High-Density Mapping Analysis of Electrical Spatiotemporal Behaviour in Atrial Fibrillation

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Sinais e Imagens Médicas), 2022, Universidade de Lisboa, Faculdade de CiênciasDoenças cardiovasculares, tais como arritmias, são a principal causa de morte no mundo, especialmente no Sul e no Este da Ásia, e nos Estados Unidos da América [1]. As arritmas são caracterizadas pela alteração no ritmo sinusal normal do coração. Em particular, a fibrilhação auricular (FA) é a arritmia cardíaca mais comum na prática clínica, contribuindo para mais de 200 mil mortes globalmente em 2017 [2]. Caracteriza-se pela contração rápida e dessincronizada das aurículas, e está associada ao aumento da mortalidade e afecta de forma negativa a qualidade de vida dos pacientes. A FA é geralmente tratada através de medicação, porém quando esta falha, a ablação por cateter é indicada, sendo um tratamento de referência para combater esta patologia. A ablação apresenta uma taxa de sucesso de aproximadamente 50% no primeiro procedimento, sendo necessário efectuar vários procedimentos para aumentar a eficácia do tratamento [3]. A detecção desta patologia envolve, numa primeira fase, a realização de um electrocardiograma (ECG) e, posteriormente um estudo electrofisiológico para saber com precisão onde se localiza e o mecanismo subjacente à mesma. Este último implica o registo da actividade eléctrica através de electrogramas (EGM) locais em diferentes pontos das aurículas e dos ventrículos, com o auxílio de sistemas de mapeamento tridimensionais (3D) electroanatómicos, sendo um procedimento invasivo. Existem diversos métodos lineares e não lineares que permitem a análise dos EGMs nos domínios do tempo, frequência, fase, entre outros, com a finalidade de melhor compreender os mecanismos subjacentes à FA e, consequentemente aumentar a taxa de sucesso do processo de ablação e melhorar a sua eficiência. Esta área de estudo progrediu significativamente, tanto a nível de hardware, como de software. Apesar disso, os métodos desenvolvidos não têm nem acrescentado benefícios adicionais, nem melhorado significativamente a taxa de sucesso do processo de ablação. Existem várias razões para tal, e grande parte deve-se ao facto destes métodos de análise estarem incorporados nos sistemas de mapeamento e o seu software ser exclusivo. Isto leva a que não consigamos perceber como é que os algoritmos funcionam nos diferentes sistemas de mapeamento para comparar as suas diferenças e semelhanças. Devido a estes constrangimentos, os investigadores são compelidos a desenvolver os seus próprios métodos de análise e técnicas de mapeamento, o que leva à existência de uma multitude de métodos e técnicas de mapeamento que parecem ser diferentes entre si, resultando em informação ambígua e conflituosa no que diz respeito aos mecanismos da FA, e a conclusões distintas entre estudos. O sucesso do tratamento poderia aumentar se tivéssemos uma melhor compreensão dos métodos de análise e da sua aplicação no contexto da FA; perceber se os métodos apontam para o mesmo fenómeno de fibrilhação, se existe alguma correlação entre os métodos, e se a informação fornecida pelos mesmos é complementar ou redundante. Assim, o objectivo deste trabalho consistiu em implementar diferentes métodos para analisar os EGMs e a estrutura 3D da aurícula esquerda (AE) de doentes com FA, numa tentativa de responder às questões que motivaram a realização deste projecto. Em última análise, ao observar os mapas 3D da AE tendo uma melhor compreensão dos métodos, poderemos identificar com precisão as regiões na AE responsáveis por iniciar a FA, e ter mais conhecimento sobre os mecanismos responsáveis pela mesma. Desta forma, o processo de ablação poderá alcançar o seu potencial. Para este projecto, foram incluídos os mapas 3D electroanatómicos da AE de dez doentes com FA paroxística ou persistente do hospital de Santa Marta, recolhidos com o sistema de mapeamento CARTO 3. Cada ponto electroanatómico dos mapas inclui as 12 derivações do ECG, e os EGMs unipolares e bipolares registados com o cateter de mapeamento Pentaray de 20 pólos. Porém, apenas os EGMs bipolares foram incluídos na análise. Processaram-se os sinais bipolares e, devido a algumas limitações, foi possível apenas a implementação de dois métodos diferentes para os analisar: um no domínio da frequência – Frequência Dominante (FD) –, e outro no domínio da Teoria da Informação – a entropia de Shannon. De seguida, criaram-se três tipos de mapas 3D electroanatómicos da AE para cada doente: um de voltagem, cuja informação foi adquirida com o sistema de mapeamento, um de FD, e outro de entropia. A informação de cada mapa estava organizada segundo um padrão de cores. Observando os diferentes tipos de mapas da AE paralelamente, foi possível comparar os métodos, e perceber que tipo de informação cada um deles fornecia, numa tentativa de melhor compreender os mecanismos da FA. Foi possível observar em algumas regiões da AE, principalmente nos mapas de voltagem e de FD, a presença de “centros de activação” ou “centros de fibrilhação”, que poderão ser os gatilhos responsáveis por desencadear ou manter o mecanismo de fibrilhação. Para confirmar se de facto aquelas regiões eram os gatilhos de fibrilhação, seria necessário submeter os doentes ao processo de ablação e queimar essas zonas; e posteriormente acompanhar os doentes para observar os efeitos do procedimento e confirmar a hipótese. Contudo, dadas as limitações do trabalho e o facto desta área de investigação ser pouco explorada, é fulcral obter um maior número de estudo comparativos entre mais métodos de diferentes domínios e confirmar se apontam ou não para o mesmo fenómeno de fibrilhação. Apesar de terem sido implementados apenas dois métodos de análise dos EGMs, o projecto permitiu a comparação entre os mesmos, uma área de estudo por onde ainda há muito para investigar. Com mais conhecimento sobre os diferentes métodos, a sua aplicação, inter-relação e adequação no estudo dos mecanismos da FA e das propriedades electrofisiológicas desta patologia, é possível desenvolver procedimentos de ablação mais eficientes e selectivos, de forma a diminuir os riscos e aumentar a taxa de sucesso do tratamento.Atrial fibrillation (AF) is the most frequent cardiac arrhythmia in clinical practice and is described by rapid and irregular contractions of the atria. Despite catheter ablation (CA) being a well-established treatment for AF, it is sub-optimal, with a success rate of approximately 50 % after a single procedure, with some patients requiring multiple procedures to achieve long-term freedom from this pathology. This prompted the proposal and development of various quantitative electrogram (EGM)-based methods along with different mapping systems with their respective mapping techniques, to better understand the mechanisms responsible for initiating and maintaining AF, thus improving ablation outcomes. However, this diversification of methods and tools resulted in disperse and inconsistent data regarding the mechanisms of AF. This work consisted of employing two different methods to analyse the electrograms (EGM): dominant frequency (DF) and Shannon entropy (ShEn). From these EGMs, metrics were then extracted and displayed in colour-coded fashion on a 3D mesh of the left atrium (LA) from patients with paroxysmal or persistent AF. The two methods were compared to understand whether or not these indicated different phenomena/mechanisms, and if these could locate sites suspected of triggering and maintaining AF. The results, while not fully conforming to the literature, allowed the comparison between different EGM analysis methods, a field of study that requires further research. Overall, this project highlighted the limited data available within the topic, hindering our understanding of AF mechanisms and development of more effective and selective ablation procedures to avoid unnecessary complications, and ultimately improve the effects of the treatment's outcomes

High-Throughput NMR Assessment of the Tertiary Structure of Food Allergens

In vitro component-resolved diagnosis of food allergy requires purified allergens that have to meet high standards of quality. These include the authentication of their conformation, which is relevant for the recognition by specific IgE antibodies from allergic patients. Therefore, highly sensitive and reliable screening methods for the analysis of proteins/allergens are required to assess their structural integrity. In the present study one-dimensional 1H Nuclear Magnetic Resonance (1D 1H-NMR) analysis was adopted for the assessment of overall structural and dynamic properties and authentication of a set of relevant food allergens, including non-specific lipid transfer proteins from apple, peach and hazelnut, 7/8S seed storage globulins from hazelnut and peanut, 11S seed storage globulins from hazelnut and peanut, caseins from cows' and goats' milk and tropomyosin from shrimp.Two sets of 1D 1H-NMR experiments, using 700 MHz and 600 MHz instruments at 298 K were carried out to determine the presence and the extent of tertiary structure. Structural similarity among members of the individual allergen families was also assessed and changes under thermal stress investigated. The nuclear magnetic resonance (NMR) results were compared with structural information available either from the literature, Protein Data Bank entries, or derived from molecular models.1D (1)H-NMR analysis of food allergens allowed their classification into molecules with rigid, extended and ordered tertiary structures, molecules without a rigid tertiary structure and molecules which displayed both features. Differences in thermal stability were also detected. In summary, 1D (1)H-NMR gives insights into molecular fold of proteins and offers an independent method for assessing structural properties of proteins

THE ILOKANO ESL LEARNER : A STUDY OF INTERLANGUAGE

Master'sMASTER OF ART

S-traizine herbicides in banana plants

Typescript.Thesis (Ph. D.)--University of Hawaii, 1967.Bibliography: leaves [105]-110.viii, 110 l illus., tablesField screening trials in Hawaii showed ametryne (2-methylmercapto-4- ethylamino-6-isopropylamino-s-triazine) to be a potentially important herbicide for bananas. Ametryne exhibited more effective weed control than atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine). Furthermore, atrazine caused injury to bananas in 2 of 3 locations used. Investigations were conducted to explain the differential selectivity of the 2 closely related s-triazine herbicides to bananas. Sand culture experiments-showed that both herbicides at concentrations of 0.4, 4, and 16 ppm in 2 liters of nutrient solution injured the plants. Plants grown in pots containing soils from the experimental fields showed increasing phytotoxicity to the herbicides in the fo1lowing order: Poamoho soil, Waimanalo soil, and Kauai soil. Ametryne was less injurious than atrazine but differences were not as pronounced as that under field conditions where ametryne did not exhibit phytotoxicity. Phytotoxicity was directly related to leachability of the herbicides and negatively related to adsorption capacity of each soil for the herbicides. Organic matter content seemed to partly explain the response observed. Selectivity appeared to be largely attributed to differential position of roots of banana plants in relation to herbicide placement rather than to inherent selectivity. Apparently, atrazine being less adsorbed by soil and more readily leached, moved to a greater depth upon receipt of a given amount of water resulting in crop injury. Laboratory studies confirmed results of greenhouse experiments that absorption, translocation and degradation of the herbicides by the plants did not account for the selectivity observed. Both of the herbicides were partly metabolized by the plants to their common hydroxy derivative and 2 other unidentified metabolites after 3 and 7 days of exposure to nutrient solutions containing C14-labelled ametryne and atrazine. When applied to the leaves with a surfactant the herbicides were absorbed and translocated in an acropetal direction to a very limited extent. Higher leaf content of free ammonia, free nitrate, and non-protein nitrogen, and lower chlorophyll content, were associated with plants receiving phytotoxic concentrations of ametryne and atrazine after 1 and 4 weeks from treatment. It appears that phytotoxic concentrations of these herbicides resulted in disturbance of the incorporation of nitrogen into more complex nitrogen containing plant constituents as proteins. In these experiments atrazine at 2 and 10 lb/A and ametryne at 10 lb/A applied to soil were phytotoxic to banana plants grown in pots. Ametryne at 2 lb/A did not injure the plants

落花生アレルゲンの分子構造解析と重イオンビーム照射によるアレルゲン欠失系統の開発

京都大学0048新制・課程博士博士(農学)甲第16123号農博第1859号新制||農||989(附属図書館)学位論文||H23||N4593(農学部図書室)28702京都大学大学院農学研究科農学専攻(主査)教授 裏出 令子, 教授 松村 康生, 教授 奥本 裕学位規則第4条第1項該当Doctor of Agricultural ScienceKyoto UniversityDA

Fate of (14C)xanthotoxin (8-methoxypsoralen) in laying hens and lactating goats

Typescript (photocopy).The metabolism of xanthotoxin, a naturally-occurring furanocoumarin photosensitizer, was studied in laying hens and lactating goats treated with a single oral dose equivalent to 10 mg xanthotoxin/kg of body weight. Within 48 hours, essentially all of the administered radiocarbon was eliminated in the excreta of the laying hens, while 92% and 3% were excreted in the urine and feces, respectively, of the goats. Of the different tissues collected, only the liver and blood of the laying hens; and the liver, blood, and muscle of the goats contained >.01% of the administered dose 7 days after treatment. Radiocarbon residues in the milk, egg white, egg yolk and egg shell were low. In the egg yolk and white, >95% of the radiocarbon present was identical in TLC behavior to xanthotoxin. Unmetabolized xanthotoxin, xanthotoxol, 6-(7-hydroxy-8-methoxycoumaryl)-acetic acid (HCA) and 6-(7-hydroxy-8- methoxycoumaryl)-hydroxy acetic acid (HCHA) were isolated and identified in the excreta of laying hens. Xanthotoxin is thus metabolized in the laying hens by O-demethylation, hydrolysis, and oxidation of the furan ring. In the goat, xanthotoxin is metabolized by O-demethylation, hydroxylation, reduction, oxidative cleavage of the furan ring, hydrolysis of the lactone ring, and conjugation to HCA, HCHA, xanthotoxol, 5,8-dihydroxypsoralen, psoralenquinone, 5-hydroxy-8- methoxypsoralen and 3{5-(6-hydroxy-7-methoxybenzofuryl]}-propanoic acid

Fate of (14C)xanthotoxin (8-methoxypsoralen) in laying hens and lactating goats

Typescript (photocopy).The metabolism of xanthotoxin, a naturally-occurring furanocoumarin photosensitizer, was studied in laying hens and lactating goats treated with a single oral dose equivalent to 10 mg xanthotoxin/kg of body weight. Within 48 hours, essentially all of the administered radiocarbon was eliminated in the excreta of the laying hens, while 92% and 3% were excreted in the urine and feces, respectively, of the goats. Of the different tissues collected, only the liver and blood of the laying hens; and the liver, blood, and muscle of the goats contained >.01% of the administered dose 7 days after treatment. Radiocarbon residues in the milk, egg white, egg yolk and egg shell were low. In the egg yolk and white, >95% of the radiocarbon present was identical in TLC behavior to xanthotoxin. Unmetabolized xanthotoxin, xanthotoxol, 6-(7-hydroxy-8-methoxycoumaryl)-acetic acid (HCA) and 6-(7-hydroxy-8- methoxycoumaryl)-hydroxy acetic acid (HCHA) were isolated and identified in the excreta of laying hens. Xanthotoxin is thus metabolized in the laying hens by O-demethylation, hydrolysis, and oxidation of the furan ring. In the goat, xanthotoxin is metabolized by O-demethylation, hydroxylation, reduction, oxidative cleavage of the furan ring, hydrolysis of the lactone ring, and conjugation to HCA, HCHA, xanthotoxol, 5,8-dihydroxypsoralen, psoralenquinone, 5-hydroxy-8- methoxypsoralen and 3{5-(6-hydroxy-7-methoxybenzofuryl]}-propanoic acid

Monitorización de la mortalidad en europa mediante gráficos de control

[EN] The increases in the average human life span along the years have being recognized and therefore, actuaries, statistician and demographers have created numerous mathematic models in order to make forecasts more accurate, since these forecasts are a crucial point for private and public institutions. This paper has as a main objetive to fit the Lee-Carter model, the Lee-Carter model with two terms and the Age-Period-Cohort to Colombia’s mortality data. The results show that the Lee-Carter with two terms model is the best fitting Colombia’s mortality rates, especially women rates. (inglés)[ES] Este trabajo propone el uso combinado de series temporales, que nos permiten realizar previsiones a partir de datos pasados, y gráficos de control EWMA, que posibilitan detectar cambios de tendencia, para explicar el comportamiento de la tasa de mortalidad estandarizada (SMR) para un conjunto de países europeos entre los años 1990 y 2009.Cabrerizo Cabanos, MM. (2015). Monitorización de la mortalidad en europa mediante gráficos de control. http://hdl.handle.net/10251/66251Archivo delegad

Synthesis of 4,5,-bis(2\u27,3\u27,4\u27,6\u27-tetra-0-acetyl-B-D-glucopyranosylthio)-1,3-dithiole-2-thione

A novel dithiole derivative containing a fully acetylated B-D-glucopyranose 3 was synthesized in 21.02 percent yield. The program of preparation involves the protection of the glucose unit via acetylation with sodium acetate in acetic anhydride at elevated temperature to produce a pentaacetylated glucopyranose 33. Subsequently, bromination in C-1\u27 was achieved by adding HBr in acetic acid to compound 33. Finally, substitution of the acetylated glucose moiety in the 4 and 5 positions of a previously prepared zinc complex generated compound 3 through a Koennig Knorr type reaction. [Note: Diagram follows]