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Linking Preventable Hospitalisation Rates to Neighbourhood Characteristics within OttawaPrud'homme, Geneviève 31 July 2012 (has links)
Enhancing primary care is key to the Canadian health care reform. Considered as an indicator of primary care access and quality, hospitalisations for ambulatory care sensitive (ACS) conditions are commonly reported by Canadian organisations as sentinel events signaling problems with the delivery of primary care. However, the literature calls for further research to identify what lies behind ACS hospitalisation rates in regions with a predominantly urban population benefiting from universal access to health care. A theoretical model was built and, using an ecological design, multiple regressions were implemented to identify which neighbourhood characteristics explained the socio-economic gradient in ACS hospitalisation rates observed in Ottawa. Among these neighbourhoods, healthy behaviour and - to a certain extent - health status were significantly associated with ACS hospitalisation rates. Evidence of an association with primary care accessibility was also signaled for the more rural neighbourhoods. Smoking prevention and cessation campaigns may be the most relevant health care strategies to push forward by policy makers hoping to prevent ACS hospitalisations in Ottawa. From a health care equity perspective, targeting these campaigns to neighbourhoods of low socio-economic status may contribute to closing the gap in ACS hospitalisations described in this current study. Reducing the socio-economic inequalities of neighbourhoods would also contribute to health equity.
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Characterization of enzyme sensitive responsive hydrogel/lipid system for triggered releaseJónsson, Pétur January 2013 (has links)
This master thesis aimed to create and characterize multilayer coatings upon mesoporous silica particles (MSP). The properties of the coating aimed for, was to have a triggerable controlled release, where a targeted enzyme within the intestine, alpha-amylase, is supposed to degrade the coating. The coating was created from a bilayer consisting of DOTAP and DOPC in a 1:3 molar ratio, which serves as a protective coating. The second layer interacting with the surroundings consisted of a starch component, amylopectin, which is degraded by alpha-amylase. The study of the coating was performed with ellipsometry, where the adsorption of the different layers of the coating on a planar silica surface and the enzyme-triggered degradation was recorded. The adsorbed amount of DOTAP/DOPC was 4,22 ± 0,11 mg/m2 and amylopectin 1,82 ± 0,94. The effects of different pH where performed, simulating the coated particle going through the gastro-intestinal system. Two enzymes alpha-amylase and phospholipase A2 (PLA2) where used for degradation of the coating. The knowledge from ellipsometry was applied to coating mesoporous silica particles and it was confirmed that the two layers had formed with zeta- potential measurement.
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Validating Integrated Human Performance Models Involving Time-critical Complex SystemsGore, Brian 29 April 2010 (has links)
The current research sets out to demonstrate a comprehensive approach to validate complex human performance models as applied to time-sensitive tasks. This document is divided into 4 sections. Section 1 (Chapters 1 – 3) outlines previous efforts in the literature that have attempted to validate complex human performance models in the field with an emphasis on manual control models, task network models, cognitive models and integrated architectures. Section 2 (Chapters 4 – 7) elaborates on a validation approach and applies it to a baseline model of a complex task in the air traffic control domain. Section 3 (Chapters 7-12) outlines the importance of adopting an iterative model development-model validation process and reports on the three model iterations in an attempt to improve the validity of the baseline model. Each model augmentation was validated using the same validation approach and measures that were defined in Section 2. Section 4 (Chapters 13-14) provides a discussion and interpretation of the model results and highlights contributions to the field of both model validation and the field of human performance modelling of complex systems.
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Non-viral gene delivery with pH-sensitive gemini nanoparticles : synthesis of gemini surfactant building blocks, characterization and in vitro screening of transfection efficiency and toxicityDonkuru, McDonald 14 January 2009
Research on self-assembling gemini surfactants and other amphiphiles for potential gene delivery applications in research as well as in clinical practice, and as alternatives to viral gene delivery vectors, is beginning to focus more on structureactivity relationships to address the current low gene delivery efficiencies of amphiphiles. Some underlying structureactivity relations are beginning to emerge. But, as a better understanding of the factors that govern the transfection abilities of amphiphile molecules emerges, development of improved non-viral vectors with clinical potential may also emerge.<p>
The research conducted for this thesis was aimed at the design, synthesis and in vitro investigation of gemini surfactants as one of a family of novel amphiphiles being investigated for gene therapeutic applications. The properties of these compounds can be controlled as well as allowed to vary naturally. Gemini surfactant-based gene delivery systems were prepared and characterized for transfer of Luciferase plasmid (pMASIA.Luc) to both COS-7 and PAM 212 cells. Characterization was accomplished using microscopy, dynamic light scattering (DLS) and zeta (ζ) potential analysis. In vitro gene expression and toxicities were evaluated in COS-7 cell and PAM 212 keratinocyte cultures.<p>
The level of in vitro transfection in general was found to correlate strongly with the structure of the gemini surfactants. Among the 12-spacer-12 surfactants, incorporation of a pH-sensitive aza (N-CH3) group, which is also steric hindrance-imposing, in the spacer chain yielded increased transfection, particularly for the 12-7N-12 surfactant. In comparison, the incorporation of the more pH-sensitive imino (N-H) group in the 12-7NH-12 surfactant yielded the highest increase in transfection among the 12-spacer-12 surfactants. The deleterious effect of steric hindrance due to the aza group is more evident when comparing the transfection efficiency of 12-5N-12 (1 × aza, higher) vs. 12-8N-12 (2 × aza, lower transfection). Another highlighted structural feature is provided by the fact that both the 12-7NH-12 and 12-7N-12 surfactants had higher transfection efficiencies than 12-5N-12 and 12-8N-12 surfactants; the first pair has trimethylene spacing, which constitutes an optimal separation between nitrogen centres, while the second pair has shorter dimethylene spacings.<p>
After expanding the structure of surfactants, transfection efficiencies were found to increase in response to increase in hydrocarbon tail length, but were much lower for surfactants with no amino functional groups, those that lacked the optimal trimethylene spacing, or those having both of these limitations in the gemini surfactant spacer. The 18-7NH-18 surfactant had the highest overall transfection in both COS-7 and PAM 212 cells. Gemini surfactant-based gene delivery systems capable of adopting both polymorphic structural phases and which could undergo pH-induced structural transition demonstrated high transfection efficiencies. Gemini surfactants with both characteristics (e.g., 12-7NH-12-based complexes are both polymorphic and pH-sensitive) had higher transfection than gemini surfactants with only one (e.g., 12-3-12-based complexes are only polymorphic).<p>
Overall, the m-7NH-m surfactants, the most efficient surfactants studied, had transfection efficiencies similar to that of the commercial Lipofectamine Plus reagent and imposed no higher toxicity on cells relative to the less efficient surfactants. Thus, the design of the m-7NH-m surfactants to enhance their transfection abilities also ensured that their toxicity to cells were kept minimal. Overall, the design, synthesis and in vitro transfection screening of gemini surfactant candidates has revealed that the m-7NH-m surfactants have the highest transfection efficiencies; they have emerged as suitable candidates for non-viral gene delivery in vivo or at higher levels. Gene delivery investigations for six of the gemini surfactant candidates are being reported for the first time.
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Salt stress tolerance in potato genotypesEtehadnia, Masoomeh 15 September 2009
Soil salinity affects over 20% of the worlds irrigated land. Potato (Solanum tuberosum L.), the most important vegetable crop worldwide, is relatively salt sensitive. However, relatively little work has been done on salt tolerance of the potato plant. This thesis investigated the methodology of treatment application and scion/rootstock effects on subsequent salt stress responses of four contrasting potato genotypes: Norland, 9506, 9120-05 [ABA-deficient mutant], and 9120-18 [ABA-normal sibling] grown hydroponically in sand. The effect of incremental salt stress were studied, using NaCl, CaCl2 and combined NaCl + CaCl2 pre- treatments as well as varying methods of ABA application with a specific focus on the role of rootstock and scion. Physiological responses of various potato genotypes to salt stress differed depending on how the salt stress was applied. An incremental salt stress regime was able to more effectively differentiate genotypes based on salt stress resistance and greater salt tolerance compared to a sudden salt shock. Generally, the ability to produce ABA was positively related to the degree of salt stress resistance, with higher ABA levels induced under incremental salt stress treatments compared to salt shock. The method of ABA application also had a marked effect on potato responses to salt stress. Slowly increasing concentrations of exogenous ABA maintained growth rates, enhanced root water content and induced more lateral shoot growth compared to a single ABA dose. The degree of salt tolerance induced by the grafted rootstock was primarily modulated by salt acclimation and was manifested in the scion as increased water content, stem diameter, dry matter accumulation, stomatal conductivity, and osmotic potential and was associated with reduced leaf necrosis. Using the salt-resistant 9506 line as a scion also significantly increased root fresh and dry weight and stem diameter as well as root water content of salt-sensitive ABA-deficient mutant rootstocks. Exogenous ABA appeared to enhance plant water status via the roots under salt stress beyond that of grafting alone. This was verified by more positive stomatal conductivity and greater upward water flow in ABA treated grafted and non-grafted plants as compared to the absence of upward water flow in non-treated grafted plants as measured via micro NMR imaging. NaCl pre-treatment produced greater salt stress resistance compared to pre-treatment with CaCl2 and was associated with a specific Na+ ion effect rather than a non-specific EC-dependent response. However, the presence of both ABA and CaCl2 appears to be necessary in order to enhance Na+ exclusion from the shoot and increases the K+/Na+ ratio.
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The potential involvement of semicarbazide-sensitive amine oxidase-mediated reactions and aldehyde stress in the aggregation, cytotoxicity and clearance of beta-amyloid related to Alzheimer's diseaseChen, Kun 13 January 2010
Beta-amyloid (Aâ) remains to be the focus of research interest of the pathogenesis of Alzheimers disease (AD). Aâ is subject to oligomerization and its polymers are cytotoxic. Advanced aggregation leads to formation of senile plaques. Depositions of Aâ surrounding the cerebral vasculature, i.e. cerebral amyloid angiopathy (CAA), occur in most AD patients. The occurrence of Aâ aggregation in AD brains is not due to over-expression of amyloid precursor protein in most cases of AD. Factors influencing Aâ polymerization are yet to be established.<p>
Aldehydes are highly reactive. They can cause protein crosslinkage. It is interesting to study whether endogenous aldehydes may be involved in Aâ polymerization process. In order to investigate the potential interaction of endogenous aldehydes with Aâ and their effects on its aggregation, various techniques including thioflavin T fluometry, dynamic light scattering, circular dichroism and atomic force microscopy were employed to assess Aâ aggregation at different stages. Formaldehyde, methylglyoxal, malondialdehyde and 4-hydroxyl-nonenal were found to enhance Aâ â-sheets formation, oligomerization and fibrillogenesis in vitro. The sizes of the oligomers are increased after interaction with the aldehydes. Lysine residues of Aâ were identified to be the primary site of interaction with aldehydes by forming Schiff bases, which may subsequently lead to intra- and inter-molecular crosslinkage. Aldehydes can also crosslink Aâ with other proteins such as apolipoprotein E and á2-macroglobulin (á2M), to form large complexes. Results suggest that aldehydes substantially increase the rate of Aâ oligomerization at each stage of fibrillogenesis.<p>
The native and formaldehyde-modified Aâ oligomers were isolated by size exclusion chromatography and their cytotoxic effects towards SH-SY5Y neuroblastoma cells were assessed using MTT, LDH and caspase-3 activity assays. The aldehyde-modified oligomers are slightly but significantly more cytotoxic compared to the native oligomers. Since aldehydes significantly increase the production of Aâ oligomers, an increase in aldehydes would enhance the total cytotoxicity, suggesting that aldehydes may potentially exacerbate neurovascular damage and neurodegeneration caused by Aâ.<p>
Low-density lipoprotein receptor related protein-1 (LRP-1) plays a crucial role in Aâ clearance via the cerebral vasculature. Semicarbazide-sensitive amine oxidase (SSAO) and LRP-1 are both richly expressed on the vascular smooth muscle cells (VSMCs). We demonstrated that SSAO-mediated deamination affects LRP-1 function using isolated VSMCs. Formaldehyde at low concentrations decreases LRP-1-mediated uptake of á2M, a substrate of LRP-1 and a carrier for Aâ. Methylamine, an SSAO substrate that is converted to formaldehyde, also inactivates LRP-1 function, but not in the presence of an SSAO inhibitor. Increased SSAO-mediated deamination can potentially impair Aâ clearance via LRP-1.<p>
In conclusion, aldehydes derived from oxidative stress and SSAO-mediated deamination induce Aâ aggregation, enhance Aâ cytotoxicity and impair Aâ clearance. The exclusive localization of SSAO on the cerebral vasculature may be responsible for the perivascular deposition of Aâ, i.e. CAA, which is associated both with vascular dementia and with AD. Vascular surface SSAO may be a novel pharmacological target for the treatment of AD.
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Validating Integrated Human Performance Models Involving Time-critical Complex SystemsGore, Brian 29 April 2010 (has links)
The current research sets out to demonstrate a comprehensive approach to validate complex human performance models as applied to time-sensitive tasks. This document is divided into 4 sections. Section 1 (Chapters 1 – 3) outlines previous efforts in the literature that have attempted to validate complex human performance models in the field with an emphasis on manual control models, task network models, cognitive models and integrated architectures. Section 2 (Chapters 4 – 7) elaborates on a validation approach and applies it to a baseline model of a complex task in the air traffic control domain. Section 3 (Chapters 7-12) outlines the importance of adopting an iterative model development-model validation process and reports on the three model iterations in an attempt to improve the validity of the baseline model. Each model augmentation was validated using the same validation approach and measures that were defined in Section 2. Section 4 (Chapters 13-14) provides a discussion and interpretation of the model results and highlights contributions to the field of both model validation and the field of human performance modelling of complex systems.
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Performance Improvement of Latex-based PSAs Using Polymer Microstructure ControlQie, Lili 02 February 2011 (has links)
This thesis aims to improve the performance of latex-based pressure-sensitive adhesives (PSAs). PSA performance is usually evaluated by tack, peel strength and shear strength. Tack and peel strength characterize a PSA’s bonding strength to a substrate while shear strength reflects a PSA’s capability to resist shear deformation. In general, increasing shear strength leads to a decrease in tack and peel strength. While there are several commercial PSA synthesis methods, the two most important methods consist of either solvent-based or latex-based techniques. While latex-based PSAs are more environmentally compliant than solvent-based PSAs, they tend to have much lower shear strength, at similar tack and peel strength levels. Therefore, the goal in this thesis was to greatly improve the shear strength of latex-based PSAs at little to no sacrifice to tack and peel strength.
In this study, controlling the polymer microstructure of latexes or their corresponding PSA films was used as the main method for improving the PSA performance. The research was sub-divided into four parts. First, the influence of chain transfer agent (CTA) and cross-linker on latex polymer microstructure was studied via seeded semi-batch emulsion polymerization of butyl acrylate (BA) and methyl methacrylate (MMA). Three techniques were used to produce the latexes: (1) adding CTA only, (2) adding cross-linker only, and (3) adding both CTA and cross-linker. It was found that using CTA and cross-linker simultaneously allows one to expand the range of latex microstructural possibilities. For example, latexes with similar gel contents but different Mc (molecular weight between cross-links) and Mw (molecular weight of sol polymers) could be produced if CTA and cross-linker concentration are both increased. However, for the corresponding PSAs with similar gel contents, the relationship between their polymer microstructure and performance was difficult to establish as almost all of the medium and high gel content PSAs showed very low tack and peel strength as well as extremely large shear strength readings.
In the second part of this thesis, in order to improve the tack and peel strength of medium and high gel content PSAs, the monomer composition and emulsifier concentration were varied. It was found that changing the monomer mixture from BA/MMA to BA/acrylic acid (AA)/2-hydroxyethyl methacrylate (HEMA) while simultaneously decreasing emulsifier concentration dramatically improved the corresponding PSAs’ shear strength as well as tack and peel strength. The addition of polar groups to the PSA increased its cohesive strength due to the presence of strong hydrogen bonding; meanwhile, PSA films’ surface tension increased.
In the third part, two series of BA/AA/HEMA latexes were generated by varying the amounts of CTA either in the absence or presence of cross-linker. The latexes produced in the absence of cross-linker exhibited significantly larger Mc and Mw compared to their counterparts with similar gel contents prepared with cross-linker. The PSAs with the larger Mc and Mw showed much larger shear strengths due to improved entanglements between the polymer chains.
In the final part of the thesis, the performance of the BA/AA/HEMA PSAs was further improved by post-heating. Compared with original latex-based PSAs with similar gel contents, heat-treated PSAs showed not only significantly improved shear strengths, but also much larger tack and peel strengths. The different shear strengths were related to the PSAs’ gel structures, which were discrete in the original PSAs but continuous in the heat-treated PSAs. The improved tack and peel strengths were related to the PSA films’ surface smoothness. During the post-heating process, the PSA polymer flowed, resulting in much smoother surfaces than the original PSA films. In addition, the effect of post-heating was related to the polymer microstructure of the untreated PSAs. Decreasing the amount of very small or very big polymers or simultaneously increasing Mc and Mw could lead to post-treated PSAs with significantly better performance. Moreover, it was found that by optimizing the polymer microstructure of the original latex-based PSAs, it was possible to obtain a treated PSA with similar or even better performance than a solvent-based PSA with similar polymer microstructure.
Our original objective was surpassed: in two cases, not only was shear strength greatly improved, but so were tack and peel strength due to the simultaneous modification of PSA bulk and surface properties.
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Dynamic Composition and Management of Virtual Devices for Ad Hoc Multimedia Service DeliveryKarmouch, Eric 30 March 2011 (has links)
Pervasive computing implies the invisibility of the technology involved in providing ubiquity, such that technology is integrated into the environment and non-intrusive. In such a manner, computing and networking resources become diffused into physical environments, enabling users to exploit their provided functionalities such that functionality is distributed, enabling it to be controlled, monitored, managed, and extended beyond what it was initially designed to do. Moreover, computer awareness moves towards user-centricity, whereby systems seamlessly adapt to the characteristics, preferences, and current situations of users and their respective surrounding environments. Users exploit such functionalities in the form of a virtual device, whereby a collection of heterogeneous devices in the vicinity of the user are behaving as one single homogeneous device for the benefit of the user in solving some given task.
This dissertation investigates the problem of dynamic composition and management of virtual devices for ad hoc multimedia service delivery and proposes an autonomous policy driven framework for virtual device management. The framework consists of a hierarchical structure of distributed elements, including autonomic elements, all working towards the self-management of virtual devices. The research presented in this dissertation addresses the functionalities of these components.
More specifically, contributions are made towards the autonomous management of virtual devices, moving away from infrastructure based schemes with heavy user involvement to decentralized and zero touch (i.e., no user involvement) solutions. In doing so, the components and methodology behind a policy-driven autonomous framework for the dynamic discovery, selection, and composition of multimodal multi-device services are presented. The framework operates in an ad hoc network setting and introduces a Service Overlay Network (SON) based definition of a virtual device.
Furthermore, device and service discovery, composition, integration, and adaptation schemes are designed for Mobile Ad hoc Network Environments (MANETs) enabling users to generate, on-the-fly, complex strong specific systems, embedding in a distributed manner, QoS models providing compositions that form the best possible virtual device at the time of need.
Experimental studies are presented to demonstrate the performance of the proposed schemes.
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Epithelial Sodium Channels in the Brain: Effect of High Salt Diet on Their ExpressionAmin, Md. Shahrier 28 June 2011 (has links)
Statement of the problem: The epithelial sodium channels (ENaC) play an important role in regulation of blood pressure (BP). Although the genes are identical in Dahl salt sensitive (S) and Dahl salt resistant (R) rats, expression of ENaC subunits is increased in kidneys of S rats on high salt diet. Intracerebroventricular (icv) infusion of ENaC blocker benzamil prevents Na+ induced hypertension. It was not known whether ENaC subunits are expressed in the brain and whether or not brain ENaC plays a role in regulation of [Na+] in CNS.
Hypothesis: 1. Epithelial sodium channels are expressed in the brain. 2. Expression of ENaC is increased in the kidneys and brain of Dahl S rats on high salt diet. 3. ENaC in the brain contributes to regulation of [Na+] in the CSF and brain interstitium.
Methods of investigation: We studied expression and distribution of the ENaC subunits and assessed the effects of icv infusion of Na+-rich aCSF in Wistar rats or high salt diet in Dahl S rats in different areas of the brain. Function of ENaC in the choroid plexus was evaluated by studying the effects of benzamil and ouabain on Na+ transport.
Major findings: In Wistar rats, both mRNA and protein of all three ENaC subunits are expressed in brain epithelia and magnocellular neurons in the supraoptic (SON) and paraventricular (PVN) nucleus. ENaC abundance is higher on the apical versus basolateral membrane of choroid cells. Benzamil decreases Na+ influx into choroid cells by 20-30% and increases CSF [Na+] by ~8 mmol/L. Na+ rich aCSF increases apical membrane expression of βENaC in the choroid cells and of α and βENaC in basolateral membrane of ependymal cells, but has no effect on neuronal ENaC. Expression of ENaC is higher in choroid cells and SON of Dahl S versus R rats and the higher expression persists on a high salt diet. High salt attenuates the ouabain blockable efflux of Na+ from choroid cells and has no effect on CSF [Na+] in Dahl R rats. In contrast, high salt does not attenuate ouabain blockable efflux of 22Na+ and CSF [Na+] increases in Dahl S.
Main Conclusion: ENaC in the brain contributes to Na+ transport into the choroid cells and appear to be involved in reabsorption of Na+ from the CSF. Aberrant regulation of Na+ transport and of Na+K+ATPase activity, might contribute to increases in CSF [Na+] in Dahl S rats on high-salt diet. ENaC in magnocellular neurons may contribute to enhanced secretion of mediators such as ‘ouabain’ leading to sympathetic hyperactivity in Dahl S rats.
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