Scientific background: It has been recognized that the blood brain barrier (BBB) presents a major obstacle to the entry of therapeutic molecules into the central nervous system (CNS). Recently, it has been discovered that, using ultrasound exposure with the presence of microbubbles to locally enhance acoustic cavitation in CNS capillaries, the CNS-blood permeability can be significantly enhanced due to the temporal opening of the blood brain barrier, thus providing a promising strategy to increase delivery of therapeutic agents into brain tumors. In consequence, understanding the mechanisms underlying molecular uptake stimulation and ultrasound-based cell modification in brain tissue is crucial, with the key requirement of a better control of the diverse aspects of the cavitation phenomenon. Given the complexity of acoustic cavitation phenomenon and drug delivery issue into brain, it is important to (i) monitor and control in-vitro and in-vivo cavitation activity, (ii) study the ultrasound-induced uptake stimulation effect on BBB-mimicking cell monolayers and (iii) evaluate the in-vivo performance of ultrasound-based BBB penetration. Description of the project: We plan to design and implement a cavitation-controlled device to facilitate ultrasound-based cell therapy, with a particular focus on the BBB opening by ultrasound. Firstly, we propose to conceive and implement an acoustic cavitation control system based on the detection of the bubble cloud, the differentiation between oscillating and collapsing bubbles and the quantification of bubble activity. This requires to study the physical aspect of cavitation phenomenon in both stable (oscillating) or inertial (collapsing) cavitation regimes. Once the appropriate indicator of each cavitation regime identified, its real-time monitoring and feedback control will be implemented on diverse technological devices for in-vitro or in-vivo applications. Secondly, the cavitation regime enhancing either brain gene therapy or BBB permeabilization would be clarified by using two specific cell line monolayers that have been found to be useful predictors of blood brain barrier permeability. The cell growth, proliferation and the molecular uptake changes induced by a given cavitation state will be followed through video-microscopy in classical two-dimensional (2D) cell cultures on classical culture substrata. The possible intracellular pathways for cavitation-induced molecular uptake will be explored by studying three major endocytosis pathways and the ultrasound-induced modulation of gene expression within cells. Finally, by employing the cavitation-controlled device, BBB will be temporarily compromised to allow successful delivery of DNA into the brain parenchyma and subsequent gene expression in brain. To reach subsequent amount of gene expression, the possibility of using smartly designed polymers will be explored to control the efficiency and expression duration of transfected DNA. The efficiency of such molecule delivery into the brain by real-time controlled focused ultrasound will be evaluated in-vivo using neurodegenerative disease animal model. Expected results: Using the proposed approach, we believe that the ultrasound-induced bioeffects could be significantly increased, as the chaotic behavior of cavitation process would be controlled. We should be able to highlight relevant biophysical and acoustical parameters quantifying ultrasound-induced cell modification and molecular uptake stimulation, depending on the external mechanical stress which cells were submitted to. Concerning the applications, brain tumors are characterized by marked resistance to radiation and chemotherapy, so that novel therapeutic approaches should be developed. By controlling cavitation process and the induced bioeffects, this project and the in-vivo technological designs are expected to enlarge the potential of therapeutic ultrasound in the field, with real societal impact.

Many people with dementia face challenges in trying to live with such a socially stigmatising diagnosis. The World Alzheimer's Report (2011) suggests that when people with dementia and their families are well prepared and supported around the diagnosis and post diagnosis, then initial feelings of shock, anger and grief are balanced by a sense of reassurance and empowerment. However, how (and if) people are told they have dementia varies widely depending on national policy and practice. Effective diagnosis sharing is a fundamental first step in any person centred approach to dementia care. Many countries are moving away from medical approaches to give more focus on person centred dementia care. There is increasing evidence around the positive benefit and impact people with dementia can bring to their own care contexts. For people with dementia this means that issues of involvement and participation, as well as positive social relationships and being connected to their community, are all important to how they live with their diagnosis. Wider family and support relationships are part of the overall picture around living with dementia, yet what we know about these relationships is limited. The research focus of this proposed international group will be to improve our understanding of how relationships work after a diagnosis. Knowing more about how relationships work will help dementia researchers, people developing national policy, people providing support and care services, and for people with dementia themselves. Internationally, each of the 3 partner countries is experiencing and predicting rapid growth in the numbers of people with dementia. The UK now has guidance and national policy on diagnosis sharing and post diagnostic support. More globally, findings from the 10/66 Dementia Research Group show a more mixed picture. In Goa, the focus on diagnosis sharing and person centred care is a very recent development. In Taiwan the number of people with dementia is expected to increase dramatically. Taiwan has a national Ten-Year Long Term Care Plan started in 2008, so person centred care is a recent development. The proposed project will support established and early career dementia researchers from UK, India and Taiwan to work together. This group will meet at a four day residential in Edinburgh in August 2012 planned to coincide with conference attendance in Scotland by the senior academics. This meeting will be an opportunity for the group to plan and write an application for research funding. The overall aim of the proposed project is to support this existing group of academics to form stronger working relationships through which to share varied national perspectives; and to agree and take forward a joint research funding proposal that will explore post diagnostic relationships for people with dementia. Longer term impact will focus on activity and outcomes relating to grant applications, collaborations and publications. The partners have been chosen to allow for a variety of practice and policy contexts and to build on and strengthen existing academic and practice relationships. Prof Shyu, from Cheng-Gung Univesrity in Taiwan has a well established career focusing on dementia care and nursing. Dr Dias is a senior academic in the Dept of Preventative and Social Medicine, Goa Medical College and is also internationally connected to many of the major dementia networks including the 10/66 Dementia Research Group. Edinburgh University will provide desk, computing, library and other academic facilities to overseas participants who would like to extend their stay as a Visiting Fellow in order to add to the individual research capacity and experience, particularly for early career researchers. Dr Heather Wilkinson will project manage to ensure event coordination, impact assessment, building and sustaining network opportunities and dissemination. The CRFR knowledge exchange team will provide project support.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.