京都大学 / 0048 / 新制・課程博士 / 博士(エネルギー科学) / 甲第22672号 / エネ博第404号 / 新制||エネ||77(附属図書館) / 京都大学大学院エネルギー科学研究科エネルギー変換科学専攻 / (主査)准教授 森下 和功, 教授 星出 敏彦, 教授 今谷 勝次 / 学位規則第4条第1項該当 / Doctor of Energy Science / Kyoto University / DGAM

Background: Mechanical thrombectomy is the gold standard for treating patients with certain acute ischemic stroke (AIS) due to large vessel occlusion (LVO). However, even with major advancements and increasing procedural volumes, acute endovascular therapy remains a high-risk procedure with a considerable 90-day mortality rate, affected by a variety of factors. Purpose: To investigate various clinical and procedural factors associated with 90-day mortality in patients undergoing mechanical thrombectomy for emergent treatment of AIS and determine which of these factors made unique contributions to post-thrombectomy prognosis. Methods: We examined a prospective registry of 323 patients treated with endovascular thrombectomy for AIS between 2016 and 2019 at a high-volume comprehensive stroke center in central Massachusetts. We developed two multivariable logistic regression models adjusting for the contributions of baseline characteristics and recanalization parameters, to identify potential predictors of mortality at 90 days. Results: Among 323 AIS patients treated with mechanical thrombectomy, the overall rate of successful recanalization was 86% and the overall post-procedure mortality rate was 29% by 90 days. After univariate analysis, a baseline multivariable model comprised of: history of stroke (OR 0.28, 95% CI 0.09 – 0.68), pre-stroke modified Rankin Scale (mRS 2: OR 3.75, 95% CI), severe admission National Institutes of Health Stroke Scale (NIHSS 21–42: OR 12.36, 95% CI 1.48 – 103.27), internal carotid artery (ICA) occlusion (OR 2.77, 95% CI 1.18 – 6.55), and posterior circulation occlusion (OR 2.69, 95% CI 1.06 – 6.83) was prognostic of 90-day mortality. A second multivariable model also found the procedural factors of: clot obtained after each pass (OR 0.49, 95% CI 0.24 – 1.00), successful recanalization (OR 0.21, 95% CI 0.06 – 0.8) and symptomatic intracranial hemorrhage (sICH; OR 17.89, 95% CI 5.22 – 61.29) to be identifiable predictors of post-thrombectomy mortality. Conclusion: Death within 90 days after thrombectomy was increased among patients with higher pre-stroke disability, higher stroke severity on admission, ICA or posterior occlusion, and those with sICH complication. A history of stroke, clot extraction after each device pass, and successful recanalization are associated with decreased 90-day mortality. These identifiable contributors may inform patient selection, prognosis evolution, and shared decision-making regarding emergent thrombectomy for treatment of AIS.

A hot isostatic press (HIP) is a system which utilises high temperatures and pressure in order to densifyand enhance the material properties of components in the aerospace, automotive and additive manufacturingindustries, to mention a few. Quintus is a world leading manufacturer of HIP systems, and this master’s thesiswork has been written in collaboration with them. A HIP consists of a cylinder which gets filled with an inert gas, a gas which is then pressurised using compressors.Inside of the cylinder are heaters which ensure that the gas and load reach the desired temperature. Quintus’HIP construction has a wire wound cylinder. This means that a pre-stressed wire is wound around the cylinderfor a number of laps, resulting in the cylinder always being in a compressive stress state, thus ensuring a safeconstruction if a crack were to propagate in the material. This construction also allows for a more slim design ofthe cylinder which is beneficial when the gas is to be cooled, as the heat gets transported through the cylinder.An alternative design to this wire wound cylinder is a so called monoblock cylinder. This is a solid, thicker,cylinder, not wound by any wire. Quintus does not manufacture the monoblock HIP system, but these HIPs areon the market and therefore Quintus is keen to learn more about them. In this work, differences in the cooling capabilities with respect to the cylinders’ strength has been investigated,regarding the wire wound and monoblock cylinders. This has been done by the means of CFD and FEM(ANSYS CFX and ANSYS Mechanical), where a simplified 2D axisymmetric model of each HIP version wasused. In CFX, both a steady state and transient simulation was run for each model in order to capture the coolingof the gas. The resulting temperature load on the cylinder was then exported to the Mechanical setup to solvefor the arising stresses of the cylinders. The results of the work showed that the wire wound HIP does indeed exceed the monoblock cylinder when itcomes to the cooling rate, especially after some time when the gas has cooled off. Neither one of the cylinderswere at risk of yielding, and the monoblock cylinder was calculated to withstand >20 000 cycles, which is alsothe fatigue life of the wire in Quintus’ HIPs. The models and boundary conditions used in this work weresubjected to approximations, but the results obtained have still brought a lot of new insights to the monoblockconstruction, and have provided a good foundation for further analyses.

The work of the Cal Poly Tissue Engineering Lab is primarily focused on the fabrication, characterization, and improvement of “Blood Vessel Mimics” (BVMs), tissue engineered constructs used to evaluate cellular response to vascular medical devices. Currently, cells are grown onto fibrous, porous tubes made using an in-house electrospinning process from PLGA, a biocompatible co-polymer. The adhesion and proliferation of cells in a BVM is reliant on the micro-scale structure of the PLGA scaffold, and as such it is of great importance for the electrospinning process to consistently produce scaffolds of similar morphologies. Additionally, it has been shown that cell proliferation increases with scaffolds of smaller fibers and pores than the current electrospinning protocol can produce. Finally, the Tissue Engineering Lab has interest in testing devices in more tortuous BVM bioreactor designs, however the use of relatively rigid PLGA scaffolds has severely limited the ability to construct more complicated vessel geometries. The overall goal of this thesis was to improve fabrication and characterization of electrospun polymer scaffolds for BVM use. The specific aims of this thesis were to: 1) Improve scaffold characterization by comparing two techniques for fiber diameter measurement and implementing a technique for pore area measurement. 2) Reduce scaffold fiber diameter and pore area by investigating humidity and solvent composition electrospinning parameters. 3) Reduce process variability by developing a more specific electrospinning protocol. 4) Improve scaffold consistency and use by understanding and reducing PLGA scaffold shrinkage. 5) Identify and evaluate more flexible polymers as potential alternatives for electrospun BVM scaffolds. In order to accomplish these aims, first, several BVM and outside literature images were taken and evaluated with current and prospective fiber diameter techniques, and with 2 prospective pore area techniques to characterize accuracy and consistency of each method. It was found that the prospective fiber diameter measurement technique was not superior to the current method. The techniques developed for pore area measurement were found to produce results that differed significantly from each other and from the published value for a given image. Next, changes to environmental and solution composition parameters were made with the hopes of reducing fiber diameter and pore area of electrospun PLGA scaffolds. Changes in relative humidity did not appear to significantly affect scaffold fiber diameter while changes to solvent composition, specifically the use of acetone, resulted in fibers significantly smaller than those regularly achieved in the BVM lab. Next, several sources of variability in the electrospinning protocol were identified and subsequently altered to improve consistency and usability. Specifically, this included redefining the precision with which PLGA mass was measured, repositioning electrical equipment to reduce the effect of stray electrostatic forces on the polymer solution jet, attempting to control the temperature and humidity inside the electrospinning enclosure, and improving the ease with which scaffolds are removed from their mandrels through alternative mandrel surface treatments. In addition to overall process variability, the issue of scaffold shrinkage during BVM use was investigated and two possible treatments, exposure to either ethanol or elevated temperatures, were proposed based on previous electrospinning literature results. Each was tested for their effectiveness in mitigating shrinkage through exposure to BVM setup-mimicking conditions. It was found that both treatments reduced scaffold shrinkage compared to control samples when exposed to BVM setup-mimicking conditions. Finally, 3 flexible polymers were selected and electrospun to compare against typical PLGA results and to conduct a kink radius test as a metric for measuring flexibility as it pertains to the proposed BVM lab application. It was concluded that two types of thermoplastic polyurethane (tPU) were not acceptable electrospinning materials for use in the BVM lab. Additionally, while polycaprolactone (PCL) could be successfully electrospun it could not undergo the amount bending required for more tortuous BVM bioreactor designs without kinking. Overall, the work in this thesis provided insight into multiple scaffold characterization techniques, reduced overall electrospinning variability in the fabrication and use of PLGA scaffolds, and defined processing parameters that have been shown to yield scaffolds with smaller morphological features than all prior Tissue Engineering Lab work. By creating better, more effective scaffolds, researchers in the Tissue Engineering Lab can more accurately mimic the structure and properties of native blood vessels; this, in turn, will result in BVM cell responses that more closely resemble that of native tissue. Creating consistent and appropriate BVMs will then lead to impactful contributions to the existing body of tissue engineering research and to better preclinical device testing.

This final thesis addresses the approach of standards and software for calculation of pressure vessels loaded by external pressure and a design of own calculation software, including a demonstration on chosen geometry. The approaches of standards and software are solved in the form of research. The practical part describes the developed software, selected technologies for development and results of the demonstration. The demonstration was carried out on two geometries and was successful.

The essence of this diploma work is to find suitable alternatives to the current situation in the river sightseeing vessels. The aim is to design an object that would offer passengers an adequate and attractive environment where they would spend their free time and which would also be appropriate supplement to the place where this vessel is located.

The design of an underwater observation vessel is the main objective during the thesis. An innovative approach will be applied in terms of modernization and design of the chosen topic. This work shows the author‘s creativity and ability to execute the required task in a specific time frame based on the appropriate level for a thesis. It reveals the steps that lead to an aesthetically balanced object from a functional product. Ergonomic standards and contemporary materials have been one of the basic knowledge.

The content of this work is the analysis of retinal vessels pulsation of video sequences acquired by experimental fundus camera based on measuring the brightness profile of the vessel. The first level of analysis in this work is the segmentation of blood vessels and diameter measurement of blood vessels during the sequence. The work contains research methods dealing with the diameter measurement and evaluation of pulsation and analysis segmentation methods using for analysing the vasculature of the retina. From these methods, a vessel tracking method was selected. In segmented video sequences is on the ground of intensity profiles analysed vessel pulsation. Analysis is also made on original dataset and results are discussed considering the frequency characteristic.

Stroke is serious neurological disease and is a major cause of death as well as disability throughout the globe. Stroke has a complex pathophysiology that involves inflammatory pathways, excitotoxicity mechanisms, oxidative damage, apoptosis, ionic imbalances, angiogenesis and neuroprotection. 85% of strokes are ischemic and occurs when a cerebral vessel, or any vessel supplying the brain, narrows or loses pressure resulting in subsequent brain ischemia and infarction downstream to the site of obstruction depriving tissues of vital oxygen and nutrients. This may be caused by either atherosclerotic thrombi or distant emboli defined as a mass of clotted blood or other material. It is estimated that over a billion people currently smoke cigarettes or use other tobacco products, seeing as smoking is a major risk factor for stroke this is of major concern. Platelets are hematopoietic cells produced by bone marrow megakaryocytes. Platelets play a role in the development of ischemic stroke primarily by means of their participation in the formation of thromboemboli, the presence of abnormal platelet function may predispose patients to a pro-thrombotic, pro-inflammatory state. The reorganization of the cytoskeleton in platelets is an important factor in the complex mechanisms found in thrombosis and haemostasis. The platelet membrane contains a large number of receptors which specifically bind agonists that stimulate the physiological platelet response. Oxidative stress is one of the mechanisms involved in the neuronal damage of stroke. Oxidative stress is a state of imbalance between free radical production, in particular, reactive oxygen species (ROS), and the ability of the organism to neutralize them, leading to progressive oxidative damage. Smoking is known to result in the generation of various free radicals. Flow cytometric analysis of the platelets of thrombo-embolic ischemic stroke patients and smokers revealed that the membranes of the two groups were altered in some form as well as an increased activation in both groups when compared to healthy individuals. Superoxide levels in the platelets were higher in smokers when compared to stroke patients, while hydrogen peroxide levels were elevated in the platelets of both groups. Superoxide was elevated in the whole blood samples of both groups. The production and subsequent reactions of reactive oxygen species appear to be influential in stroke and smoking and may likely be a crucial factor in the development of a pro-thrombotic, pro-inflammatory state which may prove to be a hallmark in the pathophysiology of stroke and smoking. Confocal microscopy and Scanning electron microscopy showed that platelets of stroke patients and smokers appear to be more activated and more prone to form tight clots. Furthermore an increased amount of superoxide is present in the platelets of stroke patients and smokers, specifically in the centre of clots. This may be an indication that once platelets have aggregated and started to fuse together, the mitochondria are expelled from the platelets and “trapped” within the clot. Atomic force microscopy also indicated both the stroke patients and smoker‟s platelets appear to be in a more activated state than the control group. Here it is apparent that some form of cytoskeletal rearrangement takes place to a more severe extent in the stroke group than in the smokers. Necrosis may be present in the platelets of stroke patients while neither apoptosis nor necrosis can be identified in the platelets of smokers however some form of membrane alteration is likely present. All the techniques used showed an increase in platelet activation in stroke patients and smokers, necrotic platelets may be present in the stroke patients while the platelet membrane of smokers seems to be altered. ROS is present and alters the platelet function of smokers and stroke patients in some way. It appears as if thrombo-embolic ischemic stroke patients and smokers‟ platelets have similar trends in activation but the processes involved to achieve this differ as there are structural differences present. These differences may prove a useful tool to further understand the pathophysiology behind thrombo-embolic ischemic stroke as well as to discover new therapeutic pathways. / Dissertation (MSc)--University of Pretoria, 2013. / gm2014 / Physiology / Unrestricted

Congenital heart defects are the most common category of birth defects, mostly affecting the blood vessels, walls, or valves of the heart. For example, pulmonary atresia occurs when the connection between the right ventricle to the main pulmonary artery is not fully formed. A heart defect such as pulmonary atresia may need surgery to close up any malformations in walls and blood vessels, and unfortunately, because the patients are infants, they will need to undergo several surgeries in their lifetime to accommodate a heart patch that will fit the size of their hearts at each stage of their life. A better solution would be to create a biomimetic vascular patch that could be anatomically accepted by the patient’s body as its own, allowing it to grow with the patient without the residue of scar tissue. Instead of propagating scar tissue in the area, it would propagate healthy cells that would integrate into the surrounding tissue. For this to become a reality, one strategy for a biomimetic vascular patch would be to build it like a blood vessel in layers, beginning with the tunica adventitia. The goal of this thesis is to engineer and design the foundation for a biomimetic vascular patch with a crimped, collagen-integrated scaffold, focusing on optimizing the mechanical properties of the hybrid structure. The crimped structure, using sine waves generated from Python code and fabricated with bioprinting technology, mimics the natural formation of collagen fibers in native blood vessels. Additionally, testing the scaffolds on the Instron allows for characterization of the mechanical behaviors of an optimal and repeatable foundation for a tissue-engineered tunica adventitia. / 2023-01-22T00:00:00Z