Is there a subgroup of long-term evolution among patients with advanced lung cancer?: Hints from the analysis of survival curves from cancer registry data

Background: Recently, with the access of low toxicity biological and targeted therapies, evidence of the existence of a long-term survival subpopulation of cancer patients is appearing. We have studied an unselected population with advanced lung cancer to look for evidence of multimodality in survival distribution, and estimate the proportion of long-term survivors. Methods: We used survival data of 4944 patients with non-small-cell lung cancer (NSCLC) stages IIIb-IV at diagnostic, registered in the National Cancer Registry of Cuba (NCRC) between January 1998 and December 2006. We fitted one-component survival model and two-component mixture models to identify short-and long-term survivors. Bayesian information criterion was used for model selection. Results: For all of the selected parametric distributions the two components model presented the best fit. The population with short-term survival (almost 4 months median survival) represented 64% of patients. The population of long-term survival included 35% of patients, and showed a median survival around 12 months. None of the patients of short-term survival was still alive at month 24, while 10% of the patients of long-term survival died afterwards. Conclusions: There is a subgroup showing long-term evolution among patients with advanced lung cancer. As survival rates continue to improve with the new generation of therapies, prognostic models considering short-and long-term survival subpopulations should be considered in clinical research.

LC-MS based methods for phytosterols determination in oenological matrices. Targeted metabolomic study of Rioja grape varieties

221 p.+ anexos

Changes in social inequalities in disability-free life expectancy in Southern Europe: the case of the Basque Country

Background: Health expectancy is a useful tool to monitor health inequalities. The evidence about the recent changes in social inequalities in healthy expectancy is relatively scarce and inconclusive, and most studies have focused on Anglo-Saxon and central or northern European countries. The objective of this study was to analyse the changes in socioeconomic inequalities in disability-free life expectancy in a Southern European population, the Basque Country, during the first decade of the 21st century. Methods: This was an ecological cross-sectional study of temporal trends on the Basque population in 1999-2003 and 2004-2008. All-cause mortality rate, life expectancy, prevalence of disability and disability free-life expectancy were calculated for each period according to the deprivation level of the area of residence. The slope index of inequality and the relative index of inequality were calculated to summarize and compare the inequalities in the two periods. Results: Disability free-life expectancy decreased as area deprivation increased both in men and in women. The difference between the most extreme groups in 2004-2008 was 6.7 years in men and 3.7 in women. Between 1999-2003 and 2004-2008, socioeconomic inequalities in life expectancy decreased, and inequalities in disability-free expectancy increased in men and decreased in women. Conclusions: This study found important socioeconomic inequalities in health expectancy in the Basque Country. These inequalities increased in men and decreased in women in the first decade of the 21st century, during which the Basque Country saw considerable economic growth.

La crítica de Ortega y Gasset a la modernidad y su lugar en la filosofía contemporánea. Problemas onto-epistemológicos

361 p.

Historia del cuidado y del papel de la enfermería durante la Guerra Civil Española: España y País Vasco : revisión Bibliográfica

[Es]La labor cuidadora es conocida desde la antigüedad y así lo demuestran los estudios realizados. En el transcurso de la historia ha existido una evolución en el concepto de la salud-enfermedad. Y a su vez la enfermería ha sufrido trasformaciones importantes, situándose hoy en día en la posición en la que se la conoce. Diferentes acontecimientos favorecieron ésta evolución, como los conflictos bélicos. Por ello se realiza un estudio durante la Guerra Civil Española (1936-1939), para conocer la situación de la enfermería en la época, los cuidados que ofrecieron las/los enfermeras/os, la importancia de la colaboración social para la realización de estos cuidados y el consecuente beneficio de todo ello. Dedicando una sección al País vasco. Se realiza una revisión bibliográfica recurriendo principalmente a fuentes primarias para la obtención de documentación. Dando como resultado, un estudio histórico de carácter analítico-sintético. Se obtiene como resultado una visión global de la labor cuidadora de enfermeras/os, del voluntariado y de la ayuda internacional en el transcurso del conflicto. Destaca la importancia de la formación, la disciplina, los reglamentos y guías. Resulta imprescindible señalar el importante papel que desarrolló la Cruz Roja durante todo el conflicto. El conocimiento sobre el importante papel de la enfermería y los cuidados aplicados durante la guerra, contribuye a una reflexión personal de la importancia que éstas tuvieron, y demuestra la necesidad de una indagación más profunda y amplia.

Together we have it all ! Benefits of participation in collective emotional gatherings and communal coping

244 p.

Diseño de una junta esférica flexible para un manipulador de alta precisión.

ES]El Trabajo Fin de Grado que se presenta a continuación tiene como objetivo principal el diseño de una unión flexible que formará parte de las patas de un robot de cinemática paralela. Por la propia arquitectura de estos mecanismos, y para dotar a la plataforma de movimientos precisos, esta unión, ubicada en la parte superior de las patas, debe deformarse al ser sometida a esfuerzos de flexión y torsión. Se realiza un adecuado diseño que maximice las deformaciones de dicha unión a la par que se garantiza una adecuada duración de la misma para la aplicación requerida. A su vez, se comprueba que las tensiones a las que se verá sometida no superan el límite de fluencia del material elegido. Todo ello se realiza de forma computacional mediante el método de los elementos finitos.

Insights into mechanism kinematics for protein motion simulation

Background: The high demanding computational requirements necessary to carry out protein motion simulations make it difficult to obtain information related to protein motion. On the one hand, molecular dynamics simulation requires huge computational resources to achieve satisfactory motion simulations. On the other hand, less accurate procedures such as interpolation methods, do not generate realistic morphs from the kinematic point of view. Analyzing a protein's movement is very similar to serial robots; thus, it is possible to treat the protein chain as a serial mechanism composed of rotational degrees of freedom. Recently, based on this hypothesis, new methodologies have arisen, based on mechanism and robot kinematics, to simulate protein motion. Probabilistic roadmap method, which discretizes the protein configurational space against a scoring function, or the kinetostatic compliance method that minimizes the torques that appear in bonds, aim to simulate protein motion with a reduced computational cost. Results: In this paper a new viewpoint for protein motion simulation, based on mechanism kinematics is presented. The paper describes a set of methodologies, combining different techniques such as structure normalization normalization processes, simulation algorithms and secondary structure detection procedures. The combination of all these procedures allows to obtain kinematic morphs of proteins achieving a very good computational cost-error rate, while maintaining the biological meaning of the obtained structures and the kinematic viability of the obtained motion. Conclusions: The procedure presented in this paper, implements different modules to perform the simulation of the conformational change suffered by a protein when exerting its function. The combination of a main simulation procedure assisted by a secondary structure process, and a side chain orientation strategy, allows to obtain a fast and reliable simulations of protein motion.

Colaboración en las prestaciones y la documentación de Kdenlive.

[Es]Con el paso de los años, el uso de tecnologías de edición de vídeo ha ido cobrando protagonismo, tanto dentro del mundo del arte cinematográfico, como en reportajes, o, en los últimos años, en vídeos subidos por usuarios a redes sociales. Por otra parte, el software libre se ha ido expandiendo en todos los sectores, proporcionando a los usuarios código de calidad sin tener que pagar las licencias de otros programas similares. Por ello, se decide por optar por la colaboración en Kdenlive, un editor de vídeo de código libre desarrollado en KDE. Este programa cuenta con una multitud de potentes herramientas, y está basado en torno a una comunidad de desarrolladores, que trabajan con el objetivo de crear el editor de vídeo no lineal más avanzado de GNU/Linux. Mediante este trabajo, se pretende contribuir a dicho programa mediante el diseño y codificación de una nueva funcionalidad para el programa, a la vez que colaborar con la documentación ofrecida por los desarrolladores del programa con el objetivo de ayudar a nuevos desarrolladores a incorporarse al desarrollo de la aplicación de una manera más sencilla.

La crisis actual: una visión desde la transparencia y las medidas al respecto

[ES]Este trabajo tiene como objetivo fundamental, valorar si podría haber sido distinto el transcurso de la crisis actual de haber existido mayor transparencia. Al mismo tiempo, también se tratan de observar tanto las medidas actuales como futuras tomadas al respecto. Para ello, se plantean una serie de objetivos secundarios con la finalidad de conseguir de esta manera guiar el desarrollo ordenado de los acontecimientos. Uno de estos objetivos es ver cuál ha sido el origen y desarrollo de la crisis. Para ello, se ha planteado el surgimiento de las hipotecas subprime, base de un sistema que empezó a fallar cuando muchas de estas fueron insolventes. Además, la globalización del sistema financiero contribuyó a que el número de afectados por la titulización de estas hipotecas, un procedimiento muy habitual entonces, fuese mayor. De esta manera, la crisis que surgió originariamente en Estados Unidos pasó a afectar prácticamente a todos los demás países. Otros de los objetivos, están centrados alrededor de la falta de transparencia, sus consecuencias y las medidas paliativas tomadas tanto presentes como futuras. Todo esto se ha planteado acerca de varios aspectos, pero quizás los más importante son los que tratan acerca de la transparencia de los procedimientos bancarios, los cuales debido a su opacidad contribuyeron a generar desconfianza en el sistema interbancario, derivando en un colapso del mismo y en crisis de liquidez.

Nazioarteko finantza krisia:Europako herrialde kaltetuenetan izandako ondorioak

[EU]2008.urtetik pairatzen ari garen krisialdia mundu osoko ekonomietan izan du eragina. Depresio Handitik krisi larriena izaten ari dena Estatu batuetan hasi eta bereziki herrialde garatuetan barreiatu ditu bere efektu negatiboak. Testuinguru honetan, lanaren helburu nagusia izango da krisiaren ondorioz gehien kaltetuak izan diren Europako herrialdeen arteko ezaugarri antzeko eta ezberdinak ezagutzea. Horretarako erabilitako metodologia, analitiko-sintetikoa izanik. Aukeratutako herrialdeen ezaugarri nabarmenak aztertu eta gero, bakoitzean krisiaren eraginak azaltzen dituzten faktore esanguratsuenak identifikatu ditugu. Bukatzeko, faktore horiek herriz herri errepikatzen diren edo, aldiz, desberdinak diren ondorioztatzea dugu helburu.

Involvement of ANXA5 and ILKAP in Susceptibility to Malignant Melanoma

Single nucleotide-polymorphisms (SNPs) are a source of diversity among human population, which may be responsible for the different individual susceptibility to diseases and/or response to drugs, among other phenotypic traits. Several low penetrance susceptibility genes associated with malignant melanoma (MM) have been described, including genes related to pigmentation, DNA damage repair and oxidative stress pathways. In the present work, we conducted a candidate gene association study based on proteins and genes whose expression we had detected altered in melanoma cell lines as compared to normal melanocytes. The result was the selection of 88 loci and 384 SNPs, of which 314 fulfilled our quality criteria for a case-control association study. The SNP rs6854854 in ANXA5 was statistically significant after conservative Bonferroni correction when 464 melanoma patients and 400 controls were analyzed in a discovery Phase I. However, this finding could not be replicated in the validation phase, perhaps because the minor allele frequency of SNP rs6854854 varies depending on the geographical region considered. Additionally, a second SNP (rs6431588) located on ILKAP was found to be associated with melanoma after considering a combined set of 1,883 MM cases and 1,358 disease-free controls. The OR was 1.29 (95% CI 1.12-1.48; p-value= 4x10(-4)). Both SNPs, rs6854854 in ANXA5 and rs6431588 in ILKAP, show population structure, which, assuming that the Spanish population is not significantly structured, suggests a role of these loci on a specific genetic adaptation to different environmental conditions. Furthermore, the biological relevance of these genes in MM is supported by in vitro experiments, which show a decrease in the transcription levels of ANXA5 and ILKAP in melanoma cells compared to normal melanocytes.

Pharmacogenetics of MicroRNAs and MicroRNAs Biogenesis Machinery in Pediatric Acute Lymphoblastic Leukemia

Despite the clinical success of acute lymphoblastic leukemia (ALL) therapy, toxicity is frequent. Therefore, it would be useful to identify predictors of adverse effects. In the last years, several studies have investigated the relationship between genetic variation and treatment-related toxicity. However, most of these studies are focused in coding regions. Nowadays, it is known that regions that do not codify proteins, such as microRNAs (miRNAs), may have an important regulatory function. MiRNAs can regulate the expression of genes affecting drug response. In fact, the expression of some of those miRNAs has been associated with drug response. Genetic variations affecting miRNAs can modify their function, which may lead to drug sensitivity. The aim of this study was to detect new toxicity markers in pediatric B-ALL, studying miRNA-related polymorphisms, which can affect miRNA levels and function. We analyzed 118 SNPs in pre-miRNAs and miRNA processing genes in association with toxicity in 152 pediatric B-ALL patients all treated with the same protocol (LAL/SHOP). Among the results found, we detected for the first time an association between rs639174 in DROSHA and vomits that remained statistically significant after FDR correction. DROSHA had been associated with alterations in miRNAs expression, which could affect genes involved in drug transport. This suggests that miRNA-related SNPs could be a useful tool for toxicity prediction in pediatric B-ALL.

Geochemical characterization of the fire-fountain fed deposits of Las Herrerias volcano (Campo de Calatrava Volcanic Field, Ciudad Real)

The Las Herrerias volcano (Bolanos de Calatrava, Campo de Calatrava Volcanic Field) is characterized by the great amount and variety of fire-fountain fed deposits. All these deposits are compositionally similar, being constituted by magnesium-rich (MgO = 11.58-4.19%), aluminium-poor (Al2O3 = 9.64-10.99%) highly sodic (Na2O = 2.24-3.81%) melanephelinites, with high contents in rare earth-elements (10x-200x chondrite), particularly in light-rare earth elements with respect to the heavy ones [(La/Lu)(N) = 32-35]. Contrary to the equivalent melanephelinites of this volcanic field, the relatively low contents in Ni (233-286 ppm), Cr (393-520 ppm) and magnesium number (Mg* = 45-54) indicate that these rocks do not correspond with primary melts. On the other hand, the variable distribution of clinopyroxene in the magma during eruption would be responsible for the slight compositional differences observed in the studied samples. Finally, we argue that these fire fountains were developed in a continental intraplate setting.

El sacrificio de Alcestis

[ES] La tragedia griega exige, para su comprensión, remitirse al contexto social y cultural en que fue compuesta. Tomar como referente el conocimiento que nosotros tenemos del modo de vida y pensamiento de entonces es algo fundamental, si se quiere entender la forma de actuar de las mujeres y de los hombres trágicos, como Alcestis y Admeto. Vistos bajo esta perspectiva, dejan de ser la heroína romántica y el pérfido esposo, para convertirse ella en el paradigma del ideal femenino en una sociedad donde el padre es el miembro más preciado de la familia, y él en el varón irreprochable. Todo esto bajo un discurso, el trágico, que se complace en difuminar la frontera mediadora entre lo masculino y lo femenino.