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.

Digital health technologies (DHT) comprise a broad range of applications such as telehealth, wearable devices and smart-phone and tablet applications (apps). However, whilst national and international policies present ambitious plans for DHT to revolutionise healthcare, there has been little consideration of how they can be successfully integrated into healthcare systems and processes. This is important as many reports show that even well designed DHT fail to be adopted or are quickly abandoned in clinical practice, meaning that their potential to transform healthcare is lost. Stroke rehabilitation presents an ideal opportunity to use DHT to improve patient outcomes. Pressures on services mean that the amount of rehabilitation that can be directly delivered by staff, particularly for the arm, falls far short of that known to be beneficial resulting in sub-optimal outcomes for many people and reduced quality of life. With the numbers of people surviving a stroke set to double in the next 15 years, DHT provides an attractive, innovative, practical and engaging way for staff to prescribe additional rehabilitation and improve recovery for people after stroke, within current service constraints. However, DHT are not widely used in rehabilitation and the factors that influence their use in clinical practice are not known. This project seeks to identify and understand the factors that will influence the use of DHT in healthcare. It will employ this knowledge to design, implement and evaluate a DHT intervention, using rehabilitation after stroke as a case example. The project has 3 initial phases. In phase 1, the evidence considering if and how DHT are used in healthcare will be reviewed, to explore the factors influencing their use. A national survey, observations of practice, questionnaires and interviews will describe current practice and explore the behaviours and beliefs of people after stroke, rehabilitation staff and service managers about using DHT. This information will be used to develop a theory about, and framework of, the factors influencing the use of DHT in healthcare rehabilitation. In phase 2, the theory and framework will be used to co-design, create and undertake initial testing of an app and intervention to supplement routine rehabilitation for the arm after stroke with rehabilitation staff, stroke survivors and DHT developers from our in-house innovation lab. In phase 3, the initial feasibility, acceptability and costs of the app and intervention to supplement stroke rehabilitation at a single NHS trust will be evaluated. Data from interviews, questionnaires and generated by the app will investigate how it was used in practice. These findings will be used to further refine the theory and framework developed in Phase 1 and the app and intervention developed in Phase 2. In the second period of the fellowship (Phase 4), a multi-site feasibility study of the app and intervention will be conducted. The project outputs will also be used to guide and assess the use of other forms of DHT (e.g. virtual reality) in stroke rehabilitation and their transferability to support and evaluate DHT in other healthcare settings will be evaluated. This project will transform how DHT can be used in healthcare by generating a clear theory and framework and providing practical tools which detail the factors that must be considered in the design, implementation and evaluation of DHT. It will provide guidance on how patients and healthcare staff can co-design DHT and design a future trial of the effectiveness of the app and intervention. Its results will benefit technology developers and researchers by helping them design and utilise DHT to improve patient outcomes and enable healthcare organisations and policy-makers to consider the vital processes and resources required to realise the vision of a truly innovative and DHT-enabled healthcare service.

Myriad interactions between DNA and proteins that take place throughout the length of an organism's genome ultimately allow cells to read, repair, package, and copy DNA sequence. How cells properly orchestrate and control these critical DNA:protein interactions is a fundamental question in biology. A unifying theme across such diverse DNA:protein interactions is that they always require some form of local mechanical distortion of DNA like bending, twisting, or kinking. Therefore, DNA:protein interactions can potentially be modulated and controlled by the local mechanical properties of DNA such as its bendability. Structural studies, dynamic experiments, and computational works have suggested that the mechanical properties of the DNA polymer are not constant, but vary along its length depending on local sequence, via a "mechanical code". Over decades, this has given rise to the hypothesis that sequence may be able to significantly control the local mechanical properties of DNA, and via it, control the critical DNA:protein interactions that in turn allow sequence itself to be read, repaired, copied, and packaged. In other words, via the mechanical code, DNA sequence might be able to control its own regulation. If this hypothesis is true, because of its potential generality and likelihood of relevance in all examples of DNA:protein interactions in all organisms, it would represent a transformative step in our understanding of life and in our ability to control it. Towards this end, we recently developed high-throughput experimental methods to measure, for the first time, how the mechanical properties of DNA vary with sequence along large regions of the genomes of various organisms. Via other experiments, we showed that these sequence-encoded variations in DNA bendability regulate critical processes related to the reading, copying, and packaging of DNA. Genetic information in DNA sequence is further modified by chemical alterations to DNA such as methylation (addition of a methyl group mainly to the cytosine base of DNA). DNA methylation is of fundamental importance in altering which genes along DNA are expressed. While certain cellular factors have been found to recognise methylated DNA, how DNA methylation achieves so many broad downstream effects is not fully understood. Recently, it has been suggested that one of the ways in which DNA methylation could exercise control over DNA transactions is by modifying the local physical and mechanical properties of DNA. If true, DNA methylation might allow cells to dynamically alter the "mechanical code" itself, as a means of gaining a broad regulatory handle on many different DNA:protein interactions. A significant roadblock to exploring this hypothesis has been the lack of high-throughput methods to provide the basic characterization of how DNA methylation, at various points along an organism's vast genome, alter the local mechanical properties of DNA depending on local sequence context. Here we propose to extend the capabilities of our high-throughput experimental techniques to make it possible to characterize the mechanical consequences of DNA methylation in high-throughput throughout the genome. We will compare our findings with other genome wide data, and perform other high-throughput biochemical experiments on how DNA sequence and methylation affect protein:DNA interactions. We expect to develop a comprehensive understanding of how DNA methylation, via its impact on the local physical properties of DNA, impacts the local structure of chromatin and the expression of individual genes. As DNA methylation accompanies processes like embryonic development, cellular adaptation to environmental changes, and genetic diseases like cancers, this project lays the foundations for future efforts at understanding how such critically important processes in biology might, in part, achieve their effects by gaining a handle on the physical properties of DNA.

The Earth's magnetic field sits within the changeable, dynamic environment of the solar wind. The interaction of the two regimes drives rapid reconfigurations of the Earth's field, which induce currents to flow in conductors on the ground. These Geomagnetically Induced Currents (GICs) can be 10s to 100s of Amps, and can cause transformer heating and higher harmonics in power grids, degradation to metal pipelines, and signalling malfunctions on railway systems. The Lloyd's of London 2013 Space Weather report concluded that a once-in-a-Century event 'would cause major disruption to transport, food supplies, emergency and hospital services amongst other things...The absence of such fundamental services could lead to major and widespread social unrest, riots and theft with ramifications for the insurance industry and society in general'. The cost of such an event to the UK has been estimated at £0.9-15.9 billion, and while such huge events are rare, smaller, damaging, events are routinely observed. The key to predicting the location and magnitude of GICs is understanding the chain of causality from the Sun to the Earth's surface, and having instrumentation in key locations to make the measurements required for forecasting. Typical solar wind structures that drive powerful GICs have been identified, and can provide some early warning of extreme dynamics in the Earth's system. The other end of the chain, inducing currents in conductors on the ground due to a variable magnetic field, may be addressed through the application of Faraday's Law, given the conductivity of the local regolith, and the conductivity, length and orientation of the conductor. Typically, this research is funded by individual nations focussing on operational risk to their own critical infrastructure, and therefore the global picture is less well understood. The missing link required for accurate GIC forecasting is the physics of the central part of the chain: understanding how the highly dynamic ionospheric current systems generate the geomagnetic disturbances that drive GICs measured in infrastructure, thus enabling the coupling of existing solar wind/magnetosphere models with ground-based conductivity maps. We will use data from ground-based magnetometers (>200 stations) spread across every continent, to determine the location, timing and intensity of all geomagnetic disturbances over an eight-year period (2010-2017). These signatures will be related to their ionospheric drivers using a constellation of 66 satellites in low-Earth orbit which provide continual 2-minute snapshots of the magnetic energy stored in the system during this time period, and accurately characterise the location, direction and magnitude of the ionospheric current systems. The novelty of this approach is combining these two data sets for the first time to allow a global, statistical analysis over an entire solar maximum period. We will largely focus on high latitude regions (including northern Europe, Canada and the northern United States) where the most intense GICs are observed. Our work is relevant to space weather service providers (such as the UK Met Office), the energy and rail industries, and governments who monitor risk to critical infrastructure, as well as for future infrastructure planning. We will also study equatorial and mid-latitude disturbances, as these have the potential to disrupt infrastructure supporting major population centres, and the combination of equatorial and higher-latitude events could be highly damaging to infrastructure on a continental scale (such as in South America). This work will be a pathfinder for the feasibility of nowcasting, and perhaps even forecasting, of GICs, using acombination of existing satellite networks and solar wind monitors.

The CBES group at the UCL Bartlett School of Graduate Studies received its Platform Award in 2006 and the funding has facilitated a period of sustained success. Platform funding has been of critical value in helping us to retain key staff, to innovate and in providing the flexibility to be adventurous. We have also been able to enhance our knowledge exchange/transfer work and international collaboration. This has been reflected in the quality, growth and range of our activities. The Platform funding thus enabled us to establish a multi-disciplinary, world-leading research group which has dramatically increased in size, resulted in world leading academic publications, seeded a new Institute (Energy), developed new methods of interdisciplinary and systems working and won international prizes. CBES was submitted to and awarded the highest percentage (35%) of world leading rated researchers of any UK university in the 2008 Research Assessment Exercise (RAE) - Architecture and the Built Environment Panel. Building on the work directly supported or indirectly facilitated by the current Platform Grant, and also responding to new opportunities, the strategic direction of this continuation proposal represents a step change for CBES. During the period of the current Platform Grant, CBES was primarily interested in developing multi-disciplinary solutions to the practical problems of designing, constructing and managing environments within and around buildings. In the next quinquennium we will strengthen our world-leading position. We propose a strategic programme of activity in a timely new research direction - the unintended consequences of decarbonising the built environment . We aim to transform understanding of this urgent issue that will have enormous impact internationally.In order to predict the possible future states of such a complex socio-technical system, conventional scientific approaches that may have been appropriate for systems capable of being analysed into simple components are no longer applicable. Instead, we need to bring radically new approaches and ways of thinking to bear. We need to develop and extend our multi- and inter- disciplinary ways of working and be informed by modern complexity science. The initial Platform grant has helped set up a group that includes building scientists, heritage scientists, economists, systems modellers and social scientists. The renewal will enable the group to focus on this urgent problem, to develop appropriate research methods and help develop real-world solutions within the required timescale. The number of Investigators has increased from 11 at the start of the existing Platform Grant to 13 in the renewal - a vital expansion to enable the inclusion of a wider range of disciplines. Nevertheless, facilitated by Platform funding, we will now need to form a whole new set of additional alliances to support the development of our proposed work.One of the key achievements of the current Platform Grant has been the spinning off of the newly formed UCL Energy Institute (EI). CBES is thus ideally placed to benefit from the extensive and diverse range of energy demand reduction work at the EI. However, the EI is not funded to study unintended consequences and this Platform renewal will thus perfectly complement EI activity. Via Platform funding and in partnership with the EI, CBES aims to develop a new concentration of world-leading research excellence in this field. We will establish a regional hub for research collaboration with local universities which will ensure that benefits from Platform funding are felt more widely than UCL alone.