Conclusions 1. In comparison to the Ringer‘s acetate solution the use of HyperHaes® solution after coronary artery bypass surgery had positive effect on haemodynamic parameters: cardiac index increased (p<0.05), systolic volume index increased (p<0.05), cardiac afterload decreased, that is pulmonary vascular resistance index decreased (p<0.05) and systemic vascular resistance index decreased (p<0.05); the difference between the central and peripheral temperatures in experimental group (p<0.05). 2. The oxygen transport was more effective (oxygen delivery index increased (p<0.05)) when HyperHaes® solution was used in comparison to Ringer‘s acetate solution. 3. No substantial effect of HyperHaes® solution on the duration of artificial lung ventilation and intrapulmonary shunt size was defined. 4. The use of HyperHaes® solution influenced substantially some parameters of homeostasis (serum sodium concentration increased (p<0.05), serum potassium concentration decreased (p<0.05)) in compa-rison to Ringer‘s acetate solution. 5. Higher diuresis (p<0.01), lower need for the infusion therapy for the first 24 hours (p<0.05), lower total fluid balance (p<0.01) were determined in HyperHaes® group versus Ringer‘s acetate group. 6. No adverse effects (disturbances of homeostasis, neurologic symptoms, increased bleeding through mediastinal tubes, anaphylactic reactions) were noted in patients who received HyperHaes® solution.

Sarcolemmal chloride channels and associated cell volume regulatory pathways have been shown to be important in local ischemic preconditioning (IPC) induced protection against myocardial ischemia/reperfusion injury. Similarities between intracellular pathways in remote (rIPC) and classic IPC suggest that these mechanisms may also play an important role in rIPC. rIPC protected cultured rabbit ventricular cardiomyocytes against necrosis caused by 75 minutes simulated ischemia followed by 60 minutes simulated reperfusion. The protective effect was abolished by chloride channel blockade using 50 μM indanyloxyacetic acid 94 (IAA-94). rIPC also reduced peak cardiomyocyte swelling during exposure to 200 mOsm hypo-osmotic buffer. The reduction in peak swelling was also abolished by IAA-94. These results suggest that the protective effect of rIPC is achieved, at least in part, by enhancing cell volume regulation and that this effect is dependent on the availability of chloride channels in a similar fashion to local IPC.

The incidence of differentiated thyroid cancer (DTC) is rising, but controversy exists in many aspects of its treatment. This study described the change in incidence of DTC in Ontario, variations in management including extent of thyroidectomy and the influence of provider volume, and the impact of these parameters on recurrence and thyroid cancer-specific death (TCSD). A population-based study identified all new cases of DTC between 1992-2007. The incidence of DTC increased dramatically (annual percentage change 7.6%). Linkage to administrative databases revealed that extent of thyroidectomy is influenced by various factors including patient gender, age, year of diagnosis, surgeon specialty, and hospital setting, but not provider volume. Total thyroidectomy is associated with a lower recurrence rate. There is a significant association between provider volume and recurrence, with lower volume surgeons having a higher recurrence risk. Extent of thyroidectomy and provider volume did not influence TCSD. Such variations in management may lead to disparities in health outcomes.

Sarcolemmal chloride channels and associated cell volume regulatory pathways have been shown to be important in local ischemic preconditioning (IPC) induced protection against myocardial ischemia/reperfusion injury. Similarities between intracellular pathways in remote (rIPC) and classic IPC suggest that these mechanisms may also play an important role in rIPC. rIPC protected cultured rabbit ventricular cardiomyocytes against necrosis caused by 75 minutes simulated ischemia followed by 60 minutes simulated reperfusion. The protective effect was abolished by chloride channel blockade using 50 μM indanyloxyacetic acid 94 (IAA-94). rIPC also reduced peak cardiomyocyte swelling during exposure to 200 mOsm hypo-osmotic buffer. The reduction in peak swelling was also abolished by IAA-94. These results suggest that the protective effect of rIPC is achieved, at least in part, by enhancing cell volume regulation and that this effect is dependent on the availability of chloride channels in a similar fashion to local IPC.

The incidence of differentiated thyroid cancer (DTC) is rising, but controversy exists in many aspects of its treatment. This study described the change in incidence of DTC in Ontario, variations in management including extent of thyroidectomy and the influence of provider volume, and the impact of these parameters on recurrence and thyroid cancer-specific death (TCSD). A population-based study identified all new cases of DTC between 1992-2007. The incidence of DTC increased dramatically (annual percentage change 7.6%). Linkage to administrative databases revealed that extent of thyroidectomy is influenced by various factors including patient gender, age, year of diagnosis, surgeon specialty, and hospital setting, but not provider volume. Total thyroidectomy is associated with a lower recurrence rate. There is a significant association between provider volume and recurrence, with lower volume surgeons having a higher recurrence risk. Extent of thyroidectomy and provider volume did not influence TCSD. Such variations in management may lead to disparities in health outcomes.

Protein folding is the process during which an extended and unstructured polypeptide converts to its compact folded structure that is most often the functional state. The process has been characterized extensively in dilute buffer in-vitro during the last decades but the actual biological place for this process is the inside of living cells. The cytoplasm of a cell is filled with a plethora of different macromolecules that together occupy up to 40% of the total volume. This large amount of macromolecules restricts the available space to each individual molecule, which has been termed macromolecular crowding. Macromolecular crowding results in excluded volume effects and also increases chances for non-specific interactions. Macromolecular crowding should favor reactions that lead to a decrease in the total occupied volume by all molecules, such as folding reactions. Theoretical models have predicted that the stability of protein folded states should increase in presence of macromolecular crowding due to unfavorable effects on the extended unfolded state. To understand protein folding and function in living systems, we need to have a defined quantitative link between in-vitro dilute conditions (where most biophysical experiments are made) and in-vivo crowded conditions. An important question is thus how macromolecular crowding modifies the biophysical properties of a protein. The work underlying this thesis focused on how macromolecular crowding tunes protein equilibrium stability and kinetic folding processes. To mimic the crowded cellular environment, synthetic sugar-based polymers (Dextrans of different sizes and Ficoll 70) were used as crowding agents (crowders) in controlled in-vitro experiments. In contrast to previous studies which often have focused on one protein and one crowder at a time, the goal here was to make systematic analyses of how size, shape and concentration of the crowders affect both equilibrium and kinetic properties of structurally-different proteins. Three model proteins (cytochrome c, apoazurin and apoflavodoxin) were investigated under crowding by Ficoll 70 and different-size Dextrans, using various spectroscopic techniques such as far-UV circular dichroism and intrinsic tryptophan fluorescence. Thermodynamic models were applied to explain the experimental results. It was discovered that equilibrium stability of all three proteins increased in presence of crowding agents in a crowder concentration dependent manner. The stabilization effect was around 2-3 kJ/mol, larger for the various Dextrans than for Ficoll 70 at the same g/l, but independent of Dextran size (in the range 20 to 70 kDa). To further investigate the cause for the stabilization a theoretical crowding model was applied. In this model, Dextran and Ficoll were modeled as elongated rods and the protein was represented as a sphere, where the folded sphere representation was smaller than the unfolded sphere representation. It is notable that the observed stability changes could be reproduced by this model taking only steric interactions into account. This correlation showed that when using sugar-based crowding agents, excluded volume effects could be studied in isolation and there were no contributions from nonspecific interactions. Time-resolved experiments with apoazurin and apoflavodoxin revealed an increase in the folding rate constants while the unfolding rates were invariant in the presence of crowding agents. For apoflavodoxin and cytochrome c, the presence of crowding agents also altered the folding pathway such that it became more homogeneous (cytochrome c) and it gave less misfolding (apoflavodoxin). These results showed that macromolecular crowding restricts the conformational space of the unfolded polypeptide chain, makes the conformations more compact which, in turn, eliminates access to certain pathways. The results from kinetic and equilibrium measurements on three model proteins, together with available data from the literature, demonstrate that macromolecular crowding effects due to volume exclusion are in the order of a few kJ/mol. Considering the numerous concentration balances and cross-dependent reactions of the cellular machinery, small changes in energetics/kinetics of the magnitudes found here can still have dramatic consequences for cellular fitness. In fact local and transient changes in macromolecular crowding levels may be a way to tune biochemical reactions without invoking gene expression.

The physico-chemical characteristics of soymilk particles and the gelation properties of soymilk were investigated as a function of soymilk protein concentration, by preparing soymilk samples from different water-to-bean ratios. Particles from different soymilk protein concentrations showed similar protein composition and surface hydrophobicity, but different -potential, size and protein content. The particle voluminosity was derived using a relation between the effective refractive index of soymilk and the turbidity parameter determined experimentally. For the first time, experimental data was compared to theoretical models, drawing general conclusions about colloidal properties of soymilk particles. Protein concentration and the rate of acidification did not have a significant effect on the acid-induced gelation of soymilk. Results demonstrated that decreased charge is a prerequisite for particle aggregation, which is driven by hydrogen bridging. This thesis provides soymilk processors with general principles on the colloidal behaviour of soymilk, valuable information for new product development and better process design. / Soybean Growers of Ontario, Natural Sciences and Engineering Research Council of Canada

Transformation induced plasticity (TRIP) steels are a class of steels with exceptional formability properties, due mainly to the presence of meta-stable retained austenite which transforms to martensite under loading, locally hardening the steel. The volume fraction and mechanical stability of the retained austenite play an important role in producing the high formabilities of TRIP steels. In this thesis, two separate morphologies of retained austenite, equiaxed versus lamellar, have been produced through thermo-mechanical processing of a single common TRIP steel chemistry. The sheet formability characteristics of these two microstructures were examined, with varying volume fractions of retained austenite, through uniaxial tensile and in-plane plane-strain (IPPS) testing. It was found that higher levels of retained austenite produced better formability properties for both microstructures and strain paths. In uniaxial tension it was seen that the the lamellar microstructure attained higher strains at maximum load, and exhibited more sustained instantaneous n values than the equiaxed structure, despite having a lower volume fraction of retained austenite. IPPS testing was performed using an optical measurement of local strain and a comparative forming limit based on differences in strain rate between a developing neck and the surrounding material. It was found that the lamellar microstructure performed better than the equiaxed microstructure for this strain path, achieving higher strains before reaching the comparative forming limit. / Thesis (Master, Mechanical and Materials Engineering) -- Queen's University, 2010-01-25 16:36:07.598

MRI-guided prostate needle biopsy requires compensation for organ motion between target planning and needle placement. Two questions are studied and answered in this work: is rigid registration sufficient in tracking the targets with a maximum error of 3 mm (smaller than average prostate tumor size) and how many intra-operative slices are required to obtain this accuracy? We developed rigid and deformable multislice- to-volume registration algorithms for tracking the biopsy targets within the prostate. Three orthogonal plus additional transverse intra-operative slices were acquired in the approximate center of the prostate and registered with a high-resolution target planning volume. Simulated intra-operative data, phantom data, and MRI-guided robotic prostate biopsy data were used to assess tracking accuracy. Registration tests on simulated intra-operative data with 3, 4, and 5 slices were performed to evaluate the effect on registration error and time. Results: Using three orthogonal slices pro- vides sufficient accuracy. Convergence test results on phantom images demonstrated 100% success rate for initial misalignment of 5mm. Average registration errors for the patient data were 2.55mm and 2.05mm for the rigid and deformable algorithms, respectively. The algorithm was able to capture rigid biopsy target displacements of maximum 8mm and non-rigid displacements of maximum 1.5mm. Rigid tracking appears to be promising. Deformable registration does not seem warranted. / Thesis (Master, Electrical & Computer Engineering) -- Queen's University, 2010-07-13 16:41:52.223

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