Theoretical Foundations Catheter ablation is an intervention focused on targeted removal of or damage to an area that causes arrhythmias. This intervention began to be performed at the turn of the 1980s and 1990s because it had been found that treatment with antiarrhythmic drugs was expensive and the drugs had to be taken throughout patients' lives. Thanks to its high success rate and low risk of complications, it has been used in the treatment of supraventricular tachyarrhythmias. At present, the success rate is around 75 %, and the intervention sometimes needs to be repeated to achieve its desired effect. Objectives of the thesis The first objective was to find out whether patients with a history of catheter ablation changed their personal and professional lives. The second objective was to map out which areas of the patients' live were affected most by the catheter ablation treatment. The third objective was to find out about differences in the patients' lives before and after catheter ablation. Research questions V1: In what areas are the patients' lives limited most? V2: What changes have occurred in their lives after catheter ablation? Methodology The research part of the thesis was carried out using a qualitative survey conducted by means of semi-structured interviews with patients suffering from arrhythmias. The total of 9 respondents, 5 males and 4 females, were interviewed. The information obtained was processed using programme Atlas.ti. The results are presented as networks created in this programme. Results The research questions can be answered using the data obtained from the respondents suffering from arrhythmias. The first research question was aimed at finding out in what areas the patients' lives were limited most. It was found out, through the semi-structured interviews, that the most limited area was personal life, in which arrhythmia caused most difficulties to the respondents during sports activities. Because of their health problems, most of the respondents limited their sports activities or abandoned them altogether in favour of their health. Other problems are caused during physical strain and under physical load. That was also the thing that the addressed respondents preferred to avoid. The respondents are also limited in the performance of their work, when the main cause of their problems is psychological stress, mental stress resulting in arrhythmia symptoms in the respective respondents. The second research question examined what changes occurred in their lives after catheter ablation. The changes that occurred related to the care of the family and the household in which they are able to engage in multiple activities. The respondents were able to pay more attention to their families by whom they are encouraged in the treatment. There was an overall improvement in their health, enabling better integration into everyday life. The most frequently mentioned area of changes was sport. During the period after catheter ablation, the respondents began to return gradually to their hobbies. Conclusion The thesis describes the restrictions that arrhythmia caused to the respondents and also the changes that have occurred in the individual respondents after catheter ablation treatment. The results can be used in practice in the education of patients who wait for the catheter ablation treatment and in subsequent measures using the prepared mind maps.

Made available in DSpace on 2014-10-09T12:28:05Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:01:23Z (GMT). No. of bitstreams: 0 / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Made available in DSpace on 2014-10-09T12:28:05Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:01:23Z (GMT). No. of bitstreams: 0 / A usinagem de estruturas micrométricas pode ser feita com pulsos laser de nano, pico ou fentossegundos. Destes, porém, somente os mais curtos podem resultar em uma interação não térmica com a matéria, o que evita a fusão, formação de rebarba e zona afetada pelo calor. Devido à sua baixa potência média, contudo, a sua utilização na produção em massa somente pode ser considerada em casos muito especiais, isto é, quando o processamento não-térmico é essencial. Este é o caso da usinagem de semicondutores, aços elétricos, produção de MEMS (sistemas micro eletro-mecânicos), de micro canais e diversos dispositivos médicos e biológicos. Assim, visando a produção destes tipos de estruturas, uma estação de trabalho foi construída com capacidade de controlar os principais parâmetros de processo necessários para uma usinagem micrométrica com laser de pulsos ultracurtos. Os principais problemas deste tipo de estação são o controle da fluência e do posicionamento do ponto focal. Assim, o controle do diâmetro do feixe (no foco) e da energia devem ser feitos com grande precisão. Além disso, o posicionamento do ponto focal com precisão micrométrica nos três eixos, também é de fundamental importância. O sistema construído neste trabalho apresenta soluções para estes problemas, utilizando diversos sensores e posicionadores controlados simultaneamente por um único programa. A estação de trabalho recebe um feixe vindo de um laser de pulsos ultracurtos localizado em outro laboratório, e manipula este feixe de maneira a focalizá-lo com precisão na superfície da amostra a ser usinada. Os principais parâmetros controlados dinamicamente são a energia, o número de pulsos e o posicionamento individual de cada um deles. A distribuição espacial da intensidade, a polarização e as vibrações também foram medidas e otimizadas. O sistema foi testado e aferido com medidas de limiar de ablação do silício, que é um material bastante estudado neste regime de operação laser. Os resultados, quando confrontados com a literatura, mostram a confiabilidade e a precisão do sistema. A automatização, além de aumentar esta precisão, também aumentou a rapidez na obtenção dos resultados. Medidas de limiar de ablação também foram realizadas para o metal molibdênio, levando a resultados ainda não vistos na literatura. Assim, de acordo com o objetivo inicial, o sistema foi desenvolvido e está pronto para utilização em estudos que levem à produção de estruturas micrométricas. / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

An important step in the more efficient use of PICA (Phenolic Impregnated Carbon Ablator) as a Thermal Protection System (TPS) material for spacecraft is the understanding of its pyrolysis mechanics. The gases released during pyrolysis and their subsequent interaction with the reactive plasma environment is not yet well understood. The surface recession of PICA as it ablates during testing only makes the study and characterization of the chemical reactions more difficult. To this end, a probe has been designed for this study to simulate, in steady state, the pyrolysis gases within the UVM 30kW Inductively Coupled Plasma (ICP) Torch Facility. This probe, which is an extension of previous work done at UVM, has been used to inject Carbon Dioxide, Hydrogen, and a mixture of the two into pure Argon and dilute Nitrogen, Oxygen, and air plasmas. During testing, spatially resolved, pointwise, line of sight emission measurements were taken in the boundary layer region. These results were then compared to temporally resolved PICA emission data taken in a previous study. After the correct temporal PICA scan was found the data sets closely matched. This indicates that the gas-injection probe is a viable method to simulate pyrolysis in a steady state environment. The key pyrolysis species of CN, NH, OH, Hydrogen Alpha (Hα), and Hydrogen Beta (Hβ) were spatially traced along the stagnation line for the pure Hydrogen and mixture injection cases. These measurements show evidence of spatial relationships between NH and Hα as well as between OH and Hβ. They also show that all of the molecules tend to follow the same general trend spatially. The work done for this study has both reintegrated gas-injection capability into the UVM facility as well as laid the groundwork for future gas-injection testing within the facility. Spatial emission analysis techniques currently being developed at UVM will provide a more resolved picture of the interactions occurring in the boundary layer once completed.

The necessity of elemental analysis techniques to solve forensic problems continues to expand as the samples collected from crime scenes grow in complexity. Laser ablation ICP-MS (LA-ICP-MS) has been shown to provide a high degree of discrimination between samples that originate from different sources. In the first part of this research, two laser ablation ICP-MS systems were compared, one using a nanosecond laser and another a femtosecond laser source for the forensic analysis of glass. The results showed that femtosecond LA-ICP-MS did not provide significant improvements in terms of accuracy, precision and discrimination, however femtosecond LA-ICP-MS did provide lower detection limits. In addition, it was determined that even for femtosecond LA-ICP-MS an internal standard should be utilized to obtain accurate analytical results for glass analyses. In the second part, a method using laser induced breakdown spectroscopy (LIBS) for the forensic analysis of glass was shown to provide excellent discrimination for a glass set consisting of 41 automotive fragments. The discrimination power was compared to two of the leading elemental analysis techniques, µXRF and LA-ICP-MS, and the results were similar; all methods generated >99% discrimination and the pairs found indistinguishable were similar. An extensive data analysis approach for LIBS glass analyses was developed to minimize Type I and II errors en route to a recommendation of 10 ratios to be used for glass comparisons. Finally, a LA-ICP-MS method for the qualitative analysis and discrimination of gel ink sources was developed and tested for a set of ink samples. In the first discrimination study, qualitative analysis was used to obtain 95.6% discrimination for a blind study consisting of 45 black gel ink samples provided by the United States Secret Service. A 0.4% false exclusion (Type I) error rate and a 3.9% false inclusion (Type II) error rate was obtained for this discrimination study. In the second discrimination study, 99% discrimination power was achieved for a black gel ink pen set consisting of 24 self collected samples. The two pairs found to be indistinguishable came from the same source of origin (the same manufacturer and type of pen purchased in different locations). It was also found that gel ink from the same pen, regardless of the age, was indistinguishable as were gel ink pens (four pens) originating from the same pack.

The use of thin-film techniques for the fabrication of microfluidic devices has gained attention over the last decade, particularly for three-dimensional channel structures. The reasons for this include effective use of chip volume, mechanical flexibility, dead volume reduction, enhanced design capabilities, integration of passive elements, and scalability. Several fabrication techniques have been adapted for use on thin films: laser ablation and hot embossing are popular for channel fabrication, and lamination is widely used for channel enclosure. However, none of the previous studies have been able to achieve a strong bond that is reliable under moderate positive pressures. The present work aims to develop a thin-film process that provides design versatility, speed, channel profile homogeneity, and the reliability that others fail to achieve. The three building blocks of the proposed baseline were fifty-micron poly(methyl methacrylate) thin films as substrates, channel patterning by laser ablation, and device assembly by thermal-fusion bonding. Channel fabrication was characterized and tuned to produce the desired dimensions and surface roughness. Thermal bonding was performed using an adapted mechanical testing device and optimized to produce the maximum bonding strength without significant channel deformation. Bonding multilayered devices, incorporating conduction lines, and integrating various types of membranes as passive elements demonstrated the versatility of the process. Finally, this baseline was used to fabricate a droplet generator and a DNA detection chip based on micro-bead agglomeration. It was found that a combination of low laser power and scanning speed produced channel surfaces with better uniformity than those obtained with higher values. In addition, the implemented bonding technique provided the process with the most reliable bond strength reported, so far, for thin-film microfluidics. Overall, the present work proved to be versatile, reliable, and fast, making it a good candidate to reproduce several on-chip functions. Future work includes implementing thick-substrate bonding techniques to further improve the process and decrease energy requirements.

Les métastases hépatiques compliquent l'évolution de 50% des cancers colorectaux (CCR). Plus de la moitié des patients présentent une récidive à distance avec métastases occultes pour lesquelles une chirurgie peut être réalisée dans moins de 20% des cas. L'ablation par radiofréquence (RFA) induit une réponse lymphocytaire T qui n'est pas évaluée après une intervention chirurgicale seule. L'immunothérapie combinée à la RFA pourrait potentialiser cet effet conduisant à une réponse tumorale à distance. Nous proposons une approche qui combine la RFA avec hydrogel thermoreversible libérant des agents immunomodulateurs (GMCSF et BCG) sur le site du traitementPremièrement, nous nous sommes intéressés à la sélection et à la caractérisation de la formulation optimale d’hydrogel par des techniques physicochimiques. Les propriétés de l'hydrogel ont été étudiées par rhéologie et des tests de muco-adhésion ont été mis en place. Le temps de résidence de l'hydrogel et de la protéine dans la zone tumorale a été démontré par imagerie optique. De plus, la cinétique de libération et l'intégrité du GMCSF encapsulé ont été déterminées. Ensuite, nous avons démontré l’efficacité de l’association de la RFA avec le dépôt local de l’hydrogel immunomodulatuer sur un modèle murin de cancer colorectal. En effet, nous avons observé une survie améliorée des animaux et régression complète des tumeurs distantes chez les animaux traités par la combinaison complète. Cette réponse est caractérisée par un niveau élevé de sécrétion de cytokines pro-inflammatoires par les cellules T CD4 et TCD8 et une augmentation de l’infiltrat lymphocytaire dans les tumeurs. Ceci a permis d'envisager une association avec l'immunothérapie anti-PD1 dans le traitement de macrométastases échappant au traitement combiné RFA avec l’hydrogel immunomodulateur. En effet, l’immunothérapie dans le traitement du cancer colorectal métastatique présente une efficacité limitée chez les patients. Notre travail propose a démontré que l’efficacité de l’immunomodulation locale dans l’amélioration des réponses immunitaires dans le cancer colorectal. Ces résultats permettent de reconsidérer l’utilisation de l’immunothérapie chez les patients atteints de CCR métastatique non MSI. / Liver metastases complicate the progression of 50% of colorectal cancers (CRC). More than half of the patients have recurrent remissions with occult metastases for which surgery can be performed in less than 20% of cases. Radiofrequency ablation (RFA) induces a T lymphocyte response that is not observed after surgery alone. Combined immunotherapy with RFA may potentiate this effect leading to a distant tumor response. We propose an approach that combines RFA with thermoreversible hydrogel releasing immunomodulatory agents (GMCSF and BCG) at the treatment site.First, we focused on the selection and characterization of the optimal hydrogel formulation by physicochemical techniques. The properties of the hydrogel were studied by rheology and mucoadhesion tests were set up. The residence time of the hydrogel and the protein in the tumor zone was demonstrated by optical imaging. In addition, the release kinetics and integrity of the encapsulated GMCSF were determined. Then, we demonstrated the effectiveness of the combination of RFA with the local deposition of the immunomodulatory hydrogel on a mouse model of colorectal cancer. Indeed, we observed improved survival of animals and complete regression of distant tumors the complete treatment group. This response is characterized by a high level of pro-inflammatory cytokine secreted by CD4 and TCD8 T cells and an increase Lymphocytes infiltrating tumors. The immune escape of large lesions was reversed by association with anti-PD1 immunotherapy Indeed, immunotherapy in the treatment of metastatic colorectal cancer has limited efficacy in patients. Our work has demonstrated the effectiveness of local immunomodulation in improving immune responses in colorectal cancer. These results make it possible to reconsider the use of immunotherapy in patients with non-MSI metastatic CRC.

Title: Characterization and focusing of capillary-discharge XUV-laser beam for purposes of thin-film deposition Author: Peter Pira Department: Department of Surface and Plasma Science Supervisor: doc. RNDr. Jan Wild, CSc., Department of Surface and Plasma Science Abstract: The paper deals with the first results of the interaction of a desk-top high repetition rate XUV laser (wavelength of 46.9 nm) radiation with materials suitable for optoelectronics, in particular the ionic crystals CsI, LiF, etc. Using surface physics methods (AFM, DIC Normanski microscopy) pulse laser imprints were investigated. Based on the results obtained, general information on the nature of ablation and desorption was obtained, which were compared with the results of the XUV-ABLATOR modified code modeling. Plasma arising from ablation was examined by a modified Langmuir probe system. The main result is the pulse laser deposition of thin films of Bi and CsI. Keywords: ablation, Pulsed Laser Deposition, XUV laser

We investigate the conditions under which electron irradiation of single-walled carbon nanotube (SWCNT) bundles with 2 keV electrons produces an increase in the Raman D peak. We find that an increase in the D peak does not occur when SWCNTs are preheated in situ at 600 C for 1 h in ultrahigh vacuum (UHV) before irradiation is performed. Exposing SWCNTs to air or other gases after preheating in UHV and before irradiation results in an increase in the D peak. Small diameter SWCNTs that are not preheated or preheated and exposed to air show a significant increase in the D and G bands after irradiation. X-ray photoelectron spectroscopy shows no chemical shifts in the C1s peak of SWCNTs that have been irradiated versus SWCNTs that have not been irradiated, suggesting that the increase in the D peak is not due to chemisorption of adsorbates on the nanotubes.

The goal of this thesis is to propose and investigate a method of predicting depth of a laser dissection pulse in soft tissue without acquiring material properties of the tissue target or measuring the laser output. The method proposed is similar to what is used by laser surgical operators today, but uses regression learning to perform on-the fly predictions in place of a skilled laser surgeon. Power of the laser and the ablation depth were recorded for 57 samples and fed into the regression algorithm. Data exclusion was performed using Temperature before laser action as criteria. A linear and logarithmic model was explored using random points from the data post-exclusion, validation RMSE ranged from 135-200 micrometer. A linear and logarithmic model was explored using data points below a moving power threshold and validated with data points above said threshold, validation RMSE ranged from 108-170 micrometer. The t.test performed showed there was not a significant difference between the linear and the logarithmic models' goodness of fit metrics, but it did show there was a significant difference between the model building methods (randomly selected data points, moving power threshold). The method of building a model using lower power levels to predict larger power levels had better goodness of fit metrics than the method of selecting data points at random. In the future, this method could be used to help approximate the laser settings for surgery on a procedural basis, and allow for surgeons to perform at a higher skill level with less training.