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Conventional drug solubilisation strategies limit the understanding of the full potential of poorly water-soluble drugs during drug screening. Here, I propose a screening approach in which poorly water-soluble drugs are entrapped in poly (2- (methacryloyloxyethyl phosphorylcholine)-poly(2-(diisopropylaminoethyl methacryate) (PMPC-PDPA) or Angiopep-2-poly(ethylene glycol)-PDPA (AP-PEG-PDPA) polymersomes (POs) to enhance drug solubility and facilitate intracellular delivery. By using a human paediatric glioma cell model, I demonstrated that PMPC-PDPA and AP-PEG-PDPA POs mediated intracellular delivery of cytotoxic and epigenetic drugs by receptor-mediate endocytosis. Additionally, when delivered in combination, drug-loaded PMPC-PDPA and AP-PEG-PDPA POs triggered both an enhanced drug efficacy and synergy compared to that of a conventional combinatorial screening. Hence, our comprehensive synergy analysis illustrates that our screening methodology, in which PMPC-PDPA and AP-PEG-PDPA POs are used for intracellular co-delivery of drugs, allows us to identify potent synergistic profiles of anticancer drugs.

Exercise interventions are effective in preventing falls, however, few have involved people living with dementia and explored their experiences. The aim of this PhD thesis was to fill this gap by exploring the experiences of dyads (formed of a person living with mild-to-moderate dementia and their informal carer) taking part in a Tai Chi intervention program, including class and home-practice. Participants' acceptability of and adherence to the Tai Chi intervention was studied alongside the Intervention Pilot Phase (3/4 weeks long) and the Randomised Controlled Trial Phase (20 weeks long) of the TAi ChI for people with demenTia (TACIT) Trial respectively, to inform how to enable their sustained participation in this exercise intervention. Participants recruited from localities in the South of England's experiences were explored using qualitative methods. These included field notes (at both phases) to record researchers' observations during the classes and participants (n = 10 dyads and n = 22 dyads, respectively) and instructors' feedback at the end of each class, 2 focus groups (n = 7 dyads, 1 at each site in the Pilot Intervention Phase) and 15 dyadic interviews (in the Randomised Controlled Trial Phase). Thematic analysis was used to inductively code the field notes and transcripts, which were then deductively linked to theory. Findings suggest that a dementia friendly approach to the design of the intervention based on repetition and individualised support enacted participants' enjoyment and mastery of Tai Chi. Dyads discovered a new common activity and valued the importance of incorporating home-practice into their routines. Facilitators of adherence to the intervention point towards participants' enjoyment, perceived impact on well- being, social interactions with people in a similar situation and qualities of the instructor. Main adherence barriers to the intervention were difficulty following the booklet provided to support their home-practice, as well as unexpected or recurrent health problems and competing commitments. In conclusion, people living with dementia and their informal carers could benefit from getting involved in a Tai Chi exercise program. Programmes that provide opportunities for practising Tai Chi in class and at home could provide a normalised shared interest to support communication, well-being, and quality of life.

Sumario: Introducción. 1. La formulación de una política exterior errónea: la Posición Común de 1996. 1.1. España y la Posición Común: Origen y Desarrollo. 1.2. Contexto político-internacional en el que se gesta la Posición Común. 1.3. Contenido de la Posición Común Europea hacia Cuba y las Relaciones UE-Cuba. 1.4. Gobiernos socialistas en España (2004-2012) y el cambio de actitud de la UE y de EEUU. 2. Una política más pragmática: el Acuerdo de Dialogo Político y Cooperación de 2016. 2.1. Los principios y propósitos en los que se sustenta el ADPC. 2.2. El Diálogo Político y la apertura del Diálogo sobre cooperación y política sectorial: componentes imprescindibles para asegurar las relaciones cubano-europeas. 2.3. El Comercio y la Cooperación Comercial: En busca de la intensificación de las relaciones económicas. Conclusiones.

Sustainable development is a notion which has an impact in the International Legal Order. In fact, it is an evolutive and cumulative concept. Its effects depend on how some structural principles of International Law are applied. Sustainable Development Goals (SDG), which were set down in 2015, offer an opportunity to regard the sustainable development as a «constitutional principle». As a consequence, rights and obligations could arise from this principle. The notion of sustainable development is reinforced thanks to SDG. Sustainable development various dimensions would indeed help to set it up as a fundamental principle, but, at the same time, however, they could weaken the meaning and scope of this principle. The International Community needs a principle by which the sustainable development is recognised and, at the same time, States obligations may be established, including, if necessary, international responsibility

La realidad de las instituciones económicas en África es muy compleja. La integración en este continente, aunque presenta características comunes con los esquemas de integración que tienen lugar en otras regiones del planeta, expresa, también, sus peculiaridades. Los Estados africanos han diseñado un marco de cooperación e integración económica que, a través de las diferentes regiones, tiende al establecimiento de una Comunidad económica africana, liderada desde la Unión Africana. El análisis de los diferentes procesos integracionistas en África revela no sólo la proliferación de estos acuerdos sino, también, el carácter eminentemente económico que, en la actualidad, tiene la integración africana. Los aspectos comerciales y económicos priman sobre los componentes de otra índole, aunque, en realidad, el objetivo último sea la integración política a escala continental. Los numerosos acuerdos económicos y las diferentes instituciones de esta naturaleza no facilitan una integración ordenada y sistemática y llega a constituir un obstáculo en los avances que precisa África para su desarrollo económico y social.