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401. Epidemiological Investigation of the First 135 COVID-19 Cases in Brunei: Implications for Surveillance, Control, and Travel Restrictions

Author

Wan Wen Patricia Poh, Justin Wong, Mohammad Fathi Alikhan, Wee Chian Koh, Sirajul Adli Jamaludin, Lin Naing, and Liling Chaw

Subjects
Male, Brunei, Severity of Illness Index, Infectious Disease Incubation Period, Patient Isolation, 0302 clinical medicine, Risk Factors, Interquartile range, Epidemiology, Credible interval, Medicine, Child, education.field_of_study, Incidence, Incidence (epidemiology), Articles, Middle Aged, Infectious Diseases, Psychological Distance, Child, Preschool, Epidemiological Monitoring, Quarantine, Female, medicine.symptom, Coronavirus Infections, Serial interval, Adult, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Adolescent, Pneumonia, Viral, 030231 tropical medicine, Population, Asymptomatic, Incubation period, Betacoronavirus, 03 medical and health sciences, Virology, Humans, education, Pandemics, Aged, SARS-CoV-2, business.industry, Public health, COVID-19, Infant, Outbreak, Communicable Disease Control, Parasitology, business, Basic reproduction number, Demography
Abstract

BackgroundStudies on the early introduction of SARS-CoV-2 in a naïve population have important epidemic control implications. We report findings from the epidemiological investigation of the initial 135 COVID-19 cases in Brunei and describe the impact of control measures and travel restrictions.MethodsEpidemiological and clinical information were obtained for all confirmed COVID-19 cases in Brunei, whose symptom onset was from March 9 to April 5, 2020 (covering the initial 5 weeks of the epidemic). Transmission-related measures such as reproduction number (R), incubation period, serial interval were estimated. Time-varying R was calculated to assess the effectiveness of control measures.ResultsA total of 135 cases were detected, of which 53 (39.3%) were imported. The median age was 36 years (range = 0.5 to 72). 41 (30.4%) and 13 (9.6%) were presymptomatic and asymptomatic cases respectively. The median incubation period was 5 days (IQR = 5, range = 1 to 11), and the mean serial interval was 5.39 days (sd = 4.47; 95% CI: 4.25, 6.53). R0 was between 3.88 and 5.96, and the doubling time was 1.3 days. By the 13th day of the epidemic, the Rt was under one (Rt = 0.91; 95% credible interval: 0.62, 1.32) and the epidemic was under control.ConclusionEpidemic control was achieved through a combination of public health measures, with emphasis on a test-isolate-trace approach supplemented by travel restrictions and moderate physical distancing measures but no actual lockdown. To maintain suppression, regular and ongoing testing of high-risk groups can supplement the existing surveillance program.

Published
2020

402. Case report: Hereditary angioedema in pregnancy

Author

Iona Thorne, Adam D Jakes, Anita Banerjee, Sorena Kiani-Alikhan, and John Guly

Subjects
Pediatrics, medicine.medical_specialty, Spontaneous vaginal delivery, Pregnancy, 030219 obstetrics & reproductive medicine, C1 inhibitor deficiency, business.industry, Vaginal birth, Breastfeeding, Obstetrics and Gynecology, Bradykinin, medicine.disease, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, 030228 respiratory system, chemistry, Intervention (counseling), Cases, Hereditary angioedema, medicine, business
Abstract

Hereditary angioedema (HAE) is a rare genetic condition associated with episodic swelling due to dysfunction of bradykinin regulation pathways. This is most frequently caused by low level and/or function of the C1-esterase inhibitor protein (C1INH) which is known as hereditary angioedema with C1 inhibitor deficiency (C1INH-HAE). Pregnancy and labour can precipitate an attack, but the majority of women have an uncomplicated, spontaneous vaginal delivery. Intravenous C1INH is the first-line therapy in pregnancy and breastfeeding. It should be given if any obstetric intervention is planned. Routine prophylactic administration for uncomplicated vaginal birth is not mandatory but may be appropriate if symptoms recur frequently during the third trimester. Pregnant women with C1INH-HAE should deliver in a hospital with C1INH replacement, fiberoptic intubation and front-of-neck access equipment readily available. A documented treatment plan should be developed within a multi-disciplinary team to pre-empt complications. We describe a case of C1INH-HAE diagnosed in pregnancy.

Published
2020

403. Emergence of human-adapted Salmonella enterica is linked to the Neolithization process

Author

Gunnar U. Neumann, Noah Steuri, Luis Roger Esquivel-Gomez, Alexander Herbig, Cosimo Posth, Kirsten I. Bos, Maria A. Spyrou, Marianne Ramstein, Monica Zavattaro, Jessica Beckett, Aleksandr Khokhlov, Philipp W. Stockhammer, Matthias Meyer, Maria Giuseppina Gradoli, Susanna Sabin, Stefania Vai, Ron Hübler, Wolfgang Haak, Alessandro Riga, Johannes Krause, Denise Kühnert, Antje Wissgott, Aditya Kumar Lankapalli, Felix M. Key, Anatoly R. Kantorovich, Yılmaz Selim Erdal, Albert Hafner, David Caramelli, Robin Skeates, Anja Furtwängler, Åshild J. Vågene, Sandra Lösch, Mark Achtman, Rezeda I. Tukhbatova, Marta Burri, Sabine Reinhold, Andrey B. Belinsky, Zhemin Zhou, Sarah Nagel, Vladimir E. Maslov, Svend Hansen, Nabil-Fareed Alikhan, Inga Siebke, Alexey Kalmykov, and Andrey A. Chizhevsky

Subjects
parallel evolution, 930 History of ancient world (to ca. 499), 940 History of Europe, phoN, Human pathogen, Bacterial genome size, hunter-gatherers, Genome, Article, epidemiologic transition, Prehistory, 03 medical and health sciences, pastoralists, Animals, forager, Humans, ancient DNA, farmer, Ecology, Evolution, Behavior and Systematics, Host specific, 030304 developmental biology, animal husbandry, 0303 health sciences, Genetic diversity, Ecology, biology, 030306 microbiology, pathogen emergence, Salmonella enterica, ancient Eurasian super branch, Agriculture, zoonosis, biology.organism_classification, domesticated animals, 950 History of Asia, Evolutionary biology, 570 Life sciences, Host adaptation, Neolithic revolution, ancient infectious disease convergent evolution, Genome, Bacterial
Abstract

It has been hypothesized that the Neolithic transition towards an agricultural and pastoralist economy facilitated the emergence of human adapted pathogens. Here, we recovered eight Salmonella enterica subsp. enterica genomes from human skeletons of transitional foragers, pastoralists, and agro-pastoralists in western Eurasia that were up to 6,500 years old. Despite the high genetic diversity of S. enterica all ancient bacterial genomes clustered in a single previously uncharacterized branch that contains S. enterica adapted to multiple mammalian species. All ancient bacterial genomes from prehistoric (agro-)pastoralists fall within a part of this branch that also includes the human-specific S. enterica Paratyphi C, illustrating the evolution of a human pathogen over a period of five thousand years. Bacterial genomic comparisons suggest that the earlier ancient strains were not host specific, differed in pathogenic potential, and experienced convergent pseudogenization that accompanied their downstream host adaptation. These observations support the concept that the emergence of human adapted S. enterica is linked to human cultural transformations.

Published
2020

405. Addendum to British Society for Haematology Guidelines on Investigation and Management of Antiphospholipid syndrome, 2012 ( Br. J. Haematol . 2012; 157: 47–58): use of direct acting oral anticoagulants

Author

Will Lester, Michael Laffan, Deepa R. J. Arachchillage, Keith Gomez, Thrombosis Taskforce, Raza Alikhan, and Julia A. M. Anderson

Subjects
medicine.medical_specialty, Venous thrombosis, Lupus anticoagulant, Hematology, business.industry, Antiphospholipid syndrome, Internal medicine, medicine, medicine.disease, business, Dermatology, Direct acting
Published
2020

406. About some of the factors for public administration effectiveness

Author

Alikhan М. Baimenov

Subjects
Business, Public administration, General Agricultural and Biological Sciences
Abstract

The article emphasizes that modern governments, working in unique socio-economic, historical and cultural conditions, must take into account global trends, as well as the growth of citizens’ expectations associated with the rapid development of information technologies and other factors. In such circumstances, special attention is paid to the effectiveness of public administration. The article discusses some of the significant factors impacting the effectiveness of public administration, such as the professionalization of the state apparatus, the legibility of the institutional framework, the optimization of information flows and corporate culture. In accordance with this, on the basis of work experience in the public administration system and analysis of civil service reforms in the countries of the region, the main challenges and possible solutions are shown. In the professionalization of the state apparatus, the importance of the merit principles in the selection and promotion stages of personnel through the empowerment of human resource (HR) management services, the integrity of tools and approaches at all stages of selection process, and the responsibility of the selection board are noted. The author focuses on the need to ensure a balance of powers, responsibility and resources, delimitation of powers between political and administrative civil servants, optimization of information flows. Particular importance is paid to corporate culture, which is one of the main factors affecting the efficiency of the state apparatus. It is noted that central values of corporate culture and leadership in state bodies of the countries of our region, along with generally accepted in the modern leadership theory, should be respect for the dignity, work and time of employees.

Published
2020

408. Genetic characterization of Kushum horses in Kazakhstan based on haplotypes of mtDNA and Y chromosome, and genes associated with important traits of the horses

Author

Polat Kazymbet, Yu Okuda, Masahide Nishibori, R. C. Paul, Phuong T K Pham, Kushaliye J Kaissar, Meirat Bakhtin, Trung Ba Nguyen, Takayuki Ibi, Suleimenov Zh Maratbek, Takehito Tsuji, Tetsuo Kunieda, Akhmedenov Kazhmurat, Alikhan Meldebekov, Sarsenova Bibigul, and Thu Nu Anh Le

Subjects
Genetics, Coat, Genetic diversity, Full Paper, Y chromosome, mtDNA, Equine, Haplotype, Biology, Selective breeding, Kazakhstan, Haplogroup, Breed, Genotype, Allele frequency, coat color, locomotion traits
Abstract

The Kushum is a relatively new breed of horses in Kazakhstan that was established in the middle of the 20th century through a cross between mares of Kazakhstan local horses and stallions of Thoroughbred, Trotter, and Russian Don breeds to supply military horses. To reveal the genetic characteristics of this breed, we investigated haplotypes of mitochondrial DNA (mtDNA) and single-nucleotide polymorphisms of the Y chromosome, as well as genotypes of five functional genes associated with coat color, body composition, and locomotion traits. We detected 10 mtDNA haplotypes that fell into 8 of the 17 major haplogroups of horse mtDNA, indicating a unique haplotype composition with high genetic diversity. We also found two Y-chromosomal haplotypes in Kushum horses, which likely originated from Trotter and/or Don breeds. The findings regarding the mtDNA and Y-chromosomal haplotypes are concordant with the documented maternal and paternal origins of the Kushum horses. The allele frequencies of ASIP, MC1R, and MATP associated with coat color were consistent with the coat color variations of Kushum horses. The allele frequencies of MSTN associated with endurance performance and those of DMRT3 associated with gait suggested that the observed allele frequencies of these genes were the result of selective breeding for these traits. As a result of this study, we were able to obtain useful information for a better understanding of the origin and breeding history of the Kushum horse breed using molecular markers.

Published
2020

409. Future-proofing and maximizing the utility of metadata: The PHA4GE SARS-CoV-2 contextual data specification package

Author

Emma J Griffiths, Ruth E Timme, Catarina Inês Mendes, Andrew J Page, Nabil-Fareed Alikhan, Dan Fornika, Finlay Maguire, Josefina Campos, Daniel Park, Idowu B Olawoye, Paul E Oluniyi, Dominique Anderson, Alan Christoffels, Anders Gonçalves da Silva, Rhiannon Cameron, Damion Dooley, Lee S Katz, Allison Black, Ilene Karsch-Mizrachi, Tanya Barrett, Anjanette Johnston, Thomas R Connor, Samuel M Nicholls, Adam A Witney, Gregory H Tyson, Simon H Tausch, Amogelang R Raphenya, Brian Alcock, David M Aanensen, Emma Hodcroft, William W L Hsiao, Ana Tereza R Vasconcelos, and Duncan R MacCannell

Subjects
Metadata, SARS-CoV-2, COVID-19, Humans, Reproducibility of Results, Health Informatics, Genomics, Public Health, Computer Science Applications
Abstract

Background The Public Health Alliance for Genomic Epidemiology (PHA4GE) (https://pha4ge.org) is a global coalition that is actively working to establish consensus standards, document and share best practices, improve the availability of critical bioinformatics tools and resources, and advocate for greater openness, interoperability, accessibility, and reproducibility in public health microbial bioinformatics. In the face of the current pandemic, PHA4GE has identified a need for a fit-for-purpose, open-source SARS-CoV-2 contextual data standard. Results As such, we have developed a SARS-CoV-2 contextual data specification package based on harmonizable, publicly available community standards. The specification can be implemented via a collection template, as well as an array of protocols and tools to support both the harmonization and submission of sequence data and contextual information to public biorepositories. Conclusions Well-structured, rich contextual data add value, promote reuse, and enable aggregation and integration of disparate datasets. Adoption of the proposed standard and practices will better enable interoperability between datasets and systems, improve the consistency and utility of generated data, and ultimately facilitate novel insights and discoveries in SARS-CoV-2 and COVID-19. The package is now supported by the NCBI’s BioSample database.

Published
2022

410. Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

Author

Aggarwal, Dinesh, Warne, Ben, Jahun, Aminu S., Hamilton, William L., Fieldman, Thomas, du Plessis, Louis, Hill, Verity, Blane, Beth, Watkins, Emmeline, Wright, Elizabeth, Hall, Grant, Ludden, Catherine, Myers, Richard, Hosmillo, Myra, Chaudhry, Yasmin, Pinckert, Malte L., Georgana, Iliana, Izuagbe, Rhys, Leek, Danielle, Nsonwu, Olisaeloka, Hughes, Gareth J., Packer, Simon, Page, Andrew J., Metaxaki, Marina, Fuller, Stewart, Weale, Gillian, Holgate, Jon, Brown, Christopher A., Orton, Alexandra, Douthwaite, Julie, Rees, Steve, Brown, Christopher, Clark, Roger, Jones, Daniel R., Kuenzi, Fred, Rankin, Jennifer, Waddell, Ian, Maxwell, Patrick, Matheson, Nicholas, Abell, Chris, Braithwaite, Vickie, Brierley, Craig, Crowcroft, Jon, Dahal, Aastha, Faulkner, Kathryn, Glover, Michael, Goodfellow, Ian, Greatorex, Jane, James, Laura, Lehner, Paul, Leslie, Ian, Liddell, Kathleen, Margolis, Ben, Morgan, Sally, Sheridan, Linda, Valletta, Sally, Vignoles, Anna, Vinnell, Martin, Wills, Mark, Hilborne, Sarah, Berry, Sarah, Kahkeshi, Mahin Bagheri, Hancock, Dawn, Winster, Jennifer, Enright, Jessica, Samworth, Richard, Samtani, Vijay, Ahmadi-Assalemi, Gabriela, Feather, Tom, Goodall, Robin, Hoensch, Steve, Johnson, Dean, Hunt, Martin, Mathieson, Nick, Nikitina, Katya, Sheldrake, Zara, Keen, Martin, Sato, Aris, Connor, David, Tolhurst, Jonathan, Williman, Jack, Hollamby, Victoria, Jordan, Sinead, Fatseas, Tania, Taylor, Peter, Georgiou, Christine, Caspersz, Michelle, McNulty, Claire, Davies, Richard, Clarke, Rebecca, Danaei, Darius, Dyer, Rory, Glew, Rob, Lambson, Oliver, Gibbs, Karen, Mozdzen, Barbara, Raub, Gabor, Radecki, Asako, White, Phil, Hughes, Robert, Gransden, Lucie, Ceaser, Matt, Sing, Robert, Wilson, Karl, Parlikad, Ajith, Dhada, Maharshi, Ridgman, Tom, Mungovan, Diane, Matthews, Steve, Searle, Paul, Mills, John, Neely, Andy, Henderson, Robert, Murphy, Edna, Russell, Matthew, Freeling, Anthony, Poppitt, Steve, Tynan, Jo, Knapton, James, Marchetti, Filippo, Angelis, Daniela De, Feltwell, Theresa, Hadjirin, Nazreen F., Jahun, Aminu, Pinckert, Malte, Shaw, Ashley, Chaudhry, Afzal, Brown, Nicholas M., Mactavous, Lenette, Hannan, Sophie, Hosaja, Aleksandra, Leong, Clare, Wright, Jo, Quinnell, Natalie, Workman, Chris, Ferris, Mark, Wright, Giles, Brooks, Ellena, Carabelli, Alessandro M., Churcher, Carol M., Galai, Katerina, Girgis, Sophia T., Gupta, Ravi K., McManus, Georgina M., Palmer, Sophie, Peacock, Sharon J., Smith, Kim S., Allara, Elias, Bibby, David, Bishop, Chloe, Bosworth, Andrew, Bradshaw, Daniel, Chalker, Vicki, Chand, Meera, Dabrera, Gavin, Ellaby, Nicholas, Gallagher, Eileen, Groves, Natalie, Harrison, Ian, Hartman, Hassan, Hopes, Richard, Hubb, Jonathan, Hutchings, Stephanie, Lackenby, Angie, Ledesma, Juan, Lee, David, Manesis, Nikos, Manso, Carmen, Mbisa, Tamyo, Miah, Shahjahan, Muir, Peter, Osman, Husam, Patel, Vineet, Pearson, Clare, Platt, Steven, Pymont, Hannah M., Ramsay, Mary, Robinson, Esther, Schaefer, Ulf, Thornton, Alicia, Twohig, Katherine A., Vipond, Ian B., Williams, David, Aigrain, Louise, Alderton, Alex, Amato, Roberto, Ariani, Cristina V., Barrett, Jeff, Bassett, Andrew R., Beale, Mathew A., Beaver, Charlotte, Bellis, Katherine L., Betteridge, Emma, Bonfield, James, Bronner, Iraad F., Chapman, Michael H. S., Danesh, John, Davies, Robert, Dorman, Matthew J., Drury, Eleanor, Durham, Jillian, Farr, Ben W., Foulser, Luke, Goncalves, Sonia, Goodwin, Scott, Gourtovaia, Marina, Jackson, David K., James, Keith, Jamrozy, Dorota, Johnston, Ian, Kane, Leanne, Kay, Sally, Keatley, Jon-Paul, Kwiatkowski, Dominic, Langford, Cordelia F., Lawniczak, Mara, Lensing, Stefanie V., Leonard, Steven, Letchford, Laura, Lewis, Kevin, Liddle, Jennifier, Livett, Rich, Lo, Stephanie, Makunin, Alex, Martincorena, Inigo, McCarthy, Shane, McGuigan, Samantha, Moll, Robin J., Nelson, Rachel, Oliver, Karen, Palmer, Steve, Park, Naomi R., Patel, Minal, Prestwood, Liam, Puethe, Christoph, Quail, Michael A., Rajan, Diana, Rajatileka, Shavanthi, Redshaw, Nicholas M., Scott, Carol, Shirley, Lesley, Sillitoe, John, Thurston, Scott A. J., Tonkin-Hill, Gerry, Tovar-Corona, Jaime M., Weldon, Danni, Whitwham, Andrew, Attwood, Stephen W., Zamudio, Marina Escalera, Francois, Sarah, Gutierrez, Bernardo, Kraemer, Moritz U. G., Raghwani, Jayna, Vasylyeva, Tetyana I., Zarebski, Alex E., Alikhan, Nabil-Fareed, Aydin, Alp, Baker, David J., de Oliveira Martins, Leonardo, Kay, Gemma L., Le-Viet, Thanh, Mather, Alison E., Meadows, Lizzie, O’Grady, Justin, Rudder, Steven, Trotter, Alexander J., Illingworth, Chris J., Jackson, Chris, Aranday-Cortes, Elihu, Asamaphan, Patawee, Broos, Alice, Carmichael, Stephen N., da Silva Filipe, Ana, Hughes, Joseph, Jesudason, Natasha G., Johnson, Natasha, Li, Kathy K., Mair, Daniel, Nichols, Jenna, Nickbakhsh, Seema, Niebel, Marc O., Nomikou, Kyriaki, Orton, Richard J., Robertson, David L., Shah, Rajiv N., Shepherd, James G., Singer, Joshua B., Starinskij, Igor, Thomson, Emma C., Tong, Lily, Vattipally, Sreenu, Ash, Amy, Koshy, Cherian, Cortes, Nick, Kidd, Stephen, Lynch, Jessica, Moore, Nathan, Mori, Matilde, Wise, Emma, Curran, Tanya, Fairley, Derek J., McKenna, James P., Adams, Helen, Bonsall, David, Fraser, Christophe, Golubchik, Tanya, Cogger, Benjamin J., Hassan-Ibrahim, Mohammed O., Malone, Cassandra S., Reynolds, Nicola, Wantoch, Michelle, Afifi, Safiah, Beer, Robert, John, Michaela, Maksimovic, Joshua, McCluggage, Kathryn, Morgan, Sian, Spellman, Karla, Bresner, Catherine, Connor, Thomas R., Fuller, William, Guest, Martyn, Gulliver, Huw, Kitchen, Christine, Marchbank, Angela, Merrick, Ian, Munn, Robert, Price, Anna, Southgate, Joel, Workman, Trudy, Patel, Amita, Snell, Luke B., Batra, Rahul, Charalampous, Themoula, Edgeworth, Jonathan, Nebbia, Gaia, Beckett, Angela H., Robson, Samuel C., Aanensen, David M., Abudahab, Khalil, Menegazzo, Mirko, Taylor, Ben E. W., Underwood, Anthony P., Yeats, Corin A., Berry, Louise, Boswell, Tim, Clark, Gemma, Fleming, Vicki M., Howson-Wells, Hannah C., Jones, Carl, Joseph, Amelia, Khakh, Manjinder, Lister, Michelle M., Smith, Wendy, Willingham, Iona, Bird, Paul, Fallon, Karlie, Helmer, Thomas, Holmes, Christopher, Tang, Julian, Blakey, Victoria, Campbell, Sharon, Raviprakash, Veena, Sheriff, Nicola, Williams, Lesley-Anne, Carlile, Matthew, Debebe, Johnny, Holmes, Nadine, Loose, Matthew W., Moore, Christopher, Sang, Fei, Wright, Victoria, Coll, Francesc, Betancor, Gilberto, Signell, Adrian W., Wilson, Harry D., Davis, Thomas, Eldirdiri, Sahar, Kenyon, Anita, Torok, M. Estee, Lowe, Hannah, Moses, Samuel, Bedford, Luke, Moore, Jonathan, Stonehouse, Susanne, Awan, Ali R., Fisher, Chloe L., BoYes, John, Atkinson, Laura, Breuer, Judith, Brown, Julianne R., Harris, Kathryn A., Lee, Jack C. D., Shah, Divya, Storey, Nathaniel, Flaviani, Flavia, Alcolea-Medina, Adela, Vernet, Gabrielle, Williams, Rebecca, Chapman, Michael R., Chatterton, Wendy, Heaney, Judith, Levett, Lisa J., Pusok, Monika, Xu-McCrae, Li, Bashton, Matthew, Smith, Darren, Young, Greg, Bolt, Frances, Cox, Alison, Holmes, Alison, Madona, Pinglawathee, Mookerjee, Siddharth, Price, James, Randell, Paul A., Boyd, Olivia, Nascimento, Fabricia F., Geidelberg, Lily, Johnson, Rob, Jorgensen, David, Ragonnet-Cronin, Manon, Rowan, Aileen, Siveroni, Igor, Taylor, Graham P., Volz, Erik M., Smollett, Katherine L., Loman, Nicholas J., McMurray, Claire, McNally, Alan, Nicholls, Sam, Poplawski, Radoslaw, Quick, Joshua, Rowe, Will, Stockton, Joanne, Nunez, Rocio T. Martinez, Breen, Cassie, Cowell, Angela, Mason, Jenifer, O’Toole, Elaine, Robinson, Trevor I., Watts, Joanne, Sluga, Graciela, Ahmad, Shazaad S. Y., George, Ryan P., Machin, Nicholas W., Halstead, Fenella, Hogsden, Wendy, Sivaprakasam, Venkat, Carden, Holli, Hale, Antony D., Harper, Katherine L., Macfarlane-Smith, Louissa R., Burton-Fanning, Shirelle, Collins, Jennifer, Eltringham, Gary, Payne, Brendan AI., Taha, Yusri, Waugh, Sheila, O’Brien, Sarah, Rushton, Steven, Blacow, Rachel, Bradley, Amanda, Maclean, Alasdair, Mollett, Guy, Dewar, Rebecca, McHugh, Martin P., Templeton, Kate E., Wastenge, Elizabeth, Coupland, Lindsay, Dervisevic, Samir, Meader, Emma J., Stanley, Rachael, Smith, Louise, Barton, Edward, Graham, Clive, Padgett, Debra, Scott, Garren, Greenaway, Jane, Swindells, Emma, McCann, Clare, Nelson, Andrew, Yew, Wen Chyin, Andersson, Monique, Crook, Derrick, Eyre, David, Justice, Anita, Peto, Timothy, Duckworth, Nichola, Sloan, Tim J., Walsh, Sarah, Bicknell, Kelly, Chauhan, Anoop J., Elliott, Scott, Glaysher, Sharon, Impey, Robert, Lloyd, Allyson, Wyllie, Sarah, Levene, Nick, Monaghan, Lynn, Bradley, Declan T., Wyatt, Tim, Curran, Martin D., Parmar, Surendra, Holden, Matthew T. G., Shaaban, Sharif, Adams, Alexander, Asad, Hibo, Birchley, Alec, Bull, Matthew, Coombes, Jason, Corden, Sally, Cottrell, Simon, Craine, Noel, Cronin, Michelle, Davies, Alisha, Lacy, Elen De, Downing, Fatima, Edwards, Sue, Evans, Johnathan M., Fina, Laia, Gaskin, Amy, Gatica-Wilcox, Bree, Gifford, Laura, Gilbert, Lauren, Graham, Lee, Heyburn, David, Hilvers, Ember, Howe, Robin, Jones, Hannah, Jones, Rachel, Jones, Sophie, Kumziene-SummerhaYes, Sara, McKerr, Caoimhe, Moore, Catherine, Morgan, Mari, Pacchiarini, Nicole, Perry, Malorie, Plimmer, Amy, Rey, Sara, Shankar, Giri, Taylor, Sarah, Watkins, Joanne, Williams, Chris, Casey, Anna, Ratcliffe, Liz, Acheson, Erwan, Molnar, Zoltan, Simpson, David A., Thompson, Thomas, Auckland, Cressida, Ellard, Sian, Jones, Christopher R., Knight, Bridget A., Masoli, Jane A. H., Haque, Tanzina, Hart, Jennifer, Irish-Tavares, Dianne, Mahungu, Tabitha W., Witele, Eric, Dadrah, Ashok, Fenton, Melisa L., Saluja, Tranprit, Symmonds, Amanda, Bourgeois, Yann, Scarlett, Garry P., Cook, Kate, Dent, Hannah, Fearn, Christopher, Goudarzi, Salman, Loveson, Katie F., Paul, Hannah, Evans, Cariad, Johnson, Kate, Partridge, David G., Raza, Mohammad, Baker, Paul, Bonner, Stephen, Essex, Sarah, Liggett, Steven, Lyons, Ronan A., Mahanama, Adhyana I. K., Saeed, Kordo, Samaraweera, Buddhini, Silveira, Siona, Wilson-Davies, Eleri, Emanuela, P., Bayzid, Nadua, Cotic, Marius, Ensell, Leah, Hartley, John A., Jannoo, Riaz, Karamani, Angeliki, Kristiansen, Mark, Lowe, Helen L., Roy, Sunando, Westhorpe, Adam P., Williams, Rachel J., Williams, Charlotte A., Jeremiah, Sarah, Prieto, Jacqui A., Berry, Lisa, Grammatopoulos, Dimitris, Jones, Katie, Pandey, Sarojini, Beggs, Andrew, Richter, Alex, Ashcroft, Fiona, Best, Angus, Crawford, Liam, Cumley, Nicola, Mayhew, Megan, Megram, Oliver, Mirza, Jeremy, Moles-Garcia, Emma, Percival, Benita, Bucca, Giselda, Hesketh, Andrew R., Smith, Colin P., Davidson, Rose K., Balcazar, Carlos E., Gallagher, Michael D., O’Toole, Áine, Rambaut, Andrew, Rooke, Stefan, Stanton, Thomas D., Williams, Thomas, Williamson, Kathleen A., Bewshea, Claire M., Farbos, Audrey, Harrison, James W., Jeffries, Aaron R., Manley, Robin, Michell, Stephen L., Michelsen, Michelle L., Sambles, Christine M., Studholme, David J., Temperton, Ben, Warwick-Dugdale, Joanna, Darby, Alistair C., Eccles, Richard, Gemmell, Matthew, Gregory, Richard, Haldenby, Sam T., Hiscox, Julian A., Hughes, Margaret, Iturriza-Gomara, Miren, Jackson, Kathryn A., Lucaci, Anita O., Nelson, Charlotte, Paterson, Steve, Rainbow, Lucille, Turtle, Lance, Vamos, Edith E., Webster, Hermione J., Whitehead, Mark, Wierzbicki, Claudia, Angyal, Adrienn, Brown, Rebecca, de Silva, Thushan I., Freeman, Timothy M., Gallis, Marta, Green, Luke R., Groves, Danielle C., Keeley, Alexander J., Lindsey, Benjamin B., Louka, Stavroula F., Parker, Matthew D., Parsons, Paul J., Smith, Nikki, Tucker, Rachel M., Wang, Dennis, Whiteley, Max, Wyles, Matthew, Zhang, Peijun, Alam, Mohammad T., Baxter, Laura, Bridgewater, Hannah E., Brown, Paul E., Cheng, Jeffrey K. J., Constantinidou, Chrystala, Frost, Lucy R., Ott, Sascha, Stark, Richard, Taylor-Joyce, Grace, Unnikrishnan, Meera, Cerda, Alberto C., Merrill, Tammy V., Wilson, Rebekah E., Ball, Jonathan, Chappell, Joseph G., McClure, Patrick C., Tsoleridis, Theocharis, Buck, David, de Cesare, Mariateresa, Green, Angie, MacIntyre-Cockett, George, Todd, John A., Trebes, Amy, Gunson, Rory N., Cormie, Claire, Dias, Joana, Forrest, Sally, Gill, Harmeet K., Higginson, Ellen E., Kermack, Leanne M., Maes, Mailis, Ruis, Chris, Sridhar, Sushmita, Young, Jamie, Howes, Rob, McFarlane, Duncan, Dougan, Gordon, Pybus, Oliver G., Maxwell, Patrick H., Weekes, Michael P., Illingworth, Chris, Harrison, Ewan M., Matheson, Nicholas J., Goodfellow, Ian G., The Cambridge Covid-19 testing Centre, University of Cambridge Asymptomatic COVID-19 Screening Programm, The COVID-19 Genomics UK (COG-UK) Consortium, Aggarwal, Dinesh [0000-0002-5938-8172], Warne, Ben [0000-0003-1326-0373], Hill, Verity [0000-0002-3509-8146], Pinckert, Malte [0000-0002-6072-5949], Leek, Danielle [0000-0001-5367-3354], Pybus, Oliver [0000-0001-6619-6112], Weekes, Michael [0000-0002-0030-2784], Apollo - University of Cambridge Repository, Jahun, Aminu S [0000-0002-4585-1701], Hamilton, William L [0000-0002-3330-353X], du Plessis, Louis [0000-0003-0352-6289], Blane, Beth [0000-0002-0996-9091], Wright, Elizabeth [0000-0002-8378-9072], Hall, Grant [0000-0003-3928-3979], Chaudhry, Yasmin [0000-0002-2386-3269], Pinckert, Malte L [0000-0002-6072-5949], Izuagbe, Rhys [0000-0001-8080-2510], Nsonwu, Olisaeloka [0000-0002-3024-700X], Hughes, Gareth J [0000-0002-3781-0117], Packer, Simon [0000-0002-9157-3650], Page, Andrew J [0000-0001-6919-6062], Metaxaki, Marina [0000-0002-4552-1622], Weale, Gillian [0000-0003-4728-5915], Brown, Christopher A [0000-0001-7773-0878], Peacock, Sharon J [0000-0002-1718-2782], Pybus, Oliver G [0000-0002-8797-2667], Weekes, Michael P [0000-0003-3196-5545], Harrison, Ewan M [0000-0003-2720-0507], Matheson, Nicholas J [0000-0002-3318-1851], Goodfellow, Ian G [0000-0002-9483-510X], Jahun, Aminu [0000-0002-4585-1701], Hosmillo, Myra [0000-0002-3514-7681], McFarlane, Duncan [0000-0002-1558-7823], Dougan, Gordon [0000-0003-0022-965X], Peacock, Sharon [0000-0002-1718-2782], Weekes, Michael [0000-0003-3196-5545], Illingworth, Christopher [0000-0002-0030-2784], Harrison, Ewan [0000-0003-2720-0507], Matheson, Nicholas [0000-0002-3318-1851], and Goodfellow, Ian [0000-0002-9483-510X]

Subjects
Universities, 631/326/325/2483, Science, education, University of Cambridge Asymptomatic COVID-19 Screening Programme Consortium, General Physics and Astronomy, Cambridge Covid-19 testing Centre, 45/23, Genome, Viral, General Biochemistry, Genetics and Molecular Biology, COVID-19 Genomics UK (COG-UK) Consortium, Risk Factors, The COVID-19 Genomics UK (COG-UK) Consortium, Humans, Students, Phylogeny, 631/326/596/4130, Multidisciplinary, SARS-CoV-2, article, COVID-19, virus diseases, C500, General Chemistry, Genomics, C700, 692/700/478/174, United Kingdom, The Cambridge Covid-19 testing Centre, RNA, Viral, 631/326/596/2562, Contact Tracing, 631/326/596/2563
Abstract

Understanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics., Nature Communications, 13, ISSN:2041-1723

Published
2022

411. Additional file 1 of Attenuated androgen discontinuation in patients with hereditary angioedema: a commented case series

Author

Maurer, Marcus, Magerl, Markus, Ayg��ren-P��rs��n, Emel, Bork, Konrad, Farkas, Henriette, Longhurst, Hilary, Kiani���Alikhan, Sorena, Bouillet, Laurence, Boccon-Gibod, Isabelle, Cancian, Mauro, Zanichelli, Andrea, and Launay, David

Subjects
immune system diseases, food and beverages, cardiovascular diseases, urologic and male genital diseases, skin and connective tissue diseases
Abstract

Additional file 1. Word document.doc; Patient cases; Further details of attenuated androgen discontinuation in hereditary angioedema cases series.

Published
2022
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412. Dynamics of Salmonella enterica and antimicrobial resistance in the Brazilian poultry industry and global impacts on public health

Author

Nabil-Fareed Alikhan, Luisa Zanolli Moreno, Luis Ricardo Castellanos, Marie Anne Chattaway, Jim McLauchlin, Martin Lodge, Justin O’Grady, Roxana Zamudio, Emma Doughty, Liljana Petrovska, Marcos Paulo Vieira Cunha, Terezinha Knöbl, Andrea Micke Moreno, and Alison E. Mather

Subjects
Sulfonamides, Cancer Research, Salmonella enterica, beta-Lactams, Poultry, Anti-Bacterial Agents, Salmonella, Tetracyclines, Drug Resistance, Bacterial, Genetics, Animals, GRÃ-BRETANHA, Public Health, Chickens, Molecular Biology, Brazil, Genetics (clinical), Ecology, Evolution, Behavior and Systematics
Abstract

Non-typhoidal Salmonella enterica is a common cause of diarrhoeal disease; in humans, consumption of contaminated poultry meat is believed to be a major source. Brazil is the world’s largest exporter of chicken meat globally, and previous studies have indicated the introduction of Salmonella serovars through imported food products from Brazil. Here we provide an in-depth genomic characterisation and evolutionary analysis to investigate the most prevalent serovars and antimicrobial resistance (AMR) in Brazilian chickens and assess the impact to public health of products contaminated with S. enterica imported into the United Kingdom from Brazil. To do so, we examine 183 Salmonella genomes from chickens in Brazil and 357 genomes from humans, domestic poultry and imported Brazilian poultry products isolated in the United Kingdom. S. enterica serovars Heidelberg and Minnesota were the most prevalent serovars in Brazil and in meat products imported from Brazil into the UK. We extended our analysis to include 1,259 publicly available Salmonella Heidelberg and Salmonella Minnesota genomes for context. The Brazil genomes form clades distinct from global isolates, with temporal analysis suggesting emergence of these Salmonella Heidelberg and Salmonella Minnesota clades in the early 2000s, around the time of the 2003 introduction of the Enteritidis vaccine in Brazilian poultry. Analysis showed genomes within the Salmonella Heidelberg and Salmonella Minnesota clades shared resistance to sulphonamides, tetracyclines and beta-lactams conferred by sul2, tetA and blaCMY-2 genes, not widely observed in other co-circulating serovars despite similar selection pressures. The sul2 and tetA genes were concomitantly carried on IncC plasmids, whereas blaCMY-2 was either co-located with the sul2 and tetA genes on IncC plasmids or independently on IncI1 plasmids. Long-term surveillance data collected in the UK showed no increase in the incidence of Salmonella Heidelberg or Salmonella Minnesota in human cases of clinical disease in the UK following the increase of these two serovars in Brazilian poultry. In addition, almost all of the small number of UK-derived genomes which cluster with the Brazilian poultry-derived sequences could either be attributed to human cases with a recent history of foreign travel or were from imported Brazilian food products. These findings indicate that even should Salmonella from imported Brazilian poultry products reach UK consumers, they are very unlikely to be causing disease. No evidence of the Brazilian strains of Salmonella Heidelberg or Salmonella Minnesota were observed in UK domestic chickens. These findings suggest that introduction of the Salmonella Enteritidis vaccine, in addition to increasing antimicrobial use, could have resulted in replacement of salmonellae in Brazilian poultry flocks with serovars that are more drug resistant, but less associated with disease in humans in the UK. The plasmids conferring resistance to beta-lactams, sulphonamides and tetracyclines likely conferred a competitive advantage to the Salmonella Minnesota and Salmonella Heidelberg serovars in this setting of high antimicrobial use, but the apparent lack of transfer to other serovars present in the same setting suggests barriers to horizontal gene transfer that could be exploited in intervention strategies to reduce AMR. The insights obtained reinforce the importance of One Health genomic surveillance.

Published
2022

413. RETROPERITONEAL LEIOMYOSARCOMA FATAL SPONTANEOUS RUPTURE: LITERATURE REVIEW AND PRESENTATION OF EXTREMELY RARE CASE

Author

Tajibayev, Talgat, Galimzhan Esenaliev, Nurlybek Omarov, Abdreshit, Alikhan, and Dilyar Maripzhanov

Subjects
spontaneous rupture of leiomyosarcoma, retroperitoneal hematoma, забрюшинная саркома, разрыв, забрюшинная гематома, rupture, забрюшинные лейомиосаркомы, спонтанный разрыв лейомиосаркомы, retroperitoneal leiomyosarcomas, retroperitoneal sarcoma, hemoperitoneum, гемоперитонеум
Abstract

Retroperitoneal sarcoma (RPS) is a heterogeneous group of malignant tumors with an incidence of approximately 1 case per 100,000 population per year, which includes leiomyosarcoma. Leiomyosarcoma is a malignant neoplasm with smooth muscles differentiation. It is the second most common sarcoma affecting the retroperitoneal space. In this article, we describe a case of fatal hematoma of the retroperitoneal space, caused by spontaneous rupture of leiomyosarcoma. A 65-year-old woman presented with severe pain in her left side and hypovolemic shock. After an additional examination of hemodynamic stabilization, she was operated on an emergency basis. The tumor was removed and the bleeding was stopped. The patient was transferred to the intensive care unit (ICU) after surgery, despite the ongoing intensive therapy, the condition remained extremely serious, against which the deterioration result from cardiac arrest and death is occurred. In the world literature, spontaneous rupture of retroperitoneal leiomyosarcoma is described in isolated cases. Moreover, the main publications are aimed at managing patients with tumors of the retroperitoneal space only in a planned manner. Thus, this case could be of clinical interest among emergency medical practitioners as well as in the scientific community. Literature search for a review of the problem was carried out in the following scientific databases and search engines: PubMed, Web of Science, Scopus, Google Scholar, eLIBRARY., Забрюшинная саркома представляет собой гетерогенную группу злокачественных опухолей с частотой возникновения примерно 1 случай на 100 000 населения в год, в которую входит лейомиосаркома. Лейомиосаркома представляет собой злокачественное новообразование с дифференцировкой гладкой мускулатуры. Это вторая по распространенности саркома, поражающая забрюшинное пространство. В данной статье нами описывается случай фатальной гематомы забрюшинного пространства, причиной которой явился спонтанный разрыв образования – лейомиосаркомы. Шестидесяти пятилетняя женщина поступила с сильными болями в левом боку и гиповолемическим шоком. После дообследования стабилизации гемодинамики оперирована в экстренном порядке, выполнено удаление образования и остановка кровотечения. После операции больная переведена в отделение ОАРиИТ, несмотря на проводимую интенсивную терапию, состояние оставалось крайне тяжелым, на фоне которого наступило ухудшение остановка сердечной деятельности и смерть. В мировой литературе спонтанный разрыв лейомиосаркомыза брюшинного пространства описывается в единичных случаях. Более того основные публикации направлены на ведение пациентов с опухолями забрюшинного пространства лишь в плановом порядке. Таким образом, данный случай мог бы представлять клинический интерес среди практикующих врачей экстренной службы, а также в научном обществе. Поиск литературы для обзора проблемы проводился в следующих научных базах данных и поисковых системах: PubMed, WebofScience, Scopus, GoogleScholar, eLIBRARY.

Published
2022
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414. sj-pdf-1-pqx-10.1177_10986111211066353 ��� Supplemental Material for Re-examining the Use of Force Continuum: Why Resistance is Not the Only Driver of Use of Force Decisions

Author

McLean, Kyle, Alikhan, Arif, and Alpert, Geoffrey P.

Subjects
160299 Criminology not elsewhere classified, FOS: Law
Abstract

Supplemental Material, sj-pdf-1-pqx-10.1177_10986111211066353 for Re-examining the Use of Force Continuum: Why Resistance is Not the Only Driver of Use of Force Decisions by Kyle McLean, Arif Alikhan and Geoffrey P. Alpert in Police Quarterly

Published
2022
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417. Investigating the feasibility of recruitment to an observational, quality-of-life study of patients diagnosed with atrial fibrillation (AF) who have experienced a bleed while anticoagulated: EQUAL-AF feasibility study protocol

Author

Hayley A. Hutchings, Kirsty Lanyon, Steven Lister, Raza Alikhan, Julian Halcox, Gail Holland, Arfon Hughes, Rhys Jenkins, Hamish Laing, Trudie Lobban, Diane Owen, Kevin G. Pollock, Ceri Todd, and Kathie Wareham

Subjects
Medicine (miscellaneous)
Abstract

Background Oral anticoagulation therapies (OATs) are often prescribed in conjunction with medications to restore normal heart rate rhythm which can limit the risk of an atrial fibrillation (AF) related stroke and systemic thromboembolism. However, they are associated with the serious side effect of bleeding. Both clinically relevant nonmajor bleeding (CRNMB) and major bleeding while anticoagulated are believed to have a significant impact on patient quality of life (QoL). There is currently limited research into the effect bleeding has on QoL. The aim of this study is to evaluate the feasibility of identifying and recruiting patients diagnosed with AF, who are taking OATs and have recently experienced a bleed and collecting information on their QoL. Methods We will recruit a minimum of 50 patients to this cross-sectional, observational study. We will recruit from general practices, secondary care, and through an online AF forum. We will ask participants to complete three validated patient-reported outcome measures (PROMs), EQ5D, AFEQT, and PACT-Q, approximately 4 weeks following a bleed and again 3 months later. We will randomly select a subset of 10 participants (of those who agree to be interviewed) to undergo a structured interview with a member of the research team to explore the impact of bleeding on their QoL and to gain feedback on the three PROMs used. We will undertake a descriptive analysis of the PROMs and demographic data. We will analyse the qualitative interviews thematically to identify key themes. Discussion We aim to establish if it is possible to recruit patients and use PROMs to collect information regarding how patient QoL is affected when they experience either a clinically relevant non-major bleed (CRNMB) or major bleed while taking OATs for the management of AF. We will also explore the appropriateness, or otherwise, of the three identified PROMs for assessing quality of life following a bleed. PROMs Three PROMs were selected following a literature review of similar QoL studies and using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist for comparison. A review of the current literature produced no suitable validated PROM to record QoL experiences in patients who have been diagnosed with AF and have experienced a bleed while anticoagulated. As such, the EQ5D, AFEQT, and PACT-Q (part 2) were deemed most appropriate for use in this feasibility study. Trial registration The trial has been adopted onto the NIHR Portfolio (ID no. 47771) and registered with www.ClinicalTrials.gov (no. NCT04921176) retrospectively registered in June 2021.

Published
2022

418. Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Author

Harry D Wilson, Elaine O'Toole, Andrew Bassett, Moritz U. G. Kraemer, Beth Blane, Scott Goodwin, Giri Shankar, Joseph Hughes, Lucy R. Frost, Alicia Thornton, Scott Elliott, Tammy V Merrill, Sheila Waugh, Alexander Adams, Peter Muir, Graciela Sluga, Rebecca Williams, Hannah Dent, Christophe Fraser, Shavanthi Rajatileka, John C. Hartley, Luke B Snell, Benjamin J Cogger, Lance Turtle, Alex Makunin, John A. Todd, Victoria Wright, Daniela De Angelis, James McKenna, Dinesh Aggarwal, Jonathan K. Ball, Jillian Durham, Garren Scott, Thushan I de Silva, Veena Raviprakash, Hannah M Pymont, Jason Coombes, Anita Lucaci, Luke R. Green, Leigh M Jackson, Hermione J. Webster, Louis du Plessis, David A. Jackson, Minal Patel, Áine O'Toole, Ravi Gupta, Marc Niebel, Garry Scarlett, Rajiv Shah, Guy Mollett, Kathy Li, Rory Gunson, Matthew Bashton, Carl Jones, Sara Kumziene-Summerhayes, Zoltan Molnar, Siona Silveira, Malte L Pinckert, Catherine Ludden, Angeliki Karamani, Leanne Kane, Brendan A I Payne, Alan McNally, Clare M. McCann, Holli Carden, Mohammad Raza, Alison E. Mather, Kate B. Cook, Amy Gaskin, David J. Williams, Shaun R. Seaman, Christopher I. Jones, Gilberto Betancor, Matthew T. G. Holden, Jennifier Liddle, Meera Unnikrishnan, Angie Green, Ben Taylor, Kelly Bicknell, Alexander J. Trotter, Emma Meader, Leanne M Kermack, Nathaniel Storey, Michelle Cronin, Sally Forrest, Sarah Jeremiah, Asad Zaidi, M Morgan, Alasdair MacLean, Thomas R. Connor, Johnathan M Evans, Rachael Stanley, Ryan P George, Nadine Holmes, Richard H. Myers, Christine Sambles, Bernardo Gutierrez, Jeffrey K. J. Cheng, Tim Wyatt, Natasha Jesudason, Lindsay Coupland, Monika Pusok, Manon Ragonnet-Cronin, Jenifer Mason, Joshua Maksimovic, Russell Hope, Alison Holmes, David Simpson, Radoslaw Poplawski, Amelia Joseph, Erwan Acheson, James Bonfield, Mara K. N. Lawniczak, Sascha Ott, Lesley-Anne Williams, Jessica Lynch, Graham P. Taylor, Anita Kenyon, Elizabeth Wastenge, Megan Mayhew, Adhyana I K Mahanama, Stavroula F Louka, Chloe Bishop, Esther Robinson, Darren Smith, Anne M. Presanis, Matthew Carlile, Thomas D Stanton, Dennis Wang, Katerina Galai, Adam P Westhorpe, Flavia Flaviani, Michelle Wantoch, Max Whiteley, Yann Bourgeois, Matthew Gemmell, Mary Ramsay, A Lloyd, Simon Thelwall, Hannah C. Howson-Wells, Joseph G. Chappell, Steve Paterson, Gary Eltringham, Robert Impey, Siddharth Mookerjee, Steven Platt, Emma Swindells, Laura Letchford, Alex Alderton, Lee Graham, Safiah Afifi, David C. Lee, Cassie Breen, Melisa Louise Fenton, Benita Percival, Adrian W Signell, Tanya Golubchik, Ian B Vipond, Eleri Wilson-Davies, Angie Lackenby, Laura Atkinson, Sarojini Pandey, Nazreen F. Hadjirin, Michael A Chapman, Huw Gulliver, Joana Dias, Grant Hall, Antony D Hale, Hassan Hartman, Alp Aydin, Louise Smith, Ashok Dadrah, Johnny Debebe, Sarah Walsh, Stephanie W. Lo, Andrew Bosworth, Bridget Knight, Hannah E Bridgewater, Nadua Bayzid, Gemma L. Kay, Richard Gregory, Sally Kay, Ellena Brooks, Andre Charlett, Georgina M McManus, Riaz Jannoo, Victoria Blakey, Carol Scott, Rachel Nelson, Liz Ratcliffe, Gerry Tonkin-Hill, Verity Hill, Joanne D. Stockton, Danielle Leek, Steven Leonard, Stephanie Hutchings, Jonathan D. Moore, Kathryn Ann Harris, Sophie Jones, Venkat Sivaprakasam, Amy Plimmer, Tanzina Haque, Katherine L. Bellis, Khalil Abudahab, Dianne Irish-Tavares, Gaia Nebbia, Kathryn A Jackson, Stephen W Attwood, Daniel Mair, Sreenu Vattipally, Susanne Stonehouse, Ian Merrick, Lucille Rainbow, Mathew A. Beale, Angela Helen Beckett, Ember Hilvers, Thomas Helmer, Jenna Nichols, Giselda Bucca, Salman Goudarzi, Christopher Ruis, Surendra Parmar, Angela Cowell, Alberto C Cerda, Divya K. Shah, Judith Heaney, E. Thomson, Kyriaki Nomikou, Nicole Pacchiarini, Katherine L Harper, Fatima Downing, M. Estée Török, Michelle L Michelsen, Aaron R. Jeffries, Jennifer Collins, Christopher Williams, Katie F. Loveson, Steven Rudder, Theocharis Tsoleridis, Robert Davies, David Robertson, Katherine Smollett, Kathryn McCluggage, Liam Crawford, Inigo Martincorena, Charlotte Beaver, Oliver Megram, Karla Spellman, Sam Haldenby, Emma Betteridge, William D. Fuller, Will P. M. Rowe, Cherian Koshy, Tim E. A. Peto, Alison Cox, Natasha Johnson, Tanya Curran, Sharif Shaaban, Tamyo Mbisa, Cordelia Langford, Eric Witele, Andrew J. Page, Christoph Puethe, Nicola Reynolds, Paul W Bird, Louise Aigrain, Ronan Lyons, Amy Trebes, Sally Corden, Steven Rushton, Jack Cd Lee, Jane Greenaway, Hibo Asad, Amanda Bradley, Mohammed O Hassan-Ibrahim, Shane McCarthy, Fei Sang, Matthew Loose, Hannah Jones, Keith D. James, Chloe L Fisher, Chrystala Constantinidou, Alex G. Richter, Jane A. H. Masoli, Michael Gallagher, Vicki M. Fleming, Anna Price, Amy Ash, Michaela John, Alex Zarebski, Fenella D. Halstead, John Danesh, Christine Kitchen, Aminu S Jahun, Mark Whitehead, Julianne R Brown, Catherine Bresner, Marius Cotic, Stefanie V Lensing, Nick Levene, Louissa R Macfarlane-Smith, Wendy Hogsden, Cressida Auckland, Eleanor Drury, Richard Eccles, Jennifer Hart, Seema Nickbakhsh, Alisha Davies, David M. Aanensen, Shirelle Burton-Fanning, Ben Farr, Buddhini Samaraweera, Sarah Wyllie, Hannah Lowe, Richard J. Orton, Martin D. Curran, Carol Churcher, Karen Oliver, Elihu Aranday-Cortes, Wen Yew, Thanh Le-Viet, Matthew Parker, Katherine A Twohig, Shahjahan Miah, Samuel M. Nicholls, G MacIntyre-Cockett, Tranprit Saluja, Charlotte Nelson, Vicki Chalker, Roberto Amato, Ellen Higginson, Timothy M. Freeman, Christopher W Holmes, Yasmin Chaudhry, Elias Allara, Alec Birchley, Iraad Bronner, Emma Moles-Garcia, Angus I. Best, Anna L. Casey, Audrey Farbos, Nicholas W Machin, David W Eyre, Tim Boswell, Charlotte A Williams, Elen De Lacy, Matthew J. Bull, Matilde Mori, Carmen F. Manso, Peijun Zhang, Sahar Eldirdiri, Dimitris Grammatopoulos, Corin Yeats, Claudia Wierzbicki, David G Partridge, Kordo Saeed, Nichola Duckworth, David J. Studholme, Harmeet K Gill, Juan Ledesma, Thomas R. A. Davis, Sushmita Sridhar, Clive Graham, Husam Osman, Julian A. Hiscox, Helen Adams, Christopher Fearn, Fabrícia F. Nascimento, Ulf Schaefer, James W. Harrison, Andrew J. Nelson, Joshua Quick, Mohammad Tauqeer Alam, Liam Prestwood, Nikos Manesis, Julian Tang, Justin O'Grady, Sophia T Girgis, Louise Berry, Gemma Clark, Marina Escalera Zamudio, Karlie Fallon, Tim J Sloan, Joanne Watkins, Clare Pearson, Andrew D Beggs, Rachel Williams, Luke Bedford, Trevor Robinson, Nicholas M Redshaw, Richard Hopes, Mirko Menegazzo, Katherine Twohig, Gabrielle Vernet, Steven Liggett, Mariateresa de Cesare, Derrick W. Crook, Dominic P. Kwiatkowski, Mark Kristiansen, Miren Iturriza-Gomara, Christopher I. Moore, Claire Cormie, Olivia Boyd, Nikki Smith, Noel Craine, Kathleen A. Williamson, John Boyes, Sian Ellard, Cristina V. Ariani, Wendy Chatterton, David Bonsall, Kevin Lewis, David Jorgensen, Ian Harrison, Christopher Jackson, Martin P McHugh, Danni Weldon, Michael A. Quail, Amita Patel, Lily Geidelberg, Myra Hosmillo, Judith Breuer, Cariad Evans, Edward Barton, Trudy Workman, Derek Fairley, Vineet Patel, Daniel Bradshaw, Robin Manley, Scott Aj Thurston, John Sillitoe, Monique Andersson, Sharon J. Peacock, Jamie Lopez-Bernal, Thomas Thompson, Nabil-Fareed Alikhan, Ben Temperton, Paul Baker, Robin J Moll, Laura Gifford, Nicholas J. Loman, Jayna Raghwani, Jacqui Prieto, Andrew Hesketh, Oliver G. Pybus, Adela Alcolea-Medina, David Buck, Gregory R Young, Alistair C. Darby, Sónia Gonçalves, Aileen G. Rowan, Tabitha Mahungu, Nicholas Ellaby, Jon-Paul Keatley, Lily Tong, Robert Beer, Martyn Guest, Lisa J Levett, Ali R Awan, Iliana Georgana, Paul E Brown, Li Xu-McCrae, Stephen P. Kidd, Sara Rey, Shazaad Ahmad, Danielle C. Groves, Tetyana I. Vasylyeva, David F. Bibby, Nathan Moore, Fiona Ashcroft, Igor Starinskij, Hannah Paul, Claire McMurray, Michael Spencer Chapman, Carlos Balcazar, Joanna Warwick-Dugdale, Pinglawathee Madona, Edith Vamos, Lesley Shirley, Kate Templeton, Luke Foulser, Igor Siveroni, Ewan M. Harrison, Sian Morgan, Diana Rajan, S Taylor, Laia Fina, Naomi Park, Sarah J. O'Brien, Alessandro M Carabelli, Angela Marchbank, Sunando Roy, Leonardo de Oliveira Martins, Steve Palmer, Jonathan Hubb, Alexander J Keeley, Francesc Coll, Malorie Perry, Paul J. Parsons, Anthony Underwood, Patawee Asamaphan, William L Hamilton, Tommy Nyberg, Sophie Palmer, Amanda Symmonds, Anoop Chauhan, Robert Johnson, Christopher J. R. Illingworth, James Shepherd, Wendy Smith, Rich Livett, Rachel Blacow, Margaret Hughes, Jeremy Mirza, Joanne Watts, Jonathan D. Edgeworth, Sarah François, Sue Edwards, Adrienn Angyal, Thomas N. Williams, Marta Gallis, Lauren Gilbert, Paul Randell, Kate Johnson, Eileen Gallagher, Nick Cortes, Yusri Taha, Leah Ensell, Emanuela Pelosi, Stefan Rooke, Michelle Lister, Ana da Silva Filipe, Cassandra S Malone, Themoula Charalampous, Benjamin B Lindsey, Natalie Groves, Colin Smith, Ross J Harris, Rebekah E Wilson, Stephen Bonner, Richard Stark, Sharon Campbell, Nicola Sheriff, Helen L Lowe, Rachel Jones, Ben Warne, Rose K Davidson, Declan Bradley, Ian Johnston, Jeffrey C. Barrett, Joshua B Singer, Shirin Aliabadi, Andrew Whitwham, Patrick McClure, Samuel Robson, Sharon Glaysher, Robert J. Munn, Emma L. Wise, Laura Baxter, Kim S Smith, Catherine Moore, Bree Gatica-Wilcox, Alice Broos, Sarah Essex, David Baker, Manjinder Khakh, Dorota Jamrozy, Rachel Tucker, Ian Goodfellow, S.E. Moses, Nicola Cumley, Robin Howe, Meera Chand, James I. Price, Marina Gourtovaia, Debra Padgett, Jaime Tovar-Corona, Stephen L. Michell, Matthew J. Dorman, Lizzie Meadows, David Heyburn, Iona Willingham, Rocio Martinez Nunez, Grace Taylor-Joyce, Claire M Bewshea, Anita Justice, Simon Cottrell, Rebecca C H Brown, Jamie Young, Gavin Dabrera, Matthew Wyles, Stephen Carmichael, Lisa Berry, Frances Bolt, Andrew Rambaut, Samir Dervisevic, Erik M. Volz, Rahul Batra, Caoimhe McKerr, Samantha McGuigan, Katie Jones, Mailis Maes, Rebecca Dewar, Mary Sinnathamby, Joel Southgate, and Lynn Monaghan

Subjects
medicine.medical_specialty, business.industry, Proportional hazards model, Public health, Hazard ratio, Attendance, C500, Vaccination, Infectious Diseases, Relative risk, Internal medicine, Cohort, medicine, business, Cohort study
Abstract

Background: \ud The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes.\ud \ud Methods: \ud This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status.\ud \ud Findings: \ud Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low.\ud \ud Interpretation: \ud This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant.\ud \ud Funding: \ud Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research.

Published
2022

419. Bureaucracy and Cooperation

Author

Alikhan Baimenov

Subjects
media_common.quotation_subject, Political science, 0502 economics and business, 05 social sciences, 050602 political science & public administration, Bureaucracy, Public administration, 050203 business & management, 0506 political science, media_common
Published
2022

421. Immunoglobulin abnormalities are frequent in patients with lupus nephritis

Author

Cuadrado, M. J., Calatayud, I., Urquizu-Padilla, M., Wijetilleka, S., Kiani-Alikhan, S., and Karim, M. Y.

Subjects
lcsh:Diseases of the musculoskeletal system, Lupus nephritis, immune system diseases, hemic and lymphatic diseases, Hypogammaglobulinemia, B-cells, SLE, Immunoglobulins, Clinical sciences, lcsh:RC925-935, Rituximab, Research Article, Autoimmune
Abstract

Hypogammaglobulinemia is a complication of B-cell targeting therapies (BCTT), used in vasculitis, rheumatoid arthritis and systemic lupus erythematosus (SLE). Since autoimmune diseases are associated with underlying and induced immune abnormalities, several societies recommend assessing immune function before and during rituximab treatment. In SLE, polyclonal hypergammaglobulinemia is the typical alteration of gammaglobulins, though hypogammaglobulinemia has also been reported. This is a cross-sectional study describing immunoglobulin levels measured as part of routine care in patients with lupus nephritis, a group with multiple factors contributing to immunoglobulin abnormalities, including immune dysregulation, immunosuppression and nephrotic syndrome. Polyclonal hypergammaglobulinemia occurred in 15/83 (18.1%) patients. In contrast, low levels of immunoglobulins were found as follows: selective IgA deficiency 2/83 (2.4%), reduced IgG levels 7/83 (8.4%), reduced IgM 14/83 (16.9%). Only 1 patient required immunoglobulin replacement. Immunoglobulin abnormalities are frequently found in lupus nephritis, ranging from polyclonal hypergammaglobulinemia to hypogammglobulinemia. Consequently, immunoglobulin levels should be assessed prior to commencing BCTT.Other Information Published in: BMC Rheumatology License: http://creativecommons.org/licenses/by/4.0/See article on publisher's website: http://dx.doi.org/10.1186/s41927-019-0079-2

Published
2022
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422. Additional file 1 of Investigating the feasibility of recruitment to an observational, quality-of-life study of patients diagnosed with atrial fibrillation (AF) who have experienced a bleed while anticoagulated: EQUAL-AF feasibility study protocol

Author

Hutchings, Hayley A., Lanyon, Kirsty, Lister, Steven, Alikhan, Raza, Halcox, Julian, Holland, Gail, Hughes, Arfon, Jenkins, Rhys, Laing, Hamish, Lobban, Trudie, Owen, Diane, Pollock, Kevin G., Todd, Ceri, and Wareham, Kathie

Abstract

Additional file 1: EQUAL-AF Interview Questions.

Published
2022
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423. Efficacy And Safety Of Bradykinin B2 Receptor Inhibition With Oral PHVS416 In Treating Hereditary Angioedema Attacks: Results Of RAPIDe-1 Phase 2 Trial

Author

Marcus Maurer, John Anderson, Emel Aygören-Pürsün, Laurence Bouillet, María Luisa Baeza, Hugo Chapdelaine, Danny Cohn, Aurélie Du-Thanh, Olivier Fain, Henriette Farkas, Jens Greve, Mar Guilarte, David Hagin, Roman Hakl, Joshua Jacobs, Aharon Kessell, Sorena Kiani-Alikhan, Pavlína Králíčková, Huamin Li, Ramon Lleonart Bellfill, Markus Magerl, Michael Manning, Avner Reshef, Bruce Ritchie, Giuseppe Spadaro, Maria Staevska, Petra Staubach, Marcin Stobiecki, Gordon Sussman, Michael Tarzi, Anna Valerieva, William Yang, Marie-Helene Jouvin, Rafael Crabbé, Simone van Leeuwen, Huaihou Chen, Li Zhu, Jochen Knolle, Anne Lesage, Peng Lu, and Marc Riedl

Subjects
Immunology, Immunology and Allergy
Published
2023

425. Reply to 'Rifampin and clindamycin are safe long-term'

Author

Ali Alikhan and Christopher Sayed

Subjects
medicine.medical_specialty, medicine.drug_class, business.industry, Clindamycin, Antibiotics, Dermatology, Staphylococcal Infections, medicine.disease, Anti-Bacterial Agents, Term (time), medicine, Humans, Hidradenitis suppurativa, Rifampin, business, medicine.drug
Published
2023

426. Rare missense variants in Tropomyosin‐4 (TPM4) are associated with platelet dysfunction, cytoskeletal defects, and excessive bleeding

Author

Stapley, Rachel J., Poulter, Natalie S., Khan, Abdullah O., Smith, Christopher W., Bignell, Patricia, Fratter, Carl, Lester, Will, Lowe, Gillian, Morgan, Neil V., Morgan, Neil, Watson, Steve, Harrison, Paul, Lordkipanidze, Marie, Mumford, Andrew D., Mundell, Stuart J., Gissen, Paul, Daly, Martina E., Clark, Justin, Williams, Mike, Motwani, Jayashree, Marshall, Dianne, Lawson, Natalie, Nyatanga, Priscilla, Mann, Pat, Kirwan, Julie, Percy, Charles, Green, Pam, Hupston, Helen, Nagapachetty, Koomaravel, Dwenger, Elizabeth, Rourke, Ann O, Pope, Martin, Edmead, Camillia, Greenway, April, Makris, Michael, Payne, Jeanette, Pavord, Sue, Gooding, Richard, Dattani, Rashesh, Grimley, Gerry Dolan, Charlotte, Stokley, Simone, Astwood, Emma, Longmuir, Karyn, Chang, Cherry, Foros, Merri, Kightley, Michelle, Trower, Linda, Thachil, Jecko, Bolton Maggs, Paula, Hay, Charlie, Pike, Gill, Will, Andrew, Grainger, John, Foulkes, Matt, Fareh, Mona, Talks, Kate, Biss, Tina, Kesteven, Patrick, Hanley, John, Vowles, Julie, Basey, Lesley, Knaggs, Kevin, Barnes, Michelle, Collins, Peter, Rayment, Rachel, Alikhan, Raza, Rebecca Morris, Ana Guerrero, Mansell, Dianne, Toh, Cheng Hock, Martlew, Vanessa, Murphy, Elaine, Lachmann, Robin, Rose, Peter, Chapman, Oliver, Lokare, Anand, Marshall, Kathryn, Khan, Naseem, Keeling, David, Curry, Nikki, Giangrande, Paul, Austin, Steve, Bevan, David, Alamelu, Jayanthi, Allsup, David, Fletcher, Andrew, Gladstone, Katherine, Fenwick, Jeanette, Woods, Philippa, Camp, Darren, James, Beki, Preston, Suzie, Spencer, Collette, Pike, Alexandra, Lai‐Wah, Chung, Thomas, Angela, Myers, Bethan, Evans, Gillian, Elliot, Kim, Davies, Karen, Graham, Charlotte, Foad, Miranda, and Smith, Jacqueline

Published
2022
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429. Genomic reconstruction of the SARS-CoV-2 epidemic in England

Author

Vöhringer, HS, Sanderson, T, Sinnott, M, De Maio, N, Nguyen, T, Goater, R, Schwach, F, Harrison, I, Hellewell, J, Ariani, CV, Gonçalves, S, Jackson, DK, Johnston, I, Jung, AW, Saint, C, Sillitoe, J, Suciu, M, Goldman, N, Panovska-Griffiths, J, Abnizova, I, Aigrain, L, Alderton, A, Ali, M, Allen, L, Amato, R, Anderson, R, Ariani, C, Austin-Guest, S, Bala, S, Barrett, J, Bassett, A, Battleday, K, Beal, J, Beale, M, Beaver, C, 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, SK, Bush, R, Caetano, C, Cagan, A, Carter, N, Cartwright, J, Monteiro, TC, 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, Davies, R, Dawson, J, Day, C, Densem, A, Dibling, T, Dockree, C, Dodd, D, Dogga, S, Dorman, M, Dougan, G, Dougherty, M, Dove, A, Drummond, L, Drury, E, Dudek, M, Durham, J, Durrant, L, Easthope, E, Eckert, S, Ellis, P, Farr, B, Fenton, M, Ferrero, M, Flack, N, Fordham, H, Forsythe, G, Foulser, L, Francis, M, Fraser, A, Freeman, A, Galvin, A, Garcia-Casado, M, Gedny, A, Girgis, S, Glover, J, Goncalves, S, Goodwin, S, Gould, O, Gourtovaia, M, 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, James, K, Jamrozy, D, Verdejo, CJ, Jones, M, Kallepally, K, Kane, L, Kay, K, Kay, S, Keatley, J, Keith, A, King, A, Kitchin, L, Kleanthous, M, Klimekova, M, Korlevic, P, Krasheninnkova, K, Lane, G, Langford, C, Laverack, A, Law, K, Lawniczak, M, Lensing, S, Leonard, S, Letchford, L, Lewis, K, Lewis-Wade, A, Liddle, J, Lin, Q, Lindsay, S, Linsdell, S, Livett, R, Lo, S, Long, R, Lovell, J, Ludden, C, Mack, J, Maddison, M, Makunin, A, Mamun, I, Mansfield, J, Marriott, N, Martin, M, Mayho, M, McCarthy, S, McClintock, J, McGuigan, S, McHugh, S, McMinn, L, Meadows, C, Mobley, E, Moll, R, Morra, M, Morrow, L, Murie, K, Nash, S, Nathwani, C, Naydenova, P, Neaverson, A, Nelson, R, Nerou, E, Nicholson, J, Nimz, T, Noell, GG, O’Meara, S, Ohan, V, Oliver, K, Olney, C, Ormond, D, Oszlanczi, A, Palmer, S, Pang, YF, Pardubska, B, Park, N, Parmar, A, Patel, G, Patel, M, Payne, M, Peacock, S, Petersen, A, Plowman, D, Preston, T, Prestwood, L, Puethe, C, Quail, M, Rajan, D, Rajatileka, S, 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, EM, Roopra, D, Rose, M, Rudd, L, Sadri, R, Salmon, N, Saul, D, Scott, C, Seekings, P, Shirley, L, Simms, A, 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, CD, Sousa, C, Souster, E, Sparkes, A, Spencer-Chapman, M, Squares, J, Stanley, R, Steed, C, Stickland, T, Still, I, Stratton, MR, Strickland, M, Swann, A, Swiatkowska, A, Sycamore, N, Swift, E, Symons, E, Szluha, S, Taluy, E, Tao, N, Taylor, K, Taylor, S, Thompson, S, Thompson, M, Thomson, M, Thomson, N, Thurston, S, Tonkin-Hill, G, Toombs, D, Topping, B, Tovar-Corona, J, Ungureanu, D, Uphill, J, Urbanova, J, Van Vuuren, PJ, Vancollie, V, Voak, P, Walker, D, Walker, M, Waller, M, Ward, G, Weatherhogg, C, Webb, N, Weldon, D, Wells, A, Wells, E, Westwood, L, Whipp, T, Whiteley, T, Whitton, G, Whitwham, A, Widaa, S, Williams, M, Wilson, M, Wright, S, Robson, SC, Connor, TR, Loman, NJ, Golubchik, T, Martinez Nunez, RT, Bonsall, D, Rambaut, A, Snell, LB, Corden, S, Nastouli, E, Nebbia, G, Lythgoe, K, Torok, ME, Goodfellow, IG, Prieto, JA, Saeed, K, Houlihan, C, Frampton, D, Hamilton, WL, Witney, AA, Bucca, G, Pope, CF, Moore, C, Thomson, EC, Harrison, EM, Smith, CP, Rogan, F, Beckwith, SM, Murray, A, Singleton, D, Eastick, K, Sheridan, LA, Randell, P, Jackson, LM, Fairley, DJ, Loose, MW, Watkins, J, Moses, S, Nicholls, S, Bull, M, Smith, DL, Aanensen, DM, Aggarwal, D, Shepherd, JG, Curran, MD, Parmar, S, Parker, MD, Williams, C, Glaysher, S, Underwood, AP, Bashton, M, Pacchiarini, N, Loveson, KF, Byott, M, Carabelli, AM, Templeton, KE, de Silva, TI, Wang, D, Langford, CF, Gunson, RN, Cottrell, S, O’Grady, J, Kwiatkowski, D, Lillie, PJ, Cortes, N, Moore, N, Thomas, C, Burns, PJ, Mahungu, TW, Liggett, S, Beckett, AH, Holden, MTG, Levett, LJ, Osman, H, Hassan-Ibrahim, MO, Simpson, DA, Chand, M, Gupta, RK, Darby, AC, Paterson, S, Pybus, OG, Volz, EM, de Angelis, D, Robertson, DL, Page, AJ, Bassett, AR, Wong, N, Taha, Y, Erkiert, MJ, Spencer Chapman, MH, Dewar, R, McHugh, MP, Mookerjee, S, Aplin, S, Harvey, M, Sass, T, Umpleby, H, Wheeler, H, McKenna, JP, Warne, B, Taylor, JF, Chaudhry, Y, Izuagbe, R, Jahun, AS, Young, GR, McMurray, C, McCann, CM, Nelson, A, Elliott, S, Lowe, H, Price, A, Crown, MR, Rey, S, Roy, S, Temperton, B, Shaaban, S, Hesketh, AR, Laing, KG, Monahan, IM, Heaney, J, Pelosi, E, Silviera, S, Wilson-Davies, E, Fryer, H, Adams, H, du Plessis, L, Johnson, R, Harvey, WT, Hughes, J, Orton, RJ, Spurgin, LG, Bourgeois, Y, Ruis, C, O’Toole, Á, Fraser, C, Edgeworth, J, Breuer, J, Michell, SL, Todd, JA, John, M, Buck, D, Gajee, K, Kay, GL, Peacock, SJ, Heyburn, D, Kitchman, K, McNally, A, Pritchard, DT, Dervisevic, S, Muir, P, Robinson, E, Vipond, BB, Ramadan, NA, Jeanes, C, Catalan, J, Jones, N, da Silva Filipe, A, Fuchs, M, Miskelly, J, Jeffries, AR, Park, NR, Ash, A, Koshy, C, Barrow, M, Buchan, SL, Mantzouratou, A, Clark, G, Holmes, CW, Campbell, S, Davis, T, Tan, NK, Brown, JR, Harris, KA, Kidd, SP, Grant, PR, Xu-McCrae, L, Cox, A, Madona, P, Pond, M, Randell, PA, Withell, KT, Graham, C, Denton-Smith, R, Swindells, E, Turnbull, R, Sloan, TJ, Bosworth, A, Hutchings, S, Pymont, HM, Casey, A, Ratcliffe, L, Jones, CR, Knight, BA, Haque, T, Hart, J, Irish-Tavares, D, Witele, E, Mower, C, Watson, LK, Collins, J, Eltringham, G, Crudgington, D, Macklin, B, Iturriza-Gomara, M, Lucaci, AO, McClure, PC, Carlile, M, Holmes, N, Storey, N, Rooke, S, Yebra, G, Craine, N, Perry, M, Alikhan, N-F, Bridgett, S, Cook, KF, Fearn, C, Goudarzi, S, Lyons, RA, Williams, T, Haldenby, ST, Davies, RM, Batra, R, Blane, B, Spyer, MJ, Smith, P, Yavus, M, Williams, RJ, Mahanama, AIK, Samaraweera, B, Girgis, ST, Hansford, SE, Green, A, Bellis, KL, Dorman, MJ, Quick, J, Poplawski, R, Reynolds, N, Mack, A, Morriss, A, Whalley, T, Patel, B, Georgana, I, Hosmillo, M, Pinckert, ML, Stockton, J, Henderson, JH, Hollis, A, Stanley, W, Yew, WC, Myers, R, Thornton, A, Adams, A, Annett, T, Asad, H, Birchley, A, Coombes, J, Evans, JM, Fina, L, Gatica-Wilcox, B, Gilbert, L, Graham, L, Hey, J, Hilvers, E, Jones, S, Jones, H, Kumziene-Summerhayes, S, McKerr, C, Powell, J, Pugh, G, Trotter, AJ, Williams, CA, Kermack, LM, Foulkes, BH, Gallis, M, Hornsby, HR, Louka, SF, Pohare, M, Wolverson, P, Zhang, P, MacIntyre-Cockett, G, Trebes, A, Moll, RJ, Ferguson, L, Goldstein, EJ, Maclean, A, Tomb, R, Starinskij, I, Thomson, L, Southgate, J, Kraemer, MUG, Raghwani, J, Zarebski, AE, Boyd, O, Geidelberg, L, Illingworth, CJ, Jackson, C, Pascall, D, Vattipally, S, Freeman, TM, Hsu, SN, Lindsey, BB, Tovar-Corona, JM, Cox, M, Abudahab, K, Menegazzo, M, Taylor, BEW, Yeats, CA, Mukaddas, A, Wright, DW, de Oliveira Martins, L, Colquhoun, R, Hill, V, Jackson, B, McCrone, JT, Medd, N, Scher, E, Keatley, J-P, Curran, T, Morgan, S, Maxwell, P, Eldirdiri, S, Kenyon, A, Holmes, AH, Price, JR, Wyatt, T, Mather, AE, Skvortsov, T, Hartley, JA, Guest, M, Kitchen, C, Merrick, I, Munn, R, Bertolusso, B, Lynch, J, Vernet, G, Kirk, S, Wastnedge, E, Idle, G, Bradley, DT, Poyner, J, Mori, M, Jones, O, Wright, V, Brooks, E, Churcher, CM, Fragakis, M, Galai, K, Jermy, A, Judges, S, McManus, GM, Smith, KS, Westwick, E, Attwood, SW, Bolt, F, Davies, A, De Lacy, E, Downing, F, Edwards, S, Meadows, L, Jeremiah, S, Smith, N, Charalampous, T, Patel, A, Berry, L, Boswell, T, Fleming, VM, Howson-Wells, HC, Joseph, A, Khakh, M, Lister, MM, Bird, PW, Fallon, K, Helmer, T, McMurray, CL, Odedra, M, Shaw, J, Tang, JW, Willford, NJ, Blakey, V, Raviprakash, V, Sheriff, N, Williams, L-A, Feltwell, T, Bedford, L, Cargill, JS, Hughes, W, Moore, J, Stonehouse, S, Atkinson, L, Lee, JCD, Shah, D, Alcolea, A, Ohemeng-Kumi, N, Ramble, J, Sehmi, J, Williams, R, Chatterton, W, Pusok, M, Everson, W, Castigador, A, Macnaughton, E, El Bouzidi, K, Lampejo, T, Sudhanva, M, Breen, C, Sluga, G, Ahmad, SSY, George, RP, Machin, NW, Binns, D, James, V, Blacow, R, Coupland, L, Smith, L, Barton, E, Padgett, D, Scott, G, Cross, A, Mirfenderesky, M, Greenaway, J, Cole, K, Clarke, P, Duckworth, N, Walsh, S, Bicknell, K, Impey, R, Wyllie, S, Hopes, R, Bishop, C, Chalker, V, Gifford, L, Molnar, Z, Auckland, C, Evans, C, Johnson, K, Partridge, DG, Raza, M, Baker, P, Bonner, S, Essex, S, Murray, LJ, Lawton, AI, Burton-Fanning, S, Payne, BAI, Waugh, S, Gomes, AN, Kimuli, M, Murray, DR, Ashfield, P, Dobie, D, Ashford, F, Best, A, Crawford, L, Cumley, N, Mayhew, M, Megram, O, Mirza, J, Moles-Garcia, E, Percival, B, Ensell, L, Lowe, HL, Maftei, L, Mondani, M, Chaloner, NJ, Cogger, BJ, Easton, LJ, Huckson, H, Lewis, J, Lowdon, S, Malone, CS, Munemo, F, Mutingwende, M, Nicodemi, R, Podplomyk, O, Somassa, T, Beggs, A, Richter, A, Cormie, C, Dias, J, Forrest, S, Higginson, EE, Maes, M, Young, J, Davidson, RK, Jackson, KA, Turtle, L, Keeley, AJ, Ball, J, Byaruhanga, T, Chappell, JG, Dey, J, Hill, JD, Park, EJ, Fanaie, A, Hilson, RA, Yaze, G, Afifi, S, Beer, R, Maksimovic, J, Masters, KM, Spellman, K, Bresner, C, Fuller, W, Marchbank, A, Workman, T, Shelest, E, Debebe, J, Sang, F, Zamudio, ME, Francois, S, Gutierrez, B, Vasylyeva, TI, Flaviani, F, Ragonnet-Cronin, M, Smollett, KL, Broos, A, Mair, D, Nichols, J, Nomikou, K, Tong, L, Tsatsani, I, O’Brien, S, Rushton, S, Sanderson, R, Perkins, J, Cotton, S, Gallagher, A, Allara, E, Pearson, C, Bibby, D, Dabrera, G, Ellaby, N, Gallagher, E, Hubb, J, Lackenby, A, Lee, D, Manesis, N, Mbisa, T, Platt, S, Twohig, KA, Morgan, M, Aydin, A, Baker, DJ, Foster-Nyarko, E, Prosolek, SJ, Rudder, S, Baxter, C, Carvalho, SF, Lavin, D, Mariappan, A, Radulescu, C, Singh, A, Tang, M, Morcrette, H, Bayzid, N, Cotic, M, Balcazar, CE, Gallagher, MD, Maloney, D, Stanton, TD, Williamson, KA, Manley, R, Michelsen, ML, Sambles, CM, Studholme, DJ, Warwick-Dugdale, J, Eccles, R, Gemmell, M, Gregory, R, Hughes, M, Nelson, C, Rainbow, L, Vamos, EE, Webster, HJ, Whitehead, M, Wierzbicki, C, Angyal, A, Green, LR, Whiteley, M, Bronner, IF, Farr, BW, Lensing, SV, McCarthy, SA, Quail, MA, Redshaw, NM, Thurston, SAJ, Rowe, W, Gaskin, A, Le-Viet, T, Birney, E, Volz, E, Funk, S, Martincorena, I, Barrett, JC, and Gerstung, M

Abstract

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.

Published
2021

430. High Resolution Reservoir Simulator Driven Custom Scripts as the Enabler for Solving Reservoir to Surface Network Coupling Challenges

Author

Kanat Aktassov, Dauletbek Ayaganov, Kanat Imagambetov, Ruslan Alissov, Said Muratbekov, Zhaksylyk Kali, Bagdad Amangaliyev, Dmitry Sidorov, and Alikhan Kurmankulov

Abstract

This paper presents a practical methodology of optimizing and building a detailed field surface network system by using the high-resolution reservoir simulator driven custom-made Python scripts to efficiently predict the future performance of the vast oil and gas-condensate carbonate field. All existing surface hydraulic tables are quality checked and lifting issue constraints corrected. Pressure losses at the wellhead chokes incorporated into the high-resolution reservoir simulator in the form of equation by using the custom scripts instead of a table format to calculate gas rate dependent pressure losses more precisely. Consequently, all 400+ surface production system manifolds, pipes and well chokes Horizontal Flow Performance (HFP) tables are updated and coupled to the reservoir simulator through Field Management (FM) controller which in turn generates Inflow Performance Relationship (IPR) tables for the coupled wells and passes them to solve the network. The methodology described in this paper applied for a complex field development planning of the Karachaganak. At present, reservoir management strategy requires constant balancing effort to uniformly spread gas re-injection into the lower Voidage Replacement Ratio areas in the Upper Gas-Condensate part of the reservoir due to reservoir heterogeneity. Additionally, an increase in field and wells gas-oil ratio and water-cut creates bottlenecks in the surface gathering system and requires robust solutions to decongest the surface network. Current simulation tools are not always effective due longer run times and simulation instability due to complex network system. As a solution, project-specific network balancing challenges are resolved by incorporating custom-made scripts into the high-resolution simulator. Faster and flexible integrated model based on hydraulic tables reproduced the historical pressure losses of the surface pipelines at similar resolution and generated accurate prediction profiles in a twice-quicker time than existing reservoir simulator. Overall, this approach helped to generate more stable production profiles by identifying bottlenecks in the surface network and evaluate future projects with more confidence by achieving a significant CAPEX cost savings. The comprehensive guidelines provided in this paper can aid reservoir modeling by setting up flexible integrated models to account for surface network effects. The value of incorporating Python scripts demonstrated to implement non-standard and project specific network balancing solutions leveraging on the flexibility and the openness of the modelling tool.

Published
2021

431. SARS-CoV-2 variants of concern dominate in Lahore, Pakistan in April 2021

Author

Muhammad Bilal Sarwar, Muhammad Yasir, Nabil-Fareed Alikhan, Nadeem Afzal, Leonardo de Oliveira Martins, Thanh Le Viet, Alexander J. Trotter, Sophie J. Prosolek, Gemma L. Kay, Ebenezer Foster-Nyarko, Steven Rudder, David J. Baker, Sidra Tul Muntaha, Muhammad Roman, Mark A. Webber, Almina Shafiq, Bilquis Shabbir, Javed Akram, Andrew J. Page, and Shah Jahan

Subjects
Adult, Aged, 80 and over, Male, COVID-19 Vaccines, SARS-CoV-2, COVID-19, General Medicine, Genome, Viral, Pathogens and Epidemiology, sequencing, Middle Aged, genomic epidemiology, Young Adult, NGS, Humans, Female, Pakistan, ARTIC, Pandemics, genome, Phylogeny, Research Articles, Aged
Abstract

The SARS-CoV-2 pandemic continues to expand globally, with case numbers rising in many areas of the world, including the Indian sub-continent. Pakistan has one of the world’s largest populations, of over 200 million people and is experiencing a severe third wave of infections caused by SARS-CoV-2 that began in March 2021. In Pakistan, during the third wave until now only 12 SARS-CoV-2 genomes have been collected and among these nine are from Islamabad. This highlights the need for more genome sequencing to allow surveillance of variants in circulation. In fact, more genomes are available among travellers with a travel history from Pakistan, than from within the country itself. We thus aimed to provide a snapshot assessment of circulating lineages in Lahore and surrounding areas with a combined population of 11.1 million. Within a week of April 2021, 102 samples were sequenced. The samples were randomly collected from two hospitals with a diagnostic PCR cutoff value of less than 25 cycles. Analysis of the lineages shows that the Alpha variant of concern (first identified in the UK) dominates, accounting for 97.9 % (97/99) of cases, with the Beta variant of concern (first identified in South Africa) accounting for 2.0 % (2/99) of cases. No other lineages were observed. In depth analysis of the Alpha lineages indicated multiple separate introductions and subsequent establishment within the region. Eight samples were identical to genomes observed in Europe (seven UK, one Switzerland), indicating recent transmission. Genomes of other samples show evidence that these have evolved, indicating sustained transmission over a period of time either within Pakistan or other countries with low-density genome sequencing. Vaccines remain effective against Alpha, however, the low level of Beta against which some vaccines are less effective demonstrates the requirement for continued prospective genomic surveillance.

Published
2021

432. PB1938: 4WHIM: EVALUATING MAVORIXAFOR, AN ORAL CXCR4 ANTAGONIST, IN PATIENTS WITH WHIM SYNDROME VIA A GLOBAL PHASE 3, RANDOMIZED, PLACEBO-CONTROLLED TRIAL WITH OPEN-LABEL EXTENSION

Author

D. C. Dale, L. Alsina, A. Azar, R. Badolato, Y. Bertrand, A. Deya, K. E. Dickerson, N. Ezra, H. Hasle, H. J. Kang, S. Kiani-Alikhan, T. Kuijpers, A. Kulagin, D. Langguth, C. Levin, O. Neth, J. Peake, C. E. Rutten, A. Shcherbina, T. K. Tarrant, M. G. Vossen, C. A. Wysocki, A. Belschner, D. Cadavid, Y. Hu, H. Jiang, R. MacLeod, W. Tang, M. Tillinger, and J. Donadieu

Subjects
Hematology
Published
2022

433. An Evaluation of the Referral Process From General Practice (Gp) to the North-West Community Mental Health Team (Nw Cmht)

Author

Kathryn Flew, Christiana Elisha-Aboh, and Shaharyar Alikhan

Subjects
Psychiatry and Mental health
Abstract

AimsAs more emphasis is placed on a move from the traditional hospital-based practice to care in the community, CMHTs are becoming the main channel for delivering specialist care in England. Access to most CMHTs occurs via written referrals, which vary significantly in content and quality. Such variability and inconsistency with the information provided can impact on the triage process and delay access to treatment for patients, making the process unnecessarily protracted and time consuming. One key factor that would drive the success and survival of CMHTs is how they gate-keep their service. This starts by adopting formal strategies when vetting and screening referrals. The aims were to determine if NW CMHT is responding to referrals appropriately, to consider if service users received good quality correspondence about referral decisions and if the outcomes of such meetings were properly documented.MethodsThe NW CMHT consists of 4 pods (A to D) and the audit included all GP referrals assessed by pod B over a month. A sample size of 28 referrals was included in the audit and the referrals were from 16 different GP practices. Data were obtained from patient electronic records and entered onto a SmartSurvey form for ease of collection prior to results being analysed.Results32% of referrals came from two GP surgeries. Areas of good practice included all referrals being discussed within 4 days of receipt, and 50% reviewed by the next day. For referrals identified as needing further information and discussion, this was also done quickly between 2–5 days of receiving the referral. Also 68% of service users (SU) had a letter sent out to them within 2–5 days. It was unclear in 75% of referrals whether the SU was aware of the referral to NW CMHT and the reasons for the referral were only ‘fully’ documented in 57%.ConclusionThe vast majority of GP referrals were treated in a timely manner, even if additional data gathering was needed and multiple referral discussions had. Recommendations included addressing the lack of consistency in documentation of referral discussions, developing effective ways to cut back on clinical time lost gathering what should be standard information, and education of GP practices around making good quality referrals. It was felt that a review of the referral forms would be beneficial, however a barrier to this change was that this is a trust wide form and there would need to be consensus across all CMHT localities.

Published
2022

434. Challenging situations in patients with cancer‐associated thrombosis—Further clarification required in the British Society for Haematology guidelines—Response.

Author

Alikhan, Raza, Gomez, Keith, Maraveyas, Anthony, Noble, Simon, Young, Annie, and Thomas, Mari

Subjects
*NURSE practitioners, *MEDICAL personnel, *EVIDENCE-based medicine, *VENOUS thrombosis, *NON-medical prescribing, *NURSE prescribing
Abstract

This document is a response to correspondence regarding the British Society for Haematology guidelines on cancer-associated thrombosis (CAT). The authors acknowledge the complexity of CAT management and the challenges in creating guidelines for a diverse patient population. They explain that the graphical abstract in the guidelines is not meant to replace the guidelines themselves but rather provide a framework for decision-making. The authors also address concerns about the lack of justification in the graphical abstract and emphasize the importance of integrating external guidelines with individual clinical expertise. They acknowledge that the published clinical studies on CAT have limitations and that their recommendations are influenced by their clinical experience. The authors suggest that areas of clinical uncertainty or debate can be covered in supplementary articles. They conclude by stating that a forthcoming article will address the issues raised in more detail. [Extracted from the article]

Published
2024
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436. Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report

Author

Matthew Buckland, Kenneth G. C. Smith, Jimstan Periselneris, Sorena Kiani-Alikhan, M. Estée Török, Luke W. Meredith, Paul A. Lyons, James Galloway, Stuart Bloor, Ane Ogbe, Nicholas J Matheson, Hossain Delowar Akther, Laura Bergamaschi, John Bradley, Erik J.M. Toonen, Lorinda Turner, Lourdes Ceron-Gutierrez, Sofia Grigoriadou, Ian Goodfellow, Lise J Estcourt, Joanne D. Stockton, Josh Quick, Carl Philipp Hackstein, Nicholas Screaton, Willem H. Ouwehand, Tiffeney Mann, Devan Vaghela, James Thaventhiran, Heli Harvala, Anna Yakovleva, Paul Klenerman, Rainer Doffinger, Ian B. Wilkinson, Nicholas J. Loman, Michael Hunter, Sara Lear, B. Paul Morgan, David J. Roberts, William L Hamilton, Peter Nelson, Paul J. Lehner, Vinicius A Vieira, Nicholas M. Provine, Caoimhe Nic Fhogartaigh, Frederica Mescia, Tanya I. Coulter, Lisa Devlin, Anna Smielewska, Wioleta M. Zelek, Buckland, Matthew S. [0000-0002-5646-4707], Ogbe, Ane [0000-0001-7774-7215], Mescia, Frederica [0000-0002-2759-4027], Toonen, Erik J. M. [0000-0001-9039-635X], Vieira, Vinicius Adriano [0000-0002-4901-0424], Kiani-Alikhan, Sorena [0000-0002-1299-4415], Ouwehand, Willem H. [0000-0002-7744-1790], Lyons, Paul A. [0000-0001-7035-8997], Lehner, Paul J. [0000-0001-9383-1054], Matheson, Nicholas J. [0000-0002-3318-1851], Thaventhiran, James E. D. [0000-0001-8616-074X], Apollo - University of Cambridge Repository, Buckland, Matthew S [0000-0002-5646-4707], Toonen, Erik JM [0000-0001-9039-635X], Ouwehand, Willem H [0000-0002-7744-1790], Lyons, Paul A [0000-0001-7035-8997], Lehner, Paul J [0000-0001-9383-1054], Matheson, Nicholas J [0000-0002-3318-1851], and Thaventhiran, James ED [0000-0001-8616-074X]

Subjects
0301 basic medicine, Male, 692/699/249/2512, General Physics and Astronomy, Drug resistance, 13/1, 0302 clinical medicine, Pandemic, Medicine, Multidisciplinary, Alanine, biology, article, Humoral, Antivirals, 13/31, Treatment Outcome, 030220 oncology & carcinogenesis, Primary immunodeficiency disorders, 631/326/596/1296, Antibody, Adult, Fever, Science, Antiviral Agents, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 692/699/255/2514, Immunity, In vivo, Humans, Lymphocyte Count, 631/326/596/4130, Pneumonitis, business.industry, SARS-CoV-2, fungi, COVID-19, General Chemistry, medicine.disease, Adenosine Monophosphate, Complement system, Immunity, Humoral, 030104 developmental biology, Viral infection, Humoral immunity, Immunology, biology.protein, business
Abstract

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients., Remdesivir is under evaluation for treatment of COVID-19 in clinical trials. Here, the authors report results of remdesivir treatment in a patient with COVID-19 and the genetic antibody deficiency XLA. They show a temporally correlated clinical and virological response, suggesting that remdesivir can reduce SARS-CoV-2 replication in patients.

Published
2020
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439. Attenuated androgen discontinuation in patients with hereditary angioedema: a commented case series

Author

Maurer, Marcus, primary, Magerl, Markus, additional, Aygören-Pürsün, Emel, additional, Bork, Konrad, additional, Farkas, Henriette, additional, Longhurst, Hilary, additional, Kiani‑Alikhan, Sorena, additional, Bouillet, Laurence, additional, Boccon-Gibod, Isabelle, additional, Cancian, Mauro, additional, Zanichelli, Andrea, additional, and Launay, David, additional

Published
2022
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446. Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Author

Twohig, Katherine A, primary, Nyberg, Tommy, additional, Zaidi, Asad, additional, Thelwall, Simon, additional, Sinnathamby, Mary A, additional, Aliabadi, Shirin, additional, Seaman, Shaun R, additional, Harris, Ross J, additional, Hope, Russell, additional, Lopez-Bernal, Jamie, additional, Gallagher, Eileen, additional, Charlett, Andre, additional, De Angelis, Daniela, additional, Presanis, Anne M, additional, Dabrera, Gavin, additional, Koshy, Cherian, additional, Ash, Amy, additional, Wise, Emma, additional, Moore, Nathan, additional, Mori, Matilde, additional, Cortes, Nick, additional, Lynch, Jessica, additional, Kidd, Stephen, additional, Fairley, Derek, additional, Curran, Tanya, additional, McKenna, James, additional, Adams, Helen, additional, Fraser, Christophe, additional, Golubchik, Tanya, additional, Bonsall, David, additional, Hassan-Ibrahim, Mohammed, additional, Malone, Cassandra, additional, Cogger, Benjamin, additional, Wantoch, Michelle, additional, Reynolds, Nicola, additional, Warne, Ben, additional, Maksimovic, Joshua, additional, Spellman, Karla, additional, McCluggage, Kathryn, additional, John, Michaela, additional, Beer, Robert, additional, Afifi, Safiah, additional, Morgan, Sian, additional, Marchbank, Angela, additional, Price, Anna, additional, Kitchen, Christine, additional, Gulliver, Huw, additional, Merrick, Ian, additional, Southgate, Joel, additional, Guest, Martyn, additional, Munn, Robert, additional, Workman, Trudy, additional, Connor, Thomas, additional, Fuller, William, additional, Bresner, Catherine, additional, Snell, Luke, additional, Patel, Amita, additional, Charalampous, Themoula, additional, Nebbia, Gaia, additional, Batra, Rahul, additional, Edgeworth, Jonathan, additional, Robson, Samuel, additional, Beckett, Angela, additional, Aanensen, David, additional, Underwood, Anthony, additional, Yeats, Corin, additional, Abudahab, Khalil, additional, Taylor, Ben, additional, Menegazzo, Mirko, additional, Clark, Gemma, additional, Smith, Wendy, additional, Khakh, Manjinder, additional, Fleming, Vicki, additional, Lister, Michelle, additional, Howson-Wells, Hannah, additional, Berry, Louise, additional, Boswell, Tim, additional, Joseph, Amelia, additional, Willingham, Iona, additional, Jones, Carl, additional, Holmes, Christopher, additional, Bird, Paul, additional, Helmer, Thomas, additional, Fallon, Karlie, additional, Tang, Julian, additional, Raviprakash, Veena, additional, Campbell, Sharon, additional, Sheriff, Nicola, additional, Blakey, Victoria, additional, Williams, Lesley-Anne, additional, Loose, Matthew, additional, Holmes, Nadine, additional, Moore, Christopher, additional, Carlile, Matthew, additional, Wright, Victoria, additional, Sang, Fei, additional, Debebe, Johnny, additional, Coll, Francesc, additional, Signell, Adrian, additional, Betancor, Gilberto, additional, Wilson, Harry, additional, Eldirdiri, Sahar, additional, Kenyon, Anita, additional, Davis, Thomas, additional, Pybus, Oliver, additional, du Plessis, Louis, additional, Zarebski, Alex, additional, Raghwani, Jayna, additional, Kraemer, Moritz, additional, Francois, Sarah, additional, Attwood, Stephen, additional, Vasylyeva, Tetyana, additional, Escalera Zamudio, Marina, additional, Gutierrez, Bernardo, additional, Torok, M. Estee, additional, Hamilton, William, additional, Goodfellow, Ian, additional, Hall, Grant, additional, Jahun, Aminu, additional, Chaudhry, Yasmin, additional, Hosmillo, Myra, additional, Pinckert, Malte, additional, Georgana, Iliana, additional, Moses, Samuel, additional, Lowe, Hannah, additional, Bedford, Luke, additional, Moore, Jonathan, additional, Stonehouse, Susanne, additional, Fisher, Chloe, additional, Awan, Ali, additional, BoYes, John, additional, Breuer, Judith, additional, Harris, Kathryn, additional, Brown, Julianne, additional, Shah, Divya, additional, Atkinson, Laura, additional, Lee, Jack, additional, Storey, Nathaniel, additional, Flaviani, Flavia, additional, Alcolea-Medina, Adela, additional, Williams, Rebecca, additional, Vernet, Gabrielle, additional, Chapman, Michael, additional, Levett, Lisa, additional, Heaney, Judith, additional, Chatterton, Wendy, additional, Pusok, Monika, additional, Xu-McCrae, Li, additional, Smith, Darren, additional, Bashton, Matthew, additional, Young, Gregory, additional, Holmes, Alison, additional, Randell, Paul, additional, Cox, Alison, additional, Madona, Pinglawathee, additional, Bolt, Frances, additional, Price, James, additional, Mookerjee, Siddharth, additional, Ragonnet-Cronin, Manon, additional, F. Nascimento, Fabricia, additional, Jorgensen, David, additional, Siveroni, Igor, additional, Johnson, Rob, additional, Boyd, Olivia, additional, Geidelberg, Lily, additional, Volz, Erik, additional, Rowan, Aileen, additional, Taylor, Graham, additional, Smollett, Katherine, additional, Loman, Nicholas, additional, Quick, Joshua, additional, McMurray, Claire, additional, Stockton, Joanne, additional, Nicholls, Sam, additional, Rowe, Will, additional, Poplawski, Radoslaw, additional, McNally, Alan, additional, Martinez Nunez, Rocio, additional, Mason, Jenifer, additional, Robinson, Trevor, additional, O'Toole, Elaine, additional, Watts, Joanne, additional, Breen, Cassie, additional, Cowell, Angela, additional, Sluga, Graciela, additional, Machin, Nicholas, additional, Ahmad, Shazaad, additional, George, Ryan, additional, Halstead, Fenella, additional, Sivaprakasam, Venkat, additional, Hogsden, Wendy, additional, Illingworth, Chris, additional, Jackson, Chris, additional, Thomson, Emma, additional, Shepherd, James, additional, Asamaphan, Patawee, additional, Niebel, Marc, additional, Li, Kathy, additional, Shah, Rajiv, additional, Jesudason, Natasha, additional, Tong, Lily, additional, Broos, Alice, additional, Mair, Daniel, additional, Nichols, Jenna, additional, Carmichael, Stephen, additional, Nomikou, Kyriaki, additional, Aranday-Cortes, Elihu, additional, Johnson, Natasha, additional, Starinskij, Igor, additional, da Silva Filipe, Ana, additional, Robertson, David, additional, Orton, Richard, additional, Hughes, Joseph, additional, Vattipally, Sreenu, additional, Singer, Joshua, additional, Nickbakhsh, Seema, additional, Hale, Antony, additional, Macfarlane-Smith, Louissa, additional, Harper, Katherine, additional, Carden, Holli, additional, Taha, Yusri, additional, Payne, Brendan, additional, Burton-Fanning, Shirelle, additional, Waugh, Sheila, additional, Collins, Jennifer, additional, Eltringham, Gary, additional, Rushton, Steven, additional, O'Brien, Sarah, additional, Bradley, Amanda, additional, Maclean, Alasdair, additional, Mollett, Guy, additional, Blacow, Rachel, additional, Templeton, Kate, additional, McHugh, Martin, additional, Dewar, Rebecca, additional, Wastenge, Elizabeth, additional, Dervisevic, Samir, additional, Stanley, Rachael, additional, Meader, Emma, additional, Coupland, Lindsay, additional, Smith, Louise, additional, Graham, Clive, additional, Barton, Edward, additional, Padgett, Debra, additional, Scott, Garren, additional, Swindells, Emma, additional, Greenaway, Jane, additional, Nelson, Andrew, additional, McCann, Clare, additional, Yew, Wen, additional, Andersson, Monique, additional, Peto, Timothy, additional, Justice, Anita, additional, Eyre, David, additional, Crook, Derrick, additional, Sloan, Tim, additional, Duckworth, Nichola, additional, Walsh, Sarah, additional, Chauhan, Anoop, additional, Glaysher, Sharon, additional, Bicknell, Kelly, additional, Wyllie, Sarah, additional, Elliott, Scott, additional, Lloyd, Allyson, additional, Impey, Robert, additional, Levene, Nick, additional, Monaghan, Lynn, additional, Bradley, Declan, additional, Wyatt, Tim, additional, Allara, Elias, additional, Pearson, Clare, additional, Osman, Husam, additional, Bosworth, Andrew, additional, Robinson, Esther, additional, Muir, Peter, additional, Vipond, Ian, additional, Hopes, Richard, additional, Pymont, Hannah, additional, Hutchings, Stephanie, additional, Curran, Martin, additional, Parmar, Surendra, additional, Lackenby, Angie, additional, Mbisa, Tamyo, additional, Platt, Steven, additional, Miah, Shahjahan, additional, Bibby, David, additional, Manso, Carmen, additional, Hubb, Jonathan, additional, Chand, Meera, additional, Ramsay, Mary, additional, Bradshaw, Daniel, additional, Thornton, Alicia, additional, Myers, Richard, additional, Schaefer, Ulf, additional, Groves, Natalie, additional, Lee, David, additional, Williams, David, additional, Ellaby, Nicholas, additional, Harrison, Ian, additional, Hartman, Hassan, additional, Manesis, Nikos, additional, Patel, Vineet, additional, Bishop, Chloe, additional, Chalker, Vicki, additional, Ledesma, Juan, additional, Twohig, Katherine, additional, Holden, Matthew, additional, Shaaban, Sharif, additional, Birchley, Alec, additional, Adams, Alexander, additional, Davies, Alisha, additional, Gaskin, Amy, additional, Plimmer, Amy, additional, Gatica-Wilcox, Bree, additional, McKerr, Caoimhe, additional, Moore, Catherine, additional, Williams, Chris, additional, Heyburn, David, additional, De Lacy, Elen, additional, Hilvers, Ember, additional, Downing, Fatima, additional, Shankar, Giri, additional, Jones, Hannah, additional, Asad, Hibo, additional, Coombes, Jason, additional, Watkins, Joanne, additional, Evans, Johnathan, additional, Fina, Laia, additional, Gifford, Laura, additional, Gilbert, Lauren, additional, Graham, Lee, additional, Perry, Malorie, additional, Morgan, Mari, additional, Bull, Matthew, additional, Cronin, Michelle, additional, Pacchiarini, Nicole, additional, Craine, Noel, additional, Jones, Rachel, additional, Howe, Robin, additional, Corden, Sally, additional, Rey, Sara, additional, Kumziene-SummerhaYes, Sara, additional, Taylor, Sarah, additional, Cottrell, Simon, additional, Jones, Sophie, additional, Edwards, Sue, additional, O'Grady, Justin, additional, Page, Andrew, additional, Mather, Alison, additional, Baker, David, additional, Rudder, Steven, additional, Aydin, Alp, additional, Kay, Gemma, additional, Trotter, Alexander, additional, Alikhan, Nabil-Fareed, additional, de Oliveira Martins, Leonardo, additional, Le-Viet, Thanh, additional, Meadows, Lizzie, additional, Casey, Anna, additional, Ratcliffe, Liz, additional, Simpson, David, additional, Molnar, Zoltan, additional, Thompson, Thomas, additional, Acheson, Erwan, additional, Masoli, Jane, additional, Knight, Bridget, additional, Ellard, Sian, additional, Auckland, Cressida, additional, Jones, Christopher, additional, Mahungu, 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Williams, Charlotte, additional, Cotic, Marius, additional, Bayzid, Nadua, additional, Westhorpe, Adam, additional, Hartley, John, additional, Jannoo, Riaz, additional, Lowe, Helen, additional, Karamani, Angeliki, additional, Ensell, Leah, additional, Prieto, Jacqui, additional, Jeremiah, Sarah, additional, Grammatopoulos, Dimitris, additional, Pandey, Sarojini, additional, Berry, Lisa, additional, Jones, Katie, additional, Richter, Alex, additional, Beggs, Andrew, additional, Best, Angus, additional, Percival, Benita, additional, Mirza, Jeremy, additional, Megram, Oliver, additional, Mayhew, Megan, additional, Crawford, Liam, additional, Ashcroft, Fiona, additional, Moles-Garcia, Emma, additional, Cumley, Nicola, additional, Smith, Colin, additional, Bucca, Giselda, additional, Hesketh, Andrew, additional, Blane, Beth, additional, Girgis, Sophia, additional, Leek, Danielle, additional, Sridhar, Sushmita, additional, Forrest, Sally, additional, Cormie, Claire, additional, Gill, Harmeet, additional, Dias, Joana, additional, Higginson, Ellen, additional, Maes, Mailis, additional, Young, Jamie, additional, Kermack, Leanne, additional, Gupta, Ravi, additional, Ludden, Catherine, additional, Peacock, Sharon, additional, Palmer, Sophie, additional, Churcher, Carol, additional, Hadjirin, Nazreen, additional, Carabelli, Alessandro, additional, Brooks, Ellena, additional, Smith, Kim, additional, Galai, Katerina, additional, McManus, Georgina, additional, Ruis, Chris, additional, Davidson, Rose, additional, Rambaut, Andrew, additional, Williams, Thomas, additional, Balcazar, Carlos, additional, Gallagher, Michael, additional, O'Toole, Áine, additional, Rooke, Stefan, additional, Hill, Verity, additional, Williamson, Kathleen, additional, Stanton, Thomas, additional, Michell, Stephen, additional, Bewshea, Claire, additional, Temperton, Ben, additional, Michelsen, Michelle, additional, Warwick-Dugdale, Joanna, additional, Manley, Robin, additional, Farbos, Audrey, additional, Harrison, James, additional, Sambles, Christine, additional, Studholme, David, additional, Jeffries, Aaron, additional, Jackson, Leigh, additional, Darby, Alistair, additional, Hiscox, Julian, additional, Paterson, Steve, additional, Iturriza-Gomara, Miren, additional, Jackson, Kathryn, additional, Lucaci, Anita, additional, Vamos, Edith, additional, Hughes, Margaret, additional, Rainbow, Lucille, additional, Eccles, Richard, additional, Nelson, Charlotte, additional, Whitehead, Mark, additional, Turtle, Lance, additional, Haldenby, Sam, additional, Gregory, Richard, additional, Gemmell, Matthew, additional, Wierzbicki, Claudia, additional, Webster, Hermione, additional, de Silva, Thushan, additional, Smith, Nikki, additional, Angyal, Adrienn, additional, Lindsey, Benjamin, additional, Groves, Danielle, additional, Green, Luke, additional, Wang, Dennis, additional, Freeman, Timothy, additional, Parker, Matthew, additional, Keeley, Alexander, additional, Parsons, Paul, additional, Tucker, Rachel, additional, Brown, Rebecca, additional, Wyles, Matthew, additional, Whiteley, Max, additional, Zhang, Peijun, additional, Gallis, Marta, additional, Louka, Stavroula, additional, Constantinidou, Chrystala, additional, Unnikrishnan, Meera, additional, Ott, Sascha, additional, Cheng, Jeffrey, additional, Bridgewater, Hannah, additional, Frost, Lucy, additional, Taylor-Joyce, Grace, additional, Stark, Richard, additional, Baxter, Laura, additional, Alam, Mohammad, additional, Brown, Paul, additional, Aggarwal, Dinesh, additional, Cerda, Alberto, additional, Merrill, Tammy, additional, Wilson, Rebekah, additional, McClure, Patrick, additional, Chappell, Joseph, additional, Tsoleridis, Theocharis, additional, Ball, Jonathan, additional, Buck, David, additional, Todd, John, additional, Green, Angie, additional, Trebes, Amy, additional, MacIntyre-Cockett, George, additional, de Cesare, Mariateresa, additional, Alderton, Alex, additional, Amato, Roberto, additional, Ariani, Cristina, additional, Beale, Mathew, additional, Beaver, Charlotte, additional, Bellis, Katherine, additional, Betteridge, Emma, additional, Bonfield, James, additional, Danesh, John, additional, Dorman, Matthew, additional, Drury, Eleanor, additional, Farr, Ben, additional, Foulser, Luke, additional, Goncalves, Sonia, additional, Goodwin, Scott, additional, Gourtovaia, Marina, additional, Harrison, Ewan, additional, Jackson, David, additional, Jamrozy, Dorota, additional, Johnston, Ian, additional, Kane, Leanne, additional, Kay, Sally, additional, Keatley, Jon-Paul, additional, Kwiatkowski, Dominic, additional, Langford, Cordelia, additional, Lawniczak, Mara, additional, Letchford, Laura, additional, Livett, Rich, additional, Lo, Stephanie, additional, Martincorena, Inigo, additional, McGuigan, Samantha, additional, Nelson, Rachel, additional, Palmer, Steve, additional, Park, Naomi, additional, Patel, Minal, additional, Prestwood, Liam, additional, Puethe, Christoph, additional, Quail, Michael, additional, Rajatileka, Shavanthi, additional, Scott, Carol, additional, Shirley, Lesley, additional, Sillitoe, John, additional, Spencer Chapman, Michael, additional, Thurston, Scott, additional, Tonkin-Hill, Gerry, additional, Weldon, Danni, additional, Rajan, Diana, additional, Bronner, Iraad, additional, Aigrain, Louise, additional, Redshaw, Nicholas, additional, Lensing, Stefanie, additional, Davies, Robert, additional, Whitwham, Andrew, additional, Liddle, Jennifier, additional, Lewis, Kevin, additional, Tovar-Corona, Jaime, additional, Leonard, Steven, additional, Durham, Jillian, additional, Bassett, Andrew, additional, McCarthy, Shane, additional, Moll, Robin, additional, James, Keith, additional, Oliver, Karen, additional, Makunin, Alex, additional, Barrett, Jeff, additional, and Gunson, Rory, additional

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2022
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447. Future-proofing and maximizing the utility of metadata: The PHA4GE SARS-CoV-2 contextual data specification package

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Griffiths, Emma J, primary, Timme, Ruth E, additional, Mendes, Catarina Inês, additional, Page, Andrew J, additional, Alikhan, Nabil-Fareed, additional, Fornika, Dan, additional, Maguire, Finlay, additional, Campos, Josefina, additional, Park, Daniel, additional, Olawoye, Idowu B, additional, Oluniyi, Paul E, additional, Anderson, Dominique, additional, Christoffels, Alan, additional, da Silva, Anders Gonçalves, additional, Cameron, Rhiannon, additional, Dooley, Damion, additional, Katz, Lee S, additional, Black, Allison, additional, Karsch-Mizrachi, Ilene, additional, Barrett, Tanya, additional, Johnston, Anjanette, additional, Connor, Thomas R, additional, Nicholls, Samuel M, additional, Witney, Adam A, additional, Tyson, Gregory H, additional, Tausch, Simon H, additional, Raphenya, Amogelang R, additional, Alcock, Brian, additional, Aanensen, David M, additional, Hodcroft, Emma, additional, Hsiao, William W L, additional, Vasconcelos, Ana Tereza R, additional, and MacCannell, Duncan R, additional

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2022
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