Utilidad de un registro de vida real para la estratificación pronóstica y tratamiento de los pacientes con enfermedad tromboembólica venosa

La enfermedad tromboembólica venosa (ETEV), que engloba la trombosis venosa profunda (TVP) y la tromboembolia pulmonar (TEP), es un problema de salud mundial. La TEP es la tercera causa más común de muerte cardiovascular, después del infarto agudo de miocardio y del ictus, y es la primera causa prevenible de muerte hospitalaria. El tratamiento de elección de los pacientes con TEP y compromiso hemodinámico es la fibrinolisis sistémica. Por otro lado, los pacientes estables con TEP deben recibir anticoagulación con heparina de bajo peso molecular (HBMP), heparina no fraccionada (HNF) o fondaparinux como puente a la anticoagulación oral (acenocumarol, dabigatrán o edoxabán). De forma alternativa, los pacientes estables pueden recibir tratamiento con rivaroxabán o apixabán desde el momento del diagnóstico de la enfermedad. Las guías de práctica clínica proporcionan recomendaciones para el tratamiento de la ETEV, pero solo una minoría de estas recomendaciones se basan en una evidencia científica fuerte. Los ensayos clínicos (ECs) aportan la evidencia científica más robusta sobre la eficacia y seguridad de las intervenciones médicas. Sin embargo, no siempre es viable realizar ECs por su alta complejidad, alto coste, largo periodo de tiempo de desarrollo del proyecto y poca representatividad. Igualmente, en numerosas ocasiones los ECs aleatorizados no son factibles por razones éticas, logísticas, económicas o de otro tipo. En esos escenarios, los investigadores utilizan los datos observacionales procedentes de un registro de vida real para poder sacar conclusiones. Para la presente tesis, los datos clínicos de los pacientes con ETEV han sido extraídos del registro RIETE (Registro Informatizado de Pacientes con Enfermedad TromboEmbólica). Este registro multicéntrico, internacional, prospectivo comenzó en 2001 para la inclusión de pacientes de forma consecutiva con diagnóstico confirmado objetivamente de TEP y TVP. El objetivo de RIETE es proporcionar información acerca de la historia natural y del pronóstico de pacientes con diagnóstico confirmado de ETEV. En la actualidad hay más de 111.520 pacientes incluidos. Esta tesis está realizada por compendio de artículos, siendo los resúmenes los siguientes: 1. Evaluar el significado pronóstico de la frecuencia cardiaca (FC) en pacientes con TEP aguda sintomática Es bien conocido la importancia de la FC en los pacientes con ETEV. Se utiliza para 1) valorar la probabilidad pretest en pacientes estables hemodinámicamente con sospecha de TEP, 2) estratificar el riesgo de muerte o complicaciones en pacientes estables hemodinámicamente ya diagnosticados de TEP o 3) para valorar respuesta al tratamiento prescrito. Sin embargo, no se ha estudiado bien la asociación entre la FC y el pronóstico de la TEP ni tampoco se conocen los puntos de corte óptimos de FC para identificar a los pacientes de riesgo bajo y a los de riesgo intermedio-alto. Usando los pacientes incluidos en RIETE, se utilizó regresión logística para evaluar la asociación entre la FC en el momento del diagnóstico y el pronóstico de la TEP. Nuestros resultados demuestran que existe una relación positiva entre la FC y la mortalidad por cualquier causa y por la propia TEP durante los 30 primeros días después del diagnóstico. En los pacientes estables con TEP aguda sintomática, cuanto mayor es la FC mayor es el riesgo de mortalidad por cualquier causa y por la propia TEP. La modificación de los puntos de corte de la FC en las escalas PESIs y BOVA mejora su sensibilidad y especificidad, respectivamente. 2. Evaluar la validez de los resultados de los estudios observaciones frente a los ensayos clínicos respecto a la eficacia y seguridad de los tratamientos de la ETEV Se desconoce si los estudios observacionales que utilizan un análisis de propensión proporcionan resultados de eficacia y seguridad de los tratamientos de ETEV similares a los de los ECs aleatorizados. Se realizó una búsqueda sistemática en las bases de datos PubMed y Web of Science para identificar estudios observacionales que utilizaron un análisis de propensión, ECs y metaanálisis de ECs que evaluaron la eficacia de diferentes tratamientos para pacientes con ETEV. Se identificaron siete tratamientos diferentes evaluados por estudios observacionales y ECs. De manera global, los resultados de eficacia de los estudios observacionales no fueron distintos a los de los ECs. Sin embargo, para dos de los siete tratamientos evaluados (trombolisis vs. anticoagulación para la TEP; enoxaparina una vs. dos veces al día para la ETEV), los estudios observacionales proporcionaron resultados de eficacia significativamente opuestos a los de los ECs. Para otros dos tratamientos (rivaroxabán vs. antagonistas de la vitamina K para la ETEV; tratamiento domiciliario vs. hospitalario para TVP) se identificó una diferencia sustancial (aunque no significativa) en la magnitud del efecto observado entre los estudios observacionales y los ECs. Esta comparación sistemática sugiere que los resultados de eficacia de los tratamientos para la ETEV obtenidos por estudios observacionales que utilizan un análisis de propensión y por ECs son similares, aunque ocasionalmente se observan diferencias en la dirección o en la magnitud del efecto estimado. 3. Evaluar la eficacia y seguridad de la fibrinolisis sistémica a dosis reducidas comparada con la fibrinolisis sistémica a dosis completas En los pacientes hemodinámicamente inestables con TEP, las guías recomiendan el tratamiento con fibrinolisis sistémica a dosis completas si no existen contraindicaciones para su uso. Nuestro análisis comparó la eficacia y seguridad del tratamiento fibrinolítico a dosis reducidas vs. dosis completas para pacientes con TEP aguda sintomática incluidos en el registro RIETE. Los resultados mostraron un riesgo no significativamente mayor de muerte por cualquier causa, de muerte por la propia TEP y de recurrencia trombótica no mortal, y un riesgo no significativamente menor de sangrado grave para los pacientes que recibieron dosis reducidas vs. dosis completas. En conclusión, para pacientes con TEP aguda sintomática que requieren fibrinolisis sistémica, los resultados de este análisis no demuestran diferencias significativas en términos de eficacia y seguridad entre las dosis reducidas y las dosis completas de fibrinolisis sistémica

Influence of continental history on the ecological specialization and macroevolutionary processes in the mammalian assemblage of South America: Differences between small and large mammals

Background: This paper tests Vrba's resource-use hypothesis, which predicts that generalist species have lower specialization and extinction rates than specialists, using the 879 species of South American mammals. We tested several predictions about this hypothesis using the biomic specialization index (BSI) for each species, which is based on its geographical range within different climate-zones. The four predictions tested are: (1) there is a high frequency of species restricted to a single biome, which henceforth are referred to as stenobiomic species, (2) certain clades are more stenobiomic than others, (3) there is a higher proportion of biomic specialists in biomes that underwent through major expansion-contraction alternation due to the glacial-interglacial cycles, (4) certain combinations of inhabited biomes occur more frequently among species than do others. Results: Our results are consistent with these predictions. (1) We found that 42 % of the species inhabit only one biome. (2) There are more generalists among species of Carnivora than in clades of herbivores. However, Artiodactyla, shows a distribution along the specialization gradient different from the one expected. (3) Biomic specialists are predominant in tropical rainforest and desert biomes. Nevertheless, we found some differences between small and large mammals in relation to these results. Stenobiomic species of micromammalian clades are more abundant in most biomes than expected by chance, while in the case of macromammalian clades stenobiomic species are more frequent than expected in tropical rainforest, tropical deciduous woodland and desert biomes only. (4) The most frequent combinations of inhabited biomes among the South American mammals are those with few biomes, i.e., the ones that suffered a higher rate of vicariance due to climatic cycles. Conclusion: Our results agree with the resource-use hypothesis and, therefore, with a major role of the past climatic changes as drivers of mammalian evolution. Nevertheless, deviations from the expectations indicate the importance of differences in reproductive traits and paleobiogeographic history for the macroevolutionary processes involved. In the case of South American mammals, the Pliocene Great American Biotic Interchange strongly influences the ecological characteristics of this assemblage. Furthermore, the Andes have acted as a fertile ground for speciation in environments prone to vicariance. Finally, the micromammals appear as more prone to biomic specialization than larger species. These factors are responsible for some of the differences found between South America and Africa in the studied pattern. For example, the extensive South American mountain ranges favour a higher number of combinations of inhabited biomes in comparison with Africa

Temporal pyramid Matching of local binary sub-patterns for hand-gesture recognition

Human–computer Interaction systems based on hand-gesture recognition are nowadays of great interest to establish a natural communication between humans and machines. However, the visual recognition of gestures and other human poses remains a challenging problem. In this paper, the original volumetric spatiograms of local binary patterns descriptor has been extended to efficiently and robustly encode the spatial and temporal information of hand gestures. This enhancement mitigates the dimensionality problems of the previous approach, and considers more temporal information to achieve a higher recognition rate. Excellent results have been obtained, outperforming other existing approaches of the state of the art

Interdisciplinary Learning at University: Assessment of an Interdisciplinary Experience Based on the Case Study Methodology

In the current context, higher education faces the challenge of preparing future professionals to respond to society’s increasingly complex problems. However, the search for solutions means adopting new ways of working that promote multidimensionality through collaboration and an interdisciplinary outlook. In this change of paradigm, universities should work on the development of sustainability education, promoting critical reflection and the necessary skills to generate a change in thinking and real practice for sustainability, through incorporation of methodologies that foster collaborative teaching and working. The main aim of the present study was to design, implement, and assess an experience based on the case study methodology, approached from an interdisciplinary perspective. By designing repeated pretest–posttest measures, we analyzed changes in learning skills linked to interdisciplinarity, such as collaborative work, participation, motivation, and interdisciplinary thinking. The sample comprised 539 university undergraduates from Social Education, Primary Education, and Psychology degree courses. The results confirmed that the methodology used improved interdisciplinary outlook, participation, cooperation, and motivation. The implications of this type of innovative experience for the teaching–learning process of university students are discussed.The Research Project was sponsored by the University of the Basque Country (Spain), with grant number EHU-HBT19-20, Cod. 133

Novel Multi-Feature Bag-of-Words Descriptor via Subspace Random Projection for Efficient Human-Action Recognition

Human-action recognition through local spatio-temporal features have been widely applied because of their simplicity and its reasonable computational complexity. The most common method to represent such features is the well-known Bag-of-Words approach, which turns a Multiple-Instance Learning problem into a supervised learning one, which can be addressed by a standard classifier. In this paper, a learning framework for human-action recognition that follows the previous strategy is presented. First, spatio-temporal features are detected. Second, they are described by HOG-HOF descriptors, and then represented by a Bag of Words approach to create a feature vector representation. The resulting high dimensional features are reduced by means of a subspace-random-projection technique that is able to retain almost all the original information. Lastly, the reduced feature vectors are delivered to a classifier called Citation K-Nearest Neighborhood, especially adapted to Multiple-Instance Learning frameworks. Excellent results have been obtained, outperforming other state-of-the art approaches in a public database

Influence of continental history on the ecological specialization and macroevolutionary processes in the mammalian assemblage of South America: differences between small and large mammals

Background. This paper tests Vrba's resource-use hypothesis, which predicts that generalist species have lower specialization and extinction rates than specialists, using the 879 species of South American mammals. We tested several predictions about this hypothesis using the biomic specialization index (BSI) for each species, which is based on its geographical range within different climate-zones. The four predictions tested are: (1) there is a high frequency of species restricted to a single biome, which henceforth are referred to as stenobiomic species, (2) certain clades are more stenobiomic than others, (3) there is a higher proportion of biomic specialists in biomes that underwent through major expansion-contraction alternation due to the glacial-interglacial cycles, (4) certain combinations of inhabited biomes occur more frequently among species than do others. Results. Our results are consistent with these predictions. (1) We found that 42 % of the species inhabit only one biome. (2) There are more generalists among species of Carnivora than in clades of herbivores. However, Artiodactyla, shows a distribution along the specialization gradient different from the one expected. (3) Biomic specialists are predominant in tropical rainforest and desert biomes. Nevertheless, we found some differences between small and large mammals in relation to these results. Stenobiomic species of micromammalian clades are more abundant in most biomes than expected by chance, while in the case of macromammalian clades stenobiomic species are more frequent than expected in tropical rainforest, tropical deciduous woodland and desert biomes only. (4) The most frequent combinations of inhabited biomes among the South American mammals are those with few biomes, i.e., the ones that suffered a higher rate of vicariance due to climatic cycles. Conclusion. Our results agree with the resource-use hypothesis and, therefore, with a major role of the past climatic changes as drivers of mammalian evolution. Nevertheless, deviations from the expectations indicate the importance of differences in reproductive traits and paleobiogeographic history for the macroevolutionary processes involved. In the case of South American mammals, the Pliocene Great American Biotic Interchange strongly influences the ecological characteristics of this assemblage. Furthermore, the Andes have acted as a fertile ground for speciation in environments prone to vicariance. Finally, the micromammals appear as more prone to biomic specialization than larger species. These factors are responsible for some of the differences found between South America and Africa in the studied pattern. For example, the extensive South American mountain ranges favour a higher number of combinations of inhabited biomes in comparison with Africa.Facultad de Ciencias Naturales y Muse

Human-computer interaction based on visual hand-gesture recognition using volumetric spatiograms of local binary patterns

A more natural, intuitive, user-friendly, and less intrusive Human–Computer interface for controlling an application by executing hand gestures is presented. For this purpose, a robust vision-based hand-gesture recognition system has been developed, and a new database has been created to test it. The system is divided into three stages: detection, tracking, and recognition. The detection stage searches in every frame of a video sequence potential hand poses using a binary Support Vector Machine classifier and Local Binary Patterns as feature vectors. These detections are employed as input of a tracker to generate a spatio-temporal trajectory of hand poses. Finally, the recognition stage segments a spatio-temporal volume of data using the obtained trajectories, and compute a video descriptor called Volumetric Spatiograms of Local Binary Patterns (VS-LBP), which is delivered to a bank of SVM classifiers to perform the gesture recognition. The VS-LBP is a novel video descriptor that constitutes one of the most important contributions of the paper, which is able to provide much richer spatio-temporal information than other existing approaches in the state of the art with a manageable computational cost. Excellent results have been obtained outperforming other approaches of the state of the art

First optical observations in the turbidity maximum zone in the Río de la Plata estuary: a challenge for atmospheric correction algorithms

The Río de la Plata (RdP) estuary, located at 35°S on the southwestern Atlantic Ocean, is a shallow and large-scale plain, which drains the second largest basin in South America. The RdP river carries high amounts of nutrients, suspended particulate and dissolved organic matter to the adjacent shelf waters and is considered among the most turbid estuaries in the world. A turbidity maximum and a sharp surface front defining its seaward edge is a distinctive feature of this estuary. Such high sediment loads represent a challenge to atmospheric correction algorithms which usually rely on the assumption of zero waterleaving reflectance in the near infrared (NIR) or short wave infrared (SWIR) parts of the spectrum. Uncertainties of the primary remote sensing products have never been quantified in RdP before due to lack of in situ measurements. In February and April 2013 two field campaigns were performed in the turbidity maximum zone where water reflectance was measured and surface water samples were collected for turbidity and total suspended particle concentration determinations. A match-up analysis was performed to evaluate the performance of five atmospheric correction algorithms on MODIS-Aqua data that use the NIR and/or SWIR bands to estimate the aerosols optical properties in a pixel-by-pixel basis and from clear water pixels and then applied to the whole image. Satellite retrievals of remote sensing reflectance at the visible bands of Aqua sensor generally showed quite large uncertainties and constant underestimation (largest at the blue bands), whereas the uncertainties in the NIR bands were the lowest

Obesity attenuates the effect of sleep apnea on active TGF-ss 1 levels and tumor aggressiveness in patients with melanoma

Active transforming growth factor-β1 (TGF-β1), a cytokine partially regulated by hypoxia and obesity, has been related with poor prognosis in several tumors. We determine whether obstructive sleep apnea (OSA) increases serum levels of active TGF-β1 in patients with cutaneous melanoma (CM), assess their relationship with melanoma aggressiveness and analyze the factors related to TGF-β1 levels in obese and non-obese OSA patients. In a multicenter observational study, 290 patients with CM were underwent sleep studies. TGF-β1 was increased in moderate-severe OSA patients vs. non-OSA or mild OSA patients with CM. In OSA patients, TGF-β1 levels correlated with mitotic index, Breslow index and melanoma growth rate, and were increased in presence of ulceration or higher Clark levels. In CM patients, OSA was associated with higher TGF-β1 levels and greater melanoma aggressiveness only in non-obese subjects. An in vitro model showed that IH-induced increases of TGF-β1 expression in melanoma cells is attenuated in the presence of high leptin levels. In conclusion, TGF-β1 levels are associated with melanoma aggressiveness in CM patients and increased in moderate-severe OSA. Moreover, in non-obese patients with OSA, TGF-β1 levels correlate with OSA severity and leptin levels, whereas only associate with leptin levels in obese OSA patients