Chronic diseases are a major challenge for human health in the 21st century. The UK and worldwide burden of chronic disease is expected to increase in future years. Chronic Obstructive Pulmonary Disease (COPD) is an important chronic disease of the chest and is a leading cause of disability among older people. Muscle wasting and weakness is an important feature of COPD. Patients with muscle wasting are more disabled, have a poorer prognosis and require more healthcare resources. Loss of muscle bulk and function is important because it may be a treatable consequence of a condition in which the underlying lung disease is usually irreversible. The value of this approach is illustrated by the benefits of physical training, which have been clearly demonstrated in COPD. However, little is known about the causes of muscle wasting and weakness or the mechanisms by which physical training improves muscle function in COPD. We have recently identified genes involved in the regulation of muscle wasting and growth in healthy young and elderly humans and demonstrated that the functioning of these genes is profoundly affected by periods of immobility and exercise. Recent work has also demonstrated that dietary supplementation of protein enhances muscle growth during exercise training in healthy humans. We will extend these observations to study muscle wasting and growth in the clinical setting of COPD. We will study the functioning of genes recently identified as important in the regulation of muscle growth and wasting in patients with COPD compared with healthy volunteers of the same age. We will also study the effects of an eight-week lower limb strength-training programme on the functioning of these genes. This will help us understand how training works and how training affects the genes that regulate muscle growth. It may be beneficial to supplement individuals with additional dietary protein at the time of training. We will test this theory by randomly allocating patients in the study to receive a protein rich drink or a non-nutritive placebo after each bout of training. We will also measure muscle bulk and muscle function during the study. This research will provide new insights into the genetic mechanisms of muscle wasting and weakness and how the functioning of these genes can be influenced by interventions such as training and nutrition. This information will be a significant advance in the development of new treatments aimed at improving muscle function in chronic diseases such as COPD.

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.

Tuberculosis is a curable disease but still remains one of the biggest killers in the world. It kills nearly 2 million people worldwide every year and 98% of tuberculosis deaths are in the developing world affecting mostly young adults in their productive years. A quarter of a million tuberculosis deaths are also infected with HIV which weakens human immune systems, most of these people are in Africa. Tuberculosis especially affects the most vulnerable populations including children, the poorest and malnourished. Tuberculosis is caused by the bacterium called Mycobacterium tuberculosis. One important characteristics of this disease is that the bacterium has an unusual ability to grow and survive for extended periods of time in human body. Therefore, it has been estimated that 2 billion people, equal to one third of the world's total population, are infected with the bacterium in whom it causes unnoticeable latent infection that gives rise to a 5-10% lifetime risk of active tuberculosis. These persistent bacteria cannot be cultured using standard microbiological methods and are not killed by the current tuberculosis drugs. Therefore, tuberculosis treatment needs at least 6 months with four drugs to cure the patients. This long-term treatment is extremely difficult to implement especially in developing countries because of lack of affordability in both patients and healthcare services and limited infrastructure. It is important that treatment duration is shortened using effective tuberculosis drugs as it will significantly reduce patient suffering, side effect and expenses incurred by both patients and their families. In addition, shorter TB treatment duration may allow an earlier return of patients to their productive activities. The proposed research aims to identify and quantify those persistent bacteria in tuberculosis infected mice before and during treatment with new drugs to predict the outcome of tuberculosis treatment. The persistent bacteria will be "woken" by the addition of resuscitation promoting factors (RPFs) which are proteins produced by M. tuberculosis to restart growth. We have shown in our recent study that in mice there were persistent bacteria which depended on RPFs to grow. High-dose rifampicin which was added in the current treatment drug regimen was able to kill RPF-dependent persistent bacteria, as a result, treatment was cut short with no disease relapse. This meant that if we are able to remove RPF-dependent bacteria from patents, the treatment duration could be shortened with reduced relapse rate. In this proposal, we will apply the same principals and techniques which we have learnt from studying mice using a set of novel drug regimens to predict the outcome of human tuberculosis treatment, especially disease relapse. We will set up a model system in mice as a test bed to evaluate the potencies of new drug regimens before usage of them in much more expensive and time-consuming human testing.

The Department of Health (DH) and the NHS are particularly exercised by climate change. Whereas the occupants of other building types might consider raising their comfort temperature thresholds a little in summer and suspend the use of mechanical cooling, NHS patients' well being and safety may well be compromised by higher summer temperatures. In fact the DH and the NHS are hit by a double whammy, the pressure to reduce energy consumption, colliding with the pressure to protect their patients and staff from overheating, the dangers of which were manifest in recent years' summer heatwaves. Innovative low energy design strategies and techniques will be required both for new buildings and, most importantly, for the existing building stock, the 27,701,676 square metres of the NHS Retained Estate. However there are many barriers to the implementation of such innovative interventions in NHS buildings, patient safety being paramount. Worries include the inability to achieve stable temperature control and safe ventilation (the airborne transmission of pathogens is an emerging science as our colleague Dr.Cath Noakes freely admits), the proliferation in the use of medical equipment adding heat to hospital interiors and the mechanics of modern contractual arrangements which place private companies in charge of the Facilities Management of health buildings, which, unsurprisingly, given the penalties they face, are ultra-cautious about adopting change.This project, 'Design and delivery of Robust Hospital Environments in a Changing Climate' (DeDeRHECC), will investigate these conundra to come up with economical and practical low energy refurbishment strategies for existing hospitals. It will derive a closer definition of resilience in the context of an acute hospital and, most particularly, the criteria set for hospital environments for the various categories of space found in hospitals; non-clinical, patient rooms, diagnostic and treatment, even operating theatres. The team is sceptical that these all align into a cherent requirement and will review UK and US criteria. Using four sets of hospital sites drawn from the project's four participating major NHS Trusts, it will 'catalogue' basic hospital building types from this sizeable sample of NHS stock, identify those most frequently occurring, assess their current resilience to climate change and propose appropriate solutions or clusters of interventions for each 'type'. It will model these ideas so that relative energy savings can be quantified and their resilience to warming external temperatures determined. It will cost them. It will calculate the lifetime running costs and energy savings and assess Value for Money. It will also examine the procurement environment in which these innovative solutions need to be delivered, the protocols by which refurbishment projects are designed, approved and implemented. Their delivery will incur risks. The project will take innovative risk assessment tools for change, developed for engineering design, and apply them to these future large and medium scale construction projects. It will develop processes to make the integration of these innovative, low energy interventions into hospital refurbishment projects smoother and more familiar to those who will be delivering them. It will produce guidance and worked examples in text and web form and, most significantly, as a DVD film of participants discussing the challenges, their anxieties, the ideas and how to deliver them. Accompanying animations will communicate the strategies and communications vividly and quickly to very busy people.

Since 2001 government policy has created a new set of professionals, Emergency Care Practitioners (ECPs), and a new style of urgent healthcare provision to support the vision of a healthcare service designed around the patient. ECPs are paramedics and nurses with additional training to treat patients at home, in minor injuries units or to stabilise patients for transport to specialist clinical units. Although professional training has been developed for ECPs there has been no research to look at the technologies needed to support this new role. This project is looking at emergency and urgent care work in detail. We propose that supporting technologies can be delivered as Smart Pods with three components: a vehicle/docking system, a treatment (vehicle) unit and a treatment package system (equipment and consumables). The first stage of the project is to model the operational systems to determine the distribution of the vehicle/docking systems for the Smart Pods to deliver the right care at the right time in the right place. At the same time we will be working with clinical partners in the East Midlands and South West to look at 4-6 treatment types (including chest pain, minor head injuries, minor illnesses and falls). These treatment types will be analysed in detail in A&E departments, minor injuries units and ambulance services to look for similarities and differences in clinical practice to provide the framework for the treatment packages and initial data for the layout in the treatment (vehicle) unit. We will propose a standardised pathway for the treatment types and will use a simulation mannequin to test the clinical treatment unit layout in a laboratory with doctors, nurses and ECPs.We will start working on the design of the vehicle by reviewing the current systems and looking at distribution and delivery systems in other industries, e.g. military, car breakdown services, food delivery. We will look at how new emergency care vehicles are ordered, purchased and manufactured and compare this with other low-volume vehicle manufacturing (e.g. Lotus, Maclaren) to help us develop viable solutions. This information will be used to look at both manufacturing and purchasing issues to explore if the Smart Pods concept is viable.Vehicle engineering and associated systems options will be surveyed, in particular chassis/drive chain and intelligent vehicle technologies and we will consider sustainability issues in terms of full life-cycle energy usage. Computer models and animation scenarios covering the full range of proposed SmartPod applications will be developed. The final part of this first phase of the project will start to consider issues of implementation in more depth with patient groups representing people affected by a range of urgent and emergency care conditions. We will also consult members of the lay public, clinicians, and those involved in the planning for, managing, and evaluating urgent and emergency care to investigate views on change in the provision of urgent and emergency care and to identify any unanticipated challenges (e.g. political, organisational, cultural) in implementing change.