-mean-square (RMS) peak amplitude and the length of time to recover back to baseline was noted (r=0.681, n=3).

For future studies, multiple EMG measurements should be applied to improve the amount of information collected during voluntary exercise. Lastly, this technique may have usage with not just BOLD MRI scans, but with various other techniques such as near infrared spectroscopy (NIRS), and diffusion tensor imaging (DTI) in order to further probe muscle physiology.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: Two commonly used methods for detecting disease and injury in muscle are magnetic resonance imaging (MRI), and electromyography (EMG). EMG provides information about the electrical activity of muscle during exercise, while MRI scans give two or three dimensional images of the body. Using these two techniques at the same time, provides the opportunity to obtain greater physiological information of muscle during and after exercise. The goal of this work was to design and create an EMG system that functioned alongside MRI scans. However, combining these two techniques presented several challenges that needed to be solved before this was possible. These issues were resolved and diminished by utilizing specific hardware and software solutions alongside rigorous testing. Additionally, results from the combination of these two techniques have demonstrated there is great potential for future studies. In conclusion, using EMG and MRI together is feasible, and allows for further investigation into muscle physiology.


title: MARRIAGE AS A TECHNOLOGY OF THE SELF: SEX, GENDER AND JURISTIC INVERSION IN THE SOTERIOLOGY OF IMĀMĪ LAW

contributor:
Takim, Liyakat
Rothenberg, Celia
Fadel, Mohammad
Religious Studies

subject: islamic law, marriage, gender, shia law, Imāmī law, theology, salvation, zina, nushuz, nushūz, wife-beating, divorce, Twelver Shīʿism

abstract: A study of Imāmī Islamic law, gender and soteriology; marriage and divorce as technologies of the self.

abstract:
This dissertation explores marriage in Muslim Imāmī juristic law as an embodiment of a set of practices that are aimed at cultivating the pious and virtuous self. As a ritual practice for mainstream Imāmī jurists, marriage (and its corollary activities, e.g. sex) was a mode of pietistic self-fashioning and hence a technology of the self. When faced with the strong possibility or inevitability of marital breakdown, and the sexual sins that may have come about as a result of this breakdown, Imāmī jurists opted for creating a space for women’s prerogative to divorce in which the marriage could end whilst still upholding Islam as a program for the circumvention of sin and the production of īmān. Divorce, in this sense, can be thought of as a safety mechanism and extension of marriage’s program for the nurturing of a pietistic psychology in men and women. The textual and gendered discourse of juristic law was therefore aimed at creating a legal program for individuals so as to maintain the normative Muslim’s ontological bond with God through a series of regulations, disciplines, bodily practices and juristically permitted gendered power inversions that promoted soteriological success.
This study argues that the primary concern of Imāmī jurists was not to maintain a gendered hierarchy as the current dominant scholarship holds, but to prevent sin, especially zinā, the corruption of the qalb (metaphysical heart) and ultimately avoid damnation in the Hereafter. For Imāmī jurists, marriage was not just a procedural practice of rights and duties, but a mode of self-development and a platform through which an eschatological battle against sexual sin and the Devil took place in.
When patriarchy, or more specifically, asymmetrical power relations between (actual/potential) wives and husbands (or guardians) conflicted with the soteriological aims of juristic discourse, the former was inverted. The study concludes that maintaining gender hierarchy was not integral to the cosmology of juristic practice (even in its premodern discourse); it was maintaining the normative believer’s ontological bond with God and saving him/her, as well as the believing community, from damnation. Theological concerns for salvation - and the cultivation of the pious self that made salvation possible – is what animated Imāmī juristic discourse and not patriarchy whether it was obtained from the source-texts (Qur’an, ḥadīth) or social custom (ʿurf).
This study undertakes this task by observing six key areas in the Imāmī tradition where notions of salvation and spiritual ontology in marriage/divorce figure the most prominently: juristic preliminaries on marriage and zinā, interfaith marriage, prepubescent marriage, temporary marriage with zānīyahs, nushūz and khulʿ divorce.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: cAMP-independent and dependent regulation of Pseudomonas aeruginosa twitching motility

contributor:
Burrows, Lori L.
Biochemistry and Biomedical Sciences

subject:
Pseudomonas aeruginosa
Type IV Pilus
Twitching motility

abstract: Type IVa pili (T4aP) are long, retractile, filamentous, surface appendages involved in cellular surface adhesion, biofilm formation, DNA uptake, and a unique form of motility called ‘twitching’. They are a critical virulence factor in a number of bacteria, including the opportunistic pathogen Pseudomonas aeruginosa, a major cause of hospital-acquired infections. T4aP function is controlled by a number of different regulatory proteins and systems. A putative chemosensory system termed ‘Chp’, controls levels of the second messenger molecule cyclic adenosine monophosphate (cAMP). cAMP works with a cAMP receptor protein called Vfr to control expression of ~200 virulence genes, including those that are required to make T4aP. cAMP levels are regulated by proteins outside the Chp system, including the bitopic inner membrane protein, FimV. This study examines the role of the Chp system and FimV in T4aP regulation. Both proteins are required for regulation of cAMP levels, while the Chp system also has a cAMP-independent role in regulating twitching. FimV has been shown to regulate cAMP levels, possibly connecting to the Chp system through a scaffold protein, FimL. We present the structure of a conserved cytoplasmic region of FimV, and show that this region is required for connecting FimV to the Chp system. We also characterize the cAMP-independent role of FimV, confirming that it is distinct from that of the Chp system, and is involved in localizing T4P regulatory proteins. We also provide evidence that the cAMP-independent role of the Chp system is to mediate the balance between T4P extension and retraction, possibly through denoting the ‘front’ of a motile cell. Together, these data help to resolve the cAMP-independent and –dependent pathways controlling twitching motility.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Pseudomonas aeruginosa is a bacterium that causes infection in people with weakened immune systems. One key factor it uses to cause infection is the type IVa pilus (T4aP), a filamentous appendage displayed on the cell surface. T4aP can repeatedly extend and retract, and are involved in attachment to host cells, and movement along surfaces. When T4aP cannot extend or retract, the bacteria cannot cause infection. Many proteins work together to control T4aP function – this study focuses on two of them. They have one overlapping function, controlling levels of a signalling molecule needed to make T4aP. We also show that they have a second, non-overlapping function. One is involved in controlling the extension/retraction balance, possibly by marking the front of a cell, while the other may localize pilus-related proteins within a cell. This work helps us understand how P. aeruginosa makes T4aP, and provides information helpful to understanding control of virulence.


title: Putting Pottery in Place: A Social Landscape Perspective on the Late Formative Upper Desaguadero Valley, Bolivia

contributor:
Roddick, Andrew
Anthropology

subject:
Archaeology
Landscape Studies
Ceramics
Andean Archaeology
Bolivia
Lake Titicaca
Paste Analysis

abstract:
Recent archaeological investigations demonstrate that landscapes of the past are not just passive backdrops to people's practices, but rather play a key role in social, cultural, political, and economic processes. Archaeologists have typically studied landscapes by analysing settlement patterns and architecture, yet newer approaches include the study of production practices such as pottery or stone-tool production. One such approach focuses on the ‘taskscape’, which includes skilled agents, and daily tasks occurring on the landscape. Scholars using this framework consider the rhythms and the embodied experience of people in specific places, and explore both the social relationships and ecological affordances of landscapes. Archaeologists, in particular, have considered the embedded nature of daily tasks performed on the landscape, and the material remains of these tasks. In this project I focus on the taskscapes of the Late Formative Period (200 B.C.- A.D. 500), in the Upper Desaguadero Valley, just south of Lake Titicaca in Bolivia. Little is known of Late Formative landscapes, a period prior to the rise of the Tiwanaku state. I study Upper Desaguadero landscapes to contribute to scholarship exploring the social, political and economic changes of the Late Formative Period, prior to the emergence of the Tiwanaku state.
I study ceramics from two recently excavated sites, Khonkho Wankane and Iruhito. My research explores the difference between Khonkho Wankane and Iruhito taskscapes and whether this is evident through ceramics. Potters’ choices during production are based on their taskscapes, which can affect the materials selected for the paste (the mixture of clay and inclusions), to how the vessels were decorated. Pottery was not only made but also used during daily tasks and thus pottery usage can be used to examine taskscapes. I conduct attribute analysis, with particular attention to paste. For a more detailed analysis of paste I employ a Dino-Lite digital USB microscope. The digital USB microscope is portable, affordable and time efficient, allowing for analysis to be conducted in the field. This method is promising for ceramic analysis, as it encourages standardization and inter-site comparisons. Ultimately, this tool provides quick yet detailed insights into past social landscapes.

abstract: Thesis

abstract: Master of Arts (MA)


title: Cationic Nanogel Carriers for siRNA delivery to the Posterior Segment of the Eye

contributor:
Sheardown, Heather
Biomedical Engineering

subject: Nanogels; Biomaterials; Gene therapy; Ocular disease; Drug load/release; siRNA; Cationic; Nanoparticles; Degradable; pH-sensitive

abstract:
Current treatment for posterior segment ocular diseases requires intravitreal injections administered every 4-6 weeks. The potential for siRNA to be used to treat these diseases is extremely attractive due to the specificity of these molecules and their potential for making long term changes to the expression patterns of the cells.  Due to physiological recognition, however siRNA undergoes rapid degradation upon application. The development of cationic nanogels using polymeric “smart” biomaterials with degradable components to transport siRNA is described.   pH – sensitive N, N dimethylaminoethyl methacrylate (DMAEMA) was crosslinked with thermo-sensitive diethylene glycol methacrylate (DEGMA), by free radical emulsion-precipitation polymerization. Size, charge and morphology were analyzed to assess potential as a nanovehicle.  Through modification of the particle composition, cationic nanogels, determined by zeta potential, with sizes of approximately 160 nm confirmed with dynamic light scattering (DLS), were synthesized.   A composition of 55:45 (DEGMA:DMAEMA); a size and charge ideal for cellular uptake. These particles had minimal impact on cell proliferation and exhibited spherical morphology when imaged by TEM at physiological pH.  The structure was maintained between pH 3.5-9. Sensitivity to pH was shown by DLS through swelling at physiological pH, which may be useful can be taken advantage of in future studies for loading and release.
Degradation with a reducing agent was shown using gel permeation chromatography, DLS and turbidity analysis.  The results suggest this formula will undergo degradation in the cell. Reducing environments mimicking intracellular conditions that promoted degradation of the crosslinker showed enhanced release of dexamethasone phosphate as a model drug. Ongoing work is focused on examining gene silencing using these formulations.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Natural and Anthropogenic Sources Controlling Regional Groundwater Geochemistry on the Niagara Peninsula

contributor:
Slater, Gregory
Hamilton, Stewart
Earth and Environmental Sciences

subject: geochemistry, hydrogeology, Niagara Peninsula, Niagara, stable isotopes, carbon isotopes, sulfur isotopes, tritium, water isotopes, ABB, Appalachian Basin Brines, southern Ontario, gas wells, hierarchical cluster analysis, HCA, groundwater evolution, thermogenic methane, biogenic methane, sulfate, evaporite dissolution, anthropogenic, road salt, karst, carbonate dissolution, bedrock aquifers, sediment thickness, Salina, Niagara Escarpment, Onondaga Escarpment, hydrogeochemistry

abstract: Groundwater chemistry on the Niagara Peninsula has been identified as highly mineralized in comparison to groundwaters collected from the same bedrock formations elsewhere in southern Ontario. Three geochemical zones were discerned using hierarchical cluster analysis and other geochemical and isotopic methods. The Escarpment Zone, located along the Niagara and Onondaga Escarpments, is characterized by unconfined aquifer conditions, parameters reflective of surficial contaminants, including road salt, and elevated HCO3, DOC, NO3-, coliform bacteria and tritium. In contrast, in the Salina Zone thick, low-permeability sediments and gypsiferous bedrock results in highly mineralized groundwaters with Ca-SO4 geochemical facies and elevated S2-, Ca2+, Mg2+, K+, Na+, SO42-, Cl-, Br-, Sr2+, NH4+ and CH4. The Guelph Zone contains the lowest electrical conductivity of the three zones and elevated F-. Outliers exist with groundwater geochemistry that differs from the local geochemical zone and the host aquifer. These sites have elevated SO42- (>1000 to 5200 mg/L) with depleted δ34SSO4 (-2.2 to 14.3‰ VCDT) signatures that differs starkly from Devonian and Silurian evaporites (~20 to 32 ‰) in the host formations. This exogenic SO4 was identified in a cross-formational northeast – southwest linear trend crossing three major groundwater flow systems. The lack of down-stream impact in these systems and tritium groundwater ages that are typically only decades old indicate a young, non-geological origin and implicate anthropogenic activities. Additionally, nine samples were identified with elevated methane concentrations and δ13CCH4 signatures within the thermogenic range. As thermogenic methane is not produced within shallow aquifers and would be short-lived in the presence of the ubiquitous sulfate, these samples imply recent upward migration of methane from depth through vertical conduits. Taken together, the evidence supports large-scale upward movement of fluids in the centre of the Niagara geochemical anomaly and more sporadic upward transport of gases over a wider area of the peninsula. The most likely vector is through corroded and leaking casings or boreholes of abandoned (century) gas wells that are common across the peninsula.

abstract: Thesis

abstract: Master of Science (MSc)


title: Good Kids, mad Schools

contributor:
Fudge Schormans, Ann
Social Work

subject:
Mental Health
Mental Illness
Critical Disability
Mad Studies
Friendship
Haters Beware
Schools
Students
Neoliberalism
Medical Model
Gangsta
Ontario

abstract: The western world has long viewed ‘mental illness’ from a biomedical perspective; treating the brain the same way it treats physical issues, through diagnosis, medication and clinical intervention. We however tend to forget that a person is interdependent on her or his environment, and resultantly we frame the person as ill or weak rather than the environment as sick, or ‘mad’.  With this thesis I assess how mental health and ‘mental illness’ are being framed within secondary schools in the province of Ontario (Canada).   I achieve this by analyzing mental health strategies using a theoretical lens developed from Critical Disability Theory and Mad Studies.  Through use of a Critical Discourse Analysis (CDA) I analyzed a total of 4 mental health strategies from the federal government, the Ontario government and 2 Ontario school boards.   My findings indicated that these mental health strategies generally subscribe to a medical or individualized understandings of mental health, and overlook the disabling influence that the school environment can have on the student.  By minimizing the role of the social and physical environment on student mental health schools are reinforcing the dominant discourse, which is that distresses in mental health are the result of an individual deficit caused by a brain defect or personal weakness.  This discourse has far reaching consequences that may contribute to many Ontario students not receiving the support they desire.  I contend that social workers employed by school boards can be influential in challenging these dominant framings of mental health and carry forward the standpoint that the school environment and its social structures play a principal role in the mental health of students.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: Understanding Perspectives of Key Stakeholders in Planning, Producing and Applying Infectious Disease Models

contributor:
Baumann, Andrea
Global Health

subject:
Infectious Disease
Mathematical Modelling
Public Health

abstract:
Background: Infectious disease outbreaks are amongst the most threatening of disasters, capable of affecting the health and economies of millions of people around the world in a single occurrence. Mathematical models are a tool that can be used to synthesize information from different disciplines into a comprehensive model, which can further be used to guide public health in making appropriate economic and social decisions. However, the integration of modelling within public health is not maximized. This study aims to explore perceptions of key stakeholders in planning, producing and applying infectious disease mathematical models in public health.

Methodology: Data was collected using semi-structured key informant interviews with key stakeholder groups (n=19), academic modellers (n=6), government modellers (n=5), government end-users (n=5) and professionals and practitioners who are end-users (n=4). Data was analyzed with thematic analysis with NVivo 11 (QSR International). A stakeholder analysis was used to map out the interrelatedness of key stakeholder issues, and a thematic analysis was used to abstract themes of collaboration between stakeholders, challenges with data and perceptions of predictive modelling.

Results and Conclusion: The findings of this study identify and organize important insights and recommendations required to optimize the utilization of infectious disease mathematical models in public health decision-making. The findings suggest that models that are most applicable to public health problems often go through iterative collaborations between end-users and modellers. The findings also suggest that there are growing challenges when it comes to the collection and interpretation of sources of infectious disease data and that mathematical models are valuable when used for understanding infectious disease outbreaks and/or interventions, rather than projecting the course of a specific outbreak. This study recommends actions be taken in education, practice and research to minimize the existing gap between mathematical models of infectious disease and their application for public health decision-making.

abstract: Thesis

abstract: Master of Science (MSc)


title: Cannabis Use and Methadone Maintenance Treatment Outcomes in Patients with Opioid Use Disorder

contributor:
Samaan, Zainab
Neuroscience

subject:
Cannabis
Methadone
Opioids
Methadone Maintenance Treatment
Addiction

abstract:
Background: Methadone maintenance treatment (MMT) is a commonly prescribed therapy for patients with opioid use disorder, yet inter-individual variability in terms of treatment response is evident. Given the high prevalence of cannabis use in this population, this thesis aims to elucidate the association between cannabis use and MMT outcomes.
Methods: We conducted a systematic review and meta-analysis to comprehensively evaluate the literature and quality of evidence, as well as to identify gaps in the literature to inform future research. We then conducted a cross-sectional study investigating sex differences in the association between cannabis use and illicit opioid use in MMT patients. We employed a multivariable logistic regression analysis to assess the influence of any cannabis use as well as heaviness of cannabis use within men and women.
Results: The systematic review included 22 observational studies. Results revealed the low quality of available evidence as well as substantial heterogeneity among studies. We identified several limitations in the evidence base including reliance on crude measures of cannabis use and inadequate consideration of confounding variables. Our cross-sectional study included a sample of 777 patients on MMT. Consistent with previous research, we found cannabis use to be unrelated to illicit opioid use in the entire sample. However when we stratified the analysis by sex, we found cannabis use was associated with increased odds of having concurrent illicit opioid use.
Conclusion: Results of this thesis suggest certain populations within MMT patients may be at higher risk of experiencing adverse effects of cannabis in terms of treatment outcomes. Future work can build on the results of these studies to identify unique risk factors for patients in order to inform the use of tailored treatment options to improve MMT effectiveness.

abstract: Thesis

abstract: Master of Science (MSc)


title: Surface Modification of a Blood Contacting Polydimethylsiloxane Microfluidic Oxygenator

contributor:
Brash, John
Fusch, Christoph
Biomedical Engineering

abstract: Our collaborative lab group has conceptualized the 'artificial placenta', a lung assist device (LAD) for preterm and term neonates suffering from respiratory insufficiency. The device is connected to the infant by reopening the umbilical vessels, drawing blood through the extracorporeal LAD and back to the body using the natural pressure drop of the heart. Polydimethylsiloxane is the material of choice used for the LAD due to advantageous gas transfer properties; however, the inner microfluidic channels come into direct contact with blood. Therefore, surface modification is required to prevent coagulation. A novel antithrombin-heparin (ATH) covalent complex with high anticoagulant activity is used to coat the surface via the use of polydopamine (PDA) as a ‘bioglue.’ Dopamine has the ability to self-polymerize over many substrates (organic or inorganic) when subject to alkaline conditions in aqueous solution. The layer of PDA formed on the substrate (PDMS) may then be modified with specific proteins to create a bioactive surface. ATH modified onto PDMS discs via PDA showed strong monolayer coverage (0.23 μg/cm2) and remained relatively stable in blood up to 72 hours. When modified onto LAD oxygenator units via PDA and subject to flow conditions, ATH again showed strong monolayer coverage and remained in blood over 2 days. Specific bioactivity was also preserved. Another approach to surface modification is using tissue plasminogen activator (tPA) to induce fibrinolysis. Rather than preventing coagulation, a fibrinolytic surface could lyse clots as they form. tPA converts plasminogen into plasmin, which then degrades fibrin clots. PDMS-PDA discs modified with tPA in a similar manner to ATH showed strong surface coverage and stability in plasma, and tPA remained active against various activity assays. Eventually, a dual anticoagulant and fibrinolytic surface with ATH and tPA may be possible.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: Predicting Speech Intelligibility and Quality from Model Auditory Nerve Fiber Mean-rate and Spike-timing Activity

contributor:
Bruce, Ian
Electrical and Computer Engineering

subject:
envelope
temporal fine-structure
auditory periphery model
recovered envelope
neurogram

abstract:
This dissertation examines the prediction of speech intelligibility and quality using simulated auditory nerve fiber activity.  The relationship of neural mean-rate and spike-timing activity to the perceptual salience of the envelope (ENV) and temporal fine-structure (TFS) of
speech is indistinct.  TFS affects neural temporal coding in two ways.  TFS produces phase-locked spike-timing responses and narrowband cochlear filtering of TFS generates recovered ENV.  These processes, with direct encoding of ENV to mean-rate responses, are the established transduction processes.  We postulate that models based on mean-rate (over a time-window of approx. 6 to 16 ms) and spike-timing cues should produce accurate predictions of subjectively graded speech.  Two studies are presented.

The first study examined the contribution of mean-rate and spike-timing cues to predicting intelligibility.  The relative level of mean-rate and spike-timing cues were manipulated using chimaerically vocoded speech.  The Spectro-Temporal Modulation Index (STMI) and
Neurogram SIMilarity (NSIM) were used to quantify the mean-rate and spike-timing activity.  Linear regression models were developed using the STMI and NSIM.  An interpretable model combining the STMI and the fine-timing NSIM demonstrated the most accurate
predictions of the graded speech.

The second study examined the contribution of mean-rate and spike-timing cues for predicting the quality of enhanced wideband speech.  The mean-rate and fine-timing NSIM were used to quantify the mean-rate and spike-timing activity.  Linear regression
models were developed using the NSIM measures and optimization of the NSIM was investigated.  A quality-optimized model with intermediate temporal resolution had the best predictive performance.

The modelling approach used here allows for the study of normal and impaired hearing.  It supports the design of hearing-aid processing algorithms and furthers the understanding how TFS cues might be applied in cochlear implant stimulation schemes.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: This dissertation examines how auditory nerve fiber activity can be used to predict speech intelligibility and quality.  A model of the cochlea is used to generate simulated auditory nerve fiber responses to speech stimuli and the information conveyed by the corresponding spike-events is quantified using different measures of neural activity.  A set of predictive models are constructed in a systematic manner using these neural measures and used to estimate the perceptual scoring of intelligibility and quality of normal-hearing listeners for two speech datasets.  The results indicate that a model combining a measure of average neural discharge activity with a measure of instantaneous activity provides the best prediction accuracy.  This work contributes to the knowledge of neural coding in the cochlea and higher centers of the brain and facilitates the development of hearing-aid and cochlear implant processing strategies.