A New Multidisciplinary Home Care Telemedicine System to Monitor Stable Chronic Human Immunodeficiency Virus-Infected Patients: A Randomized Study

BACKGROUND: Antiretroviral therapy has changed the natural history of human immunodeficiency virus (HIV) infection in developed countries, where it has become a chronic disease. This clinical scenario requires a new approach to simplify follow-up appointments and facilitate access to healthcare professionals. METHODOLOGY: We developed a new internet-based home care model covering the entire management of chronic HIV-infected patients. This was called Virtual Hospital. We report the results of a prospective randomised study performed over two years, comparing standard care received by HIV-infected patients with Virtual Hospital care. HIV-infected patients with access to a computer and broadband were randomised to be monitored either through Virtual Hospital (Arm I) or through standard care at the day hospital (Arm II). After one year of follow up, patients switched their care to the other arm. Virtual Hospital offered four main services: Virtual Consultations, Telepharmacy, Virtual Library and Virtual Community. A technical and clinical evaluation of Virtual Hospital was carried out. FINDINGS: Of the 83 randomised patients, 42 were monitored during the first year through Virtual Hospital (Arm I) and 41 through standard care (Arm II). Baseline characteristics of patients were similar in the two arms. The level of technical satisfaction with the virtual system was high: 85% of patients considered that Virtual Hospital improved their access to clinical data and they felt comfortable with the videoconference system. Neither clinical parameters [level of CD4+ T lymphocytes, proportion of patients with an undetectable level of viral load (p = 0.21) and compliance levels >90% (p = 0.58)] nor the evaluation of quality of life or psychological questionnaires changed significantly between the two types of care. CONCLUSIONS: Virtual Hospital is a feasible and safe tool for the multidisciplinary home care of chronic HIV patients. Telemedicine should be considered as an appropriate support service for the management of chronic HIV infection. TRIAL REGISTRATION: Clinical-Trials.gov: NCT01117675.

A stereological study of synapse number in the epileptic human hippocampus

Hippocampal sclerosis is the most frequent pathology encountered in resected mesial temporal structures from patients with intractable temporal lobe epilepsy (TLE). Here, we have used stereological methods to compare the overall density of synapses and neurons between non-sclerotic and sclerotic hippocampal tissue obtained by surgical resection from patients with TLE. Specifically, we examined the possible changes in the subiculum and CA1, regions that seem to be critical for the development and/or maintenance of seizures in these patients. We found a remarkable decrease in synaptic and neuronal density in the sclerotic CA1, and while the subiculum from the sclerotic hippocampus did not display changes in synaptic density, the neuronal density was higher. Since the subiculum from the sclerotic hippocampus displays a significant increase in neuronal density, as well as a various other neurochemical changes, we propose that the apparently normal subiculum from the sclerotic hippocampus suffers profound alterations in neuronal circuits at both the molecular and synaptic level that are likely to be critical for the development or maintenance of seizure activity

Study and analysis of the Leap Motion sensor and the Software Development Kit (SDK) for the implementation of visual Human Computer Interfaces

En este proyecto, se presenta un informe técnico sobre la cámara Leap Motion y el Software Development Kit correspondiente, el cual es un dispositivo con una cámara de profundidad orientada a interfaces hombre-máquina. Esto es realizado con el propósito de desarrollar una interfaz hombre-máquina basada en un sistema de reconocimiento de gestos de manos. Después de un exhaustivo estudio de la cámara Leap Motion, se han realizado diversos programas de ejemplo con la intención de verificar las capacidades descritas en el informe técnico, poniendo a prueba la Application Programming Interface y evaluando la precisión de las diferentes medidas obtenidas sobre los datos de la cámara. Finalmente, se desarrolla un prototipo de un sistema de reconocimiento de gestos. Los datos sobre la posición y orientación de la punta de los dedos obtenidos de la Leap Motion son usados para describir un gesto mediante un vector descriptor, el cual es enviado a una Máquina Vectores Soporte, utilizada como clasificador multi-clase.

Advanced morphometric techniques applied to the study of human brain anatomy

El desarrollo de las técnicas de imágenes por resonancia magnética han permitido el estudio y cuantificación, in vivo, de los cambios que ocurren en la morfología cerebral ligados a procesos tales como el neurodesarrollo, el envejecimiento, el aprendizaje o la enfermedad. Un gran número de métodos de morfometría han sido desarrollados con el fin de extraer la información contenida en estas imágenes y traducirla en indicadores de forma o tamaño, tales como el volumen o el grosor cortical; marcadores que son posteriormente empleados para encontrar diferencias estadísticas entre poblaciones de sujetos o realizar correlaciones entre la morfología cerebral y, por ejemplo, la edad o la severidad de determinada enfermedad. A pesar de la amplia variedad de biomarcadores y metodologías de morfometría, muchos estudios sesgan sus hipótesis, y con ello los resultados experimentales, al empleo de un número reducido de biomarcadores o a al uso de una única metodología de procesamiento. Con el presente trabajo se pretende demostrar la importancia del empleo de diversos métodos de morfometría para lograr una mejor caracterización del proceso que se desea estudiar. En el mismo se emplea el análisis de forma para detectar diferencias, tanto globales como locales, en la morfología del tálamo entre pacientes adolescentes con episodios tempranos de psicosis y adolescentes sanos. Los resultados obtenidos demuestran que la diferencia de volumen talámico entre ambas poblaciones de sujetos, previamente descrita en la literatura, se debe a una reducción del volumen de la región anterior-mediodorsal y del núcleo pulvinar del tálamo de los pacientes respecto a los sujetos sanos. Además, se describe el desarrollo de un estudio longitudinal, en sujetos sanos, que emplea simultáneamente distintos biomarcadores para la caracterización y cuantificación de los cambios que ocurren en la morfología de la corteza cerebral durante la adolescencia. A través de este estudio se revela que el proceso de “alisado” que experimenta la corteza cerebral durante la adolescencia es consecuencia de una disminución de la profundidad, ligada a un incremento en el ancho, de los surcos corticales. Finalmente, esta metodología es aplicada, en un diseño transversal, para el estudio de las causas que provocan el decrecimiento tanto del grosor cortical como del índice de girificación en adolescentes con episodios tempranos de psicosis. ABSTRACT The ever evolving sophistication of magnetic resonance image techniques continue to provide new tools to characterize and quantify, in vivo, brain morphologic changes related to neurodevelopment, senescence, learning or disease. The majority of morphometric methods extract shape or size descriptors such as volume, surface area, and cortical thickness from the MRI image. These morphological measurements are commonly entered in statistical analytic approaches for testing between-group differences or for correlations between the morphological measurement and other variables such as age, sex, or disease severity. A wide variety of morphological biomarkers are reported in the literature. Despite this wide range of potentially useful biomarkers and available morphometric methods, the hypotheses and findings of the grand majority of morphological studies are biased because reports assess only one morphometric feature and usually use only one image processing method. Throughout this dissertation biomarkers and image processing strategies are combined to provide innovative and useful morphometric tools for examining brain changes during neurodevelopment. Specifically, a shape analysis technique allowing for a fine-grained assessment of regional thalamic volume in early-onset psychosis patients and healthy comparison subjects is implemented. Results show that disease-related reductions in global thalamic volume, as previously described by other authors, could be particularly driven by a deficit in the anterior-mediodorsal and pulvinar thalamic regions in patients relative to healthy subjects. Furthermore, in healthy adolescents different cortical features are extracted and combined and their interdependency is assessed over time. This study attempts to extend current knowledge of normal brain development, specifically the largely unexplored relationship between changes of distinct cortical morphological measurements during adolescence. This study demonstrates that cortical flattening, present during adolescence, is produced by a combination of age-related increase in sulcal width and decrease in sulcal depth. Finally, this methodology is applied to a cross-sectional study, investigating the mechanisms underlying the decrease in cortical thickness and gyrification observed in psychotic patients with a disease onset during adolescence.

A study of the mechanical behaviour of the human aortic artery by means of non-linear finite element models

En la presente tesis desarrollamos una estrategia para la simulación numérica del comportamiento mecánico de la aorta humana usando modelos de elementos finitos no lineales. Prestamos especial atención a tres aspectos claves relacionados con la biomecánica de los tejidos blandos. Primero, el análisis del comportamiento anisótropo característico de los tejidos blandos debido a las familias de fibras de colágeno. Segundo, el análisis del ablandamiento presentado por los vasos sanguíneos cuando estos soportan cargas fuera del rango de funcionamiento fisiológico. Y finalmente, la inclusión de las tensiones residuales en las simulaciones en concordancia con el experimento de apertura de ángulo. El análisis del daño se aborda mediante dos aproximaciones diferentes. En la primera aproximación se presenta una formulación de daño local con regularización. Esta formulación tiene dos ingredientes principales. Por una parte, usa los principios de la teoría de la fisura difusa para garantizar la objetividad de los resultados con diferentes mallas. Por otra parte, usa el modelo bidimensional de Hodge-Petruska para describir el comportamiento mesoscópico de los fibriles. Partiendo de este modelo mesoscópico, las propiedades macroscópicas de las fibras de colágeno son obtenidas a través de un proceso de homogenización. En la segunda aproximación se presenta un modelo de daño no-local enriquecido con el gradiente de la variable de daño. El modelo se construye a partir del enriquecimiento de la función de energía con un término que contiene el gradiente material de la variable de daño no-local. La inclusión de este término asegura una regularización implícita de la implementación por elementos finitos, dando lugar a resultados de las simulaciones que no dependen de la malla. La aplicabilidad de este último modelo a problemas de biomecánica se estudia por medio de una simulación de un procedimiento quirúrgico típico conocido como angioplastia de balón. In the present thesis we develop a framework for the numerical simulation of the mechanical behaviour of the human aorta using non-linear finite element models. Special attention is paid to three key aspects related to the biomechanics of soft tissues. First, the modelling of the characteristic anisotropic behaviour of the softue due to the collagen fibre families. Secondly, the modelling of damage-related softening that blood vessels exhibit when subjected to loads beyond their physiological range. And finally, the inclusion of the residual stresses in the simulations in accordance with the opening-angle experiment The modelling of damage is addressed with two major and different approaches. In the first approach a continuum local damage formulation with regularisation is presented. This formulation has two principal ingredients. On the one hand, it makes use of the principles of the smeared crack theory to avoid the mesh size dependence of the structural response in softening. On the other hand, it uses a Hodge-Petruska bidimensional model to describe the fibrils as staggered arrays of tropocollagen molecules, and from this mesoscopic model the macroscopic material properties of the collagen fibres are obtained using an homogenisation process. In the second approach a non-local gradient-enhanced damage formulation is introduced. The model is built around the enhancement of the free energy function by means of a term that contains the referential gradient of the non-local damage variable. The inclusion of this term ensures an implicit regularisation of the finite element implementation, yielding mesh-objective results of the simulations. The applicability of the later model to biomechanically-related problems is studied by means of the simulation of a typical surgical procedure, namely, the balloon angioplasty.

Safety study of transcranial static magnetic field stimulation (tSMS) of the human cortex

Transcranial static magnetic field stimulation (tSMS) in humans reduces cortical excitability. Objective: The objective of this study was to determine if prolonged tSMS (2 h) could be delivered safely in humans. Safety limits for this technique have not been described. Methods: tSMS was applied for 2 h with a cylindric magnet on the occiput of 17 healthy subjects. We assessed tSMS-related safety aspects at tissue level by measuring levels of neuron-specific enolase (NSE,a marker of neuronal damage) and S100 (a marker of glial reactivity and damage). We also included an evaluation of cognitive side effects by using a battery of visuomotor and cognitive tests. Results: tSMS did not induce any significant increase in NSE or S100. No cognitive alteration was detected. Conclusions: Our data indicate that the application of tSMS is safe in healthy human subjects, at least within these parameters