Keele University, officially known as the University of Keele, is a public research university located about 3 miles from Newcastle-under-Lyme, Staffordshire, England. Keele was granted university status by Royal Charter in 1962 and was originally founded in 1949 as the 'University College of North Staffordshire'.The university occupies a 620 acres rural campus close to the village of Keele and has a science park and a conference centre, making it the largest main campus university in the UK. The university's School of Medicine operates the clinical part of their courses from a separate campus at the University Hospital of North Staffordshire. The school of nursing and midwifery is based at the nearby clinical education centre. Wikipedia.
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: INFRADEV-3-2015 | Award Amount: 31.03M | Year: 2015
The nations of Europe are distributed around some of the most complex and dynamic geological systems on the planet and understanding these is essential to the security of livelihoods and economic power of Europeans. Many of the solutions to the grand challenges in the geosciences have been led by European scientists the understanding of stratigraphy (the timing and distribution of layers of sediment on Earth) and the discovery of the concept of plate tectonics being among the most significant. Our ability to monitor the Earth is rapidly evolving through development of new sensor technology, both on- and below-ground and from outer space; we are able to deliver this information with increasing rapidity, integrate it, provide solutions to geological understanding and furnish essential information for decision makers. Earth science monitoring systems are distributed across Europe and the globe and measure the physico-chemical characteristics of the planet under different geological regimes. EPOS will bring together 24 European nations and combine national Earth science facilities, the associated data and models together with the scientific expertise into one integrated delivery system for the solid Earth. This infrastructure will allow the Earth sciences to achieve a step change in our understanding of the planet; it will enable us to prepare for geo-hazards and to responsibly manage the subsurface for infrastructure development, waste storage and the use of Earths resources. With a European Research Infrastructure Consortium (ERIC) to be located in Rome (Italy), EPOS will provide an opportunity for Europe to maintain world-leading European Earth sciences and will represent a model for pan-European federated infrastructure.
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-23-2014 | Award Amount: 6.96M | Year: 2015
Childrens health affects the future of Europe children are citizens, future workers, parents and carers. Children are dependent on society to provide effective health services (UN Convention on the Rights of the Child). Models of child primary health care vary widely across Europe based on two broad alternatives (primary care paediatricians or generic family doctors), and a variety of models of school health and adolescent direct access services. There is little research to show which model(s) are best, implying that some are inefficient or ineffective, with sub-optimal outcomes. MOCHA will draw on networks, earlier child health projects and local agents to model and evaluate child primary care in all 30 EU/EEA countries. Scientific partners from 11 European countries, plus partners from Australia and USA, encompassing medicine, nursing, economics, informatics, sociology and policy management, will: Categorise the models, and school health and adolescent services Develop innovative measures of quality, outcome, cost, and workforce of each, and apply them using policy documents, routine statistics, and available electronic data sets Assess effects on equality, and on continuity of care with secondary care. Systematically obtain stakeholder views. Indicate optimal future patterns of electronic records and big data to optimise operation of the model(s). The results will demonstrate the optimal model(s) of childrens primary care with a prevention and wellness focus, with an analysis of factors (including cultural) which might facilitate adoption, and indications for policy makers of both the health and economic gains possible. The project will have a strong dissemination programme throughout to ensure dialogue with public, professionals, policy makers, and politicians. The project will take 42 months (36 of scientific work plus start up and close), and deliver major awareness and potential benefit for European childrens health and healthy society.
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: FETOPEN-1-2014 | Award Amount: 3.47M | Year: 2016
Neurodegenerative diseases, such as Parkinsons disease, are a major public health issue given the aging population in Europe and beyond. While curative pharmacological treatment of these diseases is not in sight, cell replacement therapies (CTs) are considered very promising, in particular with the advent of stem-cell reprogramming technologies. However, a fundamental challenge in the medical application of CTs in the brain of patients lies in the lack of control of cell behaviour at the site of transplantation, and particularly their differentiation and oriented growth. The aim of this project is to introduce a fundamentally new concept for remote control of cellular functions by means of magnetic manipulation. The technology is based on magnetic nanoparticles functionalized with proteins involved in cellular signalling cascades. These biofunctionalized MNPs (bMNPs) will be delivered into target cells, where they act as intracellular signalling platforms activatable in a spatially and temporally controlled manner by external magnetic fields. The project will focus on engineering these tools for the control of neuronal cell programming and fibre outgrowth by hijacking Wnt and neurotrophin signalling, respectively, with the ulti-mate objective of advancing cell replacement therapies for PD using dopaminergic precursor neurons. To achieve this ambitious goal, we have gathered an interdisciplinary consortium interfacing scientists having cutting-edge know-how in bMNP engineering, surface functionalization and cellular nanobiophysics with renowned experts in neuronal cell differentiation, stem-cell reprogramming and regenerative (nano-)medicine. By exploiting this complementary expertise, a novel, versatile technology for magnetic control of intracellular signalling is envis-aged, which will be a breakthrough for remote actuation of cellular functions and its successful implementation in CTs for neurodegenerative diseases and injuries within the following decade.
Southworth J.,Keele University
Monthly Notices of the Royal Astronomical Society | Year: 2012
I measure the physical properties of 38 transiting extrasolar planetary systems, bringing the total number studied within the Homogeneous Studies project to 82. Transit light curves are modelled using the jktebop code, with careful attention paid to limb darkening, orbital eccentricity and contaminating light. The physical properties of each system are obtained from the photometric parameters, published spectroscopic measurements and five sets of theoretical stellar model predictions. Statistical errors are assessed using Monte Carlo and residual permutation algorithms and propagated via a perturbation algorithm. Systematic errors are estimated from the interagreement between results calculated using five theoretical stellar models. The headline result is a major upward revision of the radius of the planet in the OGLE-TR-56 system, from 1.23-1.38 to 1.734 ± 0.051 ± 0.029R Jup (statistical and systematic errors, respectively). Its density is three times lower than previously thought. This change comes from the first complete analysis of published high-quality photometry. Significantly larger planetary radii are also found for Kepler-15, KOI-428, WASP-13, WASP-14 and WASP-21 compared to previous work. I present the first results based on Kepler short-cadence data for Kepler-14, Kepler-15 and KOI-135. More extensive long-cadence data from the Kepler satellite are used to improve the measured properties of KOI-196, KOI-204, KOI-254, KOI-423 and KOI-428. The stellar component in the KOI-428 system is the largest known to host a transiting planet, at 2.48 ± 0.17 ± 0.20R ⊙. Detailed analyses are given for HAT-P-3, HAT-P-6, HAT-P-9, HAT-P-14 and WASP-12, based on more extensive data sets than considered in previous studies. Detailed analyses are also presented for the CoRoT systems 17, 18, 19, 20 and 23; Kepler-7, -12 and -17; KOI-254; OGLE-TR-111, -113, -132 and L9 and TrES-4. I revisit the correlations between orbital period and surface gravity, and orbital period and mass of the transiting planets, finding both to be significant at the 4σ level. I conclude by discussing the opportunities for follow-up observations, the sky positions and the discovery rate of the known transiting planets. © 2012 The Author Monthly Notices of the Royal Astronomical Society © 2012 RAS.
Exley C.,Keele University
Coordination Chemistry Reviews | Year: 2012
The coordination chemistry of a metal ion defines its optimal association with a biomolecule such that its binding by specific ligands on that molecule confers function and biological purpose. Aluminium is a non-essential metal with no known biological role which means that its coordination neurochemistry defines aluminium's putative role in a number of neurodegenerative diseases. In examining this chemistry it is found that very little is known about the complexes formed and ligands involved in aluminium's interactions with neurochemically-relevant ligands. Aluminium's action as a pro-oxidant as well as an excitotoxin are highlighted while the evidence for its interactions with amyloid beta, tau and DNA are discussed and it is concluded that it is too early to discount these ligands as targets for the neurotoxicity of aluminium. © 2012 Elsevier B.V.
Ndosi M.,Keele University
Annals of the rheumatic diseases | Year: 2014
OBJECTIVE: To determine the clinical effectiveness and cost-effectiveness of nurse-led care (NLC) for people with rheumatoid arthritis (RA).METHODS: In a multicentre pragmatic randomised controlled trial, the assessment of clinical effects followed a non-inferiority design, while patient satisfaction and cost assessments followed a superiority design. Participants were 181 adults with RA randomly assigned to either NLC or rheumatologist-led care (RLC), both arms carrying out their normal practice. The primary outcome was the disease activity score (DAS28) assessed at baseline, weeks 13, 26, 39 and 52; the non-inferiority margin being DAS28 change of 0.6. Mean differences between the groups were estimated controlling for covariates following per-protocol (PP) and intention-to-treat (ITT) strategies. The economic evaluation (NHS and healthcare perspectives) estimated cost relative to change in DAS28 and quality-adjusted life-years (QALY) derived from EQ5D.RESULTS: Demographics and baseline characteristics of patients under NLC (n=91) were comparable to those under RLC (n=90). Overall baseline-adjusted difference in DAS28 mean change (95% CI) for RLC minus NLC was -0.31 (-0.63 to 0.02) for PP and -0.15 (-0.45 to 0.14) for ITT analyses. Mean difference in healthcare cost (RLC minus NLC) was £710 (-£352, £1773) and -£128 (-£1263, £1006) for PP and ITT analyses, respectively. NLC was more cost-effective with respect to cost and DAS28, but not in relation to QALY utility scores. In all secondary outcomes, significance was met for non-inferiority of NLC. NLC had higher 'general satisfaction' scores than RLC in week 26.CONCLUSIONS: The results provide robust evidence to support non-inferiority of NLC in the management of RA.TRIAL REGISTRATION: ISRCTN29803766. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Southworth J.,Keele University
Monthly Notices of the Royal Astronomical Society | Year: 2011
I calculate the physical properties of 32 transiting extrasolar planet and brown-dwarf systems from existing photometric observations and measured spectroscopic parameters. The systems studied include 15 observed by the CoRoT satellite, 10 by Kepler and five by the Deep Impact spacecraft. Inclusion of the objects studied in previous papers leads to a sample of 58 transiting systems with homogeneously measured properties. The Kepler data include observations from Quarter 2, and my analyses of several of the systems are the first to be based on short-cadence data from this satellite. The light curves are modelled using the jktebop code, with attention paid to the treatment of limb darkening, contaminating light, orbital eccentricity, correlated noise and numerical integration over long exposure times. The physical properties are derived from the light-curve parameters, spectroscopic characteristics of the host star and constraints from five sets of theoretical stellar model predictions. An alternative approach using a calibration from eclipsing binary star systems is explored and found to give comparable results whilst imposing a much smaller computational burden. My results are in good agreement with published properties for most of the transiting systems, but discrepancies are identified for CoRoT-5, CoRoT-8, CoRoT-13, Kepler-5 and Kepler-7. Many of the error bars quoted in the literature are underestimated. Refined orbital ephemerides are given for CoRoT-8 and for the Kepler planets. Asteroseismic constraints on the density of the host stars are in good agreement with the photometric equivalents for HD17156 and TrES-2, but not for HAT-P-7 and HAT-P-11. Complete error budgets are generated for each transiting system, allowing identification of the observations best-suited to improve measurements of their physical properties. Whilst most systems would benefit from further photometry and spectroscopy, HD17156, HD80606, HAT-P-7 and TrES-2 are now extremely well characterized. HAT-P-11 is an exceptional candidate for studying starspots. The orbital ephemerides of some transiting systems are becoming uncertain and they should be re-observed in the near future. The primary results from the current work and from previous papers in the series have been placed in an online catalogue, from where they can be obtained in a range of formats for reference and further study. TEPCat is available at © 2011 The Author. Monthly Notices of the Royal Astronomical Society © 2011 RAS.
Agency: GTR | Branch: EPSRC | Program: | Phase: Research Grant | Award Amount: 337.55K | Year: 2017
The most common form of dementia is Alzheimers disease, a neurodegenerative disorder that reportedly affects 30 million people worldwide, yet for which there is no cure and only limited opportunities for accurate diagnosis and treatment. The disease is characterised by pathological hallmarks in the brain including dense amyloid protein aggregates (plaques) that are deposited outside cells in the grey matter of the brain, together with significant damage internally in neurons due to tangles of abnormal tau protein. These plaques and tangles are understood to contribute to the death of neurons and the progressive degeneration of the brain. Exactly how this degeneration is mediated by these protein deposits is not yet properly understood. However, oxidative stress damage to neurons, catalysed by highly reactive chemical species known as free radicals, is understood to play a significant role. In addition, substantial evidence now suggests that the dysregulation of iron resulting in a harmful excess of reactive (ferrous) iron in the brain, is a contributing factor in the disease, and may be implicated in the processes leading to oxidative stress. Interactions between aberrant protein deposits and iron, as well as other metals, are common features of neurodegenerative disorders. In Alzheimers disease, metal-protein interactions are hypothesized to contribute to the formation of deposits containing reactive (harmful) iron observed post-mortem in diseased brain tissue. In addition, unusual calcium bio-mineralisation has been observed within areas of aberrant protein deposition suggesting that calcium could also play a significant role in the disease. Identifying these mineral products is an important first step in describing this aspect of Alzheimers disease. However in order to make progress in diagnosing and treating the disease, it is necessary to understand how the metal-protein interactions contribute to the disease process at a level facilitating therapeutic intervention, and the extent to which resulting iron and calcium mineralization in the protein deposits can serve as an early-stage marker of the disease. We aim to explore the chemical and mineral state of iron and calcium in Alzheimers disease brain tissue using sensitive and specific analytical methods, as well performing experiments to investigate how metal-protein interactions can lead to the initiation and evolution (both chemical and structural) of the protein deposits. Further, we will assess how the metal-protein aggregates formed in human brain tissue, as well as those created artificially, respond to treatments with the metal chelating agents that are currently being developed as potential drug therapies for Alzheimers and other neurodegenerative conditions. To ensure the success of this project we have assembled a unique interdisciplinary research team, with a strong international track record, to build upon our successful preliminary work in this area, applying a combination of advanced synchrotron x-ray microscopy and mass spectrometry techniques to probe nanoscale variations in the bio-inorganic chemistry occurring in Alzheimers tissue. An important aspect of the project is that in all cases we will support our evaluation using these specialist techniques, with conventional imaging and histology. From this we will build a comprehensive description of this fundamental process in Alzheimers disease, addressing key outstanding questions about the metal-protein interactions and how they may be modified. The parallels between aberrant protein deposition and altered handling of iron and other metals in related disorders, will allow the approach developed in this project to be readily translated, enabling equivalent impact for other forms of neurodegenerative disease. With clinical advances in chelation therapy and improved scope to track brain iron status non-invasively by clinical MRI, this project is not just timely but also urgent.
Agency: GTR | Branch: EPSRC | Program: | Phase: Research Grant | Award Amount: 808.84K | Year: 2016
Advances in conventional cancer treatments such as chemotherapy and radiotherapy have provided vast improvements in cancer survival rates over recent years. However these techniques inevitably lead to the damage of some healthy tissue and cells, resulting in harmful side effects. Many researchers around the world are therefore working to develop targeted cancer therapies that are tumor-specific, and so destroy cancer cells without affecting surrounding healthy tissue. One such technique, known as hyperthermia, uses heat sources to induce cancer cell death by transiently raising the local temperature in the tumor to above 42 deg C. However, generating local heating in a controlled and non-invasive fashion is difficult with conventional techniques. An alternative method is to use magnetic hyperthermia (or thermotherapy) which is an experimental cancer treatment that uses microscopic magnetic particles (nanoparticles) that are only 1/5000th of the width of a human hair. These nanoparticles can channel the energy from an external high-frequency alternating magnetic field in order to create local hot spots. As heating can only occur where nanoparticles are present, the technique is truly local and effects can be obtained by accumulating nanoparticles within tumors. Magnetic hyperthermia has produced encouraging results that show it can reduce the size of tumors, and in recent clinical trials where it was combined with radiotherapy, a significant effect on cancer survival times was reported. However these results were achieved by dispersing very concentrated magnetic nanoparticle fluids around the tumor. Although this represents local heating of the tumor, in order to prevent the cancer from spreading it is essential to kill each and every cancer cell, and so a cellular level heating effect is required. Much work has therefore focused on labelling individual cancer cells with magnetic nanoparticles, either by binding them to cell membranes or by allowing them to be engulfed by the cells. In principle these particles should then be able to heat the cells directly to trigger cell death. However the results of such experiments to date have been somewhat disappointing because it seems the magnetic and heating properties of the nanoparticles can change once they are associated with cells. In order to understand this behaviour it is first necessary to be able to probe the properties of the nanoparticles in real cellular environments, and to see how these vary depending on the microscopic location of the particles, i.e. where they reside inside or externally to cells. The ability to make such measurements would enable a systematic evaluation of how the design and location of the nanoparticles, as well as the magnetic field conditions used, could favourably enhance the magnetic properties and consequently the cellular level heating. Such a study would dramatically boost research on magnetic hyperthermia, taking it much closer to realisation as a viable clinical therapy. However at present no such instrument exists in order to perform this work. Therefore the aim of this project is to create a new type of microscope that can probe both the magnetic and heating properties of nanoparticles in cellular environments. This will be done by exploiting the magnetic dependence of certain optical phenomena, such as the well-known Faraday effect, and combining them with specialist fluorescence based techniques to measure local temperature. As the various components of the instrument take shape they will be used to evaluate the performance of a range of bespoke nanoparticles in order to understand how sufficiently strong cellular-level magnetic hyperthermia effects can be achieved. We are confident that the new instrument produced in this project will provide the step-change advancement required in nanoparticle evaluation to enable magnetic hyperthermia to be a viable and essential technology in the fight against cancer.
Agency: Cordis | Branch: H2020 | Program: ERC-COG | Phase: ERC-CoG-2015 | Award Amount: 2.43M | Year: 2016
TransPhorm will pioneer a transformative technology platform based on Nitrogen Vacancy (NV) magnetometry to enable the structure and function of transmembrane proteins (TMPs) to be studied in their native state with unprecedented sensitivity and resolution. TMPs reside in the membrane of biological cells and are critical to cellular function and communication. It is essential that TMPs are characterised in their native state as their structure and function is dependent on their interaction with the local environment. This is technically demanding and despite previous attempts using a multitude of complementary techniques no single method has provided a suitable solution. Here a breakthrough approach will be taken to demonstrate in situ TMP characterisation with single molecule sensitivity, nanoscale spatial resolution and millisecond measurement speed. The concepts proposed in TransPhorm are distinct from current implementations of NV magnetometry for detection and mapping of weak magnetic fields originating from external nuclear spins. Here magnetic field mapping will be achieved using a totally new approach based on widefield, high speed structured illumination total internal reflection microscopy. The concepts TransPhorm are built on will also enable structural and functional single molecular characterisation with high specificity by exploiting the outstanding sensitivity to the local environment of fluorine-19 Nuclear Magnetic Resonance (NMR) reporters and the ion selectivity of sodium-23 and potassium-39 NMR spectroscopy. In short, TransPhorm will deliver a ground-breaking technology to far surpass current state-of-the-art techniques and provide the extreme sensitivity needed to understand the molecular scale dynamic changes that underpin TMP function. Overall the strategy and technologies proposed here will pave an untravelled path to the realisation of nanoscale NMR imaging and deliver tremendous scientific gains.