Self-deception as a mechanism for the maintenance of drug addiction

Resumen tomado de la publicaci??n

On intentional and social agents with graded attitudes

La principal contribución de esta Tesis es la propuesta de un modelo de agente BDI graduado (g-BDI) que permita especificar una arquitetura de agente capaz de representar y razonar con actitudes mentales graduadas. Consideramos que una arquitectura BDI más exible permitirá desarrollar agentes que alcancen mejor performance en entornos inciertos y dinámicos, al servicio de otros agentes (humanos o no) que puedan tener un conjunto de motivaciones graduadas. En el modelo g-BDI, las actitudes graduadas del agente tienen una representación explícita y adecuada. Los grados en las creencias representan la medida en que el agente cree que una fórmula es verdadera, en los deseos positivos o negativos permiten al agente establecer respectivamente, diferentes niveles de preferencias o de rechazo. Las graduaciones en las intenciones también dan una medida de preferencia pero en este caso, modelan el costo/beneficio que le trae al agente alcanzar una meta. Luego, a partir de la representación e interacción de estas actitudes graduadas, pueden ser modelados agentes que muestren diferentes tipos de comportamiento. La formalización del modelo g-BDI está basada en los sistemas multi-contextos. Diferentes lógicas modales multivaluadas se han propuesto para representar y razonar sobre las creencias, deseos e intenciones, presentando en cada caso una axiomática completa y consistente. Para tratar con la semántica operacional del modelo de agente, primero se definió un calculus para la ejecución de sistemas multi-contextos, denominado Multi-context calculus. Luego, mediante este calculus se le ha dado al modelo g-BDI semántica computacional. Por otra parte, se ha presentado una metodología para la ingeniería de agentes g-BDI en un escenario multiagente. El objeto de esta propuesta es guiar el diseño de sistemas multiagentes, a partir de un problema del mundo real. Por medio del desarrollo de un sistema recomendador en turismo como caso de estudio, donde el agente recomendador tiene una arquitectura g-BDI, se ha mostrado que este modelo es valioso para diseñar e implementar agentes concretos. Finalmente, usando este caso de estudio se ha realizado una experimentación sobre la flexibilidad y performance del modelo de agente g-BDI, demostrando que es útil para desarrollar agentes que manifiesten conductas diversas. También se ha mostrado que los resultados obtenidos con estos agentes recomendadores modelizados con actitudes graduadas, son mejores que aquellos alcanzados por los agentes con actitudes no-graduadas.

Sexual presence and intentional dynamics: deviant and non-deviant sexual self-regulation from the first person stance

Child molesters (n=13) and sexually non-deviant subjects (n=29) were immersed with virtual characters depicting relevant sexual features while their sexual arousal and gaze behaviour were assessed to characterize their sexual preferences and intentional dynamics. Sexual arousal was measured using circumferential penile plethysmography (PPG). Gaze behaviour dynamics was derived from average gaze radial angular deviation (GRAD) and GRAD coefficient of variation (GRADCV). Results show distinct sexual arousal profiles according to sexual preferences and point towards the existence of specific gaze behaviour dynamics guided by sexual intentions. Theoretical interpretations are based on the ecological psychology of J.J. Gibson and the integrated theory of sexual offending (Ward, 2009; Ward & Beech, 2006). Theoretical underpinnings coming from these approaches are advocated as being especially well suited to explain how virtual reality can help probing into child molesters’ phenomenology as lived from the first-person stance.

Efficacy of a combined drug therapy for ameliorating noise-induced hearing loss

Experiments investigated the median effective dose of antiepileptic drugs and synthetic glucocorticoids for the prevention and treatment of noise-induced hearing loss for C57BL/6J mice. We also tested the possible synergistic effects of combining drugs from the two drug families.

Scope and Limitations of The Co-Drug Approach to Topical Drug Delivery

Many currently available drugs show unfavourable physicochemical properties for delivery into or across the skin and temporary chemical modulation of the penetrant is one option to achieve improved delivery properties. Pro-drugs are chemical derivatives of an active drug which is covalently bonded to an inactive pro-moiety in order to overcome pharmaceutical and pharmacokinetic barriers. A pro-drug relies upon conversion within the body to release the parent active drug (and pro-moiety) to elicit its pharmacological effect. The main drawback of this approach is that the pro-moiety is essentially an unwanted ballast which, when released, can lead to adverse effects. The term ‘co-drug’ refers to two or more therapeutic compounds active against the same disease bonded via a covalent chemical linkage and it is this approach which is reviewed for the first time in the current article. For topically applied co-drugs, each moiety is liberated in situ, either chemically or enzymatically, once the stratum corneum barrier has been overcome by the co-drug. Advantages include synergistic modulation of the disease process, enhancement of drug delivery and pharmacokinetic properties and the potential to enhance stability by masking of labile functional groups. The amount of published work on co-drugs is limited but the available data suggest the co-drug concept could provide a significant therapeutic improvement in dermatological diseases. However, the applicability of the co-drug approach is subject to strict limitations pertaining mainly to the availability of compatible moieties and physicochemical properties of the overall molecule.

Combination therapy: opportunities and challenges for polymer-drug conjugates as anticancer nanomedicines.

The discovery of new molecular targets and the subsequent development of novel anticancer agents are opening new possibilities for drug combination therapy as anticancer treatment. Polymer-drug conjugates are well established for the delivery of a single therapeutic agent, but only in very recent years their use has been extended to the delivery of multi-agent therapy. These early studies revealed the therapeutic potential of this application but raised new challenges (namely, drug loading and drugs ratio, characterisation, and development of suitable carriers) that need to be addressed for a successful optimisation of the system towards clinical applications.

Polymer-drug conjugates for combination anticancer therapy: investigating the mechanism of action.

We developed a family of polymer-drug conjugates carrying the combination of the anticancer agent epirubicin (EPI) and nitric oxide (NO). EPI-PEG-(NO)8, carrying the highest content of NO, displayed greater activity in Caco-2 cells while it decreased toxicity against endothelium cells and cardiomyocytes with respect to free EPI. FACS and confocal microscopy confirmed conjugates internalization. Light scattering showed formation of micelle whose size correlated with internalization rate. EPI-PEG-(NO)8 showed increased bioavailability in mice compared to free EPI.