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3. Correction: Characterising illness stages and recovery trajectories of eating disorders in young people via remote measurement technology (STORY): a multi-centre prospective cohort study protocol

Author

Kuehne, Carina, Phillips, Matthew D., Moody, Sarah, Bryson, Callum, Campbell, Iain C., Conde, Pauline, Cummins, Nicholas, Desrivières, Sylvane, Dineley, Judith, Dobson, Richard, Douglas, Daire, Folarin, Amos, Gallop, Lucy, Hemmings, Amelia, İnce, Başak, Mason, Luke, Rashid, Zulqarnain, Bromell, Alice, Sims, Christopher, Allen, Karina, Bailie, Chantal, Bains, Parveen, Basher, Mike, Battisti, Francesca, Baudinet, Julian, Bristow, Katherine, Dawson, Nicola, Dodd, Lizzie, Frater, Victoria, Freudenthal, Robert, Gripton, Beth, Kan, Carol, Khor, Joel W. T., Kotze, Nicus, Laverack, Stuart, Martin, Lee, Maxwell, Sarah, McDonald, Sarah, McKnight, Delysia, McKay, Ruairidh, Merrin, Jessica, Nash, Mel, Nicholls, Dasha, Palmer, Shirlie, Pearce, Samantha, Roberts, Catherine, Serpell, Lucy, Severs, Emilia, Simic, Mima, Staton, Amelia, Westaway, Sian, Sharpe, Helen, and Schmidt, Ulrike

Published
2024
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4. Characterising illness stages and recovery trajectories of eating disorders in young people via remote measurement technology (STORY): a multi-centre prospective cohort study protocol

Author

Kuehne, Carina, Phillips, Matthew D., Moody, Sarah, Bryson, Callum, Campbell, Iain C., Conde, Pauline, Cummins, Nicholas, Desrivières, Sylvane, Dineley, Judith, Dobson, Richard, Douglas, Daire, Folarin, Amos, Gallop, Lucy, Hemmings, Amelia, İnce, Başak, Mason, Luke, Rashid, Zulqarnain, Bromell, Alice, Sims, Christopher, Allen, Karina, Bailie, Chantal, Bains, Parveen, Basher, Mike, Battisti, Francesca, Baudinet, Julian, Bristow, Katherine, Dawson, Nicola, Dodd, Lizzie, Frater, Victoria, Freudenthal, Robert, Gripton, Beth, Kan, Carol, Khor, Joel W. T., Kotze, Nicus, Laverack, Stuart, Martin, Lee, Maxwell, Sarah, McDonald, Sarah, McKnight, Delysia, McKay, Ruairidh, Merrin, Jessica, Nash, Mel, Nicholls, Dasha, Palmer, Shirlie, Pearce, Samantha, Roberts, Catherine, Serpell, Lucy, Severs, Emilia, Simic, Mima, Staton, Amelia, Westaway, Sian, Sharpe, Helen, and Schmidt, Ulrike

Published
2024
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5. Characterising illness stages and recovery trajectories of eating disorders in young people via remote measurement technology (STORY): a multi-centre prospective cohort study protocol

Author

Carina Kuehne, Matthew D. Phillips, Sarah Moody, Callum Bryson, Iain C. Campbell, Pauline Conde, Nicholas Cummins, Sylvane Desrivières, Judith Dineley, Richard Dobson, Daire Douglas, Amos Folarin, Lucy Gallop, Amelia Hemmings, Başak İnce, Luke Mason, Zulqarnain Rashid, Alice Bromell, Christopher Sims, Karina Allen, Chantal Bailie, Parveen Bains, Mike Basher, Francesca Battisti, Julian Baudinet, Katherine Bristow, Nicola Dawson, Lizzie Dodd, Victoria Frater, Robert Freudenthal, Beth Gripton, Carol Kan, Joel W. T. Khor, Nicus Kotze, Stuart Laverack, Lee Martin, Sarah Maxwell, Sarah McDonald, Delysia McKnight, Ruairidh McKay, Jessica Merrin, Mel Nash, Dasha Nicholls, Shirlie Palmer, Samantha Pearce, Catherine Roberts, Lucy Serpell, Emilia Severs, Mima Simic, Amelia Staton, Sian Westaway, Helen Sharpe, Ulrike Schmidt, and EDIFY consortium

Subjects
Eating disorders, Recovery, Progression, Clinical staging, Remote measurement technology, Longitudinal monitoring, Psychiatry, RC435-571
Abstract

Abstract Background Eating disorders (EDs) are serious, often chronic, conditions associated with pronounced morbidity, mortality, and dysfunction increasingly affecting young people worldwide. Illness progression, stages and recovery trajectories of EDs are still poorly characterised. The STORY study dynamically and longitudinally assesses young people with different EDs (restricting; bingeing/bulimic presentations) and illness durations (earlier; later stages) compared to healthy controls. Remote measurement technology (RMT) with active and passive sensing is used to advance understanding of the heterogeneity of earlier and more progressed clinical presentations and predictors of recovery or relapse. Methods STORY follows 720 young people aged 16–25 with EDs and 120 healthy controls for 12 months. Online self-report questionnaires regularly assess ED symptoms, psychiatric comorbidities, quality of life, and socioeconomic environment. Additional ongoing monitoring using multi-parametric RMT via smartphones and wearable smart rings (‘Ōura ring’) unobtrusively measures individuals’ daily behaviour and physiology (e.g., Bluetooth connections, sleep, autonomic arousal). A subgroup of participants completes additional in-person cognitive and neuroimaging assessments at study-baseline and after 12 months. Discussion By leveraging these large-scale longitudinal data from participants across ED diagnoses and illness durations, the STORY study seeks to elucidate potential biopsychosocial predictors of outcome, their interplay with developmental and socioemotional changes, and barriers and facilitators of recovery. STORY holds the promise of providing actionable findings that can be translated into clinical practice by informing the development of both early intervention and personalised treatment that is tailored to illness stage and individual circumstances, ultimately disrupting the long-term burden of EDs on individuals and their families.

Published
2024
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6. Stratified analyses refine association between TLR7 rare variants and severe COVID-19

Author

Jannik Boos, Caspar I. van der Made, Gayatri Ramakrishnan, Eamon Coughlan, Rosanna Asselta, Britt-Sabina Löscher, Luca V.C. Valenti, Rafael de Cid, Luis Bujanda, Antonio Julià, Erola Pairo-Castineira, J. Kenneth Baillie, Sandra May, Berina Zametica, Julia Heggemann, Agustín Albillos, Jesus M. Banales, Jordi Barretina, Natalia Blay, Paolo Bonfanti, Maria Buti, Javier Fernandez, Sara Marsal, Daniele Prati, Luisa Ronzoni, Nicoletta Sacchi, Joachim L. Schultze, Olaf Riess, Andre Franke, Konrad Rawlik, David Ellinghaus, Alexander Hoischen, Axel Schmidt, Kerstin U. Ludwig, Valeria Rimoldi, Elvezia M. Paraboschi, Alessandra Bandera, Flora Peyvandi, Giacomo Grasselli, Francesco Blasi, Francesco Malvestiti, Serena Pelusi, Cristiana Bianco, Lorenzo Miano, Angela Lombardi, Pietro Invernizzi, Alessio Gerussi, Giuseppe Citerio, Andrea Biondi, Maria Grazia Valsecchi, Marina Elena Cazzaniga, Giuseppe Foti, Ilaria Beretta, Mariella D'Angiò, Laura Rachele Bettini, Xavier Farré, Susana Iraola-Guzmán, Manolis Kogevinas, Gemma Castaño-Vinyals, Koldo Garcia-Etxebarria, Beatriz Nafria, Mauro D'Amato, Adriana Palom, Colin Begg, Sara Clohisey, Charles Hinds, Peter Horby, Julian Knight, Lowell Ling, David Maslove, Danny McAuley, Johnny Millar, Hugh Montgomery, Alistair Nichol, Peter J.M. Openshaw, Alexandre C. Pereira, Chris P. Ponting, Kathy Rowan, Malcolm G. Semple, Manu Shankar-Hari, Charlotte Summers, Timothy Walsh, Latha Aravindan, Ruth Armstrong, Heather Biggs, Ceilia Boz, Adam Brown, Richard Clark, Audrey Coutts, Judy Coyle, Louise Cullum, Sukamal Das, Nicky Day, Lorna Donnelly, Esther Duncan, Angie Fawkes, Paul Fineran, Max Head Fourman, Anita Furlong, James Furniss, Bernadette Gallagher, Tammy Gilchrist, Ailsa Golightly, Fiona Griffiths, Katarzyna Hafezi, Debbie Hamilton, Ross Hendry, Andy Law, Dawn Law, Rachel Law, Sarah Law, Rebecca Lidstone-Scott, Louise Macgillivray, Alan Maclean, Hanning Mal, Sarah McCafferty, Ellie Mcmaster, Jen Meikle, Shona C. Moore, Kirstie Morrice, Lee Murphy, Sheena Murphy, Mybaya Hellen, Wilna Oosthuyzen, Chenqing Zheng, Jiantao Chen, Nick Parkinson, Trevor Paterson, Katherine Schon, Andrew Stenhouse, Mihaela Das, Maaike Swets, Helen Szoor-McElhinney, Filip Taneski, Lance Turtle, Tony Wackett, Mairi Ward, Jane Weaver, Nicola Wrobel, Marie Zechner, Gill Arbane, Aneta Bociek, Sara Campos, Neus Grau, Tim Owen Jones, Rosario Lim, Martina Marotti, Marlies Ostermann, Christopher Whitton, Zoe Alldis, Raine Astin-Chamberlain, Fatima Bibi, Jack Biddle, Sarah Blow, Matthew Bolton, Catherine Borra, Ruth Bowles, Maudrian Burton, Yasmin Choudhury, David Collier, Amber Cox, Amy Easthope, Patrizia Ebano, Stavros Fotiadis, Jana Gurasashvili, Rosslyn Halls, Pippa Hartridge, Delordson Kallon, Jamila Kassam, Ivone Lancoma-Malcolm, Maninderpal Matharu, Peter May, Oliver Mitchelmore, Tabitha Newman, Mital Patel, Jane Pheby, Irene Pinzuti, Zoe Prime, Oleksandra Prysyazhna, Julian Shiel, Melanie Taylor, Carey Tierney, Suzanne Wood, Anne Zak, Olivier Zongo, Stephen Bonner, Keith Hugill, Jessica Jones, Steven Liggett, Evie Headlam, Nageswar Bandla, Minnie Gellamucho, Michelle Davies, Christopher Thompson, Marwa Abdelrazik, Dhanalakshmi Bakthavatsalam, Munzir Elhassan, Arunkumar Ganesan, Anne Haldeos, Jeronimo Moreno-Cuesta, Dharam Purohit, Rachel Vincent, Kugan Xavier, Kumar Rohit, Frater Alasdair, Malik Saleem, Carter David, Jenkins Samuel, Zoe Lamond, Wall Alanna, Jaime Fernandez-Roman, David O. Hamilton, Emily Johnson, Brian Johnston, Maria Lopez Martinez, Suleman Mulla, David Shaw, Alicia A.C. Waite, Victoria Waugh, Ingeborg D. Welters, Karen Williams, Anna Cavazza, Maeve Cockrell, Eleanor Corcoran, Maria Depante, Clare Finney, Ellen Jerome, Mark McPhail, Monalisa Nayak, Harriet Noble, Kevin O'Reilly, Evita Pappa, Rohit Saha, Sian Saha, John Smith, Abigail Knighton, David Antcliffe, Dorota Banach, Stephen Brett, Phoebe Coghlan, Ziortza Fernandez, Anthony Gordon, Roceld Rojo, Sonia Sousa Arias, Maie Templeton, Megan Meredith, Lucy Morris, Lucy Ryan, Amy Clark, Julia Sampson, Cecilia Peters, Martin Dent, Margaret Langley, Saima Ashraf, Shuying Wei, Angela Andrew, Archana Bashyal, Neil Davidson, Paula Hutton, Stuart McKechnie, Jean Wilson, David Baptista, Rebecca Crowe, Rita Fernandes, Rosaleen Herdman-Grant, Anna Joseph, Denise O'Connor, Meryem Allen, Adam Loveridge, India McKenley, Eriko Morino, Andres Naranjo, Richard Simms, Kathryn Sollesta, Andrew Swain, Harish Venkatesh, Jacyntha Khera, Jonathan Fox, Gillian Andrew, Lucy Barclay, Marie Callaghan, Rachael Campbell, Sarah Clark, Dave Hope, Lucy Marshall, Corrienne McCulloch, Kate Briton, Jo Singleton, Sohphie Birch, Lutece Brimfield, Zoe Daly, David Pogson, Steve Rose, Ceri Battle, Elaine Brinkworth, Rachel Harford, Carl Murphy, Luke Newey, Tabitha Rees, Marie Williams, Sophie Arnold, Petra Polgarova, Katerina Stroud, Eoghan Meaney, Megan Jones, Anthony Ng, Shruti Agrawal, Nazima Pathan, Deborah White, Esther Daubney, Kay Elston, Lina Grauslyte, Musarat Hussain, Mandeep Phull, Tatiana Pogreban, Lace Rosaroso, Erika Salciute, George Franke, Joanna Wong, Aparna George, Laura Ortiz-Ruiz de Gordoa, Emily Peasgood, Claire Phillips, Michelle Bates, Jo Dasgin, Jaspret Gill, Annette Nilsson, James Scriven, Carlos Castro Delgado, Deborah Dawson, Lijun Ding, Georgia Durrant, Obiageri Ezeobu, Sarah Farnell-Ward, Abiola Harrison, Rebecca Kanu, Susannah Leaver, Elena Maccacari, Soumendu Manna, Romina Pepermans Saluzzio, Joana Queiroz, Tinashe Samakomva, Christine Sicat, Joana Texeira, Edna Fernandes Da Gloria, Ana Lisboa, John Rawlins, Jisha Mathew, Ashley Kinch, William James Hurt, Nirav Shah, Victoria Clark, Maria Thanasi, Nikki Yun, Kamal Patel, Sara Bennett, Emma Goodwin, Matthew Jackson, Alissa Kent, Clare Tibke, Wiesia Woodyatt, Ahmed Zaki, Azmerelda Abraheem, Peter Bamford, Kathryn Cawley, Charlie Dunmore, Maria Faulkner, Rumanah Girach, Helen Jeffrey, Rhianna Jones, Emily London, Imrun Nagra, Farah Nasir, Hannah Sainsbury, Clare Smedley, Tahera Patel, Matthew Smith, Srikanth Chukkambotla, Aayesha Kazi, Janice Hartley, Joseph Dykes, Muhammad Hijazi, Sarah Keith, Meherunnisa Khan, Janet Ryan-Smith, Philippa Springle, Jacqueline Thomas, Nick Truman, Samuel Saad, Dabheoc Coleman, Christopher Fine, Roseanna Matt, Bethan Gay, Jack Dalziel, Syamlan Ali, Drew Goodchild, Rhiannan Harling, Ravi Bhatterjee, Wendy Goddard, Chloe Davison, Stephen Duberly, Jeanette Hargreaves, Rachel Bolton, Miriam Davey, David Golden, Rebecca Seaman, Shiney Cherian, Sean Cutler, Anne Emma Heron, Anna Roynon-Reed, Tamas Szakmany, Gemma Williams, Owen Richards, Yusuf Cheema, Hollie Brooke, Sarah Buckley, Jose Cebrian Suarez, Ruth Charlesworth, Karen Hansson, John Norris, Alice Poole, Alastair Rose, Rajdeep Sandhu, Brendan Sloan, Elizabeth Smithson, Muthu Thirumaran, Veronica Wagstaff, Alexandra Metcalfe, Mark Brunton, Jess Caterson, Holly Coles, Matthew Frise, Sabi Gurung Rai, Nicola Jacques, Liza Keating, Emma Tilney, Shauna Bartley, Parminder Bhuie, Sian Gibson, Amanda Lyle, Fiona McNeela, Jayachandran Radhakrishnan, Alistair Hughes, Bryan Yates, Jessica Reynolds, Helen Campbell, Maria Thompsom, Steve Dodds, Stacey Duffy, Sandra Greer, Karen Shuker, Ascanio Tridente, Reena Khade, Ashok Sundar, George Tsinaslanidis, Isobel Birkinshaw, Joseph Carter, Kate Howard, Joanne Ingham, Rosie Joy, Harriet Pearson, Samantha Roche, Zoe Scott, Hollie Bancroft, Mary Bellamy, Margaret Carmody, Jacqueline Daglish, Faye Moore, Joanne Rhodes, Mirriam Sangombe, Salma Kadiri, Maria Croft, Ian White, Victoria Frost, Maia Aquino, Rajeev Jha, Vinodh Krishnamurthy, Lai Lim, Li Lim, Edward Combes, Teishel Joefield, Sonja Monnery, Valerie Beech, Sallyanne Trotman, Christine Almaden-Boyle, Pauline Austin, Louise Cabrelli, Stephen Cole, Matt Casey, Susan Chapman, Clare Whyte, Yolanda Baird, Aaron Butler, Indra Chadbourn, Linda Folkes, Heather Fox, Amy Gardner, Raquel Gomez, Gillian Hobden, Luke Hodgson, Kirsten King, Michael Margarson, Tim Martindale, Emma Meadows, Dana Raynard, Yvette Thirlwall, David Helm, Jordi Margalef, Kristine Criste, Rebecca Cusack, Kim Golder, Hannah Golding, Oliver Jones, Samantha Leggett, Michelle Male, Martyna Marani, Kirsty Prager, Toran Williams, Belinda Roberts, Karen Salmon, Peter Anderson, Katie Archer, Karen Austin, Caroline Davis, Alison Durie, Olivia Kelsall, Jessica Thrush, Charlie Vigurs, Laura Wild, Hannah-Louise Wood, Helen Tranter, Alison Harrison, Nicholas Cowley, Michael McAlindon, Andrew Burtenshaw, Stephen Digby, Emma Low, Aled Morgan, Naiara Cother, Tobias Rankin, Sarah Clayton, Alex McCurdy, Cecilia Ahmed, Balvinder Baines, Sarah Clamp, Julie Colley, Risna Haq, Anne Hayes, Jonathan Hulme, Samia Hussain, Sibet Joseph, Rita Kumar, Zahira Maqsood, Manjit Purewal, Leonie Benham, Zena Bradshaw, Joanna Brown, Melanie Caswell, Jason Cupitt, Sarah Melling, Stephen Preston, Nicola Slawson, Emma Stoddard, Scott Warden, Bethan Deacon, Ceri Lynch, Carla Pothecary, Lisa Roche, Gwenllian Sera Howe, Jayaprakash Singh, Keri Turner, Hannah Ellis, Natalie Stroud, Jodie Hunt, Joy Dearden, Emma Dobson, Andy Drummond, Michelle Mulcahy, Sheila Munt, Grainne O'Connor, Jennifer Philbin, Chloe Rishton, Redmond Tully, Sarah Winnard, Susanne Cathcart, Katharine Duffy, Alex Puxty, Kathryn Puxty, Lynne Turner, Jane Ireland, Gary Semple, Kate Long, Simon Whiteley, Elizabeth Wilby, Bethan Ogg, Amanda Cowton, Andrea Kay, Melanie Kent, Kathryn Potts, Ami Wilkinson, Suzanne Campbell, Ellen Brown, Julie Melville, Jay Naisbitt, Rosane Joseph, Maria Lazo, Olivia Walton, Alan Neal, Peter Alexander, Schvearn Allen, Joanne Bradley-Potts, Craig Brantwood, Jasmine Egan, Timothy Felton, Grace Padden, Luke Ward, Stuart Moss, Susannah Glasgow, Lynn Abel, Michael Brett, Brian Digby, Lisa Gemmell, James Hornsby, Patrick MacGoey, Pauline O'Neil, Richard Price, Natalie Rodden, Kevin Rooney, Radha Sundaram, Nicola Thomson, Bridget Hopkins, Laura Thrasyvoulou, Heather Willis, Martyn Clark, Martina Coulding, Edward Jude, Jacqueline McCormick, Oliver Mercer, Darsh Potla, Hafiz Rehman, Heather Savill, Victoria Turner, Charlotte Downes, Kathleen Holding, Katie Riches, Mary Hilton, Mel Hayman, Deepak Subramanian, Priya Daniel, Oluronke Adanini, Nikhil Bhatia, Maines Msiska, Rebecca Collins, Ian Clement, Bijal Patel, A. 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Webster, Anne Hudson, Andrea Webster, Elaine Stephenson, Louise McCormack, Victoria Slater, Rachel Nixon, Helen Hanson, Maggie Fearby, Sinead Kelly, Victoria Bridgett, Philip Robinson, Julie Camsooksai, Charlotte Humphrey, Sarah Jenkins, Henrik Reschreiter, Beverley Wadams, Yasmin Death, Victoria Bastion, Daphene Clarke, Beena David, Harriet Kent, Rachel Lorusso, Gamu Lubimbi, Sophie Murdoch, Melchizedek Penacerrada, Alastair Thomas, Jennifer Valentine, Ana Vochin, Retno Wulandari, Brice Djeugam, Gillian Bell, Katy English, Amro Katary, Louise Wilcox, Michelle Bruce, Karen Connolly, Tracy Duncan, Helen T-Michael, Gabriella Lindergard, Samuel Hey, Claire Fox, Jordan Alfonso, Laura Jayne Durrans, Jacinta Guerin, Bethan Blackledge, Jade Harris, Martin Hruska, Ayaa Eltayeb, Thomas Lamb, Tracey Hodgkiss, Lisa Cooper, Joanne Rothwell, Angela Allan, Felicity Anderson, Callum Kaye, Jade Liew, Jasmine Medhora, Teresa Scott, Erin Trumper, Adriana Botello, Liana Lankester, Nikitas Nikitas, Colin Wells, Bethan Stowe, Kayleigh Spencer, Craig Brandwood, Lara Smith, Katie Birchall, Laurel Kolakaluri, Deborah Baines, Anila Sukumaran, Elena Apetri, Cathrine Basikolo, Laura Catlow, Bethan Charles, Paul Dark, Reece Doonan, Alice Harvey, Daniel Horner, Karen Knowles, Stephanie Lee, Diane Lomas, Chloe Lyons, Tracy Marsden, Danielle McLaughlan, Liam McMorrow, Jessica Pendlebury, Jane Perez, Maria Poulaka, Nicola Proudfoot, Melanie Slaughter, Kathryn Slevin, Vicky Thomas, Danielle Walker, Angiy Michael, Matthew Collis, Tracey Cosier, Gemma Millen, Neil Richardson, Natasha Schumacher, Heather Weston, James Rand, Nicola Baxter, Steven Henderson, Sophie Kennedy-Hay, Christopher McParland, Laura Rooney, Malcolm Sim, Gordan McCreath, Louise Akeroyd, Shereen Bano, Matt Bromley, Lucy Gurr, Tom Lawton, James Morgan, Kirsten Sellick, Deborah Warren, Brian Wilkinson, Janet McGowan, Camilla Ledgard, Amelia Stacey, Kate Pye, Ruth Bellwood, Michael Bentley, Jeremy Bewley, Zoe Garland, Lisa Grimmer, Bethany Gumbrill, Rebekah Johnson, Katie Sweet, Denise Webster, Georgia Efford, Karen Convery, Deirdre Fottrell-Gould, Lisa Hudig, Jocelyn Keshet-Price, Georgina Randell, Katie Stammers, Maria Bokhari, Vanessa Linnett, Rachael Lucas, Wendy McCormick, Jenny Ritzema, Amanda Sanderson, Helen Wild, Anthony Rostron, Alistair Roy, Lindsey Woods, Sarah Cornell, Fiona Wakinshaw, Kimberley Rogerson, Jordan Jarmain, Robert Parker, Amie Reddy, Ian Turner-Bone, Laura Wilding, Peter Harding, Caroline Abernathy, Louise Foster, Andrew Gratrix, Vicky Martinson, Priyai Parkinson, Elizabeth Stones, Llucia Carbral-Ortega, Georgia Bercades, David Brealey, Ingrid Hass, Niall MacCallum, Gladys Martir, Eamon Raith, Anna Reyes, Deborah Smyth, Letizia Zitter, Sarah Benyon, Suzie Marriott, Linda Park, Samantha Keenan, Elizabeth Gordon, Helen Quinn, Kizzy Baines, Lenka Cagova, Adama Fofano, Lucie Garner, Helen Holcombe, Sue Mepham, Alice Michael Mitchell, Lucy Mwaura, Krithivasan Praman, Alain Vuylsteke, Julie Zamikula, Bally Purewal, Vanessa Rivers, Stephanie Bell, Hayley Blakemore, Borislava Borislavova, Beverley Faulkner, Emma Gendall, Elizabeth Goff, Kati Hayes, Matt Thomas, Ruth Worner, Kerry Smith, Deanna Stephens, Louise Mew, Esther Mwaura, Richard Stewart, Felicity Williams, Lynn Wren, Sara-Beth Sutherland, Emily Bevan, Jane Martin, Dawn Trodd, Geoff Watson, Caroline Wrey Brown, Amy Collins, Waqas Khaliq, Estefania Treus Gude, Olugbenga Akinkugbe, Alasdair Bamford, Emily Beech, Holly Belfield, Michael Bell, Charlene Davies, Gareth A.L. Jones, Tara McHugh, Hamza Meghari, Lauran O'Neill, Mark J. Peters, Samiran Ray, Ana Luisa Tomas, Iona Burn, Geraldine Hambrook, Katarina Manso, Ruth Penn, Pradeep Shanmugasundaram, Julie Tebbutt, Danielle Thornton, Jade Cole, Rhys Davies, Donna Duffin, Helen Hill, Ben Player, Emma Thomas, Angharad Williams, Denise Griffin, Nycola Muchenje, Mcdonald Mupudzi, Richard Partridge, Jo-Anna Conyngham, Rachel Thomas, Mary Wright, Maria Alvarez Corral, Reni Jacob, Cathy Jones, Craig Denmade, Sarah Beavis, Katie Dale, Rachel Gascoyne, Joanne Hawes, Kelly Pritchard, Lesley Stevenson, Amanda Whileman, Patricia Doble, Joanne Hutter, Corinne Pawley, Charmaine Shovelton, Marius Vaida, Deborah Butcher, Susie O'Sullivan, Nicola Butterworth-Cowin, Norfaizan Ahmad, Joann Barker, Kris Bauchmuller, Sarah Bird, Kay Cawthron, Kate Harrington, Yvonne Jackson, Faith Kibutu, Becky Lenagh, Shamiso Masuko, Gary H. Mills, Ajay Raithatha, Matthew Wiles, Jayne Willson, Helen Newell, Alison Lye, Lorenza Nwafor, Claire Jarman, Sarah Rowland-Jones, David Foote, Joby Cole, Roger Thompson, James Watson, Lisa Hesseldon, Irene Macharia, Luke Chetam, Jacqui Smith, Amber Ford, Samantha Anderson, Kathryn Birchall, Kay Housley, Sara Walker, Leanne Milner, Helena Hanratty, Helen Trower, Patrick Phillips, Simon Oxspring, Ben Donne, Catherine Jardine, Dewi Williams, Alasdair Hay, Rebecca Flanagan, Gareth Hughes, Scott Latham, Emma McKenna, Jennifer Anderson, Robert Hull, Kat Rhead, Carina Cruz, Natalie Pattison, Rob Charnock, Denise McFarland, Denise Cosgrove, Ashar Ahmed, Anna Morris, Srinivas Jakkula, Asifa Ali, Megan Brady, Sam Dale, Annalisa Dance, Lisa Gledhill, Jill Greig, Kathryn Hanson, Kelly Holdroyd, Marie Home, Diane Kelly, Ross Kitson, Lear Matapure, Deborah Melia, Samantha Mellor, Tonicha Nortcliffe, Jez Pinnell, Matthew Robinson, Lisa Shaw, Ryan Shaw, Lesley Thomis, Alison Wilson, Tracy Wood, Lee-Ann Bayo, Ekta Merwaha, Tahira Ishaq, Sarah Hanley, Meg Hibbert, Dariusz Tetla, Chrsitopher Woodford, Latha Durga, Gareth Kennard-Holden, Debbie Branney, Jordan Frankham, Sally Pitts, Nigel White, Shondipon Laha, Mark Verlander, Alexandra Williams, Abdelhakim Altabaibeh, Ana Alvaro, Kayleigh Gilbert, Louise Ma, Loreta Mostoles, Chetan Parmar, Kathryn Simpson, Champa Jetha, Lauren Booker, Anezka Pratley, Colene Adams, Anita Agasou, Tracie Arden, Amy Bowes, Pauline Boyle, Mandy Beekes, Heather Button, Nigel Capps, Mandy Carnahan, Anne Carter, Danielle Childs, Denise Donaldson, Kelly Hard, Fran Hurford, Yasmin Hussain, Ayesha Javaid, James Jones, Sanal Jose, Michael Leigh, Terry Martin, Helen Millward, Nichola Motherwell, Rachel Rikunenko, Jo Stickley, Julie Summers, Louise Ting, Helen Tivenan, Louise Tonks, Rebecca Wilcox, Maureen Holland, Natalie Keenan, Marc Lyons, Helen Wassall, Chris Marsh, Mervin Mahenthran, Emma Carter, Thomas Kong, Helen Blackman, Ben Creagh-Brown, Sinead Donlon, Natalia Michalak-Glinska, Sheila Mtuwa, Veronika Pristopan, Armorel Salberg, Eleanor Smith, Sarah Stone, Charles Piercy, Jerik Verula, Dorota Burda, Rugia Montaser, Lesley Harden, Irving Mayangao, Cheryl Marriott, Paul Bradley, Celia Harris, Susan Anderson, Eleanor Andrews, Janine Birch, Emma Collins, Kate Hammerton, Ryan O'Leary, Michele Clark, Sarah Purvis, Russell Barber, Claire Hewitt, Annette Hilldrith, Karen Jackson-Lawrence, Sarah Shepardson, Maryanne Wills, Susan Butler, Silvia Tavares, Amy Cunningham, Julia Hindale, Sarwat Arif, Sarah Bean, Karen Burt, Michael Spivey, Carrie Demetriou, Charlotte Eckbad, Sarah Hierons, Lucy Howie, Sarah Mitchard, Lidia Ramos, Alfredo Serrano-Ruiz, Katie White, Fiona Kelly, Daniele Cristiano, Natalie Dormand, Zohreh Farzad, Mahitha Gummadi, Kamal Liyanage, Brijesh Patel, Sara Salmi, Geraldine Sloane, Vicky Thwaites, Mathew Varghese, Anelise C. Zborowski, John Allan, Tim Geary, Gordon Houston, Alistair Meikle, Peter O'Brien, Miranda Forsey, Agilan Kaliappan, Anne Nicholson, Joanne Riches, Mark Vertue, Elizabeth Allan, Kate Darlington, Ffyon Davies, Jack Easton, Sumit Kumar, Richard Lean, Daniel Menzies, Richard Pugh, Xinyi Qiu, Llinos Davies, Hannah Williams, Jeremy Scanlon, Gwyneth Davies, Callum Mackay, Joannne Lewis, Stephanie Rees, Metod Oblak, Monica Popescu, Mini Thankachen, Andrew Higham, Kerry Simpson, Jayne Craig, Rosie Baruah, Sheila Morris, Susie Ferguson, Amy Shepherd, Luke Stephen Prockter Moore, Marcela Paola Vizcaychipi, Laura Gomes de Almeida Martins, Jaime Carungcong, Inthakab Ali Mohamed Ali, Karen Beaumont, Mark Blunt, Zoe Coton, Hollie Curgenven, Mohamed Elsaadany, Kay Fernandes, Sameena Mohamed Ally, Harini Rangarajan, Varun Sarathy, Sivarupan Selvanayagam, Dave Vedage, Matthew White, Mandy Gill, Paul Paul, Valli Ratnam, Sarah Shelton, Inez Wynter, Siobhain Carmody, Valerie Joan Page, Claire Marie Beith, Karen Black, Suzanne Clements, Alan Morrison, Dominic Strachan, Margaret Taylor, Michelle Clarkson, Stuart D'Sylva, Kathryn Norman, Fiona Auld, Joanne Donnachie, Ian Edmond, Lynn Prentice, Nikole Runciman, Dario Salutous, Lesley Symon, Anne Todd, Patricia Turner, Abigail Short, Laura Sweeney, Euan Murdoch, Dhaneesha Senaratne, Michaela Hill, Thogulava Kannan, Wild Laura, Rikki Crawley, Abigail Crew, Mishell Cunningham, Allison Daniels, Laura Harrison, Susan Hope, Ken Inweregbu, Sian Jones, Nicola Lancaster, Jamie Matthews, Alice Nicholson, Gemma Wray, Helen Langton, Rachel Prout, Malcolm Watters, Catherine Novis, Anthony Barron, Ciara Collins, Sundeep Kaul, Heather Passmore, Claire Prendergast, Anna Reed, Paula Rogers, Rajvinder Shokkar, Meriel Woodruff, Hayley Middleton, Oliver Polgar, Claire Nolan, Kanta Mahay, Dawn Collier, Anil Hormis, Victoria Maynard, Cheryl Graham, Rachel Walker, Ellen Knights, Alicia Price, Alice Thomas, Chris Thorpe, Teresa Behan, Caroline Burnett, Jonathan Hatton, Elaine Heeney, Atideb Mitra, Maria Newton, Rachel Pollard, Rachael Stead, Vishal Amin, Elena Anastasescu, Vikram Anumakonda, Komala Karthik, Rizwana Kausar, Karen Reid, Jacqueline Smith, Janet Imeson-Wood, Denise Skinner, Jane Gaylard, Dee Mullan, Julie Newman, Alison Brown, Vikki Crickmore, Gabor Debreceni, Joy Wilkins, Liz Nicol, Rosie Reece-Anthony, Mark Birt, Alison Ghosh, Emma Williams, Louise Allen, Eva Beranova, Nikki Crisp, Joanne Deery, Tracy Hazelton, Alicia Knight, Carly Price, Sorrell Tilbey, Salah Turki, Sharon Turney, Joshua Cooper, Cheryl Finch, Sarah Liderth, Alison Quinn, Natalia Waddington, Tina Coventry, Susan Fowler, Michael MacMahon, Amanda McGregor, Anne Cowley, Judith Highgate, Jane Gregory, Susan O'Connell, Tim Smith, Luigi Barberis, Shameer Gopal, Nichola Harris, Victoria Lake, Stella Metherell, Elizabeth Radford, Amelia Daniel, Joanne Finn, Rajnish Saha, Nikki White, Phil Donnison, Fiona Trim, Beena Eapen, Jenny Birch, Laura Bough, Josie Goodsell, Rebecca Tutton, Patricia Williams, Sarah Williams, Barbara Winter-Goodwin, Ailstair Nichol, Kathy Brickell, Michelle Smyth, Lorna Murphy, Samantha Coetzee, Alistair Gales, Igor Otahal, Meena Raj, Craig Sell, Paula Hilltout, Jayne Evitts, Amanda Tyler, Joanne Waldron, Kate Beesley, Sarah Board, Agnieszka Kubisz-Pudelko, Alison Lewis, Jess Perry, Lucy Pippard, Di Wood, Clare Buckley, Peter Barry, Neil Flint, Patel Rekha, Dawn Hales, Lara Bunni, Claire Jennings, Monica Latif, Rebecca Marshall, Gayathri Subramanian, Peter J. McGuigan, Christopher Wasson, Stephanie Finn, Jackie Green, Erin Collins, Bernadette King, Andy Campbell, Sara Smuts, Joseph Duffield, Oliver Smith, Lewis Mallon, Watkins Claire, Liam Botfield, Joanna Butler, Catherine Dexter, Jo Fletcher, Atul Garg, Aditya Kuravi, Poonam Ranga, Emma Virgilio, Zakaula Belagodu, Bridget Fuller, Anca Gherman, Olumide Olufuwa, Remi Paramsothy, Carmel Stuart, Naomi Oakley, Charlotte Kamundi, David Tyl, Katy Collins, Pedro Silva, June Taylor, Laura King, Charlotte Coates, Maria Crowley, Phillipa Wakefield, Jane Beadle, Laura Johnson, Janet Sargeant, Madeleine Anderson, Ailbhe Brady, Rebekah Chan, Jeff Little, Shane McIvor, Helena Prady, Helen Whittle, Bijoy Mathew, Ben Attwood, Penny Parsons, Geraldine Ward, Pamela Bremmer, West Joe, Baird Tracy, Ruddy Jim, Ellie Davies, Sonia Sathe, Catherine Dennis, Alastair McGregor, Victoria Parris, Sinduya Srikaran, Anisha Sukha, Noreen Clarke, Jonathan Whiteside, Mairi Mascarenhas, Avril Donaldson, Joanna Matheson, Fiona Barrett, Marianne O'Hara, Laura Okeefe, Clare Bradley, Christine Eastgate-Jackson, Helder Filipe, Daniel Martin, Amitaa Maharajh, Sara Mingo Garcia, Glykeria Pakou, Mark De Neef, Kathy Dent, Elizabeth Horsley, Muhmmad Nauman Akhtar, Sandra Pearson, Dorota Potoczna, Sue Spencer, Melanie Clapham, Rosemary Harper, Una Poultney, Polly Rice, Rachel Mutch, Lisa Armstrong, Hayley Bates, Emma Dooks, Fiona Farquhar, Brigid Hairsine, Chantal McParland, Sophie Packham, Rehana Bi, Barney Scholefield, Lydia Ashton, Linsha George, Sophie Twiss, David Wright, Manish Chablani, Amy Kirkby, Kimberley Netherton, Kim Davies, Linda O'Brien, Zohra Omar, Emma Perkins, Tracy Lewis, Isobel Sutherland, Karen Burns, Dr Ben Chandler, Kerry Elliott, Janine Mallinson, Alison Turnbull, Prisca Gondo, Bernard Hadebe, Abdul Kayani, Bridgett Masunda, Taya Anderson, Dan Hawcutt, Laura O'Malley, Laura Rad, Naomi Rogers, Paula Saunderson, Kathryn Sian Allison, Deborah Afolabi, Jennifer Whitbread, Dawn Jones, Rachael Dore, Matthew Halkes, Pauline Mercer, Lorraine Thornton, Joy Dawson, Sweyn Garrioch, Melanie Tolson, Jonathan Aldridge, Ritoo Kapoor, David Loader, Karen Castle, Sally Humphreys, Ruth Tampsett, Katherine Mackintosh, Amanda Ayers, Wendy Harrison, Julie North, Suzanne Allibone, Roman Genetu, Vidya Kasipandian, Amit Patel, Ainhi Mac, Anthony Murphy, Parisa Mahjoob, Roonak Nazari, Lucy Worsley, Andrew Fagan, Thomas Bemand, Ethel Black, Arnold Dela Rosa, Ryan Howle, Shaman Jhanji, Ravishankar Rao Baikady, Kate Colette Tatham, Benjamin Thomas, Dina Bell, Rosalind Boyle, Katie Douglas, Lynn Glass, Emma Lee, Liz Lennon, Austin Rattray, Abigail Taylor, Rachel Anne Hughes, Helen Thomas, Alun Rees, Michaela Duskova, Janet Phipps, Suzanne Brooks, Michelle Edwards, Sheena Quaid, Ekaterina Watson, Adam Brayne, Emma Fisher, Jane Hunt, Peter Jackson, Duncan Kaye, Nicholas Love, Juliet Parkin, Victoria Tuckey, Lynne Van Koutrik, Sasha Carter, Benedict Andrew, Louise Findlay, Katie Adams, Jen Service, Alison Williams, Claire Cheyne, Anne Saunderson, Sam Moultrie, Miranda Odam, Kathryn Hall, Isheunesu Mapfunde, Charlotte Willis, Alex Lyon, Chunda Sri-Chandana, Joslan Scherewode, Lorraine Stephenson, Sarah Marsh, John Hardy, Henry Houlden, Eleanor Moncur, Ambreen Tariq, Arianna Tucci, Maria Hobrok, Ronda Loosley, Heather McGuinness, Helen Tench, Rebecca Wolf-Roberts, Val Irvine, Benjamin Shelley, Claire Gorman, Abhinav Gupta, Elizabeth Timlick, Rebecca Brady, Barry Milligan, Arianna Bellini, Jade Bryant, Anton Mayer, Amy Pickard, Nicholas Roe, Jason Sowter, Alex Howlett, Katy Fidler, Emma Tagliavini, and Kevin Donnelly

Subjects
SARS-CoV-2, host genetics, toll-like receptor 7, targeted sequencing, rare variants, variant collapsing analysis, Genetics, QH426-470
Abstract

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

Published
2024
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7. Combined high rates of alternative breeding strategies unexpectedly found among populations of a solitary nesting raptor

Author

Robert N. Rosenfield, Sarah A. Sonsthagen, William E. Stout, Timothy G. Driscoll, Andrew C. Stewart, Paul N. Frater, and Sandra L. Talbot

Subjects
Accipiter cooperii, alternative mating strategies, conspecific brood parasitism, extra‐pair paternity, floaters, Ecology, QH540-549.5
Abstract

Abstract Social monogamy is the prevalent mating system in birds, but alternative strategies of extra‐pair paternity (EPP) and conspecific brood parasitism (CBP) occur in many species. Raptors are virtually absent in discussions of broad taxonomic reviews regarding EPP and CBP likely because these strategies are mostly absent or at low frequency; CBP is unreported in solitary nesting raptors. In contrast, we found high frequencies of EPP (16%–31%) and CBP (15%–26%) nests among three populations of Cooper's Hawks (Accipiter cooperii) across the northern breeding range of this solitary nesting, socially monogamous species. EPP and CBP combined occurred in 42%–46% of all nests among populations and hence unexpectedly were nearly equivalent to proportions of genetically monogamous nests. Select covariates failed to predict presence of EPP and CBP in part because virtually all extra‐pair adults were uncaught and likely were floaters. We found no support for the hypothesis that territorial females traded copulations for food to maximize energy intake for increased production. Our unique discoveries enhance knowledge of the extent and diversity of alternative breeding strategies among groups of avian and other animal species.

Published
2024
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8. Correction: Characterising illness stages and recovery trajectories of eating disorders in young people via remote measurement technology (STORY): a multi-centre prospective cohort study protocol

Author

Carina Kuehne, Matthew D. Phillips, Sarah Moody, Callum Bryson, Iain C. Campbell, Pauline Conde, Nicholas Cummins, Sylvane Desrivières, Judith Dineley, Richard Dobson, Daire Douglas, Amos Folarin, Lucy Gallop, Amelia Hemmings, Başak İnce, Luke Mason, Zulqarnain Rashid, Alice Bromell, Christopher Sims, Karina Allen, Chantal Bailie, Parveen Bains, Mike Basher, Francesca Battisti, Julian Baudinet, Katherine Bristow, Nicola Dawson, Lizzie Dodd, Victoria Frater, Robert Freudenthal, Beth Gripton, Carol Kan, Joel W. T. Khor, Nicus Kotze, Stuart Laverack, Lee Martin, Sarah Maxwell, Sarah McDonald, Delysia McKnight, Ruairidh McKay, Jessica Merrin, Mel Nash, Dasha Nicholls, Shirlie Palmer, Samantha Pearce, Catherine Roberts, Lucy Serpell, Emilia Severs, Mima Simic, Amelia Staton, Sian Westaway, Helen Sharpe, Ulrike Schmidt, and EDIFY consortium

Subjects
Psychiatry, RC435-571
Published
2024
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9. Influence of Curriculum Structure on Early Skill Learning during a Virtual Throwing Task

Author

Frater-Baird, Rebecca, Patil, Gaurav, Richardson, Michael J, and Nalepka, Patrick

Subjects
Psychology, Action, Behavioral Science, Motor control, Skill acquisition and learning
Abstract

Perceptual-motor tasks offer redundant solutions to achieve a goal. However, not all solutions are equally robust to error-producing variability and thus, skill learning requires the search for behaviors that are error-tolerant. Throwing a ball to hit a target is a skill that has been studied via the “skittles” task, a simplified 2-dimensional throwing environment. The study investigated whether participants learning the skittles task benefit from task scaffolding via the placements of targets provided by either a human confederate posing as a teacher, or by the participant. These groups were compared to a third sample who received an unstructured curriculum consisting of randomly placed targets. The results demonstrate that participants in the unstructured training condition were better able to perceive the task’s underlying solution geometry, compared to scaffolding provided by a human. Future work will explore methods to design training curricula that are more efficient in facilitating perceptual-motor skill development.

Published
2023

10. Impact of interrupting antiretroviral therapy started during primary HIV-1 infection on plasma neurofilament light chain protein, a marker of neuronal injury: The SPARTAC trial

Author

Jasmini Alagaratnam, Wolfgang Stöhr, Elizabeth Hamlyn, Kholoud Porter, Jamie Toombs, Amanda Heslegrave, Henrik Zetterberg, Magnus Gisslén, Jonathan Underwood, Mauro Schechter, Pontiano Kaleebu, Giuseppe Tambussi, Sabine Kinloch, Jose M. Miro, Anthony D. Kelleher, Abdel Babiker, John Frater, Alan Winston, and Sarah Fidler

Subjects
HIV-1, Neurofilaments, Anti-retroviral agents, Viral rebound, Primary HIV infection, Microbiology, QR1-502, Public aspects of medicine, RA1-1270
Abstract

Objective: Antiretroviral therapy (ART)-conferred suppression of HIV replication limits neuronal injury and inflammation. ART interruption tests efficacy in HIV cure trials and viral rebound after ART interruption may induce neuronal injury. We investigated the impact of protocol-defined ART interruption, commenced during primary HIV-1 infection (PHI) on a biomarker of neuro-axonal injury (neurofilament light protein (NfL)), and its associations with inflammation (D-dimer and interleukin-6 (IL-6)) and HIV-1 reservoir size (total HIV-1 DNA). Design: Retrospective study measuring plasma NfL in 83 participants enrolled in SPARTAC randomised to receive 48-weeks ART initiated during PHI, followed by ART interruption. Methods: NfL (Simoa immunoassay, Quanterix™) was measured before ART, after 48 weeks on ART, and 12 weeks after stopping ART. Plasma D-dimer and IL-6, and total HIV-1 DNA in peripheral CD4+ T-cells results were available in a subset of participants. Longitudinal NfL changes were assessed using mixed models, and associations with clinical and laboratory parameters using linear regression. Results: NfL decreased following 48-weeks ART (geometric mean 6.9 to 5.8 pg/mL, p = 0.006) with no further significant change up to 12-weeks post-stopping ART despite viral rebound in the majority of participants (median 1.7 to 3.9 plasma HIV-1 RNA log10 copies/mL). Higher baseline NfL was independently associated with higher plasma HIV-1 RNA (p = 0.020) and older age (p = 0.002). While NfL was positively associated with D-dimer (n = 48; p = 0.002), there was no significant association with IL-6 (n = 48) or total HIV-1 DNA (n = 51). Conclusions: Using plasma NfL as a surrogate marker, a decrease in neuro-axonal injury was observed in a cohort of participants following ART initiation during PHI, with no evidence of neuro-axonal injury rebound following ART interruption for up to 12 weeks, despite viral rebound in the majority of participants.

Published
2024
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14. Prevalence of resistance-associated viral variants to the HIV-specific broadly neutralising antibody 10-1074 in a UK bNAb-naïve population

Author

Panagiota Zacharopoulou, Ming Lee, Thiago Oliveira, John Thornhill, Nicola Robinson, Helen Brown, Sabine Kinloch, Philip Goulder, Julie Fox, Sarah Fidler, M. Azim Ansari, and John Frater

Subjects
HIV - human immunodeficiency virus, primary HIV infection (PHI), broadly neutralising antibodies, 10-1074, resistance screening, Immunologic diseases. Allergy, RC581-607
Abstract

Broadly neutralising antibodies (bNAbs) targeting HIV show promise for both prevention of infection and treatment. Among these, 10-1074 has shown potential in neutralising a wide range of HIV strains. However, resistant viruses may limit the clinical efficacy of 10-1074. The prevalence of both de novo and emergent 10-1074 resistance will determine its use at a population level both to protect against HIV transmission and as an option for treatment. To help understand this further, we report the prevalence of pre-existing mutations associated with 10-1074 resistance in a bNAb-naive population of 157 individuals presenting to UK HIV centres with primary HIV infection, predominantly B clade, receiving antiretroviral treatment. Single genome analysis of HIV proviral envelope sequences showed that 29% of participants’ viruses tested had at least one sequence with 10-1074 resistance-associated mutations. Mutations interfering with the glycan binding site at HIV Env position 332 accounted for 95% of all observed mutations. Subsequent analysis of a larger historic dataset of 2425 B-clade envelope sequences sampled from 1983 to 2019 revealed an increase of these mutations within the population over time. Clinical studies have shown that the presence of pre-existing bNAb mutations may predict diminished therapeutic effectiveness of 10-1074. Therefore, we emphasise the importance of screening for these mutations before initiating 10-1074 therapy, and to consider the implications of pre-existing resistance when designing prevention strategies.

Published
2024
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15. Gonadal androgens are associated with decreased type I interferon production by plasmacytoid dendritic cells and increased IgG titres to BNT162b2 following co-vaccination with live attenuated influenza vaccine in adolescents

Author

Oliver L. Sampson, Cecilia Jay, Emily Adland, Anna Csala, Nicholas Lim, Stella M. Ebbrecht, Lorna C. Gilligan, Angela E. Taylor, Sherley Sherafin George, Stephanie Longet, Lucy C. Jones, Ellie Barnes, John Frater, Paul Klenerman, Susie Dunachie, Miles Carrol, James Hawley, Wiebke Arlt, Andreas Groll, and Philip Goulder

Subjects
type I interferon, plasmacytoid dendritic cell, immune sex difference, androgen, adolescent vaccination, Immunologic diseases. Allergy, RC581-607
Abstract

mRNA vaccine technologies introduced following the SARS-CoV-2 pandemic have highlighted the need to better understand the interaction of adjuvants and the early innate immune response. Type I interferon (IFN-I) is an integral part of this early innate response that primes several components of the adaptive immune response. Women are widely reported to respond better than men to tri- and quadrivalent influenza vaccines. Plasmacytoid dendritic cells (pDCs) are the primary cell type responsible for IFN-I production, and female pDCs produce more IFN-I than male pDCs since the upstream pattern recognition receptor Toll-like receptor 7 (TLR7) is encoded by X chromosome and is biallelically expressed by up to 30% of female immune cells. Additionally, the TLR7 promoter contains several putative androgen response elements, and androgens have been reported to suppress pDC IFN-I in vitro. Unexpectedly, therefore, we recently observed that male adolescents mount stronger antibody responses to the Pfizer BNT162b2 mRNA vaccine than female adolescents after controlling for natural SARS-CoV-2 infection. We here examined pDC behaviour in this same cohort to determine the impact of IFN-I on anti-spike and anti-receptor-binding domain IgG titres to BNT162b2. Through flow cytometry and least absolute shrinkage and selection operator (LASSO) modelling, we determined that serum-free testosterone was associated with reduced pDC IFN-I, but contrary to the well-described immunosuppressive role for androgens, the most bioactive androgen dihydrotestosterone was associated with increased IgG titres to BNT162b2. Also unexpectedly, we observed that co-vaccination with live attenuated influenza vaccine boosted the magnitude of IgG responses to BNT162b2. Together, these data support a model where systemic IFN-I increases vaccine-mediated immune responses, yet for vaccines with intracellular stages, modulation of the local IFN-I response may alter antigen longevity and consequently improve vaccine-driven immunity.

Published
2024
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16. Therapeutic vaccination following early antiretroviral therapy elicits highly functional T cell responses against conserved HIV-1 regions

Author

Jakub Kopycinski, Hongbing Yang, Gemma Hancock, Matthew Pace, Ellen Kim, John Frater, Wolfgang Stöhr, Tomás Hanke, Sarah Fidler, Lucy Dorrell, and RIVER trial study group

Subjects
Medicine, Science
Abstract

Abstract ‘Kick and kill’ cure strategies aim to induce HIV protein expression in latently infected cells (kick), and thus trigger their elimination by cytolytic T cells (kill). In the Research in Viral Eradication of HIV Reservoirs trial (NCT02336074), people diagnosed with primary HIV infection received immediate antiretroviral therapy (ART) and were randomised 24 weeks later to either a latency-reversing agent, vorinostat, together with ChAdV63.HIVconsv and MVA.HIVconsv vaccines, or ART alone. This intervention conferred no reduction in HIV-1 reservoir size over ART alone, despite boosting virus-specific CD4+ and CD8+ T cells. The effects of the intervention were examined at the cellular level in the two trial arms using unbiased computational analysis of polyfunctional scores. This showed that the frequency and polyfunctionality of virus-specific CD4+ and CD8+ T cell populations were significantly increased over 12 weeks post-vaccination, compared to the ART-only arm. HIV-specific IL-2-secreting CD8+ T cells also expanded significantly in the intervention arm and were correlated with antiviral activity against heterologous HIV in vitro. Therapeutic vaccination during ART commenced in primary infection can induce functional T cell responses that are phenotypically similar to those of HIV controllers. Analytical therapy interruption may help determine their ability to control HIV in vivo.

Published
2023
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18. Forgetting in delayed recognition as generative compression with decreasing capacity

Author

Frater, Csenge, Nagy, David G., and Orbán, Gergő

Subjects
Artificial Intelligence, Psychology, Machine learning, Memory, Semantic memory
Abstract

Recent research has proposed that systematic biases in human memory -- while seemingly highlighting a proclivity for failure -- can be understood as hallmarks of optimised lossy compression. Specifically, a form of compression termed semantic compression whereby an internal model of the environment is recruited to encode memories. Semantic compression casts memory errors in the normative framework of information theory, describing how limited memory resources should be distributed to optimise recall performance. Notably, the theory does not define a single best compression, rather a continuum of trade-offs between utilised capacity and expected distortion is possible. However, possible consequences of this characteristic feature have not been tested explicitly. Here we test the idea that gradual degradation of memories with time corresponds to a decrease in the amount of resources allocated to store memories. We apply the general framework to remembering synthetic words in a delayed recognition experiment and find that subjects are indeed less sensitive to intrusions generated by our model than generic distortions, and that delay length modulates recall rates in line with the predictions of the theory.

Published
2022

20. Extraction-Free RT-PCR Surveillance Testing and Reporting for SARS-CoV-2

Author

Patrick R. Carney, Tyler Duellman, Jia-Yi Chan, Lauren Wells, Michael Tessmer, Leah Frater-Rubsam, Molly Zeller, Mark Field, James Speers, Kelly Tyrrell, Luke Thompson, Michael Bondurant, Tami Morin, Tamra Dagnon, Brian Goff, Corissa Runde, Sandra Splinter-Bondurant, Charles Konsitzke, Patrick Kelly, Christopher A. Bradfield, and Joshua Hyman

Subjects
SARS-CoV-2, COVID-19, RT-PCR, surveillance, Specialties of internal medicine, RC581-951
Abstract

The COVID-19 pandemic necessitated sensitive, fast, and inexpensive testing for the virus in 2020 prior to the widespread availability of vaccines. Early testing efforts were limited by bottlenecks on reagents, low-throughput testing options, and the slow return of test results. In this paper, we detail the testing pipeline we established at the University of Wisconsin-Madison for rapid, inexpensive, and sensitive surveillance testing for SARS-CoV-2, and we highlight the strengths of the platform that would allow it to be applied to other disease surveillance projects, SARS-CoV-2 variant testing, or future pandemics. This pipeline can be quickly established for further accreditation and clinical application.

Published
2023
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24. Red Blood Cell Distribution Width as a Biomarker in Type 2 Diabetes Mellitus: Technical Notes [Letter]

Author

Frater JL

Subjects
diabetes mellitus red blood cell distribution width complete blood cell count automated hematology preanalytical phase analytical phase, Specialties of internal medicine, RC581-951
Abstract

John L Frater Department of Pathology and Immunology, Washington University, St. Louis, MO, USACorrespondence: John L Frater, Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8118, St. Louis, MO, 63110-1093, USA, Tel +1 314 362-1553, Email jfrater@wustl.edu

Published
2023

26. Survey on Error Concealment Strategies and Subjective Testing of 3D Videos

Author

Hasan, Md Mehedi, Frater, Michael, and Arnold, John

Subjects
Computer Science - Multimedia
Abstract

Over the last decade, different technologies to visualize 3D scenes have been introduced and improved. These technologies include stereoscopic, multi-view, integral imaging and holographic types. Despite increasing consumer interest; poor image quality, crosstalk or side effects of 3D displays and also the lack of defined broadcast standards has hampered the advancement of 3D displays to the mass consumer market. Also, in real time transmission of 3DTV sequences over packet-based networks may results in visual quality degradations due to packet loss and others. In the conventional 2D videos different extrapolation and directional interpolation strategies have been used for concealing the missing blocks but in 3D, it is still an emerging field of research. Few studies have been carried out to define the assessment methods of stereoscopic images and videos. But through industrial and commercial perspective, subjective quality evaluation is the most direct way to evaluate human perception on 3DTV systems. This paper reviews the state-of-the-art error concealment strategies and the subjective evaluation of 3D videos and proposes a low complexity frame loss concealment method for the video decoder. Subjective testing on prominent datasets videos and comparison with existing concealment methods show that the proposed method is very much efficient to conceal errors of stereoscopic videos in terms of computation time, comfort and distortion.

Published
2018

27. Binocular Rivalry - Psychovisual Challenge in Stereoscopic Video Error Concealment

Author

Hasan, Md Mehedi, Arnold, John F., and Frater, Michael R.

Subjects
Computer Science - Multimedia
Abstract

During Stereoscopic 3D (S3D) video transmission, one or both views can be affected by bit errors and packet losses caused by adverse channel conditions, delay or jitter. Typically, the Human Visual System (HVS) is incapable of aligning and fusing stereoscopic content if one view is affected by artefacts caused by compression, transmission and rendering with distorted patterns being perceived as alterations of the original which presents a shimmering effect known as binocular rivalry and is detrimental to a user's Quality of Experience (QoE). This study attempts to quantify the effects of binocular rivalry for stereoscopic videos. Existing approaches, in which one or more frames are lost in one or both views undergo error concealment, are implemented. Then, subjective testing is carried out on the error concealed 3D video sequences. The evaluations provided by these subjects were then combined and analysed using a standard Student t-test thus quantifying the impact of binocular rivalry and allowing the impact to be compared with that of monocular viewing. The main focus is implementing error-resilient video communication, avoiding the detrimental effects of binocular rivalry and improving the overall QoE of viewers., Comment: 11 pages, 9 Figures

Published
2018

28. Recommendations for analytical antiretroviral treatment interruptions in HIV research trials—report of a consensus meeting

Author

Julg, Boris, Dee, Lynda, Ananworanich, Jintanat, Barouch, Dan H, Bar, Katharine, Caskey, Marina, Colby, Donn J, Dawson, Liza, Dong, Krista L, Dubé, Karine, Eron, Joseph, Frater, John, Gandhi, Rajesh T, Geleziunas, Romas, Goulder, Philip, Hanna, George J, Jefferys, Richard, Johnston, Rowena, Kuritzkes, Daniel, Li, Jonathan Z, Likhitwonnawut, Udom, van Lunzen, Jan, Martinez-Picado, Javier, Miller, Veronica, Montaner, Luis J, Nixon, Douglas F, Palm, David, Pantaleo, Giuseppe, Peay, Holly, Persaud, Deborah, Salzwedel, Jessica, Salzwedel, Karl, Schacker, Timothy, Sheikh, Virginia, Søgaard, Ole S, Spudich, Serena, Stephenson, Kathryn, Sugarman, Jeremy, Taylor, Jeff, Tebas, Pablo, Tiemessen, Caroline T, Tressler, Randall, Weiss, Carol D, Zheng, Lu, Robb, Merlin L, Michael, Nelson L, Mellors, John W, Deeks, Steven G, and Walker, Bruce D

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, HIV/AIDS, Sexually Transmitted Infections, Infectious Diseases, Clinical Research, Clinical Trials and Supportive Activities, Infection, Anti-Retroviral Agents, HIV Infections, Humans, Sustained Virologic Response, Viral Load, Withholding Treatment, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

Analytical antiretroviral treatment interruption (ATI) is an important feature of HIV research, seeking to achieve sustained viral suppression in the absence of antiretroviral therapy (ART) when the goal is to measure effects of novel therapeutic interventions on time to viral load rebound or altered viral setpoint. Trials with ATIs also intend to determine host, virological, and immunological markers that are predictive of sustained viral control off ART. Although ATI is increasingly incorporated into proof-of-concept trials, no consensus has been reached on strategies to maximise its utility and minimise its risks. In addition, differences in ATI trial designs hinder the ability to compare efficacy and safety of interventions across trials. Therefore, we held a meeting of stakeholders from many interest groups, including scientists, clinicians, ethicists, social scientists, regulators, people living with HIV, and advocacy groups, to discuss the main challenges concerning ATI studies and to formulate recommendations with an emphasis on strategies for risk mitigation and monitoring, ART resumption criteria, and ethical considerations. In this Review, we present the major points of discussion and consensus views achieved with the goal of informing the conduct of ATIs to maximise the knowledge gained and minimise the risk to participants in clinical HIV research.

Published
2019

29. Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses

Author

Aiste Dijokaite-Guraliuc, Raksha Das, Daming Zhou, Helen M. Ginn, Chang Liu, Helen M.E. Duyvesteyn, Jiandong Huo, Rungtiwa Nutalai, Piyada Supasa, Muneeswaran Selvaraj, Thushan I. de Silva, Megan Plowright, Thomas A.H. Newman, Hailey Hornsby, Alexander J. Mentzer, Donal Skelly, Thomas G. Ritter, Nigel Temperton, Paul Klenerman, Eleanor Barnes, Susanna J. Dunachie, Cornelius Roemer, Thomas P. Peacock, Neil G. Paterson, Mark A. Williams, David R. Hall, Elizabeth E. Fry, Juthathip Mongkolsapaya, Jingshan Ren, David I. Stuart, Gavin R. Screaton, Christopher Conlon, Alexandra Deeks, John Frater, Siobhan Gardiner, Anni Jämsén, Katie Jeffery, Tom Malone, Eloise Phillips, Barbara Kronsteiner-Dobramysl, Priyanka Abraham, Sagida Bibi, Teresa Lambe, Stephanie Longet, Tom Tipton, Miles Carrol, and Lizzie Stafford

Subjects
CP: Immunology, CP: Microbiology, Biology (General), QH301-705.5
Abstract

Summary: In November 2021, Omicron BA.1, containing a raft of new spike mutations, emerged and quickly spread globally. Intense selection pressure to escape the antibody response produced by vaccines or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection then led to a rapid succession of Omicron sub-lineages with waves of BA.2 and then BA.4/5 infection. Recently, many variants have emerged such as BQ.1 and XBB, which carry up to 8 additional receptor-binding domain (RBD) amino acid substitutions compared with BA.2. We describe a panel of 25 potent monoclonal antibodies (mAbs) generated from vaccinees suffering BA.2 breakthrough infections. Epitope mapping shows potent mAb binding shifting to 3 clusters, 2 corresponding to early-pandemic binding hotspots. The RBD mutations in recent variants map close to these binding sites and knock out or severely knock down neutralization activity of all but 1 potent mAb. This recent mAb escape corresponds with large falls in neutralization titer of vaccine or BA.1, BA.2, or BA.4/5 immune serum.

Published
2023
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30. Slow progression of pediatric HIV associates with early CD8+ T cell PD-1 expression and a stem-like phenotype

Author

Vinicius Vieira, Nicholas Lim, Alveera Singh, Ellen Leitman, Reena Dsouza, Emily Adland, Maximilian Muenchhoff, Julia Roider, Miguel Marin Lopez, Julieta Carabelli, Jennifer Giandhari, Andreas Groll, Pieter Jooste, Julia G. Prado, Christina Thobakgale, Krista Dong, Photini Kiepiela, Andrew J. Prendergast, Gareth Tudor-Williams, John Frater, Bruce D. Walker, Thumbi Ndung’u, Veron Ramsuran, Alasdair Leslie, Henrik N. Kløverpris, and Philip Goulder

Subjects
AIDS/HIV, Immunology, Medicine
Abstract

HIV nonprogression despite persistent viremia is rare among adults who are naive to antiretroviral therapy (ART) but relatively common among ART-naive children. Previous studies indicate that ART-naive pediatric slow progressors (PSPs) adopt immune evasion strategies similar to those described in natural hosts of SIV. However, the mechanisms underlying this immunophenotype are not well understood. In a cohort of early-treated infants who underwent analytical treatment interruption (ATI) after 12 months of ART, expression of PD-1 on CD8+ T cells immediately before ATI was the main predictor of slow progression during ATI. PD-1+CD8+ T cell frequency was also negatively correlated with CCR5 and HLA-DR expression on CD4+ T cells and predicted stronger HIV-specific T lymphocyte responses. In the CD8+ T cell compartment of PSPs, we identified an enrichment of stem-like TCF-1+PD-1+ memory cells, whereas pediatric progressors and viremic adults had a terminally exhausted PD-1+CD39+ population. TCF-1+PD-1+ expression on CD8+ T cells was associated with higher proliferative activity and stronger Gag-specific effector functionality. These data prompted the hypothesis that the proliferative burst potential of stem-like HIV-specific cytotoxic cells could be exploited in therapeutic strategies to boost the antiviral response and facilitate remission in infants who received early ART with a preserved and nonexhausted T cell compartment.

Published
2023
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31. The RIO trial: rationale, design, and the role of community involvement in a randomised placebo-controlled trial of antiretroviral therapy plus dual long-acting HIV-specific broadly neutralising antibodies (bNAbs) in participants diagnosed with recent HIV infection—study protocol for a two-stage randomised phase II trial

Author

Lee, Ming Jie, Collins, Simon, Babalis, Daphne, Johnson, Nicholas, Falaschetti, Emanuela, Prevost, A. Toby, Ashraf, Ambreen, Jacob, Milaana, Cole, Tom, Hurley, Lisa, Pace, Matthew, Ogbe, Ane, Khan, Maryam, Zacharopoulou, Panagiota, Brown, Helen, Sutherland, Euan, Box, Hanna, Fox, Julie, Deeks, Steven, Horowitz, Jill, Nussenzweig, Michel C., Caskey, Marina, Frater, John, and Fidler, Sarah

Published
2022
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32. Divergent trajectories of antiviral memory after SARS-CoV-2 infection

Author

Tomic, Adriana, Skelly, Donal T., Ogbe, Ane, O’Connor, Daniel, Pace, Matthew, Adland, Emily, Alexander, Frances, Ali, Mohammad, Allott, Kirk, Azim Ansari, M., Belij-Rammerstorfer, Sandra, Bibi, Sagida, Blackwell, Luke, Brown, Anthony, Brown, Helen, Cavell, Breeze, Clutterbuck, Elizabeth A., de Silva, Thushan, Eyre, David, Lumley, Sheila, Flaxman, Amy, Grist, James, Hackstein, Carl-Philipp, Halkerston, Rachel, Harding, Adam C., Hill, Jennifer, James, Tim, Jay, Cecilia, Johnson, Síle A., Kronsteiner, Barbara, Lie, Yolanda, Linder, Aline, Longet, Stephanie, Marinou, Spyridoula, Matthews, Philippa C., Mellors, Jack, Petropoulos, Christos, Rongkard, Patpong, Sedik, Cynthia, Silva-Reyes, Laura, Smith, Holly, Stockdale, Lisa, Taylor, Stephen, Thomas, Stephen, Tipoe, Timothy, Turtle, Lance, Vieira, Vinicius Adriano, Wrin, Terri, Pollard, Andrew J., Lambe, Teresa, Conlon, Chris P., Jeffery, Katie, Travis, Simon, Goulder, Philip, Frater, John, Mentzer, Alex J., Stafford, Lizzie, Carroll, Miles W., James, William S., Klenerman, Paul, Barnes, Eleanor, Dold, Christina, and Dunachie, Susanna J.

Published
2022
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35. BreakAlign: a Perl program to align chimaeric (split) genomic NGS reads and allow visual confirmation of novel retroviral integrations

Author

Emanuele Marchi, Mathew Jones, Paul Klenerman, John Frater, Gkikas Magiorkinis, and Robert Belshaw

Subjects
NGS, Retrovirus, Provirus, Integration, Insertion, Detection, Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background Retroviruses replicate by integrating a DNA copy into a host chromosome. Detecting novel retroviral integrations (ones not in the reference genome sequence of the host) from genomic NGS data is bioinformatically challenging and frequently produces many false positives. One common method of confirmation is visual inspection of an alignment of the chimaeric (split) reads that span a putative novel retroviral integration site. We perceived the need for a program that would facilitate this by producing a multiple alignment containing both the viral and host regions that flank an integration. Results BreakAlign is a Perl program that uses blastn to produce such a multiple alignment. In addition to the NGS dataset and a reference viral sequence, the program requires either (a) the ~ 500nt host genome sequence that spans the putative integration or (b) coordinates of this putative integration in an installed copy of the reference human genome (multiple integrations can be processed automatically). BreakAlign is freely available from https://github.com/marchiem/breakalign and is accompanied by example files allowing a test run. Conclusion BreakAlign will confirm and facilitate characterisation of both (a) germline integrations of endogenous retroviruses and (b) somatic integrations of exogenous retroviruses such as HIV and HTLV. Although developed for use with genomic short-read NGS (second generation) data and retroviruses, it should also be useful for long-read (third generation) data and any mobile element with at least one conserved flanking region.

Published
2022
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36. The RIO trial: rationale, design, and the role of community involvement in a randomised placebo-controlled trial of antiretroviral therapy plus dual long-acting HIV-specific broadly neutralising antibodies (bNAbs) in participants diagnosed with recent HIV infection—study protocol for a two-stage randomised phase II trial

Author

Ming Jie Lee, Simon Collins, Daphne Babalis, Nicholas Johnson, Emanuela Falaschetti, A. Toby Prevost, Ambreen Ashraf, Milaana Jacob, Tom Cole, Lisa Hurley, Matthew Pace, Ane Ogbe, Maryam Khan, Panagiota Zacharopoulou, Helen Brown, Euan Sutherland, Hanna Box, Julie Fox, Steven Deeks, Jill Horowitz, Michel C. Nussenzweig, Marina Caskey, John Frater, and Sarah Fidler

Subjects
HIV, Primary infection, Broadly neutralising antibodies, Antiretroviral therapy, Virological remission, T cell Immunity, Medicine (General), R5-920
Abstract

Abstract Background Antiretroviral therapy (ART) has led to dramatic improvements in survival for people living with HIV, but is unable to cure infection, or induce viral control off therapy. Designing intervention trials with novel agents with the potential to confer a period of HIV remission without ART remains a key scientific and community goal. We detail the rationale, design, and outcomes of a randomised, placebo-controlled trial of two HIV-specific long-acting broadly neutralising antibodies (bNAbs): 3BNC117-LS and 10-1074-LS, which target CD4 binding site and V3 loop respectively, on post-treatment viral control. Methods RIO is a randomised, placebo-controlled, double-blinded prospective phase II study. Eligible individuals will have started ART within 3 months of primary HIV infection and have viral sequences that appear to be sensitive to both bNAbs. It will randomise 72 eligible participants 1:1 to the following arms via a two-stage design. In Stage 1, arm A participants are given dual long-acting (LS-variants) bNAbs infusions, followed by intensively monitored Analytical Treatment Interruption (ATI) (n = 36); in arm B, participants receive placebo infusions followed by ATI. The primary endpoint will be time to viral rebound within 36 weeks after ATI. Upon viral rebound, the participant and researcher are unblinded. Participants in arm A recommence ART and complete the study. Participants in arm B are invited to restart ART and enroll into Stage 2 where they will receive open-label LS bNAbs, followed by a second ATI 24 weeks after. Secondary and exploratory endpoints include adverse events, time to undetectable viraemia after restarting ART, immunological markers, HIV proviral DNA, serum bNAb concentrations in blood, bNAb resistance at viral rebound, and quality of life measures. Discussion The two-stage design was determined in collaboration with community involvement. This design allows all participants the option to receive bNAbs. It also tests the hypothesis that bNAbs may drive sustained HIV control beyond the duration of detectable bNAb concentrations. Community representatives were involved at all stages. This included the two-stage design, discussion on the criteria to restart ART, frequency of monitoring visits off ART, and reducing the risk of onward transmission to HIV-negative partners. It also included responding to the challenges of COVID-19. Trial registration The protocol is registered on Clinical.trials.gov and EudraCT and has approval from UK Ethics and MHRA.

Published
2022
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37. Divergent trajectories of antiviral memory after SARS-CoV-2 infection

Author

Adriana Tomic, Donal T. Skelly, Ane Ogbe, Daniel O’Connor, Matthew Pace, Emily Adland, Frances Alexander, Mohammad Ali, Kirk Allott, M. Azim Ansari, Sandra Belij-Rammerstorfer, Sagida Bibi, Luke Blackwell, Anthony Brown, Helen Brown, Breeze Cavell, Elizabeth A. Clutterbuck, Thushan de Silva, David Eyre, Sheila Lumley, Amy Flaxman, James Grist, Carl-Philipp Hackstein, Rachel Halkerston, Adam C. Harding, Jennifer Hill, Tim James, Cecilia Jay, Síle A. Johnson, Barbara Kronsteiner, Yolanda Lie, Aline Linder, Stephanie Longet, Spyridoula Marinou, Philippa C. Matthews, Jack Mellors, Christos Petropoulos, Patpong Rongkard, Cynthia Sedik, Laura Silva-Reyes, Holly Smith, Lisa Stockdale, Stephen Taylor, Stephen Thomas, Timothy Tipoe, Lance Turtle, Vinicius Adriano Vieira, Terri Wrin, OPTIC Clinical Group, PITCH Study Group, C-MORE Group, Andrew J. Pollard, Teresa Lambe, Chris P. Conlon, Katie Jeffery, Simon Travis, Philip Goulder, John Frater, Alex J. Mentzer, Lizzie Stafford, Miles W. Carroll, William S. James, Paul Klenerman, Eleanor Barnes, Christina Dold, and Susanna J. Dunachie

Subjects
Science
Abstract

The engagement of immunological memory is a key component to the protective anti-SARS-CoV-2 B and T cell responses. Here the authors assess the B and T cells of a cohort of UK healthcare workers in response to infection and longitudinally track the compartment showing distinct trajectories following early priming.

Published
2022
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38. Expression of type I interferon-associated genes at antiretroviral therapy interruption predicts HIV virological rebound

Author

P. Zacharopoulou, E. Marchi, A. Ogbe, N. Robinson, H. Brown, M. Jones, L. Parolini, M. Pace, N. Grayson, P. Kaleebu, H. Rees, S. Fidler, P. Goulder, P. Klenerman, and J. Frater

Subjects
Medicine, Science
Abstract

Abstract Although certain individuals with HIV infection can stop antiretroviral therapy (ART) without viral load rebound, the mechanisms under-pinning ‘post-treatment control’ remain unclear. Using RNA-Seq we explored CD4 T cell gene expression to identify evidence of a mechanism that might underpin virological rebound and lead to discovery of associated biomarkers. Fourteen female participants who received 12 months of ART starting from primary HIV infection were sampled at the time of stopping therapy. Two analysis methods (Differential Gene Expression with Gene Set Enrichment Analysis, and Weighted Gene Co-expression Network Analysis) were employed to interrogate CD4+ T cell gene expression data and study pathways enriched in post-treatment controllers versus early rebounders. Using independent analysis tools, expression of genes associated with type I interferon responses were associated with a delayed time to viral rebound following treatment interruption (TI). Expression of four genes identified by Cox-Lasso (ISG15, XAF1, TRIM25 and USP18) was converted to a Risk Score, which associated with rebound (p

Published
2022
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40. Differential Immunodominance Hierarchy of CD8+ T-Cell Responses in HLA-B*27:05- and -B*27:02-Mediated Control of HIV-1 Infection

Author

Adland, Emily, Hill, Matilda, Lavandier, Nora, Csala, Anna, Edwards, Anne, Chen, Fabian, Radkowski, Marek, Kowalska, Justyna D, Paraskevis, Dimitrios, Hatzakis, Angelos, Valenzuela-Ponce, Humberto, Pfafferott, Katja, Williams, Ian, Pellegrino, Pierre, Borrow, Persephone, Mori, Masahiko, Rockstroh, Jürgen, Prado, Julia G, Mothe, Beatriz, Dalmau, Judith, Martinez-Picado, Javier, Tudor-Williams, Gareth, Frater, John, Stryhn, Anette, Buus, Soren, Teran, Gustavo Reyes, Mallal, Simon, John, Mina, Buchbinder, Susan, Kirk, Gregory, Martin, Jeffrey, Michael, Nelson, Fellay, Jacques, Deeks, Steve, Walker, Bruce, Avila-Rios, Santiago, Cole, David, Brander, Christian, Carrington, Mary, and Goulder, Philip

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Sexually Transmitted Infections, Infectious Diseases, HIV/AIDS, Clinical Research, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, CD8-Positive T-Lymphocytes, Genes, MHC Class I, HIV Infections, HIV-1, HLA-B27 Antigen, Humans, Immunodominant Epitopes, Viral Load, gag Gene Products, Human Immunodeficiency Virus, nef Gene Products, Human Immunodeficiency Virus, CD8(+) T cell, HIV Gag, HIV Nef, HLA, HLA-B*27, human immunodeficiency virus, CD8+ T cell, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05-restricted CD8+ T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8+ T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLA-B*27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02-restricted CD8+ T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8+ T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLA-B*27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8+ T-cell responses that dominate HIV-specific CD8+ T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV.IMPORTANCE CD8+ T cells play a central role in successful control of HIV infection and have the potential also to mediate the eradication of viral reservoirs of infection. The principal means by which protective HLA class I molecules, such as HLA-B*27:05 and HLA-B*57:01, slow HIV disease progression is believed to be via the particular HIV-specific CD8+ T cell responses restricted by those alleles. We focus here on HLA-B*27:05, one of the best-characterized protective HLA molecules, and the closely related HLA-B*27:02, which differs by only 3 amino acids and which has not been well studied in relation to control of HIV infection. We show that HLA-B*27:02 is also protective against HIV disease progression, but the CD8+ T-cell immunodominance hierarchy of HLA-B*27:02 differs strikingly from that of HLA-B*27:05. These findings indicate that the immunodominant HLA-B*27:02-restricted Nef response adds to protection mediated by the Gag and Pol specificities that dominate anti-HIV CD8+ T-cell activity in HLA-B*27:05-positive subjects.

Published
2018

41. Transcriptional Modulation of Human Endogenous Retroviruses in Primary CD4+ T Cells Following Vorinostat Treatment

Author

White, Cory H, Beliakova-Bethell, Nadejda, Lada, Steven M, Breen, Michael S, Hurst, Tara P, Spina, Celsa A, Richman, Douglas D, Frater, John, Magiorkinis, Gkikas, and Woelk, Christopher H

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Human Genome, Genetics, Infectious Diseases, Sexually Transmitted Infections, Clinical Research, HIV/AIDS, 5.1 Pharmaceuticals, Infection, Good Health and Well Being, Antirheumatic Agents, CD4-Positive T-Lymphocytes, Cells, Cultured, Endogenous Retroviruses, Gene Expression Regulation, HIV Infections, HIV-1, Histone Deacetylase Inhibitors, Humans, Immunity, Proviruses, Terminal Repeat Sequences, Virus Activation, Virus Latency, Vorinostat, human endogenous retroviruses, histone deacetylase inhibitor, primary CD4(+) T cells, total RNA-Seq, long terminal repeat, primary CD4+ T cells, Biochemistry and cell biology
Abstract

The greatest obstacle to a cure for HIV is the provirus that integrates into the genome of the infected cell and persists despite antiretroviral therapy. A "shock and kill" approach has been proposed as a strategy for an HIV cure whereby drugs and compounds referred to as latency-reversing agents (LRAs) are used to "shock" the silent provirus into active replication to permit "killing" by virus-induced pathology or immune recognition. The LRA most utilized to date in clinical trials has been the histone deacetylase (HDAC) inhibitor-vorinostat. Potentially, pathological off-target effects of vorinostat may result from the activation of human endogenous retroviruses (HERVs), which share common ancestry with exogenous retroviruses including HIV. To explore the effects of HDAC inhibition on HERV transcription, an unbiased pharmacogenomics approach (total RNA-Seq) was used to evaluate HERV expression following the exposure of primary CD4+ T cells to a high dose of vorinostat. Over 2,000 individual HERV elements were found to be significantly modulated by vorinostat, whereby elements belonging to the ERVL family (e.g., LTR16C and LTR33) were predominantly downregulated, in contrast to LTR12 elements of the HERV-9 family, which exhibited the greatest signal, with the upregulation of 140 distinct elements. The modulation of three different LTR12 elements by vorinostat was confirmed by droplet digital PCR along a dose-response curve. The monitoring of LTR12 expression during clinical trials with vorinostat may be indicated to assess the impact of this HERV on the human genome and host immunity.

Published
2018

45. Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern

Author

Donal T. Skelly, Adam C. Harding, Javier Gilbert-Jaramillo, Michael L. Knight, Stephanie Longet, Anthony Brown, Sandra Adele, Emily Adland, Helen Brown, Medawar Laboratory Team, Tom Tipton, Lizzie Stafford, Alexander J. Mentzer, Síle A. Johnson, Ali Amini, OPTIC (Oxford Protective T cell Immunology for COVID-19) Clinical Group, Tiong Kit Tan, Lisa Schimanski, Kuan-Ying A. Huang, Pramila Rijal, PITCH (Protective Immunity T cells in Health Care Worker) Study Group, C-MORE/PHOSP-C Group, John Frater, Philip Goulder, Christopher P. Conlon, Katie Jeffery, Christina Dold, Andrew J. Pollard, Alex Sigal, Tulio de Oliveira, Alain R. Townsend, Paul Klenerman, Susanna J. Dunachie, Eleanor Barnes, Miles W. Carroll, and William S. James

Subjects
Science
Abstract

Understanding the effect of vaccination on emerging SARS-CoV-2 variants of concern is of increasing importance. Here, James et al. report that two doses of vaccination with the Pfizer-BioNTech vaccine induce more robust immune responses to the B.1.1.7 and B.1.351 SARS-CoV-2 lineages than does natural infection.

Published
2021
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47. Re: Hazem Orabi, Lauren Howard, Christopher L. Amling, et al. Red Blood Cell Distribution Width Is Associated with All-cause Mortality but Not Adverse Cancer-specific Outcomes in Men with Clinically Localized Prostate Cancer Treated with Radical Prostatectomy: Findings Based on a Multicenter Shared Equal Access Regional Cancer Hospital Registry. Eur Urol Open Sci 2022;37:106–12

Author

John L. Frater

Subjects
Diseases of the genitourinary system. Urology, RC870-923, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2022
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48. Impact of antiretroviral therapy in primary HIV infection on natural killer cell function and the association with viral rebound and HIV DNA following treatment interruption

Author

Matthew Pace, Ane Ogbe, Jacob Hurst, Nicola Robinson, Jodi Meyerowitz, Natalia Olejniczak, John P. Thornhill, Mathew Jones, Anele Waters, Julianne Lwanga, Kristen Kuldanek, Rebecca Hall, Panagiota Zacharopoulou, Genevieve E. Martin, Helen Brown, Nneka Nwokolo, Dimitra Peppa, Julie Fox, Sarah Fidler, and John Frater

Subjects
HIV-human immunodeficiency virus, NK cell, viral rebound, antiretroviral (ARV), treatment interruption (TI), Immunologic diseases. Allergy, RC581-607
Abstract

Natural Killer (NK) cells play a key role in controlling HIV replication, with potential downstream impact on the size of the HIV reservoir and likelihood of viral rebound after antiretroviral therapy (ART) cessation. It is therefore important to understand how primary HIV infection (PHI) disrupts NK cell function, and how these functions are restored by early ART. We examined the impact of commencing ART during PHI on phenotypic and functional NK cell markers at treatment initiation (baseline), 3 months, 1 year, and 2 years in seven well-characterised participants in comparison to HIV seronegative volunteers. We then examined how those NK cell properties differentially impacted by ART related to time to viral rebound and HIV DNA levels in 44 individuals from the SPARTAC trial who stopped ART after 48 weeks treatment, started during PHI. NK cell markers that were significantly different between the seven people with HIV (PWH) treated for 2 years and HIV uninfected individuals included NKG2C levels in CD56dim NK cells, Tim-3 expression in CD56bright NK cells, IFN-γ expressed by CD56dim NK cells after IL-12/IL-18 stimulation and the fraction of Eomes-/T-bet+ in CD56dim and CD56bright NK cells. When exploring time to viral rebound after stopping ART among the 44 SPARTAC participants, no single NK phenotypic marker correlated with control. Higher levels of IL-12/IL-18 mediated NK cell degranulation at baseline were associated with longer times to viral rebound after treatment interruption (P=0.028). Additionally, we found higher fractions of CD56dim NK cells in individuals with lower levels of HIV DNA (P=0.048). NKG2A and NKp30 levels in CD56neg NK cells were higher in patients with lower HIV DNA levels (p=0.00174, r=-0.49 and p=0.03, r= -0.327, respectively) while CD27 levels were higher in those with higher levels of HIV DNA (p=0.026). These data show NK cell functions are heterogeneously impacted by HIV infection with a mixed picture of resolution on ART, and that while NK cells may affect HIV DNA levels and time to viral rebound, no single NK cell marker defined delayed viral rebound.

Published
2022
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50. T-cell and antibody responses to first BNT162b2 vaccine dose in previously infected and SARS-CoV-2-naive UK health-care workers: a multicentre prospective cohort study

Author

Adrienn Angyal, PhD, Stephanie Longet, PhD, Shona C Moore, PhD, Rebecca P Payne, DPhil, Adam Harding, MSc, Tom Tipton, PhD, Patpong Rongkard, MSc, Mohammad Ali, MD, Luisa M Hering, MSc, Naomi Meardon, MBChB, James Austin, PhD, Rebecca Brown, PhD, Donal Skelly, PhD, Natalie Gillson, BSc, Sue L Dobson, MSc, Andrew Cross, PhD, Gurjinder Sandhar, MSc, Jonathan A Kilby, MSc, Jessica K Tyerman, BSc, Alexander R Nicols, MSc, Jarmila S Spegarova, PhD, Hema Mehta, DPhil, Hailey Hornsby, MSc, Rachel Whitham, MSc, Christopher P Conlon, ProfPhD, Katie Jeffery, PhD, Philip Goulder, ProfDPhil, John Frater, ProfPhD, Christina Dold, PhD, Matthew Pace, PhD, Ane Ogbe, PhD, Helen Brown, BSc, M Azim Ansari, DPhil, Emily Adland, PhD, Anthony Brown, BSc, Meera Chand, FRCPath, Adrian Shields, PhD, Philippa C Matthews, PhD, Susan Hopkins, PhD, Victoria Hall, PhD, William James, ProfDPhil, Sarah L Rowland-Jones, ProfDM, Paul Klenerman, ProfPhD, Susanna Dunachie, ProfPhD, Alex Richter, ProfPhD, Christopher J A Duncan, DPhil, Eleanor Barnes, ProfPhD, Miles Carroll, ProfPhD, Lance Turtle, PhD, Thushan I de Silva, PhD, Adam Harding, Adam Watson, Adrian Shields, Adrienn Angyal, Ahmed Alhussni, Alex Richter, Alexander Nicols, Alexandra Deeks, Alice Webb-Bridges, Andrew Cross, Ane Ogbe, Anni Jämsén, Anthony Brown, Anu Chawla, Christina Dold, Christopher Duncan, Christopher Conlon, Donal Skelly, Denise O'Donnell, Eleanor Barnes, Emily Adland, Esme Weeks, Gurjinder Sandhar, Hailey Hornsby, Helen Brown, Hema Mehta, Hibatullah Abuelgasim, Huiyuan Xiao, James Austin, Jarmila Spegarova, Jennifer Holmes, Jenny Haworth, Jessica Tyerman, John Frater, Jonathan Kilby, Joseph Cutteridge, Katie Jeffery, Katy Lillie, Lance Turtle, Leigh Romaniuk, Lucy Denly, Luisa Hering, M. Azim Ansari, Matthew Pace, Meera Chand, Miles Carroll, Mohammad Ali, Mwila Kasanyinga, Naomi Meardon, Natalie Gillson, Patpong Rongkard, Paul Klenerman, Philip Goulder, Philippa Matthews, Rachel Whitham, Rebecca Brown, Rebecca Payne, Robert Wilson, Sarah Rowland-Jones, Sarah Thomas, Shona Moore, Siobhan Gardiner, Stephanie Longet, Stephanie Tucker, Sue Dobson, Susan Hopkins, Susanna Dunachie, Syed Adlou, Thushan de Silva, Tom Tipton, Victoria Hall, William James, Allan Lawrie, Nikki Smith, Helena Turton, Amira Zawia, Martin Bayley, Alex Fairman, Kate Harrington, Rosemary Kirk, Louise Marsh, Lisa Watson, Steven Wood, Benjamin Diffey, Chris Jones, Lauren Lett, Gareth Platt, Krishanthi Subramaniam, Daniel Wootton, Brendan Payne, Sophie Hambleton, Sinead Kelly, Judith Marston, Sonia Poolan, Dianne Turner, Muzlifah Haniffa, Emily Stephenson, Sandra Adele, Hossain Delowar Akhter, Senthil Chinnakannan, Catherine de Lara, Timothy Donnison, Carl-Philipp Hackstein, Lian Lee, Nicholas Lim, Tom Malone, Eloise Phillips, Narayan Ramamurthy, Nichola Robinson, Oliver Sampson, David Eyre, Beatrice Simmons, Lizzie Stafford, Alexander Mentzer, Ali Amini, Carolina Arancibia-Cárcamo, Nicholas Provine, Simon Travis, Stavros Dimitriadis, Sile Johnson, Sarah Foulkes, Jameel Khawam, Edgar Wellington, Javier Gilbert-Jaramillo, Michael Knight, Maeva Dupont, Emily Horner, James Thaventhiran, and Jeremy Chalk

Subjects
Medicine (General), R5-920, Microbiology, QR1-502
Abstract

Summary: Background: Previous infection with SARS-CoV-2 affects the immune response to the first dose of the SARS-CoV-2 vaccine. We aimed to compare SARS-CoV-2-specific T-cell and antibody responses in health-care workers with and without previous SARS-CoV-2 infection following a single dose of the BNT162b2 (tozinameran; Pfizer–BioNTech) mRNA vaccine. Methods: We sampled health-care workers enrolled in the PITCH study across four hospital sites in the UK (Oxford, Liverpool, Newcastle, and Sheffield). All health-care workers aged 18 years or older consenting to participate in this prospective cohort study were included, with no exclusion criteria applied. Blood samples were collected where possible before vaccination and 28 (±7) days following one or two doses (given 3–4 weeks apart) of the BNT162b2 vaccine. Previous infection was determined by a documented SARS-CoV-2-positive RT-PCR result or the presence of positive anti-SARS-CoV-2 nucleocapsid antibodies. We measured spike-specific IgG antibodies and quantified T-cell responses by interferon-γ enzyme-linked immunospot assay in all participants where samples were available at the time of analysis, comparing SARS-CoV-2-naive individuals to those with previous infection. Findings: Between Dec 9, 2020, and Feb 9, 2021, 119 SARS-CoV-2-naive and 145 previously infected health-care workers received one dose, and 25 SARS-CoV-2-naive health-care workers received two doses, of the BNT162b2 vaccine. In previously infected health-care workers, the median time from previous infection to vaccination was 268 days (IQR 232–285). At 28 days (IQR 27–33) after a single dose, the spike-specific T-cell response measured in fresh peripheral blood mononuclear cells (PBMCs) was higher in previously infected (n=76) than in infection-naive (n=45) health-care workers (median 284 [IQR 150–461] vs 55 [IQR 24–132] spot-forming units [SFUs] per 106 PBMCs; p

Published
2022
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