title: Prospective Development and Validation of a Malignancy Scoring System During Endobronchial Ultrasound Evaluation of Mediastinal Lymph Nodes for Lung and Esophageal Cancer

title: Clinical Utility of Lymph Node Features during EBUS

contributor:
Hanna, Wael C.
Health Research Methodology

subject: Endobronchial ultrasound, lung cancer, NSCLC, esophageal cancer, lymph nodes

abstract:
Background: At the time of endobronchial ultrasound (EBUS) staging, ultrasonographic features can be used to predict mediastinal lymph node (LN) malignancy. Predictive tools have been developed, however they have not gained widespread use due to lack of research demonstrating validity and reliability. We sought to develop a novel predictive tool, the Canada Score, capable of predicting malignancy and potentially guide LN biopsy decision making.
Methods: We prospectively analyzed the ultrasonographic features of LNs from patients with NSCLC. Ultrasonographic features were identified by a single experienced endoscopist, this data was used to develop the Canada Score. Pathological specimens were used as the gold standard for determination of malignancy. Videos were then circulated to endoscopists across Canada, who were also asked to identify ultrasonographic features for each LN. Hosmer- Lemeshow test, logistic regression, receiver operator characteristic (ROC) curve, and Gwet’s AC1 analyses were used to test the performance, discriminatory capacity, and inter-rater reliability of the Canada Score.
Results: A total of 300 LNs from 140 patients were analyzed by 12 endoscopists across 7 Canadian centres. Backwards elimination was used to create a multivariate model. Hosmer-Lemeshow test and ROC curves indicated the model was well-calibrated (chi2=11.86, p=0.1567) with good discriminatory power (c- statistic= 0.72 ±0.042, 95%CI: 0.64-0.80). Beta-coefficients were used to create a simplified score out of four. Evaluation of the tool showed that LNs scoring 3 or 4 had odds ratios of 15.17 (p<0.0001) and 50.56 (p=0.001), respectively for predicting malignancy. A score of 4/4 was associated with 99.59% specificity and a positive likelihood ratio of 22.78. Inter-rater reliability for a score ≥ 3 was 0.81 ± 0.02 (95%CI: 0.77-0.85).
Conclusions: The Canada Score shows excellent performance in identifying malignant LN at the time of EBUS. A cut-off of ≥ 3 has the potential to inform decision-making regarding biopsy or repeat/mediastinoscopy if the initial results are inconclusive.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: During lymph node staging for lung and esophageal cancer, specific features of lymph nodes can be seen. Using diagnostic tools these features can be used to predict whether a lymph node is cancerous or benign. However, many of these diagnostic tools are inaccurate or unreliable. To address this, this thesis aimed to develop a novel diagnostic tool based on lymph node features seen during staging procedures and determine its clinical usefulness and application to the wider lung and esophageal cancer population. This thesis also aimed to use improved methods to develop this diagnostic tool such that patient and clinician experiences would be significantly improved. The results of this thesis may contribute to a reduction in the number of repeat procedures required for patients undergoing staging prior to their treatment for lung and esophageal cancers.


title: Low-light Stereo Image Enhancement Using Convolutional Neural Network

contributor:
Shirani, Shahram
Wu, Xiaolin
Electrical and Computer Engineering

abstract:
We present a method that can increase the quality of a low-light stereo image. While traditional stereo imaging methods have focused on estimating depth from stereo images, our method utilizes stereo images to enhance the low-light condition. The critical challenge for enhancing the low-light condition of stereo images is the disparity
between the left and the right images. We proposed an end-to-end convolutional neural network to enhance the low-light condition in stereo images without estimating the disparity. Our proposed network has two sub-networks: the  rst network learns how to enhance the low-light condition of stereo images in luminance, and the second network learns how to reconstruct a normal-light full-color image from enhanced luminance and chrominance of the input image. Our two-stage joint network enhances the low-light condition of stereo images significantly more than single-image low-light enhancement method.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Protein-protein interactions that mediate cell cycle events.

contributor:
Guarne, Alba
Biochemistry and Biomedical Sciences

subject: Cell cycle, crystallography, protein interactions.

abstract: Molecular recognition is at the core of all biological processes whereby protein-protein interactions (PPI) relay messages to drive signaling events. However, many regulatory responses are driven by weak or transient PPI. These interactions are difficult to study using structural biology techniques because they are labile and result in heterogeneous populations. Moreover, interactions reconstituted using peptides are difficult to interpret because they lack context. In this thesis, I characterized key signaling complexes implicated in the replication checkpoint response (Dbf4-Rad53-Cdc7 complex), mitosis (Dbf4-Cdc5 complex), and DNA mismatch repair (clamp-MutL complex). I solved the crystal structures of the Dbf4-Rad53 and clamp-MutL weak complexes by generating fusions of the binding partners. The structures revealed that Dbf4 and MutL undergo subtle conformational movements upon engaging their binding partners, which were sufficient to alter both interfaces. Overall, the structures offer insight as to how Rad53 could inhibit Dbf4-Cdc7 during the replication checkpoint and how the clamp could activate MutL during mismatch repair. Acquiring the Dbf4-Cdc5 co-crystal structure required optimization the Dbf4 peptide. The Dbf4-Cdc5 and Dbf4-Rad53 complexes were relatable because both interactions were phosphorylation-independent even though Rad53 and Cdc5 are known to recognize phosphorylated targets. Dbf4 engaged a binding site on Cdc5 located opposite to the phosphoepitope binding pocket, which is reminiscent to its interaction with Rad53. Collectively, the structures of Dbf4 and its binding partners reveal that Rad53 and Cdc5 function beyond phosphoepitope recognition whereby they utilize additional binding surfaces to engage substrates.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: A FEASIBILITY STUDY OF A PRE-IMPLANTATION NURSE-LED EDUCATIONAL INTERVENTION FOR PRIMARY PREVENTION IMPLANTABLE CARDIOVERTER DEFIBRILLATOR CANDIDATES

title: FEASIBILITY OF AN INTERVENTION FOR DEFIBRILLATOR CANDIDATES

contributor:
Carroll, Sandra L.
Nursing

subject: patient education; implantable cardioverter defibrillator; health teaching; psychosocial support; feasibility

abstract:
Background: Implantable cardioverter defibrillators (ICDs) deliver therapy in the form of an internal shock should a life-threatening arrhythmia occur. Literature suggests that patients have misconceptions regarding ICD therapy and unmet information needs.
Purpose: This study assessed the feasibility of delivering a pre-implantation nurse-led educational intervention to ICD candidates.
Methods: ICD candidates attending an outpatient preoperative clinic were invited to participate. Consented participants were randomized to standard care or standard care plus an educational intervention. The educational intervention addressing information gaps identified in the ICD literature was delivered during the preoperative visit. The primary outcome was feasibility with the following targeted rates, (1) 80% recruitment; (2) ≥ 95% consent; (3) 90% randomization; (4) ≥ 90% completion of questionnaires; (5) 80% of intervention sessions delivered less than 45 minutes; and (6) 90% of intervention content delivered. At baseline, demographic data and Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety scores were collected. Four weeks post-ICD implantation, participants completed the PROMIS anxiety measure, Florida Patient Acceptance Survey (FPAS), and Florida Shock Anxiety Scale (FSAS).
Results: Twenty patients consented to the study (10 standard care/10 standard care plus the educational intervention). Feasibility outcomes achieved were, (1) recruitment rate of 80%; (2) consent rate of 87%; (3) 100% randomization; (4) 80% completion of questionnaires; (5) 100% of intervention sessions completed in less than 45 minutes; and (6) intervention checklist completion rate of 100%. The four-week mean (SD) FPAS scores were 80.0 (13.4) in the intervention group compared to 77.0 (16.5) in standard care. Mean (SE) four-week PROMIS
scores were 45.4 (6.4) in the intervention group and 43.7 (8.6) in standard care. Mean FSAS (SD) scores were 14.7 (4.6) in the intervention group and 13.3 (3.9) in standard care.
Conclusion: The results demonstrated feasibility of delivering a pre-implantation nurse-led educational intervention in an outpatient clinic setting to ICD candidates. Further studies to evaluate the effectiveness of the intervention on patient-reported outcomes are warranted.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: An ICD is a medical device placed under the skin that can fix a dangerous heart rhythm. It can do so by shocking the patient’s heart if the ICD senses a dangerous heart rhythm. This study was done to determine if it is practical to deliver education to patients before they receive their ICD. Some patients feel they do not receive enough information before getting an ICD. No studies have tested how education before receiving an ICD can impact a patient’s quality of life. In this study, ten people received usual care while ten people received usual care and ICD education from a nurse before ICD implantation. The results of this study determined that it was practical for nurses to deliver ICD teaching before the ICD was implanted. A future study testing the impact of education on the quality of life of ICD patients can and should be completed.


title: Modeling of inclusion evolution in Ladle Metallurgy Furnace

contributor:
Coley, Kenneth S.
Irons, Gordon A.
Sun, Stanley
Materials Science and Engineering

subject:
Ladle Furnace
Kinetis
Non-metallic inclusions
steelmaking

abstract:
The Ladle Metallurgy Furnace (LMF) in secondary steelmaking processing allows (1) the adjustment of the chemical composition by ferroalloy addition, (2) temperature control by electrical reheating (3) homogenization of chemical composition by argon stirring (4) desulphurization and (5) control of inclusions produced during steel deoxidation. The solid oxide inclusions not only cause nozzle clogging during the continuous casting process and reduce production efficiency, but they are also harmful to the properties of the steel product. In the case of aluminum killed steel, calcium treatment of steel is typically employed to modify the solid alumina inclusions or magnesium aluminate inclusions to liquid or partially liquid calcium aluminates. Injected calcium in form of calcium wire creates calcium bubbles. A portion of calcium dissolves into the steel and diffuses into the steel bulk. However, during the dissolution process some of the injected calcium reacts, close to the injection plume, with dissolved sulfur and oxygen in the steel to form calcium sulfide and calcium oxide inclusions [1].
During ladle treatment of aluminum killed steel the inclusions which form initially are typically alumina. As the dissolved oxygen content of the steel is reduced to very low levels magnesium may be reduced from the slag  and subsequently react with the inclusions resulting in a shift towards higher contents of MgO and formation of magnesium aluminate spinel. Magnesium may originate from the top slag, ferro alloys or refractories. Therefore, magnesium aluminate spinels are almost always present before calcium injection and any consideration of calcium treatment should also consider the  modification of spinel in addition to alumina. The current work develops a fundamental kinetic model to describe the evolution of the inclusion population during ladle treatment of aluminum killed steels. The model builds on previous work in the author’s laboratory predicting the kinetics of slag metal reactions during ladle treatment and the transformation of alumina to magnesium aluminate spinel. The model addresses the modification of alumina inclusions by calcium and considers mass transfer of species to the inclusion-steel interface and diffusion within the calcium aluminate phases formed on the inclusion. The dissolution of calcium from calcium bubbles into the steel and formation of oxide and sulfide inclusions at the plume is coupled with the kinetic model for inclusion modification. It is found that rate of supply of calcium to the inclusions controls the overall rate of transformation. The inclusion-steel kinetic model is then coupled with the previously developed steel-slag kinetic model. The coupled inclusion-steel-slag kinetic model is applied to the chemical composition changes in molten steel, slag, and evolution of inclusions in the ladle. The result of calculations is found to agree well with industrial heats for species in the steel as well as inclusions during Ca treatment. The kinetic model is further extended to model the modification of spinel inclusions by calcium treatment.
Coupling the model for inclusions modification to a multi component kinetic model for the slag-steel reactions in the ladle furnace allowed prediction of the change of average composition of inclusions which was subsequently verified using plant data from ArcelorMittal Dofasco operations. Good agreement between the experimental and calculated average composition of inclusions was obtained for most of the industrial heats. Finally, a sensitivity analysis of the coupled kinetic model was performed to compare the effect of the different processing conditions including sulphur content, stirring, total oxygen, slag composition and reoxidation, on the evolution path of inclusions.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: MENTAL FATIGUE AND SELF-REGULATION OF PHYSICAL ACTIVITY BEHAVIOUR

contributor:
Bray, Steven
Kinesiology

subject:
exercise performance
cognitive control
motivation
self-control

abstract:
Exerting cognitive control can lead to mental fatigue and impair self-regulation of subsequent physical performance. However, current understanding is limited due to a number of factors. First, studies have employed manipulations involving either high or low cognitive demands, failing to test whether a dose-response relationship exists between mental fatigue and physical performance. Second, the role of several psychological variables among the mental fatigue – physical performance relationship remains unclear. Third, current literature lacks generalizability in that existing findings have largely been derived from studies involving active samples performing physical tasks that the general population may not commonly engage in for health and fitness benefits. Lastly, there has been little research examining intervention strategies that may attenuate the effects of mental fatigue on physical activity behaviour. This dissertation aimed to advance our understanding of self-regulation of physical activity behaviour in response to mental fatigue by addressing shortcomings within the literature discussed above.
Study 1 examined whether a dose-response relationship exists for mental fatigue and physical performance. Results showed a performance threshold exists between 4 and 6 minutes of exposure to a mentally fatiguing cognitive control task. Beyond this threshold, task self-efficacy also showed uniform reductions which mediated the mental fatigue – physical performance change relationship. Findings are consistent with previous research and reveal self-efficacy is a key variable that accounts for the negative effects of mental fatigue on physical performance.
Study 2 investigated the hypothesis that offering a performance contingent monetary incentive would attenuate the negative carryover effects of mental fatigue on physical performance. Findings showed mental fatigue caused characteristic declines in physical performance; however, incentives countered the effects of mental fatigue and led to performances equal to those witnessed in a non-fatigued state. Interestingly, incentives did not provide any additional benefit for performance when not fatigued. Findings support motivational accounts of self-regulation, although incentives may lack practicality and may not be a cost-effective means to alter exercise behaviour.
Study 3 examined the effect of mental fatigue on intended physical exertion and exercise performance reflective of current public health guidelines for physical activity in a sample comprised of insufficiently active university students. Findings showed mental fatigue alters the amount of physical effort people are willing to invest in an exercise workout and follow through with those intentions by doing less work and exercising at a lower heart rate intensity.  These are the first results showing people may deliberately adjust their physical effort to cope with mental fatigue.
Study 4 investigated whether heart rate biofeedback moderates the effects of mental fatigue on vigorous-intensity exercise reflective of current public health physical activity guidelines and the effects of mental fatigue on pre-exercise motivational cognitions. Results showed mental fatigue was associated with decreases in intended physical effort and commitment to vigorous-intensity exercise goals which corresponded with reductions in exercise intensity (i.e., HRAVE) and total work performed when people exercised without feedback. However, HR biofeedback attenuated the negative carryover effects of mental fatigue on exercise behaviour, restoring exercise intensity and performance to levels witnessed in a non-fatigued state. Similar to incentives, biofeedback offered no further benefits for performance when not fatigued. Findings align with predictions of Control Theory and suggest biofeedback using widely available physical activity monitors in combination with goals can improve intensity-based physical activity guideline adherence when confronted with barriers such as mental fatigue.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Effortful cognitive control exertion can lead to mental fatigue and impair self-regulation of subsequent physical performance. However, current understanding is limited due to a number of factors. This thesis addressed several gaps in the literature through a systematic examination of potential mediators and moderators of the mental fatigue - physical performance relationship. Findings revealed downstream physical performance impairments are dependent on exceeding a critical mental fatigue threshold. Reductions in pre-exercise cognitions including self-efficacy, intended physical exertion and goal commitment all correspond with negative changes in exercise performance. Evidence also highlights the generalizability of fatigue-induced effects by demonstrating that insufficiently active people engaging in exercise for health and fitness benefits down-regulate exercise performance in the face of mental fatigue. Incentives and heart rate biofeedback can attenuate the effects of mental fatigue on physical performance. Collectively, evidence provides insight for theories of self-control and can be interpreted within Muller and Apps (2018) neurocognitive framework of motivational fatigue.


title: Paternal obesity is associated with hypoxia and angiogenesis in female placenta and mediates placental development

contributor:
Sloboda, Deborah
Biochemistry and Biomedical Sciences

subject: Paternal obesity

subject: ER stress

subject: Placenta

subject: Angiogenesis

subject: Pregnancy

subject: Developmental origins of health and disease

abstract:
While the impacts of maternal obesity on placental development have been extensively
studied, the role of the father’s health in regulating placentation is less understood. Paternal
obesity is associated with offspring metabolic dysfunction, but the mechanism regulating this
association is unclear. We investigated how paternal diet-induced obesity impacted placental
vascular development, associated cellular stress pathways, and markers of placental endocrine function and macronutrient transport across gestation in a murine model. We found that paternal obesity is associated with placental hypoxia as measured by CAIX and HIF1α at E14.5 which persisted to E18.5. Hypoxia was associated with increased VEGF protein levels, as well as its pro-angiogenic receptor, VEGFR2 in male and female E14.5 placentae, although, this increase was apparent only in females at E18.5. The proportion of placental tissue that was immunopositive for the endothelial cell marker CD31 was increased in female but not male E18.5 placentae. Paternal obesity was associated with cellular stress as measured by the three branches of the unfolded protein response (UPR): ATF6, PERK, and IRE1α. However, despite increased phosphorylation of PERK and IRE1α in placental tissue derived from obese fathers, there was no impact on downstream signal transducers. Pro-apoptotic Bcl2 family members’ transcript levels were reduced at E18.5 in placentae from obese fathers, but this did not correspond to any changes in cleaved casp-3 protein levels. Placental lactogen and macronutrient transporter transcript levels were similar between groups across gestation, although Igf2 transcripts were increased in female placenta from obese fathers at both mid and late gestation. Thus, paternal obesity results in placental hypoxia and VEGF mediated sex specific changes in vascularization with a pro-angiogenic response occurring in females. Future studies will investigate whether paternal obesity impairs early placental implantation, resulting in poor vascularization and hypoxia at E18.5.

abstract: Thesis

abstract: Master of Science (MSc)


title: AN ANALYSIS INTO THE FUNCTIONING OF THE S. INTERMEDIUS B196 STREPTOCOCCUS INVASION LOCUS

title: THE STREPTOCOCCUS INVASION LOCUS IN S. INTERMEDIUS B196

contributor:
Surette, Michael
Biochemistry and Biomedical Sciences

subject:
sil
streptococcus invasion locus

abstract:
The Streptococcus Anginosus Group (SAG) is a group of Gram-positive cocci
which require carbon dioxide to grow. They are commensal members of the
healthy upper respiratory, gastrointestinal and female urogenital tract; however,
they are most commonly known as major pathogens in brain and liver abscesses,
forming both mono- and polymicrobial infections. The Streptococcus invasion
locus (sil), first identified as a virulence factor in Group A Streptococcus (GAS),
has recently been identified in the SAG. The sil locus in GAS is a two component
quorum-sensing system composed of three operons: silAB, coding for a two
component system; silE/D/CR, coding for an ABC transporter and a signal
peptide, and silC, which overlaps silCR on the opposite strand. The presence of
exogenous SilCR activates SilA, which in turn upregulates the transcription of the
silE/D/CR operon. In the SAG, however, silCR and silED have distinct promoters,
and the SAG sil system lacks the silC gene. In this study, I examined the
transcriptional dynamics of the sil system in S. intermedius B196. I determined
that SilA is the major regulator of the genes in the sil system, being one of the
first genes of the system to be expressed, and likely upregulates its own
transcription. I also found evidence suggesting that, despite having its own
promoter, silCR transcription may still be driven by the silED promoter. I also
found evidence that suggests silED may be responsible for the export and/or
processing of bacteriocins targeting closely related species or strains.

abstract: Thesis

abstract: Master of Science (MSc)

abstract:
The Streptococcus are a group of bacteria known for causing diseases
ranging from strep throat to flesh-eating disease; however, many species of
Streptococcus are usually non-pathogenic, and live in our bodies without causing
harm. One group of these bacteria, the Streptococcus Anginosus Group (SAG), is
commonly found in our mouths and gut and usually cause no harm; however, in
some cases it can cause infections. How these organisms switch from being nonpathogenic
to pathogenic is unknown, but recently a gene network that appears
to play a role in infection, the Streptococcus invasion locus (sil), was identified in
the SAG. This gene network senses the signals released by other bacteria with
the network, and only turns on when enough signal is present. The goal of this
study is to examine how the system works in the SAG in order to determine how
these bacteria coordinate sil gene expression.


title: The Cultural Politics of Racial Neoliberalism in the Contemporary British Novel

contributor:
Brophy, Sarah
English and Cultural Studies

subject:
Neoliberalism
Critical Race Studies
Contemporary British Writing

abstract: This dissertation responds to the notion that the economic success and social integration of one imaginary figure, the “model minority,” can explain the downward mobility of another, the “white working class” in post-Brexit Britain. Through intersectional readings of Black and Asian British fiction written during and after Margaret Thatcher’s prime ministership, I examine the model minority myth as providing a racist explanation for rising inequality, but also as a burdensome imperative of neoliberal aspiration to which racialized British subjects are increasingly subject. I trace the origins of this exclusionary account of racialized belonging to the account in Salman Rushdie’s The Satanic Verses of the political possibilities resulting from the collapse of anti-racist solidarities under the sign of Black British identity in the 1980s. I show that the author’s non-fictional responses to the subsequent controversy known as the Rushdie Affair work to close off these possibilities, serving instead to justify Islamophobia one specific means by which racial neoliberalism functions as what David Theo Goldberg calls “racism without racism.” I develop this analysis of Islamophobia as form of racial neoliberalism by turning to two novels that depict coming of age for diasporic Muslim British women, contrasting Monica Ali’s Brick Lane as a normative narrative of feminist becoming through assimilation with Leila Aboulela’s Minaret, which complicates the agency assumed to be conferred on “Third World Women” who migrate to the Global North. In my third and final chapter, I trace the model minority trope across differences in Black and Asian British communities as evidence of the empty aspiration of “post-racial” Britain, contrasting the attempt in Gautam Malkani’s Londonstani to posit the figure of the “rudeboy” as an alternative “outsider” figure of aspiration, with Zadie Smith’s “insider” depiction of the social alienation that results from approaching the embodiment of this racialized ideal in NW.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: This dissertation discusses the influence of neoliberalism—the idea that capitalism represents the ideal model of organization for every aspect of human life—on Black and Asian British writing from the 1980s to the present. In the context of mainstream analysis of the June 2016 Brexit vote as an expression of “white working class” disaffection with rising inequality, I focus on how coming-of-age narratives by Black and Asian writers complicate an unspoken implication of this popular explanation: that neoliberal reforms have unduly advantaged so-called “model” racial minorities. Through readings that emphasize how the Muslim and/as racialized protagonists of these texts experience the recoding of racism either in the covert guise of Islamophobia or through the aspirational idea that Britain is “post-racial,” I demonstrate the highly tenuous nature of what social and political belonging racialized subjects can find amid the increasing individualism of contemporary British society.


title: Enhancing Biosensor Performance with Omniphobic Lubricant-Infused Coatings

contributor:
Didar, Tohid
Biomedical Engineering

subject:
Biosensor
Biofouling
Coating
Coagulation
Nonspecific Binding
Surface Blocking
Lubricant-Infused
Omniphobicity
DNA Microarray
Dissolved Oxygen

abstract:
Point-of-care testing brings diagnosis and treatment monitoring to the site of the patient. It heavily relies on biosensors, which leverage the interactions between a target biomarker and a bioreceptor, to deliver fast and accurate results. However, non-specific binding of molecules and microorganisms on the biointerface can interfere with biomarker-bioreceptor interactions and diminish a biosensor’s sensitivity, specificity, and stability. In turn, this can lead to false diagnoses and ineffective treatments. Omniphobic-lubricant infused (OLI) coatings exhibit slippery, self-cleaning characteristics that repel untargeted molecules and microorganisms to augment the biosensor’s performance.
In this work, we investigate the proficiency of OLI coatings in two specific applications: dissolved oxygen sensing and DNA biosensing. First, in water quality monitoring, an OLI coating is applied to the selectively permeable membranes of a dissolved oxygen sensor. Over a three-week incubation period in an environment with accelerated bacterial growth, the coated membranes exhibit a 160% higher reproducibility (10% deviation in sensitivity) and lower biofilm formation (96° static contact angle) in comparison to unmodified membranes (26%, 32°). The second application is in DNA biosensing, where a novel OLI coating uses carbon dioxide plasma activation to embed oligonucleotide probes. It demonstrates an optimized balance of slippery repellency (76° static contact angle, 10° sliding angle) and biosensing functionality, 19% longer clotting times than conventional blocking conditions, and equal sensitivity to PLL-PEG when capturing target DNA in whole blood. Going forward, our research will continue to expand the use of OLI coatings in biosensing applications, particularly exploiting its antibiofouling and anticoagulative capabilities.

abstract: Thesis

abstract: Master of Applied Science (MASc)

abstract: Biosensors are an integral tool in delivering quick and accurate point-of-care diagnosis and treatment monitoring. However, their performance can be impeded by the non-specific binding of undesirable molecules and microorganisms on the sensing surface. Omniphobic lubricant-infused (OLI) coatings have been shown to suppress biofouling and blood clotting on surfaces through exceptional repellency. This thesis focuses on the implementation of OLI coatings in biosensing applications. It investigates the antibiofouling capacity of an OLI coating on a membrane for dissolved oxygen detection. Then, it discusses a novel coating with integrated DNA biosensing functionality for working directly with blood samples. The enclosed work demonstrates that the OLI coating empowers biosensors to deliver more effective point-of-care testing.


title: Synthesis and Study of Click-Crosslinked Polyanionic Hydrogel Networks

contributor:
Stöver, Harald D.H.
Chemistry and Chemical Biology

subject: hydrogels polymers

abstract:
Cell encapsulation aims to treat a variety of hormone- and enzyme-deficiency disorders by immobilizing therapeutic cells within a semi-permeable protective membrane.  The membrane allows for in-diffusion of oxygen and nutrients and out-diffusion of waste and therapeutic proteins while simultaneously providing protection from immune cells and antibodies. Many cell therapies aim to provide long-term treatment for diseases, and designing materials that can match the longevity is critical.  Synthetic polymers offer an attractive route to long-term encapsulation due to their tunable degradability and the ease of incorporating reactive moieties for covalent crosslinking.
The primary goal of the work presented in this thesis was the development of non-degradable covalently crosslinked hydrogels formed by mutually reactive polymers for use as cell immobilizing platforms.  Due to research showing that polycations incite immune responses in vivo this project aimed to avoid the use of polycations entirely.  The covalent crosslinking occurs in the presence of cells, making it essential to select reactions that do not require toxic catalysts or form offensive by-products.  Diels-Alder and thiol-ene Michael Addition click reactions were chosen due to their proven cytocompatibility and modular nature.
In chapters 2 and 3, poly(methyl vinyl ether-alt-maleic anhydride) (PMMAn) was functionalized with furfurylamine (FFA) and N-2-(aminoethyl)maleimide (MAL) to form PMM-FFA and PMM-MAL, Diels-Alder reactive furan- and maleimide-bearing pendant polymers.  Aqueous solutions of the polymers form bulk gels at higher concentrations (>5% w/v) and the chemical and physical properties of the gels were investigated and found to be highly tunable, with promise for use in controlled drug delivery applications.  Alginate-templated matrix beads were also prepared at significantly lower polymer loading percentages (0.5 – 1.5% w/v each) and at physiological pH, and properties such as swellability and permeability were explored. This work demonstrates the first use of Diels-Alder crosslinking to reinforce alginate beads, and the matrix beads were found to have good initial cell viability post-encapsulation with 3T3 cells.
In chapter 4, PMMAn was functionalized with cysteamine vinyl sulfone (CVS) to form PMM-CVS, a vinyl sulfone-bearing pendant polymer, and aqueous solutions were mixed with equimolar PEG-dithiol to form bulk hydrogels at concentrations between 2.5 and 7.5% w/v PMM-CVS.  Thiol-ene crosslinking allowed for much more rapid gelation compared to the Diels-Alder system.  Physical and chemical properties of the gels were explored, and excellent cytocompatibility of the crosslinking reaction was demonstrated.  The ability to rapidly post-functionalize the gels in a step-wise fashion offers a versatile route to post-modification with various molecules.  In chapter 5, PMMAn was functionalized with 2-pyridylthio cysteamine (SPy) to form PMM-SPy, a protected thiol.  Alginate-templated matrix beads containing PMM-CVS and PMM-SPy were treated with TCEP to deprotect the thiol, allowing covalent crosslinking to occur in a controlled manner.  Physical and chemical properties of the beads were explored in detail and the system was found to be highly tunable.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: Cell encapsulation aims to treat various hormone- and enzyme-deficiency disorders such as diabetes mellitus by encapsulating cells within a protective membrane that permits the in-diffusion of oxygen and nutrients and the outward diffusion of waste and therapeutic proteins, such as insulin.  The membrane must also protect the encapsulated cells from the immune system. The primary goal of this project was to design polymeric materials for use in cell encapsulation.  A series of mutually reactive polymers were developed, and the resulting polymeric hydrogels were characterized for suitability in biomedical applications by exploring properties such as swelling, stiffness, porosity and cytocompatibility. The materials were found to have tunable physical properties, and good cytocompatibility, showing promise for future use in cell encapsulation.


title: Investigating the developmental roles for the functional amyloid system of Streptomyces venezuelae

contributor:
Elliot, Marie
Biology

subject: Streptomyces, chaplin, amyloid

abstract:
Amyloid proteins are found in all domains of life, and have a number of defining characteristics, including considerable β-sheet secondary structure and the ability to self-assemble into large, insoluble fibers. These insoluble aggregates are often deleterious to the cell, evidenced by amyloid proteins being involved in Alzheimer’s, Parkinson’s, and Huntington’s disease. Remarkably however, some organisms have found ways to circumvent the toxicity of amyloid proteins, and instead co-opt them as beneficial aspects of their development and survival. An example of this can be seen in the bacteria genus Streptomyces. Streptomyces bacteria have a complex, multicellular life cycle that involves progressing through a number of distinct developmental stages. The reproductive phase of the life cycle requires the activity of amyloid-forming proteins known as chaplins - hydrophobic proteins that polymerize on the cell surface, ultimately promoting reproductive development.
Due to limitations in other model Streptomyces, key questions regarding the function of chaplins have not yet been addressed. The emerging model species Streptomyces venezuelae is unique given its rapid growth, its ability to develop in liquid, and its potential to adopt two distinct life cycle programs. This work sought to characterize how chaplins influence these processes. We created a number of chaplin mutants, and determined that chaplins contribute to these process in mostly redundant ways, but when deleted in bulk cause significant phenotypic changes. We have also shown that the requirement of chaplins in development goes beyond what was previously understood - as their loss affects development in all classical life cycle stages, and further impacts alternative life cycle programs. To understanding how chaplins are regulated in S. venezuelae, mutagenesis screens were conducted to identify mutants with altered chaplin regulation. These yielded promising candidates for further investigation. Collectively, this work has advanced our understanding of chaplin proteins, specifically how they are regulated, and how they affect various modes of Streptomyces growth and development.

abstract: Thesis

abstract: Master of Science (MSc)


title: HETEROGENEITY AND CENTRALITY OF “DARK PERSONALITY” WITHIN TEAMS, EMERGENCE OF SHARED LEADERSHIP, AND TEAM PERFORMANCE: TEST OF A MODERATED-MEDIATION MODEL

contributor:
Hackett, Rick
Business Administration

abstract: This dissertation aims to advance understanding of team composition, processes, and performance by shifting from the much-studied five-factor model of personality and focusing on “dark personality” (i.e. the “Dark Triad”: Machiavellianism, Psychopathy, and Narcissism) and adopting a social network analysis approach. The research responds to a call to explore dark personality’s manifestation within -- and impact on -- teams. Specifically, in this study I examine within-team heterogeneity in dark personality and its impact on team performance, with the emergence of shared leadership as mediator of this relationship. Additionally, I examine two proposed moderators of the relationship between within-team dark triad heterogeneity and shared leadership emergence -- team network centrality of the team member scoring highest on the Dark Triad, and team mean Dark Triad score. The results suggest Dark Triad heterogeneity did not impact team performance and the hypothesized mediating role of shared leadership was not supported. Moreover, moderated-mediation by the aforementioned moderators also did not receive support. Nonetheless, this research makes a uniquely valuable contribution to scholarship on leadership within teams by offering a framework that bridges literatures on social network analysis, teams, leadership, and the dark triad and should have implications for team selection and performance.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


title: Properties and Function of the HSV Transactivator ATOR VP16 Expressed in Yeast Saccharomyces cerevisiae

contributor:
Capone, John
Biochemistry

subject:
HSV transactivator VP16
yeast saccharomyces cerevisiae
saccharomyces cerevisiae

abstract: Herpes simplex virus protein VP16 activates immediate-early (IE) viral gene expression upon infection. VP16-mediated transactivation depends on formation of a multi protein complex with cellular factors on a cis-acting TAATGARA T sequence present in the IE promoters. The potent acidic activation domain, contained within the carboxyl terminus of VP16, is dispensable for the complex formation. The amino terminal part of VP16, which is inert in transactivation in mammalian cells, is sufficient for selective interactions with cellular factors, one of which has been identified as the ubiquitous transcription factor Oct-1. The yeast two-hybrid system was utilized to isolate the cellular factor(s) necessary in addition to Oct-1 for VP16 induced complex formation. This system, designed to directly clone proteins interacting with a given protein of interest, employs the yeast transcriptional activator GAL4. An interaction between VP16 and the cellular factor(s), fused to GAL4 DNA binding and activation domain, respectively, reconstitutes a hybrid transactivator that stimulates expression of a reporter lacZ gene in yeast. Thus, (beta)-galactosidase activity serves as a positive signal for protein-protein interaction. As a prelude of using this method for isolation of VP16-interacting cellular proteins, the system was tested with HSV-1 protein vhs, known to bind to VP16 in vitro. The obtained data demonstrated an interaction between VP16 and vhs in the two-hybrid system and deletion analysis revealed that VP16 sequence contained within the first 369 amino acids is required for binding to vhs. Thus, VP16 residues necessary for interaction with vhs in vivo coincide with these identified previously for VP16-vhs complex formation in vitro. VP16 fused to the GAL4 DNA binding domain activated expression of the reporter lacZ gene in yeast, despite the absence of its acidic activation domain. Deletion analysis showed that the amino terminal 369 residues of VP16 were sufficient for transactivation in yeast. Similar GAL4-VP16 derivatives were inactive in mammalian cells as measured by transient transfection assays. Thus, unlike in yeast, VP16 lacking the acidic activation domain is deficient in transactivation in mammalian cells even if it is directly bound to a promoter. VP16 sequences required for complex formation with vhs overlaps with those implicated in interaction with the mammalian factors, indicating that this region is involved in protein-protein interactions with both cellular and viral factors. Consistent with this, VP16 interaction with a yeast factor supplying an activation domain in trans would explain VP16-dependent transactivation in the absence of its acidic activation domain. Alternatively, a yeast specific activation domain might be present in the amino terminal part of VP16.

abstract: Thesis

abstract: Master of Science (MS)


title: PEPDB Construction and Large-Scale Analysis of ESTS

contributor:
Golding, G. B.
Biology

subject:
construction
large-scale analysis
ESTs

abstract:
The Protist EST program (PEP) aims to explore the diversity of eukaryotic genomes, in a systematic and comprehensive way. A main element of the PEP initiative is to establish a database, the Protist EST Database (PEPdb), which is the centerpiece of the PEP collaboration. The major functions of the PEPdb are management of the data generated by
PEP, analysis of these data, and to allow collected sequence information to be accessed via the Internet by PEP members or other users. In this project, a consistent and easy to use relational database was implemented. All information about PEP members, Publications, Libraries and ESTs can be stored in the database system. The operations are achieved by
a friendly user interface. This database stores about 10000 records and is displayed on the web site "http://info.biology.mcmaster.ca/ling/estHome.html" for demonstration. An analysis of ESTs from the ciliated protozoan Tetrahymena thermophila was undertaken. A total of 3740 non-redundant gene assemblies and singletons from TIGR were analyzed. These sequences have been compared against the NCBI non-redundant protein and nucleotide databases using BLASTX and BLASTN to identify putative genes. Of 850 highly significant matches with an expect value cut-off of 10^-20 , 35.5% represent genes previously cloned from T. thermophila, and 64.5% had significant similarity to genes from other organisms deposited in the NCBI. There are 26 sequences (3.1%) that matched signal transduction proteins, including Rac, Ras, MAPK, ERK1, PKC, cAMP and 14-3-3 (a protein involved in signal transduction, exocytosis and cell cycle regulation). This result indicates that T. thermophila likely encodes the MAPK/ERK signaling pathway. About 53
sequences (6.2%) matched to cytoskeleton proteins which were divided into two groups. The first group matched genes coding for microtubules, especially to tubulin genes. The other group matched to microfilament genes including one actin, three actin-related and one profilin proteins. There were no sequences similar to intermediate filaments. Comparison of the EST counts from one gene provide absolute estimates of mRNA expression levels. The most abundant genes represented are enolase, SerH3 and Tubulin. Among 850 highly significant similarities, 196 were restricted to the ciliophora. GRL and SerH are ciliate-specific genes. There were 508 sequences that had highly significant matches (expect
value < 10^-20) to human genes. Approximately 189 of them were present in humans but not found in the completely sequenced Saccharomyces cerevisiae. Based on Venn diagram analysis, T. thermophila contains abundant Eukaryotic specific proteins and many prokaryotic-like genes, and some metabolic enzymes in T. thermophila are also present in
plants. These results support the fact that T. thermophila is an excellent unicellular model system for gene discovery and functional analysis.

abstract: Thesis

abstract: Master of Science (MS)


title: Biotechnologies of the Self: The Human Genome Project and Modern Subjectivity

title: Biotechnologies of the Self

contributor:
Allen, Barry
Philosophy

subject:
biotechnology
human genome project
modern subjectivity
subjectivity

abstract: Recent research in human genetics has sparked popular interest in genetic explanations for all human phenomena. In turn, bioethicists have been busy responding to their own call for stringent guidelines for the use of genetic information. But bioethicists in general fail to attend to deeper considerations of the nature of scientific knowledge and its role in the transformation of human subjectivity. For this reason, bioethicists are accessories after the fact to that transformation, and hence in order to study that change we must displace bioethical analyses of the Human Genome Project --that is, displace virtually all of the literature on the HGP. In this thesis, I offer a different and more radical interpretation of the role of scientific knowledge in altering our conception of what it is to be a human being. Physicians, genetic counsellors, and other experts in our gene culture offer fundamentally questionable and yet practically unquestioned genetic explanations of who and what we really are. These genetic experts, by virtue of their prestigious position in our economy of knowledge, impute needs only they can satisfy, impart a vocabulary only they are invited (and certified) to understand, and draw us into new networks of administration and control at the subcellular level. Drawing on the work of Duden, Foucault, Illich, and Poerksen, I argue that our attraction to technoscientific understandings of our "essence" is dangerous and disabling, and I sketch a strategy of resistance.

abstract: Thesis

abstract: Master of Arts (MA)


title: The Effects of Biological Sex and Ovarian Hormones on Exercise-Induced Neuroplasticity

contributor:
Nelson, Aimee
Kinesiology

subject: TMS, Biological Sex, Ovarian Hormones, Exercise

abstract: Acute aerobic exercise alters neurotrophic and growth factor concentrations, increases neural activity and improves cognitive and motor function. Additionally, acute exercise increases excitation and reduces inhibition in the motor cortex as assessed via transcranial magnetic stimulation (TMS). The propensity for exercise-induced neuroplasticity may be greater in females, as females show greater neuroplasticity induction following non-invasive brain stimulation (NIBS) compared to males. In females, NIBS yields greater neuroplasticity during ovulation, when estradiol levels are higher, compared to menstruation, suggesting that ovarian hormones may also impact exercise-induced neuroplasticity. To date, it is unknown whether biological sex and ovarian hormones impact neuroplasticity induced by acute aerobic exercise. The present thesis investigated the effects of biological sex and ovarian hormones on the magnitude and direction of neuroplasticity induced by acute aerobic exercise. Fourteen females and fourteen age- and fitness-matched males participated in two sessions in which dependent measures were acquired before and following a single bout of aerobic exercise. Females were tested in the follicular (~day 7) and luteal (~day 21) phases of the menstrual cycle and males were also tested on two occasions separated by ~14 days. The exercise intervention consisted of 5 minutes of warm up, 20 minutes of moderate intensity continuous cycling at 65-70% maximal heart rate, and 5 minutes cool down. TMS was used to obtain motor evoked potential (MEP) recruitment curves and short interval intracortical inhibition (SICI) from the right first dorsal interosseous muscle. Blood measures of estradiol, progesterone, testosterone, and brain-derived neurotrophic factor were assessed before exercise on both testing sessions. Results indicated that only females showed increases in MEP recruitment curve following exercise, and this occurred regardless of menstrual cycle phase. SICI did not change following exercise for males or females on either testing session. The estrogen to progesterone ratio in females was greater in the follicular phase compared to the luteal phase. There was a trend towards greater serum BDNF levels in females in the luteal phase compared to the follicular phase. Sex hormones and BDNF levels did not vary across sessions in males. These findings indicate biological sex, but not ovarian hormones, is an important factor to consider when inducing neuroplasticity using acute exercise.

abstract: Thesis

abstract: Master of Science (MSc)


title: Kaiso regulates tumor-suppressing microRNA-31 and microRNA-200c in triple negative breast cancer (TNBC) cells

contributor:
Daniel, Juliet
Biology

abstract: Breast cancer (BC) is a leading cause of death among women worldwide. Despite a recent decline in BC rates due to improved detection and therapeutic options, women diagnosed with the triple negative breast cancer (TNBC) subtype have a poor prognosis relative to other BC subtypes. As TNBCs do not express the estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor-2 (HER2) that are commonly targeted in hormone positive subtypes, they have limited treatment options. While some progress has been made at unraveling the molecular mechanisms behind TNBC, there is still a large knowledge gap regarding how these tumors initiate and progress in such an aggressive manner. Increasingly, the role of microRNA deregulation has been linked to TNBC tumorigenesis. Recently, the transcription factor Kaiso was implicated in the regulation of the pleiotropically acting microRNA-31 (miR-31) and tumor-suppressing microRNA-200c (miR-200c) that promote tumor migration and invasion in prostate cancer. Notably Kaiso is highly expressed in TNBC, relative to other BC subtypes, and high Kaiso expression correlates with poor survival. Herein, we show that Kaiso expression is inversely correlated with miR-31 and miR-200c expression in the TNBC cell lines (MDA-MB-231 and Hs578T). Upon Kaiso depletion, there is an increased expression of these microRNAs and reduced expression of their downstream targets. Misexpression of miR-31 and miR-200c in parental and Kaiso-depleted TNBC cells affects their migratory ability. We also show that Kaiso associates with the promoter regions of both miR-31 and miR-200c. Collectively, these results imply that Kaiso is a regulator of miR-31 and miR-200c, which are important suppressors of epithelial mesenchymal transition (EMT) but are highly downregulated in TNBC. Our findings  reveal a novel mechanism for Kaiso in the promotion of TNBC tumorigenesis.

abstract: Thesis

abstract: Master of Science (MSc)


title: Manipulation of space and time in the tactile universe

contributor:
Goldreich, Daniel
Neuroscience

subject: Neuroscience Psychophysics Touch Tactile Illusion Rabbit Cutaneous Perception Prior Low-speed Taps Bayesian Expectation Likelihood Sensation Probabilistic Strength Time Skin Model Contraction Dilation Saltation

abstract: The study of tactile illusions like visual illusions can reveal the brain's processing strategies. A famous tactile illusion is the cutaneous rabbit illusion. Fundamental to this illusion is the perceptual length contraction phenomenon: two taps that occur in rapid succession on the forearm are perceived as occurring closer together than they were physically placed. Our lab previously proposed a Bayesian probabilistic model that views perception as a compromise between expectation (prior experience) and sensation (likelihood of sensorineural data given hypothesized tap locations). The model proposes a low-speed prior, an expectation based on experience that objects tend to be stationary or to move slowly on the skin. When the sensation of space is unclear (e.g., taps are weak), the model predicts that expectation will strongly influence perception. Consistent with this prediction, our lab previously showed that the use of weaker taps causes more pronounced perceptual length contraction. Here we report psychophysical tests on 64 participants, which confirmed this finding. Our study also used stimulus sequences consisting of a weak and a strong tap, for which the Bayesian model predicts an asymmetric perceptual length contraction, such that the weaker tap location will be perceived to shift more than the stronger tap. The experimental results confirmed this prediction, providing further support for our Bayesian probabilistic model as an explanation for perceptual length contraction. However, our results revealed a discrepancy in the data at the smaller SOAs, which showed less length contraction than predicted. We hypothesized that participants might overestimate the smaller SOAs, an effect our lab defines as time dilation. Accordingly, in a second study we investigated the effects of varying SOA and lengths on perceived SOA. The model predicts more pronounced time dilation at smaller SOAs and larger lengths. The psychophysical data from 37 participants confirmed the trends predicted by the model.

abstract: Thesis

abstract: Master of Science (MSc)


title: Truncated Stellar Discs in X-ray Rich Environments

contributor:
Parker, Laura
Physics and Astronomy

abstract: We study the dependence of galaxy disc components on environment using a sample of Sloan Digital Sky Survey Data Release 7 galaxies with structural parameters obtained via bulge-disc decompositions. We define two group environments based on X-ray richness at fixed halo mass, with an X-ray rich group sample and an X-ray poor group sample, and compare disc properties of galaxies in these environments to an isolated field population. At low bulge mass, we find evidence for galaxy stellar disc truncation in X-ray rich groups compared to both galaxies in X-ray poor groups and in the isolated field. Additionally, we show that galaxies in X-ray rich groups have smaller disc-to-total mass ratios than their isolated field counterparts. We find that our results are largely independent of group-centric position and halo mass; with the exception that disc truncation is slightly enhanced near the centres of large halos. Our findings demonstrate that galaxy stellar disc properties are sensitive to the X-ray brightness of their host group, more-so than local density parameters, suggesting that IGM-dependent hydrodynamic processes play a role in disc truncation. We suggest that ram-pressure stripping or starvation could be the mechanisms responsible for these results.

abstract: Thesis

abstract: Master of Science (MSc)


title: Template Directed Ligation of RNA Oligomers

contributor:
Higgs, Paul
Physics and Astronomy

subject:
Origins
Astrobiology
RNA World

abstract: The key to the RNA world hypothesis is the ribozyme, an information and catalytic agent that preceded proteins and DNA. Prior to ribozymes the sequences of RNA needed to build up to a length that could potentially be a ribozyme. This research focuses on computational modelling of hydrolysis, polymerization, and template-directed ligation to determine sequence patterns and characteristics that may have emerged due to these simple processes. A model containing L- and D-chirality monomers is used that incorporates the advantage of being a uniform chirality to achieve chiral symmetry breaking. Another chirality model is used where being uniform provides no advantage and a symmetry breaking still occurs. Beyond chirality we look at nucleobase models where we use a two letter alphabet containing adenine and uracil to determine symmetry breaking in sequence space. This results in self-complementary sequences dominating this model at all ligation rates but under certain initial conditions including high concentration, other types of sequences can be dominant. If a third base, guanine is added to this model a wobble base is created. In these models the self-complementary sequences containing uracil are the most prevalent due to uracil’s ability to pair with both adenine and guanine. Finally, upon adding a fourth base to the model guanine also becomes a wobble pair and the sequences containing uracil and guanine dominate the system for low ligation rates but at higher rates the uniform uracil and guanine sequences dominate. For each model a version is run with the templating reaction scaling linearly with the number of binding sites and without, where all templates are equally good. Generally, the scaling causes symmetry breakings at lower ligation values for each model.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: The origin of life on Earth is a long-debated question that has been asked by nearly every civilization to have existed. This research addresses the origin of life in the context of the RNA World theory, which proposes that the first kind of replicating molecules were RNA strands, specifically, catalytic RNA sequences, called ribozymes. We carry out computer simulations of the formation and break-up of short RNA strands. Strands can grow by joining together randomly, or due to the action of template strands. We find that, if this process occurs repeatedly, the RNA strands in the mixture move towards states in which groups of sequences that are good templates for one another occur together at high concentrations. By studying the possible states that arise in this reaction mixture, we hope to learn about the first replicating RNA strands that lead to the origin of life.


title: CADMIUM EXPOSURE ALTERS GENE EXPRESSION OF LENS, RETINA, AND EYE-RELATED GENES IN ZEBRAFISH AND HUMAN LENS EPITHELIAL CELLS

contributor:
McArthur, Andrew
Biochemistry and Biomedical Sciences

subject:
Environmental Toxicology
RNA-Seq
Cadmium

abstract:
Vision is a crucial aspect of life for humans and animals. Impaired vision can lead
to reduced quality of life along with other complications. Cataracts are a leading
cause of impaired vision and blindness worldwide. Cataracts develop as a process of
aging, although several environmental and lifestyle factors increase the risk of this
disease. The toxic metal cadmium (Cd) has been associated with cataract formation
and other ocular diseases such as macular degeneration. Cadmium exposure experiments
were conducted to investigate potential pathways or mechanisms by which
Cd may contribute to cataract formation and ocular disease. Zebra fish larvae (72,
96, and 120 hours post fertilization), adult zebra sh (6-month male, 10-month male,
and 10-month female) and the B3 human lens epithelial (HLE) cell line were acutely
exposed to varying concentrations of Cd. Transcriptomic changes relative to control
(0 μM Cd) were determined using microarray analysis for zebra sh larvae and
RNA sequencing (RNA-Seq) for adult zebra sh and HLE cells. Gene Ontology (GO)
enrichment analysis for the zebra sh larvae exposure (50 μM Cd for 4 or 8 hours)
enriched the "retina development in camera-type eye" term, and genes involved in
enrichment (dnmt1, ccna2, fen1, mcm3 and slbp) were down-regulated. Gene set
enrichment analysis (GSEA) for the 10-month male zebra sh exposure (50 μM Cd
for 4 hours) enriched the "embryonic eye morphogenesis" gene set and signi ficant
genes involved in enrichment (tcf7l1a, pitx2, fzd8a, sfrp5, lmx1bb, mfap2, six3b, lum,
phactr4b, and foxc1a) were down-regulated. GSEA for the 10-month female zebra sh
(50 μM Cd for 4 hours) enriched the "photoreceptor cell differentiation" gene set and
signi cant genes involved in enrichment (odc1, thrb, and ush2a) were up-regulated.
GO enrichment analysis for up-regulated genes in the HLE cell exposure (10 μM Cd
for 4 hours) enriched the terms "eye development" (22 genes) and "lens development
in camera-type eye" (CITED2, SKIL, CRYAB, SLC7A11, TGFB2, EPHA2, BCAR3,
WNT5B, and BMP4). These results show cadmium is capable of altering transcription
of eye-related genes in both zebra sh and human models, which may contribute
to the formation of ocular disease. Many of these genes are involved in lens and
retina development, yet they are also associated with diseases in these eye structures.
Future studies could assess the consequences of altered transcription of these genes
which could help elucidate the mechanisms of these changes and the overall effect of
cadmium exposure on ocular disease. Ultimately, our study characterized the regulation
of eye-related genes in response to Cd exposure and provided valuable knowledge
laying the foundation for identi fication of the molecular mechanisms contributing to
ocular diseases.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: The eye is a sphere-like organ which is important for visualizing your surroundings. It is composed of many different structures such as the cornea, lens and retina. Many eye diseases have been characterized by abnormalities in eye structures; for example, a cataract occurs when the lens becomes cloudy and unable to focus light while macular degeneration is defined by progressive deterioration of the retinal macula region. While these diseases can occur through the natural aging process, certain environmental factors can increase risk. Exposure to cadmium, a toxic heavy metal which causes negative effects in animals, has shown to be associated with eye disease like cataracts and macular degeneration. In order to expand on this knowledge, we exposed both zebrafish and human lens cells to cadmium. By utilizing different experimental methods such as microarray analysis and RNA sequencing, eye-related genes which were affected by cadmium were revealed. Identifying the relationship between eye diseases, cadmium and gene expression will help identify the mechanism by which cadmium contributes to eye disease formation.


title: Identification and validation of DKK1 as a novel candidate therapeutic target for glioblastoma

title: DKK1 as a novel candidate therapeutic target of glioblastoma

contributor:
Singh, Sheila
Biochemistry and Biomedical Sciences

subject: Glioblastoma, DKK1, cancer stem cells, brain tumour initiating cells, patient-derived xenograft model

abstract: Glioblastoma (GBM) is a very aggressive and invasive tumour that relapses within nine months of diagnosis and remains incurable despite advances in multimodal therapy including surgical resection, chemotherapy and radiation.  Poor patient outcome has been correlated to specific markers of brain tumour initiating cells (BTIC) and intratumoural heterogeneity (ITH), which have also been associated with treatment resistance and tumour recurrence.  ITH can be explained at the cellular level by the existence of multiple populations of cancer cells, including some which have acquired stemness properties like self-renewal, proliferation, and multilineage differentiation, also known as cancer stem cells (CSCs).  In brain tumours, CSCs or BTICs, have been shown to be resistant to both chemotherapy and radiation treatment, allowing them to escape therapy and consequently generate for tumour recurrence.  As a result, therapies that focus on targeting the BTIC compartment within the bulk GBM tumour would provide better treatment and prognosis for patients.  To profile GBM BTICs we conducted two transcriptomic screens.  The first compared GBM BTICs to neural stem cells (NSCs), their healthy counterparts, and for the second we developed a pipeline utilizing a dynamic BTIC patient-derived xenograft (PDX) model of human GBM recurrence allowing for the profiling of GBM BTICs at engraftment, after chemoradiotherapy delivery in a phase we have termed "minimal residual disease" (MRD), and at tumour recurrence.  In this study, Dickkopf-1 (DKK1) was identified as a potential therapeutic target for GBM from each transcriptomic screen and was studied using short hairpin knockdowns, blockade with monoclonal antibodies, and subsequent functional stem cell assays.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Glioblastoma (GBM) is a very aggressive tumour that relapses within nine months of diagnosis and remains incurable despite chemotherapy, radiation, and surgery.  Relapse is believed to be caused by the presence of a wide variety of cell types, including cancer stem cells (CSCs), which have been shown to be resistant to both chemotherapy and radiation in GBM.  As a result, therapies that focus on targeting the CSCs within the bulk GBM tumour would provide better treatment for patients.  In this study, we analyzed this cell population by conducting two screens.  The first compared the level at which genes are expressed in GBM CSCs in comparison to how they are expressed in their healthy counterparts, neural stem cells, whereas the second compared the primary patient GBM tumour to its relapsed form in a mouse model of the disease.  In this study, the protein Dickkopf-1 (DKK1) was identified and validated as a potential therapeutic target of GBM using well established molecular and stem cell functional assays.


title: The 21st Century Classroom: Technology as a Transformative Tool in Educational Routines, Rules, and Rituals

contributor:
Davies, Scott
Sociology

subject:
education
student engagement
digital technologies
social inequality

abstract:
This dissertation discusses a current niche in sociological literature: technology and interaction rituals in elementary schools. In particular, it examines the relationship between classroom interactions and the increasing available new forms of technologies (i.e. iPads, robotics kits, Smart boards) that are finding their way into schools. In doing so, I consider what new interactions and digital tools might mean for student engagement in what has now become known as the “21st century classroom”. Two pivotal sociological theories are utilized in this project: 1) Collins (2004) interaction ritual (IR) theory and 2) Bourdieu’s (1974; 1986) concept of cultural capital. Both are valuable in understanding how the introduction of digital tools in mainstream schools can influence or change interactions between and among students and teachers in classrooms, how they may impact student engagement gaps. Traditionally speaking, schools have long valued and rewarded certain types of interactions—student obedience alongside teacher authority, an orderly and compliant classroom, emphasis on more traditional teaching and so forth. Student engagement was not necessarily a point of interest, as was having a systematic classroom. However, perhaps technology is beginning to change those valuations, and create new types of classroom interactions that are unique to the 21st century—classrooms that have a more student-centered pedagogy, whereby teachers work in tandem with students to engross them in the learning process, and where student engagement is more much valued. If this is true, this may be a sign of some new emerging types of IRs that are beginning to surface in the presence of technology.
	Collins' (2004) theory of IR focuses on the emotional input and feedback of individuals that transpire in interactions among actors, which in the case of classrooms, consist of teachers and students. The theory holds that interactions produce or deplete “emotional energy” of participants depending on many key factors (physical co-presence, exclusivity of group, mutual focus/mood, bodily synchronization). A successful ritual is one in which participants have a mutual focus on a particular “symbol” or “emblem” unique to that group. Through this research, I propose that technology can serve as that “emblem” to group membership, and as a result, can facilitate new kinds of IR. “Cultural capital”, in comparison, is usually considered to be a collection of symbolic elements such as skills, tastes, clothing, materials, credentials and so on that one acquires by being a member of a particular social class.  In education, cultural capital can refer to having valued sets of skills and knowledge that are aligned with school rewards. Traditionally, this usually meant a middle-upper class advantage in schooling, as students of more affluent families were able to learn valued kinds of skill sets to help them achieve better in school. However, with the advent of new technologies, I question whether notions of cultural capital have changed as a result, and whether possessing a digital skillset is in and of itself, a new type of valued capital. Can new technologies produce more equalizing experiences for students of varying SES backgrounds?
To explore the possibility of digital tools in classrooms creating new sets of rituals with new kinds of valued cultural capital, this study adopts a qualitative methodology, consisting of elementary classroom observations, interviews, and focus groups with teachers and students in ten school boards across Ontario, Canada. My research discusses three integrated themes. I begin by asking first, how have technologies transformed the ways in which students and teachers interact with, and amongst each other? By providing a new medium for both teacher pedagogy and student learning, this has major implications for classroom engagement. Secondly, I explore the possibility that one unintended consequence of using digital resources (compared to more traditional print media), has been a reduction in home-based inequalities, and a more “even playing field” for students of varying SES. With the ease, accessibility, and affordability of technology today, students in vary capacities are exposed to new valued skillsets. Lastly, I consider how technology can be a type of “leveler” for different kinds of students, which can allow them to participate and facilitate new types of ritual inclusions. I focus both on gendered interactions and exchanges between students with special needs as examples. The exploration of these three themes guides my research on the use of educational technologies across classrooms. These have important implications for sociologists, educational researchers, and policy-makers alike.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)


contributor:
Milliken, Bruce
Psychology

subject: Psychology Memory Attention Learning Repetition Spacing

abstract:
DOCTOR OF PHILOSOPHY (2018) McMaster University (Psychology)
TITLE: The Repetition Decrement Effect: A Direct Measure of Encoding Costs Attributable to Prior Experience
AUTHOR: Robert Nathan Collins, B.Sc. (hons.) (Memorial University of Newfoundland), Master of Applied Social Psychology (Memorial University of Newfoundland)
SUPERVISOR: Professor Bruce Milliken
NUMBER OF PAGES: xviii, 195

abstract: The brain is the single most expensive organ in the human body (Berg, Tymoczko, & Stryer, 2002).  Given that energy is scarce, evolutionary pressures ought to promote the development of cognitive systems that efficiently attend to and learn our environment (Christie & Schrater, 2015).  One way of achieving efficiency involves reducing the amount of resources we devote to information that is already well-learned.  Although the idea that attention is biased against redundancy is well supported (Posner & Cohen, 1984; Tipper, 1985), evidence for a similar bias in learning and memory is less clear.  The classic spacing effect (Ebbinghaus, 1885) does imply that immediate repetitions triggers ‘deficient processing’ and poor memory relative to spaced repetitions (Hintzman, 1976).   However, the link between the spacing effect and deficient processing relies on indirect inference.  In this thesis, I propose that the repetition decrement effect (Rosner, López-Benítez, D’Angelo, Thomson, & Milliken, 2018) is a direct measure of deficient processing.  The repetition decrement effect is a recognition memory deficit for words presented twice at study relative to words presented only once.  In this thesis, this effect occurred when: (1) the first presentation of two identical words was poorly processed, and (2) the second presentation of two identical words followed immediately after the first.  When repetitions were spaced, repetition always improved recognition.  The interaction between repetition and spacing provides evidence that the repetition decrement effect is driven by the same ‘deficient processing’ mechanism that underlies the spacing effect.  An instance model of memory (based on Minerva-AL; Jamieson, Crump, and Hannah, 2012) that mathematically formalises this deficient processing mechanism successfully predicted both the repetition decrement and spacing effects.  The repetition decrement effect represents the strongest evidence to date that, like attention, learning mechanisms are mediated by an adaptive system that biases against the processing of redundant information.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: The brain is the single most energy demanding organ in the human body.  Consequently, evolution ought to have produce adaptations that minimise redundant brain activity.  One way to minimise redundant brain activity is to avoid re-learning what has already been learned.  Counter-intuitively, this idea implies that we learn more when we know less and learn less when we know more.  The present thesis focuses on a phenomenon I call the repetition decrement effect – poor memory for a word studied twice relative to a word studied once.  This effect occurred when: (1) the first presentation of the word was ignored, and (2) the repetition of the word was immediate.  These characteristics link the repetition decrement effect to the classic spacing effect and support the theory that our brain attempts to minimise energy expenditure related to the learning of redundant information.


title: ENVIRONMENTAL FACTORS REGULATE DEVELOPMENTAL RATE IN  C. ELEGANS

title: INVESTIGATING THE IMPACT OF BACTERIAL DIET ON DEVELOPMENTAL RATE IN THE MODEL ORGANISM CAENORHABDITIS ELEGANS

contributor:
MacNeil, Lesley
Biochemistry

subject:
C. elegans
amino acids
TOR
developmental rate
bacteria

abstract: Environmental factors, such as diet, can have a significant impact on the health of animals, influencing lifespan, development, and disease progression. The model organism Caenorhabditis elegans is a bacterivore whose development is characterized by an invariant pattern of cell division. This study investigated how C. elegans developmental rate is altered in response to 48 different bacterial diets. The bacterial species studied had a wide range of effects on developmental progression, with some bacteria dramatically decreasing developmental rate, while others caused developmental arrest in early larval stages. From these analyses, Staphylococcus species that caused very slow development of animals in the L1 stage were selected for further characterization. The slow developmental rate observed in these animals was rescued by supplementation with essential amino acids. Genetic analysis revealed that these effects were mediated through TOR signaling and were independent of insulin signaling. Loss of daf-15(raptor), a central component of TOR complex 1, inhibited the rescuing effects of the amino acid supplementation on developmental rate, suggesting that the slow development induced by Staphylococcus could be rescued by activating the TORC1 pathway. Autophagy, negatively regulated by TOR, is increased in worms fed Staphylococcus species, suggesting TOR activity is reduced, and supplementation through amino acids reduced autophagy. These data suggest that TOR signaling is reduced in C. elegans in response to certain bacterial diets, resulting in decreased developmental rate, and that this effect may be due to amino acid deficiency.

abstract: Thesis

abstract: Master of Science (MSc)


title: FLUOXETINE: EXAMINING THE SELECTIVE SEROTONIN RE-UPTAKE INHIBITOR’S EFFECTS ON SEROTONIN AND HEDGEHOG SIGNALING IN THE PANCREATIC BETA CELL

contributor:
Holloway, Alison
Medical Sciences

subject: Fluoxetine, Beta Cell, Pancreas, INS-1, Hedgehog Signaling, Serotonin, Insulin, Type 2 Diabetes, Depression

abstract: Major depressive disorder (MDD) is one of the most common psychiatric illnesses worldwide, with pharmacotherapy as a first-line option for the management of this illness. The National Center for Health Statistics found that the use of antidepressants has increased by more than 4 fold in the last 20 years. While SSRI’s act centrally to treat MDD, their peripheral effects are often overlooked. Interestingly, components of the serotonergic system including the serotonin transporter (SERT), serotonin receptors, and enzymes important for serotonin synthesis (tryptophan hydroxylase 1 and 2; Tph1 and Tph2) are affected by SSRI treatment both centrally and peripherally. This disruption of serotonin signaling in the pancreas is of particular interest as there is a considerable link between the serotonin and hedgehog signaling pathways, both of which are important for pancreatic beta cell function. I hypothesize that pancreatic beta cell exposure to the SSRI fluoxetine in vitro will lead to altered hedgehog signaling ultimately resulting in a disruption in insulin secretion.

abstract: Thesis

abstract: Master of Science in Medical Sciences (MSMS)


title: The Concept of Ownership in Rust and Swift

contributor:
Sekerinski, Emil
Franek, Frantisek
Computing and Software

subject:
Memory Management
Ownership
Programming Languages
Rust
Swift
C
C++
Java
Memory Safety
Cognitive Programming Skills

abstract: There is a great number of programming languages and they follow various paradigms such as imperative, functional, or logic programming among the major ones and various methodologies such as structured approach or object-oriented or object-centered approach. A memory management design of a programming language is one of the most important features to help facilitate reliable design. There are two wide-spread approaches in memory management: manual memory management and automatic memory management, known as Garbage Collection (GC for short). Recently, a third approach to memory management called Ownership has emerged. Ownership management is adapted in two recent languages Rust and Swift. Rust follows a deterministic syntax-driven memory management depending on static ownership rules implemented and enforced by the rustc compiler. Though the Rust approach eliminates to a high degree memory problems such as memory leak, dangling pointer and use after free, it has a steep learning costs. Swift also implements ownership concept in Automatic Reference Counting ARC. Though the ownership concept is adapted in Swift, it is not a memory safe language because of possibility of strong reference cycles. In this research, a demonstration of the ownership in Rust and Swift will be discussed and illustrated, followed by analysis of the consequences of memory issues related to each design. The comparison of Rust and Swift is based on ownership, memory safety, usability and programming paradigm in each language. As an illustration, an experiment to compare the elapsed times of two different structures and their algorithms, Binary Tree and Array are presented. The results illustrate and compare the performances of the same programs written in Rust, Swift, C, C++, and Java.

abstract: Thesis

abstract: Master of Science (MSc)


title: Hemispherical Dish Microconcentrators for Light-Trapping in Silicon Solar Cells

contributor:
KLEIMAN, RAFAEL
Engineering Physics

subject:
SOLAR CELL
SILICON
SOLAR ENERGY
PHOTOVOLTAICS
LIGHT TRAPPING
MICROCONCENTRATOR
HEMISPHERICAL
CONCENTRATOR

abstract:
To improve the performance of solar energy converters and its implementation as a more sustainable electricity source worldwide, researchers have been trying to increase the efficiency of photovoltaic devices while lowering their costs. Conversion efficiency of solar cells can be enhanced through light trapping structures and concentration of incoming light. Light trapping is usually realized by texturization of the solar cell’s surfaces, while concentration is achieved by addition of external apparatus, such as reflectors.
A novel design for silicon solar cells is proposed in this thesis, which contains hemispherical dish microconcentrators for light trapping purposes. Through a process flow that includes maskless photolithography, thermal reflow, and metallization via sputtering, the microconcentrators were fabricated and demonstrated to have good concentration properties. Further studies need to be done for optimization of the hemispherical structures, as well as successfully perform the proposed upconverting photolithography for auto-aligned exposure of the photoresist at the microconcentrator’s focus, thus allowing a complete solar cell to be created based on this design.

abstract: Thesis

abstract: Master of Applied Science (MASc)


title: THE ROLE OF ION-MOTIVE ATPASES IN THE INSECT GUT

contributor:
O'Donnell, Michael
Biology

subject:
Insect
Physiology
V-ATPase
Na+/K+ ATPase
ion-transport

abstract: The present set of studies examines the roles of two ion-motive enzymes, vacuolar-type H+-ATPase (VA) and Na+/K+ ATPase (NKA), in energizing transepithelial ion transport across the larval caecum and midgut epithelia of Drosophila melanogaster and Aedes aegypti. Even though both VA and NKA are expressed in insect epithelia, VA was considered the more important enzyme until the early 2000 because the ion transport was unaffected by the NKA inhibitor ouabain in many insect epithelia, a phenomenon termed the ‘ouabain paradox’. This paradox was resolved by the discovery of an organic anion transporter (OATP) that is colocalized with NKA and prevents the actions of ouabain on NKA. Since the resolution of the ouabain paradox, this is the first set of studies that investigates the role of NKA in energizing ion transport across the caeca and midgut of insects. First, I show that both VA and NKA are expressed in the caecum and the midgut. Moreover, the ATPase enzyme activities of VA and NKA are quantitatively similar within each region of the gut that was studied, suggesting that both ATPases may be important for establishing favourable electrochemical gradients for transport of ions across the gut. I used ATPase inhibitors to demonstrate that cation transport is dependent on the actions of both VA and NKA. Furthermore, this is the first set of studies that provides an insight into the ion transport mechanisms of the gastric caecum, an organ that is understudied in insects. In Aedes aegypti, I show that 5-hydroxytryptamine regulates the VA-rich cells of the gastric caecum, and therefore the rates of ion transport of these cells. Additionally, I also show that rearing salinity conditions for Aedes aegypti larvae alters the expression patterns of VA and NKA in the gastric caecum. In freshwater, increased activity of VA and NKA energizes transport of ions into the lumen of the caecum that likely maintains fluid volumes and ionic composition at levels appropriate for digestion and absorption. Overall, these studies provide novel information for caeca and midgut-specific actions of VA and NKA in insects, and present a number of new avenues for future research.

abstract: Thesis

abstract: Doctor of Philosophy (PhD)

abstract: This thesis focuses on investigating the roles of two enzymes, vacuolar-type H+-ATPase (VA) and Na+/K+ ATPase (NKA), which utilize energy to transport electrically charged atoms (ions) across the cells of the insect gut. Although VA was considered the more important of the two enzymes until the early 2000s, I have demonstrated that NKA also plays a role in maintaining insect gut function in fruit flies and mosquito larvae. Furthermore, the activities of both enzymes are dependent on the salinity of the medium in which mosquito larvae are reared, suggesting that they play a role in maintaining the ionic composition of the gut fluids in freshwater larvae. Additionally, I have also demonstrated that a neurochemical, serotonin, can modulate the activity of gut cells in mosquito larvae. Overall, this thesis provides novel information on the actions of VA and NKA in the insect gut, and presents a number of new avenues for future research.


title: “We Can't Help You Here”: Exploring the Experiences of Youth with Undiagnosed Mental Health Concerns who are Streamed into Alternative Education

contributor:
Joseph, Ameil
Social Work

subject:
mental health
alternative education
peer support
mad studies
critical disability studies
arts-informed process
youth

abstract: Relying on the perspectives of critical disability studies and mad studies, this graduate thesis seeks to uncover the experiences of youth with undiagnosed mental health issues who have been streamed into alternative education. Guided by methodological principles of interpretive phenomenological analysis and arts-informed inquiry, the 5 participants in this study were invited to a focus group where they could engage in an arts-based activity, meant to provide the opportunity to reflect on their experience, build rapport with the researcher, express themselves through alternative means, and connect with peers who have shared experience. Participants were then invited to discuss their experiences with the topic in a one-on-one, semi-structured interview. This study reveals the ways in which the system of education, school communities, teachers, and social workers can support youth who are not diagnosed with a mental illness but still experience mental health challenges that impede on their school experience. Supported by mad studies, this study reveals how peer support has become the method of mental health response and treatment through which students feel is most effective. This study also challenges medical hegemony and the ways in which access to services is dependent on medical diagnoses. Finally, this study reminds stakeholders of the value of building trusting and empathic relationships between school staff and students. School communities and school boards are challenged to think about the structuring of their systems, and the ways in which they may present barriers to the success of all students regardless of ability and/or need.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: Diffusion Modelling of Picosecond Laser Pulse Propagation in Turbid Media

title: Diffusion Modelling of Light Propagation in Turbid Media

contributor:
Patterson, M. S.
Engineering Physics

subject:
diffusion model
picosecond laser pulse
turbid media

abstract:
The increasing use of visible and near infrared light in therapeutic and diagnostic techniques has created a need to model its propagation in tissue. One of the fundamental objectives of such a model is the noninvasive evaluation of the optical properties of tissue. The focus of this thesis was the development of the diffusion approximation in the semi-infinite, slab, cylindrical and spherical geometries. This development required the derivation of approximate boundary conditions which included the zero, extrapolated and partial current boundary conditions. Calculations of the fluence and its related quantities arising from the extrapolated boundary condition were found to be in excellent agreement with the results of the more rigorous partial current boundary condition.
A preliminary evaluation of the validity of diffusion theory was performed by comparing its predictions to exact analytical calculations of the fluence in an infinite medium as well as Monte Carlo simulations of the reflectance and transmittance in 1-dimensional planar geometries. In all cases the agreement at late times was excellent. A practical test of the diffusion model was accomplished with the analysis of the reflectance data from a phantom of known optical properties in both the semi-infinite and slab geometries. The model performed well at low concentrations of added absorber, but a considerable discrepancy was found at the highest concentration. A systematic examination of the accuracy of the diffusion model as a function of the fundamental parameters is required to resolve this inconsistency. Approximate expressions describing the equivalent information in the frequency domain were also developed for a semi-infinite medium. These expressions were then used to analyze the phase and modulation obtained from phantoms of known optical properties. Once again reasonable results were obtained at low concentrations of added absorber while a significant discrepancy arose at the highest concentration. The resolution of these discrepancies requires further investigation.

abstract: Thesis

abstract: Master of Engineering (ME)


title: Leadership and Resistance

contributor:
Sinding, Christina
Social Work

subject: Leadership Resistance

abstract:
Identity and resistance in social work leadership is a fairly recent area in the study of leadership. A significant amount of the literature discusses leadership, identity and resistance from the standpoint of managerialism, where the leader’s character is defined by their response to managing and eliminating staff workplace resistance. This study offers a contrasting approach to the managerial notions of leadership, identity and resistance. This study examines social work leadership in the context of the justice-oriented resistance work leaders do and how their identities inform the strategies they engage.  A small qualitative study was done from a critical perspective to better understand how social work leaders in the social services engage in resistance work when encountering social injustices in their organization.
The findings were organized around three central themes form the interviews. The first theme was how the participants understood resistance or what were they fighting for in their work. Participants were fighting for respectful relationships with service users, and fighting against the implications of social inequalities embedded in policies and directives that are not beneficial to service users. The second theme focused on the strategies the participants engaged in their resistance work. Participants identified the deliberate use of language, awareness and activation of values, and the use of their power and role as leaders. The third theme was how their identities influenced the resistance work they engaged in. The participants drew on their personal histories which have framed their identities to inform the manner in which they resist: to take up certain value positions in their work, to be critical and unafraid in their resistance, and to have strong loyalties to their communities. The results of this study extend the literature on leadership by highlighting resistance not in a passive manner but in the sense of consciously taking actions with consequences. It was apparent the participants engaged in micro political actions and adopted strategies to counter the negative effects of policies and attitudes that promote social inequalities.

abstract: Thesis

abstract: Master of Social Work (MSW)


title: EEG assessment of disordered consciousness: a framework and a case study

contributor:
Connolly, John
Neuroscience

subject:
neuroscience
electroencephalography
ERP
disorders of consciousness
coma
EEG

abstract: Assessing cognitive abilities in disorders of consciousness (DOC) relies on assessments of overt behaviour, such as the ability to follow commands. Neuroimaging has shown that absence of overt behavior does not necessarily indicate absence of covert cognition, raising questions about behaviour-only assessment. Several electroencephalographic (EEG) markers of higher cognitive functions (event-related potentials; ERPs) have shown the potential to differentiate between DOC states, as well as predict awakening and condition upon emergence. However, no one ERP has emerged with sensitivity and specificity high enough to be widely accepted, showing that further investigation is needed. More recently, evidence has emerged for fluctuations of ERP detectability in DOC over the course of several hours, and for prognostic power of changes in ERP presentation between testing sessions. This investigation builds on such findings towards improving evaluation of cognition in DOC. A testing battery combining several well-known auditory ERPs was administered to a comatose patient over a 24-hour period during two recording sessions one week apart, as well as to a sample of healthy young adults. The patient scored 3 and 6 on the Glasgow Coma Scale (GCS) during the first and second session, respectively. The results show that changes in GCS score were accompanied by changes in ERP detectability. The results also suggest detectability fluctuations over the course of 24 hours, which in turn suggests that repeated testing is necessary for complete evaluation. Future work should validate these findings with a larger sample; additionally, establishing population norms for single-subject prevalence, latency, and amplitude of ERPs would improve confidence in interpreting patient results. With the current understanding of both healthy and DOC ERPs, detecting ERP presence may contribute to a positive DOC prognosis with a degree of confidence, but caution must be exercised in making negative prognoses or high-stakes care decisions based on ERP absence.

abstract: Thesis

abstract: Master of Science (MSc)

abstract: Assessing cognitive abilities in disorders of consciousness such as coma currently relies on assessments of overt behaviour, such as the ability to follow commands or react to a stimulus. Neuroimaging has shown that absence of overt behavior does not necessarily indicate absence of covert cognition, raising questions about behaviour-only assessment. This study describes a neuroimaging testing battery aimed at evaluating a hierarchy of cognitive functions without the need for a behavioural response by measuring brain activity driven by auditory stimulation. This battery was administered to a comatose patient over a 24-hour period during two recording sessions one week apart, as well as to a sample of healthy young adults. The results show that changes in the patient’s condition between testing sessions was accompanied by detectable and quantifiable change in their stimulus-driven brain activity. The results also suggest fluctuations in the patient’s ability to produce detectable responses over the course of 24 hours, which in turn suggests that repeated testing is necessary for a complete evaluation. Overall, neuroimaging provides a promising avenue for non-behavioral assessment of cognition, which will greatly benefit a population whose physical faculties may be compromised.