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1. Development of a pseudo-typed virus particle based method to determine the efficacy of virucidal agents

Author

Jordan Thomas, Farah Mughal, Kelly J. Roper, Aurelia Kotsiri, Wejdan Albalawi, Abdullateef Alshehri, Yugandhar B. S. Reddy, Sayandip Mukherjee, Georgios Pollakis, William A. Paxton, and Michael Hoptroff

Subjects
Medicine, Science
Abstract

Abstract The ongoing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has highlighted the threat that viral outbreaks pose to global health. A key tool in the arsenal to prevent and control viral disease outbreaks is disinfection of equipment and surfaces with formulations that contain virucidal agents (VA). However, assessment of the efficacy of virus inactivation often requires live virus assays or surrogate viruses such as Modified Vaccinia Virus Ankara (MVA), which can be expensive, time consuming and technically challenging. Therefore, we have developed a pseudo-typed virus (PV) based approach to assess the inactivation of enveloped viruses with a fast and quantitative output that can be adapted to emerging viruses. Additionally, we have developed a method to completely remove the cytotoxicity of virucidal agents while retaining the required sensitivity to measure PV infectivity. Our results indicated that the removal of cytotoxicity was an essential step to accurately measure virus inactivation. Further, we demonstrated that there was no difference in susceptibility to virus inactivation between PVs that express the envelopes of HIV-1, SARS-CoV-2, and Influenza A/Indonesia. Therefore, we have developed an effective and safe alternative to live virus assays that enables the rapid assessment of virucidal activity for the development and optimization of virucidal reagents.

Published
2024
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2. Quantifying neutralising antibody responses against SARS-CoV-2 in dried blood spots (DBS) and paired sera

Author

Kelly J. Roper, Jordan Thomas, Wejdan Albalawi, Emily Maddocks, Susan Dobson, Abdullateef Alshehri, Francesco G. Barone, Murielle Baltazar, Malcolm G. Semple, Antonia Ho, Lance Turtle, ISARIC4C Consortium, William A. Paxton, and Georgios Pollakis

Subjects
Medicine, Science
Abstract

Abstract The ongoing SARS-CoV-2 pandemic was initially managed by non-pharmaceutical interventions such as diagnostic testing, isolation of positive cases, physical distancing and lockdowns. The advent of vaccines has provided crucial protection against SARS-CoV-2. Neutralising antibody (nAb) responses are a key correlate of protection, and therefore measuring nAb responses is essential for monitoring vaccine efficacy. Fingerstick dried blood spots (DBS) are ideal for use in large-scale sero-surveillance because they are inexpensive, offer the option of self-collection and can be transported and stored at ambient temperatures. Such advantages also make DBS appealing to use in resource-limited settings and in potential future pandemics. In this study, nAb responses in sera, venous blood and fingerstick blood stored on filter paper were measured. Samples were collected from SARS-CoV-2 acutely infected individuals, SARS-CoV-2 convalescent individuals and SARS-CoV-2 vaccinated individuals. Good agreement was observed between the nAb responses measured in eluted DBS and paired sera. Stability of nAb responses was also observed in sera stored on filter paper at room temperature for 28 days. Overall, this study provides support for the use of filter paper as a viable sample collection method to study nAb responses.

Published
2023
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3. The flow of anisotropic nanoparticles in solution and in blood

Author

Jordan Thomas Lovegrove, Ben Kent, Stephan Förster, Christopher J. Garvey, and Martina H. Stenzel

Subjects
anisotropic nanoparticles, blood, drug delivery, microfluidic, microscopy, small angle X‐ray scattering, Biotechnology, TP248.13-248.65
Abstract

Abstract The alignment of anisotropic nanoparticles in flow has been used for a range of applications such as the preparation of strong fibres and the assembly of in‐plane aligned 1D‐nanoobjects that are used for electronic devices, sensors, energy and biological application. Important is also the flow behaviour of nanoparticles that were designed for nanomedical applications such as drug delivery. It is widely observed that non‐spherical nanoparticles have longer circulation times and a more favourable biodistribution. To be able to understand this behaviour, researchers have turned to analyzing the flow of non‐spherical nanoparticles in the blood stream. In this review, an overview of microfluidic techniques that are used to monitor the alignment of anisotropic nanoparticles in solution will be provided, which includes analysis by small angle X‐ray scattering (SAXS) and polarized light microscopy. The flow of these nanoparticles in blood is then discussed as the presence of red blood cells causes margination of some nanoparticles. Using fluorescence microscopy, the extent of margination can be identified, which coincides with the ability of nanoparticles to adhere to the cells grown along the wall. While these studies are mainly carried out in vitro using blood, initial investigations in vivo were able to confirm the unusual flow of anisotropic nanoparticles.

Published
2023
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4. The ecology of viruses in urban rodents with a focus on SARS-CoV-2

Author

Adam M. Fisher, George Airey, Yuchen Liu, Matthew Gemmell, Jordan Thomas, Eleanor G. Bentley, Mark A. Whitehead, William A. Paxton, Georgios Pollakis, Steve Paterson, and Mark Viney

Subjects
Urban, rodents, virus, virome, COVID, zoonosis, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

ABSTRACTWild animals are naturally infected with a range of viruses, some of which may be zoonotic. During the human COVID pandemic there was also the possibility of rodents acquiring SARS-CoV-2 from people, so-called reverse zoonoses. To investigate this, we sampled rats (Rattus norvegicus) and mice (Apodemus sylvaticus) from urban environments in 2020 during the human COVID-19 pandemic. We metagenomically sequenced lung and gut tissue and faeces for viruses, PCR screened for SARS-CoV-2, and serologically surveyed for anti-SARS-CoV-2 Spike antibodies. We describe the range of viruses that we found in these two rodent species. We found no molecular evidence of SARS-CoV-2 infection, though in rats we found lung antibody responses and evidence of neutralization ability that are consistent with rats being exposed to SARS-CoV-2 and/or exposed to other viruses that result in cross-reactive antibodies.

Published
2023
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6. Glycan dependent phenotype differences of HIV-1 generated from macrophage versus CD4+ T helper cell populations

Author

Edwin J. Heeregrave, Jordan Thomas, Toni M. van Capel, Esther C. de Jong, Georgios Pollakis, and William A. Paxton

Subjects
HIV-1, macrophages, T helper, glycan, phenotypes, Immunologic diseases. Allergy, RC581-607
Abstract

Human immunodeficiency virus type 1 (HIV-1) is able to infect a variety of cell types with differences in entry efficiency and replication kinetics determined by the host cell type or the viral phenotype. The phenotype of the virus produced from these various cell types, including infectivity, co-receptor usage and neutralisation sensitivity, may also be affected by the characteristics of the producing cell. This can be due to incorporation of variant cell-specific molecules or differences in post-translational modifications of the gp41/120 envelope. In this study we produced genetically identical virus strains from macrophages, CD4-enriched lymphocytes as well as Th1 and Th2 CD4+ cell lines and compared each different virus stock for their infectivity in various cell types and sensitivity to neutralisation. In order to study the effect of the producer host cell on the virus phenotype, virus stocks were normalised on infectivity and were sequenced to confirm env gene homogeneity. Virus production by Th1 or Th2 cells did not compromise infectivity of the variant cell types tested. We observed no difference in sensitivity to co-receptor blocking agents upon viral passage through Th1 and Th2 CD4+ cell lineages nor did this affect DC-SIGN-mediated viral capture as measured in a transfer assay to CD4+ lymphocytes. Virus produced by macrophages was comparably sensitive to CC-chemokine inhibition as was virus generated from the array of CD4+ lymphocytes. We identified that virus produced from macrophages was fourteen times more resistant to 2G12 neutralisation than virus produced from CD4+ lymphocytes. Macrophage-produced dual-tropic (R5/X4) virus was six times more efficiently transmitted to CD4+ cells than lymphocyte-derived HIV-1 (p

Published
2023
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7. SARS-CoV-2 antibody responses associate with sex, age and disease severity in previously uninfected people admitted to hospital with COVID-19: An ISARIC4C prospective study

Author

Eleanor Parker, Jordan Thomas, Kelly J. Roper, Samreen Ijaz, Tansy Edwards, Federica Marchesin, Ksenia Katsanovskaja, Lauren Lett, Christopher Jones, Hayley E. Hardwick, Chris Davis, Elen Vink, Sarah E. McDonald, Shona C. Moore, Steve Dicks, Keerthana Jegatheesan, Nicola J. Cook, Joshua Hope, Peter Cherepanov, Myra O. McClure, J. Kenneth Baillie, Peter J. M. Openshaw, Lance Turtle, Antonia Ho, Malcolm G. Semple, William A. Paxton, Richard S. Tedder, Georgios Pollakis, and ISARIC4C Investigators

Subjects
SARS-CoV-2, immunology, COVID-19, virus, disease, serology, Immunologic diseases. Allergy, RC581-607
Abstract

The SARS-CoV-2 pandemic enables the analysis of immune responses induced against a novel coronavirus infecting immunologically naïve individuals. This provides an opportunity for analysis of immune responses and associations with age, sex and disease severity. Here we measured an array of solid-phase binding antibody and viral neutralising Ab (nAb) responses in participants (n=337) of the ISARIC4C cohort and characterised their correlation with peak disease severity during acute infection and early convalescence. Overall, the responses in a Double Antigen Binding Assay (DABA) for antibody to the receptor binding domain (anti-RBD) correlated well with IgM as well as IgG responses against viral spike, S1 and nucleocapsid protein (NP) antigens. DABA reactivity also correlated with nAb. As we and others reported previously, there is greater risk of severe disease and death in older men, whilst the sex ratio was found to be equal within each severity grouping in younger people. In older males with severe disease (mean age 68 years), peak antibody levels were found to be delayed by one to two weeks compared with women, and nAb responses were delayed further. Additionally, we demonstrated that solid-phase binding antibody responses reached higher levels in males as measured via DABA and IgM binding against Spike, NP and S1 antigens. In contrast, this was not observed for nAb responses. When measuring SARS-CoV-2 RNA transcripts (as a surrogate for viral shedding) in nasal swabs at recruitment, we saw no significant differences by sex or disease severity status. However, we have shown higher antibody levels associated with low nasal viral RNA indicating a role of antibody responses in controlling viral replication and shedding in the upper airway. In this study, we have shown discernible differences in the humoral immune responses between males and females and these differences associate with age as well as with resultant disease severity.

Published
2023
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9. Safety and effects of SGLT-2 inhibitor use among LVAD patients with type 2 diabetes mellitus

Author

Matthew Cagliostro, Prabhjot Hundal, Peter Ting, Sonika Patel, Sangita Sudarshan, Jordan Thomas, Kathleen Morris, Donna M. Mancini, Noah Moss, Anuradha Lala, Ashwin Ravichandran, and Sumeet S. Mitter

Subjects
SGLT2 inhibitors (SGLT2i), Heart failure, Left ventricular assist device (LVAD), Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

SGLT-2 inhibitors have been shown to confer reduced risk of adverse cardiovascular events in patients with heart failure, and have also been studied preliminarily among heart transplant patients, with overall positive findings. Use of SGLT-2 inhibitors among patients with durable mechanical circulatory support has not been studied. Here we present our results from a combined retrospective cohort of LVAD patients on SGLT-2 inhibitors at two major academic centers, which showed a good safety profile but prompted questions for further investigation. We advocate for further research into the safety and impact of SGLT-2 inhibitors among LVAD patients.

Published
2022
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10. Impact of post-arrest care variation on hospital performance after out-of-hospital cardiac arrest

Author

Ryan Huebinger, Jordan Thomas, Benjamin S. Abella, John Waller-Delarosa, Rabab Al-Araji, Richard Witkov, Normandy Villa, Peter Nikonowicz, Taylor Renbarger, Micah Panczyk, and Bentley Bobrow

Subjects
Cardiac arrest, Out-of-Hospital Cardiac Arrest, Post-arrest care, TTM, PCI, Specialties of internal medicine, RC581-951
Abstract

Background: Large variation exists for out-of-hospital-cardiac-arrest (OHCA) prehospital care, but less is known about variations in post-arrest care. We sought to evaluate variation in post-arrest care in Texas as well as factors associated with higher performing hospitals. Methods: We analyzed data in Texas Cardiac Arrest Registry to Enhance Survival (TX-CARES), including all adult, non-traumatic OHCAs from 1/1/2014 through 12/31/ 2020 that survived to hospital admission. We first evaluated variability in provisions of post-arrest care and outcomes. We then stratified hospitals into quartiles based on their rate of survival and evaluated the association between improving quartiles and care. Lastly, we evaluated for outliers in post-arrest care and outcomes using a mixed-effect regression model. Results: We analyzed 7,842 OHCAs admitted to 146 hospitals. We identified large variations in post-arrest care, including targeted temperature management (TTM) (IQR 7.0–51.1%), left heart catheterization (LHC) (IQ 0–25%), and percutaneous coronary intervention (PCI) (IQR 0–10.3%). Higher performing hospital quartiles were associated with higher rates of TTM (aOR 1.42, 95% CI 1.36–1.49), LHC (aOR 2.07, 95% CI 1.92–2.23), and PCI (aOR 2.02, 95% CI 1.81–2.25); but lower rates of bystander CPR (aOR 0.90, 95% CI 0.87–0.94). We identified numerous performance outlier hospitals; 39 for TTM, 34 for PCI, 9 for survival to discharge, and 24 for survival with good neurologic function. Conclusions: Post-arrest care varied widely across Texas hospitals. Hospitals with higher rates of survival to discharge had increased rates of TTM, LHC, and PCI but not bystander CPR.

Published
2022
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11. Implementation of corticosteroids in treatment of COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK: prospective, cohort study

Author

Fiina Närhi, BMedSci, S Ramani Moonesinghe, ProfMD[Res], Susan D Shenkin, PhD, Thomas M Drake, MBChB, Rachel H Mulholland, MSci, Cara Donegan, BSc, Jake Dunning, PhD, Cameron J Fairfield, MBChB, Michelle Girvan, BSc, Hayley E Hardwick, Antonia Ho, PhD, Gary Leeming, BA, Jonathan S Nguyen-Van-Tam, ProfPhD, Riinu Pius, PhD, Clark D Russell, MBChB, Catherine A Shaw, PhD, Rebecca G Spencer, LLM, Lance Turtle, PhD, Peter J M Openshaw, ProfPhD, J Kenneth Baillie, ProfPhD, Ewen M Harrison, ProfPhD, Malcolm G Semple, ProfPhD, Annemarie B Docherty, PhD, J Kenneth Baillie, Malcolm G Semple, Peter JM Openshaw, Gail Carson, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, Wendy S Barclay, Debby Bogaert, Meera Chand, Kanta Chechi, Graham S Cooke, Ana da Silva Filipe, Thushan de Silva, Annemarie B Docherty, Gon¸alo dos Santos Correia, Marc-Emmanuel Dumas, Jake Dunning, Tom Fletcher, Christopher A Green, William Greenhalf, Julian Griffin, Rishi K Gupta, Ewen M Harrison, Julian A Hiscox, Antonia YW Ho, Peter W Horby, Samreen Ijaz, Say Khoo, Paul Klenerman, Andrew Law, Matthew Lewis, Sonia Liggi, Wei Shen Lim, Lynn Maslen, Alexander J Mentzer, Laura Merson, Alison M Meynert, Shona C Moore, Mahdad Noursadeghi, Michael Olanipekun, Anthonia Osagie, Massimo Palmarini, Carlo Palmieri, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Clark D Russell, Vanessa Sancho-Shimizu, Caroline Sands, Janet T Scott, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Olivia V Swann, Zoltan Takats, Panteleimon Takis, Richard S Tedder, AA Roger Thompson, Emma C Thomson, Ryan S Thwaites, Lance CW Turtle, Maria Zambon, Hayley Hardwick, Chloe Donohue, Fiona Griffiths, Wilna Oosthuyzen, Cara Donegan, Rebecca G Spencer, Lisa Norman, Riinu Pius, Thomas M Drake, Cameron J Fairfield, Stephen R Knight, Kenneth A Mclean, Derek Murphy, Catherine A Shaw, Jo Dalton, Michelle Girvan, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Daniel Plotkin, James Lee, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, Victoria Shaw, Sarah E McDonald, Seán Keating, Katie A. Ahmed, Jane A Armstrong, Milton Ashworth, Innocent G Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin WA Catterall, Jordan J Clark, Emily A Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis WS Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Rebecca L Jensen, Christopher B Jones, Trevor R Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S Miah, Joanna Middleton, Joyce Mitchell, Ellen G Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E Shaw, Rebecca K Shears, Benjamin Small, Krishanthi S Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Sarah McCafferty, Richard Clark, Angie Fawkes, Kirstie Morrice, Alan Maclean, Nicola Wrobel, Lorna Donelly, Audrey Coutts, Katarzyna Hafezi, Louise MacGillivray, Tammy Gilchrist, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, Sam Allen, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Colin Berry, Nicola Best, Pieter Bothma, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Andrew Drummond, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Lillian Norris, Matthew K. O'Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Tim Planche, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Bobby Ruge, Brendan Ryan, Taranprit Saluja, Matthias Schmid, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Nick Vallotton, Rama Vancheeswaran, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Sarah Sarah, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wootton, Andrew Workman, Bryan Yates, and Peter Young

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Summary: Background: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. Methods: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. Findings: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. Interpretation: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. Funding: UK National Institute for Health Research and UK Medical Research Council.

Published
2022
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12. The HCV Envelope Glycoprotein Down-Modulates NF-κB Signalling and Associates With Stimulation of the Host Endoplasmic Reticulum Stress Pathway

Author

Lindsay G. A. McKay, Jordan Thomas, Wejdan Albalawi, Antoine Fattaccioli, Marc Dieu, Alessandra Ruggiero, Jane A. McKeating, Jonathan K. Ball, Alexander W. Tarr, Patricia Renard, Georgios Pollakis, and William A. Paxton

Subjects
immunity, HIV-LTR, HCV, NF-κB, endoplasmic reticulum stress, Immunologic diseases. Allergy, RC581-607
Abstract

Following acute HCV infection, the virus establishes a chronic disease in the majority of patients whilst few individuals clear the infection spontaneously. The precise mechanisms that determine chronic HCV infection or spontaneous clearance are not completely understood but are proposed to be driven by host and viral genetic factors as well as HCV encoded immunomodulatory proteins. Using the HIV-1 LTR as a tool to measure NF-κB activity, we identified that the HCV E1E2 glycoproteins and more so the E2 protein down-modulates HIV-1 LTR activation in 293T, TZM-bl and the more physiologically relevant Huh7 liver derived cell line. We demonstrate this effect is specifically mediated through inhibiting NF-κB binding to the LTR and show that this effect was conserved for all HCV genotypes tested. Transcriptomic analysis of 293T cells expressing the HCV glycoproteins identified E1E2 mediated stimulation of the endoplasmic reticulum (ER) stress response pathway and upregulation of stress response genes such as ATF3. Through shRNA mediated inhibition of ATF3, one of the components, we observed that E1E2 mediated inhibitory effects on HIV-1 LTR activity was alleviated. Our in vitro studies demonstrate that HCV Env glycoprotein activates host ER Stress Pathways known to inhibit NF-κB activity. This has potential implications for understanding HCV induced immune activation as well as oncogenesis.

Published
2022
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13. The impact of viral mutations on recognition by SARS-CoV-2 specific T cells

Author

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

Subjects
Phylogenetics, Molecular biology, Immunology, Immune response, Virology, Science
Abstract

Summary: We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.

Published
2021
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14. HIV and SARS-CoV-2 Co-Infection: From Population Study Evidence to In Vitro Studies

Author

Chiara Stefani, Tobia Fantoni, Michele Bissoli, Jordan Thomas, and Alessandra Ruggiero

Subjects
HIV-1, SARS-CoV-2, co-infections, anti-retroviral drugs, Science
Abstract

Human immunodeficiency virus type 1 (HIV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused two major viral outbreaks during the last century. Two major aspects of HIV-1 and SARS-CoV-2 co-infection have been extensively investigated and deserve attention. First, the impact of the co-infection on the progression of disease caused by HIV-1 or SARS-CoV-2. Second, the impact of the HIV-1 anti-retroviral treatment on SARS-CoV-2 infection. In this review, we aim to summarize and discuss the works produced since the beginning of the SARS-CoV-2 pandemic ranging from clinical studies to in vitro experiments in the context of co-infection and drug development.

Published
2022
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15. Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study

Author

David Price, Mark Roberts, Andrew Walden, Jason Kendall, Clark D Russell, Natalie Pattison, Daniel B Hawcutt, George Koshy, Adam Finn, Ellen G Murphy, Ewen M Harrison, Maria Zambon, Michael Murphy, Tom Solomon, Carrol Gamble, Laura Marsh, Nicholas Barrett, Nigel Chee, Paul Dark, Clive Graham, Andrew Law, Richard J Mellanby, Gail Carson, Jake Dunning, Laura Merson, Ingeborg Welters, Stephen R Knight, Thomas M Drake, Tamas Szakmany, Robert Thompson, Richard Smith, Ian Handel, Kenneth A McLean, Sam Douthwaite, David Baxter, Patrick Lillie, Dougal Atkinson, Chris Dunn, James Moon, Paul Klenerman, Catherine Hartley, Mandeep Phull, Pieter Bothma, Craig Morris, Adam Wolverson, Ana Alegria, Lawrence Wilson, Susan Jain, James Limb, Vanessa Linnett, Chris Dawson, Jason Cupitt, Sam Waddy, Guy Rousseau, Andrew Burtenshaw, Devender Roberts, Samreen Ijaz, Mark Nelson, Anthony Evans, Meera Chand, Wei Shen Lim, Catherine A Shaw, Cameron J Fairfield, Timothy S Walsh, Anil Hormis, Peter W Horby, Marlies Ostermann, Tim Reynolds, Mark Lyttle, Bryan Yates, Chloe Donohue, Anil Sharma, Jenny Child, Elaine Hardy, Julian A Hiscox, Debby Bogaert, Richard Stewart, Martin Williams, Adriano G Rossi, Catherine Cosgrove, David M Griffith, William Greenhalf, Thapas Nagarajan, Saye Khoo, Annemarie B Docherty, Christopher A Green, Hayley E Hardwick, Riinu Pius, Lisa Norman, Louise Sigfrid, Sophie Halpin, Clare Jackson, J Kenneth Baillie, Malcolm G Semple, Manu Shankar-Hari, Carlo Palmieri, Lance Turtle, Stuart Hartshorn, Rishi K Gupta, Tom Fletcher, Michelle Girvan, Peter J M Openshaw, Beatrice Alex, Benjamin Bach, Wendy S Barclay, Graham S Cooke, Alexander J Mentzer, Alison M Meynert, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Vanessa Sancho-Shimizu, Janet T Scott, Shiranee Sriskandan, David Stuart, Charlotte Summers, Richard S Tedder, Emma C Thomson, Ryan S Thwaites, Lance C W Turtle, Hayley Hardwick, Wilna Oosthuyzen, Fiona Griffiths, Derek Murphy, Jo Dalton, Egle Saviciute, Stephanie Roberts, Janet Harrison, Marie Connor, Gary Leeming, Ross Hendry, Victoria Shaw, Sarah McDonald, Katie A Ahmed, Jane A Armstrong, Milton Ashworth, Innocent G Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Jordan J Clark, Emily A Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Philip Dyer, Angela Elliott, Lewis W S Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Rebecca L Jensen, Christopher B Jones, Trevor R Jones, Shadia Khandaker, Katharine King, Robyn T Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S Miah, Joanna Middleton, Joyce Mitchell, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Debby Sales, Victoria E Shaw, Rebecca K Shears, Benjamin Small, Krishanthi S Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jordan Thomas, Erwan Trochu, Eve Wilcock, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Brian Angus, Abdul Ashish, Shahedal Bari, Gavin Barlow, Stella Barnass, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Nicola Best, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Vikki Caruth, David Chadwick, Duncan Chambler, Srikanth Chukkambotla, Tom Clark, Paul Collini, Maria-Teresa Cutino-Moguel, Samir Dervisevic, Phil Donnison, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Duncan Fullerton, Sanjeev Garg, Atul Garg, Jo Godden, Arthur Goldsmith, Daniel Harvey, Peter Havalda, Maria Hobrok, Luke Hodgson, Michael Jacobs, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, Shondipon Laha, Susan Larkin, Tamas Leiner, Jeff Little, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, Elinoor Moore, Patrick Morgan, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Megan Nagel, Igor Otahal, Mark Pais, Selva Panchatsharam, Hassan Paraiso, Brij Patel, Justin Pepperell, Mark Peters, Stefania Pintus, Jagtur Singh Pooni, Frank Post, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Neil Richardson, Alistair Rose, Brendan Ryan, Taranprit Saluja, Aarti Shah, Prad Shanmuga, Anna Shawcross, Jeremy Sizer, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Pradeep Subudhi, Kate Tatham, Jo Thomas, Chris Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Andrew Ustianowski, Nick Vallotton, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Rachel Wake, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Meme Wijesinghe, Stephen Winchester, Martin Wiselka, Andrew Workman, Peter Young, James Scott-Brown, Will Reynolds, Jolanta Tanianis-Hughes, Chrisopher Fegan, Danai Papakonstantinou, Effrossyni Gkrania-Klotsas, Kerri Devine, Daniel G Wootton, Padmasayee Papineni, Benjamin W A Catterall, Lara Lavelle-Langham, Emily Cass, Alejandra Doce Carracedo, Lisa Flaherty, Nicole Maziere, Hannah Massey, Anthony Holmes, Nicola Carlucci, Matthew K O'Shea, Libby van Tonder, Emma A Hurst, Natalie Z Homer, Scott G Denham, Paul A Holloway, Romit J Samanta, Ana da Silva Filipe, Thushan de Silva, A A Roger Thompson, Ruth Lyons, Murray Wham, Sara Clohisey, Sara McDonald, Seán Keating, Lorna Finch, P Matthew Ridley, J Eunice Zhang, Lee Murphy, Nicola Wrobel, Sarah McCafferty, Kirstie Morrice, Alan MacLean, Erin L Aldera, Sneha Basude, Steven Laird, and Antonia Ying Wai Ho

Subjects
Medicine
Abstract

Objectives The steroid hormone vitamin D has roles in immunomodulation and bone health. Insufficiency is associated with susceptibility to respiratory infections. We report 25-hydroxy vitamin D (25(OH)D) measurements in hospitalised people with COVID-19 and influenza A and in survivors of critical illness to test the hypotheses that vitamin D insufficiency scales with illness severity and persists in survivors.Design Cross-sectional study.Setting and participants Plasma was obtained from 295 hospitalised people with COVID-19 (International Severe Acute Respiratory and emerging Infections Consortium (ISARIC)/WHO Clinical Characterization Protocol for Severe Emerging Infections UK study), 93 with influenza A (Mechanisms of Severe Acute Influenza Consortium (MOSAIC) study, during the 2009–2010 H1N1 pandemic) and 139 survivors of non-selected critical illness (prior to the COVID-19 pandemic). Total 25(OH)D was measured by liquid chromatography-tandem mass spectrometry. Free 25(OH)D was measured by ELISA in COVID-19 samples.Outcome measures Receipt of invasive mechanical ventilation (IMV) and in-hospital mortality.Results Vitamin D insufficiency (total 25(OH)D 25–50 nmol/L) and deficiency (

Published
2021
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17. Measuring the Success of HIV-1 Cure Strategies

Author

Jordan Thomas, Alessandra Ruggiero, William A. Paxton, and Georgios Pollakis

Subjects
HIV-1, persistence, latency, latent reservoir, DNA/RNA quantification, Microbiology, QR1-502
Abstract

HIV-1 eradication strategies aim to achieve viral remission in the absence of antiretroviral therapy (ART). The development of an HIV-1 cure remains challenging due to the latent reservoir (LR): long-lived CD4 T cells that harbor transcriptionally silent HIV-1 provirus. The LR is stable despite years of suppressive ART and is the source of rebound viremia following therapy interruption. Cure strategies such as “shock and kill” aim to eliminate or reduce the LR by reversing latency, exposing the infected cells to clearance via the immune response or the viral cytopathic effect. Alternative strategies include therapeutic vaccination, which aims to prime the immune response to facilitate control of the virus in the absence of ART. Despite promising advances, these strategies have been unable to significantly reduce the LR or increase the time to viral rebound but have provided invaluable insight in the field of HIV-1 eradication. The development and assessment of an HIV-1 cure requires robust assays that can measure the LR with sufficient sensitivity to detect changes that may occur following treatment. The viral outgrowth assay (VOA) is considered the gold standard method for LR quantification due to its ability to distinguish intact and defective provirus. However, the VOA is time consuming and resource intensive, therefore several alternative assays have been developed to bridge the gap between practicality and accuracy. Whilst a cure for HIV-1 infection remains elusive, recent advances in our understanding of the LR and methods for its eradication have offered renewed hope regarding achieving ART free viral remission.

Published
2020
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18. Recommendations on best available science for the United States National Seismic Hazard Model

Author

Anderson, John G, Atkinson, Gail M, Baker, Jack W, Campbell, Kenneth W, DeShon, Heather R, Jordan, Thomas H, Kelson, Keith I, Shome, Nilesh, and Stewart, Jonathan P

Abstract

The 50 state update to the 2023 United States National Seismic Hazard Model (NSHM) is the latest in a sequence published by the U. S. Geological Survey (USGS). The 2023 NSHM is intended for use in building codes and similar applications at return periods of 475 years (corresponding to exceedance probabilities of 10% in 50 years) or longer. In reviewing the model, the NSHM Program Steering Committee, consisting of the authors of this paper, considered the characteristics of “best available science” that are applicable to the NSHM. Best available science must perform better than the previous NSHM, and there should be no available alternatives that could improve the models. The following are suggested characteristics of “best available science”:A) Clear objectivesB) Rigorous conceptual modelC) Timely, relevant and inclusiveD) Verified and reproducibleE) Validated intermediate and final modelsF) Replicable within uncertaintiesG) Peer reviewedH) Permanent documentationThis article focuses on the justification for, and intent of, the above criteria for best available science.

Published
2024

19. Measuring Proviral HIV-1 DNA: Hurdles and Improvements to an Assay Monitoring Integration Events Utilising Human Alu Repeat Sequences

Author

Eva Malatinkova, Jordan Thomas, Ward De Spiegelaere, Sofie Rutsaert, Anna Maria Geretti, Georgios Pollakis, William A. Paxton, Linos Vandekerckhove, and Alessandra Ruggiero

Subjects
integrated HIV-1, Alu-gag, Alu-5LTR, quantification, reservoir, Science
Abstract

Integrated HIV-1 DNA persists despite antiretroviral therapy and can fuel viral rebound following treatment interruption. Hence, methods to specifically measure the integrated HIV-1 DNA portion only are important to monitor the reservoir in eradication trials. Here, we provide an up-to-date overview of the literature on the different approaches used to measure integrated HIV-1 DNA. Further, we propose an implemented standard-curve free assay to quantify integrated HIV-1 DNA, so-called Alu-5LTR PCR, which utilises novel primer combinations. We tested the Alu-5LTR PCR in 20 individuals on suppressive ART for a median of nine years; the results were compared to those produced with the standard-free Alu-gag assay. The numbers of median integrated HIV-1 DNA copies were 5 (range: 1–12) and 14 (5–26) with the Alu-gag and Alu-5LTR, respectively. The ratios between Alu-gag vs Alu-5LTR results were distributed within the cohort as follows: most patients (12/20, 60%) provided ratios between 2–5, with 3/20 (15%) and 5/20 (25%) being below or above this range, respectively. Alu-5LTR assay sensitivity was also determined using an “integrated standard”; the data confirmed the increased sensitivity of the assay, i.e., equal to 0.25 proviruses in 10,000 genomes. This work represents an improvement in the field of measuring proviral HIV-1 DNA that could be employed in future HIV-1 persistence and eradication studies.

Published
2021
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20. Schistosoma mansoni soluble egg antigen (SEA) and recombinant Omega-1 modulate induced CD4+ T-lymphocyte responses and HIV-1 infection in vitro.

Author

Emily Eim Mouser, Georgios Pollakis, Hermelijn H Smits, Jordan Thomas, Maria Yazdanbakhsh, Esther C de Jong, and William A Paxton

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Parasitic helminths evade, skew and dampen human immune responses through numerous mechanisms. Such effects will likely have consequences for HIV-1 transmission and disease progression. Here we analyzed the effects that soluble egg antigen (SEA) from Schistosoma mansoni had on modulating HIV-1 infection and cytokine/chemokine production in vitro. We determined that SEA, specifically through kappa-5, can potently bind to DC-SIGN and thereby blocks DC-SIGN mediated HIV-1 trans-infection (p

Published
2019
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21. Author Correction: GLORIA - A globally representative hyperspectral in situ dataset for optical sensing of water quality

Author

Lehmann, Moritz K, Gurlin, Daniela, Pahlevan, Nima, Alikas, Krista, Conroy, Ted, Anstee, Janet, Balasubramanian, Sundarabalan V, Barbosa, Cláudio CF, Binding, Caren, Bracher, Astrid, Bresciani, Mariano, Burtner, Ashley, Cao, Zhigang, Dekker, Arnold G, Di Vittorio, Courtney, Drayson, Nathan, Errera, Reagan M, Fernandez, Virginia, Ficek, Dariusz, Fichot, Cédric G, Gege, Peter, Giardino, Claudia, Gitelson, Anatoly A, Greb, Steven R, Henderson, Hayden, Higa, Hiroto, Rahaghi, Abolfazl Irani, Jamet, Cédric, Jiang, Dalin, Jordan, Thomas, Kangro, Kersti, Kravitz, Jeremy A, Kristoffersen, Arne S, Kudela, Raphael, Li, Lin, Ligi, Martin, Loisel, Hubert, Lohrenz, Steven, Ma, Ronghua, Maciel, Daniel A, Malthus, Tim J, Matsushita, Bunkei, Matthews, Mark, Minaudo, Camille, Mishra, Deepak R, Mishra, Sachidananda, Moore, Tim, Moses, Wesley J, Nguyễn, Hà, Novo, Evlyn MLM, Novoa, Stéfani, Odermatt, Daniel, O’Donnell, David M, Olmanson, Leif G, Ondrusek, Michael, Oppelt, Natascha, Ouillon, Sylvain, Pereira Filho, Waterloo, Plattner, Stefan, Verdú, Antonio Ruiz, Salem, Salem I, Schalles, John F, Simis, Stefan GH, Siswanto, Eko, Smith, Brandon, Somlai-Schweiger, Ian, Soppa, Mariana A, Spyrakos, Evangelos, Tessin, Elinor, van der Woerd, Hendrik J, Vander Woude, Andrea, Vandermeulen, Ryan A, Vantrepotte, Vincent, Wernand, Marcel R, Werther, Mortimer, Young, Kyana, and Yue, Linwei

Subjects
Data Management and Data Science, Information and Computing Sciences
Published
2023

22. GLORIA - A globally representative hyperspectral in situ dataset for optical sensing of water quality

Author

Lehmann, Moritz K, Gurlin, Daniela, Pahlevan, Nima, Alikas, Krista, Conroy, Ted, Anstee, Janet, Balasubramanian, Sundarabalan V, Barbosa, Cláudio CF, Binding, Caren, Bracher, Astrid, Bresciani, Mariano, Burtner, Ashley, Cao, Zhigang, Dekker, Arnold G, Di Vittorio, Courtney, Drayson, Nathan, Errera, Reagan M, Fernandez, Virginia, Ficek, Dariusz, Fichot, Cédric G, Gege, Peter, Giardino, Claudia, Gitelson, Anatoly A, Greb, Steven R, Henderson, Hayden, Higa, Hiroto, Rahaghi, Abolfazl Irani, Jamet, Cédric, Jiang, Dalin, Jordan, Thomas, Kangro, Kersti, Kravitz, Jeremy A, Kristoffersen, Arne S, Kudela, Raphael, Li, Lin, Ligi, Martin, Loisel, Hubert, Lohrenz, Steven, Ma, Ronghua, Maciel, Daniel A, Malthus, Tim J, Matsushita, Bunkei, Matthews, Mark, Minaudo, Camille, Mishra, Deepak R, Mishra, Sachidananda, Moore, Tim, Moses, Wesley J, Nguyễn, Hà, Novo, Evlyn MLM, Novoa, Stéfani, Odermatt, Daniel, O’Donnell, David M, Olmanson, Leif G, Ondrusek, Michael, Oppelt, Natascha, Ouillon, Sylvain, Pereira Filho, Waterloo, Plattner, Stefan, Verdú, Antonio Ruiz, Salem, Salem I, Schalles, John F, Simis, Stefan GH, Siswanto, Eko, Smith, Brandon, Somlai-Schweiger, Ian, Soppa, Mariana A, Spyrakos, Evangelos, Tessin, Elinor, van der Woerd, Hendrik J, Vander Woude, Andrea, Vandermeulen, Ryan A, Vantrepotte, Vincent, Wernand, Marcel R, Werther, Mortimer, Young, Kyana, and Yue, Linwei

Subjects
Earth Sciences, Geomatic Engineering, Engineering
Abstract

The development of algorithms for remote sensing of water quality (RSWQ) requires a large amount of in situ data to account for the bio-geo-optical diversity of inland and coastal waters. The GLObal Reflectance community dataset for Imaging and optical sensing of Aquatic environments (GLORIA) includes 7,572 curated hyperspectral remote sensing reflectance measurements at 1 nm intervals within the 350 to 900 nm wavelength range. In addition, at least one co-located water quality measurement of chlorophyll a, total suspended solids, absorption by dissolved substances, and Secchi depth, is provided. The data were contributed by researchers affiliated with 59 institutions worldwide and come from 450 different water bodies, making GLORIA the de-facto state of knowledge of in situ coastal and inland aquatic optical diversity. Each measurement is documented with comprehensive methodological details, allowing users to evaluate fitness-for-purpose, and providing a reference for practitioners planning similar measurements. We provide open and free access to this dataset with the goal of enabling scientific and technological advancement towards operational regional and global RSWQ monitoring.

Published
2023

23. Playing vs. nonplaying aerobic training in tennis: physiological and performance outcomes.

Author

Vincent Pialoux, Cyril Genevois, Arnaud Capoen, Scott C Forbes, Jordan Thomas, and Isabelle Rogowski

Subjects
Medicine, Science
Abstract

This study compared the effects of playing and nonplaying high intensity intermittent training (HIIT) on physiological demands and tennis stroke performance in young tennis players. Eleven competitive male players (13.4 ± 1.3 years) completed both a playing and nonplaying HIIT session of equal distance, in random order. During each HIIT session, heart rate (HR), blood lactate, and ratings of perceived exertion (RPE) were monitored. Before and after each HIIT session, the velocity and accuracy of the serve, and forehand and backhand strokes were evaluated. The results demonstrated that both HIIT sessions achieved an average HR greater than 90% HRmax. The physiological demands (average HR) were greater during the playing session compared to the nonplaying session, despite similar lactate concentrations and a lower RPE. The results also indicate a reduction in shot velocity after both HIIT sessions; however, the playing HIIT session had a more deleterious effect on stroke accuracy. These findings suggest that 1) both HIIT sessions may be sufficient to develop maximal aerobic power, 2) playing HIIT sessions provide a greater physiological demand with a lower RPE, and 3) playing HIIT has a greater deleterious effect on stroke performance, and in particular on the accuracy component of the ground stroke performance, and should be incorporated appropriately into a periodization program in young male tennis players.

Published
2015
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25. Effect of beta-alanine supplementation on the onset of blood lactate accumulation (OBLA) during treadmill running: Pre/post 2 treatment experimental design

Author

Misic Mark, Lukaszuk Judith, Jordan Thomas, and Umoren Josephine

Subjects
Nutrition. Foods and food supply, TX341-641, Sports medicine, RC1200-1245
Abstract

Abstract Background β-Alanine (βA) has been shown to improve performance during cycling. This study was the first to examine the effects of βA supplementation on the onset of blood lactate accumulation (OBLA) during incremental treadmill running. Methods Seventeen recreationally-active men (mean ± SE 24.9 ± 4.7 yrs, 180.6 ± 8.9 cm, 79.25 ± 9.0 kg) participated in this randomized, double-blind, placebo-controlled pre/post test 2-treatment experimental design. Subjects participated in two incremental treadmill tests before and after 28 days of supplementation with either βA (6.0 g·d-1)(βA, n = 8) or an equivalent dose of Maltodextrin as the Placebo (PL, n = 9). Heart rate, percent heart rate maximum (%HRmax), %VO2max@OBLA (4.0 mmol.L-1 blood lactate concentration) and VO2max (L.min-1) were determined for each treadmill test. Friedman test was used to determine within group differences; and Mann-Whitney was used to determine between group differences for pre and post values (p < 0.05). Results The βA group experienced a significant rightward shift in HR@OBLA beats.min-1 (p < 0.01) pre/post (161.6 ± 19.2 to 173.6 ± 9.9) but remained unchanged in the PL group (166.8 ± 15.8 to 169.6 ± 16.1). The %HRmax@OBLA increased (p < 0.05) pre/post in the βA group (83.0% ± 9.7 to 88.6% ± 3.7) versus no change in the PL group (86.3 ± % 4.8 to 87.9% ± 7.2). The %VO2max@OBLA increased (p < 0.05) in the βA group pre/post (69.1 ± 11.0 to 75.6 ± 10.7) but remained unchanged in the PL group (73.3 ± 7.3 to 74.3 ± 7.3). VO2max (L.min-1) decreased (p < 0.01) in the βA group pre/post (4.57 ± 0.8 to 4.31 ± 0.8) versus no change in the PL group (4.04 ± 0.7 to 4.18 ± 0.8). Body mass kg increased (p < 0.05) in the βA group pre/post (77.9 ± 9.0 to 78.3 ± 9.3) while the PL group was unchanged (80.6 ± 9.1 to 80.4 ± 9.0). Conclusions βA supplementation for 28 days enhanced sub-maximal endurance performance by delaying OBLA. However, βA supplemented individuals had a reduced aerobic capacity as evidenced by the decrease in VO2max values post supplementation.

Published
2010
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26. Dimension of ergodic measures projected onto self-similar sets with overlaps

Author

Jordan, Thomas and Rapaport, Ariel

Subjects
Mathematics - Dynamical Systems, 28A78 37C45
Abstract

For self-similar sets on $\mathbb{R}$ satisfying the exponential separation condition we show that the natural projections of shift invariant ergodic measures is equal to $\min\{1,\frac{h}{-\chi}\}$, where $h$ and $\chi$ are the entropy and Lyapunov exponent respectively. The proof relies on Shmerkin's recent result on the $L^{q}$ dimension of self-similar measures. We also use the same method to give results on convolutions and orthogonal projections of ergodic measures projected onto self-similar sets., Comment: 16 pages. A few details have been clarified and section 5 has been expanded. Now accepted in the Proceedings of the LMS

Published
2019
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27. Effects of concentrated poultry operations and cropland manure application on antibiotic resistant Escherichia coli and nutrient pollution in Chesapeake Bay watersheds.

Author

Amato, Heather, Wong, Nora, Pelc, Carey, Taylor, Kishana, Price, Lance, Altabet, Mark, Jordan, Thomas, and Graham, Jay

Subjects
Antibiotic resistance, Chesapeake Bay, Concentrated animal feeding operations, E. coli, Nutrient pollution, Poultry litter, Animals, Anti-Bacterial Agents, Bays, Crops, Agricultural, Escherichia coli, Humans, Manure, Nutrients, Poultry
Abstract

Manure from poultry operations is typically applied to nearby cropland and may affect nutrient loading and the spread of antibiotic resistance (ABR). We analyzed the concentrations of nitrogen and phosphorus and the occurrence of ABR in Escherichia coli (E. coli) and extra-intestinal pathogenic E. coli isolates from streams draining 15 small (

Published
2020

28. Effects of concentrated poultry operations and cropland manure application on antibiotic resistant Escherichia coli and nutrient pollution in Chesapeake Bay watersheds

Author

Amato, Heather K, Wong, Nora M, Pelc, Carey, Taylor, Kishana, Price, Lance B, Altabet, Mark, Jordan, Thomas E, and Graham, Jay P

Subjects
Antimicrobial Resistance, Infection, Animals, Anti-Bacterial Agents, Bays, Crops, Agricultural, Escherichia coli, Humans, Manure, Nutrients, Poultry, Concentrated animal feeding operations, Poultry litter, Nutrient pollution, Antibiotic resistance, E. coli, Chesapeake Bay, Environmental Sciences
Abstract

Manure from poultry operations is typically applied to nearby cropland and may affect nutrient loading and the spread of antibiotic resistance (ABR). We analyzed the concentrations of nitrogen and phosphorus and the occurrence of ABR in Escherichia coli (E. coli) and extra-intestinal pathogenic E. coli isolates from streams draining 15 small (

Published
2020

29. Birkhoff and Lyapunov spectra on planar self-affine sets

Author

Bárány, Balázs, Jordan, Thomas, Käenmäki, Antti, and Rams, Michał

Subjects
Mathematics - Dynamical Systems, Primary 28A80, Secondary 37L30, 37D35, 28D20
Abstract

Working on strongly irreducible planar self-affine sets satisfying the strong open set condition, we calculate the Birkhoff spectrum of continuous potentials and the Lyapunov spectrum., Comment: 32 pages, 1 figure

Published
2018

31. Birkhoff spectrum for piecewise monotone interval maps

Author

Jordan, Thomas and Rams, Michal

Subjects
Mathematics - Dynamical Systems
Abstract

For piecewise monotone interval maps we look at Birkhoff spectra for regular potential functions. This means considering the Hausdorff dimension of the set of points for which the Birkhoff average of the potential takes a fixed value. In the uniformly hyperbolic case we obtain complete results, in the case with parabolic behaviour we are able to describe the part of the sets where the lower Lyapunov exponent is positive. In addition we give some lower bounds on the full spectrum in this case. This is an extension of work of Hofbauer on the entropy and Lyapunov spectra., Comment: 22 pages

Published
2017

32. Dimensions of equilibrium measures on a class of planar self-affine sets

Author

Fraser, Jonathan, Jordan, Thomas, and Jurga, Natalia

Subjects
Mathematics - Dynamical Systems, Mathematics - Classical Analysis and ODEs, 37C45, 28A80
Abstract

We study equilibrium measures (K\"aenm\"aki measures) supported on self-affine sets generated by a finite collection of diagonal and anti-diagonal matrices acting on the plane and satisfying the strong separation property. Our main result is that such measures are exact dimensional and the dimension satisfies the Ledrappier-Young formula, which gives an explicit expression for the dimension in terms of the entropy and Lyapunov exponents as well as the dimension of the important coordinate projection of the measure. In particular, we do this by showing that the K\"aenm\"aki measure is equal to the sum of (the pushforwards) of two Gibbs measures on an associated subshift of finite type., Comment: 20 pages. A few minor clarifications made and some typos corrected. To appear in the Journal of Fractal Geometry

Published
2017

34. Hard rock landforms generate 130 km ice shelf channels through water focusing in basal corrugations.

Author

Jeofry, Hafeez, Ross, Neil, Le Brocq, Anne, Graham, Alastair GC, Li, Jilu, Gogineni, Prasad, Morlighem, Mathieu, Jordan, Thomas, and Siegert, Martin J

Subjects
MD Multidisciplinary
Abstract

Satellite imagery reveals flowstripes on Foundation Ice Stream parallel to ice flow, and meandering features on the ice-shelf that cross-cut ice flow and are thought to be formed by water exiting a well-organised subglacial system. Here, ice-penetrating radar data show flow-parallel hard-bed landforms beneath the grounded ice, and channels incised upwards into the ice shelf beneath meandering surface channels. As the ice transitions to flotation, the ice shelf incorporates a corrugation resulting from the landforms. Radar reveals the presence of subglacial water alongside the landforms, indicating a well-organised drainage system in which water exits the ice sheet as a point source, mixes with cavity water and incises upwards into a corrugation peak, accentuating the corrugation downstream. Hard-bedded landforms influence both subglacial hydrology and ice-shelf structure and, as they are known to be widespread on formerly glaciated terrain, their influence on the ice-sheet-shelf transition could be more widespread than thought previously.

Published
2018

35. Using open-science workflow tools to produce SCEC CyberShake physics-based probabilistic seismic hazard models

Author

Callaghan, Scott, primary, Maechling, Philip J., additional, Silva, Fabio, additional, Su, Mei-Hui, additional, Milner, Kevin R., additional, Graves, Robert W., additional, Olsen, Kim B., additional, Cui, Yifeng, additional, Vahi, Karan, additional, Kottke, Albert, additional, Goulet, Christine A., additional, Deelman, Ewa, additional, Jordan, Thomas H., additional, and Ben-Zion, Yehuda, additional

Published
2024
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36. The Assouad dimension of self-affine carpets with no grid structure

Author

Fraser, Jonathan M. and Jordan, Thomas

Subjects
Mathematics - Classical Analysis and ODEs, Mathematics - Dynamical Systems, Mathematics - Number Theory, 37C45, 28A80
Abstract

Previous study of the Assouad dimension of planar self-affine sets has relied heavily on the underlying IFS having a `grid structure', thus allowing for the use of approximate squares. We study the Assouad dimension of a class of self-affine carpets which do not have an associated grid structure. We find that the Assouad dimension is related to the box and Assouad dimensions of the (self-similar) projection of the self-affine set onto the first coordinate and to the local dimensions of the projection of a natural Bernoulli measure onto the first coordinate. In a special case we relate the Assouad dimension of the Przytycki-Urba\'nski sets to the lower local dimensions of Bernoulli convolutions., Comment: 14 pages, to appear in Proc. Amer. Math. Soc

Published
2016

37. Pointwise perturbations of countable Markov maps

Author

Jordan, Thomas, Munday, Sara, and Sahlsten, Tuomas

Subjects
Mathematics - Dynamical Systems, 37C15, 37C30, 37L30
Abstract

We study the pointwise perturbations of countable Markov maps with infinitely many inverse branches and establish the following continuity theorem: Let $T_k$ and $T$ be expanding countable Markov maps such that the inverse branches of $T_k$ converge pointwise to the inverse branches of $T$ as $k \to \infty$. Then under suitable regularity assumptions on the maps $T_k$ and $T$ the following limit exists: $$\lim_{k \to \infty} \dim_\mathrm{H} \{x : \theta_k'(x) \neq 0\} = 1,$$ where $\theta_k$ is the topological conjugacy between $T_k$ and $T$ and $\dim_\mathrm{H}$ stands for the Hausdorff dimension. This is in contrast with the fact that other natural quantities measuring the singularity of $\theta_k$ fail to be continuous in this manner under pointwise convergence such as the H\"older exponent of $\theta_k$ or the Hausdorff dimension $\dim_\mathrm{H} (\mu \circ \theta_k)$ for the preimage of the absolutely continuous invariant measure $\mu$ for $T$. As an application we obtain a perturbation theorem in non-uniformly hyperbolic dynamics for conjugacies between intermittent Manneville-Pomeau maps $x \mapsto x + x^{1+\alpha} \mod 1$ when varying the parameter $\alpha$., Comment: 34 pages, 3 figures

Published
2016
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39. A study demonstrating users’ preference for the adapted-REQUITE patient-reported outcome questionnaire over PRO-CTCAE® in patients with lung cancer

Author

Jordan, Thomas, primary, Nuamek, Thitikorn, additional, Fornacon-Wood, Isabella, additional, Califano, Raffaele, additional, Coote, Joanna, additional, Harris, Margaret, additional, Mistry, Hitesh, additional, Taylor, Paul, additional, Woolf, David, additional, and Faivre-Finn, Corinne, additional

Published
2024
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40. A shape-anisotropic reflective polarizer in a stomatopod crustacean.

Author

Jordan, Thomas M, Wilby, David, Chiou, Tsyr-Huei, Feller, Kathryn D, Caldwell, Roy L, Cronin, Thomas W, and Roberts, Nicholas W

Subjects
Animals, Crustacea, Microscopy, Interference, Anisotropy, Optical Phenomena, Microscopy, Interference, Biochemistry and Cell Biology, Other Physical Sciences
Abstract

Many biophotonic structures have their spectral properties of reflection 'tuned' using the (zeroth-order) Bragg criteria for phase constructive interference. This is associated with a periodicity, or distribution of periodicities, parallel to the direction of illumination. The polarization properties of these reflections are, however, typically constrained by the dimensional symmetry and intrinsic dielectric properties of the biological materials. Here we report a linearly polarizing reflector in a stomatopod crustacean that consists of 6-8 layers of hollow, ovoid vesicles with principal axes of ~550 nm, ~250 nm and ~150 nm. The reflection of unpolarized normally incident light is blue/green in colour with maximum reflectance wavelength of 520 nm and a degree of polarization greater than 0.6 over most of the visible spectrum. We demonstrate that the polarizing reflection can be explained by a resonant coupling with the first-order, in-plane, Bragg harmonics. These harmonics are associated with a distribution of periodicities perpendicular to the direction of illumination, and, due to the shape-anisotropy of the vesicles, are different for each linear polarization mode. This control and tuning of the polarization of the reflection using shape-anisotropic hollow scatterers is unlike any optical structure previously described and could provide a new design pathway for polarization-tunability in man-made photonic devices.

Published
2016

41. Symmetry examples in open quantum dynamics

Author

Jordan, Thomas F. and Seo, San Ha

Subjects
Quantum Physics
Abstract

Dependent symmetries, symmetries that depend on the situation of the subsystem in a larger closed system, are explored by looking at simple examples. This is a new kind of symmetry in the open quantum dynamics of a subsystem Each symmetry implies a particular form for the results of the open dynamics. The forms exhibit the symmetries very simply. It is shown directly, without assuming anything about the symmetry, that the dynamics produces the form, but knowing the symmetry and the form it implies can reduce what needs to be done to work out the dynamics; pieces can be deduced from the symmetry rather that calculated from the dynamics. Symmetries can be related to constants of the motion in new ways. A quantity might be a dependent constant of the motion, constant only for particular situations of the subsystem in the larger system. In particular, a generator of dependent symmetries could represent a quantity that is a dependent constant of the motion for the same situations as for the symmetries. The examples present a variety of possibilities. Sometimes a generator of dependent symmetries does represent a dependent constant of the motion. Sometimes it does not. Sometimes no quantity is a dependent constant of the motion. Sometimes every quantity is., Comment: 18 pages, presentation improved

Published
2014

42. Symmetries in open quantum dynamics

Author

Jordan, Thomas F.

Subjects
Quantum Physics
Abstract

Simple examples are used to introduce and examine symmetries of open quantum dynamics that can be described by unitary operators. For the Hamiltonian dynamics of an entire closed system, the symmetry takes the expected form which, when the Hamiltonian has a lower bound, says that the unitary symmetry operator commutes with the Hamiltonian operator. There are many more symmetries that are only for the open dynamics of a subsystem. Examples show how these symmetries alone can reveal properties of the dynamics and reduce what needs to be done to work out the dynamics. A symmetry of the open dynamics of a subsystem can even imply properties of the dynamics for the entire system that are not implied by the symmetries of the dynamics of the entire system. The symmetries are generally not related to constants of the motion for the open dynamics of the subsystem. There are many symmetries that cannot be seen in the Schrodinger picture as symmetries of dynamical maps of density matrices for the subsystem. There are symmetries of the open dynamics of a subsystem that depend only on the dynamics. In the simplest examples, these are also symmetries of the dynamics of the entire system. There are many more symmetries, of a new kind, that also depend on correlations, or absence of correlations, between the subsystem and the rest of the entire system, or on the state of the rest of the entire system., Comment: 28 pages, presentation improved

Published
2014

43. Packing spectra for Bernoulli measures supported on Bedford-McMullen carpets

Author

Jordan, Thomas and Rams, Michał

Subjects
Mathematics - Dynamical Systems, 28A78 37C45
Abstract

In this paper we consider the packing spectra for local dimension of Bernoulli measures supported on Bedford-McMullen carpets. We show that typically the packing dimension of the regular set is smaller than the packing dimension of the attractor. We also consider a specific class of measures for which we are able to calculate the packing spectrum exactly and we show that the packing spectrum is discontinuous as a function on the space of Bernoulli measures., Comment: 26 pages

Published
2014

45. QUANTIFYING COARSE SEDIMENT CONNECTIVITY IN MOUNTAIN WATERSHEDS

Author

Gilbert, Jordan Thomas and Gilbert, Jordan Thomas

Abstract

Sediment connectivity is a framework for conceptualizing how sediment moves from source to sink across landscapes. Quantifying connectivity is challenging due to variation in sediment detachment and transport processes and their rates across different process domains. Within the Bitterroot River basin of Western Montana, process domains differ based on glaciation history, and resulting morphological differences; the Bitterroot Mountains were glaciated during the Pleistocene, and the Sapphires/Southern Bitterroots were not. Quantifying longitudinal connectivity requires estimating sediment transport from reach to reach throughout drainage basins. Previously, transport equations suitable for application in mountain rivers have been limited. I present a new transport equation for estimating fractional bedload transport in poorly-sorted, coarse-bedded rivers. This framework builds on existing fractional transport frameworks, and uses new methods to estimate the fraction of boundary shear stress acting on mobile grains, and convert pebble counts to areas to better represent relative exposure to the flow. The equations produce results in Bitterroot Basin streams that compare well with measurements of sediment yield for the region. In order to apply the fractional sediment transport formula across entire drainage networks, I developed a new algorithm for extrapolating grain size measurements across basins. Applying the algorithm to various sub-basins of the Bitterroot River produced predictions within ~5% of measured grain sizes on the phi grain size scale. For quantifying hillslope-channel connectivity, I developed a deposit evolution model that simulates fluvial recruitment and transport of sediment from mass wasting deposits, and the resulting morphological change through time. Debris flow deposits affect sediment yield and connectivity for years to decades in the study area, depending on the size of the deposit and slope of the channel. Rockfall deposits serve as lasti

Published
2024

47. Unified Structural Representation of the southern California crust and upper mantle

Author

Shaw, John H, Plesch, Andreas, Tape, Carl, Suess, M Peter, Jordan, Thomas H, Ely, Geoffrey, Hauksson, Egill, Tromp, Jeroen, Tanimoto, Toshiro, Graves, Robert, Olsen, Kim, Nicholson, Craig, Maechling, Philip J, Rivero, Carlos, Lovely, Peter, Brankman, Charles M, and Munster, Jason

Subjects
velocity structure, fault models, southern California, tomography, seismic wave propagation, strong ground motions, Physical Sciences, Earth Sciences, Geochemistry & Geophysics
Abstract

We present a new, 3D description of crust and upper mantle velocity structure in southern California implemented as a Unified Structural Representation (USR). The USR is comprised of detailed basin velocity descriptions that are based on tens of thousands of direct velocity (Vp, Vs) measurements and incorporates the locations and displacement of major fault zones that influence basin structure. These basin descriptions were used to developed tomographic models of crust and upper mantle velocity and density structure, which were subsequently iterated and improved using 3D waveform adjoint tomography. A geotechnical layer (GTL) based on Vs30 measurements and consistent with the underlying velocity descriptions was also developed as an optional model component. The resulting model provides a detailed description of the structure of the southern California crust and upper mantle that reflects the complex tectonic history of the region. The crust thickens eastward as Moho depth varies from 10 to 40 km reflecting the transition from oceanic to continental crust. Deep sedimentary basins and underlying areas of thin crust reflect Neogene extensional tectonics overprinted by transpressional deformation and rapid sediment deposition since the late Pliocene. To illustrate the impact of this complex structure on strong ground motion forecasting, we simulate rupture of a proposed M 7.9 earthquake source in the Western Transverse Ranges. The results show distinct basin amplification and focusing of energy that reflects crustal structure described by the USR that is not captured by simpler velocity descriptions. We anticipate that the USR will be useful for a broad range of simulation and modeling efforts, including strong ground motion forecasting, dynamic rupture simulations, and fault system modeling. The USR is available through the Southern California Earthquake Center (SCEC) website (http://www.scec.org).

Published
2015

48. Fourier transforms of Gibbs measures for the Gauss map

Author

Jordan, Thomas and Sahlsten, Tuomas

Subjects
Mathematics - Dynamical Systems, Mathematics - Classical Analysis and ODEs, Mathematics - Number Theory, 42A38 (Primary), 11K50, 37C30, 60F10 (Secondary)
Abstract

We investigate under which conditions a given invariant measure $\mu$ for the dynamical system defined by the Gauss map $x \mapsto 1/x \mod 1$ is a Rajchman measure with polynomially decaying Fourier transform $$|\widehat{\mu}(\xi)| = O(|\xi|^{-\eta}), \quad \text{as } |\xi| \to \infty.$$ We show that this property holds for any Gibbs measure $\mu$ of Hausdorff dimension greater than $1/2$ with a natural large deviation assumption on the Gibbs potential. In particular, we obtain the result for the Hausdorff measure and all Gibbs measures of dimension greater than $1/2$ on badly approximable numbers, which extends the constructions of Kaufman and Queff\'elec-Ramar\'e. Our main result implies that the Fourier-Stieltjes coefficients of the Minkowski's question mark function decay to $0$ polynomially answering a question of Salem from 1943. As an application of the Davenport-Erd\H{o}s-LeVeque criterion we obtain an equidistribution theorem for Gibbs measures, which extends in part a recent result by Hochman-Shmerkin. Our proofs are based on exploiting the nonlinear and number theoretic nature of the Gauss map and large deviation theory for Hausdorff dimension and Lyapunov exponents., Comment: v3: 29 pages; peer-reviewed version, fixes typos and added more elaborations, and included comments on Salem's problem. To appear in Math. Ann

Published
2013

49. Self-affine sets with non-compactly supported random perturbations

Author

Jordan, Thomas and Jurga, Natalia

Subjects
Mathematics - Dynamical Systems
Abstract

In this note we consider the Hausdorff dimension of self-affine sets with random perturbations. We extend previous work in this area by allowing the random perturbation to be distributed according to distributions with unbounded support as long as the measure of the tails of the distribution decay super polynomially., Comment: 18 pages. A few typographical errors have been corrected and some clarifications have been made. Now accepted for publication in 'Annales Academi{\ae} Scientiarum Fennic{\ae}, Mathematica'

Published
2013

50. Transience and multifractal analysis

Author

Iommi, Godofredo, Jordan, Thomas, and Todd, Mike

Subjects
Mathematics - Dynamical Systems
Abstract

We study dimension theory for dissipative dynamical systems, proving a conditional variational principle for the quotients of Birkhoff averages restricted to the recurrent part of the system. On the other hand, we show that when the whole system is considered (and not just its recurrent part) the conditional variational principle does not necessarily hold. Moreover, we exhibit the first example of a topologically transitive map having discontinuous Lyapunov spectrum. The mechanism producing all these pathological features on the multifractal spectra is transience, that is, the non-recurrent part of the dynamics., Comment: Some updates following referee suggestions

Published
2013

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