Analysis of spontaneous MEG activity in mild cognitive impairment and Alzheimer's disease using spectral entropies and statistical complexity measures

Alzheimer's disease (AD) is the most common cause of dementia. Over the last few years, a considerable effort has been devoted to exploring new biomarkers. Nevertheless, a better understanding of brain dynamics is still required to optimize therapeutic strategies. In this regard, the characterization of mild cognitive impairment (MCI) is crucial, due to the high conversion rate from MCI to AD. However, only a few studies have focused on the analysis of magnetoencephalographic (MEG) rhythms to characterize AD and MCI. In this study, we assess the ability of several parameters derived from information theory to describe spontaneous MEG activity from 36 AD patients, 18 MCI subjects and 26 controls. Three entropies (Shannon, Tsallis and Rényi entropies), one disequilibrium measure (based on Euclidean distance ED) and three statistical complexities (based on Lopez Ruiz–Mancini–Calbet complexity LMC) were used to estimate the irregularity and statistical complexity of MEG activity. Statistically significant differences between AD patients and controls were obtained with all parameters (p < 0.01). In addition, statistically significant differences between MCI subjects and controls were achieved by ED and LMC (p < 0.05). In order to assess the diagnostic ability of the parameters, a linear discriminant analysis with a leave-one-out cross-validation procedure was applied. The accuracies reached 83.9% and 65.9% to discriminate AD and MCI subjects from controls, respectively. Our findings suggest that MCI subjects exhibit an intermediate pattern of abnormalities between normal aging and AD. Furthermore, the proposed parameters provide a new description of brain dynamics in AD and MCI.

Modelos de métrica para sistemas electrónicos de adquisición de datos y de procesamiento para investigación clínica con dispositivos cardiacos implantables

RESUMEN Las enfermedades cardiovasculares constituyen en la actualidad la principal causa de mortalidad en el mundo y se prevé que sigan siéndolo en un futuro, generando además elevados costes para los sistemas de salud. Los dispositivos cardiacos implantables constituyen una de las opciones para el diagnóstico y el tratamiento de las alteraciones del ritmo cardiaco. La investigación clínica con estos dispositivos alcanza gran relevancia para combatir estas enfermedades que tanto afectan a nuestra sociedad. Tanto la industria farmacéutica y de tecnología médica, como los propios investigadores, cada día se ven involucrados en un mayor número de proyectos de investigación clínica. No sólo el incremento en su volumen, sino el aumento de la complejidad, están generando mayores gastos en las actividades asociadas a la investigación médica. Esto está conduciendo a las compañías del sector sanitario a estudiar nuevas soluciones que les permitan reducir los costes de los estudios clínicos. Las Tecnologías de la Información y las Comunicaciones han facilitado la investigación clínica, especialmente en la última década. Los sistemas y aplicaciones electrónicos han proporcionado nuevas posibilidades en la adquisición, procesamiento y análisis de los datos. Por otro lado, la tecnología web propició la aparición de los primeros sistemas electrónicos de adquisición de datos, que han ido evolucionando a lo largo de los últimos años. Sin embargo, la mejora y perfeccionamiento de estos sistemas sigue siendo crucial para el progreso de la investigación clínica. En otro orden de cosas, la forma tradicional de realizar los estudios clínicos con dispositivos cardiacos implantables precisaba mejorar el tratamiento de los datos almacenados por estos dispositivos, así como para su fusión con los datos clínicos recopilados por investigadores y pacientes. La justificación de este trabajo de investigación se basa en la necesidad de mejorar la eficiencia en la investigación clínica con dispositivos cardiacos implantables, mediante la reducción de costes y tiempos de desarrollo de los proyectos, y el incremento de la calidad de los datos recopilados y el diseño de soluciones que permitan obtener un mayor rendimiento de los datos mediante la fusión de datos de distintas fuentes o estudios. Con este fin se proponen como objetivos específicos de este proyecto de investigación dos nuevos modelos: - Un modelo de recuperación y procesamiento de datos para los estudios clínicos con dispositivos cardiacos implantables, que permita estructurar y estandarizar estos procedimientos, con el fin de reducir tiempos de desarrollo Modelos de Métrica para Sistemas Electrónicos de Adquisición de Datos y de Procesamiento para Investigación Clínica con Dispositivos Cardiacos Implantables de estas tareas, mejorar la calidad del resultado obtenido, disminuyendo en consecuencia los costes. - Un modelo de métrica integrado en un Sistema Electrónico de Adquisición de Datos (EDC) que permita analizar los resultados del proyecto de investigación y, particularmente del rendimiento obtenido del EDC, con el fin de perfeccionar estos sistemas y reducir tiempos y costes de desarrollo del proyecto y mejorar la calidad de los datos clínicos recopilados. Como resultado de esta investigación, el modelo de procesamiento propuesto ha permitido reducir el tiempo medio de procesamiento de los datos en más de un 90%, los costes derivados del mismo en más de un 85% y todo ello, gracias a la automatización de la extracción y almacenamiento de los datos, consiguiendo una mejora de la calidad de los mismos. Por otro lado, el modelo de métrica posibilita el análisis descriptivo detallado de distintos indicadores que caracterizan el rendimiento del proyecto de investigación clínica, haciendo factible además la comparación entre distintos estudios. La conclusión de esta tesis doctoral es que los resultados obtenidos han demostrado que la utilización en estudios clínicos reales de los dos modelos desarrollados ha conducido a una mejora en la eficiencia de los proyectos, reduciendo los costes globales de los mismos, disminuyendo los tiempos de ejecución, e incrementando la calidad de los datos recopilados. Las principales aportaciones de este trabajo de investigación al conocimiento científico son la implementación de un sistema de procesamiento inteligente de los datos almacenados por los dispositivos cardiacos implantables, la integración en el mismo de una base de datos global y optimizada para todos los modelos de dispositivos, la generación automatizada de un repositorio unificado de datos clínicos y datos de dispositivos cardiacos implantables, y el diseño de una métrica aplicada e integrable en los sistemas electrónicos de adquisición de datos para el análisis de resultados de rendimiento de los proyectos de investigación clínica. ABSTRACT Cardiovascular diseases are the main cause of death worldwide and it is expected to continue in the future, generating high costs for health care systems. Implantable cardiac devices have become one of the options for diagnosis and treatment of cardiac rhythm disorders. Clinical research with these devices has acquired great importance to fight against these diseases that affect so many people in our society. Both pharmaceutical and medical technology companies, and also investigators, are involved in an increasingly number of clinical research projects. The growth in volume and the increase in medical research complexity are contributing to raise the expenditure level associated with clinical investigation. This situation is driving health care sector companies to explore new solutions to reduce clinical trial costs. Information and Communication Technologies have facilitated clinical research, mainly in the last decade. Electronic systems and software applications have provided new possibilities in the acquisition, processing and analysis of clinical studies data. On the other hand, web technology contributed to the appearance of the first electronic data capture systems that have evolved during the last years. Nevertheless, improvement of these systems is still a key aspect for the progress of clinical research. On a different matter, the traditional way to develop clinical studies with implantable cardiac devices needed an improvement in the processing of the data stored by these devices, and also in the merging of these data with the data collected by investigators and patients. The rationale of this research is based on the need to improve the efficiency in clinical investigation with implantable cardiac devices, by means of reduction in costs and time of projects development, as well as improvement in the quality of information obtained from the studies and to obtain better performance of data through the merging of data from different sources or trials. The objective of this research project is to develop the next two models: • A model for the retrieval and processing of data for clinical studies with implantable cardiac devices, enabling structure and standardization of these procedures, in order to reduce the time of development of these tasks, to improve the quality of the results, diminish therefore costs. • A model of metric integrated in an Electronic Data Capture system (EDC) that allow to analyze the results of the research project, and particularly the EDC performance, in order to improve those systems and to reduce time and costs of the project, and to get a better quality of the collected clinical data. As a result of this work, the proposed processing model has led to a reduction of the average time for data processing by more than 90 per cent, of related costs by more than 85 per cent, and all of this, through automatic data retrieval and storage, achieving an improvement of quality of data. On the other hand, the model of metrics makes possible a detailed descriptive analysis of a set of indicators that characterize the performance of each research project, allowing inter‐studies comparison. This doctoral thesis results have demonstrated that the application of the two developed models in real clinical trials has led to an improvement in projects efficiency, reducing global costs, diminishing time in execution, and increasing quality of data collected. The main contributions to scientific knowledge of this research work are the implementation of an intelligent processing system for data stored by implantable cardiac devices, the integration in this system of a global and optimized database for all models of devices, the automatic creation of an unified repository of clinical data and data stored by medical devices, and the design of a metric to be applied and integrated in electronic data capture systems to analyze the performance results of clinical research projects.

Facing informatics via three level complexity views

In informatics there is one kind of complexity that is perceived by everyone. It is the complexity of a concrete, isolated object, normally situated completely within one of the branches universally recognized by the scientific and technical community. Examples of this are the complexity of integrated electronic circuits, the complexity of lgorithms and the complexity of software. The first complexity deals with the number of circuit components, the second with computation time and the third with the number of necessary mental discriminations. In arder to illustrate my point, I will take up the last complexity, which, m o reo ver, is the least well-known.

Towards a conceptual remodeling of information technologies based on a broad consideration of complexity

Actas.

Proposal of a three level complexity model for office automation

Office automation is one of the fields where the complexity related with technologies and working environments can be best shown. This is the starting point we have chosen to build up a theoretical model that shows us a scene quite different from the one traditionally considered. Through the development of the model, the levels of complexity associated with office automation and office environments have been identified, establishing a relationship between them. Thus, the model allows to state a general principle for sociotechnical design of office automation systems, comprising the ontological distinctions needed to properly evaluate each particular technology and its virtual contribution to office automation. From this fact comes the model's taxonomic ability to draw a global perspective of the state-of-art in office automation technologies.

Efficient algorithms for dynamic probabilistic safety assessment. An application to convex damage domain.

The design of nuclear power plant has to follow a number of regulations aimed at limiting the risks inherent in this type of installation. The goal is to prevent and to limit the consequences of any possible incident that might threaten the public or the environment. To verify that the safety requirements are met a safety assessment process is followed. Safety analysis is as key component of a safety assessment, which incorporates both probabilistic and deterministic approaches. The deterministic approach attempts to ensure that the various situations, and in particular accidents, that are considered to be plausible, have been taken into account, and that the monitoring systems and engineered safety and safeguard systems will be capable of ensuring the safety goals. On the other hand, probabilistic safety analysis tries to demonstrate that the safety requirements are met for potential accidents both within and beyond the design basis, thus identifying vulnerabilities not necessarily accessible through deterministic safety analysis alone. Probabilistic safety assessment (PSA) methodology is widely used in the nuclear industry and is especially effective in comprehensive assessment of the measures needed to prevent accidents with small probability but severe consequences. Still, the trend towards a risk informed regulation (RIR) demanded a more extended use of risk assessment techniques with a significant need to further extend PSA’s scope and quality. Here is where the theory of stimulated dynamics (TSD) intervenes, as it is the mathematical foundation of the integrated safety assessment (ISA) methodology developed by the CSN(Consejo de Seguridad Nuclear) branch of Modelling and Simulation (MOSI). Such methodology attempts to extend classical PSA including accident dynamic analysis, an assessment of the damage associated to the transients and a computation of the damage frequency. The application of this ISA methodology requires a computational framework called SCAIS (Simulation Code System for Integrated Safety Assessment). SCAIS provides accident dynamic analysis support through simulation of nuclear accident sequences and operating procedures. Furthermore, it includes probabilistic quantification of fault trees and sequences; and integration and statistic treatment of risk metrics. SCAIS comprehensively implies an intensive use of code coupling techniques to join typical thermal hydraulic analysis, severe accident and probability calculation codes. The integration of accident simulation in the risk assessment process and thus requiring the use of complex nuclear plant models is what makes it so powerful, yet at the cost of an enormous increase in complexity. As the complexity of the process is primarily focused on such accident simulation codes, the question of whether it is possible to reduce the number of required simulation arises, which will be the focus of the present work. This document presents the work done on the investigation of more efficient techniques applied to the process of risk assessment inside the mentioned ISA methodology. Therefore such techniques will have the primary goal of decreasing the number of simulation needed for an adequate estimation of the damage probability. As the methodology and tools are relatively recent, there is not much work done inside this line of investigation, making it a quite difficult but necessary task, and because of time limitations the scope of the work had to be reduced. Therefore, some assumptions were made to work in simplified scenarios best suited for an initial approximation to the problem. The following section tries to explain in detail the process followed to design and test the developed techniques. Then, the next section introduces the general concepts and formulae of the TSD theory which are at the core of the risk assessment process. Afterwards a description of the simulation framework requirements and design is given. Followed by an introduction to the developed techniques, giving full detail of its mathematical background and its procedures. Later, the test case used is described and result from the application of the techniques is shown. Finally the conclusions are presented and future lines of work are exposed.

A Complexity Architecture for Information Technologies: a Three-Year Didactic Experiment

One medium-term strategy for helping in the management of complexity is the introduction of a conceptual complexity component in the very centre of university curricula. In very few areas is the growth of complexity as evident as in the information technologies (ITs), the focus of the work presented in the current paper. We have therefore developed an integrated way of tackling the specific field of information technologies by means of an approach,to complexity. The content of this paper describes the guidelines of our research effort, placing an emphasis on informatics. Concepts of complexity based on the system metaphor have been substantially drawn upon in this exercise and are thus presented in some detail. Also described is a didactic experiment conducted by the author and designed to provide a new and integrating approach to University curricula for future professionals. The students' "discovery" of complexity is the focal point of the experiment. The findings of this effort are encouraging and call for the continuation and expansion of this experiment.

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".

Performance metrics for small-signal stability assessment of DC-distributed power-system-architecture comparisons

The objective of this paper is to provide performance metrics for small-signal stability assessment of a given system architecture. The stability margins are stated utilizing a concept of maximum peak criteria (MPC) derived from the behavior of an impedance-based sensitivity function. For each minor-loop gain defined at every system interface, a single number to state the robustness of stability is provided based on the computed maximum value of the corresponding sensitivity function. In order to compare various power-architecture solutions in terms of stability, a parameter providing an overall measure of the whole system stability is required. The selected figure of merit is geometric average of each maximum peak value within the system. It provides a meaningful metrics for system comparisons: the best system in terms of robust stability is the one that minimizes this index. In addition, the largest peak value within the system interfaces is given thus detecting the weakest point of the system in terms of robustness.

A 3D multi-objective optimization planning algorithm for wireless sensor networks

The complexity of planning a wireless sensor network is dependent on the aspects of optimization and on the application requirements. Even though Murphy's Law is applied everywhere in reality, a good planning algorithm will assist the designers to be aware of the short plates of their design and to improve them before the problems being exposed at the real deployment. A 3D multi-objective planning algorithm is proposed in this paper to provide solutions on the locations of nodes and their properties. It employs a developed ray-tracing scheme for sensing signal and radio propagation modelling. Therefore it is sensitive to the obstacles and makes the models of sensing coverage and link quality more practical compared with other heuristics that use ideal unit-disk models. The proposed algorithm aims at reaching an overall optimization on hardware cost, coverage, link quality and lifetime. Thus each of those metrics are modelled and normalized to compose a desirability function. Evolutionary algorithm is designed to efficiently tackle this NP-hard multi-objective optimization problem. The proposed algorithm is applicable for both indoor and outdoor 3D scenarios. Different parameters that affect the performance are analyzed through extensive experiments; two state-of-the-art algorithms are rebuilt and tested with the same configuration as that of the proposed algorithm. The results indicate that the proposed algorithm converges efficiently within 600 iterations and performs better than the compared heuristics.

A Schwarz lemma for Kahler affine metrics and the canonical potential of a proper convex cone

This is an account of some aspects of the geometry of Kahler affine metrics based on considering them as smooth metric measure spaces and applying the comparison geometry of Bakry-Emery Ricci tensors. Such techniques yield a version for Kahler affine metrics of Yau s Schwarz lemma for volume forms. By a theorem of Cheng and Yau, there is a canonical Kahler affine Einstein metric on a proper convex domain, and the Schwarz lemma gives a direct proof of its uniqueness up to homothety. The potential for this metric is a function canonically associated to the cone, characterized by the property that its level sets are hyperbolic affine spheres foliating the cone. It is shown that for an n -dimensional cone, a rescaling of the canonical potential is an n -normal barrier function in the sense of interior point methods for conic programming. It is explained also how to construct from the canonical potential Monge-Ampère metrics of both Riemannian and Lorentzian signatures, and a mean curvature zero conical Lagrangian submanifold of the flat para-Kahler space.

Objective metrics for functional evaluation of upper limb during the ADL of drinking: application in SCI

Three-dimensional kinematic analysis provides quantitative assessment of upper limb motion and is used as an outcome measure to evaluate movement disorders. The aim of the present study is to present a set of kinematic metrics for quantifying characteristics of movement performance and the functional status of the subject during the execution of the activity of daily living (ADL) of drinking from a glass. Then, the objective is to apply these metrics in healthy people and a population with cervical spinal cord injury (SCI), and to analyze the metrics ability to discriminate between healthy and pathologic people. 19 people participated in the study: 7 subjects with metameric level C6 tetraplegia, 4 subjects with metameric level C7 tetraplegia and 8 healthy subjects. The movement was recorded with a photogrammetry system. The ADL of drinking was divided into a series of clearly identifiable phases to facilitate analysis. Metrics describing the time of the reaching phase, the range of motion of the joints analyzed, and characteristics of movement performance such as the efficiency, accuracy and smoothness of the distal segment and inter-joint coordination were obtained. The performance of the drinking task was more variable in people with SCI compared to the control group in relation to the metrics measured. Reaching time was longer in SCI groups. The proposed metrics showed capability to discriminate between healthy and pathologic people. Relative deficits in efficiency were larger in SCI people than in controls. These metrics can provide useful information in a clinical setting about the quality of the movement performed by healthy and SCI people during functional activities.

Canonical Correlation Analysis for Interpreting Airborne Laser Scanning Metrics along the Lorenz Curve of Tree Size Inequality

Canonical Correlation Analysis for Interpreting Airborne Laser Scanning Metrics along the Lorenz Curve of Tree Size Inequality

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.