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601 results on '"Eyre, D."'

1. Genomic epidemiology and longitudinal sampling of ward wastewater environments and patients reveals complexity of the transmission dynamics of blaKPC-carbapenemase-producing Enterobacterales in a hospital setting.

Author

Stoesser, N, George, R, Aiken, Z, Phan, H T T, Lipworth, S, Quan, T P, Mathers, A J, Maio, N De, Seale, A C, Eyre, D W, Vaughan, A, Swann, J, Peto, T E A, Crook, D W, Cawthorne, J, Dodgson, A, Walker, A S, and Group, TRACE Investigators

Published
2024
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3. The investigation of tube sampling disturbance using transparent soil and particle image velocimetry

Author

Hover, Eyre D.

Subjects
620, S Agriculture (General), TA Engineering (General). Civil engineering (General)
Abstract

A small-scale physical modelling system was developed and employed to investigate the effects of tube sampling. Amorphous silica and an oil blend of matching refractive index were mixed to form a transparent soil. Black glass beads were embedded within the soil body on the vertical central plane. After consolidation in a Perspex box, a glass model sampler was pushed into the transparent soil. Movements within the soil body were recorded using digital photography; these images were later analysed by Particle Image Velocimetry. The centreline strain path (CSP) of the sample during tube penetration was calculated and compared to existing analytical and numerical models’ strain predictions, and some degree of correlation was observed. However, it is shown that the CSP is not constant throughout the sample, but varies with depth below the base of the borehole. It was also noticed that after tube penetration, significant residual extensive strains remain for soil on the centreline of the specimen. Different tube geometries were tested and a correlation was found between strain magnitudes and the Area Ratio, Inside Clearance Ratio and the Outer Cutting Edge Taper Angle. It was also found that samples taken in normally consolidated soils were more heavily disturbed than those in lightly overconsolidated soils. After removal from the soil model, samples were stored for six months and volumetric strains within them, set up by a redistribution of pore fluid pressures, were found to be small, typically less than 1%. Soil at the edge of the sampler wall reduced in volume, while the centre swelled. Specimens were thereafter extruded from the sampling tube and the strain path created by this step was quantified. It was found that extrusion compresses the soil while still inside the tube, with soil closest to the extruder more significantly affected. All of these parts of the sampling process contribute to the overall sample disturbance and can therefore have an effect on the sample’s measured properties.

Published
2014

5. Self-Aware SGD: Reliable Incremental Adaptation Framework for Clinical AI Models

Author

Thakur, A, Armstrong, J, Youssef, A, Eyre, D, and Clifton, DA

Subjects
Health Information Management, Health Informatics, Electrical and Electronic Engineering, Computer Science Applications
Abstract

Healthcare is dynamic as demographics, diseases, and therapeutics constantly evolve. This dynamic nature induces inevitable distribution shifts in populations targeted by clinical AI models, often rendering them ineffective. Incremental learning provides an effective method of adapting deployed clinical models to accommodate these contemporary distribution shifts. However, since incremental learning involves modifying a deployed or in-use model, it can be considered unreliable as any adverse modification due to maliciously compromised or incorrectly labelled data can make the model unsuitable for the targeted application. This paper introduces self-aware stochastic gradient descent (SGD), an incremental deep learning algorithm that utilises a contextual bandit-like sanity check to only allow reliable modifications to a model. The contextual bandit analyses incremental gradient updates to isolate and filter unreliable gradients. This behaviour allows self-aware SGD to balance incremental training and integrity of a deployed model. Experimental evaluations on the Oxford University Hospital datasets highlight that self-aware SGD can provide reliable incremental updates for overcoming distribution shifts in challenging conditions induced by label noise

Published
2023
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6. Radiotranscriptomic Phenotyping Of Cytokine-driven Arterial Inflammation Predicts The Clinical Significance Of Different Covid-19 Variants: Insights From The Uk C19crc National Flagship Programme

Author

Xie, C., primary, Kotanidis, C., additional, Siddique, M., additional, Thomas, S., additional, Polkinghorne, M., additional, Chauhan, J., additional, Patel, P., additional, Lumley, S., additional, Shaw, R., additional, Andersson, M., additional, Eyre, D., additional, Tomlins, P., additional, Shirodaria, C., additional, Neubauer, S., additional, Deanfield, J., additional, Shaw, L., additional, Blankstein, R., additional, Channon, K., additional, and Antoniades, C., additional

Published
2023
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7. Treatment of enteric fever (typhoid and paratyphoid fever) with cephalosporins

Author

Kuehn, R, Stoesser, N, Eyre, D, Darton, TC, Basnyat, B, and Parry, CM

Subjects
Adult, Ofloxacin, Adolescent, Ceftriaxone, Azithromycin, Cephalosporins, Anti-Bacterial Agents, Chloramphenicol, Anti-Infective Agents, Cefixime, Ciprofloxacin, Recurrence, Paratyphoid Fever, Humans, Pakistan, Pharmacology (medical), Typhoid Fever, Child, Fluoroquinolones, Monobactams
Abstract

Background Typhoid and paratyphoid (enteric fever) are febrile bacterial illnesses common in many low‐ and middle‐income countries. The World Health Organization (WHO) currently recommends treatment with azithromycin, ciprofloxacin, or ceftriaxone due to widespread resistance to older, first‐line antimicrobials. Resistance patterns vary in different locations and are changing over time. Fluoroquinolone resistance in South Asia often precludes the use of ciprofloxacin. Extensively drug‐resistant strains of enteric fever have emerged in Pakistan. In some areas of the world, susceptibility to old first‐line antimicrobials, such as chloramphenicol, has re‐appeared. A Cochrane Review of the use of fluoroquinolones and azithromycin in the treatment of enteric fever has previously been undertaken, but the use of cephalosporins has not been systematically investigated and the optimal choice of drug and duration of treatment are uncertain. Objectives To evaluate the effectiveness of cephalosporins for treating enteric fever in children and adults compared to other antimicrobials. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, the WHO ICTRP and ClinicalTrials.gov up to 24 November 2021. We also searched reference lists of included trials, contacted researchers working in the field, and contacted relevant organizations. Selection criteria We included randomized controlled trials (RCTs) in adults and children with enteric fever that compared a cephalosporin to another antimicrobial, a different cephalosporin, or a different treatment duration of the intervention cephalosporin. Enteric fever was diagnosed on the basis of blood culture, bone marrow culture, or molecular tests. Data collection and analysis We used standard Cochrane methods. Our primary outcomes were clinical failure, microbiological failure and relapse. Our secondary outcomes were time to defervescence, duration of hospital admission, convalescent faecal carriage, and adverse effects. We used the GRADE approach to assess certainty of evidence for each outcome. Main results We included 27 RCTs with 2231 total participants published between 1986 and 2016 across Africa, Asia, Europe, the Middle East and the Caribbean, with comparisons between cephalosporins and other antimicrobials used for the treatment of enteric fever in children and adults. The main comparisons are between antimicrobials in most common clinical use, namely cephalosporins compared to a fluoroquinolone and cephalosporins compared to azithromycin. Cephalosporin (cefixime) versus fluoroquinolones Clinical failure, microbiological failure and relapse may be increased in patients treated with cefixime compared to fluoroquinolones in three small trials published over 14 years ago: clinical failure (risk ratio (RR) 13.39, 95% confidence interval (CI) 3.24 to 55.39; 2 trials, 240 participants; low‐certainty evidence); microbiological failure (RR 4.07, 95% CI 0.46 to 36.41; 2 trials, 240 participants; low‐certainty evidence); relapse (RR 4.45, 95% CI 1.11 to 17.84; 2 trials, 220 participants; low‐certainty evidence). Time to defervescence in participants treated with cefixime may be longer compared to participants treated with fluoroquinolones (mean difference (MD) 1.74 days, 95% CI 0.50 to 2.98, 3 trials, 425 participants; low‐certainty evidence). Cephalosporin (ceftriaxone) versus azithromycin Ceftriaxone may result in a decrease in clinical failure compared to azithromycin, and it is unclear whether ceftriaxone has an effect on microbiological failure compared to azithromycin in two small trials published over 18 years ago and in one more recent trial, all conducted in participants under 18 years of age: clinical failure (RR 0.42, 95% CI 0.11 to 1.57; 3 trials, 196 participants; low‐certainty evidence); microbiological failure (RR 1.95, 95% CI 0.36 to 10.64, 3 trials, 196 participants; very low‐certainty evidence). It is unclear whether ceftriaxone increases or decreases relapse compared to azithromycin (RR 10.05, 95% CI 1.93 to 52.38; 3 trials, 185 participants; very low‐certainty evidence). Time to defervescence in participants treated with ceftriaxone may be shorter compared to participants treated with azithromycin (mean difference of −0.52 days, 95% CI −0.91 to −0.12; 3 trials, 196 participants; low‐certainty evidence). Cephalosporin (ceftriaxone) versus fluoroquinolones It is unclear whether ceftriaxone has an effect on clinical failure, microbiological failure, relapse, and time to defervescence compared to fluoroquinolones in three trials published over 28 years ago and two more recent trials: clinical failure (RR 3.77, 95% CI 0.72 to 19.81; 4 trials, 359 participants; very low‐certainty evidence); microbiological failure (RR 1.65, 95% CI 0.40 to 6.83; 3 trials, 316 participants; very low‐certainty evidence); relapse (RR 0.95, 95% CI 0.31 to 2.92; 3 trials, 297 participants; very low‐certainty evidence) and time to defervescence (MD 2.73 days, 95% CI −0.37 to 5.84; 3 trials, 285 participants; very low‐certainty evidence). It is unclear whether ceftriaxone decreases convalescent faecal carriage compared to the fluoroquinolone gatifloxacin (RR 0.18, 95% CI 0.01 to 3.72; 1 trial, 73 participants; very low‐certainty evidence) and length of hospital stay may be longer in participants treated with ceftriaxone compared to participants treated with the fluoroquinolone ofloxacin (mean of 12 days (range 7 to 23 days) in the ceftriaxone group compared to a mean of 9 days (range 6 to 13 days) in the ofloxacin group; 1 trial, 47 participants; low‐certainty evidence). Authors' conclusions Based on very low‐ to low‐certainty evidence, ceftriaxone is an effective treatment for adults and children with enteric fever, with few adverse effects. Trials suggest that there may be no difference in the performance of ceftriaxone compared with azithromycin, fluoroquinolones, or chloramphenicol. Cefixime can also be used for treatment of enteric fever but may not perform as well as fluoroquinolones. We are unable to draw firm general conclusions on comparative contemporary effectiveness given that most trials were small and conducted over 20 years previously. Clinicians need to take into account current, local resistance patterns in addition to route of administration when choosing an antimicrobial.

Published
2022
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8. SARS-CoV-2 evolution during treatment of chronic infection

Author

Kemp, S. A., Collier, D. A., Datir, R. P., Ferreira, I. A. T. M., Gayed, S., Jahun, A., Hosmillo, M., Rees-Spear, C., Mlcochova, P., Lumb, I. U., Roberts, D. J., Chandra, A., Temperton, N., Baker, S., Dougan, G., Hess, C., Kingston, N., Lehner, P. J., Lyons, P. A., Matheson, N. J., Owehand, W. H., Saunders, C., Summers, C., Thaventhiran, J. E. D., Toshner, M., Weekes, M. P., Bucke, A., Calder, J., Canna, L., Domingo, J., Elmer, A., Fuller, S., Harris, J., Hewitt, S., Kennet, J., Jose, S., Kourampa, J., Meadows, A., O'Brien, C., Price, J., Publico, C., Rastall, R., Ribeiro, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Bullman, B., Dunmore, B. J., Fawke, S., Graf, S., Hodgson, J., Huang, C., Hunter, K., Jones, E., Legchenko, E., Matara, C., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Pond, N., Shih, J., Sutcliffe, R., Tilly, T., Treacy, C., Tong, Z., Wood, J., Wylot, M., Bergamaschi, L., Betancourt, A., Bower, G., Cossetti, C., De Sa, A., Epping, M., Gleadall, N., Grenfell, R., Hinch, A., Huhn, O., Jackson, S., Jarvis, I., Lewis, D., Marsden, J., Nice, F., Okecha, G., Omarjee, O., Perera, M., Richoz, N., Romashova, V., Yarkoni, N. S., Sharma, R., Stefanucci, L., Stephens, J., Strezlecki, M., Turner, L., De Bie, E. M. D. D., Bunclark, K., Josipovic, M., Mackay, M., Rossi, S., Selvan, M., Spencer, S., Yong, C., Ansaripour, A., Michael, A., Mwaura, L., Patterson, C., Polwarth, G., Polgarova, P., di Stefano, G., Fahey, C., Michel, R., Bong, S. -H., Coudert, J. D., Holmes, E., Allison, J., Butcher, H., Caputo, D., Clapham-Riley, D., Dewhurst, E., Furlong, A., Graves, B., Gray, J., Ivers, T., Kasanicki, M., Le Gresley, E., Linger, R., Meloy, S., Muldoon, F., Ovington, N., Papadia, S., Phelan, I., Stark, H., Stirrups, K. E., Townsend, P., Walker, N., Webster, J., Robson, S. C., Loman, N. J., Connor, T. R., Golubchik, T., Martinez Nunez, R. T., Ludden, C., Corden, S., Johnston, I., Bonsall, D., Smith, C. P., Awan, A. R., Bucca, G., Estee Torok, M., Saeed, K., Prieto, J. A., Jackson, D. K., Hamilton, W. L., Snell, L. B., Moore, C., Harrison, E. M., Goncalves, S., Fairley, D. J., Loose, M. W., Watkins, J., Livett, R., Moses, S., Amato, R., Nicholls, S., Bull, M., Smith, D. L., Barrett, J., Aanensen, D. M., Curran, M. D., Parmar, S., Aggarwal, D., Shepherd, J. G., Parker, M. D., Glaysher, S., Bashton, M., Underwood, A. P., Pacchiarini, N., Loveson, K. F., Carabelli, A. M., Templeton, K. E., Langford, C. F., Sillitoe, J., de Silva, T. I., Wang, D., Kwiatkowski, D., Rambaut, A., O'Grady, J., Cottrell, S., Holden, M. T. G., Thomson, E. C., Osman, H., Andersson, M., Chauhan, A. J., Hassan-Ibrahim, M. O., Lawniczak, M., Alderton, A., Chand, M., Constantinidou, C., Unnikrishnan, M., Darby, A. C., Hiscox, J. A., Paterson, S., Martincorena, I., Robertson, D. L., Volz, E. M., Page, A. J., Pybus, O. G., Bassett, A. R., Ariani, C. V., Spencer Chapman, M. H., K. K., Li, Shah, R. N., Jesudason, N. G., Taha, Y., Mchugh, M. P., Dewar, R., Jahun, A. S., Mcmurray, C., Pandey, S., Mckenna, J. P., Nelson, A., Young, G. R., Mccann, C. M., Elliott, S., Lowe, H., Temperton, B., Roy, S., Price, A., Rey, S., Wyles, M., Rooke, S., Shaaban, S., de Cesare, M., Letchford, L., Silveira, S., Pelosi, E., Wilson-Davies, E., O'Toole, A., Hesketh, A. R., Stark, R., du Plessis, L., Ruis, C., Adams, H., Bourgeois, Y., Michell, S. L., Gramatopoulos, D., Edgeworth, J., Breuer, J., Todd, J. A., Fraser, C., Buck, D., John, M., Kay, G. L., Palmer, S., Peacock, S. J., Heyburn, D., Weldon, D., Robinson, E., Mcnally, A., Muir, P., Vipond, I. B., Boyes, J., Sivaprakasam, V., Salluja, T., Dervisevic, S., Meader, E. J., Park, N. R., Oliver, K., Jeffries, A. R., Ott, S., da Silva Filipe, A., Simpson, D. A., Williams, C., Masoli, J. A. H., Knight, B. A., Jones, C. R., Koshy, C., Ash, A., Casey, A., Bosworth, A., Ratcliffe, L., Xu-McCrae, L., Pymont, H. M., Hutchings, S., Berry, L., Jones, K., Halstead, F., Davis, T., Holmes, C., Iturriza-Gomara, M., Lucaci, A. O., Randell, P. A., Cox, A., Madona, P., Harris, K. A., Brown, J. R., Mahungu, T. W., Irish-Tavares, D., Haque, T., Hart, J., Witele, E., Fenton, M. L., Liggett, S., Graham, C., Swindells, E., Collins, J., Eltringham, G., Campbell, S., Mcclure, P. C., Clark, G., Sloan, T. J., Jones, C., Lynch, J., Warne, B., Leonard, S., Durham, J., Williams, T., Haldenby, S. T., Storey, N., Alikhan, N. -F., Holmes, N., Carlile, M., Perry, M., Craine, N., Lyons, R. A., Beckett, A. H., Goudarzi, S., Fearn, C., Cook, K., Dent, H., Paul, H., Davies, R., Blane, B., Girgis, S. T., Beale, M. A., Bellis, K. L., Dorman, M. J., Drury, E., Kane, L., Kay, S., Mcguigan, S., Nelson, R., Prestwood, L., Rajatileka, S., Batra, R., Williams, R. J., Kristiansen, M., Green, A., Justice, A., Mahanama, A. I. K., Samaraweera, B., Hadjirin, N. F., Quick, J., Poplawski, R., Kermack, L. M., Reynolds, N., Hall, G., Chaudhry, Y., Pinckert, M. L., Georgana, I., Moll, R. J., Thornton, A., Myers, R., Stockton, J., Williams, C. A., Yew, W. C., Trotter, A. J., Trebes, A., MacIntyre-Cockett, G., Birchley, A., Adams, A., Plimmer, A., Gatica-Wilcox, B., Mckerr, C., Hilvers, E., Jones, H., Asad, H., Coombes, J., Evans, J. M., Fina, L., Gilbert, L., Graham, L., Cronin, M., Kumziene-Summerhayes, S., Taylor, S., Jones, S., Groves, D. C., Zhang, P., Gallis, M., Louka, S. F., Starinskij, I., Jackson, C., Gourtovaia, M., Tonkin-Hill, G., Lewis, K., Tovar-Corona, J. M., James, K., Baxter, L., Alam, M. T., Orton, R. J., Hughes, J., Vattipally, S., Ragonnet-Cronin, M., Nascimento, F. F., Jorgensen, D., Boyd, O., Geidelberg, L., Zarebski, A. E., Raghwani, J., Kraemer, M. U. G., Southgate, J., Lindsey, B. B., Freeman, T. M., Keatley, J. -P., Singer, J. B., de Oliveira Martins, L., Yeats, C. A., Abudahab, K., Taylor, B. E. W., Menegazzo, M., Danesh, J., Hogsden, W., Eldirdiri, S., Kenyon, A., Mason, J., Robinson, T. I., Holmes, A., Hartley, J. A., Curran, T., Mather, A. E., Shankar, G., Jones, R., Howe, R., Morgan, S., Wastenge, E., Chapman, M. R., Mookerjee, S., Stanley, R., Smith, W., Peto, T., Eyre, D., Crook, D., Vernet, G., Kitchen, C., Gulliver, H., Merrick, I., Guest, M., Munn, R., Bradley, D. T., Wyatt, T., Beaver, C., Foulser, L., Churcher, C. M., Brooks, E., Smith, K. S., Galai, K., Mcmanus, G. M., Bolt, F., Coll, F., Meadows, L., Attwood, S. W., Davies, A., De Lacy, E., Downing, F., Edwards, S., Scarlett, G. P., Jeremiah, S., Smith, N., Leek, D., Sridhar, S., Forrest, S., Cormie, C., Gill, H. K., Dias, J., Higginson, E. E., Maes, M., Young, J., Wantoch, M., Jamrozy, D., Lo, S., Patel, M., Hill, V., Bewshea, C. M., Ellard, S., Auckland, C., Harrison, I., Bishop, C., Chalker, V., Richter, A., Beggs, A., Best, A., Percival, B., Mirza, J., Megram, O., Mayhew, M., Crawford, L., Ashcroft, F., Moles-Garcia, E., Cumley, N., Hopes, R., Asamaphan, P., Niebel, M. O., Gunson, R. N., Bradley, A., Maclean, A., Mollett, G., Blacow, R., Bird, P., Helmer, T., Fallon, K., Tang, J., Hale, A. D., Macfarlane-Smith, L. R., Harper, K. L., Carden, H., Machin, N. W., Jackson, K. A., Ahmad, S. S. Y., George, R. P., Turtle, L., O'Toole, E., Watts, J., Breen, C., Cowell, A., Alcolea-Medina, A., Charalampous, T., Patel, A., Levett, L. J., Heaney, J., Rowan, A., Taylor, G. P., Shah, D., Atkinson, L., Lee, J. C. D., Westhorpe, A. P., Jannoo, R., Lowe, H. L., Karamani, A., Ensell, L., Chatterton, W., Pusok, M., Dadrah, A., Symmonds, A., Sluga, G., Molnar, Z., Baker, P., Bonner, S., Essex, S., Barton, E., Padgett, D., Scott, G., Greenaway, J., Payne, B. A. I., Burton-Fanning, S., Waugh, S., Raviprakash, V., Sheriff, N., Blakey, V., Williams, L. -A., Moore, J., Stonehouse, S., Smith, L., Davidson, R. K., Bedford, L., Coupland, L., Wright, V., Chappell, J. G., Tsoleridis, T., Ball, J., Khakh, M., Fleming, V. M., Lister, M. M., Howson-Wells, H. C., Boswell, T., Joseph, A., Willingham, I., Duckworth, N., Walsh, S., Wise, E., Moore, N., Mori, M., Cortes, N., Kidd, S., Williams, R., Gifford, L., Bicknell, K., Wyllie, S., Lloyd, A., Impey, R., Malone, C. S., Cogger, B. J., Levene, N., Monaghan, L., Keeley, A. J., Partridge, D. G., Raza, M., Evans, C., Johnson, K., Abnizova, I., Aigrain, L., Ali, M., Allen, L., Anderson, R., Ariani, C., Austin-Guest, S., Bala, S., Bassett, A., Battleday, K., Beal, J., Beale, M., Bellany, S., Bellerby, T., Bellis, K., Berger, D., Berriman, M., Betteridge, E., Bevan, P., Binley, S., Bishop, J., Blackburn, K., Bonfield, J., Boughton, N., Bowker, S., Brendler-Spaeth, T., Bronner, I., Brooklyn, T., Buddenborg, S. K., Bush, R., Caetano, C., Cagan, A., Carter, N., Cartwright, J., Monteiro, T. C., Chapman, L., Chillingworth, T. -J., Clapham, P., Clark, R., Clarke, A., Clarke, C., Cole, D., Cook, E., Coppola, M., Cornell, L., Cornwell, C., Corton, C., Crackett, A., Cranage, A., Craven, H., Craw, S., Crawford, M., Cutts, T., Dabrowska, M., Davies, M., Dawson, J., Day, C., Densem, A., Dibling, T., Dockree, C., Dodd, D., Dogga, S., Dougherty, M., Dove, A., Drummond, L., Dudek, M., Durrant, L., Easthope, E., Eckert, S., Ellis, P., Farr, B., Fenton, M., Ferrero, M., Flack, N., Fordham, H., Forsythe, G., Francis, M., Fraser, A., Freeman, A., Galvin, A., Garcia-Casado, M., Gedny, A., Girgis, S., Glover, J., Goodwin, S., Gould, O., Gray, A., Gray, E., Griffiths, C., Gu, Y., Guerin, F., Hamilton, W., Hanks, H., Harrison, E., Harrott, A., Harry, E., Harvison, J., Heath, P., Hernandez-Koutoucheva, A., Hobbs, R., Holland, D., Holmes, S., Hornett, G., Hough, N., Huckle, L., Hughes-Hallet, L., Hunter, A., Inglis, S., Iqbal, S., Jackson, A., Jackson, D., Verdejo, C. J., Jones, M., Kallepally, K., Kay, K., Keatley, J., Keith, A., King, A., Kitchin, L., Kleanthous, M., Klimekova, M., Korlevic, P., Krasheninnkova, K., Lane, G., Langford, C., Laverack, A., Law, K., Lensing, S., Lewis-Wade, A., Liddle, J., Lin, Q., Lindsay, S., Linsdell, S., Long, R., Lovell, J., Mack, J., Maddison, M., Makunin, A., Mamun, I., Mansfield, J., Marriott, N., Martin, M., Mayho, M., Mccarthy, S., Mcclintock, J., Mchugh, S., Mcminn, L., Meadows, C., Mobley, E., Moll, R., Morra, M., Morrow, L., Murie, K., Nash, S., Nathwani, C., Naydenova, P., Neaverson, A., Nerou, E., Nicholson, J., Nimz, T., Noell, G. G., O'Meara, S., Ohan, V., Olney, C., Ormond, D., Oszlanczi, A., Pang, Y. F., Pardubska, B., Park, N., Parmar, A., Patel, G., Payne, M., Peacock, S., Petersen, A., Plowman, D., Preston, T., Puethe, C., Quail, M., Rajan, D., Rance, R., Rawlings, S., Redshaw, N., Reynolds, J., Reynolds, M., Rice, S., Richardson, M., Roberts, C., Robinson, K., Robinson, M., Robinson, D., Rogers, H., Rojo, E. M., Roopra, D., Rose, M., Rudd, L., Sadri, R., Salmon, N., Saul, D., Schwach, F., Scott, C., Seekings, P., Shirley, L., Simms, A., Sinnott, M., Sivadasan, S., Siwek, B., Sizer, D., Skeldon, K., Skelton, J., Slater-Tunstill, J., Sloper, L., Smerdon, N., Smith, C., Smith, J., Smith, K., Smith, M., Smith, S., Smith, T., Sneade, L., Soria, C. D., Sousa, C., Souster, E., Sparkes, A., Spencer-Chapman, M., Squares, J., Steed, C., Stickland, T., Still, I., Stratton, M., Strickland, M., Swann, A., Swiatkowska, A., Sycamore, N., Swift, E., Symons, E., Szluha, S., Taluy, E., Tao, N., Taylor, K., Thompson, S., Thompson, M., Thomson, M., Thomson, N., Thurston, S., Toombs, D., Topping, B., Tovar-Corona, J., Ungureanu, D., Uphill, J., Urbanova, J., Jansen Van, P., Vancollie, V., Voak, P., Walker, D., Walker, M., Waller, M., Ward, G., Weatherhogg, C., Webb, N., Wells, A., Wells, E., Westwood, L., Whipp, T., Whiteley, T., Whitton, G., Whitwham, A., Widaa, S., Williams, M., Wilson, M., Wright, S., Farr, B. W., Quail, M. A., Thurston, S. A. J., Bronner, I. F., Redshaw, N. M., Lensing, S. V., Balcazar, C. E., Gallagher, M. D., Williamson, K. A., Stanton, T. D., Michelsen, M. L., Warwick-Dugdale, J., Manley, R., Farbos, A., Harrison, J. W., Sambles, C. M., Studholme, D. J., Lackenby, A., Mbisa, T., Platt, S., Miah, S., Bibby, D., Manso, C., Hubb, J., Dabrera, G., Ramsay, M., Bradshaw, D., Schaefer, U., Groves, N., Gallagher, E., Lee, D., Williams, D., Ellaby, N., Hartman, H., Manesis, N., Patel, V., Ledesma, J., Twohig, K. A., Allara, E., Pearson, C., Cheng, J. K. J., Bridgewater, H. E., Frost, L. R., Taylor-Joyce, G., Brown, P. E., Tong, L., Broos, A., Mair, D., Nichols, J., Carmichael, S. N., Smollett, K. L., Nomikou, K., Aranday-Cortes, E., Johnson, N., Nickbakhsh, S., Vamos, E. E., Hughes, M., Rainbow, L., Eccles, R., Nelson, C., Whitehead, M., Gregory, R., Gemmell, M., Wierzbicki, C., Webster, H. J., Fisher, C. L., Signell, A. W., Betancor, G., Wilson, H. D., Nebbia, G., Flaviani, F., Cerda, A. C., Merrill, T. V., Wilson, R. E., Cotic, M., Bayzid, N., Thompson, T., Acheson, E., Rushton, S., O'Brien, S., Baker, D. J., Rudder, S., Aydin, A., Sang, F., Debebe, J., Francois, S., Vasylyeva, T. I., Zamudio, M. E., Gutierrez, B., Marchbank, A., Maksimovic, J., Spellman, K., Mccluggage, K., Morgan, M., Beer, R., Afifi, S., Workman, T., Fuller, W., Bresner, C., Angyal, A., Green, L. R., Parsons, P. J., Tucker, R. M., Brown, R., Whiteley, M., Rowe, W., Siveroni, I., Le-Viet, T., Gaskin, A., Johnson, R., Sharrocks, K., Blane, E., Modis, Y., Leigh, K. E., Briggs, J. A. G., van Gils, M. J., Smith, K. G. C., Bradley, J. R., Doffinger, R., Ceron-Gutierrez, L., Barcenas-Morales, G., Pollock, D. D., Goldstein, R. A., Smielewska, A., Skittrall, J. P., Gouliouris, T., Goodfellow, I. G., Gkrania-Klotsas, E., Illingworth, C. J. R., Mccoy, L. E., Gupta, R. K., Medical Microbiology and Infection Prevention, AII - Infectious diseases, Collier, Dami A [0000-0001-5446-4423], Jahun, Aminu [0000-0002-4585-1701], Temperton, Nigel [0000-0002-7978-3815], Modis, Yorgo [0000-0002-6084-0429], Briggs, John AG [0000-0003-3990-6910], Goldstein, Richard A [0000-0001-5148-4672], Skittrall, Jordan P [0000-0002-8228-3758], Gkrania-Klotsas, Effrossyni [0000-0002-0930-8330], McCoy, Laura E [0000-0001-9503-7946], Gupta, Ravindra K [0000-0001-9751-1808], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Male, Time Factors, viruses, Passive, Antibodies, Viral, CITIID-NIHR BioResource COVID-19 Collaboration, 2.1 Biological and endogenous factors, Viral, Aetiology, Neutralizing, Lung, Phylogeny, neutralising antibodies, Infectivity, education.field_of_study, Genome, Multidisciplinary, Alanine, biology, High-Throughput Nucleotide Sequencing, Viral Load, Spike Glycoprotein, Virus Shedding, Adenosine Monophosphate, Aged, Antibodies, Neutralizing, COVID-19, Chronic Disease, Genome, Viral, Humans, Immune Evasion, Immune Tolerance, Immunization, Passive, Immunosuppression Therapy, Mutagenesis, Mutant Proteins, Mutation, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Evolution, Molecular, Infectious Diseases, Pneumonia & Influenza, Antibody, Infection, Viral load, Biotechnology, Evolution, General Science & Technology, antibody escape, Convalescent plasma, 030106 microbiology, Population, evasion, Antibodies, Virus, Article, Vaccine Related, resistance, 03 medical and health sciences, Immune system, COVID-19 Genomics UK (COG-UK) Consortium, Biodefense, Genetics, Viral shedding, education, COVID-19 Serotherapy, QR355, Prevention, Wild type, Molecular, Pneumonia, Virology, COVID-19 Drug Treatment, Coronavirus, Emerging Infectious Diseases, Good Health and Well Being, 030104 developmental biology, biology.protein, Immunization, immune suppression, mutation
Abstract

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for virus infection through the engagement of the human ACE2 protein1 and is a major antibody target. Here we show that chronic infection with SARS-CoV-2 leads to viral evolution and reduced sensitivity to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma, by generating whole-genome ultra-deep sequences for 23 time points that span 101 days and using in vitro techniques to characterize the mutations revealed by sequencing. There was little change in the overall structure of the viral population after two courses of remdesivir during the first 57 days. However, after convalescent plasma therapy, we observed large, dynamic shifts in the viral population, with the emergence of a dominant viral strain that contained a substitution (D796H) in the S2 subunit and a deletion (ΔH69/ΔV70) in the S1 N-terminal domain of the spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype were reduced in frequency, before returning during a final, unsuccessful course of convalescent plasma treatment. In vitro, the spike double mutant bearing both ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, while maintaining infectivity levels that were similar to the wild-type virus.The spike substitution mutant D796H appeared to be the main contributor to the decreased susceptibility to neutralizing antibodies, but this mutation resulted in an infectivity defect. The spike deletion mutant ΔH69/ΔV70 had a twofold higher level of infectivity than wild-type SARS-CoV-2, possibly compensating for the reduced infectivity of the D796H mutation. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing antibodies in immunosuppressed individuals.

Published
2021

9. The Social Origins of Students Identified as Gifted and Talented in England: A Geo-Demographic Analysis

Author

Campbell, R. J., Muijs, R. D., Neelands, J. G. A., Robinson, W., Eyre, D., and Hewston, R.

Abstract

The English education system has been shown over a long period to be catering poorly for the educational needs of gifted and talented students. In the last five years, however, a national policy and an associated strategy have been established, distinctively attempting to embed core provisions for gifted and talented students in the mainstream school system. A major thrust of this "English model" is to identify and support students from those lower socio-economic groups, and ethnic minorities, which historically have been under-represented in higher education. This social inclusivity dimension to the national policy raises substantive challenges for policy research and development. This paper provides a detailed geo-demographic analysis of over 37,000 gifted and talented students admitted to the National Academy for Gifted and Talented Youth in England in 2003/2005. The analysis shows that the National Academy, whilst having a student membership skewed towards groups with high levels of cultural and economic capital, had nonetheless reached significant numbers of students in the poorest areas, something over 3000 students, and 8% of students identified as gifted and talented at this stage. Possible explanations for the profile of gifted and talented students' social origins are raised, and an intervention project arising from the analysis is outlined. (Contains 6 tables.)

Published
2007
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12. Divergent trajectories of antiviral memory after SARS-CoV-2 infection

Author

Tomic, A, Skelly, DT, Ogbe, A, O’Connor, D, Pace, M, Adland, E, Alexander, F, Ali, M, Allott, K, Azim Ansari, M, Belij-Rammerstorfer, S, Bibi, S, Blackwell, L, Brown, A, Brown, H, Cavell, B, Clutterbuck, EA, de Silva, T, Eyre, D, Lumley, S, Flaxman, A, Grist, J, Hackstein, C-P, Halkerston, R, Harding, AC, Hill, J, James, T, Jay, C, Johnson, SA, Kronsteiner, B, Lie, Y, Linder, A, Longet, S, Marinou, S, Matthews, PC, Mellors, J, Petropoulos, C, Rongkard, P, Sedik, C, Silva-Reyes, L, Smith, H, Stockdale, L, Taylor, S, Thomas, S, Tipoe, T, Turtle, L, Vieira, VA, Wrin, T, Stafford, L, Abuelgasim, H, Alhussni, A, Arancibia-Cárcamo, CV, Borak, M, Cutteridge, J, Deeks, A, Denly, L, Dimitriadis, S, Fassih, S, Foord, T, Fordwoh, T, Holmes, J, Horsington, B, Kerneis, S, Kim, D, Lillie, K, Morrow, J, O’Donnell, D, Ritter, TG, Simmons, B, Taylor, A, Thomas, SR, Warren, Y, Watson, AJR, Weeks, E, Wilson, R, Young, R, Duncan, CJA, Moore, SC, Payne, R, Richter, A, Rowland-Jones, S, Mentzer, AJ, Cassar, MP, Dong, T, Fries, A, Gilbert-Jaramillo, J, Ho, L-P, Knight, JC, Neubauer, S, Peng, Y, Petousi, N, Raman, B, Talbot, NP, Pollard, AJ, Lambe, T, Conlon, CP, Jeffery, K, Travis, S, Goulder, P, Frater, J, Carroll, MW, James, WS, Klenerman, P, Barnes, E, Dold, C, and Dunachie, SJ

Abstract

The trajectories of acquired immunity to severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We present a detailed longitudinal cohort study of UK healthcare workers prior to vaccination, presenting April-June 2020 with asymptomatic or symptomatic infection. Here we show a highly variable range of responses, some of which (T cell interferon-gamma ELISpot, N-specific antibody) wane over time, while others (spike-specific antibody, B cell memory ELISpot) are stable. We use integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling OverNight) to explore this heterogeneity. We identify a subgroup of participants with higher antibody responses and interferon-gamma ELISpot T cell responses, and a robust trajectory for longer term immunity associates with higher levels of neutralising antibodies against the infecting (Victoria) strain and also against variants B.1.1.7 (alpha) and B.1.351 (beta). These variable trajectories following early priming may define subsequent protection from severe disease from novel variants.

Published
2022

13. Antibody responses and correlates of protection in the general population after two doses of the ChAdOx1 or BNT162b2 vaccines

Author

Wei, J, Pouwels, K, Stoesser, N, Matthews, P, Diamond, I, Studley, R, Rourke, E, Cook, D, Bell, J, Newton, J, Farrar, J, Howarth, A, Marsden, B, Hoosdally, S, Jones, EY, Stuart, D, Crook, D, Peto, T, Walker, AS, Eyre, D, and team, COVID-19 Infection Survey

Subjects
General Medicine, General Biochemistry, Genetics and Molecular Biology
Abstract

Antibody responses are an important part of immunity after Coronavirus Disease 2019 (COVID-19) vaccination. However, antibody trajectories and the associated duration of protection after a second vaccine dose remain unclear. In this study, we investigated anti-spike IgG antibody responses and correlates of protection after second doses of ChAdOx1 or BNT162b2 vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United Kingdom general population. In 222,493 individuals, we found significant boosting of anti-spike IgG by the second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2. After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. Older individuals and males had lower peak levels with BNT162b2 but not ChAdOx1, whereas declines were similar across ages and sexes with ChAdOX1 or BNT162b2. Prior infection significantly increased antibody peak level and half-life with both vaccines. Anti-spike IgG levels were associated with protection from infection after vaccination and, to an even greater degree, after prior infection. At least 67% protection against infection was estimated to last for 2–3 months after two ChAdOx1 doses, for 5–8 months after two BNT162b2 doses in those without prior infection and for 1–2 years for those unvaccinated after natural infection. A third booster dose might be needed, prioritized to ChAdOx1 recipients and those more clinically vulnerable.

Published
2022

16. DOP20 Functional viral neutralisation responses after SARS-CoV-2 infection in Inflammatory Bowel Disease patients receiving infusion therapies: Report from the ICARUS-IBD Consortium

Author

Wellens, J, primary, Edmans, M, additional, Obolski, U, additional, Marlow, L, additional, Brann, S, additional, Dunachie, S, additional, Eyre, D, additional, Helmus, D, additional, Barnes, E, additional, Colombel, J F, additional, Wong, S Y, additional, Klenerman, P, additional, Lindsay, J O, additional, Thompson, C P, additional, and Satsangi, J, additional

Published
2022
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17. Real-world evaluation of AI driven COVID-19 triage for emergency admissions: External validation & operational assessment of lab-free and high-throughput screening solutions

Author

Soltan, A, Yang, J, Pattanshetty, R, Novak, A, Yang, Y, Rohanian, O, Beer, S, Soltan, M, Thickett, D, Fairhead, R, Zhu, T, Eyre, D, Clifton, D, and Collaborative, CURIAL Translational

Abstract

Background Uncertainty in patients' COVID-19 status contributes to treatment delays, nosocomial transmission, and operational pressures in hospitals. However, the typical turnaround time for laboratory PCR remains 12–24 h and lateral flow devices (LFDs) have limited sensitivity. Previously, we have shown that artificial intelligence-driven triage (CURIAL-1.0) can provide rapid COVID-19 screening using clinical data routinely available within 1 h of arrival to hospital. Here, we aimed to improve the time from arrival to the emergency department to the availability of a result, do external and prospective validation, and deploy a novel laboratory-free screening tool in a UK emergency department. Methods We optimised our previous model, removing less informative predictors to improve generalisability and speed, developing the CURIAL-Lab model with vital signs and readily available blood tests (full blood count [FBC]; urea, creatinine, and electrolytes; liver function tests; and C-reactive protein) and the CURIAL-Rapide model with vital signs and FBC alone. Models were validated externally for emergency admissions to University Hospitals Birmingham, Bedfordshire Hospitals, and Portsmouth Hospitals University National Health Service (NHS) trusts, and prospectively at Oxford University Hospitals, by comparison with PCR testing. Next, we compared model performance directly against LFDs and evaluated a combined pathway that triaged patients who had either a positive CURIAL model result or a positive LFD to a COVID-19-suspected clinical area. Lastly, we deployed CURIAL-Rapide alongside an approved point-of-care FBC analyser to provide laboratory-free COVID-19 screening at the John Radcliffe Hospital (Oxford, UK). Our primary improvement outcome was time-to-result, and our performance measures were sensitivity, specificity, positive and negative predictive values, and area under receiver operating characteristic curve (AUROC). Findings 72 223 patients met eligibility criteria across the four validating hospital groups, in a total validation period spanning Dec 1, 2019, to March 31, 2021. CURIAL-Lab and CURIAL-Rapide performed consistently across trusts (AUROC range 0·858–0·881, 95% CI 0·838–0·912, for CURIAL-Lab and 0·836–0·854, 0·814–0·889, for CURIAL-Rapide), achieving highest sensitivity at Portsmouth Hospitals (84·1%, Wilson's 95% CI 82·5–85·7, for CURIAL-Lab and 83·5%, 81·8–85·1, for CURIAL-Rapide) at specificities of 71·3% (70·9–71·8) for CURIAL-Lab and 63·6% (63·1–64·1) for CURIAL-Rapide. When combined with LFDs, model predictions improved triage sensitivity from 56·9% (51·7–62·0) for LFDs alone to 85·6% with CURIAL-Lab (81·6–88·9; AUROC 0·925) and 88·2% with CURIAL-Rapide (84·4–91·1; AUROC 0·919), thereby reducing missed COVID-19 cases by 65% with CURIAL-Lab and 72% with CURIAL-Rapide. For the prospective deployment of CURIAL-Rapide, 520 patients were enrolled for point-of-care FBC analysis between Feb 18 and May 10, 2021, of whom 436 received confirmatory PCR testing and ten (2·3%) tested positive. Median time from arrival to a CURIAL-Rapide result was 45 min (IQR 32–64), 16 min (26·3%) sooner than with LFDs (61 min, 37–99; log-rank p

Published
2021
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21. Contributor contact details

Author

Orazem, M.E., primary, Norsworthy, R., additional, Tribollet, B., additional, Meyer, M., additional, Hopkins, P., additional, Liu, C., additional, Shankar, A., additional, Orazem, M.E., additional, Riemer, D.P., additional, Sastri, V.S., additional, Bubenik, T., additional, Kowalski, A., additional, Eyre, D., additional, Brockhaus, S., additional, Ginten, M., additional, Klein, S., additional, Teckert, M., additional, Stawicki, O., additional, Oevermann, D., additional, Meyer, S., additional, Storey, D., additional, and Brossia, S., additional

Published
2014
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24. Crtap and p3h1 knock out zebrafish support defective collagen chaperoning as the cause of their osteogenesis imperfecta phenotype

Author

Tonelli, F, primary, Cotti, S, additional, Leoni, L, additional, Besio, R, additional, Gioia, R, additional, Marchese, L, additional, Giorgetti, S, additional, Villani, S, additional, Gistelinck, C, additional, Wagener, R, additional, Kobbe, B, additional, Fiedler, I A K, additional, Larionova, D, additional, Busse, B, additional, Eyre, D, additional, Rossi, A, additional, Witten, P E, additional, and Forlino, A, additional

Published
2021
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26. Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies

Author

Collier, D. A., De Marco, A., Ferreira, I. A. T. M., Meng, B., Datir, R. P., Walls, A. C., Kemp, S. A., Bassi, J., Pinto, D., Silacci-Fregni, C., Bianchi, S., Tortorici, M. A., Bowen, J., Culap, K., Jaconi, S., Cameroni, E., Snell, G., Pizzuto, M. S., Pellanda, A. F., Garzoni, C., Riva, A., Baker, S., Dougan, G., Hess, C., Kingston, N., Lehner, P. J., Lyons, P. A., Matheson, N. J., Owehand, W. H., Saunders, C., Summers, C., Thaventhiran, J. E. D., Toshner, M., Weekes, M. P., Bucke, A., Calder, J., Canna, L., Domingo, J., Elmer, A., Fuller, S., Harris, J., Hewitt, S., Kennet, J., Jose, S., Kourampa, J., Meadows, A., O'Brien, C., Price, J., Publico, C., Rastall, R., Ribeiro, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Bullman, B., Dunmore, B. J., Fawke, S., Graf, S., Hodgson, J., Huang, C., Hunter, K., Jones, E., Legchenko, E., Matara, C., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Pond, N., Shih, J., Sutcliffe, R., Tilly, T., Treacy, C., Tong, Z., Wood, J., Wylot, M., Bergamaschi, L., Betancourt, A., Bower, G., Cossetti, C., De Sa, A., Epping, M., Grenfell, R., Hinch, A., Huhn, O., Jackson, S., Jarvis, I., Lewis, D., Marsden, J., Nice, F., Okecha, G., Omarjee, O., Perera, M., Richoz, N., Romashova, V., Yarkoni, N. S., Sharma, R., Stefanucci, L., Stephens, J., Strezlecki, M., Turner, L., De Bie, E. M. D. D., Bunclark, K., Josipovic, M., Mackay, M., Rossi, S., Selvan, M., Spencer, S., Yong, C., Ansaripour, A., Michael, A., Mwaura, L., Patterson, C., Polwarth, G., Polgarova, P., di Stefano, G., Fahey, C., Michel, R., Bong, S. -H., Coudert, J. D., Holmes, E., Allison, J., Butcher, H., Caputo, D., Clapham-Riley, D., Dewhurst, E., Furlong, A., Graves, B., Gray, J., Ivers, T., Kasanicki, M., Le Gresley, E., Linger, R., Meloy, S., Muldoon, F., Ovington, N., Papadia, S., Phelan, I., Stark, H., Stirrups, K. E., Townsend, P., Walker, N., Webster, J., Mccoy, L. E., Smith, K. G. C., Bradley, J. R., Temperton, N., Ceron-Gutierrez, L., Barcenas-Morales, G., Robson, S. C., Loman, N. J., Connor, T. R., Golubchik, T., Martinez Nunez, R. T., Ludden, C., Corden, S., Johnston, I., Bonsall, D., Smith, C. P., Awan, A. R., Bucca, G., Torok, M. E., Saeed, K., Prieto, J. A., Jackson, D. K., Hamilton, W. L., Snell, L. B., Moore, C., Harrison, E. M., Goncalves, S., Fairley, D. J., Loose, M. W., Watkins, J., Livett, R., Moses, S., Amato, R., Nicholls, S., Bull, M., Smith, D. L., Barrett, J., Aanensen, D. M., Curran, M. D., Parmar, S., Aggarwal, D., Shepherd, J. G., Parker, M. D., Glaysher, S., Bashton, M., Underwood, A. P., Pacchiarini, N., Loveson, K. F., Carabelli, A. M., Templeton, K. E., Langford, C. F., Sillitoe, J., de Silva, T. I., Wang, D., Kwiatkowski, D., Rambaut, A., O'Grady, J., Cottrell, S., Holden, M. T. G., Thomson, E. C., Osman, H., Andersson, M., Chauhan, A. J., Hassan-Ibrahim, M. O., Lawniczak, M., Alderton, A., Chand, M., Constantinidou, C., Unnikrishnan, M., Darby, A. C., Hiscox, J. A., Paterson, S., Martincorena, I., Robertson, D. L., Volz, E. M., Page, A. J., Pybus, O. G., Bassett, A. R., Ariani, C. V., Spencer Chapman, M. H., K. K., Li, Shah, R. N., Jesudason, N. G., Taha, Y., Mchugh, M. P., Dewar, R., Jahun, A. S., Mcmurray, C., Pandey, S., Mckenna, J. P., Nelson, A., Young, G. R., Mccann, C. M., Elliott, S., Lowe, H., Temperton, B., Roy, S., Price, A., Rey, S., Wyles, M., Rooke, S., Shaaban, S., de Cesare, M., Letchford, L., Silveira, S., Pelosi, E., Wilson-Davies, E., Hosmillo, M., O'Toole, A., Hesketh, A. R., Stark, R., du Plessis, L., Ruis, C., Adams, H., Bourgeois, Y., Michell, S. L., Gramatopoulos, D., Edgeworth, J., Breuer, J., Todd, J. A., Fraser, C., Buck, D., John, M., Kay, G. L., Palmer, S., Peacock, S. J., Heyburn, D., Weldon, D., Robinson, E., Mcnally, A., Muir, P., Vipond, I. B., Boyes, J., Sivaprakasam, V., Salluja, T., Dervisevic, S., Meader, E. J., Park, N. R., Oliver, K., Jeffries, A. R., Ott, S., da Silva Filipe, A., Simpson, D. A., Williams, C., Masoli, J. A. H., Knight, B. A., Jones, C. R., Koshy, C., Ash, A., Casey, A., Bosworth, A., Ratcliffe, L., Xu-McCrae, L., Pymont, H. M., Hutchings, S., Berry, L., Jones, K., Halstead, F., Davis, T., Holmes, C., Iturriza-Gomara, M., Lucaci, A. O., Randell, P. A., Cox, A., Madona, P., Harris, K. A., Brown, J. R., Mahungu, T. W., Irish-Tavares, D., Haque, T., Hart, J., Witele, E., Fenton, M. L., Liggett, S., Graham, C., Swindells, E., Collins, J., Eltringham, G., Campbell, S., Mcclure, P. C., Clark, G., Sloan, T. J., Jones, C., Lynch, J., Warne, B., Leonard, S., Durham, J., Williams, T., Haldenby, S. T., Storey, N., Alikhan, N. -F., Holmes, N., Carlile, M., Perry, M., Craine, N., Lyons, R. A., Beckett, A. H., Goudarzi, S., Fearn, C., Cook, K., Dent, H., Paul, H., Davies, R., Blane, B., Girgis, S. T., Beale, M. A., Bellis, K. L., Dorman, M. J., Drury, E., Kane, L., Kay, S., Mcguigan, S., Nelson, R., Prestwood, L., Rajatileka, S., Batra, R., Williams, R. J., Kristiansen, M., Green, A., Justice, A., Mahanama, A. I. K., Samaraweera, B., Hadjirin, N. F., Quick, J., Poplawski, R., Kermack, L. M., Reynolds, N., Hall, G., Chaudhry, Y., Pinckert, M. L., Georgana, I., Moll, R. J., Thornton, A., Myers, R., Stockton, J., Williams, C. A., Yew, W. C., Trotter, A. J., Trebes, A., MacIntyre-Cockett, G., Birchley, A., Adams, A., Plimmer, A., Gatica-Wilcox, B., Mckerr, C., Hilvers, E., Jones, H., Asad, H., Coombes, J., Evans, J. M., Fina, L., Gilbert, L., Graham, L., Cronin, M., Kumziene-Summerhayes, S., Taylor, S., Jones, S., Groves, D. C., Zhang, P., Gallis, M., Louka, S. F., Starinskij, I., Jackson, C., Gourtovaia, M., Tonkin-Hill, G., Lewis, K., Tovar-Corona, J. M., James, K., Baxter, L., Alam, M. T., Orton, R. J., Hughes, J., Vattipally, S., Ragonnet-Cronin, M., Nascimento, F. F., Jorgensen, D., Boyd, O., Geidelberg, L., Zarebski, A. E., Raghwani, J., Kraemer, M. U. G., Southgate, J., Lindsey, B. B., Freeman, T. M., Keatley, J. -P., Singer, J. B., de Oliveira Martins, L., Yeats, C. A., Abudahab, K., Taylor, B. E. W., Menegazzo, M., Danesh, J., Hogsden, W., Eldirdiri, S., Kenyon, A., Mason, J., Robinson, T. I., Holmes, A., Hartley, J. A., Curran, T., Mather, A. E., Shankar, G., Jones, R., Howe, R., Morgan, S., Wastenge, E., Chapman, M. R., Mookerjee, S., Stanley, R., Smith, W., Peto, T., Eyre, D., Crook, D., Vernet, G., Kitchen, C., Gulliver, H., Merrick, I., Guest, M., Munn, R., Bradley, D. T., Wyatt, T., Beaver, C., Foulser, L., Churcher, C. M., Brooks, E., Smith, K. S., Galai, K., Mcmanus, G. M., Bolt, F., Coll, F., Meadows, L., Attwood, S. W., Davies, A., De Lacy, E., Downing, F., Edwards, S., Scarlett, G. P., Jeremiah, S., Smith, N., Leek, D., Sridhar, S., Forrest, S., Cormie, C., Gill, H. K., Dias, J., Higginson, E. E., Maes, M., Young, J., Wantoch, M., Jamrozy, D., Lo, S., Patel, M., Hill, V., Bewshea, C. M., Ellard, S., Auckland, C., Harrison, I., Bishop, C., Chalker, V., Richter, A., Beggs, A., Best, A., Percival, B., Mirza, J., Megram, O., Mayhew, M., Crawford, L., Ashcroft, F., Moles-Garcia, E., Cumley, N., Hopes, R., Asamaphan, P., Niebel, M. O., Gunson, R. N., Bradley, A., Maclean, A., Mollett, G., Blacow, R., Bird, P., Helmer, T., Fallon, K., Tang, J., Hale, A. D., Macfarlane-Smith, L. R., Harper, K. L., Carden, H., Machin, N. W., Jackson, K. A., Ahmad, S. S. Y., George, R. P., Turtle, L., O'Toole, E., Watts, J., Breen, C., Cowell, A., Alcolea-Medina, A., Charalampous, T., Patel, A., Levett, L. J., Heaney, J., Rowan, A., Taylor, G. P., Shah, D., Atkinson, L., Lee, J. C. D., Westhorpe, A. P., Jannoo, R., Lowe, H. L., Karamani, A., Ensell, L., Chatterton, W., Pusok, M., Dadrah, A., Symmonds, A., Sluga, G., Molnar, Z., Baker, P., Bonner, S., Essex, S., Barton, E., Padgett, D., Scott, G., Greenaway, J., Payne, B. A. I., Burton-Fanning, S., Waugh, S., Raviprakash, V., Sheriff, N., Blakey, V., Williams, L. -A., Moore, J., Stonehouse, S., Smith, L., Davidson, R. K., Bedford, L., Coupland, L., Wright, V., Chappell, J. G., Tsoleridis, T., Ball, J., Khakh, M., Fleming, V. M., Lister, M. M., Howson-Wells, H. C., Boswell, T., Joseph, A., Willingham, I., Duckworth, N., Walsh, S., Wise, E., Moore, N., Mori, M., Cortes, N., Kidd, S., Williams, R., Gifford, L., Bicknell, K., Wyllie, S., Lloyd, A., Impey, R., Malone, C. S., Cogger, B. J., Levene, N., Monaghan, L., Keeley, A. J., Partridge, D. G., Raza, M., Evans, C., Johnson, K., Betteridge, E., Farr, B. W., Goodwin, S., Quail, M. A., Scott, C., Shirley, L., Thurston, S. A. J., Rajan, D., Bronner, I. F., Aigrain, L., Redshaw, N. M., Lensing, S. V., Mccarthy, S., Makunin, A., Balcazar, C. E., Gallagher, M. D., Williamson, K. A., Stanton, T. D., Michelsen, M. L., Warwick-Dugdale, J., Manley, R., Farbos, A., Harrison, J. W., Sambles, C. M., Studholme, D. J., Lackenby, A., Mbisa, T., Platt, S., Miah, S., Bibby, D., Manso, C., Hubb, J., Dabrera, G., Ramsay, M., Bradshaw, D., Schaefer, U., Groves, N., Gallagher, E., Lee, D., Williams, D., Ellaby, N., Hartman, H., Manesis, N., Patel, V., Ledesma, J., Twohig, K. A., Allara, E., Pearson, C., Cheng, J. K. J., Bridgewater, H. E., Frost, L. R., Taylor-Joyce, G., Brown, P. E., Tong, L., Broos, A., Mair, D., Nichols, J., Carmichael, S. N., Smollett, K. L., Nomikou, K., Aranday-Cortes, E., Johnson, N., Nickbakhsh, S., Vamos, E. E., Hughes, M., Rainbow, L., Eccles, R., Nelson, C., Whitehead, M., Gregory, R., Gemmell, M., Wierzbicki, C., Webster, H. J., Fisher, C. L., Signell, A. W., Betancor, G., Wilson, H. D., Nebbia, G., Flaviani, F., Cerda, A. C., Merrill, T. V., Wilson, R. E., Cotic, M., Bayzid, N., Thompson, T., Acheson, E., Rushton, S., O'Brien, S., Baker, D. J., Rudder, S., Aydin, A., Sang, F., Debebe, J., Francois, S., Vasylyeva, T. I., Zamudio, M. E., Gutierrez, B., Marchbank, A., Maksimovic, J., Spellman, K., Mccluggage, K., Morgan, M., Beer, R., Afifi, S., Workman, T., Fuller, W., Bresner, C., Angyal, A., Green, L. R., Parsons, P. J., Tucker, R. M., Brown, R., Whiteley, M., Bonfield, J., Puethe, C., Whitwham, A., Liddle, J., Rowe, W., Siveroni, I., Le-Viet, T., Gaskin, A., Johnson, R., Abnizova, I., Ali, M., Allen, L., Anderson, R., Ariani, C., Austin-Guest, S., Bala, S., Bassett, A., Battleday, K., Beal, J., Beale, M., Bellany, S., Bellerby, T., Bellis, K., Berger, D., Berriman, M., Bevan, P., Binley, S., Bishop, J., Blackburn, K., Boughton, N., Bowker, S., Brendler-Spaeth, T., Bronner, I., Brooklyn, T., Buddenborg, S. K., Bush, R., Caetano, C., Cagan, A., Carter, N., Cartwright, J., Monteiro, T. C., Chapman, L., Chillingworth, T. -J., Clapham, P., Clark, R., Clarke, A., Clarke, C., Cole, D., Cook, E., Coppola, M., Cornell, L., Cornwell, C., Corton, C., Crackett, A., Cranage, A., Craven, H., Craw, S., Crawford, M., Cutts, T., Dabrowska, M., Davies, M., Dawson, J., Day, C., Densem, A., Dibling, T., Dockree, C., Dodd, D., Dogga, S., Dougherty, M., Dove, A., Drummond, L., Dudek, M., Durrant, L., Easthope, E., Eckert, S., Ellis, P., Farr, B., Fenton, M., Ferrero, M., Flack, N., Fordham, H., Forsythe, G., Francis, M., Fraser, A., Freeman, A., Galvin, A., Garcia-Casado, M., Gedny, A., Girgis, S., Glover, J., Gould, O., Gray, A., Gray, E., Griffiths, C., Gu, Y., Guerin, F., Hamilton, W., Hanks, H., Harrison, E., Harrott, A., Harry, E., Harvison, J., Heath, P., Hernandez-Koutoucheva, A., Hobbs, R., Holland, D., Holmes, S., Hornett, G., Hough, N., Huckle, L., Hughes-Hallet, L., Hunter, A., Inglis, S., Iqbal, S., Jackson, A., Jackson, D., Verdejo, C. J., Jones, M., Kallepally, K., Kay, K., Keatley, J., Keith, A., King, A., Kitchin, L., Kleanthous, M., Klimekova, M., Korlevic, P., Krasheninnkova, K., Lane, G., Langford, C., Laverack, A., Law, K., Lensing, S., Lewis-Wade, A., Lin, Q., Lindsay, S., Linsdell, S., Long, R., Lovell, J., Mack, J., Maddison, M., Mamun, I., Mansfield, J., Marriott, N., Martin, M., Mayho, M., Mcclintock, J., Mchugh, S., Mcminn, L., Meadows, C., Mobley, E., Moll, R., Morra, M., Morrow, L., Murie, K., Nash, S., Nathwani, C., Naydenova, P., Neaverson, A., Nerou, E., Nicholson, J., Nimz, T., Noell, G. G., O'Meara, S., Ohan, V., Olney, C., Ormond, D., Oszlanczi, A., Pang, Y. F., Pardubska, B., Park, N., Parmar, A., Patel, G., Payne, M., Peacock, S., Petersen, A., Plowman, D., Preston, T., Quail, M., Rance, R., Rawlings, S., Redshaw, N., Reynolds, J., Reynolds, M., Rice, S., Richardson, M., Roberts, C., Robinson, K., Robinson, M., Robinson, D., Rogers, H., Rojo, E. M., Roopra, D., Rose, M., Rudd, L., Sadri, R., Salmon, N., Saul, D., Schwach, F., Seekings, P., Simms, A., Sinnott, M., Sivadasan, S., Siwek, B., Sizer, D., Skeldon, K., Skelton, J., Slater-Tunstill, J., Sloper, L., Smerdon, N., Smith, C., Smith, J., Smith, K., Smith, M., Smith, S., Smith, T., Sneade, L., Soria, C. D., Sousa, C., Souster, E., Sparkes, A., Spencer-Chapman, M., Squares, J., Steed, C., Stickland, T., Still, I., Stratton, M., Strickland, M., Swann, A., Swiatkowska, A., Sycamore, N., Swift, E., Symons, E., Szluha, S., Taluy, E., Tao, N., Taylor, K., Thompson, S., Thompson, M., Thomson, M., Thomson, N., Thurston, S., Toombs, D., Topping, B., Tovar-Corona, J., Ungureanu, D., Uphill, J., Urbanova, J., Van, P. J., Vancollie, V., Voak, P., Walker, D., Walker, M., Waller, M., Ward, G., Weatherhogg, C., Webb, N., Wells, A., Wells, E., Westwood, L., Whipp, T., Whiteley, T., Whitton, G., Widaa, S., Williams, M., Wilson, M., Wright, S., Harvey, W., Virgin, H. W., Lanzavecchia, A., Piccoli, L., Doffinger, R., Wills, M., Veesler, D., Corti, D., and Gupta, R. K.

Subjects
0301 basic medicine, Male, Models, Molecular, Passive, Antibodies, Viral, Neutralization, 0302 clinical medicine, Models, Monoclonal, 80 and over, Viral, Neutralizing antibody, Neutralizing, Aged, 80 and over, Vaccines, Vaccines, Synthetic, Multidisciplinary, biology, Antibodies, Monoclonal, C500, Middle Aged, C700, Spike Glycoprotein, Vaccination, Spike Glycoprotein, Coronavirus, Female, Angiotensin-Converting Enzyme 2, Antibody, Aged, Antibodies, Neutralizing, COVID-19, COVID-19 Vaccines, HEK293 Cells, Humans, Immune Evasion, Immunization, Passive, Mutation, Neutralization Tests, SARS-CoV-2, medicine.drug_class, B100, Monoclonal antibody, Antibodies, Virus, 03 medical and health sciences, Immune system, medicine, COVID-19 Serotherapy, QR355, Synthetic, Molecular, Virology, Coronavirus, 030104 developmental biology, Immunization, biology.protein, 030217 neurology & neurosurgery
Abstract

Transmission of SARS-CoV-2 is uncontrolled in many parts of the world; control is compounded in some areas by the higher transmission potential of the B.1.1.7 variant1, which has now been reported in 94 countries. It is unclear whether the response of the virus to vaccines against SARS-CoV-2 on the basis of the prototypic strain will be affected by the mutations found in B.1.1.7. Here we assess the immune responses of individuals after vaccination with the mRNA-based vaccine BNT162b22. We measured neutralizing antibody responses after the first and second immunizations using pseudoviruses that expressed the wild-type spike protein or a mutated spike protein that contained the eight amino acid changes found in the B.1.1.7 variant. The sera from individuals who received the vaccine exhibited a broad range of neutralizing titres against the wild-type pseudoviruses that were modestly reduced against the B.1.1.7 variant. This reduction was also evident in sera from some patients who had recovered from COVID-19. Decreased neutralization of the B.1.1.7 variant was also observed for monoclonal antibodies that target the N-terminal domain (9 out of 10) and the receptor-binding motif (5 out of 31), but not for monoclonal antibodies that recognize the receptor-binding domain that bind outside the receptor-binding motif. Introduction of the mutation that encodes the E484K substitution in the B.1.1.7 background to reflect a newly emerged variant of concern (VOC 202102/02) led to a more-substantial loss of neutralizing activity by vaccine-elicited antibodies and monoclonal antibodies (19 out of 31) compared with the loss of neutralizing activity conferred by the mutations in B.1.1.7 alone. The emergence of the E484K substitution in a B.1.1.7 background represents a threat to the efficacy of the BNT162b2 vaccine.

Published
2021

27. COVID-19: Rapid antigen detection for SARS-CoV-2 by lateral flow assay: A national systematic evaluation of sensitivity and specificity for mass-testing

Author

Peto, T., Affron, D., Afrough, B., Agasu, A., Ainsworth, M., Allanson, A., Allen, K., Allen, C., Archer, L., Ashbridge, N., Aurfan, I., Avery, M., Badenoch, E., Bagga, P., Balaji, R., Baldwin, E., Barraclough, S., Beane, C., Bell, J., Benford, T., Bird, S., Bishop, M., Bloss, A., Body, R., Boulton, R., Bown, A., Bratten, C., Bridgeman, C., Britton, D., Brooks, T., Broughton-Smith, M., Brown, P., Buck, B., Butcher, E., Byrne, W., Calderon, G., Campbell, S., Carr, O., Carter, P., Carter, D., Cathrall, M., Catton, M., Chadwick, J., Chapman, D., Chau, K.K., Chaudary, T., Chidavaenzi, S., Chilcott, S., Choi, B., Claasen, H., Clark, S., Clarke, R., Clarke, D., Clayton, R., Collins, K., Colston, R., Connolly, J., Cook, E., Corcoran, M., Corley, B., Costello, L., Coulson, C., Crook, A., Crook, D.W., D'Arcangelo, S., Darby, M-A, Davis, J., de Koning, R., Derbyshire, P., Devall, P., Dolman, M., Draper, N., Driver, M., Dyas, S., Eaton, E., Edwards, J., Elderfield, R., Ellis, K., Ellis, G., Elwell, S., Evans, R., Evans, B., Evans, M., Eyre, D., Fahey, C., Fenech, V., Field, J., Field, A., Foord, T., Fowler, T., French, M., Fuchs, H., Gan, J., Gernon, J., Ghadiali, G., Ghuman, N., Gibbons, K., Gill, G., Gilmour, K., Goel, A., Gordon, S., Graham, T., Grassam-Rowe, A., Green, D., Gronert, A., Gumsley-Read, T., Hall, C., Hallis, B., Hammond, S., Hammond, P., Hanney, B., Hardy, V., Harker, G., Harris, A., Havinden-Williams, M., Hazell, E., Henry, J., Hicklin, K., Hollier, K., Holloway, B., Hoosdally, S.J., Hopkins, S., Hughes, L., Hurdowar, S., Hurford, S-A, Jackman, J., Jackson, H., Johns, R., Johnston, S., Jones, J., Kanyowa, T., Keating-Fedders, K., Kempson, S., Khan, I., Khulusi, B., Knight, T., Krishna, A., Lahert, P., Lampshire, Z., Lasserson, D., Lee, K., Lee, L.Y.W., Legard, A., Leggio, C., Liu, J., Lockett, T., Logue, C., Lucas, V., Lumley, S.F., Maripuri, V., Markham, D., Marshall, E., Matthews, P.C., Mckee, S., McKee, D.F., McLeod, N., McNulty, A., Mellor, F., Michel, R., Mighiu, A., Miller, J., Mirza, Z., Mistry, H., Mitchell, J., Moeser, M.E., Moore, S., Muthuswamy, A., Myers, D., Nanson, G., Newbury, M., Nicol, S., Nuttall, H., Nwanaforo, J.J., Oliver, L., Osbourne, W., Osbourne, J., Otter, A., Owen, J., Panchalingam, S., Papoulidis, D., Pavon, J.D., Peace, A., Pearson, K., Peck, L., Pegg, A., Pegler, S., Permain, H., Perumal, P., Peto, L., Peto, T.E.A., Pham, T., Pickford, H.L., Pinkerton, M., Platton, M., Price, A., Protheroe, E., Purnell, H., Rawden, L., Read, S., Reynard, C., Ridge, S., Ritter, T.G., Robinson, J., Robinson, P., Rodger, G., Rowe, C., Rowell, B., Rowlands, A., Sampson, S., Saunders, K., Sayers, R., Sears, J., Sedgewick, R., Seeney, L., Selassie, A., Shail, L., Shallcross, J., Sheppard, L., Sherkat, A., Siddiqui, S., Sienkiewicz, A., Sinha, L., Smith, J., Smith, E., Stanton, E., Starkey, T., Stawiarski, A., Sterry, A., Stevens, J., Stockbridge, M., Stoesser, N., Sukumaran, A., Sweed, A., Tatar, S., Thomas, H., Tibbins, C., Tiley, S., Timmins, J., Tomas-Smith, C., Topping, O., Turek, E., Neibler, T., Trigg-Hogarth, K., Truelove, E., Turnbull, C., Tyrrell, D., Vaughan, A., Vertannes, J., Vipond, R., Wagstaff, L., Waldron, J., Walker, P., Walker, A.S., Walters, M., Wang, J.Y., Watson, E., Webberley, K., Webster, K., Westland, G., Wickens, I., Willcocks, J., Willis, H., Wilson, S., Wilson, B., Woodhead, L., Wright, D., Xavier, B., Yelnoorkar, F., Zeidan, L., Zinyama, R., Peto, T., Affron, D., Afrough, B., Agasu, A., Ainsworth, M., Allanson, A., Allen, K., Allen, C., Archer, L., Ashbridge, N., Aurfan, I., Avery, M., Badenoch, E., Bagga, P., Balaji, R., Baldwin, E., Barraclough, S., Beane, C., Bell, J., Benford, T., Bird, S., Bishop, M., Bloss, A., Body, R., Boulton, R., Bown, A., Bratten, C., Bridgeman, C., Britton, D., Brooks, T., Broughton-Smith, M., Brown, P., Buck, B., Butcher, E., Byrne, W., Calderon, G., Campbell, S., Carr, O., Carter, P., Carter, D., Cathrall, M., Catton, M., Chadwick, J., Chapman, D., Chau, K.K., Chaudary, T., Chidavaenzi, S., Chilcott, S., Choi, B., Claasen, H., Clark, S., Clarke, R., Clarke, D., Clayton, R., Collins, K., Colston, R., Connolly, J., Cook, E., Corcoran, M., Corley, B., Costello, L., Coulson, C., Crook, A., Crook, D.W., D'Arcangelo, S., Darby, M-A, Davis, J., de Koning, R., Derbyshire, P., Devall, P., Dolman, M., Draper, N., Driver, M., Dyas, S., Eaton, E., Edwards, J., Elderfield, R., Ellis, K., Ellis, G., Elwell, S., Evans, R., Evans, B., Evans, M., Eyre, D., Fahey, C., Fenech, V., Field, J., Field, A., Foord, T., Fowler, T., French, M., Fuchs, H., Gan, J., Gernon, J., Ghadiali, G., Ghuman, N., Gibbons, K., Gill, G., Gilmour, K., Goel, A., Gordon, S., Graham, T., Grassam-Rowe, A., Green, D., Gronert, A., Gumsley-Read, T., Hall, C., Hallis, B., Hammond, S., Hammond, P., Hanney, B., Hardy, V., Harker, G., Harris, A., Havinden-Williams, M., Hazell, E., Henry, J., Hicklin, K., Hollier, K., Holloway, B., Hoosdally, S.J., Hopkins, S., Hughes, L., Hurdowar, S., Hurford, S-A, Jackman, J., Jackson, H., Johns, R., Johnston, S., Jones, J., Kanyowa, T., Keating-Fedders, K., Kempson, S., Khan, I., Khulusi, B., Knight, T., Krishna, A., Lahert, P., Lampshire, Z., Lasserson, D., Lee, K., Lee, L.Y.W., Legard, A., Leggio, C., Liu, J., Lockett, T., Logue, C., Lucas, V., Lumley, S.F., Maripuri, V., Markham, D., Marshall, E., Matthews, P.C., Mckee, S., McKee, D.F., McLeod, N., McNulty, A., Mellor, F., Michel, R., Mighiu, A., Miller, J., Mirza, Z., Mistry, H., Mitchell, J., Moeser, M.E., Moore, S., Muthuswamy, A., Myers, D., Nanson, G., Newbury, M., Nicol, S., Nuttall, H., Nwanaforo, J.J., Oliver, L., Osbourne, W., Osbourne, J., Otter, A., Owen, J., Panchalingam, S., Papoulidis, D., Pavon, J.D., Peace, A., Pearson, K., Peck, L., Pegg, A., Pegler, S., Permain, H., Perumal, P., Peto, L., Peto, T.E.A., Pham, T., Pickford, H.L., Pinkerton, M., Platton, M., Price, A., Protheroe, E., Purnell, H., Rawden, L., Read, S., Reynard, C., Ridge, S., Ritter, T.G., Robinson, J., Robinson, P., Rodger, G., Rowe, C., Rowell, B., Rowlands, A., Sampson, S., Saunders, K., Sayers, R., Sears, J., Sedgewick, R., Seeney, L., Selassie, A., Shail, L., Shallcross, J., Sheppard, L., Sherkat, A., Siddiqui, S., Sienkiewicz, A., Sinha, L., Smith, J., Smith, E., Stanton, E., Starkey, T., Stawiarski, A., Sterry, A., Stevens, J., Stockbridge, M., Stoesser, N., Sukumaran, A., Sweed, A., Tatar, S., Thomas, H., Tibbins, C., Tiley, S., Timmins, J., Tomas-Smith, C., Topping, O., Turek, E., Neibler, T., Trigg-Hogarth, K., Truelove, E., Turnbull, C., Tyrrell, D., Vaughan, A., Vertannes, J., Vipond, R., Wagstaff, L., Waldron, J., Walker, P., Walker, A.S., Walters, M., Wang, J.Y., Watson, E., Webberley, K., Webster, K., Westland, G., Wickens, I., Willcocks, J., Willis, H., Wilson, S., Wilson, B., Woodhead, L., Wright, D., Xavier, B., Yelnoorkar, F., Zeidan, L., and Zinyama, R.

Abstract

Background Lateral flow device (LFD) viral antigen immunoassays have been developed around the world as diagnostic tests for SARS-CoV-2 infection. They have been proposed to deliver an infrastructure-light, cost-economical solution giving results within half an hour. Methods LFDs were initially reviewed by a Department of Health and Social Care team, part of the UK government, from which 64 were selected for further evaluation from 1st August to 15th December 2020. Standardised laboratory evaluations, and for those that met the published criteria, field testing in the Falcon-C19 research study and UK pilots were performed (UK COVID-19 testing centres, hospital, schools, armed forces). Findings 4/64 LFDs so far have desirable performance characteristics (orient Gene, Deepblue, Abbott and Innova SARS-CoV-2 Antigen Rapid Qualitative Test). All these LFDs have a viral antigen detection of >90% at 100,000 RNA copies/ml. 8951 Innova LFD tests were performed with a kit failure rate of 5.6% (502/8951, 95% CI: 5.1–6.1), false positive rate of 0.32% (22/6954, 95% CI: 0.20–0.48). Viral antigen detection/sensitivity across the sampling cohort when performed by laboratory scientists was 78.8% (156/198, 95% CI 72.4–84.3). Interpretation Our results suggest LFDs have promising performance characteristics for mass population testing and can be used to identify infectious positive individuals. The Innova LFD shows good viral antigen detection/sensitivity with excellent specificity, although kit failure rates and the impact of training are potential issues. These results support the expanded evaluation of LFDs, and assessment of greater access to testing on COVID-19 transmission. Funding Department of Health and Social Care. University of Oxford. Public Health England Porton Down, Manchester University NHS Foundation Trust, National Institute of Health Research.

Published
2021

30. Student-Teacher Curriculum Learning via Reinforcement Learning: Predicting Hospital Inpatient Admission Location

Author

El-Bouri, R., Eyre, D., Watkinson, P., Tingting Zhu, and Clifton, D. A.

Subjects
FOS: Computer and information sciences, 00Bxx, Computer Science - Machine Learning, I.5, Statistics - Machine Learning, Computer Vision and Pattern Recognition (cs.CV), ComputingMilieux_COMPUTERSANDEDUCATION, Computer Science - Computer Vision and Pattern Recognition, Machine Learning (stat.ML), Machine Learning (cs.LG)
Abstract

Accurate and reliable prediction of hospital admission location is important due to resource-constraints and space availability in a clinical setting, particularly when dealing with patients who come from the emergency department. In this work we propose a student-teacher network via reinforcement learning to deal with this specific problem. A representation of the weights of the student network is treated as the state and is fed as an input to the teacher network. The teacher network's action is to select the most appropriate batch of data to train the student network on from a training set sorted according to entropy. By validating on three datasets, not only do we show that our approach outperforms state-of-the-art methods on tabular data and performs competitively on image recognition, but also that novel curricula are learned by the teacher network. We demonstrate experimentally that the teacher network can actively learn about the student network and guide it to achieve better performance than if trained alone., 16 pages, 31 figures, In Proceedings of the 37th International Conference on Machine Learning

Published
2020

49. Impact of intended and relative dose intensity of R‐CHOP in a large, consecutive cohort of elderly diffuse large B‐cell lymphoma patients treated with curative intent: no difference in cumulative incidence of relapse comparing patients by age

Author

Eyre, T. A., primary, Martinez‐Calle, N., additional, Hildyard, C., additional, Eyre, D. W., additional, Plaschkes, H., additional, Griffith, J., additional, Wolf, J., additional, Fields, P., additional, Gunawan, A., additional, Oliver, R., additional, Djebbari, F., additional, Booth, S., additional, McMillan, A., additional, Fox, C. P., additional, Bishton, M. J., additional, Collins, G. P., additional, and Hatton, C. S. R., additional

Published
2019
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50. Estimating crack widths in steel fibre-reinforced concrete

Author

Sotiris Psomas, Colin Michael Eddie, and Eyre D. Hover

Subjects
Materials science, business.industry, 0211 other engineering and technologies, Modulus, 020101 civil engineering, 02 engineering and technology, Structural engineering, Bending, Strain hardening exponent, 0201 civil engineering, Cracking, Brittleness, Flexural strength, Mechanics of Materials, General Materials Science, Composite material, business, Ductility, Beam (structure), 021101 geological & geomatics engineering, Civil and Structural Engineering
Abstract

The use of steel fibres as reinforcement for sprayed concrete tunnel linings offers significant potential savings in time and cost. These provide a degree of crack control and an increase in ductility to the otherwise brittle material, and while the properties of steel fibre-reinforced concrete (SFRC) are well understood, its ability to control cracks is not quantifiable or justifiable in the design of concrete sections. This paper describes the novel application of particle image velocimetry (PIV) to the study of cracking in plain concrete and SFRC four-point flexural beam tests. Strain hardening under bending was observed, as was the propagation of multiple cracks (multicracking) in SFRC beams, in contrast to the brittle failure of the plain concrete specimen. The stress–strain behaviour of the material was quantified by means of digital photographs of the test, and Young's modulus of the SFRC was found to be similar to that of plain concrete. Cracks on the side of the beam as small as 0·05 mm and up to 4 mm were measured with an error

Published
2015
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