Dissertations / Theses on the topic 'MRAS TECHNIQUE'

Staphylococcus aureus is a bacterial pathogen that is believed to be the most common agent of human infectious disease, causing conditions ranging from common skin lesions to life-threatening illnesses. S. aureus has also shown a remarkable ability to develop resistance to antimicrobial treatment, making infections difficult to treat. In the post-genomic era, proteomic studies analyzing the protein complement of a genome in a particular organism at any given time, have gained real significance. This result is largely due to dynamic changes in protein expression profiles which can lead wide alterations in physiology and behavior. For proteomics, it is necessary to maximize protein concentration and to devise a method that can be easily employed and provide reproducible results. Most proteomic studies of S. aureus involve 2D gel electrophoresis (2-DE); however, 2-DE has many drawbacks. Proteins that are too large, hydrophobic, acidic, or basic are poorly resolved. Multi-dimensional protein identification (MudPIT) allows complex protein samples to be analyzed in solution. As yet, there has not been a study involving solely 2D liquid chromatography followed by mass spectrometric analysis in S. aureus ; therefore we sought to catalogue the intracellular proteome and secretome of a commonly used and well-studied lab strain, SH1000. This was conducted during post-exponential and stationary phases of growth so as to understand its adaptation over time by utilizing differential protein synthesis. We found cytoplasmic proteins involved in glycolysis to be highly expressed in post-exponential phase while proteins involved in tricarboxylic acid cycle to be prevalent in stationary phase. We also found production of agr-regulated secreted toxins and proteases to be upregulated in stationary phase. In addition to this we employed proteomic approaches to quantitatively profile the secretomes of leading clinical isolates of S. aureus, as such a study is currently lacking. These included the two most common hospital-associated S. aureus strains (USA100 and USA200), and the two most common community-associated S. aureus strains (USA300 and USA400). We found agr-regulated proteins are generally upregulated in CA-MRSA strains USA300 and USA400 and surface-associated proteins to be upregulated in HA-MRSA strains USA100 and USA200. This finding concurs with literature regarding transcriptomic studies showing a hyperactive agr in CA-MRSA strains compared to HA-MRSA strains.

This thesis presents different state estimation techniques for speed sensorlees field oriented control of induction motors. The theoretical basis of each algorithm is explained in detail and its performance is tested with simulations and experiments individually. First, a stochastical nonlinear state estimator, Extended Kalman Filter (EKF) is presented. The motor model designed for EKF application involves rotor speed, dq-axis rotor fluxes and dq-axis stator currents. Thus, using this observer the rotor speed and rotor fluxes are estimated simultaneously. Different from the widely accepted use of EKF, in which it is optimized for either steady-state or transient operations, here using adjustable noise level process algorithm the optimization of EKF has been done for both states
the steady-state and the transient-state of operations. Additionally, the measurement noise immunity of EKF is also investigated. Second, Unscented Kalman Filter (UKF), which is an updated version of EKF, is proposed as a state estimator for speed sensorless field oriented control of induction motors. UKF state update computations, different from EKF, are derivative free and they do not involve costly calculation of Jacobian matrices. Moreover, variance of each state is not assumed Gaussian, therefore a more realistic approach is provided by UKF. In this work, the superiority of UKF is shown in the state estimation of induction motor. Third, Model Reference Adaptive System is studied as a state estimator. Two different methods, back emf scheme and reactive power scheme, are applied to MRAS algorithm to estimate rotor speed. Finally, a flux estimator and an open-loop speed estimator combination is employed to observe stator-rotor fluxes, rotor-flux angle and rotor speed. In flux estimator, voltage model is assisted by current model via a closed-loop to compensate voltage model&rsquo
s disadvantages.

Nous présentons dans cette thèse un nouveau modèle statistique de forme et l'utilisons pour la segmentation d'images avec a priori. Ce modèle est représenté par un champ de Markov. Les noeuds du graphe correspondent aux points de contrôle situés sur le contour de la forme géométrique, et les arêtes du graphe représentent les dépendances entre les points de contrôle. La structure du champ de Markov est déterminée à partir d'un ensemble de formes, en utilisant des techniques d'apprentissage de variétés et de groupement non-supervisé. Les contraintes entre les points sont assurées par l'estimation des fonctions de densité de probabilité des longueurs de cordes normalisées. Dans une deuxième étape, nous construisons un algorithme de segmentation qui intègre le modèle statistique de forme, et qui le relie à l'image grâce à un terme région, à travers l'utilisation de diagrammes de Voronoi. Dans cette approche, un contour de forme déformable évolue vers l'objet à segmenter. Nous formulons aussi un algorithme de segmentation basé sur des détecteurs de points d'intérêt, où le terme de régularisation est lié à l'apriori de forme. Dans ce cas, on cherche à faire correspondre le modèle aux meilleurs points candidats extraits de l'image par le détecteur. L'optimisation pour les deux algorithmes est faite en utilisant des méthodes récentes et efficaces. Nous validons notre approche à travers plusieurs jeux de données en 2D et en 3D, pour des applications de vision par ordinateur ainsi que l'analyse d'images médicales.

Seventy-four methicillin-resistant Staphylococcus aureus (MRSA) from two Malaysian hospitals were characterised by both phenotypic and genotypic techniques. These isolates were collected over an 18 year time period in the years, 1982, 1989, 1994 and 2000. All of the Malaysian MRSA isolates were found to be multiresistant and resistant to at least five different antimicrobial agents. Over 30% of them were non-typable by the International Basic Set of bacteriophages. The majority of the typable isolates were susceptible to the group III phages, especially phage 85. The majority of the isolates carried one to six plasmids. Only two isolates were plasmid free. The plasmid profiles of these isolates, other than the 1982 isolates, were very similar to each other. Contour-clamped homogeneous electric field (CHEF) gel electrophoresis was used to examine the genetic relatedness of the isolates. Twenty-six CHEF patterns were found among the isolates. These CHEF patterns were closely related to each other. The predominant CHEF pattern A was found in the 1982, 1989 and 1994 isolates. The CHEF patterns of the year 2000 isolates were different to CHEF pattern A, but still closely related. All of the isolates were found to carry the Allotype III SCCmec and have coagulase-gene type 24. Multilocus sequence typing was preformed on the isolates with CHEF pattern A collected in different years. These isolates were found to have either sequence type 239 (ST239), or its single locus variant. The predominant Malaysian clone belongs to the pandemic clone ST239-MRSA-III that is pandemic in Asian countries. (Enright, 2003, Ko et al., 2005).A 1.5 kb cryptic plasmid found in Malaysian isolates was indistinguishable from a cryptic plasmid found in an Australian isolate. A 3.0 kb cryptic plasmid found in Malaysian isolates was undistinguishable from a 3.0 kb plasmid found in Singaporean isolates. Class II multiresistance plasmids of 28, 30.5 and 35 kb were commonly found together in many Malaysian MRSA isolates. Both the 28 and 30.5 kb plasmids encode resistance to the heavy-metals and nucleic acid-binding (NAB) compounds. The 35 kb plasmid carries heavy-metal and NAB resistance but also encodes β-lactamase. Structurally these three plasmids are almost identical and probably have the same origin. The differences observed between these plasmids is probably due to excision or partial deletion of the β-lactamase transposon of the original plasmid. The 28 kb plasmid is identical to the 28 kb plasmid of Singaporean and some Australian isolates. A 20 kb plasmid in Indonesian isolates was found to be closely related to these three plasmids. A conjugative plasmid, pWBG707, conferring trimethoprim-resistance was found in Malaysian isolates. It did not carry either of the two staphylococcal trimethoprim-resistance genes, dfrA and dfrD. (Lyon and Skurray, 1987, Dale et al., 1995b) It either encodes a novel resistance gene or the recently discovered dfrG gene. (Sekiguchi et al., 2005) pWBG707 was also found to mobilise a small 3.0 kb kanamycin-resistance plasmid during conjugation.The mecR1 and mecI genes regulating the transcription of the methicillin-resistance gene, mecA, were also examined in the isolates. The Malaysian isolate, WBG7422, with the predominant CHEF pattern A has a nonsense mutation in its mecI gene that disables it. However, its mecR1 gene is intact. The eastern Australia MRSA (EA MRSA), WBG525, has a CHEF pattern that is closely related to the Malaysian predominant CHEF pattern A and its mecI gene has a mutation identical to the Malaysian isolate. Unlike the Malaysian isolate however, its mecR1 gene has a 166 bp deletion. Both WBG7422 and WBG525 express Class III heterogeneous methicillin resistance. However, WBG525 has more highly resistant cell in its population than WBG7422. The loss of aminoglycoside resistance, together with c. 114 kb of chromosomal DNA, was observed in some Malaysian isolates. The deleted segment was found to carry the aacA-aphD gene that encodes a bifunctional aminoglycoside-modifying enzyme conferring resistance to many of the aminoglycosides. The Malaysian isolates were compared with MRSA from different countries. These MRSA included 18 epidemic MRSA (EMRSA) from the United Kingdom, 15 Australian nosocomial MRSA, five classical MRSA, 22 community-acquired MRSA (CMRSA) from Australia and New Zealand and 46 nosocomial MRSAs from eight Asian-Pacific countries and South Africa. These Asian-Pacific countries were Australia, PR China, Hong Kong, Indonesia, Japan, Philippines, Singapore and Taiwan.The CHEF patterns of most of the Asian-Pacific and South African isolates were closely related to the Malaysian isolates. Isolates from Singapore, Indonesia and Philippines were found to have an identical CHEF pattern to the Malaysian CHEF patterns A5. The Asian-Pacific and South African isolates, including the Malaysian isolates, were found to be closely related to EMRSA-1, -4 and -7. These EMRSA belong to the ST239-MRSA-III clone and are coagulase-gene type 24. The isolates from Japan were the only Asian-Pacific isolates not related to the other Asian-Pacific isolates and EMRSAs. EMRSA-1 and EA MRSA have the same 166 bp deletion in their mecR1 gene. Both of these strains have closely related CHEF patterns, the same sequence type, coagulase-gene type and SCCmec. These results indicate that these two strains belongs to the same clone and confirms the international spread of this clone in the early 1980s. However, the Malaysian isolates have CHEF patterns that are more closely related to EMRSA-4 than to EMRSA-1. Similar to the Malaysian isolates EMRSA-4 has an intact mecR1 gene. The CMRSA isolates were not related to any of the nosocomial MRSA. They also have very diverse genetic backgrounds but carry less diverse SCCmec allotypes. Most of the CMRSA carry either Allotype IV or V SCCmec These results show that the spread of Malaysian MRSA is due to a single clonal expansion. Infection control measures would have to have been more efficient if this clone was to have been contained. The Malaysian epidemic clone is the Asian pandemic clone, ST239-MRSA-III. The Malaysian isolates and EMRSA-4 probably share the same ancestor.The presence of the same MRSA strain in Malaysian hospitals and in the hospitals of neighbouring countries indicates that the inter-hospital spread of an epidemic MRSA has occurred. This observation also suggests that the infection control measures in Malaysian hospitals have not been totally effective. The ineffectiveness of infection control has left Malaysian hospitals vulnerable to the future importation of new pandemic clones and/or highly virulent or resistant clones.

Seventy-four methicillin-resistant Staphylococcus aureus (MRSA) from two Malaysian hospitals were characterised by both phenotypic and genotypic techniques. These isolates were collected over an 18 year time period in the years, 1982, 1989, 1994 and 2000. All of the Malaysian MRSA isolates were found to be multiresistant and resistant to at least five different antimicrobial agents. Over 30% of them were non-typable by the International Basic Set of bacteriophages. The majority of the typable isolates were susceptible to the group III phages, especially phage 85. The majority of the isolates carried one to six plasmids. Only two isolates were plasmid free. The plasmid profiles of these isolates, other than the 1982 isolates, were very similar to each other. Contour-clamped homogeneous electric field (CHEF) gel electrophoresis was used to examine the genetic relatedness of the isolates. Twenty-six CHEF patterns were found among the isolates. These CHEF patterns were closely related to each other. The predominant CHEF pattern A was found in the 1982, 1989 and 1994 isolates. The CHEF patterns of the year 2000 isolates were different to CHEF pattern A, but still closely related. All of the isolates were found to carry the Allotype III SCCmec and have coagulase-gene type 24. Multilocus sequence typing was preformed on the isolates with CHEF pattern A collected in different years. These isolates were found to have either sequence type 239 (ST239), or its single locus variant. The predominant Malaysian clone belongs to the pandemic clone ST239-MRSA-III that is pandemic in Asian countries. (Enright, 2003, Ko et al., 2005).
A 1.5 kb cryptic plasmid found in Malaysian isolates was indistinguishable from a cryptic plasmid found in an Australian isolate. A 3.0 kb cryptic plasmid found in Malaysian isolates was undistinguishable from a 3.0 kb plasmid found in Singaporean isolates. Class II multiresistance plasmids of 28, 30.5 and 35 kb were commonly found together in many Malaysian MRSA isolates. Both the 28 and 30.5 kb plasmids encode resistance to the heavy-metals and nucleic acid-binding (NAB) compounds. The 35 kb plasmid carries heavy-metal and NAB resistance but also encodes β-lactamase. Structurally these three plasmids are almost identical and probably have the same origin. The differences observed between these plasmids is probably due to excision or partial deletion of the β-lactamase transposon of the original plasmid. The 28 kb plasmid is identical to the 28 kb plasmid of Singaporean and some Australian isolates. A 20 kb plasmid in Indonesian isolates was found to be closely related to these three plasmids. A conjugative plasmid, pWBG707, conferring trimethoprim-resistance was found in Malaysian isolates. It did not carry either of the two staphylococcal trimethoprim-resistance genes, dfrA and dfrD. (Lyon and Skurray, 1987, Dale et al., 1995b) It either encodes a novel resistance gene or the recently discovered dfrG gene. (Sekiguchi et al., 2005) pWBG707 was also found to mobilise a small 3.0 kb kanamycin-resistance plasmid during conjugation.
The mecR1 and mecI genes regulating the transcription of the methicillin-resistance gene, mecA, were also examined in the isolates. The Malaysian isolate, WBG7422, with the predominant CHEF pattern A has a nonsense mutation in its mecI gene that disables it. However, its mecR1 gene is intact. The eastern Australia MRSA (EA MRSA), WBG525, has a CHEF pattern that is closely related to the Malaysian predominant CHEF pattern A and its mecI gene has a mutation identical to the Malaysian isolate. Unlike the Malaysian isolate however, its mecR1 gene has a 166 bp deletion. Both WBG7422 and WBG525 express Class III heterogeneous methicillin resistance. However, WBG525 has more highly resistant cell in its population than WBG7422. The loss of aminoglycoside resistance, together with c. 114 kb of chromosomal DNA, was observed in some Malaysian isolates. The deleted segment was found to carry the aacA-aphD gene that encodes a bifunctional aminoglycoside-modifying enzyme conferring resistance to many of the aminoglycosides. The Malaysian isolates were compared with MRSA from different countries. These MRSA included 18 epidemic MRSA (EMRSA) from the United Kingdom, 15 Australian nosocomial MRSA, five classical MRSA, 22 community-acquired MRSA (CMRSA) from Australia and New Zealand and 46 nosocomial MRSAs from eight Asian-Pacific countries and South Africa. These Asian-Pacific countries were Australia, PR China, Hong Kong, Indonesia, Japan, Philippines, Singapore and Taiwan.
The CHEF patterns of most of the Asian-Pacific and South African isolates were closely related to the Malaysian isolates. Isolates from Singapore, Indonesia and Philippines were found to have an identical CHEF pattern to the Malaysian CHEF patterns A5. The Asian-Pacific and South African isolates, including the Malaysian isolates, were found to be closely related to EMRSA-1, -4 and -7. These EMRSA belong to the ST239-MRSA-III clone and are coagulase-gene type 24. The isolates from Japan were the only Asian-Pacific isolates not related to the other Asian-Pacific isolates and EMRSAs. EMRSA-1 and EA MRSA have the same 166 bp deletion in their mecR1 gene. Both of these strains have closely related CHEF patterns, the same sequence type, coagulase-gene type and SCCmec. These results indicate that these two strains belongs to the same clone and confirms the international spread of this clone in the early 1980s. However, the Malaysian isolates have CHEF patterns that are more closely related to EMRSA-4 than to EMRSA-1. Similar to the Malaysian isolates EMRSA-4 has an intact mecR1 gene. The CMRSA isolates were not related to any of the nosocomial MRSA. They also have very diverse genetic backgrounds but carry less diverse SCCmec allotypes. Most of the CMRSA carry either Allotype IV or V SCCmec These results show that the spread of Malaysian MRSA is due to a single clonal expansion. Infection control measures would have to have been more efficient if this clone was to have been contained. The Malaysian epidemic clone is the Asian pandemic clone, ST239-MRSA-III. The Malaysian isolates and EMRSA-4 probably share the same ancestor.
The presence of the same MRSA strain in Malaysian hospitals and in the hospitals of neighbouring countries indicates that the inter-hospital spread of an epidemic MRSA has occurred. This observation also suggests that the infection control measures in Malaysian hospitals have not been totally effective. The ineffectiveness of infection control has left Malaysian hospitals vulnerable to the future importation of new pandemic clones and/or highly virulent or resistant clones.

The objective of this essay is to approach a larger comprehension of the drama of George Bernard Shaw. The essay studies the combination of ideas and aesthetics in the play Mrs Warren’s Profession; how theatrical and mainly literary aesthetics interplay with political ideas and what the consequence of this combination is. The study illustrates that the dramatic method consists of using ideas as effective theatrical tools to move the reader/viewer by thought and not by sentiment. The study also illustrates that a key to understanding Shaw’s drama can be found in the construction of operas and symphonies; musical theoretic constructions are an integrated dramatic technique in Mrs Warren’s Profession. The study shows that it is a play with a political and social purpose; to raise awareness of the mechanisms of prostitution. The play does not use simplifications in terms of good and evil. It questions conventionality, unveils social hypocrisy and attempts to disillusion the reader/viewer. The antithesis between realism and idealism is an important source of dynamics and constitutes one of the principal aesthetical constructions.

El cáncer es una de las principales causas de muerte en el mundo. Los tumores cerebrales tienen una incidencia relativamente baja en comparación con otras patologías cancerígenas más generalizadas, pero la prognosis de algunos es muy pobre, contribuyendo significativamente a su morbilidad. La gestión clínica de una masa anormal en el cerebro es materia delicada y difícil, por lo que los expertos han de basarse en mediciones indirectas no invasivas de las características del tumor y de su crecimiento. En la práctica radiológica actual, estas mediciones se realizan a menudo mediante técnicas de resonancia magnética (MR), como la imagen (MRI) y la espectroscopia (MRS). La vasta información contenida en las señales de MR les hace ideales para la aplicación de técnicas de reconocimiento de patrones (PR). Durante las dos últimas décadas, estas técnicas se han aplicado con éxito al problema de la extracción de conocimiento a partir de datos de tumores cerebrales humanos, para su diagnóstico y pronóstico. No obstante, la discriminación de algunos tipos y subtipos de tumores, así como la delimitación precisa del área tumoral, continúan siendo un reto para los investigadores. En esta tesis, abordamos tales retos mediante la aplicación de un conjunto de técnicas avanzadas de PR. En primera instancia, se implementaron una variedad de técnicas comunes y bien conocidas en una herramienta integrada de software. Esta fue utilizada en tareas de reducción de dimensionalidad (DR), clasificación y evaluación de modelos, para el desarrollo de clasificadores apropiados para analizar datos de MRS. Posteriormente, se profundizó en el desarrollo de métodos de extracción de características (FE), para proponer un método que proporciona prototipos de señal interpretables a partir de los datos de MRS. En una siguiente fase, dos técnicas de descomposición espectral fueron utilizadas para extraer fuentes de MRS e identificar la que proporciona mejores resultados en el contexto de problemas de neuro-oncología, utilizando datos de MRS de un solo vóxel (SV). El mejor y más adecuado método de extracción de fuentes resultante se utilizó posteriormente para derivar fuentes correlacionadas con los espectros promedio de los tipos de tejidos estudiados. El primer enfoque se aplicó también en el contexto de datos de múltiples vóxeles (MV), donde se propone un mecanismo para delimitar la zona patológica del tumor. Las contribuciones se pueden resumir de la siguiente manera. En primer lugar, el desarrollo de una herramienta de software que ha permitido reproducir clasificadores previamente publicados, así como probar nuevas hipótesis. También se ha contribuido con un método de FE, cuyo rendimiento es comparable a su contraparte más comúnmente utilizada en el análisis de datos de MRS, al tiempo que mejora su interpretación. Por otra parte, hemos identificado la variante de descomposición espectral que mejor se adapta al análisis de datos de SV MRS, llamada Convex Non-negative Matrix Factorisation (NMF), mostrando su capacidad para discriminar entre tejido sano, necrosis y tumor en proliferación activa, con resultados que son comparables a los obtenidos en modo supervisado. Con los datos de MV, los resultados obtenidos evidencian que es posible conseguir una delimitación precisa de la zona patológica mediante la aplicación de Convex-NMF. Con esta tesis, ofrecemos una herramienta a radiólogos espectroscopistas para facilitar el desarrollo de clasificadores para el análisis de datos de MRS, en un amplio grupo de tipos tumorales. También ofrecemos una alternativa no supervisada para mejorar la discriminación entre tipos y subtipos tumorales, colocando este enfoque un paso por delante de los métodos supervisados clásicos. Esto nos ha permitido hacer frente a una de las principales fuentes de incertidumbre en el manejo clínico de tumores cerebrales: la dificultad de delimitar adecuadamente el área patológica.
Cancer is a leading cause of death worldwide. Tumours of the Central Nervous System and, among them, brain tumours have a relatively low incidence as compared to other more widespread cancer pathologies, but the prognosis of some of them is very poor, contributing significantly to morbidity. The clinical management of an abnormal mass in the brain is sensitive and difficult, making experts to rely on non-invasive indirect measurements of the tumour characteristics and growth. In current radiological practice, these data measurements are often provided by magnetic resonance (MR) techniques, such as imaging (MRI) and spectroscopy (MRS). The rich information contained in MR signals makes them ideally suited to the application of pattern recognition (PR) techniques. Over the last two decades, these techniques have been successfully used to address the problem of knowledge extraction from human brain tumour data, for their diagnosis and prognosis. Nevertheless, the discrimination of some tumour types and subtypes, along with the accurate delimitation of the tumour area, remained challenging. In this thesis, we approach these challenges using a set of advanced PR techniques. A variety of common and well-known dimensionality reduction (DR), classification, and evaluation methods are first gathered in a software tool, used for the development of classifiers that are suitable for the analysis of MRS data. We then delve into the feature extraction (FE) family of DR methods to propose a method that is robust in the presence of noise, not prone to overfitting, and which also provides interpretation of the extracted MRS signal prototypes. Two spectral decomposition techniques, in different algorithmic variants, are subsequently used to extract the sources of the MRS signals and identify the one that provides better results in the context of neuro-oncology, using single-voxel (SV) MRS data. The best and most adequate source extraction method is then used to derive sources correlated with the mean spectra of known tissue types. The former, an unsupervised approach, is also applied in this thesis in the multi-voxel (MV) context, where we propose a mechanism for delimiting the pathological area of the tumour. The contributions of this thesis can be summarised as follows. First, the development of a software tool allowed us to reproduce previously published MRS-based classifiers, and test new hypotheses that led to new publications. We also contributed a FE method, whose performance is comparable to its most commonly used counterpart in MRS data analysis, while improving on the interpretability. Moreover, we identified the spectral decomposition variant that best suits the analysis of SV MRS data, namely Convex Non-negative Matrix Factorisation (NMF), and showed its ability to discriminate between healthy tissue, necrosis, and actively proliferating tumour, with results that are comparable to those obtained in fully supervised mode. For MV data, we successfully benchmarked alternative spectral decomposition methods, and provided evidence supporting that very accurate delimitation can be achieved through the application of Convex-NMF. With this thesis, we provide spectroscopists with a tool that facilitates the development of classifiers for the analysis of MRS data, for a large group of tumour types; allowing them to concentrate on the interpretation of the results, without requiring a specialised mathematical expertise for testing their hypotheses. We also provide an unsupervised alternative to improve the discrimination between tumour types and subtypes, placing this approach one step ahead of classical label-requiring supervised methods for detection of the increasingly recognised molecular subtype heterogeneity within human brain tumours. This also allowed us to accurately tackle one of the main sources of uncertainty in the clinical management of brain tumours, which is the difficulty of appropriately delimiting the pathological area.

Nous présentons dans cette thèse une approche nouvelle de la segmentation d’images, avec des descripteurs a priori utilisant des champs de Markov d’ordre supérieur. Nous représentons le modèle de forme par un graphe de distribution de points qui décrit les informations a priori des invariants de pose grâce à des cliques L1 discrètes d’ordre supérieur. Chaque clique de triplet décrit les variations statistiques locales de forme par des mesures d’angle,ce qui assure l’invariance aux transformations globales (translation, rotation et échelle). L’apprentissage d’une structure de graphe discret d’ordre supérieur est réalisé grâce à l’apprentissage d’un champ de Markov aléatoire utilisant une décomposition duale, ce qui renforce son efficacité tout en préservant sa capacité à rendre compte des variations.Nous introduisons la connaissance a priori d’une manière innovante pour la segmentation basée sur un modèle. Le problème de la segmentation est ici traité par estimation statistique d’un maximum a posteriori (MAP). L’optimisation des paramètres de la modélisation- c’est à dire de la position des points de contrôle - est réalisée par le calcul d’une fonction d’énergie globale de champs de Markov (MRF). On combine ainsi les calculs statistiques régionaux et le suivi des frontières avec la connaissance a priori de la forme.Les descripteurs invariants sont estimés par des potentiels de Markov d’ordre 2, tandis que les caractéristiques régionales sont transposées dans un espace de caractéristiques et calculées grâce au théorème de la Divergence.De plus, nous proposons une nouvelle approche pour la segmentation conjointe de l’image et de sa modélisation ; cette méthode permet d’obtenir une segmentation plus fine lorsque la délimitation précise d’un objet est recherchée. Un modèle graphique combinant l’information a priori et les informations de pixel est développé pour réaliser l’unité des modules "top-down" et "bottom-up". La cohérence entre l’image et sa modélisation est assurée par une décomposition qui associe les parties du modèle avec la labellisation de chaque pixel.Les deux champs de Markov d’ordre supérieur considérés sont optimisés par les algorithmes de l’état de l’art. Les résultats prometteurs dans les domaines de la vision par ordinateur et de l’imagerie médicale montrent le potentiel de cette méthode appliquée à la segmentation
In this thesis, we propose a novel framework for knowledge-based segmentation using high-order Markov Random Fields (MRFs). We represent the shape model as a point distribution graphical model which encodes pose invariant shape priors through L1 sparse higher order cliques. Each triplet clique encodes the local shape variation statistics on the angle measurements which inherit invariance to global transformations (i.e. translation,rotation and scale). A sparse higher-order graph structure is learned through MRF training using dual decomposition, producing boosting efficiency while preserving its ability to represent the shape variation.We incorporate the prior knowledge in a novel framework for model-based segmentation.We address the segmentation problem as a maximum a posteriori (MAP) estimation in a probabilistic framework. A global MRF energy function is defined to jointly combine regional statistics, boundary support as well as shape prior knowledge for estimating the optimal model parameters (i.e. the positions of the control points). The pose-invariant priors are encoded in second-order MRF potentials, while regional statistics acting on a derived image feature space can be exactly factorized using Divergence theorem. Furthermore, we propose a novel framework for joint model-pixel segmentation towardsa more refined segmentation when exact boundary delineation is of interest. Aunified model-based and pixel-driven integrated graphical model is developed to combine both top-down and bottom-up modules simultaneously. The consistency between the model and the image space is introduced by a model decomposition which associates the model parts with pixels labeling. Both of the considered higher-order MRFs are optimized efficiently using state-of the-art MRF optimization algorithms. Promising results on computer vision and medical image applications demonstrate the potential of the proposed segmentation methods

The large size of the datasets produced by medical imaging protocols contributes to the success of supervised discriminative methods for semantic labelling of images. Our study makes use of a general and efficient emerging framework, discriminative random forests, for the detection of brain lesions in multi-modal magnetic resonance images (MRIs). The contribution is three-fold. First, we focus on segmentation of brain lesions which is an essential task to diagnosis, prognosis and therapy planning. A context-aware random forest is designed for the automatic multi-class segmentation of MS lesions, low grade and high grade gliomas in MR images. It uses multi-channel MRIs, prior knowledge on tissue classes, symmetrical and long-range spatial context to discriminate lesions from background. Then, we investigate the promising perspective of estimating the brain tumor cell density from MRIs. A generative-discriminative framework is presented to learn the latent and clinically unavailable tumor cell density from model-based estimations associated with synthetic MRIs. The generative model is a validated and publicly available biophysiological tumor growth simulator. The discriminative model builds on multi-variate regression random forests to estimate the voxel-wise distribution of tumor cell density from input MRIs. Finally, we present the "Spatially Adaptive Random Forests" which merge the benefits of multi-scale and random forest methods and apply it to previously cited classification and regression settings. Quantitative evaluation of the proposed methods are carried out on publicly available labeled datasets and demonstrate state of the art performance.

L'analyse des structures curvilignes en 3 dimensions est un problème difficile en analyse d'images. En effet, ces structures sont fines, facilement corrompues par le bruit et présentent une géométrie complexe. Depuis plusieurs années, de nombreuses méthodes spécialement dédiées au traitement d'images contenant des structures curvilignes ont vu le jour. Ces méthodes concernent diverses applications en science des matériaux, télédétection ou encore en imagerie médicale. Malgré cela, l'analyse des structures curvilignes demeure une tâche complexe.Dans cette présentation nous parlerons de la caractérisation des structures curvilignes pour l'analyse d'images. Nous présenterons en premier lieu une nouvelle méthode appelée RORPO, à partir de laquelle deux caractéristiques peuvent être calculées. La première est une caractéristique d'intensité, qui préserve l'intensité des structures curvilignes tout en réduisant celle des autres structures. La deuxième est une caractéristique de direction, qui fournit en chaque point d'une image, la direction d'une structure curviligne potentielle.RORPO, contrairement à la plupart des méthodes de la littérature, est une méthode non locale, non linéaire et mieux adaptées à l'anisotropie intrinsèque des structures curvilignes. Cette méthode repose sur une notion récente de Morphologie Mathématique: les opérateurs par chemins.RORPO peut directement servir au filtrage d'images contenant des structures curvilignes, afin de spécifiquement les préserver, mais aussi de réduire le bruit. Mais les deux caractéristiques de RORPO peuvent aussi être utilisées comme information a priori sur les structure curvilignes, afin d'être intégrées dans une méthode plus complexe d'analyse d'image.Dans un deuxième temps, nous présenterons ainsi un terme de régularisation destiné à la segmentation variationnelle, utilisant les deux caractéristiques de RORPO.L'information apportée par ces deux caractéristiques permet de régulariser les structures curvilignes seulement dans la direction de leur axe principal. De cette manière, ces structures sont mieux préservées, et certaines structures curvilignes déconnectées par le bruit peuvent aussi être reconnectées.Des résultats en 2D et 3D de ces méthodes seront enfin présentées sur des images de vaisseaux sanguins provenant de diverses modalités
The analysis of curvilinear structures in 3D images is a complex and challenging task. Curvilinear structures are thin, easily corrupted by noise and present a complex geometry. Despite the numerous applications in material sciences, remote sensing and medical imaging and the large number of dedicated methods developed the last few years, the detection of such structures remains a difficult problem.In this thesis, we work on the characterization of curvilinear structures. We first propose a new framework called RORPO, to characterize such structures through two features: an intensity feature which preserves the intensity of curvilinear structures while decreasing the intensity of other structures, and a directional feature providing at each point, the direction of the curvilinear structure.RORPO, unlike classic other state of the art methods, is non-local and non-linear, which are desirable properties adapted to the intrinsic anisotropy of curvilinear structures. RORPO is based on recent advances in mathematical morphology: the path operators.We provide a full description of the structural and algorithmic details of RORPO, and we also conduct a quantitative comparative study of our features with three popular curvilinear structure analysis filters: the Frangi Vesselness, the Optimally Oriented Flux, and the Hybrid Diffusion with Continuous Switch.Besides the straightforward filtering application, both RORPO features are designed to be used as prior information to characterize curvilinear structures. We propose a regularization term for variational segmentation which embed these features. Classic regularization terms are not adapted to curvilinear structures and usually lead to the loss of most of the low-contrasted ones. We propose to only regularize curvilinear structures along their main axis thanks to both RORPO features. This directional regularization better preserves curvilinear structures but also reconnect parts of these structures which may have been disconnected by noise.We present results of the segmentation of retinal images with the Chan et al. model either with the classic total variation or our directional regularization term. This confirm that our regularization term is better suited for images with curvilinear structures

A new method of adaptive impulse control is developed to precisely and quickly control the position of machine components subject to friction. Friction dominates the forces affecting fine positioning dynamics. Friction can depend on payload, velocity, step size, path, initial position, temperature, and other variables. Control problems such as steady-state error and limit cycles often arise when applying conventional control techniques to the position control problem. Studies in the last few decades have shown that impulsive control can produce repeatable displacements as small as ten nanometers without limit cycles or steady-state error in machines subject to dry sliding friction. These displacements are achieved through the application of short duration, high intensity pulses. The relationship between pulse duration and displacement is seldom a simple function. The most dependable practical methods for control are self-tuning; they learn from online experience by adapting an internal control parameter until precise position control is achieved. To date, the best known adaptive pulse control methods adapt a single control parameter. While effective, the single parameter methods suffer from sub-optimal settling times and poor parameter convergence. To improve performance while maintaining the capacity for ultimate precision, a new control method referred to as Adaptive Impulse Control (AIC) has been developed. To better fit the nonlinear relationship between pulses and displacements, AIC adaptively tunes a set of parameters. Each parameter affects a different range of displacements. Online updates depend on the residual control error following each pulse, an estimate of pulse sensitivity, and a learning gain. After an update is calculated, it is distributed among the parameters that were used to calculate the most recent pulse. As the stored relationship converges to the actual relationship of the machine, pulses become more accurate and fewer pulses are needed to reach each desired destination. When fewer pulses are needed, settling time improves and efficiency increases. AIC is experimentally compared to conventional PID control and other adaptive pulse control methods on a rotary system with a position measurement resolution of 16000 encoder counts per revolution of the load wheel. The friction in the test system is nonlinear and irregular with a position dependent break-away torque that varies by a factor of more than 1.8 to 1. AIC is shown to improve settling times by as much as a factor of two when compared to other adaptive pulse control methods while maintaining precise control tolerances.

The induction motors are the most famous and widely used machines in most of the industrial as well as in domestic applications due to its simplicity and low cost. When the variable speed applications are required the induction machines are used. For induction machines, variable speed drives requires both fast torque response as well as wide operating range of speed. Indirect vector control of induction motor is somewhat predictive method, where the speed of the rotor flux is predicted from slip speed and rotor speed. The rotor speed may be obtained either from the estimation method or from speed sensors. If due to a temperature change, there is any variation in the rotor time constant it may lead to uneven orientation of the flux and hence dynamic performance of the drive deteriorates. The continuous online estimation of rotor time constant or rotor resistance is very crucial for the flux orientation which subjected to the change of rotor time constant for variation in temperature. Due to lost in orientation of the flux, the coupling effect makes the performance of the induction motor drive slightly sluggish. Model reference adaptive system (MRAS) method is incorporated for the online estimation of the machine parameter. Model reference adaptive system controller using the reactive power (Q) is presented here, for the online estimation of the rotor resistance to maintain the flux orientation constant and fixed in an indirect vector control of induction motor drive. The formation of MRAS with the steady-state and instantaneous reactive power eliminates the estimation of flux. Reactive power based MRAS estimator is less prone to the integral problems like drift and saturation. Simulation results have presented to confirm the effectiveness of the technique.

碩士
國立海洋大學
導航與通訊系碩士班
91
In the VHF Digital Link, STDMA (Self-Organized Time Division Multiple Access) employs the GNSS (Global Navigation Satellite System) to fix the position and obtain the precision time simultaneously, and then utilizes the self-organization algorithm to allocate the time slot for data transmission. Without reliance on a master station, the mobile stations can communicate with each other more easily. Estimation of synchronization and STDMA Algorithm are the key issues for the STDMA based AIS (Automatic Identification System). In case of losing the primary time source, timing estimation has to be performed to maintain the system operation. We assume that all the stations in the network would function as a secondary time source to the failed station. Measuring the time of arrival of a transmitted signal from other station can be treated as a measurement of sensor with observation noise. On the other hand, the sync state of the station, reporting rate and the signal to noise ratio related to the distance between two stations determine the precision and resolution of the measurement. Accordingly, we label the available stations with the multiresolution status. Utilizing the concept of multisensor data fusion and multiresolution technique, we obtain a more accurate time estimate.

This thesis examines the documentation process of a collection of contemporary objects made by a Northern Tutchone artist, Mrs. Gertie Tom, from Whitehorse, Yukon Territory. The beaded moosehide objects were purchased by the University of British Columbia Museum of Anthropology between 1992 and 1994, and include a vest, a 'shell' belt, gloves, moccasins, mittens, and a hat. The documentation process included Mrs. Tom documenting her objects in her own words. This thesis investigates the steps, cost, and time involved in documenting the six objects. It also explores how object documentation fits within museological debates on access, collections management, and current museology. Museums are facing an increasingly changing environment. Originating people are requesting changes in the relationship between museums and objects. The cost of caring for museum collections is increasing and many objects within these collections are inadequately documented and consequently of little value for research. At the same time, museums continue to collect. In addition, many scholars think the future of museums is in current and controversial ideas rather than objects. The single, often paternalistic, museum message is being challenged, and people are arguing for museums to exhibit a variety of voices and opinions. This thesis answers the questions: What does this project contribute to issues of collections access, especially with reference to First Nations material? What costs are involved in documenting museum collections? Does documentation improve information available on collections? Does it allow people, not just objects, to become an integral part of museums and to bring new ideas and issues to museums? Although the documentation process required a commitment of time and money, my research confirms that having people document their own objects is beneficial in reference to current museological issues. The information provided by Mrs. Tom not only documents her objects but offers insight into other aspects of her life and Northern Tutchone culture in general. The documentation, in addition to providing answers to questions such as provenience, use, and materials, reveals ideas and interpretations of the objects from Mrs. Tom's point of view. Having Mrs. Tom document her objects in her own words means she, rather than the museum, is the authoritative voice. In an effort to bring a balance between objects and ideas, museums should only acquire objects they can afford to document.

Professional Doctorate - Doctor of Philosophy (PhD)
Multiple sclerosis (MS) is an immune-mediated neuronal disorder in which inflammatory cells attack the myelin of the central nervous system, leading to varying extents of neuroaxonal injury, demyelination and gliosis by affecting both the brain and spinal cord. In the last few decades, conventional MRI techniques, sensitive at detecting MS plaques in the brain and spinal cord, have been the main imaging tool for diagnosis and on-going monitoring for MS pathology, reflecting inflammatory activity via T2 lesions and brain damage via atrophy measurements. However, MRI features of MS are not specific to its pathological substrates which contribute to the development of permanent disability. Presently, MRI is not able to quantify the damage in normal appearing white matter and has technical limitations in detecting and quantifying damage to grey matter. Also, the clinical manifestations of MS plaques in different anatomical locations such as spinal cord and optic nerves are variable. A non-invasive, advanced MR technique of one-dimensional (1D) magnetic resonance spectroscopy (H-MRS) is capable of exploring the metabolic alterations of the MS brain in relatively small volumes of interest. This has the potential to provide molecular biomarkers for early detection and to monitor disease progression of the MS brain. This technique may allow better understanding of the pathophysiology of symptoms and aid in the development of new treatments. In this thesis, the diurnal stability and long-term repeatability and reliability of in-vitro and in-vivo measurements at 3 Tesla have been investigated to prove the validity of H-MRS technique in clinical settings. This study demonstrates the stability of neurometabolite levels in longitudinal studies (over extended periods of time) and the reliable detection and distinction of neurometabolites between healthy controls (HCs) and MS patients. The findings of the study showed H-MRS is reliable and had minimal diurnal variations. Disease modifying therapies (DMT) for multiple sclerosis treatment were deemed vital to understand the underlying pathology resulting in disease progression and therefore assist in developing new meaningful imaging biomarkers to evaluate the clinical efficacy of treatment radiologically. Few studies have used 1D H-MRS to monitor the response to DMT in relapsing-remitting MS (RRMS) and to assess if immunomodulatory therapies can reverse or prevent the progression of neuronal injury. Dimethyl fumarate (DMF), an oral DMT for MS, displays anti-oxidative properties, thought to be via modulation of glutathione (GSH). A longitudinal study was designed to evaluate the impact of DMF treatment longitudinally over 24 months (five time points) on hippocampal neurometabolites in RRMS patients using single voxel 1D H-MRS techniques at short TE and 3T. This study showed that cross-sectional analysis confirmed the importance of hippocampal NAA and increase in myo-inositol as indicators of axonal loss and gliosis in RRMS cohort compared to HCs. This study also showed that DMF treatment may impact on hippocampal metabolism, specifically GSH levels, which supports its assumed anti-oxidant mode of action, resulting in an anti-inflammatory effect in the MS brain following DMF treatment. This study is the first to illustrate a change in hippocampal metabolism associated with the onset of treatment with DMF in RRMS patients. This thesis also investigated the impact of DMF treatment on the pre-frontal cortex (PFC) and posterior cingulate gyrus (PCG) metabolic profiles at pre- and post-treatment onset at four time points using 1D H-MRS technique. The correlation between brain metabolites and severity of clinical and neuropsychological symptoms were analysed at three time points at baseline, 12 and 24 months following the initiation of DMF treatment in the regions responsible for cognitive functioning; PFC and PCG. This study showed significant cross-sectional reductions in N-acetylaspartate (NAA) in PFC and PCG and increase in PFC tCho in RRMS cohort compared to HCs. DMF treatment showed the mean NAA levels in PFC and PCG were altered significantly over the 24-month treatment period, but stabilised and didn’t significantly change between 1st and 2nd year of treatment. This study demonstrated that 1D H-MRS is a sensitive marker of disease activity with several metabolites correlating with clinical parameters, but also capable to detect a treatment effects prior to volumetric change. This study suggested that PCG and PFC regions may be sensitive to the progression of clinical and cognitive disabilities of MS patients and may play an important role in monitoring cognitive performance. Injectable DMTs (interferon and glatiramer acetate) as well as oral DMTs (fingolimod and DMF) have not only shown the reduction of relapse rate and T2 lesion load but also brain atrophy, which seems to be related to long term disease on disability. Additionally, the efficacy of these DMTs have also been evaluated using 1D H-MRS methods in a cross-sectional fashion. This study is the first in-vivo investigation of the impact of these treatments on the hippocampus, PFC and PCG metabolism in RRMS patients. RRMS patients, on therapy for a minimum of 6 months, with no new clinical symptoms or change in their disability status in the last 6 months were included in the study. This study also established the association between clinical symptoms in MS patients especially cognitive function and neurometabolites as well as volumetric changes. We also confirmed the importance of NAA and myo-inositol (m-Ins) as indicators of axonal loss and gliosis. This study demonstrated hippocampal metabolic correlation with memory, disability scale and TARCS; PCG with memory, CSF volume and TARCS; while PFC metabolites correlated with attention, depression and anxiety. The cross-sectional nature of our findings warrants longitudinal investigations to further clarify clinical effects of fingolimod and injectables, and to determine associations between hippocampus, PFC and PCG metabolic levels and treatment efficacy. Clinically, three-dimensional magnetic resonance spectroscopic imaging (3D MRSI) is more suitable than single voxel method due to the former’s ability to obtain important metabolic information with extended brain coverage. This thesis investigated the performance of fast MRSI techniques at short TE and 3T, using LASER sequence with adiabatic gradient-offset independent adiabaticity wideband pulse (GOIA-W)[16,4]. This fast MRSI techniques coupled with tissue segmentation of the brain were used to identify neurometabolic differences in normal appearing white matter (NAWM) and white matter lesions (WML) of RRMS patients compared to age and sex-matched HCs. This study used a novel post-processing analysis pipeline and three binary support vector machine (SVM) classification that allowed individual small voxel analysis to demonstrate true nature of NAWM and WML and distinguish tissue types. Our findings of significant changes in NAWM and more so in WML of MS patients compared with healthy voxels using spiral 3D MRSI indicates that the metabolic abnormalities (reduced NAA and increased m-Ins) in RRMS are associated with a gradual loss of axonal integrity and astrogliosis in white matter. This study demonstrates the benefit of MRSI in evaluating MS neurometabolic changes in damaged NAWM. SVM of MRSI data in the MS brain may be suited for clinical monitoring and progression of MS patients.

碩士
國立高雄師範大學
人力與知識管理研究所
103
Methicillin-resistant Staphylococcus aureus (MRSA) is a multi-drug-resistant pathogenic bacteria that receive the most attention. Different strains of S. aureus can produce toxins and cause skin, wounds, osteomyelitis, pneumonia, bacteremia, and other infections. Infection is mainly spread through direct physical contact, skin wounds, crowded environment, and poor personal hygiene may also cause infection. Patients infected with MRSA bacteremia within 30 days mortality was 34%. Selection of antibiotics mainly depends on microbial culture and antibiotic sensitivity test. The purpose of this study is predict outcome of patients with MRSA bacteremia using data mining techniques to provide better management of patient therapy. We used MRSA persistence in bacteremia after 7 days, 30 days, and death as endpoints in patients receiving a traditional vancomycin therapy. In this study, we used 29 risk factors associated with MRSA bacteremia. Our results showed that we are able to predict the 7-day persistence of MRSA in blood cultures at accuracy ranged 82.0% ~ 86.6%; death of patient within 30 days at accuracy ranged 53.4% ~ 69.2%. Such a prediction method can be applied in hospitals by use of a prospective study to collect patient data in order to establish their predictive models.

Dissertação de Mestrado Integrado em Engenharia Biomédica apresentada à Faculdade de Ciências e Tecnologia
As doenças neurodegenerativas incluem várias condições caracterizadas por uma degeneração contínua e acentuada dos neurónios no cérebro. A prevalência dessas doenças tem aumentado em todo o mundo e os tratamentos disponíveis são, na sua maioria, sintomáticos. Portanto, a carga física, emocional e económica para esses doentes e cuidadores é devastadora, enquanto a degeneração vai progredindo nos indivíduos afetados. As doenças neurodegenerativas do movimento, como a Doença de Parkinson (PD) e Huntington (HD), são caracterizadas por graves défices motores, acompanhados de disfunções emocionais e cognitivas. Estas disfunções têm sido relacionadas com alterações no controlo excitatório/inibitório (E/I) pela desconexão progressiva no ciclo gânglios de base-tálamo-cortical. O tónus excitatório e inibitório pode ser avaliado, in vivo, por Espectroscopia de Ressonância Magnética de protão (1H-MRS), pois permite estimar indiretamente os níveis de GABA (inibitório) e Glutamato (excitatório).Portanto, o objetivo deste projeto é estudar o equilíbrio excitatório/inibitório, in vivo, no córtex frontal de doentes HD e DP, comparando as razões de Glx (combinação de glutamato e glutamina) e GABA em indivíduos com essas doenças e controlos saudáveis emparelhados para idade e sexo.Setenta doentes (27HD; 27 DP; 16 controles) foram submetidos a um protocolo de Ressonância Magnética a 3T incluindo aquisição de imagens estruturais, funcionais e de espectroscopia. Neste estudo, a análise foi focada em dados de 1H-MRS, adquiridos num voxel de 27mL no lobo pré-frontal. Como o GABA é difícil de resolver no espectro de protão, devido à sua baixa concentração e contaminação do sinal por sinais sobrepostos, foi usada uma abordagem de edição espetral através da sequência de pulso MEGA-PRESS. O processamento de dados espectrais foi realizado usando o Gannet e a análise estatística foi realizada no software estatístico R. Um doente de Huntington foi excluído, pois os dados de MRS não foram adquiridos na mesma região anatómica.Após uma avaliação visual inicial de controlo de qualidade dos espectros, 44 conjuntos de dados foram descartados. A nossa hipótese é que o movimento excessivo, ao qual a MRS é particularmente sensível, foi o artefato predominante que contribuiu para a alta taxa de rejeição. No entanto, vários fatores que afetam a qualidade do sinal podem ser considerados: permanecer completamente imóvel é um desafio para doentes com PD e HD em neuroimagem; o movimento leva ao deslocamento do voxel causando artefatos de contaminação por volumes parciais; o lobo frontal é uma área particularmente sensível para aquisição de MRS devido a artefatos de suscetibilidade; realizar 1H-MRS após fMRI pode produzir desvios de frequência devido aos gradientes aplicados; etc. Encontramos algumas tendências nos níveis de GABA e Glx entre os grupos, mas não foram estatisticamente significativas e os resultados são inconclusivos.Um debate sobre as medidas de avaliação de qualidade e métodos recentes de correção de artefatos foi brevemente realizado. Estudos futuros de 1H-MRS focando em populações especiais propensas ao movimento, como populações clínicas, e também em recém-nascidos e crianças pequenas devem ter um desenho de estudo e plano de análise de dados ainda mais criteriosos, tendo em consideração as taxas de exclusão de dados devido aos critérios de garantia de qualidade, o protocolo de aquisição e algoritmos de processamento de dados.
Neurodegenerative diseases span several conditions characterized by a continuous and massive neural degeneration in distinct brain regions. The prevalence of these disorders is rising worldwide, and the available treatments are mostly symptomatic. Therefore, the physical, emotional, and economic burden to these patients and caregivers is devastating while degeneration progresses in the afflicted individuals. Neurodegenerative movement disorders, such as Parkinson’s (PD) and Huntington’s Disease (HD) are characterized by severe motor deficits accompanied with emotional and cognitive dysfunctions. These dysfunctions have been related with alterations on excitatory/inhibitory (E/I) control with a progressive disconnection in basal ganglia-thalamocortical loops. Excitatory and inhibitory tonus may be evaluated, in vivo, using proton Magnetic Resonance Spectroscopy (1H-MRS) since it allows to indirectly estimate GABA (inhibitory) and Glutamate (excitatory) levels. Therefore, the objective of this project is to study the Excitatory/Inhibitory balance, in vivo, in the frontal cortex of HD and PD patients by comparing Glx (pool of glutamate and glutamine) to GABA ratios between these clinical disorders with healthy age- and gender- adjusted Control participants. Seventy patients (27HD; 27 PD; 16 Controls) were submitted to a 3T MRI protocol including structural, functional, and spectroscopic imaging. In this study, analysis was focused on 1H-MRS data, acquired in a 27mL voxel in the prefrontal lobe. Since GABA is difficult to resolve in the proton spectra, due to its low concentration and signal contamination by overlapping signals, a J-difference editing approach was used with MEGA-PRESS pulse sequence. Spectral data processing was performed using Gannet and statistical analysis was performed using R statistical software. One HD patient was excluded since MRS data was not acquired in the same anatomical region.After an initial visual quality control assessment of the spectra 44 datasets were discarded. We do hypothesize that excessive motion, to which MRS is particularly sensitive, was the predominant artifact contributing for the high rate of dropouts. Nonetheless several factors affecting the signal quality may be considered: staying completely still is a challenge for neuroimaging PD and HD patients; motion leads to voxel misplacement and partial volume artifacts; the frontal lobe is a particularly sensitive area for MRS acquisition due to susceptibility artifacts; performing the 1H-MRS after fMRI may produce frequency drifts due to the applied gradients; etc. We found some trends on GABA and Glx levels between groups, yet these were not statistically significant, and results are thus inconclusive.A discussion on the quality assurance measures, which are often absent in the literature, and recent artifacts correction methods was briefly performed. Future 1H-MRS studies focusing special populations prone to movement such as clinical patients, and also infants and small children must have an even more thorough study design and data analysis plan, accounting for dropout rates due to quality assurance criteria, the acquisition protocol, and data processing algorithms.
FCT
Outro - Centro 2020; Referência: SAICT 000016 BIGDATIMAGE (CENTRO-01-0145-FEDER-000016)
Outro - Santa Casa da Misericórdia de Lisboa (SCML); Referência: 1ª Edição do Prémio Neurociências Mantero Belard (2013)

RESUMO - As infeções por MRSA estão associadas a altas taxas de mortalidade, doença prolongada e internamento hospitalar prolongado. Para diminuir as infeções por MRSA, a maioria das instituições realizam o rastreio de pacientes na admissão. O rastreio laboratorial de MRSA pode ser realizado através de diferentes metodologias, sendo as mais utilizadas a cultura em meios cromogénicos e as técnicas rápidas de biologia molecular. As primeiras apresentam um custo mais baixo, mas podem demorar até 48 horas a produzir resultados e as segundas são mais rápidas (2 horas) mas apresentam um custo mais elevado. O principal objetivo do trabalho desenvolvido foi avaliar o impacto económico da implementação de uma técnica rápida de biologia molecular para rastreio de pacientes colonizados com MRSA num hospital privado português. Assim, pretendeu-se avaliar se a introdução desta nova metodologia, apresentava redução de custos comparativamente à anterior. Identificaram-se todos os indivíduos que realizaram o rastreio de MRSA (n = 2418), num hospital privado da região da grande Lisboa, entre janeiro de 2016 e dezembro de 2018. A metodologia anterior (meios cromogénicos), apesar de mais barata, é mais demorada obrigando ao isolamento dos pacientes durante a espera dos resultados. Para comparar as duas metodologias, considerou-se os custos não só do rastreio laboratorial, mas também do isolamento dos pacientes, que nos casos dos pacientes com rastreio negativo, revelavam-se custos desnecessários. Durante o período em análise, o tempo médio evitável de isolamento foi de 49,3 horas, sendo o número total de dias de isolamento evitável de 1808,1 e os custos totais para 49,3 horas de isolamento evitável de 753,96 €. Tendo em conta a prevalência de MRSA da instituição, 12 %, o impacto económico da utilização da nova técnica foi de 460 104,12 €, mostrando assim que em termos globais a implementação da nova técnica traduziu-se numa redução de custos totais. Este estudo reforçou a importância de se utilizarem técnicas rápidas de biologia molecular para o rastreio de MRSA, visto serem técnicas mais rápidas e que permitem apenas o isolamento de indivíduos que apresentem um rastreio positivo, evitando o isolamento desnecessário.
ABSTRACT - MRSA infections are associated with high mortality rates, prolonged illness and prolonged hospital stay. To decrease MRSA infections, most institutions screen patients on admission. Laboratory screening for MRSA can be performed using different methodologies, the most used ones being culture in chromogenic media and rapid molecular biology techniques. The former have a lower cost, but can take up to 48 hours to produce results and the latter is faster (2 hours) but have a higher cost. The main objective of the work developed was to evaluate the economic impact of implementing a rapid molecular biology technique for screening patients colonized with MRSA in a Portuguese private hospital. Thus, it was intended to assess whether the introduction of this new methodology presented a cost reduction compared to the previous one. All individuals who underwent MRSA screening (n = 2418) were identified in a private hospital in the Greater Lisbon region between January 2016 and December 2018. The previous methodology (chromogenic media), although cheaper, is longer, forcing patients to be isolated while waiting for the results. To compare the two methodologies, we considered the costs not only of laboratory screening, but also of isolating patients, which in the cases of patients with negative screening, proved to be unnecessary costs. During the period under analyze, the average avoidable isolation time was 49,3 hours, with the total number of preventable isolation days being 1808,1 and the total costs for 49,3 hours of preventable isolation was 753,96 €. Taking into account the institution's prevalence of MRSA (12%) the economic impact of using the new technique was 460104,12 €, thus showing that in global terms the implementation of the new technique resulted in a reduction in total costs. This study reinforced the importance of using fast molecular biology techniques for screening MRSA, as they are faster techniques that allow only the isolation of individuals who have a positive screening, avoiding unnecessary isolation.