Paradigma auditivo en resonancia magnética funcional como marcador predictivo en primeros episodios psicóticos

Esta tesis doctoral pretende profundizar en el conocimiento de aquellos fenómenos que tienen lugar en el cerebro de una persona que experimenta un primer episodio del espectro de la psicosis. En este sentido, la literatura reciente señala la importancia de una adecuada intervención precoz tras la aparición de la sintomatología psicótica. Así, nace hace unos años la literatura científica sobre los PEP (Primeros Episodios Psicóticos), y se ponen en marcha unidades (UPEP) de intervención precoz en todo el mundo. En este sentido, se inicia también la búsqueda de marcadores biológicos (biomarcadores) para intentar predecir el curso de la enfermedad y permitir una adecuada intervención. Uno de estos marcadores es la neuroimagen, tanto estructural como funcional. En nuestro caso, hemos utilizado pruebas de RMf (Resonancia Magnética Funcional) para estudiar longitudinalmente a pacientes de la UPEP del Hospital Clínico de Valencia. Durante la prueba, se ha utilizado un paradigma auditivo emocional. Hemos realizado en primer lugar una revisión sistemática de la literatura sobre el seguimiento longitudinal en RMf de pacientes con un PEP. En total, obtuvimos una muestra reducida, de 31 trabajos, lo que evidencia la dificultad de realizar seguimientos longitudinales con este tipo de pacientes y esta metodología de estudio. En general, la mayoría de estudios han empleado tareas de tipo cognitivo y en la modalidad visual, y han encontrado un efecto general de hipoactivación en la resonancia basal, que se normaliza con los efectos del tratamiento. Esta hipoactivación se ha encontrado principalmente en el córtex prefrontal. En el segundo trabajo, hemos reunido una muestra de 35 pacientes de la UPEP con, al menos, 2 escáneres realizados con el citado paradigma con un intervalo medio de 25 meses entre ambas pruebas. El principal resultado encontrado en este estudio fue el del descenso, a nivel longitudinal, de una elevada activación encontrada en el grupo de pacientes, especialmente en el hipocampo, pero también en la amígdala. Así, el paradigma auditivo emocional ofrece una interesante imagen de la trayectoria longitudinal en activación cerebral de los pacientes en un PEP. Sin embargo, una importante variabilidad fue también detectada respecto a las trayectorias de activación. Por este motivo se decidió realizar un análisis más detallado de casos en particular, por lo que se realizó un tercer trabajo de estudio de casos, comparando las trayectorias clínicas y de neuroimagen de dos pacientes con un debut similar. En los resultados de este estudio, podemos observar que, efectivamente, el paradigma permite distinguir resultados diferentes que encajan con la diferente evolución clínica de ambas pacientes Así, el paradigma auditivo emocional medido en pruebas de RMf parece revelar información útil para la prognosis de un primer episodio psicótico, aunque resulta necesario analizar cada caso de manera particular y exhaustiva. Asimismo, parece que la aproximación metodológica basada en áreas y activaciones específicas parece menos apropiada para medir procesos cerebrales complejos, recomendando así la utilización de fórmulas que midan el funcionamiento cerebral en términos de redes y circuitos y enlazarlo así con hipótesis explicativas más prometedoras como el modelo de saliencia aberrante.This doctoral thesis aims to deepen the knowledge of those phenomena that take place in the brain of a person who experiences a first episode of the spectrum of psychosis. In this sense, recent literature points to the importance of adequate early intervention after the appearance of psychotic symptoms. Thus, the scientific literature on PEP (First Psychotic Episodes) was born a few years ago, and early intervention units (UPEP) were launched around the world. In this sense, the search for biological markers (biomarkers) is also initiated to try to predict the course of the disease and allow an adequate intervention. One of these markers is neuroimaging, both structural and functional. In our case, we have used fMRI (Functional Magnetic Resonance) tests to longitudinally study patients from the UPEP of the Hospital Clínico de Valencia. During the test, an emotional auditory paradigm was used. We have first conducted a systematic review of the literature on longitudinal follow-up in fMRI of patients with a PEP. In total, we obtained a small sample of 31 studies, which shows the difficulty of longitudinal follow-ups with this type of patients and this study methodology. In general, most studies have employed cognitive and visual tasks, and have found a general effect of hypoactivation on baseline resonance, which normalizes with the effects of treatment. This hypoactivation has been found mainly in the prefrontal cortex. In the second work, we have gathered a sample of 35 patients from the UPEP with at least 2 scans performed with the aforementioned paradigm with an average interval of 25 months between both tests. The main result found in this study was the decrease, at the longitudinal level, of a high activation found in the group of patients, especially in the hippocampus, but also in the amygdala. Thus, the emotional auditory paradigm offers an interesting image of the longitudinal trajectory in brain activation of patients in a PEP. However, an important variability was also detected with respect to activation trajectories. For this reason, it was decided to carry out a more detailed analysis of particular cases, so a third case study work was carried out, comparing the clinical and neuroimaging trajectories of two patients with a similar debut. In the results of this study, we can observe that, indeed, the paradigm allows to distinguish different results that fit with the different clinical evolution of both patients Thus, the emotional auditory paradigm measured in fMRI tests seems to reveal useful information for the prognosis of a first psychotic episode, although it is necessary to analyze each case in a particular and exhaustive way. Likewise, it seems that the methodological approach based on specific areas and activations seems less appropriate to measure complex brain processes, thus recommending the use of formulas that measure brain functioning in terms of networks and circuits and thus link it with more promising explanatory hypotheses such as the aberrant salience model

Applying A Methodology For Educating Students With Special Needs: A Case Study

The introduction of innovative educational technologies opens up new ways of interacting with students. We propose to exploit this potential to help in the education of children with special needs. We analyze the state of the art of tools supporting the teaching process, focusing on the omissions of existing research. We propose a new framework to help throughout the whole teaching process and describe its application to Proyecto Aprender (Learn Project), an educational resource targeting children with learning difficulties. Finally, we outline some conclusions and current/future research lines

Unconventional mechanism of virtual-state population through dissipation

Virtual states are a central concept in quantum mechanics. By definition, the probability of finding a quantum system in a virtual state should be vanishingly small at all times. In contrast to this notion, we report a phenomenon occurring in open quantum systems by which virtual states can acquire a sizable population in the long-time limit, even if they are not directly coupled to any dissipative channel. This means that the situation in which the virtual state remains unpopulated can be metastable. We describe this effect by introducing a two-step adiabatic elimination method, which we termed hierarchical adiabatic elimination, that allows one to obtain analytical expressions of the timescale of metastability in general open quantum systems. We show how these results can be relevant for practical questions such as the generation of stable and metastable entangled states in dissipative systems of interacting qubit

Unconventional mechanism of virtual-state population through dissipation

Virtual states are a central concept in quantum mechanics. By definition, the probability of finding a quantum system in a virtual state should be vanishingly small at all times. In contrast to this notion, we report a phenomenon occurring in open quantum systems by which virtual states can acquire a sizable population in the long-time limit, even if they are not directly coupled to any dissipative channel. This means that the situation in which the virtual state remains unpopulated can be metastable. We describe this effect by introducing a two-step adiabatic elimination method, which we termed hierarchical adiabatic elimination, that allows one to obtain analytical expressions of the timescale of metastability in general open quantum systems. We show how these results can be relevant for practical questions such as the generation of stable and metastable entangled states in dissipative systems of interacting qubit

Building Accessible Flash Applications: an XML-Based Toolkit

The use of Flash as a web-based multimedia development tool has spread lately. Although a big effort has gone into improving its accessibility, there are still accessibility gaps requiring programming or purchase from another supplier. This makes building an accessible Flash application an ad hoc, complex and time-consuming task. With the aim of lightening the accessibility-related workload, we have implemented a toolkit that helps to create accessible multimedia Flash resources. This toolkit specifies the accessibility features as XML configuration files. It includes a library that works like a wrapper abstracting the logic layer of the different events and iterations from the physical layer. This way, new functionalities can easily be added. Additionally, it has been successfully used to build teaching and teaching support systems

A Framework to Support Development of Learning Applications for Disabled Children

Multimedia resources are an important tool that can be used by teachers in the classroom as a learning aid for learners with disabilities or by parents and children at home. However, disabled children are not always able to use existing assistive technologies because they are not experienced enough, suffer from medium/profound disability, or simply do not have the financial resources to buy commercial tools. Additionally, today’s adapted tools are not always valid for a broad spectrum of disabled users and often focus on a user group. We claim that potential applications and resources for people with special needs must self-adapt to user capabilities and skills, reducing the use of external assistive technologies. In this paper, we present a guide for developers to create accessible applications and resources that reduce workload

Discovery of distant RR Lyrae stars in the Milky Way using DECam

We report the discovery of distant RR Lyrae stars, including the most distant known in the Milky Way, using data taken in the $g-$band with the Dark Energy Camera as part of the High cadence Transient Survey (HiTS; 2014 campaign). We detect a total of 173 RR Lyrae stars over a ~120 deg^2 area, including both known RR Lyrae and new detections. The heliocentric distances d_H of the full sample range from 9 to >200 kpc, with 18 of them beyond 90 kpc. We identify three sub-groups of RR Lyrae as members of known systems: the Sextans dwarf spheroidal galaxy, for which we report 46 new discoveries, and the ultra-faint dwarf galaxies Leo IV and Leo V. Following an MCMC methodology, we fit spherical and ellipsoidal profiles of the form rho(R) ~ R^n to the radial density distribution of RR Lyrae in the Galactic halo. The best fit corresponds to the spherical case, for which we obtain a simple power-law index of n=-4.17^{+0.18}_{-0.20}, consistent with recent studies made with samples covering shorter distances. The pulsational properties of the outermost RR Lyrae in the sample (d_H>90 kpc) differ from the ones in the halo population at closer distances. The distribution of the stars in a Period-Amplitude diagram suggest they belong to Oosterhoff-intermediate or Oosterhoff II groups, similar to what is found in the ultra-faint dwarf satellites around the Milky Way. The new distant stars discovered represent an important addition to the few existing tracers of the Milky Way potential in the outer halo.Comment: Accepted for publication in The Astrophysical Journa

Serendipitous discovery of RR Lyrae stars in the Leo V ultra-faint galaxy

During the analysis of RR Lyrae stars discovered in the High cadence Transient Survey (HiTS) taken with the Dark Energy Camera at the 4-m telescope at Cerro Tololo Inter-American Observatory, we found a group of three very distant, fundamental mode pulsator RR Lyrae (type ab). The location of these stars agrees with them belonging to the Leo V ultra-faint satellite galaxy, for which no variable stars have been reported to date. The heliocentric distance derived for Leo V based on these stars is 173 +/- 5 kpc. The pulsational properties (amplitudes and periods) of these stars locate them within the locus of the Oosterhoff II group, similar to most other ultra-faint galaxies with known RR Lyrae stars. This serendipitous discovery shows that distant RR Lyrae stars may be used to search for unknown faint stellar systems in the outskirts of the Milky Way.Comment: Accepted in ApJ Letter

Main immunological hypotheses of the canine demodicosis

1 recurso en línea (páginas 61-69).Canine demodicosis is a common cutaneous condition in dogs, characterized by a proliferative increase of mites from the genus Demodex. Despite its high prevalence, the onset and development of demodicosis are still unknown; however, they are primarily associated to an immune dysfunction. The immune system plays an important role controlling mites in healthy animals as well as on the development of the disease in sick animals. The immune mechanisms that lead to an unbalance in the innate and adaptive systems, as well as the mite mechanisms to evade the immune system remain unknown. Consequently, various hypotheses have been proposed to try explaining possible immune mechanisms. This paper aims to conduct an updated review of the main hypotheses related to the immune mechanisms associated to demodicosis in dogs.La demodicosis canina es una enfermedad dermatológica común en perros; se presenta por un aumento en la proliferación de los ácaros del género Demodex spp., pero, a pesar de su alta prevalencia, su aparición y desarrollo son aún desconocidos, sin embargo, se asocian, principalmente, a una inmunodisfunción. El sistema inmune juega un papel importante tanto en el control del ácaro en animales sanos como en el desarrollo de la enfermedad en enfermos; en estos últimos se desconocen los mecanismos inmunitarios que llevan al desbalance en el sistema innato y adaptativo y a la evasión del sistema inmune por el ácaro; debido a esto se han postulado hipótesis que, en conjunto, tratan de explicar los posibles mecanismos inmunológicos. El presente artículo revisa las principales hipótesis inmunológicas relacionadas con la presentación de demodicosis en perros.Bibliografía: página 69

Plan de mejora del proceso de elaboración de queso fundido Quesillo en la planta de lácteos Las Mesas, Santo Tomás, Chontales.

Este trabajo consiste en el desarrollo de una propuesta de plan de mejora del proceso de elaboración de queso fundido (Quesillo) en la planta de lácteos “Las Mesas”, Santo Tomás, Chontales. El actual proceso de producción en la planta se realiza de manera artesanal, esto representa una problemática, debido a que al elaborarse el producto de forma manual se invierte más tiempo, su rendimiento disminuye y en caso de exportación se requiere mayor número de días