MRSA is a 'super-bug' that is difficult to control using antibiotics, and is most common in hospitals. Around 1 in 10 people admitted to hospital will contract an infection during their stay. You can become infected through physical contact with either another infected person or a surface like a door handle already touched by an infected person. If you are really ill, as many people are in hospital, the infection can kill you. There are ways to limit the spread of MRSA in hospitals, including healthcare workers following strict hygiene measures such as washing their hands between patients, isolating infected patients and even closing down hospital wards where infections occur. The problem is that each option can cost a lot of money which could otherwise be used to treat patients and nobody knows the best way to use these different options together to manage an outbreak of MRSA.Researchers have turned to computer modelling to help them understand how to manage the complicated range of factors involved in spreading the infection. The models show that the pattern of movements of healthcare workers among patients is really important and if the activities of healthcare workers are managed properly then spread can be limited. Also crucial is the degree to which healthcare workers follow the hygiene measures. Effective training of healthcare workers on the importance of following the hygiene rules can also limit spread. Most important of all, the models show that each individual person involved can make a big difference to the occurrence and spread of the disease. To decide how to manage the spread of infection in a particular ward, you need to know about the ward layout and the people that work and are being treated in that ward. Unfortunately, none of the models cater for differences in the behaviour of individual healthcare workers and the health of individual patients. Also, these models do not represent the layout of the ward, and how healthcare workers move around in the ward itself. We have developed a computer model that takes into account both the layout and the individuals in a hospital ward. We will add data about healthcare worker behaviour, healthcare activities among patients and individual patient health from a special study ward in a hospital into the model. We will also include data from different studies on the different ways to manage the spread of MRSA. We will combine our MRSA spread model with an existing training tool to teach healthcare workers about the importance of following the hygiene rules. We will clearly demonstrate to them how many patients one careless person can infect, and how careful they need to be to help reduce infections. This training tool uses a computer game approach to provide an interesting way of teaching.Since the computer model predicts realistic outcomes, it can also be used by managers to choose the best method of containing an ongoing outbreak. We will use artificially intelligent search techniques to identify the best way of combining different approaches to contain the spread. The same approach can also be used by managers to identify ways of reducing infections in the first place, and to plan ahead by getting the computer to simulate different possible scenarios and to identify ways of dealing with them. The system that we are aiming to build will help hospitals manage the spread of MRSA in a cost-effective way. It will show hospital managers possible ways of limiting spread in their hospital, and teach healthcare workers about the difference they can make in reducing the chance of an outbreak.

Despite recent advances in our understanding of corneal structure and the methods used to test corneal tissue in the lab, it is still impossible to measure corneal properties in-vivo. The inability to determine the basic biomechanical properties (such as hyperelasticity, hysteresis and viscoelasticity) in-vivo had a serious adverse effect on our ability to optimise treatments or predict their outcome, and made it necessary to rely on average properties obtained ex-vivo.This project aims to make in-vivo measurement of corneal biomechanical properties a reality. It seeks to cover the research needs underpinning the development of this technology and address two fundamental questions that have prevented progress in this field. The two questions revolve around the extraction of the material's stress-strain behaviour from the overall cornea's response to mechanical actions. Once these obstacles are removed, the path to establish in-vivo measurement technology becomes straightforward.There are significant potential benefits that can be achieved if corneal biomechanical properties could be measured in-vivo. The examples include better design of implants to restore clear vision in keratoconus patients, better planning of refractive surgery procedures that currently result in unexpected aberrations in 1:7 of patients, and the ability to eliminate effect of corneal stiffness on intraocular pressure measurements, which are required for glaucoma management. These potential developments will mean significant benefits to patients, healthcare services and medical device manufacturers.The research starts with an experimental study to determine the regional variation of corneal and scleral hyperelasticity, hysteresis and viscoelasticity. The study will use 3D digital imaging of human eye globes subjected to cycles of both intraocular pressure and external applanation forces and aim to address the key gaps in knowledge in ocular biomechanics.With maps of biomechanical properties established, numerical analysis tools will be built to embody these maps, in addition to existing knowledge on the biomechanical, topographic and micro-structural characteristics of the human eye. The tools, which will be custom built, will be validated against ocular behaviour data obtained experimentally before using them to develop conceptual techniques to measure corneal biomechanics in-vivo.Two types of property measurement techniques, based on contact and non-contact methods, will be assessed. In both cases, corneal response to a mechanical action is correlated to corneal stress-strain behaviour. This exercise will focus on the key research questions, and aim to formalise an analysis procedure to extract the cornea's stress-strain behaviour from its mechanical response, and to exclude the effects of intraocular pressure and cornea's geometric parameters on the results.The results of the numerical study will be assessed using proof-of-concept prototypes both experimentally on human eye globes and on volunteers within a clinical setting. The tests are intended to validate the numerical findings, cast light onto the characteristics of ocular deformation under mechanical actions, and provide initial results which will be important for the conduct of future clinical studies on fully operational device prototypes.Overall, the project addresses a challenging problem that is affecting progress in several areas of patient care in ophthalmology. It seeks to overcome the main barriers to making the in-vivo measurement of corneal properties a reality. The project follows a systematic approach where necessary knowledge about ocular behaviour is generated and a predictive tool of ocular mechanical response built before assessing the property measurement methods. With the knowledge and understanding to be generated in this project, research and development can progress to embody the new technology into medical devices suitable for clinical use.

People suffering from cancer are typically treated with either surgery, radiotherapy or chemotherapy. Currently the world's most widely used chemotherapeutic drugs are platinum-based; a leading example is cisplatin, a compound containing platinum with a 2+ charge. It is generally accepted that the anticancer activity of cisplatin and other closely related platinum compounds arises from their ability to damage DNA in cancer cells leading to cell death.The existing platinum drugs are highly toxic to both healthy and cancerous cells in the body. As a result, serious side-effects of treatment are a frequent and serious problem in chemotherapy. These side-effects can be so severe that treatment has to be stopped, leading to treatment failure and ultimately to the death of the patient. In some cases the cancerous cells in the bodies of patients become resistant after repeated doses of the drugs; then the cells are not killed by the drug and the cancer is not cured. This research project aims to develop new platinum anticancer drugs which work in a different way to cisplatin. If the platinum drug could be made harmless until it enters the cancer cells and then be activated only in the tumour tissue, this would greatly reduce unwanted side-effects, allow treatment of cisplatin-resistant tumours, and may also allow treatment of a wider range of cancers. Our proposed strategy is a new one. We will use compounds containing platinum with a 4+ charge. These will not be reactive towards cells and must be converted to platinum 2+ compounds before they kill cells. We will activate them specifically in cancer and not in other normal cells using a directed fine beam of light. To introduce even greater selectivity for cancer cells, we will tag the compounds with labels that are selectively recognised and taken up by cancer cells in preference to normal cells (peptides, antibodies). Our strategy will introduce new mechanisms for killing cancer cells, just what is needed to circumvent resistance to current platinum drugs. Our encouraging preliminary data suggest that we can make compounds that are more effective than cisplatin itself.Exciting is the prospect of using new optical devices to activate our compounds. These photonic crystal fibres can deliver laser light of a very precise colour over long distances. This should lead to more controllable activation and perhaps the prospect of reaching internal sites of the human body which are currently inaccessible to irradiation.This research project aims to design (with the help of computer predictions), synthesise and characterise new photoactivatable platinum complexes. The synthesis of these complexes is anticipated to be challenging since they must be made without direct exposure to light. They will be tested for features such as stability, solubility and cell uptake, and their photoactive properties determined. Extensive investigation into the spectroscopic properties of these new complexes will be carried out and much use will be made of nuclear magnetic resonance techniques to understand the mechanisms through which these complexes change chemically following activation by light. We will also use standard chemical techniques such as mass spectrometry, UV-Vis spectroscopy, and X-ray crystallography to fully characterise our new compounds. The distribution of the platinum complexes within cells and the selective platination of DNA and proteins and activity of the complexes towards different types of cancer cells will also be investigated.Since longer wavelengths of light (e.g. red light) penetrate tissue more deeply than shorter (e.g. blue light); a challenge will be to design compounds which are activated by irradiation of light with these longer wavelengths. This may be possible through using compounds which are able to absorb two photons at once, or by careful design of the ligands on the complexes.

Communication is the essence of life. We communicate in many ways, but it is our ability to speak which enables us to chat in every-day situations. An estimated quarter of a million people in the UK alone are unable to speak and are at risk of isolation. They depend on Voice Output Communication Aids (VOCAs) to compensate for their disability. However, the current state of the art VOCAs are only able to produce computerised speech at an insufficient rate of 8 to 10 words per minute (wpm). For some users who are unable to use a keyboard, rates are even slower. For example, Professor Stephen Hawking recently doubled his spoken communication rate to 2 wpm by incorporating a more efficient word prediction system and common shortcuts into his VOCA software. Despite three decades of developing VOCAs, face-to-face communication rates remain prohibitively slow. Users seldom go beyond basic needs based utterances as rates remain, at best, 10 times slower than natural speech. Compared to the average of 150-190 wpm for typical speech, aided communication rates make conversation almost impossible. ACE-LP brings together research expertise in Augmentative and Alternative Communication (AAC) (University of Dundee), Intelligent Interactive Systems (University of Cambridge), and Computer Vision and Image Processing (University of Dundee) to develop a predictive AAC system that will address these prohibitively slow communication rates by introducing the use of multimodal sensor data to inform state of the art language prediction. For the first time a VOCA system will not only predict words and phrases; we aim to provide access to extended conversation by predicting narrative text elements tailored to an ongoing conversation. In current systems users sometimes pre-store monologue 'talks', but sharing personal experiences (stories) interactively using VOCAs is rare. Being able to relate experience enables us to engage with others and allows us to participate in society. In fact, the bulk of our interaction with others is through the medium of conversational narrative, i.e. sharing personal stories. Several research projects have prototyped ways in which automatically gathered data and language processing can support disabled users to communicate easily and at higher rates. However, none have succeeded in harnessing the potential of such technology to design an integrated communication system which automatically extracts meaningful data from different sources, transforms this into conversational text elements and presents results in such a way that people with severe physical disabilities can manipulate and select conversational items for output through a speech synthesiser quickly and with minimal physical and cognitive effort. This project will develop technology which will leverage contextual data (e.g. information about location, conversational partners and past conversations) to support language prediction within an onscreen user interface which will adapt depending on the conversational topic, the conversational partner, the conversational setting and the physical ability of the nonspeaking person. Our aim is to improve the communication experience of nonspeaking people by enabling them to tell their stories easily, at more acceptable speeds.

In the diagnosis and treatment of disease, clinicians base their decisions on understanding of the many factors that contribute to medical conditions, together with the particular circumstances of each patient. This is a "modelling" process, in which the patient's data are matched with an existing conceptual framework to guide selection of a treatment strategy based on experience. Now, after a long gestation, the world of in silico medicine is bringing sophisticated mathematics and computer simulation to this fundamental aspect of healthcare, adding to - and perhaps ultimately replacing - less structured approaches to disease representation. The in silico specialisation is now maturing into a separate engineering discipline, and is establishing sophisticated mathematical frameworks, both to describe the structures and interactions of the human body itself, and to solve the complex equations that represent the evolution of any particular biological process. So far the discipline has established excellent applications, but it has been slower to succeed in the more complex area of soft tissue behaviour, particularly across wide ranges of length scales (subcellular to organ). This EPSRC SoftMech initiative proposes to accelerate the development of multiscale soft-tissue modelling by constructing a generic mathematical multiscale framework. This will be a truly innovative step, as it will provide a common language with which all relevant materials, interactions and evolutions can be portrayed, and it will be designed from a standardised viewpoint to integrate with the totality of the work of the in silico community as a whole. In particular, it will integrate with the EPSRC MultiSim multiscale musculoskeletal simulation framework being developed by SoftMech partner Insigneo, and it will be validated in the two highest-mortality clinical areas of cardiac disease and cancer. The mathematics we will develop will have a vocabulary that is both rich and extensible, meaning that we will equip it for the majority of the known representations required but design it with an open architecture allowing others to contribute additional formulations as the need arises. It will already include novel constructions developed during the SoftMech project itself, and we will provide many detailed examples of usage drawn from our twin validation domains. The project will be seriously collaborative as we establish a strong network of interested parties across the UK. The key elements of the planned scientific advances relate to the feedback loop of the structural adaptations that cells make in response to mechanical and chemical stimuli. A major challenge is the current lack of models that operate across multiple length scales, and it is here that we will focus our developmental activities. Over recent years we have developed mathematical descriptions of the relevant mechanical properties of soft tissues (arteries, myocardium, cancer cells), and we have access to new experimental and statistical techniques (such as atomic force microscopy, MRI, DT-MRI and model selection), meaning that the resulting tools will bring much-need facilities and will be applicable across problems, including wound healing and cancer cell proliferation. The many detailed outputs of the work include, most importantly, the new mathematical framework, which will immediately enable all researchers to participate in fresh modelling activities. Beyond this our new methods of representation will simplify and extend the range of targets that can be modelled and, significantly, we will be devoting major effort to developing complex usage examples across cancer and cardiac domains. The tools will be ready for incorporation in commercial products, and our industrial partners plan extensions to their current systems. The practical results of improved modelling will be a better understanding of how our bodies work, leading to new therapies for cancer and cardiac disease.