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3. Cellular and molecular mechanisms underpinning microglial activation during remyelination

Author

Lloyd, Amy Frances, Miron, Veronique, Pollard, Jeffrey, and Williams, Anna

Subjects
616.8, remyelination, microglia, Multiple Sclerosis, inflammatory microglia, inflammatory microglial death
Abstract

Failed regeneration of myelin in the central nervous system (CNS) contributes to axon loss/dysfunction in prevalent neurodegenerative disorders, for which there is an unmet need for effective therapies. Previous work from this lab has demonstrated that remyelination requires a transition in microglia activation from pro-inflammatory (inducible nitric oxide synthase (iNOS)+) to pro-regenerative (arginase-1 (Arg-1+)). However, the mechanisms underpinning microglia activation remain unknown, and the assumption that in situ tissue macrophages can transition in activation state has never been substantiated. Here, unexpectedly it is revealed that microglia activation during remyelination is driven by their death and subsequent repopulation. More specifically, pro-inflammatory microglia undergo controlled necrosis (necroptosis), followed by repopulation via residual microglia and CNS-resident Nestin+ cell differentiation into microglia. Blocking necroptosis prevented microglial death and maintained their pro-inflammatory (iNOS+) activation, which consequently hindered remyelination. In human brain tissue, necroptosing and repopulating microglia were only significantly increased in white matter lesions with a high potential for remyelination. These results overturn current assumptions that following injury, microglia simply switch their activation from an initial pro-inflammatory phenotype to become pro-regenerative. Impairment in microglia death and/or repopulation may thus underpin the chronic pro-inflammatory microglia activation associated with failed remyelination in human pathology, highlighting a novel therapeutic strategy in the treatment of chronic inflammatory and neurodegenerative diseases.

Published
2019

4. Development, implementation and evaluation of an evidence-based paediatric early warning system improvement programme: the PUMA mixed methods study

Author

Allen, Davina, Lloyd, Amy, Edwards, Dawn, Hood, Kerenza, Huang, Chao, Hughes, Jacqueline, Jacob, Nina, Lacy, David, Moriarty, Yvonne, Oliver, Alison, Preston, Jennifer, Sefton, Gerri, Sinha, Ian, Skone, Richard, Strange, Heather, Taiyari, Khadijeh, Thomas-Jones, Emma, Trubey, Rob, Tume, Lyvonne, Powell, Colin, and Roland, Damian

Published
2022
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5. Safety and immunogenicity of concomitant administration of COVID-19 vaccines (ChAdOx1 or BNT162b2) with seasonal influenza vaccines in adults in the UK (ComFluCOV): a multicentre, randomised, controlled, phase 4 trial

Author

Adams, Kirsty, Alaee, Seema, Aley, Parvinder K., Allum, Emma, Anthony, Sally, Ashton, Kate, Awal, Tanya, Barnett, Liz, Barratt, Alison, Barron, Charlotte, Baum, Holly, Beard, Chloe, Bennett, Lorna, Bird, Samuel, Bishop, Sarah, Bisset, Jess, Bodalia, Pritesh, Bowles, Jane, Bowyer, Catherine, Bradburn, Kirstie, Bray, Jonathan J.H., Bressington, Catherine, Brimfield, Matthew, Broad, Lauren, Brown, Pauline, Brydon-Hill, Ruth, Burge, Sharon, Carmichael, David, Chohan, Gurjit, Clark, Tonia, Close, Adrianne, Coleman, Tom, Cowley, Claire, Cranfield, Charlotte, Cross, Eleanor, D'Agostino, Alyssa, D'Arcangelo, Silvia, David Otter, Ashley, Davies, Kate, Davies, Catrin, Davies, Ru, Davies, Louisa, Driver, Kimberley, Eglinton, Charlotte, Ekblad, Charlotte, Eldridge, Emma, Evans, Teriann, Evans, Mim, Evans, Isabel, F Mujadidi, Yama, Farrow, Amanda, Faulkner, Beverley, Feltham, Sally, Figueirido, Susan, Ford, Jamie, Foxwell, David, Frayling, Sharon, Gardiner, Sophie, Gooch, Karen E., Goodwin, Jayne, Halliday, Alice, Hamal, Shama, Harrhy, Sarah, Harris, Andrew, Haxton, Lesley, Haynes, Matthew, Hazell, Mae, Hembrough, Tracey, Hewson, Jacqueline, Hicks, Bethany, Higgins, Thomas, Hill, Michelle, Hills, Alex, Hilton, Zoe, Hitchings, Benjamin, Hua, Cheryl, Iftikhar, Hina, Iqbal, Attya, Jones, Laura, Jones, Nicola, Kellett Wright, Johanna, Kidd, Sarah, Kirby, Alison, Knibbs, Lucy, Lamb, Jenny, Langton, Helen, Leach, Rwth, Lewis-Clarke, Phoebe, Lloyd, Amy, Maclean, Kirsty, Manning, Nicola, Marriott, Anthony, McFadzean, Isobel Joy, McLaughlin, Maeve, McQueen, Alison, Mills, Bianca, Naik, Gurudutt, Nicholls, Lisa, Norman, Chris, Northcott, Keren, Nyland, Kerry, Oliver, Catherine, Oliver, Elizabeth, Oliver, Jennifer, Owen, Diana, Paterson, Jemma, Pearce, Lauren, Pegler, Suzannah, Price, Zoe, Pynsent, William B., Ramos, Lidia, Rampling, Tommy, Rea, David, Regan, Karen, Riaz, Tawassal, Ricamara, Marivic, Rice, Danielle, Rich, Melody, Roots, Marianne, Ryan, Kathryn Ann, Sakagami, Yukari, Salem, Ahmed, Salter-Hewitt, Jade, Samuels, Michelle, Santoloce, Silvia, Seaman, Siwan, Seneviratne, Michael, Shankland, Sara, Silva, Louise, Smart, Katie, Smith, Rachel M., Smith, Joyce, Stringer, Rebecca, Talbot, Helen, Tarling, Teresa, Taylor, Sarah Louise, Thomas, Amy, Tilzey, Grace, Townley, Gina, Trembath, Lisa, Turkentine, Kate, Turner, Kelly, Tyler, Jenny, Ugoji, Jacinta, Wale, Katharine, Walker-Smith, Terrie, Walton, Maggie, Warnes, Barbara, Whittley, Sarah, Williams, Jennie, Williams, Gail, Williamson, Kevin, Yim, Yee Ting Nicole, Youlden, Nicola, Lazarus, Rajeka, Baos, Sarah, Cappel-Porter, Heike, Carson-Stevens, Andrew, Clout, Madeleine, Culliford, Lucy, Emmett, Stevan R, Garstang, Jonathan, Gbadamoshi, Lukuman, Hallis, Bassam, Harris, Rosie A, Hutton, David, Jacobsen, Nick, Joyce, Katherine, Kaminski, Rachel, Libri, Vincenzo, Middleditch, Alex, McCullagh, Liz, Moran, Ed, Phillipson, Adrian, Price, Elizabeth, Ryan, John, Thirard, Russell, Todd, Rachel, Snape, Matthew D, Tucker, David, Williams, Rachel Lauren, Nguyen-Van-Tam, Jonathan S, Finn, Adam, and Rogers, Chris A

Published
2021
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9. 17α-Ethinyl estradiol-3-sulfate increases survival and hemodynamic functioning in a large animal model of combined traumatic brain injury and hemorrhagic shock: a randomized control trial

Author

Mayer, Andrew R., Dodd, Andrew B., Rannou-Latella, Julie G., Stephenson, David D., Dodd, Rebecca J., Ling, Josef M., Mehos, Carissa J., Robertson-Benta, Cidney R., Pabbathi Reddy, Sharvani, Kinsler, Rachel E., Vermillion, Meghan S., Gigliotti, Andrew P., Sicard, Veronik, Lloyd, Amy L., Erhardt, Erik B., Gill, Jessica M., Lai, Chen, Guedes, Vivian A., and Chaudry, Irshad H.

Published
2021
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14. Duchenne muscular dystrophy and reproductive decision-making : implications of newborn screening

Author

Lloyd, Amy

Subjects
616.7
Abstract

Newborn screening programmes once focused on identifying treatable conditions. In recent years, increasing numbers of untreatable genetic conditions have been included in newborn screening programmes, on the premise that families will benefit from the provision of information, support and reproductive choice. However, there is a paucity of research documenting families' experiences of newborn screening and the implications of screening for untreatable conditions. This study focuses on one untreatable condition, Duchenne muscular dystrophy (DMD). Using both quantitative and qualitative methods, this study explores the implications of two different diagnostic pathways for reproductive decision-making newborn screening and a later clinical diagnosis (which occurs when the child is an average age of 4.5 years). Quantitative data on reproductive behaviour were collected from 72 families 38 families who received a later clinical diagnosis (LCD) in the west of Scotland, and 34 families in Wales, who received a diagnosis through newborn screening (NBS), between 1990 and 2006. Qualitative data (in-depth interviews) were collected from a subset of 19 families to explore reproductive decision-making 8 families from the LCD cohort, and 11 families from the NBS cohort. The quantitative data highlighted varied effects of providing families with an earlier awareness of risk. Families in the newborn screening cohort were more likely to continue family building, and significantly more likely to use prenatal testing (p=0.05). However, there was no association between carrier risk and reproductive behaviour and little difference in the number of second affected boys. Participants in the qualitative interviews were often ambivalent about the provision of reproductive choice. Mothers' descriptions of the importance of "choice" were juxtaposed against accounts of "ignorant bliss", profound appreciation of the "carefree years", and relief at the avoidance of "difficult decisions". The medical information provided to families was often perceived to lack experiential validity. In addition, few families felt supported. The findings suggest a need for greater consideration of the true value of providing information, "choice" and support.

Published
2009

15. Multiple common susceptibility variants near BMP pathway loci GREM1, BMP4, and BMP2 explain part of the missing heritability of colorectal cancer.

Author

Tomlinson, Ian PM, Carvajal-Carmona, Luis G, Dobbins, Sara E, Tenesa, Albert, Jones, Angela M, Howarth, Kimberley, Palles, Claire, Broderick, Peter, Jaeger, Emma EM, Farrington, Susan, Lewis, Annabelle, Prendergast, James GD, Pittman, Alan M, Theodoratou, Evropi, Olver, Bianca, Walker, Marion, Penegar, Steven, Barclay, Ella, Whiffin, Nicola, Martin, Lynn, Ballereau, Stephane, Lloyd, Amy, Gorman, Maggie, Lubbe, Steven, COGENT Consortium, CORGI Collaborators, EPICOLON Consortium, Howie, Bryan, Marchini, Jonathan, Ruiz-Ponte, Clara, Fernandez-Rozadilla, Ceres, Castells, Antoni, Carracedo, Angel, Castellvi-Bel, Sergi, Duggan, David, Conti, David, Cazier, Jean-Baptiste, Campbell, Harry, Sieber, Oliver, Lipton, Lara, Gibbs, Peter, Martin, Nicholas G, Montgomery, Grant W, Young, Joanne, Baird, Paul N, Gallinger, Steven, Newcomb, Polly, Hopper, John, Jenkins, Mark A, Aaltonen, Lauri A, Kerr, David J, Cheadle, Jeremy, Pharoah, Paul, Casey, Graham, Houlston, Richard S, and Dunlop, Malcolm G

Subjects
COGENT Consortium, CORGI Collaborators, EPICOLON Consortium, Humans, Colorectal Neoplasms, Genetic Predisposition to Disease, Intercellular Signaling Peptides and Proteins, Case-Control Studies, Signal Transduction, Gene Frequency, Quantitative Trait, Heritable, Polymorphism, Single Nucleotide, Aged, Middle Aged, Male, Genetic Variation, Genome-Wide Association Study, Bone Morphogenetic Protein 2, Bone Morphogenetic Protein 4, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, Genetics, Developmental Biology
Abstract

Genome-wide association studies (GWAS) have identified 14 tagging single nucleotide polymorphisms (tagSNPs) that are associated with the risk of colorectal cancer (CRC), and several of these tagSNPs are near bone morphogenetic protein (BMP) pathway loci. The penalty of multiple testing implicit in GWAS increases the attraction of complementary approaches for disease gene discovery, including candidate gene- or pathway-based analyses. The strongest candidate loci for additional predisposition SNPs are arguably those already known both to have functional relevance and to be involved in disease risk. To investigate this proposition, we searched for novel CRC susceptibility variants close to the BMP pathway genes GREM1 (15q13.3), BMP4 (14q22.2), and BMP2 (20p12.3) using sample sets totalling 24,910 CRC cases and 26,275 controls. We identified new, independent CRC predisposition SNPs close to BMP4 (rs1957636, P = 3.93×10(-10)) and BMP2 (rs4813802, P = 4.65×10(-11)). Near GREM1, we found using fine-mapping that the previously-identified association between tagSNP rs4779584 and CRC actually resulted from two independent signals represented by rs16969681 (P = 5.33×10(-8)) and rs11632715 (P = 2.30×10(-10)). As low-penetrance predisposition variants become harder to identify-owing to small effect sizes and/or low risk allele frequencies-approaches based on informed candidate gene selection may become increasingly attractive. Our data emphasise that genetic fine-mapping studies can deconvolute associations that have arisen owing to independent correlation of a tagSNP with more than one functional SNP, thus explaining some of the apparently missing heritability of common diseases.

Published
2011

16. Astrocyte-oligodendrocyte interaction regulates central nervous system regeneration

Author

Molina-Gonzalez, Irene, primary, Holloway, Rebecca K., additional, Jiwaji, Zoeb, additional, Dando, Owen, additional, Kent, Sarah A., additional, Emelianova, Katie, additional, Lloyd, Amy F., additional, Forbes, Lindsey H., additional, Mahmood, Ayisha, additional, Skripuletz, Thomas, additional, Gudi, Viktoria, additional, Febery, James A., additional, Johnson, Jeffrey A., additional, Fowler, Jill H., additional, Kuhlmann, Tanja, additional, Williams, Anna, additional, Chandran, Siddharthan, additional, Stangel, Martin, additional, Howden, Andrew J. M., additional, Hardingham, Giles E., additional, and Miron, Veronique E., additional

Published
2023
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17. Astrocyte-Oligodendrocyte interaction regulates central nervous system regeneration

Author

Molina-Gonzalez, Irene, primary, Holloway, Rebecca K., additional, Jiwaji, Zoeb, additional, Dando, Owen, additional, Emelianova, Katie, additional, Lloyd, Amy F., additional, Forbes, Lindsey H., additional, Mahmood, Ayisha, additional, Skripuletz, Thomas, additional, Gudi, Viktoria, additional, Febery, James A., additional, Johnson, Jeffrey A., additional, Fowler, Jill H., additional, Kuhlmann, Tanja, additional, Williams, Anna, additional, Chandran, Siddharthan, additional, Stangel, Martin, additional, Howden, Andrew J.M., additional, Hardingham, Giles E., additional, and Miron, Veronique E., additional

Published
2022
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19. Neutrophil proteomics identifies temporal changes and hallmarks of delayed recovery in COVID19

Author

Long, Merete B, primary, Howden, Andrew JM, additional, Keir, Holly R, additional, Rollings, Christina M, additional, Giam, Yan Hui, additional, Pembridge, Thomas, additional, Delgado, Lilia, additional, Abo-Leyah, Hani, additional, Lloyd, Amy F, additional, Sollberger, Gabriel, additional, Hull, Rebecca, additional, Gilmour, Amy, additional, Hughes, Chloe, additional, New, Benjamin JM, additional, Cassidy, Diane, additional, Shoemark, Amelia, additional, Richardson, Hollian, additional, Lamond, Angus I, additional, Cantrell, Doreen A, additional, Chalmers, James D, additional, and Brenes, Alejandro J, additional

Published
2022
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20. Paediatric early warning systems: not a simple answer to a complex question

Author

Roland, Damian, primary, Powell, Colin, additional, Lloyd, Amy, additional, Trubey, Robert, additional, Tume, Lyvonne, additional, Sefton, Gerri, additional, Huang, Chao, additional, Taiyari, Katie, additional, Strange, Heather, additional, Jacob, Nina, additional, Thomas-Jones, Emma, additional, Hood, Kerenza, additional, and Allen, Davina, additional

Published
2022
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21. Deep proteomic analysis of human microglia and model systems reveal fundamental biological differences ofin vitroandex vivocells

Author

Lloyd, Amy F, primary, Martinez-Muriana, Anna, additional, Hou, Pengfei, additional, Davis, Emma, additional, Mancuso, Renzo, additional, Brenes, Alejandro J, additional, Geric, Ivana, additional, Snellinx, An, additional, Craessaerts, Katleen, additional, Theys, Tom, additional, Fiers, Mark, additional, De Strooper, Bart, additional, and Howden, Andrew JM, additional

Published
2022
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22. A three-talk model for shared decision making: multistage consultation process

Author

Elwyn, Glyn, Durand, Marie Anne, Song, Julia, Aarts, Johanna, Barr, Paul J, Berger, Zackary, Cochran, Nan, Frosch, Dominick, Galasiński, Dariusz, Gulbrandsen, Pål, Han, Paul K J, Härter, Martin, Kinnersley, Paul, Lloyd, Amy, Mishra, Manish, Perestelo-Perez, Lilisbeth, Scholl, Isabelle, Tomori, Kounosuke, Trevena, Lyndal, Witteman, Holly O, and Van der Weijden, Trudy

Published
2017
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24. Paediatric early warning systems: not a simple answer to a complex question.

Author

Roland, Damian, Powell, Colin, Lloyd, Amy, Trubey, Robert, Tume, Lyvonne, Sefton, Gerri, Chao Huang, Taiyari, Katie, Strange, Heather, Jacob, Nina, Thomas-Jones, Emma, Hood, Kerenza, and Allen, Davina

Subjects
PEDIATRICS, RAPID response teams, CHILD health services, YOUNG adults, PEDIATRIC intensive care, CLINICAL trials monitoring
Published
2023
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25. A prospective, mixed-methods, before and after study to identify the evidence base for the core components of an effective Paediatric Early Warning System and the development of an implementation package containing those core recommendations for use in the UK: Paediatric early warning system – utilisation and mortality avoidance– the PUMA study protocol

Author

Thomas-Jones, Emma, Lloyd, Amy, Roland, Damian, Sefton, Gerri, Tume, Lyvonne, Hood, Kerry, Huang, Chao, Edwards, Dawn, Oliver, Alison, Skone, Richard, Lacy, David, Sinha, Ian, Preston, Jenny, Mason, Brendan, Jacob, Nina, Trubey, Robert, Strange, Heather, Moriarty, Yvonne, Grant, Aimee, Allen, Davina, and Powell, Colin

Published
2018
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28. Additional file 5 of Development, implementation and evaluation of an evidence-based paediatric early warning system improvement programme: the PUMA mixed methods study

Author

Allen, Davina, Lloyd, Amy, Edwards, Dawn, Hood, Kerenza, Huang, Chao, Hughes, Jacqueline, Jacob, Nina, Lacy, David, Moriarty, Yvonne, Oliver, Alison, Preston, Jennifer, Sefton, Gerri, Sinha, Ian, Skone, Richard, Strange, Heather, Taiyari, Khadijeh, Thomas-Jones, Emma, Trubey, Rob, Tume, Lyvonne, Powell, Colin, and Roland, Damian

Abstract

Additional file 5. Summary of paediatric early warning system improvement initiatives across all case studies.

Published
2022
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29. Additional file 3 of Development, implementation and evaluation of an evidence-based paediatric early warning system improvement programme: the PUMA mixed methods study

Author

Allen, Davina, Lloyd, Amy, Edwards, Dawn, Hood, Kerenza, Huang, Chao, Hughes, Jacqueline, Jacob, Nina, Lacy, David, Moriarty, Yvonne, Oliver, Alison, Preston, Jennifer, Sefton, Gerri, Sinha, Ian, Skone, Richard, Strange, Heather, Taiyari, Khadijeh, Thomas-Jones, Emma, Trubey, Rob, Tume, Lyvonne, Powell, Colin, and Roland, Damian

Subjects
Data_FILES
Abstract

Additional file 3. Summary of exploratory and sensitivity analyses.

Published
2022
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30. Additional file 1 of Development, implementation and evaluation of an evidence-based paediatric early warning system improvement programme: the PUMA mixed methods study

Author

Allen, Davina, Lloyd, Amy, Edwards, Dawn, Hood, Kerenza, Huang, Chao, Hughes, Jacqueline, Jacob, Nina, Lacy, David, Moriarty, Yvonne, Oliver, Alison, Preston, Jennifer, Sefton, Gerri, Sinha, Ian, Skone, Richard, Strange, Heather, Taiyari, Khadijeh, Thomas-Jones, Emma, Trubey, Rob, Tume, Lyvonne, Powell, Colin, and Roland, Damian

Abstract

Additional file 1: Table 1. Summary of theories that inform OUTCOME.

Published
2022
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31. Development, implementation and evaluation of an early warning system improvement programme for children in hospital: the PUMA mixed-methods study

Author

Allen, Davina, primary, Lloyd, Amy, additional, Edwards, Dawn, additional, Grant, Aimee, additional, Hood, Kerenza, additional, Huang, Chao, additional, Hughes, Jacqueline, additional, Jacob, Nina, additional, Lacy, David, additional, Moriarty, Yvonne, additional, Oliver, Alison, additional, Preston, Jennifer, additional, Sefton, Gerri, additional, Skone, Richard, additional, Strange, Heather, additional, Taiyari, Khadijeh, additional, Thomas-Jones, Emma, additional, Trubey, Robert, additional, Tume, Lyvonne, additional, Powell, Colin, additional, and Roland, Damian, additional

Published
2022
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33. Safety and immunogenicity of concomitant administration of COVID-19 vaccines (ChAdOx1 or BNT162b2) with seasonal influenza vaccines in adults in the UK (ComFluCOV): a multicentre, randomised, controlled, phase 4 trial

Author

Lazarus, Rajeka, primary, Baos, Sarah, additional, Cappel-Porter, Heike, additional, Carson-Stevens, Andrew, additional, Clout, Madeleine, additional, Culliford, Lucy, additional, Emmett, Stevan R, additional, Garstang, Jonathan, additional, Gbadamoshi, Lukuman, additional, Hallis, Bassam, additional, Harris, Rosie A, additional, Hutton, David, additional, Jacobsen, Nick, additional, Joyce, Katherine, additional, Kaminski, Rachel, additional, Libri, Vincenzo, additional, Middleditch, Alex, additional, McCullagh, Liz, additional, Moran, Ed, additional, Phillipson, Adrian, additional, Price, Elizabeth, additional, Ryan, John, additional, Thirard, Russell, additional, Todd, Rachel, additional, Snape, Matthew D, additional, Tucker, David, additional, Williams, Rachel Lauren, additional, Nguyen-Van-Tam, Jonathan S, additional, Finn, Adam, additional, Rogers, Chris A, additional, Adams, Kirsty, additional, Alaee, Seema, additional, Aley, Parvinder K., additional, Allum, Emma, additional, Anthony, Sally, additional, Ashton, Kate, additional, Awal, Tanya, additional, Barnett, Liz, additional, Barratt, Alison, additional, Barron, Charlotte, additional, Baum, Holly, additional, Beard, Chloe, additional, Bennett, Lorna, additional, Bird, Samuel, additional, Bishop, Sarah, additional, Bisset, Jess, additional, Bodalia, Pritesh, additional, Bowles, Jane, additional, Bowyer, Catherine, additional, Bradburn, Kirstie, additional, Bray, Jonathan J.H., additional, Bressington, Catherine, additional, Brimfield, Matthew, additional, Broad, Lauren, additional, Brown, Pauline, additional, Brydon-Hill, Ruth, additional, Burge, Sharon, additional, Carmichael, David, additional, Chohan, Gurjit, additional, Clark, Tonia, additional, Close, Adrianne, additional, Coleman, Tom, additional, Cowley, Claire, additional, Cranfield, Charlotte, additional, Cross, Eleanor, additional, D'Agostino, Alyssa, additional, D'Arcangelo, Silvia, additional, David Otter, Ashley, additional, Davies, Kate, additional, Davies, Catrin, additional, Davies, Ru, additional, Davies, Louisa, additional, Driver, Kimberley, additional, Eglinton, Charlotte, additional, Ekblad, Charlotte, additional, Eldridge, Emma, additional, Evans, Teriann, additional, Evans, Mim, additional, Evans, Isabel, additional, F Mujadidi, Yama, additional, Farrow, Amanda, additional, Faulkner, Beverley, additional, Feltham, Sally, additional, Figueirido, Susan, additional, Ford, Jamie, additional, Foxwell, David, additional, Frayling, Sharon, additional, Gardiner, Sophie, additional, Gooch, Karen E., additional, Goodwin, Jayne, additional, Halliday, Alice, additional, Hamal, Shama, additional, Harrhy, Sarah, additional, Harris, Andrew, additional, Haxton, Lesley, additional, Haynes, Matthew, additional, Hazell, Mae, additional, Hembrough, Tracey, additional, Hewson, Jacqueline, additional, Hicks, Bethany, additional, Higgins, Thomas, additional, Hill, Michelle, additional, Hills, Alex, additional, Hilton, Zoe, additional, Hitchings, Benjamin, additional, Hua, Cheryl, additional, Iftikhar, Hina, additional, Iqbal, Attya, additional, Jones, Laura, additional, Jones, Nicola, additional, Kellett Wright, Johanna, additional, Kidd, Sarah, additional, Kirby, Alison, additional, Knibbs, Lucy, additional, Lamb, Jenny, additional, Langton, Helen, additional, Leach, Rwth, additional, Lewis-Clarke, Phoebe, additional, Lloyd, Amy, additional, Maclean, Kirsty, additional, Manning, Nicola, additional, Marriott, Anthony, additional, McFadzean, Isobel Joy, additional, McLaughlin, Maeve, additional, McQueen, Alison, additional, Mills, Bianca, additional, Naik, Gurudutt, additional, Nicholls, Lisa, additional, Norman, Chris, additional, Northcott, Keren, additional, Nyland, Kerry, additional, Oliver, Catherine, additional, Oliver, Elizabeth, additional, Oliver, Jennifer, additional, Owen, Diana, additional, Paterson, Jemma, additional, Pearce, Lauren, additional, Pegler, Suzannah, additional, Price, Zoe, additional, Pynsent, William B., additional, Ramos, Lidia, additional, Rampling, Tommy, additional, Rea, David, additional, Regan, Karen, additional, Riaz, Tawassal, additional, Ricamara, Marivic, additional, Rice, Danielle, additional, Rich, Melody, additional, Roots, Marianne, additional, Ryan, Kathryn Ann, additional, Sakagami, Yukari, additional, Salem, Ahmed, additional, Salter-Hewitt, Jade, additional, Samuels, Michelle, additional, Santoloce, Silvia, additional, Seaman, Siwan, additional, Seneviratne, Michael, additional, Shankland, Sara, additional, Silva, Louise, additional, Smart, Katie, additional, Smith, Rachel M., additional, Smith, Joyce, additional, Stringer, Rebecca, additional, Talbot, Helen, additional, Tarling, Teresa, additional, Taylor, Sarah Louise, additional, Thomas, Amy, additional, Tilzey, Grace, additional, Townley, Gina, additional, Trembath, Lisa, additional, Turkentine, Kate, additional, Turner, Kelly, additional, Tyler, Jenny, additional, Ugoji, Jacinta, additional, Wale, Katharine, additional, Walker-Smith, Terrie, additional, Walton, Maggie, additional, Warnes, Barbara, additional, Whittley, Sarah, additional, Williams, Jennie, additional, Williams, Gail, additional, Williamson, Kevin, additional, Yim, Yee Ting Nicole, additional, and Youlden, Nicola, additional

Published
2021
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34. Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer

Author

Wang, Yufei, McKay, James D, Rafnar, Thorunn, Wang, Zhaoming, Timofeeva, Maria N, Broderick, Peter, Zong, Xuchen, Laplana, Marina, Wei, Yongyue, Han, Younghun, Lloyd, Amy, Delahaye-Sourdeix, Manon, Chubb, Daniel, Gaborieau, Valerie, Wheeler, William, Chatterjee, Nilanjan, Thorleifsson, Gudmar, Sulem, Patrick, Liu, Geoffrey, Kaaks, Rudolf, Henrion, Marc, Kinnersley, Ben, Vallée, Maxime, Le Calvez-Kelm, Florence, Stevens, Victoria L, Gapstur, Susan M, Chen, Wei V, Zaridze, David, Szeszenia-Dabrowska, Neonilia, Lissowska, Jolanta, Rudnai, Peter, Fabianova, Eleonora, Mates, Dana, Bencko, Vladimir, Foretova, Lenka, Janout, Vladimir, Krokan, Hans E, Gabrielsen, Maiken Elvestad, Skorpen, Frank, Vatten, Lars, Njølstad, Inger, Chen, Chu, Goodman, Gary, Benhamou, Simone, Vooder, Tonu, Välk, Kristjan, Nelis, Mari, Metspalu, Andres, Lener, Marcin, Lubiński, Jan, Johansson, Mattias, Vineis, Paolo, Agudo, Antonio, Clavel-Chapelon, Francoise, Bueno-de-Mesquita, H Bas, Trichopoulos, Dimitrios, Khaw, Kay-Tee, Johansson, Mikael, Weiderpass, Elisabete, Tjønneland, Anne, Riboli, Elio, Lathrop, Mark, Scelo, Ghislaine, Albanes, Demetrius, Caporaso, Neil E, Ye, Yuanqing, Gu, Jian, Wu, Xifeng, Spitz, Margaret R, Dienemann, Hendrik, Rosenberger, Albert, Su, Li, Matakidou, Athena, Eisen, Timothy, Stefansson, Kari, Risch, Angela, Chanock, Stephen J, Christiani, David C, Hung, Rayjean J, Brennan, Paul, Landi, Maria Teresa, Houlston, Richard S, and Amos, Christopher I

Published
2014
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35. A type I IFN, prothrombotic hyperinflammatory neutrophil signature is distinct for COVID-19 ARDS­­­

Author

Reyes, Leila, Sanchez Garcia, Manuel Alejandro, Morrison, Tyler, Howden, Andrew J M, Watts, Emily R, Arienti, Simone, Sadiku, Pranvera, Coelho, Patricia, Mirchandani, Ananda S, Zhang, Ailiang, Hope, David, Clark , Sarah K, Singleton, Jo, Johnston, Shonna, Grecian, Rob, Poon, Azin S., McNamara, Sarah, Harper, Isla, Fourman, Max Head, Brenes, Alejandro J, Pathak, Shalini, Lloyd, Amy, Rodriguez Blanco, Gio, von Kriegsheim, Alexander, Ghesquiere, Bart, Vermaelen, Wesley, Cologna, Camilla T, Dhaliwal, Kevin, Hirani, Nik, Dockrell, David H, Whyte, Moira K B, Griffith, David M, Cantrell, Doreen, and Walmsley, Sarah R

Abstract

Background: Acute respiratory distress syndrome (ARDS) is a severe critical condition with a high mortality that is currently in focus given that it is associated with mortality caused by coronavirus disease 2019 (COVID-19). Neutrophils play a key role in the lung injury characteristic of non-COVID-19 ARDS and there is also accumulating evidence of neutrophil mediated lung injury in patients who succumb to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Methods: We undertook a functional proteomic and metabolomic survey of circulating neutrophil populations, comparing patients with COVID-19 ARDS and non-COVID-19 ARDS to understand the molecular basis of neutrophil dysregulation.Results: Expansion of the circulating neutrophil compartment and the presence of activated low and normal density mature and immature neutrophil populations occurs in ARDS, irrespective of cause. Release of neutrophil granule proteins, neutrophil activation of the clotting cascade and upregulation of the Mac-1 platelet binding complex with formation of neutrophil platelet aggregates is exaggerated in COVID-19 ARDS. Importantly, activation of components of the neutrophil type I interferon responses is seen in ARDS following infection with SARS-CoV-2, with associated rewiring of neutrophil metabolism, and the upregulation of antigen processing and presentation. Whilst dexamethasone treatment constricts the immature low density neutrophil population, it does not impact upon prothrombotic hyperinflammatory neutrophil signatures.Conclusions: Given the crucial role of neutrophils in ARDS and the evidence of a disordered myeloid response observed in COVID-19 patients, this work maps the molecular basis for neutrophil reprogramming in the distinct clinical entities of COVID-19 and non-COVID-19 ARDS.

Published
2021

37. Additional file 1 of 17��-Ethinyl estradiol-3-sulfate increases survival and hemodynamic functioning in a large animal model of combined traumatic brain injury and hemorrhagic shock: a randomized control trial

Author

Mayer, Andrew R., Dodd, Andrew B., Rannou-Latella, Julie G., Stephenson, David D., Dodd, Rebecca J., Ling, Josef M., Mehos, Carissa J., Robertson-Benta, Cidney R., Pabbathi Reddy, Sharvani, Kinsler, Rachel E., Vermillion, Meghan S., Gigliotti, Andrew P., Sicard, Veronik, Lloyd, Amy L., Erhardt, Erik B., Gill, Jessica M., Lai, Chen, Guedes, Vivian A., and Chaudry, Irshad H.

Abstract

Additional file 1. Supplemental Materials.

Published
2021
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40. ­­­­­­­A type I IFN, prothrombotic hyperinflammatory neutrophil signature is distinct for COVID-19 ARDS­­­

Author

Reyes, Leila, primary, A. Sanchez-Garcia, Manuel, additional, Morrison, Tyler, additional, Howden, Andy J. M., additional, Watts, Emily R., additional, Arienti, Simone, additional, Sadiku, Pranvera, additional, Coelho, Patricia, additional, Mirchandani, Ananda S., additional, Zhang, Ailiang, additional, Hope, David, additional, Clark, Sarah K., additional, Singleton, Jo, additional, Johnston, Shonna, additional, Grecian, Robert, additional, Poon, Azin, additional, McNamara, Sarah, additional, Harper, Isla, additional, Fourman, Max Head, additional, Brenes, Alejandro J., additional, Pathak, Shalini, additional, Lloyd, Amy, additional, Blanco, Giovanny Rodriguez, additional, von Kriegsheim, Alex, additional, Ghesquiere, Bart, additional, Vermaelen, Wesley, additional, Cologna, Camila T., additional, Dhaliwal, Kevin, additional, Hirani, Nik, additional, Dockrell, David H., additional, Whyte, Moira K. B., additional, Griffith, David, additional, Cantrell, Doreen A., additional, and Walmsley, Sarah R., additional

Published
2021
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41. Survey of familial glioma and role of germline p16 INK4A /p14 ARF and p53 mutation

Author

Robertson, Lindsay B., Armstrong, Georgina N., Olver, Bianca D., Lloyd, Amy L., Shete, Sanjay, Lau, Ching, Claus, Elizabeth B., Barnholtz-Sloan, Jill, Lai, Rose, Il’yasova, Dora, Schildkraut, Joellen, Bernstein, Jonine L., Olson, Sara H., Jenkins, Robert B., Yang, Ping, Rynerason, Amanda L., Wrensch, Margaret, McCoy, Lucie, Wienkce, John K., McCarthy, Bridget, Davis, Faith, Vick, Nicholas A., Johansen, Christoffer, Bødtcher, Hanne, Sadetzki, Siegal, Bruchim, Revital Bar-Sade, Yechezkel, Galit Hirsh, Andersson, Ulrika, Melin, Beatrice S., Bondy, Melissa L., and Houlston, Richard S.

Published
2010
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42. Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis

Author

Whiffin, Nicola, Hosking, Fay J., Farrington, Susan M., Palles, Claire, Dobbins, Sara E., Zgaga, Lina, Lloyd, Amy, Kinnersley, Ben, Gorman, Maggie, Tenesa, Albert, Broderick, Peter, Wang, Yufei, Barclay, Ella, Hayward, Caroline, Martin, Lynn, Buchanan, Daniel D., Win, Aung Ko, Hopper, John, Jenkins, Mark, Lindor, Noralane M., Newcomb, Polly A., Gallinger, Steve, Conti, David, Schumacher, Fred, Casey, Graham, Liu, Tao, Campbell, Harry, Lindblom, Annika, Houlston, Richard S., Tomlinson, Ian P., and Dunlop, Malcolm G.

Published
2014
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44. Optimising paediatric afferent component early warning systems: a hermeneutic systematic literature review and model development

Author

Jacob, Nina, Moriarty, Yvonne, Lloyd, Amy, Mann, Mala, Tume, Lyvonne N, Sefton, Gerri, Powell, Colin, Roland, Damian, Trubey, Robert, Hood, Kerenza, and Allen, Davina

Subjects
Evidence-Based Medicine, Clinical Deterioration, track and trigger scores, early warning scores, Paediatrics, Hospitals, Pediatric, Intensive Care Units, Pediatric, PEWS, Pediatrics, Severity of Illness Index, children, systematic review, Health Status Indicators, Humans, Child, Original Research, Monitoring, Physiologic
Abstract

Objective To identify the core components of successful early warning systems for detecting and initiating action in response to clinical deterioration in paediatric inpatients. Methods A hermeneutic systematic literature review informed by translational mobilisation theory and normalisation process theory was used to synthesise 82 studies of paediatric and adult early warning systems and interventions to support the detection of clinical deterioration and escalation of care. This method, which is designed to develop understanding, enabled the development of a propositional model of an optimal afferent component early warning system. Results Detecting deterioration and initiating action in response to clinical deterioration in paediatric inpatients involves several challenges, and the potential failure points in early warning systems are well documented. Track and trigger tools (TTT) are commonly used and have value in supporting key mechanisms of action but depend on certain preconditions for successful integration into practice. Several supplementary interventions have been proposed to improve the effectiveness of early warning systems but there is limited evidence to recommend their wider use, due to the weight and quality of the evidence; the extent to which systems are conditioned by the local clinical context; and the need to attend to system component relationships, which do not work in isolation. While it was not possible to make empirical recommendations for practice, the review methodology generated theoretical inferences about the core components of an optimal system for early warning systems. These are presented as a propositional model conceptualised as three subsystems: detection, planning and action. Conclusions There is a growing consensus of the need to think beyond TTTs in improving action to detect and respond to clinical deterioration. Clinical teams wishing to improve early warning systems can use the model to consider systematically the constellation of factors necessary to support detection, planning and action and consider how these arrangements can be implemented in their local context. PROSPERO registration number CRD42015015326.

Published
2019

48. Proteomics identifies a type I IFN, prothrombotic hyperinflammatory circulating COVID-19 neutrophil signature distinct from non-COVID-19 ARDS

Author

Reyes, Leila, primary, Sanchez-Garcia, Manuel A., additional, Morrison, Tyler, additional, Howden, Andrew J.M., additional, Watts, Emily R., additional, Arienti, Simone, additional, Sadiku, Pranvera, additional, Coelho, Patricia, additional, Mirchandani, Ananda S, additional, Hope, David, additional, Clark, Sarah K., additional, Singleton, Jo, additional, Johnston, Shonna, additional, Grecian, Robert, additional, Poon, Azin, additional, Mcnamara, Sarah, additional, Harper, Isla, additional, Fourman, Max Head, additional, Brenes, Alejandro J., additional, Pathak, Shalini, additional, Lloyd, Amy, additional, Blanco, Gio Rodriguez, additional, Kriegsheim, Alex von, additional, Ghesquiere, Bart, additional, Vermaelen, Wesley, additional, Cologna, Camila T., additional, Dhaliwal, Kevin, additional, Hirani, Nik, additional, Dockrell, David, additional, Whyte, Moira K., additional, Griffith, David, additional, Cantrell, Doreen A., additional, and Walmsley, Sarah R., additional

Published
2020
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49. Survey of familial glioma and role of germline p16INK4A/p14ARF and p53 mutation

Author

Robertson, Lindsay B., Armstrong, Georgina N., Olver, Bianca D., Lloyd, Amy L., Shete, Sanjay, Lau, Ching, Claus, Elizabeth B., Barnholtz-Sloan, Jill, Lai, Rose, Ilʼyasova, Dora, Schildkraut, Joellen, Bernstein, Jonine L., Olson, Sara H., Jenkins, Robert B., Yang, Ping, Rynerason, Amanda L., Wrensch, Margaret, McCoy, Lucie, Wienkce, John K., McCarthy, Bridget, Davis, Faith, Vick, Nicholas A., Johansen, Christoffer, Bødtcher, Hanne, Sadetzki, Siegal, Bruchim, Revital Bar-Sade, Yechezkel, Galit Hirsh, Andersson, Ulrika, Melin, Beatrice S., Bondy, Melissa L., and Houlston, Richard S.

Published
2010
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50. The ability of observer and self-report measures to capture shared decision making in clinical practice in the United Kingdom: a mixed-methods study

Author

Williams, Denitza, Edwards, Adrian, Wood, Fiona, Lloyd, Amy, Brain, Katherine, Thomas, Nerys, Prichard, Alison, Goodland, Annwen, Sweetland, Helen, McGarrigle, Helen, Hill, Gwenllian, and Joseph-Williams, Natalie

Abstract

Objectives: To examine how observer and self-report measures of shared decision-making (SDM) evaluate the decision-making activities that patients and clinicians undertake in routine consultations.\ud \ud Design: Multi-method study using observational and self-reported measures of SDM and qualitative analysis.\ud \ud Setting: Breast care and predialysis teams who had already implemented SDM.\ud \ud Participants: Breast care consultants, clinical nurse specialists and patients who were making decisions about treatment for early-stage breast cancer. Predialysis clinical nurse specialists and patients who needed to make dialysis treatment decisions.\ud \ud Methods Consultations were audio recorded, transcribed and thematically analysed. SDM was measured using Observer OPTION-5 and a dyadic SureScore self-reported measure.\ud \ud Results: Twenty-two breast and 21 renal consultations were analysed. SureScore indicated that clinicians and patients felt SDM was occurring, but scores showed ceiling effects for most participants, making differentiation difficult. There was mismatch between SureScore and OPTION-5 score data, the latter showing that each consultation lacked at least some elements of SDM. Highest scoring items using OPTION-5 were ‘incorporating patient preferences into decisions’ for the breast team (mean 18.5, range 12.5–20, SD 2.39) and ‘eliciting patient preferences to options’ for the renal team (mean 16.15, range 10–20, SD 3.48). Thematic analysis identified that the SDM encounter is difficult to measure because decision-making is often distributed across encounters and time, with multiple people, it is contextually adapted and can involve multiple decisions.\ud \ud Conclusions: Self-reported measures can broadly indicate satisfaction with SDM, but do not tell us about the quality of the interaction and are unlikely to capture the multi-staged nature of the SDM process. Observational measures provide an indication of the extent to which elements of SDM are present in the observed consultation, but cannot explain why some elements might not be present or scored lower. Findings are important when considering measuring SDM in practice.

Published
2019

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