VictorJuiz/thesis huggingface dataset:
Grey and White Matter Density on Computed Tomography in Pediatric Traumatic Brain Injury: Automated Digital Measurement Algorithm Classifying Cerebral Injury
Keywords: cerebral edema
cerebral swelling
computed tomography
digital measurement
grey white matter
traumatic brain injury

Background: This project assessed an automated digital measurement algorithmâ s ability to predict pediatric functional outcome after traumatic brain injury by quantifying detectable cerebral edema on computed tomography scans. Methods: Developed with consideration to brain maturity and time from injury to scan, the algorithm was applied to day-of-injury computed tomography scans of 118 children (age: 0-17 years) with traumatic brain injury. Regions of interest median Hounsfield units were analyzed using Medical Image Processing, Analysis and Visualization software. Results: Grey-white matter ratio (p = 0.019) and age (p = 0.034) were significantly associated with functional outcome. The most predictive algorithmic model (area under the curve = 0.868) included samples from the caudate nuclei, thalami and putamen; frontal, temporal and occipital lobes; and grey-white matter ratio. Conclusions: Cerebral edema can be measured quantitatively using digital methods and the model from this study has high predictability for functional outcome following pediatric traumatic brain injury.
Phosphorus and Potassium Content of Commonly Consumed Meat, Poultry and Fish Products in Patients with Chronic Kidney Disease
Keywords: Additives
Chronic Kidney Disease
Meat
Phosphorus
Potassium
Poultry

Patients with chronic kidney disease (CKD) are advised to limit their intake of phosphorus and potassium, yet there is uncertainty concerning the actual content of these minerals in the Canadian food supply. In order to gain insight into the contribution of food additives to phosphorus and potassium intake, we chemically analyzed phosphorus, potassium, sodium and protein content of commonly consumed meat, poultry and fish (MPF) products. A food frequency questionnaire administered to patients receiving dialysis (n=67) identified unbreaded chicken, ground beef, steak, white fish, beef burgers, deli ham, shrimp and bacon as commonly consumed MPF. Phosphorus and potassium content was significantly (P
Derivation of Patient-specific Alveolar Type II Cells from Surfactant Protein-B Deficient Induced Pluripotent Stem Cells
Keywords: gene therapy
induced pluripotent stem cells
lung biology
surfactant deficiency

Surfactant protein B (SFTPB) deficiency is a fatal disease affecting newborn babies. A mutation in the surfactant protein B gene results in the inability to reduce surface tension and ultimately, death. This thesis shows that induced pluripotent stem (iPS) cells derived from patient specific SFTPB deficient fibroblasts can be differentiated into alveolar type II cells using a variety of methods including 2D and 3D culture. The iPS cells are also a target for gene therapy with a lentivirus vector containing the wild type sequence of the SFTPB gene, inserted into both wild type and SFTPB deficient iPS cells. These cells were differentiated into lamellar body containing, surfactant expressing alveolar type II cells and the transfected SFTPB deficient cells showed gene and protein expression of surfactant protein B. These findings suggest that a lethal disease can be targeted and reversed, the first step towards a potential cure for a vulnerable population.
Manufacturing and Characterization of Chitin Nanowhisker/Polyolefin Nanocomposites
Keywords: chitin
crystallinity
masterbatch
nanocomposite
polyolefin
water vapor barrier

This thesis discusses the potential large scale production of polymer nanocomposites using polypropylene and high density polyethylene with chitin nanowhiskers (CNW). Fabrication of the nanocomposites with and without compatibilization were prepared over a range of CNW loading through melt compounding. The processing techniques tested included direct melt compounding, and a two step masterbatch dilution process. Three studies were investigated to build an understanding of the composite structure-property relationship based on morphological, thermal, water barrier, mechanical, and rheological properties. The addition of CNW and compatibilizer provided mechanical reinforcement and improvements in water barrier. However, the CNW significantly affected the crystallinities of the composites, which impacted its overall properties. Finally, the masterbatch diluted composites maintained good mechanical and water barrier compared to the neat polymer, but the directly compounded composites were still better. Therefore, further optimization of this process is required to maximize CNW dispersion, which also greatly affected the composite properties.
Application of Chemical Structure-based Parameters of Drug Substances and Polymers to Predict Kinetics of Drug Release from Polymer Coated Pellets
Keywords: Drug-Polymer
Group Contribution Method
Partition
Permeability
Polymer
Solubility

The purpose of this thesis is to correlate drug substance properties that are easily calculated or obtained in literature with drug-polymer partition and permeability values. Initially, partition and permeability values were determined experimentally using a side-by-side diffusion cell and values were correlated with drug substance properties mentioned above. The drug-polymer squared solubility parameter, aqueous solubility and molar volume resulted in the best correlations. The empirical correlations, paracetmaol dissolution data (obtained from literature) and AP-CADÂŠ software were utilized to predict the release profile of a similarly coated metoprolol pellet. Verification took place with a comparison of the predicted metoprolol AP-CADÂŠ release profile and metoprolol dissolution data obtained from literature. Results met equivalence criteria outlined by the F1 and F2 difference and similarity factor. Therefore, the methodology and correlations identified could be used as a starting point in formulation studies, thus eliminating various experiments.
In-situ Microrobot Fabrication Using Magnetic Guidance
Keywords: bending
fabrication
in-situ
magnetic
microrobotics

Mobile microrobots are typically fabricated in a multi-step microfabrication process and then transported into an enclosed workspace for operation. In this thesis an in-situ microrobot fabrication method is presented by magnetically bending a polymer filament into a desire shape as it is fed through a hot needle which is inserted into the workspace. The mechanics of filament bending and the behavior of the bending zone is studied. A shape planner is developed for automated fabrication control of a desired shape. The capability of the method in shape creation is also analyzed. Millimeter-scale planar and 3D robotic devices of different shapes are fabricated using the developed fabrication system prototype. Functional microrobotic devices are also created to show the utility of the fabrication method for creating complex microrobot shapes remotely in enclosed environments for advanced microrobotic applications.
Associations of Circulating Second Messenger Glycerophosphatidylcholines with Cardiovascular Disease Risk Factors in Adolescents
Keywords: Cardiovascular disease
Inflammation
Lipidomics
Lysophosphatidylcholine
Obesity
Platelet-activating factor

Circulating glycerophosphatidylcholines and their second messenger metabolites (smGPCs) are phospholipids that modulate risk for cardiovascular disease (CVD). CVD is a slow-progressing disease culminating by acute vascular events or chronic vascular conditions in middle-to-late adulthood, but its pre-clinical stages may already occur during adolescence. We investigated whether circulating smGPCs are associated with CVD risk factors – excess visceral fat, elevated blood pressure, insulin resistance, and low-grade inflammation – in a population-based sample of adolescents as part of the Saguenay Youth Study. Several of the smGPCs were associated with multiple CVD-risk factors and may serve as novel biomarkers of early CVD development; the most significant of these were PC(16:0/2:0) and LPC(14:1/0:0). Mediation tests revealed that PC(16:0/2:0) mediated the directed relationship between VF and blood pressure or C-reactive protein, and LPC(14:1/0:0) mediated the directed relationship between VF and fasting insulin. Elucidating pathways regulating circulating levels of these smGPCs may provide new pharmaceutical targets of CVD.
Predictors of Cancer Cell Response to Metformin
Keywords: Biomarkers
Cancer
Drug Repositioning
Metabolism
Metformin
Radiotherapy

There is great interest in transitioning the antidiabetic drug metformin for use in cancer, with evidence suggesting it can improve outcome following radiotherapy (RT). Its benefit may arise from inhibiting cancer cell proliferation, abrogating tumour hypoxia through respiratory inhibition, or directly radiosensitizing cancer cells. With metformin entering clinical trials, it is crucial to identify relevant biomarkers for patient benefit. AMPK and p53 were previously identified to facilitate metformin's radiosensitization, while OCT and MATE transporters mediate its intracellular concentration: we thus investigated these as contributors to metformin's radiosensitizing, anti-proliferative, or respiratory-inhibitory effects. We found that loss of AMPK or p53 exacerbated sensitivity to metformin's inhibition of proliferation, while OCT expression was sufficient to confer response to metformin's respiratory inhibition. Together, loss of AMPK and p53 signaling, and OCT expression, represent putative biomarkers of response to inhibition of proliferation and respiration, respectively, and may be further explored in a clinical setting.
Longitudinal Measures of Lung Function in Healthy Infants
Keywords: Infant Lung Development
Longitudinal
Multiple Breath Washout
Physiology
Pulmonary Function Testing

Effective treatment of paediatric pulmonary disease relies on early diagnostics, and thus requires pulmonary function testing. Before infant pulmonary function testing can be applied to detect disease, it must first be understood in health, especially in the context of the developing lung. Adult studies have suggested that the rapid expansion of alveoli leads to faster growth in the lung parenchyma with respect to the conducting airways. By longitudinally evaluating lung function parameters that approximate the size of the parenchyma and the airways in infants, it can be determined whether dysanapsis is present in this young age group. However, while we were unable to find functional dysanapsis in tidal breathing measures, it was found when comparing forced flow and volumetric measures. This indicates that while the airways are proportionally larger in youngest infants, rapid parenchymal expansion leads a decrease in the relative size of these airways compared to overall lung volume.
Molecular Phylogeny of the Neotropical Knifefishes of the Order Gymnotiformes (Actinopterygii)
Keywords: Evolution
Gymnotiformes
Phylogeny
Systematics

The order Gymnotiformes, the Neotropical electric knifefishes, is comprised of 200+ species divided into the families Apteronotidae, Gymnotidae, Hypopomidae, Rhamphichthyidae, and Sternopygidae. These species inhabit a variety of freshwater habitats throughout Central and South America. To date, attempts at resolving the internal relationships of Gymnotiformes have yet to produce an unambiguous species-level phylogeny. In order to resolve the phylogeny, I collected molecular data from seven nuclear and two mitochondrial genes for 197 species and performed parsimony and Bayesian phylogenetic analyses. All families were recovered as monophyletic with the exception of Gymnotidae; the electric eel Electrophorus, previously considered a member of this family, was instead found to be sister to all other Gymnotiformes. The topologies resulting from this study provide a highly-resolved species phylogeny which will form the basis for future studies of species diversification and ecological and evolutionary patterns.
Microfluidic Device for Co-culturing Lung Airway Cells on a Suspended Hydrogel: Towards a Biomimetic Lung Airway Model
Keywords: airway
in vitro
microfabrication
microfluidics
suspended microfluidics
thermoplastics

Organ-on-a-chip technologies have made significant strides in recapitulating the complex multicellular 3D architectures, tissue-tissue interfaces and the physiologically relevant mechanical and biological properties of in vivo tissue microenvironments. To accelerate current drug development processes, new and improved in vitro models that reconstitute the complex in vivo microenvironment of human tissues are needed. Local disruptions to the lung airway epithelium are known to elicit specific cellular responses leading to the progression of a myriad of respiratory diseases, making it a crucial target for conducting disease mechanism and drug development studies. We aimed to develop and perform preliminary assessment on a microfluidic-based in vitro model that mimics the in vivo tissue microenvironments of the human airway. By leveraging microfabrication techniques and surface tension principles to integrate co-culture of airway cells on stable air- liquid interfaces, we demonstrated a microfluidic platform that allows more efficient 3D culture experiments and enables high-throughput co-culture studies of the airway tissue.
Gene Association Studies of Clozapine Response: A Dopamine System Approach
Keywords: Antipsychotics
Clozapine
Personalized Medicine
Pharmocogenetics
Schizophrenia
Treatment Response

The antipsychotic clozapine (CLZ) is under-utilized due to its life-threatening side-effects despite superior efficacy for treatment-resistant schizophrenia (SCZ). Thus, predictors for response could help inform drug administration decisions. Given the genetic basis for response, we aimed to identify genetic predictors and build a preliminary genetic model for CLZ efficacy. Since CLZâ s targets the DA system, we investigated a DA D2 receptor (DRD2) gene variant implicated in SCZ risk in a recent genome-wide association study. We observed that the A-allele was associated with better CLZ response. We also examined the association between catechol-O-methyltransferase gene (COMT) polymorphism Val158Met and antipsychotic response, observing that Met/Met was associated with greater improvement. Lastly, we developed a genetic model for response, consisting of four polymorphisms from the DRD2, serotonin-6 receptor (5-HT6), brain-derived neurotrophic factor (BDNF), and neurexin-1 genes (NRXN1) (Adjusted R2=52%, sensitivity=70%, specificity=47%). While replication is required, our findings identify several potential genetic predictors of response.
Feasibility of an Online Cognitive Environmental Enrichment Intervention for Patients with Moderate-to-severe Traumatic Brain Injury
Keywords: Cognitive intervention
Environmental enrichment
Feasibility
Neurodegeneration
Neuropsychology
Traumatic brain injury

Recent research has documented progressive cognitive and neural decline in the chronic stages of moderate-to-severe traumatic brain injury (TBI). Offsetting this putative neurodegeneration offers a new target for cognitive neurorehabilitation. Cognitive environmental enrichment (C-EE; novel, challenging, and engaging cognitive stimulation) delivered early post-TBI has been shown to buffer against neurodegeneration in humans and animals. Some online "brain games" (which can be accessed by patients regardless of location or mobility restrictions) offer intensive cognitive stimulation that meet the criteria for C-EE. Here, the feasibility of administering a home-based, online "brain game" suite to 11 moderate-to-severe TBI patients who participated in 12 weeks of intensive cognitive training was examined. Modest adherence and attrition, high acceptability of the program, and promising findings on limited-efficacy testing involving neuropsychological outcomes were observed. Online cognitive training is a feasible and potentially efficacious intervention for TBI patients. Means of improving adherence are discussed.
Oxidative Stress and BDNF as Putative Biomarkers of Cognitive Flexibility in Adolescent Bipolar Disorder
Keywords: adolescent
BDNF
Biomarkers
cognition
Oxidative stress
psychiatry

Executive dysfunction is common and impairing in bipolar disorder (BD), and its pathophysiology is poorly understood. Oxidative stress (OS) and brain-derived neurotrophic factor (BDNF) have been implicated in executive deficits of adult BD, but have not been studied in youth. Serum levels of OS and BDNF were measured in 30 BD and 25 healthy control (HC) adolescents. The intra-extra-dimensional (IED) set-shifting task assessed executive function, particularly cognitive flexibility. High and low BDNF subgroups were defined by median split. IED performance was impaired in BD subjects. LPH and BDNF had opposite correlations in BD and control subjects. LPH and IED performance was oppositely correlated between BD and control subjects. These correlations became stronger when parsed by BDNF. LPH and BDNF have an altered interaction in BD that is relevant to executive function. Antioxidant interventions to improve executive function may be warranted, especially when guided by BDNF levels.
The Mechanistic Function of the NOD-like Receptor NLRX1 in Apoptosis and Cell Death in the Nervous System
Keywords: Apoptosis
Cell Death
NLRX1
SARM1
Stroke
Wallerian Degeneration

The mitochondrial protein NLRX1 belongs to the family of cytosolic nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs). NLRs respond to invasive pathogens, and danger signals released from dead or dying cells. The function of NLRX1 was previously reported to be in anti-viral immunity, however we propose a non-immune role for this protein in apoptosis. We show here the function of NLRX1 to be inhibitory to extrinsic apoptosis and permissive to intrinsic apoptosis. Furthermore, we validate the previously reported interaction between NLRX1 and sterile-α and TIR motif containing protein 1 (SARM1). SARM1 is expressed in the nervous system, and has a pro-apoptotic function in addition to its role in promoting Wallerian degeneration. We found NLRX1 to have both SARM1-dependent and -independent functions during apoptosis. Furthermore, we test NLRX1 function during Wallerian degeneration following axotomy, and a central nervous system injury model involving ischemic stroke.
Integration of Selectively Transparent and Conducting Photonic Crystals (STCPCs) in Tandem Silicon Photovoltaics
Keywords: multi-junction
photonic crystals
photonics
photovoltaics
solar
solar cells

A proof-of-concept integration of the Selectively Transparent and Conducting Photonic Crystal (STCPC) as a spectrally tunable intermediate reflector (IR) is reported for an amorphous-silicon (a-Si:H)/crystalline-silicon heterojunction (c-Si HJ) tandem solar cell. Optical and electrical studies present the simulation, fabrication, and testing of the tandem cells with no IR, Zinc Oxide IR (ZIR), and STCPC IR. The STCPC IR showed current-density (JSC) increases of up to 17.1% over no IR, and 13.2% over the ZIR. A small relative efficiency decrease of 10% in the STCPC case relative to the ZIR case was observed from the lack of optimal interface layers. Additionally, the effect of varying STCPC reflection band centre peak positions (480, 530, 580 and 630 nm) was examined. External quantum efficiency and JSC enhancements were observed in these cases, though these structures require electrical interface optimization to completely avail the benefits of STCPC integration in tandem silicon/other material photovoltaic systems.
Women in Jamaican Dancehall: Rethinking Jamaican Dancehall through a Women-Centered Informal Economy Approach.
Keywords: Dancehall
Economic Mobility
Income Generatig Practices
Informal Economy
Transnational
Women in Jamaican Dancehall

Some academic discussions that address women who participate in Jamaican Dancehall have taken the position that these women lack morality and agency and have internalized sexist norms (Lake 1996). This is because of the overtly sexual nature of the cultural expression. This research project aimed to expand the conversation concerning these women by investigating how female dancehall dancers, models and auxiliaries (designers, beauticians and vendors) make a living from Dancehall's informal economy. Through empirical evidence, this research will suggest that women who participate in Jamaican dancehall have subjectively and economically benefited from the informal economy that is embedded in dancehall.
Microfluidic Preparation of Air- and Moisture-sensitive Precursor Solutions and Semiconductor Nanocrystals
Keywords: air-sensitive techniques
flow chemistry
microfluidics
Schlenk line
semiconductor nanocrystals

Syntheses of a wide range of air- and moisture-sensitive chemistries are conducted in dedicated, capital-intensive setups that are not amenable to automation and offer only limited process control and scalability. Here, we demonstrate a compact Schlenk-line-to go (SL2G) platform that overcomes these limitations. Case studies of semiconductor precursor solutions and colloidal nanomaterials are presented. The rapid and reproducible preparation of precursor solutions and NCs is achieved by a microfabricated sparger that promotes rapid mixing and temperature control. We expect the benchtop SL2G platform to enable air- and moisture-sensitive syntheses to be conducted independent of a fume hood or a glovebox and in a manner that is scalable, automatable, and compatible with flow chemistry.
A RhoGEF that Promotes Par6-aPKC Pathway Activity for Establishing Epithelial Polarity in Drosophila
Keywords: Drosophila
Epithelial Polarity
Polarity Protein Complex

Apical-basal polarity is important for the integrity of Drosophila embryonic epithelia. Polarity is established when Cdc42, a Rho GTPase, activates the conserved Par6/atypical protein kinase C (aPKC) complex, and recruits them to the apical domain. However, the RhoGEF that activates Cdc42 in Drosophila is unknown. Through an shRNA screen, I isolated the RhoGEF CG10188 which when knocked down produced similar defects as aPKC mutants. Furthermore, disruption of CG10188 and aPKC together enhanced the defects observed with either single disruption, demonstrating a genetic interaction between the two. However, aPKC localization appears to be independent of CG10188 regulation. Lastly, mammalian proteins that share high sequence identity with CG10188 have been previously shown to activate RhoA, another Rho GTPase, suggesting that CG10188 could be upstream of either Cdc42-Par6-aPKC or Drosophila RhoA (Rho1). Overall, my results suggest that CG10188 is a novel polarity regulator that promotes epithelial development in the Drosophila embryo.
Consumption of Non-cow's Milk and 25-Hydroxyvitamin D Levels in Early Childhood
Keywords: early childhood
Pediatrics
public health policy
TARGet Kids!
vitamin d

Non cow’s milk includes goat’s milk and plant-based milk beverages. Vitamin D fortification of non-cow’s milk is voluntary in North America. The effect of non-cow’s milk on serum 25-hydrxovytamin D levels is unclear. Through two studies, I aimed to determine the association between non-cow’s milk consumption (both animal and plant based) and 25-hydroxyvitamin D serum levels in early childhood. Children ages 1-6 years were recruited through the TARGet Kids! practice based research network between 2008 and 2013. Non-cow’s milk consumption, 25-hydroxyvitamin D serum levels and clinically relevant covariates were collected. In study 1, I identified a dose dependent association between higher non-cow’s milk consumption and lower 25-hydroxyvitmian D levels. In study 2, I demonstrated that consumption of plant-based milk beverages was associated with lower 25-hydroxyvitamin D; the magnitude of this association was both smaller and in the opposite direction to the relationship of both cow’s milk and goat’s milk and 25-hydroxyvitamin D.