EPSRC Centre for New Mathematical Sciences Capabilities for Healthcare Technologies

As quality of life constantly improves, the average lifespan will continue to increase. Underlining this improvement is the vast amount of the UK government's support to NHS (£133.5 billion in year 2011/12) and the UK pharmaceutical industry's R&D large investment (4.9 billion to R&D in year 2011/12). The expectation of quality healthcare is inevitably high from all stakeholders. Fortunately recent advances in science and technology have enabled us to work towards personalised medicine and preventative care. This approach calls for a collective effort of researchers from a vast spectrum of specialised subjects.
Advances in science and engineering is often accompanied by major development of mathematical sciences, as the latter underpin all other sciences. The UoL Centre will consist of a large and multidisciplinary team of applied and pure mathematicians, and statisticians together with healthcare researchers, clinicians and industrialists, collaborating with 15 HEIs and 40 NHS trusts plus other industrial partners and including our strongest groups:
MRC Centre in Drug Safety Science, Centre for Cell imaging (CCI for live 3D and 4D imaging), Centre for Mathematical Imaging Techniques (unique in UK), Liverpool Biomedical EM unit, MRC Regenerative Medicine Hub, NIHR Health Protection Research Units, MRC Hub for Trials Methodology Research.
Several research themes are highlighted below:
Firstly, an improved understanding of the interaction dynamics of cells and tissues is crucial to developing effective future cures for cancer. Much of the current work is in 2D, with restrictive assumptions and without access to real data for modelling. We shall use the unparalleled real data of cell interactions in a 3D setting, generated at UoL's CCI. The real-life images obtained will have low contrast and noise and they will be analysed and enhanced by our imaging team through developing accurate and high resolution imaging models. The main imaging tools needed are segmentation methods (identifying objects such as cells and tissues regions in terms of sizes, shapes and precise boundaries). We shall propose and study a class of new 3D models, using our imaging data and analysis tools, to investigate and predict the spatial-temporal dynamics.
Secondly, better models of how drugs are delivered to cells in tissues will improve personalised predictions of drug toxicity. We shall combine novel-imaging data of drug penetration into 3D experimental model systems with multi-scale mathematical models which scale-up from the level of cells to these model systems, with the ultimate aim of making better in-vitro to in-vivo predictions.
Thirdly, there exist many competing models and software for imaging processing. However, for real images that have noise and are of low contrast, few methods are robust and accurate. To improve the modelling, applied and pure mathematicians team up to consider using more sophisticated tools of hyperbolic geometry and Riemann surfaces and fractional calculus to meet the demand for accuracy, and, applied mathematicians and statisticians will team up to design better data fidelity terms to model image discrepancies.
Fourthly, resistance to current antibiotics means that previously treatable diseases are becoming deadly again. To understand and mitigate this, a better understanding is needed for how this resistance builds up across the human interaction networks and how it depends on antibiotic prescribing practices. To understand these scenarios, the mathematics competition in heterogeneous environments needs to be better understood. Our team links mathematical experts in analysing dynamical systems with experts in antimicrobial resistance and GPs to determine strategies that will mitigate or slow the development of anti-microbial resistance.
Our research themes are aligned with, and will add value to, existing and current UoL and Research Council strategic investments, activities and future plans.

Our team of applied, pure mathematicians and statisticians together with healthcare researchers, clinicians and industrialists will collaborate with 15 HEIs and 40 NHS trusts plus other industrial partners. Therefore the impact on the wide community is more pronounced and immediate than a responsive mode grant.

Academic impact. To the healthcare community, the proposed work will provide an insightful understanding of personalised medicine and preventative care. To the mathematical sciences community, the proposed work will advance several new directions in mathematics and statistics that will lead to high impact publications and high profile public addresses at major conferences. We see researchers in these communities as direct beneficiaries of the Centre.

The primary means of reaching out to users is by our User Engagement Forum via a series of Knowledge Exchange activities including visitor programmes; advisory service and maths and healthcare 'clinics'; summer schools; pump priming projects and activities to engage HEIs and industries; impact and public engagement activities; joint seminar series; workshops around specific problems. Some will be run with other EPSRC centres.

Economic Impact. The UK pharmaceutical industry in 2007 contributed £8.4 billion to the UK's GDP, investing 4.3 billion to R&D which is the third-highest share of global pharmaceutical R&D. The NHS budget for the UK was £133.5 billion in 2011/12 and medicines account for 10% of the NHS budget i.e. £13.4 billion. The Centre will make major contributions to UK R&D:
(i). Aided by image technologies, understanding the progression of the disease process is important to enable the industry target relevant biological processes. (ii). Incorporation of protein/cell level dynamics into tissues is necessary and essential to predict the overall toxicity. This study will lead to treatments optimised for specific patients. The pharmaceutical industry interests in drugs with less side-effects and stratified medicine. It will benefit from this Centre's new analysis tools and the UoL's MRC Centre in Drug Safety Science and MRC Regenerative Medicine Hub and Trials Hub in terms of extensive experimental data, computational simulations and scientific insights on tissues; therefore, we expect this impact to continue to be facilitated with our long-term collaborative partners and new parties to perform proof-of-principle trials.

Through existing and established connections, we would build further engagement including conversion of our results into commercial products.

Societal Impact. Cancer is due to uncontrolled growth and spread of abnormal cells. Our proposed work, aiming for better understanding of cells and tissues, is crucial to combat cancer. There were 14M new sufferers (8M deaths) with 338K in UK alone in 2012. Research impact is of massive scale.

With aging, plaque due to cholesterol, calcium, and fibrous tissue can build up in arteries and due to such, they can narrow and stiffen. Coronary angioplasty and stenting are to improve blood flow in the body's arteries and veins, with 75,000 procedures performed in England per year. Our study will optimise designs to minimise side effects. It will be conducted with clinicians. Benefit and publicity to NHS are immediate.

There is considerable concern in the society with common infectious diseases, which lead to 300M illnesses and more than 5M deaths each year worldwide with Ebola outbreak well-known and anti-microbial resistance posed as massive challenge. Finding a model for it by scaling up from small/local network information to large/global networks to understand diseases' network is of vital importance to Healthcare policy makers and service providers.

We will use these to engage the public at annual Science Festivals. We believe that these will not only raise awareness of the complexity in disease networks, but also generate interest in the community fascinated by bio-mimic system.