Academic literature on the topic '004:61'

As algas e as cianobactérias produzem uma grande diversidade de compostos com atividade biológica direta sobre microrganismos ou agem como ativadores de mecanismos de resistência em plantas. Em vista disso, foi investigada a manifestação dos sintomas causados pelo Tobacco mosaic virus (TMV) em plantas de fumo previamente tratadas com cianobactérias ou algas. Quando as folhas plantas de fumo foram tratadas dois dias antes da inoculação, foi verificado que suspensões de células dos isolados de cianobactérias 004/02, 008/02, Anabaena sp. e Nostoc sp. 61; e do isolado de alga 061/02, bem como as preparações do conteúdo intracelular do isolado 004/02 (4 C) e do filtrado do meio de cultivo do isolado 061/02 (61 M) apresentaram efeito na redução do número de lesões locais provocadas por TMV em folhas de plantas fumo, cultivar TNN. Além disso, foi observado que os isolados Anabaena sp., Nostoc sp. 21 (cianobactéria), Nostoc sp. 61 e 090/02 (alga) mostraram efeito direto sobre o vírus semi-purificado. Em vista disso, pode-se sugerir que os isolados estudados sintetizam compostos que agem diretamente sobre o TMV e/ou ativam o mecanismo de defesa de plantas contra fitopatógenos.

Penelitian ini dilatar belakangi rendahnya keterampilan membaca permulaan siswa kelas I SDN 004 Salo. Salah satu solusi untuk mengatasi masalah ini adalah dengan menggunakan media kartu kata. Tujuan penelitian ini untuk meningkatkan keterampilan membaca siswa kelas I pada tema Diriku dengan menggunakan media kartu kata. Metode penelitian ini adalah Penelitian Tindakan Kelas (PTK) yang dilaksanakan dalam dua siklus. Setiap siklus terdiri dari dua pertemuan dan empat tahapan yakni perencanaan, pelaksanaan, observasi, refleksi, dan waktu penelitian dilaksanakan pada Juli sampai September. Subjek penelitian ini siswa kelas I yaitu berjumlah 21 orang. Teknik pengumpulan berupa dokumentasi, observasi dan tes. Hasil penelitian ini disimpulkan bahwa keterampilan membaca permulaan siswa dengan tema Diriku pada siklus I tergolong kurang dengan presentase ketuntasan siswa dengan nilai rata-rata 61% Sedangkan pada siklus II mengalami peningkatan baik yakni ketuntasan siswa 85%. Dengan demikian dapat disimpulkan bahwa dengan menggunakan media kartu kata dapat meningkatkan keterampilan membaca permulaan siswa kelas I SDN 004 Salo.

This study is peneilitian class action was motivated by the low learning PJKO fourth grade students SD Negeri 004 Tembilahan Kota. This is evident from the acquisition value of the average students who are still under the KKM is equal to 56,00 being KKM specified value is 61, other than that of the 20 students only 7 (35.00%) students who completed their study results. Based on this the researchers applied media with the aim of improving student learning outcomes PJOK. This classroom action research conducted in SD Negeri 004 Tembilahan Kota in the fourth grade with the number of students 20 students, the study was conducted 2 cycles and be done with four stages: planning, implementation, observation, and reflection. The results showed that after the implementation of learning media, learning outcomes PJOK increase, evidenced by the acquisition: "At the initial data is the number of students who completed 7 students (35.00%) with an average nilaia 56.00, in the first cycle increased by the number of students who completed totaling 13 students (65.00%) with the average value of students increased to 72.50. And the second cycle learning outcomes increased with the number of students who completed the acquisition of up to 19 students (95.00%) with the acquisition value by an average of 83.25. Based on this acquisition can be concluded that the application of instructional media can improve learning outcomes PJOK fourth grade students SD Negeri 004 Tembilahan Kota.

Adolescent pregnancy and sexually transmitted disease rates in the United States are among the highest among developed nations. A survey of female adolescent family planning patients (N = 249) indicated that teens 13 to 16 years of age were more likely than teens 17 to 1 9 years of age to discuss sexual behavior with adult, nonparental relatives (43% vs. 26%, p = .007). Teens with a prior pregnancy were more likely than never-pregnant teens to report parental discussion of contraception choices (83% vs. 53%, p = .004) and of sites for contraceptive care (61% vs. 37%, p = .0023). Adolescents rely on a complex network of family and peers for communication about sexuality. Social work clinical and community skills facilitate family-centered reproductive health training and counseling for improved reproductive health of U.S. adolescents.

We analyzed 2502 patients with acute myeloid leukemia at diagnosis for NRAS mutations around the hot spots at codons 12, 13, and 61 and correlated the results to cytomorphology, cytogenetics, other molecular markers, and prognostic relevance of these mutations. Two hundred fifty-seven (10.3%) of 2502 patients had NRAS mutations (NRASmut). Most mutations (112 of 257; 43.6%) were found at codon 12, mostly resulting in changes from glycine to asparagine. The history of AML did not differ significantly in association with NRAS mutations. The subgroups with inv(16)/t(16;16) and inv(3)/t(3;3) showed a significantly higher frequency of NRASmut (50 of 133, 37.6% [P < .001], and 11 of 41, 26.8% [P = .004], respectively) than the total cohort. In addition, in these 2 subgroups, mutations of codon 61 were significantly overrepresented (both P < .001). In contrast, NRAS mutations were significantly underrepresented in t(15;17) (2 of 102; 2%; P = .005) in the subgroup with MLL/11q23 rearrangements (3 of 77; 3.9%; P = .061) and in the complex aberrant karyotype (4 of 258; 1.6%; P < .001). Overall, we did not find a significant prognostic impact of NRASmut for overall survival, event-free survival, and disease-free survival. However, there was a trend to better survival in most subgroups, especially when other molecular markers (FLT3-LM, MLL-PTD, and NPM) were taken into account.

OBJETIVOS: Caracterizar idosos com insuficiência renal crônica submetidos à hemodiálise em um hospital escola e identificar níveis de depressão na população estudada. MÉTODOS: Trata-se de uma pesquisa descritiva - exploratória, de natureza quantitativa utilizando a Geriatric Depression Scale (GDS) e questionário de caracterização populacional, sendo entrevistados 61 pacientes. Na análise dos dados foi utilizado método quantitativo progressivo (porcentagem) e correlação de Spearmann. RESULTADOS: A média de idade foi de 69,97±7,51 anos, 57% eram do sexo masculino, 79% de cor branca, 72% eram casados, sendo 26% analfabetos. A média de respostas depressivas foi 10,43±4,37, o que sugere humor normal-levemente deprimido na população em geral. CONCLUSÃO: Houve correlação estatisticamente significativa entre renda mensal familiar e escolaridade (valor p=0, 004) e escore GDS e analfabetismo (p=0,028), mostrando que os analfabetos apresentaram mais respostas depressivas, sugerindo menor capacidade de adaptabilidade/resiliência desses indivíduos à doença e suas implicações.

AbstractFolate is an essential B vitamin required forde novopurine and thymidylate synthesis, and for the remethylation of homocysteine to form methionine. Folate deficiency has been associated with placenta-related pregnancy complications, as have SNP in genes of the folate-dependent enzymes, methionine synthase (MTR) and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1). We aimed to determine the effect of altered folate metabolism on placental cell proliferation, viability and invasive capacity and on progesterone and human chorionic gonadotropin (hCG) secretion. Human placental choriocarcinoma (JEG-3) cells cultured in low folic acid (FA) (2 nm) demonstrated 13 % (P<0·001) and 26 % (P<0·001) lower proliferation, 5·5 % (P=0·025) and 7·5 % (P=0·004) lower invasion capacity, and 5 to 7·5 % (P=0·004–0·025) lower viability compared with control (20 nm) or supplemented (100 nm) cells, respectively. FA concentration had no effect on progesterone or hCG secretion. Small interfering RNA (siRNA) knockdown ofMTRgene and protein expression resulted in 17·7 % (P<0·0001) lower proliferation and 61 % (P=0·014) higher progesterone secretion, but had no effect on cell invasion and hCG secretion. siRNA knockdown ofMTHFD1gene expression in the absence of detectable changes in protein expression resulted in 10·3 % (P=0·001) lower cell proliferation, but had no effect on cell invasion and progesterone or hCG secretion. Our data indicate that impaired folate metabolism can result in lower trophoblast proliferation, and could alter viability, invasion capacity and progesterone secretion, which may explain in part the observed associations between folate and placenta-related complications.

Objective In this systematic review and meta-analysis, we aimed to compare drug-coated balloon (DCB) to drug-eluting stent (DES) in patients with femoropopliteal lesions in terms of restenosis, target lesion revascularization (TLR), and mortality. Methods A comprehensive literature search was performed through PubMed, Scopus, and Embase databases. The intervention group was patients receiving percutaneous balloon angioplasty using the DCB. The control group was patients receiving percutaneous intervention using the DES. The primary outcome was restenosis, and the secondary outcomes were TLR and mortality. Results There were 4 studies comprising 812 patients (906 lesions) included in this systematic review and meta-analysis. The rate of restenosis was .19 [.13, .26] in DCB and .24 [.20, .28] in DES. There was a trend toward lower rate of restenosis (OR .73 [.52, 1.03], P = .074; I2: 46.3%) for DCB use compared to DES use. The rate of TLR was .11 [.08, .14] in DCB and .17 [.14, .21] in DES. TLR was lower (OR .61 [.41, .92], P = .017; I2: 1.2%) in the DCB group compared to the DES group. There were no significant differences in mortality (OR 1.38 [.78, 2.44], P = .268; I2: 0%) among the two groups. Meta-regression analysis showed that the rate of restenosis in DCB in this pooled analysis was affected by sex (reference: male, coefficient −.004, P = .009), smoking (coefficient: .003, P = .010), and total occlusion (coefficient: .008, P = .004). Conclusion DCB use in patients with femoropopliteal lesion was associated with similar rate of restenosis, lower TLR, and similar mortality rate compared to DES use.

This study compared the dietary intakes of supplementing (SA) and non-supplementing athletes (NSA). Twenty-five female master athletes (mean age = 50.4 yr) participated in the study (SA = 16, NSA = 9). Four-day diet records were analyzed using Nutritionist V. Statistical significance (p < .005) was determined by independent t tests. No significant differences were observed in intakes of kilocalories (SA = 2079 ± 628 kcals, NSA = 2001 ± 435 kcals), protein (SA = 104 ± 75 g, NSA = 84 ± 35 g), fat (SA = 65 ± 39 g, NSA = 61 ± 22 g), or carbohydrates (SA = 269 ± 112 g, NSA = 277 ± 43 g). Mean intakes exceeded Dietary Reference Intake (DRI) guidelines for all micro-nutrients except calcium and vitamin E (NSA = 79% and 87% of DRI, respectively). SA had significantly greater total intakes than NSA for calcium (p = .0001), magnesium (p = .004), vitamin C (p = .003), and vitamin E (p = .001). Results suggest that female master athletes may rely on dietary supplements rather than nutrient-dense food choices to provide daily nutritional needs.

Abstract We examined whether the associations between marital quality and mental health were equally strong among dyads in which one spouse was providing care to a spouse (n = 155), parent (n = 61), or another adult (n = 176). Using Wave 2 of the NSHAP and actor-partner interdependence (APIM) models, we found significant differences (p=.004) among groups. Marital quality was negatively associated with one’s own depressive symptoms (b=-1.29) for husbands in the spousal caregiver group, whereas marital quality was negatively associated with one’s own depressive symptoms for wives in both the parental (b=-1.27) and other adult (b=-1.96) caregiver groups. The only partner effect was the negative association between wives’ marital quality and husbands’ depressive symptoms (b=-2.59) among dyads in which one spouse was a parental caregiver. These results point to the importance of understanding the context of caregiving when examining the protective effect of spouses’ marital quality on mental health.

Objetivos La medicina traslacional requiere la explotación integrada de información biomédica para dar soporte a la investigación, sin embargo, resulta difícil el acceso al conocimiento biomédico, por ser heterogéneo y estar distribuido entre distintos sistemas de información. El objetivo principal de esta tesis es la investigación y desarrollo de soluciones basadas en las tecnologías de la Web Semántica para la integración de conocimiento biomédico utilizado en medicina traslacional. Metodología Para conseguir este objetivo, primero se lleva a cabo un estudio del estado del arte que incluye los formatos de representación más comunes de la información biomédica, las tecnologías de la Web Semántica y su aplicación en el ámbito biomédico, las propuestas de transformación de contenidos a representación semántica y los sistemas de integración de repositorios heterogéneos. Después, la solución propuesta se formaliza en tres pasos: (1) formalización de una metodología de transformación genérica de información, (2) formalización de un proceso de integración de recursos heterogéneos basado en transformación a una ontología OWL, (3) formalización de una plataforma de integración, gestión y explotación de información biomédica. Todas estas soluciones se implementan en herramientas web. Por último, las soluciones propuestas se validan en cuatro escenarios diferentes: clasificación automática de pacientes a partir de sus datos clínicos dentro un programa de cribado de cáncer de colon y recto; transformación entre modelos clínicos CEM y arquetipos openEHR; creación de un repositorio integrado de genes ortólogos, enfermedades y anotaciones sobre secuencias genómicas; representación OWL de bases de datos de componentes químicos. Resultados Como resultado se obtiene: • Un modelo de transformación genérica de datos. Está compuesto de reglas de correspondencia que permiten la transformación de instancias de entrada a una representación según un modelo de salida, de reglas de identidad que identifican instancias redundantes, y que usa patrones de diseño para realizar transformaciones más complejas. • Un modelo de integración de información biomédica heterogénea, que aplica el modelo de transformación y tiene como modelo de salida una arquitectura ontológica (ontología OWL y patrones de diseño de contenido ontológico) para la transformación e integración de recursos heterogéneos en un repositorio único. • Una plataforma de integración, gestión y explotación de información biomédica, que explota distintas representaciones OWL de modelos clínicos e incluye métodos de validación, anotación, comparación, y búsqueda semántica, además de permitir la ejecución de procesos de transformación e integración. • Dos herramientas web que implementación las soluciones. SWIT realiza la transformación de información a representación RDF/OWL, mientras que ArchMS implementa la plataforma integrada que permite la gestión y explotación de modelos y datos clínicos y su explotación en repositorios semánticos junto a otros recursos biomédicos externos. Conclusiones Los estándares de información clínica tratan de favorecer la interoperabilidad semántica de la información, mientras que propuestas como Linked Open Data fomentan la publicación y enlazado de los datos biomédicos. Sin embargo, los lenguajes utilizados para representar modelos clínicos resultan insuficientes para su gestión, mientras que la mayoría de métodos de publicación de datos en la Web de Datos no tienen en cuenta la semántica del contenido y son difíciles de generalizar. Utilizar modelos globales basados en ontologías OWL en la transformación e integración de contenidos permite definir una transformación dirigida por la semántica del dominio y utilizar esta semántica para explotar el repositorio final. OWL permite validar y comparar el contenido atendiendo a su semántica y facilita la integración de recursos. Las herramientas desarrolladas han demostrado ser efectivas en su utilización en distintos escenarios de validación, creando repositorios semánticos abiertos que contribuyen al desarrollo de la Web de Datos y permitiendo su explotación en el espacio tecnológico de la Web Semántica.
Summary Aims of the thesis Translational medicine requires intensive collaboration between different areas of biomedical informatics. However, this collaboration is difficult due to the fact that the biomedical knowledge generated by the different disciplines has the quality of being distributed and heterogeneous. This thesis aims to assist translational research by improving the integrated exploitation of biomedical information through the use of Semantic Web technologies. Methodology The methodology proposed is based on the analysis of the state of art, the formalization of the proposed methods, their implementation and their validation in application domains. The analysis of the state of art includes the study of the most common representation formats for biomedical information, the application of Semantic Web technologies to the biomedical domain, methods of content transformation to semantic representation and existing proposals for integrating heterogeneous repositories. The proposed solution is formalized in three steps: (1) formalization of a generic methodology for semantic data transformation, (2) formalization of a heterogeneous resources integration process based on the transformation into an OWL ontology, (3) formalization of an integrated platform for managing and exploiting the biomedical information. All these proposed solutions are implemented in web tools. The solutions have been validated in four different scenarios: study of clinical data from patients of a colorectal screening program for performing automatic classification of the patients; transformation between CEM clinical models and openEHR archetypes; creation of an integrated repository about orthologous genes, genetic disorders and information about genomic sequences annotations; transformation of a dataset of chemical components into an OWL representation. Results The main contributions of this work are: • A generic data transformation model between structured representation schemata. The definition of mappings transforms input instances into a representation guided by the output model. Identity rules identify redundant instances. The accepted input and output models are defined by a metamodel and the use of design pattern allows making more complex transformations. • A heterogeneous biomedical information integration model. Through the instantiation of the transformation model with an output model defined by an ontological architecture (OWL ontology and ontology design content patterns), different heterogeneous resources are transformed and integrated. • A platform for integrating, managing and exploiting biomedical information. The platform selects the most suitable OWL representations for clinical models and includes semantic methods for validating, annotating, comparing and searching together with the defined transformation and integration models. • Implementation of the transformation and integration models, and the integrated platform in two web applications. SWIT implements the transformation model while AchMS implements the integrated platform. Conclusions Al the clinical level, Electronic Health Record standards intend the achievement of semantic interoperability, while initiatives like Linked Open Data pursues the publication and sharing of biomedical datasets. However, the syntactic nature of languages used for clinical models representation is not enough for their management, while methods for datasets publication in the Web of Data make a syntactic transformation, guided by the logical schema of the source representation and there exists problems in the generalization of the methods. The use of global models based on OWL ontologies for representing information content allows the definition of transformation processes driven by the domain semantics, which can be exploited in the final repository. An OWL representation allows the validation and comparison of the content attending to its semantic, making easier the integration of different resources. The developed tools have demonstrated their effectiveness in different validation scenarios, creating semantic open datasets that will contribute to the development of the Web of Data and allowing their exploitation in the Semantic Web technological space.

The current approaches for the induction of medical procedural knowledge suffer from several drawbacks: the structures produced may not be explicit medical structures, they are only based on statistical measures that do not necessarily respect medical criteria which can be essential to guarantee medical correct structures, or they are not prepared to deal with the incremental arrival of new data. In this thesis we propose a methodology to automatically induce medically correct clinical algorithms (CAs) from hospital databases. These CAs are represented according to the SDA knowledge model. The methodology considers relevant background knowledge and it is able to work in an incremental way. The methodology has been tested in the domains of hypertension, diabetes mellitus and the comborbidity of both diseases. As a result, we propose a repository of background knowledge for these pathologies and provide the SDA diagrams obtained. Later analyses show that the results are medically correct and comprehensible when validated with health care professionals.

This thesis explores techniques, models and algorithms for an efficient management of Cloud systems and how to apply them to the healthcare sector in order to improve current treatments. It presents two Cloud-based eHealth applications to telemonitor and control smoke-quitting and hypertensive patients. Different Cloud-based models were obtained and used to develop a Cloudbased infrastructure where these applications are deployed. The results show that these applications improve current treatments and that can be scaled as computing requirements grow. Multiple Cloud architectures and models were analyzed and then implemented using different techniques and scenarios. The Smoking Patient Control (S-PC) tool was deployed and tested in a real environment, showing a 28.4% increase in long-term abstinence. The Hypertension Patient Control (H-PC) tool, was successfully designed and implemented, and the computing boundaries were measured
Aquesta tesi explora tèniques, models i algorismes per una gestió eficient en sistemes al Núvol i com aplicar-ho en el sector de la salut per tal de millorar els tractaments actuals. Presenta dues aplicacions de salut electrònica basades en el Núvol per telemonitoritzar i controlar pacients fumadors i hipertensos. S'ha obtingut diferents models basats en el Núvol i s'han utilitzat per a desenvolupar una infraestructura on desplegar aquestes aplicacions. Els resultats mostren que aquestes aplicacions milloren els tractaments actuals així com escalen a mesura que els requeriments computacionals augmenten. Múltiples arquitectures i models han estat analitzats i implementats utilitzant diferents tècniques i escenaris. L'aplicació Smoking Patient Control (S-PC) ha estat desplegada i provada en un entorn real, aconseguint un augment del 28,4% en l'absistinència a llarg termini de pacients fumadors. L'aplicació Hypertension Patient Control (H-PC) ha estat dissenyada i implementada amb èxit, i els seus límits computacionals han estat mesurats.
Esta tesis explora ténicas, modelos y algoritmos para una gestión eficiente de sistemas en la Nube y como aplicarlo en el sector de la salud con el fin de mejorar los tratamientos actuales. Presenta dos aplicaciones de salud electrónica basadas en la Nube para telemonitorizar y controlar pacientes fumadores e hipertensos. Se han obtenido diferentes modelos basados en la Nube y se han utilizado para desarrollar una infraestructura donde desplegar estas aplicaciones. Los resultados muestran que estas aplicaciones mejoran los tratamientos actuales así como escalan a medida que los requerimientos computacionales aumentan. Múltiples arquitecturas y modelos han sido analizados e implementados utilizando diferentes técnicas y escenarios. La aplicación Smoking Patient Control (S-PC) se ha desplegado y provado en un entorno real, consiguiendo un aumento del 28,4% en la abstinencia a largo plazo de pacientes fumadores. La aplicación Hypertension Patient Control (H-PC) ha sido diseñada e implementada con éxito, y sus límites computacionales han sido medidos.

La indústria alimentària incorpora als aliments extractes d’origen natural rics en molècules bioactives amb la finalitat de convertir-los en aliments funcionals, és a dir, que tinguin propietats beneficioses per a la salut més enllà del seu valor nutricional. Un dels principals reptes és millorar l'eficiència en la selecció de nous compostos bioactius per accelerar el desenvolupament de nous aliments funcionals. Les tècniques computacionals, com ara el cribratge virtual, poden exercir un paper essencial en la fase inicial del descobriment de noves substàncies bioactives. Durant la tesi s’han desenvolupat i validat diferents protocols de cribatge virtual per a IKK-2 i 11-HSD1 (dianes involucrades en inflamació crònica), els quals han permès trobar compostos i extractes d’origen natural amb propietats anti-inflamatòries. Aquests compostos bioactius poden ser de gran utilitat com a additius en l’alimentació funcional, ja que poden presentar activitat semblant a la dels fàrmacs emprats en el tractament de malalties cardiovasculars.
One of the main challenges in nutrigenomics is improving the efficiency of the selection (which is currently time consuming and expensive) of new bioactive compounds in order to expedite the development of new functional foods. Computational techniques, such as virtual screening, may play an essential role in accelerating the early stages of the discovery of new bioactive substances by efficiently searching for compounds that could activate or inhibit a known target. So, by modulating specific target functions in the body, molecules that act as IKK-2 or 11β-HSD1 inhibitors have beneficial physiological effects that can be of interest for preventing, retarding and/or reversing the metabolic syndrome. Because of their anti-inflammatory properties, natural extracts that contain these molecules have a promising role as ingredients in new functional foods. Therefore, this PhD thesis will focus on the development of virtual screening workflows that predict natural products that can inhibit both targets.

La retinopatia diabètica és una malaltia crònica i una de les principals causes de ceguesa i discapacitat visual en els pacients diabètics. L'examen ocular a través d'imatges de la retina és utilitzat pels metges per detectar les lesions relacionades amb aquesta malaltia. En aquesta tesi, explorem diferents mètodes innovadors per a la classificació automàtica del grau de malaltia utilitzant imatges del fons d'ull. Per a aquest propòsit, explorem mètodes basats en l'extracció i classificació automàtica, basades en xarxes neuronals profundes. A més, dissenyem un nou mètode per a la interpretació dels resultats. El model està concebut de manera modular per a que pugui ser utilitzat en d'altres xarxes i dominis de classificació. Demostrem experimentalment que el nostre model d'interpretació és capaç de detectar lesions de retina a la imatge únicament a partir de la informació de classificació. A més, proposem un mètode per comprimir la representació interna de la informació de la xarxa. El mètode es basa en una anàlisi de components independents sobre la informació del vector d'atributs intern de la xarxa generat pel model per a cada imatge. Usant el nostre mètode d'interpretació esmentat anteriorment també és possible visualitzar aquests components en la imatge. Finalment, presentem una aplicació experimental del nostre millor model per classificar imatges de retina d'una població diferent, concretament de l'Hospital de Reus. Els mètodes proposats arriben al nivell de rendiment de l'oftalmòleg i són capaços d'identificar amb gran detall les lesions presents en les imatges, que es dedueixen només de la informació de classificació de la imatge.
La retinopatía diabética es una enfermedad crónica y una de las principales causas de ceguera y discapacidad visual en los pacientes diabéticos. El examen ocular a través de imágenes de la retina es utilizado por los médicos para detectar las lesiones relacionadas con esta enfermedad. En esta tesis, exploramos diferentes métodos novedosos para la clasificación automática del grado de enfermedad utilizando imágenes del fondo de la retina. Para este propósito, exploramos métodos basados en la extracción y clasificación automática, basadas en redes neuronales profundas. Además, diseñamos un nuevo método para la interpretación de los resultados. El modelo está concebido de manera modular para que pueda ser utilizado utilizando otras redes y dominios de clasificación. Demostramos experimentalmente que nuestro modelo de interpretación es capaz de detectar lesiones de retina en la imagen únicamente a partir de la información de clasificación. Además, proponemos un método para comprimir la representación interna de la información de la red. El método se basa en un análisis de componentes independientes sobre la información del vector de atributos interno de la red generado por el modelo para cada imagen. Usando nuestro método de interpretación mencionado anteriormente también es posible visualizar dichos componentes en la imagen. Finalmente, presentamos una aplicación experimental de nuestro mejor modelo para clasificar imágenes de retina de una población diferente, concretamente del Hospital de Reus. Los métodos propuestos alcanzan el nivel de rendimiento del oftalmólogo y son capaces de identificar con gran detalle las lesiones presentes en las imágenes, que se deducen solo de la información de clasificación de la imagen.
Diabetic Retinopathy is a chronic disease and one of the main causes of blindness and visual impairment for diabetic patients. Eye screening through retinal images is used by physicians to detect the lesions related with this disease. In this thesis, we explore different novel methods for the automatic diabetic retinopathy disease grade classification using retina fundus images. For this purpose, we explore methods based in automatic feature extraction and classification, based on deep neural networks. Furthermore, as results reported by these models are difficult to interpret, we design a new method for results interpretation. The model is designed in a modular manner in order to generalize its possible application to other networks and classification domains. We experimentally demonstrate that our interpretation model is able to detect retina lesions in the image solely from the classification information. Additionally, we propose a method for compressing model feature-space information. The method is based on a independent component analysis over the disentangled feature space information generated by the model for each image and serves also for identifying the mathematically independent elements causing the disease. Using our previously mentioned interpretation method is also possible to visualize such components on the image. Finally, we present an experimental application of our best model for classifying retina images of a different population, concretely from the Hospital de Reus. The methods proposed, achieve ophthalmologist performance level and are able to identify with great detail lesions present on images, inferred only from image classification information.

En aquesta tesi es presenta un model de coneixement clínic basat en taules de decisió que permet representar les fases de diagnòstic, tractament i pronòstic de diferents malalties. Les taules de decisió que s'obtenen per a cada fase del model han estat utilitzades per representar malalties reals a partir de guies de pràctica clínica. En el cas del diagnòstic s'han representat les vuit causes secundàries més comuns de la hipertensió arterial. En el cas del tractament i pronòstic s'han representat set diferents xocs en emergències. Les taules de decisió que hem obtingut per a cadascuna de les malalties s'han utilitzat com a base per crear dues eines d'entrenament mèdic, dirigides a residents. Totes dues eines s'han provat a l'Hospital Clínic de Barcelona amb diferents grups de residents. Després de les proves s'ha conclòs que les taules de decisió són adequades per a la representació del coneixement mèdic en totes tres fases. A més, les eines d'aprenentatge han estat efectives a l'hora d'ensenyar els procediments mèdics, especialment als residents amb menys experiència prèvia.
En esta tesis se presenta un modelo de conocimiento clínico basado en tablas de decisión que permite representar las fases de diagnostico, tratamiento y pronostico de distintas enfermedades. Las tablas de decisión que se obtienen para cada fase del modelo han sido utilizadas para representar enfermedades reales a partir de guías de práctica clínica. En el caso del diagnóstico se han representado las ocho causas secundarias más comunes de la hipertensión arterial. En el caso del tratamiento y pronóstico se han representado siete diferentes shocks en emergencias. Las tablas de decisión que hemos obtenido para cada una de las enfermedades se han usado como base para crear dos herramientas de entrenamiento médico, dirigido a residentes. Ambas herramientas se han probado en el Hospital Clínic de Barcelona con distintos grupos de residentes. Tras las pruebas se ha concluido que las tablas de decisión son adecuadas para la representación del conocimiento medico en las tres fases. Además, las herramientas de aprendizaje han sido efectivas a la hora de enseñar los procedimientos médicos, en especial a los residentes con menos experiencia previa.
In this thesis a clinical knowledge model based on decision tables is presented. This model allows us to represent the stages of diagnosis, treatment, and prognosis of different diseases. The decision tables obtained for each phase of the model have been used to represent real diseases from clinical practice guidelines. In the case of diagnosis, we represented eight of the most common secondary causes of hypertension. For the treatment and prognosis we represented seven different emergency shocks. The decision tables obtained for each disease have been used as the basis for two medical training tools aimed to residents. Both tools have been tested in the Hospital Clínic de Barcelona with different groups of residents. After testing, it was concluded that decision tables are suitable for the representation of medical knowledge in all three phases. In addition, the learning tools have been effective in teaching medical procedures, especially for untrained residents.

Volume visualization is a method of extracting information from volumetric data using interactive graphics. Volume visualization aims to assist visual interpretation of data by creating three-dimensional models that reproduce real objects with sufficient detail and speed to support interactive manipulation. Illustrative rendering enhances the perception of features in a volume. Volume rendering has two major goals: to obtain high quality images in real time, and to determine how to explore volume datasets in an effective way. In this thesis we advance in these two lines. We propose several methods to approximate global illumination with low computational cost, permitting realistic and illustrative rendering. We also present a method to automatically define transfer functions given a target distribution. In addition, we introduce a method to automatize the creation of exploded views. Finally, we explore techniques to select the best viewpoints for a volume. Several of our contributions are based on information theory.
La visualització de volums és un mètode per extreure informació de dades volumètriques mitjançant imatges interactives. L’objectiu és assistir la interpretació visual de dades creant models tridimensionals que reprodueixen objectes reals amb suficient detall i velocitat per permetre’n la manipulació interactivament. La visualització il·lustrativa millora la percepció de les característiques d'un volum. La visualització de volums té dos objectius principals: obtenir imatges d’alta qualitat en temps real, i determinar com explorar volums d'una manera efectiva. En aquesta tesi avancem en aquestes dues línies. Proposem diversos mètodes per aproximar la il·luminació global amb baix cost computacional, permetent la visualització realista i il·lustrativa. També presentem un mètode per definir automàticament funcions de transferència donada una distribució objectiu. A més, presentem un mètode per automatitzar la creació d’exploded views. Finalment, explorem tècniques per seleccionar els millors punts de vista d’un volum. Diverses de les contribucions estan basades en la teoria de la informació.

The understanding of certain data often requires the collection of similar data from different places to be analysed and interpreted. Multi-agent systems (MAS), interoperability standards (DICOM, HL7 or EN13606) and clinical Ontologies, are facilitating data interchange among different clinical centres around the world. However, as more and more data becomes available, and more heterogeneous this data gets, the task of accessing and exploiting the large number of distributed repositories to extract useful knowledge becomes increasingly complex. Beyond the existing networks and advances for data transfer, data sharing protocols to support multilateral agreements are useful to exploit the knowledge of distributed Data Warehouses. The access to a certain data set in a federated Data Warehouse may be constrained by the requirement to deliver another specific data set. When bilateral agreements between two nodes of a network are not enough to solve the constraints for accessing to a certain data set, multilateral agreements for data exchange can be a solution. The research carried out in this PhD Thesis comprises the design and implementation of a Multi-Agent System for multilateral exchange agreements of clinical data, and evaluate how those multilateral agreements increase the percentage of data collected by a single node from the total amount of data available in the network. Different strategies to reduce the number of messages needed to achieve an agreement are also considered. The results show that with this collaborative sharing scenario the percentage of data collected dramatically improve from bilateral agreements to multilateral ones, up to reach almost all data available in the network.

This thesis deals with the detection of new multiple sclerosis (MS) lesions in longitudinal brain magnetic resonance (MR) imaging. This disease is characterized by the presence of lesions in the brain, predominantly in the white matter (WM) tissue of the brain. The detection and quantification of new lesions are crucial to follow-up MS patients. Moreover, the manual detection of these new lesions is not only time-consuming, but is also prone to intra- and inter-observer variability. Therefore, the development of automated techniques for the detection MS lesions is a major challenge
Aquesta tesi es centra en la detecció automàtica de lesions noves d'esclerosi múltiple (EM) en estudis longitudinals del cervell mitjançant l'ús d'imatges de ressonància magnètica (RM). Aquesta malaltia es caracteritza per la presència de lesions al cervell, predominantment en el teixit de la matèria blanca, i la detecció i la quantificació de les noves lesions són elements crucials per al seguiment dels pacients. No obstant això, la detecció manual d'aquestes noves lesions no només requereix de molt temps, sinó que també és propensa a la variabilitat intra- i inter-observador. Cal tenir en compte que les lesions d'EM són molt petites en comparació amb tot el cervell. Per tant, el desenvolupament de tècniques automàtiques per a la detecció de lesions d'EM és un gran repte

La retinopatia diabètica (RD) és una de les complicacions més comunes associades a la diabetis mellitus (DM). El seu adequat control requereix la implementació de programes de cribratge. En aquest treball es presenta un estudi prospectiu d'un total de 15.396 pacients caucàsics amb DM, que representen el 86,53% del total de pacients amb DM en les nostres àrees bàsiques de salut, amb un període de seguiment de 8 anys (2007- 2014). Tots els pacients van ser examinats amb una mitjana de 3,18 ± 1,11 visites al llarg de l'estudi. En els nostres resultats s'observa un augment en la incidència de la RD i edema macular diabètic (EMD), especialment en els pacients joves entre 31 i 70 anys, relacionat amb un mal control metabòlic. A més d'un augment de costos en la RD arran de la introducció dels nous tractaments amb anti-VEGF per l'EMD. La periodicitat dels controls de cribratge recomanats és d'1 any per a pacients amb DM2, i als 5 anys del diagnòstic en pacients amb DM1, segons les recomanacions de diferents societats científiques. No obstant això, amb la periodicitat recomanada només es criben un 30% de pacients a l'any. En els nostres resultats, la detecció de la retinopatia diabètica cada 2,5 anys és cost-efectiva, però s'ha d'ajustar als factors de risc de cada pacient. Per això, hem dissenyat un suport d'ajuda a la presa de decisions clíniques que pugui determinar amb una sensibilitat i especificitat del 80%, la probabilitat de desenvolupar retinopatia diabètica en cada pacient. L'ús d'aquest model informàtic pretén ajudar els metges a determinar la millor periodicitat de cribratge per a cada persona, de manera que es proporcioni una atenció adequada i s'emprin els recursos humans, materials i econòmics d'una manera més eficient.
La retinopatía diabética (RD) es una de las complicaciones más comunes asociadas a la diabetes mellitus (DM). Su adecuado control requiere la implementación de programas de cribado. En este trabajo se presenta un estudio prospectivo de un total de 15 396 pacientes caucásicos con DM, que representan el 86,53% del total de pacientes con DM en nuestras áreas básicas de salud, con un período de seguimiento de 8 años (2007-2014). Todos los pacientes fueron examinados con una media de 3,18 ± 1,11 visitas a lo largo del estudio. En nuestros resultados se observa un aumento en la incidencia de RD y edema macular diabético (EMD), especialmente en los pacientes jóvenes entre 31 y 70 años, relacionado con un mal control metabólico. Además de un aumento de costes en la RD a raíz de la introducción de los nuevos tratamientos con anti-VEGF para el EMD. La periodicidad de los controles de cribado recomendados es de 1 año para pacientes con DM2, y a los 5 años del diagnóstico en pacientes con DM1, según las recomendaciones de diferentes sociedades científicas. Sin embargo, con la periodicidad recomendada solo se criban un 30% de pacientes al año. En nuestros resultados, la detección de la retinopatía diabética cada 2,5 años es coste-efectiva, pero debe ajustarse a los factores de riesgo de cada paciente. Por ello, hemos diseñado un soporte de ayuda a la toma de decisiones clínicas que pueda determinar con una sensibilidad y especificidad del 80%, la probabilidad de desarrollar retinopatía diabética en cada paciente. El uso de este modelo informático pretende ayudar a los médicos a determinar la mejor periodicidad de cribado para cada persona, de manera que se proporcione una atención adecuada y se empleen los recursos humanos, materiales y económicos de una manera más eficiente.
Diabetic retinopathy (DR) is one of the most usual morbidities associated to diabetes mellitus (DM). Its appropriate control requires the implementation of expensive screening programs. This paper reports a prospective population-based study of a total of 15 396 Caucasian patients with DM, who represent 86.53% of the total patients with DM in our health care areas, were studied over an 8-year follow-up period (2007-2014). All patients were screened with a mean follow-up of 3.18 ±1.11 times for each patient over the 8 years. An increase in the incidence of DR and diabetic macular oedema (DMO) was observed, especially in the younger patients aged between 31 and 70 years. This is linked to bad metabolic control of DM. Our results suggest a greater number of ocular complications in the near future, if these current findings are not addressed. Furthermore, our results reveal an increased costs in DR since the new treatments with anti-VEGF for DMO. The periodicity of screening controls recommended in patients with DM is 1 year in DM2, and after five years of diagnosis in DM1 patients, according to the recommendations of different scientific societies. However, with the recommended periodicity, only a screening rate estimated at 30% per year. Screening for diabetic retinopathy every 2.5 years is cost-effective in our results, but should be adjusted to a patient's personal risk factors. Thus, we have build a classifier which may determine, with sensitivity and especifity levels over 80%, whether a diabetic person is likely to develop retinopathy. The use of this model in a decision support tool may help doctors to determine the best screening periodicity for each person, so that an appropriate care is provided and human, material and economic resources are more efficiently employed.