Major progress has been made over the last two decades in reducing deaths in young children from the world's poorest countries, however death rates in newborn babies remain high. Bacterial infection is one of the commonest causes of illness and death in newborn babies across the world but is particularly problematic in low income settings. Resistance to commonly used antibiotics is increasingly seen in infections affecting young babies, and in some countries this is resulting in babies developing serious infections which cannot be treated with locally available antibiotics. Cheap, effective, readily available strategies to reduce neonatal infections are urgently required. Babies are often infected by bacteria that colonise their skin shortly after they are born. One method of reducing infection in young babies could therefore be to apply antiseptics to the birth canal of women in labour and to the skin of newborn babies to reduce the number of bacteria found on babies' skin. Finding out whether antiseptic use could reduce the number of babies developing infections will need a large, complex trial over multiple sites, but currently the best antiseptic regime to use for such a trial is not known. Our proposed study sets out to provide this information. We plan to compare two different antiseptics which are used routinely in hospitals in the care of babies and women in labour: chlorhexidine (CHG) and octenidine (OCT). We will look at how well these two antiseptics reduce the amount of bacterial present when they are applied to the birth canal of a mother and to the skin of a baby. We will also compare different frequencies of applying the antiseptics to determine which schedule works best. The study will enroll women and babies presenting to a government hospital in Malawi, one of the poorest countries in the world, and will allocate them to receive one of the antiseptic regimes. The number of bacteria present in the birth canal (women) and skin (babies) after antiseptic is applied will be tested using skin swabs. This study will carefully collect data on whether antiseptic causes skin irritation or any other problems, and will collect data from women about how acceptable it is to have antiseptic applied whilst they are in labour. The information we collect as part of this study will help decide how we design a future large study to see if antiseptics can reduce the number of serious infections occurring in young babies.

Stroke is a major cause of death and disability, commonly caused by blood clots blocking large or small blood vessels of the brain. About one in five strokes are caused by disruption of blood flow in small vessels causing a lacunar stroke. This arises from diseased or hardened small blood vessels, known as small vessel disease (SVD). It can also cause widespread damage with loss of brain tissue structure, called leukoaraiosis. Lacunar stroke and leukoaraiosis is the most common cause of vascular dementia and a major cause of declining memory and thinking abilities that occurs with normal ageing. SVD is particularly common in individuals of African and African-Caribbean ancestry. It is not known why some people acquire SVD or what exactly causes it. Evidence suggests that genetic or inherited factors are important in increasing risk. However, the culprit genes have not yet been identified. New technology allows us to screen the whole of our genetic material to identify new genes causing diseases. We will examine brain scans and blood samples from stroke sufferers to try and identify genes associated with SVD in both White and Black stroke sufferers. Discovering new genes could lead to new treatments in this important disease.

A recent British Heart Foundation survey showed that cardiovascular diseases (CVD) such as angina, heart attack, heart failure, and stroke cause one quarter of all deaths in the UK. CVD also costs the UK over £29 billion a year in healthcare plus loss of work days. These figures caused by CVD numbers will increase as the number of elderly people in our population continues to grow. It is clear we need new drugs to treat CVD. A decrease in the diameter of the open space or 'lumen' of our blood vessels produces high blood pressure and reduces blood flowing to our organs - both these problems increase the risk of us developing CVD. It is known that when muscle cells found in the walls of blood vessels contract too much they decrease the lumen diameter. Our research focuses on understanding what causes these muscle cells to contract too much. By knowing more about these muscle cells and how they control lumen diameter of blood vessels we will help develop new drugs to treat CVD. The amount of calcium inside these muscle cells is highly associated with contraction of these muscle cells and therefore the lumen diameter of blood vessels. When calcium levels increase too much it causes the muscle cells to excessively contract and reduce the lumen of blood vessels. We investigate proteins, called TRPC1, which form specialised holes called channels that are found in the membrane that surrounds muscle cells. When these TRPC1 channels are opened they allow calcium to be transported into muscle cells. If we could find a way to reduce TRPC1 channels from opening, we could reduce the amount of calcium entering muscle cells, which would reduce contraction of these cells, and prevent the diameter of blood vessels from becoming too small: this would be an excellent strategy for treating CVD. In this proposal, we plan to investigate what causes TRPC1 channels to open and let calcium into muscle cells using the blood vessels of mice, which are an excellent animal species for allowing us to understand what happens in human blood vessels. Our research will greatly advance our knowledge on TRPC1 channels and on how the lumen diameter of blood vessels may be controlled. This will directly help in the development of new treatments for CVD. TRPC1 channels also control the level of calcium in cells from other parts of the body such as the brain, kidneys and lungs. Therefore our studies will also help understand diseases involving a variety of other body systems.