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1. Revisiting the origins of the Sobemovirus genus: A case for ancient origins of plant viruses.

Author: Mahan Ghafari, Merike Sõmera, Cecilia Sarmiento, Annette Niehl, Eugénie Hébrard, Theocharis Tsoleridis, Jonathan Ball, Benoît Moury, Philippe Lemey, Aris Katzourakis, and Denis Fargette
Subjects: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract: The discrepancy between short- and long-term rate estimates, known as the time-dependent rate phenomenon (TDRP), poses a challenge to extrapolating evolutionary rates over time and reconstructing evolutionary history of viruses. The TDRP reveals a decline in evolutionary rate estimates with the measurement timescale, explained empirically by a power-law rate decay, notably observed in animal and human viruses. A mechanistic evolutionary model, the Prisoner of War (PoW) model, has been proposed to address TDRP in viruses. Although TDRP has been studied in animal viruses, its impact on plant virus evolutionary history remains largely unexplored. Here, we investigated the consequences of TDRP in plant viruses by applying the PoW model to reconstruct the evolutionary history of sobemoviruses, plant pathogens with significant importance due to their impact on agriculture and plant health. Our analysis showed that the Sobemovirus genus dates back over four million years, indicating an ancient origin. We found evidence that supports deep host jumps to Poaceae, Fabaceae, and Solanaceae occurring between tens to hundreds of thousand years ago, followed by specialization. Remarkably, the TDRP-corrected evolutionary history of sobemoviruses was extended far beyond previous estimates that had suggested their emergence nearly 9,000 years ago, a time coinciding with the Neolithic period in the Near East. By incorporating sequences collected through metagenomic analyses, the resulting phylogenetic tree showcases increased genetic diversity, reflecting a deep history of sobemovirus species. We identified major radiation events beginning between 4,600 to 2,000 years ago, which aligns with the Neolithic period in various regions, suggesting a period of rapid diversification from then to the present. Our findings make a case for the possibility of deep evolutionary origins of plant viruses.
Published: 2024
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2. Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

Author: Anna L. McNaughton, Robert S. Paton, Matthew Edmans, Jonathan Youngs, Judith Wellens, Prabhjeet Phalora, Alex Fyfe, Sandra Belij-Rammerstorfer, Jai S. Bolton, Jonathan Ball, George W. Carnell, Wanwisa Dejnirattisai, Christina Dold, David W. Eyre, Philip Hopkins, Alison Howarth, Kreepa Kooblall, Hannah Klim, Susannah Leaver, Lian Ni Lee, César López-Camacho, Sheila F. Lumley, Derek C. Macallan, Alexander J. Mentzer, Nicholas M. Provine, Jeremy Ratcliff, Jose Slon-Compos, Donal Skelly, Lucas Stolle, Piyada Supasa, Nigel Temperton, Chris Walker, Beibei Wang, Duncan Wyncoll, Oxford Protective T Cell Immunology for COVID-19 (OPTIC) consortium, Scottish National Blood Transfusion Service (SNBTS) consortium, Peter Simmonds, Teresa Lambe, John Kenneth Baillie, Malcolm G. Semple, Peter J.M. Openshaw, International Severe Acute Respiratory and emerging Infection Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) investigators, Uri Obolski, Marc Turner, Miles Carroll, Juthathip Mongkolsapaya, Gavin Screaton, Stephen H. Kennedy, Lisa Jarvis, Eleanor Barnes, Susanna Dunachie, José Lourenço, Philippa C. Matthews, Tihana Bicanic, Paul Klenerman, Sunetra Gupta, and Craig P. Thompson
Subjects: Immunology, Infectious disease, Medicine
Abstract: The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal outcomes with coronavirus disease 2019 (COVID-19) is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to an intensive care unit (ICU) with fatal COVID-19 outcomes, but not in individuals with nonfatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to an ICU with fatal and nonfatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an “original antigenic sin” type response.
Published: 2022
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3. Saliva for COVID-19 Testing: Simple but Useless or an Undervalued Resource?

Author: Sara Pijuan-Galito, Francesco Saverio Tarantini, Hannah Tomlin, Harry Jenkins, Jamie Louise Thompson, Danielle Scales, Amy Stroud, Ana Tellechea Lopez, James Hassall, Philip G. McTernan, Andy Coultas, Asta Arendt-Tranholm, Caroline Reffin, Ian Hill, I-ning Lee, Siyu Wu, Joanne Porte, Joseph Chappell, Katarzyna Lis-Slimak, Kazuyo Kaneko, Lara Doolan, Mairead Ward, Martin Stonebridge, Mohammad Ilyas, Patrick McClure, Patrick Tighe, Penny Gwynne, Ralph Hyde, Jonathan Ball, Claire Seedhouse, Andrew V. Benest, Moira Petrie, and Chris Denning
Subjects: SARS-CoV-2, lateral flow, polymerase chain reaction, COVID-19, nasopharyngeal swab, saliva, Microbiology, QR1-502
Abstract: During the COVID-19 pandemic, countries with robust population-based asymptomatic testing were generally successful in controlling virus spread, hence reducing hospitalizations and deaths. This effectiveness inspired widespread asymptomatic surveillance for COVID-19/SARS-CoV-2 globally. Polarized vaccination programs, coupled with the relatively short-lived immunity vaccines provide, mean that reciprocal cross-border exchanges of each new variant are likely, as evidenced by Delta and Gamma, and asymptomatic testing will be required for the foreseeable future. Reliance on nasopharyngeal swabs contributes to “testing fatigue” arising due to difficulties in standardizing administration, unpleasantness, and inappropriateness of use in younger people or individuals with special needs. There has also been erosion in confidence of testing due to variable and/or poor accuracy of lateral flow devices to detect COVID-19. Here, we question why saliva-based PCR assays are not being used more widely, given that standardization is easy and this non-invasive test is suitable for everyone, providing high sensitivity and accuracy. We reflect on our experience with the University of Nottingham COVID-19 Asymptomatic Testing, where (as of October 2021) 96,317 samples have been processed by RT-qPCR from 23,740 repeat saliva donors, yielding 465 positive cases. We challenge myths that saliva is difficult to process, concluding that it is an undervalued resource for both asymptomatic and symptomatic detection of SARS-CoV-2 genomes to an accuracy of >99% and a sensitivity of 1–10 viral copies/μl. In July 2021, our data enabled Nottingham to become the first UK University to gain accreditation and the first UK institute to gain this accolade for saliva.
Published: 2021
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4. The impact of viral mutations on recognition by SARS-CoV-2 specific T cells

Author: Thushan I. de Silva, Guihai Liu, Benjamin B. Lindsey, Danning Dong, Shona C. Moore, Nienyun Sharon Hsu, Dhruv Shah, Dannielle Wellington, Alexander J. Mentzer, Adrienn Angyal, Rebecca Brown, Matthew D. Parker, Zixi Ying, Xuan Yao, Lance Turtle, Susanna Dunachie, Mala K. Maini, Graham Ogg, Julian C. Knight, Yanchun Peng, Sarah L. Rowland-Jones, Tao Dong, David M. Aanensen, Khalil Abudahab, Helen Adams, Alexander Adams, Safiah Afifi, Dinesh Aggarwal, Shazaad S.Y. Ahmad, Louise Aigrain, Adela Alcolea-Medina, Nabil-Fareed Alikhan, Elias Allara, Roberto Amato, Tara Annett, Stephen Aplin, Cristina V. Ariani, Hibo Asad, Amy Ash, Paula Ashfield, Fiona Ashford, Laura Atkinson, Stephen W. Attwood, Cressida Auckland, Alp Aydin, David J. Baker, Paul Baker, Carlos E. Balcazar, Jonathan Ball, Jeffrey C. Barrett, Magdalena Barrow, Edward Barton, Matthew Bashton, Andrew R. Bassett, Rahul Batra, Chris Baxter, Nadua Bayzid, Charlotte Beaver, Angela H. Beckett, Shaun M. Beckwith, Luke Bedford, Robert Beer, Andrew Beggs, Katherine L. Bellis, Louise Berry, Beatrice Bertolusso, Angus Best, Emma Betteridge, David Bibby, Kelly Bicknell, Debbie Binns, Alec Birchley, Paul W. Bird, Chloe Bishop, Rachel Blacow, Victoria Blakey, Beth Blane, Frances Bolt, James Bonfield, Stephen Bonner, David Bonsall, Tim Boswell, Andrew Bosworth, Yann Bourgeois, Olivia Boyd, Declan T. Bradley, Cassie Breen, Catherine Bresner, Judith Breuer, Stephen Bridgett, Iraad F. Bronner, Ellena Brooks, Alice Broos, Julianne R. Brown, Giselda Bucca, Sarah L. Buchan, David Buck, Matthew Bull, Phillipa J. Burns, Shirelle Burton-Fanning, Timothy Byaruhanga, Matthew Byott, Sharon Campbell, Alessandro M. Carabelli, James S. Cargill, Matthew Carlile, Silvia F. Carvalho, Anna Casey, Anibolina Castigador, Jana Catalan, Vicki Chalker, Nicola J. Chaloner, Meera Chand, Joseph G. Chappell, Themoula Charalampous, Wendy Chatterton, Yasmin Chaudhry, Carol M. Churcher, Gemma Clark, Phillip Clarke, Benjamin J. Cogger, Kevin Cole, Jennifer Collins, Rachel Colquhoun, Thomas R. Connor, Kate F. Cook, Jason Coombes, Sally Corden, Claire Cormie, Nicholas Cortes, Marius Cotic, Seb Cotton, Simon Cottrell, Lindsay Coupland, MacGregor Cox, Alison Cox, Noel Craine, Liam Crawford, Aidan Cross, Matthew R. Crown, Dorian Crudgington, Nicola Cumley, Tanya Curran, Martin D. Curran, Ana da Silva Filipe, Gavin Dabrera, Alistair C. Darby, Rose K. Davidson, Alisha Davies, Robert M. Davies, Thomas Davis, Daniela de Angelis, Elen De Lacy, Leonardo de Oliveira Martins, Johnny Debebe, Rebecca Denton-Smith, Samir Dervisevic, Rebecca Dewar, Jayasree Dey, Joana Dias, Donald Dobie, Matthew J. Dorman, Fatima Downing, Megan Driscoll, Louis du Plessis, Nichola Duckworth, Jillian Durham, Kirstine Eastick, Lisa J. Easton, Richard Eccles, Jonathan Edgeworth, Sue Edwards, Kate El Bouzidi, Sahar Eldirdiri, Nicholas Ellaby, Scott Elliott, Gary Eltringham, Leah Ensell, Michelle J. Erkiert, Marina Escalera Zamudio, Sarah Essex, Johnathan M. Evans, Cariad Evans, William Everson, Derek J. Fairley, Karlie Fallon, Arezou Fanaie, Ben W. Farr, Christopher Fearn, Theresa Feltwell, Lynne Ferguson, Laia Fina, Flavia Flaviani, Vicki M. Fleming, Sally Forrest, Ebenezer Foster-Nyarko, Benjamin H. Foulkes, Luke Foulser, Mireille Fragakis, Dan Frampton, Sarah Francois, Christophe Fraser, Timothy M. Freeman, Helen Fryer, Marc Fuchs, William Fuller, Kavitha Gajee, Katerina Galai, Abbie Gallagher, Eileen Gallagher, Michael D. Gallagher, Marta Gallis, Amy Gaskin, Bree Gatica-Wilcox, Lily Geidelberg, Matthew Gemmell, Iliana Georgana, Ryan P. George, Laura Gifford, Lauren Gilbert, Sophia T. Girgis, Sharon Glaysher, Emily J. Goldstein, Tanya Golubchik, Andrea N. Gomes, Sónia Gonçalves, Ian G. Goodfellow, Scott Goodwin, Salman Goudarzi, Marina Gourtovaia, Clive Graham, Lee Graham, Paul R. Grant, Luke R. Green, Angie Green, Jane Greenaway, Richard Gregory, Martyn Guest, Rory N. Gunson, Ravi K. Gupta, Bernardo Gutierrez, Sam T. Haldenby, William L. Hamilton, Samantha E. Hansford, Tanzina Haque, Kathryn A. Harris, Ian Harrison, Ewan M. Harrison, Jennifer Hart, John A. Hartley, William T. Harvey, Matthew Harvey, Mohammed O. Hassan-Ibrahim, Judith Heaney, Thomas Helmer, John H. Henderson, Andrew R. Hesketh, Jessica Hey, David Heyburn, Ellen E. Higginson, Verity Hill, Jack D. Hill, Rachel A. Hilson, Ember Hilvers, Matthew T.G. Holden, Amy Hollis, Christopher W. Holmes, Nadine Holmes, Alison H. Holmes, Richard Hopes, Hailey R. Hornsby, Myra Hosmillo, Catherine Houlihan, Hannah C. Howson-Wells, Jonathan Hubb, Hannah Huckson, Warwick Hughes, Joseph Hughes, Margaret Hughes, Stephanie Hutchings, Giles Idle, Chris J. Illingworth, Robert Impey, Dianne Irish-Tavares, Miren Iturriza-Gomara, Rhys Izuagbe, Chris Jackson, Ben Jackson, Leigh M. Jackson, Kathryn A. Jackson, David K. Jackson, Aminu S. Jahun, Victoria James, Keith James, Christopher Jeanes, Aaron R. Jeffries, Sarah Jeremiah, Andrew Jermy, Michaela John, Rob Johnson, Kate Johnson, Ian Johnston, Owen Jones, Sophie Jones, Hannah Jones, Christopher R. Jones, Neil Jones, Amelia Joseph, Sarah Judges, Gemma L. Kay, Sally Kay, Jon-Paul Keatley, Alexander J. Keeley, Anita Kenyon, Leanne M. Kermack, Manjinder Khakh, Stephen P. Kidd, Maimuna Kimuli, Stuart Kirk, Christine Kitchen, Katie Kitchman, Bridget A. Knight, Cherian Koshy, Moritz U.G. Kraemer, Sara Kumziene-Summerhayes, Dominic Kwiatkowski, Angie Lackenby, Kenneth G. Laing, Temi Lampejo, Cordelia F. Langford, Deborah Lavin, Andrew I. Lawton, Jack Lee, David Lee, Stefanie V. Lensing, Steven Leonard, Lisa J. Levett, Thanh Le-Viet, Jonathan Lewis, Kevin Lewis, Jennifier Liddle, Steven Liggett, Patrick J. Lillie, Michelle M. Lister, Rich Livett, Stephanie Lo, Nicholas J. Loman, Matthew W. Loose, Stavroula F. Louka, Katie F. Loveson, Sarah Lowdon, Hannah Lowe, Helen L. Lowe, Anita O. Lucaci, Catherine Ludden, Jessica Lynch, Ronan A. Lyons, Katrina Lythgoe, Nicholas W. Machin, George MacIntyre-Cockett, Andrew Mack, Ben Macklin, Alasdair Maclean, Emily Macnaughton, Pinglawathee Madona, Mailis Maes, Laurentiu Maftei, Adhyana I.K. Mahanama, Tabitha W. Mahungu, Daniel Mair, Joshua Maksimovic, Cassandra S. Malone, Daniel Maloney, Nikos Manesis, Robin Manley, Anna Mantzouratou, Angela Marchbank, Arun Mariappan, Inigo Martincorena, Rocio T. Martinez Nunez, Alison E. Mather, Patrick Maxwell, Megan Mayhew, Tamyo Mbisa, Clare M. McCann, Shane A. McCarthy, Kathryn McCluggage, Patrick C. McClure, J.T. McCrone, Martin P. McHugh, James P. McKenna, Caoimhe McKerr, Georgina M. McManus, Claire L. McMurray, Claire McMurray, Alan McNally, Lizzie Meadows, Nathan Medd, Oliver Megram, Mirko Menegazzo, Ian Merrick, Stephen L. Michell, Michelle L. Michelsen, Mariyam Mirfenderesky, Jeremy Mirza, Julia Miskelly, Emma Moles-Garcia, Robin J. Moll, Zoltan Molnar, Irene M. Monahan, Matteo Mondani, Siddharth Mookerjee, Christopher Moore, Jonathan Moore, Nathan Moore, Catherine Moore, Helen Morcrette, Sian Morgan, Mari Morgan, Matilde Mori, Arthur Morriss, Samuel Moses, Craig Mower, Peter Muir, Afrida Mukaddas, Florence Munemo, Robert Munn, Abigail Murray, Leanne J. Murray, Darren R. Murray, Manasa Mutingwende, Richard Myers, Eleni Nastouli, Gaia Nebbia, Andrew Nelson, Charlotte Nelson, Sam Nicholls, Jenna Nichols, Roberto Nicodemi, Kyriaki Nomikou, Justin O’Grady, Sarah O'Brien, Mina Odedra, Natasha Ohemeng-Kumi, Karen Oliver, Richard J. Orton, Husam Osman, xeine O'Toole, Nicole Pacchiarini, Debra Padgett, Andrew J. Page, Emily J. Park, Naomi R. Park, Surendra Parmar, David G. Partridge, David Pascall, Amita Patel, Bindi Patel, Steve Paterson, Brendan A.I. Payne, Sharon J. Peacock, Clare Pearson, Emanuela Pelosi, Benita Percival, Jon Perkins, Malorie Perry, Malte L. Pinckert, Steven Platt, Olga Podplomyk, Manoj Pohare, Marcus Pond, Cassie F. Pope, Radoslaw Poplawski, Jessica Powell, Jennifer Poyner, Liam Prestwood, Anna Price, James R. Price, Jacqui A. Prieto, David T. Pritchard, Sophie J. Prosolek, Georgia Pugh, Monika Pusok, Oliver G. Pybus, Hannah M. Pymont, Michael A. Quail, Joshua Quick, Clara Radulescu, Jayna Raghwani, Manon Ragonnet-Cronin, Lucille Rainbow, Diana Rajan, Shavanthi Rajatileka, Newara A. Ramadan, Andrew Rambaut, John Ramble, Paul A. Randell, Paul Randell, Liz Ratcliffe, Veena Raviprakash, Mohammad Raza, Nicholas M. Redshaw, Sara Rey, Nicola Reynolds, Alex Richter, David L. Robertson, Esther Robinson, Samuel C. Robson, Fiona Rogan, Stefan Rooke, Will Rowe, Sunando Roy, Steven Rudder, Chris Ruis, Steven Rushton, Felicity Ryan, Kordo Saeed, Buddhini Samaraweera, Christine M. Sambles, Roy Sanderson, Theo Sanderson, Fei Sang, Thea Sass, Emily Scher, Garren Scott, Carol Scott, Jasveen Sehmi, Sharif Shaaban, Divya Shah, Jessica Shaw, Ekaterina Shelest, James G. Shepherd, Liz A. Sheridan, Nicola Sheriff, Lesley Shirley, John Sillitoe, Siona Silviera, David A. Simpson, Aditi Singh, Dawn Singleton, Timofey Skvortsov, Tim J. Sloan, Graciela Sluga, Ken Smith, Kim S. Smith, Perminder Smith, Darren L. Smith, Louise Smith, Colin P. Smith, Nikki Smith, Katherine L. Smollett, Luke B. Snell, Thomas Somassa, Joel Southgate, Karla Spellman, Michael H. Spencer Chapman, Lewis G. Spurgin, Moira J. Spyer, Rachael Stanley, William Stanley, Thomas D. Stanton, Igor Starinskij, Joanne Stockton, Susanne Stonehouse, Nathaniel Storey, David J. Studholme, Malur Sudhanva, Emma Swindells, Yusri Taha, Ngee Keong Tan, Julian W. Tang, Miao Tang, Ben E.W. Taylor, Joshua F. Taylor, Sarah Taylor, Ben Temperton, Kate E. Templeton, Claire Thomas, Laura Thomson, Emma C. Thomson, Alicia Thornton, Scott A.J. Thurston, John A. Todd, Rachael Tomb, Lily Tong, Gerry Tonkin-Hill, M. Estee Torok, Jaime M. Tovar-Corona, Amy Trebes, Alexander J. Trotter, Ioulia Tsatsani, Robyn Turnbull, Katherine A. Twohig, Helen Umpleby, Anthony P. Underwood, Edith E. Vamos, Tetyana I. Vasylyeva, Sreenu Vattipally, Gabrielle Vernet, Barry B. Vipond, Erik M. Volz, Sarah Walsh, Dennis Wang, Ben Warne, Joanna Warwick-Dugdale, Elizabeth Wastnedge, Joanne Watkins, Louisa K. Watson, Sheila Waugh, Hermione J. Webster, Danni Weldon, Elaine Westwick, Thomas Whalley, Helen Wheeler, Mark Whitehead, Max Whiteley, Andrew Whitwham, Claudia Wierzbicki, Nicholas J. Willford, Lesley-Anne Williams, Rebecca Williams, Cheryl Williams, Chris Williams, Charlotte A. Williams, Rachel J. Williams, Thomas Williams, Catryn Williams, Kathleen A. Williamson, Eleri Wilson-Davies, Eric Witele, Karen T. Withell, Adam A. Witney, Paige Wolverson, Nick Wong, Trudy Workman, Victoria Wright, Derek W. Wright, Tim Wyatt, Sarah Wyllie, Li Xu-McCrae, Mehmet Yavus, Geraldine Yaze, Corin A. Yeats, Gonzalo Yebra, Wen C. Yew, Gregory R. Young, Jamie Young, Alex E. Zarebski, Peijun Zhang, J. Kenneth Baillie, Malcolm G. Semple, Peter J.M. Openshaw, Gail Carson, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, Wendy S. Barclay, Debby Bogaert, Kanta Chechi, Graham S. Cooke, Annemarie B. Docherty, Gonçalo dos Santos Correia, Marc-Emmanuel Dumas, Jake Dunning, Tom Fletcher, Christopher A. Green, William Greenhalf, Julian L. Griffin, Rishi K. Gupta, Ewen M. Harrison, Julian A. Hiscox, Antonia Ying Wai Ho, Peter W. Horby, Samreen Ijaz, Saye Khoo, Paul Klenerman, Andrew Law, Matthew R. Lewis, Sonia Liggi, Wei Shen Lim, Lynn Maslen, Laura Merson, Alison M. Meynert, Mahdad Noursadeghi, Michael Olanipekun, Anthonia Osagie, Massimo Palmarini, Carlo Palmieri, William A. Paxton, Georgios Pollakis, Nicholas Price, Clark D. Russell, Vanessa Sancho-Shimizu, Caroline J. Sands, Janet T. Scott, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Olivia V. Swann, Zoltan Takats, Panteleimon Takis, Richard S. Tedder, A.A. Roger Thompson, Ryan S. Thwaites, Maria Zambon, Hayley Hardwick, Chloe Donohue, Fiona Griffiths, Wilna Oosthuyzen, Cara Donegan, Rebecca G. Spencer, Jo Dalton, Michelle Girvan, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Daniel Plotkin, James Lee, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, Victoria Shaw, Sarah E. McDonald, Seán Keating, Katie A. Ahmed, Jane A. Armstrong, Milton Ashworth, Innocent G. Asiimwe, Siddharth Bakshi, Samantha L. Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin W.A. Catterall, Jordan J. Clark, Emily A. Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis W.S. Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Rebecca L. Jensen, Christopher B. Jones, Trevor R. Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A. Livoti, Maria Mancini, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S. Miah, Joanna Middleton, Joyce Mitchell, Ellen G. Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E. Shaw, Rebecca K. Shears, Benjamin Small, Krishanthi S. Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Nicola Wrobel, Sarah McCafferty, Kirstie Morrice, Alan MacLean, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Sam Allen, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Colin Berry, Nicola Best, Pieter Bothma, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Phil Donnison, Sam Douthwaite, Andrew Drummond, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B. Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Lillian Norris, Matthew K. O'Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Tim Planche, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Bobby Ruge, Brendan Ryan, Taranprit Saluja, Matthias L. Schmid, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Nick Vallotton, Rama Vancheeswaran, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G. Wootton, Andrew Workman, Bryan Yates, and Peter Young
Subjects: Phylogenetics, Molecular biology, Immunology, Immune response, Virology, Science
Abstract: Summary: We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.
Published: 2021
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5. Identification of immune correlates of fatal outcomes in critically ill COVID-19 patients.

Author: Jonathan Youngs, Nicholas M Provine, Nicholas Lim, Hannah R Sharpe, Ali Amini, Yi-Ling Chen, Jian Luo, Matthew D Edmans, Panagiota Zacharopoulou, Wentao Chen, Oliver Sampson, Robert Paton, William J Hurt, David A Duncan, Anna L McNaughton, Vincent N Miao, Susannah Leaver, Duncan L A Wyncoll, Jonathan Ball, Philip Hopkins, Oxford Immunology Network Covid-19 response T cell Consortium, Oxford Protective T cell Immunology for COVID-19 (OPTIC) Clinical team, Donal T Skelly, Eleanor Barnes, Susanna Dunachie, Graham Ogg, Teresa Lambe, Ian Pavord, Alex K Shalek, Craig P Thompson, Luzheng Xue, Derek C Macallan, Philip Goulder, Paul Klenerman, and Tihana Bicanic
Subjects: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract: Prior studies have demonstrated that immunologic dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of the immunologic drivers of death in the most critically ill patients. We performed immunophenotyping of viral antigen-specific and unconventional T cell responses, neutralizing antibodies, and serum proteins in critically ill patients with SARS-CoV-2 infection, using influenza infection, SARS-CoV-2-convalescent health care workers, and healthy adults as controls. We identify mucosal-associated invariant T (MAIT) cell activation as an independent and significant predictor of death in COVID-19 (HR = 5.92, 95% CI = 2.49-14.1). MAIT cell activation correlates with several other mortality-associated immunologic measures including broad activation of CD8+ T cells and non-Vδ2 γδT cells, and elevated levels of cytokines and chemokines, including GM-CSF, CXCL10, CCL2, and IL-6. MAIT cell activation is also a predictor of disease severity in influenza (ECMO/death HR = 4.43, 95% CI = 1.08-18.2). Single-cell RNA-sequencing reveals a shift from focused IFNα-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 -a feature not observed in severe influenza. We conclude that fatal COVID-19 infection is driven by uncoordinated inflammatory responses that drive a hierarchy of T cell activation, elements of which can serve as prognostic indicators and potential targets for immune intervention.
Published: 2021
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6. Provision of critical care for the elderly in Europe: a retrospective comparison of national healthcare frameworks in intensive care units

Author: Antonio Artigas, Nuno Catorze, Bernhard Wernly, Wojciech Szczeklik, Raimund Helbok, Pål Klepstad, Emmanuel Guerot, Tim Rahmel, Kelly Tiercelet, Louise Bell, Clare Bolger, Helder Filipe, Michael Reay, Jean-Pierre Quenot, Saad Nseir, Didier Thévenin, Maurizio Cecconi, Susan Dowling, Jason Cupitt, Willem Dieperink, Henning Ebelt, Philipp Eller, Patrick Meybohm, Rene Schmutz, Michael Joannidis, Sally Humphreys, Filippo Boroli, Gerardo Aguilar, Jørund Langørgen, Malte Kelm, Marcus Franz, Hans Flaatten, Christian Jung, Michael Beil, Susannah Leaver, Bertrand Guidet, Tom Dormans, Jonathan Ball, Patrick Morgan, Nick Spittle, Tom Lawton, Diederik Gommers, Antoine Romen, Camilla Brorsson, Ana Rita Santos, JANE EVANS, Ala Khaled, Hazem Ahmed, Madhu Balasubramaniam, Simon Dubler, Jean-Philippe Rigaud, Michael Schuster, Julien Maizel, Christophe Vinsonneau, Carole Boulanger, Jeremy Henning, Catia Cillóniz, Michael Spivey, Kiran Salaunkey, Raphael Romano Bruno, Stephan Binnebössel, Sviri Sigal, Peter Vernon van Heerden, Ariane Boumendil, Brian Marsh, Rui Moreno, Sandra Oeyen, Bernardo Bollen Pinto, Sten Mikael Walther, Joerg C Schefold, Jesper Fjølner, Tilemachos Zafeiridis, Dylan de Lange, Joke Nollet, Nikolaas de Neve, Pieter De Buysscher, Walter Swinnen, Marijana Mikačić, Anders Bastiansen, Andreas Husted, Bård E S Dahle, Christine Cramer, Christoffer Sølling, Dorthe Ørsnes, Jakob Edelberg Thomsen, Jonas Juul Pedersen, Mathilde Hummelmose Enevoldsen, Thomas Elkmann, Agnieszka Kubisz-Pudelko, Alan Pope, Amy Collins, Ashok S Raj, Christian Frey, Ciaran Hart, Dominic Spray, Georgina Randell, Ingeborg D Welters, Irina Grecu, Jenny Lord, Joanne Jones, Julie North, Laura Ortiz-Ruiz De Gordoa, Marcela Vizcaychipi, Maria Faulkner, McDonald Mupudzi, Megan Lea-Hagerty, Nicholas Love, Nigel White, Patricia Williams, Phillipa Wakefield, Rachel Savine, Reni Jacob, Richard Innes, Ritoo Kapoor, Steve Rose, Tarkeshwari Mane, Vongayi Ogbeide, Waqas Khaliq, Yolanda Baird, Arnaud Galbois, Cyril Charron, Guillaume Besch, Guillaume Savary, Hervé Mentec, Jean-Luc Chagnon, Jeremy Castaneray, Jérémy Rosman, Lucie Vettoretti, Maud Mousset Hovaere, Messika Messika, Michel Djibré, Nathalie Rolin, Philippe Burtin, Pierre Garcon, Xavier Valette, Christian Rabe, Eberhard Barth, Kristina Fuest, Michael Horacek, Sebastian Allgäuer, Stefan J Schaller, Stefan Schering, Stephan Steiner, Thorben Dieck, Tobias Graf, Anastasia Koutsikou, Aristeidis Vakalos, Bogdan Raitsiou, Elli Niki Flioni, Evangelia Neou, Fotios Tsimpoukas, Georgios Papathanakos, Giorgos Marinakis, Ioannis Koutsodimitropoulos, Kounougeri Aikaterini, Nikoletta Rovina, Stylliani Kourelea, Tasioudis Polychronis, Vasiiios Zidianakis, Vryza Konstantinia, Zoi Aidoni, Catherine Motherway, Chris Read, Ignacio Martin-Loeches, Andrea Neville Cracchiolo, Aristide Morigi, Italo Calamai, Stefania Brusa, Ahmed Elhadi, Ahmed Tarek, Wesal Ali Belkhair, Alexander D Cornet, Evavan Boven, Jasper Haringman, Lenneke Haas, Lettie van den Berg, Oscar Hoiting, Peter de Jager, Rik T Gerritsen, Alena Breidablik, Anita Slapgard, Anne-Karin Rime, Bente Jannestad, Britt Sjøbøe, Eva Rice, Finn H Andersen, Hans Frank Strietzel, Jan Peter Jensen, Kirsti Tøien, Kristian Strand, Michael Hahn, Aleksandra Biernacka, Anna Kluzik, Bartosz Kudlinski, Dariusz Maciejewski, Dorota Studzińska, Hubert Hymczak, Jan Stefaniak, Joanna Solek-Pastuszka, Joanna Zorska, Katarzyna Cwyl, Lukasz J Krzych, Maciej Zukowski, Małgorzata Lipińska-Gediga, Marek Pietruszko, Mariusz Piechota, Marta Serwa, Miroslaw Czuczwar, Mirosław Ziętkiewicz, Natalia Kozera, Paweł Nasiłowski, Paweł Sendur, Paweł Zatorski, Piotr Galkin, Ryszard Gawda, Urszula Kościuczuk, Waldemar Cyrankiewicz, Wojciech Gola, Alexandre Fernandes Pinto, Ana Margarida Fernandes, Cristina Sousa, Inês Barros, Isabel Amorim Ferreira, Jacobo Bacariza Blanco, João Teles Carvalho, Jose Maia, Nuno Candeias, Vladislav Belskiy, Africa Lores, Angela Prado Mira, David Perez-Torres, Emilio Maseda, Enver Rodriguez, Estefania Prol-Silva, Gaspar Eixarch, Gemma Gomà, Gonzalo Navarro Velasco, MariánIrazábal Jaimes, Mercedes Ibarz Villamayor, Noemí Llamas Fernández, Patricia Jimeno Cubero, Sonia López-Cuenca, Teresa Tomasa, Anders Sjöqvist, Fredrik Schiöler, Henrik Westberg, Jessica Nauska, Joakim Sivik, Johan Berkius, Karin Kleiven Thiringer, Lina DeGeer, Sten Walther, Leila Hergafi, Philippe Eckert, Ismail Yıldız, Ihor Yovenko, Yuriy Nalapko, and Richard Pugh
Subjects: Medicine
Abstract: Objectives In Europe, there is a distinction between two different healthcare organisation systems, the tax-based healthcare system (THS) and the social health insurance system (SHI). Our aim was to investigate whether the characteristics, treatment and mortality of older, critically ill patients in the intensive care unit (ICU) differed between THS and SHI.Setting ICUs in 16 European countries.Participants In total, 7817 critically ill older (≥80 years) patients were included in this study, 4941 in THS and 2876 in the SHI systems.Primary and secondary outcomes measures We chose generalised estimation equations with robust standard errors to produce population average adjusted OR (aOR). We adjusted for patient-specific variables, health economic data, including gross domestic product (GDP) and human development index (HDI), and treatment strategies.Results In SHI systems, there were higher rates of frail patients (Clinical Frailty Scale>4; 46% vs 41%; p
Published: 2021
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7. Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7

Author: Bo Meng, Steven A. Kemp, Guido Papa, Rawlings Datir, Isabella A.T.M. Ferreira, Sara Marelli, William T. Harvey, Spyros Lytras, Ahmed Mohamed, Giulia Gallo, Nazia Thakur, Dami A. Collier, Petra Mlcochova, Lidia M. Duncan, Alessandro M. Carabelli, Julia C. Kenyon, Andrew M. Lever, Anna De Marco, Christian Saliba, Katja Culap, Elisabetta Cameroni, Nicholas J. Matheson, Luca Piccoli, Davide Corti, Leo C. James, David L. Robertson, Dalan Bailey, Ravindra K. Gupta, Samuel C. Robson, Nicholas J. Loman, Thomas R. Connor, Tanya Golubchik, Rocio T. Martinez Nunez, Catherine Ludden, Sally Corden, Ian Johnston, David Bonsall, Colin P. Smith, Ali R. Awan, Giselda Bucca, M. Estee Torok, Kordo Saeed, Jacqui A. Prieto, David K. Jackson, William L. Hamilton, Luke B. Snell, Catherine Moore, Ewan M. Harrison, Sonia Goncalves, Derek J. Fairley, Matthew W. Loose, Joanne Watkins, Rich Livett, Samuel Moses, Roberto Amato, Sam Nicholls, Matthew Bull, Darren L. Smith, Jeff Barrett, David M. Aanensen, Martin D. Curran, Surendra Parmar, Dinesh Aggarwal, James G. Shepherd, Matthew D. Parker, Sharon Glaysher, Matthew Bashton, Anthony P. Underwood, Nicole Pacchiarini, Katie F. Loveson, Kate E. Templeton, Cordelia F. Langford, John Sillitoe, Thushan I. de Silva, Dennis Wang, Dominic Kwiatkowski, Andrew Rambaut, Justin O’Grady, Simon Cottrell, Matthew T.G. Holden, Emma C. Thomson, Husam Osman, Monique Andersson, Anoop J. Chauhan, Mohammed O. Hassan-Ibrahim, Mara Lawniczak, Alex Alderton, Meera Chand, Chrystala Constantinidou, Meera Unnikrishnan, Alistair C. Darby, Julian A. Hiscox, Steve Paterson, Inigo Martincorena, Erik M. Volz, Andrew J. Page, Oliver G. Pybus, Andrew R. Bassett, Cristina V. Ariani, Michael H. Spencer Chapman, Kathy K. Li, Rajiv N. Shah, Natasha G. Jesudason, Yusri Taha, Martin P. McHugh, Rebecca Dewar, Aminu S. Jahun, Claire McMurray, Sarojini Pandey, James P. McKenna, Andrew Nelson, Gregory R. Young, Clare M. McCann, Scott Elliott, Hannah Lowe, Ben Temperton, Sunando Roy, Anna Price, Sara Rey, Matthew Wyles, Stefan Rooke, Sharif Shaaban, Mariateresa de Cesare, Laura Letchford, Siona Silveira, Emanuela Pelosi, Eleri Wilson-Davies, Myra Hosmillo, Áine O’Toole, Andrew R. Hesketh, Richard Stark, Louis du Plessis, Chris Ruis, Helen Adams, Yann Bourgeois, Stephen L. Michell, Dimitris Gramatopoulos, Jonathan Edgeworth, Judith Breuer, John A. Todd, Christophe Fraser, David Buck, Michaela John, Gemma L. Kay, Steve Palmer, Sharon J. Peacock, David Heyburn, Danni Weldon, Esther Robinson, Alan McNally, Peter Muir, Ian B. Vipond, John Boyes, Venkat Sivaprakasam, Tranprit Salluja, Samir Dervisevic, Emma J. Meader, Naomi R. Park, Karen Oliver, Aaron R. Jeffries, Sascha Ott, Ana da Silva Filipe, David A. Simpson, Chris Williams, Jane A.H. Masoli, Bridget A. Knight, Christopher R. Jones, Cherian Koshy, Amy Ash, Anna Casey, Andrew Bosworth, Liz Ratcliffe, Li Xu-McCrae, Hannah M. Pymont, Stephanie Hutchings, Lisa Berry, Katie Jones, Fenella Halstead, Thomas Davis, Christopher Holmes, Miren Iturriza-Gomara, Anita O. Lucaci, Paul Anthony Randell, Alison Cox, Pinglawathee Madona, Kathryn Ann Harris, Julianne Rose Brown, Tabitha W. Mahungu, Dianne Irish-Tavares, Tanzina Haque, Jennifer Hart, Eric Witele, Melisa Louise Fenton, Steven Liggett, Clive Graham, Emma Swindells, Jennifer Collins, Gary Eltringham, Sharon Campbell, Patrick C. McClure, Gemma Clark, Tim J. Sloan, Carl Jones, Jessica Lynch, Ben Warne, Steven Leonard, Jillian Durham, Thomas Williams, Sam T. Haldenby, Nathaniel Storey, Nabil-Fareed Alikhan, Nadine Holmes, Christopher Moore, Matthew Carlile, Malorie Perry, Noel Craine, Ronan A. Lyons, Angela H. Beckett, Salman Goudarzi, Christopher Fearn, Kate Cook, Hannah Dent, Hannah Paul, Robert Davies, Beth Blane, Sophia T. Girgis, Mathew A. Beale, Katherine L. Bellis, Matthew J. Dorman, Eleanor Drury, Leanne Kane, Sally Kay, Samantha McGuigan, Rachel Nelson, Liam Prestwood, Shavanthi Rajatileka, Rahul Batra, Rachel J. Williams, Mark Kristiansen, Angie Green, Anita Justice, Adhyana I.K. Mahanama, Buddhini Samaraweera, Nazreen F. Hadjirin, Joshua Quick, Radoslaw Poplawski, Leanne M. Kermack, Nicola Reynolds, Grant Hall, Yasmin Chaudhry, Malte L. Pinckert, Iliana Georgana, Robin J. Moll, Alicia Thornton, Richard Myers, Joanne Stockton, Charlotte A. Williams, Wen C. Yew, Alexander J. Trotter, Amy Trebes, George MacIntyre-Cockett, Alec Birchley, Alexander Adams, Amy Plimmer, Bree Gatica-Wilcox, Caoimhe McKerr, Ember Hilvers, Hannah Jones, Hibo Asad, Jason Coombes, Johnathan M. Evans, Laia Fina, Lauren Gilbert, Lee Graham, Michelle Cronin, Sara Kumziene-Summerhayes, Sarah Taylor, Sophie Jones, Danielle C. Groves, Peijun Zhang, Marta Gallis, Stavroula F. Louka, Igor Starinskij, Chris Jackson, Marina Gourtovaia, Gerry Tonkin-Hill, Kevin Lewis, Jaime M. Tovar-Corona, Keith James, Laura Baxter, Mohammad T. Alam, Richard J. Orton, Joseph Hughes, Sreenu Vattipally, Manon Ragonnet-Cronin, Fabricia F. Nascimento, David Jorgensen, Olivia Boyd, Lily Geidelberg, Alex E. Zarebski, Jayna Raghwani, Moritz U.G. Kraemer, Joel Southgate, Benjamin B. Lindsey, Timothy M. Freeman, Jon-Paul Keatley, Joshua B. Singer, Leonardo de Oliveira Martins, Corin A. Yeats, Khalil Abudahab, Ben E.W. Taylor, Mirko Menegazzo, John Danesh, Wendy Hogsden, Sahar Eldirdiri, Anita Kenyon, Jenifer Mason, Trevor I. Robinson, Alison Holmes, James Price, John A. Hartley, Tanya Curran, Alison E. Mather, Giri Shankar, Rachel Jones, Robin Howe, Sian Morgan, Elizabeth Wastenge, Michael R. Chapman, Siddharth Mookerjee, Rachael Stanley, Wendy Smith, Timothy Peto, David Eyre, Derrick Crook, Gabrielle Vernet, Christine Kitchen, Huw Gulliver, Ian Merrick, Martyn Guest, Robert Munn, Declan T. Bradley, Tim Wyatt, Charlotte Beaver, Luke Foulser, Sophie Palmer, Carol M. Churcher, Ellena Brooks, Kim S. Smith, Katerina Galai, Georgina M. McManus, Frances Bolt, Francesc Coll, Lizzie Meadows, Stephen W. Attwood, Alisha Davies, Elen De Lacy, Fatima Downing, Sue Edwards, Garry P. Scarlett, Sarah Jeremiah, Nikki Smith, Danielle Leek, Sushmita Sridhar, Sally Forrest, Claire Cormie, Harmeet K. Gill, Joana Dias, Ellen E. Higginson, Mailis Maes, Jamie Young, Michelle Wantoch, Dorota Jamrozy, Stephanie Lo, Minal Patel, Verity Hill, Claire M. Bewshea, Sian Ellard, Cressida Auckland, Ian Harrison, Chloe Bishop, Vicki Chalker, Alex Richter, Andrew Beggs, Angus Best, Benita Percival, Jeremy Mirza, Oliver Megram, Megan Mayhew, Liam Crawford, Fiona Ashcroft, Emma Moles-Garcia, Nicola Cumley, Richard Hopes, Patawee Asamaphan, Marc O. Niebel, Rory N. Gunson, Amanda Bradley, Alasdair Maclean, Guy Mollett, Rachel Blacow, Paul Bird, Thomas Helmer, Karlie Fallon, Julian Tang, Antony D. Hale, Louissa R. Macfarlane-Smith, Katherine L. Harper, Holli Carden, Nicholas W. Machin, Kathryn A. Jackson, Shazaad S.Y. Ahmad, Ryan P. George, Lance Turtle, Elaine O’Toole, Joanne Watts, Cassie Breen, Angela Cowell, Adela Alcolea-Medina, Themoula Charalampous, Amita Patel, Lisa J. Levett, Judith Heaney, Aileen Rowan, Graham P. Taylor, Divya Shah, Laura Atkinson, Jack C.D. Lee, Adam P. Westhorpe, Riaz Jannoo, Helen L. Lowe, Angeliki Karamani, Leah Ensell, Wendy Chatterton, Monika Pusok, Ashok Dadrah, Amanda Symmonds, Graciela Sluga, Zoltan Molnar, Paul Baker, Stephen Bonner, Sarah Essex, Edward Barton, Debra Padgett, Garren Scott, Jane Greenaway, Brendan A.I. Payne, Shirelle Burton-Fanning, Sheila Waugh, Veena Raviprakash, Nicola Sheriff, Victoria Blakey, Lesley-Anne Williams, Jonathan Moore, Susanne Stonehouse, Louise Smith, Rose K. Davidson, Luke Bedford, Lindsay Coupland, Victoria Wright, Joseph G. Chappell, Theocharis Tsoleridis, Jonathan Ball, Manjinder Khakh, Vicki M. Fleming, Michelle M. Lister, Hannah C. Howson-Wells, Louise Berry, Tim Boswell, Amelia Joseph, Iona Willingham, Nichola Duckworth, Sarah Walsh, Emma Wise, Nathan Moore, Matilde Mori, Nick Cortes, Stephen Kidd, Rebecca Williams, Laura Gifford, Kelly Bicknell, Sarah Wyllie, Allyson Lloyd, Robert Impey, Cassandra S. Malone, Benjamin J. Cogger, Nick Levene, Lynn Monaghan, Alexander J. Keeley, David G. Partridge, Mohammad Raza, Cariad Evans, Kate Johnson, Emma Betteridge, Ben W. Farr, Scott Goodwin, Michael A. Quail, Carol Scott, Lesley Shirley, Scott A.J. Thurston, Diana Rajan, Iraad F. Bronner, Louise Aigrain, Nicholas M. Redshaw, Stefanie V. Lensing, Shane McCarthy, Alex Makunin, Carlos E. Balcazar, Michael D. Gallagher, Kathleen A. Williamson, Thomas D. Stanton, Michelle L. Michelsen, Joanna Warwick-Dugdale, Robin Manley, Audrey Farbos, James W. Harrison, Christine M. Sambles, David J. Studholme, Angie Lackenby, Tamyo Mbisa, Steven Platt, Shahjahan Miah, David Bibby, Carmen Manso, Jonathan Hubb, Gavin Dabrera, Mary Ramsay, Daniel Bradshaw, Ulf Schaefer, Natalie Groves, Eileen Gallagher, David Lee, David Williams, Nicholas Ellaby, Hassan Hartman, Nikos Manesis, Vineet Patel, Juan Ledesma, Katherine A. Twohig, Elias Allara, Clare Pearson, Jeffrey K.J. Cheng, Hannah E. Bridgewater, Lucy R. Frost, Grace Taylor-Joyce, Paul E. Brown, Lily Tong, Alice Broos, Daniel Mair, Jenna Nichols, Stephen N. Carmichael, Katherine L. Smollett, Kyriaki Nomikou, Elihu Aranday-Cortes, Natasha Johnson, Seema Nickbakhsh, Edith E. Vamos, Margaret Hughes, Lucille Rainbow, Richard Eccles, Charlotte Nelson, Mark Whitehead, Richard Gregory, Matthew Gemmell, Claudia Wierzbicki, Hermione J. Webster, Chloe L. Fisher, Adrian W. Signell, Gilberto Betancor, Harry D. Wilson, Gaia Nebbia, Flavia Flaviani, Alberto C. Cerda, Tammy V. Merrill, Rebekah E. Wilson, Marius Cotic, Nadua Bayzid, Thomas Thompson, Erwan Acheson, Steven Rushton, Sarah O’Brien, David J. Baker, Steven Rudder, Alp Aydin, Fei Sang, Johnny Debebe, Sarah Francois, Tetyana I. Vasylyeva, Marina Escalera Zamudio, Bernardo Gutierrez, Angela Marchbank, Joshua Maksimovic, Karla Spellman, Kathryn McCluggage, Mari Morgan, Robert Beer, Safiah Afifi, Trudy Workman, William Fuller, Catherine Bresner, Adrienn Angyal, Luke R. Green, Paul J. Parsons, Rachel M. Tucker, Rebecca Brown, Max Whiteley, James Bonfield, Christoph Puethe, Andrew Whitwham, Jennifier Liddle, Will Rowe, Igor Siveroni, Thanh Le-Viet, Amy Gaskin, Rob Johnson, Irina Abnizova, Mozam Ali, Laura Allen, Ralph Anderson, Cristina Ariani, Siobhan Austin-Guest, Sendu Bala, Jeffrey Barrett, Andrew Bassett, Kristina Battleday, James Beal, Mathew Beale, Sam Bellany, Tristram Bellerby, Katie Bellis, Duncan Berger, Matt Berriman, Paul Bevan, Simon Binley, Jason Bishop, Kirsty Blackburn, Nick Boughton, Sam Bowker, Timothy Brendler-Spaeth, Iraad Bronner, Tanya Brooklyn, Sarah Kay Buddenborg, Robert Bush, Catarina Caetano, Alex Cagan, Nicola Carter, Joanna Cartwright, Tiago Carvalho Monteiro, Liz Chapman, Tracey-Jane Chillingworth, Peter Clapham, Richard Clark, Adrian Clarke, Catriona Clarke, Daryl Cole, Elizabeth Cook, Maria Coppola, Linda Cornell, Clare Cornwell, Craig Corton, Abby Crackett, Alison Cranage, Harriet Craven, Sarah Craw, Mark Crawford, Tim Cutts, Monika Dabrowska, Matt Davies, Joseph Dawson, Callum Day, Aiden Densem, Thomas Dibling, Cat Dockree, David Dodd, Sunil Dogga, Matthew Dorman, Gordon Dougan, Martin Dougherty, Alexander Dove, Lucy Drummond, Monika Dudek, Laura Durrant, Elizabeth Easthope, Sabine Eckert, Pete Ellis, Ben Farr, Michael Fenton, Marcella Ferrero, Neil Flack, Howerd Fordham, Grace Forsythe, Matt Francis, Audrey Fraser, Adam Freeman, Anastasia Galvin, Maria Garcia-Casado, Alex Gedny, Sophia Girgis, James Glover, Oliver Gould, Andy Gray, Emma Gray, Coline Griffiths, Yong Gu, Florence Guerin, Will Hamilton, Hannah Hanks, Ewan Harrison, Alexandria Harrott, Edward Harry, Julia Harvison, Paul Heath, Anastasia Hernandez-Koutoucheva, Rhiannon Hobbs, Dave Holland, Sarah Holmes, Gary Hornett, Nicholas Hough, Liz Huckle, Lena Hughes-Hallet, Adam Hunter, Stephen Inglis, Sameena Iqbal, Adam Jackson, David Jackson, Carlos Jimenez Verdejo, Matthew Jones, Kalyan Kallepally, Keely Kay, Jon Keatley, Alan Keith, Alison King, Lucy Kitchin, Matt Kleanthous, Martina Klimekova, Petra Korlevic, Ksenia Krasheninnkova, Greg Lane, Cordelia Langford, Adam Laverack, Katharine Law, Stefanie Lensing, Amanah Lewis-Wade, Jennifer Liddle, Quan Lin, Sarah Lindsay, Sally Linsdell, Rhona Long, Jamie Lovell, Jon Lovell, James Mack, Mark Maddison, Aleksei Makunin, Irfan Mamun, Jenny Mansfield, Neil Marriott, Matt Martin, Matthew Mayho, Jo McClintock, Sandra McHugh, Liz MapcMinn, Carl Meadows, Emily Mobley, Robin Moll, Maria Morra, Leanne Morrow, Kathryn Murie, Sian Nash, Claire Nathwani, Plamena Naydenova, Alexandra Neaverson, Ed Nerou, Jon Nicholson, Tabea Nimz, Guillaume G. Noell, Sarah O’Meara, Valeriu Ohan, Charles Olney, Doug Ormond, Agnes Oszlanczi, Yoke Fei Pang, Barbora Pardubska, Naomi Park, Aaron Parmar, Gaurang Patel, Maggie Payne, Sharon Peacock, Arabella Petersen, Deborah Plowman, Tom Preston, Michael Quail, Richard Rance, Suzannah Rawlings, Nicholas Redshaw, Joe Reynolds, Mark Reynolds, Simon Rice, Matt Richardson, Connor Roberts, Katrina Robinson, Melanie Robinson, David Robinson, Hazel Rogers, Eduardo Martin Rojo, Daljit Roopra, Mark Rose, Luke Rudd, Ramin Sadri, Nicholas Salmon, David Saul, Frank Schwach, Phil Seekings, Alison Simms, Matt Sinnott, Shanthi Sivadasan, Bart Siwek, Dale Sizer, Kenneth Skeldon, Jason Skelton, Joanna Slater-Tunstill, Lisa Sloper, Nathalie Smerdon, Chris Smith, Christen Smith, James Smith, Katie Smith, Michelle Smith, Sean Smith, Tina Smith, Leighton Sneade, Carmen Diaz Soria, Catarina Sousa, Emily Souster, Andrew Sparkes, Michael Spencer-Chapman, Janet Squares, Robert Stanley, Claire Steed, Tim Stickland, Ian Still, Mike Stratton, Michelle Strickland, Allen Swann, Agnieszka Swiatkowska, Neil Sycamore, Emma Swift, Edward Symons, Suzanne Szluha, Emma Taluy, Nunu Tao, Katy Taylor, Sam Taylor, Stacey Thompson, Mark Thompson, Mark Thomson, Nicholas Thomson, Scott Thurston, Dee Toombs, Benjamin Topping, Jaime Tovar-Corona, Daniel Ungureanu, James Uphill, Jana Urbanova, Philip Jansen Van, Valerie Vancollie, Paul Voak, Danielle Walker, Matthew Walker, Matt Waller, Gary Ward, Charlie Weatherhogg, Niki Webb, Alan Wells, Eloise Wells, Luke Westwood, Theo Whipp, Thomas Whiteley, Georgia Whitton, Sara Widaa, Mia Williams, Mark Wilson, and Sean Wright
Subjects: SARS-CoV-2, COVID-19, antibody escape, neutralizing antibodies, infectivity, spike mutation, Biology (General), QH301-705.5
Abstract: Summary: We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of receptor binding motif replacements such as N439K and Y453F, known to increase binding affinity to the ACE2 receptor and confer antibody escape. In vitro, we show that, although ΔH69/V70 itself is not an antibody evasion mechanism, it increases infectivity associated with enhanced incorporation of cleaved spike into virions. ΔH69/V70 is able to partially rescue infectivity of spike proteins that have acquired N439K and Y453F escape mutations by increased spike incorporation. In addition, replacement of the H69 and V70 residues in the Alpha variant B.1.1.7 spike (where ΔH69/V70 occurs naturally) impairs spike incorporation and entry efficiency of the B.1.1.7 spike pseudotyped virus. Alpha variant B.1.1.7 spike mediates faster kinetics of cell-cell fusion than wild-type Wuhan-1 D614G, dependent on ΔH69/V70. Therefore, as ΔH69/V70 compensates for immune escape mutations that impair infectivity, continued surveillance for deletions with functional effects is warranted.
Published: 2021
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8. Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Author: Mark S Graham, PhD, Carole H Sudre, PhD, Anna May, MA, Michela Antonelli, PhD, Benjamin Murray, MSc, Thomas Varsavsky, MSc, Kerstin Kläser, MSc, Liane S Canas, PhD, Erika Molteni, PhD, Marc Modat, PhD, David A Drew, PhD, Long H Nguyen, MD, Lorenzo Polidori, MSc, Somesh Selvachandran, MSc, Christina Hu, MA, Joan Capdevila, PhD, Alexander Hammers, ProfPhD, Andrew T Chan, ProfMD, Jonathan Wolf, MA, Tim D Spector, ProfPhD, Claire J Steves, PhD, Sebastien Ourselin, ProfPhD, Cherian Koshy, Amy Ash, Emma Wise, Nathan Moore, Matilde Mori, Nick Cortes, Jessica Lynch, Stephen Kidd, Derek J Fairley, Tanya Curran, James P McKenna, Helen Adams, Christophe Fraser, Tanya Golubchik, David Bonsall, Mohammed O Hassan-Ibrahim, Cassandra S Malone, Benjamin J Cogger, Michelle Wantoch, Nicola Reynolds, Ben Warne, Joshua Maksimovic, Karla Spellman, Kathryn McCluggage, Michaela John, Robert Beer, Safiah Afifi, Sian Morgan, Angela Marchbank, Anna Price, Christine Kitchen, Huw Gulliver, Ian Merrick, Joel Southgate, Martyn Guest, Robert Munn, Trudy Workman, Thomas R Connor, William Fuller, Catherine Bresner, Luke B Snell, Amita Patel, Themoula Charalampous, Gaia Nebbia, Rahul Batra, Jonathan Edgeworth, Samuel C Robson, Angela H Beckett, David M Aanensen, Anthony P Underwood, Corin A Yeats, Khalil Abudahab, Ben EW Taylor, Mirko Menegazzo, Gemma Clark, Wendy Smith, Manjinder Khakh, Vicki M Fleming, Michelle M Lister, Hannah C Howson-Wells, Louise Berry, Tim Boswell, Amelia Joseph, Iona Willingham, Carl Jones, Christopher Holmes, Paul Bird, Thomas Helmer, Karlie Fallon, Julian Tang, Veena Raviprakash, Sharon Campbell, Nicola Sheriff, Victoria Blakey, Lesley-Anne Williams, Matthew W Loose, Nadine Holmes, Christopher Moore, Matthew Carlile, Victoria Wright, Fei Sang, Johnny Debebe, Francesc Coll, Adrian W Signell, Gilberto Betancor, Harry D Wilson, Sahar Eldirdiri, Anita Kenyon, Thomas Davis, Oliver G Pybus, Louis du Plessis, Alex E Zarebski, Jayna Raghwani, Moritz UG Kraemer, Sarah Francois, Stephen W Attwood, Tetyana I Vasylyeva, Marina Escalera Zamudio, Bernardo Gutierrez, M. Estee Torok, William L Hamilton, Ian G Goodfellow, Grant Hall, Aminu S Jahun, Yasmin Chaudhry, Myra Hosmillo, Malte L Pinckert, Iliana Georgana, Samuel Moses, Hannah Lowe, Luke Bedford, Jonathan Moore, Susanne Stonehouse, Chloe L Fisher, Ali R Awan, John BoYes, Judith Breuer, Kathryn Ann Harris, Julianne Rose Brown, Divya Shah, Laura Atkinson, Jack CD Lee, Nathaniel Storey, Flavia Flaviani, Adela Alcolea-Medina, Rebecca Williams, Gabrielle Vernet, Michael R Chapman, Lisa J Levett, Judith Heaney, Wendy Chatterton, Monika Pusok, Li Xu-McCrae, Darren L Smith, Matthew Bashton, Gregory R Young, Alison Holmes, Paul Anthony Randell, Alison Cox, Pinglawathee Madona, Frances Bolt, James Price, Siddharth Mookerjee, Manon Ragonnet-Cronin, Fabricia F. Nascimento, David Jorgensen, Igor Siveroni, Rob Johnson, Olivia Boyd, Lily Geidelberg, Erik M Volz, Aileen Rowan, Graham P Taylor, Katherine L Smollett, Nicholas J Loman, Joshua Quick, Claire McMurray, Joanne Stockton, Sam Nicholls, Will Rowe, Radoslaw Poplawski, Alan McNally, Rocio T Martinez Nunez, Jenifer Mason, Trevor I Robinson, Elaine O'Toole, Joanne Watts, Cassie Breen, Angela Cowell, Graciela Sluga, Nicholas W Machin, Shazaad S Y Ahmad, Ryan P George, Fenella Halstead, Venkat Sivaprakasam, Wendy Hogsden, Chris J Illingworth, Chris Jackson, Emma C Thomson, James G Shepherd, Patawee Asamaphan, Marc O Niebel, Kathy K Li, Rajiv N Shah, Natasha G Jesudason, Lily Tong, Alice Broos, Daniel Mair, Jenna Nichols, Stephen N Carmichael, Kyriaki Nomikou, Elihu Aranday-Cortes, Natasha Johnson, Igor Starinskij, Ana da Silva Filipe, David L Robertson, Richard J Orton, Joseph Hughes, Sreenu Vattipally, Joshua B Singer, Seema Nickbakhsh, Antony D Hale, Louissa R Macfarlane-Smith, Katherine L Harper, Holli Carden, Yusri Taha, Brendan AI Payne, Shirelle Burton-Fanning, Sheila Waugh, Jennifer Collins, Gary Eltringham, Steven Rushton, Sarah O'Brien, Amanda Bradley, Alasdair Maclean, Guy Mollett, Rachel Blacow, Kate E Templeton, Martin P McHugh, Rebecca Dewar, Elizabeth Wastenge, Samir Dervisevic, Rachael Stanley, Emma J Meader, Lindsay Coupland, Louise Smith, Clive Graham, Edward Barton, Debra Padgett, Garren Scott, Emma Swindells, Jane Greenaway, Andrew Nelson, Clare M McCann, Wen C Yew, Monique Andersson, Timothy Peto, Anita Justice, David Eyre, Derrick Crook, Tim J Sloan, Nichola Duckworth, Sarah Walsh, Anoop J Chauhan, Sharon Glaysher, Kelly Bicknell, Sarah Wyllie, Scott Elliott, Allyson Lloyd, Robert Impey, Nick Levene, Lynn Monaghan, Declan T Bradley, Tim Wyatt, Elias Allara, Clare Pearson, Husam Osman, Andrew Bosworth, Esther Robinson, Peter Muir, Ian B Vipond, Richard Hopes, Hannah M Pymont, Stephanie Hutchings, Martin D Curran, Surendra Parmar, Angie Lackenby, Tamyo Mbisa, Steven Platt, Shahjahan Miah, David Bibby, Carmen Manso, Jonathan Hubb, Meera Chand, Gavin Dabrera, Mary Ramsay, Daniel Bradshaw, Alicia Thornton, Richard Myers, Ulf Schaefer, Natalie Groves, Eileen Gallagher, David Lee, David Williams, Nicholas Ellaby, Ian Harrison, Hassan Hartman, Nikos Manesis, Vineet Patel, Chloe Bishop, Vicki Chalker, Juan Ledesma, Katherine A Twohig, Matthew T.G. Holden, Sharif Shaaban, Alec Birchley, Alexander Adams, Alisha Davies, Amy Gaskin, Amy Plimmer, Bree Gatica-Wilcox, Caoimhe McKerr, Catherine Moore, Chris Williams, David Heyburn, Elen De Lacy, Ember Hilvers, Fatima Downing, Giri Shankar, Hannah Jones, Hibo Asad, Jason Coombes, Joanne Watkins, Johnathan M Evans, Laia Fina, Laura Gifford, Lauren Gilbert, Lee Graham, Malorie Perry, Mari Morgan, Matthew Bull, Michelle Cronin, Nicole Pacchiarini, Noel Craine, Rachel Jones, Robin Howe, Sally Corden, Sara Rey, Sara Kumziene-SummerhaYes, Sarah Taylor, Simon Cottrell, Sophie Jones, Sue Edwards, Justin O'Grady, Andrew J Page, Alison E Mather, David J Baker, Steven Rudder, Alp Aydin, Gemma L Kay, Alexander J Trotter, Nabil-Fareed Alikhan, Leonardo de Oliveira Martins, Thanh Le-Viet, Lizzie Meadows, Anna Casey, Liz Ratcliffe, David A Simpson, Zoltan Molnar, Thomas Thompson, Erwan Acheson, Jane AH Masoli, Bridget A Knight, Sian Ellard, Cressida Auckland, Christopher R Jones, Tabitha W Mahungu, Dianne Irish-Tavares, Tanzina Haque, Jennifer Hart, Eric Witele, Melisa Louise Fenton, Ashok Dadrah, Amanda Symmonds, Tranprit Saluja, Yann Bourgeois, Garry P Scarlett, Katie F Loveson, Salman Goudarzi, Christopher Fearn, Kate Cook, Hannah Dent, Hannah Paul, David G Partridge, Mohammad Raza, Cariad Evans, Kate Johnson, Steven Liggett, Paul Baker, Stephen Bonner, Sarah Essex, Ronan A Lyons, Kordo Saeed, Adhyana I.K Mahanama, Buddhini Samaraweera, Siona Silveira, Emanuela Pelosi, Eleri Wilson-Davies, Rachel J Williams, Mark Kristiansen, Sunando Roy, Charlotte A Williams, Marius Cotic, Nadua Bayzid, Adam P Westhorpe, John A Hartley, Riaz Jannoo, Helen L Lowe, Angeliki Karamani, Leah Ensell, Jacqui A Prieto, Sarah Jeremiah, Dimitris Grammatopoulos, Sarojini Pandey, Lisa Berry, Katie Jones, Alex Richter, Andrew Beggs, Angus Best, Benita Percival, Jeremy Mirza, Oliver Megram, Megan Mayhew, Liam Crawford, Fiona Ashcroft, Emma Moles-Garcia, Nicola Cumley, Colin P Smith, Giselda Bucca, Andrew R Hesketh, Beth Blane, Sophia T Girgis, Danielle Leek, Sushmita Sridhar, Sally Forrest, Claire Cormie, Harmeet K Gill, Joana Dias, Ellen E Higginson, Mailis Maes, Jamie Young, Leanne M Kermack, Ravi Kumar Gupta, Catherine Ludden, Sharon J Peacock, Sophie Palmer, Carol M Churcher, Nazreen F Hadjirin, Alessandro M Carabelli, Ellena Brooks, Kim S Smith, Katerina Galai, Georgina M McManus, Chris Ruis, Rose K Davidson, Andrew Rambaut, Thomas Williams, Carlos E Balcazar, Michael D Gallagher, Áine O'Toole, Stefan Rooke, Verity Hill, Kathleen A Williamson, Thomas D Stanton, Stephen L Michell, Claire M Bewshea, Ben Temperton, Michelle L Michelsen, Joanna Warwick-Dugdale, Robin Manley, Audrey Farbos, James W Harrison, Christine M Sambles, David J Studholme, Aaron R Jeffries, Alistair C Darby, Julian A Hiscox, Steve Paterson, Miren Iturriza-Gomara, Kathryn A Jackson, Anita O Lucaci, Edith E Vamos, Margaret Hughes, Lucille Rainbow, Richard Eccles, Charlotte Nelson, Mark Whitehead, Lance Turtle, Sam T Haldenby, Richard Gregory, Matthew Gemmell, Claudia Wierzbicki, Hermione J Webster, Thushan I de Silva, Nikki Smith, Adrienn Angyal, Benjamin B Lindsey, Danielle C Groves, Luke R Green, Dennis Wang, Timothy M Freeman, Matthew D Parker, Alexander J Keeley, Paul J Parsons, Rachel M Tucker, Rebecca Brown, Matthew Wyles, Max Whiteley, Peijun Zhang, Marta Gallis, Stavroula F Louka, Chrystala Constantinidou, Meera Unnikrishnan, Sascha Ott, Jeffrey K.J. Cheng, Hannah E. Bridgewater, Lucy R. Frost, Grace Taylor-Joyce, Richard Stark, Laura Baxter, Mohammad T. Alam, Paul E Brown, Dinesh Aggarwal, Alberto C Cerda, Tammy V Merrill, Rebekah E Wilson, Patrick C McClure, Joseph G Chappell, Theocharis Tsoleridis, Jonathan Ball, David Buck, John A Todd, Angie Green, Amy Trebes, George MacIntyre-Cockett, Mariateresa de Cesare, Alex Alderton, Roberto Amato, Cristina V Ariani, Mathew A Beale, Charlotte Beaver, Katherine L Bellis, Emma Betteridge, James Bonfield, John Danesh, Matthew J Dorman, Eleanor Drury, Ben W Farr, Luke Foulser, Sonia Goncalves, Scott Goodwin, Marina Gourtovaia, Ewan M Harrison, David K Jackson, Dorota Jamrozy, Ian Johnston, Leanne Kane, Sally Kay, Jon-Paul Keatley, Dominic Kwiatkowski, Cordelia F Langford, Mara Lawniczak, Laura Letchford, Rich Livett, Stephanie Lo, Inigo Martincorena, Samantha McGuigan, Rachel Nelson, Steve Palmer, Naomi R Park, Minal Patel, Liam Prestwood, Christoph Puethe, Michael A Quail, Shavanthi Rajatileka, Carol Scott, Lesley Shirley, John Sillitoe, Michael H Spencer Chapman, Scott AJ Thurston, Gerry Tonkin-Hill, Danni Weldon, Diana Rajan, Iraad F Bronner, Louise Aigrain, Nicholas M Redshaw, Stefanie V Lensing, Robert Davies, Andrew Whitwham, Jennifier Liddle, Kevin Lewis, Jaime M Tovar-Corona, Steven Leonard, Jillian Durham, Andrew R Bassett, Shane McCarthy, Robin J Moll, Keith James, Karen Oliver, Alex Makunin, Jeff Barrett, and Rory N Gunson
Subjects: Public aspects of medicine, RA1-1270
Abstract: Summary: Background: The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods: We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings: From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation: The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding: Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society.
Published: 2021
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9. Deaths in people from Black, Asian and minority ethnic communities from both COVID-19 and non-COVID causes in the first weeks of the pandemic in London: a hospital case note review

Author: Nigel Kennea, Richard Hartopp, Jonathan Ball, Michael Richard Perkin, Sarah Heap, Agatha Crerar-Gilbert, Wendy Albuquerque, Serena Haywood, Zoe Avila, and Kate Hutt
Subjects: Medicine
Abstract: Objective To undertake a case review of deaths in a 6-week period during the COVID-19 pandemic commencing with the first death in the hospital from COVID-19 on 12th of March 2020 and contrast this with the same period in 2019.Setting A large London teaching hospital.Participants Three groups were compared: group 1—COVID-19-associated deaths in the 6-week period (n=243), group 2—non-COVID deaths in the same period (n=136) and group 3—all deaths in a comparison period of the same 6 weeks in 2019 (n=194).Primary and secondary outcome measures This was a descriptive analysis of death case series review and as such no primary or secondary outcomes were pre-stipulated.Results Deaths in patients from the Black, Asian and minority ethnic (BAME) communities in the pandemic period significantly increased both in the COVID-19 group (OR=2.43, 95% CI=1.60–3.68, p
Published: 2020
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10. Refinement of the zebrafish embryo developmental toxicity assay

Author: Jente Hoyberghs, Chloé Bars, Casper Pype, Kenn Foubert, Miriam Ayuso Hernando, Chris Van Ginneken, Jonathan Ball, and Steven Van Cruchten
Subjects: Zebrafish Embryo Developmental Toxicity Assay (ZEDTA), Science
Abstract: Several pharmaceutical and chemical companies are using the zebrafish embryo as an alternative to animal testing for early detection of developmental toxicants. Unfortunately, the protocol of this zebrafish embryo assay varies between labs, resulting in discordant data for identical compounds. The assay also has some limitations, such as low biotransformation capacity and fewer morphological endpoints in comparison with the in vivo mammalian developmental toxicity studies. Consequently, there is a need to standardize and further optimize the assay for developmental toxicity testing. We developed a Zebrafish Embryo Developmental Toxicity Assay (ZEDTA) that can be extended with a metabolic activation system and/or skeletal staining to increase its sensitivity. As such, the ZEDTA can be used as a modular system depending on the compound of interest. • Our protocol is customized with a metabolic activation system for test compounds, using human liver microsomes. This system ensures exposure of zebrafish embryos to metabolites that are relevant for human risk and safety assessment. As human liver microsomes are toxic for the zebrafish embryo, we developed a preincubation system with an ultracentrifugation and subsequent dilution step. • Additionally, we developed a skeletal staining protocol that can be added to the ZEDTA modular system. Our live Alizarin Red staining method detects several bone structures in 5-day old zebrafish larvae in a consistent manner.
Published: 2020
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11. Otimização hemodinâmica em trauma grave: uma revisão sistemática e metanálise

Author: Carlos Corredor, Nishkantha Arulkumaran, Jonathan Ball, Michael R Grounds, Mark A Hamilton, Andrew Rhodes, and Maurizio Cecconi
Subjects: Ferimentos e lesões, Índices de gravidade do trauma, Choque hemorrágico, Hidratação/métodos, Hemodinâmica/fisiologia, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Objetivo: O trauma grave pode associar-se a ocorrência de importante choque hemorrágico e ao comprometimento da perfusão dos órgãos. Formulamos a hipótese de que o tratamento direcionado por objetivo conferiria benefícios em termos de morbidade e mortalidade, em casos graves de trauma. Métodos: Realizamos uma busca sistemática nas bases de dados MedLine, Embase e Cochrane Controlled Clinical Trials Register com relação a pacientes vítimas de trauma grave. A mortalidade foi o desfecho primário dessa revisão. Os desfechos secundários incluíram taxas de complicações, duração da permanência no hospital e na unidade de terapia intensiva, e o volume de fluidos administrados. A metanálise foi realizada utilizando o programa de computador RevMan, e os dados apresentados são as odds ratios (OR) para desfechos dicotomizados e as diferenças médias e diferenças médias padrão para desfechos contínuos. Resultados: Foram analisados quatro estudos clínicos randomizados e controlados, que incluíram 419 pacientes. O risco de mortalidade foi significantemente reduzido nos pacientes com tratamento direcionado por objetivo, em comparação ao grupo controle (OR=0,56; IC95%: 0,34-0,92). A duração da permanência na unidade de terapia intensiva (DM: 3,7 dias; IC95%: 1,06-6,5) e no hospital (DM: 3,5 dias; IC95%: 2,75-4,25) foi significantemente mais curta no grupo de pacientes do grupo tratado conforme o protocolo. Não houve diferenças nos relatos relativos a volume total de fluidos infundidos e a transfusões sanguíneas. A heterogeneidade nos relatos entre os estudos impediu uma análise quantitativa das complicações. Conclusão: Após a ocorrência de trauma grave, o uso precoce de tratamento direcionado por objetivo se associou com mortalidade mais baixa e com menos dias de permanência na unidade de terapia intensiva e no hospital. Os achados desta análise devem ser interpretados com cautela, em razão da importante heterogeneidade e do número pequeno de estudos clínicos randomizados e controlados, que foram incluídos na análise.
Published: 2014
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12. Description of adult and third instar larva of Trichostetha curlei sp. n. (Coleoptera, Scarabaeidae, Cetoniinae) from the Cape region of South Africa

Author: Renzo Perissinotto, Petr Šípek, and Jonathan Ball
Subjects: Zoology, QL1-991
Abstract: A new high altitude montane species of Trichostetha Burmeister, 1842 is described from the Elandsberg range of the Western Cape interior. This represents the 14th species of the genus and the first to be reported with a description of its larva. It is a significant addition to the growing number of species that exhibit no adult feeding behaviour and a short period of activity restricted to the onset of summer. Larvae dwell in rock crevices, feeding on decomposing plant matter. The genus Trichostetha is heterogeneous and the complex variability observed in some species, especially T. capensis (Linnaeus, 1767), requires the re-instatement of taxa that were recently synonymised. Thus, T. bicolor Péringuey, 1907 is here re-proposed as a separate species and T. capensis hottentotta (Gory & Percheron, 1833) as a separate subspecies. Conversely, T. alutacea Allard, 1994 is recognised as a dark variety of T. signata (Fabricius, 1775) and is, consequently, synonymised with this species.
Published: 2014
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13. The Double Diamond Model: In Pursuit of Simplicity and Flexibility

Author: Kochanowska, Magda, Gagliardi, Weronika Rochacka, with reference to Jonathan Ball, Tosi, Francesca, Editor-in-Chief, Germak, Claudio, Series Editor, Zurlo, Francesco, Series Editor, Jinyi, Zhi, Series Editor, Pozzatti Amadori, Marilaine, Series Editor, Caon, Maurizio, Series Editor, Raposo, Daniel, editor, Neves, João, editor, and Silva, José, editor
Published: 2022
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14. National Gallery

Author: Jonathan Ball, Jonathan Ball
Published: 2019

15. The Effect of an Accelerated Renal Replacement Therapy Initiation Is Not Modified by Baseline Risk

Author: Federico Angriman, Bruno L. Ferreyro, Natalia Angeloni, Bruno R. da Costa, Ron Wald, Sean M. Bagshaw, Neill K.J. Adhikari, Rinaldo Bellomo, Didier Dreyfuss, Bin Du, Martin P. Gallagher, Stéphane Gaudry, François Lamontagne, Michael Joannidis, Kathleen D. Liu, Daniel F. McAuley, Shay P. McGuinness, Alistair D. Nichol, Marlies Ostermann, Paul M. Palevsky, Haibo Qiu, Ville Pettilä, Antoine G. Schneider, Orla M. Smith, Suvi T. Vaara, Matthew Weir, Glenn M. Eastwood, Leah Peck, Helen Young, Peter Kruger, Gordon Laurie, Emma Saylor, Jason Meyer, Ellen Venz, Krista Wetzig, Craig French, Forbes McGain, John Mulder, Gerard Fennessy, Sathyajith Koottayi, Samantha Bates, Miriam Towns, Rebecca Morgan, Anna Tippett, Andrew Udy, Chris Mason, Elisa Licari, Dashiell Gantner, Jason McClure, Alistair Nichol, Phoebe McCracken, Jasmin Board, Emma Martin, Shirley Vallance, Meredith Young, Chelsey Vladic, Steve McGloughlin, David Gattas, Heidi Buhr, Jennifer Coles, Debra Hutch, James Wun, Louise Cole, Christina Whitehead, Julie Lowrey, Kristy Masters, Rebecca Gresham, Victoria Campbell, David Gutierrez, Jane Brailsford, Loretta Forbes, Lauren Murray, Teena Maguire, Martina NiChonghaile, Neil Orford, Allison Bone, Tania Elderkin, Tania Salerno, Tim Chimunda, Jason Fletcher, Emma Broadfield, Sanjay Porwal, Cameron Knott, Catherine Boschert, Julie Smith, Angus Richardson, Dianne Hill, Graeme Duke, Peter Oziemski, Santiago Cegarra, Peter Chan, Deborah Welsh, Stephanie Hunter, Owen Roodenburg, John Dyett, Nicos Kokotsis, Max Moser, Yang Yang, Laven Padayachee, Joseph Vetro, Himangsu Gangopadhyay, Melissa Kaufman, Angaj Ghosh, Simone Said, Alpesh Patel, Shailesh Bihari, Elisha Matheson, Xia Jin, Tapaswi Shrestha, Kate Schwartz, Rosalba Cross, Winston Cheung, Helen Wong, Mark Kol, Asim Shah, Amanda Y. Wang, Zoltan Endre, Celia Bradford, Pierre Janin, Simon Finfer, Naomi Diel, Jonathan Gatward, Naomi Hammond, Anthony Delaney, Frances Bass, Elizabeth Yarad, Hergen Buscher, Claire Reynolds, Nerilee Baker, Romuald Bellmann, Andreas Peer, Julia Hasslacher, Paul Koglberger, Sebastian Klein, Klemens Zotter, Anna Brandtner, Armin Finkenstedt, Adelheid Ditlbacher, Frank Hartig, Dietmar Fries, Mirjam Bachler, Bettina Schenk, Martin Wagner, Philipp Eller, Thomas Staudinger, Esther Tiller, Peter Schellongowski, Andja Bojic, Eric A. Hoste, Stephanie Bracke, Luc De Crop, Daisy Vermeiren, Fernando Thome, Bianca Chiella, Lucia Fendt, Veronica Antunes, Frédérick D'Aragon, Charles St-Arnaud, Michael Mayette, Élaine Carbonnaeu, Joannie Marchand, Marie-Hélène Masse, Marilène Ladouceur, Alexis F. Turgeon, François Lauzier, David Bellemare, Charles Langis Francoeur, Guillaume LeBlanc, Gabrielle Guilbault, Stéphanie Grenier, Eve Cloutier, Annick Boivin, Charles Delisle-Thibault, Panagiota Giannakouros, Olivier Costerousse, Jean-François Cailhier, François-Martin Carrier, Ali Ghamraoui, Martine Lebrasseur, Fatna Benettaib, Maya Salamé, Dounia Boumahni, Ying Tung Sia, Jean-François Naud, Isabelle Roy, Henry T. Stelfox, Stacey Ruddell, Braden J. Manns, Shelley Duggan, Dominic Carney, Jennifer Barchard, Richard P. Whitlock, Emilie Belley-Cote, Nevena Savija, Alexandra Sabev, Troy Campbell, Thais Creary, Kelson Devereaux, Shira Brodutch, Claudio Rigatto, Bojan Paunovic, Owen Mooney, Anna Glybina, Oksana Harasemiw, Michelle Di Nella, John Harmon, Navdeep Mehta, Louis Lakatos, Nicole Haslam, Francois Lellouche, Mathieu Simon, Ying Tung, Patricia Lizotte, Pierre-Alexandre Bourchard, Bram Rochwerg, Tim Karachi, Tina Millen, John Muscedere, David Maslove, J. Gordon Boyd, Stephanie Sibley, John Drover, Miranda Hunt, Ilinca Georgescu, Randy Wax, Ilan Lenga, Kavita Sridhar, Andrew Steele, Kelly Fusco, Taneera Ghate, Michael Tolibas, Holly Robinson, Matthew A. Weir, Ravi Taneja, Ian M. Ball, Amit Garg, Eileen Campbell, Athena Ovsenek, Sean van Diepen, Nadia Baig, Sheldon Magder, Han Yao, Ahsan Alam, Josie Campisi, Erika MacIntyre, Ella Rokosh, Kimberly Scherr, Stephen Lapinsky, Sangeeta Mehta, Sumesh Shah, Daniel J. Niven, Michael Russell, Kym Jim, Gillian Brown, Kerry Oxtoby, Adam Hall, Luc Benoit, Colleen Sokolowski, Bhanu Prasad, Jag Rao, Shelley Giebel, Demetrios J. Kutsogiannis, Patricia Thompson, Tayne Thompson, Robert Cirone, Kanthi Kavikondala, Mark Soth, France Clarke, Alyson Takaoka, David Mazer, Karen Burns, Jan Friedrich, David Klein, Gyan Sandhu, Marlene Santos, Imrana Khalid, Jennifer Hodder, Peter Dodek, Najib Ayas, Victoria Alcuaz, Gabriel Suen, Oleksa Rewa, Gurmeet Singh, Sean Norris, Neil Gibson, Castro Arias, Aysha Shami, Celine Pelletier, Alireza Zahirieh, Andre Amaral, Nicole Marinoff, Navjot Kaur, Adic Perez, Jane Wang, Gregory Haljan, Christopher Condin, Lauralyn McIntyre, Brigette Gomes, Rebecca Porteous, Irene Watpool, Swapnil Hiremath, Edward Clark, Margaret S. Herridge, Felicity Backhouse, M. Elizabeth Wilcox, Karolina Walczak, Vincent Ki, Asheer Sharman, Martin Romano, R.T. Noel Gibney, Adam S. Romanovsky, Lorena McCoshen, Gordon Wood, Daniel Ovakim, Fiona Auld, Gayle Carney, Meili Duan, Xiaojun Ji, Dongchen Guo, Zhili Qi, Jin Lin, Meng Zhang, Lei Dong, Jingfeng Liu, Pei Liu, Deyuan Zhi, Guoqiang Bai, Yu Qiu, Ziqi Yang, Jing Bai, Zhuang Liu, Haizhou Zhuang, Haiman Wang, Jian Li, Mengya Zhao, Xiao Zhou, Xianqing Shi, Baning Ye, Manli Liu, Jing Wu, Yongjian Fu, Dali Long, Yu Pan, Jinlong Wang, Huaxian Mei, Songsong Zhang, Mingxiang Wen, Enyu Yang, Sijie Mu, Jianquan Li, Tingting Hu, Bingyu Qin, Min Li, Cunzhen Wang, Xin Dong, Kaiwu Wang, Haibo Wang, Jianxu Yang, Chuanyao Wang, Dongxin Wang, Nan Li, Zhui Yu, Song Xu, Lan Yao, Guo Hou, Zhou Liu, Liping Lu, Yingtao Lian, Chunting Wang, Jichen Zhang, Ruiqi Ding, Guoqing Qi, Qizhi Wang, Peng Wang, Zhaoli Meng, Man Chen, Xiaobo Hu, Xiandi He, Shibing Zhao, Lele Hang, Rui Li, Suhui Qin, Kun Lu, Shijuan Dun, Cheng Liu, Qi Zhou, Zhenzhen Chen, Jing Mei, Minwei Zhang, Hao Xu, Jincan Lin, Qindong Shi, Lijuan Fu, Qinjing Zeng, Hongye Ma, Jinqi Yan, Lan Gao, Hongjuan Liu, Lei Zhang, Hao Li, Xiaona He, Jingqun Fan, Litao Guo, Yu Liu, Xue Wang, Jingjing Sun, Zhongmin Liu, Juan Yang, Lili Ding, Lulu Sheng, Xingang Liu, Jie Yan, Quihui Wang, Yifeng Wang, Dan Zhao, Shuangping Zhao, Chenghuan Hu, Jing Li, Fuxing Deng, Haibo Qui, Yi Yang, Min Mo, Chun Pan, Changde Wu, Yingzi Huang, Lili Huang, Airan Liu, Anna-Maija Korhonen, Sanna Törnblom, Sari Sutinen, Leena Pettilä, Jonna Heinonen, Eliria Lappi, Taria Suhonen, Sari Karlsson, Sanna Hoppu, Ville Jalkanen, Anne Kuitunen, Markus Levoranta, Jaakko Långsjö, Sanna Ristimäki, Kaisa Malila, Anna Wootten, Simo Varila, Mikko J Järvisalo, Outi Inkinen, Satu Kentala, Keijo Leivo, Paivi Haltia, Jean-Damien Ricard, Jonathan Messika, Abirami Tiagarajah, Malo Emery, Aline Dechanet, Coralie Gernez, Damien Roux, Laurent Martin-Lefevre, Maud Fiancette, Isabelle Vinatier, Jean Claude Lacherade, Gwenhaël Colin, Christine Lebert, Marie-Ange Azais, Aihem Yehia, Caroline Pouplet, Matthieu Henry- Lagarrigue, Amélie Seguin, Laura Crosby, Julien Maizel, Dimitri Titeca-Beauport, Alain Combes, Ania Nieszkowska, Paul Masi, Alexandre Demoule, Julien Mayaux, Martin Dres, Elise Morawiec, Maxens Decalvele, Suela Demiri, Morgane Faure, Clémence Marios, Maxime Mallet, Marie Amélie Ordon, Laura Morizot, Marie Cantien, François Pousset, Florent Poirson, Yves Cohen, Laurent Argaud, Martin Cour, Laurent Bitker, Marie Simon, Romain Hernu, Thomas Baudry, Sylvie De La Salle, Adrien Robine, Nicholas Sedillot, Xavier Tchenio, Camille Bouisse, Sylvie Roux, Fabienne Tamion, Steven Grangé, Dorothée Carpentier, Guillaume Chevrel, Luis Ensenyat-Martin, Sophie Marque, Jean-Pierre Quenot, Pascal Andreu, Auguste Dargent, Audrey Large, Nicolas Chudeau, Mickael Landais, Benoit Derrien, Jean Christophe Callahan, Christophe Guitton, Charlène Le Moal, Alain Robert, Karim Asehnoune, Raphaël Cinotti, Nicolas Grillot, Dominique Demeure, Christophe Vinsonneau, Imen Rahmani, Mehdi Marzouk, Thibault Dekeyser, Caroline Sejourne, Mélanie Verlay, Fabienne Thevenin, Lucie Delecolle, Didier Thevenin, Bertrand Souweine, Elisabeth Coupez, Mireille Adda, Jean-Pierre Eraldi, Antoine Marchalot, Nicolas De Prost, Armand Mekontso Dessap, Keyvan Razazi, Ferhat Meziani, Julie Boisrame-Helms, Raphael Clere-Jehl, Xavier Delabranche, Christine Kummerlen, Hamid Merdji, Alexandra Monnier, Yannick Rabouel, Hassene Rahmani, Hayat Allam, Samir Chenaf, Vincenta Franja, Bertrand Pons, Michel Carles, Frédéric Martino, Régine Richard, Benjamin Zuber, Guillaume Lacave, Karim Lakhal, Bertrand Rozec, Hoa Dang Van, Éric Boulet, Fouad Fadel, Cedric Cleophax, Nicolas Dufour, Caroline Grant, Marie Thuong, Jean Reignier, Emmanuel Canet, Laurent Nicolet, Thierry Boulain, Mai-Anh Nay, Dalila Benzekri, François Barbier, Anne Bretagnol, Toufik Kamel, Armelle Mathonnet, Grégoire Muller, Marie Skarzynski, Julie Rossi, Amandine Pradet, Sandra Dos Santos, Aurore Guery, Lucie Muller, Luis Felix, Julien Bohé, Guillaume Thiéry, Nadia Aissaoui, Damien Vimpere, Morgane Commeureuc, Jean-Luc Diehl, Emmanuel Guerot, Orfeas Liangos, Monika Wittig, Alexander Zarbock, Mira Küllmar, Thomas van Waegeningh, Nadine Rosenow, Kathy Brickell, Peter Doran, Patrick T. Murray, Giovanni Landoni, Rosalba Lembo, Alberto Zangrillo, Giacomo Monti, Margherita Tozzi, Matteo Marzaroli, Gaetano Lombardi, Gianluca Paternoster, Michelangelo Vitiello, Shay McGuinness, Rachael Parke, Magdalena Butler, Eileen Gilder, Keri-Anne Cowdrey, Samantha Wallace, Jane Hallion, Melissa Woolett, Philippa Neal, Karina Duffy, Stephanie Long, Colin McArthur, Catherine Simmonds, Yan Chen, Rachael McConnochie, Lynette Newby, David Knight, Seton Henderson, Jan Mehrtens, Stacey Morgan, Anna Morris, Kymbalee Vander Hayden, Tara Burke, Matthew Bailey, Ross Freebairn, Lesley Chadwick, Penelope Park, Christine Rolls, Liz Thomas, Ulrike Buehner, Erin Williams, Jonathan Albrett, Simon Kirkham, Carolyn Jackson, Troy Browne, Jennifer Goodson, David Jackson, James Houghton, Owen Callender, Vicki Higson, Owen Keet, Clive Dominy, Paul Young, Anna Hunt, Harriet Judd, Cassie Lawrence, Shaanti Olatunji, Yvonne Robertson, Charlotte Latimer-Bell, Deborah Hendry, Agnes Mckay-Vucago, Nina Beehre, Eden Lesona, Leanlove Navarra, Chelsea Robinson, Ryan Jang, Andrea Junge, Bridget Lambert, Michel Thibault, Philippe Eckert, Sébastien Kissling, Erietta Polychronopoulos, Elettra Poli, Marco Altarelli, Madeleine Schnorf, Samia Abed Mallaird, Claudia Heidegger, Aurelie Perret, Philippe Montillier, Frederic Sangla, Seigenthaller Neils, Aude De Watteville, Mandeep-Kaur Phull, Aparna George, Nauman Hussain, Tatiana Pogreban, Steve Lobaz, Alison Daniels, Mishell Cunningham, Deborah Kerr, Alice Nicholson, Pradeep Shanmugasundaram, Judith Abrams, Katarina Manso, Geraldine Hambrook, Elizabeth McKerrow, Juvy Salva, Stephen Foulkes, Matthew Wise, Matt Morgan, Jenny Brooks, Jade Cole, Tracy Michelle Davies, Helen Hill, Emma Thomas, Marcela Vizcaychipi, Behrad Baharlo, Jaime Carungcong, Patricia Costa, Laura Martins, Ritoo Kapoor, Tracy Hazelton, Angela Moon, Janine Musselwhite, Ben Shelley, Philip McCall, Gill Arbane, Aneta Bociek, Martina Marotti, Rosario Lim, Sara Campos, Neus Grau Novellas, Armando Cennamo, Andrew Slack, Duncan Wyncoll, Luigi Camporota, Simon Sparkes, Rosalinde Tilley, Austin Rattray, Gayle Moreland, Jane Duffy, Elizabeth McGonigal, Philip Hopkins, Clare Finney, John Smith, Harriet Noble, Hayley Watson, Claire-Louise Harris, Emma Clarey, Eleanor Corcoran, James Beck, Clare Howcroft, Nora Youngs, Elizabeth Wilby, Bethan Ogg, Adam Wolverson, Sandra Lee, Susie Butler, Maryanne Okubanjo, Julia Hindle, Ingeborg Welters, Karen Williams, Emily Johnson, Julie Patrick-Heselton, David Shaw, Victoria Waugh, Richard Stewart, Esther Mwaura, Lynn Wren, Louise Mew, Sara-Beth Sutherland, Jane Adderley, Jim Ruddy, Margaret Harkins, Callum Kaye, Teresa Scott, Wendy Mitchell, Felicity Anderson, Fiona Willox, Vijay Jagannathan, Michele Clark, Sarah Purv, Andrew Sharman, Megan Meredith, Lucy Ryan, Louise Conner, Cecilia Peters, Dan Harvey, Ashraf Roshdy, Amy Collins, Malcolm Sim, Steven Henderson, Nigel Chee, Sally Pitts, Katie Bowman, Maria Dilawershah, Luke Vamplew, Elizabeth Howe, Paula Rogers, Clara Hernandez, Clara Prendergast, Jane Benton, Alex Rosenberg, Lui G. Forni, Alice Grant, Paula Carvelli, Ajay Raithatha, Sarah Bird, Max Richardson, Matthew Needham, Claire Hirst, Jonathan Ball, Susannah Leaver, Luisa Howlett, Carlos Castro Delgado, Sarah Farnell-Ward, Helen Farrah, Geraldine Gray, Gipsy Joseph, Francesca Robinson, Ascanio Tridente, Clare Harrop, Karen Shuker, Derek McLaughlan, Judith Ramsey, Sharon Meehan, Bernd Oliver Rose, Rosie Reece-Anthony, Babita Gurung, Tony Whitehouse, Catherine Snelson, Tonny Veenith, Andy Johnston, Lauren Cooper, Ron Carrera, Karen Ellis, Emma Fellows, Samanth Harkett, Colin Bergin, Elaine Spruce, Liesl Despy, Stephanie Goundry, Natalie Dooley, Tracy Mason, Amy Clark, Gemma Dignam, Geraldine Ward, Ben Attwood, Penny Parsons, Sophie Mason, Michael Margarson, Jenny Lord, Philip McGlone, Luke E. Hodgson, Indra Chadbourn, Raquel Gomez, Jordi Margalef, Rinus Pretorius, Alexandra Hamshere, Joseph Carter, Hazel Cahill, Lia Grainger, Kate Howard, Greg Forshaw, Zoe Guy, Kianoush B. Kashani, Robert C. Albright, Amy Amsbaugh, Anita Stoltenberg, Alexander S. Niven, Matthew Lynch, AnnMarie O'Mara, Syed Naeem, Sairah Sharif, Joyce McKenney Goulart, Ashita Tolwani, Claretha Lyas, Laura Latta, Azra Bihorac, Haleh Hashemighouchani, Philip Efron, Matthew Ruppert, Julie Cupka, Sean Kiley, Joshua Carson, Peggy White, George Omalay, Sherry Brown, Laura Velez, Alina Marceron, Javier A. Neyra, Juan Carlos Aycinena, Madona Elias, Victor M. Ortiz-Soriano, Caroline Hauschild, and Robert Dorfman
Subjects: Renal Replacement Therapy, Pulmonary and Respiratory Medicine, Critical Illness, Medicine and Health Sciences, Humans, Acute Kidney Injury
Published: 2022
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16. The Effects of RBC Concentration on the Viscoelastic Assessment of Coagulation*

Author: Jonathan Ball
Subjects: Critical Care and Intensive Care Medicine
Published: 2023
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17. Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Author: S. Cotton, M.P. McHugh, R. Dewar, J.G. Haas, K. Templeton, Samuel C. Robson, Thomas R. Connor, Nicholas J. Loman, Tanya Golubchik, Rocio T. Martinez Nunez, David Bonsall, Andrew Rambaut, Luke B. Snell, Rich Livett, Catherine Ludden, Sally Corden, Eleni Nastouli, Gaia Nebbia, Ian Johnston, Jacqui A. Prieto, Kordo Saeed, David K. Jackson, Catherine Houlihan, Dan Frampton, William L. Hamilton, Adam A. Witney, Giselda Bucca, Cassie F. Pope, Catherine Moore, Emma C. Thomson, Teresa Cutino-Moguel, Ewan M. Harrison, Colin P. Smith, Fiona Rogan, Shaun M. Beckwith, Abigail Murray, Dawn Singleton, Kirstine Eastick, Liz A. Sheridan, Paul Randell, Leigh M. Jackson, Cristina V. Ariani, Sónia Gonçalves, Derek J. Fairley, Matthew W. Loose, Joanne Watkins, Samuel Moses, Sam Nicholls, Matthew Bull, Roberto Amato, Darren L. Smith, David M. Aanensen, Jeffrey C. Barrett, Beatrix Kele, Dinesh Aggarwal, James G. Shepherd, Martin D. Curran, Surendra Parmar, Matthew D. Parker, Catryn Williams, Sharon Glaysher, Anthony P. Underwood, Matthew Bashton, Nicole Pacchiarini, Katie F. Loveson, Matthew Byott, Alessandro M. Carabelli, Kate E. Templeton, Sharon J. Peacock, Thushan I. de Silva, Dennis Wang, Cordelia F. Langford, John Sillitoe, Rory N. Gunson, Simon Cottrell, Justin O’Grady, Dominic Kwiatkowski, Patrick J. Lillie, Nicholas Cortes, Nathan Moore, Claire Thomas, Phillipa J. Burns, Tabitha W. Mahungu, Steven Liggett, Angela H. Beckett, Matthew TG. Holden, Lisa J. Levett, Husam Osman, Mohammed O. Hassan-Ibrahim, David A. Simpson, Meera Chand, Ravi K. Gupta, Alistair C. Darby, Steve Paterson, Oliver G. Pybus, Erik M. Volz, Daniela de Angelis, David L. Robertson, Andrew J. Page, Inigo Martincorena, Louise Aigrain, Andrew R. Bassett, Nick Wong, Yusri Taha, Michelle J. Erkiert, Michael H. Spencer Chapman, Rebecca Dewar, Martin P. McHugh, Siddharth Mookerjee, Stephen Aplin, Matthew Harvey, Thea Sass, Helen Umpleby, Helen Wheeler, James P. McKenna, Ben Warne, Joshua F. Taylor, Yasmin Chaudhry, Rhys Izuagbe, Aminu S. Jahun, Gregory R. Young, Claire McMurray, Clare M. McCann, Andrew Nelson, Scott Elliott, Hannah Lowe, Anna Price, Matthew R. Crown, Sara Rey, Sunando Roy, Ben Temperton, Sharif Shaaban, Andrew R. Hesketh, Kenneth G. Laing, Irene M. Monahan, Judith Heaney, Emanuela Pelosi, Siona Silviera, Eleri Wilson-Davies, Helen Fryer, Helen Adams, Louis du Plessis, Rob Johnson, William T. Harvey, Joseph Hughes, Richard J. Orton, Lewis G. Spurgin, Yann Bourgeois, Chris Ruis, Áine O'Toole, Marina Gourtovaia, Theo Sanderson, Christophe Fraser, Jonathan Edgeworth, Judith Breuer, Stephen L. Michell, John A. Todd, Michaela John, David Buck, Kavitha Gajee, Gemma L. Kay, David Heyburn, Themoula Charalampous, Adela Alcolea-Medina, Katie Kitchman, Alan McNal, David T. Pritch, Samir Dervisevic, Peter Muir, Esther Robinson, Barry B. Vipond, Newara A. Ramadan, Christopher Jeanes, Danni Weldon, Jana Catalan, Neil Jones, Ana da Silva Filipe, Chris Williams, Marc Fuchs, Julia Miskelly, Aaron R. Jeffries, Karen Oliver, Naomi R. Park, Amy Ash, Cherian Koshy, Magdalena Barrow, Sarah L. Buchan, Anna Mantzouratou, Gemma Clark, Christopher W. Holmes, Sharon Campbell, Thomas Davis, Ngee Keong Tan, Julianne R. Brown, Kathryn A. Harris, Stephen P. Kidd, Paul R. Grant, Li Xu-McCrae, Alison Cox, Pinglawathee Madona, Marcus Pond, Paul A. Randell, Karen T. Withell, Cheryl Williams, Clive Graham, Rebecca Denton-Smith, Emma Swindells, Robyn Turnbull, Tim J. Sloan, Andrew Bosworth, Stephanie Hutchings, Hannah M. Pymont, Anna Casey, Liz Ratcliffe, Christopher R. Jones, Bridget A. Knight, Tanzina Haque, Jennifer Hart, Dianne Irish-Tavares, Eric Witele, Craig Mower, Louisa K. Watson DipHE, Jennifer Collins, Gary Eltringham, Dorian Crudgington, Ben Macklin, Miren Iturriza-Gomara, Anita O. Lucaci, Patrick C. McClure, Matthew Carlile, Nadine Holmes, Christopher Moore, Nathaniel Storey, Stefan Rooke, Gonzalo Yebra, Noel Craine, Malorie Perry, Nabil-Fareed Alikhan, Stephen Bridgett, Kate F. Cook, Christopher Fearn, Salman Goudarzi, Ronan A. Lyons, Thomas Williams, Sam T. Haldenby, Jillian Durham, Steven Leonard, Robert M. Davies, Rahul Batra, Beth Blane, Moira J. Spyer, Perminder Smith, Mehmet Yavus, Rachel J. Williams, Adhyana IK. Mahanama, Buddhini Samaraweera, Sophia T. Girgis, Samantha E. Hansford, Angie Green, Charlotte Beaver, Katherine L. Bellis, Matthew J. Dorman, Sally Kay, Liam Prestwood, Shavanthi Rajatileka, Joshua Quick, Radoslaw Poplawski, Nicola Reynolds, Andrew Mack, Arthur Morriss, Thomas Whalley, Bindi Patel, Iliana Georgana, Myra Hosmillo, Malte L. Pinckert, Joanne Stockton, John H. Henderson, Amy Hollis, William Stanley, Wen C. Yew, Richard Myers, Alicia Thornton, Alexander Adams, Tara Annett, Hibo Asad, Alec Birchley, Jason Coombes, Johnathan M. Evans, Laia Fina, Bree Gatica-Wilcox, Lauren Gilbert, Lee Graham, Jessica Hey, Ember Hilvers, Sophie Jones, Hannah Jones, Sara Kumziene-Summerhayes, Caoimhe McKerr, Jessica Powell, Georgia Pugh, Sarah Taylor, Alexander J. Trotter, Charlotte A. Williams, Leanne M. Kermack, Benjamin H. Foulkes, Marta Gallis, Hailey R. Hornsby, Stavroula F. Louka, Manoj Pohare, Paige Wolverson, Peijun Zhang, George MacIntyre-Cockett, Amy Trebes, Robin J. Moll, Lynne Ferguson, Emily J. Goldstein, Alasdair Maclean, Rachael Tomb, Igor Starinskij, Laura Thomson, Joel Southgate, Moritz UG. Kraemer, Jayna Raghwani, Alex E. Zarebski, Olivia Boyd, Lily Geidelberg, Chris J. Illingworth, Chris Jackson, David Pascall, Sreenu Vattipally, Timothy M. Freeman, Sharon N. Hsu, Benjamin B. Lindsey, Keith James, Kevin Lewis, Gerry Tonkin-Hill, Jaime M. Tovar-Corona, MacGregor Cox, Khalil Abudahab, Mirko Menegazzo, Ben EW. Taylor, Corin A. Yeats, Afrida Mukaddas, Derek W. Wright, Leonardo de Oliveira Martins, Rachel Colquhoun, Verity Hill, Ben Jackson, J.T. McCrone, Nathan Medd, Emily Scher, Jon-Paul Keatley, Tanya Curran, Sian Morgan, Patrick Maxwell, Ken Smith, Sahar Eldirdiri, Anita Kenyon, Alison H. Holmes, James R. Price, Tim Wyatt, Alison E. Mather, Timofey Skvortsov, John A. Hartley, Martyn Guest, Christine Kitchen, Ian Merrick, Robert Munn, Beatrice Bertolusso, Jessica Lynch, Gabrielle Vernet, Stuart Kirk, Elizabeth Wastnedge, Rachael Stanley, Giles Idle, Declan T. Bradley, Nicholas F. Killough, Jennifer Poyner, Matilde Mori, Owen Jones, Victoria Wright, Ellena Brooks, Carol M. Churcher, Laia Delgado Callico, Mireille Fragakis, Katerina Galai, Andrew Jermy, Sarah Judges, Anna Markov, Georgina M. McManus, Kim S. Smith, Peter MD. Thomas-McEwen, Elaine Westwick, Stephen W. Attwood, Frances Bolt, Alisha Davies, Elen De Lacy, Fatima Downing, Sue Edwards, Lizzie Meadows, Sarah Jeremiah, Nikki Smith, Luke Foulser, Amita Patel, Louise Berry, Tim Boswell, Vicki M. Fleming, Hannah C. Howson-Wells, Amelia Joseph, Manjinder Khakh, Michelle M. Lister, Paul W. Bird, Karlie Fallon, Thomas Helmer, Claire L. McMurray, Mina Odedra, Jessica Shaw, Julian W. Tang, Nicholas J. Willford, Victoria Blakey, Veena Raviprakash, Nicola Sheriff, Lesley-Anne Williams, Theresa Feltwell, Luke Bedford, James S. Cargill, Warwick Hughes, Jonathan Moore, Susanne Stonehouse, Laura Atkinson, Jack CD. Lee, Divya Shah, Natasha Ohemeng-Kumi, John Ramble, Jasveen Sehmi, Rebecca Williams, Wendy Chatterton, Monika Pusok, William Everson, Anibolina Castigador, Emily Macnaughton, Kate El Bouzidi, Temi Lampejo, Malur Sudhanva, Cassie Breen, Graciela Sluga, Shazaad SY. Ahmad, Ryan P. George, Nicholas W. Machin, Debbie Binns, Victoria James, Rachel Blacow, Lindsay Coupland, Louise Smith, Edward Barton, Debra Padgett, Garren Scott, Aidan Cross, Mariyam Mirfenderesky, Jane Greenaway, Kevin Cole, Phillip Clarke, Nichola Duckworth, Sarah Walsh, Kelly Bicknell, Robert Impey, Sarah Wyllie, Richard Hopes, Chloe Bishop, Vicki Chalker, Ian Harrison, Laura Gifford, Zoltan Molnar, Cressida Auckland, Cariad Evans, Kate Johnson, David G. Partridge, Mohammad Raza, Paul Baker, Stephen Bonner, Sarah Essex, Leanne J. Murray, Andrew I. Lawton, Shirelle Burton-Fanning, Brendan AI. Payne, Sheila Waugh, Andrea N. Gomes, Maimuna Kimuli, Darren R. Murray, Paula Ashfield, Donald Dobie, Fiona Ashford, Angus Best, Liam Crawford, Nicola Cumley, Megan Mayhew, Oliver Megram, Jeremy Mirza, Emma Moles-Garcia, Benita Percival, Megan Driscoll, Leah Ensell, Helen L. Lowe, Laurentiu Maftei, Matteo Mondani, Nicola J. Chaloner, Benjamin J. Cogger, Lisa J. Easton, Hannah Huckson, Jonathan Lewis, Sarah Lowdon, Cassandra S. Malone, Florence Munemo, Manasa Mutingwende, Roberto Nicodemi, Olga Podplomyk FD, Thomas Somassa, Andrew Beggs, Alex Richter, Claire Cormie, Joana Dias, Sally Forrest, Ellen E. Higginson, Mailis Maes, Jamie Young, Rose K. Davidson, Kathryn A. Jackson, Alexander J. Keeley, Jonathan Ball, Timothy Byaruhanga, Joseph G. Chappell, Jayasree Dey, Jack D. Hill, Emily J. Park, Arezou Fanaie, Rachel A. Hilson, Geraldine Yaze, Stephanie Lo, Safiah Afifi, Robert Beer, Joshua Maksimovic, Kathryn McCluggage, Karla Spellman, Catherine Bresner, William Fuller, Angela Marchbank, Trudy Workma, Ekaterina Shelest, Johnny Debebe, Fei Sang, Sarah Francois, Bernardo Gutierrez, Tetyana I. Vasylyeva, Flavia Flaviani, Manon Ragonnet-Cronin, Katherine L. Smollett, Alice Broos, Daniel Mair, Jenna Nichols, Kyriaki Nomikou, Lily Tong, Ioulia Tsatsani, Sarah O'Brien, Steven Rushton, Roy Sanderson, Jon Perkins, Seb Cotton, Abbie Gallagher, Elias Allara, Clare Pearson, David Bibby, Gavin Dabrer, Nicholas Ellaby, Eileen Gallagher, Jonathan Hubb, Angie Lackenby, David Lee, Nikos Manesis, Tamyo Mbisa, Steven Platt, Katherine A. Twohig, Mari Morgan, Alp Aydin, David J. Baker, Ebenezer Foster-Nyarko, Sophie J. Prosolek, Steven Rudder, Chris Baxter, Sílvia F. Carvalho, Deborah Lavin, Arun Mariappan, Clara Radulescu, Aditi Singh, Miao Tang, Helen Morcrette, Nadua Bayzid, Marius Cotic, Carlos E. Balcazar, Michael D. Gallagher, Daniel Maloney, Thomas D. Stanton, Kathleen A. Williamson, Robin Manley, Michelle L. Michelsen, Christine M. Sambles, David J. Studholme, Joanna Warwick-Dugdale, Richard Eccles, Matthew Gemmell, Richard Gregory, Margaret Hughes, Charlotte Nelson, Lucille Rainbow, Edith E. Vamos, Hermione J. Webster, Mark Whitehead, Claudia Wierzbicki, Adrienn Angyal, Luke R. Green, Max Whiteley, Emma Betteridge, Iraad F. Bronner, Ben W. Farr, Scott Goodwin, Stefanie V. Lensing, Shane A. McCarthy, Michael A. Quail, Diana Rajan, Nicholas M. Redshaw, Carol Scott, Lesley Shirley, Scott AJ. Thurston, Will Rowe, Amy Gaskin, Thanh Le-Viet, James Bonfield, Jennifier Liddle, Andrew Whitwham, University of St Andrews. School of Medicine, University of St Andrews. Infection and Global Health Division, and Apollo - University of Cambridge Repository
Subjects: Microbiology (medical), MCC, Introduction, SARS-CoV-2, NDAS, COVID-19, Care homes, General Medicine, NIS, Patient Discharge, Hospitals, Hospitalization, Infectious Diseases, SDG 3 - Good Health and Well-being, RA0421, RA0421 Public health. Hygiene. Preventive Medicine, Humans, Hospital discharge
Abstract: COG-UK is supported by funding from the MRC part of UK Research & Innovation, the National Institute of Health Research (Grant code MC_PC_19027), and Genome Research Limited, operating as the Welcome Sanger Institute. Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine. Publisher PDF
Published: 2023

18. Understanding and addressing vaccine hesitancy in the context of COVID-19: development of a digital intervention

Author: Caroline Barker, Kavita Vedhara, Joanne R Morling, Ru Jia, Trudie Chalder, Tricia M. McKeever, Robert Bennett, Jonathan Ball, Lindy G. Durrant, Holly Knight, Katherine Bradbury, Kieran Ayling, Katherine Baker, and Tony Avery
Subjects: Vaccines, education.field_of_study, Medical education, COVID-19 Vaccines, SARS-CoV-2, Vaccination, Population, Public Health, Environmental and Occupational Health, Motivational interviewing, Psychological intervention, COVID-19, Context (language use), General Medicine, motivational interviewing, Systematic review, vaccine hesitancy, Humans, Vaccination Hesitancy, Thematic analysis, Public engagement, education, Psychology, intervention, Original Research
Abstract: Objectives: Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) was identified in late 2019, spreading to over 200 countries and resulting in almost two million deaths worldwide. The emergence of safe and effective vaccines provides a route out of the pandemic, with vaccination uptake of 75–90% needed to achieve population protection. Vaccine hesitancy is problematic for vaccine rollout; global reports suggest only 73% of the population may agree to being vaccinated. As a result, there is an urgent need to develop equitable and accessible interventions to address vaccine hesitancy at the population level. Study Design & Method: we report the development of a scalable digital intervention seeking to address COVID-19 vaccine hesitancy and enhance uptake of COVID-19 vaccines in the United Kingdom. Guided by motivational interviewing (MI) principles, the intervention includes a series of therapeutic dialogues addressing 10 key concerns of vaccine-hesitant individuals. Development of the intervention occurred linearly across four stages. During stage 1, we identified common reasons for COVID-19 vaccine hesitancy through analysis of existing survey data, a rapid systematic literature review, and public engagement workshops. Stage 2 comprised qualitative interviews with medical, immunological, and public health experts. Rapid content and thematic analysis of the data provided evidence-based responses to common vaccine concerns. Stage 3 involved the development of therapeutic dialogues through workshops with psychological and digital behaviour change experts. Dialogues were developed to address concerns using MI principles, including embracing resistance and supporting self-efficacy. Finally, stage 4 involved digitisation of the dialogues and pilot testing with members of the public. Discussion: the digital intervention provides an evidence-based approach to addressing vaccine hesitancy through MI principles. The dialogues are user-selected, allowing exploration of relevant issues associated with hesitancy in a non-judgmental context. The text-based content and digital format allow for rapid modification to changing information and scalability for wider dissemination.
Published: 2021
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19. Assessing the Potential of using Sentinel-1 and 2 or high-resolution aerial imagery data with Machine Learning and Data Science Techniques to Model Peatland Restoration Progress – a Northern Scotland case study

Author: Jonathan Ball, Alessandro Gimona, Neil Cowie, Mark Hancock, Daniela Klein, Gillian Donaldson-Selby, and Rebekka R.E. Artz
Subjects: General Earth and Planetary Sciences
Abstract: Peatland is a globally important store of carbon. Peatland restoration efforts are being increasingly undertaken yet effective monitoring of landscape-scale restoration projects has been limited. A particular gap in our understanding is the length of time required before a site reaches the target state. To address this, a classification model based on remote sensing data was developed for a peatland restoration area on blanket bog in northern Scotland, UK, to evaluate whether post-restoration trajectories followed predictable trends over time. The model was trained against a chronosequence of sites within a 20 × 10 km study area that are being restored following drainage and intensive non-native afforestation. Two versions of the model were created to compare the accuracy obtainable from the suite of Sentinel-2 satellite data versus sub-metre resolution aerial imagery from GetMapping (RGB and IR). The Sentinel-2 based model greatly outperformed the aerial imagery-based model. Adding surface slope to the classification did not significantly improve the accuracy of prediction. Prediction of starting and target land covers was very robust, and both the most recent and oldest restoration sites were well predicted spatially. The main uncertainties in the model were within sites of intermediate restoration age, and sites which underwent additional treatments after the initial restoration. Using standard vegetation and wetness indices as indicators, it was possible to track the progression of areas that had been felled and rewetted towards the spectral signal of the control blanket bog locations. A further study examined the use of multiple years of satellite data (2015–2021) and including Sentinel-1 SAR imagery, and confirmed the findings obtained with only a single climatically average year, and furthermore examined the efficacy of different restoration methods. We observed consistent trends of restoration sites beginning to resemble the target hydrologically and ecologically functional blanket bog state after 10–20 years post intervention.
Published: 2023
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20. Impact of the Calder's Wharf development on Docklands Light Railway tunnels, London, UK

Author: Nicholas John Langdon, Richard Jonathan Ball, and David Peter Giles
Subjects: Engineering, Wharf, business.industry, Redevelopment, Block (telecommunications), Earth and Planetary Sciences (miscellaneous), Forensic engineering, Geotechnical Engineering and Engineering Geology, business, Ground movement
Abstract: This paper describes the redevelopment of Calder's Wharf, London, a four-storey block of residential units. As part of this redevelopment a detailed finite-element and ground movement analysis was ...
Published: 2021
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21. 186 A Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Trial of Efficacy and Safety of Riluzole in Acute Spinal Cord Injury Study (RISCIS)

Author: Michael G. Fehlings, Ali Moghaddamjou, James S. Harrop, Ralph Stanford, Jonathan Ball, Bizhan Aarabi, Brian Freeman, James D. Guest, Shekar N. Kurpad, James M. Schuster, Ahmad Nassr, Karl M. Schmitt, Jefferson R. Wilson, Darrel S. Brodke, Faiz U. Ahmad, Albert Yee, Zack Ray, Nathaniel P. Brooks, Jason Wilson, Branko Kopjar, and Paul M. Arnold
Subjects: Surgery, Neurology (clinical)
Published: 2023
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22. Prophylactic Treatment of COVID-19 in Care Homes Trial (PROTECT-CH)

Author: Philip M Bath, Jonathan Ball, Matthew Boyd, Heather Gage, Matthew Glover, Maureen Godfrey, Bruce Guthrie, Jonathan Hewitt, Robert Howard, Thomas Jaki, Edmund Juszczak, Daniel Lasserson, Paul Leighton, Val Leyland, Wei Shen Lim, Pip Logan, Garry Meakin, Alan Montgomery, Reuben Ogollah, Peter Passmore, Philip Quinlan, Caroline Rick, Simon Royal, Susan D Shenkin, Clare Upton, and Adam L Gordon
Abstract: BackgroundCoronavirus disease 2019 (COVID-19) is associated with significant mortality and morbidity in care homes. Novel or repurposed antiviral drugs may reduce infection and disease severity through reducing viral replication and inflammation.ObjectiveTo compare the safety and efficacy of antiviral agents (ciclesonide, niclosamide) for preventing SARS-CoV-2 infection and COVID-19 severity in care home residents.DesignCluster-randomised open-label blinded endpoint platform clinical trial testing antiviral agents in a post-exposure prophylaxis paradigm.SettingCare homes across all four United Kingdom member countries.ParticipantsCare home residents 65 years of age or older.InterventionsCare homes were to be allocated at random by computer to 42 days of antiviral agent plus standard care versus standard of care and followed for 60 days after randomisation.Main outcome measuresThe primary four-level ordered categorical outcome with participants classified according to the most serious of all-cause mortality, all-cause hospitalisation, SARS-CoV-2 infection and no infection. Analysis using ordinal logistic regression was by intention to treat. Other outcomes included the components of the primary outcome and transmission.ResultsDelays in contracting between NIHR and the manufacturers of potential antiviral agents significantly delayed any potential start date. Having set up the trial (protocol, approvals, insurance, website, database, routine data algorithms, training materials), the trial was stopped in September 2021 prior to contracting of care homes and general practitioners in view of the success of vaccination in care homes with significantly reduced infections, hospitalisations and deaths. As a result, the sample size target (based on COVID-19 rates and deaths occurring in February-June 2020) became unfeasible.LimitationsCare home residents were not approached about the trial and so were not consented and did not receive treatment. Hence, the feasibility of screening, consent, treatment and data acquisition, and potential benefit of post exposure prophylaxis were never tested. Further, contracting between the University of Nottingham and the PIs, GPs and care homes was not completed, so the feasibility of contracting with all the different groups at the scale needed was not tested.ConclusionsThe role of post exposure prophylaxis of COVID-19 in care home residents was not tested because of changes in COVID-19 incidence, prevalence and virulence as a consequence of the vaccination programme that rendered the study unfeasible. Significant progress was made in describing and developing the infrastructure necessary for a large scale Clinical Trial of Investigational Medicinal Products in care homes in all four UK nations.Future workThe role of post-exposure prophylaxis of COVID-19 in care home residents remains to be defined. Significant logistical barriers to conducting research in care homes during a pandemic need to be removed before such studies are possible in the required short timescale.
Published: 2022
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23. Open versus percutaneous tracheostomy in COVID-19: a multicentre comparison and recommendation for future resource utilisation

Author: Jonathan Ball, Ricard Simo, Stephen Tricklebank, Elizabeth Yeung, Arun Takhar, Phillip Hopkins, K. Fan, Pavol Surda, W. Khaliq, Aleix Rovira, Ram Kumar, Deborah Dawson, Asit Arora, Stephen Whebell, Joe Zhang, and Imran Ahmed
Subjects: Adult, medicine.medical_specialty, Percutaneous, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, 03 medical and health sciences, 0302 clinical medicine, Mechanical ventilation, Tracheostomy, London, medicine, Humans, 030223 otorhinolaryngology, Pandemics, Retrospective Studies, Pneumonitis, business.industry, SARS-CoV-2, COVID-19, General Medicine, medicine.disease, Respiration, Artificial, Miscellaneous, Percutaneous tracheostomy, Otorhinolaryngology, 030220 oncology & carcinogenesis, Emergency medicine, Surgical tracheostomy, Neurosurgery, business, Vascular Surgical Procedures, Cohort study
Abstract: Purpose The COVID-19 pandemic placed an unprecedented demand on critical care services for the provision of mechanical ventilation. Tracheostomy formation facilitates liberation from mechanical ventilation with advantages for both the patient and wider critical care resource, and can be performed using both percutaneous dilatational and surgical techniques. We compared outcomes in those patients undergoing percutaneous dilatational tracheostomy to those undergoing surgical tracheostomy and make recommendations for provision of tracheostomy services in any future surge. Methods Multicentre multidisciplinary retrospective observational cohort study including 201 patients with COVID-19 pneumonitis admitted to an ICU in one of five NHS Trusts within the South London Adult Critical Care Network who required mechanical ventilation and subsequent tracheostomy. Results Percutaneous dilatational tracheostomy was performed in 124 (62%) of patients, and surgical tracheostomy in 77 (38%) of patients. There was no difference between percutaneous dilatational tracheostomy and surgical tracheostomy in either the rate of peri-operative complications (16.9 vs. 22.1%, p = 0.46), median [IQR(range)] time to decannulation [19.0 (15.0–30.2 (5.0–65.0)] vs. 21.0 [15.5–36.0 (5.0–70.0) days] or mortality (13.7% vs. 15.6%, p = 0.84). Of the 172 patients that were alive at follow-up, two remained ventilated and 163 were decannulated. Conclusion In patients with COVID-19 pneumonitis that require tracheostomy to facilitate weaning from mechanical ventilation, there was no difference in outcomes between those patients that had percutaneous dilatational tracheostomy compared with those that had surgical tracheostomy. Planning for future surges in COVID-19-related critical care demands should utilise all available resource and expertise. Supplementary Information The online version contains supplementary material available at 10.1007/s00405-020-06597-1.
Published: 2021

24. Human Parainfluenza 2 & 4: clinical and genetic epidemiology in the UK, 2013-2017, reveals distinct disease features and co-circulating genomic subtypes

Author: Akhil Chellapuri, Matthew Smitheman, Joseph Chappell, Gemma Clark, Hannah Howson-Wells, Louise Berry, Jonathan Ball, William Irving, Alexander Tarr, and Charles McClure
Abstract: Background Human Parainfluenza viruses (HPIV) comprise of four members of the genetically distinct genera of Respirovirus (HPIV1&3) and Orthorubulavirus (HPIV2&4), causing significant upper and lower respiratory tract infections worldwide, particularly in children. However, despite frequent molecular diagnosis, they are frequently considered collectively or with HPIV4 overlooked entirely. We therefore investigated clinical and viral epidemiological distinctions of the relatively less prevalent Orthorubulaviruses HPIV2&4 at a regional UK hospital across four autumn/winter epidemic seasons. Methods A retrospective audit of clinical features of all HPIV2 or HPIV4 RT-PCR-positive patients, diagnosed between 1st September 2013 and 12th April 2017 was undertaken, alongside sequencing of viral genome fragments in a representative subset of samples. Results Infection was observed across all age groups, but predominantly in children under nine and adults over 40, with almost twice as many HPIV4 as HPIV2 cases. Fever, abnormal haematology, elevated C-reactive protein and hospital admission were more frequently seen in HPIV2 than HPIV4 infection. Each of the four seasonal peaks of either HPIV2, HPIV4 or both, closely matched that of RSV, occurring in November and December and preceding that of Influenza A. A subset of viruses were partially sequenced, indicating co-circulation of multiple subtypes of both HPIV2&4, but with little variation between each epidemic season or from limited global reference sequences. Conclusions Despite being closest known genetic relatives, our data indicates a potential difference in associated disease between HPIV2 and HPIV4, with more hospitalisation seen in HPIV2 mono-infected individuals, but a greater overall number of HPIV4 cases.
Published: 2022
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25. Attempting to Bridge the Gap: Comparison of Clinical Characteristics, Ultrasound, and Final Surgical Pathology of Emergency Department vs Outpatient Clinic Patients Undergoing Cholecystectomy

Author: Whitney T Martin, Katherine B Snyder, Kenneth Stewart, Zoona Sarwar, William Starr, Anna Grady, Jonathan Ball, Alexander R Raines, and Alisa M Cross
Subjects: Surgery
Published: 2022
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26. The Politics of Knives

Author: Jonathan Ball
Published: 2012

27. Frailty is associated with long-term outcome in patients with sepsis who are over 80 years old: results from an observational study in 241 European ICUs

Author: Nigel White, Jenny Lord, Angela Prado Mira, Ala Khaled, Hubert Hymczak, Kristian Strand, Lenneke E M Haas, Mirosław Czuczwar, Lettie van den Berg, Pieter De Buysscher, Małgorzata Lipińska-Gediga, Simon Dubler, Michel Djibré, Ignacio Martin-Loeches, Georgina Randell, Diederik Gommers, Jose Maia, Patrick Meybohm, Wojciech Gola, Lina De Geer, Tom Lawton, Jonas Juul Pedersen, Isabel Amorim Ferreira, Kristina Fuest, Marcus Franz, McDonald Mupudzi, Kounougeri Aikaterini, Zoi Aidoni, Anastasia Koutsikou, Joakim Sivik, Hans Flaatten, Catia Cilloniz, Paweł Zatorski, Sally Humphreys, Henrik Westberg, Eva Rice, Peter de Jager, Helder Filipe, Stefania Brusa, Maria Faulkner, Jan Stefaniak, Cyril Charron, Nuno Candeias, Sten Walther, Nathalie Rolin, Muhammed Elhadi, Marta Serwa, Sebastian Allgäuer, Thomas Elkmann, Philipp Eller, Jean-Luc Chagnon, Gonzalo Navarro Velasco, Raimund Helbok, Catherine Motherway, Dorota Studzińska, Alan Pope, Ahmed Tarek, Cristina Sousa, Natalia Kozera, Michael Horacek, Camilla Brorsson, Tom Dormans, Nuno Catorze, Michael Joannidis, Andrea Neville Cracchiolo, Walter Swinnen, Oscar Hoiting, Africa Lores, Dominic Spray, Vladislav Belskiy, Marijana Mikačić, Rachel Savine, Tim Rahmel, Christoffer Sølling, Fredrik Schiöler, Henning Ebelt, Urszula Kościuczuk, Marek Pietruszko, Alexander D Cornet, Vasiiios Zidianakis, Bogdan Raitsiou, Ana Rita Santos, Nick Spittle Nick Spittle, Jan Peter Jensen, Alena Breidablik Alena Breidablik, Wojciech Szczeklik, Joerg C. Schefold, Karin Kleiven Thiringer, Alexandre Fernandes Pinto, Antoine Romen, Ingeborg D Welters, Nikolaas de Neve, Joanne Jones, Carole Boulanger, Ciaran Hart, Georgios Papathanakos, Jessica Nauska, Gaspar Eixarch, Pål Klepstad, Wesal Ali Belkhair, Ximena Watson, Brian Marsh, Emmanuel Guerot, Michael W. Schuster, Julie North, Bartosz Kudlinski, Alessandro Morandi, Stefan Schering, Fotios Tsimpoukas, Mercedes Ibarz, Ioannis Koutsodimitropoulos, Maurizio Cecconi, David Perez-Torres, Stephan Steiner, Agnieszka Kubisz-Pudelko, Johan Berkius, Phillipa Wakefield, Joanna Zorska, Anne-Karin Rime, Jacobo Bacariza Blanco, Reni Jacob, Guillaume Besch, Jane Evans, Mathilde Hummelmose Enevoldsen, Jasper Haringman, Xavier Valette, Pierre Garçon, Waldemar Cyrankiewicz, Megan Lea-Hagerty, Jason Cupitt, Yolanda Baird, Eberhard Barth, Stylliani Kourelea, Christine Cramer, Gerardo Aguilar, Christophe Vinsonneau, Maud Mousset Hovaere, Hans Frank Strietzel, Patricia Jimeno Cubero, René Schmutz, Aristide Morigi, Jonathan Ball, Raphael Romano Bruno, Kirsti Tøien, Ahmed Elhadi, Susan Dowling, Antonio Artigas, Aleksandra Biernacka, Clare Bolger, Italo Calamai, Dorthe Ørsnes, Giorgos Marinakis, Amy Collins, Leila Hergafi, Didier Thevenin, Michael Spivey, Bård E S Dahle, Willem Dieperink, Lucie Vettoretti, Vryza Konstantinia, Tasioudis Polychronis, Laura Ortiz-Ruiz De Gordoa, Julien Maizel, Louise Bell, Nicholas Love, Christian Frey, Joanna Solek-Pastuszka, Richard Pugh, Stefan J. Schaller, Hervé Mentec, Mercedes Ibarz Villamayor, Ritoo Kapoor, W. Khaliq, Gemma Gomà, Patrick Morgan, Finn H. Andersen, Madhu Balasubramaniam, Irina Grecu, Filippo Boroli, Saad Nseir, Mariusz Piechota, Ana M. Fernandes, Katarzyna Cwyl, Elli Niki Flioni, Jørund Langørgen, Kiran Salaunkey, Jean-Pierre Quenot, Philippe Burtin, Michael Reay, Ryszard Gawda, Ariane Boumendil, Anders Bastiansen, Hazem Ahmed, Evangelia Neou, Ihor Yovenko, Rik T Gerritsen, Bente Jannestad, Tarkeshwari Mane, Richard Innes, Kelly Tiercelet, Christian Jung, Rui Moreno, Maciej Zukowski, Dariusz Maciejewski, Dylan W. de Lange, Jeremy Henning, Paweł Nasiłowski, Estefania Prol-Silva, Tilemachos Zafeiridis, Lukasz J Krzych, Jérémy Rosman, Tobias Graf, Sonia López-Cuenca, Marcela Vizcaychipi, Jeremy Castaneray, Steve Rose, Vongayi Ogbeide, Arnaud Galbois, Yuriy Nalapko, Sandra Oeyen, Joke Nollet, Ismail Yıldız, Chris Read, Philippe Eckert, Ashok Raj, Anita Slapgard, Anna Kluzik, Mirosław Ziętkiewicz, Christian Rabe, Guillaume Savary, Noemí Llamas Fernández, João Teles Carvalho, Nikoletta Rovina, Jakob Edelberg Thomsen, Britt Sjøbøe, Andreas Husted, Jean-Philippe Rigaud, Bertrand Guidet, Piotr Galkin, Marián Irazábal Jaimes, Anders Sjöqvist, Paweł Sendur, Thorben Dieck, A. Vakalos, Enver Rodriguez, Jesper Fjølner, Eva van Boven, Inês Barros, Susannah Leaver, Patricia Williams, Messika Messika, Emilio Maseda, Michael Hahn, Teresa Tomasa, and Critical Care
Subjects: Aging, medicine.medical_specialty, intensive care units, 80 jaar en ouder, Comorbidity, frailty, elderly, law.invention, Sepsis, sepsis, 03 medical and health sciences, intensive care afdelingen, 0302 clinical medicine, law, Intensive care, kwetsbaarheid, sterfte, ouderen, medicine, 80 and over, Humans, 030212 general & internal medicine, Hospital Mortality, Prospective Studies, Prospective cohort study, business.industry, Mortality rate, Hazard ratio, 030208 emergency & critical care medicine, General Medicine, medicine.disease, Intensive care unit, mortality, aged, Emergency medicine, SOFA score, Geriatrics and Gerontology, business, aged, 80 and over
Abstract: Background Sepsis is one of the most frequent reasons for acute intensive care unit (ICU) admission of very old patients and mortality rates are high. However, the impact of pre-existing physical and cognitive function on long-term outcome of ICU patients ≥ 80 years old (very old intensive care patients (VIPs)) with sepsis is unclear. Objective To investigate both the short- and long-term mortality of VIPs admitted with sepsis and assess the relation of mortality with pre-existing physical and cognitive function. Design Prospective cohort study. Setting 241 ICUs from 22 European countries in a six-month period between May 2018 and May 2019. Subjects Acutely admitted ICU patients aged ≥80 years with sequential organ failure assessment (SOFA) score ≥ 2. Methods Sepsis was defined according to the sepsis 3.0 criteria. Patients with sepsis as an admission diagnosis were compared with other acutely admitted patients. In addition to patients’ characteristics, disease severity, information about comorbidity and polypharmacy and pre-existing physical and cognitive function were collected. Results Out of 3,596 acutely admitted VIPs with SOFA score ≥ 2, a group of 532 patients with sepsis were compared to other admissions. Predictors for 6-month mortality were age (per 5 years): Hazard ratio (HR, 1.16 (95% confidence interval (CI), 1.09–1.25, P 4): HR, 1.34 (95% CI, 1.18–1.51, P Conclusions There is substantial long-term mortality in VIPs admitted with sepsis. Frailty, age and disease severity were identified as predictors of long-term mortality in VIPs admitted with sepsis.
Published: 2021

28. Clockfire

Author: Jonathan Ball
Published: 2006

29. Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

Author: Derek C. Macallan, David W Eyre, J Slon-Campos, Susannah Leaver, Jai S Bolton, Lian Lee, Jeremy Ratcliff, Kreepa Kooblall, Christopher J. Walker, Marc Turner, Beibei Wang, Judith Wellens, José Lourenço, Christina Dold, Sheila F Lumley, Paul M. Matthews, Hannah Klim, J K Baillie, George Carnell, Juthathip Mongkolspaya, Philip Hopkins, Piyada Supasa, Alexander J. Mentzer, Duncan Wyncoll, Lucas Stolle, Wanwisa Dejnirattisai, Susanna Dunachie, Miles W. Carroll, Nigel Temperton, E Barnes, Robert S. Paton, Prabhjeet Phalora, Sandra Belij-Rammerstorfer, Sunetra Gupta, Stephen Kennedy, Malcom G Semple, Teresa Lambe, Provine N, Tihana Bicanic, Matthew Edmans, Alex Fyfe, Gavin R. Screaton, Donal T. Skelly, Anna L McNaughton, Paul Klenerman, Craig Thompson, Cesar Lopez-Camacho, Peter J. M. Openshaw, Lisa Jarvis, Uri Obolski, A Howarth, Jonathan Youngs, Investigators I, Peter Simmonds, and Jonathan Ball
Subjects: 2019-20 coronavirus outbreak, Immune system, Antibody response, Coronavirus disease 2019 (COVID-19), viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, virus diseases, Spike Protein, Biology, Coronavirus Infections, Epitope
Abstract: SummaryIt is unclear whether prior endemic coronavirus infections affect COVID-19 severity. Here, we show that in cases of fatal COVID-19, antibody responses to the SARS-COV-2 spike are directed against epitopes shared with endemic beta-coronaviruses in the S2 subunit of the SARS-CoV-2 spike protein. This immune response is associated with the compromised production of ade novoSARS-CoV-2 spike response among individuals with fatal COVID-19 outcomes.
Published: 2021
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30. SARS-CoV-2 transmission from the healthcare setting into the home: a prospective longitudinal cohort study

Author: Ben A Marson, Patrick J. Tighe, Jonathan Ball, Anthony Kelly, Jayne Newham, Adeel Ikram, Alexander W. Tarr, Benjamin J Ollivere, Alan Norrish, Richard A. Urbanowicz, Simon Craxford, Lola Cusin, Ana M. Valdes, Guruprasad P. Aithal, Stuart Astbury, Waheed Ashraf, Amrita Vijay, and Jessica Nightingale
Subjects: medicine.medical_specialty, education.field_of_study, business.industry, Public health, Incidence (epidemiology), Population, Context (language use), Odds ratio, medicine, Seroprevalence, education, business, Blood sampling, Cohort study, Demography
Abstract: Objective To assess the incidence of symptomatic and asymptomatic SARS-CoV-2 seropositivity in healthcare workers and subsequent transmission to their close contacts within their household. To assess changes in immunoglobulin (Ig) and neutralising antibodies (nAbs) in exposed participants. Setting Two acute National Health Service (NHS) hospitals within the East Midlands region of England. Background The UK has been one of the most severely affected countries during the COVID-19 pandemic. Transmission from healthcare workers to the wider community is a potential major vector for spread of SARS-CoV-2 which is not well described in the current literature. Methods Healthcare workers (HCW) were recruited from two Hospitals within the East Midlands of England and underwent serial blood sampling for anti-SARS-CoV-2 antibodies (both nucleocapsid and spike protein for IgG, IgM and IgA) between 20 April and 30 July 2020, with the presence of neutralising antibodies (nAbs) assessed for positive participants. Cohabitees of the volunteers were invited to attend testing in July -August 2020 and underwent identical serological testing as the HCWs. Results 633 healthcare professionals were recruited. 178 household contacts of 137 professionals volunteered for the study. 18% of healthcare professionals (115 out of 633) tested as seropositive during the study period, compared to an estimated seroprevalence of 7% within the general population. The rate of symptomatic COVID-19 was 27.5% compared to an asymptomatic rate of 15.1%. Rates of positivity declined across the study period for all immunoglobulins (overall positivity from 16.7% to 6.9%). 7.2% of the cohabitees tested as seropositive. 58 cohabitees lived with a serologically positive HCW; this group had a seropositive rate of 15.5%, compared to 2.5% of cohabitees without a seropositive HCW, a six-fold increase in risk (Odds ratio 7.16 95% CI 1.86 to 27.59), p = 0.0025). Given the observed decay rates and data from Public Health England, we estimate that the proportion of seropositive cohabitees living with a seropositive HCW at the height of the first wave could have been as high as 44%. 110 out of 115 (95.7%) HCWs and 12 out of 13 (92.3%) cohabitees who tested positive developed detectable nAbs. 56.5% (65 out of 115) of SARS-CoV-2 positive HCWs developed a neutralising titre with an IC50≥1/300; no cohabitee achieved this level.. Conclusions Transmission of SARS-CoV-2 between healthcare professionals and their home contacts appears to be a significant factor of viral transmission, but, even accounting for the decline in seropositivity over time, less than 44% of adult cohabitees of seropositive healthcare workers became seropositive. Routine screening and priority vaccination of both healthcare professionals and their close contacts should be implemented to reduce viral transmission from hospitals to the community. SUMMARY BOXES Section 1: What is already known on this topic Healthcare workers (HCWs) have increased rates of SARS-CoV-2 infection compared with the general population due, at least in part, to high levels of occupational exposure. IgA, IgM and IgG are detectable for most patients after 11 days post SARS-CoV-2 infection but all decline in the weeks following SAR-CoV-2 exposure. Rates of transmission to healthcare workers, and therefore subsequent transmission to their close contacts, may be reduced with effective PPE. Section 2: What this study adds The amount of neutralising antibodies formed may be dependent on IgG response as it is much lower among seropositive cohabitees than seropositive healthcare workers. NHS Healthcare workers had a far greater seroprevalence of SARS-CoV-2 infection compared to the general population. Cohabitees of positive healthcare workers have a 6-fold increased risk of developing serological evidence of SARS-CoV-2 infection compared to the general population. Despite this increased risk, transmission at home is less than 50% even from highly exposed healthcare workers, but remains an important potential vector of transmission from hospitals to the wider community. Research into context Evidence before this study We searched PubMed for articles published between January 1 2020 and January 27, 2021 with the terms “Covid-19”, “healthcare workers”, and “transmission” “home {NOT nursing} or household”. We did not restrict our search by language or type of publication. We identified 38 studies of which only one assessed the prevalence among HCW households using Canadian national databases. Our PubMed search yielded only one serological study within the German Healthcare system, which suggested very low transmission from healthcare workers to their close cohabitees. Added value of this study To our knowledge, this is the largest longitudinal serological cohort study assessing transmission of SARS-CoV-2 infection from the UK healthcare environment to the home (n = 633 healthcare workers, 178 cohabitees). Our findings showed that serological evidence within the HCW was high with 18% of healthcare professionals (115 out of 633) tested as seropositive during the study period, compared to an estimated seroprevalence of 7% within the general population. A cohabitee of a seropositive HCW had a six-fold increase of being seropositive themselves compared to a baseline rate of 2.5%. Despite this increased risk, transmission at home is less than 50% even from highly exposed healthcare workers, but remains an important potential vector of transmission from hospitals to the wider community. Rates of positivity declined across the study period for all immunoglobulins (overall positivity from 16.7% to 6.9%). Given the observed decay rates and data from Public Health England, we estimate that the proportion of seropositive cohabitees living with a seropositive HCW at the height of the first wave could have been as high as 44%. Implications of all available evidence Understanding the transmission during the first wave from the healthcare setting into the home and the extent of such transmissions is essential to understand containment strategies of novel SARS-CoV-2 variants or to understand viral transmission of future respiratory viruses. NHS workers appeared to be at an increased risk of contracting of SARS-CoV-2 infection compared to the HCWs of other nations; we hypothesise that this may be related to a scarcity of appropriate personal protective equipment during the initial wave of SARS-CoV-2. Healthcare workers (HCWs) have increased rates of SARS-CoV-2 infection compared with the general population. An infected HCW, whether symptomatic or not, appears to be a significant bridge for transmission of SARS-CoV-2 to their close home contacts.
Published: 2021
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31. Tracheostomy care and decannulation during the COVID-19 pandemic. A multidisciplinary clinical practice guideline

Author: Enyi Ofo, Tunde Odutoye, Abigail Walker, Dagan O. Lonsdale, Jonathan Ball, Ricard Simo, Sally Archer, Neil Foden, Sarah Ann Little, Pavol Surda, Asit Arora, Alison Dinham, Y G Karagama, Deborah Dawson, Aleix Rovira, and Chrysostomos Tornari
Subjects: medicine.medical_specialty, Audit, Review Article, 03 medical and health sciences, 0302 clinical medicine, Tracheostomy, Multidisciplinary approach, Health care, Pandemic, London, medicine, Infection control, Humans, Tracheostomy care, Prospective Studies, 030223 otorhinolaryngology, Intensive care medicine, Pandemics, COVID, Multidisciplinary, Novel coronavirus, business.industry, SARS-CoV-2, COVID-19, General Medicine, Guideline, Otorhinolaryngology, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, business
Abstract: PURPOSE: Traditional critical care dogma regarding the benefits of early tracheostomy during invasive ventilation has had to be revisited due to the risk of COVID-19 to patients and healthcare staff. Standard practises that have evolved to minimise the risks associated with tracheostomy must be comprehensively reviewed in light of the numerous potential episodes for aerosol generating procedures. We meet the urgent need for safe practise standards by presenting the experience of two major London teaching hospitals, and synthesise our findings into an evidence-based guideline for multidisciplinary care of the tracheostomy patient. METHODS: This is a narrative review presenting the extensive experience of over 120 patients with tracheostomy, with a pragmatic analysis of currently available evidence for safe tracheostomy care in COVID-19 patients. RESULTS: Tracheostomy care involves many potentially aerosol generating procedures which may pose a risk of viral transmission to staff and patients. We make a series of recommendations to ameliorate this risk through infection control strategies, equipment modification, and individualised decannulation protocols. In addition, we discuss the multidisciplinary collaboration that is absolutely fundamental to safe and effective practise. CONCLUSION: COVID-19 requires a radical rethink of many tenets of tracheostomy care, and controversy continues to exist regarding the optimal techniques to minimise risk to patients and healthcare workers. Safe practise requires a coordinated multidisciplinary team approach to infection control, weaning and decannulation, with integrated processes for continuous prospective data collection and audit.
Published: 2021

32. Evaluating the effects of SARS-CoV-2 Spike mutation D614G on transmissibility and pathogenicity

Author: Erik Volz, Verity Hill, John T. McCrone, Anna Price, David Jorgensen, Áine O’Toole, Joel Southgate, Robert Johnson, Ben Jackson, Fabricia F. Nascimento, Sara M. Rey, Samuel M. Nicholls, Rachel M. Colquhoun, Ana da Silva Filipe, James Shepherd, David J. Pascall, Rajiv Shah, Natasha Jesudason, Kathy Li, Ruth Jarrett, Nicole Pacchiarini, Matthew Bull, Lily Geidelberg, Igor Siveroni, Ian Goodfellow, Nicholas J. Loman, Oliver G. Pybus, David L. Robertson, Emma C. Thomson, Andrew Rambaut, Thomas R. Connor, Cherian Koshy, Emma Wise, Nick Cortes, Jessica Lynch, Stephen Kidd, Matilde Mori, Derek J. Fairley, Tanya Curran, James P. McKenna, Helen Adams, Christophe Fraser, Tanya Golubchik, David Bonsall, Catrin Moore, Sarah L. Caddy, Fahad A. Khokhar, Michelle Wantoch, Nicola Reynolds, Ben Warne, Joshua Maksimovic, Karla Spellman, Kathryn McCluggage, Michaela John, Robert Beer, Safiah Afifi, Sian Morgan, Angela Marchbank, Christine Kitchen, Huw Gulliver, Ian Merrick, Martyn Guest, Robert Munn, Trudy Workman, William Fuller, Catherine Bresner, Luke B. Snell, Themoula Charalampous, Gaia Nebbia, Rahul Batra, Jonathan Edgeworth, Samuel C. Robson, Angela Beckett, Katie F. Loveson, David M. Aanensen, Anthony P. Underwood, Corin A. Yeats, Khalil Abudahab, Ben E.W. Taylor, Mirko Menegazzo, Gemma Clark, Wendy Smith, Manjinder Khakh, Vicki M. Fleming, Michelle M. Lister, Hannah C. Howson-Wells, Louise Berry, Tim Boswell, Amelia Joseph, Iona Willingham, Paul Bird, Thomas Helmer, Karlie Fallon, Christopher Holmes, Julian Tang, Veena Raviprakash, Sharon Campbell, Nicola Sheriff, Matthew W. Loose, Nadine Holmes, Christopher Moore, Matthew Carlile, Victoria Wright, Fei Sang, Johnny Debebe, Francesc Coll, Adrian W. Signell, Gilberto Betancor, Harry D. Wilson, Theresa Feltwell, Charlotte J. Houldcroft, Sahar Eldirdiri, Anita Kenyon, Thomas Davis, Oliver Pybus, Louis du Plessis, Alex Zarebski, Jayna Raghwani, Moritz Kraemer, Sarah Francois, Stephen Attwood, Tetyana Vasylyeva, M. Estee Torok, William L. Hamilton, Ian G. Goodfellow, Grant Hall, Aminu S. Jahun, Yasmin Chaudhry, Myra Hosmillo, Malte L. Pinckert, Iliana Georgana, Anna Yakovleva, Luke W. Meredith, Samuel Moses, Hannah Lowe, Felicity Ryan, Chloe L. Fisher, Ali R. Awan, John Boyes, Judith Breuer, Kathryn Ann Harris, Julianne Rose Brown, Divya Shah, Laura Atkinson, Jack C.D. Lee, Adela Alcolea-Medina, Nathan Moore, Nicholas Cortes, Rebecca Williams, Michael R. Chapman, Lisa J. Levett, Judith Heaney, Darren L. Smith, Matthew Bashton, Gregory R. Young, John Allan, Joshua Loh, Paul A. Randell, Alison Cox, Pinglawathee Madona, Alison Holmes, Frances Bolt, James Price, Siddharth Mookerjee, Aileen Rowan, Graham P. Taylor, Manon Ragonnet-Cronin, Rob Johnson, Olivia Boyd, Erik M. Volz, Kirstyn Brunker, Katherine L. Smollett, Joshua Quick, Claire McMurray, Joanne Stockton, Sam Nicholls, Will Rowe, Radoslaw Poplawski, Rocio T. Martinez-Nunez, Jenifer Mason, Trevor I. Robinson, Elaine O'Toole, Joanne Watts, Cassie Breen, Angela Cowell, Catherine Ludden, Graciela Sluga, Nicholas W. Machin, Shazaad S.Y. Ahmad, Ryan P. George, Fenella Halstead, Venkat Sivaprakasam, James G. Shepherd, Patawee Asamaphan, Marc O. Niebel, Kathy K. Li, Rajiv N. Shah, Natasha G. Jesudason, Yasmin A. Parr, Lily Tong, Alice Broos, Daniel Mair, Jenna Nichols, Stephen N. Carmichael, Kyriaki Nomikou, Elihu Aranday-Cortes, Natasha Johnson, Igor Starinskij, Richard J. Orton, Joseph Hughes, Sreenu Vattipally, Joshua B. Singer, Antony D. Hale, Louissa R. Macfarlane-Smith, Katherine L. Harper, Yusri Taha, Brendan A.I. Payne, Shirelle Burton-Fanning, Sheila Waugh, Jennifer Collins, Gary Eltringham, Kate E. Templeton, Martin P. McHugh, Rebecca Dewar, Elizabeth Wastenge, Samir Dervisevic, Rachael Stanley, Reenesh Prakash, Claire Stuart, Ngozi Elumogo, Dheeraj K. Sethi, Emma J. Meader, Lindsay J. Coupland, Will Potter, Clive Graham, Edward Barton, Debra Padgett, Garren Scott, Emma Swindells, Jane Greenaway, Andrew Nelson, Wen C. Yew, Paola C. Resende Silva, Monique Andersson, Robert Shaw, Timothy Peto, Anita Justice, David Eyre, Derrick Crooke, Sarah Hoosdally, Tim J. Sloan, Nichola Duckworth, Sarah Walsh, Anoop J. Chauhan, Sharon Glaysher, Kelly Bicknell, Sarah Wyllie, Ethan Butcher, Scott Elliott, Allyson Lloyd, Robert Impey, Nick Levene, Lynn Monaghan, Declan T. Bradley, Elias Allara, Clare Pearson, Peter Muir, Ian B. Vipond, Richard Hopes, Hannah M. Pymont, Stephanie Hutchings, Martin D. Curran, Surendra Parmar, Angie Lackenby, Tamyo Mbisa, Steven Platt, Shahjahan Miah, David Bibby, Carmen Manso, Jonathan Hubb, Meera Chand, Gavin Dabrera, Mary Ramsay, Daniel Bradshaw, Alicia Thornton, Richard Myers, Ulf Schaefer, Natalie Groves, Eileen Gallagher, David Lee, David Williams, Nicholas Ellaby, Ian Harrison, Hassan Hartman, Nikos Manesis, Vineet Patel, Chloe Bishop, Vicki Chalker, Husam Osman, Andrew Bosworth, Esther Robinson, Matthew T.G. Holden, Sharif Shaaban, Alec Birchley, Alexander Adams, Alisha Davies, Amy Gaskin, Amy Plimmer, Bree Gatica-Wilcox, Caoimhe McKerr, Catherine Moore, Chris Williams, David Heyburn, Elen De Lacy, Ember Hilvers, Fatima Downing, Giri Shankar, Hannah Jones, Hibo Asad, Jason Coombes, Joanne Watkins, Johnathan M. Evans, Laia Fina, Laura Gifford, Lauren Gilbert, Lee Graham, Malorie Perry, Mari Morgan, Michelle Cronin, Noel Craine, Rachel Jones, Robin Howe, Sally Corden, Sara Rey, Sara Kumziene-Summerhayes, Sarah Taylor, Simon Cottrell, Sophie Jones, Sue Edwards, Justin O’Grady, Andrew J. Page, John Wain, Mark A. Webber, Alison E. Mather, David J. Baker, Steven Rudder, Muhammad Yasir, Nicholas M. Thomson, Alp Aydin, Ana P. Tedim, Gemma L. Kay, Alexander J. Trotter, Rachel A.J. Gilroy, Nabil-Fareed Alikhan, Leonardo de Oliveira Martins, Thanh Le-Viet, Lizzie Meadows, Anastasia Kolyva, Maria Diaz, Andrew Bell, Ana Victoria Gutierrez, Ian G. Charles, Evelien M. Adriaenssens, Robert A. Kingsley, Anna Casey, David A. Simpson, Zoltan Molnar, Thomas Thompson, Erwan Acheson, Jane A.H. Masoli, Bridget A. Knight, Andrew Hattersley, Sian Ellard, Cressida Auckland, Tabitha W. Mahungu, Dianne Irish-Tavares, Tanzina Haque, Yann Bourgeois, Garry P. Scarlett, David G. Partridge, Mohammad Raza, Cariad Evans, Kate Johnson, Steven Liggett, Paul Baker, Sarah Essex, Ronan A. Lyons, Laura G. Caller, Sergi Castellano, Rachel J. Williams, Mark Kristiansen, Sunando Roy, Charlotte A. Williams, Patricia L. Dyal, Helena J. Tutill, Yasmin N. Panchbhaya, Leysa M. Forrest, Paola Niola, Jacqueline Findlay, Tony T. Brooks, Artemis Gavriil, Lamia Mestek-Boukhibar, Sam Weeks, Sarojini Pandey, Lisa Berry, Katie Jones, Alex Richter, Andrew Beggs, Colin P. Smith, Giselda Bucca, Andrew R. Hesketh, Ewan M. Harrison, Sharon J. Peacock, Sophie Palmer, Carol M. Churcher, Katherine L. Bellis, Sophia T. Girgis, Plamena Naydenova, Beth Blane, Sushmita Sridhar, Chris Ruis, Sally Forrest, Claire Cormie, Harmeet K. Gill, Joana Dias, Ellen E. Higginson, Mailis Maes, Jamie Young, Leanne M. Kermack, Nazreen F. Hadjirin, Dinesh Aggarwal, Luke Griffith, Tracey Swingler, Rose K. Davidson, Thomas Williams, Carlos E. Balcazar, Michael D. Gallagher, Áine O'Toole, Stefan Rooke, Rachel Colquhoun, Jordan Ashworth, J.T. McCrone, Emily Scher, Xiaoyu Yu, Kathleen A. Williamson, Thomas D. Stanton, Stephen L. Michell, Claire M. Bewshea, Ben Temperton, Michelle L. Michelsen, Joanna Warwick-Dugdale, Robin Manley, Audrey Farbos, James W. Harrison, Christine M. Sambles, David J. Studholme, Aaron R. Jeffries, Alistair C. Darby, Julian A. Hiscox, Steve Paterson, Miren Iturriza-Gomara, Kathryn A. Jackson, Anita O. Lucaci, Edith E. Vamos, Margaret Hughes, Lucille Rainbow, Richard Eccles, Charlotte Nelson, Mark Whitehead, Lance Turtle, Sam T. Haldenby, Richard Gregory, Matthew Gemmell, Dominic Kwiatkowski, Thushan I. de Silva, Nikki Smith, Adrienn Angyal, Benjamin B. Lindsey, Danielle C. Groves, Luke R. Green, Dennis Wang, Timothy M. Freeman, Matthew D. Parker, Alexander J. Keeley, Paul J. Parsons, Rachel M. Tucker, Rebecca Brown, Matthew Wyles, Chrystala Constantinidou, Meera Unnikrishnan, Sascha Ott, Jeffrey K.J. Cheng, Hannah E. Bridgewater, Lucy R. Frost, Grace Taylor-Joyce, Richard Stark, Laura Baxter, Mohammad T. Alam, Paul E. Brown, Patrick C. McClure, Joseph G. Chappell, Theocharis Tsoleridis, Jonathan Ball, Dimitris Grammatopoulos, David Buck, John A. Todd, Angie Green, Amy Trebes, George MacIntyre-Cockett, Mariateresa de Cesare, Cordelia Langford, Alex Alderton, Roberto Amato, Sonia Goncalves, David K. Jackson, Ian Johnston, John Sillitoe, Steve Palmer, Mara Lawniczak, Matt Berriman, John Danesh, Rich Livett, Lesley Shirley, Ben Farr, Mike Quail, Scott Thurston, Naomi Park, Emma Betteridge, Danni Weldon, Scott Goodwin, Rachel Nelson, Charlotte Beaver, Laura Letchford, David A. Jackson, Luke Foulser, Liz McMinn, Liam Prestwood, Sally Kay, Leanne Kane, Matthew J. Dorman, Inigo Martincorena, Christoph Puethe, Jon-Paul Keatley, Gerry Tonkin-Hill, Christen Smith, Dorota Jamrozy, Mathew A. Beale, Minal Patel, Cristina Ariani, Michael Spencer-Chapman, Eleanor Drury, Stephanie Lo, Shavanthi Rajatileka, Carol Scott, Keith James, Sarah K. Buddenborg, Duncan J. Berger, Gaurang Patel, Maria V. Garcia-Casado, Thomas Dibling, Samantha McGuigan, Hazel A. Rogers, Adam D. Hunter, Emily Souster, Alexandra S. Neaverson, Medical Research Council (MRC), Pascall, David [0000-0002-7543-0860], and Apollo - University of Cambridge Repository
Subjects: Genome, Genetic analysis, 0302 clinical medicine, Clade, 11 Medical and Health Sciences, Genetics, 0303 health sciences, education.field_of_study, Phylogenetic tree, Virulence, C500, COG-UK Consortium, C700, Transmissibility (vibration), 3. Good health, founder effect, Spike Glycoprotein, Coronavirus, epidemiology, Viral load, Population, Glycine, B100, Genomics, Genome, Viral, Biology, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, evolution, Humans, education, 030304 developmental biology, Aspartic Acid, Whole Genome Sequencing, Biochemistry, Genetics and Molecular Biology(all), SARS-CoV-2, COVID-19, spike, The COVID-19 Genomics UK Consortium, A300, 06 Biological Sciences, United Kingdom, Amino Acid Substitution, Evolutionary biology, Mutation, Biological dispersal, 030217 neurology & neurosurgery, Founder effect, Developmental Biology
Abstract: Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant., Graphical Abstract, Highlights • Increasing frequency of SARS-CoV-2 D614G is consistent with a selective advantage • Phylodynamic analyses do not show significantly different growth of D614G clusters • There is no association of D614G replacement with greater severity of infection • The D614G replacement is associated with higher viral loads and younger patient age, Analysis of the spread and frequency of SARS-CoV-2 D614G in the United Kingdom suggests a selective advantage for this strain that is associated with higher viral loads in younger patients but not higher COVID-19 clinical severity or mortality.
Published: 2021
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33. Fatal COVID-19 Outcomes are Associated with an Antibody Response Targeting Epitopes Shared with Endemic Coronaviruses

Author: J Kenneth Baillie, Lian Lee, José Lourenço, Piyada Supasa, Beibei Wang, J Slon-Campos, Stephen Kennedy, Lisa Jarvis, Philippa C Matthews, Peter J. M. Openshaw, Isaric C Investigators, George Carnell, Eleanor Barnes, Jeremy Ratcliff, Duncan Wyncoll, Prabhjeet Phalora, Craig Thompson, Wanwisa Dejnirattisai, Marc Turner, Judith Wellens, Alex Fyfe, Kreepa Kooblall, Cesar Lopez-Camacho, Alison Howarth, Christopher J. Walker, Philip Hopkins, Nigel Temperton, Lucas Stolle, Gavin R. Screaton, Donal T. Skelly, Susannah Leaver, Alexander J. Mentzer, Jai S Bolton, Sunetra Gupta, Teresa Lambe, Susanna Dunachie, Robert S. Paton, Tihana Bicanic, Hannah Klim, Peter Simmonds, Jonathan Ball, Uri Obolski, Sandra Belij-Rammerstorfer, Jonathan Youngs, Juthathip Mongkolspaya, Nicholas M. Provine, Derek C. Macallan, David W Eyre, Malcolm G Semple, Anna L McNaughton, Paul Klenerman, Christina Dold, Sheila F Lumley, Miles W. Carroll, and Matthew Edmans
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), education, Declaration, Medical research, Meso scale, Antibody response, Informed consent, Donation, Political science, Family medicine, medicine, Spike (database), health care economics and organizations
Abstract: It is unclear whether prior endemic coronavirus infections affect COVID-19 severity. Here, we show that in cases of fatal COVID-19, antibody responses to the SARS-COV-2 spike are directed against epitopes shared with endemic beta-coronaviruses in the S2 subunit of the SARS-CoV-2 spike protein. This immune response is associated with the compromised production of a de novo SARS-CoV-2 spike response among individuals with fatal COVID-19 outcomes. Funding: This work was supported by the Georg and Emily von Opel Foundation, the National Institute for Health Research (NIHR) [award CO-‐CIN-‐01], the Medical Research Council [grant MC_PC_19059], ME was supported by The Leona M. and Harry B. Helmsley Charitable Trust on May 31, 2021 for the project titled, "ICARUS –IBD: International study of COVID-‐19 Antibody Response Under Sustained immune suppression in Inflammatory Bowel Disease. RP also supported by funds provided under Professor RW Snow’s Wellcome Trust Principal Fellowship (# 212176). Meso Scale Diagnostics (USA) provided loan of equipment, reagents and technical support. JSB was supported by funding from the Biotechnology and Biological Sciences Research Council (BBSRC) [grant number BB/M011224/1]. CPT was funded by an ERC research grant UNIFLUVAC’ and two MRC CiC grants (Ref: BR00140). ALM is funded by a NIHR Research Capability Funding grant. HJK is supported by The Future of Humanity Institute at the University of Oxford DPhil Scholarship program. DE is funded by the Robertson Foundation. The funders played no role in the design, execution or reporting of the study. Declaration of Interest: DE declares lecture fees from Gilead. CPT and SG hold funding from Blue Water Vaccines. All others have nothing to disclose. Ethical Approval: Ethical approval was obtained for the Scottish National Blood Transfusion Service (SNBTS) anonymous archive -‐ IRAS project number 18005. SNBTS blood donors gave fully informed consent to virological testing, donation was made under the SNBTS Blood Establishment Authorisation and the study was approved by the SNBTS Research and Sample Governance Committee.
Published: 2021
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34. Deaths in people from Black, Asian and minority ethnic communities from both COVID-19 and non-COVID causes in the first weeks of the pandemic in London: a hospital case note review

Author: Zoe Avila, Michael R. Perkin, Kate Hutt, Nigel Kennea, Sarah Heap, Wendy Albuquerque, A Agatha Crerar-Gilbert, Serena Haywood, Richard Hartopp, and Jonathan Ball
Subjects: Male, Coronavirus disease 2019 (COVID-19), Epidemiology, Pneumonia, Viral, coronavirus, Ethnic group, Black People, Comorbidity, Betacoronavirus, Asian People, Cause of Death, London, Pandemic, medicine, Humans, ethnicity co-morbidity deprivation, In patient, Pandemics, Minority Groups, Aged, Retrospective Studies, Cause of death, Aged, 80 and over, SARS-CoV-2, business.industry, COVID-19, Retrospective cohort study, General Medicine, medicine.disease, Hospitals, Survival Rate, Medicine, Female, Case note, Coronavirus Infections, business, Demography
Abstract: ObjectiveTo undertake a case review of deaths in a 6-week period during the COVID-19 pandemic commencing with the first death in the hospital from COVID-19 on 12th of March 2020 and contrast this with the same period in 2019.SettingA large London teaching hospital.ParticipantsThree groups were compared: group 1—COVID-19-associated deaths in the 6-week period (n=243), group 2—non-COVID deaths in the same period (n=136) and group 3—all deaths in a comparison period of the same 6 weeks in 2019 (n=194).Primary and secondary outcome measuresThis was a descriptive analysis of death case series review and as such no primary or secondary outcomes were pre-stipulated.ResultsDeaths in patients from the Black, Asian and minority ethnic (BAME) communities in the pandemic period significantly increased both in the COVID-19 group (OR=2.43, 95% CI=1.60–3.68, pConclusionsThere was no evidence of COVID-19 deaths occurring disproportionately in the elderly compared with non-COVID deaths in this period in 2020 and 2019. Deaths in the BAME communities were over-represented in both COVID-19 and non-COVID groups, highlighting the need for detailed research in order to fully understand the influence of ethnicity on susceptibility to illness, mortality and health-seeking behaviour during the pandemic.
Published: 2020

35. Insights from compassionate use of tocilizumab for COVID‐19 to inform appropriate design of randomised controlled trials

Author: Arvind Kaul, Mickey Koh, Emma H. Baker, Vinodh Kumar, Daniel M. Forton, Sanjeev Krishna, Sarah Edwards, Susannah Leaver, Kamal V. Patel, Jonathan Ball, and Thomas S. Harrison
Subjects: Pharmacology, Compassionate Use Trials, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, Compassionate Use, COVID-19, Antibodies, Monoclonal, Humanized, COVID-19 Drug Treatment, chemistry.chemical_compound, Tocilizumab, Treatment Outcome, chemistry, Research Design, Medicine, Humans, Pharmacology (medical), business, Intensive care medicine, Cytokine Release Syndrome, Letter to the Editor, Randomized Controlled Trials as Topic
Published: 2020

36. Improving antibiotic stewardship in COVID-19: Bacterial co-infection is less common than with influenza

Author: Tihana Bicanic, Amber Arnold, Jonathan Ball, Philip Hopkins, Jonathan Youngs, and Duncan Wyncoll
Subjects: Microbiology (medical), Antibiotic stewardship, biology, Coronavirus disease 2019 (COVID-19), business.industry, Bacterial co-infection, COVID-19, biology.organism_classification, medicine.disease, Virology, Article, Influenza, Infectious Diseases, Pandemic, Coinfection, Antimicrobial stewardship, Antibiotic Stewardship, Medicine, business, Betacoronavirus, Coronavirus Infections, Co infection
Published: 2020

37. Venous Thromboembolism in Critically Ill Patients Requires Significant Reconsideration

Author: Jonathan Ball
Subjects: medicine.medical_specialty, business.industry, Critically ill, Heparin, Critical Illness, MEDLINE, Anticoagulants, Venous Thromboembolism, Critical Care and Intensive Care Medicine, Intensive Care Units, medicine, Humans, Intensive care medicine, business, Venous thromboembolism
Published: 2020

38. Response to Tocilizumab in Severe COVID-19

Author: Emma H Baker, Kamal Patel, Jonathan Ball, Sarah Edwards, Thomas S Harrison, Arvind Kaul, Mickey Koh, Sanjeev Krishna, Vinodh Kumar, Susannah Leaver, and Daniel M Forton
Abstract: Background: Since the COVID-19 pandemic began in December 2019 no specific therapy for managing severe complications of infection has emerged, although this is under intensive investigation. Progressive pneumonia and multi-organ complications are managed with supportive care and COVID-19 has a mortality of >50% when ventilatory support is needed.Methods: We implemented a compassionate use protocol for tocilizumab, a humanised monoclonal anti-Il-6 receptor antibody. Patients with severe COVID-19 requiring oxygen or ventilation, and complicated by hyperinflammation and the cytokine release syndrome (CRS) received tocilizumab (8 mg/kg up to a maximum of 800 mg, with the option of a second dose given after 12-24 hours). CRS was defined as having at least three of: D-dimer above the upper limit of normal (ULN), rising C-reactive protein (CRP), ferritin >1000 ng/mL and lactate dehydrogenase (LDH) greater than the ULN.Oral consent for prescription of an off-label medicine was obtained from patients, their next of kin or representative, whenever possible. The treatment protocol adhered to the Monitored Emergency Use of Unregistered and Investigational Interventions of the WHO.Findings: Of seventeen patients with severe COVID-19 seen between 3-12th April 2020, eleven patients (seven ventilated and four receiving high flow oxygen) were treated with tocilizumab. Treatment normalised temperatures within 48 hours and was associated with a significant fall in CRP from 311 (138-332) (median, IQR mg/L) to 110 (58-184) (p = 0·001). For the group, oxygen requirements fell by 60±32% (95% CI 38-81) over 1 week (p
Published: 2020
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39. Peatland restoration age (Scotland, UK) can be better reproduced by a classification model based on Sentinel-2 than with high resolution aerial imagery

Author: Gillian Donaldson-Selby, Rebekka R. E. Artz, Daniela Klein, Neil Cowie, Jonathan Ball, Alessandro Gimona, Catherine Smart, and Mark H. Hancock
Subjects: Peat, High resolution, Environmental science, Cartography, Aerial imagery
Abstract: Damage to peatland globally causes significant contributions to the current net greenhouse gas emissions and pose a further future risk as such damaged peatlands are vulnerable to future climatic stress. Globally, peatland restoration efforts are rapidly increasing in scale as natural climate solutions, yet relatively little effort has been it into effective monitoring of landscape scale restoration projects. We developed a classification model that uses remote observations (Sentinel-2 or national scale aerial imagery from Getmapping) to detect restoration efficacy by training it against a dataset from a chronosequence of spatially collocated peatland restoration sites that had previously been converted to plantation forestry. The Sentinel-2 based model greatly outperformed the aerial imagery-based model (RGB and IR, 25 and 50 cm, respectively). Adding slope to the classification improved kappa by less than 0.02. Prediction of the starting (forestry) and target (restored) state was very robust, and both recent and the oldest restoration sites were spatially well predicted. The main model uncertainties lie with sites of intermediate age, where on-the-ground restoration trajectories based on vegetation composition also differ the most, and with sites where additional layers of management after the initial restoration management have been applied.
Published: 2020
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40. Cost-Effectiveness Analysis of Baseline Testing for Resistance-Associated Polymorphisms to Optimize Treatment Outcome in Genotype 1 Noncirrhotic Treatment-Naïve Patients With Chronic Hepatitis C Virus

Author: Christopher G. Fawsitt, Peter Vickerman, Graham S. Cooke, Nicky J. Welton, Eleanor Barnes, Jonathan Ball, Diana Brainard, Gary Burgess, John Dillon, Graham Foster, Charles Gore, Neil Guha, Rachel Halford, Kevin Whitby, Chris Holmes, Anita Howe, Emma Hudson, Sharon Hutchinson, William Irving, Salim Khakoo, Paul Klenerman, Natasha Martin, Benedetta Massetto, Tamyo Mbisa, John McHutchison, Jane McKeating, John McLauchlan, Alec Miners, Andrea Murray, Peter Shaw, Peter Simmonds, Chris Spencer, Emma Thomson, Nicole Zitzmann, Medical Research Council (MRC), National Institute for Health Research, and Wellcome Trust
Subjects: Male, hepatitis C virus, Time Factors, Cost effectiveness, Economics, Cost-Benefit Analysis, Social Sciences, Hepacivirus, Viral Nonstructural Proteins, medicine.disease_cause, THERAPY, State Medicine, chemistry.chemical_compound, resistance-associated polymorphisms, 0302 clinical medicine, Business & Economics, Genotype, Medicine, 030212 general & internal medicine, NS5A RESISTANCE, Molecular Targeted Therapy, media_common, Health Policy, Cost-effectiveness analysis, Markov Chains, 3. Good health, Models, Economic, Treatment Outcome, Molecular Diagnostic Techniques, baseline testing, Health Policy & Services, 030211 gastroenterology & hepatology, TRIAL, Female, Quality-Adjusted Life Years, PEGINTERFERON, RIBAVIRIN, Life Sciences & Biomedicine, Drug, INTERFERON, Adult, medicine.medical_specialty, Hepatitis C virus, media_common.quotation_subject, Antiviral Agents, Article, Drug Costs, 1117 Public Health and Health Services, Decision Support Techniques, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, Drug Resistance, Viral, Humans, HEB, NS5A, 1402 Applied Economics, cost-effectiveness, Science & Technology, Polymorphism, Genetic, business.industry, Ribavirin, Decision Trees, Public Health, Environmental and Occupational Health, STOP HCV Consortium, Hepatitis C, Chronic, United Kingdom, Health Care Sciences & Services, chemistry, Outcomes research, business
Abstract: Objectives Direct-acting antivirals containing nonstructural protein 5A (NS5A) inhibitors administered over 8 to 12 weeks are effective in ∼95% of patients with hepatitis C virus. Nevertheless, patients resistant to NS5A inhibitors have lower cure rates over 8 weeks (, Highlights • Although direct-acting antivirals containing nonstructural protein 5A (NS5A) inhibitors administered over 8 to 12 weeks are effective in ∼95% of patients with hepatitis C virus (HCV), the licensed duration of therapy may be unnecessary or less effective for selected patients. Patients with resistance to NS5A inhibitors have lower cure rates over 8 weeks and would benefit more from standard 12-week treatment. Conversely, nonresistant patients generally do not require 12-week treatment; 8-week treatment produces comparable cure rates. Testing for resistance to NS5A inhibitors at baseline and optimizing treatment duration accordingly is one method that could be used to improve patient outcomes. Nevertheless, the potential benefits of resistance testing must be considered in the context of the added cost of the resistance test. • This is the first study to consider the cost-effectiveness of baseline testing in genotype 1 noncirrhotic treatment-naïve patients. Furthermore, it is the first to consider it in the context of a shortened treatment duration of 8 weeks, which has been shown to be cost-effective versus standard 12-week treatment for many commonly used direct-acting antivirals. • Baseline testing has a low probability of being the most cost-effective treatment strategy if first- and second-line drug prices per 12-week course are high (>£20k). Nevertheless, if drug costs are low (£22k).
Published: 2020
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41. Changing the Position

Author: Jonathan Ball
Subjects: medicine.medical_specialty, Lung, business.industry, medicine.medical_treatment, MEDLINE, Critical Care and Intensive Care Medicine, Tissue Donors, Position (obstetrics), medicine.anatomical_structure, Chain (algebraic topology), medicine, Humans, Lung transplantation, Radiology, business, Lung Transplantation
Published: 2019
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42. Response to comments to 'Open versus percutaneous tracheostomy in COVID-19: a multicentre comparison and recommendationfor future resource utilisation'

Author: Pavol Surda, Stephen Tricklebank, K. Fan, Ram Kumar, Aleix Rovira, Asit Arora, Joe Zhang, Arun Takhar, Imran Ahmed, Jonathan Ball, Ricard Simo, Elizabeth Yeung, Deborah Dawson, Stephen Whebell, W. Khaliq, and Phillip Hopkins
Subjects: 2019-20 coronavirus outbreak, medicine.medical_specialty, Otorhinolaryngology, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine, Percutaneous tracheostomy, Head and neck surgery, General Medicine, Intensive care medicine, business, Letter to the Editor
Published: 2021
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43. Improving the Interpretation of D-Dimer Levels to Reduce the Imaging Burden of False-Positive Patients With Suspected Thromboembolism*

Author: Jonathan Ball
Subjects: medicine.medical_specialty, business.industry, Critical Illness, MEDLINE, Critical Care and Intensive Care Medicine, Interpretation (model theory), Fibrin Fibrinogen Degradation Products, Thromboembolism, D-dimer, Critical illness, Humans, Medicine, business, Intensive care medicine
Published: 2020
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44. Deliver Safer Care by Inventing Additional Intrusive Pop-Up Alerts to Interrupt Clinician Workflows?*

Author: Jonathan Ball
Subjects: World Wide Web, Decision support system, Workflow, Guideline adherence, business.industry, SAFER, MEDLINE, Medicine, Interrupt, Critical Care and Intensive Care Medicine, business
Published: 2020
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45. Oxford Desk Reference: Critical Care

Author: James Thomas and Jonathan Ball
Abstract: Oxford Desk Reference: Critical Care second edition is a clinical guide reflecting best practice and training pathways. Each topic is laid out in a concise entry, allowing rapid access to information. The second edition includes new sections on tissue perfusion monitoring and paediatric and maternal critical care, as well as expanded coverage of cardiovascular monitoring, myocardial infarction, and respiratory therapy techniques. New self-assessment questions support FFICM (Fellow of the Faculty of Intensive Care Medicine) and EDIC (European Diploma of Intensive Care) revision as well as continuing medical education reflection. Covering the entire discipline in an easy-to-read format, this is the definitive clinical reference for critical care, ideal for trainees, consultants, advanced care practitioners, and nurses.
Published: 2019
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46. A Cost-Effectiveness Analysis of Shortened Direct-Acting Antiviral Treatment in Genotype 1 Noncirrhotic Treatment-Naive Patients With Chronic Hepatitis C Virus

Author: Christopher G. Fawsitt, Peter Vickerman, Graham Cooke, Nicky J. Welton, Eleanor Barnes, Jonathan Ball, Diana Brainard, Gary Burgess, John Dillon, Graham Foster, Charles Gore, Neil Guha, Rachel Halford, Kevin Whitby, Chris Holmes, Anita Howe, Emma Hudson, Sharon Hutchinson, William Irving, Salim Khakoo, Paul Klenerman, Natasha Martin, Benedetta Massetto, Tamyo Mbisa, John McHutchison, Jane McKeating, John McLauchlan, Alec Miners, Andrea Murray, Peter Shaw, Peter Simmonds, Chris Spencer, Emma Thomson, Nicole Zitzmann, Consortium, Stop-HCV, Barnes, E, Hudson, E, Klenerman, P, Zitzmann, N, National Institute for Health Research, and Medical Research Council (MRC)
Subjects: Cyclopropanes, hepatitis C virus, Aminoisobutyric Acids, Cost effectiveness, Cost-Benefit Analysis, Hepacivirus, medicine.disease_cause, State Medicine, Therapy naive, 0302 clinical medicine, Genotype, 030212 general & internal medicine, Sulfonamides, cost effectiveness, 030503 health policy & services, Health Policy, shortened treatment duration, Cost-effectiveness analysis, Markov Chains, 3. Good health, Health Policy & Services, 0305 other medical science, Direct acting, medicine.medical_specialty, Macrocyclic Compounds, Proline, Lactams, Macrocyclic, Hepatitis C virus, Antiviral Agents, Heterocyclic Compounds, 4 or More Rings, Article, Virus, 1117 Public Health and Health Services, 03 medical and health sciences, Leucine, Quinoxalines, Internal medicine, medicine, Humans, 1402 Applied Economics, cost-effectiveness, direct-acting antivirals, business.industry, Decision Trees, Public Health, Environmental and Occupational Health, Hepatitis C, Chronic, United Kingdom, Confidence interval, Carbamates, Sofosbuvir, business, STOP-HCV Consortium
Abstract: Background Direct-acting antivirals are successful in curing hepatitis C virus infection in more than 95% of patients treated for 12 weeks, but they are expensive. Shortened treatment durations, which may have lower cure rates, have been proposed to reduce costs. Objectives To evaluate the lifetime cost-effectiveness of different shortened treatment durations for genotype 1 noncirrhotic treatment-naive patients. Methods Assuming a UK National Health Service perspective, we used a probabilistic decision tree and Markov model to compare 3 unstratified shortened treatment durations (8, 6, and 4 weeks) against a standard 12-week treatment duration. Patients failing shortened first-line treatment were re-treated with a 12-week treatment regimen. Parameter inputs were taken from published studies. Results The 8-week treatment duration had an expected incremental net monetary benefit of £7737 (95% confidence interval £3242-£11 819) versus the standard 12-week treatment, per 1000 patients. The 6-week treatment had a positive incremental net monetary benefit, although some uncertainty was observed. The probability that the 8- and 6-week treatments were the most cost-effective was 56% and 25%, respectively, whereas that for the 4-week treatment was 17%. Results were generally robust to sensitivity analyses, including a threshold analysis that showed that the 8-week treatment was the most cost-effective at all drug prices lower than £40 000 per 12-week course. Conclusions Shortening treatments licensed for 12 weeks to 8 weeks is cost-effective in genotype 1 noncirrhotic treatment-naive patients. There was considerable uncertainty in the estimates for 6- and 4-week treatments, with some indication that the 6-week treatment may be cost-effective., Highlights • The cost effectiveness of direct-acting antiviral treatment for chronic hepatitis C virus has been well documented, although the cost of treatment is considerable. Shortened treatment durations have been proposed to reduce costs, albeit at the expense of potentially curing fewer patients. • Shortening treatment duration from 12 to 8 weeks using direct-acting antiviral therapy is cost-effective for treatment of mild chronic hepatitis C virus in genotype 1 noncirrhotic treatment-naive patients, provided a re-treatment strategy is adopted for patients who fail first-line treatment. • There was considerable uncertainty in the cost-effectiveness estimates for the 6- and 4-week shortened treatments, with some indication that the 6-week treatment may be cost-effective, but the 4-week treatment may not. More robust evidence on the efficacy of the 6- and 4-week shortened treatment durations is needed.
Published: 2019
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47. The Lightning of Possible Storms

Author: Jonathan Ball and Jonathan Ball
Subjects: Short stories, Canadian--21st century
Abstract: Winner of the 2021 Margaret Laurence Award for Fiction Aleya's world starts to unravel after a cafÉ customer leaves behind a collection of short stories. Surprised and disturbed to discover that it has been dedicated to her, Aleya delves into the strange book...A mad scientist seeks to steal his son's dreams. A struggling writer, skilled only at destruction, finds himself courted by Hollywood. A woman seeks to escape her body and live inside her dreams. Citizens panic when a new city block manifests out of nowhere. The personification of capitalism strives to impress his cutthroat boss.The more Aleya reads, the deeper she sinks into the mysterious writer's work, and the less real the world around her seems. Soon, she's overwhelmed as a new, more terrifying existence takes hold.The Lightning of Possible Storms blends humour and horror, doom and daylight, offering myriad possible storms.Praise for Jonathan Ball:'Cheerfully horrifying, and full of the unexpected, The Lightning of Possible Storms is an entertaining Borgesian foray into the existential dread of writing itself.'—Saleema Nawaz, author of Songs for the End of the World'This collection is so beautifully written and expertly composed—it is rich, layered, and complex. In every story, characters are forced to confront their secret, subterranean selves, their suppressed longings and anxieties, and the stories will linger with you long after you've finished them, much like the last strains of a beloved song. Witty, sad, sardonic, each story is its own masterpiece. This collection confirms Jonathan Ball as one of Canada's very best writers.'—Suzette Mayr, author of Dr. Edith Vane and the Hares of Crawley Hall
Published: 2020

48. National Gallery

Author: Jonathan Ball and Jonathan Ball
Abstract: Jonathan Ball's fourth poetry book, the first in seven years, swirls chaos and confession together. At the book's heart is a question: Why create art? A series of poetic sequences torment themselves over this question, offering few answers and taking fewer prisoners. Loose sonnets that consider the artistic creations of Leatherface, monster-killer from The Texas Chain Saw Massacre, sit alongside Rilkean elegies for an iPhone. Surreal meditations on the collage work of Guy Maddin are followed by all of the lines from Melville's Moby-Dick that mention “salt.” Politicians and painters jostle while absurdist humour crashes into stark admissions of vulnerability in the wake of having children. A startling diversity of styles and subjects feed into the maelstrom of The National Gallery, and its dark currents will draw you in to drown.
Published: 2019

49. Abstract 5677: Recurrent transcriptionally active ESR1 fusions render therapeutic vulnerabilities to kinase inhibition in advanced breast cancer

Author: Dan R. Robinson, Xuxu Gou, Meenakshi Anurag, Jonathan Ball, Jonathan T. Lei, Adrian V. Lee, Matthew J. Ellis, Beom-Jun Kim, Michael Caldwell, Saif Rehman, Kevin P. White, and Sinem Seker
Subjects: Cancer Research, Oncology, business.industry, Advanced breast, Cancer research, Medicine, Cancer, Kinase inhibition, business, medicine.disease
Abstract: Background: We recently reported two ESR1 fusions (ESR1-YAP1 and ESR1-PCDH11X) that drive endocrine therapy (ET) resistance and metastasis in estrogen receptor positive (ER+) metastatic breast cancer (MBC) (PMC6171747). Here we report additional ESR1 fusions with diverse C-terminal partner genes - ESR1-DAB2, ESR1-GYG1, ESR1-SOX9, ESR1-ARNT2, ESR1-PCMT1 and ESR1-ARID1B. Their functional characteristics and effects on kinase biology will be described. Methods: ESR1 fusions were identified by RNA-seq in MBC using ChimeraScan to detect fusion junction reads. ESR1 fusion cDNA constructs were expressed in ER+ breast cancer cell lines. An alamarBlue assay assessed cell proliferation. RNA-seq followed by mRNA-qPCR assessed the transcriptional properties. A scratch wound assay assessed cell motility. A Kinase Inhibitor Pulldown (KIP) mass spectrometry-based assay was conducted to examine ESR1 fusion-driven druggable kinases. Results: All fusions retained the first 6 exons (e6) of ESR1, fused in-frame to C-terminal sequences of diverse partner genes. In addition to ESR1-YAP1 and ESR1-PCDH11X fusions, ESR1-SOX9 and ESR1-ARNT2 drove fulvestrant-resistant growth. RNA-seq revealed fusion-specific transcriptional signatures indicating enrichment of estrogen responsive and epithelial-to-mesenchymal transition (EMT) pathways that were confirmed by mRNA-qPCR. Transcriptionally active ESR1 fusions also promoted hormone-independent cell motility. KIP profiling demonstrated an increase in protein abundance of multiple receptor tyrosine kinases including RET and insulin like growth factor 1 receptor (IGF1R) in T47D cells expressing active ESR1 fusion proteins, both of which have been previously implicated in driving ET and MBC. Both proteins were also elevated in a patient-derived xenograft naturally harboring the ESR1-YAP1 fusion. Combinatorial inhibition of RET and IGF1R significantly suppressed ESR1 fusion-driven cell growth in vitro. Neither transcriptional activation nor kinase upregulation was observed in other ESR1-e6 fusions. Lastly, we report recurrent examples of specific known active ESR1 fusions: ESR1-PCDH11X (3 examples) (TEMPUS unpublished data) and ESR1-ARNT2 (2 examples) (PMC6872491). Conclusion: A subset of ESR1-e6 fusions are active, drive ET resistance and metastasis/EMT in experimental models. When ESR1 is fused in-frame with another transcriptional regulator, activity is predictable. However, recurrent partners that have non-transcriptional roles (PCDH11X) suggests cDNA expression-based functional screens should be continued. A common pattern of kinase activation indicates that ESR1 fusion specific therapeutic strategies could be devised. Citation Format: Xuxu Gou, Jonathan Lei, Beom-Jun Kim, Meenakshi Anurag, Sinem Seker, Saif Rehman, Adrian V. Lee, Kevin White, Michael Caldwell, Jonathan Ball, Dan R. Robinson, Matthew J. Ellis. Recurrent transcriptionally active ESR1 fusions render therapeutic vulnerabilities to kinase inhibition in advanced breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5677.
Published: 2020
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50. Effectiveness of an antifungal stewardship programme at a London teaching hospital 2010–16

Author: Hasan Al-Ghusein, Rachel Wake, Matthias Klammer, Jonathan Youngs, Laura Whitney, Mickey Koh, Stephen Glass, Tihana Bicanic, Angela Houston, and Jonathan Ball
Subjects: 0301 basic medicine, Microbiology (medical), Adult, Male, medicine.medical_specialty, Antifungal Agents, Adolescent, 030106 microbiology, Pharmacist, Pharmacy, Drug resistance, Microbial Sensitivity Tests, Flucytosine, 03 medical and health sciences, Antimicrobial Stewardship, Young Adult, 0302 clinical medicine, Drug Resistance, Fungal, Amphotericin B, London, Medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Prospective Studies, Hospitals, Teaching, Aged, Candida, Pharmacology, Voriconazole, Aged, 80 and over, business.industry, Incidence (epidemiology), Candidemia, Health Care Costs, Middle Aged, Survival Analysis, Drug Utilization, Infectious Diseases, Treatment Outcome, Emergency medicine, Female, business, Fluconazole, medicine.drug
Abstract: Background\ud The need for antifungal stewardship is gaining recognition with increasing incidence of invasive fungal infection (IFI) and antifungal resistance alongside the high cost of antifungal drugs. Following an audit showing suboptimal practice we initiated an antifungal stewardship programme and prospectively evaluated its impact on clinical and financial outcomes.\ud \ud Patients and methods\ud From October 2010 to September 2016, adult inpatients receiving amphotericin B, echinocandins, intravenous fluconazole, flucytosine or voriconazole were reviewed weekly by an infectious diseases consultant and antimicrobial pharmacist. Demographics, diagnosis by European Organization for Research and Treatment of Cancer (EORTC) criteria, drug, indication, advice, acceptance and in-hospital mortality were recorded. Antifungal consumption and expenditure, and candidaemia species and susceptibility data were extracted from pharmacy and microbiology databases.\ud \ud Results\ud A total of 432 patients were reviewed, most commonly receiving AmBisome® (35%) or intravenous fluconazole (29%). Empirical treatment was often unnecessary, with 82% having no evidence of IFI. Advice was given in 64% of reviews (most commonly de-escalating or stopping treatment) and was followed in 84%. Annual antifungal expenditure initially reduced by 30% (£0.98 million to £0.73 million), then increased to 20% above baseline over a 5 year period; this was a significantly lower rise compared with national figures, which showed a doubling of expenditure over the same period. Inpatient mortality, Candida species distribution and rates of resistance were not adversely affected by the intervention.\ud \ud Conclusions\ud Provision of specialist input to optimize antifungal prescribing resulted in significant cost savings without compromising on microbiological or clinical outcomes. Our model is readily implementable by hospitals with high numbers of at-risk patients and antifungal expenditure.
Published: 2019

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