Highly specific, sensitive sensors interfaced with portable, easy-to use, low-cost instruments are needed for rapid point-of-care infection diagnostics, and will lead to better targeted therapy, shorter time to treatment and reduced morbidity. In this project, we propose to realise a generic, flexible, compact sensing platform with high sensitivity and selectivity. The system will comprise a low-cost instrument employing cheap, disposable generic sensor chips that can be readily committed to specific analytes, from small molecules to proteins and DNA, by using conventional surface modification techniques. Paper-based fluidics will be used to deliver analytes straightforwardly from a drop to the sensor surface or, where required, fluidic microsystems may be easily integrated. The sensing system will be demonstrated with clinical samples from patients who have been exposed to controlled infection to whooping cough and for the analysis of priority pathogens such as ebola and plague. This proposal builds upon our recent work on waveguide-enhanced Raman spectroscopy (WERS) to realise a sensor chip which shows surface enhancements comparable to those of surface enhanced Raman spectroscopy (SERS) with improved application flexibility and manufacturability, and upon joint work between Dstl and Chemistry on surface enhanced Raman approaches to bioanalyte detection. The proposed biosensing platform will have widespread application at the point of care for patients, in the detection of infection and the diagnosis of disease, and for broader applications such as environmental monitoring and security, and will be flexibly configurable for specific settings and analytical challenges. The desktop instrument, employing plug-in disposable sensor chips with simple operation will be appropriate for use in the GP's surgery, the ward, or in remote communities.

RESEARCH CONTEXT An estimated 25,000 foreign fighters have been recruited to Islamic State (IS) from over 100 counties around the world. While shocking in itself, this reflects only the militant end-product of the radicalisation process. Before militancy emerges, IS supporters use mainstream social media in English to socialise, radicalise and recruit foreigners. For example, the fourth IS 'Clanging of the Swords' film racked up millions of views on video-sharing platforms, and created vast excitement among those who followed ISIS online. This use of online communications in English by supporters of Islamic State (IS) presents two unprecedented research opportunities: first, to predict the spread of extremism in English-speaking populations; and second, to understand how online communications shape people's understanding of IS and its opponents. However, currently there is no method to analyse longitudinal social media data to investigate the processes underlying the radicalisation of social media users. The proposed research provides a timely opportunity to refine methods, software and analytics to maximise the impact that psychology and computer science can make to countering extremism. The central research questions are how and why people develop allegiance to extremist groups through communicating online. To do this, we will develop the functionalities and capabilities of an existing software suite that can harvest and analyse large volumes of publicly-available Twitter data ('Tweets'). AIMS AND OBJECTIVES The central aim of this project is to develop conceptually-grounded social media analytics software to investigate the socialisation and radicalisation of mainstream users. As a by-product of this process, and secondary aim, we will establish how supporters of radical Islam use online communications in English to affect how their target audience defines both themselves and their opponents in relation to IS. APPLICATIONS AND BENEFITS This project will deliver a software tool that can analyse longitudinal big data. This software will be open source and freely available. This means that it will have the potential to make a big impact in social science. It will be applicable to, and usable by, any researcher or practitioner interested in analysing social media data. PROJECT TEAM Our project brings together a multi-disciplinary team of academics and will be steered by end-users, mediated by Defence Science and Technology Laboratory, whose expertise will enable us to maximise the usefulness and applicability of the software tools. On the academic side, we have assembled a team with interdisciplinary strengths in computer science, psychology and social media data analysis to understand the needs of social scientists and successfully develop technology that will become fully embedded in social science and social media research.

Nerve agents are amongst the most deadly chemicals known to man and continue to pose a significant societal threat. Nerve agents function by inhibiting chemicals in the brain that affect the nervous system. Thus, nerve agents cause seizures in the brain which can lead to severe brain damage and even death. Several drugs are used as initial treatments for nerve agent poisoning, but these are sometimes ineffective and can themselves be harmful. In addition, the greater the delay between exposure to the nerve agent and the provision of treatment, for example on the battlefield, the lower the likelihood of the effectiveness of these treatments. Consequently, new and better treatment options are needed to protect against the effects of nerve agents. Current methods used for testing new drug effectiveness for the treatment of nerve agent poisoning are largely reliant on the use of rodents. Such experiments are slow and costly, and usually involve severe procedures, such as the surgical implantation of electrodes in the brain and exposure to nerve agents. There is a requirement to develop higher throughput methods for identifying novel treatments, that are also more ethically favourable than those currently available. The non-protected 4-days post-fertilisation (dpf) larval zebrafish could prove invaluable as they have been shown to be responsive to a range of seizure-inducing drugs and can be tested quickly and easily in large numbers. Scientists from the universities of Portsmouth and Exeter will build on previous NC3Rs-funded work to transfer a non-protected larval zebrafish seizure model to Dstl, where the methods can be used to identify novel treatments for nerve agent poisoning. Dr Parker is a zebrafish behavioural expert, and will develop behavioural measures of seizures in 4dpf larvae. Many of the protocols were developed during Dr Parker's work on an NC3Rs project grant at Queen Mary, London (PI Caroline Brennan). Dr Winter is an expert in examining the brain during seizures in zebrafish using advanced imaging techniques, some of which have been developed during an ongoing NC3Rs studentship. His team will focus on developing approaches assessing seizure activity in the 4dpf zebrafish brain to understand model relevance for predicting effects in mammals. The end users at Dstl will utilise this approach for the identification and development of novel treatments for nerve agent poisoning. Dstl colleagues will promote the wider uptake of this approach, and the zebrafish as a model for assessing chemical toxicity, within the international defence research community. This approach could replace a significant number of rodents used in testing novel treatments against nerve agent toxicity, thus reducing overall rodent use by an estimated 75%. Limited rodent experiments would remain only for confirmatory purposes. Our approach could therefore prevent the yearly global use of at least 1500 rodents in these severe protocols. In addition to the direct replacement of rodents, the data generated in non- protected zebrafish larvae can also be used to refine remaining rodent studies to ensure that appropriate non-toxic doses are used. Refinement will also result from the identification and ruling out of any putative treatments with undesirable properties prior to escalation to rodent models. Dstl actively participates in a number of international research collaborations including bilateral arrangements with European countries and an important multinational agreement between the Australia, Canada, the UK and the USA, the CBR Memorandum of Understanding (MOU). Dr Kearn will use these arrangements and his position as UK lead for a predictive toxicology task under the CBR MOU to share data and methodologies from this project, champion its outputs and influence other Nations' programmes to encourage uptake of this technology.

Nutrients are essential for phytoplankton growth in the sea. Phytoplankton take up nutrients from the surrounding water and the extent of their growth is largely dependent on nutrient availability. Nitrate and phosphate are vital nutrients and their presence in light-rich surface waters can sustain algal blooms. Phytoplankton draw down carbon dioxide from the atmosphere and in shelf seas can lock this carbon up in the sediments. In this project we will investigate the idea that the seasonal supply of nutrients to shelf seas is controlled by physical mixing processes at the shelf edge. This will be carried out using new sensors capable of determining nitrate and phosphate in-situ which will be deployed on underwater gliders for up to 3 weeks at a time. Underwater gliders are autonomous vehicles that, after launching from close to the coast, can "fly" to a sampling site and send back data via a satellite link. We will use four glider missions over a seasonal timescale (June & Sept 2013, Jan & April 2014) in order to gain a fundamental insight into the annual supply of nutrients to the highly productive shelf seas around the Malin Shelf. Alongside the nutrient sensors on the gliders will be three other sensors, a conductivity and temperature sensor, an oxygen sensor and a sensor which can determine chlorophyll a which is used as a proxy for phytoplankton biomass in the water. For each mission we will use two gliders to simultaneously characterise both the on- and off-shelf concentration gradients. These glider missions will be integrated into a large NERC-funded consortium, FASTNEt, which aims to identify the physical processes that facilitate the exchange of water across the edge of the north-west European shelf and understand how they evolve across the seasons. FASTNEt will be deploying long-term, shelf-edge current meter moorings and another underwater autonomous vehicle, the Autosub Long Range (ALR) in the same location. The use of sensors deployed on gliders allow us to increase the spatial and temporal coverage of data that would not be possible from traditional shipboard measurements, that cannot be carried out in stormy conditions. The combination of in-depth knowledge of the physical processes occurring at the Malin Shelf along with accurate high resolution nutrient data from the sensors means that we will be able to investigate what controls nutrient supply to the photic zone and how this impacts on the phytoplankton growth. Additionally, we will be trialling new deployment methodologies for these underwater gliders - using fast day-boats to take them as far offshore as possible from a coastal base. Our data will be freely available and we will share our findings with end-users (such as the UK government's Department for Environment, Food and Rural Affairs who are responsible for fisheries, and the UK Met Office) throughout the project.

Nerve agents are amongst the most deadly chemicals known to man and continue to pose a significant societal threat. Nerve agents function by inhibiting chemicals in the brain that affect the nervous system. Thus, nerve agents cause seizures in the brain which can lead to severe brain damage and even death. Several drugs are used as initial treatments for nerve agent poisoning, but these are sometimes ineffective and can themselves be harmful. In addition, the greater the delay between exposure to the nerve agent and the provision of treatment, for example on the battlefield, the lower the likelihood of the effectiveness of these treatments. Consequently, new and better treatment options are needed to protect against the effects of nerve agents. Current methods used for testing new drug effectiveness for the treatment of nerve agent poisoning are largely reliant on the use of rodents. Such experiments are slow and costly, and usually involve severe procedures, such as the surgical implantation of electrodes in the brain and exposure to nerve agents. There is a requirement to develop higher throughput methods for identifying novel treatments, that are also more ethically favourable than those currently available. The non-protected 4-days post-fertilisation (dpf) larval zebrafish could prove invaluable as they have been shown to be responsive to a range of seizure-inducing drugs and can be tested quickly and easily in large numbers. Scientists from the universities of Portsmouth and Exeter will build on previous NC3Rs-funded work to transfer a non-protected larval zebrafish seizure model to Dstl, where the methods can be used to identify novel treatments for nerve agent poisoning. Dr Parker is a zebrafish behavioural expert, and will develop behavioural measures of seizures in 4dpf larvae. Many of the protocols were developed during Dr Parker's work on an NC3Rs project grant at Queen Mary, London (PI Caroline Brennan). Dr Winter is an expert in examining the brain during seizures in zebrafish using advanced imaging techniques, some of which have been developed during an ongoing NC3Rs studentship. His team will focus on developing approaches assessing seizure activity in the 4dpf zebrafish brain to understand model relevance for predicting effects in mammals. The end users at Dstl will utilise this approach for the identification and development of novel treatments for nerve agent poisoning. Dstl colleagues will promote the wider uptake of this approach, and the zebrafish as a model for assessing chemical toxicity, within the international defence research community. This approach could replace a significant number of rodents used in testing novel treatments against nerve agent toxicity, thus reducing overall rodent use by an estimated 75%. Limited rodent experiments would remain only for confirmatory purposes. Our approach could therefore prevent the yearly global use of at least 1500 rodents in these severe protocols. In addition to the direct replacement of rodents, the data generated in non- protected zebrafish larvae can also be used to refine remaining rodent studies to ensure that appropriate non-toxic doses are used. Refinement will also result from the identification and ruling out of any putative treatments with undesirable properties prior to escalation to rodent models. Dstl actively participates in a number of international research collaborations including bilateral arrangements with European countries and an important multinational agreement between the Australia, Canada, the UK and the USA, the CBR Memorandum of Understanding (MOU). Dr Kearn will use these arrangements and his position as UK lead for a predictive toxicology task under the CBR MOU to share data and methodologies from this project, champion its outputs and influence other Nations' programmes to encourage uptake of this technology.