Understanding audiences from industry sectors in knowledge exchange

This essay discusses the concept of Knowledge Exchange between industry and academia. In particular it focuses on ways in which academic organisations can learn about different industry sectors in order to identify potential Knowledge Exchange partners and how they operate. Three case studies of scoping approaches taken in the understanding of these audiences are presented followed by a discussion of their different strengths and weaknesses. This essay concludes with presentation of an initial framework for scoping and suggestions for where this work can be developed in the future

Development of indole sulfonamides as cannabinoid receptor negative allosteric modulators

This Letter was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Scottish Universities Life Sciences Alliance (SULSA) in 2011Peer reviewedPostprin

Phosphorylation of ezrin on Thr567 is required for the synergistic activation of cell spreading by EPAC1 and protein kinase A in HEK293T cells

Recent studies have demonstrated that the actin binding protein, ezrin, and the cAMP-sensor, EPAC1, cooperate to induce cell spreading in response to elevations in intracellular cAMP. To investigate the mechanisms underlying these effects we generated a model of EPAC1-dependent cell spreading based on the stable transfection of EPAC1 into HEK293T (HEK293T–EPAC1) cells. We found that direct activation of EPAC1 with the EPAC-selective analogue, 8-pCPT-2′-O-Me-cAMP (007), promoted cell spreading in these cells. In addition, co-activation of EPAC1 and PKA, with a combination of the adenylate cyclase activator, forskolin, and the cAMP phosphodiesterase inhibitor, rolipram, was found to synergistically enhance cell spreading, in association with cortical actin bundling and mobilisation of ezrin to the plasma membrane. PKA activation was also associated with phosphorylation of ezrin on Thr567, as detected by an electrophoretic band mobility shift during SDS-PAGE. Inhibition of PKA activity blocked ezrin phosphorylation and reduced the cell spreading response to cAMP elevation to levels induced by EPAC1-activation alone. Transfection of HEK293T–EPAC1 cells with inhibitory ezrin mutants lacking the key PKA phosphorylation site, ezrin-Thr567Ala, or the ability to associate with actin, ezrin-Arg579Ala, promoted cell arborisation and blocked the ability of EPAC1 and PKA to further promote cell spreading. The PKA phospho-mimetic mutants of ezrin, ezrin-Thr567Asp had no effect on EPAC1-driven cell spreading. Our results indicate that association of ezrin with the actin cytoskeleton and phosphorylation on Thr567 are required, but not sufficient, for PKA and EPAC1 to synergistically promote cell spreading following elevations in intracellular cAMP

In Vitro Assay Development and HTS of Small-Molecule Human ABAD/17β-HSD10 Inhibitors as Therapeutics in Alzheimer's Disease

This research was funded by the Scottish Universities Life Science Alliance (SULSA) assay development fund. This research was also kindly supported by The Rosetrees Trust and The Alzheimer’s Society, specifically The Barcopel Foundation, and partly funded by the MSD Scottish Life Sciences fund. As part of an ongoing contribution to Scottish life sciences, MSD Limited, a global health care leader, has given substantial monetary funding to the Scottish Funding Council for distribution via SULSA to develop and deliver a high-quality drug discovery research and training program.A major hallmark of Alzheimer’s disease (AD) is the formation of neurotoxic aggregates composed of the amyloid-β peptide (Aβ). Aβ has been recognized to interact with numerous proteins, resulting in pathological changes to the metabolism of patients with AD. One such mitochondrial metabolic enzyme is amyloid-binding alcohol dehydrogenase (ABAD), where altered enzyme function caused by the Aβ-ABAD interaction is known to cause mitochondrial distress and cytotoxic effects, providing a feasible therapeutic target for AD drug development. Here we have established a high-throughput screening platform for the identification of modulators to the ABAD enzyme. A pilot screen with a total of 6759 compounds from the NIH Clinical Collections (NCC) and SelleckChem libraries and a selection of compounds from the BioAscent diversity collection have allowed validation and robustness to be optimized. The pilot screen revealed 16 potential inhibitors in the low µM range against ABAD with favorable physicochemical properties for blood-brain barrier penetration.PostprintPeer reviewe

Digital Diabetes Dudes

The Dudes project explored young people’s experiences of living with diabetes and how they would like to be supported in self-management using digital resources. In the early stages of development, Dudes is an interactive online education site for young people living with type 1 diabetes, situated within My Diabetes My Way. Dudes aims to support young people aged 17-25 years to understand selfmanagement for their lifestyle, and has been developed by a collaborative team from Edinburgh Napier University, NHS Lothian and the University of Dundee. It was accepted by the Digital Health & Care Institute as part of an integrated ‘Digital Diabetes’ programme of projects seeking to develop digital resources to support self-management. The Dudes Experience Lab took place in November 2016, following Pre- and General Labs exploring themes and questions that cut across the projects in the Digital Diabetes programme (commenced November 2015). This report describes the Experience Lab activity for the Dudes project and a detailed set of findings. It begins by providing project background and aims, and summarises the relevant findings of the Preand General Labs (described in full in previous reports). The findings are mapped onto the objectives of the Dudes project, presenting a detailed discussion of the current experiences of young people, in terms of the insights, attitudes and actions that relate to self-management. Feedback on existing resources for young people are presented, and information gaps and opportunities are identified. Finally, the report presents design requirements, concepts and scenarios of use for the enriched young person’s zone, and the conclusions of the Experience Lab Team

Digital Diabetes

The Digital Diabetes programme is a portfolio of seven promising innovation projects funded by the Digital Health & Care Institute (DHI) aiming to support engagement in self-management of diabetes.  Experience Labs were developed by the Institute of Design Innovation at The Glasgow School of Art, aiming to offer a safe and creative environment where researchers, businesses, civic partners and service users can collaborate on innovative solutions to the health and care challenges facing our society.  The aim of the Digital Diabetes Experience Labs was to bring together people living with diabetes, carers, clinicians and representatives from the voluntary sector to understand how people would like to be supported to engage in self-management. Three Experience Labs were designed and facilitated by the Experience Lab Team, involving: people living with diabetes in rural locations (Lab 1: Inverness), people living with diabetes in urban locations and carers (Lab 2: Glasgow), and health professionals and representatives from the third sector who support people living with diabetes (Lab 3: Perth).  The Lab findings are presented as a model of diabetes self-management, describing the key factors that determine how well someone will engage in self-management, and the people and things that support them.  Factors include the person’s attitude towards diabetes and the relative importance it has in their life and access to personal insight about their condition. Opportunities for new digital tools to support personal insight and positive attitudes towards diabetes were identified. Insightful and motivating conversations with trusted health professionals and their community (including peers and support organisations) were seen as key to supporting engagement in self-management. Further findings relate to the differences between type 1 and type 2 diabetes, in particular the need for short term insight to improve control of type 1, in contrast with the need for insight to relate short term decisions to longer term consequences for people living with type 2.  Three key opportunities for design innovation to support diabetes self-management were identified: i) tools to generate personal insight including visual presentation of data; ii) tools to support insightful and motivational conversations; and iii) tools to give feedback on progress

Geoelectric field measurement, modelling and validation during geomagnetic storms in the UK

Significant geoelectric fields are produced by the interaction of rapidly varying magnetic fields with the conductive Earth, particularly during intense geomagnetic activity. Though usually harmless, large or sustained geoelectric fields can damage grounded infrastructure such as high-voltage transformers and pipelines via Geomagnetically Induced Currents (GICs). A key aspect of understanding the effects of space weather on grounded infrastructure is through the spatial and temporal variation of the geoelectric field. Globally, there are few long-term monitoring sites of the geoelectric field, so in 2012 measurements of the horizontal surface field were started at Lerwick, Eskdalemuir and Hartland observatories in the UK. Between 2012 and 2020, the maximum value of the geoelectric field observed was around 1 V/km in Lerwick, 0.5 V/km in Eskdalemuir and 0.1 V/km in Hartland during the March 2015 storm. These long-term observations also allow comparisons with models of the geoelectric field to be made. We use the measurements to compute magnetotelluric impedance transfer functions at each observatory for periods from 20 to 30,000 seconds. These are then used to predict the geoelectric field at the observatory sites during selected storm times that match the recorded fields very well (correlation around 0.9). We also compute geoelectric field values from a thin-sheet model of Britain, accounting for the diverse geological and bathymetric island setting. We find the thin-sheet model captures the peak and phase of the band-passed geoelectric field reasonably well, with linear correlation of around 0.4 in general. From these two modelling approaches, we generate geoelectric field values for historic storms (March 1989 and October 2003) and find the estimates of past peak geoelectric fields of up to 1.75 V/km in Eskdalemuir. However, evidence from high voltage transformer GIC measurements during these storms suggests these estimates are likely to represent an underestimate of the true value

Digital Diabetes IDDEAS and GDS

The IDDEAS and GDS projects seek to develop innovative new resources for My Diabetes My Way* (MDMW) to support people living with diabetes to gain insight from health and lifestyle data to improve self-management. The IDDEAS and GDS projects were proposed by the Clinical and Technical Leads from the MDMW team, both based at the University of Dundee. The projects were accepted by the Digital Health & Care Institute as part of an integrated ‘Digital Diabetes’ programme of seven projects seeking to develop digital resources to support selfmanagement. The IDDEAS project aims to enable communication and data transfer between NHS Scotland diabetes platforms (MDMW and SCI-Diabetes) and third party and commercial products. This would give patients choice in terms of the application(s) they use to meet their needs. The GDS project aims to develop automated algorithms to analyse data obtained from home blood glucose monitoring and trigger automated clinical decision alerts and feedback for healthcare professionals and patients (via SMS) based on patterns in glucose readings. The technical aspects of the IDDEAS and GDS projects are being developed within DHI Factory projects. The Experience Lab Team were tasked with working with the intended end users to understand how they would like to collect, share, see and use their health and lifestyle data within MDMW, and understand the acceptability of the proposed innovations and how they could best support self-management. Experience Lab activity for these projects began with Pre-Labs in late 2015, and developed through General Labs in 2016, culminating in a dedicated Niche Lab in early 2017

Digital Diabetes Dashboard

The Digital Dashboard Experience Lab project explored what information is meaningful to share in a virtual consultation between a health professional and a person living with diabetes, and developed ideas for digital tools to support this experience. The project was proposed by partners at the University of the Highlands and Islands and NHS Highland, who are trialling video conferencing (VC) technology within virtual diabetes clinics to overcome increasing demand on the service and reduce travel burdens. The concept for the Dashboard emerged in response to challenges experienced in collaboratively discussing diabetes data during the virtual consultation. The project proposal was accepted by the Digital Health & Care Institute as part of an integrated ‘Digital Diabetes’ programme of projects seeking to develop digital resources to support self-management. The Digital Dashboard Experience Lab took place in December 2016, following Pre- and General Labs, which explored themes and questions that cut across the projects in the Digital Diabetes programme (commenced November 2015). This report describes the Experience Lab activity for the Digital Dashboard project and presents a detailed set of findings. It begins by providing project background and aims, and summarises the relevant findings of the Pre- and General Labs (described in full in previous reports). Three overarching themes emerged: Empowerment and Readiness, Equity and Collaboration, and Timeliness of Information and Insight; offering insight into the current consultation from the perspectives of both people living with diabetes and health professionals. These insights and ideas are mapped onto the Before, During and After stages of a virtual consultation, offering recommendations for the design of digital tools and content to support meaningful and personcentred consultations. The report sets out a concept for the ideal Digital Dashboard and explains its use throughout the virtual consultation. Finally, conclusions are presented, and next steps for the development of the Digital Dashboard are discussed