VictorJuiz/thesis huggingface dataset:
Non-structural Deterrents and Opportunistic Dispersal in an Invasive Fish: The Role of Among-Individual Variation on Common Carp Movement

Dispersal decisions are often made at the level of the individual, but among-individual variation in dispersal behaviour is rarely considered in aquatic conservation and invasion control. To address this challenge, my thesis applied concepts of behavioural ecology to invasion biology. Using an invasive fish, Common Carp (Cyprinus carpio), as my study species, I examined the influence of among-individual behavioural variation on opportunistic dispersal and on the effectiveness of non-structural deterrents - methods used to limit the movement of non-native fishes. My thesis is comprised of a brief literature review and four research chapters that incorporate lab and field techniques to describe movement behaviours. My first research chapter (chapter 2) used choice-arena experiments to determine whether Common Carp express consistent individual differences in their avoidance behaviour of non-structural deterrents. I found CO2 levels required to force movement towards acoustic and stroboscopic stimuli varied across individuals. In chapter 3, these same deterrents were deployed at an outdoor fishway with more realistic field conditions. Native and non-native fish passage across the fishway was quantified to determine whether a behavioural deterrent (sound) can produce an avoidance response sufficient for conservation applications. This is the first study to find a phylogenetic signal in fish responses to a non-structural deterrent. In chapter 4, individuals captured at the fishway were measured for morphology,subjected to laboratory behavioural trials and then released to be acoustically tracked. Significant flooding provided individuals with a rare dispersal opportunity into a wetland. I found dispersal success was correlated with behaviour in the field, but not a behavioural syndrome expressed in lab tests. Finally, in chapter 5, I investigated whether Common Carp would consistently avoid a physiological deterrent (CO2) at the fishway. I observed a 10-fold decrease in Common Carp catch rates during stimulus activation and, unlike in chapter 3, there was no phylogenetic signal in avoidance responses. This research contributes to our understanding of how animals make dispersal decisions and the role of behavioural variation on biological invasions, and uses behavioural ecology techniques to advance applied aquatic conservation.

Keywords: Acoustic
Barrier
Behavioural Ecology
Biological Invasion
Common Carp
Conservation
Advisor: Mandrak, Nicholas E.
Evaluation of a Choosing Wisely Canada Initiative to Reduce Unnecessary Testing in the Emergency Department

Up to 30% of healthcare services in Canada are unnecessary and finding ways to reduce such care is critical for upholding quality of care and patient safety. This research consists of three overlapping studies investigating ways to reduce unnecessary care and the impacts of those interventions. Specifically, this research begins with a literature search to determine what is already known about interventions to reduce unnecessary care, using the example of pediatric imaging in the emergency department (ED). Building on these learnings, we evaluated the emergency department of hospital that was an early adopter of Choosing Wisely Canada (CWC)—a campaign to reduce unnecessary tests, treatments, and procedures. Specifically, the ED made changes and mandated adherence to medical directives. After analyzing their laboratory data using an interrupted time series analysis, we found significant reductions across most of the observed tests. We followed this quantitative study with semi-structured interviews from hospital leadership and ED clinicians to identify what was particularly impactful about the CWC intervention. We conclude by discussing what other healthcare organizations can learn from our research and how they can adapt our findings to suit their needs. We also discuss the challenges and benefits to using real hospital data extracted from the electronic medical record. Overall, reducing unnecessary care has become a priority for many healthcare organizations and our learnings could support these institutions in their endeavors to combat such services.

Keywords: Health Informatics
resource stewardship
Advisor: Levinson, Wendy
Synthesis and Modification of Metal-encoded Microbeads for Applications in Mass Cytometry

Mass cytometry (MC) is an emerging bioanalytical technique analyzing the signals of isotopic labels on cell and microbead samples with high-order multiplexing and high-throughput potential. Microbeads for MC applications have to be encoded with heavy metals and surface-functionalized for bioconjugation. Several approaches of metal encoding polymeric microbeads have been reported by former members of our group. The most effective approach was the multistage dispersion polymerization of styrene in the presence of polyvinylpyrrolidone (PVP) with lanthanide salts and acrylic acid. However, these reactions did not allow control over metal content. I used this trial-and-error approach to synthesize 7-element encoded microbeads as effective reference beads for MC applications. For bead-based assays, I developed new chemistry involving polymerizable derivatives of diethylenetriamine pentaacetic acid (DTPA), a chelator that forms thermodynamically stable complexes with all trivalent lanthanide ions. By introducing these complexes into the two-stage dispersion polymerization reaction, I could synthesize 2–3 um diameter metal-encoded polystyrene microbeads with over 100-fold variation in metal content.Then I turned my attention to surface modification to enable attachment of bioaffinity agents to the bead surface. Previous attempts in our group had led to only low levels of antibody attachment. In my most successful approach, I was able to use the PVP on the microbead surface to facilitate coating the microbeads with a thin silica shell. I investigated this chemistry in detail, which required the delicate synthesis of microbeads of similar size using PVP samples of different molecular weight. The molecular weight of PVP had a profound effect on the thickness and roughness of the silica shell, and this in turn affected the number of NeutrAvidin molecules that could be attached to the surface. These microbeads were able to bind biotinylated goat-anti-mouse antibodies, that in turn were effective at selective binding to mouse antibodies. As a demonstration of bead-based assays in MC, I designed and synthesize a panel of 11 metal-encoded microbeads as classifier beads. The surface of these microbeads was modified with antibodies to capture target cytokines. Proof-of-concept experiments were carried out to explore assay conditions for multiplex bead-based immunoassays of cytokines using MC.

Advisor: Winnik, Mitchell A
Exploring the Associations of Parenting by Lying with Psychosocial Adjustment, Dishonesty, and Culture

Parents aim to instill the value of honesty in their children from a young age (Engels et al., 2006). However, parents often use lying as a means of influencing their child’s behavioural and emotional states – a practice which has been referred to as ‘parenting by lying’ (Heyman et al., 2009). To date, limited research has explored the practice of parenting by lying and its associations with lying and psychosocial functioning in children. Thus, the goal of my dissertation is to broaden the existing research on parenting by lying by exploring the associations of this practice with the development of lying and psychosocial functioning in childhood and adulthood. I achieve this through conducting three novel studies that uniquely and significantly contribute to the current understanding of parenting by lying. More specifically, in Chapter 2, I explored the long-term associations of parenting by lying in childhood with lying and psychosocial functioning in a sample of Turkish adults. I found that adults who recalled higher levels of parenting by lying in childhood lied to their parents more and experienced greater psychosocial adjustment difficulties in adulthood, in particular secondary psychopathic traits. In Chapter 3, I discovered novel categories of parenting by lying, as well as identified predictors of parenting by lying within a sample of Singaporean parents. In addition to discovering two new parental lie categories, I found that parents who reported greater religiosity lied less to their children. Lastly, in Chapter 4, I investigated the association of parenting by lying with lying and the expression of psychosocial difficulties in childhood. I found that parents who reported using more parenting by lying strategies had children who lied more, and that children who lied more experienced greater psychosocial adjustment difficulties. Overall, the collective results of my dissertation suggest that the practice of parenting by lying may have short- and long-term negative associations with the development of honesty and psychosocial adjustment. These results can be used to inform parents/caregivers, teachers, and clinicians on the importance of effectively communicating with children in order to promote optimal development.

Keywords: development
lying
parenting by lying
psychosocial functioning
Advisor: Lee, Kang
Determinants of Immunity against the Meningococcus

Neisseria meningitidis is a major cause of sepsis and meningitis worldwide, but is also a regular colonizer of the human nasopharynx. Invasive meningococcal infections are associated with high rates of morbidity and mortality, despite the availability of effective antibiotic treatment options. Vaccination is therefor the most effective way to protect people against N. meningitidis. Vaccines have been developed to target this bacterial pathogen since the early 1900’s, with varying levels of success. A successful meningococcal vaccine must be capable of preventing invasive N. meningitidis infections, to thereby protect the vaccinated individual from succumbing to infection. An ideal meningococcal vaccine should also prevent nasal colonization, thereby limiting the spread N. meningitidis and thus eliciting herd immunity within a vaccinated population. Within this thesis, I aimed characterize vaccine elicited immune processes necessary for protection against meningococcal nasal colonization and invasive sepsis. To characterize vaccine elicited protection against nasal colonization I took advantage of a “humanized” mouse model of N. meningitidis nasal infection, wherein expression of human CEACAM1 allows N. meningitidis to colonize the murine nose. I reveal that protection against nasal colonization is absolutely reliant on B cells and neutrophils, suggesting that opsonophagocytosis plays a major role in prevention of nasal colonization. To characterize vaccine elicited protection against invasive infections I utilized a mouse model of N. meningitidis sepsis. Previous findings haveiii revealed an important role for meningococcal specific IgG and complement activation in conferring protection against invasive infections. Here, I reveal that protection can occur in mice lacking either complement or IgG. Protection in the absence of complement relies on high antibody titer and my data suggests that phagocytic cells are necessary to clear the bacterial infection. Protection in the absence of IgG is reliant on bacterial specific IgM. Taken together, my findings provide novel insight into the mechanism of vaccine elicited protection against N. meningitidis. This mechanistic insight can be used to guide development of improved vaccines.

Keywords: complement
herd immunity
Neisseria meningitidis
neutrophils
vaccine
Advisor: Gray-Owen, Scott D
Understanding Patterns and Estimating Relative Effects of Long-term Bisphosphonate Therapy and Drug Holidays

Osteoporosis is a disease of low bone mass that causes debilitating fractures. Oral bisphosphonates (alendronate, risedronate, and etidronate) are first-line therapy for osteoporosis. Guidelines recommend at least three to five years of initial bisphosphonate therapy. Thereafter, most patients can undergo a bisphosphonate drug holiday for up to 3 years, as bisphosphonates have extended half-lives and continue to provide fracture protection after therapy discontinuation. However, the relative anti-fracture benefit of different bisphosphonates during drug holidays is uncertain. Risedronate has a shorter half-life in bone than alendronate, and thus fracture protection during risedronate drug holidays may be shorter. This research aimed to provide evidence on long-term oral bisphosphonate therapy and drug holidays using a series of population-based studies. First, Study 1 described time trends in oral bisphosphonate initiation and characteristics of older adults starting therapy in Ontario, Canada over 20 years. Then, Study 2 identified patterns of long-term oral bisphosphonate exposure (≥3 years with ≥80% adherence) using a cohort study design. Lastly, Study 3 examined the comparative anti-fracture benefits of risedronate versus alendronate therapy during drug holidays. Study 1 showed that alendronate and risedronate have largely replaced etidronate and found important changes in patient characteristics over time. Study 2 identified that 60% of patients initiating alendronate or risedronate had a period of long-term exposure. Finally, long-term therapy with risedronate was associated with a modestly increased hip fracture risk compared to alendronate during drug holidays longer than 2 years (HR=1.18 [95% CI 1.04 to 1.34]) in Study 3. The findings from this thesis highlight oral bisphosphonates as a mainstay of osteoporosis therapy, demonstrate that most patients starting oral bisphosphonates have long-term use, and suggest that drug holidays after risedronate therapy should be limited to 2 years. Further research is required to examine the comparative benefits and harms of long-term oral bisphosphonate therapy versus other osteoporosis treatments.

Keywords: BISPHOSPHONATES
DRUG THERAPY
EPIDEMIOLOGY
HEALTHCARE ADMINISTRATIVE DATA
OSTEOPOROSIS
PHARMACOEPIDEMIOLOGY
Advisor: Cadarette, Suzanne M
Platonis Imitator: Cicero’s Reception of Platonic Philosophy

This dissertation explores Cicero’s reception of Plato in his late period philosophical works. I argue that Cicero modernizes Platonic philosophy in order to engage with contemporary Hellenistic philosophical debates. Cicero uses a variety of interpretative strategies (translation, historicization, exegesis) to demonstrate that Plato’s doctrines are live options alongside the dominant theories of Hellenistic philosophy. This modernizing approach is consistent with, and an expression of, Cicero’s Academic skepticism: Cicero is not a Platonist; rather he uses Plato dialectically to counter and oppose rival philosophical positions, and ultimately treats Platonic philosophy as an integral part of the Academic’s inquiry after the truth. The first two chapters establish the intellectual context for Cicero’s undertaking by rethinking Cicero’s relationship with his Academic teacher, Antiochus of Ascalon. In Chapter I, I re-evaluate Antiochus’ idiosyncratic view on the history of the Platonic Academy and show that Antiochus’ project is also one of modernization. This provides the relevant background for Chapter II, in which I argue against the view that Cicero takes an ‘Antiochian’ approach to Plato. I establish, through an examination of a debate about the nature of virtue and happiness, that Cicero often employs rival interpretations of Platonic philosophy to challenge Antiochus’ account of the Academy. Chapter III looks at Cicero’s treatments of the Platonic forms. Cicero’s arguments in favor of forms directly counters the Stoic and Antiochian rejections of the forms. While there is no single “theory of forms” in Cicero’s works, there is a family resemblance among his various discussions, each tailored to different argumentative and epistemological contexts. Chapter IV offers an extended examination of the arguments for the immortality of the soul in the first book of the Tusculan Disputations. Here we find Cicero at his most virtuosic as an exegete of Plato, synthesizing elements from a range of Platonic dialogues into a novel Academic defense of immortality. This dissertation, then, shows Cicero to be an independent, creative, and innovative interpreter of Plato. In turn, we gain a better appreciation of both Cicero’s overall philosophical project in his late period works, as well as the central significance of Plato in late Hellenistic philosophy.

Keywords: Cicero
Plato
Scepticism
Skepticism
Advisor: Allen, James
Designing Stimuli-Responsive Amino Acid and Peptide Hydrogel Biomaterials as Functional Entrapment Matrices

Supramolecular gels are a fascinating class of soft materials that have attracted significant attention in recent years. Chemical polymer gels have received the most attention but are often limited by their lack of degradability and issues associated with biocompatibility. Physical supramolecular gels are composed of small molecule gelators that assemble into supramolecular network structures; the resulting space is filled with solvent. Peptide-based gels are advantageous as they are composed by small amino acid components and possess reversible supramolecular assemblies through non-covalent interactions in response to various stimuli. The stimuli- responsive properties of these hydrogels allow the design of materials that can be tailored for the purpose of a specific property and function of the gel material depending on the application. Stimuli-responsive peptides that alter properties as a function of pH, redox, temperature, and enzymes offer the potential to create materials with tunable characteristics. Peptide-based gel materials are also particularly attractive in many biomedical applications as they are biocompatible and biodegradable, and they encapsulate solvent similar to that of soft tissues and the extracellular matrix of cells. In this thesis, the stimuli-responsive properties (pH, redox, temperature, and solvent), as well as the biocompatible nature of the peptide gels are highlighted. Dipeptides, peptides bonded to metal scaffolds, peptide amphiphiles, and amino acid amphiphiles are all synthesized and explored for gelation, and fully characterized in terms of their supramolecular behaviour, morphological, and mechanical properties. We explore the properties of gels that are heat sensitive, respond to redox agents, and only gel in a very narrow pH range. The gel compounds are then explored as functional entrapment matrices for catalytic enzymes, as a biomimetic matrix for tissue regeneration, and as an entrapment matrix for drugs in delivery applications. The work in this thesis highlights the usability of these gels as a base matrix and their ability to incorporate and entrap various biomolecules which holds great future promise for the development of biomaterials for many biomedical applications.

Keywords: Amino acids
Biomaterials
Hydrogels
Peptides
Supramolecular Chemistry
Advisor: Kraatz, Heinz-Bernhard
Cerebral Hemodynamics, Oxygen Metabolism and Brain Growth in Congenital Heart Disease

Congenital heart disease (CHD) is the most common birth defect in children. Neurodevelopmental deficits and brain injury are recognized as common comorbidities. Furthermore, fetal and neonatal brain growth has been shown to be stunted in addition to delayed brain maturation and these are associated with severity of cardiac defect. Various clinical factors likely contribute to the pathophysiology of these observations, though the role of hemodynamic changes due to the cardiac defect has yet to be elucidated. The objective of this thesis is to investigate the relationships between cerebral hemodynamics and oxygen metabolism on brain growth and explore the longitudinal changes of these parameters and effects on brain growth trajectory in fetuses and neonates with the most complex forms of CHD: single ventricles (SV) and transposition of the great arteries (TGA). Fetal and neonatal cerebral blood flow and oxygen content was measured using MRI-based techniques to derive cerebral oxygen delivery (CDO2) and consumption (CVO2). Brain development indices included volumetric analyses and clinical evaluations of development. Fetally, ascending aorta saturations, CDO2, CVO2, were found to be predictive of neonatal brain size. Preoperatively, cerebral blood flow (CBF) was found to be similar between neonates with CHD and controls, however, CDO2 was reduced, mainly driven by reductions to arterial saturations. Age at surgery was a strong predictor of postoperative brain volume and composite language scores in infants with TGA. Earlier surgical correction of cardiac anatomy, which improves arterial saturation, may support optimal brain growth and developmental outcomes. Longitudinal profiles of various cerebral hemodynamic and metabolic parameters in TGA and SV revealed that CVO2 increases over time in TGA but demonstrates a decline in SV patients. This pattern was also reflected in their brain growth trajectories. Furthermore, it was found that CDO2 was improved postoperatively in SV through an increase in hemoglobin concentration maintaining similar CDO2 to TGA. Surgical and clinical management differences between SV and TGA manifest in their physiological adaptations observed postoperatively suggesting inherent differences in cerebral oxygen metabolism between the two groups, where SV have impaired oxygen utility which may be a driver of their poor brain growth trajectories.

Advisor: Seed, Mike
Post, Martin
Effect of Engineered Nanoparticles-treated Root Canal Biofilm on Macrophage Plasticity and Interactions with Human Periodontal Ligament Fibroblast

The intracanal microbes, particularly in proximity to the apical foramen, often result in chronic inflammation of the periapical tissues that might lead to compromised post-treatment healing. Macrophages (MQ), which are major constituents of periapical lesions, respond to microbial factors and exhibit a key role in the pathogenesis as well as the healing of apical periodontitis owing to their functional plasticity. Depending on the microenvironmental cues, they polarize into pro-inflammatory (M1) or anti-inflammatory/pro-wound healing (M2) phenotype. MQ crosstalk with other immune cells and periradicular multipotent cells, such as periodontal ligament fibroblasts (PdLF), via soluble inflammatory signals, to regulate the disease/healing outcomes. Engineered chitosan-based nanoparticles (CSnp) that possess effective antibacterial activities could favorably interact with host cells by virtue of their inherent bioactivity and customized physicochemical properties. Herein, we aimed to (1) understand the influence of residual root canal biofilm on MQ-PdLF interaction, and (2) evaluate the effect of engineered CSnp on modulating residual biofilm-mediated inflammatory response of MQ and their interaction with PdLF. An ex-vivo model of Enterococcus faecalis biofilm in root canals was characterized to evaluate the inflammatory response to untreated versus treated biofilms. Engineered CSnp dispersed in carboxymethyl chitosan (CMCS) resulted in significant reduction of 6-week-old biofilm compared to conventional disinfection (P

Keywords: immunomodulation
Engineered chitosan nanoparticles
Enterococcus faecalis biofilm
macrophage polarization
proteomics
root canal disinfection
Advisor: Kishen, Anil