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1. Immunogenicity, safety, and reactogenicity of heterologous COVID-19 primary vaccination incorporating mRNA, viral-vector, and protein-adjuvant vaccines in the UK (Com-COV2): a single-blind, randomised, phase 2, non-inferiority trial

Author

Stuart, ASV, Shaw, RH, Liu, X, Greenland, M, Aley, PK, Andrews, NJ, Cameron, JC, Charlton, S, Clutterbuck, EA, Collins, AM, Darton, T, Dinesh, T, Duncan, CJA, England, A, Faust, SN, Ferreira, DM, Finn, A, Goodman, AL, Green, CA, Hallis, B, Heath, PT, Hill, H, Horsington, BM, Lambe, T, Lazarus, R, Libri, V, Lillie, PJ, Mujadidi, YF, Payne, R, Plested, EL, Provstgaard-Morys, S, Ramasamy, MN, Ramsay, M, Read, RC, Robinson, H, Screaton, GR, Singh, N, Turner, DPJ, Turner, PJ, Vichos, I, White, R, Nguyen-Van-Tam, JS, Snape, MD, Com-COV2 Study Group, and Group, Com-COV2 Study

Subjects
Male, qv_268.5, wa_115, COVID-19/prevention & control, Adjuvants, Vaccine/administration & dosage, qw_806, qw_805, Immunogenicity, Vaccine, Medicine, General & Internal, General & Internal Medicine, parasitic diseases, Humans, Single-Blind Method, 11 Medical and Health Sciences, Aged, COVID-19 Vaccines/administration & dosage, Science & Technology, qv_4, Vaccination/adverse effects, mRNA Vaccines/administration & dosage, Articles, General Medicine, Middle Aged, United Kingdom, Com-COV2 Study Group, 2019-nCoV Vaccine mRNA-1273/administration & dosage, wf_140, qw_160, Female, BNT162 Vaccine/administration & dosage, Life Sciences & Biomedicine, Immunization, Secondary/adverse effects, ChAdOx1 nCoV-19/administration & dosage
Abstract

Background Given the importance of flexible use of different COVID-19 vaccines within the same schedule to facilitate rapid deployment, we studied mixed priming schedules incorporating an adenoviral-vectored vaccine (ChAdOx1 nCoV-19 [ChAd], AstraZeneca), two mRNA vaccines (BNT162b2 [BNT], Pfizer–BioNTech, and mRNA-1273 [m1273], Moderna) and a nanoparticle vaccine containing SARS-CoV-2 spike glycoprotein and Matrix-M adjuvant (NVX-CoV2373 [NVX], Novavax). Methods Com-COV2 is a single-blind, randomised, non-inferiority trial in which adults aged 50 years and older, previously immunised with a single dose of ChAd or BNT in the community, were randomly assigned (in random blocks of three and six) within these cohorts in a 1:1:1 ratio to receive a second dose intramuscularly (8–12 weeks after the first dose) with the homologous vaccine, m1273, or NVX. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentrations measured by ELISA in heterologous versus homologous schedules at 28 days after the second dose, with a non-inferiority criterion of the GMR above 0·63 for the one-sided 98·75% CI. The primary analysis was on the per-protocol population, who were seronegative at baseline. Safety analyses were done for all participants who received a dose of study vaccine. The trial is registered with ISRCTN, number 27841311. Findings Between April 19 and May 14, 2021, 1072 participants were enrolled at a median of 9·4 weeks after receipt of a single dose of ChAd (n=540, 47% female) or BNT (n=532, 40% female). In ChAd-primed participants, geometric mean concentration (GMC) 28 days after a boost of SARS-CoV-2 anti-spike IgG in recipients of ChAd/m1273 (20 114 ELISA laboratory units [ELU]/mL [95% CI 18 160 to 22 279]) and ChAd/NVX (5597 ELU/mL [4756 to 6586]) was non-inferior to that of ChAd/ChAd recipients (1971 ELU/mL [1718 to 2262]) with a GMR of 10·2 (one-sided 98·75% CI 8·4 to ∞) for ChAd/m1273 and 2·8 (2·2 to ∞) for ChAd/NVX, compared with ChAd/ChAd. In BNT-primed participants, non-inferiority was shown for BNT/m1273 (GMC 22 978 ELU/mL [95% CI 20 597 to 25 636]) but not for BNT/NVX (8874 ELU/mL [7391 to 10 654]), compared with BNT/BNT (16 929 ELU/mL [15 025 to 19 075]) with a GMR of 1·3 (one-sided 98·75% CI 1·1 to ∞) for BNT/m1273 and 0·5 (0·4 to ∞) for BNT/NVX, compared with BNT/BNT; however, NVX still induced an 18-fold rise in GMC 28 days after vaccination. There were 15 serious adverse events, none considered related to immunisation. Interpretation Heterologous second dosing with m1273, but not NVX, increased transient systemic reactogenicity compared with homologous schedules. Multiple vaccines are appropriate to complete primary immunisation following priming with BNT or ChAd, facilitating rapid vaccine deployment globally and supporting recognition of such schedules for vaccine certification. Funding UK Vaccine Task Force, Coalition for Epidemic Preparedness Innovations (CEPI), and National Institute for Health Research. NVX vaccine was supplied for use in the trial by Novavax.

Published
2022

2. Hydra I: An extensible multi-source-finder comparison and cataloguing tool

Author

Boyce, M. M., Hopkins, A. M., Riggi, S., Rudnick, L., Ramsay, M., Hale, C. L., Marvil, J., Whiting, M., Venkataraman, P., O'Dea, C. P., Baum, S. A., Gordon, Y. A., Vantyghem, A. N., Dionyssiou, M., Andernach, H., Collier, J. D., English, J., Koribalski, B. S., Leahy, D., Michałowski, M. J., Safi-Harb, S., Vaccari, M., Alexander, E., Cowley, M., Kapinska, A. D., Robotham, A. S. G., and Tang, H.

Subjects
D.2.13, D.2.4, D.2.6, D.2.8, D.2.10, D.2.11, FOS: Physical sciences, Astrophysics - Instrumentation and Methods for Astrophysics, Instrumentation and Methods for Astrophysics (astro-ph.IM)
Abstract

The latest generation of radio surveys are now producing sky survey images containing many millions of radio sources. In this context it is highly desirable to understand the performance of radio image source finder (SF) software and to identify an approach that optimises source detection capabilities. We have created Hydra to be an extensible multi-SF and cataloguing tool that can be used to compare and evaluate different SFs. Hydra, which currently includes the SFs Aegean, Caesar, ProFound, PyBDSF, and Selavy, provides for the addition of new SFs through containerisation and configuration files. The SF input RMS noise and island parameters are optimised to a 90\% ''percentage real detections'' threshold (calculated from the difference between detections in the real and inverted images), to enable comparison between SFs. Hydra provides completeness and reliability diagnostics through observed-deep ($\mathcal{D}$) and generated-shallow ($\mathcal{S}$) images, as well as other statistics. In addition, it has a visual inspection tool for comparing residual images through various selection filters, such as S/N bins in completeness or reliability. The tool allows the user to easily compare and evaluate different SFs in order to choose their desired SF, or a combination thereof. This paper is part one of a two part series. In this paper we introduce the Hydra software suite and validate its $\mathcal{D/S}$ metrics using simulated data. The companion paper demonstrates the utility of Hydra by comparing the performance of SFs using both simulated and real images., Comment: Paper accepted for publication in PASA

Published
2023
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3. Hydra II: Characterisation of Aegean, Caesar, ProFound, PyBDSF, and Selavy source finders

Author

Boyce, M. M., Hopkins, A. M., Riggi, S., Rudnick, L., Ramsay, M., Hale, C. L., Marvil, J., Whiting, M., Venkataraman, P., O'Dea, C. P., Baum, S. A., Gordon, Y. A., Vantyghem, A. N., Dionyssiou, M., Andernach, H., Collier, J. D., English, J., Koribalski, B. S., Leahy, D., Michałowski, M. J., Safi-Harb, S., Vaccari, M., Alexander, E., Cowley, M., Kapinska, A. D., Robotham, A. S. G., and Tang, H.

Subjects
FOS: Physical sciences, D.2.8, Astrophysics - Instrumentation and Methods for Astrophysics, Instrumentation and Methods for Astrophysics (astro-ph.IM)
Abstract

We present a comparison between the performance of a selection of source finders using a new software tool called Hydra. The companion paper, Paper~I, introduced the Hydra tool and demonstrated its performance using simulated data. Here we apply Hydra to assess the performance of different source finders by analysing real observational data taken from the Evolutionary Map of the Universe (EMU) Pilot Survey. EMU is a wide-field radio continuum survey whose primary goal is to make a deep ($20\mu$Jy/beam RMS noise), intermediate angular resolution ($15^{\prime\prime}$), 1\,GHz survey of the entire sky south of $+30^{\circ}$ declination, and expecting to detect and catalogue up to 40 million sources. With the main EMU survey expected to begin in 2022 it is highly desirable to understand the performance of radio image source finder software and to identify an approach that optimises source detection capabilities. Hydra has been developed to refine this process, as well as to deliver a range of metrics and source finding data products from multiple source finders. We present the performance of the five source finders tested here in terms of their completeness and reliability statistics, their flux density and source size measurements, and an exploration of case studies to highlight finder-specific limitations., Comment: Paper accepted for publication in PASA

Published
2023
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4. Impact of priming interval on reactogenicity, peak immunological response and waning after homologous and heterologous COVID-19 vaccine schedules: Exploratory analyses of Com-COV, a randomised control trial

Author

Shaw, RH, Liu, X, Stuart, ASV, Greenland, M, Aley, PK, Andrews, NJ, Cameron, JC, Charlton, S, Clutterbuck, EA, Collins, AM, Dejnirattisai, W, Dinesh, T, Faust, SN, Ferreira, DM, Finn, A, Green, CA, Hallis, B, Heath, PT, Hill, H, Lambe, T, Lazarus, R, Libri, V, Long, F, Mujadidi, YF, Plested, EL, Morey, ER, Provstgaard-Morys, S, Ramasamy, MN, Ramsay, M, Read, RC, Robinson, H, Screaton, GR, Singh, N, Turner, DPJ, Turner, P, Vichos, J, Walker, LL, White, R, Nguyen-Van-Tam, JS, Snape, MD, Com-COV Study Group, and National Institute for Health and Care Research

Subjects
1103 Clinical Sciences, 1117 Public Health and Health Services, 1199 Other Medical and Health Sciences
Abstract

Background: Priming COVID-19 vaccine schedules have been deployed at variable intervals globally, which may influence immune persistence and the relative importance of third-dose ‘booster’ programmes. Here, we report on the impact of 4- versus 12-week priming intervals on reactogenicity and the persistence of immune response up to 6 months following homologous and heterologous priming schedules using BNT162b2 (BNT, tozinameran, Comirnaty, Pfizer/BioNTech) and ChAdOx1 nCoV-19 (ChAd, Vaxzevria, AstraZeneca). Methods: Com-COV is a participant-blinded, randomised immunogenicity trial. Results are reported here for the ‘General’ cohort, in which adults aged over 50 years were randomised to four homologous and heterologous schedules using BNT and ChAd with 4- or 12-week priming intervals. Immunogenicity analyses were on the intention-to-treat population (ITT), without evidence of COVID-19 infection at baseline or for the trial duration, with the purpose of describing the effect of priming interval on humoral and cellular immune response at peak and later timepoints, in addition to the effects on reactogenicity and safety Findings: Between 11th–26th Feb 2021, 730 participants were randomised in the general cohort, with 77-89 per arm in the ITT analysis. At 28-days and 6-months post-second dose, the geometric mean concentration (GMC) of anti-SARS-CoV-2 spike IgG was significantly higher in 12- versus 4-week interval arms for homologous schedules. In heterologous arms, there was only a significant difference between intervals for the BNT/ChAd arm at 28-days. Pseudotyped virus neutralisation titres were significantly higher in all 12-week versus 4-week schedules, 28-days post-second dose, with geometric mean ratios 1.4 (95%CI: 1.1-1.8, BNT/BNT), 1.5 (95%CI: 1.2-1.9, ChAd/BNT), 1.6 (95%CI 1.3-2.1, BNT/ChAd) and2.4 (95%CI: 1.7-3.2, ChAd/ChAd). At 6 months post-second dose, anti-spike IgG GMCs fell to 0.17-0.24 of the 28-day post-second dose value across all eight study arms, with only BNT/BNT displaying a slightly slower decay for the 12-week versus 4-week schedule in the adjusted analysis. The rank order of schedules by humoral response was unaffected by interval with BNT/BNT remaining the most immunogenic by antibody response. T-cell responses were reduced in all 12-week priming intervals versus their 4-week counterparts. 12-week schedules for BNT/BNT and ChAd/BNT schedules were up to 80% less reactogenic than 4-week schedules. Interpretation: These data support flexibility in priming interval in all studied COVID-19 vaccine schedules. Longer priming intervals may result in lower reactogenicity in schedules with BNT as a second-dose and higher humoral immunogenicity in homologous schedules, but overall lower T-cell responses across all schedules. Future vaccines employing these novel platforms may benefit from prolonged-interval schedules. ISRCTN:69254139, EudraCT:2020-005085-33.

Published
2022

5. 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

6. An integrated national scale SARS-CoV-2 genomic surveillance network

Author

Aanensen, DM, Abudahab, K, Adams, A, Afifi, S, Alam, MT, Alderton, A, Alikhan, N-F, Allan, J, Almsaud, M, Alrezaihi, A, Alruwaili, M, Amato, R, Andersson, M, Angyal, A, Aranday-Cortes, E, Ariani, C, Armstrong, SD, Asamaphan, P, Attwood, S, Aydin, A, Badhan, A, Baker, D, Baker, P, Balcazar, CE, Ball, J, Barton, AE, Bashton, M, Baxter, L, Beale, M, Beaver, C, Beckett, A, Beer, R, Beggs, A, Bell, A, Bellis, KL, Bentley, EG, Berriman, M, Betteridge, E, Bibby, D, Bicknell, K, Birchley, A, Black, G, Blane, B, Bloomfield, S, Bolt, F, Bonsall, DG, Bosworth, A, Bourgeois, Y, Boyd, O, Bradshaw, D, Breuer, J, Bridgewater, H, Brooks, T, Broos, A, Brown, JR, Brown, RL, Brunker, K, Bucca, G, Buck, D, Bull, M, Butcher, E, Caddy, SL, Caller, LG, Cambell, S, Carlile, M, Carmichael, S, Carrilero, L, Castellano, S, Chaloner, J, Chand, M, Chapman, MR, Chappell, J, Charles, I, Chauhan, AJ, Chawla, A, Cheng, E, Churcher, CM, Clark, G, Clark, JJ, Collins, J, Colquhoun, R, Connor, TR, Constantinidou, C, Coombes, J, Corden, S, Cottrell, S, Cowell, A, Curran, MD, Curran, T, Dabrera, G, Danesh, J, Darby, AC, De Cesare, M, Martins, LDO, De Silva, TI, Debebe, B, Dervisevic, S, Dewar, RA, Dia, M, Dorman, M, Dougan, G, Dover, L, Downing, F, Drury, E, Du Plessis, L, Dyal, PL, Eccles, R, Edwards, S, Ellaby, N, Elliott, S, Eltringham, G, Elumogo, N, Essex, S, Evans, CM, Evans, J, Nascimento, FF, Fairley, DJ, Farr, B, Feltwell, T, Ferguson, N, Filipe, ADS, Findlay, J, Forrest, LM, Forrest, S, Foulser, L, Francois, S, Fraser, C, Frost, L, Gallagher, E, Gallagher, MD, Garcia-Dorival, I, Gaskin, A, Gatica-Wilcox, B, Gavriil, A, Geidelberg, L, Gemmell, M, Gerada, A, Gifford, L, Gilbert, L, Gilmore, P, Gilroy, R, Girgis, S, Glaysher, S, Golubchik, T, Goncalves, S, Goodfellow, I, Goodwin, S, Graham, C, Graham, L, Grammatopoulos, D, Green, A, Green, LR, Greenaway, J, Gregory, R, Groves, DC, Groves, N, Guest, M, Gunson, R, Haldenby, S, Hall, G, Hamilton, WL, Han, X, Harris, KA, Harrison, EM, Hartley, C, Herrera, C, Hesketh, A, Heyburn, D, Hill, V, Hiscox, JA, Holden, M, Holmes, A, Holmes, N, Holt, GS, Hopes, R, Hosmillo, M, Houldcroft, CJ, Howson-Wells, H, Hubb, J, Hughe, J, Hughes, M, Hutchings, S, Impey, R, Iturriza-Gomara, M, Jackson, A, Jackson, B, Jackson, DK, Jahun, AS, James, K, Jamrozy, D, Jeffries, A, Jesudason, N, John, M, Johnson, J, Johnson, KJ, Johnson, N, Johnston, I, Jones, B, Jones, R, Jones, S, Jorgensen, D, Kane, L, Kay, GL, Kay, S, Keatley, J-P, Keeley, AJ, Khakh, M, Khokhar, FA, Kitchen, C, Knight, B, Kolyva, A, Kraemer, M, Kristiansen, M, Kumziene-Summerhayes, S, Kwiatkowski, D, Lackenby, A, Langford, C, Lawniczak, M, Thanh, L-V, Lee, D, Letchford, L, Li, K, Li, L, Liggett, S, Lindsey, BB, Livett, R, Lloyd, A, Lo, S, Lockhart, M, Loh, J, Loman, NJ, Loose, M, Lucaci, A, Ludden, C, Luu, L, Lyons, RA, MacIntyre-Cockett, G, MacLean, A, Mair, D, Maksimovic, J, Manley, R, Manso, C, Manson, J, Martincorena, I, Masoli, J, Mather, AE, Mbisa, T, McCluggage, K, McClure, P, McCrone, JT, McDonald, S, McHugh, MP, McKenna, JM, McMinn, L, McMurray, C, Meadows, L, Menegazzo, M, Meredith, LW, Merrick, I, Mestek-Boukhibar, L, Miah, S, Michell, S, Michelsen, ML, Molnar, Z, Moore, C, Moore, N, Morgan, M, Morgan, S, Muddyman, D, Muir, DA, Muir, P, Myers, R, Nastouli, E, Naydenova, P, Nelson, A, Nelson, C, Nelson, R, Nicholls, S, Nichols, J, Niebel, M, Niola, P, Nomikou, K, O'Grady, J, O'Toole, AN, O'Toole, E, Olateju, C, Orton, RJ, Osman, H, Ott, S, Pacchiarini, N, Padgett, D, Page, AJ, Palmer, S, Panchbhaya, YN, Pandey, S, Park, N, Parker, MD, Parkhill, J, Parr, YA, Parsons, PJ, Partridge, DG, Patel, M, Patterson, S, Payne, B, Peacock, SJ, Penrice-Randal, R, Perry, M, Platt, S, Poplawski, R, Prakash, R, Prestwood, L, Price, A, Price, JR, Puethe, C, Pybus, O, Pymont, H, Quail, M, Quick, J, Raghwani, J, Ragonnet-Cronin, M, Rahman, S, Rainbow, L, Rajatileka, S, Rambaut, A, Ramsay, M, Randell, PA, Randle, NP, Raviprakash, V, Raza, M, Silva, PR, Rey, S, Richter, A, Robertson, DL, Robinson, TI, Robson, SC, Rooke, S, Rowan, A, Rowe, W, Roy, S, Rudder, S, Ruis, C, Sang, F, Scarlett, G, Schaefer, U, Scott, C, Scott, G, Sethi, D, Shaaban, S, Shah, R, Sharma, P, Shawli, GT, Shepherd, J, Sherriff, N, Shirley, L, Sillitoe, J, Simpson, DA, Singer, JB, Siveroni, I, Smith, C, Smith, CP, Smith, DL, Smith, N, Smith, W, Smith-Palmer, A, Smollett, K, Southgate, J, Spellman, K, Spencer-Chapman, M, Sridhar, S, Stanley, R, Stark, R, Stewart, JP, Stockton, J, Stuart, C, Studholme, D, Swainston, N, Swindells, E, Taha, Y, Tariq, MA, Taylor, B, Taylor, GP, Taylor, S, Taylor-Joyce, G, Tedim, AP, Temperton, B, Templeton, KE, Thomson, EC, Thomson, NM, Thornton, A, Thurston, S, Todd, J, Tong, L, Tonkin-Hill, G, Torok, ME, Trebes, A, Trotter, AJ, Tsoleridis, T, Tucker, RM, Tutill, HJ, Underwood, A, Unnikrishnan, M, Vamos, E, Vasylyeva, T, Vattipally, S, Victoria, A, Vipond, B, Volz, EM, Wain, J, Wang, D, Warwick-Dugdale, J, Wastnedge, E, Watkins, J, Watts, J, Webber, M, Weeks, S, Weldon, D, Whitehead, M, Williams, CA, Williams, C, Williams, D, Williams, R, Williams, TC, Wise, E, Wright, V, Wyles, MD, Wyllie, S, Yakovleva, A, Yasir, M, Yeats, C, Yew, WC, Young, GR, Yu, X, and Zarebski, A

Subjects
Microbiology (medical), Scale (ratio), SARS-CoV-2, viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, COVID-19 Genomics UK (COG-UK) consortiumcontact@cogconsortium.uk, C500, Genome, Viral, Genomics, Biology, C700, Microbiology, Article, Infectious Diseases, Virology, Humans, Cartography
Abstract

The Coronavirus Disease 2019 (COVID-19) Genomics UK Consortium (COG-UK) was launched in March, 2020, with £20 million support from UK Research and Innovation, the UK Department of Health and Social Care, and Wellcome Trust. The goal of this consortium is to sequence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for up to 230 000 patients, health-care workers, and other essential workers in the UK with COVID-19, which will help to enable the tracking of SARS-CoV-2 transmission, identify viral mutations, and integrate with health data to assess how the viral genome interacts with cofactors and consequences of COVID-19.

Published
2020

7. Community-Based Logging andDe FactoDecentralization

Author

Ramsay M. Ravenel

Subjects
Opportunity cost, Renewable Energy, Sustainability and the Environment, business.industry, Geography, Planning and Development, Logging, Environmental resource management, Forest management, Forestry, Management, Monitoring, Policy and Law, Public administration, Felling, Boom, Decentralization, Community forestry, Political science, Illegal logging, business, Food Science
Abstract

This paper considers the emergence of community-based logging in West Kalimantan, Indonesia at the end of the timber boom in the mid-1990s. It begins with an overview of the relevant laws and regulations and describes community-based logging before the era reformasi that began with the ouster of President Suharto in May 1998. The paper argues that the Indonesian Selective Felling System (TPTI) both in theory and in practice has severely compromised the quality of Indonesia's natural production forests. The spatial heterogeneity of concession logging has encouraged reentry by teams of small-scale loggers who face lower operational and opportunity costs, and who have appropriated management and financial systems from the departed concessionaires. The paper then contrasts community-based logging with conventional forest management systems and critiques decentralization and illegal logging discourses. From these critiques, I suggest that the de facto decentralization described by Rhee (2000) actually...

Published
2004

8. Illegal Logging in the Tropics

Author

Ilmi M. E. Granoff and Ramsay M. Ravenel

Subjects
Renewable Energy, Sustainability and the Environment, business.industry, Geography, Planning and Development, Environmental resource management, Tropics, Forestry, Management, Monitoring, Policy and Law, Private sector, Variety (cybernetics), Deforestation, Social conflict, Illegal logging, business, Enforcement, Protected area, Environmental planning, Food Science
Abstract

Illegal logging is a policy problem that has arisen from the failure of protected area and sustainable forestry remedies for deforestation. Nevertheless, illegal logging in some parts of the world is a centuries-old problem rooted in social conflicts over access to forest resources. We synthesize the papers in this volume, which analyze illegal logging issues in a variety of countries-Indonesia, Vietnam, India, Cameroon, Benin, and Mexico—and from a variety of analytical perspectives—anthropologic, economic, political science, legal, and conservationist. We describe illegal logging activities and analyze the roles of key stakeholders such as governments, the private sector, local communities, and non-governmental organizations. We summarize the major policy recommendations presented by the authors in this volume, which include: broad anti-corruption initiatives beyond the forest sector, information-based approaches, conventional regulation and enforcement, and market mechanisms. Illegal logging i...

Published
2004

9. Introduction to Illegal Logging in the Tropics

Author

Ilmi M. E. Granoff and Ramsay M. Ravenel

Subjects
Renewable Energy, Sustainability and the Environment, business.industry, Geography, Planning and Development, Environmental resource management, Tropics, Forestry, Management, Monitoring, Policy and Law, Public administration, Environmental studies, Framing (social sciences), Political science, Illegal logging, business, Food Science
Abstract

On March 29-30, 2002, the Yale Chapter of the International Society of Tropical Foresters convened social and natural scientists, resource managers, policy-makers, community leaders and other interested parties to share experiences, strategies, successes and failures in addressing illegal logging and corruption. The conference explored the framing of the illegal logging problem, the extent of the problem, its perceived causes, and potential solutions. Thirteen papers were presented at the conference entitled Illegal Logging in the Tropics: The Ecology, Economics and Policy or Resource Misuse held at the Yale School of Forestry and Environmental Studies on March 29-30, 2002. This introduction presents a brief overview of the illegal logging issue and describes the papers presented in this volume.

Published
2004

10. An unusual transmission event of Neisseria meningitidis serogroup W135 type 2a in a healthcare setting, England, 2012

Author

Puleston R, Beck C, Tahir M, Bardhan M, Charlemagne P, Alves C, Ladhani S, Conall Watson, Ramsay M, Kaczmarksi E, Borrow R, Gray S, Hadlington D, Weinbren M, Bhattacharjee D, and Inglis N

Subjects
Adult, Male, Cross Infection, Adolescent, Middle Aged, Hospitalization, Meningococcal Infections, Young Adult, England, Neisseria meningitidis, Serogroup W-135, Humans, Female, Contact Tracing, Child, Respiratory Tract Infections, Aged
Published
2012

11. A possible outbreak of hepatitis A associated with semi-dried tomatoes, England, July-November 2011

Author

Carvalho C, Thomas H, Balogun K, Richard Tedder, Pebody R, Ramsay M, and Ngui S

Subjects
Adult, Male, Adolescent, Genotyping Techniques, Hepatitis A, Middle Aged, Disease Outbreaks, Foodborne Diseases, Epidemiologic Studies, Young Adult, England, Solanum lycopersicum, Humans, Female, Serotyping, Child, Hepatitis A Virus, Human, Netherlands
Abstract

In October 2011, two primary cases of hepatitis A virus (HAV) infection with identical HAV genotype IB strains to those seen in other outbreaks associated with semi-dried tomatoes were reported in England. Both cases had consumed semi-dried tomatoes. Epidemiological investigations revealed two additional cases of genotype IB strains with different sequences who also reported having consumed semi-dried tomatoes. In November, five cases of HAV infection with closely related strains were identified in the Netherlands. A foodborne multiple-strain outbreak is suspected.

Published
2012

13. Pulmonary-Hepatic vascular Disorders (PHD)

Author

Rodrıguez Roisin, R., Krowka, M. J., Herve´, P. h., Fallon, M. B., Barbera´, on behalf of the ERS Task Force Pulmonary–Hepatic Vascular Disorders Scientific Committee J. A., Caneva, J. O., Garcıa Paga, J. C., Garcıa Valdecasas, J. C., Kawut, S., Lebrec, D., Navarro, D., Navasa, M., Ramsay, M. A. E., Rodes, J., Rolla, Giovanni, Sitbon, O., and Wagner, P. D.

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Portopulmonary hypertension, Pathology, Lung, biology, business.industry, Hypertension, Pulmonary, Vasodilation, medicine.disease, Oxygen tension, Nitric oxide, Nitric oxide synthase, chemistry.chemical_compound, medicine.anatomical_structure, chemistry, Internal medicine, Cardiology, biology.protein, Medicine, Humans, business, Hepatopulmonary syndrome, Blood vessel, Hepatopulmonary Syndrome
Abstract

⇓“The tantalizing problem of the connective link in cirrhotic patients between oxygen unsaturation and possible arteriovenous shunting in the lungs remains unsolved, and any relation between arterial unsaturation and pulmonary vasodilation remains obscure.” Fig. 1.— Working model of molecular alterations in the pulmonary microcirculation in experimental hepatopulmonary syndrome (HPS). a) In the normal microvasculature, a balance of vasoconstrictive and vasodilatory factors, including paracrine endothelin (ET)-1-mediated vasoconstriction through the ETA receptor (▪) on smooth muscle cells (SMCs) and ET-1-mediated vasodilatation mediated through the ETB receptor (□) linked to endothelial nitric oxide synthase (eNOS) in endothelial cells (ECs), maintain tone. b) During the development of HPS, a number of alterations, both directly and indirectly related to hepatic injury and portal hypertension, result in the production or release of mediators into the venous circulation, where they influence the pulmonary microcirculation. Increased expression of pulmonary endothelial ETB receptors and increased hepatic production and release of ET-1 contribute to an increase in eNOS expression and enhanced nitric oxide (NO) production in the microvascular endothelium during the initiation of HPS. Tumour necrosis factor (TNF)-α-mediated accumulation of intravascular macrophage-like cells also occurs after chronic common bile duct ligation. Haem oxygenase (HO)-1 and inducible nitric oxide synthase (iNOS) expression increase in these cells and contribute to the progression of HPS. CO: carbon monoxide. Fig. 2.— Algorithm for screening and therapeutic decisions in hepatopulmonary syndrome (HPS). OLT: orthotopic liver transplantation; P a,O2: arterial oxygen tension; P A–a,O2: alveolar–arterial oxygen tension difference; CEE: contrast-enhanced echocardiography; PFT: pulmonary function test; MAA: macroaggregated albumin. #: high-resolution thoracic computed tomographic scanning is highly recommended in order to exclude chronic respiratory comorbid conditions; ¶: high risk for post-operative OLT mortality. 1 mmHg=0.133 kPa. Fig. 3.— Plot demonstrating the relationship between cardiac output ( Q ') and transpulmonary pressure gradient (TPG; mean pulmonary arterial …

Published
2004

18. The epidemiology of rubella in England and Wales before and after the 1994 measles and rubella vaccination campaign: fourth joint report from the PHLS and the National Congenital Rubella Surveillance Programme

Author

Miller E, Waight P, Gay N, Ramsay M, Vurdien J, Morgan-Capner P, Hesketh L, Brown D, Pat Tookey, and Peckham C

Subjects
Adult, Male, Wales, Adolescent, Incidence, Measles Vaccine, Rubella Syndrome, Congenital, Infant, Newborn, Infant, Mumps Vaccine, Antibodies, Viral, Disease Outbreaks, England, Pregnancy, Seroepidemiologic Studies, Child, Preschool, Humans, Female, Rubella Vaccine, Vaccines, Combined, Pregnancy Complications, Infectious, Child, Saliva, Measles-Mumps-Rubella Vaccine, Rubella
Abstract

The national immunisation campaign carried out in the United Kingdom in November 1994 was designed to give children aged 5 to 16 years of age a single dose of a combined measles and rubella vaccine. Its main objective was to prevent an epidemic of measles predicted in school age children. The rubella component of the vaccine was included in order to reduce the high level of susceptibility to rubella in young adult males and thus reduce the risk of transmission from this group to pregnant women. Susceptibility to rubella in children aged 5 to 16 years has fallen from 15.7% to 3.4% since the measles and rubella campaign. Despite this the incidence of laboratory confirmed rubella rose substantially in 1996, largely on account of cases among males aged 17 to 24 years, who were not vaccinated in the 1994 campaign and about 16% of whom are susceptible. The impact of the resurgence on the incidence of infection in pregnancy has been relatively limited, due to the low level of susceptibility in the antenatal population (2% in nulliparous and 1.2% in parous women for 1994/5). No cases of congenital rubella arising from administration of measles and rubella vaccine during the campaign have been identified. The numbers of babies born with congenital rubella and terminations of pregnancy for rubella arising from the 1996 resurgence are expected to be similar to those that followed the 1993 resurgence. The reduction in susceptibility in future cohorts of young men who received measles and rubella vaccine in the 1994 campaign should prevent future resurgences after the year 2000. If a second dose of measles, mumps, and rubella (MMR) vaccine had not been introduced, susceptibility levels in the school age population would have risen to about 12% in the future. The effect of the second dose of MMR vaccine introduced for children aged 4 to 5 years in October 1996 will be assessed through serological surveillance.

19. A platform for genomics in South Africa [4]

Author

Hide, W., Mizrahi, V., Venkatesh, B., Brenner, S., Simpson, A., Blatch, G., Soodyall, H., Denby, K., Wingfield, M., Wingfield, B., Helden, P., Ramesar, R., Dorrington, R., Kelso, J., Oppon, E., Goyvaerts, E., Ramsay, M., Villiers, E., Carel van Heerden, Allsopp, B., and Seoighe, C.

25. A platform for genomics in South Africa

Author

Hide W, Mizrahi V, Venkatesh B, Brenner S, Simpson A, Blatch G, Soodyall H, Denby K, Wingfield M, Wingfield B, van Helden P, Ramesar R, Dorrington R, Janet Kelso, Oppon E, Goyvaerts E, Ramsay M, de Villiers E, van Heerden C, Allsopp B, and Seoighe C

Subjects
South Africa, Animals, Humans, Genomics, Ecosystem

27. World title boxing: From early beginnings to the first bell

Author

Robert J. Schinke and Ramsay, M.

Subjects
lcsh:Sports, lcsh:GV557-1198.995, Boxing, psychology, lcsh:Sports medicine, lcsh:RC1200-1245, competition, performance
Abstract

There is scant literature where applied sport scientists have considered first hand experiences preparing professional boxers for world title bouts. The present submission reflects more than 10 years of applied experience working with professional boxers, residing in Canada. What follows is a composite of sequential steps that ownership and coaching staff of one Canadian management group have tried leading up to more than 20 world title bout experiences. The strategies proposed have been built progressively over time, and what follows is a general overview of a more detailed pre-bout structure from shortly in advance of a world title bout offer to the moment when the athlete enters the ring to perform. We propose that an effective structure is founded upon detailed a priori preparation, tactical decisions throughout bout preparation, and a thorough understanding by the athlete of what he will encounter during the title bout

28. Increase in invasive Streptococcus pyogenes and Streptococcus pneumoniae infections in England, December 2010 to January 2011

Author

Zakikhany K, Ma, Degail, Lamagni T, Waight P, Guy R, Zhao H, Efstratiou A, Richard Pebody, George R, and Ramsay M

Subjects
Adult, Aged, 80 and over, Male, Adolescent, Streptococcus pyogenes, Incidence, Microbial Sensitivity Tests, Middle Aged, Pneumococcal Infections, Young Adult, Streptococcus pneumoniae, England, Risk Factors, Child, Preschool, Population Surveillance, Streptococcal Infections, Influenza, Human, Humans, Female, Seasons, Child, Aged
Abstract

Increases in invasive Streptococcus pyogenes and S. pneumoniae above the seasonally expected levels are currently being seen in England. Preliminary analyses suggest that the high level of influenza activity seen this winter may be contributing to an increased risk of concurrent invasive bacterial and influenza infections in children and young adults.

30. A randomised trial of timed delivery for the compromised preterm fetus: Short term outcomes and bayesian interpretation

Author

Bulck, B., Kalakoutis, G. M., Sak, P., Schneider, K. T. M., Major, T., Karpathios, S. E., Tullia Todros, Arduini, D., Tranquilli, A., Tenore, A. C., Roncaglia, N., Frusca, T., Groningen, A. Z., Weinans, M. J. N., Leiden, A. Z., Roosmalen, J., De Heel, Zaandam, Slikke, J. W., Geijn, H., Pernet, P. J. M., Wolf, H., Utrecht, A. Z., Stigter, R. H., Wilczynski, J., Vasco, E., Rashid, M., Novak-Antolic, Z., Danielian, P., Jenkinson, S. D., Welch, C. R., Griffin, C., Gee, H., Tuffnell, D., Cresswell, J., Tariq, T., Sengupta, B., Tydeman, G., Kumarendran, M. K., Churchill, D., Bewley, S., Fusi, L., Lindow, S. W., Johal, W., Fairlie, F. M., Neales, K., Thornton, J. G., Scudamore, I., Konje, J., Walkinshaw, S. A., Griffiths, M., Dawson, A., Mires, G., Johanson, R., Fraser, R. B., Hendy Ibbs, P., Steel, S. A., Ramsay, M., Robins, J. B., Heard, M. J., Tonge, H. M., Manyonda, I. T., Walker, J., Maresh, M., Yoong, A., Soothill, P., Cameron, H., Byrne, D., Beattie, B., Bober, S., Felber, B., Isaac, E., Liddle, L., Mcghee, T., Rowsell, P., Howie, P., Field, D., Levene, M., Lilford, R. J., Grant, A., Steer, P., Breart, G., Torgeson, D., Hornbuckle, J., Vail, A., Spiegelhalter, D., and Athena Institute

Subjects
SDG 3 - Good Health and Well-being
Abstract

Objectives. To compare the effect of delivering early to pre-empt terminal hypoxaemia with delaying for as long as possible to increase maturity. Design. A randomised controlled trial. Setting. 69 hospitals in 13 European countries. Participants. Pregnant women with fetal compromise between 24 and 36 weeks, an umbilical artery Doppler waveform recorded and clinical uncertainty whether immediate delivery was indicated. Methods. The interventions were 'immediate delivery' or 'delay until the obstetrician is no longer uncertain'. The data monitoring and analysis were Bayesian. Main outcome measures. 'Survival to hospital discharge' and 'developmental quotient at two years of age', this latter to be reported later. Results. Of 548 women (588 babies) recruited, outcomes were available on 547 mothers (587 babies). The median time-to-delivery intervals were 0.9 days in the immediate group and 4.9 days in the delay group. Total deaths prior to discharge were 29 (10%) in the immediate group versus 27 (9%) in the delay group (odds ratio 1.1, 95% CI 0.61-1.8). Total caesarean sections were 249 (91%) in the immediate group versus 217 (79%) in the delay group: (OR 2.7; 95% CI 1.6-4.5). These odds ratios were similar for those randomised at gestational ages above or below 30 weeks. Interpretation. The lack of difference in overall mortality suggests that clinicians participating in this trial were on average prepared to randomise at about the correct equivocal threshold between delivery and delay. However, there was insufficient evidence to convince enthusiasts for either immediate or delayed delivery that they were wrong.

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