NIHRDataInsights/HRCSData huggingface dataset:
Title: An Extraordinary Photochemical Reaction of Pyrrole - A New Tool for Molecular Complexity
Funder: Engineering and Physical Sciences Research Council

Abstract: This proposal aims to explore a powerful photochemical reaction recently discovered in our laboratory. A variety of N-butenyl substituted pyrroles have been found to undergo an extraordinary photocycloaddition/rearrangement sequence to give tricyclic fused aziridines of high molecular complexity. Early studies have shown that as long as the pyrrole bears an electron withdrawing group on the 2-position the reaction sequence is highly tolerant of substitution. We will investigate the scope of the cycloaddition reaction by examining the effects of side chain substitution with a variety of cyclic and acyclic alkenes. The resulting aziridines will themselves be reactive species and should undergo a number of useful bond forming ring opening reactions. Once developed and understood the methodology will be applied as the key step in a very short synthesis of the alkaloid dendrobine. Overall the work in this proposal should serve to highlight the value of photochemistry and photochemical technology in modern chemical synthesis.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: Multivariate Bayesian Modelling of Skewness and Kurtosis With Applications in Biostatistics
Funder: Engineering and Physical Sciences Research Council

Abstract: We will study, from a Bayesian point of view, joint models for mixed responses such as continuous and discrete responses. Many of these models are motivated by longitudinal measurements obtained from clinical trials. A specific example of this is the longitudinal study of CD4 cell counts on individuals infected by the Human Immunodeficiency Virus (HIV) under a treatment with antiretroviral drugs. One of the interests in this context is the time elapsed from the infection to the presence of Acquired Immune Deficiency Syndrome (AIDS) and its relationship with the time evolution of some key biomedical indicators. This requires joint modelling of longitudinal and survival processes, which is the main area of application of this research proposal. Firstly, we will explore copulas for jointly modelling mixed responses, and compare various options by formal model comparison methods. Alternative approaches, based on designing new classes of flexible multivariate distributions will then be developed in detail. In addition, we need to propose priors for the model parameters. We will explore both informative and noninformative priors, and for the improper priors we will derive conditions for the existence of the posterior distribution. The use of appropriate MCMC methods will be necessary for efficiently conducting inference. Such methods will be developed and computer code will be made available freely. Most of these advances (developing classes of flexible multivariate distribution, formulating appropriate priors for constructing Bayesian models, proving posterior existence in these models, dealing with model uncertainty and with censored, missing or rounded observations, and implementing MCMC samplers for inference with such models) will be of substantial interest in themselves for the development of statistical methodology and have a much wider applicability as they could be used in a wide variety of applied fields. Nevertheless, in this project, we will focus specifically on applications in biostatistics. The aim is to substantially increase our understanding of disease progression and our methodology will also allow for the modelling of indicators of quality of life.


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE
Title: Ultrasonic Needles based on Mn-doped Ternary Piezocrystals
Funder: Engineering and Physical Sciences Research Council

Abstract: Ternary piezocrystals is the name given to a new group of single crystal piezoelectric materials that have a much higher mechanical Q and much higher energy densities than the binary compositions. Ternary piezocrystals have properties that are now sufficient for enabling their incorporation in high power ultrasonic devices. Their doped counterparts are a very recent development offering previously unavailable properties. Most importantly for high power ultrasonic transducers, they have increased the mechanical Q from around 100 to nearly 1000. However, completely new ultrasonic transducer configurations are needed to exploit fully this increased performance. Through characterisation and incorporation of doped ternary piezocrystal materials, and by capitalising on their significant potential for transducer enhancements, we will be able to create next generation high performance, high power ultrasonic devices for surgery. We will particularly investigate their integration in novel orthopaedic devices, aiming at the extremely challenging and potentially disruptive technology of ultrasonically-assisted needles. For minimally invasive, highly accurate, interventional surgery via direct penetration through bone, we will deliver devices offering the clinician entirely new and potentially transformational capabilities in a range of clinical applications including oncology, neurosurgery, orthopaedics, bone biopsy, regional anaesthesia and rheumatology. In meeting this challenge, we will develop new techniques for characterisation of the materials and create designs for novel transducers, based on the measured characteristics, for actuation of power ultrasonic surgical tools. We will research a new class of devices in the form of bone-penetrating ultrasonic needles that can be realised with doped ternary piezocrystals to permit the highly challenging surgical tasks of (i) direct delivery of therapeutic drugs to targets within or obscured by bone, (ii) gaining access within medullary canals and inside cranial sinuses/cavities for surgical procedures, and (iii) obtaining biopsies from the inside of the bone for diagnosis. Binary compositions of the new materials are already replacing conventional piezoceramics in biomedical imaging applications and adoption of these and the newer ternary compositions for other high value applications will increase as on-going efforts to scale up crystal growth techniques mature. This project will thus position the UK in the forefront of research, while simultaneously offering transformative research in ultrasonic devices for surgery.


Research activity codes: 5.4 SURGERY
Health categories: GENERIC HEALTH RELEVANCE
Title: Inverse Problems for Magnetic Induction Tomography
Funder: Engineering and Physical Sciences Research Council

Abstract: Magnetic Induction Tomography (MIT) is a relatively new, non-invasive imaging technique which has applications in both industrial and clinical settings. In essence, it is capable of reconstructing the electromagnetic parameters (permittivity, permeability and conductivity) of an object from measurements made on its surface. An MIT device consists of two sets of coils placed around the boundary of the object to be imaged. The first set of coils is used for the purpose of excitation, and by passing a current through each coil in turn, a primary magnetic field is created. The second set of coils is then used for measurement. This procedure causes an eddy current when each of the primary magnetic fields interacts with a conducting body inducing secondary magnetic fields, and hence voltages, that are measured in the second set of coils. Enabling MIT to take the step from being an experimental technique, which has already received some clinical interest, to become a viable imaging technique for the detection and monitoring of conditions, such as cerebral stroke, requires a step change in the quality of the reconstruction of the electromagnetic parameters and, therefore, an improvement of the computational approach used for the solution of the inverse problem. To achieve this we propose to solve the inverse Maxwell problem with a variational algorithm. Although a proof of concept of this work exists, in order to make this algorithm effective in a clinical environment, and hence applicable to the MIT problem, an implementation using high performance computing is needed, this research proposal aims to address this issue.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE
Title: Optimising Magnetic Susceptibility Mapping to Enhance MRI of Microbubbles
Funder: Engineering and Physical Sciences Research Council

Abstract: Microbubbles (MBs) are an established ultrasound contrast agent but there has been significant recent interest in developing them as a contrast agent for Magnetic Resonance Imaging (MRI). MRI of MBs is useful because of its potential for combined applications in targeted imaging for monitoring and guidance of focused ultrasound therapies and drug and gene delivery. So far, MRI of synthesized MBs has been based on decreases in the MRI signal magnitude. Here, I propose to detect MBs using MRI magnetic susceptibility mapping which uses the phase of the complex MRI signal in gradient-echo MRI sequences. MBs have a different susceptibility than tissue; therefore the central idea here is that MBs present in an area of tissue will change its susceptibility so that it stands out as a bright or dark area in a MRI susceptibility map. I am one of the pioneers of susceptibility mapping: a new method which offers several advantages over conventional magnitude-based imaging. Susceptibility maps promise to enhance MRI of MBs because they are calculated from phase images which have higher contrast-to-noise ratios than standard magnitude images. The contrast in susceptibility maps directly represents the intrinsic magnetic susceptibility in an area and therefore has the potential to measure the MB concentration in that area. The susceptibility of MBs can be selected and tailored for different clinical applications so that MBs create bright (positive) contrast in susceptibility maps. All these advantages of MRI susceptibility mapping mean that it would improve the clinical applicability of MBs as a dual-modality contrast agent for MRI and ultrasound. Susceptibility mapping could also enhance MRI guidance and monitoring of MB-mediated drug and gene delivery and MB-enhanced focused-ultrasound surgery which is currently in use for treating uterine fibroids and is being developed to treat liver, bone, prostate and brain diseases. An EPSRC First Grant will be a springboard for a research programme which will ultimately lead to the development of a broad range of optimised MRI susceptibility-based techniques for diagnostic and therapeutic applications in preclinical models of disease and clinical imaging.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE
Title: Sound bullets for enhanced biomedical ultrasound systems
Funder: Engineering and Physical Sciences Research Council

Abstract: Ultrasound is used in many applications, including medical imaging, non-destructive evaluation, therapeutic ultrasound etc. In all these cases, there is usually a need for the formation of images or the creation of a focal region. Current methods for the


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;5.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: GENERIC HEALTH RELEVANCE
Title: Learning to learn how to design drugs
Funder: Engineering and Physical Sciences Research Council

Abstract: A key step in developing a new drug is to learn quantitative structure activity relationships (QSARs). These are mathematical functions that predict how well chemical compounds will act as drugs. QSARs are used to guide the synthesis of new drugs. The current situation is: 1) There is a vast range of approaches to learning QSARs. 2) It is clear from theory and practice that the best QSAR approach depends on the type of problem. 3) Currently the QSAR scientist has little to guide her/him on which QSAR approach to choose for a specific problem. We therefore propose to make a step-change in QSAR research. We will utilise newly available public domain chemoinformatic databases, and in-house datasets, to systematically run extensive comparative QSAR experiments. We will then generalise these results to learn which target-type/ compound-type/ compound-representation /learning-method combinations work best together. We do not propose to develop any new QSAR method. Rather, we will learn how to better apply existing QSAR methods. This approach is called "meta-learning", using machine learning to learn about QSAR leaning. We will make the knowledge we learn publically available to guide and improve future QSAR learning.


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: BESiDE - The Built Environment for Social Inclusion in the Digital Economy
Funder: Arts and Humanities Research Council

Abstract: BESiDE's research asks the question: How can the built environment facilitate physical activity and wellbeing in care homes? Our goal is to transform the network of stakeholders involved in care environments into a virtuous cycle of design improvement, in which architects, professional bodies, academics, policy makers, charities, and care home providers are all motivated to pursue improvement in the built environment for older adults. With changes in population demographics resulting in a growing number of care homes, economic, health and ethical considerations demand that attention be directed to effective means of creating an enabling built environment to provide older adults with healthy and socially fulfilling lives. This research addresses a significant knowledge gap focussed on measures to mitigate problems and enhance the experience of older people within the built environment. A fundamental impact of ageing is that a person's needs and abilities change; however, the built environment is failing to respond to these changes. Despite current legislative statutes and design guidance, little is known from empirical evidence (generated by older people, their family and care providers) about enabling and disabling elements of the built environment. These elements have never been defined to support the advancement of building and digital technology design. Through systematic analysis of the failings and successes of older people's care environments, BESiDE research will identify how better-informed building design can facilitate greater mobility, physical activity, social connectedness and wellbeing of older people. BESiDE's aims are to: 1) Actively involve and inform professional practices of architecture and design through research focussed on failings and successes of the built environment (internal and external) across the experience of ageing. 2) Impact professional practice through developing digital technologies within the built environment to promote greater mobility, improved quality of life, physical activity and connectivity of older people. 3) Inform policy, through BESiDE's Advisory Board and Project Partners, as to what designs and digital interventions encourage activity and how these can be engineered to facilitate increased wellbeing in older people. Collaboration across disciplines of computing, architecture, healthcare, medicine of old age and design will drive this work forward and build the UK's capability in supporting older people within the built environment. Engagement with older people and stakeholders will shape understanding of barriers to wellbeing within the built environment.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE
Title: MyPLACE: Mobility and PLace for the Age-friendly City Environment
Funder: Arts and Humanities Research Council

Abstract: The aim of this project is to develop and test through real-world research, a digital platform and toolkit that will enable members of the public to engage with local councils and other organisations more effectively in the research, planning and design of the urban environment. The specific domain of this project is people's experiences of mobility and access to the urban environment, and how this changes with age. The project is a collaboration with City Councils in the Northeast Region, and Newcastle's' Age Friendly city initiative. Through VoiceNorth will engage members of the public in the project as co-researchers and co-designers, to collect a body of quantitative and qualitative data on older people's experiences of mobility in the built environment, and to co-design digital tools, information and services to enhance that experience. To achieve this we will design and develop a toolkit of digital sensors to capture evidence and experiences from older people's journeys through and social interactions within the city centre. We will combine this evidence with social research data through interactive architectural visualisations which will support citizens and stakeholder in participatory design of the age friendly city. We will also develop a participatory design platform which will allow members of the general public to access, comment, and vote on design issues, and to add their own experiences of access and the built environment. This extended public engagement in the research and design activities will offer a new model of public engagement in civic decision making. The toolkit and platform will be validated through the design of and deployment of digital interventions in the city. We will also document our findings for policy makers and other stakeholders regionally and nationally.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: GENERIC HEALTH RELEVANCE
Title: Dispersion of localised releases in a street network (DIPLOS)
Funder: Engineering and Physical Sciences Research Council

Abstract: The security threat level from international terrorism, introduced by the UK Security Service, has been classified as either "severe" or "critical" for much of its six-year history, and currently remains as "substantial" (source: MI5 web site). Part of th


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: GENERIC HEALTH RELEVANCE
Title: Nanoenabled Peptide Pills - Unlocking the Potential of Therapeutic Peptides
Funder: Engineering and Physical Sciences Research Council

Abstract: The poor bioavailability of peptides, nature's own 'drugs', limits their therapeutic application. The molecular envelope technology (MET) delivery platform allows their use as nano-enabled 'Peptide Pills'. The multi-disciplinary 'Peptide Pill' consortium, comprising drug delivery scientists, neuroscientists, physicists, chemical engineers and clinicians, will develop the pain peptide pill METDoloron. It is estimated that 20% of European adults suffer from chronic pain, which is often inadequately controlled by opioids. Additionally opioids can sometimes cause life threatening side effects. METDoloron avoids these problems by targeting a different receptor to currently used opioids, using an endogenous peptide derivative_x000D_ and is therefore expected to have a significant impact on the large (US$ 50 billion), fragmented, and growing global market for pain therapeutics. The project partners will confirm METDoloron pharmacology, investigate nanoparticle transport mechanisms, establish scale-up and manufacturing processes, and confirm product (GLP) safety thus creating know-how in biophotonics, pain therapy, flow reactor design and nanoparticle processing techniques. First in man clinical trials will commence on conclusion of this project.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: GENERIC HEALTH RELEVANCE
Title: Wegner estimates and universality for non-Hermitian matrices
Funder: Engineering and Physical Sciences Research Council

Abstract: In the theory of probability the Central Limit Theorem (CLT) explains why the distribution of the mean of random variables from any distribution follows the Gaussian curve. Although the first observation of this behaviour is due to de Moivre in the 18th century, it was only in the 20th century that the CLT was rigorously proven. A similar phenomenon appears in the theory of random matrices and is called universality. In this context, the universality conjecture asserts that the eigenvalue statistics of large random matrices depend only on the symmetries of the matrices, and are independent of the precise probability densities that govern their stochastic behavior. Furthermore, in the limit of large dimension, the eigenvalues are distributed as if the entries were drawn from the Gaussian distribution. This conjecture is akin to the CLT and has deep philosophical and practical consequences. It is observed in numerics and experiments that many physical systems demonstrate the same behavior independently of the precise details of interactions among their constituent elements. This property of random matrices is conjectured to hold more generally. In particular, it fulfils one of the central objectives in mathematical physics: the derivation of macroscopic properties of large systems, despite unknown or random specifics of interactions. So far, it has been proven only in a few specific cases, such as the Wigner ensemble. The goal of this project is to prove universality of various eigenvalue statistics for ensembles consisting of non-Hermitian random matrices. Such ensembles have been studied in both mathematics and physics literature and despite far-reaching applications in various fields of study, are not very well understood. By looking at the work on Hermitian random matrices, we can postulate which theorems should be true in the non-Hermitian case. Despite the slow and steady progress in the area, we see that several difficult and important problems yet remain to be solved. In particular, the study of eigenvalue correlation functions still falls far behind its Hermitian counterpart.


Research activity codes: 1.4 METHODOLOGIES AND MEASUREMENTS
Health categories: GENERIC HEALTH RELEVANCE
Title: Towards a Micro milliKelvin Cooler Array
Funder: Engineering and Physical Sciences Research Council

Abstract: This application seeks to demonstrate a 4 K to millikelvin micro cooler through the demonstration of a new concept. Low temperature cryogenics has always been a relatively large scale technology i.e. dilution refrigerators and adiabatic demagnetisation refrigerators (Adr). Recent advances at MSSL in the millikelvin cryocooler (mKCC), solid state heat switches and magnet design enables a new concept of cooling in the 4 K to millikelvin region which enables a dramatic reduction in size. For example, the mKCC which provides 1 uW of cooling power at 100 mK, could be reduced from 5.6 (d) x 12 (w) x 30 (h) cm to a size of 4 (d) x 5 (w) x 5 (h) cm by using the new micro cooler concept. The ultimate coupling of this millikelvin micro cooler to higher temperature micro coolers, offers the prospect of a complete 300 K to 100 millikelvin micro cooler that could be used to cool state-of-the-art cryogenic detectors (e.g. Microwave Kinetic Inductance Detectors MKIDs) and quantum computers in a very compact, portable system. In this application we seek the funds to demonstrate this concept by constructing a small prototype system which will have a continuous 100 mK cooling power of 0.3 uW, when interfaced at 4 K and have predicted dimensions of only 3 x 2 x 5 cm. This concept enables very easy adaptation for higher cooling powers and lower temperatures.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE