Honey bees provide both economic and societal benefits, from the honey and other commodities that they produce to the pollination services they provide. The loss of honey bee colonies and the current threats to their health are of considerable concern to bee-keepers and biologists alike. This project seeks to examine how a particular aspect of honey bee biology – the symbiotic microbiome – impacts upon honey bee health. Studies in other systems reveal heritable microbes as important modulators of disease susceptibility. This project will utilize the extensive network of bee samples across the US and UK to establish geographical patterns of heritable microbe presence in bees, and links to apiculture practice. It will then use state of the art transcriptomic and genomic approaches to establish the links between Arsenophonus, a heritable symbiont known in bees, and bee health. It will then, combine with professional agencies responsible for bee health to use these results to modify apiculture practice to establish better bee husbandry. Aside the research science completed, the project will train an EU scientist in state of the art genomic technologies and translation from discovery to applied science. It will further transfer the training gained to EU hosts, both in discovery science and application.

Cryptococcal meningitis is a frequently lethal fungal infection of the lining of the brain. The most common predisposing condition is advanced AIDS, although cryptococcal meningitis may occur in other circumstances where there is impairment of systemic immunity. Cryptococcal meningitis affects approximately one million people in the world each year and the mortality rate is 60-70%. Recent estimates suggest that cryptococcal meningitis kills more people in sub-Saharan Africa each year than tuberculosis. Unfortunately, there are relatively few active antifungal drugs to treat this infection and each has significant limitations. The best clinical outcomes result from early rapid killing of the fungus in the brain. In the UK this is usually achieved with induction therapy that consists of 2-weeks of intravenous antifungal therapy. Unfortunately, in much of the developing world, it is simply not possible to administer intravenous drugs for any length of time. Hence, the best therapy is not given and clinical outcomes are persistently unsatisfactory. This research aims to develop new induction regimens that can be used in the developing world. Shorter regimens (even a single day) would facilitate the use of optimal induction therapy and represents an important mechanism to improve clinical outcomes. We will conduct all our research using well-validated experimental models of cryptococcal meningitis. We will study antifungal agents alone and in combination to understand the relationship between concentrations of drug(s) in the brain and the killing of the fungus. We will then use mathematical models and computer simulation techniques to identify human antifungal regimens that we predict will result in the same or better activity to the current standard of care that is delivered in the UK. After the completion of this research, we will seek further funding to conduct clinical trials in subSaharan Africa to test these new regimens. Our research offers the real possibility of making significant advances for the care of patients with a lethal and neglected disease.

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.

In the UK, declining levels of physical activity are contributing to an epidemic of obesity and alarming increases in preventable conditions such as cardiovascular disease and diabetes. Previous efforts to promote physical activity have largely failed. However, a powerful motivator for an active lifestyle, already present in many households, has been overlooked. 1 in 4 households in the UK own dogs, yet despite having a furry pal ready to ‘go walkies‘, some owners still do not walk their dogs or walk them only rarely. This study by researchers at the University of Liverpool will examine the aspects of the human-dog relationship that cause some people to walk their dogs, and others not. It will use a combination of face-to-face interviews with dog owners, observational studies and questionnaire surveys. A key focus will be the involvement of children in activities with dogs that may prevent childhood obesity. If all dog owners walked for at least 30 minutes every day, they would meet recommended physical activity guidelines. Many dogs would also live much healthier and happier lives. This study will inform the best methods to motivate walking that is beneficial to the health of both people and dogs.

It is estimated that adverse reactions to drugs constitute the 4th most common cause of death in the USA. In the UK, adverse drug reactions (ADRs) are a financial burden on the health services, a major cause of drug withdrawals for the pharmaceutical industry and a life-threatening experience for some patients. A recent survey indicated that 6.5% of hospital admissions were due to ADRs costing the Nation #466 million annually. With the increasing emphasis on polypharmacy and multidrug combination therapy, this situation is set to worsen. At the individual level, whilst many ADRs are relatively mild and self-limiting, in some cases ? in particular the allergic or hypersensitivity reactions ? they can result in permanent disability or fatality. Several recent high profile incidences of adverse drug reactions, for example the withdrawal of Vioxx (a COX2 inhibitor) because of heart attacks and the TGN1412 incident in Northwick Park in 6 healthy volunteers, have undermined confidence in existing preclinical testing procedures, and subsequent safety assessment in man. Despite this, our understanding of ADRs and the mechanisms underlying them are seriously deficient. ADRs are complex biological events which require broad-based expertise and meticulously conducted clinical studies to address. The Centre for Drug Safety Science will provide a unique infrastructure for studying the mechanisms of ADRs and will provide a focus for establishing the critical mass of expertise required to make a real impression on the incidence, prediction and management of such reactions, both within the health services and pharmaceutical industry. Our mission therefore is to create a world-class centre for the investigation of fundamental mechanisms by which adverse drug reactions which are important in our clinics and hospitals, with the overall aim of preventing such reactions through (a) better design of drugs, (b) identifying the factors by which ADRs only occur in some patients, and (c) develop better tests to identify these ADRs early before the reactions develop or become more severe. Another important effect of creating the Centre will be to increase scientific expertise in this area which is important for our healthcare system, regulatory agencies and pharmaceutical industry.