Contributions to presence-based systems for deploying ubiquitous communication services

Next-Generation Networks (NGNs) will converge the existing fixed and wireless networks. These networks rely on the IMS (IP Multimedia Subsystem), introduced by the 3GPP. The presence service came into being in instant messaging applications. A user¿s presence information consists in any context that is necessary for applications to handle and adapt the user's communications. The presence service is crucial in the IMS to deploy ubiquitous services. SIMPLE is the standard protocol for handling presence and instant messages. This protocol disseminates users' presence information through subscriptions, notifications and publications. SIMPLE generates much signaling traffic for constantly disseminating presence information and maintaining subscriptions, which may overload network servers. This issue is even more harmful to the IMS due to its centralized servers. A key factor in the success of NGNs is to provide users with always-on services that are seamlessly part of their daily life. Personalizing these services according to the users' needs is necessary for the success of these services. To this end, presence information is considered as a crucial tool for user-based personalization. This thesis can be briefly summarized through the following contributions: We propose filtering and controlling the rate of presence publications so as to reduce the information sent over access links. We probabilistically model presence information through Markov chains, and analyzed the efficiency of controlling the rate of publications that are modeled by a particular Markov chain. The reported results show that this technique certainly reduces presence overload. We mathematically study the amount of presence traffic exchanged between domains, and analyze the efficiency of several strategies for reducing this traffic. We propose an strategy, which we call Common Subscribe (CS), for reducing the presence traffic exchanged between federated domains. We compare this strategy traffic with that generated by other optimizations. The reported results show that CS is the most efficient at reducing presence traffic. We analyze the load in the number of messages that several inter-domain traffic optimizations cause to the IMS centralized servers. Our proposed strategy, CS, combined with an RLS (i.e., a SIMPLE optimization) is the only optimization that reduces the IMS load; the others increase this load. We estimate the efficiency of the RLS, thereby concluding that the RLS is not efficient under certain circumstances, and hence this optimization is discouraged. We propose a queuing system for optimizing presence traffic on both the network core and access link, which is capable to adapt the publication and notification rate based on some quality conditions (e.g, maximum delay). We probabilistically model this system, and validate it in different scenarios. We propose, and implement a prototype of, a fully-distributed platform for handling user presence information. This approach allows integrating Internet Services, such as HTTP or VoIP, and optimizing these services in an easy, user-personalized way. We have developed SECE (Sense Everything, Control Everything), a platform for users to create rules that handle their communications and Internet Services proactively. SECE interacts with multiple third-party services for obtaining as much user context as possible. We have developed a natural-English-like formal language for SECE rules. We have enhanced SECE for discovering web services automatically through the Web Ontology Language (OWL). SECE allows composing web services automatically based on real-world events, which is a significant contribution to the Semantic Web. The research presented in this thesis has been published through 3 book chapters, 4 international journals (3 of them are indexed in JCR), 10 international conference papers, 1 demonstration at an international conference, and 1 national conferenceNext-Generation Networks (NGNs) son las redes de próxima generación que soportaran la convergencia de redes de telecomunicación inalámbricas y fijas. La base de NGNs es el IMS (IP Multimedia Subsystem), introducido por el 3GPP. El servicio de presencia nació de aplicaciones de mesajería instantánea. La información de presencia de un usuario consiste en cualquier tipo de información que es de utilidad para manejar las comunicaciones con el usuario. El servicio de presencia es una parte esencial del IMS para el despliegue de servicios ubicuos. SIMPLE es el protocolo estándar para manejar presencia y mensajes instantáneos en el IMS. Este protocolo distribuye la información de presencia de los usuarios a través de suscripciones, notificaciones y publicaciones. SIMPLE genera mucho tráfico por la diseminación constante de información de presencia y el mantenimiento de las suscripciones, lo cual puede saturar los servidores de red. Este problema es todavía más perjudicial en el IMS, debido al carácter centralizado de sus servidores. Un factor clave en el éxito de NGNs es proporcionar a los usuarios servicios ubicuos que esten integrados en su vida diaria y asi interactúen con los usuarios constantemente. La personalización de estos servicios basado en los usuarios es imprescindible para el éxito de los mismos. Para este fin, la información de presencia es considerada como una herramienta base. La tesis realizada se puede resumir brevemente en los siguientes contribuciones: Proponemos filtrar y controlar el ratio de las publicaciones de presencia para reducir la cantidad de información enviada en la red de acceso. Modelamos la información de presencia probabilísticamente mediante cadenas de Markov, y analizamos la eficiencia de controlar el ratio de publicaciones con una cadena de Markov. Los resultados muestran que este mecanismo puede efectivamente reducir el tráfico de presencia. Estudiamos matemáticamente la cantidad de tráfico de presencia generada entre dominios y analizamos el rendimiento de tres estrategias para reducir este tráfico. Proponemos una estrategia, la cual llamamos Common Subscribe (CS), para reducir el tráfico de presencia entre dominios federados. Comparamos el tráfico generado por CS frente a otras estrategias de optimización. Los resultados de este análisis muestran que CS es la estrategia más efectiva. Analizamos la carga en numero de mensajes introducida por diferentes optimizaciones de tráfico de presencia en los servidores centralizados del IMS. Nuestra propuesta, CS, combinada con un RLS (i.e, una optimización de SIMPLE), es la unica optimización que reduce la carga en el IMS. Estimamos la eficiencia del RLS, deduciendo que un RLS no es eficiente en ciertas circunstancias, en las que es preferible no usar esta optimización. Proponemos un sistema de colas para optimizar el tráfico de presencia tanto en el núcleo de red como en la red de acceso, y que puede adaptar el ratio de publicación y notificación en base a varios parametros de calidad (e.g., maximo retraso). Modelamos y analizamos este sistema de colas probabilísticamente en diferentes escenarios. Proponemos una arquitectura totalmente distribuida para manejar las información de presencia del usuario, de la cual hemos implementado un prototipo. Esta propuesta permite la integracion sencilla y personalizada al usuario de servicios de Internet, como HTTP o VoIP, asi como la optimizacón de estos servicios. Hemos desarrollado SECE (Sense Everything, Control Everything), una plataforma donde los usuarios pueden crear reglas para manejar todas sus comunicaciones y servicios de Internet de forma proactiva. SECE interactúa con una multitud de servicios para conseguir todo el contexto possible del usuario. Hemos desarollado un lenguaje formal que parace como Ingles natural para que los usuarios puedan crear sus reglas. Hemos mejorado SECE para descubrir servicios web automaticamente a través del lenguaje OWL (Web Ontology Language)

Use of microperimetry to evaluate hydroxychloroquine and chloroquine retinal toxicity

To check the ability of microperimetry to detect early retinal damage in patients with rheumatism taking hydroxychloroquine (HCQ), chloroquine (CQ), or both, and to describe the microperimetric alterations attributable to these drugs and their correlation with some clinical variables

Ecto-calreticulin expression in multiple myeloma correlates with a failed anti-tumoral immune response and bad prognosis

Immunogenic cell death (ICD) has been proposed to be a crucial process for antitumor immunosurveillance. ICD is characterized by the exposure and emission of Damage Associated Molecular Patterns (DAMP), including calreticulin (CRT). A positive correlation between CRT exposure or total expression and improved anticancer immunosurveillance has been found in certain cancers, usually accompanied by favorable patient prognosis. In the present study, we sought to evaluate CRT levels in the plasma membrane of CD38+ bone marrow mononuclear cells (BMMCs) isolated from 71 patients with varying degrees of multiple myeloma (MM) disease and examine the possible relationship between basal CRT exposure and the bone marrow immune microenvironment, as well as its connection with different clinical markers. Data show that increased levels of cell surface-CRT were associated with more aggressive clinical features and with worse clinical prognosis in MM. High CRT expression in MM cells was associated with increased infiltration of NK cells, CD8+ T lymphocytes and dendritic cells (DC), indicative of an active anti-tumoral immune response, but also with a significantly higher presence of immunosuppressive Treg cells and increased expression of PD-L1 in myeloma cells

Design of a UMTS/GPRS Assisted Mesh Network (UAMN)

Wireless Mesh or multi-hop networks (WMNs) are well known thanks to its simplicity on deployment and the lack of infrastructure. These two advantages come with some drawbacks. WMNs have limitations with the support of Quality of Service (QoS), they do not assure coverage or even connectivity, and security, management and monitoring are not considered key requirements. In order to benefit of mesh networks and use them as an operator graded network, it is necessary to either improve mesh networks to fulfill all these requirements or use an alternative network that offers full availability, connectivity and security to assist the mesh network. Considering the two options, the second is the one selected making use of GPRS/UMTS as an assistant network. The document describes a set of requirements and the design of the functionalities needed to build an operator graded network using the cellular GPRS/UMTS. The aspects covered in the design are: security, quality of service, mobility, self configuration and optimization. The last point, optimization, is not directly involved with mesh networking, but it is an improvement easy to achieve when using a gateway node to access the Internet through a GPRS/UMTS connection. The design of the solution not only considers functionality, but also feasibility employing of the shelve elements. The mesh nodes and gateways are built on top of Linux operating system with the aim to reuse previous results and open source software. The final objective of the project is to build a usable system to be used as a proof of concept.Peer Reviewe

Development of an activity disease score in patients with uveitis (UVEDAI)

To develop a disease activity index for patients with uveitis (UVEDAI) encompassing the relevant domains of disease activity considered important among experts in this field. The steps for designing UVEDAI were: (a) Defining the construct and establishing the domains through a formal judgment of experts, (b) A two-round Delphi study with a panel of 15 experts to determine the relevant items, (c) Selection of items: A logistic regression model was developed that set ocular inflammatory activity as the dependent variable. The construct "uveitis inflammatory activity" was defined as any intraocular inflammation that included external structures (cornea) in addition to uvea. Seven domains and 15 items were identified: best-corrected visual acuity, inflammation of the anterior chamber (anterior chamber cells, hypopyon, the presence of fibrin, active posterior keratic precipitates and iris nodules), intraocular pressure, inflammation of the vitreous cavity (vitreous haze, snowballs and snowbanks), central macular edema, inflammation of the posterior pole (the presence and number of choroidal/retinal lesions, vascular inflammation and papillitis), and global assessment from both (patient and physician). From all the variables studied in the multivariate model, anterior chamber cell grade, vitreous haze, central macular edema, inflammatory vessel sheathing, papillitis, choroidal/retinal lesions and patient evaluation were included in UVEDAI. UVEDAI is an index designed to assess the global ocular inflammatory activity in patients with uveitis. It might prove worthwhile to motorize the activity of this extraarticular manifestation of some rheumatic diseases

Comparative Study of Infliximab Versus Adalimumab in Refractory Uveitis Due to Behçet's Disease: National Multicenter Study of 177 Cases

Objective: To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as a first-line biologic drug over 1 year of treatment in a large series of patients with refractory uveitis due to Behçet's disease (BD). Methods: We conducted an open-label multicenter study of IFX versus ADA for BD-related uveitis refractory to conventional nonbiologic treatment. IFX or ADA was chosen as the first-line biologic agent based on physician and patient agreement. Patients received 3-5 mg/kg intravenous IFX at 0, 2, and 6 weeks and every 4-8 weeks thereafter, or 40 mg subcutaneous ADA every other week without a loading dose. Ocular parameters were compared between the 2 groups. Results: The study included 177 patients (316 affected eyes), of whom 103 received IFX and 74 received ADA. There were no significant baseline differences between treatment groups in main demographic features, previous therapy, or ocular sign severity. After 1 year of therapy, we observed an improvement in all ocular parameters in both groups. However, patients receiving ADA had significantly better outcomes in some parameters, including improvement in anterior chamber inflammation (92.31% versus 78.18% for IFX; P = 0.06), improvement in vitritis (93.33% versus 78.95% for IFX; P = 0.04), and best-corrected visual acuity (mean ± SD 0.81 ± 0.26 versus 0.67 ± 0.34 for IFX; P = 0.001). A nonsignificant difference was seen for macular thickness (mean ± SD 250.62 ± 36.85 for ADA versus 264.89 ± 59.74 for IFX; P = 0.15), and improvement in retinal vasculitis was similar between the 2 groups (95% for ADA versus 97% for IFX; P = 0.28). The drug retention rate was higher in the ADA group (95.24% versus 84.95% for IFX; P = 0.042). Conclusion: Although both IFX and ADA are efficacious in refractory BD-related uveitis, ADA appears to be associated with better outcomes than IFX after 1 year of follow-up

Bioequivalence Study of Clonazepam 2 mg Tablets in Colombian Healthy Volunteers

RESUMEN: Con el fin de determinar la bioequivalencia de dos formulaciones de tabletas de 2 mg de clonazepam: Sedatril®/Clonazepam MK (Tecnoquímicas S. A., Cali, Colombia) como producto de prueba y Rivotril® (Roche Químicos e Farmacéuticas S. A., Río de Janeiro, Brasil), como producto de referencia, se realizó un estudio de bioequivalencia en 26 voluntarios sanos. Los productos de prueba y de referencia se administraron en condiciones de ayuno de acuerdo con un diseño cruzado aleatorio de dosis única, con dos secuencias, dos tratamientos y un período de lavado de 28 días. Las muestras de sangre se obtuvieron desde las 0 hasta las 96 horas después de la administración del medicamento. Los niveles plasmáticos de clonazepam se determinaron con un método validado por cromatografía líquida de alta eficiencia con detección ultravioleta (HPLC/UV, siglas en inglés). Los parámetros farmacocinéticos ABC0-96, ABC0-∞, Cmax , Tmax, t1/2, and ke se determinaron de los perfiles plasmáticos concentración-tiempo por el método no compartimental. El test de bioequivalencia se realizó con los datos transformados a logaritmo natural (ln) de ABC0-∞ and Cmax. Los intervalos de confianza del 90% para la relación producto de prueba/producto de referencia fueron de 87,9% a 103,6% y 84,4% a 104,0%, respectivamente. Estos resultados estuvieron dentro de los rangos de aceptación del 80,0% al 125%, establecidos por la FDA y se concluyó que ambos productos son bioequivalentes.ABSTRACT: In order to determine the bioequivalence of two formulations of clonazepam 2 mg tablets: Sedatril® / Clonazepam MK (Tecnoquímicas S. A., Cali, Colombia) as a test product and Rivotril® (Roche Químicos e Farmacêuticas S. A., Rio de Janeiro, Brazil) as a reference product, a bioavailability study was performed in 26 healthy volunteers. Test and reference products were administered under fasting conditions following a single dose, two-sequences, two treatments, crossover randomized design with a 28-day-washout period. Blood samples were obtained from 0 to 96 hours after dosing. Plasma clonazepam levels were determined by a validated high performance liquid chromatography with UV detection method (HPLC/UV). ABC0-96, ABC0-∞, Cmax, Tmax, t1/2, and ke , pharmacokinetic parameters were determined from plasma level-time profiles by a noncompartmental method. ln-trasformed ABC0-∞ and Cmax were tested for bioequivalence. 90%-confidence intervals for test/reference ratio of these parameters were 87.9% to 103.6% and 84.4% to 104.0%, respectively. These results were within the FDA acceptance range of 80% to 125% and it was concluded that both products were bioequivalent

Cross-disease Meta-analysis of Genome-wide Association Studies for Systemic Sclerosis and Rheumatoid Arthritis Reveals IRF4 as a New Common Susceptibility Locus

Objectives: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that share clinical and immunological characteristics. To date, several shared SSc- RA loci have been identified independently. In this study, we aimed to systematically search for new common SSc-RA loci through an inter-disease meta-GWAS strategy. Methods: We performed a meta-analysis combining GWAS datasets of SSc and RA using a strategy that allowed identification of loci with both same-direction and opposingdirection allelic effects. The top single-nucleotide polymorphisms (SNPs) were followed-up in independent SSc and RA case-control cohorts. This allowed us to increase the sample size to a total of 8,830 SSc patients, 16,870 RA patients and 43,393 controls. Results: The cross-disease meta-analysis of the GWAS datasets identified several loci with nominal association signals (P-value < 5 x 10-6), which also showed evidence of association in the disease-specific GWAS scan. These loci included several genomic regions not previously reported as shared loci, besides risk factors associated with both diseases in previous studies. The follow-up of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these two diseases (Pcombined = 3.29 x 10-12). In addition, the analysis of the biological relevance of the known SSc-RA shared loci pointed to the type I interferon and the interleukin 12 signaling pathways as the main common etiopathogenic factors. Conclusions: Our study has identified a novel shared locus, IRF4, for SSc and RA and highlighted the usefulness of cross-disease GWAS meta-analysis in the identification of common risk loci