Hypogammaglobulinemia in BLT Humanized Mice – An Animal Model of Primary Antibody Deficiency

Primary antibody deficiencies present clinically as reduced or absent plasma antibodies without another identified disorder that could explain the low immunoglobulin levels. Bone marrow-liver-thymus (BLT) humanized mice also exhibit primary antibody deficiency or hypogammaglobulinemia. Comprehensive characterization of B cell development and differentiation in BLT mice revealed other key parallels with primary immunodeficiency patients. We found that B cell ontogeny was normal in the bone marrow of BLT mice but observed an absence of switched memory B cells in the periphery. PC-KLH immunizations led to the presence of switched memory B cells in immunized BLT mice although plasma cells producing PCor KLH- specific IgG were not detected in tissues. Overall, we have identified the following parallels between the humoral immune systems of primary antibody deficiency patients and those in BLT mice that make this in vivo model a robust and translational experimental platform for gaining a greater understanding of this heterogeneous array of humoral immunodeficiency disorders in humans: (i) hypogammaglobulinemia; (ii) normal B cell ontogeny in bone marrow; and (iii) poor antigen-specific IgG response to immunization. Furthermore, the development of strategies to overcome these humoral immune aberrations in BLT mice may in turn provide insights into the pathogenesis of some primary antibody deficiency patients which could lead to novel clinical interventions for improved humoral immune function

Web-based OERs in Computer Networks

Learning and teaching processes are continually changing. Therefore, design of learning technologies has gained interest in educators and educational institutions from secondary school to higher education. This paper describes the successfully use in education of social learning technologies and virtual laboratories designed by the authors, as well as videos developed by the students. These tools, combined with other open educational resources based on a blended-learning methodology, have been employed to teach the subject of Computer Networks. We have verified not only that the application of OERs into the learning process leads to a significantly improvement of the assessments, but also that the combination of several OERs enhances their effectiveness. These results are supported by, firstly, a study of both students’ opinion and students’ behaviour over five academic years, and, secondly, a correlation analysis between the use of OERs and the grades obtained by students

Safe cooperation between human operators and visually controlled industrial manipulators

Industrial tasks can be improved substantially by making humans and robots collaborate in the same workspace. The main goal of this chapter is the development of a human-robot interaction system which enables this collaboration and guarantees the safety of the human operator. This system is composed of two subsystems: the human tracking system and the robot control system. The human tracking system deals with the precise real-time localization of the human operator in the industrial environment. It is composed of two systems: an inertial motion capture system and an Ultra-WideBand localization system. The robot control system is based on visual servoing. A safety behaviour which stops the normal path tracking of the robot is performed when the robot and the human are too close. This safety behaviour has been implemented through a multi-threaded software architecture in order to share information between both systems. Thereby, the localization measurements obtained by the human tracking system are processed by the robot control system to compute the minimum human-robot distance and determine if the safety behaviour must be activated.Spanish Ministry of Science and Innovation and the Spanish Ministry of Education through the projects DPI2005-06222 and DPI2008-02647 and the grant AP2005-1458

Hypogammaglobulinemia in BLT Humanized Mice – An Animal Model of Primary Antibody Deficiency

Primary antibody deficiencies present clinically as reduced or absent plasma antibodies without another identified disorder that could explain the low immunoglobulin levels. Bone marrow-liver-thymus (BLT) humanized mice also exhibit primary antibody deficiency or hypogammaglobulinemia. Comprehensive characterization of B cell development and differentiation in BLT mice revealed other key parallels with primary immunodeficiency patients. We found that B cell ontogeny was normal in the bone marrow of BLT mice but observed an absence of switched memory B cells in the periphery. PC-KLH immunizations led to the presence of switched memory B cells in immunized BLT mice although plasma cells producing PC- or KLH- specific IgG were not detected in tissues. Overall, we have identified the following parallels between the humoral immune systems of primary antibody deficiency patients and those in BLT mice that make this in vivo model a robust and translational experimental platform for gaining a greater understanding of this heterogeneous array of humoral immunodeficiency disorders in humans: (i) hypogammaglobulinemia; (ii) normal B cell ontogeny in bone marrow; and (iii) poor antigen-specific IgG response to immunization. Furthermore, the development of strategies to overcome these humoral immune aberrations in BLT mice may in turn provide insights into the pathogenesis of some primary antibody deficiency patients which could lead to novel clinical interventions for improved humoral immune function

Diseño de itinerarios de aprendizaje sobre Moodle para asignaturas de redes de computadores basados en virtualización mediante software libre

El diseño de recursos educacionales y materiales didácticos vía on-line permite mejorar el aprendizaje autónomo y a distancia (o no presencial). El proceso de convergencia Europea del Espacio de Educación Superior determina que el empleo de este tipo de recursos dota al estudiante de más flexibilidad, aunque la metodología de educación dominante sea la tradicional (es decir, las clases presenciales). Los recursos educacionales on-line juegan un rol importante en este contexto. En trabajos previos se ha experimentado diseñando cursos con ayuda de un LCMS (Learning Content Management System) como el Moodle corporativo de la UA, incorporando documentos SCORM para diseñar lecciones de autoevaluación, con laboratorios virtuales y otras herramientas de simulación de diseño propio (KIVANS, applets KIVANS+EJS). En esta nueva red se pretende generar nuevos recursos didácticos basados en software libre. Ninguno de los laboratorios virtuales desarrollados hasta ahora permiten a los alumnos poner en práctica los desarrollos de las clases presenciales a distancia. Para ello, usando el software de libre distribución GNS3, y teniendo como base la configuración de la red del laboratorio L24 de la EPS, se pretende construir un entorno virtual que simule las posibilidades reales de este laboratorio

Virtualización de Redes de Computadores con GNS3: Evaluación de soluciones para el aprendizaje a distancia

El diseño de los recursos educativos permite a los estudiantes modificar su proceso de aprendizaje. En particular, los recursos educativos on-line descargables han sido utilizados con éxito en la educación en ingeniería en los últimos años. Por lo general, estos recursos son gratuitos y accesibles desde la web. Además, son diseñados y desarrollados por profesores y usados por sus estudiantes. Pero, rara vez se desarrollan por los estudiantes con el fin de ser utilizados por otros estudiantes. En este artículo, profesores y estudiantes trabajan juntos para implementar recursos educativos de libre distribución, que puedan ser utilizados por los estudiantes para mejorar el proceso de aprendizaje de redes de computadores en los estudios de ingeniería. En particular, se virtualizan topologías de red para modelar redes LAN (Local Area Network) y MAN (Metropolitan Area Network) con el fin de simular el comportamiento de los enlaces y nodos cuando están interconectados con diferente diseño físico y lógico. Para ello, usando el software de libre distribución GNS3, y teniendo como base la configuración de la red del laboratorio L24 de la EPS, se construye un entorno virtual que simula las posibilidades reales de este laboratorio

On the relationship between head circumference, brain size, prenatal long-chain PUFA/5-methyltetrahydrofolate supplementation and cognitive abilities during childhood

Head circumference in infants has been reported to predict brain size, total grey matter volume (GMV) and neurocognitive development. However, it is unknown whether it has predictive value on regional and subcortical brain volumes. We aimed to explore the relationship between several head circumference measurements since birth and distributions of GMV and subcortical volumes at later childhood. We examined seventy-four, Caucasian, singleton, term-born infants born to mothers randomised to receive fish oil and/or 5-methyltetrahydrofolate or placebo prenatal supplementation. We assessed head circumference at birth and at 4 and 10 years of age and cognitive abilities at 7 years of age. We obtained brain MRI at 10 years of age, on which we performed voxel-based morphometry, cortical surface extraction and subcortical segmentation. Analyses were controlled for sex, age, height, weight, family status, laterality and total intracranial volume. Prenatal supplementation did not affect head circumference at any age, cognitive abilities or total brain volumes. Head circumference at 4 years presented the highest correlation with total GMV, white matter volume and brain surface area, and was also strongly associated with GMV of frontal, temporal and occipital areas, as well as with caudate nucleus, globus pallidus, putamen and thalamus volumes. As relationships between brain volumes in childhood and several outcomes extend into adulthood, we have found that ages between 0 and 4 years as the optimal time for brain growth; postnatal factors might have the most relevant impact on structural maturation of certain cortical areas and subcortical nuclei, independent of prenatal supplementation

Experiences on using Arduino for laboratory experiments of Automatic Control and Robotics

The free hardware platforms have become very important in engineering education in recent years. Among these platforms, Arduino highlights, characterized by its versatility, popularity and low price. This paper describes the implementation of four laboratory experiments for Automatic Control and Robotics courses at the University of Alicante, which have been developed based on Arduino and other existing equipment. Results were evaluated taking into account the views of students, concluding that the proposed experiments have been attractive to them, and they have acquired the knowledge about hardware configuration and programming that was intended

Metodología docente para la incorporación de laboratorios virtuales en el plan de estudios del master universitario en automática y robótica

En este artículo se describe la metodología empleada para el desarrollo y coordinación de las asignaturas obligatorias del Máster Universitario en Automática y Robótica de la Universidad de Alicante. Se ha trabajado en adecuar las guías docentes a la metodología mediante el trabajo colaborativo de los distintos profesores coordinadores de las asignaturas con el objetivo de garantizar que todos los conceptos necesarios sean cubiertos y complementados entre las asignaturas, apoyándose en mapas conceptuales. Otro aspecto en el que se ha hecho un especial énfasis en la metodología propuesta ha sido introducir como parte de las actividades teóricas y/o prácticas el uso de laboratorios virtuales remotos. Los laboratorios virtuales sirven de apoyo a la teoría para mostrar simulaciones y resultados prácticos mediante la interacción con equipamiento real. Además, muchas de estas herramientas admiten que el alumnado pueda trabajar a distancia desde sus casas, lo que redunda en la posibilidad de autoaprendizaje e incluso la realización de prácticas a distancia

Clinical and economic impact of current ALK rearrangement testing in Spain compared with a hypothetical no-testing scenario

Background: Currently biomarkers play an essential role in diagnosis, treatment, and management of cancer. In non-small cell lung cancer (NSCLC) determination of biomarkers such as ALK, EGFR, ROS1 or PD-L1 is mandatory for an adequate treatment decision. The aim of this study is to determine the clinical and economic impact of current anaplastic lymphoma kinase testing scenario in Spain. Methods: A joint model, composed by decision-tree and Markov models, was developed to estimate the long-term health outcomes and costs of NSCLC patients, by comparing the current testing scenario for ALK in Spain vs a hypothetical no-testing. The current distribution of testing strategies for ALK determination and their sensitivity and specificity data were obtained from the literature. Treatment allocation based on the molecular testing result were defined by a panel of Spanish experts. To assess long-term effects of each treatment, 3-states Markov models were developed, where progression-free survival and overall survival curves were extrapolated using exponential models. Medical direct costs (expressed in €, 2019) were included. A lifetime horizon was used and a discount rate of 3% was applied for both costs and health effects. Several sensitivity analyses, both deterministic and probabilistic, were performed in order test the robustness of the analysis. Results: We estimated a target population of 7628 NSCLC patients, including those with non-squamous histology and those with squamous carcinomas who were never smokers. Over the lifetime horizon, the current ALK testing scenario produced additional 5060 and 3906 life-years and quality-adjusted life-years (QALY), respectively, compared with the no-testing scenario. Total direct costs were increased up to € 51,319,053 for testing scenario. The incremental cost-effectiveness ratio was 10,142 €/QALY. The sensitivity analyses carried out confirmed the robustness of the base-case results, being the treatment allocation and the test accuracy (sensitivity and specificity data) the key drivers of the model. Conclusions: ALK testing in advanced NSCLC patients, non-squamous and never-smoker squamous, provides more than 3000 QALYs in Spain over a lifetime horizon. Comparing this gain in health outcomes with the incremental costs, the resulting incremental cost-effectiveness ratio reinforces that testing non-squamous and never-smoker squamous NSCLC is a cost-effective strategy in Spain