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1,064 results on '"Rowlands J"'

1. Noise Correlations in a 1D Silicon Spin Qubit Array

Author

Donnelly, M. B., Rowlands, J., Kranz, L., Hsueh, Y. L., Chung, Y., Timofeev, A. V., Geng, H., Singh-Gregory, P., Gorman, S. K., Keizer, J. G., Rahman, R., and Simmons, M. Y.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

Correlated noise across multi-qubit architectures is known to be highly detrimental to the operation of error correcting codes and the long-term feasibility of quantum processors. The recent discovery of spatially dependent correlated noise in multi-qubit architectures of superconducting qubits arising from the impact of cosmic radiation and high-energy particles giving rise to quasiparticle poisoning within the substrate has led to intense investigations of mitigation strategies to address this. In contrast correlated noise in semiconductor spin qubits as a function of distance has not been reported to date. Here we report the magnitude, frequency and spatial dependence of noise correlations between four silicon quantum dot pairs as a function of inter-dot distance at frequencies from 0.3mHz to 1mHz. We find the magnitude of charge noise correlations, quantified by the magnitude square coherence $C_{xy}$, are significantly suppressed from $>0.5$ to $<0.1$ as the inter-dot distance increases from 75nm to 300nm. Using an analytical model we confirm that, in contrast to superconducting qubits, the dominant source of correlated noise arises from low frequency charge noise from the presence of two level fluctuators (TLFs) at the native silicon-silicon dioxide surface. Knowing this, we conclude with an important and timely discussion of charge noise mitigation strategies., Comment: 9 pages, 4 figures, 1 table

Published
2024

2. A high-resolution CMOS imaging detector for the search of neutrinoless double $\beta$ decay in $^{82}$Se

Author

Chavarria, A. E., Galbiati, C., Li, X., and Rowlands, J. A.

Subjects
Physics - Instrumentation and Detectors, High Energy Physics - Experiment, High Energy Physics - Phenomenology, Nuclear Experiment
Abstract

We introduce high-resolution solid-state imaging detectors for the search of neutrinoless double $\beta$ decay. Based on the present literature, imaging devices from amorphous $^{82}$Se evaporated on a complementary metal-oxide-semiconductor (CMOS) active pixel array could have the energy and spatial resolution to produce two-dimensional images of ionizing tracks of utmost quality, effectively akin to an electronic bubble chamber in the double $\beta$ decay energy regime. Still to be experimentally demonstrated, a detector consisting of a large array of these devices could have very low backgrounds, possibly reaching $10^{-7}$/(kg y) in the neutrinoless decay region of interest (ROI), as it may be required for the full exploration of the neutrinoless double $\beta$ decay parameter space in the most unfavorable condition of a strongly quenched nucleon axial coupling constant., Comment: 13 pages, 5 figures

Published
2016
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3. An epistemic case for democracy : analysing the performance of voting groups

Author

Rowlands, J. J. and Wolff, Jonathan

Subjects
100
Abstract

This thesis argues that, given certain assumptions, democracies are epistemically superior to other forms of government. Using quantitative results calculated with Condorcet's Jury Theorem, it will assess the performance of different voting groups. These groups will be models of current systems of governance or those that could feasibly be adopted. To achieve this it will have to argue for the plausibility of two main claims. Firstly that there is a true choice open to voters in political decisions and secondly that democracies are better able to identify correct choices than alternative forms of government.

Published
2015

4. Origin of n- and p-type conductivity in undoped $\alpha$-PbO: role of defects

Author

Berashevich, J., Rowlands, J. A., and Reznik, A.

Subjects
Condensed Matter - Materials Science
Abstract

The first principles calculations (GGA) have been applied to study the crystallographic defects in $\alpha$-PbO in order to understand an origin of $n$- and $p$-type conductivity in otherwise undoped $\alpha$-PbO. It was found that deposition in the oxygen-deficient environment to be defined in our simulations by the Pb-rich/O-poor limit stimulates a formation of the O vacancies and the Pb interstitials both to be characterized by quite low formation energies $\sim$ 1.0 eV. The O vacancy being occupied by two electrons shifts a balance of electrons and holes between these two defects to excess of electrons (four electrons against two holes) that causes the $n$-type doping. For the Pb-poor/O-rich limit, an excess of oxygen triggers a formation of the O interstitials characterized by such a low formation energy that spontaneous appearance of this defect is predicted. It is shown that the concentration of the O interstitials is able to reach the extreme magnitude equal to number of the possible defect sites ($\sim 10^{22}$cm$^{-3}$). The localized state formed by the O interstitial is occupied by two holes and because there are no other defects in reasonable concentration to balance the hole redundancy, $p$-type doping is induced., Comment: 5 pages, 3 figures

Published
2013
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5. Self-passivation of vacancies in \alpha-PbO

Author

Berashevich, J., Rowlands, J. A., and Reznik, A.

Subjects
Condensed Matter - Materials Science
Abstract

We introduce a self-passivation of single lead (Pb) and oxygen (O) vacancies in the \alpha-PbO compound through formation of a Pb-O vacancy pair. The preferential mechanism for pair formation involves initial development of the single Pb vacancy which, by weakening the covalent bonding, sets up the crystal lattice for an appearance of the O vacancy. Binding of the Pb and O vacancies occurs through the ionization interactions. Since no dangling bonds appear at the Pb-O pair site, this defect has a minor effect on the electronic properties. In such, vacancy self-passivation offers a practical way to improve the transport properties in thermally grown PbO layers., Comment: 4 pages, 4 figures

Published
2013
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6. Lead monoxide $\alpha$-PbO: electronic properties and point defect formation

Author

Berashevich, J., Semeniuk, O., Rubel, O., Rowlands, J. A., and Reznik, A.

Subjects
Condensed Matter - Materials Science, Physics - Computational Physics
Abstract

The electronic properties of polycrystalline lead oxide consisting of a network of single-crystalline $\alpha$-PbO platelets and the formation of the native point defects in $\alpha$-PbO crystal lattice are studied using first principles calculations. The $\alpha$-PbO lattice consists of coupled layers interaction between which is too low to produce high efficiency interlayer charge transfer. In practice, the polycrystalline nature of $\alpha$-PbO causes the formation of lattice defects in such a high concentration that defect-related conductivity becomes the dominant factor in the interlayer charge transition. We found that the formation energy for the O vacancies is low, such vacancies are occupied by two electrons in the zero charge state and tend to donate their electrons to the Pb vacancies that leads to ionization of both vacancies.The vacancies introduce localized states in the band gap which can affect charge transport. The O vacancy forms a defect state at 1.03 eV above the valence band which can act as a deep trap for electrons, while the Pb vacancy forms a shallow trap for holes located just 0.1 eV above the valence band. Charge de-trapping from O vacancies can be accounted for the experimentally found dark current decay in ITO/PbO/Au structures., Comment: 7 pages, 5 figures

Published
2012
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7. Unipolar Time-Differential Pulse Response with a Solid-State Charpak Photoconductor

Author

Goldan, A. H., Tousignant, O., Karim, K. S., and Rowlands, J. A.

Subjects
Physics - Instrumentation and Detectors, Physics - Medical Physics
Abstract

We demonstrate, for the first time, a high granularity multi-well solid-state detector (MWSD) with the unipolar time-differential property for ultrafast pulse response. Results show a speed improvement factor of up to ~400 for amorphous selenium MWSD. The significance of the results presented here is the ability to reach the intrinsic physical limit for detector pulse speed by transitioning from the slow transit-time-limited response which depends on the bulk carrier transport mechanism, to the ultrafast dispersion-limited response which depends on the spatial spreading of the collected carrier packet. Furthermore, the proposed structure is the practical approach for achieving stable avalanche multiplication gain in large-area direct radiation detectors., Comment: 14 pages, 4 figures

Published
2012
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8. Solid-State Charpak Detector with Unipolar and Ultrafast Time-Differential Pulse Response

Author

Goldan, A. H., Tousignant, O., Rowlands, J. A., and Karim, K. S.

Subjects
Physics - Instrumentation and Detectors
Abstract

For the first time we have fabricated a high granularity micropattern solid-state detector (MSSD) with the unipolar time-differential property for ultrafast pulse response. Optical, x-ray, and gamma-ray photoconductivity measurements prove the unipolar time-differential response with a speed improvement factor of ~400 for amorphous selenium MSSD. The significance of the results presented here is the ability to reach the intrinsic physical limit for detector pulse speed by transitioning from the transit-time-limited response, which depends on the bulk carrier transport mechanism, to range-limited response set by the spatial dispersion of the photo-induced carrier cloud. Furthermore, the combination of the time-differential and the avalanche-multiplication properties of the proposed micropattern solid-state detector can yield another great leap forward in the field of radiation detectors with applications ranging from high-energy, nuclear, and astro- physics, to industrial and medical diagnostics, and crystallography., Comment: This paper has been withdrawn by the author due to a crucial error in the discussion. Also, a newer version has been uploaded with a new title

Published
2012

14. Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

Author

Meng, B., Abdullahi, A., Ferreira, I. A. T. M., Goonawardane, N., Saito, A., Kimura, I., Yamasoba, D., Gerber, P. P., Fatihi, S., Rathore, S., Zepeda, S. K., Papa, G., Kemp, S. A., Ikeda, T., Toyoda, M., Tan, T. S., Kuramochi, J., Mitsunaga, S., Ueno, T., Shirakawa, K., Takaori-Kondo, A., Brevini, T., Mallery, D. L., Charles, O. J., Baker, S., Dougan, G., Hess, C., Kingston, N., Lehner, P. J., Lyons, P. A., Matheson, N. J., Ouwehand, W. H., Saunders, C., Summers, C., Thaventhiran, J. E. D., Toshner, M., Weekes, M. P., Maxwell, P., Shaw, A., 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., Graf, S., Hodgson, J., Huang, C., Hunter, K., Jones, E., Legchenko, E., Matara, C., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Shih, J., Sutcliffe, R., Tilly, T., Treacy, C., Tong, Z., Wood, J., Wylot, M., Betancourt, A., Bower, G., Cossetti, C., De Sa, A., Epping, M., Fawke, S., Gleadall, N., Grenfell, R., Hinch, A., Jackson, S., Jarvis, I., Krishna, B., Nice, F., Omarjee, O., Perera, M., Potts, M., Richoz, N., Romashova, V., Stefanucci, L., Strezlecki, M., Turner, L., De Bie, E. M. D. D., Bunclark, K., Josipovic, M., Mackay, M., Butcher, H., Caputo, D., Chandler, M., Chinnery, P., Clapham-Riley, D., Dewhurst, E., Fernandez, C., Furlong, A., Graves, B., Gray, J., Hein, S., Ivers, T., Le Gresley, E., Linger, R., Kasanicki, M., King, R., Meloy, S., Moulton, A., Muldoon, F., Ovington, N., Papadia, S., Penkett, C. J., Phelan, I., Ranganath, V., Paraschiv, R., Sage, A., Sambrook, J., Scholtes, I., Schon, K., Stark, H., Stirrups, K. E., Townsend, P., Walker, N., Webster, J., Butlertanaka, E. P., Tanaka, Y. L., Ito, J., Uriu, K., Kosugi, Y., Suganami, M., Oide, A., Yokoyama, M., Chiba, M., Motozono, C., Nasser, H., Shimizu, R., Kitazato, K., Hasebe, H., Irie, T., Nakagawa, S., Wu, J., Takahashi, M., Fukuhara, T., Shimizu, K., Tsushima, K., Kubo, H., Kazuma, Y., Nomura, R., Horisawa, Y., Nagata, K., Kawai, Y., Yanagida, Y., Tashiro, Y., Tokunaga, K., Ozono, S., Kawabata, R., Morizako, N., Sadamasu, K., Asakura, H., Nagashima, M., Yoshimura, K., Cardenas, P., Munoz, E., Barragan, V., Marquez, S., Prado-Vivar, B., Becerra-Wong, M., Caravajal, M., Trueba, G., Rojas-Silva, P., Grunauer, M., Gutierrez, B., Guadalupe, J. J., Fernandez-Cadena, J. C., Andrade-Molina, D., Baldeon, M., Pinos, A., Bowen, J. E., Joshi, A., Walls, A. C., Jackson, L., Martin, D., Smith, K. G. C., Bradley, J., Briggs, J. A. G., Choi, J., Madissoon, E., Meyer, K. B., Mlcochova, P., Ceron-Gutierrez, L., Doffinger, R., Teichmann, S. A., Fisher, A. J., Pizzuto, M. S., de Marco, A., Corti, D., Hosmillo, M., Lee, J. H., James, L. C., Thukral, L., Veesler, D., Sigal, A., Sampaziotis, F., Goodfellow, I. G., Sato, K., and Gupta, R. K.

Subjects
Adult, Male, COVID-19 Vaccines, Virus Replication, Membrane Fusion, Antibodies, Cell Line, Tissue Culture Techniques, Chlorocebus aethiops, 80 and over, Animals, Humans, Viral, Neutralizing, Lung, Aged, Multidisciplinary, Virulence, SARS-CoV-2, Immune Sera, Cell Membrane, Serine Endopeptidases, COVID-19, Convalescence, Middle Aged, Virus Internalization, Spike Glycoprotein, Intestines, Coronavirus, Nasal Mucosa, Mutation, Female, Angiotensin-Converting Enzyme 2, Aged, 80 and over, Antibodies, Neutralizing, Antibodies, Viral, Spike Glycoprotein, Coronavirus
Abstract

The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and has multiple mutations in its spike protein2. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis.

Published
2022
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17. Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

Author

Collier, D. A., Ferreira, I. A. T. M., Kotagiri, P., Datir, R. P., Lim, E. Y., Touizer, E., Meng, B., Abdullahi, 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., Maxwell, P., Shaw, A., 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., Krishna, B., Lewis, D., Marsden, J., Nice, F., Okecha, G., Omarjee, O., Perera, M., Potts, M., Richoz, N., Romashova, V., Yarkoni, N. S., Sharma, R., Stefanucci, L., Stephens, J., Strezlecki, M., Turner, L., D. D. De Bie E. M., Bunclark, K., Josipovic, M., Mackay, M., Michael, A., Rossi, S., Selvan, M., Spencer, S., Yong, C., Ansaripour, 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., Smith, K. G. C., Bradley, J. R., Ceron-Gutierrez, L., Cortes-Acevedo, P., Barcenas-Morales, G., Linterman, M. A., Mccoy, L. E., Davis, C., Thomson, E., Mckinney, E., Doffinger, R., Wills, M., Gupta, R. K., Collier, Dami A [0000-0001-5446-4423], Datir, Rawlings P [0000-0003-0521-2144], Smith, Kenneth GC [0000-0003-3829-4326], Linterman, Michelle A [0000-0001-6047-1996], McCoy, Laura E [0000-0001-9503-7946], Thomson, Emma [0000-0003-1482-0889], Lyons, Paul A [0000-0001-7035-8997], Gupta, Ravindra K [0000-0001-9751-1808], and Apollo - University of Cambridge Repository

Subjects
Male, 0301 basic medicine, Aging, Secondary, T-Lymphocytes, Antibodies, Viral, Neutralization, 0302 clinical medicine, 80 and over, Medicine, Viral, Neutralizing, Adult, Aged, Aged, 80 and over, Antibodies, Neutralizing, Autoantibodies, B-Lymphocytes, BNT162 Vaccine, COVID-19 Vaccines, Female, Health Personnel, Humans, Immunization, Secondary, Immunoglobulin A, Immunoglobulin Class Switching, Immunoglobulin G, Immunologic Memory, Inflammation, Interferon-gamma, Interleukin-2, Middle Aged, SARS-CoV-2, Somatic Hypermutation, Immunoglobulin, Spike Glycoprotein, Coronavirus, Vaccination, Vaccines, Synthetic, Immunity, Sars-Cov-2, Vaccines, education.field_of_study, Multidisciplinary, biology, Spike Glycoprotein, 030220 oncology & carcinogenesis, Antibody, Population, Article, Antibodies, 03 medical and health sciences, Immune system, Immunoglobulin, education, business.industry, Synthetic, Somatic Hypermutation, Vaccine efficacy, Coronavirus, 030104 developmental biology, Immunization, Immunology, biology.protein, business
Abstract

Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating., Nature, 596 (7872), ISSN:0028-0836, ISSN:1476-4687

Published
2021
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20. 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

21. Open Book Professional Accountancy Examinations

Author

Rowlands, J. E. and Forsyth, D.

Abstract

This article describes the structure and rationale for an open-book approach in professional accountancy examinations. The concept of knowledge management and the recognition that some knowledge ought to be embedded in the minds of professional accountants while other knowledge ought to be readily accessible and capable of application forms the basis of this approach to open book assessment. The literature is examined and provides a context for the approach adopted. An initial analysis of an open-book examination provided a positive indication as to the feasibility of the proposals. Testing in a post-graduate accounting class was carried out with the results providing tentative support for this approach to open book assessment. (Contains 2 tables and 1 note.)

Published
2006

25. Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease

Author

Bergamaschi, L., Mescia, F., Turner, L., Hanson, A. L., Kotagiri, P., Dunmore, B. J., Ruffieux, H., de Sa, A., Huhn, O., Morgan, M. D., Gerber, P. P., Wills, M. R., Baker, S., Calero-Nieto, F. J., Doffinger, R., Dougan, G., Elmer, A., Goodfellow, I. G., Gupta, R. K., Hosmillo, M., Hunter, K., Kingston, N., Lehner, P. J., Matheson, N. J., Nicholson, J. K., Petrunkina, A. M., Richardson, S., Saunders, C., Thaventhiran, J. E. D., Toonen, E. J. M., Weekes, M. P., Gottgens, B., Toshner, M., Hess, C., Bradley, J. R., Lyons, P. A., Smith, K. G. C., Allison, J., Ansaripour, A., Betancourt, A., Bong, S. -H., Bower, G., Bucke, A., Bullman, B., Bunclark, K., Butcher, H., Calder, J., Canna, L., Caputo, D., Clapham-Riley, D., Cossetti, C., Coudert, J. D., de Bie, E. M. D. D., Dewhurst, E., di Stefano, G., Domingo, J., Epping, M., Fahey, C., Fawke, S., Fuller, S., Furlong, A., Gleadall, N., Graf, S., Graves, B., Gray, J., Grenfell, R., Harris, J., Hewitt, S., Hinch, A., Hodgson, J., Holmes, E., Huang, C., Ivers, T., Jackson, S., Jarvis, I., Jones, E., Kennet, J., Jose, S., Josipovic, M., Kasanicki, M., Kourampa, J., Laurenti, E., Legchenko, E., Le Gresley, E., Lewis, D., Linger, R., Mackay, M., Marioni, J. C., Marsden, J., Martin, J., Matara, C., Meadows, A., Meloy, S., Mende, N., Michael, A., Michel, R., Mwaura, L., Muldoon, F., Nice, F., O'Brien, C., O'Donnell, C., Okecha, G., Omarjee, O., Ovington, N., Owehand, W. H., Papadia, S., Patterson, C., Perera, M., Phelan, I., Pointon, L., Polgarova, P., Polwarth, G., Pond, N., Price, J., Publico, C., Rastall, R., Ribeiro, C., Richoz, N., Romashova, V., Rossi, S., Rowlands, J., Ruffolo, V., Yarkoni, N. S., Sharma, R., Shih, J., Selvan, M., Spencer, S., Stefanucci, L., Stark, H., Stephens, J., Stirrups, K. E., Strezlecki, M., Summers, C., Sutcliffe, R., Tilly, T., Tong, Z., Tordesillas, H., Treacy, C., Townsend, P., Walker, N., Webster, J., Wilson, N. K., Wood, J., Wylot, M., Yong, C., Mescia, Federica [0000-0002-2759-4027], Hanson, Aimee [0000-0002-0231-8771], Ruffieux, Helene [0000-0002-7113-2540], Morgan, Michael [0000-0003-0757-0711], Wills, Mark [0000-0001-8548-5729], Baker, Stephen [0000-0003-1308-5755], Dougan, Gordon [0000-0003-0022-965X], Gupta, Ravindra [0000-0001-9751-1808], Hosmillo, Myra [0000-0002-3514-7681], Kingston, Nathalie [0000-0002-9190-2231], Lehner, Paul [0000-0001-9383-1054], Matheson, Nicholas [0000-0002-3318-1851], Richardson, Sylvia [0000-0003-1998-492X], Thaventhiran, James [0000-0001-8616-074X], Weekes, Michael [0000-0003-3196-5545], Gottgens, Berthold [0000-0001-6302-5705], Toshner, Mark [0000-0002-3969-6143], Bradley, John [0000-0002-7774-8805], Lyons, Paul [0000-0001-7035-8997], Smith, Kenneth [0000-0003-3829-4326], Apollo - University of Cambridge Repository, and Collaboration, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, Immunology, Disease, macromolecular substances, immune pathology, Biology, CD8-Positive T-Lymphocytes, Systemic inflammation, Lymphocyte Activation, Severity of Illness Index, Article, Oxidative Phosphorylation, 03 medical and health sciences, recovery, 0302 clinical medicine, Immunophenotyping, Immune system, Immunopathology, Bystander effect, medicine, Immunology and Allergy, Humans, complement, Longitudinal Studies, systemic inflammation, bystander CD8+ T cell, SARS-CoV-2, Gene Expression Profiling, Interleukin, COVID-19, interferon, Prognosis, TNF-α, Biomarkers, Cytokines, Disease Susceptibility, Host-Pathogen Interactions, Inflammation Mediators, Phenotype, Reactive Oxygen Species, Transcriptome, 030104 developmental biology, Infectious Diseases, 030220 oncology & carcinogenesis, Tumor necrosis factor alpha, medicine.symptom
Abstract

The kinetics of the immune changes in COVID-19 across severity groups have not been rigorously assessed. Using immunophenotyping, RNA sequencing, and serum cytokine analysis, we analyzed serial samples from 207 SARS-CoV2-infected individuals with a range of disease severities over 12 weeks from symptom onset. An early robust bystander CD8+ T cell immune response, without systemic inflammation, characterized asymptomatic or mild disease. Hospitalized individuals had delayed bystander responses and systemic inflammation that was already evident near symptom onset, indicating that immunopathology may be inevitable in some individuals. Viral load did not correlate with this early pathological response but did correlate with subsequent disease severity. Immune recovery is complex, with profound persistent cellular abnormalities in severe disease correlating with altered inflammatory responses, with signatures associated with increased oxidative phosphorylation replacing those driven by cytokines tumor necrosis factor (TNF) and interleukin (IL)-6. These late immunometabolic and immune defects may have clinical implications., Graphical abstract, The immune changes that underlie COVID-19 severity have not been fully defined. By analyzing a longitudinal cohort of COVID-19 patients and integrating inflammatory factors, immunophenotyping, and transcriptome data, Bergamaschi et al. identify both early and persistent immune changes that distinguish mild and/or asymptomatic from more severe disease.

Published
2021

26. Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME

Author

Godoy, Patricio, Hewitt, Nicola J., Albrecht, Ute, Andersen, Melvin E., Ansari, Nariman, Bhattacharya, Sudin, Bode, Johannes Georg, Bolleyn, Jennifer, Borner, Christoph, Böttger, Jan, Braeuning, Albert, Budinsky, Robert A., Burkhardt, Britta, Cameron, Neil R., Camussi, Giovanni, Cho, Chong-Su, Choi, Yun-Jaie, Craig Rowlands, J., Dahmen, Uta, Damm, Georg, Dirsch, Olaf, Donato, María Teresa, Dong, Jian, Dooley, Steven, Drasdo, Dirk, Eakins, Rowena, Ferreira, Karine Sá, Fonsato, Valentina, Fraczek, Joanna, Gebhardt, Rolf, Gibson, Andrew, Glanemann, Matthias, Goldring, Chris E. P., Gómez-Lechón, María José, Groothuis, Geny M. M., Gustavsson, Lena, Guyot, Christelle, Hallifax, David, Hammad, Seddik, Hayward, Adam, Häussinger, Dieter, Hellerbrand, Claus, Hewitt, Philip, Hoehme, Stefan, Holzhütter, Hermann-Georg, Houston, J. Brian, Hrach, Jens, Ito, Kiyomi, Jaeschke, Hartmut, Keitel, Verena, Kelm, Jens M., Kevin Park, B., Kordes, Claus, Kullak-Ublick, Gerd A., LeCluyse, Edward L., Lu, Peng, Luebke-Wheeler, Jennifer, Lutz, Anna, Maltman, Daniel J., Matz-Soja, Madlen, McMullen, Patrick, Merfort, Irmgard, Messner, Simon, Meyer, Christoph, Mwinyi, Jessica, Naisbitt, Dean J., Nussler, Andreas K., Olinga, Peter, Pampaloni, Francesco, Pi, Jingbo, Pluta, Linda, Przyborski, Stefan A., Ramachandran, Anup, Rogiers, Vera, Rowe, Cliff, Schelcher, Celine, Schmich, Kathrin, Schwarz, Michael, Singh, Bijay, Stelzer, Ernst H. K., Stieger, Bruno, Stöber, Regina, Sugiyama, Yuichi, Tetta, Ciro, Thasler, Wolfgang E., Vanhaecke, Tamara, Vinken, Mathieu, Weiss, Thomas S., Widera, Agata, Woods, Courtney G., Xu, Jinghai James, Yarborough, Kathy M., and Hengstler, Jan G.

Published
2013
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27. List of Contributors

Author

Agarwal, Sanjiv, primary, Ahmad, F., additional, Almada, Anthony L., additional, Aruoma, Okezie I., additional, Bahorun, Theeshan, additional, Baig, Mirza E., additional, Bhupathiraju, Kiran, additional, Burdock, George A., additional, Carabin, Ioana G., additional, Chahar, Digambar, additional, Chong, Leighton K., additional, Coppens, Patrick, additional, Das, Amitava, additional, Dhunnoo, Mayuri, additional, Downs, Bernard W., additional, Fu, Peter P., additional, Ghosh, Dilip, additional, Golakoti, Trimurtulu, additional, Gulati, Om P., additional, Harrison, John R., additional, Hoadley, James E., additional, Hordvik, Stein, additional, Houlahan, Greta, additional, Hu, Chun, additional, Ikeda, Hideko, additional, Jackson, Michelle C., additional, Keservani, Raj K., additional, Kim, Ji Yeon, additional, Kim, Seong Ju, additional, Kochetkova, Alla A., additional, Krishnaraju, Alluri V, additional, Nath, Deb Kumar, additional, Lau, Teck-Chai, additional, Lee, Hyong Joo, additional, Lewis, Claudia A., additional, McGee, Nikita, additional, Morar, Sandra, additional, Moriyama, Hiroyoshi, additional, Neergheen-Bhujun, Vidushi S., additional, Nestmann, Earle R., additional, Ohama, Hirobumi, additional, Ottaway, Peter Berry, additional, Pettman, Simon, additional, Radosevich, Jennifer, additional, Rawson, Nancy E., additional, Rowlands, J. Craig, additional, Sen, Chandan K., additional, Sengupta, Krishanu, additional, Shao, Andrew, additional, Sharma, Anil K., additional, Sheveleva, Svetlana A., additional, Shimizu, Makoto, additional, Smirnova, Elena A., additional, Sukhanov, Boris P., additional, Tutelyan, Victor A., additional, Udell, Lawrence J., additional, Wyszumiala, Edward, additional, Xia, Qingsu, additional, Yeevani, Chandra S., additional, and Zawistowski, Jerzy, additional

Published
2014
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30. 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

31. Intersectionality and Invisible Victims: Reflections on Data Challenges and Vicarious Trauma in Femicide, Family and Intimate Partner Homicide Research

Author

Cullen, P, Dawson, M, Price, J, Rowlands, J, Cullen, P, Dawson, M, Price, J, and Rowlands, J

Abstract

Rigorous, comprehensive and timely research are the cornerstone of social and transformative change. For researchers responding to femicide, family and intimate partner homicide, there are substantial challenges around accessing robust data that is complete and fully representative of the experiences and social identities of those affected. This raises questions of how certain social identities are privileged and how the lens of intersectionality may be constrained or enabled through research. Further, there is limited insight into the emotional labour and safety for researchers, and how they experience and mitigate vicarious trauma. We examine these issues through a shared critical reflection and conclude with key recommendations to address the challenges and issues identified. Four researchers examining and responding to femicide, family and intimate partner homicide in Australia, Canada and the United Kingdom shared and evaluated their critical reflection. We drew on our experiences and offer insights into processes, impacts and unintended consequences of fatality reviews and research initiatives. There are substantial limitations in accessibility and completeness of data, which has unintended consequences for the construction of social identities of those affected, including how multiple forms of exclusion and structural oppression are represented. Our experiences as researchers are complex and have driven us to implement strategies to mitigate vicarious trauma. We assert that these issues can be addressed by reconceptualizing the goals of data collection and fostering collaborative discussions among those involved in data collection and violence prevention to strengthen research, prevention efforts and safety for all involved.

Published
2021

41. Effective control of SARS-CoV-2 transmission between healthcare workers during a period of diminished community prevalence of COVID-19

Author

Jones, N. K., Rivett, L., Sparkes, D., Forrest, S., Sridhar, S., Young, J., Pereira-Dias, J., Cormie, C., Gill, H., Reynolds, N., Wantoch, M., Routledge, M., Warne, B., Levy, J., Jimenez, W. D. C., Samad, F. N. B., Mcnicholas, C., Ferris, M., Gray, J., Gill, M., Curran, M. D., Fuller, S., Chaudhry, A., Shaw, A., Bradley, J. R., Hannon, G. J., Goodfellow, I. G., Dougan, G., Smith, K. G. C., Lehner, P. J., Wright, G., Matheson, N. J., Baker, S., Weekes, M. P., Bradley, J., Goodfellow, I., Gupta, R., Lyons, P. A., Torok, M. E., Toshner, M., Kean, I., Caddy, S., Caller, L., Feltwell, T., Hall, G., Hamilton, W., Hosmillo, M., Houldcroft, C., Jahun, A., Khokhar, F., Meredith, L., Yakovleva, A., Butcher, H., Caputo, D., Clapham-Riley, D., Dolling, H., Furlong, A., Graves, B., Gresley, E. L., Kingston, N., Papadia, S., Stark, H., Stirrups, K. E., Webster, J., Calder, J., Harris, J., Hewitt, S., Kennet, J., Meadows, A., Rastall, R., Brien, C. O., Price, J., Publico, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Hannon, G., Brookes, K., Canna, L., Cruz, I., Dempsey, K., Elmer, A., Escoffery, N., Jones, H., Ribeiro, C., Saunders, C., Wright, A., Nyagumbo, R., Roberts, A., Bucke, A., Hargreaves, S., Johnson, D., Narcorda, A., Read, D., Sparke, C., Worboys, L., Lagadu, K., Mactavous, L., Gould, T., Raine, T., Mather, C., Ramenatte, N., Vallier, A. -L., Kasanicki, M., Eames, P. -J., Thake, L., Bartholomew, N., Brown, N., Curran, M., Parmar, S., Zhang, H., Bowring, A., Martell, G., Quinnell, N., Wright, J., Murphy, H., Dunmore, B. J., Legchenko, E., Graf, S., Huang, C., Hodgson, J., Hunter, K., Martin, J., Mescia, F., Odonnell, C., Pointon, L., Shih, J., Sutcliffe, R., Tilly, T., Tong, Z., Treacy, C., Wood, J., Bergamaschi, L., Betancourt, A., Bowyer, G., De Sa, A., Epping, M., Hinch, A., Huhn, O., Jarvis, I., Lewis, D., Marsden, J., Mccallum, S., Nice, F., Omarjee, O., Perera, M., Romashova, N., Strezlecki, M., Yarkoni, N. S., Turner, L., Bailey, B., Doughton, R., Workman, C., Trotter, C., David, W., Jimenez, C., Jones, Nick K [0000-0003-4475-7761], Sridhar, Sushmita [0000-0001-7453-7482], Hannon, Gregory J [0000-0003-4021-3898], Goodfellow, Ian G [0000-0002-9483-510X], Lehner, Paul J [0000-0001-9383-1054], Matheson, Nicholas J [0000-0002-3318-1851], Weekes, Michael P [0000-0003-3196-5545], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Male, Infectious Disease Transmission, global health, Occupational safety and health, Hospitals, University, Patient-to-Professional, 0302 clinical medicine, COVID-19 Testing, Patient Admission, Nasopharynx, Pandemic, Epidemiology, Prevalence, Medicine, Infection control, Mass Screening, 030212 general & internal medicine, Viral, Biology (General), Family Characteristics, General Neuroscience, Infectious, human biology, virus diseases, General Medicine, Middle Aged, Hospitals, 3. Good health, virology, Community-Acquired Infections, Occupational Diseases, England, epidemiology, Female, medicine.symptom, Symptom Assessment, Coronavirus Infections, Hospital Units, Adult, medicine.medical_specialty, Infectious Disease Transmission, Patient-to-Professional, QH301-705.5, Health Personnel, infectious disease, Science, Pneumonia, Viral, Real-Time Polymerase Chain Reaction, Asymptomatic, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Betacoronavirus, Disease Transmission, Disease Transmission, Infectious, Humans, human, Human Biology and Medicine, Hospitals, Teaching, Pandemics, Mass screening, Asymptomatic Diseases, emerging pathogens, University, Infection Control, General Immunology and Microbiology, business.industry, Clinical Laboratory Techniques, SARS-CoV-2, Teaching, COVID-19, Pneumonia, medicine, occupational health, Contact Tracing, Program Evaluation, 030104 developmental biology, Epidemiology and Global Health, Emergency medicine, business, Research Advance, Contact tracing
Abstract

Previously, we showed that 3% (31/1032)of asymptomatic healthcare workers (HCWs) from a large teaching hospital in Cambridge, UK, tested positive for SARS-CoV-2 in April 2020. About 15% (26/169) HCWs with symptoms of coronavirus disease 2019 (COVID-19) also tested positive for SARS-CoV-2 (Rivett et al., 2020). Here, we show that the proportion of both asymptomatic and symptomatic HCWs testing positive for SARS-CoV-2 rapidly declined to near-zero between 25th April and 24th May 2020, corresponding to a decline in patient admissions with COVID-19 during the ongoing UK ‘lockdown’. These data demonstrate how infection prevention and control measures including staff testing may help prevent hospitals from becoming independent ‘hubs’ of SARS-CoV-2 transmission, and illustrate how, with appropriate precautions, organizations in other sectors may be able to resume on-site work safely.

Published
2020

42. Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission

Author

Rivett, L., Sridhar, S., Sparkes, D., Routledge, M., Jones, N. K., Forrest, S., Young, J., Pereira-Dias, J., Hamilton, W. L., Ferris, M., Torok, M. E., Meredith, L., Curran, M. D., Fuller, S., Chaudhry, A., Shaw, A., Samworth, R. J., Bradley, J. R., Dougan, G., Smith, K. G. C., Lehner, P. J., Matheson, N. J., Wright, G., Goodfellow, I. G., Baker, S., Weekes, M. P., Lyons, P. A., Toshner, M., Warne, B., Scott, J. B., Cormie, C., Gill, H., Kean, I., Maes, M., Reynolds, N., Wantoch, M., Caddy, S., Caller, L., Feltwell, T., Hall, G., Hosmillo, M., Houldcroft, C., Jahun, A., Khokhar, F., Yakovleva, A., Butcher, H., Caputo, D., Clapham-Riley, D., Dolling, H., Furlong, A., Graves, B., Gresley, E. L., Kingston, N., Papadia, S., Stark, H., Stirrups, K. E., Webster, J., Calder, J., Harris, J., Hewitt, S., Kennet, J., Meadows, A., Rastall, R., Brien, C. O., Price, J., Publico, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Brookes, K., Canna, L., Cruz, I., Dempsey, K., Elmer, A., Escoffery, N., Jones, H., Ribeiro, C., Saunders, C., Wright, A., Nyagumbo, R., Roberts, A., Bucke, A., Hargreaves, S., Johnson, D., Narcorda, A., Read, D., Sparke, C., Warboys, L., Lagadu, K., Mactavous, L., Gould, T., Raine, T., Mather, C., Ramenatte, N., Vallier, A. -L., Kasanicki, M., Eames, P. -J., Mcnicholas, C., Thake, L., Bartholomew, N., Brown, N., Parmar, S., Zhang, H., Bowring, A., Martell, G., Quinnell, N., Wright, J., Murphy, H., Dunmore, B. J., Legchenko, E., Graf, S., Huang, C., Hodgson, J., Hunter, K., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Shih, J., Sutcliffe, R., Tilly, T., Tong, Z., Treacy, C., Wood, J., Bergamaschi, L., Betancourt, A., Bowyer, G., A. D., Sa, Epping, M., Hinch, A., Huhn, O., Jarvis, I., Lewis, D., Marsden, J., Mccallum, S., Nice, F., Rivett, Lucy [0000-0002-2781-9345], Lehner, Paul J [0000-0001-9383-1054], Matheson, Nicholas J [0000-0002-3318-1851], Goodfellow, Ian G [0000-0002-9483-510X], Weekes, Michael P [0000-0003-3196-5545], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Male, medicine, global health, 0302 clinical medicine, COVID-19 Testing, Epidemiology, Pandemic, Health care, Infection control, 030212 general & internal medicine, Viral, Biology (General), Asymptomatic Infections, Nose, 0303 health sciences, Transmission (medicine), COVID-19, SARS-CoV-2, emerging pathogens, epidemiology, human, human biology, infectious disease, occupational health, virology, virus, Betacoronavirus, COVID-19 Vaccines, Coronavirus Infections, Female, Humans, Infection Control, Pandemics, Pneumonia, Viral, Real-Time Polymerase Chain Reaction, United Kingdom, Clinical Laboratory Techniques, Health Personnel, General Neuroscience, virus diseases, General Medicine, 3. Good health, medicine.anatomical_structure, medicine.symptom, Research Article, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), QH301-705.5, Science, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), education, Asymptomatic, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Internal medicine, Throat, Infectious disease (athletes), Human Biology and Medicine, 030304 developmental biology, General Immunology and Microbiology, business.industry, Pneumonia, 030104 developmental biology, Epidemiology and Global Health, Carriage, business
Abstract

Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19)>7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff., eLife digest Patients admitted to NHS hospitals are now routinely screened for SARS-CoV-2 (the virus that causes COVID-19), and isolated from other patients if necessary. Yet healthcare workers, including frontline patient-facing staff such as doctors, nurses and physiotherapists, are only tested and excluded from work if they develop symptoms of the illness. However, there is emerging evidence that many people infected with SARS-CoV-2 never develop significant symptoms: these people will therefore be missed by ‘symptomatic-only’ testing. There is also important data showing that around half of all transmissions of SARS-CoV-2 happen before the infected individual even develops symptoms. This means that much broader testing programs are required to spot people when they are most infectious. Rivett, Sridhar, Sparkes, Routledge et al. set out to determine what proportion of healthcare workers was infected with SARS-CoV-2 while also feeling generally healthy at the time of testing. Over 1,000 staff members at a large UK hospital who felt they were well enough to work, and did not fit the government criteria for COVID-19 infection, were tested. Amongst these, 3% were positive for SARS-CoV-2. On closer questioning, around one in five reported no symptoms, two in five very mild symptoms that they had dismissed as inconsequential, and a further two in five reported COVID-19 symptoms that had stopped more than a week previously. In parallel, healthcare workers with symptoms of COVID-19 (and their household contacts) who were self-isolating were also tested, in order to allow those without the virus to quickly return to work and bolster a stretched workforce. Finally, the rates of infection were examined to probe how the virus could have spread through the hospital and among staff – and in particular, to understand whether rates of infection were greater among staff working in areas devoted to COVID-19 patients. Despite wearing appropriate personal protective equipment, healthcare workers in these areas were almost three times more likely to test positive than those working in areas without COVID-19 patients. However, it is not clear whether this genuinely reflects greater rates of patients passing the infection to staff. Staff may give the virus to each other, or even acquire it at home. Overall, this work implies that hospitals need to be vigilant and introduce broad screening programmes across their workforces. It will be vital to establish such approaches before ‘lockdown’ is fully lifted, so healthcare institutions are prepared for any second peak of infections.

Published
2020

43. The Effect of Aspect Ratio on Wall Pressure Fluctuations at a Wing-Plate Junction

Author

Awasthi, M, Rowlands, J, Moreau, DJ, Doolan, CJ, Awasthi, M, Rowlands, J, Moreau, DJ, and Doolan, CJ

Abstract

Measurements of the wall pressure fluctuations near a wing-plate junction were made for wings with three different aspect ratios (AR) of 0.2, 0.5, and 1.0 at several angles of attack. The chord-based Reynolds number for each wing was 274,000. The results show that the wall pressure fluctuations are a function of wing AR for cases where AR≤ 1.0. For each wing, the pressure fluctuations are highest upstream of the wing leading-edge due to three-dimensional flow separation; wings with AR = 1.0 and 0.5 show comparable levels, while those with AR = 0.2 show lower fluctuation levels over a wide frequency range. Downstream of the leading-edge, the pressure fluctuations decay rapidly on both sides of the wing until the maximum thickness location after which little variation is observed. The pressure fluctuations downstream of the leading-edge on the suction-side were observed to be comparable for AR = 0.2 and 0.5, while those for AR = 1.0 were higher in magnitude. On the pressure-side, the pressure fluctuations near the leading-edge are a weak function of AR; however, those further downstream remain independent of AR. The pressure fluctuations aft of the wing on the suction-side are more coherent for lower ARs and show higher convection velocity, possibly due to an interaction between the tip and the junction flows for lower ARs.

Published
2020

44. Incorporating New Technologies Into Toxicity Testing and Risk Assessment: Moving From 21st Century Vision to a Data-Driven Framework

Author

Thomas, Russell S., Philbert, Martin A., Auerbach, Scott S., Wetmore, Barbara A., Devito, Michael J., Cote, Ila, Rowlands, J. Craig, Whelan, Maurice P., Hays, Sean M., Andersen, Melvin E., Meek, M. E. (Bette), Reiter, Lawrence W., Lambert, Jason C., Clewell, Harvey J., III, Stephens, Martin L., Zhao, Q. Jay, Wesselkamper, Scott C., Flowers, Lynn, Carney, Edward W., Pastoor, Timothy P., Petersen, Dan D., Yauk, Carole L., and Nong, Andy

Published
2013
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47. The health consequences of early soy consumption

Author

Badger, Thomas M., Ronis, Martin J.J., Hakkak, Reza, Rowlands, J. Craig, and Korourian, Soheila

Subjects
Soyfoods -- Health aspects, Infant formulas -- Health aspects, Medicine, Preventive -- Planning, Food/cooking/nutrition
Abstract

Infants fed soy formula are the segment of the U. S. population that consumes the most soy. Before birth and after weaning, most Americans are not exposed to appreciable levels of soyfoods other than foods that have small amounts of processed soy components. The opposite scenario occurs in Asia, because Asians are more likely to consume relatively high levels of soyfoods throughout life, except between birth and weaning, when breastfeeding or milk-based formula are common. Soy formula is made with soy protein isolate containing isoflavones (SPI+) and supports normal growth and development in term infants. Recent data suggest that there are no long-term adverse effects of early exposure to soy formula through young adulthood. It is as yet unknown whether soy formula consumption by infants will result in health problems or benefits upon aging, but multigenerational animal studies with diets made with SPI+ have not revealed any problems. Soy isoflavones can function as estrogen agonists, antagonists or selective estrogen receptor modulators, depending on the conditions, and much research has focused on health effects of purified isoflavones. Results from several studies suggest that the effects of diets made with SPI+ differ significantly from those of diets to which purified soy isoflavones are added. Furthermore, it seems that soy protein processed to contain lower levels of isoflavones also provides significant health benefits. Further research is needed to confirm the results of the few studies that have been conducted and new studies are needed to investigate the more subtle effects that could occur during development or that could surface later in life. KEY WORDS: * soy * genistein * development * infant formula * disease prevention

Published
2002

50. Soy and whey proteins downregulate DMBA-induced liver and mammary gland CYP1 expression in female rats. (Nutrition and Cancer)

Author

Rowlands, J. Craig, He, Ling, Hakkak, Reza, Ronis, Martin J.J., and Badger, Thomas M.

Subjects
Protein metabolism -- Physiological aspects, Whey products -- Health aspects, Soyfoods -- Health aspects, Diet in disease -- Research, Cytochrome P-450 -- Health aspects, Cancer -- Health aspects, Food/cooking/nutrition
Abstract

One possible mechanism by which diet may reduce cancer risk is through enhancement of metabolic systems that prevent activation of carcinogens or accelerate carcinogen inactivation. We studied the effects of diet and 7,12-dimethylbenz-(a)anthracene (DMBA) on hepatic and mammary gland CYP1A1, CYP1A2 and CYP1B1 enzymes in female Sprague-Dawley rats. Diets (AIN-93G) were fed from conception to adulthood, and DMBA was given by oral gavage at age 48-50 d. The protein sources of diets were casein (CAS), soy protein isolate (SPI) or whey protein hydrolysate (WPH). The DMBA-induced hepatic ethoxyresorufin-O-deethylase and methoxyresorufin-O-demethylase activities and CYP1A1 protein and mRNA expression were lower (P < 0.05) in SPI-fed rats compared with those fed casein. Differences in mammary gland CYP1 expression were also observed with decreased DMBA induction (P < 0.05) of all three CYP1 proteins and mRNAs in rats fed either SPI or WPH compared with those fed CAS. Most notable were the decreased constitutive and DMBA-induced mammary gland expression of CYP1B1 protein of 93 and 96%, respectively, in the SPI-fed rats relative to the CAS-fed controls. The diet-induced changes in CYP1 enzyme expression were consistent with changes in the AhR and ARNT transcription factors that regulate them. Decreased (P < 0.05) mammary constitutive AhR and ARNT proteins were measured in SPI-fed rats. There was also a 100% increase in constitutive AhR protein in the WPH-fed rats that paralleled a 100% increase in constitutive CYP1B1 protein in the mammary gland. These results demonstrate the importance of diet in regulation of phase I metabolism in liver and mammary gland, and suggest a potential mechanism by which soy or whey proteins reduce DMBA-induced mammary tumor incidence. KEY WORDS: * cytochrome P450 * rats * soy protein * whey protein * casein.

Published
2001

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