Thesis (doctoral)--Lund University, 1993. / Added t.p. with thesis statement inserted.

Thesis (Ph. D.)--Biomedical Engineering, Georgia Institute of Technology, 2006. / Vito, Raymond, Committee Member ; Nerem, Robert, Committee Chair ; Eskin, Suzanne, Committee Member ; Hanson, Stephen, Committee Member ; Gibbons, Gary, Committee Member.

Small vessel disease (SVD) accounts for approximately 25% of all strokes and 45% of all dementias. Although the small vessels cannot be visualised with conventional neuroimaging, the pathological changes in the cerebral white and deep grey matter secondary to SVD has been adopted as markers of SVD. These are best appreciated with magnetic resonance imaging (MRI) and includes recent small subcortical infarcts, white matter hyperintensity (WMH), lacunes, cerebral microbleeds and enlarged perivascular spaces (PVSs). There are however a number of outstanding questions regarding these surrogate neuroimaging markers of SVD and how these markers may influence clinical management. First, although a high burden of microbleeds have been associated with an increased risk of intracerebral haemorrhage (ICH) and possibly recurrent ischaemic stroke in patients with TIA or ischaemic stroke, how microbleeds should influence antithrombotic treatment use after TIA or ischaemic stroke remains uncertain. Second, the long-term prognostic implications of enlarged PVSs in patients with TIA or ischaemic stroke have not been studied. Third, although previous studies have shown possible ethnic differences in prevalence of microbleeds, whether there are any ethnic differences in prevalence of other neuroimaging markers of SVD remains unclear. Fourth, although a Total SVD Score was recently proposed to measure the global SVD burden, the prognostic value of this score in patients with TIA or ischaemic stroke has yet to be studied. Fifth, the relationships of long-term premorbid blood pressure with global SVD burden is unknown. Finally, the age and sex specific associations between renal impairment, carotid and cerebral pulsatility with burden of SVD has yet to be studied. The aim of my thesis was therefore to determine the clinical correlates, ethnic differences and long-term prognostic implications of a range of neuroimaging markers and global burden of SVD. I also aimed to determine the relationships of global SVD burden with long-term mean premorbid blood pressure, renal impairment and carotid pulsatiltiy. I have collected, collated and analysed clinical and neuroimaging data from two independent cohorts - the Oxford Vascular Study (OXVASC) and The University of Hong Kong (HKU). In particular I worked as one of the Clinical Research Fellows at OXVASC and was involved in regular recruitment, assessment and follow up of study patients. In OXVASC, 1080 predominantly Caucasians with TIA or ischaemic stroke who had a cerebral MRI performed at baseline was recruited during 2004 to 2014. I interpreted all these MRIs, specifically coding the burden of microbleeds, enlarged perivascular spaces and lacunes. I was involved in obtaining funding and developing the HKU cohort, which includes 1003 predominantly Chinese with ischaemic stroke recruited during 2008-2014 who had a cerebral MRI performed at baseline. I saw about 25% of the patients in the cohort and was involved in interpreting all of the MRIs of the cohort. All patients from both cohorts were followed-up regularly and adverse events including recurrent ischaemic stroke and ICH was determined. Presence and burden of periventricular and subcortical WMH, lacunes, microbleeds, basal ganglia and centrum semiovale PVSs was determined for all patients and the global burden of SVD estimated according to the Total SVD Score. There are several clinically relevant findings in this thesis. First, I have shown that in Caucasians and Chinese with ≥5 microbleeds, withholding antiplatelet drugs during the first year after TIA or ischaemic stroke may be inappropriate, especially early after TIA. However, the risk of ICH is likely to outweigh any benefit thereafter. Second, I have shown that TIA or ischaemic stroke patients with microbleeds on warfarin had an increased risk of subsequent ICH. However, this risk was not different from that of antiplatelet users with microbleeds. Third, I have shown that a high burden of MRI-visible basal ganglia PVSs is independently associated with an increased risk of recurrent ischaemic stroke, but not ICH. However, the prognostic value of MRI-visible centrum semiovale PVSs in the TIA or ischaemic stroke population is limited. Fourth, I demonstrated significant ethnic differences in underlying prevalence and burden of neuroimaging markers of SVD - Chinese had a greater prevalence of microbleeds, lacunes and subcortical WMH, whilst Caucasians had a greater prevalence of periventricular WMH and PVSs. Fifth, I validated the Total SVD Score and showed that the SVD Score is able to predict risk of recurrent ischaemic stroke and ICH in Caucasians and Chinese, but is unable to identify patients at high risk of ICH from those at high risk of recurrent ischaemic stroke. Sixth, I showed that mean premorbid blood pressure, especially diastolic blood pressure measurements taken 10-20 years prior to TIA or ischaemic stroke was most strongly associated with global SVD burden suggesting a latency effect of hypertension on the pathogenesis of SVD. Finally, I demonstrated age-specific associations between renal impairment, internal carotid artery pulsatility index and SVD burden.

Orientador: Fernando de Azevedo Silva / Banca: Alvaro Manoel de Souza Soares / Banca: Silvana Aparecida Barbosa / Resumo: Este trabalho estuda a distribuição de tensões através do método dos elementos finitos em componentes típicos de um vaso de pressão. As diretrizes e metodologia utilizadas nas análises estão de acordo com o código ASME. O vaso de pressão foi estudado para suportar as cargas mais comuns previstas em um projeto de equipamento de processo deste porte. As análises numéricas foram feitas com o software comercial ANSYS e comparados com resultados analíticos previstos no código ASME para os casos mais simples, onde foi obtida a validação dos resultados. Os casos mais complexos foram analisados apenas por soluções numéricas. Todos os casos obtiveram resultados abaixo das tensões admissíveis e de acordo com a metodologia do código, confirmando a viabilidade de análises deste tipo para os casos onde a solução analítica se torna muito conservativa. / Abstract: Riveted lap joints represent a critical element in metallic airframe construction when designing against fatigue. These elements are widely used in the aerospace industry, so the study of the fatigue's properties and variables has been increasingly broad. The variable that has shown to have a high influence on the fatigue strength of riveted joints is the clamping force applied to the riveting process. The life of the part tends to be higher when the clamping force applied is increased. The finite element method, which is a calculation tool applied in various fields of activity and has become an indispensable step of mechanical design, is used in this dissertation for the analysis of a riveted lap joint of aeronautic use. The joint is simulated considering the stages of the manufacturing process and application, in order to perform analysis of mechanical behavior and calculate the fatigue life. Through an experimental test of monotonic tensile, strain values were obtained with strain-gauges, and is made the correlation of these data with the numerical model to validate the modeling. Finally two more tests are made with different clamping forces, in order to check the influence of this variation in fatigue life of the joint. / Mestre

My thesis deals with the design of an experimental emergency cooling device of the reactor pressure vessel (RPV). It consists of two parts, the theoretical one and practical one. Different molten corium cooling methods in terms of their efficiency and comparison are introduced in the theoretical part. The design of an experimental emergency cooling device, which incorporates a model channel past the reactor pressure vessel , is presented in the practical part. The cooling device consists of a model channel past the reactor pressure vessel, condensator, which takes away the heat generated by the reactor pressure vessel and the pump of a secondary loop. Next, thermal and hydraulic calculations are given in this section. The conclusion is devoted to the evaluation of particular cooling technologies and their comparison in terms of nuclear and technical safety.

The Tissue Engineering Research Lab at California Polytechnic State University, San Luis Obispo focuses on creating tissue-engineered blood vessel mimics (BVMs) for use in preclinical testing of vascular devices. These BVMs are composed of electrospun scaffolds made of an assortment of polymers that are seeded with different cell types. This integration of polymers with cells leads to the need for biocompatibility testing of the polymer scaffolds. Many of the lab’s newest scaffolds have not been fully characterized for biologic interactions. Therefore, the first aim of this thesis developed methods for in vitro cytotoxicity testing of polymers used in the fabrication of BVMs. This included cytotoxicity testing using direct contact and elution-based methods, along with fluorescent staining to visualize the scaffold effects on cells. The second aim of this thesis implemented the newly developed cytotoxicity protocols to evaluate the biocompatibility of existing polymers, ePTFE and PLGA, used in the tissue engineering lab. The results demonstrated that ePTFE and PLGA were noncytotoxic to cells. The third aim of this thesis evaluated the biocompatibility of novel polymers used to fabricate BVMs: PLGA with salt, PLLA, and PCL. Elution-based methods concluded that PLGA with salt, PLLA, and PCL were noncytotoxic to cells; however, the direct contact method illustrated PLGA with salt and PCL were mildly cytotoxic at 24 and 48 hours. Potential causes of this variability include the addition of salt to PLGA, dissolving PCL in dichloromethane, inadequate sample sizing, and the inherent differences between the test methods. Overall, this thesis developed and implemented methods to evaluate the biocompatibility of polymer scaffolds used in the BVM model, and found that ePTFE, PLGA, and PLLA scaffold materials were biocompatible and could be implemented in future BVM setups without concerns. Meanwhile, PLGA with salt and PCL’s toxicity was mild enough to urge future cytotoxicity testing on PLGA with salt and PCL before further use in the lab.

No description available.

In treating cancer with hyperthermia, an understanding of the heat losses associated with the presence of a large functioning blood vessel in or proximal to a treatment area is needed in order to optimize any protocol. A three-dimensional computer model based on the Bioheat transfer equation (BHTE) has been developed to account for temperature changes in and around functioning blood vessels during laser-induced hyperthermia. The light source is modelled using an approximation to the transport theory solution for an isotropic point source in an infinite homogeneous tissue medium with anistropic scattering. The derived BHTE's for tissue, vessel and blood are solved for temperature using the implicit finite differences method. The validity of the model was tested by comparing predicted temperatures to measured temperatures from a series of dynamic phantom studies using two vessel diameters and three flow rates. Large experimental temperature variations were observed and increased proportionally with increasing thermal gradients. The model consistently over-estimates (~ 1-2C) absolute temperatures close to the source and under-estimates (~ 1-2C) them far from the source. This could be due to uncertainties associated with the estimated thermal conductivity and measured optical properties of the tissue material. Both model and experiments show a small convective heat loss due to the presence of a blood vessel. The model predicts that at high flow rates, temperature reductions of 2C or greater are limited to distances less than 0.3 cm from the surface of a 0.144 cm (outer diameter) vessel and less than 0.8 cm from the surface of a 0.40 cm vessel. The vessel has a negligible effect on temperatures at distances greater than ~ 1.75 cm. The predicted temperature change due to blood flow and the measured change agree to within experimental errors. There was better agreement with the larger diameter vessel. / Thesis / Master of Science (MS)

A major limitation in tissue engineering is the lack of nondestructive methods to assess the development of tissue scaffolds undergoing preconditioning in bioreactors. Due to significant optical scattering in most scaffolding materials, current microscope-based imaging methods cannot "see" through thick and optically opaque tissue constructs. To address this deficiency, we developed a scanning fiber imaging method capable of nondestructive imaging of fluorescently labeled cells through a thick and optically opaque vascular scaffold, contained in a bioreactor. This imaging modality is based on local excitation of fluorescent cells, acquisition of fluorescence through the scaffold, and fluorescence mapping based on the position of the excitation light. To evaluate the capability and accuracy of the imaging system, human endothelial cells, stably expressing green fluorescent protein (GFP), were imaged through a fibrous scaffold. Without sacrificing the scaffolds, we nondestructively visualized the distribution of GFP-labeled endothelial cells on the luminal surface through a ~500 µm thick tubular scaffold at cell-level resolutions and distinct localization. These results were similar to control images obtained using an optical microscope with direct line-of-sight access. Through a detailed quantitative analysis, we demonstrated that this method achieved a resolution of the order of 20-30 µm, with 10% or less deviation from standard optical microscopy. Furthermore, we demonstrated that the penetration depth of the imaging method exceeded that of confocal laser scanning microscopy by more than a factor of 2. Our imaging method also possesses a working distance (up to 8 cm) much longer than that of a standard confocal microscopy system, which can significantly facilitate bioreactor integration. This method will enable nondestructive monitoring of endothelial cells seeded on the lumen of a tissue-engineered vascular graft during preconditioning in vitro, as well as for other tissue-engineered constructs in the future. / Ph. D.

Considering the unlikely core melt down scenario for a light water reactor (LWR) a possible failure mode of the reactor pressure vessel (RPV) and its failure time has to be investigated for a determination of the loadings on the containment. Worldwide several experiments have been performed accompanied with material properties evaluation, theoretical, and numerical work. At the Institute of Safety Research of the FZR a finite element model has been de-veloped simulating the thermal processes and the viscoplastic behaviour of the ves-sel wall. An advanced model for creep and material damage has been established and has been validated using experimental data. The thermal and the mechanical calculations are sequentially and recursively coupled. The model is capable of evalu-ating fracture time and fracture position of a vessel with an internally heated melt pool. The model was applied to pre- and post test calculations for the FOREVER test se-ries representing the lower head RPV of a PWR in the geometrical scale of 1:10. These experiments were performed at the Royal Institute of Technology in Stock-holm. The results of the calculations can be summarised as follows: # The creeping process is caused by the simultaneous presence of high tem-perature (>600 °C) and pressure (>1 MPa) # The hot focus region is the most endangered zone exhibiting the highest creep strain rates. # The exact level of temperature and pressure has an influence on the vessel failure time but not on the failure position # The failure time can be predicted with an uncertainty of 20 to 25%. This uncer-tainty is caused by the large scatter and the high temperature sensitivity of the viscoplastic properties of the RPV steel. # Contrary to the hot focus region, the lower centre of the vessel head exhibits a higher strength because of the lower temperatures in this zone. The lower part moves down without significant deformation. Therefore it can be assumed, that the vessel failure can be retarded or prevented by supporting this range. # The development of a gap between melt crust and vessel wall could not be proofed. First calculations for a PWR geometry were performed to work out differences and commonalities between prototypic scenarios and scaled experiments. The results of the FOREVER-experiments cannot be transferred directly to PWR geometry. The geometrical, mechanical and thermal relations cannot be scaled in the same way. Because of the significantly higher temperature level, a partial ablation of the vessel wall has to be to expected in the PWR scenario, which is not the case in the FOREVER tests. But nevertheless the FOREVER tests are the only integral in-vessel retention experiments up to now and they led to a number of important insights about the behaviour of a vessel under the loading of a melt pool and pressure.