title: Determining a Rodent Model to Investigate Glutamate as a Mechanism Underlying Statin Myalgia

contributor:
Hawke, Thomas
Health Sciences

subject: glutamate, HMG-CoA reductase inhibitor, muscle, myalgia, statins

abstract:
HMG-CoA reductase inhibitors, known commonly as statins are one of the most widely
prescribed medications worldwide. Statins reduce circulating cholesterol levels and are very effective at reducing one’s risk for all-cause and cardiovascular mortality. Though generally well tolerated, statin-associated muscle symptoms (SAMS) present in more than a quarter of statin users. The most common SAMS is myalgia or muscle pain. Statin myalgia often presents in the absence of myofibre damage, making its origin and treatment ambiguous. There are numerous rodent models for statin myopathy in the literature, but surprisingly there is no representation of statin myalgia that we are aware of. This is shocking given the high prevalence of statin myalgia compared to statin myopathy. Recently, our lab published an in vitro model of statin myalgia that focused on elevated xCT transporter activity and interstitial glutamate. This model explains that pain perceived in statin myalgia is the result of statins’ downstream ability to elevate skeletal muscle interstitial glutamate concentrations, thereby activating peripheral nociceptors. The studies herein aimed to create an in vivo rodent model of statin myalgia based on the aforementioned in vitro model. We hypothesized that glutamate, sampled by way of skeletal muscle microdialysis, would be elevated in the skeletal muscle interstitium of rats following statin treatment. Drawing conclusions on the role of glutamate in statin myalgia was not a straightforward process and required multiple model adjustments due to confounding variables. Additionally, many of the recognized effects of statins that were assumed from human and in vitro studies did not translate well to our rodent model. This was the first attempt at creating an in vivo model of statin myalgia and evidence suggests that a rodent model may not be an appropriate representation of what occurs in humans. While these studies also raised doubt on the efficacy of rodent models for SAMS investigations in general and highlighted the importance of having standardized models, certain limitations and assumptions of our model must be addressed before concrete conclusions can be drawn.

abstract: Thesis

abstract: Statins, a class of cholesterol-lowering medications, are one of the most widely prescribed medications worldwide. They have been demonstrated to be very effective at reducing one’s risk of cardiovascular-related death. Statins are generally very well tolerated, however, the most common negative side effects of their use are muscle related and include muscle pain, muscle inflammation and muscle damage. Muscle pain is the most common of these symptoms to present and interestingly, often presents without any clinical indication of muscle damage. The lack of a physical explanation for what is causing this pain makes treating statin-associated muscle pain quite difficult. A lot of effort has gone into determining the mechanism(s) for statin-associated muscle damage, however, there is a gap when it comes to investigating the mechanism(s) for statin-associated muscle pain. The studies herein, therefore, aimed to bridge this gap and investigated a potential mechanism for statin-associated muscle pain in a rodent model. The foundation for this model was built on a cell culture model that was previously developed in our lab. Our data suggest that a rodent model for statin-associated muscle pain may not be an appropriate representation of what occurs in humans. In particular, reduced blood cholesterol and substantial skeletal muscle oxidative stress were not demonstrated in our model as they have been in humans and in cell culture studies. This raised concern around the efficacy of rodent models for statin associated muscle symptoms in general and highlighted the importance of having standardized models. The differences between human/cell culture studies and rodent models also made it difficult to draw firm conclusions on whether the mechanism for statin myalgia investigated herein is supported.


title: The Effects of Elevated Serotonin (5-HT) Signaling on Brown Adipose Tissue

contributor: Medical Sciences (Cell Biology and Metabolism)

subject:
Serotonin
SSRI
Obesity
Brown Adipose Tissue
Antidepressants

abstract: Inhibiting peripheral serotonin (5-HT) synthesis has been shown to prevent the development of diet-induced obesity, glucose intolerance, insulin resistance and hepatic lipid deposition and to increase brown adipose tissue (BAT) thermogenic capacity. This thesis investigated 1) what effects 5-HT has on brown adipocytes (BAs), 2) if 5-HT and/or selective serotonin reuptake inhibitors (SSRIs) impair BAT function, 3) if 5-HT directly inhibits BA via a receptor-mediated mechanism, 4) which 5-HT receptor is predominantly expressed in BAT, 5) if 5-HT receptor antagonism improves BAT function and 6) if 5-HT receptor inhibition reduces SSRI induced weight gain. In murine BAs, 5-HT at concentrations ≥100 μM acutely reduced lipolysis, lipid accumulation and glycolytic flux but did not impair oxygen consumption; whereas 10 nM 5-HT reduced Ucp1 promoter activity via an extracellular receptor-mediated mechanism. Acute injection of 5-HT or the selective serotonin reuptake inhibitor (SSRI) Paroxetine decreased BA T thermogenic capacity and energy expenditure (EE), respectively. Mice lacking the serotonin transporter gene (Slc6a4-/- mice) had increased adiposity, decreased locomotor activity and increased food intake. However, male Slc6a4-/- mice had increased BAT thermogenic capacity, in contrast to the reduced EE expenditure following acute administration of Paroxetine. Using, RNA-Seq analysis and measurements of canonical 5-HT receptor second messengers (i.e. Ca2+ and cAMP transients), 5-HT2A was identified as the highest expressed 5-HT receptor in murine and human BAs and the only detected active 5-HT receptor in murine BAs. Genetic elimination of 5-HT2A prevented 5-HT induced increases in Ca2+ transient peaks and decreases in Ppargc1a mRNA expression in cultured BAs. In vivo ablation of 5-HT2A in adipose tissue increased BAT thermogenic capacity. Furthermore, in silico analyses predicted that pharmacological inhibition of 5- HT2A would induce a thermogenic program. In vitro, 5-HT2A receptor antagonists eliminated 5-HT induced Ca2+ transients and in vivo, a single injection of a peripherally-restricted 5-HT2A antagonist (Xylamidine) prevented 5-HT-induced impairments in BAT-mediated EE. Chronic administration of Xylamidine to chow- fed mice for 5-weeks improved BA T thermogenesis. Co-administration of Xylamidine with Paroxetine, however, did not attenuate Paroxetine-induced weight gain but did improve BAT functional capacity Therefore, 5-HT2A antagonism improves BAT thermogenic capacity but does not increase EE. This represents a novel therapeutic approach for increasing thermogenic capacity that may be used in conjunction with BAT activating strategies to increase EE and attenuate obesity.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Obesity is a growing global pandemic caused by excessive energy intake over energy expenditure (EE). Some medications, such as certain selective serotonin (5-HT) reuptake inhibitor (SSRI) type antidepressants, also contribute to weight gain via reasons which are not fully understood. Currently available weight- loss medications decrease energy intake but do not affect EE. Recently, inhibiting the production of 5-HT outside the brain decreased weight gain in a model of obesity. Furthermore, this was associated with an improvement in the activity of a specialized type of adipose tissue, called brown adipose tissue (BAT). BAT is capable of expending energy in the form of thermogenesis and thus when active increases energy expenditure. We hypothesized that 5-HT impairs BAT activity and that blocking 5-HT activity may reduce weight gain in a model of antidepressant- induced weight gain. Herein, we investigated whether elevating 5-HT or increasing 5-HT downstream signaling modified BAT activity, which 5-HT receptor(s) is/are predominantly expressed in brown adipocytes (BAs), and what the effect on BAT would be if this/these receptors were eliminated. We found that in cell culture “supraphysiological” doses of 5-HT acutely impaired BA lipid mobilization and glucose metabolism; whereas, circulating concentrations of 5-HT impaired expression of select mitochondrial genes when serotonin transport was reduced. In mice, acute injections of high dose 5-HT attenuated BAT activity in response to an adrenergic stimulus. Acute treatment with an SSRI decreased EE and locomotor activity. Mice genetically lacking the serotonin transporter (the target of SSRIs) had increased weight gain (particularly fat mass), increased food intake and reduced locomotor activity, but improved BAT functional capacity. We subsequently identified that the predominantly expressed and active receptor in BAs was the 5- HT2A receptor. Genetically eliminating the 5-HT2A receptor in BAs prevented 5- HT’s reduction of a major mitochondrial gene expression regulator and improved BAT functional capacity in mice. Inhibiting 5-HT2A with a 5-HT2A brain impermeable antagonist, Xylamidine, increased BAT functional capacity in mice. Treating mice with Paroxetine (Paxil®), a SSRI known to increase weight gain, and Xylamidine did not attenuate Paroxetine-induced weight gain nor increase EE but did improve BAT functional capacity. In conclusion, we found that 1) chronic treatment with physiological levels of 5-HT impaired BAT functional capacity, 2) elimination/inhibition of adipocyte 5-HT2A improved BAT functional capacity in vivo and 3) inhibiting peripheral 5-HT2A alone did not attenuate Paroxetine- induced weight gain.


title: MUTUALLY COUPLED SWITCHED RELUCTANCE MACHINES: FUNDAMENTALS, MODELING, AND CONTROL

contributor:
Emadi, Ali
Electrical and Computer Engineering

abstract:
Switched reluctance machines (SRMs) have gained more interest in the past decades due to their simple and robust structure. SRMs are classified into conventional SRMs (CSRMs) and mutually coupled SRMs (MCSRMs). CSRMs are based on single-phase excitation and torque is produced by the rate of change of self inductance. On the other hand, MCSRMs are based on multi-phase excitation and torque is produced by the rate of change of both self and mutual inductances. The drive system of CSRMs consists of the asymmetric half-bridge converter and the hysteresis current controller. That drive system is limiting the SRMs to be widely used since most applications are using AC motors where the standard voltage inverter and the vector control are used. Thus, in order to replace an AC motor with SRM, the converter and controller used need to be changed and not only the motor. That issue is solved in this thesis.

This thesis presents the fundamentals and operating principles of MCSRMs. A literature review of the existing modeling and control methods of MCSRMs is introduced, followed by a performance comparison for MCSRMs with different winding configurations and different control methods. After analysing the existing control and modeling methods in literature of MCSRMs, the focus of this thesis will be on MCSRMs controlled by sinusoidal currents. I preferred sinusoidal current excitation as it enables using the standard voltage source inverter and the standard vector control with the regular modulation schemes such as sinusoidal pulse width modulation or space vector modulation.

In order to test the performance of MCSRM with sinusoidal current excitation, a dynamic model is required that can predict the phase currents and electro-magnetic torque when a given voltage is applied. Hence, a new modeling method is introduced in this thesis that is based on vector representation of motor dynamics instead of instantaneous values. The proposed modeling method reduces the size of the look-up tables and the computational steps of finite element analysis (FEA) by 50% compared to other methods. It has also the minimum error compared to other methods.

After having an accurate dynamic model, next is to apply the vector control on the MCSRM and observe the motor performance. It will be concluded in this thesis that the standard vector control could not create sinusoidal currents due to the effect of spatial harmonics. Those harmonics are due to the slotting effect of the stator and they are usually ignored in AC motors. However, they cannot be ignored in MCSRM due to the high saliency of stator and rotor poles. Thus, a simple and effective spatial harmonics compensation method is introduced to eliminate the spatial harmonics of phase currents in MCSRM.

So far we have an accurate dynamic model and we can ensure sinusoidal current excitation. The next step is how to choose the sinusoidal currents to optimize the motor performance. In order to answer that question, a comprehensive analysis of power factor, torque ripple, and efficiency of MCSRM with sinusoidal current excitation is done. That analysis is then used to optimize the motor performance in terms of power factor, efficiency, and torque ripple.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Evaluating the Relationship between Dietary Intake at the Time Immediately Before and After the Introduction of Solid Foods and the Gut Microbiome in Full-Term Infants: A Longitudinal Study

contributor:
Morrison, Katherine
Medical Sciences

subject:
infant nutrition
gut microbiome
introduction of solid foods

abstract:
Background: The introduction of solid foods is an important dietary event during infancy and is associated with a time of dramatic shifts in gut microbial composition. The influence of solid food introduction on gut bacterial dynamics remains understudied.
Methods: 15 healthy, full-term, vaginally born, and breast-fed infants of the Baby, Food and Mi sub-study of the Baby & Mi Study were investigated. Caregivers were asked to collect daily stool samples and food diaries for 17 days, commencing three days prior to the introduction of solids. Additional stool samples were available up to one year as part of the Baby and Mi study. The exposure of interest, nutritional patterns, was analyzed using food composition output from ESHA’s Food Processor. The number of food items and food groups introduced were used to calculate dietary diversity scores. The outcome of interest, gut bacterial dynamics, was analyzed using RStudio.
Results: The mean (SD) age at the introduction of solid foods is 5.5 (0.66) months (n = 15). Over the study period, the proportion of estimated energy intake from solid foods was low (7.5%; SD 6.74%) (n = 14). Alpha diversity increased over time and was highest at 1 year. The gut microbial community influenced by dominant bacterial taxa changed with increasing age. With introduction of solids, individual community composition changed, though to a varying extent. Shannon alpha diversity was directly associated with calories from carbohydrates, particularly daily fiber intake. The infant’s dietary diversity score was directly associated with alpha diversity and was also positively associated with the degree of change occurring in this time period.
Conclusion: Fiber intake and the dietary diversity scores had the closest relationships to the gut microbiome’s alpha diversity and community structure in infants at the time of solid food introduction.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: The introduction of solid foods is an important life-event during infancy. This is also when the gut microbiome is developing to its mature state. Since nutrition is an important factor influencing the microbiome, investigating the dietary choices at the introduction to solid foods is the aim of the following study. Here, daily stool samples and food diary entries were collected for 15 healthy, breast-fed infants. It is important to measure the diversity of the bacteria in the gut of an individual (alpha) and between people (beta), as well as bacteria present. Carbohydrates drive the change in alpha diversity, especially fiber. Feeding infants a diet with many different foods shows increased alpha diversity and change in the microbiome immediately after introduction. Interestingly, the infant gut microbiome reacts to fiber in a manner comparable to the adult gut microbiome, i.e. increased bacterial diversity, which is associated with better health outcomes in adults.


title: Therapeutic targeting of metastatic recurrences of pediatric medulloblastoma by selective kinase and histone deacetylase inhibitors

contributor:
Singh, Sheila Kumari
Biochemistry and Biomedical Sciences

subject:
Medulloblastoma
Metastatic recurrence
Targeted therapy
Leptomeningeal metastasis

abstract:
Medulloblastoma (MB) is the most common malignant pediatric brain tumour. Of its four distinct molecular subgroups (WNT, SHH, Group 3, and Group 4), Group 3 MB patients hold the worst clinical prognosis due to their high incidence of tumour recurrence and metastasis to the spinal leptomeninges. Relapsed Group 3 MB patients, particularly those with MYC amplification (known as Group 3𝛾), carry a mortality rate of nearly 100%, given the paucity of effective therapeutic options currently available. The most common cause of mortality amongst these patients is leptomeningeal metastasis, yet this metastatic disease is poorly characterized. Our understanding of MB tumour recurrence and leptomeningeal metastasis is further encumbered by the rare clinical opportunities at which specimens may be collected from relapsed patients. We were able to circumvent this obstacle by establishing a patient-derived xenograft mouse-adapted therapy model, which mimics the treatments administered in the clinic and in turn, recapitulates both local and metastatic human MB recurrence. This model system enabled the collection of valuable, patient-derived Group 3𝛾 MB tumour cells from the spinal leptomeninges at relapse. It provides an opportunity for chemical screening, with the aim of identifying small molecule inhibitors capable of eradicating these cells. Existing studies on MB leptomeningeal dissemination at diagnosis suggest that effective treatments may target signalling proteins, such as phosphatidylinositol 3-kinases and histone deacetylases (HDACs). Therefore, I hypothesized that selective kinase and HDAC inhibitors would pose as effective therapies against Group 3𝛾 MB metastatic recurrences.

In this thesis, I conducted a high-throughput screen of 640 kinase inhibitors and robust testing of novel HDAC6-selective inhibitors against these treatment-refractory, metastatic cells. Here, I showed that metastatic recurrences of Group 3𝛾 MB are therapeutically vulnerable to selective inhibitors of checkpoint kinase 1 (CHK1), platelet-derived growth factor receptor beta (PDGFRβ), and HDAC6. Functional studies demonstrated that these inhibitors selectively target the aggressive, migratory Group 3𝛾 MB cells, while sparing healthy neural stem cells. They also showed effective blood-brain-barrier penetration in silico and in vitro, while significantly reducing MB tumour cell properties that are often associated with treatment failure. Taken together, my thesis highlights specific inhibitors of CHK1, PDGFRβ, and HDAC6 that effectively target MB tumour cells that fuel treatment-refractory leptomeningeal metastases. With additional preclinical validation, these compounds may serve as potent therapeutic options to extend survival and improve the quality of life for patients that are ostensibly limited to palliation.

abstract: Thesis

abstract: Master of Science (MSc)

abstract:
Medulloblastoma is an aggressive brain cancer in children. While current standard treatment improves patient survival, 30-40% of all medulloblastoma patients relapse at local (brain) or metastatic (spine) sites. Medulloblastoma metastatic recurrences remain poorly understood, yet they result in an alarmingly high mortality rate amongst patients due to inadequate treatment options currently available. Specific molecular targets are common in both medulloblastoma and metastatic cancer research. These targets are particularly important in governing cell signalling pathways that regulate tumour growth and migration. Therefore, treatment against these targets may be effective at preventing medulloblastoma metastatic recurrences.

As the collection of local and metastatic tumour samples at patient relapse are rare, the Singh lab developed an animal model that mimics human medulloblastoma recurrence. In this thesis, recurrent medulloblastoma metastases were isolated from our established animal model and tested against compounds that inhibit the specific molecular targets previously implicated in medulloblastoma and other metastatic tumours. We identified potent compounds that effectively target these metastatic cells. Next, we determined which compounds spared healthy cells and were able to penetrate the brain, given our future objective of targeting these MB cells from their source to ultimately prevent metastasis. The identified compounds substantially reduced the ability of these cells to divide. With further investigation, these compounds may pose as effective therapeutic agents to treat human medulloblastoma patients with metastatic recurrences.


title: Nonlinear waves on metric graphs

contributor:
Pelinovsky, Dmitry
Mathematics and Statistics

subject:
Nonlinear PDEs
Stability Analysis
Linear Operators
Spectral Problems
Standing Waves
Morse index

abstract:
We study the nonlinear Schrödinger (NLS) equation on star graphs with the Neumann-
Kirchhoff (NK) boundary conditions at the vertex. We analyze the stability of standing
wave solutions of the NLS equation by using different techniques.
We consider a half-soliton state of the NLS equation, and by using normal forms,
we prove it is nonlinearly unstable due to small perturbations that grow slowly in time.
Moreover, under certain constraints on parameters of the generalized NK conditions, we
show the existence of a family of shifted states, which are parametrized by a translational
parameter. We obtain the spectral stability/instability result for shifted states by using
the Sturm theory for counting the Morse indices of the shifted states. For the spectrally
stable shifted states, we show that the momentum of the NLS equation is not conserved
which results in the irreversible drift of the family of shifted states towards the vertex of
the star graph. As a result, the spectrally stable shifted states are nonlinearly unstable.
We also study the NLS equation on star graphs with a delta-interaction at the vertex.
The presence of the interaction modifies the NK boundary conditions by adding an
extra parameter. Depending on the value of the parameter, the NLS equation admits
symmetric and asymmetric standing waves with either monotonic or non-monotonic
structure on each edge. By using the Sturm theory approach, we prove the orbital
instability of the standing waves.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Engineering α-1 Proteinase Inhibitor to Target Neutrophil Serine Proteinase PR3

contributor: Medical Sciences (Blood and Cardiovascular)

subject:
molecular biology
phage display
serpins
α-1 Proteinase Inhibitor
granulomatosis with polyangiitis
protein engineering
biopanning

abstract:
Activated neutrophils release a neutrophil serine proteinase (NSP) called Proteinase 3 (PR3). In granulomatosis with polyangiitis (GPA), an autoimmune vasculitis, enhanced PR3 release results in endothelial damage. Serine proteinase inhibitors (serpins) such as α-1 proteinase inhibitor (API) inhibit NSPs through the serpin’s reactive center loop (RCL). However, API is known to bind PR3 with a low specificity, compared to its main inhibitory target Human Neutrophil Elastase (HNE). The current treatment for GPA is immunosuppression, which leaves patients immunocompromised. Thus, the overall aim of this study was to engineer an API variant with a higher specificity to PR3 than HNE, which could serve as a possible novel therapeutic strategy for GPA.
We created an API expression library, hypervariable at RCL residues A355-I356-P357-M358-S359, and expressed it in a T7 bacteriophage display system. This phage library was then biopanned for PR3 binding. Two conditions were used for each round of biopanning: experimental, with PR3, and the negative control, without PR3. The library was biopanned for a total of five consecutive rounds, with the product of one screen serving as the starting material for the next. A bacterial mass lysate screen was also employed to further probe the library with PR3.
The phage-display and bacterial lysate screens resulted in the selection of two novel variants API-DA (D357/A358) and API-N (N359). Serpin-proteinase gel complexing assays indicated that API-N formed complex with PR3 similar to API-WT (wild-type), while API-DA was mainly cleaved as a substrate. There was no significant difference between the second order rate constants of API-N and API-WT reactions with PR3. Rate constants for API-DA binding to PR3 or for API-HNE reactions were not completed due to novel coronavirus (COVID-19) restrictions. However, this project successfully demonstrated the ability to screen a hypervariable API phage library with PR3, yielding two new novel API variants.

abstract: Thesis

abstract: Master of Science in Medical Sciences (MSMS)

abstract: When harmful substances enter our body such as bacteria or viruses, we have ways of protecting ourselves from them. One of those ways is through a cell called the neutrophil. This is an immune cell that can release “fighting tools” into our blood to combat the harm. Some of these tools are called proteins. One of those proteins is Proteinase 3. However, sometimes our neutrophils can be activated without the presence of viruses or bacteria by products made in our bodies called autoantibodies. When this happens, too many of the “fighting tool” Proteinase 3 is released leading to damage to the tubes or vessels that our blood flows through. This project aimed to find a new possible way to stop these extra fighting tools from doing harm to our body. We did this by creating a library of different proteins that can stop Proteinase 3 once it is released by the neutrophil.


title: DEVELOPMENT AND PILOT STUDY OF THE CHILDHOOD AUTISM SOCIAL SKILLS ASSESSMENT

contributor:
Hall, Geoffrey
Psychology

subject: Autism Assessment

abstract:
Background: Autism Spectrum Disorder (ASD) has two defining deficits: social communication and stereotyped and repetitive behaviour. This pilot study trialled 5 tasks based on current literature to measure the social cognitive skills of children with ASD, titled the Childhood Autism Social Skills Assessment (CASSA). The five tasks were designed to measure performance-based differences in children with ASD using response time and accuracy to compare 13 controls and 12 autism groups. Quantitative differences were found between the children with autism and the neurotypical controls, as well qualitative results which will be used to increase validity and reliability for these tasks in the future.

Methods: The CASSA was administered within a single session. 27 youth aged 6-17 (13 with ASD, 14 Controls) were assessed using the 5 CASSA tasks.  Participants’ parents completed standardized questionnaires as supplemental information. The CASSA is made up of five sections which are the Emotional Stroop, Navon, Blur into Focus, Theory of Mind, and McGurk tasks. The Emotional Stroop task is based on creating the Stroop Effect using an emotional face with an incongruent emotional word over the bridge of the nose. The Navon task measures reaction time of participant’s ability to recognize a target number that may or may not be embedded within a large number made up of small numbers. The Blur-to-focus task requires the participant to identify the emotion displayed on faces (Happy, Sad, Angry or Afraid), that start blurred and gradually come into focus. The CASSA measures Theory of Mind (ToM) development by a series of cartoons depicting the interaction of two children, whose situations become increasingly more complex as the task goes on.

Results and Conclusions: Results indicate that the CASSA may be used as an addition to a clinical assessment battery, specifically using the Navon, Emotional Stroop, and Blur into Focus tasks which were able to produce statistically significant performance differences between groups. The CASSA has the potential to aid in diagnosis as part of a battery as well as to allow researchers and clinicians to assess social skills through electronic assessment.

abstract: Thesis

abstract: Master of Science (MSc)


title: Simulation and Optimization of Nanowire-Based Betavoltaic Generators

contributor:
LaPierre, Ray
Novog, Dave
Engineering Physics

subject:
Betavoltaics
Nanowire
Simulation
Optimization
Nuclear Battery

abstract: In order to increase the efficiency of betavoltaic devices, an architecture utilizing nanowires has been developed. In this architecture, a radioisotope is deposited between a nanowire array in order to increase the fraction of beta particles captured by the semiconductor converter and minimize the energy lost to self-shielding. Previous work has prototyped such a design; however, performance was limited to an efficiency of 0.5%. This thesis outlines the design and optimization of the nanowire-based betavoltaic generator. Both the nanowire array geometry and the nanowire p-i-n diode design are optimized for maximum radiation capture and conversion efficiency, respectively. First, a model was developed in the GEANT4 Monte Carlo toolkit in order to investigate the radiation capture of various array geometries. Radioisotope sources of elemental 3H, 63Ni, and 147Pm, as well as compounds of each were examined with gallium phosphide nanowires. Overall, it was found that nanowires should be grown as long as possible to accommodate the most source material while the ratio of the diameter to array pitch can be optimized for maximum power capture. Optimized arrays presented an improvement in energy capture of approximately 6 and 15 times for 63Ni and 3H devices, respectively, while 147Pm devices indicated no improvement. Optimized array geometry was extended to both silicon and gallium arsenide and the radiation capture simulations were coupled to drift-diffusion calculations in COMSOL Multiphysics for axial junction nanowires. Following the junction optimization, devices were predicted to be between 4 and 10% efficient with power outputs ranging from 2 to 6 μW cm^-2. Despite the large improvement compared to experimental results, surface recombination was found to limit the performance of long gallium phosphide nanowires. Therefore, core-shell junctions were then investigated and found to improve upon all axial designs.                                                                                Overall, it has been determined that the nanowire device design is advantageous over planar betavoltaics due to the mitigation of self-shielding effects. Devices utilizing 10 μm long gallium phosphide core-shell nanowires with a 3H source are predicted to achieve the top performance of 12% effciency and a power density of 7 μW cm^-2. In addition, gallium phosphide and gallium arsenide devices with 63Ni are able to achieve an energy density in excess of 1 Wh cm^-2 due to the long half-life.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract:
Widely used batteries, such as lithium-polymer cells, are bulky and suffer from short discharge times or temperature sensitivity. Betavoltaics - also known as "nuclear
batteries" - offer an opportunity to surpass these issues.
Beta particles, or energetic electrons, are the result of certain nuclear decay reactions. Betavoltaic batteries create electricity from these particles, can remain active for hundreds of years, and are insensitive to environmental conditions. In addition, these particles are easy to shield, rendering them safe for users.
This work focuses on a new type of betavoltaic which uses nanowires to capture more beta particles and ultimately improve performance. These devices have been designed through a simulation-based approach that has maximized the total power output as well as effciency by fine-tuning different parameters. The designs described in this work exhibit huge improvements over conventional devices and will allow nanowire-based betavoltaics to compete with the top performing devices developed to date.


title: Cue Conflicts in Optic Flow and Body Orientation During Spatial Updating

contributor:
Sun, Hong-jin
Psychology

subject:
spatial updating
cognition

abstract: When spatial updating tasks are performed in a real-world setting, participants usually complete it with ease (e.g., Klatzky et al., 1998). However, in virtual reality (VR), when tasks are presented using optic flow, participants tend to exhibit one of two response patterns, with some participants correctly updating their headings (“turners”) and others pointing consistently in the opposite direction (“non-turners”) (e.g., Gramann et al., 2005). While research has looked at the stability and pointing characteristics of these two groups (e.g., Gramann et al., 2012; Riecke, 2008), we still do not know why non-turners exist. The following thesis studied two potential sources of cue conflict—stationary versus central visual information and sensorimotor interference—that could impact participants’ strategies using the Starfield task (Gramann et al., 2012). Occluding stationary peripheral information increased pointing errors, especially for turners. It is thus possible that turners require the peripheral information to correctly parse and process the central optic flow. Alternatively, manipulating body orientation to decrease sensorimotor interference seemed to decrease error and increase strategy consistency for both turners and non-turners. It is possible that the orientation changes allowed participants to ignore the stationary body- based cues, thereby improving spatial updating. Although these manipulations did not remove the non-turner group altogether, they provided important insights into how cue conflicts may play a role in spatial updating for VR tasks.

abstract: Thesis

abstract: Master of Science (MSc)


title: Z-wire – a micro-scaffold that supports guided tissue assembly and intramyocardium delivery for cardiac repair

subject: regenerative medicine, cardiac therapy, tissue engineering, biomaterials

abstract: Cardiovascular diseases (CVD) are the leading cause of death around the world, being responsible for 31.8% of all deaths in 2017.  The leading cause of CVD is Ischemic heart disease (IHD), which caused 8.1 million deaths in 2013. IHD occurs when coronary arteries in the heart are narrowed or blocked, preventing the flow of oxygen and blood into the cardiac muscle, which could provoke acute myocardial infarction (AMI) and ultimately lead to heart failure and death. Cardiac regenerative therapy aims to repair and refunctionalize damaged heart tissue through the application of (1) intramyocardial cell delivery, (2) epicardial cardiac patch, and (3) acellular biomaterials. These approaches have provided benefit of cell localization and tissue structure respectively. However, to improve cell retention and integration, there is a need for the intramyocardial delivery of functional tissues while preserving anisotropic muscle alignment. Here, we developed a biodegradable z-wire scaffold that supports the scalable gel-free production of an array of functional cardiac tissues in a 384-well plate format. The z-wire scaffold design supports cellular alignment, provides tunable mechanical support, and allows for hallmark tissue contraction. When the scaffold is imparted with magnetic properties, individual tissues can be assembled with macroscopic alignment under magnetic guidance. When used in combination with a customized surgical delivery tool, z-wire tissues can be injected directly into the myocardial wall, with controlled tissue orientation according to the injection path. This modular tissue engineering approach, in combination with the use of smart scaffolds, could expand opportunity in functional tissue delivery.

abstract: Thesis

abstract: Master of Science in Chemical Engineering (MSChE)


title: Leveraging Hydrological Models in Conjunction with Multi-Objective Optimization Based Methods to Design Streamflow Monitoring Networks

contributor:
Coulibaly, Paulin
Civil Engineering

subject: Network Design, Hydroloical Models

abstract:
Hydrometric data provides forcing data inputs to run hydrological models and observed output time-series to facilitate the calibration and validation process. Hydrometric monitoring networks are often designed without considering the innate relationship between data collection, model set-up, and model application. This research compares the relative effectiveness of a previously established model-based network design strategy to a newly proposed method. The traditional design method identifies a set of Pareto-optimal networks using intermediate entropy-based design objectives, facilitated by the dual entropy multi-objective optimization (DEMO) tool, and then applies models as a post-processing mechanism. Streamflow time-series from networks initially identified by DEMO are used to calibrate two semi-distributed rainfall-runoff models. The calibration process enables a reassessment for non-dominance based on the primary network design objectives, which are maximizing model performance at manually defined flood sensitive catchment outlets and minimizing network size.
The newly proposed alternative method embeds the hydrological models and their calibration process into the optimization algorithm, resulting in direct optimization based on the primary design objectives. Both techniques were applied to design networks in two large western Canadian watersheds. Bubble maps are presented to illustrate variations in the spatial distribution of optimal solution sets, with respect to both model performance at flood sensitive catchments and individual station selection frequency, for all design scenarios. Results indicate the newly proposed method provides superior results regardless of network size and that trends in the spatial distribution of optimal networks are highly case-specific. The proposed methodology can be readily adapted to address a wide variety of design applications by varying the models and model performance criteria used in the design process. The findings from this research can be used to guide future network design projects when the proposed network is intended to support one or more model-based applications.

abstract: Thesis

abstract: Master of Civil Engineering (MCE)

abstract: Engineers in the field of water resources monitor hydrometric data to maintain a record of historical conditions that can be used to guide future designs and decisions. Hydrometric data are collected from monitoring networks that should be optimally designed to ensure measurements are gathered efficiently. One of the main applications of hydrometric data are to run and calibrate hydrological models. Therefore, hydrological models can be integrated into the network design process to design monitoring networks that enhance model performance while considering the intended model application. This research introduces a new model-based approach for designing streamflow monitoring networks and compares the relative effectiveness of the new technique to previously established methods. Results indicate the new process provides superior results but is also more computationally demanding. The newly proposed methodology is adaptable and can be used to facilitate user-directed designs of hydrometric monitoring networks for a wide variety of engineering applications.


title: The Sacrament of Desire: The Poetics of Fyodor Dostoevsky and Friedrich Nietzsche in Critical Dialogue with Henri de Lubac

contributor:
Kroeker, Travis P.
Ward, Bruce
Widdicombe, Peter
Religious Studies

subject:
Theological Ethics
Political Theology
Literature and Religion
Western Religious Thought

abstract:
The general argument of this thesis contends that the poetics of Dostoevsky and Nietzsche, in particular a comparison between The Brothers Karamazov and Thus Spoke Zarathustra, remain profitable for political theological ethics. I conduct this analysis in critical comparison with the political theology of Henri de Lubac, with a focus on the question of desire and the sacramental mediation of the divine as it is embodied politically. Following de Lubac, especially in The Drama of Atheist Humanism, I argue that both Dostoesvky and Nietzsche were both deeply attuned to the fundamental human desire for the transcendent in modernity, a desire which engenders the creation of new images of the divine in order to unify society as a whole, mediating new forms of political identity. More specifically, I examine the problem of retributive desire in the poetics of The Brothers Karamazov and Thus Spoke Zarathustra as it connects with the historical development of Western Christianity and modernism. I demonstrate how their poetic formulations of retribution relates to suffering and the desire for the transcendent. In particular, I compare the characters of Dostoevsky’s novel, especially Ivan Karamazov and the Grand Inquisitor with the antagonists in the narrative of Thus Spoke Zarathustra, the “dragon” of Christian valuation and the “cold monster” of the modernist state.
Furthermore, I demonstrate that Dostoesvky, Nietzsche, and de Lubac espouse conceptions of sacramental mediation that reflect a desire for a higher social unity that circumvents imperialistic intention, stimulating new possibilities for posthumanist political community. I maintain that Zarathustra can be interpreted as the poetic embodiment of immanent Dionysian desire, mediating a conception of transcendence, expressed through the thought of eternal recurrence, which transvaluates retributively rooted Western Christianity and modernist morality. In Zarathustra, Nietzsche reimagines a politic of friendship, whereby adversarial oriented relationships spur healthier life-affirming forms of living, courageously confronting the sick, unhealthy values of Christianity and modernism. In The Brothers Karamazov, as reflected in the story of Alyosha Karamazov, Dostoevsky imagines the divine as a mystery that envelops the immanent, mediated through the Incarnation of Christ, freely embraced through the sacrifice of the self. Dionysian desire is transfigured through the power of Resurrection, generating a cruciform way of living, embodied in the active, commitment of neighbour-love and a forgiveness-oriented spirit. For de Lubac, what remains decisive is the recovery of the social meaning of the Eucharist, the sacramental self-offering of Christ mediated through the church. Like Dostoevsky, de Lubac argues for the necessity of an inner, transformative reception of the divine Word embodied socially, yet this possibility is mediated through the liturgical practice of Roman Catholicism. For the Russian Dostoevsky, the particular ecclesial form of community is less defined institutionally. His poetics accentuate the reality of an innate eucharistically oriented “social structure,” expressed as a prophetic hope for the possibility of a healthier, life-affirming politic in Western culture if incarnationally embraced by the peoples of the West.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)


title: Arterial Hypoxia in Hyperglycemic Accelerated Atherosclerosis

subject:
Diabetes
Atherosclerosis
Hypoxia
Vasa Vasorum

abstract: Individuals with diabetes mellitus (DM) have a 2 to 4-fold increased risk of cardiovascular diseases (CVD) compared to those without DM. A contributing factor to the development of CVD is atherosclerosis, a chronic inflammatory disease causing plaque build-up in medium to larger arteries. Increasing evidence suggests that hypoxia within the arterial wall is known to promote atherosclerosis, however the underlying mechanisms remain unclear. Our lab has previously shown that hyperglycemic APOE-deficient mice have impaired angiogenesis of the aortic vasa vasorum, increased arterial hypoxia, elevated vascular inflammation and accelerated atherosclerosis development at 15 weeks of age compared to normoglycemic APOE-deficient controls. The objective of this study is to elucidate the mechanisms associated with these differences, specifically the reductions in vasa vasorum. The effects of hyperglycemia and specific interventions to modulate endoplasmic reticulum stress (4-phenylbutyric acid (4PBA)), oxidative stress (n-acetyl-cysteine (NAC)) and advanced glycation end products (pyridoxamine (PX)) are examined in vivo and in vitro. Results demonstrate that human cardiac microvascular endothelial cells (HMVEC-Cs) have reduced angiogenesis in high glucose compared to normal glucose conditions in both hypoxic and normoxic environments. This may be associated with reduced expression of vascular endothelial growth factor A (VEGF-A). Treatment with PX or NAC in hypoxic, high glucose conditions increased the angiogenesis and expression of VEGF-A in HMVEC-Cs. Pilot studies suggest that PX, NAC or 4PBA supplementation are well tolerated in drinking water using STZ mouse models. Future studies should assess the direct effects of each of the chemical interventions on vasa vasorum angiogenesis, arterial hypoxia and atherosclerosis. These results suggest that oxidative stress and advanced glycation end products play a more significant role in reducing microvessel angiogenesis in vitro. Understanding of the non-canonical pathways of atherosclerosis progression in the presence of DM will facilitate the development of novel and more specific treatments for this ongoing epidemic.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Individuals with diabetes have elevated blood glucose levels which can damage blood vessels throughout the body. This damage can result in the development of cardiovascular diseases. The vasa vasorum is a distinct microvessel network that surrounds the walls of large arteries. Damage to the vasa vasorum can result in decreased oxygen supply to the artery wall, triggering low oxygen environments and accelerated atherosclerosis development. In this study we aim to investigate the mechanisms associated with high glucose induced vasa vasorum damage. Results demonstrate reduced vessel formation of human endothelial cells in high glucose conditions. This decrease correlates with advanced glycation end products and oxidative stress inducing a decreased expression of vascular endothelial growth factor A, a known stimulator of vessel formation. Understanding of the unorthodox pathways of atherosclerosis in diabetes will facilitate the development of new and more effective treatment strategies for this ongoing epidemic.


title: Routine Systematic Sampling vs. Selective Targeted Sampling of lymph nodes during mediastinal staging: A feasibility randomized controlled trial

contributor:
Hanna, Waël C.
Health Research Methodology

subject:
Non-Small Cell Lung Cancer
Mediastinal Staging
Endobronchial Ultrasound
Diagnostic Tests
Feasibility
Randomized Controlled Trial
Canada Lymph Node Score

abstract:
Background: The standard of care for mediastinal staging during endobronchial ultrasound (EBUS) is Systematic Sampling (SS) where a minimum of 3 lymph node (LN) stations are biopsied, even if they appear normal on imaging. When LNs appear normal on PET and CT, the Canada Lymph Node Score can also identify if they appear normal on EBUS. For these Triple Normal LNs, the pretest probability of malignancy is < 6%, and routine biopsy may not be required. This preliminary study introduced Selective Targeted Sampling (STS), which omits biopsy of Triple Normal LNs and compared it firsthand to SS.
Methods: A prospective, feasibility RCT was conducted to determine whether the progression of a definitive trial was warranted. Primary outcomes and their progression criterium were recruitment rate (70% acceptable minimum); procedure length (no overlap between sampling methods’ 95%CIs); and missed nodal metastasis (overlap between sampling methods’ diagnostic accuracy 95%CIs and crossing of the null for the percent difference in diagnosis). cN0-N1 NSCLC patients undergoing EBUS were randomized to the STS or SS arm. Patients in the STS arm were then crossed over to the SS arm to receive standard of care. Wilson’s CI method and McNemar’s test of paired proportions were used for statistical comparison. Surgical pathology was the reference standard.
Results: Thirty-eight patients met the eligibility criteria, and all were recruited (100%; 95%CI: 90.82 to 100.00%). The median procedure lengths, in minutes, for STS and SS were 3.07 (95%CI: 2.33 to 5.52) and 19.07 (95%CI: 15.34 to 20.05) respectively. STS had a diagnostic accuracy of 100% (95%CI: 74.65% to 100.00%), whereas SS was 93.75% (95%CI: 67.71% to 99.67%) with the inclusion of inconclusive results. Percent difference in diagnosis between sampling method was 5.35% (95%CI: -0.54% to 11.25%).
Conclusion: With the progression criteria successfully met, a subsequent multicentered, non-inferiority crossover trial comparing STS to SS is warranted.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Before deciding on treatment for patients with lung cancer, a critical step in the investigations is finding out whether the lymph nodes in the chest contain cancer. This is best done with a needle that biopsies those lymph nodes through the walls of the airway, known as endobronchial ultrasound transbronchial needle aspiration. Guidelines require that every lymph node in the chest be biopsied through a process called Systematic Sampling. However, new research has suggested that some lymph nodes may not need a biopsy. These lymph nodes are ones with a very low chance of cancer, based on their imaging tests. In this study, Selective Targeted Sampling was introduced whereby lymph nodes that appeared normal were not initially biopsied. The study followed a feasibility design, which proved sufficient patient interest, adequate safety and possible benefits in pursuing a larger trial comparing Selective Targeted Sampling to Systematic Sampling.


title: Advanced Characterization of Cementitious Materials

contributor:
Bassim, Nabil
Materials Science and Engineering

abstract:
Early-age hydration reactions contribute to early structure and strength development, which is closely related to transportation and concrete placing on site in real practice. The in-situ hydration reactions of nano Portland cement (PC) and nano PC with nano-silica up to 24 h were realized using liquid cell transmission electron microscopy (LC-TEM). The main hydrated product, calcium silicate hydrate (C-S-H) was found to shed light on a complex early stage process, where C-S-H develops according to both layered structure morphology and aggregation of building blocks. These experiments are the first application of the LC-TEM technique in real-time imaging reaction process of cementitious materials.
Also, the effects of nano-silica on microstructure evolution, phase transformation and heat release, especially in early hydration reactions up to 24 h needs further elucidation. The results indicated that the addition of nano-silica provided more nucleation sites for hydrated products leading to more well-distributed precipitates in the reaction. It was also observed that nano-silica had a strong tendency to attach to ettringite crystals and accelerated the conversion of ettringite to monosulfate.
In mortar or concrete, the pore systems and distribution of various cementitious phases were characterized using plasma focused ion beam (PFIB) and X-ray micro-computed tomography (CT) to obtain dataset of larger length scale (100s of nm to mm). A workflow working with cement mortar on PFIB was established, in which a hard Si mask was applied to minimize the curtaining effect. The 3D reconstruction models reveal fluid transport pathways through connected pores and cracks. The thickness mesh of anhydrous phases shows different dissolution rates and preferential dissolution locations. This is the first time that PFIB has been used for cementitious materials and bridges a critical mesoscale length scale that dictates some materials properties such as strength and fluid transport properties.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Cement is the binding material for concrete, which “glues” pieces of fine and coarse aggregate into concrete, which is the most widely used human-made material on the planet. Cement hydration consists of early-age and late-age chemical reactions that transforms unhydrated powder into the binding medium upon which concrete is based. This work is focused on researching structure evolution and phase transformation as well as hydration kinetics of early hydration reactions up to 24 h, and characterizing 3D structure and pore systems of mortar samples. The liquid-based reactions up to 24 h are achieved using liquid cell transmission electron microscopy, which provides insights into real-time structural evolution of main hydrated products, especially C-S-H nucleation and growth. The effects of adding nano-silica on early hydration reactions up to 24 h are also evaluated. Furthermore, the reconstruction models of pore systems show transport pathways of mortar sample.


title: The Role of Nurses in Advance Care Planning Within Long-Term Care Homes

contributor:
Kaasalainen, Sharon
Nursing

abstract:
Residents in long-term care homes (LTCHs), are often diagnosed with chronic life-limiting illnesses, require high levels of care and die with complex comorbidities. Advance care planning (ACP) is crucial in this setting because it empowers residents to have discussions with family, substitute decision-makers and healthcare providers regarding future health and personal care preferences.
Evidence suggests, that nurses are well situated to engage residents and their families in ACP.
The purpose of this study was to explore the experiences and perceptions of Registered Nurses (RNs) and Registered Practical Nurse (RPNs) in LTCHs with respect to their role in engaging residents and families in ACP discussions.
Qualitative interpretive descriptive methodology was used. Data were collected from two LTCHs in Southern Ontario with a total sample of 15 nurses (n=7 RNs, n=8 RPNs). Data were analyzed through the use of semi-structured interviews, field notes, and the researcher’s reflexivity journal. A constant comparison and inductive approach was used in the analysis of the data.
Power and authority dynamics in LTCH’s was an overarching theme in the data, that was highlighted across four sub themes: (1) Nurses lacking clarity about ACP, (2) Nurses’ uncertainty regarding their role in ACP, (3) Nurses feeling uncomfortable engaging in ACP discussions, and (4) Nurses struggling to support families in ACP discussions.
The study findings provide many implications for policy, practice, education and research for nurses working in LTCHs, healthcare providers, policy makers and administrators. Recommendations include: (1) development of policies which support from a systemic level, encouraging nurses to practice ACP within the context of Ontario’s legislation, (2) reassessing LTCH’s hierarchal structure, and developing culture change that allows a team and person-centered approach to ACP and (3) providing more and ongoing education and mentorship for nurses to build greater comfort and confidence when engaging in ACP.

abstract: Thesis

abstract: Master of Science in Nursing (MSN)


title: A Framework for Measuring Privacy Risks of YouTube

contributor:
Samavi, Reza
Computing and Software

subject: privacy framework, YouTube privacy Framework

abstract:
While privacy risks associated with known social networks such as Facebook and Instagram
are well studied, there is a limited investigation of privacy risks of YouTube
videos, which are mainly uploaded by teenagers and young adults, called YouTubers.
This research aims on quantifying the privacy risks of videos when sensitive
information about the private life of a YouTuber is being shared publicly. We developed
a privacy metric for YouTube videos called Privacy Exposure Index (PEI) extending
the existing social networking privacy frameworks. To understand the factors
moderating privacy behaviour of YouTubers, we conducted an extensive survey
of about 100 YouTubers. We have also investigated how YouTube Subscribers and
Viewers may desire to influence the privacy exposure of YouTubers through interactive
commenting on Videos or using other parallels YouTubers’ social networking
channels. For this purpose, we conducted a second survey of about 2000 viewers.
The results of these surveys demonstrate that YouTubers are concerned about their
privacy. Nevertheless inconsistent to this concern they exhibit privacy exposing behaviour
on their videos. In addition, we found YouTubers are being encouraged by
their audience to continue disclosing more personal information on new contents.
Finally, we empirically evaluated the soundness, consistency and applicability of
PEI by analyzing 100 videos uploaded by 10 YouTubers over a period of two years.

abstract: Thesis

abstract: Master of Science (MSc)


title: Lubricant-infused titanium surfaces with simultaneous anti-biofouling and targeted binding properties

contributor:
Didar, Tohid
Mechanical Engineering

subject:
Anti-biofouling surface treatment
Titanium implant

abstract: Lubricant-infused surfaces (LIS) are created by modifying chemical and physical properties of surfaces with aim of lowering surfaces energy where designed surface will possess liquid-repelling behaviors under low tilting angles. LIS has great potential to be applied on implantable devices due to it is stable anti-biofouling properties under fluidic environment. However, a few studies have reported that the existing research on implant surface uses complicated methods and high cost fabrication to create LIS on titanium implants. Furthermore, current limitation of LIS coatings for titanium implants lies in the lack of tissue integration and cell interaction. As a result, LIS prevents both bacteria and bone cells from adhering to the interface between implant and natural bone. This unselective blocking is problematic for titanium implants used in orthopaedic surgery when devices are required to possess tissue integration properties to facilitate long term fixation in the human body. The overall objective of this thesis is to apply LIS on titanium surfaces via a chemical modification technique and simultaneously integrate bio-functional features onto LIS to promote osteoblasts adhesion. In this project, chitosan and collagen were used to facilitate cell adhesion. To start with, three methods were used to immobilize chitosan on titanium to obtain the desired bio-functional LIS coatings: (1) LIS on top of (3-Glycidyloxypropyl)trimethoxysilane (GPTMS) crosslinked chitosan; (2) LIS on dip-coated chitosan; (3) LIS generated from GPTMS  and Trichloro(1H,1H,2H,2H-perfluorooctyl) silane (TPFS) mixed silanes modified titanium surface followed by chitosan functionalization. Among these modification techniques, method (3) showed optimal anti-biofouling and osseointegration properties. Since collagen is well known for increase of cell interactions, it was used via mixed silanes functionalization method. Finally, the properties were compared with chitosan coated surfaces. During tests, surface wettability was measured, anti-biofouling properties and osseointegration was examined with staphylococcus aureus and SAOS-2 cells, respectively. We found that chitosan modified surfaces using method (3) not only significantly increased cell adhesion in comparison with the other two modification methods, but also dramatically decreased bacterial adhesion compared to collagen coated LIS on titanium. Although collagen has better cell adhesion properties than chitosan, collagen coated surface significantly decreased antibiofouling properties. In conclusion, bio-functional lubricant-infused titanium surfaces created by chemical vapor deposition (CVD) method with mixed silanes is a feasible and straightforward method to immobilize biomaterials and stabilize the lubricant layer on titanium substrates. Chitosan coated LIS on titanium prevents bacterial adhesion and simultaneously promotes targeted cell binding.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: Biofouling is a major issue in implantable titanium devices such as coronary stents, plates and nails, and formation of biofilm on implants can lead to infection and failure of the device. Biofilms formed by bacterial adhesion could be resistant to antibiotics and can provoke a series of inflammatory response. Recent advances in anti-biofouling surface treatment has resulted in designing supper slippery lubricant-infused omniphobic surfaces which are inspired from the Nepenthes pitcher plant. Liquid which is tethered on the surface offers a stable liquid interface, repelling both aqueous and organic liquids meanwhile showing excellent bacteria repellency. Lubricant-infused surfaces (LIS) are resistant towards biofilm formation and produce a stable surface that prevent non-specific adhesion.  As a result of this repellent properties, LIS also repels the adhesion of desired biomolecules and cells such as osteoblasts, bone cells and growth factors which are essential factors for bone recovery at the implant-bone interface. Our motivation in this thesis is to create a lubricant-infused coating on titanium surfaces that possesses both bio-functional and blocking features. We designed surfaces that decrease implant infection caused by non-specific adhesion and simultaneously promote targeted binding of biomolecules and cells that will increase osseointegration of the implant to enable long-term fixation.


title: NEW INSIGHTS INTO CATCHMENT DYNAMICS USING NOVEL APPROACHES

title: NEW INSIGHTS INTO THE CONTROLS ON HYDROCHEMICAL BEHAVIOUR AND ECOHYDROLOGICAL DYNAMICS IN A COLD ALPINE CATCHMENT, SOUTHERN YUKON

subject: isotopes, C-Q, hysteresis, catchment, two water worlds, fluorescence, DOC

abstract: Climate warming has been extensively documented over the last few decades, with northern environments experiencing greater increases in temperature than lower and mid-latitudes. Impacts of climate warming include: an increase in the rain to snow ratio, changes in precipitation magnitude and timing, increased soil warming, permafrost thaw, latitudinal and altitudinal expansion of tree-line, proliferation of tall shrubs into tundra, intensification of the freshwater cycle, and changes to stream volume and water quality. However, forecasting how these changes will affect northern, high latitude environments is difficult due to a lack of process-based research across scales. Wolf Creek Research Basin (WCRB) in Southern Yukon is a well-established mesoscale alpine catchment comprised of three ecozones and has hydrometric and meteorological records spanning 25 years. In this thesis, extensive field campaigns generated hydrochemical, stable isotope, and high-frequency in-situ datasets that were analyzed in conjunction with historical data from WCRB to refine and advance existing conceptual models. These distinct datasets were collected within a nested experimental design to more precisely describe relationships between catchment conditions, ecohydrological processes and stream water quantity and quality beginning at the headwater scale and with scaling to the outlet of WCRB. Optical data was combined with dissolved organic carbon (DOC) concentrations to assess source areas and in-stream dissolved organic matter (DOM) quality across landscape units. Headwater DOC concentrations and fluxes from 2015-2016 were compared to the previous decade to assess changing export. In situ sensors that record chromophoric DOM (CDOM) at high frequency were paired with discharge and conductivity measurements to assess concentration-discharge relationships at event, seasonal and annual scales. Conceptual models of conductivity and major ion transport were confirmed while high-frequency CDOM-Q insights refined our understanding of DOC movement. As vegetation community composition and characteristics change, it is expected that components of the water balance will be altered at both the canopy level and within the critical zone. Compartmentalization of water within the critical zone is increasingly important to provide insights into how water cycles within catchments. Dual isotope and lc-excess approaches showed that bulk and xylem water were significantly different from the LMWL and stream water isotopes of δ2H and δ18O. Meanwhile, an increasingly enriched xylem water isotope signal overlapped with bulk soil water values as the growing season continued, which suggests the opportunistic use of available mobile soil water.

abstract: Dissertation

abstract: Doctor of Philosophy (PhD)

abstract: Climate warming has been extensively documented over the last few decades, with northern environments experiencing greater increases in temperature than lower and mid-latitudes. Impacts of climate warming include: an increase in the rain to snow ratio, changes in precipitation magnitude and timing, increased soil warming, permafrost thaw, latitudinal and altitudinal expansion of trees and shrubs becoming taller and moving to new areas. Climate change has the capacity to then affect the cycling of water leading to differences in how much water is present in streams and possibly leading to decreasing in water quality. Models and other tools are used to forecast these changes but benchmarking outcomes is difficult because northern environments are less well studied than other, more accessible locations.  New types of information, including water quality, isotope and optical datasets, were used to explore previous understanding of how processes interact in space and time.


title: DEVELOPMENT OF HYBRID APPROACHES FOR UNCERTAINTY QUANTIFICATION IN HYDROLOGICAL MODELING

contributor:
Zhong (Zoe), Li
Civil Engineering

subject:
Hydrology
Forecasting
Uncertainty analysis
Polynomial Chaos expansion
Hybrid modeing

abstract: Water is a scarce resource especially as the water demand is significantly increasing due to the rapid growth of population. Hydrological modelling has gained a lot of attention, as it is the key to predict water availability, optimize the use of water resources and develop risk mitigation schemes. There are still many challenges in hydrological modelling that researchers and designers are trying to solve. These challenges include, but not limited to: i) there is no single robust model that can perform well in all watersheds; ii) model parameters are often  associated with uncertainty, which makes the results inconclusive; iii) the required computational power for uncertainty quantification increases with the increase in model complexity; iv) some modelling assumptions to simplify computational complexity, such as parameter independence are, are often not realistic. These challenges make it difficult to provide robust hydrological predictions and/or to quantify the uncertainties within hydrological models in an efficient and accurate way. This study aims to provide more robust hydrological predictions by developing a set of hybrid approaches. Firstly, a hybrid hydrological data-driven (HHDD) model based on the integration of a physically-based hydrological model (HYMOD) and a data-driven model (artificial neural network, ANN) is developed. The HHDD model is capable of improving prediction accuracy and generating interval flow prediction results. Secondly, a hybrid probabilistic forecasting approach is developed by linking the polynomial chaos expansion (PCE) method with ANN. The results indicate that PCE-ANN can be as reliable as but much more efficient than the traditional Monte-Carlo (MC) method for probabilistic flow forecasting. Finally, a hybrid uncertainty quantification approach that can address parameter dependence is developed through the integration of principal component analysis (PCA) with PCE. The results from this dissertation research can provide valuable technical and decision support for hydrological modeling and water resources management under uncertainty.

abstract: Thesis

abstract: Doctor of Engineering (DEng)

abstract: There is a water scarcity problem in the world, so it is vital to have reliable decision support tools for effective water resources management. Researchers and decision-makers rely on hydrological modelling to predict water availability. Hydrological model results are then used for water resources allocation and risk mitigation. Hydrological modelling is not a simple process, as there are different sources of uncertainty associated with it, such as model structure, model parameters, and data. In this study, data-driven techniques are used with process-driven models to develop hybrid uncertainty quantification approaches for hydrological modelling. The overall objectives are:  i) to generate more robust probabilistic forecasts; ii) to improve the computational efficiency for uncertainty quantification without compromising accuracy; and, iii) to overcome the limitations of current uncertainty quantification methods, such as parameter interdependency. The developed hybrid approaches can be used by decision-makers in water resources management, as well as risk assessment and mitigation.


title: Derivation and validation of clinical prediction model of postoperative clinically important hypotension in patients undergoing noncardiac surgery

contributor:
Devereaux, PJ
Health Research Methodology

subject:
anesthesia
perioperative
Hypotension
noncardiac
prediction model
cohort study

abstract:
Introduction
Postoperative medical complications are often preceded by a period with hypotension. Postoperative hypotension is poorly described in the literature. Data are needed to determine the incidence and risk factors for the development of postoperative clinically important hypotension after noncardiac surgery.
Methods
The incidence of postoperative clinically important hypotension was examined in a cohort of 40,004 patients enrolled in the VISION (Vascular Events in Noncardiac Surgery Patients Cohort Evaluation) Study. Eligible patients were ≥45 years of age, underwent an in-patient noncardiac surgery procedure, and required a general or regional anesthetic. I undertook a multivariable logistic regression model to determine the predictors for postoperative clinically important hypotension. Model validation was performed using calibration and discrimination.
Results
Of the 40,004 patients included, 20,442 patients were selected for the derivation cohort, and 19,562 patients were selected for the validation cohort. The incidence of clinically important hypotension in the entire cohort was 12.4% (4,959 patients) [95% confidence interval 12.1-12.8]. Using 41 variables related to baseline characteristics, preoperative hemodynamics, laboratory characteristics, and type of surgery, I developed a model to predict the risk of clinically important postoperative hypotension (bias-corrected C-statistics: 0.73) The prediction model was slightly improved by adding intraoperative variables (bias-corrected C-statistics: 0.75). A simplified prediction model using the following variables: high-risk surgery, preoperative systolic blood pressure <130 mm Hg, preoperative heart rate >100 beats per minute, and open surgery, also predicted clinically important hypotension, albeit with less accuracy (bias-corrected C-statistics 0.68).
Conclusion
Our clinical prediction model can accurately predict patients’ risk of postoperative clinically important hypotension after noncardiac surgery. This model can help identify which patients should have enhanced monitoring after surgery and patients to include in clinical trials evaluating interventions to prevent postoperative clinically important hypotension.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: In patients undergoing noncardiac surgery, numerous patients will develop postoperative clinically important hypotension. This may lead to complications including death, stroke, and myocardial infarction. I performed a large observational study to examine which risk factors would predict clinically important postoperative hypotension. Once we have identified these risk factors, we will use them to conduct randomized trials in patients at risk of clinically important hypotension to determine if we can prevent major postoperative complications.


title: Is it Worth the Hit? Examining the Cognitive Effects of Subconcussive Impacts in Sport Using Event-related Potentials

contributor:
Connolly, John F.
Psychology

subject:
Concussion
ERP
Subconcussive
Cognitive function

abstract: Concussion is a life-altering injury that can affect people of all ages. Event-related potentials (ERPs) extracted from electroencephalography (EEG) have proven sensitive to concussion-induced cognitive deficits. The MMN, P3a, P3b, and N2b are some ERP components of interest, assessing automatic attention, attentional resource allocation, working memory, and inhibitory executive function, respectively. These ERPs can assess some common symptoms associated with concussion at a level that cannot be attained using self-report. A reduced amplitude and potentially delayed latency of the P3a and P3b is a well-replicated result in concussion research. Furthermore, recent research suggests that an alteration in amplitude of earlier peaks such as the N2b and MMN might represent an irreversible change in cognitive processing that tends to occur in the chronic stages of concussion. Many of these studies have focused on athletes, however little research has evaluated the cognitive effects of sustaining numerous blows to the head that do not result in a clinical diagnosis of concussion, as is the case for many athletes in contact sports. These blows are often referred to as subconcussive impacts. The present study examined the cognitive and neurophysiological effects of subconcussive impacts on collegiate contact-sport athletes and compared them to noncontact athletes. The athletes completed questionnaires to evaluate their health and athletic history, as well as estimates of exposure to subconcussive impacts such as position and playing time, prior to participating in three paradigms meant to assess various cognitive processes during an EEG recording. Across two experiments we demonstrated that subconcussive impacts within a season of play can result in alterations in neurophysiological markers of cognitive health. Our findings also reveal that continued involvement in contact sports can have serious implications in one’s automatic attention, resource allocation, and working memory as demonstrated by reduced ERP amplitudes in contact as compared to non-contact athletes.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: A concussion is a devastating injury that can greatly affect how an individual functions in their day-to-day life. Concussions are often discussed in the context of contact sports because of these athletes’ exposure to repeated head impacts. That said, another cause for concern is the effects of head impacts that do not result in a concussion per se – these are known as subconcussive impacts. A brain imaging technique known as electroencephalography (EEG) involves recording brain activity from sensors on the head. Conducting this recording while individuals perform tasks known to evaluate brain function offers an opportunity to assess symptoms rather than relying on a patient’s own, subjective report of their experiences. The present study investigated the use of EEG in evaluating the effects of subconcussive impacts in collegiate athletes and found that repeated head impacts can reduce cognitive health, even if they do not result in a diagnosis of concussion.


title: PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY-DERIVED BONE OUTCOMES AND RELIABILITY IN RHEUMATOID ARTHRITIS PATIENTS AND CONTROLS

title: IMAGING ANALYSIS IN RHEUMATOID ARTHRITIS PATIENTS

contributor: Medical Sciences (Division of Physiology/Pharmacology)

subject: rheumatoid arthritis

subject: imaging reliability

subject: metatarsophalangeal joints

subject: magnetic resonance imaging

subject: ultrasound

subject: bone erosions

subject: protocol development

abstract: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that affects the feet in up to 90% of patients, and can result in bone erosions. Little is known about disease activity at the metatarsophalangeal joints (MTPJs). Magnetic resonance imaging is used to visualize erosions, but does not provide quantification. Quantitative computed tomography (QCT) allows for differentiation between bone layers and quantifies volumetric bone mineral density (vBMD). We used a peripheral QCT (pQCT) scanner in MTPJs 2-5 in RA patients to determine reliability of a pQCT protocol, and then we determined the variability in vBMD between RA patients and controls. Patients (n=25) diagnosed with RA (2010 ACR criteria) were recruited from an academic Rheumatology clinic. Controls (n=27) were also recruited and matched for sex, age and ethnicity. Baseline MR data demonstrated that 80%, 64%, 40% and 20% of patients had erosions at MTPJs 2-5, respectively. One year later, MTPJs 2-5 were scanned using pQCT (XCT 2000); 2 transaxial slices were acquired per joint. A trained pQCT operator acquired 2 scans per participant with repositioning. Test-retest, intra- and inter-rater reliability were assessed blindly for total and cortical subcortical densities (mg/cm3). Reliability was reported as root mean square coefficients of variation (%RMSCV) and RMS standard deviation (RMSSD). The mean (SD) age and disease duration were 57.8 (10.2) years and 5.0 (0.9) years, respectively. Test-retest reliability was better for MTPJs 2 and 3, than MTPJs 4 and 5. Inter- and intra-rater reliability demonstrated high reproducibility. Total and cortical subcortical vBMD appeared lower in RA patients than controls. We have reliably determined vBMD using pQCT in MTPJs 2 and 3 in RA patients. The lower vBMD in MTPJ 3 suggests that RA patients may have true erosions at this joint. This research is in the early phases, but we hope to explore the correspondence between pQCT and other RA assessment tools.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Rheumatoid arthritis (RA) affects joints in the hands and feet. The bones of these joints are affected by periarticular bone loss leading to bone erosions. Magnetic resonance imaging (MRI) and X-ray are used to visualize erosions. Since erosions are characterized by a decrease in bone mineral density (BMD) leading to holes in the bone, we tested the reliability of a peripheral quantitative computed tomography (pQCT) scanner, to measure volumetric BMD (vBMD) in 25 RA patients and compared vBMD to healthy controls. The vBMD measures appeared lower in RA patients than healthy individuals in some joints. As well, there was agreement between bone erosions detected by MRI and reduced vBMD measured by pQCT. Although we could not monitor the change over time, we are hopeful that this scanner will be able to better characterize RA disease activity, with vBMD as a surrogate marker for erosion presence.


title: THE EFFECT OF WASTEWATER EFFLUENT ON THE GUT CONTENT MICROBIOME OF RAINBOW DARTER (ETHEOSTOMA CAERULEUM)

contributor:
Kidd, Karen
Wilson, Joanna
Biology

subject:
municipal wastewater effluent
fish gut microbiome
dysbiosis
ecotoxicology
aquatic toxicology
environmental contaminants
environmental pollution

abstract: MSc Thesis - The effect of wastewater effluent on the gut microbiome of rainbow darter

abstract:
The microbiome plays an important role in host physiology and can be influenced by species, diet, and environment. Municipal wastewater effluent contains a mixture of chemicals including antibiotics and antimicrobials that may affect the gut microbiome of fish living downstream of these discharges. Thus, this study examines the effect of wastewater treatment plant (WWTP) effluent on the gut microbiome of wild rainbow darter (Etheostoma cearuleum), and examines how the gut microbiome of wild fish changes in the lab.
Fish were collected from sites upstream and downstream of 2 major WWTPs along the central Grand River and gut contents were aseptically sampled. After extracting gDNA, nested PCR of the V3-V4 region of the 16S rRNA gene, and Illumina sequencing were performed. The gut microbiome of exposed fish had increased bacterial diversity and was dominated by Proteobacteria, which has been linked to altered health outcomes in mammals.
Next, rainbow darters were collected from a reference site on the Grand River. Fish were sampled in the field, after a 14 day lab acclimation, and after a 28 day exposure to environmental stressors (WWTP effluent or triclosan, an antimicrobial found in WWTP effluent). Surprisingly, there were no changes in the microbiome after exposure to environmental stressors. Major changes were observed between the field and laboratory fish suggesting that environment and diet are important factors influencing the gut microbiome. Changes in the gut microbiome continued up to 42 days in the lab, indicating longer acclimation periods may be needed.
This study showed that effluents altered the gut microbiome of fish in the field, but not in the laboratory for unknown reasons. Laboratory studies indicated that transitioning to a new environment may require greater than 14 days before achieving a stable microbiome.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Wastewater is the largest source of pollution affecting Canada’s aquatic ecosystems; effluents contain antibiotics and antimicrobials that can affect fish and other aquatic life. The gut microbiome of fish is influenced by host species, its diet, and the environment, and thus contaminants released via wastewater effluents may alter the gut microbiome of fishes in receiving waters. This study found that the gut microbiota of rainbow darter fish exposed to wastewater effluents in the central Grand River (Waterloo/Kitchener, Ontario) were dominated by Proteobacteria and had increased diversity. Wild fish transitioned to the lab were dominated by Firmicutes and had decreased bacterial diversity in the gut compared to those in the wild. Altogether, these results suggest that wild fish exposed to wastewater effluents had altered gut microbiomes; transitions to new environments and laboratory acclimation periods are important considerations when studying the fish gut microbiome.


title: Improving National Health Research Systems Performance: The Case of Research Production and Use in Cameroon

contributor:
MBUAGBAW, LAWRENCE
Health Research Methodology

subject:
National Health Research Systems
Research for Health
Evidence mapping
Decision making
Gap analysis
Cameroon
Contextualisation
Local evidence

abstract:
Background: Efficient national health research systems (NHRS) generate knowledge to improve health outcomes while accounting for local health system specificities. African NHRS have a limited capacity to generate such knowledge; and rely on global or external sources of evidence which require adaptation. However, systematic, timely and comprehensive identification of local evidence needed for adaptation is challenging. Thus, the objectives of this study are to develop a centralized database of health research from Cameroon and test its applicability for informing future research production and use.

Methods: We used an evidence mapping design. From October 2018 to May 2019, we searched 10 electronic databases and hand searched the archives of non-indexed African and Cameroonian journals. We screened titles, abstracts, and full texts based on these criteria: peer reviewed journal articles; published between 1999 and 2019; in English or French; investigating health-related outcomes in Cameroon. We extracted relevant study characteristics using a pre-established guide. We developed a coding scheme to label studies and ease searches on the database. Studies were coded independently by two reviewers and discrepancies resolved by consensus. We used the database to create evidence maps and identify knowledge gaps on sexual and reproductive health (SRH) priorities.

Results: We included 4384 studies. Most were open access (76.3%); published in English (79.7%); conducted in the Centre region (45%) with an observational design (71.6%). The domains with the highest frequency were medical specialties (89.0%), and diseases (80.4%). The most researched specialty, diseases and population were infectiology, infectious diseases, and children respectively.  Our gap maps revealed: (1) geographic and demographic disparities in the local evidence on adolescents’ contraceptive use (2) gaps in the type of local evidence needed for contextualisation and policymaking on obstetric fistula.

Conclusion:  Local evidence mapping and gap analysis can contribute to improving national research production and use in decision-making.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: National health research systems answer questions about individuals’ health and the health care system they use. To do this, it is important to determine what we already know, which questions have not been answered and where resources should be directed in the future. Cameroon’s health research system needs to improve its research production capacity. It needs to produce answers which can be used to improve the health of Cameroonians and the decisions which are made about their health care system. As a first step towards achieving these goals, we created a database of health research from Cameroon. We used the database to create maps of what we know and don’t know about health topics such as adolescents’ use of contraception. We also made recommendations for future research in this field. The database will be useful for researchers, students, health professionals, funders and stakeholders involved with health research in Cameroon


title: Digital Image Watermarking: Old and New

contributor:
Chen, Jun
Electrical and Computer Engineering

subject: Digital Watermarking

abstract:
The digital image watermarking is a process that embeds a secrete
sequence into a digital image or a video segment to protect its copyright
information.
There are several methods utilized to deal with the watermarking
problem. There are in total two different kinds: the popular neural
network and the traditional methods. And for the traditional
methods, according to their working region, they can be divided into
two groups: spatial domain-related algorithms (e.g., LSB SVD) and
transformed domain algorithms (e.g., DCT, DWT). The spatial domain
algorithms are the methods that directly work on the pixel
values of the image, while the transformed domain algorithms are
the methods that work on the rate of change of the image pixels.
In the thesis, first of all, we are going to propose a modified hybrid
the scheme, which has better results compared with the paper (Lin
and Wan 2016). Then, we are going to offer a brand-new method
concerning the LDPC-LDGM coding structure in the area of information
theory to deal with the digital watermarking problem. Notice
that this LDGM-LDPC nested code watermarking scheme only provides
a particular case example, which is implemented by one of the
teammates Dr. Mahdi, and there is still much space for improvement.
However, according to the step tests in chapter 4.4, we have
achieved a reasonably good result in imperceptibility and robustness.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: ANTIMICROBIAL RESISTANCE AND GUIDELINE RECOMMENDATIONS: CONTEXTUALIZATION AND ADAPTABILITY

contributor:
Schünemann, Holger
Health Research Methodology

subject:
Guidelines
Recommendations
Antimicrobial resistance
Contextual

abstract: BACKGROUND: Antibiotics are essential medicines and their effectiveness is under threat due to antimicrobial resistance. Guidelines are one way to conserve antibiotic effectiveness given that they are intended to modify clinician prescribing. Guidelines that provide antibiotic recommendations should make explicit contextual considerations that influence antimicrobial resistance and their downstream effects on resistance emergence. METHODS: We conducted a systematic review of tuberculosis, gonorrhoea, and respiratory tract infection guidelines and recommendations to examine how and to what extent they are considering contextual factors that influence antimicrobial resistance. We also investigated whether there are guidelines and recommendations that can be adopted or adapted to local contexts. RESULTS: We found that within 74 included guidelines, two thirds of recommendations considered antimicrobial resistance. Of which only five guidelines considered all factors required to consider local aspects such as values, resource use, acceptability, feasibility, and equity.  As such, these five guidelines can be either adopted or adapted to Canadian and other contexts. We also found that 39% of guidelines met credibility scores of 60% or greater in AGREE II domains: scope and purpose, rigor of development, and editorial independence. CLINCAL IMPLICATIONS: There are very few Infectious disease guidelines for highly prevalent diseases that do not consider all important contextual factors may influence antimicrobial resistance. Our findings can support societies and organizations, public health policy, and health care stakeholders to develop and implement guidelines that are applicable to local contexts efficiently and resourcefully. Our antimicrobial resistance recommendation framework, used in addition to GRADE Evidence to Decision frameworks, is a start to having this come to fruition.

abstract: Thesis

abstract: Master of Public Health (MPH)


title: Game Theoretic Analysis of Defence Algorithms Against Data Poisoning Attack

subject:
Machine Learning Security
Data Poisoning Attack
Game Theory

abstract: As Machine Learning (ML) algorithms are deployed to solve a wide variety of tasks in today’s world, data poisoning attack poses a significant threat to ML applications. Although numerous defence algorithms against data poisoning attack have been proposed and shown to be effective, most defence algorithms are analyzed under the assumption of fixed attack strategies, without accounting for the strategic interactions between the attacker and the defender. In this work, we perform game theoretic analysis of defence algorithms against data poisoning attacks on Machine Learning. We study the defence strategy as a competitive game between the defender and the adversary and analyze the game characteristics for several defence algorithms. We propose a game model for the poisoning attack scenario, and prove the characteristics of the Nash Equilibrium (NE) defence strategy for all distance-based defence algorithms. Based on the NE characteristics, we develop an efficient algorithm to approximate for the NE defence strategy. Using fixed attack strategies as the benchmark, we then experimentally evaluate the impact of strategic interactions in the game model. Our approach does not only provide insights about the effectiveness of the analyzed algorithms under optimal poisoning attacks, but also serves as a method for the modellers to determine capable defence algorithms and optimal strategies to employ on their ML models.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: As Machine Learning (ML) algorithms are deployed to solve a wide variety of tasks in today’s world, data poisoning attack poses a significant threat to ML applications. In this work, we study the defence against poisoning attack scenario as a competitive game between the defender and the adversary and analyze the game characteristics for several defence algorithms. Our goal is to identify the optimal defence strategy against poisoning attacks, even when the adversary responds optimally to the defence strategy. We propose a game model for the poisoning attack scenario, and develop an efficient algorithm to approximate for the Nash Equilibrium defence strategy. Our approach does not only provide insights about the effectiveness of the analyzed algorithms under optimal poisoning attacks, but also serves as a method for the modellers to determine capable defence algorithms and optimal strategies to employ on their ML models.


title: Persistent Homology and Machine Learning

contributor:
McNicholas, Sharon M.
Nicas, Andrew J.
Mathematics and Statistics

subject:
Algebraic Topology
Machine Learning
Applied Topology
Persistent Homology

abstract:
Persistent homology is a technique of topological data analysis that seeks to understand
the shape of data. We study the effectiveness of a single-layer perceptron and gradient
boosted classification trees in classifying perhaps the most well-known data set in machine learning, the MNIST-Digits, or MNIST. An alternative representation is constructed, called MNIST-PD. This construction captures the topology of the digits using persistence diagrams, a product of persistent homology. We show that the models are more effective when trained on MNIST compared to MNIST-PD. Promising evidence reveals that the topology is learned by
the algorithms.

abstract: Thesis

abstract: Master of Science (MSc)


title: RAPID RECOMMENDATIONS: IMPROVING THE EFFICIENCY AND TRUSTWORTHINESS OF SYSTEMATIC REVIEWS AND GUIDELINES

title: RAPID RECOMMENDATIONS

contributor:
Guyatt, Gordon H.
Health Research Methodology

subject:
Clinical practice guidelines
Research methods
Rapid reviews
Rapid guidelines

abstract: This thesis explores the Rapid Recommendations process, a new responsive way of creating clinical practice guidelines.

abstract:
Healthcare workers rely on clinical practice guidelines to inform their practice. However, most guidelines are not trustworthy when judged by accepted standards and they typically take several years to produce. Guideline trustworthiness is undermined by panel members who often have conflicts of interest, by including representation from only a subset of stakeholders, by failing to examine the entirety of the evidence systematically, and by rapid obsolescence. Further, they are often difficult for users to understand in limited time.
Rather than updating guidance on a fixed schedule, the Rapid Recommendations approach involves continuous monitoring of the literature and produces guidelines in response to new potentially practice-changing evidence. A collaborative network of clinicians, methodologists, and patients respond by rapidly producing trustworthy evidence syntheses and guidance. We have identified efficiencies at every step of the guideline development process.
The guideline panel does not include anyone with a financial conflict of interest and there are strict limits professional and intellectual conflicts. Systematic reviews are produced on the relative effects of each option, on prognosis, and on patient values and preferences with the explicit intent to inform the question at hand. The panel also considers practical issues. Rapid Recommendations are published in a concise multilayered user-friendly format headed by an interactive infographic that contains all of the necessary information for users need to make informed decisions at the point of care. The guideline is published simultaneously in print and electronically, including decision aids that can be used at the point of care and integrated into electronic medical records.
In this thesis, you will find a selection of exemplary publications relevant to the Rapid Recommendations process. We show that a responsive approach to rapid and trustworthy guideline creation is possible. It represents a way forward from the current limitations that plague most current clinical practice guidelines.

abstract: Thesis

abstract: Candidate in Philosophy

abstract: Healthcare workers often decide what to do in practice based on the advice of experts through clinical practice guidelines. However, most clinical practice guidelines are not completely trustworthy. Guideline authors often have conflicts of interest, do not include patients or patient views, and are created so slowly that they rapidly fall into obsolescence. This thesis explores a new way of developing clinical practice guidelines that we call Rapid Recommendations. Instead of creating them on a fixed schedule (i.e., every few years), they are created in response to new studies that might change practice. The scope is limited, and timelines are shorter, meaning that the guidelines are published sooner. The guideline authors include all stakeholders, including patients. None of the authors have any financial interests in the topic, and other conflicts are minimized. The guidelines are published on an expedited basis and in an accessible online multilayered format with infographics. This thesis includes a selection of exemplary publications relevant to the Rapid Recommendations process.