Design of a secure architecture for the exchange of biomedical information in m-Health scenarios

El paradigma de m-Salud (salud móvil) aboga por la integración masiva de las más avanzadas tecnologías de comunicación, red móvil y sensores en aplicaciones y sistemas de salud, para fomentar el despliegue de un nuevo modelo de atención clínica centrada en el usuario/paciente. Este modelo tiene por objetivos el empoderamiento de los usuarios en la gestión de su propia salud (p.ej. aumentando sus conocimientos, promocionando estilos de vida saludable y previniendo enfermedades), la prestación de una mejor tele-asistencia sanitaria en el hogar para ancianos y pacientes crónicos y una notable disminución del gasto de los Sistemas de Salud gracias a la reducción del número y la duración de las hospitalizaciones. No obstante, estas ventajas, atribuidas a las aplicaciones de m-Salud, suelen venir acompañadas del requisito de un alto grado de disponibilidad de la información biomédica de sus usuarios para garantizar una alta calidad de servicio, p.ej. fusionar varias señales de un usuario para obtener un diagnóstico más preciso. La consecuencia negativa de cumplir esta demanda es el aumento directo de las superficies potencialmente vulnerables a ataques, lo que sitúa a la seguridad (y a la privacidad) del modelo de m-Salud como factor crítico para su éxito. Como requisito no funcional de las aplicaciones de m-Salud, la seguridad ha recibido menos atención que otros requisitos técnicos que eran más urgentes en etapas de desarrollo previas, tales como la robustez, la eficiencia, la interoperabilidad o la usabilidad. Otro factor importante que ha contribuido a retrasar la implementación de políticas de seguridad sólidas es que garantizar un determinado nivel de seguridad implica unos costes que pueden ser muy relevantes en varias dimensiones, en especial en la económica (p.ej. sobrecostes por la inclusión de hardware extra para la autenticación de usuarios), en el rendimiento (p.ej. reducción de la eficiencia y de la interoperabilidad debido a la integración de elementos de seguridad) y en la usabilidad (p.ej. configuración más complicada de dispositivos y aplicaciones de salud debido a las nuevas opciones de seguridad). Por tanto, las soluciones de seguridad que persigan satisfacer a todos los actores del contexto de m-Salud (usuarios, pacientes, personal médico, personal técnico, legisladores, fabricantes de dispositivos y equipos, etc.) deben ser robustas y al mismo tiempo minimizar sus costes asociados. Esta Tesis detalla una propuesta de seguridad, compuesta por cuatro grandes bloques interconectados, para dotar de seguridad a las arquitecturas de m-Salud con unos costes reducidos. El primer bloque define un esquema global que proporciona unos niveles de seguridad e interoperabilidad acordes con las características de las distintas aplicaciones de m-Salud. Este esquema está compuesto por tres capas diferenciadas, diseñadas a la medidas de los dominios de m-Salud y de sus restricciones, incluyendo medidas de seguridad adecuadas para la defensa contra las amenazas asociadas a sus aplicaciones de m-Salud. El segundo bloque establece la extensión de seguridad de aquellos protocolos estándar que permiten la adquisición, el intercambio y/o la administración de información biomédica -- por tanto, usados por muchas aplicaciones de m-Salud -- pero no reúnen los niveles de seguridad detallados en el esquema previo. Estas extensiones se concretan para los estándares biomédicos ISO/IEEE 11073 PHD y SCP-ECG. El tercer bloque propone nuevas formas de fortalecer la seguridad de los tests biomédicos, que constituyen el elemento esencial de muchas aplicaciones de m-Salud de carácter clínico, mediante codificaciones novedosas. Finalmente el cuarto bloque, que se sitúa en paralelo a los anteriores, selecciona herramientas genéricas de seguridad (elementos de autenticación y criptográficos) cuya integración en los otros bloques resulta idónea, y desarrolla nuevas herramientas de seguridad, basadas en señal -- embedding y keytagging --, para reforzar la protección de los test biomédicos.The paradigm of m-Health (mobile health) advocates for the massive integration of advanced mobile communications, network and sensor technologies in healthcare applications and systems to foster the deployment of a new, user/patient-centered healthcare model enabling the empowerment of users in the management of their health (e.g. by increasing their health literacy, promoting healthy lifestyles and the prevention of diseases), a better home-based healthcare delivery for elderly and chronic patients and important savings for healthcare systems due to the reduction of hospitalizations in number and duration. It is a fact that many m-Health applications demand high availability of biomedical information from their users (for further accurate analysis, e.g. by fusion of various signals) to guarantee high quality of service, which on the other hand entails increasing the potential surfaces for attacks. Therefore, it is not surprising that security (and privacy) is commonly included among the most important barriers for the success of m-Health. As a non-functional requirement for m-Health applications, security has received less attention than other technical issues that were more pressing at earlier development stages, such as reliability, eficiency, interoperability or usability. Another fact that has contributed to delaying the enforcement of robust security policies is that guaranteeing a certain security level implies costs that can be very relevant and that span along diferent dimensions. These include budgeting (e.g. the demand of extra hardware for user authentication), performance (e.g. lower eficiency and interoperability due to the addition of security elements) and usability (e.g. cumbersome configuration of devices and applications due to security options). Therefore, security solutions that aim to satisfy all the stakeholders in the m-Health context (users/patients, medical staff, technical staff, systems and devices manufacturers, regulators, etc.) shall be robust and, at the same time, minimize their associated costs. This Thesis details a proposal, composed of four interrelated blocks, to integrate appropriate levels of security in m-Health architectures in a cost-efcient manner. The first block designes a global scheme that provides different security and interoperability levels accordingto how critical are the m-Health applications to be implemented. This consists ofthree layers tailored to the m-Health domains and their constraints, whose security countermeasures defend against the threats of their associated m-Health applications. Next, the second block addresses the security extension of those standard protocols that enable the acquisition, exchange and/or management of biomedical information | thus, used by many m-Health applications | but do not meet the security levels described in the former scheme. These extensions are materialized for the biomedical standards ISO/IEEE 11073 PHD and SCP-ECG. Then, the third block proposes new ways of enhancing the security of biomedical standards, which are the centerpiece of many clinical m-Health applications, by means of novel codings. Finally the fourth block, with is parallel to the others, selects generic security methods (for user authentication and cryptographic protection) whose integration in the other blocks results optimal, and also develops novel signal-based methods (embedding and keytagging) for strengthening the security of biomedical tests. The layer-based extensions of the standards ISO/IEEE 11073 PHD and SCP-ECG can be considered as robust, cost-eficient and respectful with their original features and contents. The former adds no attributes to its data information model, four new frames to the service model |and extends four with new sub-frames|, and only one new sub-state to the communication model. Furthermore, a lightweight architecture consisting of a personal health device mounting a 9 MHz processor and an aggregator mounting a 1 GHz processor is enough to transmit a 3-lead electrocardiogram in real-time implementing the top security layer. The extra requirements associated to this extension are an initial configuration of the health device and the aggregator, tokens for identification/authentication of users if these devices are to be shared and the implementation of certain IHE profiles in the aggregator to enable the integration of measurements in healthcare systems. As regards to the extension of SCP-ECG, it only adds a new section with selected security elements and syntax in order to protect the rest of file contents and provide proper role-based access control. The overhead introduced in the protected SCP-ECG is typically 2{13 % of the regular file size, and the extra delays to protect a newly generated SCP-ECG file and to access it for interpretation are respectively a 2{10 % and a 5 % of the regular delays. As regards to the signal-based security techniques developed, the embedding method is the basis for the proposal of a generic coding for tests composed of biomedical signals, periodic measurements and contextual information. This has been adjusted and evaluated with electrocardiogram and electroencephalogram-based tests, proving the objective clinical quality of the coded tests, the capacity of the coding-access system to operate in real-time (overall delays of 2 s for electrocardiograms and 3.3 s for electroencephalograms) and its high usability. Despite of the embedding of security and metadata to enable m-Health services, the compression ratios obtained by this coding range from ' 3 in real-time transmission to ' 5 in offline operation. Complementarily, keytagging permits associating information to images (and other signals) by means of keys in a secure and non-distorting fashion, which has been availed to implement security measures such as image authentication, integrity control and location of tampered areas, private captioning with role-based access control, traceability and copyright protection. The tests conducted indicate a remarkable robustness-capacity tradeoff that permits implementing all this measures simultaneously, and the compatibility of keytagging with JPEG2000 compression, maintaining this tradeoff while setting the overall keytagging delay in only ' 120 ms for any image size | evidencing the scalability of this technique. As a general conclusion, it has been demonstrated and illustrated with examples that there are various, complementary and structured manners to contribute in the implementation of suitable security levels for m-Health architectures with a moderate cost in budget, performance, interoperability and usability. The m-Health landscape is evolving permanently along all their dimensions, and this Thesis aims to do so with its security. Furthermore, the lessons learned herein may offer further guidance for the elaboration of more comprehensive and updated security schemes, for the extension of other biomedical standards featuring low emphasis on security or privacy, and for the improvement of the state of the art regarding signal-based protection methods and applications

Elaboración de metodologías, materiales y recursos didácticos para la docencia de la filosofía en educación secundaria, estudios de grado y estudios de posgrado

Memoria ID2022-061. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2022-2023

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Diseño de un contenedor digital optimizado para almacenamiento e intercambio de ADN humano

En la actualidad, la mejora de las técnicas de secuenciación de ADN y el aumento de los grupos de investigación han permitido el desarrollo de varias aplicaciones. En el ámbito de la e-salud, comienzan a catalogarse genes defectuosos que disparan la probabilidad de padecer enfermedades como cáncer, párkinson o diabetes. Analizando el genoma de un individuo, es posible detectar prematuramente estas enfermedades y llevar a cabo un tratamiento personalizado. Por otra parte, la comparación del genoma de un mismo individuo en distintos momentos de la vida permite detectar mutaciones (p.ej. debibas a radiación ionizante). Además, como el genoma de cada individuo es único y guarda estrecha relación con el de sus parientes, puede ser utilizado tanto en aplicaciones biométricas como para realizar estudios filogénicos. Para desarrollar estas aplicaciones, la secuencia de ADN es codificada digitalmente y se incorporan aquellos metadatos (datos personales, datos médicos, anotaciones sobre la secuencia, etc.) que sean pertinentes. Con este propósito, han surgido varios protocolos (HL7 genomics para e-salud, BSML, MAGE-ML) que permiten el almacenamiento e intercambio estandarizado de muestras de ADN. No obstante, éstos están diseñados para trabajar con muestras pequeñas (para aplicaciones específicas) y por ello no habilitan métodos de compresión. Además, no siempre incluyen mecanismos para la protección de los datos, tal como obliga la legislación vigente (en España, la LOPD). El objetivo de este Proyecto Fin de Carrera es diseñar un contenedor digital optimizado para el almacenamiento e intercambio de genomas humanos o partes de éstos. Éste podrá ser utilizado tanto para las aplicaciones antes descritas (p.ej. genética clínica y biometría) como para futuras aplicaciones por desarrollar. Existen tres elementos de gran interés en su diseño: la selección de un algoritmo de compresión sin pérdidas que permita reducir el tamaño del genoma (aprox. 3 GB), el desarrollo de un sistema robusto de seguridad y control de acceso según roles (p.ej. médico, investigador, sistema biométrico) y la capacidad de interoperar con los estándares ya existentes. Se implementará una interfaz gráfica que permita tanto la construcción como el acceso al contenedor según roles diferenciados. Finalmente se medirán los ratios de compresión de la secuencia genética, el overhead debido a los elementos de seguridad y los tiempos de construcción y acceso al contenedor para evaluar la calidad del diseño

Potential role of insulin receptor isoforms and IGF receptors in plaque instability of human and experimental atherosclerosis

Abstract Background Clinical complications associated with atherosclerotic plaques arise from luminal obstruction due to plaque growth or destabilization leading to rupture. We previously demonstrated that overexpression of insulin receptor isoform A (IRA) and insulin-like growth factor-I receptor (IGF-IR) confers a proliferative and migratory advantage to vascular smooth muscle cells (VSMCs) promoting plaque growth in early stages of atherosclerosis. However, the role of insulin receptor (IR) isoforms, IGF-IR or insulin-like growth factor-II receptor (IGF-IIR) in VSMCs apoptosis during advanced atherosclerosis remains unclear. Methods We evaluated IR isoforms expression in human carotid atherosclerotic plaques by consecutive immunoprecipitations of insulin receptor isoform B (IRB) and IRA. Western blot analysis was performed to measure IGF-IR, IGF-IIR, and α-smooth muscle actin (α-SMA) expression in human plaques. The expression of those proteins, as well as the presence of apoptotic cells, was analyzed by immunohistochemistry in experimental atherosclerosis using BATIRKO; ApoE−/− mice, a model showing more aggravated vascular damage than ApoE−/− mice. Finally, apoptosis of VSMCs bearing IR (IRLoxP+/+ VSMCs), or not (IR−/− VSMCs), expressing IRA (IRA VSMCs) or expressing IRB (IRB VSMCs), was assessed by Western blot against cleaved caspase 3. Results We observed a significant decrease of IRA/IRB ratio in human complicated plaques as compared to non-complicated regions. Moreover, complicated plaques showed a reduced IGF-IR expression, an increased IGF-IIR expression, and lower levels of α-SMA indicating a loss of VSMCs. In experimental atherosclerosis, we found a significant decrease of IRA with an increased IRB expression in aorta from 24-week-old BATIRKO; ApoE−/− mice. Furthermore, atherosclerotic plaques from BATIRKO; ApoE−/− mice had less VSMCs content and higher number of apoptotic cells. In vitro experiments showed that IGF-IR inhibition by picropodophyllin induced apoptosis in VSMCs. Apoptosis induced by thapsigargin was lower in IR−/− VSMCs expressing higher IGF-IR levels as compared to IRLoxP+/+ VSMCs. Finally, IRB VSMCs are more prone to thapsigargin-induced apoptosis than IRA or IRLoxP+/+ VSMCs. Conclusions In advanced human atherosclerosis, a reduction of IRA/IRB ratio, decreased IGF-IR expression, or increased IGF-IIR may contribute to VSMCs apoptosis, promoting plaque instability and increasing the risk of plaque rupture and its clinical consequences

MOESM1 of Potential role of insulin receptor isoforms and IGF receptors in plaque instability of human and experimental atherosclerosis

Additional file 1: Figure S1. Histological analysis of human carotid atherosclerotic plaques. Masson’s trichrome stain of representative non-complicated and complicated plaques of human carotid atherosclerosis. Different regions of the plaque are shown: M: media; F: fibrous region; A: atheroma; S: shoulder

Plan de fomento de la lectura

Se realizan una serie de actividades dirigidas a fomentar la lectura entre los alumnos de ESO. Las actividades propuestas tratan de presentar la lectura como actividad de ocio desligada de los aspectos académicos. Además, con ellas se espera mejorar la expresión oral y escrita de los alumnos. El plan de fomento de la lectura está compuesto de cinco acciones. La primera se denomina el libro del mes y consiste en que los alumnos lean una serie de libros a lo largo del curso y al finalizar la lectura realicen comentarios por escrito y participen en una tertulia. La segunda acción se llama Tutoría Literaria, en la que se leen fragmentos de libros con el objetivo de enganchar a los alumnos y que estos sigan en sus casas. La tercera actividad es el Viernes Literario, en la que todos los viernes se organizan actividades relacionadas con la difusión de la lectura como charlas con autores, presentaciones de libros, cuentacuentos, etc. El club de lectores es una acción dirigida a los profesores con el propósito de implicarles y difundir entre ellos la literatura actual. Y la última acción es la potenciación de la biblioteca del centro a través de la organización de exposiciones, de la elaboración del boletín de novedades y de su apertura fuera del horario lectivo. Se adjuntan materiales elaborados durante el proyecto.Madrid (Comunidad Autónoma). Consejería de Educación. Dirección General de Ordenación AcadémicaMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES

Relationship of Weather Types on the Seasonal and Spatial Variability of Rainfall, Runoff, and Sediment Yield in the Western Mediterranean Basin

Rainfall is the key factor to understand soil erosion processes, mechanisms, and rates. Most research was conducted to determine rainfall characteristics and their relationship with soil erosion (erosivity) but there is little information about how atmospheric patterns control soil losses, and this is important to enable sustainable environmental planning and risk prevention. We investigated the temporal and spatial variability of the relationships of rainfall, runoff, and sediment yield with atmospheric patterns (weather types, WTs) in the western Mediterranean basin. For this purpose, we analyzed a large database of rainfall events collected between 1985 and 2015 in 46 experimental plots and catchments with the aim to: (i) evaluate seasonal differences in the contribution of rainfall, runoff, and sediment yield produced by the WTs; and (ii) to analyze the seasonal efficiency of the different WTs (relation frequency and magnitude) related to rainfall, runoff, and sediment yield. The results indicate two different temporal patterns: the first weather type exhibits (during the cold period: autumn and winter) westerly flows that produce the highest rainfall, runoff, and sediment yield values throughout the territory; the second weather type exhibits easterly flows that predominate during the warm period (spring and summer) and it is located on the Mediterranean coast of the Iberian Peninsula. However, the cyclonic situations present high frequency throughout the whole year with a large influence extended around the western Mediterranean basin. Contrary, the anticyclonic situations, despite of its high frequency, do not contribute significantly to the total rainfall, runoff, and sediment (showing the lowest efficiency) because of atmospheric stability that currently characterize this atmospheric pattern. Our approach helps to better understand the relationship of WTs on the seasonal and spatial variability of rainfall, runoff and sediment yield with a regional scale based on the large dataset and number of soil erosion experimental stations.Spanish Government (Ministry of Economy and Competitiveness, MINECO) and FEDER Projects: CGL2014 52135-C3-3-R, ESP2017-89463-C3-3-R, CGL2014-59946-R, CGL2015-65569-R, CGL2015-64284-C2-2-R, CGL2015-64284-C2-1-R, CGL2016-78075-P, GL2008-02879/BTE, LEDDRA 243857, RECARE-FP7, CGL2017-83866-C3-1-R, and PCIN-2017-061/AEI. Dhais Peña-Angulo received a “Juan de la Cierva” postdoctoral contract (FJCI-2017-33652 Spanish Ministry of Economy and Competitiveness, MEC). Ana Lucia acknowledge the "Brigitte-Schlieben-Lange-Programm". The “Geoenvironmental Processes and Global Change” (E02_17R) was financed by the Aragón Government and the European Social Fund. José Andrés López-Tarazón acknowledges the Secretariat for Universities and Research of the Department of the Economy and Knowledge of the Autonomous Government of Catalonia for supporting the Consolidated Research Group 2014 SGR 645 (RIUS- Fluvial Dynamics Research Group). Artemi Cerdà thank the funding of the OCDE TAD/CRP JA00088807. José Martínez-Fernandez acknowledges the project Unidad de Excelencia CLU-2018-04 co-funded by FEDER and Castilla y León Government. Ane Zabaleta is supported by the Hydro-Environmental Processes consolidated research group (IT1029-16, Basque Government). This paper has the benefit of the Lab and Field Data Pool created within the framework of the COST action CONNECTEUR (ES1306)

Discovering HIV related information by means of association rules and machine learning

Acquired immunodeficiency syndrome (AIDS) is still one of the main health problems worldwide. It is therefore essential to keep making progress in improving the prognosis and quality of life of affected patients. One way to advance along this pathway is to uncover connections between other disorders associated with HIV/AIDS-so that they can be anticipated and possibly mitigated. We propose to achieve this by using Association Rules (ARs). They allow us to represent the dependencies between a number of diseases and other specific diseases. However, classical techniques systematically generate every AR meeting some minimal conditions on data frequency, hence generating a vast amount of uninteresting ARs, which need to be filtered out. The lack of manually annotated ARs has favored unsupervised filtering, even though they produce limited results. In this paper, we propose a semi-supervised system, able to identify relevant ARs among HIV-related diseases with a minimal amount of annotated training data. Our system has been able to extract a good number of relationships between HIV-related diseases that have been previously detected in the literature but are scattered and are often little known. Furthermore, a number of plausible new relationships have shown up which deserve further investigation by qualified medical experts

Diet quality index as a predictor of treatment efficacy in overweight and obese adolescents: The EVASYON study

The EVASYON Study Group.[Background & aim]: A diet quality index (DQI) is a tool that provides an overall score of an individual's dietary intake when assessing compliance with food-based dietary guidelines. A number of DQIs have emerged, albeit their associations with health-related outcomes are debated. The aim of the present study was to assess whether adherence to dietary intervention, and the overall quality of the diet, can predict body composition changes.[Methods]: To this purpose, overweight/obese adolescents (n = 117, aged: 13–16 years; 51 males, 66 females) were recruited into a multi-component (diet, physical activity and psychological support) family-based group treatment programme. We measured the adolescents' compliance and body composition at baseline and after 2 months (intensive phase) and 13 months (extensive phase) of follow-up. Also, at baseline, after 6 months, and at the end of follow-up we calculated the DQI.[Results]: Global compliance with the dietary intervention was 37.4% during the intensive phase, and 14.3% during the extensive phase. Physical activity compliance was 94.1% at 2-months and 34.7% at 13months and psychological support compliance were growing over the intervention period (10.3% intensive phase and 45.3% during extensive phase). Adolescents complying with the meal frequency criteria at the end of the extensive phase had greater reductions in FMI z-scores than those did not complying (Cohen's d = 0.53). A statistically significant association was observed with the diet quality index. DQI-A variation explained 98.1% of BMI z-score changes and 95.1% of FMI changes.[Conclusions]: We conclude that assessment of changes in diet quality could be a useful tool in predicting body composition changes in obese adolescents involved in a diet and physical activity intervention programme backed-up by psychological and family support.The study was supported by the Ministry of Health, Social Services and Equality via the Carlos III Institute of Health (FIS Grant PI051080, PI051579). The EVASYON study received the award for the best applied research project in 2009 from AESAN (Spanish Agency for Food Safety and Nutrition from the Spanish Ministry of Health and Consumer Affairs. The study was supported by Aragon's Regional Government (DGA, Diputación General de Aragón) and European Regional Development Fund.Peer reviewe