Children and young people (CYP) are experiencing a significant mental health (MH) crisis that is threatening their future. Deeply rooted health inequalities perpetuate this crisis and call for immediate action. This project will promote easy access to best practice in local arts activities that support the diverse MH needs of CYP and thus enable them to take better control of their lives. By supporting the MH of CYP the project will meet an important NHS priority contributing towards tackling the health inequalities affecting their lives. We will build on successes from Arts for the Blues (AH/W007983/1), a project that received funding from AHRC for phase one of this programme and successfully scaled up the use of an evidence-based creative psychological intervention in the North West. We will also draw on a track-record of 25+ years of engaging CYP in arts activities, and on our extensive co-production experience. Co-creation will therefore become central to this work. We will focus on CYP aged 9-13, a group at significant risk of developing MH problems whilst transitioning from childhood to early adolescence. They will be encouraged to act as co-researchers developing skills they can use after the completion of the project, ensuring direct benefits. We expect that co-creation will lead to meaningful engagement of CYP with this study that aims to generate new, scalable evidence concerning: (A) how to access arts activities that best support the MH of CYP; (B) how to evaluate arts activities that meet the diverse MH needs of CYP; (C) how to maximise the benefit of arts activities for as many CYP as possible. We will create a digital platform where evidence-based local arts activities will become easily accessible for CYP, their families, relevant organisations and services. We will do this by identifying good local arts practice that addresses the diverse MH needs of CYP, especially those who are often under-represented. Six CYP Creative Health Associates will be employed to work in areas with marked health inequalities and establish local collaborations between community partners and existing social prescribing link workers. They will also work with the research team to provide easy and sustainable access to arts activities and thus, bypass local barriers. The active involvement of Integrated Care Boards (ICBs) (e.g., Lancashire and South Cumbria and Cheshire and Mersey Care), medical leads and medical directors of CYP's MH, NHS trusts, schools and community organisations will encourage collaboration within and across systems, enabling the development of an agreed evaluation framework of best practice in arts activities. This will support streamlining access to therapeutic uses of the arts as well as scaling up and adopting the outputs from the study in the North West and beyond. Finally, we will develop and share the project outputs with our 46 non-academic national and international collaborators, making an active contribution towards tackling health inequalities that benefits the MH of CYP wherever they live.

Arthritis (swelling, pain and inflammation of the joints) affects 1 in 1000 children and young people. Arthritis of children and young people is called juvenile idiopathic arthritis (JIA). If JIA is not fully treated it causes severe pain, joint restriction swelling and stiffness, fatigue, poor growth, thinning of bones, time off school, reduced social and sporting activities and lost family life opportunities. JIA can lead to major disability that lasts well into adult life. There are many modern, powerful medicines that can be used to treat JIA better than before. However we do not yet have reliable and child-friendly tests that can predict which drug will work best for each child. Each of these drugs may also have serious side effects. At the moment, children and young people (and their families) have to wait after starting a new drug to see if it works, and whether any important side effects happen. If it does not work, or side effects crop up, only then are they allowed to try another. This "lets try it and see" approach takes time and exposes children to drugs which might not work well, yet often have important short and long term side effects. Therefore there is an urgent need to develop ways that can help to predict how an individual child will respond to each drug, and so allow children with JIA to be treated with the most appropriate medicine. This approach is now known as 'precision' or 'stratified' medicine. Early control of the arthritis allows children to return to their education, as well as full sporting and family life activities, whilst continued control of arthritis prevents disability and avoids lost opportunities in the long-term. At the moment, four major UK studies are collecting valuable data about response to treatment from children and young people with JIA across the country. Between them, these studies have a lot of data, both clinical as well as laboratory data, that can address this need. In this partnership we propose to bring these studies together to form a unique Consortium, called the Childhood Arthritis Response to Treatment Consortium (CHART). CHART will work with all the main national and international stakeholders including clinical and research collaborators, as well as families and patients who lives are affected by JIA. The overall aim of CHART is to directly improve clinical care for children with arthritis. The key aspects of the work planned in the CHART Consortium are to : 1. Find out exactly what data and samples are already available in the four major UK studies of JIA 2. Design and agree a way to share all of the data, and bring the data together 3. Agree to collect data and samples for understanding response to treatment in the same way in the future, in order to speed up progress for all children with JIA 4. Give many more children and families the opportunity to contribute to these studies by including new centres and collaborators The CHART Consortium, if established, will be one of the largest of its kind in the world. The CHART researchers will have the common goal of making treatment of JIA more individualised and precise, to help every child with arthritis return to a full normal life as quickly as possible.

Head and trunk control (trunk control) is mandatory for effective performance of everyday functional activities such as use of vision, sitting or any upper limb activity. Children with cerebral palsy (CP), spinal muscular atrophy (SMA) and inherited neuromuscular disorders (NMD) experience impairments in trunk control which are a fundamental component of their condition. Children with CP show a direct relationship between poor trunk control (orienting the head, sitting balance) and compromised function including communication by eye gaze, use of both hands for learning, play and social development, mobility and urinary incontinence. Children with more severe CP regress in their functional abilities from age 7 years. Accurate diagnosis of trunk control can enable individualised physiotherapy, when combined with treatment as usual, to improve general motor function even in severe CP (preprint). An accurate, objective tool is needed to provide evidence encompassing multiple therapies and centres. Infants with SMA1 have similar difficulty acquiring trunk control as do children with severe CP. Using Nusinersen, these children now survive, but this drug is expensive. An accurate, objective test is needed to monitor effectiveness of this and alternative drugs. The increasing muscle weakness in children with NMD (SMA2, congenital myopathy, congenital muscular dystrophy, Duchenne muscular dystrophy) leads to deterioration in trunk control with subsequent scoliosis. Objective measurement sensitive enough to detect changes in trunk control, pre-scoliosis, would enable appropriate treatment such as physiotherapy at the optimal time. Our hypothesis is that segmental trunk control can be measured objectively and efficiently, classified to seven segmental levels. This objective measurement would promote benefits in terms of new understanding of the mechanisms of trunk control, monitoring treatment and providing evidence to inform practice for all therapy strategies that aim to improve postural control and associated motor function. All current assessments suitable for use in a clinic are validated but rely on clinical judgement that must be maintained over time and between therapists, and many cannot be used for children unable to sit by themselves. They also consider the trunk as a single unit, thus losing the accurate and detailed assessment required for specialised therapy. We anticipate this objective assessment tool could lead to interventions to enhance trunk control, and thus improvement of functional skills, for thousands of children worldwide including those with greater severity of CP. Our project will i) develop live imaging analysis technology to automate the assessment of trunk control in sitting, ii) provide a cost effective and accessible tool usable within any clinic without increasing assessment time and iii) publish an online interactive database disseminating a public standard, a reference and a training resource for measuring trunk control, increasing understanding and enhancing expertise. Assessments of trunk control of children in sitting (400 CP, 20 SMA1, 40 typically developing (TD), 40 NMD) will be recorded using 3D cameras available for the home market. This dataset will include examples of all trunk control problems, body morphology and height that the clinical tool would be required to meet. Machine learning methods will be used to train and validate the automated diagnosis. The tool will be validated against expert clinical assessment and deployed as a laptop, software and two cameras, suitable for use by clinical staff in a routine clinical environment. To prepare power calculations necessary to plan clinical trials, we will collect a longitudinal dataset of 20 children with CP and 5 infants with SMA 1 during a twelve-month period.

Each year, approximately 170 babies in the UK are born with Hirschsprung's disease (HSCR). Affected babies develop an intestinal blockage, which can be life threatening, due to missing nerve cells in the lower part of their intestine (called 'aganglionic' intestine). Currently, the only treatment is surgical removal of the affected segment of the intestine. However, after surgery up to 75% of children with HSCR suffer from constipation or incontinence, and 10% of children require a permanent artificial opening of the intestine. Thus, there is a need to improve the treatment of babies and children with HSCR. We have isolated stem cells from normal segments of intestine, cultured them in a sterile dish and have shown that these cells can become nerve cells which are able to regulate bowel activity under laboratory conditions. Surprisingly, we have recently demonstrated that similar stem cells can also be found in the aganglionic segments of intestine of children with HSCR, which lack nerve cells. This novel finding opens up exciting new questions for treatment options: Is it possible to transplant the patient's own stem cells, after converting them in to nerve cells in the laboratory? Can the stem cells, while still present in the aganglionic segments of intestine, be stimulated to become new nerve cells? These possibilities could improve surgical outcomes or avoid surgery altogether. Based on these findings, the overarching aim of this project is to develop new approaches to treat patients with Hirschsprung's disease. As our previous observations showed that the stem cells present in the aganglionic intestine also give rise to nerves similar to those from normal gut, our current work is focussed on establishing to what extent the stem cells from the aganglionic intestine are the same as those from normal gut. It is also important to understand whether the stem cells isolated from aganglionic intestine can be controlled to make sure that they do not form tumours after they have been stimulated. Therefore, the main focus of the proposed project is to determine the mechanisms which regulate the behaviour of these new stem cells. This information is necessary before we can consider any use of the stem cells in therapies for patients. In this project we will isolate stem cells in the laboratory from tissue samples obtained at surgery from children with and without HSCR. Once the stem cells are isolated, they are cultured under laboratory conditions. The next step will be to assess whether the same mechanisms that regulate the behaviour of stem cells in normal bowel, also control the change of stem cells derived from aganglionic HSCR bowel in to functioning nerves in culture. Once we know what these mechanisms are, we will be able to use specific drugs to regulate the behaviour of the HSCR stem cells in order to convert them into the nerves necessary to restore normal function to the bowel. The information gained from this project is an essential prerequisite for clinical trials to test the efficacy of the stem cells isolated from aganglionic bowel to be used in stem cell therapies. Many children with Hirschsprung's disease face a lifetime of psychological, social and physical difficulties affecting them and their families. Improved outcomes from the proposed treatment have the potential to permanently change the lives of children and reduce the demands on health and social services.

In this project we will develop a strategy for making the Arts for the Blues intervention easily available to adults and children struggling with depression, low mood or anxiety. This group therapy uses visual arts, music, dance, drama and creative writing to address psychological difficulties and strengthen resources for managing them. Participants are encouraged to actively engage with simple arts-making activities with a clear therapeutic intent. These activities may include: breathing exercises to manage anxiety, free writing to support self-expression; mirroring tasks to develop relationships, use of objects to share difficult stories, engagement in rhythmical connections to address isolation (see www.artsfortheblues.com for further details on the intervention and relevant audio-visual material). Evidence suggests that arts-based interventions are more accessible and attractive for people who find it difficult to talk about their problems or who are seeking an alternative to talking therapies. This could include adults and children from diverse backgrounds, refugees and migrant communities, and those struggling with loneliness and isolation. The Arts for the Blues intervention was first developed to address mental health concerns in inner city neighbourhoods in Manchester and has since been successfully piloted in charities and schools in the North West of England, an area faced with long standing health inequalities. Participants in the arts-based groups showed marked psychological outcomes including lower scores of depression and anxiety and improved wellbeing, life functioning and social communication. In this project we will therefore ask the question: How can the Arts for the Blues intervention be scaled up for integration within healthcare and cultural organisations to tackle depression and improve wellbeing in communities across the North West of England? In order to answer this question, we will bring together artists, health professionals, existing networks and partnerships in three events in order to co-create a strategy for making the intervention readily available across the region. We will also offer workshops, focus groups and training to at least one healthcare and one cultural organisation. Throughout the process we will work alongside our Patient and Public Involvement (PPI) group to ensure our target beneficiaries have a voice. The group currently includes people using psychological services who have attended Arts for the Blues groups and will be expanded to include PPI members from project partners. Methodologically, we will adopt a realist evaluation approach which will allow us to develop a strategy that is scalable, sustainable, aligned with systems thinking and promises to offer solutions to long-standing health inequalities in the region and beyond. Over the lifetime of the project, we will produce an online toolkit to include case examples and training materials, a film with the main findings and user testimonies, and a plan for the integration of this creative form of therapy in different settings.