Personalized medicine: Has it started yet? A reconstruction of the early history

Within the last few years the field personalized medicine entered the stage. Accompanied with great hopes and expectations it is believed that this field may have the potential to revolutionize medical and clinical care by utilizing genomics information about the individual patients themselves. In this paper, we reconstruct the early footprints of personalized medicine as reflected by information retrieved from PubMed and Google Scholar. That means we are providing a data-driven perspective of this field to estimate its current status and potential problems.

Molecular Subtypes and Personalized Therapy in Metastatic Colorectal Cancer

Development of colorectal cancer occurs via a number of key pathways, with the clinicopathological features of specific subgroups being driven by underlying molecular changes. Mutations in key genes within the network of signalling pathways have been identified; however, therapeutic strategies to target these aberrations remain limited. As understanding of the biology of colorectal cancer has improved, this has led to a move toward broader genomic testing, collaborative research and innovative, adaptive clinical trial design. Recent developments in therapy include the routine adoption of wider mutational spectrum testing prior to use of targeted therapies and the first promise of effective immunotherapy for colorectal cancer patients. This review details current biomarkers in colorectal cancer for molecular stratification and for treatment allocation purposes, including open and planned precision medicine trials. Advances in our understanding, therapeutic strategy and technology will also be outlined.

Designing personalized video-based crossmedia informal learning environments beyond iTV

Tese de doutoramento, Informática (Engenharia Informática), Universidade de Lisboa, Faculdade de Ciências, 2014

Mobile application to provide personalized sightseeing tours

Tourist recommendation systems have been growing over the last years, mainly because of the use of mobile devices to get user context. This work discuss some of the most relevant systems on the field and presents PSiS Mobile, which is a mobile recommendation and planning application designed to support a tourist during his vacations. It provides recommendations about points of interest to visit based on tourist preferences and on user and sight context. Also, it suggests a visit planning which can be dynamically adapted based on current user and sight context. This tool works like a journey dairy since it records the tourist moves and tasks to help him remember how the trip was like. To conclude, some field experiences will be presented.

Personalized public transportation information

Thesis to obtain the Master of Science Degree in Computer Science and Engineering

Top Three Pharmacogenomics and Personalized Medicine Applications at the Nexus of Renal Pathophysiology and Cardiovascular Medicine.

Pharmacogenomics is a field with origins in the study of monogenic variations in drug metabolism in the 1950s. Perhaps because of these historical underpinnings, there has been an intensive investigation of 'hepatic pharmacogenes' such as CYP450s and liver drug metabolism using pharmacogenomics approaches over the past five decades. Surprisingly, kidney pathophysiology, attendant diseases and treatment outcomes have been vastly under-studied and under-theorized despite their central importance in maintenance of health, susceptibility to disease and rational personalized therapeutics. Indeed, chronic kidney disease (CKD) represents an increasing public health burden worldwide, both in developed and developing countries. Patients with CKD suffer from high cardiovascular morbidity and mortality, which is mainly attributable to cardiovascular events before reaching end-stage renal disease. In this paper, we focus our analyses on renal function before end-stage renal disease, as seen through the lens of pharmacogenomics and human genomic variation. We herein synthesize the recent evidence linking selected Very Important Pharmacogenes (VIP) to renal function, blood pressure and salt-sensitivity in humans, and ways in which these insights might inform rational personalized therapeutics. Notably, we highlight and present the rationale for three applications that we consider as important and actionable therapeutic and preventive focus areas in renal pharmacogenomics: 1) ACE inhibitors, as a confirmed application, 2) VDR agonists, as a promising application, and 3) moderate dietary salt intake, as a suggested novel application. Additionally, we emphasize the putative contributions of gene-environment interactions, discuss the implications of these findings to treat and prevent hypertension and CKD. Finally, we conclude with a strategic agenda and vision required to accelerate advances in this under-studied field of renal pharmacogenomics with vast significance for global public health.

Personalized approaches to active immunotherapy in cancer

Immunotherapy is emerging as a promising anti-cancer curative modality. However, in contrast to recent advances obtained employing checkpoint blockade agents and T cell therapies, clinical efficacy of therapeutic cancer vaccines is still limited. Most vaccination attempts in the clinic represent "off-the shelf" approaches since they target common "self" tumor antigens, shared among different patients. In contrast, personalized approaches of vaccination are tailor-made for each patient and in spite being laborious, hold great potential. Recent technical advancement enabled the first steps in the clinic of personalized vaccines that target patient-specific mutated neo-antigens. Such vaccines could induce enhanced tumor-specific immune response since neo-antigens are mutation-derived antigens that can be recognized by high affinity T cells, not limited by central tolerance. Alternatively, the use of personalized vaccines based on whole autologous tumor cells, overcome the need for the identification of specific tumor antigens. Whole autologous tumor cells could be administered alone, pulsed on dendritic cells as lysate, DNA, RNA or delivered to dendritic cells in-vivo through encapsulation in nanoparticle vehicles. Such vaccines may provide a source for the full repertoire of the patient-specific tumor antigens, including its private neo-antigens. Furthermore, combining next-generation personalized vaccination with other immunotherapy modalities might be the key for achieving significant therapeutic outcome.

Wireless privacy and personalized location-based services: the challenge of translating the legal framework into business practices

L'avancement des communications sans-fil permet l'obtention de nouveaux services bases sur l'habileté des fournisseurs de services sans-fil à déterminer avec précision, et avec l'utilisation de technologies de pistage, la localisation et position géographiquement d'appareils sans-fil Cette habileté permet d'offrir aux utilisateurs de sans-fil de nouveaux services bases sur la localisation et la position géographique de leur appareil. Le développement des services basés sur la localisation des utilisateurs de sans-fil soulevé certains problèmes relatifs à la protection de la vie privée qui doivent être considérés. En effet, l'appareil sans-fil qui suit et enregistre les mouvements de I 'utilisateur permet un système qui enregistre et entrepose tous les mouvements et activités d'un tel utilisateur ou encore qui permet l'envoi de messages non anticipes à ce dernier. Pour ce motif et afin de protéger la vie privée des utilisateurs de sans-fil, une compagnie désirant développer ou déployer une technologie permettant d'offrir ce genre de services personnalisés devra analyser l'encadrement légal touchant la protection des données personnelles--lequel est dans certains cas vague et non approprié à ce nouveau contexte--ainsi que la position de l'industrie dans ce domaine, et ce, afin d'être en mesure de traduire cet encadrement en pratiques commerciales. Cette analyse permettra d'éclairer le fournisseur de ces services sur la façon d'établir son modèle d'affaires et sur le type de technologie à développer afin d'être en mesure de remédier aux nouveaux problèmes touchant la vie privée tout en offrant ces nouveaux services aux utilisateurs de sans-fil.

Personalized 3D reconstruction of the rib cage for clinical assessment of trunk deformities

Scoliosis is a 3D deformity of the spine and rib cage. Extensive validation of 3D reconstruction methods of the spine from biplanar radiography has already been published. In this article, we propose a novel method to reconstruct the rib cage, using the same biplanar views as for the 3D reconstruction of the spine, to allow clinical assessment of whole trunk deformities. This technique uses a semi-automatic segmentation of the ribs in the postero-anterior X-ray view and an interactive segmentation of partial rib edges in the lateral view. The rib midlines are automatically extracted in 2D and reconstructed in 3D using the epipolar geometry. For the ribs not visible in the lateral view, the method predicts their 3D shape. The accuracy of the proposed method has been assessed using data obtained from a synthetic bone model as a gold standard and has also been evaluated using data of real patients with scoliotic deformities. Results show that the reconstructed ribs enable a reliable evaluation of the rib axial rotation, which will allow a 3D clinical assessment of the spine and rib cage deformities.

Managing Quality Properties of Web Service Compositions

Web services from different partners can be combined to applications that realize a more complex business goal. Such applications built as Web service compositions define how interactions between Web services take place in order to implement the business logic. Web service compositions not only have to provide the desired functionality but also have to comply with certain Quality of Service (QoS) levels. Maximizing the users' satisfaction, also reflected as Quality of Experience (QoE), is a primary goal to be achieved in a Service-Oriented Architecture (SOA). Unfortunately, in a dynamic environment like SOA unforeseen situations might appear like services not being available or not responding in the desired time frame. In such situations, appropriate actions need to be triggered in order to avoid the violation of QoS and QoE constraints. In this thesis, proper solutions are developed to manage Web services and Web service compositions with regard to QoS and QoE requirements. The Business Process Rules Language (BPRules) was developed to manage Web service compositions when undesired QoS or QoE values are detected. BPRules provides a rich set of management actions that may be triggered for controlling the service composition and for improving its quality behavior. Regarding the quality properties, BPRules allows to distinguish between the QoS values as they are promised by the service providers, QoE values that were assigned by end-users, the monitored QoS as measured by our BPR framework, and the predicted QoS and QoE values. BPRules facilitates the specification of certain user groups characterized by different context properties and allows triggering a personalized, context-aware service selection tailored for the specified user groups. In a service market where a multitude of services with the same functionality and different quality values are available, the right services need to be selected for realizing the service composition. We developed new and efficient heuristic algorithms that are applied to choose high quality services for the composition. BPRules offers the possibility to integrate multiple service selection algorithms. The selection algorithms are applicable also for non-linear objective functions and constraints. The BPR framework includes new approaches for context-aware service selection and quality property predictions. We consider the location information of users and services as context dimension for the prediction of response time and throughput. The BPR framework combines all new features and contributions to a comprehensive management solution. Furthermore, it facilitates flexible monitoring of QoS properties without having to modify the description of the service composition. We show how the different modules of the BPR framework work together in order to execute the management rules. We evaluate how our selection algorithms outperform a genetic algorithm from related research. The evaluation reveals how context data can be used for a personalized prediction of response time and throughput.

Spa Rituales Ancestrales AüA S.A.S.

Las practicas ancestrales de las culturas precolombinas cada día son mas validas en su aplicación actual para la medicina alternativa, orientada al bienestar y la salud, es un hecho que en los últimos años se observa un gran crecimiento de endemias de estrés que se presentan bajo determinadas circunstancias propias del sistema actual de vida urbana y actividades cotidianas, ocasionando recargas de tensión como respuesta a la supervivencia en un mundo agitado. La somatizacion del estrés se traduce en enfermedades fisiológicas, emocionales y anímicas, consideradas peligrosas y causantes de altos índices de morbilidad y mortalidad. AúA S.A.S. se crea como solución a este gran conflicto que azota a la humanidad, así se han incrementado las instalaciones de diversos Spa (Salud por agua) como establecimientos de bienestar y esparcimiento que incluyen terapias no solo físicas sino mentales y emocionales como un sistema holístico der salud. En los últimos años y gracias a las facilidades de movilidad y comunicaciones se observa un crecimiento acelerado del turismo de salud como sector de talla mundial, el cual apunta a un mayor desarrollo tanto a nivel nacional como internacional. Las visitas de turistas al país en interés de realizarse procedimientos tanto estéticos como médicos, permite identificar una gran oportunidad de negocio con visión sostenible y perdurable ante un futuro prometedor. En este sentido, se presenta la instauración de un Spa con rituales ancestrales como un establecimiento de salud (turismo de salud) que preste servicios a personas tanto colombianas como extranjeras interesadas en vivir una experiencia con tratamientos de relajación (turismo de bienestar). Si bien el gobierno ha impulsado nuevas políticas encaminadas al fomento de la competitividad en Colombia, a través de sectores de talla mundial, donde el turismo de salud se presenta con un fuerte potencial de crecimiento. El Programa de Transformación Productiva, es un ejemplo de lo anteriormente expresado como estrategia para lograr el desarrollo empresarial, crecimiento económico y la generación de más y mejores empleos en Colombia. AüA S.A.S ofrece servicios únicos con tiempos óptimos para resultados efectivos de relajación y bienestar, así como espacios adecuados, inspirados en los paisajes de la sierra nevada de Santa Marta y ecosistemas de la costa Caribe, teniendo un contacto más cercano con la naturaleza y sus elementos. Además de una atención y acompañamiento personalizado y servicios gratuitos de asesorías post-venta, creando un servicio nuevo de reeducación dentro del Spa y con material de cortesía dado, donde a través de libros, artículos, publicaciones, DVD y talleres a realizar el cliente cambiara su conciencia, como componentes diferenciadores y de valor agregado, saliendo de su estado patológico y con alto cubrimiento en la satisfacción de sus necesidades, creando fidelidad al cliente para que regrese. Así, en lo posible con esta información destacada de las encuestas, dentro de la investigación de mercados realizada, se puede determinar que la participación en el mercado es del 75%. El equipo emprendedor está conformado por Rosa Marina Lozano Socarrás, estudiante de Administración de Negocios Internacionales de la Universidad del Rosario. El proyecto arroja una rentabilidad del 58,22% promedio anual. El indicador VAN, determina que el proyecto arroja 60 Millones adicionales al invertir los recursos en este proyecto que en uno que rente el 33% anual, por lo tanto se sugiere continuar con el proyecto. Teniendo el indicador del Valor Presente Neto, para su cálculo es necesario la Tasa de descuento o Tasa de Interés de Oportunidad siendo del 33%, teniendo un valor de $ 60.278.254. La metodología empleada en el trabajo de grado se denota en la guía y lineamientos establecidos por el Centro de Emprendimiento de la Universidad del Rosario. Las fuentes primarias se destaca en la información de investigación de mercados a partir de encuestas, así como análisis del sector y competidores. La información secundaria se denota en el Plan de Negocios del subsector turismo de bienestar dado a conocer por el Ministerio de Industria, Comercio y Turismo.