VictorJuiz/thesis huggingface dataset:
Temporal Dynamics of Heat Pain Sensations
Keywords: Pain,
sex differences in pain
pain patterns
temporal summation
psychophysics
tonic pain
burning
adaptation
models
habituation
temporal
heat pain
temperature
pain modulation
glabrous
hairy
analgesia
chronic pain
sex
women
sex differences
sharp
pain mechanisms
a-delta
unmyelinated C fibre
brain
MPQ
pain dimensions

The moment-to-moment fluctuations in pain-evoked sensory and emotional qualities, and how the pain experience differs between sexes are not well understood. Therefore, this thesis sought to 1) characterise the temporal profiles of the most prominent noxious heat-evoked sensations, 2) characterise sex differences in these sensations, 3) evaluate the magnitude of sharp pain quality evoked in hairy and glabrous skin, and 4) determine the role of absolute stimulus temperatures on sex differences in pain adaptation and habituation. A broad-based heat pain model was developed for this study that incorporates a temporally-continuous assessment of multiple sensory and affective pain dimensions, including pain, burning, sharp, stinging, cutting, and annoyance evoked by two types (static, dynamic) of repeated prolonged noxious heat stimuli. The salient hypotheses were: 1) Burning sensations have a different temporal profile compared with sharp and other related qualities, 2) The temporal dynamics of heat pain intensity and annoyance differ between males and females, 3) Sex differences in heat pain are associated with specific pain qualities and specific types of skin, and 4) Moderate-high temperatures induce pain adaptation and habituation in females but not in males. The most prominent findings were 1) sharp, stinging and cutting sensations adapted when stimulus intensity was static, but burning sensations were evoked during static and dynamic stimulus phases, 2) pain and annoyance in women were greater than men during the dynamic phases of the first stimulus but less than men during static stimulus phases and on stimulus repetition, 3) the sex difference in pain adaptation occurred with percept-fixed stimulus intensities and with absolute stimulus temperatures, 4) the sex effects associated with dynamic stimuli occurred in hairy but not glabrous skin. These findings give new insights into the relationships between pain intensity, quality and affect and have strong implications for views on sex differences in pain sensitivity.
Ontogeny of Postcranial Robusticity among Holocene Hunter-gatherers of Southernmost Africa
Keywords: growth
hunter-gatherer
biomechanics
southern Africa
childhood
physical activity
bone mass
ontogeny

Ontogenetic patterns in postcranial robusticity are analysed in the skeletons of eighty-two juvenile Later Stone Age hunter-gatherers with estimated ages at death ranging from infancy to late adolescence. Robusticity is quantified from cross-sectional geometric properties of diaphyses at sixteen sites throughout the skeleton, using radiography and casting methods. Skeletal growth profiles for strength measures are analysed with locally-weighted regression and additional curve fitting to evaluate developmental trajectories. Ethnographic accounts of infancy and childhood in modern Ju/'hoansi (Khoesan) communities provide a culturally-relevant interpretive framework for evaluating skeletal correlates of behaviour. This research demonstrates that bone strength properties can be functionally linked to behaviour among juveniles toward the reconstruction of patterns of physical activity among prehistoric children. Postcranial strength measures vary predictably with age such that developmental patterns and timing in appositional growth can be assessed reliably. The onset of walking among Later Stone Age juveniles is evident by two years of age from proportional lower to upper limb strength measures. The lower limb continues to adapt to increasing loading demands especially in response to torsional forces, and bending in the medio-lateral plane; biomechanical shape measures illustrate the gradual development of the femoral pilaster. Individual humeral strength is symmetrical with respect to the orientation maximal bending forces experienced throughout development, but the magnitude of the functional adaptive response is greater, on average, in the right limb with more than 70% of the sample over the age of six displaying right-side dominance. Humeral asymmetry and side dominance does not emerge until late childhood, and the majority of arm strength is accrued during adolescence, relative to the sex-combined mean values for Later Stone Age adults. Evidence for sexual dimorphism in upper limb properties is evident by late adolescence whereas sex-based patterns of mobility reflected in lower limb strength have yet to emerge. These results illustrate the developmental patterns that underlie postcranial markers of subsistence activities in Later Stone Age hunter-gatherers.
An Economic Evaluation of Teratology Information Services
Keywords: Health Economics
Pregnancy
Teratology

BACKGROUND: Teratology Information Services (TIS) educate the public and health professionals via telephone regarding the safety of drugs and other exposures during pregnancy and lactation. Currently TIS consultations are free, but funding is eroding. A cost-benefit analysis may inform resource allocation. It was hypothesized that an individual TIS consultation regarding anti-depressant use during pregnancy provides a positive net benefit compared to a family doctor (FD) consultation. METHODS: A survey of international TIS was conducted to gauge TIS costs. A discrete choice experiment (DCE) was designed to assess preferences and willingness-to-pay (WTP, an estimate of benefit) for teratology counseling. DCE respondents (local community volunteers) chose between potential counseling services following an anti-depressant exposure during pregnancy. Services were described by five service attributes and one cost attribute, which were generated in focus groups. Preferences and WTP were estimated using logit regression. Incremental benefits and costs of counseling by TIS and FD were compared in a probabilistic sensitivity analysis to obtain the incremental net benefit from both a societal (productivity costs included) and health system perspective. The FD consultation was costed through OHIP billing codes. The TIS consultation was micro-costed. RESULTS: Eighteen TIS in North America and 16 international TIS completed the survey. Most TIS are small (median two employees, median budget US$69,000). The DCE had 175 respondents. The most important attribute of counseling was receiving very helpful information; information delivery methods were less important. WTP for the TIS scenario was CDN$124 (SD $12); WTP for the FD scenario was CDN$79 (SD $8). Service costs were similar for TIS and FD (approximately $32/consultation); FD had higher productivity costs. Incremental TIS benefits were likely to outweigh costs under both the societal and health system perspectives (probability 99% and 97% respectively). CONCLUSIONS: An economic evaluation of a program that delivers pregnancy health information via telephone required a novel approach. While there are some methodological challenges to valuing benefits through willingness-to-pay, it may be appropriate for valuing counseling. TIS should emphasize their ability to provide high quality information. The benefits of an individual TIS consultation on anti-depressant use during pregnancy are likely greater than the costs.
Problems in Supply Chain Location and Inventory under Uncertainty
Keywords: Operations Management
Supply Chain Management
Location
Inventory

We study three problems on supply chain location and inventory under uncertainty. In Chapter 2, we study the inventory purchasing and allocation problem in a movie rental chain under demand uncertainty. We formulate this problem as a newsvendor-like problem with multiple rental opportunities. We study several demand and return forecasting models based on comparable films using iterative maximum likelihood estimation and Bayesian estimation via Markov chain Monte Carlo simulation. Test results on data from a large movie rental firm reveal systematic under-buying of movies purchased through revenue sharing contracts and over-buying of movies purchased through standard ones. For the movies considered, the model estimates an increase in the average profit per title for new movies by 15.5% and 2.5% for revenue sharing and standard titles, respectively. We discuss the implications of revenue sharing on the profitability of both the rental firm and the studio. In Chapter 3, we focus on the effect of travel time uncertainty on the location of facilities that provide service within a given coverage radius on the transportation network. Three models - expected covering, robust covering and expected p-robust covering - are studied; each appropriate for different types of facilities. Exact and approximate algorithms are developed. The models are used to analyze the location of fire stations in the city of Toronto. Using real traffic data we show that the current system design is quite far from optimality and provide recommendations for improving the performance. In Chapter 4, we continue our analysis in Chapter 3 to study the trade-off between adding new facilities versus relocating some existing facilities. We consider a multi-objective problem that aims at minimizing the number of facility relocations while maximizing expected and worst case network coverage. Exact and approximate algorithms are developed to solve three variations of the problem and find expected--worst case trade-off curves for any given number of relocations. The models are used to analyze the addition of four new fire stations to the city of Toronto. Our results suggest that the benefit of adding four new stations is achievable, at a lower cost, by relocating 4-5 stations.
The Role of Glucagon-like Peptides in Experimental Type 1 Diabetes
Keywords: diabetes
glucagon-like peptides
GLP-1R
GLP-2
GLP-1
NOD mouse

Type 1 diabetes mellitus (T1D) is an autoimmune disorder that targets the insulin-producing β-cells. The gut may play a role in the pathogenesis of T1D, as genetically-susceptible individuals and animal models of T1D exhibit increased intestinal permeability and improving gut barrier function can interfere with the onset of diabetes. Moreover gut-derived peptides are capable of modifying barrier function and regulate β-cell mass via effects on proliferation and apoptosis. I tested whether chronic administration of glucagon-like peptide-2 (GLP-2), a peptide which potently improves gut barrier function, modifies diabetes onset in a mouse model of T1D, the non obese diabetic (NOD) mouse. Although chronic treatment with a long-acting GLP-2 analogue was associated with improved intestinal barrier function, it failed to delay the onset of T1D. Once the autoimmune attack is initiated, pathogenic T-cells infiltrate the islets and trigger the death of β-cells. Studies in animal models have revealed that β-cells exhibit a compensatory response in the initial stages of the immune attack, which eventually fails, resulting in β-cell mass deficiency and onset of T1D. Glucagon-like peptide-1 (GLP-1) exerts both proliferative and anti-apoptotic actions on β-cells. I hypothesized that chronic activation of the GLP-1 receptor (GLP-1R) would delay or prevent the loss of functional β-cell mass in the NOD mouse. I have shown that chronic administration of the GLP-1R agonist exendin-4 significantly delayed the onset of diabetes and enhanced β-cell mass. Furthermore, GLP-1R activation was associated with a reduction of islet-infiltrating immune cells, as well as changes in lymphocyte subpopulations. Consequently, I addressed whether the GLP-1R has a role in the immune system of NOD and C57Bl/6 mice. GLP-1R mRNA transcripts were detectable in several immune subpopulations, and GLP-1R activation was associated with cAMP production in primary splenocytes and thymocytes. Furthermore I demonstrated that GLP-1R signaling controls proliferation of thymocytes and lymphocytes, and is required for maintaining peripheral regulatory T-cells. In summary, these studies establish that while GLP-2R activation is not sufficient to modify disease onset in a murine model of T1D, GLP-1R activation reduces the extent of diabetes development by exerting actions on β-cells and the immune system.
Accurate Residual-distribution Schemes for Accelerated Parallel Architectures
Keywords: residual distribution
parallel architectures
GPGPU
heterogeneous architectures
computational fluid dynamics
CUDA
high order
partial differential equation
multi-dimensional upwind
multi-dimensional limiter

Residual-distribution methods offer several potential benefits over classical methods, such as a means of applying upwinding in a multi-dimensional manner and a multi-dimensional positivity property. While it is apparent that residual-distribution methods also offer higher accuracy than finite-volume methods on similar meshes, few studies have directly compared the performance of the two approaches in a systematic and quantitative manner. In this study, comparisons between residual distribution and finite volume are made for steady-state smooth and discontinuous flows of gas dynamics, governed by hyperbolic conservation laws, to illustrate the strengths and deficiencies of the residual-distribution method. Deficiencies which reduce the accuracy are analyzed and a new nonlinear scheme is proposed that closely reproduces or surpasses the accuracy of the best linear residual-distribution scheme. The accuracy is further improved by extending the scheme to fourth order using established finite-element techniques. Finally, the compact stencil, arithmetic workload, and data parallelism of the fourth-order residual-distribution scheme are exploited to accelerate parallel computations on an architecture consisting of both CPU cores and a graphics processing unit. Numerical experiments are used to assess the gains to efficiency and possible monetary savings that may be provided by accelerated architectures.
Discovery of Novel Ovarian Cancer Biomarkers via Proteomics and Mass Spectrometry
Keywords: Ovarian Cancer
Biomarkers
Chromatography
Mass Spectrometry
ELISA

Proteins secreted or shed by tumors can be found in serum. Detecting these proteins by mass spectrometry (MS) is difficult, due to the wide dynamic range of protein concentrations in serum. To circumvent this issue, we mined the conditioned media of epithelial ovarian cancer (EOC) cell lines which is a less complex fluid to work with. We hypothesize that some of the proteins shed or secreted by EOC cell lines are similar to those secreted or shed by EOC tumors and that some of these proteins can be used as biomarkers. We mined the conditioned medium of four ovarian cancer cell lines (HTB75, TOV-112D, TOV-21G and RMUG-S) by two-dimensional liquid chromatography-mass spectrometry. Our study identified 1208, 1252, 885, and 463 proteins from the HTB-75, TOV-112D, TOV-21G, and RMUG-S cell lines respectively. In all, we identified 2039 proteins from which we focused on 420 extracellular and plasma membrane proteins. High abundance proteins such as albumin and immunoglobulins, which are problematic for serum proteomics, did not interfere with our study. Several known markers of EOC including CA-125, HE4, Mesothelin, and KLK6, were identified in this study. The list of 420 extracellular and membrane proteins was cross-referenced with the proteome of ascites fluid to generate a final list of 51 potential candidates. According to Ingenuity Pathway Analysis, two of the top 10 diseases associated with our list of 51 proteins were cancer and reproductive diseases. Of the 51 candidates, 10 proteins were selected for verification in sera from ovarian cancer patients and healthy individuals. Clusterin showed a significant difference between cancer patients and normal, with sera from cancer patients showing higher levels. Another protein, NPC2, did not show a difference in sera between cancer and normals. Protein expression studies using immunohistochemistry showed that NPC2 is highly expressed in ovarian cancer tissue and absent in normal ovarian surface epithelium. In summary, clusterin and NPC2 appear to play a role in ovarian cancer pathobiology and their role in EOC need to be studied further.
New Routes to Pnictogen-containing Polymers
Keywords: inorganic chemistry
polymer
oligomer
nitrogen
phosphorus
pnictogen
hydroamination
hydrophosphination
alkyne

New synthetic routes to nitrogen- and phosphorus-containing polymers have been investigated. These routes rely on amine- and phosphine-containing monomers bearing pendant alkyne substituents, and subsequent hydroamination, oxidation, or hydrophosphination polymerization. A series of primary amines of the form H2NC6H2R2C≡CR’ (R = H or iPr; R’ = Ph, SiMe3, nBu, or p-C6H4Me) is reported. These amines are deprotonated with nBuLi to give lithium amides, which react with zirconocene compounds to provide amidozirconium complexes. Characterization is achieved by multinuclear NMR spectroscopy, IR spectroscopy, high-resolution mass spectrometry, elemental analysis, X ray crystallography, and DFT calculations. Three routes were attempted towards nitrogen-containing oligomers: (1) thermolysis of amidozirconium complexes to afford [2+2] cycloaddition polymers; (2) Ti(IV)-catalyzed hydroamination of H2NC6H4C≡CPh; (3) chemical oxidation of H2NC6H4C≡CPh. The latter two strategies resulted in distinct nitrogen-containing oligomers. The oligomer formed by Ti(NR2)4-catalyzed hydroamination (R = Me, Et) contains up to 15 repeat units in the chain, with both imine and enamine moieties, and is capped by a molecule of HNR2 (R = Me or Et) originating from the catalyst. The oligomer formed by chemical oxidation contains up to 9 repeat units in the chain. A series of phosphines of the form X2PC6H2R2C≡CR’ is reported (X = NEt2, Cl, H; R = Me, iPr; R’ = Ph, SiMe3). Characterization is achieved by multinuclear NMR spectroscopy, IR spectroscopy, high-resolution mass spectrometry, elemental analysis, and X-ray crystallography. The primary phosphines, H2PC6H2R2C≡CR’, are relatively “user-friendly” in that they are not particularly malodorous, they are isolated as solids or highly viscous liquids, and they are stable when stored under N2 in the solid state and in solution. The primary phosphine H2PC6H2iPr2C≡CPh serves as a precursor for a zirconium phosphinidene and for the secondary phosphines RP(H)C6H2iPr2C≡CPh (R = CH2iPr, CH2Ph). Hydrophosphination polymerization gives cyclic P(III)-containing oligomers, which are converted to P(V)-based macromolecules by treatment with sulfur. The oligomers contain ca. 5 to 10 repeat units, and heating to 800 °C gives rise to phosphorus-containing ceramics. The mechanism of hydrophosphination is discussed with the use of DFT calculations.
Making the Adjustment: A Grounded Theory Study of What Works and Does Not Work in Postdivorce Parenting Relationships
Keywords: divorce
parenting

This study contributes to the growing knowledge base on postdivorce parenting. Recognizing the need to facilitate a better understanding of what makes the postdivorce parenting dyad work or not work, this study explored how individuals sustain a parenting relationship with their former partners when the couple relationship ends through separation or divorce. To date, knowledge about couples’ relationships has been absent from clinical approaches to assisting postdivorce parenting relationships and consequently there has been no bridge between the theories and paradigms of the couples’ literature and those of postdivorce parenting. This exploratory study examined the experiences and perspectives of 20 individual parents in Ontario, Canada. Individual interviews were held with each of the participants. The study identified key themes illuminating an emerging understanding of postdivorce relationships. These key themes will assist to better understand the postdivorce parenting relationship. Findings suggest that practitioners should consider that: (a) the postdivorce parenting relationship is highly complex and the development of a “working” or “not working” relationship results from an interaction among a range of factors; (b) understanding couple’s research is essential to comprehending this complexity because, despite the couple relationship ending, former couples remain a dyad because they are parents; (c) even when the postdivorce parenting relationship is “not working”, men and women describe other aspects of their lives as successful. The study’s findings have implications for mental health professionals and legal professionals working with parents during and following the divorce process.
Understanding Biosolids Dynamics in a Moving Bed Biofilm Reactor
Keywords: Biofilm
Detachment
Moving Bed
Modeling
Multivariate
Calcium

Biofilm systems such as the moving bed biofilm reactor (MBBR) are finding increased application in wastewater treatment. One important process that governs MBBRs and yet is poorly understood is the rate of biofilm detachment. The detachment of cells from biofilm surfaces controls both the accumulation of biofilm and the quantity of biomass that is suspended in the bulk liquid phase. This changing balance of attached and suspended cells, in this thesis named the biosolids dynamics, can impact the efficacy of MBBRs. The goal of this research was to investigate how the biosolids dynamics are influenced by process changes relevant to applied wastewater treatment systems and suggest new routes to reactor design and optimization. To achieve this goal, the work addresses three separate but interconnected lines of inquiry. First, multivariate analysis (Principal Component Analysis, Partial Least Squares) was used to examine 2 years of historical data from an MBBR operating at a Canadian pulp mill in order to identify key process variables, perform process diagnostics, and act as a predictive tool. Secondly, the effect of calcium concentration on biofilm structure, microbiology and reactor performance was investigated in four laboratory-scale MBBRs operated at a range of calcium concentrations (1 to 300 mg/L Ca2+). It was found that above a threshold calcium concentration between 1-50 mg/L, MBBR biofilms were observed to be thicker with greater density, contain larger anoxic regions adjacent to the carrier substratum, have more proteinaceous EPS, and have altered microbial community structure. The results suggest an important role for calcium that should be considered in the design and operation of MBBRs. In the final line of inquiry, a diffusion-reaction biofilm model was adapted to represent the key processes of the MBBR. The model was found to simulate average trends observed in the lab-scale experiments allowing for quantification of the detachment rate. Transient periods of reactor starvation were also simulated by introducing a novel metabolic state function to account for down-regulation of metabolism as a result of starvation. This approach was found to accurately simulate starvation response when coupled with detachment expressions that were growth-dependant.