Southampton researchers have been celebrated by the British Medical Association (BMA) Foundation. Dr Anna Freeman and Dr Ahilanandan Dushianthan from the NIHR Southampton Biomedical Research Centre (BRC) have won research grants from the BMA Foundation. They were two of four successes for researchers at the University of Southampton. They received their awards at BMA House in London last week. Treating difficult asthma Dr Anna Freeman received the James Trust grant for research into asthma. Her team are working with patients to develop a lifestyle intervention for difficult asthma. This could help address multimorbidity. Dr Freeman is an Associate Professor and Anniversary Fellow at the University of Southampton. She is also part of the NIHR Southampton BRC’s Respiratory and Allergy theme. She said: “I am delighted to receive this award from the BMA James Trust. “The funding will support the delivery of a pilot study of a community based, multimodal intervention to tackle multimorbidity in difficult asthma. This is something which patients and clinicians both agree is necessary.” Previous work by Dr Freeman and her team has shown that treatable traits can predict future exacerbation risk. These traits include obesity, anxiety and depression, breathing pattern disorders and inactivity. Their project, known as LIBERTY, will address this through a combined 24-week intervention. Participants will receive exercise training, breathing retraining, and dietary and behaviour change support. Insights into long Covid The J Moulton grant was awarded to Dr Ahilanandan Dushianthan. He is a Consultant in General Intensive Care at University Hospital Southampton. He is also part of our BRC’s Perioperative and Critical Care theme. This funding will support Dr Dushianthan’s work into long Covid. He is investigating if symptoms could be related to reduced mitochondrial capacity following severe infection. Dr Dushianthan said: “I am extremely pleased to have secured the J Moulton grant for long Covid research. “Although most people with COVID-19 recover quickly, some experience lasting symptoms. “We need to understand why this happens to find new ways of diagnosing and treating long Covid.” Southampton success Southampton has four winners in 17 categories. The other award recipients are Prof Rami Salib and Daniel Michalik from the University of Southampton. They received the Vera Down grant for research into neurological disorders. Their work aims to aims to show that markers specific to Alzheimer’s disease can be detected in the nose. This could enable early diagnosis and monitoring. Prof Stephen Holgate, Clinical Professor of Immunopharmacology at UoS, was also at the event. He delivered the keynote speech. Image courtesy: BMA Foundation for Medical Research. Dr Ahilanandan Dushianthan (second left) and Dr Anna Freeman (third right) are honoured at BMA House in London.

Omega-3 fatty acids are sometimes known as ‘healthy fats’. They cannot be made by the body and must be obtained through food, such as fatty fish. However, fish and seafood sources of omega-3 are not sustainable and can have a harmful environmental impact. New research in our NIHR Southampton Biomedical Research Centre (BRC) is shedding light on alternative sources of omega-3. Dr Ella Baker explains how she is making advances through a one-year BRC Postdoctoral Bridging Fellowship. How did you become interested in research? I have wanted to be a ‘scientist’ for as long as I can remember. From a young age, I was always interested in understanding how things work. Biochemistry appealed to me as it investigates chemical processes that happen in living things. I was excited by the prospect of working in this field, as it opens numerous avenues for exploration and discovery. My research focuses on the metabolism, functionality, and underlying mechanisms of action of plant-derived fatty acids. I completed a PhD in Nutritional Biochemistry in 2018 under the supervision of Prof Philip Calder. My PhD focused on the anti-inflammatory effects of plant-derived fatty acids compared to fish-derived fatty acids. This got me interested in the anti-inflammatory mechanisms of action of plant fatty acids. My aim is to find sustainable alternatives to marine-derived sources. What is the healthcare challenge that you are seeking to address? I have been awarded a BRC bridging fellowship and have funding from the Wessex Innovation Fund to develop a technique that can help us understand how different fatty acids affect the way cells work. I plan to compare fatty acids from fish and from plants to see if they behave the same way. I also have funding from the i-NutriLife Diet and Health Innovation Hub for further research into plant oils. Omega-3 is important for your body and brain. Research has shown that it has many long-term health benefits. The most active omega-3 fats are called EPA and DHA. EPA and DHA are mainly found in seafood, especially fatty fish like salmon and sardines. The UK Government recommends that people should eat more fish to get enough EPA and DHA. However, fish stocks are declining fast - and many people do not like eating fish. This means that we need alternative options to address this public health challenge. What do you hope to achieve in your research at the BRC? The goal of the proposed research that I will conduct during my BRC Fellowship is to develop methodologies to understand how fatty acids from plants act on cells to have anti-inflammatory effects. This understanding will provide the evidence needed to support future human research into sustainable alternatives to omega-3s. This will be the focus of my future fellowship applications. My career goal is to become an independent researcher in the field of plant fatty acid research. How would you sum up your fellowship in three words? Opportunity, support and exciting. What's it like being an early career researcher in Southampton? Being an early career researcher at the University of Southampton has helped me develop my research skills and expertise. It is brilliant to work in such a friendly and encouraging environment. The university provides scientific excellence alongside state-of-the-art facilities. This has enabled me to establish interdisciplinary research and set me on a path to independence. What advice would you give other early career researchers? I would emphasise the importance of determination and commitment. Don’t be discouraged by rejection, as it’s common for people to apply for several funding opportunities before they are successful. Keep going - and use each setback to help you achieve your goals!

The United Nations have appointed Dame Wendy Hall to their new high-level advisory body on artificial intelligence (AI). Dame Wendy is a Regius Professor of Computer Science from the University of Southampton and Director of its Web Science Institute. She leads the Data, Health and Society theme at the NIHR Southampton Biomedical Research Centre. Dame Wendy was named the first UK artificial intelligence skills champion in 2018. International governance of AI She was selected from more than 1,800 nominees across 128 countries. She joins 31 experts from across the world. They will undertake analysis and give recommendations for the international governance of AI. Dame Wendy said: “I feel very privileged to have been appointed by the United Nations to be on this new AI advisory body. “As new AI technologies and capabilities emerge, it is so important that we harness them for good, while ensuring they don’t evolve in ways that would be harmful to society. "It is very exciting to be part of the global discussions on the best way to manage this.” Insights from her work Her role in the UN advisory body will see Dame Wendy work with experts from government, private sector and civil society. She will provide insights from the breadth of her research at Southampton. This includes the £31 million Responsible AI UK programme, known as RAI UK. This programme intends to fuel Britain’s ambitions to be a science and technology superpower. The new UN advisory body will start this month, working together for a year. It will submit its recommendations in late 2024. Read more about Dame Wendy’s pioneering work in computer science and AI in Southampton at damewendydbe.com. Image credit: University of Southampton

Southampton researchers are part of an international team that has identified an immune cell responsible for some hard-to-treat asthma cases. The researchers uncovered a group of immune cells that may drive severe asthma. These cells gather in the lungs, and appear to cause the most harm in men who develop asthma in later life. Dr Ramesh Kurukulaaratchy and Professor Hasan Arshad at the NIHR Southampton Biomedical Research Centre were involved in the study. It was led by researchers at The La Jolla Institute for Immunology (LJI) in California. Hundreds of volunteers They identified the immune cells thanks to volunteers enrolled in the NHS clinic-based WATCH study. They are called cytotoxic CD4+ tissue-resident memory T cells. The WATCH study is led by Dr Ramesh Kurukulaaratchy, Associate Professor at the University of Southampton. It follows hundreds of asthma patients of different ages, sexes and disease severities over many years. Researchers are using the study to make new connections between asthma symptoms and immune cell activity. It is supported by the NIHR Southampton Biomedical Research Centre and NIHR Southampton Clinical Research Facility. "Once you understand the role of cells like these T cells better, you can start to develop treatments that target those cells," says Dr Kurukulaaratchy. The researchers now hope to learn more about these cells and their role in asthma, to develop personalised therapies for patients. Unresponsive to treatment The new research is published in the journal Med. It suggests patients with these cells in their lungs may be more likely to have hard-to-treat, and potentially fatal, asthma attacks. Doctors usually give asthma patients a general therapy to dampen their immune response. But these cells don't respond to this treatment. Prof Pandurangan Vijayanand and Prof Gregory Seumois at LJI co-led the study. "If you are male and you develop asthma after age 40, there's a high chance this T cell population is in your lungs," says Prof Seumois. How harmful T cells drive asthma The T cells are called 'memory' cells because they react to molecules that the body has previously fought off. They help protect the body from viruses and bacteria. But this 'memory' is a big problem for asthma patients. Their misguided T cells trigger a dangerous inflammatory response to harmless molecules like pollen. Men who developed asthma later in life had an overwhelming number of these potentially harmful T cells. In this group, more than 65 percent of their CD4+ T cells were this type. Personalised asthma treatments The researchers used single-cell RNA sequencing to identify the cytotoxic CD4+ tissue-resident memory T cells. This method could help detect these cells in more patients going forward. This represents a 'paradigm shift' in asthma research, says Dr Kurukulaaratchy. Before now, scientists and clinicians separated asthma patients into just two groups: ‘T2 high’ and T2 low’. In a study published earlier this year, the team showed the importance of identifying more asthma patient subgroups. They found 93 percent of WATCH participants with severe asthma were in the T2 high category. Professor Hasan Arshad is Chair in Allergy and Clinical Immunology at the University of Southampton, and Director of The David Hide Asthma and Allergy Research Centre, Isle of Wight. He says: “We have to think of severe asthma as having different subtypes. The treatment has to be tailored according to these subtypes, because one size does not fit all." The researchers now want to use sequencing tools and other techniques to discover more asthma patient subtypes.

People across Wessex are hearing about research at virtual meetings run by University Hospital Southampton (UHS). Involving people in health and care research is about more than asking them to take part in a trial or study. Volunteers also help to shape our research activities – what we do and how we do it. We call this Patient and Public Involvement and Engagement (PPIE). This helps to ensure our trials and studies provide maximum benefit to people’s health. Virtual coffee mornings are one way our researchers can connect with the public. They are run by our PPIE team at UHS in collaboration with the Wessex Public Involvement Network (Wessex PIN). Staff have shed light on the diverse and unexpected benefits of this approach in a new paper published in UCL Press. Building relationships Opportunities for public involvement were significantly reduced at the start of the pandemic. In response, our PPIE team invited three hundred public contributors to the first researcher coffee morning in April 2020. They hoped it would help them build and maintain relationships with members of the public. More than one hundred coffee mornings have taken place since, showcasing diverse health and care research across Wessex. They also promote opportunities to take part in research. Over time, the new paper shows they have become a “safe, trusted space” for members of the public to influence and shape research. There are also advantages for researchers who choose to take part. “Research coffee mornings allowed me to develop my own meaningful and trusted relationships with public contributors, supporting future public involvement,” one researcher explained. “Several people volunteered to work with me on my research programme, and this continues outside of the coffee mornings.” Get involved The virtual coffee mornings continue to go from strength to strength and are open to all. They take place once a week, and consist of a presentation by a guest speaker and an interactive Q&A session. Recordings of past coffee mornings are available here. If you would like to find out more, please email William.Jones@uhs.nhs.uk.

New research shows that being active is good for children’s self-esteem and friendships. Insights from an international study suggest that an active lifestyle can enhance children's health-related quality of life. This is a measure of their overall health and wellbeing. Prof Keith Godfrey from the NIHR Southampton Biomedical Research Centre (BRC) was part of the study team. It also involved researchers from Singapore, France, Finland and Germany. Their analysis has been published in The Lancet Regional Health – Western Pacific. Measuring activity The NHS recommends that children and young people aged 5-18 do at least 60 minutes of moderate or vigorous intensity physical activity a day. Keeping fit from a young age can reduce the risk of major illnesses in later life. It also helps us stay a healthy weight and protects our mental health. This study analysed physical activity data from 370 children aged 8 years. They are all taking part in a birth cohort study in Singapore. Further physical activity measurements were made at age ten years. They each wore an accelerometer – which is like a smart watch – to assess their activity levels. It measured sleep, inactivity, light and moderate-to-vigorous intensity physical activity. The children also completed a questionnaire on quality of life during the follow up visit at age ten. Better quality of life Children who were more physically active had higher self-esteem and stronger friendships. Those who slept for longer also reported a higher quality of life and were more likely to do well in school. The analyses suggested that children’s quality of life was lower if sleep was replaced with inactivity. This wasn't the case when replaced with physical activity. The researchers suggest that this finding could be due to increased screen time. Previous studies have shown excessive screen time can have a negative effect on children’s health and wellbeing. The children’s movement behaviours were not, however, associated with their physical and emotional well-being. Prof Godfrey is a Professor of Epidemiology and Human Development at the University of Southampton and lead for Nutrition, Lifestyle and Metabolism in the NIHR Southampton BRC. He said: “Children’s quality of life is an area of wide concern. “The Good Childhood Report 2023 from the Children’s Society looked at how children’s wellbeing is changing over time. The analysis painted a ‘worrying picture’ for girls, as their happiness scores were significantly lower in 2020-21 than in 2009-10." Previous reports have also shown that children in the UK, especially girls, are among the most unhappy in Europe. Prof Godfrey added: “The findings from our new research point to the importance of promoting physical activity and healthy sleep. This can help improve children’s self-esteem and friendships.”

Professor Philip Calder has been awarded an international fellowship to expand the study of fatty acids. The Hagler Fellowship, awarded by Texas A&M University, will allow him to set up a new collaborative research programme in the USA. Prof Calder works within the Nutrition, Lifestyle and Metabolism theme at the NIHR Southampton Biomedical Research Centre. He was awarded one of only fourteen Hagler Fellowships for 2023-24. The fellowship will fund a research programme at Texas A&M, in collaboration with researchers in its School of Medicine. This will investigate handling and metabolism of omega-3 polyunsaturated fatty acids by the human body. Maximising the health benefits Eating more omega-3, found in oily fish, has been linked to various health benefits and a reduced risk of disease. Yet most people eat a diet high in omega-6, but low in omega-3. Humans can make the type of omega-3 found in fish, but most people are not able to do this very well. Understanding more about why people are not able to make these types of omega-3 themselves and identifying ways to overcome this will decrease reliance on fish. A prestigious fellowship The Hagler Fellowship programme has been running for 12 years, and has supported over 125 fellows. Fellowships for 2023-24 were awarded in a wide range of research fields. These covered medical research areas, such as nutrition and metabolism. They included scientific fields, such as biology, physics, chemical engineering and computer science. Some fellowships were also awarded in statistics, veterinary science, economics and educational policy. This round’s fellows include two Nobel Prize winners, Eric Maskin and Konstantin Novoselov. Both won the Nobel Prize in Physics, in 2007 and 2010 respectively. A great opportunity Apart from Prof Calder and Konstantin Novoselov, all new fellows were from the US. Prof Calder says, “I am staggered by this unsolicited award, that recognises the excellent research done by people in my team over many years. "The fellowship provides a great opportunity for me to develop new collaborations. I intend to use it to investigate the metabolism and handling of omega-3 fatty acids and to try to identify ways to promote production of these healthy fatty acids in the human body. "This will very much complement our work here in Southampton.”

Southampton researchers are developing an app to help spot signs of a respiratory infection getting worse. Respiratory tract infections (RTIs) affect parts of the body involved in breathing. This includes the nose, throat, airways and lungs. The new app will support remote monitoring of people with these illnesses by recording their coughs, breathing and speech. It uses machine learning to analyse these sounds and check if they need to see a doctor. The project is funded by UK Research and Innovation (UKRI) and led by the University of Cambridge. In Southampton, the team includes medical researchers and the Institute of Sound & Vibration Research (ISVR). Common cause of illness RTIs range from the common cold to more serious conditions, such as Pneumonia. Most get better without treatment, but some patients may need to see a GP. Prof Nick Francis is Head of School of Primary Care, Population Sciences and Medical Education at the University of Southampton. He is also part of the NIHR Southampton Biomedical Research Centre. “RTIs are the most common cause of illness, resulting in around half of all antibiotic prescriptions,” Prof Francis explained. “Most people get better quickly, but we need to notice quickly when people are getting seriously ill. If we don’t, the effect on them and on healthcare services can be large. “We have tests that help doctors identify patients who are more likely to need treatment. But these do not work well for every patient and are not useful for helping patients manage their own illness.” There are some signs, such as breathing faster, that suggest a RTI is getting worse. The infection may also affect the sound of speech and trying to breathe when speaking. Prof Francis added: “We hope to develop an app that will assess all these signs and give warning when someone with an RTI should see their doctor. It will also rate its own confidence in its prediction, which will help doctors trust machine learning in healthcare.” AI in healthcare The study has received a £590,000 grant from UKRI. It is titled RELOAD (REspiratory disease progression through LOngitudinal Audio Data machine learning). Prof Anna Barney, from the university’s ISVR, said: “Using acoustic data is an underexplored application of machine learning. The AI in this application will reassure patients when an infection is self-limiting and direct patients to a GP when it is not. This will help to ensure that GP appointments are available for those that need them.” The UKRI funding was part of a £13 million investment to boost use of AI in healthcare. Another Southampton project received funding to improve the analysis and interpretation of newly discovered variations in people’s DNA.

A new scoring system can predict how likely young children with symptoms such as wheezing are to have asthma in later life. Asthma symptoms, such as wheezing, are common in early childhood. Yet predicting which children will go on to have asthma as an adult is difficult. Prof Hasan Arshad is a Professor and Consultant in Allergy and Clinical Immunology in Southampton. He has led the development of the new scoring system, with results published in the journal Allergy. He is part of the NIHR Southampton Biomedical Research Centre (BRC). Our BRC’s Prof Graham Roberts and Dr Ramesh Kurukulaaratchy were also involved in the research. Based on children’s symptoms The new scoring system is known by the acronym ASPIRE. Symptoms that can be identified by a doctor - such as wheeze, allergies, eczema and chest infections - are used to generate a score. Each symptom is given a different weighting to indicate its importance. A higher overall score indicates an increased risk of the child having asthma at ages 10, 18 and 26 years. They developed ASPIRE using data from the Isle of Wight Birth Cohort. This is a group of 1,456 people living on the island and had visits at ages one, two, four, 10, 18 and 26 years. These visits included a detailed assessment of any allergies or asthma they had. Testing the scoring system The researchers created four versions of ASPIRE, using different symptoms and weightings. Two were then tested using data from participants in The Manchester Asthma and Allergy Study (MAAS) and The Avon Longitudinal Study of Parents and Children (ALSPAC). They showed that ASPIRE is better than the current front-runner, known as PARS. The most effective version was ASPIRE-1, which only uses recurrent wheeze and a positive skin prick test for allergies. As their previous research showed four allergies - house dust mites, cats, grass pollen and a type of mould - are most relevant to asthma, they suggest testing for these. Prof Arshad said: “We hope that ASPIRE will be used by primary care physicians, paediatricians and allergists across the world to improve the management of wheezy children, by providing a reliable risk assessment of later asthma development.” “In collaboration with Dr Zhang, Professor and Head of Biostatistics at the University of Memphis, we are now in the process of developing a webtool and mobile app to assist doctors in the use of ASPIRE in clinics.”

Southampton researchers are working with Stablepharma Ltd to trial vaccines that don’t need to be kept cold. The partners have been awarded a joint grant by Innovate UK to develop a fridge-free vaccine, SPVX02, to prevent tetanus and diphtheria. Tetanus remains an important public health problem where immunisation coverage is low. Several countries in the world still do not provide booster shots to protect their populations throughout life. One barrier that can limit some vaccines’ reach is the complex logistics of an international, temperature-controlled supply chain. Professor Saul Faust, Director of the NIHR Southampton Clinical Research Facility, will lead the clinical trials for the fridge-free vaccine. Prof Faust, Co-Lead for Microbiology, Immunology and Infection in the NIHR Southampton Biomedical Research Centre, said: ‘’This project’s success has tremendous potential for eradicating vaccine wastage and moving away from the need for the cold-chain. This will have huge benefits that will ultimately provide greater safety and effectiveness for vaccines.’’ Expanding the reach of vaccines Stablepharma uses its novel technology to convert existing approved vaccines to fridge-free versions. The vaccines they create are ‘stable’ and do not degrade at room temperature. This prevents the need for cold-chain transport, distribution and storage. The company have identified up to 60 vaccines that could be made fridge-free in this way. They hope this will dramatically increase the number of people across the world who can access these vaccines, protecting them against a wide range of preventable diseases. Responding to the new funding success, Özgür Tuncer, Stablepharma CEO & Executive Director, said: “This is a great endorsement of the work our R&D team are doing to achieve Stablepharma’s vision of making fridge-free vaccines a reality. As we know, there are vast challenges within the global cold chain, which hinder the efficient distribution and storage of vaccines.” Stablepharma recently announced plans for a pre-initial public offering (IPO) bridge-funding round later in 2023. This will progress the launch of SPVX02 (Td), a second fridge-free vaccine SPVX06 (Tetanus mono) and their mRNA research programme.

People from across our communities are having their say on how we can improve the way we work with patients and the public. Involving people in our clinical research is about more than asking them to take part in a trial or study. Volunteers also help to shape our clinical research activities. We call this Patient and Public Involvement and Engagement (PPIE). This includes working with researchers to shape what research is done, how it’s carried out and how the results are shared. These people are often referred to as ‘public partners.’ Gathering insights Our PPIE team organised a series of workshops this summer to explore co-producing research with the public. Co-production is a way of working together in equal partnership and for equal benefit. This means people who can benefit from research should be involved in shaping it from the very start. There was extremely high interest in the subject – with extra sessions required for everyone to have their say. A report on the key outcomes will be shared with event attendees in the next few weeks. Hear from people who were at the events in this blog. Get involved Opportunities to help shape our research are varied and will depend on your interests. If you would like to find out more, please email PublicInvolvement@uhs.nhs.uk.

Southampton researchers are testing a shorter course of antibiotics to treat cellulitis. Cellulitis is a deep skin infection that’s treated with antibiotics. However, antibiotics can cause side effects - and levels of resistance are rising. This means doctors are looking at ways to cut any unnecessary use. The COAT study is funded by the National Institute for Health and Care Research (NIHR). It will help determine if a five-day course of antibiotics for cellulitis is as effective as the standard seven days. Professor Nick Francis from the University of Southampton and the NIHR Southampton Biomedical Research Centre (BRC) is leading the study. It is being run by the Southampton Clinical Trials Unit (CTU). Reducing antibiotic use Cellulitis is a bacterial infection that affects the deep layers of the skin. The infection is most common in older people and those with poor circulation or a weakened immune system. Any area of the body can be affected but the legs are the most common place. The infection can spread if it’s not treated quickly. Current guidelines suggest that people with cellulitis should be given a five to seven-day course of oral antibiotics. “At the moment, almost all patients who come to their GP with cellulitis will be initially treated for the full seven days,” said Prof Francis. “This is not because of evidence from research, but more due to years of warnings to doctors about stopping treatment too soon. “However, there is increasing evidence that shorter courses are as effective. Longer courses may increase risks for individual patients, as well as the entire healthcare system as we see increases in antibiotic resistance.” Previous research has shown that shorter courses of antibiotics can be just as effective for other infections. These include pneumonia, tonsillitis and urinary infections. But there is currently very little evidence for this approach for people with cellulitis. Prof Francis continued: “This lack of evidence means GPs are reluctant to prescribe shorter courses for these patients. Our study will test whether five days of antibiotic treatment works as well as seven days to see if the guidelines can be changed.” Gathering the evidence Researchers are recruiting 350 patients with cellulitis in their legs. They will do this through GP surgeries across the UK. Half will be given the standard seven-day course of the oral antibiotic flucloxacillin. The other half will take antibiotics for five days, followed by a placebo pill for two days. “The patients will be randomly assigned to each arm of the trial and will not know whether they are having the full course of antibiotics or the shorter course and placebo,” said Sophie Varkonyi-Clifford, Trial Manager at the Southampton CTU. “Patients will report pain and other symptoms related to cellulitis before they start treatment and for a month afterwards. Their local GP surgery will also note any additional treatment or complications for the next year.” Prof Francis added: “We hope the outcomes of this trial will definitively show whether cellulitis can be effectively treated with a five-day course of antibiotics. “If the results are positive, it could lead to an update in the guidelines and a reduction in the amount of these drugs being routinely prescribed by GPs across the UK. This would be beneficial for patients and the entire health service.” Visit the COAT study website for more information.