Brain metastases have a poor prognosis and are associated with a high morbidity and mortality rate in cancer patients. The metastatic pathways and the role of the blood-brain barrier (BBB) during metastasis are not known. There is a need to better understand cancer brain metastasis and develop effective therapeutics. With META-BRAIN, I will create a human-based in vitro platform that spans the entire cancer cell journey from lung to brain and use it to address three key questions: (1) How does cancer metastasize to the brain? (2) What is the role of the BBB in cancer metastasis to the brain? and (3) How and when can cancer metastasize be treated? The META-BRAIN will provide answers to these questions by developing a truly physiologically relevant human cell-based model, that for the first time, maps the entire cancer metastasis cascade and that can also be used to study novel target proteins at the blood-tumor barrier (BTB). This model will also be used to develop novel shuttle systems for drug delivery to the brain. By integrating state-of-the-art technologies from life sciences and engineering, META-BRAIN has three main objectives: (1) Develop an in vitro model that recapitulates the metastatic cascade with in vivo-like morphology and function to study how cancer metastases to the brain, (2) Investigate the role of extracellular vesicle (EV) and circulating tumor cell (CTC) migration events with a focus on their interactions with brain endothelia, and (3) Identification of novel target proteins specific to cancerous brain and development of novel nano-shuttle systems targeting these proteins to deliver therapeutics to the brain. In summary, META-BRAIN will lead the way in the development of physiologically relevant models for other brain-invasive metastatic cancers, open new avenues for the development of therapeutic and diagnostic approaches and pave the way for nano-shuttle formulations specifically designed to overcome the BBB and BTB.

Mediation is an alternative dispute resolution (ADR) technique. If two or more parties are in disagreement, then they can take the case to a court and let the judge give the final decision. Alternatively, the disputing parties can get the help of an experienced, neutral third party (i.e., the mediator) who facilitates a negotiation and help the disagreeing parties reach an agreement short of litigation. The mediation process is private and confidential, possibly enforced by law (European Mediation Directive 2008). The rising popularity of mediation can be explained by the increasing workload of courts, by the fact that mediation is less costly than litigation, and by the desire of some control over the final decision. This proposed project aims to make a state-of-the-art economic analysis of mediation in civil and commercial matters. The main motivation behind this project is to determine optimal strategies and methods for eliminating the inefficiencies that possibly arise in mediation practices.

To discover effective strategies against antimicrobial resistance, a deeper understanding of microbial behaviour in their natural ecologies is crucial. The essential technological bottleneck that has limited our capability to explore this issue is the microenvironment provided by batch culture assays. They are incapable of mimicking natural microhabitats, quantifying individual bacteria, and revealing antibiotic resistance. Therefore, development of a theoretical and experimental framework that mimics the natural microecology of bacteria and measuring their antibiotic response to predict optimum survival strategies will provide valuable tools to investigate bacterial individuality and their changing response to antibiotics in realistic microenvironments.