Influence of crude protein content, ingredient complexity, feed form, and duration of feeding of the phase I diets on productive performance and nutrient digestibility of Iberian pigs.

The influence of CP content and ingredient complexity, feed form, and duration of feeding of the Phase I diets on growth performance and total tract apparent digestibility -TTAD- of energy and nutrients was studied in Iberian pigs weaned at 28 d of age. There were 12 dietary treatments with 2 type of feeds -high-quality, HQ; and low-quality, LQ-, 2 feed forms -pellets vs. mash-, and 3 durations -7, 14, and 21 d- of supply of the Phase I diets.

Towards measuring the complexity of introducing semantics into a company

The Semantics Difficulty Model (SDM) is a model that measures the difficult of introducing semantics technology into a company. SDM manages three descriptions of stages, which we will refer to as ?snapshots?: a company semantic snapshot, data snapshot and semantic application snapshot. Understanding a priory the complexity of introducing semantics into a company is important because it allows the organization to take early decisions, thus saving time and money, mitigating risks and improving innovation, time to market and productivity. SDM works by measuring the distance between each initial snapshot and its reference models (the company semantic snapshots reference model, data snapshots reference model, and the semantic application snapshots reference model) with Euclidian distances. The difficulty level will be "not at all difficult" when the distance is small, and becomes "extremely difficult" when the the distance is large. SDM has been tested experimentally with 2000 simulated companies with arrangements and several initial stages. The output is measured by five linguistic values: "not at all difficult, slightly difficult, averagely difficult, very difficult and extremely difficult". As the preliminary results of our SDM simulation model indicate, transforming a search application into integrated data from different sources with semantics is a "slightly difficult", in contrast with data and opinion extraction applications for which it is "very difficult".

Grapheme-color synesthetes show peculiarities in their emotional brain: cortical and subcortical evidence from VBM analysis of 3D-T1 and DTI data

Grapheme-color synesthesia is a neurological phenomenon in which viewing achromatic letters/numbers leads to automatic and involuntary color experiences. In this study, voxel-based morphometry analyses were performed on T1 images and fractional anisotropy measures to examine the whole brain in associator grapheme-color synesthetes. These analyses provide new evidence of variations in emotional areas (both at the cortical and subcortical levels), findings that help understand the emotional component as a relevant aspect of the synesthetic experience. Additionally, this study replicates previous findings in the left intraparietal sulcus and, for the first time, reports the existence of anatomical differences in subcortical gray nuclei of developmental grapheme-color synesthetes, providing a link between acquired and developmental synesthesia. This empirical evidence, which goes beyond modality-specific areas, could lead to a better understanding of grapheme-color synesthesia as well as of other modalities of the phenomenon.

Estudio Multimodal de la Funcionalidad Cortical en ratones Transgénicos con Síndrome X Frágil y la modulación del dolor

El dolor es un síntoma frecuente en la práctica médica. En España, un estudio realizado en el año 2000 demostró que cada médico atiende un promedio de 181 pacientes con dolor por mes, la mayoría de ellos con dolor crónico moderado1. Del 7%-8% de la población europea está afectada y hasta el 5% puede ser grave2-3, se estima, que afecta a más de dos millones de españoles4. En la consulta de Atención Primaria, los pacientes con dolor neuropático tienen tasas de depresión mucho mayores 5-6-7. El dolor neuropático8 es el dolor causado por daño o enfermedad que afecta al sistema somato-sensorial, es un problema de salud pública con un alto coste laboral, debido a que existe cierto desconocimiento de sus singularidades, tanto de su diagnóstico como de su tratamiento, que al fallar, el dolor se perpetúa y se hace más rebelde a la hora de tratarlo, en la mayoría de las ocasiones pasa a ser crónico. Los mecanismos fisiopatológicos son evolutivos, se trata de un proceso progresivo e integrado que avanza si no recibe tratamiento, ocasionando graves repercusiones en la calidad de vida de los pacientes afectados9. De acuerdo a Prusiner (premio nobel de medicina 1997), en todas las enfermedades neurodegenerativas hay algún tipo de proceso anormal de la función neuronal. Las enfermedades neurodegenerativas son la consecuencia de anormalidades en el proceso de ciertas proteínas que intervienen en el ciclo celular, por lo tanto da lugar al cúmulo de las mismas en las neuronas o en sus proximidades, disminuyendo o anulando sus funciones, como la enfermedad de Alzheimer y el mismo SXF. La proteína FMRP (Fragile Mental Retardation Protein), esencial para el desarrollo cognitivo normal, ha sido relacionada con la vía piramidal del dolor10-11-12. El Síndrome de X Frágil13-14 (SXF), se debe a la mutación del Gen (FMR-1). Como consecuencia de la mutación, el gen se inactiva y no puede realizar la función de sintetizar la proteína FMRP. Por su incidencia se le considera la primera causa de Deficiencia Mental Hereditaria sólo superada por el Síndrome de Down. La electroencefalografía (EEG) es el registro de la actividad bioeléctrica cerebral que ha traído el desarrollo diario de los estudios clínicos y experimentales para el descubrimiento, diagnóstico y tratamiento de un gran número de anormalidades neurológicas y fisiológicas del cerebro y el resto del sistema nervioso central (SNC) incluyendo el dolor. El objetivo de la presente investigación es por medio de un estudio multimodal, desarrollar nuevas formas de presentación diagnóstica mediante técnicas avanzadas de procesado de señal y de imagen, determinando así los vínculos entre las evaluaciones cognitivas y su correlación anatómica con la modulación al dolor presente en patologías relacionadas con proteína FMRP. Utilizando técnicas biomédicas (funcionalestructural) para su caracterización. Para llevar a cabo esta tarea hemos utilizado el modelo animal de ratón. Nuestros resultados en este estudio multimodal demuestran que hay alteraciones en las vías de dolor en el modelo animal FMR1-KO, en concreto en la modulación encefálica (dolor neuropático), los datos se basan en los resultados del estudio estructural (imagen histología), funcional (EEG) y en pruebas de comportamiento (Laberinto de Barnes). En la Histología se muestra una clara asimetría estructural en el modelo FMR1 KO con respecto al control WT, donde el hemisferio Izquierdo tiene mayor densidad de masa neuronal en KO hembras 56.7%-60.8%, machos 58.3%-61%, en WT hembras 62.7%-62.4%, machos 55%-56.2%, hemisferio derecho-izquierdo respectivamente, esto refleja una correlación entre hemisferios muy baja en los sujetos KO (~50%) con respecto a los control WT (~90%). Se encontró correlación significativa entre las pruebas de memoria a largo plazo con respecto a la asimetría hemisférica (r = -0.48, corregido <0,05). En el estudio de comportamiento también hay diferencias, los sujetos WT tuvieron 22% un de rendimiento en la memoria a largo plazo, mientras que en los machos hay deterioro de memoria de un 28% que se corresponden con la patología en humanos. En los resultados de EEG estudiados en el hemisferio izquierdo, en el área de la corteza insular, encuentran que la latencia de la respuesta al potencial evocado es menor (22vs32 15vs96seg), la intensidad de la señal es mayor para los sujetos experimentales FMR1 KO frente a los sujetos control, esto es muy significativo dados los resultados en la histología (140vs129 145vs142 mv). Este estudio multimodal corrobora que las manifestaciones clínicas del SXF son variables dependientes de la edad y el sexo. Hemos podido corroborar en el modelo animal que en la etapa de adulto, los varones con SXF comienzan a desarrollar problemas en el desempeño de tareas que requieren la puesta en marcha de la función ejecutiva central de la memoria de trabajo (almacenamiento temporal). En el análisis del comportamiento es difícil llegar a una conclusión objetiva, se necesitan más estudios en diferentes etapas de la vida corroborados con resultados histológicos. Los avances logrados en los últimos años en su estudio han sido muy positivos, de tal modo que se están abriendo nuevas vías de investigación en un conjunto de procesos que representan un gran desafío a problemas médicos, asistenciales, sociales y económicos a los que se enfrentan los principales países desarrollados, con un aumento masivo de las expectativas de vida y de calidad. Las herramientas utilizadas en el campo de las neurociencias nos ofrecen grandes posibilidades para el desarrollo de estrategias que permitan ser utilizadas en el área de la educación, investigación y desarrollo. La genética determina la estructura del cerebro y nuestra investigación comprueba que la ausencia de FMRP también podría estar implicada en la modulación del dolor como parte de su expresión patológica siendo el modelo animal un punto importante en la investigación científica fundamental para entender el desarrollo de anormalidades en el cerebro. ABSTRACT Pain is a common symptom in medical practice. In Spain, a study conducted in 2000 each medical professional treats an average of 181 patients with pain per month, most of them with chronic moderate pain. 7% -8% of the European population is affected and up to 5% can be serious, it is estimated to affect more than two million people in Spain. In Primary Care, patients with neuropathic pain have much higher rates of depression. Neuropathic pain is caused by damage or disease affecting the somatosensory system, is a public health problem with high labor costs, there are relatively unfamiliar with the peculiarities in diagnosis and treatment, failing that, the pain is perpetuated and becomes rebellious to treat, in most cases becomes chronic. The pathophysiological mechanisms are evolutionary, its a progressive, if untreated, causing severe impact on the quality of life of affected patients. According to Prusiner (Nobel Prize for Medicine 1997), all neurodegenerative diseases there is some abnormal process of neuronal function. Neurodegenerative diseases are the result of abnormalities in the process of certain proteins involved in the cell cycle, reducing or canceling its features such as Alzheimer's disease and FXS. FMRP (Fragile Mental Retardation Protein), is essential for normal cognitive development, and has been linked to the pyramidal tract pain. Fragile X Syndrome (FXS), is due to mutation of the gene (FMR-1). As a consequence of the mutation, the gene is inactivated and can not perform the function of FMRP synthesize. For its incidence is considered the leading cause of Mental Deficiency Hereditary second only to Down Syndrome. Electroencephalography (EEG) is the recording of bioelectrical brain activity, is a advancement of clinical and experimental studies for the detection, diagnosis and treatment of many neurological and physiological abnormalities of the brain and the central nervous system, including pain. The objective of this research is a multimodal study, is the development of new forms of presentation using advanced diagnostic techniques of signal processing and image, to determine the links between cognitive evaluations and anatomic correlation with pain modulation to this protein FMRP-related pathologies. To accomplish this task have used the mouse model. Our results in this study show alterations in multimodal pain pathways in FMR1-KO in brain modulation (neuropathic pain), the data are based on the results of the structural study (histology image), functional (EEG) testing and behavior (Barnes maze). Histology In structural asymmetry shown in FMR1 KO model versus WT control, the left hemisphere is greater density of neuronal mass (KO females 56.7% -60.8%, 58.3% -61% males, females 62.7% -62.4 WT %, males 55% -56.2%), respectively right-left hemisphere, this reflects a very low correlation between hemispheres in KO (~ 50%) subjects compared to WT (~ 90%) control. Significant correlation was found between tests of long-term memory with respect to hemispheric asymmetry (r = -0.48, corrected <0.05). In the memory test there are differences too, the WT subjects had 22% yield in long-term memory, in males there memory impairment 28% corresponding to the condition in humans. The results of EEG studied in the left hemisphere, in insular cortex area, we found that the latency of the response evoked potential is lower (22vs32 15vs96seg), the signal strength is higher for the experimental subjects versus FMR1 KO control subjects, this is very significant given the results on histology (140vs129 145vs142 mv). This multimodal study confirms that the clinical manifestations of FXS are dependent variables of age and sex. We have been able to corroborate in the animal model in the adult stage, males with FXS begin developing problems in the performance of tasks that require the implementation of the central executive function of working memory (temporary storage). In behavior analysis is difficult to reach an objective conclusion, more studies are needed in different life stages corroborated with histologic findings. Advances in recent years were very positive, being opened new lines of research that represent a great challenge to physicians, health care, social and economic problems facing the major developed countries, with a massive increase in life expectancy and quality. The tools used in the field of neuroscience offer us great opportunities for the development of strategies to be used in the area of education, research and development. Genetics determines the structure of the brain and our research found that the absence of FMRP might also be involved in the modulation of pain as part of their pathological expression being an important animal model in basic scientific research to understand the development of abnormalities in brain.

Three-dimensional distribution of cortical synapses: a replicated point pattern-based analysis

The biggest problem when analyzing the brain is that its synaptic connections are extremely complex. Generally, the billions of neurons making up the brain exchange information through two types of highly specialized structures: chemical synapses (the vast majority) and so-called gap junctions (a substrate of one class of electrical synapse). Here we are interested in exploring the three-dimensional spatial distribution of chemical synapses in the cerebral cortex. Recent research has showed that the three-dimensional spatial distribution of synapses in layer III of the neocortex can be modeled by a random sequential adsorption (RSA) point process, i.e., synapses are distributed in space almost randomly, with the only constraint that they cannot overlap. In this study we hypothesize that RSA processes can also explain the distribution of synapses in all cortical layers. We also investigate whether there are differences in both the synaptic density and spatial distribution of synapses between layers. Using combined focused ion beam milling and scanning electron microscopy (FIB/SEM), we obtained three-dimensional samples from the six layers of the rat somatosensory cortex and identified and reconstructed the synaptic junctions. A total volume of tissue of approximately 4500μm3 and around 4000 synapses from three different animals were analyzed. Different samples, layers and/or animals were aggregated and compared using RSA replicated spatial point processes. The results showed no significant differences in the synaptic distribution across the different rats used in the study. We found that RSA processes described the spatial distribution of synapses in all samples of each layer. We also found that the synaptic distribution in layers II to VI conforms to a common underlying RSA process with different densities per layer. Interestingly, the results showed that synapses in layer I had a slightly different spatial distribution from the other layers.

Branching angles of pyramidal cell dendrites follow common geometrical design principles in different cortical areas

Unraveling pyramidal cell structure is crucial to understanding cortical circuit computations. Although it is well known that pyramidal cell branching structure differs in the various cortical areas, the principles that determine the geometric shapes of these cells are not fully understood. Here we analyzed and modeled with a von Mises distribution the branching angles in 3D reconstructed basal dendritic arbors of hundreds of intracellularly injected cortical pyramidal cells in seven different cortical regions of the frontal, parietal, and occipital cortex of the mouse. We found that, despite the differences in the structure of the pyramidal cells in these distinct functional and cytoarchitectonic cortical areas, there are common design principles that govern the geometry of dendritic branching angles of pyramidal cells in all cortical areas.

Non uniform embedding based on relevance analysis with reduced computational complexity: application to the detection of pathologies from biosignal recordings

Nonlinear analysis tools for studying and characterizing the dynamics of physiological signals have gained popularity, mainly because tracking sudden alterations of the inherent complexity of biological processes might be an indicator of altered physiological states. Typically, in order to perform an analysis with such tools, the physiological variables that describe the biological process under study are used to reconstruct the underlying dynamics of the biological processes. For that goal, a procedure called time-delay or uniform embedding is usually employed. Nonetheless, there is evidence of its inability for dealing with non-stationary signals, as those recorded from many physiological processes. To handle with such a drawback, this paper evaluates the utility of non-conventional time series reconstruction procedures based on non uniform embedding, applying them to automatic pattern recognition tasks. The paper compares a state of the art non uniform approach with a novel scheme which fuses embedding and feature selection at once, searching for better reconstructions of the dynamics of the system. Moreover, results are also compared with two classic uniform embedding techniques. Thus, the goal is comparing uniform and non uniform reconstruction techniques, including the one proposed in this work, for pattern recognition in biomedical signal processing tasks. Once the state space is reconstructed, the scheme followed characterizes with three classic nonlinear dynamic features (Largest Lyapunov Exponent, Correlation Dimension and Recurrence Period Density Entropy), while classification is carried out by means of a simple k-nn classifier. In order to test its generalization capabilities, the approach was tested with three different physiological databases (Speech Pathologies, Epilepsy and Heart Murmurs). In terms of the accuracy obtained to automatically detect the presence of pathologies, and for the three types of biosignals analyzed, the non uniform techniques used in this work lightly outperformed the results obtained using the uniform methods, suggesting their usefulness to characterize non-stationary biomedical signals in pattern recognition applications. On the other hand, in view of the results obtained and its low computational load, the proposed technique suggests its applicability for the applications under study.

Assessing the effects of complexity in cross-temporal transferability of species distribution modelling predictions using palaeobotanical data

Valoración de la transferencia temporal de los modelos de distribución de especies para su aplicación en nuestros días utilizando datos paleobotánicos Corilus avellana y Alnus glutinosa.

Complejidad Esencial: Un argumento por la complementariedad entre ciencia y sensibilidad = Essential Complexity: An argument for complementarity between science and sensibility

Esta investigación recoge un cúmulo de intereses en torno a un modo de generar arquitectura muy específico: La producción de objetos con una forma subyacente no apriorística. Los conocimientos expuestos se apoyan en condiciones del pensamiento reciente que impulsan la ilusión por alimentar la fuente creativa de la arquitectura con otros campos del saber. Los tiempos del conocimiento animista sensible y el conocimiento objetivo de carácter científico son correlativos en la historia pero casi nunca han sido sincrónicos. Representa asimismo un intento por aunar los dos tipos de conocimiento retomando la inercia que ya se presentía a comienzos del siglo XX. Se trata por tanto, de un ensayo sobre la posible anulación de la contraposición entre estos dos mundos para pasar a una complementariedad entre ambos en una sola visión conjunta compartida. Como meta final de esta investigación se presenta el desarrollo de un sistema crítico de análisis para los objetos arquitectónicos que permita una diferenciación entre aquellos que responden a los problemas de manera completa y sincera y aquellos otros que esconden, bajo una superficie consensuada, la falta de un método resolutivo de la complejidad en el presente creativo. La Investigación observa tres grupos de conocimiento diferenciados agrupados en sus capítulos correspondientes: El primer capítulo versa sobre el Impulso Creador. En él se define la necesidad de crear un marco para el individuo creador, aquel que independientemente de las fuerzas sociales del momento presiente que existe algo más allá que está sin resolver. Denominamos aquí “creador rebelde” a un tipo de personaje reconocible a lo largo de la Historia como aquel capaz de reconocer los cambios que ese operan en su presente y que utiliza para descubrir lo nuevo y acercarse algo al origen creativo. En el momento actual ese tipo de personaje es el que intuye o ya ha intuido hace tiempo la existencia de una complejidad creciente no obviable en el pensamiento de este tiempo. El segundo capítulo desarrolla algunas Propiedades de Sistemas de actuación creativa. En él se muestra una investigación que desarrolla un marco de conocimientos científicos muy específicos de nuestro tiempo que la arquitectura, de momento, no ha absorbido ni refleja de manera directa en su manera de crear. Son temas de presencia casi ya mundana en la sociedad pero que se resisten a ser incluidos en los procesos creativos como parte de la conciencia. La mayoría de ellos hablan de precisión, órdenes invisibles, propiedades de la materia o la energía tratados de manera objetiva y apolítica. La meta final supone el acercamiento e incorporación de estos conceptos y propiedades a nuestro mundo sensible unificándolos indisociablemente bajo un solo punto de vista. El último capítulo versa sobre la Complejidad y su capacidad de reducción a lo esencial. Aquí se muestran, a modo de conclusiones, la introducción de varios conceptos para el desarrollo de un sistema crítico hacia la arquitectura de nuestro tiempo. Entre ellos, el de Complejidad Esencial, definido como aquella de carácter inevitable a la hora de responder la arquitectura a los problemas y solicitaciones crecientes a los que se enfrenta en el presente. La Tesis mantiene la importancia de informar sobre la imposibilidad en el estado actual de las cosas de responder de manera sincera con soluciones de carácter simplista y la necesidad, por tanto, de soluciones necesarias de carácter complejo. En este sentido se define asimismo el concepto de Forma Subyacente como herramienta crítica para poder evaluar la respuesta de cada arquitectura y poder tener un sistema y visión crítica sobre lo que es un objeto consistente frente a la situación a la que se enfrenta. Dicha forma subyacente se define como aquella manera de entender conjuntamente y de manera sincrónica aquello que percibimos de manera sensible inseparable de las fuerzas ocultas, creativas, tecnológicas, materiales y energéticas que sustentan la definición y entendimiento de cualquier objeto construido. ABSTRACT This research includes a cluster of interests around a specific way to generate architecture: The production of objects without an a priori underlying form. The knowledge presented is based on current conditions of thought promoting the illusion to feed the creative source of architecture with other fields of knowledge. The sensible animist knowledge and objective scientific knowledge are correlative in history but have rarely been synchronous. This research is also an attempt to combine both types of knowledge to regain the inertia already sensed in the early twentieth century. It is therefore an essay on the annulment of the opposition between these two worlds to move towards complementarities of both in a single shared vision. The ultimate goal of this research is to present the development of a critical analysis system for architectural objects that allows differentiation between those who respond to the problems sincerely and those who hide under an agreed appearance, the lack of a method for solving the complexity of the creative present. The research observes three distinct groups of knowledge contained in their respective chapters: The first chapter deals with the Creative Impulse. In it is defined the need to create a framework for the creative individual who, regardless of the current social forces, forebodes that there is something hidden beyond which is still unresolved. We define the "rebel creator" as a kind of person existing throughout history who is able to recognize the changes operating in its present and use them to discover something new and get closer to the origin of creation. At present, this type of character is the one who intuits the existence of a non obviable increasing complexity in society and thought. The second chapter presents some systems, and their properties, for creative performance. It describes the development of a framework composed of current scientific knowledge that architecture has not yet absorbed or reflected directly in her procedures. These are issues of common presence in society but are still reluctant to be included in the creative processes even if they already belong to the collective consciousness. Most of them talk about accuracy, invisible orders, properties of matter and energy, always treated from an objective and apolitical perspective. The ultimate goal pursues the approach and incorporation of these concepts and properties to the sensible world, inextricably unifying all under a single point of view. The last chapter deals with complexity and the ability to reduce it to the essentials. Here we show, as a conclusion, the introduction of several concepts to develop a critical approach to analyzing the architecture of our time. Among them, the concept of Essential Complexity, defined as one that inevitably arises when architecture responds to the increasing stresses that faces today. The thesis maintains the importance of reporting, in the present state of things, the impossibility to respond openly with simplistic solutions and, therefore, the need for solutions to complex character. In this sense, the concept of Underlying Form is defined as a critical tool to evaluate the response of each architecture and possess a critical system to clarify what is an consistent object facing a certain situation. The underlying form is then defined as a way to synchronously understand what we perceive sensitively inseparable from the hidden forces of creative, technological, material and energetic character that support the definition and understanding of any constructed object.

Logarithmical hopping encoding: a low computational complexity algorithm for image compression

LHE (logarithmical hopping encoding) is a computationally efficient image compression algorithm that exploits the Weber–Fechner law to encode the error between colour component predictions and the actual value of such components. More concretely, for each pixel, luminance and chrominance predictions are calculated as a function of the surrounding pixels and then the error between the predictions and the actual values are logarithmically quantised. The main advantage of LHE is that although it is capable of achieving a low-bit rate encoding with high quality results in terms of peak signal-to-noise ratio (PSNR) and image quality metrics with full-reference (FSIM) and non-reference (blind/referenceless image spatial quality evaluator), its time complexity is O( n) and its memory complexity is O(1). Furthermore, an enhanced version of the algorithm is proposed, where the output codes provided by the logarithmical quantiser are used in a pre-processing stage to estimate the perceptual relevance of the image blocks. This allows the algorithm to downsample the blocks with low perceptual relevance, thus improving the compression rate. The performance of LHE is especially remarkable when the bit per pixel rate is low, showing much better quality, in terms of PSNR and FSIM, than JPEG and slightly lower quality than JPEG-2000 but being more computationally efficient.

Image processing methods for human brain connectivity analysis from in-vivo diffusion MRI

The structural connectivity of the brain is considered to encode species-wise and subject-wise patterns that will unlock large areas of understanding of the human brain. Currently, diffusion MRI of the living brain enables to map the microstructure of tissue, allowing to track the pathways of fiber bundles connecting the cortical regions across the brain. These bundles are summarized in a network representation called connectome that is analyzed using graph theory. The extraction of the connectome from diffusion MRI requires a large processing flow including image enhancement, reconstruction, segmentation, registration, diffusion tracking, etc. Although a concerted effort has been devoted to the definition of standard pipelines for the connectome extraction, it is still crucial to define quality assessment protocols of these workflows. The definition of quality control protocols is hindered by the complexity of the pipelines under test and the absolute lack of gold-standards for diffusion MRI data. Here we characterize the impact on structural connectivity workflows of the geometrical deformation typically shown by diffusion MRI data due to the inhomogeneity of magnetic susceptibility across the imaged object. We propose an evaluation framework to compare the existing methodologies to correct for these artifacts including whole-brain realistic phantoms. Additionally, we design and implement an image segmentation and registration method to avoid performing the correction task and to enable processing in the native space of diffusion data. We release PySDCev, an evaluation framework for the quality control of connectivity pipelines, specialized in the study of susceptibility-derived distortions. In this context, we propose Diffantom, a whole-brain phantom that provides a solution to the lack of gold-standard data. The three correction methodologies under comparison performed reasonably, and it is difficult to determine which method is more advisable. We demonstrate that susceptibility-derived correction is necessary to increase the sensitivity of connectivity pipelines, at the cost of specificity. Finally, with the registration and segmentation tool called regseg we demonstrate how the problem of susceptibility-derived distortion can be overcome allowing data to be used in their original coordinates. This is crucial to increase the sensitivity of the whole pipeline without any loss in specificity.

Análisis de la actividad neuronal y cerebral mediante técnicas de redes complejas

El cerebro humano es probablemente uno de los sistemas más complejos a los que nos enfrentamos en la actualidad, si bien es también uno de los más fascinantes. Sin embargo, la compresión de cómo el cerebro organiza su actividad para llevar a cabo tareas complejas es un problema plagado de restos y obstáculos. En sus inicios la neuroimagen y la electrofisiología tenían como objetivo la identificación de regiones asociadas a activaciones relacionadas con tareas especificas, o con patrones locales que variaban en el tiempo dada cierta actividad. Sin embargo, actualmente existe un consenso acerca de que la actividad cerebral tiene un carácter temporal multiescala y espacialmente extendido, lo que lleva a considerar el cerebro como una gran red de áreas cerebrales coordinadas, cuyas conexiones funcionales son continuamente creadas y destruidas. Hasta hace poco, el énfasis de los estudios de la actividad cerebral funcional se han centrado en la identidad de los nodos particulares que forman estas redes, y en la caracterización de métricas de conectividad entre ellos: la hipótesis subyacente es que cada nodo, que es una representación mas bien aproximada de una región cerebral dada, ofrece a una única contribución al total de la red. Por tanto, la neuroimagen funcional integra los dos ingredientes básicos de la neuropsicología: la localización de la función cognitiva en módulos cerebrales especializados y el rol de las fibras de conexión en la integración de dichos módulos. Sin embargo, recientemente, la estructura y la función cerebral han empezado a ser investigadas mediante la Ciencia de la Redes, una interpretación mecánico-estadística de una antigua rama de las matemáticas: La teoría de grafos. La Ciencia de las Redes permite dotar a las redes funcionales de una gran cantidad de propiedades cuantitativas (robustez, centralidad, eficiencia, ...), y así enriquecer el conjunto de elementos que describen objetivamente la estructura y la función cerebral a disposición de los neurocientíficos. La conexión entre la Ciencia de las Redes y la Neurociencia ha aportado nuevos puntos de vista en la comprensión de la intrincada anatomía del cerebro, y de cómo las patrones de actividad cerebral se pueden sincronizar para generar las denominadas redes funcionales cerebrales, el principal objeto de estudio de esta Tesis Doctoral. Dentro de este contexto, la complejidad emerge como el puente entre las propiedades topológicas y dinámicas de los sistemas biológicos y, específicamente, en la relación entre la organización y la dinámica de las redes funcionales cerebrales. Esta Tesis Doctoral es, en términos generales, un estudio de cómo la actividad cerebral puede ser entendida como el resultado de una red de un sistema dinámico íntimamente relacionado con los procesos que ocurren en el cerebro. Con este fin, he realizado cinco estudios que tienen en cuenta ambos aspectos de dichas redes funcionales: el topológico y el dinámico. De esta manera, la Tesis está dividida en tres grandes partes: Introducción, Resultados y Discusión. En la primera parte, que comprende los Capítulos 1, 2 y 3, se hace un resumen de los conceptos más importantes de la Ciencia de las Redes relacionados al análisis de imágenes cerebrales. Concretamente, el Capitulo 1 está dedicado a introducir al lector en el mundo de la complejidad, en especial, a la complejidad topológica y dinámica de sistemas acoplados en red. El Capítulo 2 tiene como objetivo desarrollar los fundamentos biológicos, estructurales y funcionales del cerebro, cuando éste es interpretado como una red compleja. En el Capítulo 3, se resumen los objetivos esenciales y tareas que serán desarrolladas a lo largo de la segunda parte de la Tesis. La segunda parte es el núcleo de la Tesis, ya que contiene los resultados obtenidos a lo largo de los últimos cuatro años. Esta parte está dividida en cinco Capítulos, que contienen una versión detallada de las publicaciones llevadas a cabo durante esta Tesis. El Capítulo 4 está relacionado con la topología de las redes funcionales y, específicamente, con la detección y cuantificación de los nodos mas importantes: aquellos denominados “hubs” de la red. En el Capítulo 5 se muestra como las redes funcionales cerebrales pueden ser vistas no como una única red, sino más bien como una red-de-redes donde sus componentes tienen que coexistir en una situación de balance funcional. De esta forma, se investiga cómo los hemisferios cerebrales compiten para adquirir centralidad en la red-de-redes, y cómo esta interacción se mantiene (o no) cuando se introducen fallos deliberadamente en la red funcional. El Capítulo 6 va un paso mas allá al considerar las redes funcionales como sistemas vivos. En este Capítulo se muestra cómo al analizar la evolución de la topología de las redes, en vez de tratarlas como si estas fueran un sistema estático, podemos caracterizar mejor su estructura. Este hecho es especialmente relevante cuando se quiere tratar de encontrar diferencias entre grupos que desempeñan una tarea de memoria, en la que las redes funcionales tienen fuertes fluctuaciones. En el Capítulo 7 defino cómo crear redes parenclíticas a partir de bases de datos de actividad cerebral. Este nuevo tipo de redes, recientemente introducido para estudiar las anormalidades entre grupos de control y grupos anómalos, no ha sido implementado nunca en datos cerebrales y, en este Capítulo explico cómo hacerlo cuando se quiere evaluar la consistencia de la dinámica cerebral. Para concluir esta parte de la Tesis, el Capítulo 8 se centra en la relación entre las propiedades topológicas de los nodos dentro de una red y sus características dinámicas. Como mostraré más adelante, existe una relación entre ellas que revela que la posición de un nodo dentro una red está íntimamente correlacionada con sus propiedades dinámicas. Finalmente, la última parte de esta Tesis Doctoral está compuesta únicamente por el Capítulo 9, el cual contiene las conclusiones y perspectivas futuras que pueden surgir de los trabajos expuestos. En vista de todo lo anterior, espero que esta Tesis aporte una perspectiva complementaria sobre uno de los más extraordinarios sistemas complejos frente a los que nos encontramos: El cerebro humano. ABSTRACT The human brain is probably one of the most complex systems we are facing, thus being a timely and fascinating object of study. Characterizing how the brain organizes its activity to carry out complex tasks is highly non-trivial. While early neuroimaging and electrophysiological studies typically aimed at identifying patches of task-specific activations or local time-varying patterns of activity, there has now been consensus that task-related brain activity has a temporally multiscale, spatially extended character, as networks of coordinated brain areas are continuously formed and destroyed. Up until recently, though, the emphasis of functional brain activity studies has been on the identity of the particular nodes forming these networks, and on the characterization of connectivity metrics between them, the underlying covert hypothesis being that each node, constituting a coarse-grained representation of a given brain region, provides a unique contribution to the whole. Thus, functional neuroimaging initially integrated the two basic ingredients of early neuropsychology: localization of cognitive function into specialized brain modules and the role of connection fibres in the integration of various modules. Lately, brain structure and function have started being investigated using Network Science, a statistical mechanics understanding of an old branch of pure mathematics: graph theory. Network Science allows endowing networks with a great number of quantitative properties, thus vastly enriching the set of objective descriptors of brain structure and function at neuroscientists’ disposal. The link between Network Science and Neuroscience has shed light about how the entangled anatomy of the brain is, and how cortical activations may synchronize to generate the so-called functional brain networks, the principal object under study along this PhD Thesis. Within this context, complexity appears to be the bridge between the topological and dynamical properties of biological systems and, more specifically, the interplay between the organization and dynamics of functional brain networks. This PhD Thesis is, in general terms, a study of how cortical activations can be understood as the output of a network of dynamical systems that are intimately related with the processes occurring in the brain. In order to do that, I performed five studies that encompass both the topological and the dynamical aspects of such functional brain networks. In this way, the Thesis is divided into three major parts: Introduction, Results and Discussion. In the first part, comprising Chapters 1, 2 and 3, I make an overview of the main concepts of Network Science related to the analysis of brain imaging. More specifically, Chapter 1 is devoted to introducing the reader to the world of complexity, specially to the topological and dynamical complexity of networked systems. Chapter 2 aims to develop the biological, topological and functional fundamentals of the brain when it is seen as a complex network. Next, Chapter 3 summarizes the main objectives and tasks that will be developed along the forthcoming Chapters. The second part of the Thesis is, in turn, its core, since it contains the results obtained along these last four years. This part is divided into five Chapters, containing a detailed version of the publications carried out during the Thesis. Chapter 4 is related to the topology of functional networks and, more specifically, to the detection and quantification of the leading nodes of the network: the hubs. In Chapter 5 I will show that functional brain networks can be viewed not as a single network, but as a network-of-networks, where its components have to co-exist in a trade-off situation. In this way, I investigate how the brain hemispheres compete for acquiring the centrality of the network-of-networks and how this interplay is maintained (or not) when failures are introduced in the functional network. Chapter 6 goes one step beyond by considering functional networks as living systems. In this Chapter I show how analyzing the evolution of the network topology instead of treating it as a static system allows to better characterize functional networks. This fact is especially relevant when trying to find differences between groups performing certain memory tasks, where functional networks have strong fluctuations. In Chapter 7 I define how to create parenclitic networks from brain imaging datasets. This new kind of networks, recently introduced to study abnormalities between control and anomalous groups, have not been implemented with brain datasets and I explain in this Chapter how to do it when evaluating the consistency of brain dynamics. To conclude with this part of the Thesis, Chapter 8 is devoted to the interplay between the topological properties of the nodes within a network and their dynamical features. As I will show, there is an interplay between them which reveals that the position of a node in a network is intimately related with its dynamical properties. Finally, the last part of this PhD Thesis is composed only by Chapter 9, which contains the conclusions and future perspectives that may arise from the exposed results. In view of all, I hope that reading this Thesis will give a complementary perspective of one of the most extraordinary complex systems: The human brain.

Analysing the complexity of the model-based decision making processes within the industrial management context

PURPOSE The decision-making process plays a key role in organizations. Every decision-making process produces a final choice that may or may not prompt action. Recurrently, decision makers find themselves in the dichotomous question of following a traditional sequence decision-making process where the output of a decision is used as the input of the next stage of the decision, or following a joint decision-making approach where several decisions are taken simultaneously. The implication of the decision-making process will impact different players of the organization. The choice of the decision- making approach becomes difficult to find, even with the current literature and practitioners’ knowledge. The pursuit of better ways for making decisions has been a common goal for academics and practitioners. Management scientists use different techniques and approaches to improve different types of decisions. The purpose of this decision is to use the available resources as well as possible (data and techniques) to achieve the objectives of the organization. The developing and applying of models and concepts may be helpful to solve managerial problems faced every day in different companies. As a result of this research different decision models are presented to contribute to the body of knowledge of management science. The first models are focused on the manufacturing industry and the second part of the models on the health care industry. Despite these models being case specific, they serve the purpose of exemplifying that different approaches to the problems and could provide interesting results. Unfortunately, there is no universal recipe that could be applied to all the problems. Furthermore, the same model could deliver good results with certain data and bad results for other data. A framework to analyse the data before selecting the model to be used is presented and tested in the models developed to exemplify the ideas. METHODOLOGY As the first step of the research a systematic literature review on the joint decision is presented, as are the different opinions and suggestions of different scholars. For the next stage of the thesis, the decision-making process of more than 50 companies was analysed in companies from different sectors in the production planning area at the Job Shop level. The data was obtained using surveys and face-to-face interviews. The following part of the research into the decision-making process was held in two application fields that are highly relevant for our society; manufacturing and health care. The first step was to study the interactions and develop a mathematical model for the replenishment of the car assembly where the problem of “Vehicle routing problem and Inventory” were combined. The next step was to add the scheduling or car production (car sequencing) decision and use some metaheuristics such as ant colony and genetic algorithms to measure if the behaviour is kept up with different case size problems. A similar approach is presented in a production of semiconductors and aviation parts, where a hoist has to change from one station to another to deal with the work, and a jobs schedule has to be done. However, for this problem simulation was used for experimentation. In parallel, the scheduling of operating rooms was studied. Surgeries were allocated to surgeons and the scheduling of operating rooms was analysed. The first part of the research was done in a Teaching hospital, and for the second part the interaction of uncertainty was added. Once the previous problem had been analysed a general framework to characterize the instance was built. In the final chapter a general conclusion is presented. FINDINGS AND PRACTICAL IMPLICATIONS The first part of the contributions is an update of the decision-making literature review. Also an analysis of the possible savings resulting from a change in the decision process is made. Then, the results of the survey, which present a lack of consistency between what the managers believe and the reality of the integration of their decisions. In the next stage of the thesis, a contribution to the body of knowledge of the operation research, with the joint solution of the replenishment, sequencing and inventory problem in the assembly line is made, together with a parallel work with the operating rooms scheduling where different solutions approaches are presented. In addition to the contribution of the solving methods, with the use of different techniques, the main contribution is the framework that is proposed to pre-evaluate the problem before thinking of the techniques to solve it. However, there is no straightforward answer as to whether it is better to have joint or sequential solutions. Following the proposed framework with the evaluation of factors such as the flexibility of the answer, the number of actors, and the tightness of the data, give us important hints as to the most suitable direction to take to tackle the problem. RESEARCH LIMITATIONS AND AVENUES FOR FUTURE RESEARCH In the first part of the work it was really complicated to calculate the possible savings of different projects, since in many papers these quantities are not reported or the impact is based on non-quantifiable benefits. The other issue is the confidentiality of many projects where the data cannot be presented. For the car assembly line problem more computational power would allow us to solve bigger instances. For the operation research problem there was a lack of historical data to perform a parallel analysis in the teaching hospital. In order to keep testing the decision framework it is necessary to keep applying more case studies in order to generalize the results and make them more evident and less ambiguous. The health care field offers great opportunities since despite the recent awareness of the need to improve the decision-making process there are many opportunities to improve. Another big difference with the automotive industry is that the last improvements are not spread among all the actors. Therefore, in the future this research will focus more on the collaboration between academia and the health care sector.

Intermittent pluri-sink model and the emergence of complex heterogeneity patterns: a simple paradigm for explaining complexity in soil chemical distributions

The spatial complexity of the distribution of organic matter, chemicals, nutrients, pollutants has been demonstrated to have multifractal nature (Kravchenco et al. [1]). This fact supports the possibility of existence of some emergent heterogeneity structure built under the evolution of the system. The aim of this note is providing a consistent explanation to the mentioned results via an extremely simple model.

Horizontal gene transfer among genomes: The complexity hypothesis

Increasingly, studies of genes and genomes are indicating that considerable horizontal transfer has occurred between prokaryotes. Extensive horizontal transfer has occurred for operational genes (those involved in housekeeping), whereas informational genes (those involved in transcription, translation, and related processes) are seldomly horizontally transferred. Through phylogenetic analysis of six complete prokaryotic genomes and the identification of 312 sets of orthologous genes present in all six genomes, we tested two theories describing the temporal flow of horizontal transfer. We show that operational genes have been horizontally transferred continuously since the divergence of the prokaryotes, rather than having been exchanged in one, or a few, massive events that occurred early in the evolution of prokaryotes. In agreement with earlier studies, we found that differences in rates of evolution between operational and informational genes are minimal, suggesting that factors other than rate of evolution are responsible for the observed differences in horizontal transfer. We propose that a major factor in the more frequent horizontal transfer of operational genes is that informational genes are typically members of large, complex systems, whereas operational genes are not, thereby making horizontal transfer of informational gene products less probable (the complexity hypothesis).