NE/K011855/1Influence of population connectivity on depth-dependent diversity of deep-sea marine benthic biotaClosedResearch GrantNERCSch of Biological and Marine SciencesSpecies populations are connected to each other through both movement of adults (migration) and eggs, larvae and juveniles (dispersal). If populations become isolated from one another (i.e. are no longer connected), then through genetic mutation, drift and natural selection, they may become so different that they evolve into new biological species. Understanding how populations become isolated is critical to understanding the process of speciation. In the marine environment many species do not move as adults (e.g. corals) or move very slowly (sea urchins). This means that for different adult populations to remain connected they rely on dispersal of early life history stages. Most marine species have a larval stage that lives in the plankton for a period of time, moving with the currents, before settling in a new area. It is larval dispersal that keeps distant populations connected. So understanding patterns of larval dispersal is important to understanding connectivity. In the deep-sea (>200m) the bathyal region of the continental slope has been identified as supporting high species richness and being an area where the rate of origination of new species may also be high. The reasons for this are not clear, but given the importance of connectivity to population isolation and speciation, it follows that the key to understanding patterns of species diversity in this region lies in understanding connectivity. New research has suggested that because the speed of the currents that carry larvae decreases as you go deeper, larvae might not be able to travel as far, leading to a greater tendency for populations at bathyal depths to become isolated over a given distance, and thus increasing the chances of speciation. This study aims to test this theory by investigating how patterns of connectivity vary with depth. This will be done in 3 ways: 1) using genetic analysis (similar to DNA fingerprinting) to compare how related distant populations are and if they become less closely related as you go deeper, 2) using a model of ocean currents to simulate the movement of larvae between sites, and 3) to look at the range and abundance of species present at distant locations to see if those at shallower depths are more similar to each-other than those at bathyal depths. This research has important implications for the sustainable management of the marine environment. Humans increasingly rely on the marine environment to supply us with food, building materials, fuel, and to soak up carbon slowing the progress of human induced climate change. However, our increasing use of this environment is starting to affect is 'normal' functioning, affecting the processes that allow it to provide us with food, fuel, etc. To try to help protect and sustain these 'ecosystem functions', Governments all over the world are setting up networks of Marine Protected Areas (MPAs) to ensure against serious ecosystem disturbance and cascade effects resulting from overexploitation that ultimately impair ecosystem function. There are many questions to be answered when trying to set up an MPA network, but one important question is where to put them to make sure that the populations that live within them are not isolated from each other but are connected. This research will help answer this question in the deep sea, and thus help managers, governments and society ensure the long term health of the ocean.Who will benefit? Beneficiaries of the proposed research include UK Government Departments (Defra and Marine Scotland), and their advisory body the Joint Nature Conservation Committee. At a European level beneficiaries include the Directorate-General for Maritime Affairs and Fisheries, the Environment Directorate-General, all contracting parties to the Oslo-Paris (OSPAR) Convention, and groups who provide advice to these bodies (International Council for the Exploration of the Sea), as well as fisheries regulatory groups such as the North East Atlantic Fisheries Commission and North Western Waters Regional Advisory Council. At a Global level beneficiaries include all contracting parties to the Convention on Biological Diversity, particularly those with extensive deep-sea areas within their exclusive economic zones. In addition to society a broad cross-section of the academic community will also benefit, from evolutionary biologists to demographers, macroecologists, biogeographers and oceanographers How will they benefit? One of the biggest challenges facing marine environmental managers the world over is how to implement an 'ecologically coherent' network of marine protected areas (MPAs). This task is a requirement of national (e.g. UK Marine Act), regional (European Marine Strategy Framework Directive, OSPAR Convention), and global (Convention on Biological Diversity) policy, and the UK has a legal obligation to implement a network. In order to be successful and acceptable to those people and livelihoods affected by the potential restrictions placed on human activities within these protected areas, it is vital that decisions about where to place them are based on the best scientific data available. Although there is a small but growing body of research on MPA selection criteria including representation of habitats, percentage of target area requirements, and size of MPAs, there is very limited directed research addressing MPA network design, and specifically the spacing of MPAs within a network in order to ensure connectivity of protected populations. This situation is even more extreme for the deep-sea where data are sparse and human impacts are difficult to quantify. The proposed research aims to investigate population connectivity in the deep sea; specifically addressing potential variation in connectivity with depth, connectivity among spatially fragmented habitat (seamounts, banks, oceanic islands), and the potential for bio-oceanographic models to predict large scale connectivity patterns. The outputs of this research would provide the basis for robust scientific advice on the spacing of MPAs within a network and the importance of seamounts and banks to network coherence. In addition it would potentially provide a freely available scientifically validated tool (bio-oceanographic model) for modelling connectivity in other areas. The PIs positions on advisory bodies at European and Global levels will ensure this advice is fed straight into policy and environmental management decisions. The drivers behind the policy to conserve biodiversity are not for the sake of conservation itself, but for the sustainability of the growing human populations in terms of food and resources. Ultimately providing science to support these policy decisions is to the benefit of society as a whole.14AB3A4E-B700-4A41-AC03-924EB4EBD196Ecol, biodivers. & systematics30A65FD3A1-4060-4633-B898-A9BE66B54CF2Marine environments2088E467D8-9675-4A34-981C-F517896062B4Genetics & development509680ED77-DC70-4780-8689-8895551AC6C5Conservation Ecology107476611A-67C7-40CD-9251-0A56C12EAD65Population Ecology10387FA8AA-A599-401E-A726-B3B670F93825Ecosystem Scale Processes20EAA99485-F7C8-450C-BC5B-B8221103F2EFCommunity Ecology10145958A0-DF76-40F3-A919-A64B4E16E540Population Genetics/Evolution50EP/P002137/1The Bristol Urban Area Diagnostics PilotClosedResearch GrantEPSRCCivil EngineeringAs European Green Capital 2015 and one of the Rockefeller 100 Resilient Cities, Bristol has challenged itself to transform by 2065 into a place where citizens 'flourish' by working together to create wellbeing, and achieve this equitably and sustainably. The Bristol Urban Area can legitimately claim to be in the vanguard of such urban transformation, and yet its development pathway remains characterised by paradox, and the need to deal with some stark realities and to challenge a 'business-as-usual' mind-set if progress towards aspirational goals is to be sustained. This proposal addresses a fundamental issue: what is stopping Bristol from bridging the gap between its current situation and the desired future as encapsulated in the City's various visions and aspirations? We have forged a partnership focused on the contiguous City of Bristol and South Gloucestershire urban area. We have secured the full backing of the two local authorities, Bristol Green Capital Partnership and Bristol Health Partners, the LEP, the local business community, citizen groups, and academics from across both Universities, with tangible commitments of support. Dissolving siloes through partnership, and a genuine interdisciplinary and cross-sectoral collaboration, is core to our approach, and hence both Universities have committed to share equally the financial resources with external partners in a three-way split. It is a key strength of this project that we are able to leverage extensively on internationally leading research assets, including: 'Bristol is Open', the FP7-funded Systems Thinking for Efficient Energy Planning (STEEP), the Horizon 2020 REPLICATE project, ongoing work at the £3.5m EPSRC/ESRC International Centre for Infrastructure Futures (ICIF) and co-produced and co-designed research such as the AHRC/ESRC Connected Communities and Digital Economy funded projects including REACT Hub, Tangible Memories and Productive Margins. We also have access to a wealth of highly valuable data sources including the 2015 State of Bristol Report, Bristol's Quality of Life Survey, and the Avon Longitudinal Study of Parents & Children that has followed the health of 14,500 local families since the 1990s. We intend to build on the ICIF cognitive modelling approach which identifies the importance of challenging established mental models since these entrench a 'business-as-usual' mind-set. At the heart is co-creation and co-production, and an acknowledgement that citizen behaviour and action are essential to the delivery of desired societal outcomes such as wellbeing, equality, health, learning, and carbon neutrality. The work programme synthesises existing domain-specific diagnostic methodologies and tools to create a novel Integrated Diagnostics Framework. We believe strongly that unless an integrating framework is developed to bring together multiple viewpoints, the diagnosis of urban challenges will remain fragmented and understandings will potentially conflict. We will apply this framework in this pilot project to diagnosis complex problems across four 'Challenge Themes': Mobility & Accessibility, Health & Happiness, Equality & Inclusion and the 'Carbon Neutral' city. We have appointed 'Theme Leaders' who are all 'end users' of the diagnostics, ensuring that the process of investigation is cross-sectoral, interdisciplinary, participatory and grounded in real-world context and application. The legacy of the project will be threefold: firstly innovation in the diagnostic framework and methods needed to address urban challenges; secondly its application to the Bristol urban area and the resulting diagnostics synthesise across the four Challenge Themes; and finally the formation of an embryonic cadre of cross-sector city leaders with the capability to apply integrated diagnostics and challenge the prevailing 'business as usual' approaches.Focussing on significant challenges. The Bristol Urban Area (BUA) can legitimately claim to be in the vanguard of urban transformation, owing to numerous accolades in liveability, sustainability, and urban innovation. However, its development is characterised by paradox and there are stark realities to face. Significant progress is needed in interconnected challenges of 'health and happiness', 'mobility and accessibility', 'equality and inclusion' and 'carbon-neutral city'. Evidence on the urgency of these challenges is presented in the Case for Support. Our long-term ambition, through effective diagnoses, is to make a significant impact in these areas. Co-production with end users - partnerships for impact. The Pilot will take us part of the way towards the above goal, yet it is critical to design for impact and ensure the diagnostic framework will meet the needs of future end-users. Thus, this proposal has been co-developed with a wealth of end-users with significant influence (Bristol City Council, South Gloucestershire Council, Bristol Green Capital Partnership and Bristol Health Partners). This approach has established a dedicated set of partners, committed to the outcomes and to long-term legacy. End-users have agreed to lead 'challenge theme' investigations, creating an intimate involvement in the project and ensuring they can benefit immediately from the new knowledge. Supporting the improvement of collaborative practices for health, mobility, carbon-neutral city, equality and beyond. To resolve interconnected challenges in the context of budget constraints, effective collaborations across organisational and disciplinary boundaries are essential. An Integrated Diagnostic Framework focussed on collaborative practices will offer new ways to robustly assess and learn in real time, generating short-term, but potentially large-scale impacts on BUA's mobility and accessibility, health and happiness, inclusion and inequality and Carbon-neutral agendas. However, the framework will also be applicable to other challenges leading to an exponential potential for impact. The diagnostic framework will be publicly accessible on a prominent webpage and shared via partners (engaging at least 450 people) alongside supporting method documents, formal project reports, blogs, and simple guides to help change-makers from a variety of backgrounds replicate the diagnosis in new challenge areas. A joint training session will attract 100+ people and support leadership development. Podcasts and training materials from the session will be made available online for a wider audience. Inclusion in the October 2017 'Festival of the Future City' will secure widespread awareness and uptake amongst the public, international policy makers, academics and businesses. Exceptional support from the Local Economic Partnership, Arup and Buro Happold offers routes to impact amongst business. UoB's Cabot Institute - a coordinator for Future Cities research - will act as an ongoing conduit for the project, coordinating future funding applications, monitoring impact and organising events to ensure continuity of the partnership during any future funding gaps. Regular connection to national and international networks (e.g. UWE's WHO Collaborating Centre on Healthy Urban Environments, Core Cities network, ICLEI, the Rockefeller Resilient City Network) offers routes to impact far beyond Bristol. The legacy of this project will be threefold: first, innovation in the diagnostic framework and methods needed to address the challenges of urban living holistically; second, the application of this diagnostic approach to the BUA in order to identify the obstacles that have prevented further progress in delivering outcomes; and finally, a legacy through the formation of an embryonic cadre of cross-sectoral city leaders with the capability to use this learning to challenge the 'business as usual' approaches we experience in urban systems in BUA and the UK as a whole.D7B3C750-5146-47F0-B10D-145C65C76B3BCivil eng. & built environment1002A7EB0B0-C660-43C5-A008-F6D79527E892Urban & Land Management1002609632Investigation of the molecular mechanisms of intellectual disability using human-brain organoidsClosedStudentshipBBSRCSch of Medicine, Medical Sci & NutritionIntellectual disability (ID) is a condition characterized by significant limitation in cognitive ability and adaptive behaviours with disease onset before adulthood. ID affects 1-2% of children worldwide resulting in a high social burden. Due to recent advances in high-throughput sequencing technology, genetic studies identified more than 2500 genes associated with ID, and autosomal-recessive ID counts more than 50 % of the genetic causes of ID. A significant portion of ID cases shows an anatomical abnormality in the brain such as microcephaly and lissencephaly, suggesting a neurodevelopmental origin of the disorder. However, little is known about the molecular mechanisms underlying ID, which limits possible interventions and therapeutics of the disease. The goal of the project is to investigate the molecular mechanisms of ID using human-brain organoids. We have identified a group of ID-associated genes that encode proteins involved in RNA processing and modifications, and ID Patients with mutations in these genes have microcephaly. In this project, the function of those genes on cortical development will be investigated with the following specific objectives. Objective 1. To investigate the role of ID-associated genes in neural stem cell behaviour and neuronal migration and maturation in human forebrain organoids Objective 2. To determine transcriptomic changes upon genetic insults using single-cell RNA sequencing and identify target RNAs Objective 3. To identify the molecular mechanism of RNA processing involved in cortical development, and validate its functionality in cortical development The student will obtain fundamental concepts of brain development including neural stem cell behaviour and neuronal maturation during human cortical development and neurodevelopmental disorders. Technically, the student will learn how to culture human stem cells and brain organoids and assess neural development using immunohistochemistry, imaging, and computational analyses. Also, the student will have opportunities to learn molecular biology for genetic manipulation of ID genes and a biochemical approach to understand the RNA process6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedES/X010996/1The effects of voter ID in the UKActiveResearch GrantESRCPolitics and International RelationsThe UK 2022 Elections Act will introduce mandatory photographic voter ID for in-person voting in England, Scotland, and Wales in general elections, and also in all local elections in England from May 2023. The reform will, for the first time, make the exercise of the right to vote in UK general elections conditional on the presentation of photo ID. Government research suggests that 9 per cent of UK voters do not currently have eligible identification. This is a potentially consequential and contentious change that forms part of a wider international trend (e.g., US, India). Its proponents argue that voter ID combats electoral fraud and increases voter confidence in elections. Its opponents argue that, in contexts without national ID like the UK, it depresses electoral participation, equality, and trust in electoral fairness across a range of voter groups who are less likely to possess ID. Context Scientifically, the effects of voter ID remain poorly understood. Studies of the effects of voter ID feature contradictory findings and focus overwhelmingly on the US (Alvarez et al 2021, Atkeson et al 2010, Atkeson et al 2014, Grimmer et al 2018, Hanjal et al 2017, Stuart III et al 2016, Valentino & Neuner 2017). In the US, the recent introduction of strict voter ID laws in multiple states is accompanied by the increasing salience of concerns about electoral integrity and fairness in the public discourse. However, findings derived from the US context are of limited generalizability because responses to voter ID in the US are shaped by the political salience of race and a level of political polarization that does not apply to other developed democracies (Wilson & Rosenbluth 2014). Moreover, causally identified research designs are rare in studies of the effects of voter ID, which makes it difficult to draw robust conclusions (Highton 2017, Burden 2018, Grimmer et al 2018). Aims This project studies the effects on voters' behaviour and attitudes of the introduction of mandatory photo ID in the UK. It combines (i) original surveys that examine the effect of voter ID as it unfolds in real time in the context of English local elections and the next UK general election (likely to be held in 2024 or 2025) with the analysis of historical data on the effects of the introduction of voter ID in (i) Northern Ireland in the early 2000s, and (iii) the English voter ID trials of 2018 and 2019. Objectives The project's academic and policy objectives are: (i) To deliver the first comprehensive study of the effects of voter ID in any developed democracy on the local and national level. (ii) To contribute to political science an understanding of the effects of voter ID in the UK, a case of importance in its own right, and a country from which conclusions are more likely to generalize to other developed democracies than from the US. (iii) For experts of British politics, this is the first and only study of voter ID in the UK which employs a research design that can identify the causal effects of the reform. (iv) For the UK Government, Parliament, and the Electoral Commission, the project provides timely and politically impartial evidence of the effect of voter ID (please see Case for Support, section "7. Impact").1E29C62B-F937-485F-A347-819B1D73E892Pol. sci. & internat. studies100A0A6AC9B-B185-4F84-87EB-59ABB6D2B6A7See subject area50B4741F62-1463-4352-8277-27759FF77AADPolitical Science50MC_PC_13085Modifying a weight management intervention for people with intellectual disabilitiesClosedIntramuralMRCUNLISTEDObesity is a major health concern nationally and internationally. People who are obese are more likely to develop diseases such as diabetes and high blood pressure which affect their quality of lofe and may reduce their life expectancy. People with intellectual disabilities (ID) are more likely to be obese than people in the general population. One reason for this is that interventions to reduce obesity are not always accessible to people with ID because they are too hard to understand and follow. Slimming World (SW) has been shown to help people in the general population to lose weight but we do not know how suitable the SW intervention is for people with ID. This study will work with people with ID to identify how the SW intervention can be changed to make it more acceptable and relevant for people with ID. We will discuss what people tell us with experts from SW and together we will make changes to the intervention so that people with ID can join in with existing Slimming World groups and follow an appropriate and accessible weight management programme. We will also try the intervention with around eight people with ID to test whether it is feasible to run the modified intervention for people with ID, and make further improvements before we decide whether it is sensible to develop a study to test whether the intervention actually helps people with ID to lose weight.Obesity is a major public health concern nationally and internationally. There is a higher prevalence of obesity in adults with intellectual disabilities (ID) compared to the general population (39.3% women; 27.8% men with ID are obese compared with 25.1% women;22.7% men in the general population). Interventions shown to be clinically effective at achieving sustained weight loss in the general population are unlikely to be accessible and appropriate to this population because of their complexity. Research is needed to develop and test weight loss interventions designed to meet the needs of this population (recognising communication and literacy needs as well as broader issues of participation and inclusion). The proposed study is informed by the MRC framework and involves both development and feasibility components. The study will adopt a participatory approach to review and where necessary, modify and existing weigh management intervention (Slimming World), for use with adults (age =18) with ID who are overweight or obese (BMI>25). It will explore the feasibility and acceptability of delivering the modified intervention from the perspectives of a range of stakeholders. Only adults with the capacity to consent prior to recruitment. The study will be carried out in collaboration with eight people with ID in recognition of the importance of involving disabled people in the development of services addressing their needs. Outputs from the study will include a prototype of a modified Slimming World (SW) intervention for use with adults with ID who are overweight or obese, a protocol for establishing capacity to consent, a set of measures and procedures for collecting data from participants with ID and briefing notes on the development process to inform similar work on other issues. The study will conclude with an assessment of whether to proceed to a pilot trial made in collaboration with representatives from Sheffield University Clinical Trials Research Unit.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified2408226The development of a Core Outcome Set for evaluating the impact of Relationships and Sex Education with children with intellectual disabilityClosedStudentshipESRCSocial ScienceFrom September 2020, Relationships and Sex Education (RSE) will be compulsory in schools in England for all pupils including those with intellectual disability (ID). Pupils with ID are twice as likely to experience unintended pregnancies and sexual abuse compared to the general population. Yet little is known on how to deliver RSE for ID, what its aims and objectives should be, or what effective RSE actually means. There is thus an urgent need to identify the important outcomes of RSE for ID. I propose to do so by developing a 'Core Outcome Set' (COS); I will engage key stakeholders and identify what they think RSE for ID should be achieving and therefore what should be measured after its delivery. I will undertake: 1) a systematic search of the literature looking for any outcome measures currently used with RSE for ID 2) workshops with key stakeholders (pupils with ID, parents, teachers, school staff, policymakers and expert researchers) to gather potential outcomes that are meaningful for each group; 3) an online survey and if needed a final workshop, to reach consensus on the COS content across stakeholders; 4) exploration of whether the identified COS is usable with pupils with ID in a busy school environment. My PhD will contribute a significant first step in the successful implementation, evaluation and sustainability of RSE for education settings. Pupils with ID for the first time will be involved in the development of COS making sure their needs and opinions are incorporated in the RSE.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedMC_UU_00030/3Genomic Disorders and Cognitive DevelopmentActiveIntramuralMRCUNLISTEDAbout 1 in 100 people worldwide has intellectual disability (ID), meaning that they have significant lifelong difficulties with learning, communication and independent living skills. ID often occurs alongside other physical and mental health difficulties, meaning that people with ID require high levels of support and often have poor quality of life. Currently the support that can be provided is mainly reactive and symptom-focused - tackling problems as and when they arise. This is because, until recently, we did not know the cause of ID for the majority of people, so it was not possible to predict problems at an earlier stage and provide more effective support tailored to the cause of each person’s condition. This situation is now changing fast. New genetic testing technologies mean that it is possible to identify a specific cause in more than half of people with ID. Testing is available within the NHS, and in many global health settings. Genetic diagnosis provides new opportunities to understand each person’s ID, and use this knowledge to improve physical and mental health. To achieve this, our research aims to bridge the gaps between the molecular cause of ID and the lifelong cognitive and mental health difficulties experienced by each person.The goal of this programme is to integrate genomic medicine with cognitive neuroscience to improve our understanding of neurodevelopmental disorders, and change long-term mental health outcomes for affected individuals and their families. Toward this goal, our objectives are (1) to map the neurodevelopmental correlates of genomic variation, (2) to discover the cognitive and neural mechanisms linking genomic variation to symptoms and impairments, and (3) to investigate how genomic disorders interact with social context to influence well-being. Each genomic disorder is extremely rare – our strategy is to investigate groups of genomic disorders defined by convergent impact on physiological processes (gene functional networks). One gene functional network which is a particular focus of the programme is synaptic vesicle cycling disorders, including Synaptotagmin 1-associated and STXBP1-associated neurodevelopmental disorders. Other current projects focus on chromatinopathy disorders and Wnt-signalling disorders. Clinical presentations of genomic disorders within each functional network are complex and variable between individuals and within individuals over time. To understand this variability, we apply a transdiagnostic framework to investigate dimensional impairments and underlying cognitive and neural systems. To achieve this we use a variety of human cognitive neuroscience methods – behavioural questionnaires, interviews and structured observations; standardised neuropsychological assessments; bespoke cognitive tests; structural and functional neuroimaging via MRI; neurophysiology via MEG and EEG. We also analyse big datasets enabling larger-scale analyses of genotype-phenotype relationships. We engage in interdisciplinary collaborations with functional biologists to link molecular and cellular mechanisms to patients’ neurobiology and symptoms. To achieve clinical relevance we integrate social and biological understanding of mental health - we work closely with psychologists to connect neurobiology and cognition to lived experience and relationships. Our translational goal is to develop 4P (participatory, personalised, predictive, preventive) medicine strategies that will improve mental health and quality of life for individuals with neurodevelopmental genomic disorders and their families.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedES/W001985/1Road to recovery: Understanding the impact of COVID and recovery phases on children and young people with Intellectual Disabilities and their familiesClosedResearch GrantCOVIDSch of Health in Social ScienceIntellectual disabilities (ID) are characterised by social, and cognitive difficulties that are often associated with challenging behaviours. Increased levels of mental health issues have been reported in children and young people with Intellectual Disabilities (ID) and their caregivers. The COVID-19 response strategy entailed limiting access to education, respite care, and specialist services, therefore reducing the available support for families, with unknown consequences. The relative vulnerability of children with ID was highlighted by a recent report by the Children's Society (2020) which indicated that children with ID are more susceptible to wellbeing and mental health issues as a result of COVID and require urgent support in adapting to routine changes and understanding what is going on. These routine changes and reduction in access to services will continue for some time despite the recent implementation of the UK wide vaccination programme, further compounding mental health outcomes in children with ID and their parents. As we move into COVID transition phase, the current project will: 1) identify the family structure and social demographics of families who have a child with ID who are at greater risk of parent and child negative mental health outcomes; 2) explore the lived experiences of CYP with ID and their caregivers during COVID and transition phases 3) understand the CYP's and parent's experience of the recovery phase, including the lasting effects of COVID.57835945-1CF3-4554-A46B-1504261EB208Psychology10010E54DDB-E6DC-4DA1-B3EC-3B9564306567Child Psychology25A0A6AC9B-B185-4F84-87EB-59ABB6D2B6A7See subject area2504A22FBC-270B-490B-9264-E4ED93EFAAC7Health Psychology257E603EE4-868B-4DC0-95C0-AC11441D0126Developmental Psychology252579191Parenting Interventions for Parents of Adolescents with Intellectual DisabilitiesClosedStudentshipESRCCEDARIntellectual disability (ID) emerges during the developmental stage of a child's life and is defined by cognitive and adaptive deficits which have a lasting impact on development (Department of Health, 2001; Carulla et al., 2011). Having a child with ID is often associated with additional stressors for parents (Amaral, Dawson and Geschwind, 2011; Peer and Hillman, 2014). Further, adolescence is a significant time in development, with physical, social, emotional and cognitive changes, all of which can contribute to increased vulnerability of emotional and behavioural problems for adolescents. In addition, the onset and prevalence of mental health problems peaks during adolescence and early adulthood (Kessler et al., 2007). Therefore, the period of adolescence adds further challenges for parents of individuals with ID. Compared to their typically developing peers, adolescents with ID are more likely to exhibit emotional, behavioural and mental health problems (Ageranioti-Belanger et al., 2012; Baker et al., 2002). Increases in behavioural problems have been associated with decreases in parental well-being (Baker, 2005; Cohen et al., 2016; Giallo et al., 2015). There is a growing evidence-base to suggest that parenting interventions are effective in improving parenting, adolescent behavioural and emotional problems, family relationships and mental health and wellbeing of parents of children with ID (Brereton, Tonge, and Kiomall, 2009; Mazzucchelli, Jenkins and Sofronoff, 2018; Ward, Theule, and Cheung, 2016; Webster-Stratton and Reid, 2017). However, there is a lack of research focusing on parenting interventions for adolescents with ID. In collaboration with Herefordshire and Worcestershire Health and Care (HWHC) NHS Trust and Triple P International, this PhD aims to evaluate parenting interventions for adolescents with ID and to contribute to the evidence base in this neglected area. The aim of Study 1 is to synthesise the existing evidence on the use of parent-based interventions for adolescents with ID, by completing a systematic review of existing parenting programmes and outcomes for adolescents with ID and their parents. Study 2 aims to review and model the Building Bridges Triple P programme. We will undertake a series of consultation workshops with parents of adolescents with ID and professionals who work with these families. We will also conduct a modelling study of the Building Bridges Triple P programme to try out the programme and seek feedback from participants. Information collected will be summarised and consolidated. Study 3 aims to investigate how behavioural and emotional problem trajectories change during adolescence for individuals with ID and the relationship between parenting behaviour and the parent-child relationship and behavioural and emotional problems for adolescents with ID. To do this, we will conduct a secondary data analysis of the 1,000 Families Study dataset, using a linear mixed model to analyse the data. The overarching goal of this research is to help provide parents of adolescents with ID with appropriate support in order to improve outcomes for these families. Academically, this project will offer an in-depth understanding of parental interventions for parents of adolescents with ID, an area of research previously overlooked. The proposed research will also inform future research into the Building Bridges Triple P programme. Equally, this research will offer a valuable insight for our collaborative partners, subsequently enabling Triple P and HWHC NHS Trust to effectively tailor the support it provides to families.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified2867935Maximising the Efficiency and Effectiveness of International Development WASH Infrastructure Project ProcurementClosedStudentshipEPSRCArchitecture, Building and Civil EngIn 2017 developing countries received over 165 billion USD in official development aid, of which most is spent on delivering projects. However, International Development (ID) projects have turned project failure into a rule rather than an exception. The need for projects to be implemented efficiently and effectively is crucial, especially in the WASH sector. According to the World Health Organisation, more than four billion people lack access to safely managed sanitation with inadequate water, sanitation and hygiene leading to over 870,000 deaths annually. Therefore, to ensure that the funds available have the greatest possible impact is of critical importance; it is literally a matter of life and death. The ID sector and the projects that are procured by it, are faced with a unique array of peculiarities that are not generally encountered in conventional contexts. Issues such as high levels of corruption, complex networks of stakeholders, political or socio-economic instability, scarce resources and cultural or lingual unfamiliarity are among the many obstacles that need to be overcome. The existing theories and project management body of knowledge, including the contracts, tools, and techniques, employed to deliver projects were developed for conventional contexts. As such they do not have the necessary ability to factor in the added complexities and characteristics associated with the contexts in which ID projects are carried out. Therefore, they are not appropriate for ID projects. Very limited research has been carried out into efficient and effective means of procuring ID projects. As such, there is an urgent need for research to enable the development of specialised theories, tools and techniques that can cater for the contextual peculiarities of ID thus deliver projects in the most efficient and effective manner. Aims and objectives The main aim of the project is to develop a conceptual framework for the efficient and effective management and implementation of ID projects. The contextual characteristics under which ID projects are delivered complicate the implementation process and negate the applicability of existing theories, frameworks, tools, and techniques developed to govern contractual arrangements and manage project implementation in an efficient and effective manner. The objectives will therefore consist of: (1) Categorising the full spectrum of peculiarities and characteristics associated with ID contexts and analysis to identify their influence; (2) Identifying the essential building blocks, features, and requirements of an appropriate theory for ID projects; (3) Developing an integrative framework based through a refinement of existing theories and the development of new theories that are applicable to the contextual peculiarities of ID projects; (4) Identifying the sources of inefficiency and barriers to effectiveness during procurement processes through the application of the framework; (5) Developing a specialised suite of tools and techniques which can take the contextual factors associated with ID projects into account and thereby ensure efficient and effective implementation. Potential applications and benefits The conceptual framework created will be suitable for application to ID projects around the globe. However, the framework will also be suitable for any organisation or commercial company delivering projects in similar contexts. The outputs of the project will lead to more effective outcomes of ID projects and the gains in efficiency will allow an increased number of projects to be implemented for the available funds, therefore improving the living conditions for those most in need and, ultimately, saving lives.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedUKRI814BloodIron! Accurate Diagnosis of Iron Deficiency at First Blood TestActiveResearch GrantMRC  Iron deficiency (ID) is a major healthcare challenge, impacting quality of life, increasing mortality, and costing global health systems billions annually. Despite being inexpensive to treat and recognised for its potential to improve life quality and reduce healthcare costs when addressed early, ID remains systematically under-diagnosed and under-treated. Tackling ID presents a significant opportunity for preventative healthcare.   Context: ID has serious health and economic consequences. It reduces vaccine effectiveness, raises maternal mortality, and impairs child development. It has major detrimental impacts on conditions like heart attack, stroke and cancer leading to longer hospital stays and higher mortality. In the UK, 30% of patients with acute heart failure have ID, despite high quality evidence demonstrating that treatment improves quality of life and reduces mortality by 40-60%. Costs of ID to healthcare are huge due to ID’s compounding effects on a wide range of other conditions. The cost of anaemia to surgical care alone, when assessed in the German system, was estimated in excess of €1 billion annually. Despite these well-documented impacts, ID remains common, affecting over 5% of the UK population and up to 30% internationally.   Challenge: A critical challenge is the failure of current methods to diagnose ID early. We show that current screening using the full blood count (FBC) misses 80% of cases, only effectively detecting advanced disease, and resulting in a strong bias towards delayed diagnosis. This delay causes significant, avoidable risk. Our research demonstrates this can be overcome using a novel approach to the FBC.   Solution: We are developing innovative tools in collaboration with clinicians, scientists, and mathematicians to detect ID early. By applying machine learning to the high-dimensional FBC (HD-FBC) (individual-cell level data collected during FBC analysis) we have created models in blood donors that increase diagnostic sensitivity from 20% to over 80% while maintaining specificity. Our approach augments an existing ubiquitous test, making it scalable without significant investment. We are uniquely positioned to deliver, having curated extensive HD-FBC datasets (usually deleted post-analysis) and implemented a secure federated learning (FL) network allowing efficient model training across institutions. This ensures performance across diverse populations without compromising data privacy.   The Gap: Ensuring we can translate model performance from blood donors to the clinical setting.   Aims: To improve healthcare outcomes and reduce morbidity and mortality due to underdiagnosis of ID by improving early detection.   Gap Fund Objectives: Expand our ID detection model, trained in blood donors, to clinical cohorts at Barts Health NHS Trust. Improve stability across diverse populations by using FL to train simultaneously across large clinical and donor datasets (BartsHealth, University College London, INTERVAL trial) and validate within unrelated datasets (Amsterdam UMC, STRIDES trial) Develop protocols for prospective studies These steps will confirm performance in clinical datasets, allowing us to apply for DPFS to fund prospective impact studies   Applications and benefits: The developed model will automate real-time screening of HD-FBC samples, replacing current, ineffective screening methods. It will provide rapid diagnosis at initial blood test, reducing diagnostic delay and the need for follow-up testing. It is rapidly scalable, requiring only the addition of software to current infrastructure. Improved ID identification will enhance patient care and reduce long-term costs associated with untreated ID and its complications. By addressing this significant gap in ID management, our approach offers a practical and impactful advancement in the drive towards preventative care.  6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedES/T008873/1Understanding and supporting the psychological wellbeing of fathers of children with Intellectual Disability (ID)ClosedFellowshipESRCCEDARThis fellowship focuses on the wellbeing of parents of children with an Intellectual Disability (ID) (commonly known as a learning disability) in the UK. Individuals with a learning disability will have reduced intellectual ability, take longer to learn new things, and will require additional support according to their level of disability (mild-moderate, severe-profound) for the whole of their life. Individuals with ID can also have other specific conditions such as autism or Down's syndrome. Having a disability is not just experienced by the individual but those who care for and about the person with a disability. Despite this, research has not always considered the impact on families from a systems perspective, which means considering the child within the context of their family and exploring the impact that raising a child with ID can have on family units and members. This fellowship looks to build on my PhD work to develop a better understanding of families of children with ID, know more about their experiences, and contribute evidence which can be used to support them in the future. Therefore, a key aim will be to write-up some of my doctoral research to extend knowledge in the academic community and share findings with parents of children with ID and professionals who support them in order to improve their lives. The activities proposed in the fellowship will focus specifically on the outcomes of fathers with ID because we know little about their perspectives and experiences. Typically, when researchers have asked families to take part in research, it is mothers that respond and take part in answering questions about themselves, their child, and their family and so research evidence is often focused on mothers. This new project will consult with fathers of children with ID to share my findings and existing research and to gain their experiences in order to create a booklet with fathers, for other fathers. The aim of this work is to recognise fathers of children with ID, collaborate with them to better understand their needs, and to share information with others. The third aim of the fellowship is to conduct some new research on fathers of children with ID using some existing large-scale data. This new study will focus on fathers of children with ID, looking at the role of father wellbeing and parenting on the long-term outcomes of their children. The research will test a theory called the Family Stress Model (Conger & Donellan, 2007) which proposes that early family adversity (such as poverty) affects child development by reducing the wellbeing of parents, which then in turn increases the likelihood of negative parenting. This model has never been tested with fathers of children with ID and so will be a unique piece of research.57835945-1CF3-4554-A46B-1504261EB208Psychology33E12B3AB7-FE71-49CB-9EA4-848D86470565Education6657835945-1CF3-4554-A46B-1504261EB208Psychology33E12B3AB7-FE71-49CB-9EA4-848D86470565Education33444DE3B6-F208-4C7C-BFEC-9855F791BAE5Psychology of Education33BB/X001830/1Pig ID: developing a deep learning machine vision system to track pigs using individual biometricsClosedResearch GrantBBSRCResearchLivestock farmers are turning to agri-technology to respond to the challenges of climate change, sustainability, anti-microbial resistance and food security while efficiently producing animals with good health and welfare. Machine vision technology, where software uses 'deep learning' neural networks to automatically process video images, could provide unique insights: 24/7 live data on growth/production and behavioural change as a measure of individual animal health and welfare. Problems such as disease, lameness or harmful behaviours such as aggression and tail-biting could be automatically detected. Continuous tracking in a farm environment is challenging as pigs change shape and can lie next to or on top of each other, and the best available systems can only track pigs for minutes unless they are marked somehow (which commercial growing pigs are not). The Pig ID project represents a step-change in capability by continuously monitoring individual unmarked pigs over weeks and months as they grow. We previously developed a system which can identify (ID) individual pigs from their faces. Face ID is accurate but positioning cameras to capture pig faces is hard and does not capture whole-pen behaviour. Here we plan to develop a deep learning system using the latest neural networks to learn to recognise individual pigs, updating as they grow and continuously track their movements. First, building on our face recognition system, we will develop a remote overhead biometric ID system based on head and body features. Only when confidence in the ID of a pig is lost will frame-to-frame tracking be used as a backup until biometric ID can re-acquire the pig. In this way, continuous accurate pig identity and location will be established. Pigs grow rapidly, so their size and appearance change a lot over time. So next, we will determine how robust our trained ID and tracking system is to this change by testing it on images of the same pigs from different weeks. We will establish how robust it is to changing pig appearance and implement automatic retraining of biometric ID at regular intervals, enabling continued tracking over weeks. To date, machine vision pig tracking has only been demonstrated with one or a few groups of pigs that it has been trained on. Another crucial innovation of this project is that we will take our trained system and work to develop automated enrolment using 'open set recognition', clustering the images of a new group of pigs by similarity to learn about those new individuals. To achieve a large volume of training and validation data needed for this project, we will semi-automate by combining machine vision to find pigs in each image, with humans to confirm and label them with ID. Alongside in-person identification of pigs as a failsafe, we will develop a novel way of validating ID using visible colour and ultraviolet (UV) cameras side by side, while pigs have distinctive sun-cream markings, invisible except to the UV camera. These parallel UV images will enable human manual ground-truthing of pig ID in every frame, to check against biometric ID results from colour images where the sun-cream is invisible. Once the biometric ID system is complete, it will also be used with the UV images. It should easily learn to recognise these marked pigs providing further validation data. This project builds on our proven Face ID technology and we are continuing our previous successful collaboration, bringing together expertise in animal behaviour and welfare, and in agri-technology, particularly in applying cutting-edge machine learning techniques in machine vision/learning to real-word problems. The project has considerable commercial support, with co-funding from animal health company Zoetis under an Industrial Partnership Award. Agri Tech company Innovent Technology Ltd, pig farming and pork processing company Karro, and breeding company PIC are ready to be involved in the next stage of commercialisation.We aim to develop a new technological tool using deep learning machine vision to biometrically identify and track individual pigs. Facilitating behaviour monitoring for health and welfare, it enables a step-change in 'precision livestock farming' and has strong industry support. Training CNNs and validating their performance requires time-consuming manual labelling of ground-truth images. Obj 1 produces this manual data increasing data volume by: a) Using a semi-supervised approach with a modified Mask-RCNN for instance segmentation, and b) Developing a new approach for identity validation: simultaneous recording with a visible light video camera paired with a modified UV-detecting camera, pigs are individually marked with invisible sun-cream which appears black under UV. Our labelled, paired videos will be a valuable public resource for other researchers. Commercial growing pigs are not ID marked. Building on our existing machine vision technology which identifies ID from pig faces, a convolutional neural network (CNN) will be trained to recognise biometrics of individual pigs from above in a group (Obj 2; we have shown feasibility in previous work). Next (Obj 3), we use a refined Mask-RCNN to extract individual pigs from their surroundings and implement our trained CNN enabling spatial tracking. Our innovative 'tracking by recognition' eliminates the problem of lost ID and track-swaps due to close-proximity or occlusion, by re-establishing biometric ID. We retrain the CNN to achieve long-term tracking over weeks as pigs grow and change appearance. We will develop 'open set recognition' (Obj 4), avoiding extensive manual re-training for each new group. Previous work showed that a latent feature space can be optimised to cluster images that appear similar together (because they are from the same pig), separating them from other pigs. Obj 5 integrates 3 and 4 refining a state-of-the-art system to enrol and track individual pigs over weeks as they grow.59D39F6A-DEE0-4E48-8676-4C8374EF3C28Animal science421908FDF5-1C61-4F33-B47F-3E91675C88AAInfo. & commun. Technol.56990813BA-F64D-4C20-BF55-5D96210DAA9EArtificial Intelligence28025DC78A-9E57-454E-B2A8-23A2D69FB5BBLivestock production14A279118A-472D-4E84-9EDA-7C570B912536Image & Vision Computing28D1C81D9E-6726-4707-983C-5EEB474F6D21Animal welfare149F986742-F0F9-4D4F-9B98-6ABD7CC2CD7EAnimal behaviour142613454Identifying Anxiety in Children and Adolescents with Autism and Intellectual Disability in the CommunityActiveStudentshipESRCChild and Adolescent PsychiatryResearch has provided little insight into mental illness for half the autistic population, namely those with intellectual disability (ID). Developing interventions for anxiety is a priority for the autism community but progress has focused on autism (ASD) without ID. This project seeks to identify anxiety in autistic children with ID, who may have few or no spoken words. Use of a participatory research methodology will ensure its relevance to the needs of children with ASD+ID. The project asks: What non-verbal behaviours and physical arousal patterns are associated with anxiety? What is the relationship between autistic traits-such as communications abilities, repetitive behaviours, restricted interests and sensory sensitivities-and high levels of anxiety? And, what family and wider environmental factors differentiate children with situation-specific from those with pervasive anxiety? Focus groups and interviews will be conducted with parents, educators and therapists to better understand and document ASD+ID behaviours. Short-term and long-term arousal data, observed behaviours as well as reports on the children's autistic traits and environments will be analysed. The results will yield insight that may enable researchers and lay community members to better identify as well as understand the non-verbal expressions of and contexts associated with anxiety. The results may also point towards anxiety interventions that may be appropriate for children with ASD+ID.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedES/L010534/1Realist Evaluation of Adapted Sex Offender Treatment Programs for Men with Intellectual DisabilityClosedResearch GrantESRCSociology & Social PolicyAdapted Sex Offender Treatment Programs (ASOTPs) have, as their name implies, been modified from mainstream treatment to meet the learning needs of offenders with intellectual disability (ID). They are designed to increase the offender's sexual knowledge, understanding of victim harm, ability to recognise feelings in themselves and others, to modify offence-justifying thinking and to support individuals to develop relapse prevention skills. In this project I will explore what works on ASOTPs, for whom, in what contexts, why and how. I seek to make sense of these programs in the contexts in which they take place, in order to illuminate what social factors may help or hinder treatment success. In particular, I will examine how effective links between these forensic healthcare interventions and the offender's living context and social care provision, for instance the nature and level of supervision they receive to manage risk, during and after treatment can enhance outcomes. I aim to translate this knowledge into policy and practice recommendations, in order to inform the future targeting of public resources on the most effective treatment, supported by social care packages that can enhance effectiveness. I will evaluate two ASOTPs, one in the UK and one in Switzerland. Both deliver group cognitive behavioural therapy, lasting about 18 months. The evaluation will entail three phases. First, a literature review will be followed by interviews with twelve international key academics and practitioners who designed ASOTPs. This will illuminate in what ways ASOTPs are intended to work. Second, I will explore case studies of men who have attended ASOTPs to explain the impact the program had on them, whether and how it worked and in what contexts. There will be three types of data collection. Four focus groups with altogether 24 participants will look at the user experiences of treatment. Eighty patient files will be reviewed to examine how well the treatment worked for each person. From this a sample of 20 participants, ten for whom the treatment worked and ten for whom it did not, will be followed up through interviews with offenders and practitioners, to find out in more detail why the program did (not) work. Third, the twelve key practitioners will be revisited. Ideas that were developed from phase 1 and 2 on what works, for whom and in what circumstances will be presented to them and they will offer expert commentary. They will examine the case studies from the UK and Switzerland and tease out how wider social contexts, such as public policy and social care practice, impact on treatment success by comparing the case studies to their local contexts. From this a set of recommendations will be derived on most useful policy and practice scenarios and successful social care packages that can enhance treatment success for a particular type of person. Sex offender treatment seeks to change harmful behaviours and has the potential to contribute towards the prevention of maltreatment towards vulnerable populations. It is therefore a social issues, which is in line with the ESRC strategic priority "influencing behaviour and informing interventions". Moreover, The ESRC review of strategic priorities 2013 identified "innovation in health and social care" as a focus for the next 24 months. This project can inform this by making suggestions on better collaborations between health and social care, an issue that has also been prioritised by UK central government. In addition, penal responses to people with ID are currently being reformed. This background and the current age of austerity make this project timely, as it can inform contemporary debates and the targeting of scarce public resources on treatment that works. Throughout the project I will network with policy makers, practitioners, disabled people's organisations and interested members of the public to maximise opportunities to impact on practice and policy development.Sex offenders with ID tend to target those who are more vulnerable than themselves, including children and other people with ID (Beadle-Brown et al. 2010). There are currently almost 4 million adult (18-64) survivors of child sexual abuse in England, about 30% of whom are males (PANSI 2013). There are approximately 1.5 million people with intellectual disability (ID) in the UK. Incidence of sexual abuse increases for adults and children in this population; with Mencap et al. (2001) estimating it is four times more likely. Thus, the most important group of beneficiaries from this research are vulnerable populations, in that this work hopes to contribute to the prevention of future victims. Effective treatment of sex offenders can also indirectly benefit those who have been victimised in the past and their families. This research has the potential to contribute to them knowing that treatment programmes are effective and why, which can help them to regain trust and heal. The exact proportion of those with ID out of the over 40,000 registered sex offenders in England and Wales is unknown. Estimates are hindered by the fact that reporting of sexual offences and particularly those committed against people with ID is low and that some sex offenders with ID have been diverted from criminal justice, while the ID of others remained undetected. What we do know is that ID and other cognitive or learning difficulties such as autism or dyslexia, affect about 20-30% of the prison population (Loucks 2007). In follows that knowledge on ways of personalising interventions to cater for those with additional learning needs can potentially benefit a significant proportion of offenders. To maximise opportunities for impact I will conduct knowledge exchange activities with a range of organisations, including the Equality and Human Rights Commission, Mencap, Respond, the Prison Reform Trust and Mental Disability Advocacy Centre (Budapest). They can benefit from this research, as it will provide them with evidence to inform disability rights campaigns, both on effective treatment of offenders and also material that may inform campaigns for justice for vulnerable victim groups. In the short-term, I hope to inform the more effective targeting of adapted sex offender treatment programs for men with ID in forensic healthcare settings. Potential beneficiaries include users and professionals involved in the delivery of such programs. I will provide practice guidance on what works for whom and in what contexts to the Ministry of Justice, Department of Health and National Association of Probation Workers and Integras, a Swiss professional alliance of social pedagogy (professionals with an interest in ID), as well as to further networks of organisations that work with people with ID in Switzerland, Austria and Germany, including INSOS, Socialbern, CURAVIVA and GDFPI. Medium-term, findings from this research may help to inform more effective public spending on evidence-based programs. Personalised intervention methods can be transferred to other forensic and penal intervention programs for offenders with additional support needs, including non-sexual offenders with ID, offenders with mental health problems and those whose first language is not English. The complex evaluation methodology developed for this project can potentially be applied by other researchers to similarly complex interventions and with this benefit further offender, professional and victim groups. Long-term the targeting of evidence-based, adapted and personalised provisions for different offender groups can potentially reduce reoffending rates amongst (sex) offenders with ID and others with additional support needs and increase public confidence in the forensic health and penal systems. In order to instigate such change I am committed to the comprehensive public engagement and dissemination strategies outlined in the Pathways to Impact document.B3414B75-D8A6-4BB5-8117-3F2E8669AE2ESocial Policy36AFCF822D-6AB8-41F8-9F52-468A75CD9887Sociology24C1AD66F8-1DE7-4817-A442-45D8E8B58647Social Work36A0A6AC9B-B185-4F84-87EB-59ABB6D2B6A7See subject area1212EF5A42-656A-4790-A64C-17C87881B958Criminology24B3414B75-D8A6-4BB5-8117-3F2E8669AE2ESocial Policy24D8A44F23-A0D3-4A9E-8F23-3C9EF34FB6C1Social Work with Adults36MR/L011166/1Intellectual Disability and Mental Health: Assessing Genomic Impact on Neurodevelopment (IMAGINE)ClosedResearch GrantMRCInstitute of Child HealthIn 2010, there were nearly 1.2 million people with intellectual disabilities (ID) in England, of whom 298,000 were children under 18 years of age. Although the cause of intellectual disability can be events such as extreme prematurity, birth injury or brain infections, genetic factors could account for 85%. Some genetic risk is inherited, but not all. Recent research has shown that, during the formation of the egg or sperm, minor chromosomal structural anomalies can occur. They are known as copy number variations (CNVs). The most serious CNVs are not present in either parent, but are 'newly occurring'. Fortunately, these are rare events, but if they occur in key regions of our genome they are strongly associated with ID. Nowadays, the cost of examining a patient's DNA for CNV is coming down dramatically. In the UK nowadays, nearly all children with ID presenting to paediatric services have the test. The National Health Service (NHS) pays, and reports are stored in the UK Regional Genetics Centres (RGC). In about 14%, the test reveals a CNV that is probably the cause of ID. Up to 45,000 people each year will have these tests by 2015. Consequently, there is an enormous wealth of information about CNV held within UK RGC. Around the world, there is great interest in the genetic anomalies that cause ID (and related conditions such as autism or epilepsy). Knowing that a particular CNV may cause ID is valuable, but ID is commonly associated with severe behavioural and emotional problems too. We do not know how these relate to the genetic anomaly. In adult life, some individuals with ID go on to have more serious mental illness such as schizophrenia. We do not know why this illness develops in some people with ID but not in others. When a clinically significant CNV is found in a child with ID, families deserve to be told what the future holds for that child, and how they should best manage behavioural and educational issues to avert poor mental health outcomes. Our unique and novel programme of research aims to rectify that deficiency. Our main objective is to create a novel and comprehensive genetic knowledge base linked to detailed information about adjustment in childhood and adulthood, which we will compile from the two study phases. Our IMAGINE legacy database will be accessible to clinicians managing people with ID, not only in the UK but also around the world, and its establishment will benefit ID children and adults alike. In the first phase, we will draw on the opportunity offered by the NHS-based resource of CNV reports. Because each clinically significant CNV is rare, we will have to collect a very large sample, from all UK RGC. We will focus on behavioural adjustment in early to middle childhood, and aim to recruit around 10,000 families. We will obtain parent reports about behaviour and abilities of this sample of children online, or by telephone, using well-tested measures of behavioural adjustment, social circumstances and medical history. We will follow-up families over 2 years to allow us to assess the stability of emotional/behavioural problems, to identify the importance of environmental risks, such as parental mental health, ethnicity or poverty. In the second phase, we will focus on 4 relatively common CNV with a relatively high risk of poor mental health in adulthood. Our aim is to discover, by intensive investigation and personal assessment, additional risk and resilience influences. We will select children with the designated CNVs from the national study, study their abilities and their adjustment by home-based assessments, and follow them up over 2 years. We will also recruit adults with ID who possess the same 4 CNVs, to study long-term outcomes. They will also be visited and tested at home. In this way we aim to discover, for the first time, how the risk attaching to these important CNV manifests in childhood and adulthood, and potentially identify points for intervention to ameliorate that riskOur study will evaluate the impact of rare CNV on risk of mental health disorder in childhood and adulthood by utilizing data on individuals with ID tested by aCGH within NHS UK genetics services (~100,000 by 01/04/2014). From data mining we will identify clinically significant CNV and conduct internet-based population phenotyping (~10,000 by 31/12/2016). We will take advantage of existing NHS resources and validated, inexpensive and appropriate methodologies for on-line phenotyping [80% of UK families have internet access at home]. The study offers remarkable value for money. It will comprise two primary workstreams (WS1 & WS2), which will be closely interconnected and complementary. First, a national phenotypic 'extensive' survey of children with ID who possess CNV abnormalities reported as clinically significant from (aCGH), based on data mining from UK Regional Genetics Centres (RGC). WS1 will focus on behavioural adjustment in early to middle childhood. Nearly all assessments will be on-line, or by telephone, using standardized measures of behavioural adjustment, social circumstances and medical history. Recruitment will continue from study years 2014-2016. A baseline assessment, with follow-up at 6, 12, 18 and 24 months (2016-2018) will allow evaluation of stability of emotional/behavioural problems in relation to genotype and will measure interacting factors linked to environmental risk. WS2 will conduct 'intensive' phenotyping of individuals with CNV-associated ID, focusing on 4 genetic anomalies previously reported to be associated with high risk of adverse mental health outcome and poor adaptive functioning [deletions at 1q21.1, 15q11.2, 15q13.3, 16p11.2]. Children with the selected CNVs will be sourced from the national phenotypic study and followed up, initially over 24 months. Adults with ID carrying the same CNVs, sourced from UK NHS RGC, will be recruited to study long-term outcomes. Dedicated research teams will test participants in their homes.Our study will impact short-term upon the domains of clinical practice and quality of life for affected families. Potential economic benefits include more efficient targeting of resources and reduced familial disruption. Longer-term, knowledge arising from genetic discoveries could support partnership with industry through targeted drug development. We will work closely with stakeholders throughout this programme, including the charity UNIQUE which will be represented on Scientific Advisory Board. Clinicians Clinicians increasingly request specialist genetic investigations for children with intellectual disability [ID] (35,000 tests p.a.). Usually, the results do not translate into specific recommendations for management or prognostic statements. By linking, for the first time, genotypic data on specified CNV with standardized phenotypic data, our study will generate clinically valuable information. Unusual behaviour patterns or emotional disorders are all too readily ascribed to inappropriate parenting practices, often by parents themselves. Recognizing common disorder-specific patterns is the first step to reassuring parents, and teaching clinicians/social support staff. Impact will reduce self-blaming and stress, with resultant improved quality of life for affected families. Impact timescale < 5years. Children and Families affected by ID Our follow-up studies will measure interaction cascades between genotypic/phenotypic characteristics of ID children and their influence upon family life, friendships, learning and leisure activities. Impact of child behaviour can be reliably and easily measured across time, and may independently predict future symptoms and psychiatric disorders. Potential value includes an opportunity to measure the interactive process by which disturbed emotions and behaviour can undermine family/individual quality of life. The approach should reveal new opportunities for intervention. Effective intervention can enhance parents' economic activity (e.g. by promoting their mental health, reducing school exclusions, limiting risk of parental separation). Impact timescale <5 years. Education and Care Professionals Intellectual disability implies global impairments in cognitive skills. Yet some developmental trajectories may be preserved (exemplified by the relatively good language skills of children with Williams syndrome). Parsing the wide range of ID by CNV subtyping, may allow the identification of rare variant disorders in which islets of ability are common. Gaining such knowledge about specific CNV has implications for education planning, and fostering the maximization of individual potential. Such discoveries could inform policy on the management of children with CNV-related ID, including support required to mainstream, or provision of speech and language services. Information on environmental factors influencing emergence of challenging behaviour linked to genotypic risk could point to genotype-specific interventions, reducing risk of transfer to residential care and the associated costs. Impact timescale <5 years. Clinical Pharmacology Developmental pathways in ID overlap with autism, schizophrenia, and epilepsy. We lack a lifespan perspective on risk related to genotype. Our accelerated longitudinal cohort study, linking genotype (with, in due course, supplementary genome-sequencing) to phenotype could facilitate pathway and network analysis of complex 'omics data in high-risk populations. There are potential synergies that could lead, in longer term, to academic-pharmaceutical industry partnerships leading to the discovery of causal mechanisms and potential novel drug targets for intervention. Impact timescale <10 years. Training of skilled researchers Within the framework of the program we will be fostering the academic skills of the three junior Co-I (Mandy, St Pourcain, Baker), all of whom are on a career track to senior positions. Impact timescale <5 years.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified1937978Deficits and rescue of neuronal population coding in the sensory cortex of mouse models of autism spectrum disordersClosedStudentshipMRCSch of Molecular. Genetics & Pop HealthThe central aim of this project is to understand the effects of single gene mutations at the level of cortical networks activity in animal models of Autism Spectrum Disorders (ASDs) and Intellectual disabilities (ID). Cortical circuits are initially defined by genetic programmes, followed by neural plasticity initially driven by spontaneous and later by evoked sensory activity. The investigation of monogenic ASD/ID animal models at the cellular level has revealed multiple alterations in neuronal properties, including changes in excitability, synaptic transmission and neural plasticity. Yet, it remains largely unknown how such cellular changes affect the activity in neural circuits, and how this, in turn, leads to the diversity of phenotypes characterising ASD/ID. Moreover, recent work indicates that some of these changes are of secondary nature, and likely result from a developmental homeostatic compensation of primary defects. In this scenario, an initial defect leads to altered cellular and/or network activity, which, in turn, is compensated by cellular feedback processes. It is therefore possible that different primary causes, for instance defective plasticity in Fragile X Syndrome and SYNGAP haploinsufficiency, can lead to similar defects at the circuit level. This convergence may provide an opportunity for interventions targeting the resulting cellular and circuit dysfunction in adults. Addressing this gap in knowledge requires a comprehensive understanding of the circuit-level impairments of ASD/ID in adults. Very few studies so far have investigated network activity in disease models beyond global features such as seizures, and currently no coherent picture exists. Here, we plan to use Fmr1-/y and Syngap+/- mice as two well established ASD/ID models to determine how these mutations affect the propagation of neural activity through cortical networks, focusing on sensory areas, where inputs are readily controllable. Aims We will examine the following three hypotheses in Fmr-/y and Syngap+/- mice in this project: 1. Cortical ensemble activity is consistently altered in ASD/ID models, compared to wild type (WT) animals, and biased towards reduced representational capabilities. 2. Cortical plasticity induced by monocular deprivation is altered in ASD/ID models. 3. Pharmacological treatments that rescue behavioural ASD/ID phenotypes in mouse models will modify cortical population activity and plasticity. To uncover the relevant circuit defects in ASD/ID models, we will use 2-photon calcium imaging of more than one thousand neurons simultaneously in the primary visual and parietal cortex, and employ computational data analysis and modelling. Genetically labelling of different interneuron types will enable a detailed dissection of the circuit pathology. We will investigate changes in experience-dependent plasticity at the circuit level, which has so far not been attempted, and evaluate the circuit-wide effects of pharmacological rescue in adults. Together, these complementary approaches will (i) help relate cellular and systems level pathologies in ASD/ID, (ii) explore avenues for treatment and interventions, and (iii) provide novel computational tools for analysis and interpretation of large neural population recordings.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassifiedAH/E507115/1Inclusive New Media DesignClosedResearch GrantAHRCHumanities and Social SciencesInclusive New Media Design aims to contribute to teh social inclusion of people with disabilities in new media like the WWW. It will do this exploring the place occupied by guidelines for designing accessible websites in the work practices of new media designers. These guidelines are produced by the World Wide Web Consortium's Web Accessibility Initiative (W3C WAI), the organisation that governs the technical standards of the web, and, in many countries, including our own, they form the basis of legal documents to which new media designers should adhere. Whilst there is much activity focusing on how to implement and improve the guidelines, and there is growing awareness of them as a result of new policy, more accessible tools and their acceptance by web design gurus, no academic research has been carried out with new media designers themselves to explore how and why accessibility does or does not get taken up. Little is known about the factors within new media design practices which affect designers' perceptions of accessibility guidelines, or whether other approaches, such as the inclusion of disabled users in the design process, or highlighting exemplary and inspiring accessible design practice, are more effective in persuading designers to subscribe to the accessibility ethos. Furthermore, the guidelines are to be integrated into a process which is thought to be both intuitive and unknowable - creative design. Inclusive New Media Design will bring together these apparently contradictory forces - on the one hand, detailed technical guidelines, and on the other, intuitive design - by exploring the relationship and potential for copmpatability between the two. The project will thus be framed by current debate in the humanities, in HCI and beyond about new media work, design and creativity.\n\nWithin the project's two-year duration, a series of workshops will be run with approximately 30 new media designers with a spectrum of accessibility expertise, followed by work-based observation sessions with the designers. The early workshops will focus on problem-solving - they will ne consultative focus group sessions in which examples of accessible web design are examined and accessibility guidelines are applied in the creation of new media design solutions. In later workshops, designers will be introduced to disabled users to compare the effectiveness of integrating users into the design process with guidelines training as a means of achieving accessible web design. In the workshops, participants get free advice and consultancy from the project team, and inr eturn, they agree to the project team carrying out observations in their workplaces, analysing the websites they are working on, and discussing with them their approaches to accessibility withint he ocntext of the creative design process.\n\nThe research aims to benefit people with disabilities, by identifying effective approaches to their inclusion in the WWW. The findings will be disseminated in academic domains through journal articles, and to new media designers and developers through a project website. They will also be disseminated to the W3C and other standard bodies with the assistanceof Adobe's accessibility team and aim to inform international efforts to enhance web accessibility for people with disabilities. The project will be run from within UEL's Rix Centre for Innovation and Learning Disability, which has a track record of managing research and development within this field. The project wil address the accessibility needs for people with physical and cognitive disabilities, with particular attention to the latter, a group acknowledged internationally as historically absent from web accessibility efforts. The findings will be significant for 21st century design because they will contribute to the inclusion of people with disabilities, especially cognitive, in the WWW, and to socially inclusive new media design.0609A953-459F-4841-93C9-365A322B22A9Media1009805CE72-29DB-4698-B7D3-74A3A453C6D9Media & Communication Studies100MR/N022572/1Intellectual Disability and Mental Health: Assessing Genomic Impact on Neurodevelopment (IMAGINE)ClosedResearch GrantMRCInstitute of Child HealthIn 2013, there were 1.1 million people with intellectual disabilities (ID) in England; 224,930 were children of school age. Although the cause of such disability can be events such as extreme prematurity or brain infections, genetic factors could account for 85%. Some genetic risk is inherited, but not all. Recent research has shown that, during the formation of the egg or sperm, minor chromosomal structural anomalies can occur. They are known as copy number variations (CNVs). The most serious CNVs are not present in either parent, but are 'newly occurring'. Fortunately, these are rare events, but if they occur in key regions of our genome they are strongly associated with ID. Nowadays, the cost of examining a patient's DNA for CNV is coming down dramatically. In the UK nearly all children with ID presenting to paediatric services have the test. The National Health Service (NHS) pays, and reports are stored in the UK Regional Genetics Centres (RGC). In 10-15% the test reveals a CNV that is probably the cause of ID. Up to 45,000 people each year have these tests. Consequently, there is an enormous wealth of information about CNV held within UK RGC. Knowing that a particular CNV may cause ID is valuable, but ID is commonly associated with severe behavioural and emotional problems too. In adult life, many individuals with ID go on to have more serious mental illness, such as schizophrenia. We do not currently understand why these problems develop in some people with ID but not in others. When a clinically significant CNV is found in a child with ID, families deserve to be told what the future holds for that child, and how they should best manage behavioural and educational issues to avert poor mental health outcomes. Our unique and novel programme of research aims to rectify that deficiency. Our main objective is to create a novel and comprehensive genetic knowledge base, incorporating a wide range of rare CNV, linked to detailed information about the genetic anomaly's impact on adjustment in childhood and adulthood. We have spent the past year testing the feasibility of our MRC-funded research strategy, and have achieved all our objectives. We are now embarking on a further 3.5 year programme of research to build on the infrastructure we have created. Our IMAGINE legacy resource will be accessible to clinicians managing people with ID, not only in the UK but also around the world, and its establishment will benefit people with ID and their families throughout the lifespan. In one workstream, we are drawing on the opportunity offered by the NHS-based resource of CNV reports. We will focus on behavioural adjustment in childhood, and aim to recruit around 5,000 families nationally. We have shown that it is possible to obtain parent reports about behaviour and abilities of children online, or by telephone, using well-tested measures of behavioural adjustment, social circumstances and medical history. Families are enthusiastic to tell us about their children and they value the reports we send them, following completion of our online assessments. These provide a useful summary for schools and clinicians alike. In the other workstream, the focus is on a few relatively common CNV that are associated with a particularly high risk of poor mental health in adulthood. We select children with the designated CNVs from the national study, study their abilities and their adjustment by home-based assessments,. We will assess the severity of emotional and behavioural problems, and the importance of environmental risks, such as parental mental health, ethnicity or poverty. We will also recruit adults with ID who possess the same relatively common CNVs, to study long-term outcomes. In this way we aim to discover, for the first time, how the risk attaching to these important CNV manifests in childhood and adulthood, and potentially identify points for intervention to ameliorate that risk.Our study aims to evaluate the impact of rare CNV on risk of mental health disorder in childhood and adulthood by utilizing data on individuals with ID tested by array CGH within NHS UK genetics services. From data mining and prospective recruitment, we will focus on clinically significant CNV (and - potentially - on SNV too). We will be conducting internet-based population phenotyping on up to 5000 children by June 2019. We take advantage of existing NHS resources and validated, inexpensive and appropriate methodologies for on-line phenotyping [84% of UK families have internet access at home]. The study offers remarkable value for money. It comprises two primary workstreams (WS1 & WS2), which are closely interconnected and complementary. First, a national 'extensive' survey of children with ID who possess CNV abnormalities reported as clinically significant from aCGH, based on data mining and prospective recruitment from UK Regional Genetics Centres (RGC). WS1 focuses on behavioural adjustment in children of school age. Nearly all assessments are on-line, or by telephone, using standardized measures of behavioural adjustment, social circumstances and medical history. Recruitment commenced in 2015. WS2 is conducting an 'intensive' phenotyping of individuals with CNV-associated ID, focusing on a small number of genetic anomalies previously reported to be associated with high risk of adverse mental health outcome and poor adaptive functioning [especially deletions at 1q21.1, 15q11.2, 15q13.3, 16p11.2]. Children with the selected CNVs are sourced from the national phenotypic study. Adults with ID carrying the same CNVs, also sourced from UK NHS RGC, will be recruited to study long-term outcomes. Dedicated research teams test participants in their homes. Over the past year, we have completed a feasibility study that has achieved all our objectives. We have shown that online testing yields valid data on adjustment and that it is acceptable to families.Our study will impact short-term upon the domains of clinical practice and quality of life for affected families. Potential economic benefits include more efficient targeting of resources and reduced familial disruption. Longer-term, knowledge arising from genetic discoveries could support partnership with industry through targeted drug development. We are working closely with stakeholders throughout this programme, including the charity UNIQUE and other parent-support organizations. Clinicians in the NHS increasingly request specialist genetic investigations for children with ID. Usually, the results do not translate into specific recommendations for management or prognostic statements relating to behavioural adjustment, although families would welcome such knowledge. By linking, for the first time, genotypic data on specified CNV with standardized phenotypic data, our study will generate clinically valuable information. Unusual behaviour patterns or emotional disorders associated with ID are often ascribed to inappropriate parenting practices. Recognizing common disorder-specific patterns is the first step to reassuring parents, and educating clinicians/social support staff. Impact will reduce self-blaming and stress, with resultant improved quality of life for affected families. Impact timescale < 5years. Impact of child behaviour can be reliably and easily measured across time, and may independently predict future symptoms and psychiatric disorders, including the interactive process by which disturbed emotions and behaviour can undermine family/individual quality of life. New opportunities for intervention could ensue, thus enhancing parents' economic activity (e.g. by promoting their mental health, reducing school exclusions, limiting risk of parental separation). Impact timescale <5 years. Education and Care Professionals: Intellectual disability implies global impairments in cognitive skills. Yet some developmental trajectories may be preserved (exemplified by the relatively good language skills of children with Williams syndrome). Parsing the wide range of ID by CNV subtyping, may allow the identification of rare variant disorders in which islets of ability are common. Gaining such knowledge about specific CNV has implications for education planning, and fostering the maximization of individual potential. Such discoveries could inform policy on the management of children with CNV-related ID, including support required to mainstream, or provision of speech and language services. Information on environmental factors influencing emergence of challenging behaviour linked to genotypic risk could point to genotype-specific interventions, reducing risk of transfer to residential care and the associated costs. Impact timescale <5 years. Clinical Pharmacology Developmental pathways; in ID, such pathways overlap with autism, schizophrenia, and epilepsy. We lack a lifespan perspective on risk related to genotype. Our accelerated longitudinal cohort study, linking genotype to phenotype could facilitate pathway and network analysis of complex 'omics data in high-risk populations. There are potential synergies that could lead, in longer term, to academic-pharmaceutical industry partnerships leading to the discovery of causal mechanisms and potential novel drug targets for intervention. Impact timescale <10 years. Training of skilled researchers: Within the framework of the program we are fostering the academic skills of junior staff (NIHR-funded Academic Clinical Fellows) that are on a career track to become academic child psychiatrists. Impact timescale <5 years. International collaborations: The IMAGINE team has already been invited to participate in an international discussion group in Washington, to discuss harmonization of phenotyping protocols. This comprehensive phenotyping network would serve as the framework for a multi-center clinical trials network as candidate drugs come available. Impact timescale:<5 years6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified131334Next Generation Multiplexed Protein Screening for Clinical DiagnosticsClosedFeasibility StudiesInnovate UKInanovate has developed a proprietary technology for the detection and measurement of multiple proteins from complex samples in real-time (the Bio-ID). The Bio-ID is presently used for applications in protein biomarker discovery and validation (R&D applications), but is not presently adapted for clinical diagostic use due primarily to the format and function of the Bio-ID's disposable micro-array cartridge and associated platform interface. To address this limitation and open up the Bio-ID for use in the multi-billion dollar clinical diagnostic markets, the proposed project will develop, manufacture and demonstrate the feasibility of a disposable micro-array cartridge (and associated platform interface) that integrates sample input wells and assay, to deliver a fully self contained disposable unit compatible for use with clinical diagbostic tests in both laboatory and point-of-care settings.6CFA1E1F-F25C-4C23-8FE1-C47AE53E333EUnclassified69DB9E08-C0B1-4F33-8FD4-EDC4DF325112INANOVATE (UK) LTDLEAD_PARTICIPANT33000.025000.0