Network-based genome-wide association study of Crohn's disease

Genome-wide association studies (GWAS) have rapidly become a standard method for disease gene discovery. Many recent GWAS indicate that for most disorders, only a few common variants are implicated and the associated SNPs explain only a small fraction of the genetic risk. The current study incorporated gene network information into gene-based analysis of GWAS data for Crohn's disease (CD). The purpose was to develop statistical models to boost the power of identifying disease-associated genes and gene subnetworks by maximizing the use of existing biological knowledge from multiple sources. The results revealed that Markov random field (MRF) based mixture model incorporating direct neighborhood information from a single gene network is not efficient in identifying CD-related genes based on the GWAS data. The incorporation of solely direct neighborhood information might lead to the low efficiency of these models. Alternative MRF models looking beyond direct neighboring information are necessary to be developed in the future for the purpose of this study.^

INTEGRATIVE BIOMARKER IDENTIFICATION AND CLASSIFICATION USING HIGH THROUGHPUT ASSAYS

It is well accepted that tumorigenesis is a multi-step procedure involving aberrant functioning of genes regulating cell proliferation, differentiation, apoptosis, genome stability, angiogenesis and motility. To obtain a full understanding of tumorigenesis, it is necessary to collect information on all aspects of cell activity. Recent advances in high throughput technologies allow biologists to generate massive amounts of data, more than might have been imagined decades ago. These advances have made it possible to launch comprehensive projects such as (TCGA) and (ICGC) which systematically characterize the molecular fingerprints of cancer cells using gene expression, methylation, copy number, microRNA and SNP microarrays as well as next generation sequencing assays interrogating somatic mutation, insertion, deletion, translocation and structural rearrangements. Given the massive amount of data, a major challenge is to integrate information from multiple sources and formulate testable hypotheses. This thesis focuses on developing methodologies for integrative analyses of genomic assays profiled on the same set of samples. We have developed several novel methods for integrative biomarker identification and cancer classification. We introduce a regression-based approach to identify biomarkers predictive to therapy response or survival by integrating multiple assays including gene expression, methylation and copy number data through penalized regression. To identify key cancer-specific genes accounting for multiple mechanisms of regulation, we have developed the integIRTy software that provides robust and reliable inferences about gene alteration by automatically adjusting for sample heterogeneity as well as technical artifacts using Item Response Theory. To cope with the increasing need for accurate cancer diagnosis and individualized therapy, we have developed a robust and powerful algorithm called SIBER to systematically identify bimodally expressed genes using next generation RNAseq data. We have shown that prediction models built from these bimodal genes have the same accuracy as models built from all genes. Further, prediction models with dichotomized gene expression measurements based on their bimodal shapes still perform well. The effectiveness of outcome prediction using discretized signals paves the road for more accurate and interpretable cancer classification by integrating signals from multiple sources.

Photosynthetic parameters, chlorophyll concentration, and diffuse attenuation coefficients in the Rhode River, Maryland (USA), 1990-2009

Parameters in the photosynthesis-irradiance (P-E) relationship of phytoplankton were measured at weekly to bi-weekly intervals for 20 yr at 6 stations on the Rhode River, Maryland (USA). Variability in the light-saturated photosynthetic rate, PBmax, was partitioned into interannual, seasonal, and spatial components. The seasonal component of the variance was greatest, followed by interannual and then spatial. Physiological models of PBmax based on balanced growth or photoacclimation predicted the overall mean and most of the range, but not individual observations, and failed to capture important features of the seasonal and interannual variability. PBmax correlated most strongly with temperature and the concentration of dissolved inorganic carbon (IC), with lesser correlations with chlorophyll a, diffuse attenuation coefficient, and a principal component of the species composition. In statistical models, temperature and IC correlated best with the seasonal pattern, but temperature peaked in late July, out of phase with PBmax, which peaked in September, coincident with the maximum in monthly averaged IC concentration. In contrast with the seasonal pattern, temperature did not contribute to interannual variation, which instead was governed by IC and the additional lesser correlates. Spatial variation was relatively weak and uncorrelated with ancillary measurements. The results demonstrate that both the overall distribution of PBmax and its relationship with environmental correlates may vary from year to year. Coefficients in empirical statistical models became stable after including 7 to 10 yr of data. The main correlates of PBmax are amenable to automated monitoring, so that future estimates of primary production might be made without labor-intensive incubations.

Impacto del cambio climático sobre los usos del agua en Europa

Esta Tesis realiza una contribución metodológica al estudio del impacto del cambio climático sobre los usos del agua, centrándose particularmente en la agricultura. Tomando en consideración su naturaleza distinta, la metodología aborda de forma integral los impactos sobre la agricultura de secano y la agricultura de regadío. Para ello incorpora diferentes modelos agrícolas y de agua que conjuntamente con las simulaciones de los escenarios climáticos permiten determinar indicadores de impacto basados en la productividad de los cultivos, para el caso de la agricultura de secano, e indicadores de impacto basados en la disponibilidad de agua para irrigación, para el caso de la agricultura de regadío. La metodología toma en consideración el efecto de la variabilidad climática en la agricultura, evaluando las necesidades de adaptación y gestión asociadas a los impactos medios y a la variabilidad en la productividad de los cultivos y el efecto de la variabilidad hidrológica en la disponibilidad de agua para regadío. Considerando la gran cantidad de información proporcionada por las salidas de las simulaciones de los escenarios climáticos y su complejidad para procesarla, se ha desarrollado una herramienta de cálculo automatizada que integra diferentes escenarios climáticos, métodos y modelos que permiten abordar el impacto del cambio climático sobre la agricultura, a escala de grandes extensiones. El procedimiento metodológico parte del análisis de los escenarios climáticos en situación actual (1961-1990) y futura (2071-2100) para determinar su fiabilidad y conocer qué dicen exactamente las proyecciones climáticas a cerca de los impactos esperados en las principales variables que intervienen en el ciclo hidrológico. El análisis hidrológico se desarrolla en los ámbitos territoriales de la planificación hidrológica en España, considerando la disponibilidad de información para validar los resultados en escenario de control. Se utilizan como datos observados las series de escorrentía en régimen natural estimadas el modelo hidrológico SIMPA que está calibrado en la totalidad del territorio español. Al trabajar a escala de grandes extensiones, la limitada disponibilidad de datos o la falta de modelos hidrológicos correctamente calibrados para obtener los valores de escorrentía, muchas veces dificulta el proceso de evaluación, por tanto, en este estudio se plantea una metodología que compara diferentes métodos de interpolación y alternativas para generar series anuales de escorrentía que minimicen el sesgo con respecto a los valores observados. Así, en base a la alternativa que genera los mejores resultados, se obtienen series mensuales corregidas a partir de las simulaciones de los modelos climáticos regionales (MCR). Se comparan cuatro métodos de interpolación para obtener los valores de las variables a escala de cuenca hidrográfica, haciendo énfasis en la capacidad de cada método para reproducir los valores observados. Las alternativas utilizadas consideran la utilización de la escorrentía directa simulada por los MCR y la escorrentía media anual calculada utilizando cinco fórmulas climatológicas basadas en el índice de aridez. Los resultados se comparan además con la escorrentía global de referencia proporcionada por la UNH/GRDC que en la actualidad es el “mejor estimador” de la escorrentía actual a gran escala. El impacto del cambio climático en la agricultura de secano se evalúa considerando el efecto combinado de los riesgos asociados a las anomalías dadas por los cambios en la media y la variabilidad de la productividad de los cultivos en las regiones agroclimáticas de Europa. Este procedimiento facilita la determinación de las necesidades de adaptación y la identificación de los impactos regionales que deben ser abordados con mayor urgencia en función de los riesgos y oportunidades identificadas. Para ello se utilizan funciones regionales de productividad que han sido desarrolladas y calibradas en estudios previos en el ámbito europeo. Para el caso de la agricultura de regadío, se utiliza la disponibilidad de agua para irrigación como un indicador del impacto bajo escenarios de cambio climático. Considerando que la mayoría de estudios se han centrado en evaluar la disponibilidad de agua en régimen natural, en este trabajo se incorpora el efecto de las infraestructuras hidráulicas al momento de calcular el recurso disponible bajo escenarios de cambio climático Este análisis se desarrolla en el ámbito español considerando la disponibilidad de información, tanto de las aportaciones como de los modelos de explotación de los sistemas hidráulicos. Para ello se utiliza el modelo de gestión de recursos hídricos WAAPA (Water Availability and Adaptation Policy Assessment) que permite calcular la máxima demanda que puede atenderse bajo determinados criterios de garantía. Se utiliza las series mensuales de escorrentía observadas y las series mensuales de escorrentía corregidas por la metodología previamente planteada con el objeto de evaluar la disponibilidad de agua en escenario de control. Se construyen proyecciones climáticas utilizando los cambios en los valores medios y la variabilidad de las aportaciones simuladas por los MCR y también utilizando una fórmula climatológica basada en el índice de aridez. Se evalúan las necesidades de gestión en términos de la satisfacción de las demandas de agua para irrigación a través de la comparación entre la disponibilidad de agua en situación actual y la disponibilidad de agua bajo escenarios de cambio climático. Finalmente, mediante el desarrollo de una herramienta de cálculo que facilita el manejo y automatización de una gran cantidad de información compleja obtenida de las simulaciones de los MCR se obtiene un proceso metodológico que evalúa de forma integral el impacto del cambio climático sobre la agricultura a escala de grandes extensiones, y a la vez permite determinar las necesidades de adaptación y gestión en función de las prioridades identificadas. ABSTRACT This thesis presents a methodological contribution for studying the impact of climate change on water use, focusing particularly on agriculture. Taking into account the different nature of the agriculture, this methodology addresses the impacts on rainfed and irrigated agriculture, integrating agricultural and water planning models with climate change simulations scenarios in order to determine impact indicators based on crop productivity and water availability for irrigation, respectively. The methodology incorporates the effect of climate variability on agriculture, assessing adaptation and management needs associated with mean impacts, variability in crop productivity and the effect of hydrologic variability on water availability for irrigation. Considering the vast amount of information provided by the outputs of the regional climate model (RCM) simulations and also its complexity for processing it, a tool has been developed to integrate different climate scenarios, methods and models to address the impact of climate change on agriculture at large scale. Firstly, a hydrological analysis of the climate change scenarios is performed under current (1961-1990) and future (2071-2100) situation in order to know exactly what the models projections say about the expected impact on the main variables involved in the hydrological cycle. Due to the availability of information for validating the results in current situation, the hydrological analysis is developed in the territorial areas of water planning in Spain, where the values of naturalized runoff have been estimated by the hydrological model SIMPA, which are used as observed data. By working in large-scale studies, the limited availability of data or lack of properly calibrated hydrological model makes difficult to obtain runoff time series. So as, a methodology is proposed to compare different interpolation methods and alternatives to generate annual times series that minimize the bias with respect to observed values. Thus, the best alternative is selected in order to obtain bias-corrected monthly time series from the RCM simulations. Four interpolation methods for downscaling runoff to the basin scale from different RCM are compared with emphasis on the ability of each method to reproduce the observed behavior of this variable. The alternatives consider the use of the direct runoff of the RCMs and the mean annual runoff calculated using five functional forms of the aridity index. The results are also compared with the global runoff reference provided by the UNH/GRDC dataset, as a contrast of the “best estimator” of current runoff on a large scale. Secondly, the impact of climate change on rainfed agriculture is assessed considering the combined effect of the risks associated with anomalies given by changes in the mean and variability of crop productivity in the agro-climatic regions of Europe. This procedure allows determining adaptation needs based on the regional impacts that must be addressed with greater urgency in light of the risks and opportunities identified. Statistical models of productivity response are used for this purpose which have been developed and calibrated in previous European study. Thirdly, the impact of climate change on irrigated agriculture is evaluated considering the water availability for irrigation as an indicator of the impact. Given that most studies have focused on assessing water availability in natural regime, the effect of regulation is incorporated in this approach. The analysis is developed in the Spanish territory considering the available information of the observed stream flows and the regulation system. The Water Availability and Adaptation Policy Assessment (WAAPA) model is used in this study, which allows obtaining the maximum demand that could be supplied under certain conditions (demand seasonal distribution, water supply system management, and reliability criteria) for different policy alternatives. The monthly bias corrected time series obtained by previous methodology are used in order to assess water availability in current situation. Climate change projections are constructed taking into account the variation in mean and coefficient of variation simulated by the RCM. The management needs are determined by the agricultural demands satisfaction through the comparison between water availability under current conditions and under climate change projections. Therefore, the methodology allows evaluating the impact of climate change on agriculture to large scale, using a tool that facilitates the process of a large amount of complex information provided by the RCM simulations, in order to determine the adaptation and management needs in accordance with the priorities of the indentified impacts.

Influence of local wind speed and direction on wind power dynamics - Application to offshore very short-term forecasting

Wind power time series usually show complex dynamics mainly due to non-linearities related to the wind physics and the power transformation process in wind farms. This article provides an approach to the incorporation of observed local variables (wind speed and direction) to model some of these effects by means of statistical models. To this end, a benchmarking between two different families of varying-coefficient models (regime-switching and conditional parametric models) is carried out. The case of the offshore wind farm of Horns Rev in Denmark has been considered. The analysis is focused on one-step ahead forecasting and a time series resolution of 10 min. It has been found that the local wind direction contributes to model some features of the prevailing winds, such as the impact of the wind direction on the wind variability, whereas the non-linearities related to the power transformation process can be introduced by considering the local wind speed. In both cases, conditional parametric models showed a better performance than the one achieved by the regime-switching strategy. The results attained reinforce the idea that each explanatory variable allows the modelling of different underlying effects in the dynamics of wind power time series.

Risk assessment of the spanish national railway system

The principal risks in the railway industry are mainly associated with collisions, derailments and level crossing accidents. An understanding of the nature of previous accidents on the railway network is required to identify potential causes and develop safety systems and deploy safety procedures. Risk assessment is a process for determining the risk magnitude to assist with decision-making. We propose a three-step methodology to predict the mean number of fatalities in railway accidents. The first is to predict the mean number of accidents by analyzing generalized linear models and selecting the one that best fits to the available historical data on the basis of goodness-offit statistics. The second is to compute the mean number of fatalities per accident and the third is to estimate the mean number of fatalities. The methodology is illustrated on the Spanish railway system. Statistical models accounting for annual and grouped data for the 1992-2009 time period have been analyzed. After identifying the models for broad and narrow gauges, we predicted mean number of accidents and the number of fatalities for the 2010-18 time period.

Variation throughout the tree stem in the physical-mechanical properties of the wood of Abies alba Mill. from the Spanish Pyrenees

This study analyses the variation of main physical-mechanical properties of wood along the longitudinal and radial directions of the tree for Abies alba Mill. growing in the Spanish Pyrenees. Small clear specimens were used to study the properties of volumetric shrinkage (VS), density (?), hardness (H), bending strength (MOR), modulus of elasticity (MOE), maximum compressive strength parallel to the grain (MCS) and impact strength (K). Several models of properties variation in the longitudinal and radial directions were analyzed. Main trends of variation of properties throughout the tree stem were identified although none of them could be fitted to predictive statistical models. Along the longitudinal direction, the properties studied followed a downward trend from the base to the crown, which was not significant in all cases, indicating that no differences in quality existed. Throughout the radial direction the trend is upward for the first 40-50 growth rings, after which it slopes downwards, more gently at first until rings 70-75 and then more steeply. This behaviour is related to variation in wood structure from the pith to the bark, depending on whether the wood is juvenile, sapwood or heartwood, and to wood maturity and microfibril angle. Authors encourage carrying further studies on other populations of A. alba in the Spanish Pyrenees to check if the trends found in this study apply to other provenances.

Gestión de la fertilidad de suelos y la nutrición de plantaciones de teca (Tectona grandis L.f.) en América Central

La teca (Tectona grandis L.f.) ha sido tradicionalmente considerada como una madera preciosa en los países del SE Asiático, de donde es originaria, pero durante las últimas décadas ha alcanzado especial relevancia en el sector internacional de las maderas tropicales duras de buena calidad. La especie ha sido ampliamente establecida en América Central, donde tiene una gran importancia socioeconómica, tanto por el impacto de las grandes empresas multinacionales que gestionan grandes plantaciones en la región, como por el gran número de pequeños y medianos propietarios que han elegido esta especie para reforestar sus tierras. Pese a la gran importancia de esta especie, se ha desarrollado relativamente poca investigación acerca de su nutrición y de la gestión del suelo necesaria para su establecimiento y mantenimiento en condiciones sostenibles y productivas. En la presente Tesis Doctoral, tras realizar una amplia revisión bibliográfica, se caracterizan los suelos y la nutrición de las plantaciones de teca en América Central y se proponen varias herramientas para la mejora de su gestión. Las plantaciones de teca de América Central presentan habitualmente deficiencias de K y P, además de algunos problemas de acidez ocasionales. Estos se originan, principalmente, por la mala selección de sitio que se realizó en las últimas dos décadas del siglo XX y por el establecimiento de plantaciones de teca por pequeños propietarios en terrenos que no tienen características propicias para la especie. Además, estos problemas comunes relativos a la baja disponibilidad de P y de K en el suelo son causantes de las relativamente bajas concentraciones foliares de estos elementos (0,88±0,07% K y 0,16±0,04% P) encontradas en plantaciones de teca características de la región. Se presentan varios modelos estadísticos que permiten a los gestores: (a) usarlos como referencia para la interpretación de análisis foliares, ya que ofrecen valores que se consideran característicos de plantaciones de teca con un buen estado nutricional; (b) estimar la cantidad de nutrientes acumulados en la biomasa aérea de sus plantaciones y, sobre todo, su extracción a través de la madera en un aprovechamiento forestal, bien sea una clara o la corta final. La gran acumulación de N, P y K en plantaciones de teca ha de ser considerada como un factor fundamental en su gestión. Además, P y K adquieren mayor relevancia aún ya que su extracción del sistema a través de la madera y su escasa disponibilidad en los suelos hacen que se presente un importante desequilibrio que pone en riesgo la sostenibilidad del sistema. En ese sentido, cambiar la época de cosecha, de la actual (en Enero-Mayo) a Septiembre o Diciembre, puede reducir entre un 24 y un 28% la salida de N asociada a la extracción de madera, un 29% la de P y entre un 14 y un 43% la de K. Se estima que la concentración foliar de P es un factor limitante de la productividad de plantaciones de teca en América Central, proponiéndose un nivel crítico de 0,125%. Además, la teca presenta una tolerancia muy baja a suelos salinos, tendencia que no había sido señalada hasta el momento, siendo muy alta la probabilidad de que la plantación tenga un crecimiento lento o muy lento cuando la Saturación de Na es mayor de 1,1%. Por otro lado, se confirma que K es uno de los elementos clave en la nutrición de las plantaciones de teca en la región centroamericana, proponiéndose un nivel crítico provisional de 3,09% para la Saturación de K, por encima del cual es muy probable que la plantación tenga un crecimiento muy alto. Se ha comprobado que las técnicas estadísticas de análisis multivariante pueden ser usadas como herramientas para agrupar los rodales en base a sus similitudes en cuanto a la fertilidad del suelo y mejorar así el diseño de planes de fertilización en plantaciones con una superficie relativamente grande. De esta manera, se pueden ajustar planes de fertilización más eficientes a escala de grupos de rodales, como un primer paso hacia la selvicultura de precisión, intensificando y diversificando la gestión en función de las diferencias edáficas. Finalmente, aunque los análisis foliares y de suelos indiquen la existencia de deficiencias nutricionales, la fertilización de las plantaciones no siempre va a producir efectos positivos sobre su crecimiento si no se diseña adecuadamente teniendo en cuenta varios factores que pueden estar influyendo negativamente en dicha respuesta, como la densidad de las plantaciones (sinergias con la programación de los clareos y claras) y la elección de la dosis y del producto a aplicar (habitualmente dosis bajas de N-P-K en lugar de incluir otros nutrientes como Mg, B y Zn o usar otros productos como micorrizas, biofertilizantes etc…). ABSTRACT Teak (Tectona grandis L.f.) has been traditionally considered as a precious wood in SE Asia, where it is indigenous. However, during recent decades the species has reached worldwide relevance in the tropical high quality hardwood sector. Teak has been widely established in Central America, where it has become a key species in the forest sector due to its socioeconomic impact, either because of the big-scale plantations of transnational companies and the abundant small-scale plantations established by many farmers. Despite the relevance of the species, little research has been carried out regarding its soil fertility and nutrition management, a key issue both for sustainability and productivity. The present Thesis performs a literature review to this respect, characterize the soil fertility and the nutrition of teak plantations of Central America and propose several management tools. Soil deficiencies of K and P are usually found in teak plantations in Central America, in addition to occasional acidity problems. These problems are mainly derived of (a) a poor site selection performed during 80s and 90s; and (b) small-scale plantations by farmers in sites which are not adequate for the species. These common soil fertility problems related with P and K soil availability are probably the cause of the relatively low P and K foliar concentration (0,88±0,07% K y 0,16±0,04% P) found in representative teak plantations of the region. Several statistical models are proposed, which allow forest managers to: (a) use them as a reference for foliar analysis interpretation, as they show values considered as representative for teak plantations with an adequate nutritional status in the region; (b) estimate the amount of nutrients accumulated in the aerial biomass of the plantations and, especially, the amount of them which are extracted from the systems as wood is harvested in thinning or final clearcuts. The accumulation of N, P and K result in a key factor for teak management in the region. This turns out to be especially relevant for the P and K because their high output rate by timber extraction and the low soil availability result in an important unbalance which constitutes a risk regarding the sustainability of the system. To this respect, modifying the harvesting time from the usual right now (January-May, business as usual scenario) to September or December (proposed alternatives) can reduce between 24 and 28% the N output associated to timber extraction, 29% the P output and between 14 and 43% the K. Foliar P concentration is a main limiting factor for teak plantations productivity in Central America and a 0.125% critical level is proposed. In addition, the results show a very low tolerance for soil salinity, tendency which was not previously reported. Hence, the probability of teak plantations to have low or very low Site Index is high when Na Saturation is higher than 1.1%. On the other hand, K is confirmed as one of the key nutrients regarding teak nutrition in Central America and a 3.09% provisional critical level is proposed for K Saturation; when values are above this level the probability of having very high Site Index is high. Multivariate statistical analyses have been successfully tested to be used as tools to group forest stands according to their soil fertility similarities. Hence, more efficient fertilization plans can be designed for each group of stands, intensifying and diversifying nutritional management according to soil fertility differences. This methodology, which is considered as a first step towards precision forestry, is regarded as helpful tool to design fertilization plans in big scale plantations. Finally, even though foliar and soil analysis would point out some nutritional deficiencies in a forest stand, the results show how the fertilization is not always going to have a positive effect over forest growth if it is not adequately designed. Some factors have been identified as determinants of tree response to fertilization: density (synergisms between fertilization and thinning scheduling) and the appropriate selection of dosages and product (usually low dosages are applied and N-P-K is preferred instead of applying other nutrients such as Mg, B or Zn or using other alternatives such as mycorrhizas or biofertilizers).

Estudio del rendimiento bajo presión en los tiros libres en baloncesto, y su influencia sobre el porcentaje de acierto durante el último minuto de juego

El minuto final de un partido ajustado de baloncesto es un momento crítico que está sujeto a multitud de factores que influyen en su desarrollo. Así, el porcentaje de acierto en los tiros libres durante ese periodo de tiempo va a determinar, en muchas ocasiones, el resultado final del partido. La disminución de rendimiento (drop) en esta faceta de juego en condiciones de presión, puede estar relacionada con múltiples variables propias del contexto deportivo estudiado, como por ejemplo: los segundos restantes de posesión, la situación en el marcador (ir ganando, empatando o perdiendo), la localización del partido (jugar en casa o fuera), la fase de competición (fase regular o eliminatorias) o el nivel del equipo (mejores/peores equipos). Además, las características del jugador que realiza los lanzamientos tienen una gran importancia respecto a su edad y años de experiencia para afrontar los momentos críticos, así como el puesto de juego que ocupa en el equipo. En este sentido, la combinación de factores del contexto y del jugador, permiten interactuar en el rendimiento del lanzador en los momentos finales de partido durante sus lanzamientos de tiro libre. El presente trabajo de tesis doctoral tiene como objetivo encontrar aquellas variables más relacionadas con la disminución de rendimiento del jugador en los tiros libres durante el último minuto de juego, y la última serie de tiros libres en los partidos ajustados de baloncesto. Para alcanzar el objetivo del estudio se analizaron 124 partidos ajustados (diferencias iguales o inferiores a 2 puntos) de todas las competiciones (fase regular, playoff y copa del Rey) de la liga ACB durante las temporadas 2011-2012 a 2014-2015. Para el registro de variables se analizó el porcentaje de acierto en los tiros libres del lanzador en la liga regular, partido completo, último minuto y última serie. De este modo se trató de analizar qué variables del contexto y del jugador permitían explicar el rendimiento en los tiros libres durante el último minuto, y la última serie de tiros libres del partido. Por otro lado, se trató de conocer el grado de asociación entre el descenso del rendimiento (drop) en los momentos finales de partido, y las variables estudiadas del jugador: puesto de juego, edad, y años de experiencia profesional; mientras que las variables situacionales consideradas fueron: fase de competición, localización, clasificación, tiempo restante, y diferencia parcial en el marcador. Para el análisis de los datos se realizaron dos modelos estadísticos: 1º) un modelo de regresión lineal múltiple para conocer el efecto de las variables independientes en el porcentaje de aciertos del lanzador en el último minuto, y en la última serie de tiros libres del partido; y 2º) un análisis de regresión logística binomial para analizar la relación existente entre la probabilidad de tener un drop (disminución del rendimiento) y las características del lanzador, y las variables situacionales. Los resultados del modelo de regresión lineal múltiple mostraron efectos negativos significativos en el porcentaje de acierto en los tiros libres durante el último minuto, cuando los lanzadores son los pívots (-19,45%). Por otro lado, los resultados durante la última serie mostraron el efecto negativo significativo sobre la posición de pívot (- 19,30%) y la diferencia parcial en el marcador (-3,33%, para cada punto de diferencia en el marcador) en el porcentaje de acierto en los tiros libres. Las variables independientes edad, experiencia profesional, clasificación en la liga regular, fase de competición, localización, y tiempo restante, no revelaron efectos significativos en los modelos de regresión lineal. Los resultados de la regresión logística binomial revelaron que las variables experiencia profesional entre 13 y 18 años (OR = 4,63), jugar de alero (OR = 23,01), y jugar de base (OR = 10,68) están relacionadas con una baja probabilidad de disminuir el rendimiento durante el último minuto del partido; mientras que ir ganando, aumenta esta probabilidad (OR = 0,06). Además, los resultados de la última serie mostraron una menor disminución del rendimiento del jugador cuando tiene entre 13 y 18 años de experiencia (OR = 4,28), y juega de alero (OR = 8,06) o base (OR = 6,34). Por el contrario, las variables situacionales relacionadas con esa disminución del rendimiento del jugador son las fases eliminatorias (OR = 0,22) e ir ganando (OR = 0,04). Los resultados principales del estudio mostraron que existe una disminución del rendimiento del jugador en su porcentaje de acierto en los tiros libres durante el último minuto y en la última serie de lanzamientos del partido, y que está relacionada significativamente con la edad, experiencia profesional, puesto de juego del jugador, y diferencia parcial en el marcador. Encontrando relación también con la fase de competición, durante la última serie de tiros libres del partido. Esta información supone una valiosa información para el entrenador, y su aplicación en el ámbito competitivo real. En este sentido, la creación de simulaciones en el apartado de aplicaciones prácticas, permite predecir el porcentaje de acierto en los tiros libres de un jugador durante los momentos de mayor presión del partido, en base a su perfil de rendimiento. Lo que puede servir para realizar una toma de decisiones más idónea, con el objetivo de lograr el mejor resultado. Del mismo modo, orienta el tipo de proceso de entrenamiento que se ha de seguir, en relación a los jugadores más tendentes al drop, con el objetivo de minimizar el efecto de la presión sobre su capacidad para rendir adecuadamente en la ejecución de los tiros libres, y lograr de esta manera un rendimiento más homogéneo en todos los jugadores del equipo en esta faceta del juego, durante el momento crítico del final de partido. ABSTRACT. The final minute of a close game in basketball is a critical moment which is subject to many factors that influence its development. Thus, the success rate in free-throws during that period will determine, in many cases, the outcome of the game. Decrease of performance (drop) in this facet of play under pressure conditions, may be related to studied own multiple sports context variables, such as the remaining seconds of possession, the situation in the score (to be winning, drawing, or losing) the location of the match (playing at home or away), the competition phase (regular season or playoffs) or team level (best/worst teams). In addition, the characteristics of the player are very important related to his age and years of experience to face the critical moments, as well as his playing position into team. In this sense, the combination of factors in context and player, allows interact about performance of shooter in the final moments of the game during his free-throw shooting. The aim of this present doctoral thesis was find the most related variables to player´s drop in free throws in the last minute of the game and the last row of free-throws in closed games of basketball. To achieve the objective of the study, 124 closed games (less or equal than 2 points difference) were analyzed in every copetition in ACB league (regular season, playoff and cup) from 2011-2012 to 2014-2015 seasons. To record the variables, the percentage of success of the shooter in regular season, full game, last minute, and last row were analyzed. This way, it is tried to analyze which player and context variables explain the free-throw performance in last minute and last row of the game. On the other hand, it is tried to determine the degree of association between decrease of performance (drop) of the player in the final moments, and studied player variables: playing position, age, and years of professional experience; while considered situational variables considered were: competition phase, location, classification, remaining time, and score-line. For data analysis were performed two statistical models: 1) A multiple linear regression model to determine the effect of the independent variables in the succsess percentage of shooter at the last minute, and in the last row of free-throws in the game; and 2) A binomial logistic regression analysis to analyze the relationship between the probability of a drop (lower performance) and the characteristics of the shooter and situational variables. The results of multiple linear regression model showed significant negative effects on the free-throw percentage during last minute, when shooters are centers (-19.45%). On the other hand, results in the last series showed the significant negative effect on the center position (-19.30%) and score-line (-3.33% for each point difference in the score) in the free-throw percentage. The independent variables age, professional experience, ranking in the regular season, competition phase, location, and remaining time, revealed no significant effects on linear regression models. The results of the binomial logistic regression showed that the variables professional experience between 13 and 18 years (OR = 4.63), playing forward (OR = 23.01) and playing guard (OR = 10.68) are related to reduce the probability to decrease the performance during the last minute of the game. While wining, increases it (OR = 0.06). Furthermore, the results of the last row showed a reduction in performance degradation when player is between 13 and 18 years of experience (OR = 4.28), and playing forward (OR = 8.06) or guard (OR = 6.34). By contrast, the variables related to the decrease in performance of the player are the knockout phases (OR = 0.22) and wining (OR = 0.04). The main results of the study showed that there is a decrease in performance of the player in the percentage of success in free-throws in the last minute and last row of the game, and it is significantly associated with age, professional experience, and player position. Finding relationship with the competition phase, during last row of free-throws of the game too. This information is a valuable information for the coach, for applying in real competitive environment. In this sense, create simulations in the section of practical applications allows to predict the success rate of free-throw of a player during the most pressing moments of the game, based on their performance profile. What can be used to take more appropriate decisions in order to achieve the best result. Similarly, guides the type of training process must be followed in relation to the most favorable players to drop, in order to minimize the effect of pressure on their ability to perform properly in the execution of the free-throws. And to achieve, in this way, a more consistent performance in all team players in this facet of the game, during the critical moment in the final of the game.

Emulation of an OWC Ocean Energy Plant With PMSG and Irregular Wave Model

Ocean energy is a promising resource for renewable electricity generation that presents many advantages, such as being more predictable than wind energy, but also some disadvantages such as large and slow amplitude variations in the generated power. This paper presents a hardware-in-the-loop prototype that allows the study of the electric power profile generated by a wave power plant based on the oscillating water column (OWC) principle. In particular, it facilitates the development of new solutions to improve the intermittent profile of the power fed into the grid or the test of the OWC behavior when facing a voltage dip. Also, to obtain a more realistic model behavior, statistical models of real waves have been implemented.

HC Forum®: a web site based on an international human cytogenetic database

Familial structural rearrangements of chromosomes represent a factor of malformation risk that could vary over a large range, making genetic counseling difficult. However, they also represent a powerful tool for increasing knowledge of the genome, particularly by studying breakpoints and viable imbalances of the genome. We have developed a collaborative database that now includes data on more than 4100 families, from which we have developed a web site called HC Forum® (http://HCForum.imag.fr). It offers geneticists assistance in diagnosis and in genetic counseling by assessing the malformation risk with statistical models. For researchers, interactive interfaces exhibit the distribution of chromosomal breakpoints and of the genome regions observed at birth in trisomy or in monosomy. Dedicated tools including an interactive pedigree allow electronic submission of data, which will be anonymously shown in a forum for discussions. After validation, data are definitively registered in the database with the email of the sender, allowing direct location of biological material. Thus HC Forum® constitutes a link between diagnosis laboratories and genome research centers, and after 1 year, more than 700 users from about 40 different countries already exist.

Progression of human breast cancers to the metastatic state is linked to hydroxyl radical-induced DNA damage.

Hydroxyl radical damage in metastatic tumor DNA was elucidated in women with breast cancer, and a comparison was made with nonmetastatic tumor DNA. The damage was identified by using statistical models of modified base and Fourier transform-infrared spectral data. The modified base models revealed a greater than 2-fold increase in hydroxyl radical damage in the metastatic tumor DNA compared with the nonmetastatic tumor DNA. The metastatic tumor DNA also exhibited substantially greater base diversity than the nonmetastatic DNA, and a progression of radical-induced base damage was found to be associated with the growth of metastatic tumors. A three-dimensional plot of principal components from factor analysis, derived from infrared spectral data, also showed that the metastatic tumor DNA was substantially more diverse than the tightly grouped nonmetastatic tumor DNA. These cohesive, independently derived findings suggest that the hydroxyl radical generates DNA phenotypes with various metastatic potentials that likely contribute to the diverse physiological properties and heterogeneity characteristic of metastatic cell populations.

Scaling in geology: landforms and earthquakes.

Landforms and earthquakes appear to be extremely complex; yet, there is order in the complexity. Both satisfy fractal statistics in a variety of ways. A basic question is whether the fractal behavior is due to scale invariance or is the signature of a broadly applicable class of physical processes. Both landscape evolution and regional seismicity appear to be examples of self-organized critical phenomena. A variety of statistical models have been proposed to model landforms, including diffusion-limited aggregation, self-avoiding percolation, and cellular automata. Many authors have studied the behavior of multiple slider-block models, both in terms of the rupture of a fault to generate an earthquake and in terms of the interactions between faults associated with regional seismicity. The slider-block models exhibit a remarkably rich spectrum of behavior; two slider blocks can exhibit low-order chaotic behavior. Large numbers of slider blocks clearly exhibit self-organized critical behavior.

Dinâmica de interações intraguilda em Chrysoperla externa (Neuroptera: Chrysopidae), Harmonia axyridis (Coleoptera: Coccinellidae) com Diaphorina citri (Hemiptera: Psyllidae)

A necessidade por recursos alimentares move os insetos predadores na busca por presas, para garantir a sobrevivência. Existem vários fatores que podem influenciar o comportamento de busca e escolha por presas e, sob determinadas circunstâncias, o inseto pode escolher se alimentar de presas não alvo, como, por exemplo, inimigos naturais e assim prejudicar a população de organismos benéficos. Garantir a estabilidade do agroecossistema é uma forma de manter as populações de pragas em níveis compatíveis com a ação de inimigos naturais e, consequentemente obter o sucesso no controle biológico. Programas bem sucedidos de manejo de pragas requerem previamente a realização de estudos sobre comportamento de insetos. Com o intuito de compreender os fatores que governam o comportamento predatório e as interações ecológicas entre Harmonia axyridis e Chrysoperla externa, considerando a presença de Diaphorina citri como presa, objetivou-se estudar o efeito de interações intraguilda sobre a predação de D. citri, experimentalmente e utilizando modelos estatísticos para compreender a dinâmica de interações tróficas no contexto de potenciais guildas presentes em citros. Três experimentos distintos foram realizados para investigar o comportamento dos insetos predadores. Foram realizados testes com escolha entre larvas dos predadores C. externa e H. axyridis e testes com e sem escolha comparando machos e fêmeas do predador H. axyridis, a fim de investigar padrões de escolha de presas. O segundo experimento foi realizado para investigar o comportamento predatório entre larvas de segundo instar dos predadores sob diferentes densidades de D. citri como presa. As combinações foram: sem escolha de presas intraguilda, combinações com escolha de presas intraguilda e combinações com a presença de dois predadores da mesma espécie para possibilitar o canibalismo. As densidades de D. citri utilizadas foram 5, 10, 15, 30, 60, 80. No último experimento avaliou-se a interação entre larvas de C. externa e H. axyridis, ao longo do desenvolvimento, simulando a existência de apenas uma presa, como fonte de alimento. O desenvolvimento dos predadores foi avaliado e comparado utilizando-se duas presas diferentes, ninfas de D. citri e ovos de Ephestia kuehniella para cada larva de primeiro instar dos predadores C. externa e H. axyridis. As combinações de predadores foram as mesmas citadas no experimento anterior. Observou-se a duração do desenvolvimento larval nas diferentes combinações de predadores e presa, bem como o percentual de predações intraguilda e canibalismos ocorridos. Nem a densidade de presas, nem o tipo de presa ofertada influenciou o comportamento das larvas dos predadores para a realização de predação intraguilda ou canibalismo. O principal fator foi a diferença de idade que reflete no tamanho dos predadores, podendo direcionar a predação intraguilda ou o canibalismo e até mesmo acelerar o ciclo de desenvolvimento do predador intraguilda envolvido. Predadores em estágio inicial de vida buscaram por qualquer tipo de presa para garantir sua sobrevivência, não demonstrando qualquer padrão em suas escolhas. No caso dos adultos de H. axyridis, há diferença de comportamento entre os sexos, dependendo da densidade de presas disponíveis, fêmeas poderão ser mais ágeis na busca e consumo de presas.

The role of the social environment in non-suicidal self-injury among LGBTQ youth: A mixed methods study

Non-suicidal self-injury (NSSI), such as cutting and burning, is a widespread social problem among lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ) youth. Extant research indicates that this population is more than twice as likely to engage in NSSI than heterosexual and cisgender (non-transgender) youth. Despite the scope of this social problem, it remains relatively unexamined in the literature. Research on other risk behaviors among LGBTQ youth indicates that experiencing homophobia and transphobia in key social contexts such as families, schools, and peer relationships contributes to health disparities among this group. Consequently, the aims of this study were to examine: (1) the relationship between LGBTQ youth's social environments and their NSSI behavior, and (2) whether/how specific aspects of the social environment contribute to an understanding of NSSI among LGBTQ youth. This study was conducted using an exploratory, sequential mixed methods design with two phases. The first phase of the study involved analysis of transcripts from interviews conducted with 44 LGBTQ youth recruited from a community-based organization. In this phase, five qualitative themes were identified: (1) Violence; (2) Misconceptions, Stigma, and Shame; (3) Negotiating LGBTQ Identity; (4) Invisibility and Isolation; and (5) Peer Relationships. Results from the qualitative phase were used to identify key variables and specify statistical models in the second, quantitative, phase of the study, using secondary data from a survey of 252 LGBTQ youth. The qualitative phase revealed how LGBTQ youth, themselves, described the role of the social environment in their NSSI behavior, while the quantitative phase was used to determine whether the qualitative findings could be used to predict engagement in NSSI among a larger sample of LGBTQ youth. The quantitative analyses found that certain social-environmental factors such as experiencing physical abuse at home, feeling unsafe at school, and greater openness about sexual orientation significantly predicted the likelihood of engaging in NSSI among LGBTQ youth. Furthermore, depression partially mediated the relationships between family physical abuse and NSSI and feeling unsafe at school and NSSI. The qualitative and quantitative results were compared in the interpretation phase to explore areas of convergence and incongruence. Overall, this study's findings indicate that social-environmental factors are salient to understanding NSSI among LGBTQ youth. The particular social contexts in which LGBTQ youth live significantly influence their engagement in this risk behavior. These findings can inform the development of culturally relevant NSSI interventions that address the social realities of LGBTQ youth's lives.