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368 results on '"Walsh, Tim"'

1. Albumin Versus Balanced Crystalloid for the Early Resuscitation of Sepsis: An Open Parallel-Group Randomized Feasibility Trial. The ABC-Sepsis Trial

Author

Gray, Alasdair J., Oatey, Katherine, Grahamslaw, Julia, Irvine, Sîan, Cafferkey, John, Kennel, Titouan, Norrie, John, Walsh, Tim, Lone, Nazir, Horner, Daniel, Appelboam, Andy, Hall, Peter, Skipworth, Richard J. E., Bell, Derek, Rooney, Kevin, Shankar-Hari, Manu, Corfield, Alasdair R., Newcombe, Virginia, Chapman, Robert, Hutton, Corinne, Perkins, Gavin, Gordon, Anthony, Keating, Liza, Pallmann, Philip, Armstrong, Ruth, Pollock, Roz, Wackett, Tony, Chapman, Robert, Hutton, Corrine, Kale, Jane, Kale, Neville, Anderson, Rory, Birrell, David, Black, Polly, Blackstock, Caroline, Carter, Jonathan, Clark, Donna, Davidson, Craig, Davie, Carlyn, Rollo, Nicola Di, Ferguson, Andrew, Fethers, Nicholas, Freeman, Nicola, Gibson, Louise, Grant, Alison, Harris, Marie-Clare, James, Ed, Letham, Katy, Lynch, Stephen, McCurrach, Fiona, McKenzie, Suzi, McLaughlin, Connor, Miell, Anna, Moncur, Lyle, O’Brien, Rachel, Pickering, Gillian, Reed, Matt, Rezai, Roozbeh, Robinson, Sara, Skinner, Janet, Walker, Craig, Williams, Alison, Wilson, Emma-Beth, Di Rollo, Nicola, Carruthers, Jennifer, Cheyne, Claire, McGeough, Angela, Lidstone-Scott, Rebecca, Lynch, Stephen, Abel, Lynn, Bongale, Santosh, Currie, Susie, Kane, Donna, Keen, Rachel, Orlikowska, Izabella, Rodden, Natalie, Tait, Jennifer, Thomson, Nicola, Walker, Lauren, Smith, Kate, Brown, Ammani, Cathcart, Susanne, Maguire, Donogh, O’Mailley, Patrick, Rimmer, Dominic, Ward, Catherine, Baxter, Nicola, Denny, Fraser, Doran, Kayleigh, Dunlop, Lisa, Dunn, Jessica, Finnen, Lisa, Green, Darren, Hughes, Emma, Lowe, David, McArthur, Courtney, McLaren, Barbara, McLeish, Kirsty, McMunigal, Linda, McParland, Chris, O’Shaughnessy, Ornagh, Wilson, Mark, Armes, Roland, Brown, Craig, Cooper, Jamie, Connor, David, Collier-Wakefield, Otto, Coutts, Mandi, Cruickshank, Mairi, Ebtehadj, Bianca, Ganley, Pauline, Hiscox, John, Hartman, Catharina, Kane, Leia, Kastora, Stavroula, Lamb, Sarah, McCarthy, Sinead, Mulholland, Conal, Nadim, Imran, Noble, Jennifer, Patton, Gareth, Savage, David, Spowage-Delaney, Benjamin, Doonan, Reece, Lee, Stephanie, Strange, Joshua, Barham, Ffion, Bosanko, Clare, Bullough, Richard, Danglosi, Joan, Freeman, Elaine, Jackson, Luci-Adele, James, Robert, Jose, Louise, Lowe, Fionna, Lowther, Ashleigh, McCarthy, Ian, McConnell, David, Parry, Richard, Shirreff, Henry, Smith, Jason, Squire, Rosalyn, Battishill, Wayne, Boggaram, Girish, Chilcott, Gemma, Gagg, James, Machin, Emma, Shovelton, Charmaine, Purnell, Rebecca, Crosthwaite-Eyre, Richard, Page, George, Pitt, Andrew, Riou, Peter, Sykes, Daisy, Worth, Cassie, Zitter, Lily, Baron, Tanya, Baskaran, Dineshbabu, Beer, Sally, Bhargav, Akshay, Blamey, Helen, Brown, Charlotte, Clare-Gray, Benjamin, Davies, Matthew, Dawson, Neil, Dineen, Karen, Edgar, Iain, Erasu, Vishakha, Faisal, Muhammad, Georgiou, Dominique, Gibson, Alice, Ghataoura, Rashpal, Glover, Samuel, Gordon, Olivia, Ilyas, Sadaf, Jeffs, Aimee, Knott, Henry, Kundoor, Sneha, Martinez, Jose, McCallum, Andrew, Novak, Alex, Panduro, Tine, Pattanshetty, Ravi, Paul, Immanuel, Magallano, Rufino Roger, Razdan, Pamposh, Sambo, Tinelly, Shah, Sumaiyah, Shaikh, Ayisha, Smith, Simon, Thraves, Hannah, Tickle, Charlotte, Ang, Justin, Boyle, Adrian, Hardwick, Susie, Meynell, Kerry, Miller, Samuel, Charsley, Julia, Jolly, Sarah, Mahony, Faye, Moseley-Rodgers, Jade, Sivayoham, Narani, Sheerin, Thomas, Seel, Claire, Abdalla, Mohamed, Cameron, Gregor, Harnett, James, Ramos, Daryl, Perez, Fabiola Sevilla, White, Rachel, Abdullah, Wajiha, Ballard, Suzanna, Barnes, Katie, Clegg, Rebecca, Cousins, Elisha, Cumiskey, Simon, Elwir, Bashar, Ferriman, Alexander, Fletcher, Alison, Griffiths, Charlotte, Guiling, Paolyn, Johnson, Graham, Loach, Benjamin, Matthews, Alison, May-Moulden, Lucy, Norman, Rebecca, Seelly, Helen, Smith, Richard, Tabner, Andrew, Tilbury, Nicholas, Ward, Thomas, Wright, Lianne, Wroblewski, Heather, and Zawadzka, Marcelina

Published
2024
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3. Comparing performance on the Months of the Year Backwards test in hospitalised patients with delirium, dementia, and no cognitive impairment: an exploratory study

Author

Hasemann, Wolfgang, Duncan, Nikki, Clarke, Caoimhe, Nouzova, Eva, Süßenbach, Lisa-Marie, Keerie, Catriona, Assi, Valentina, Weir, Christopher J., Evans, Jonathan, Walsh, Tim, Wilson, Elizabeth, Quasim, Tara, Middleton, Duncan, Weir, Alexander J., Barnett, Jennifer H., Stott, David J., MacLullich, Alasdair M. J., and Tieges, Zoë

Published
2021
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9. Indo-Pacific Network Expansion

Author

Drigo, Don, Smith, Marquis, and Walsh, Tim

Subjects
United States. Defense Information Systems Agency, United States. Army, Information management, Information accessibility, Electronics, Military and naval science
Abstract

NOTE: We wish to honor the late CW4 Marquis Smith with this article. He was our dedicated teammate on these projects and many others, and a loyal servant of this [...]

Published
2021

14. biomArker-guided Duration of Antibiotic treatment in hospitalised Patients with suspecTed Sepsis (ADAPT-Sepsis): A protocol for a multicentre randomised controlled trial.

Author

Dark, Paul, Perkins, Gavin D, McMullan, Ronan, McAuley, Danny, Gordon, Anthony C, Clayton, Jonathan, Mistry, Dipesh, Young, Keith, Regan, Scott, McGowan, Nicola, Stevenson, Matt, Gates, Simon, Carlson, Gordon L, Walsh, Tim, Lone, Nazir I, Mouncey, Paul R, Singer, Mervyn, Wilson, Peter, Felton, Tim, and Marshall, Kay

Published
2023
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16. Diagnostic test accuracy of a novel smartphone application for the assessment of attention deficits in delirium in older hospitalised patients: a prospective cohort study protocol

Author

Rutter, Lisa-Marie, Nouzova, Eva, Stott, David J., Weir, Christopher J., Assi, Valentina, Barnett, Jennifer H., Clarke, Caoimhe, Duncan, Nikki, Evans, Jonathan, Green, Samantha, Hendry, Kirsty, McGinlay, Meigan, McKeever, Jenny, Middleton, Duncan G., Parks, Stuart, Shaw, Robert, Tang, Elaine, Walsh, Tim, Weir, Alexander J., Wilson, Elizabeth, Quasim, Tara, MacLullich, Alasdair M.J., and Tieges, Zoë

Published
2018
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21. In-Flight Guidance, Navigation, and Control Performance Results for the GOES-16 Spacecraft

Author

Chapel, Jim, Stancliffe, Devin, Bevacqua, Tim, Winkler, Stephen, Clapp, Brian, Rood, Tim, Freesland, Doug, Reth, Alan, Early, Derrick, Walsh, Tim, and Krimchansky, Alexander

Subjects
Spacecraft Instrumentation And Astrionics
Abstract

The Geostationary Operational Environmental Satellite-R Series (GOES-R), which launched in November 2016, is the first of the next generation geostationary weather satellites. GOES-R provides 4 times the resolution, 5 times the observation rate, and 3 times the number of spectral bands for Earth observations compared with its predecessor spacecraft. Additionally, Earth relative and Sun-relative pointing and pointing stability requirements are maintained throughout reaction wheel desaturation events and station keeping activities, allowing GOES-R to provide continuous Earth and sun observations. This paper reviews the pointing control, pointing stability, attitude knowledge, and orbit knowledge requirements necessary to realize the ambitious Image Navigation and Registration (INR) objectives of GOES-R. This paper presents a comparison between low-frequency on-orbit pointing results and simulation predictions for both the Earth Pointed Platform (EPP) and Sun Pointed Platform (SPP). Results indicate excellent agreement between simulation predictions and observed on-orbit performance, and compliance with pointing performance requirements. The EPP instrument suite includes 6 seismic accelerometers sampled at 2 KHz, allowing in-flight verification of jitter responses and comparison back to simulation predictions. This paper presents flight results of acceleration, shock response spectrum (SRS), and instrument line of sight responses for various operational scenarios and instrument observation modes. The results demonstrate the effectiveness of the dual-isolation approach employed on GOES-R. The spacecraft provides attitude and rate data to the primary Earth-observing instrument at 100 Hz, which are used to adjust instrument scanning. The data must meet accuracy and latency numbers defined by the Integrated Rate Error (IRE) requirements. This paper discusses the on-orbit IRE results, showing compliance to these requirements with margin. During the spacecraft checkout period, IRE disturbances were observed and subsequently attributed to thermal control of the Inertial Measurement Unit (IMU) mounting interface. Adjustments of IMU thermal control and the resulting improvements in IRE are presented. Orbit knowledge represents the final element of INR performance. Extremely accurate orbital position is achieved by GPS navigation at Geosynchronous Earth Orbit (GEO). On-orbit performance results are shown demonstrating compliance with the stringent orbit position accuracy requirements of GOES-R, including during station keeping activities and momentum desaturation events. As we show in this paper, the on-orbit performance of the GNC design provides the necessary capabilities to achieve GOES-R mission objectives.

Published
2017

26. Increasing Climber Performance The Search for Efficiency.

Author

Walsh, Tim and Ball, John

Abstract

The article discusses effectiveness of skills of climbing for assessment of tree canopies, and mentions similarities with athletes competing in sport climbing. Topics discussed include competition of arborist athletes in climbing events during the International Tree Climbing Competition (ITCC), consideration of factors in efficiency of climber, and increase in heart rate during climbing.

Published
2023

27. Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19:The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial

Author

Angus, Derek C, Derde, Lennie, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen, Beane, Abigail, van Bentum-Puijk, Wilma, Berry, Lindsay, Bhimani, Zahra, Bonten, Marc, Bradbury, Charlotte, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Cheng, Allen C, de Jong, Menno, Detry, Michelle, Estcourt, Lise, Fitzgerald, Mark, Goossens, Herman, Green, Cameron, Haniffa, Rashan, Higgins, Alisa M, Horvat, Christopher, Hullegie, Sebastiaan J, Kruger, Peter, Lamontagne, Francois, Lawler, Patrick R, Linstrum, Kelsey, Litton, Edward, Lorenzi, Elizabeth, Marshall, John, McAuley, Daniel, McGlothin, Anna, McGuinness, Shay, McVerry, Bryan, Montgomery, Stephanie, Mouncey, Paul, Murthy, Srinivas, Nichol, Alistair, Parke, Rachael, Parker, Jane, Rowan, Kathryn, Sanil, Ashish, Santos, Marlene, Saunders, Christina, Seymour, Christopher, Turner, Anne, van de Veerdonk, Frank, Venkatesh, Balasubramanian, Zarychanski, Ryan, Berry, Scott, Lewis, Roger J, McArthur, Colin, Webb, Steven A, Gordon, Anthony C, Writing Committee for the REMAP-CAP Investigators, Angus, Derek, Cheng, Allen, De Jong, Menno, Gordon, Anthony, Lawler, Patrick, Webb, Steve, Campbell, Lewis, Forbes, Andrew, Gattas, David, Heritier, Stephane, Higgins, Lisa, Peake, Sandra, Presneill, Jeffrey, Seppelt, Ian, Trapani, Tony, Young, Paul, Bagshaw, Sean, Daneman, Nick, Ferguson, Niall, Misak, Cheryl, Hullegie, Sebastiaan, Pletz, Mathias, Rohde, Gernot, Rowan, Kathy, Alexander, Brian, Basile, Kim, Girard, Timothy, Huang, David, Vates, Jennifer, Beasley, Richard, Fowler, Robert, McGloughlin, Steve, Morpeth, Susan, Paterson, David, Venkatesh, Bala, Uyeki, Tim, Baillie, Kenneth, Duffy, Eamon, Fowler, Rob, Hills, Thomas, Orr, Katrina, Patanwala, Asad, Tong, Steve, Netea, Mihai, Bihari, Shilesh, Carrier, Marc, Fergusson, Dean, Goligher, Ewan, Haidar, Ghady, Hunt, Beverley, Kumar, Anand, Laffan, Mike, Lawless, Patrick, Lother, Sylvain, McCallum, Peter, Middeldopr, Saskia, McQuilten, Zoe, Neal, Matthew, Pasi, John, Schutgens, Roger, Stanworth, Simon, Turgeon, Alexis, Weissman, Alexandra, Adhikari, Neill, Anstey, Matthew, Brant, Emily, de Man, Angelique, Lamonagne, Francois, Masse, Marie-Helene, Udy, Andrew, Arnold, Donald, Begin, Phillipe, Charlewood, Richard, Chasse, Michael, Coyne, Mark, Cooper, Jamie, Daly, James, Gosbell, Iain, Harvala-Simmonds, Heli, Hills, Tom, MacLennan, Sheila, Menon, David, McDyer, John, Pridee, Nicole, Roberts, David, Shankar-Hari, Manu, Thomas, Helen, Tinmouth, Alan, Triulzi, Darrell, Walsh, Tim, Wood, Erica, Calfee, Carolyn, O’Kane, Cecilia, Shyamsundar, Murali, Sinha, Pratik, Thompson, Taylor, Young, Ian, Bihari, Shailesh, Hodgson, Carol, Laffey, John, McAuley, Danny, Orford, Neil, Neto, Ary, Lewis, Roger, McGlothlin, Anna, Miller, Eliza, Singh, Vanessa, Zammit, Claire, van Bentum Puijk, Wilma, Bouwman, Wietske, Mangindaan, Yara, Parker, Lorraine, Peters, Svenja, Rietveld, Ilse, Raymakers, Kik, Ganpat, Radhika, Brillinger, Nicole, Markgraf, Rene, Ainscough, Kate, Brickell, Kathy, Anjum, Aisha, Lane, Janis-Best, Richards-Belle, Alvin, Saull, Michelle, Wiley, Daisy, Bion, Julian, Connor, Jason, Gates, Simon, Manax, Victoria, van der Poll, Tom, Reynolds, John, van Beurden, Marloes, Effelaar, Evelien, Schotsman, Joost, Boyd, Craig, Harland, Cain, Shearer, Audrey, Wren, Jess, Clermont, Giles, Garrard, William, Kalchthaler, Kyle, King, Andrew, Ricketts, Daniel, Malakoutis, Salim, Marroquin, Oscar, Music, Edvin, Quinn, Kevin, Cate, Heidi, Pearson, Karen, Collins, Joanne, Hanson, Jane, Williams, Penny, Jackson, Shane, Asghar, Adeeba, Dyas, Sarah, Sutu, Mihaela, Murphy, Sheenagh, Williamson, Dawn, Mguni, Nhlanhla, Potter, Alison, Porter, David, Goodwin, Jayne, Rook, Clare, Harrison, Susie, Williams, Hannah, Campbell, Hilary, Lomme, Kaatje, Williamson, James, Sheffield, Jonathan, van’t Hoff, Willian, McCracken, Phobe, Young, Meredith, Board, Jasmin, Mart, Emma, Knott, Cameron, Smith, Julie, Boschert, Catherine, Affleck, Julia, Ramanan, Mahesh, D’Souza, Ramsy, Pateman, Kelsey, Shakih, Arif, Cheung, Winston, Kol, Mark, Wong, Helen, Shah, Asim, Wagh, Atul, Simpson, Joanne, Duke, Graeme, Chan, Peter, Cartner, Brittney, Hunter, Stephanie, Laver, Russell, Shrestha, Tapaswi, Regli, Adrian, Pellicano, Annamaria, McCullough, James, Tallott, Mandy, Kumar, Nikhil, Panwar, Rakshit, Brinkerhoff, Gail, Koppen, Cassandra, Cazzola, Federica, Brain, Matthew, Mineall, Sarah, Fischer, Roy, Biradar, Vishwanath, Soar, Natalie, White, Hayden, Estensen, Kristen, Morrison, Lynette, Smith, Joanne, Cooper, Melanie, Health, Monash, Shehabi, Yahya, Al-Bassam, Wisam, Hulley, Amanda, Whitehead, Christina, Lowrey, Julie, Gresha, Rebecca, Walsham, James, Meyer, Jason, Harward, Meg, Venz, Ellen, Williams, Patricia, Kurenda, Catherine, Smith, Kirsy, Smith, Margaret, Garcia, Rebecca, Barge, Deborah, Byrne, Deborah, Byrne, Kathleen, Driscoll, Alana, Fortune, Louise, Janin, Pierre, Yarad, Elizabeth, Hammond, Naomi, Bass, Frances, Ashelford, Angela, Waterson, Sharon, Wedd, Steve, McNamara, Robert, Buhr, Heidi, Coles, Jennifer, Schweikert, Sacha, Wibrow, Bradley, Rauniyar, Rashmi, Myers, Erina, Fysh, Ed, Dawda, Ashlish, Mevavala, Bhaumik, Litton, Ed, Ferrier, Janet, Nair, Priya, Buscher, Hergen, Reynolds, Claire, Santamaria, John, Barbazza, Leanne, Homes, Jennifer, Smith, Roger, Murray, Lauren, Brailsford, Jane, Forbes, Loretta, Maguire, Teena, Mariappa, Vasanth, Smith, Judith, Simpson, Scott, Maiden, Matthew, Bone, Allsion, Horton, Michelle, Salerno, Tania, Sterba, Martin, Geng, Wenli, Depuydt, Pieter, De Waele, Jan, De Bus, Liesbet, Fierens, Jan, Bracke, Stephanie, Reeve, Brenda, Dechert, William, Chassé, Michaël, Carrier, François Martin, Boumahni, Dounia, Benettaib, Fatna, Ghamraoui, Ali, Bellemare, David, Cloutier, Ève, Francoeur, Charles, Lamontagne, François, D’Aragon, Frédérick, Carbonneau, Elaine, Leblond, Julie, Vazquez-Grande, Gloria, Marten, Nicole, Wilson, Maggie, Albert, Martin, Serri, Karim, Cavayas, Alexandros, Duplaix, Mathilde, Williams, Virginie, Rochwerg, Bram, Karachi, Tim, Oczkowski, Simon, Centofanti, John, Millen, Tina, Duan, Erick, Tsang, Jennifer, Patterson, Lisa, English, Shane, Watpool, Irene, Porteous, Rebecca, Miezitis, Sydney, McIntyre, Lauralyn, Brochard, Laurent, Burns, Karen, Sandhu, Gyan, Khalid, Imrana, Binnie, Alexandra, Powell, Elizabeth, McMillan, Alexandra, Luk, Tracy, Aref, Noah, Andric, Zdravko, Cviljevic, Sabina, Đimoti, Renata, Zapalac, Marija, Mirković, Gordan, Baršić, Bruno, Kutleša, Marko, Kotarski, Viktor, Vujaklija Brajković, Ana, Babel, Jakša, Sever, Helena, Dragija, Lidija, Kušan, Ira, Vaara, Suvi, Pettilä, Leena, Heinonen, Jonna, Kuitunen, Anne, Karlsson, Sari, Vahtera, Annukka, Kiiski, Heikki, Ristimäki, Sanna, Azaiz, Amine, Charron, Cyril, Godement, Mathieu, Geri, Guillaume, Vieillard-Baron, Antoine, Pourcine, Franck, Monchi, Mehran, Luis, David, Mercier, Romain, Sagnier, Anne, Verrier, Nathalie, Caplin, Cecile, Siami, Shidasp, Aparicio, Christelle, Vautier, Sarah, Jeblaoui, Asma, Fartoukh, Muriel, Courtin, Laura, Labbe, Vincent, Leparco, Cécile, Muller, Grégoire, Nay, Mai-Anh, Kamel, Toufik, Benzekri, Dalila, Jacquier, Sophie, Mercier, Emmanuelle, Chartier, Delphine, Salmon, Charlotte, Dequin, PierreFrançois, Schneider, Francis, Morel, Guillaume, L’Hotellier, Sylvie, Badie, Julio, Berdaguer, Fernando Daniel, Malfroy, Sylvain, Mezher, Chaouki, Bourgoin, Charlotte, Megarbane, Bruno, Voicu, Sebastian, Deye, Nicolas, Malissin, Isabelle, Sutterlin, Laetitia, Guitton, Christophe, Darreau, Cédric, Landais, Mickaël, Chudeau, Nicolas, Robert, Alain, Moine, Pierre, Heming, Nicholas, Maxime, Virginie, Bossard, Isabelle, Nicholier, Tiphaine Barbarin, Colin, Gwenhael, Zinzoni, Vanessa, Maquigneau, Natacham, Finn, André, Kreß, Gabriele, Hoff, Uwe, Friedrich Hinrichs, Carl, Nee, Jens, Hagel, Stefan, Ankert, Juliane, Kolanos, Steffi, Bloos, Frank, Petros, Sirak, Pasieka, Bastian, Kunz, Kevin, Appelt, Peter, Schütze, Bianka, Kluge, Stefan, Nierhaus, Axel, Jarczak, Dominik, Roedl, Kevin, Weismann, Dirk, Frey, Anna, Klinikum Neukölln, Vivantes, Reill, Lorenz, Distler, Michael, Maselli, Astrid, Bélteczki, János, Magyar, István, Fazekas, Ágnes, Kovács, Sándor, Szőke, Viktória, Szigligeti, Gábor, Leszkoven, János, Collins, Daniel, Breen, Patrick, Frohlich, Stephen, Whelan, Ruth, McNicholas, Bairbre, Scully, Michael, Casey, Siobhan, Kernan, Maeve, Doran, Peter, O’Dywer, Michael, Smyth, Michelle, Hayes, Leanne, Hoiting, Oscar, Peters, Marco, Rengers, Els, Evers, Mirjam, Prinssen, Anton, Bosch Ziekenhuis, Jeroen, Simons, Koen, Rozendaal, Wim, Polderman, F, de Jager, P, Moviat, M, Paling, A, Salet, A, Rademaker, Emma, Peters, Anna Linda, de Jonge, E, Wigbers, J, Guilder, E, Butler, M, Cowdrey, Keri-Anne, Newby, Lynette, Chen, Yan, Simmonds, Catherine, McConnochie, Rachael, Ritzema Carter, Jay, Henderson, Seton, Van Der Heyden, Kym, Mehrtens, Jan, Williams, Tony, Kazemi, Alex, Song, Rima, Lai, Vivian, Girijadevi, Dinu, Everitt, Robert, Russell, Robert, Hacking, Danielle, Buehner, Ulrike, Williams, Erin, Browne, Troy, Grimwade, Kate, Goodson, Jennifer, Keet, Owen, Callender, Owen, Martynoga, Robert, Trask, Kara, Butler, Amelia, Schischka, Livia, Young, Chelsea, Lesona, Eden, Olatunji, Shaanti, Robertson, Yvonne, José, Nuno, Amaro dos Santos Catorze, Teodoro, de Lima Pereira, Tiago Nuno Alfaro, Neves Pessoa, Lucilia Maria, Castro Ferreira, Ricardo Manuel, Pereira Sousa Bastos, Joana Margarida, Aysel Florescu, Simin, Stanciu, Delia, Zaharia, Miahela Florentina, Kosa, Alma Gabriela, Codreanu, Daniel, Marabi, Yaseen, Al Qasim, Eman, Moneer Hagazy, Mohamned, Al Swaidan, Lolowa, Arishi, Hatim, Muñoz-Bermúdez, Rosana, Marin-Corral, Judith, Salazar Degracia, Anna, Parrilla Gómez, Francisco, Mateo López, Maria Isabel, Rodriguez Fernandez, Jorge, Cárcel Fernández, Sheila, Carmona Flores, Rosario, León López, Rafael, de la Fuente Martos, Carmen, Allan, Angela, Polgarova, Petra, Farahi, Neda, McWilliam, Stephen, Hawcutt, Daniel, Rad, Laura, O’Malley, Laura, Whitbread, Jennifer, Kelsall, Olivia, Wild, Laura, Thrush, Jessica, Wood, Hannah, Austin, Karen, Donnelly, Adrian, Kelly, Martin, O’Kane, Sinéad, McClintock, Declan, Warnock, Majella, Johnston, Paul, Gallagher, Linda Jude, Mc Goldrick, Clare, Mc Master, Moyra, Strzelecka, Anna, Jha, Rajeev, Kalogirou, Michael, Ellis, Christine, Krishnamurthy, Vinodh, Deelchand, Vashish, Silversides, Jon, McGuigan, Peter, Ward, Kathryn, O’Neill, Aisling, Finn, Stephanie, Phillips, Barbara, Mullan, Dee, Oritz-Ruiz de Gordoa, Laura, Thomas, Matthew, Sweet, Katie, Grimmer, Lisa, Johnson, Rebekah, Pinnell, Jez, Robinson, Matt, Gledhill, Lisa, Wood, Tracy, Morgan, Matt, Cole, Jade, Hill, Helen, Davies, Michelle, Antcliffe, David, Templeton, Maie, Rojo, Roceld, Coghlan, Phoebe, Smee, Joanna, Mackay, Euan, Cort, Jon, Whileman, Amanda, Spencer, Thomas, Spittle, Nick, Kasipandian, Vidya, Patel, Amit, Allibone, Suzanne, Genetu, Roman Mary, Ramali, Mohamed, Ghosh, Alison, Bamford, Peter, London, Emily, Cawley, Kathryn, Faulkner, Maria, Jeffrey, Helen, Smith, Tim, Brewer, Chris, Gregory, Jane, Limb, James, Cowton, Amanda, O’Brien, Julie, Nikitas, Nikitas, Wells, Colin, Lankester, Liana, Pulletz, Mark, Birch, Jenny, Wiseman, Sophie, Horton, Sarah, Alegria, Ana, Turki, Salah, Elsefi, Tarek, Crisp, Nikki, Allen, Louise, McCullagh, Iain, Robinson, Philip, Hays, Carole, Babio-Galan, Maite, Stevenson, Hannah, Khare, Divya, Pinder, Meredith, Selvamoni, Selvin, Gopinath, Amitha, Pugh, Richard, Menzies, Daniel, Mackay, Callum, Allan, Elizabeth, Davies, Gwyneth, Puxty, Kathryn, McCue, Claire, Cathcart, Susanne, Hickey, Naomi, Ireland, Jane, Yusuff, Hakeem, Isgro, Graziella, Brightling, Chris, Bourne, Michelle, Craner, Michelle, Watters, Malcolm, Prout, Rachel, Davies, Louisa, Pegler, Suzannah, Kyeremeh, Lynsey, Arbane, Gill, Wilson, Karen, Gomm, Linda, Francia, Federica, Brett, Stephen, Sousa Arias, Sonia, Elin Hall, Rebecca, Budd, Joanna, Small, Charlotte, Birch, Janine, Collins, Emma, Henning, Jeremy, Bonner, Stephen, Hugill, Keith, Cirstea, Emanuel, Wilkinson, Dean, Karlikowski, Michal, Sutherland, Helen, Wilhelmsen, Elva, Woods, Jane, North, Julie, Sundaran, Dhinesh, Hollos, Laszlo, Coburn, Susan, Walsh, Joanne, Turns, Margaret, Hopkins, Phil, Smith, John, Noble, Harriet, Depante, Maria Theresa, Clarey, Emma, Laha, Shondipon, Verlander, Mark, Williams, Alexandra, Huckle, Abby, Hall, Andrew, Cooke, Jill, Gardiner-Hill, Caroline, Maloney, Carolyn, Qureshi, Hafiz, Flint, Neil, Nicholson, Sarah, Southin, Sara, Nicholson, Andrew, Borgatta, Barbara, Turner-Bone, Ian, Reddy, Amie, Wilding, Laura, Chamara Warnapura, Loku, Agno Sathianathan, Ronan, Golden, David, Hart, Ciaran, Jones, Jo, Bannard-Smith, Jonathan, Henry, Joanne, Birchall, Katie, Pomeroy, Fiona, Quayle, Rachael, Makowski, Arystarch, Misztal, Beata, Ahmed, Iram, KyereDiabour, Thyra, Naiker, Kevin, Stewart, Richard, Mwaura, Esther, Mew, Louise, Wren, Lynn, Willams, Felicity, Innes, Richard, Doble, Patricia, Hutter, Joanne, Shovelton, Charmaine, Plumb, Benjamin, Szakmany, Tamas, Hamlyn, Vincent, Hawkins, Nancy, Lewis, Sarah, Dell, Amanda, Gopal, Shameer, Ganguly, Saibal, Smallwood, Andrew, Harris, Nichola, Metherell, Stella, Lazaro, Juan Martin, Newman, Tabitha, Fletcher, Simon, Nortje, Jurgens, Fottrell-Gould, Deirdre, Randell, Georgina, Zaman, Mohsin, Elmahi, Einas, Jones, Andrea, Hall, Kathryn, Mills, Gary, Ryalls, Kim, Bowler, Helen, Sall, Jas, Bourne, Richard, Borrill, Zoe, Duncan, Tracey, Lamb, Thomas, Shaw, Joanne, Fox, Claire, Moreno Cuesta, Jeronimo, Xavier, Kugan, Purohit, Dharam, Elhassan, Munzir, Bakthavatsalam, Dhanalakshmi, Rowland, Matthew, Hutton, Paula, Bashyal, Archana, Davidson, Neil, Hird, Clare, Chhablani, Manish, Phalod, Gunjan, Kirkby, Amy, Archer, Simon, Netherton, Kimberley, Reschreiter, Henrik, Camsooksai, Julie, Patch, Sarah, Jenkins, Sarah, Pogson, David, Rose, Steve, Daly, Zoe, Brimfield, Lutece, Claridge, Helen, Parekh, Dhruv, Bergin, Colin, Bates, Michelle, Dasgin, Joanne, McGhee, Christopher, Sim, Malcolm, Hay, Sophie Kennedy, Henderson, Steven, Phull, Mandeep-Kaur, Zaidi, Abbas, Pogreban, Tatiana, Rosaroso, Lace Paulyn, Harvey, Daniel, Lowe, Benjamin, Meredith, Megan, Ryan, Lucy, Hormis, Anil, Walker, Rachel, Collier, Dawn, Kimpton, Sarah, Oakley, Susan, Rooney, Kevin, Rodden, Natalie, Hughes, Emma, Thomson, Nicola, McGlynn, Deborah, Walden, Andrew, Jacques, Nicola, Coles, Holly, Tilney, Emma, Vowell, Emma, Schuster-Bruce, Martin, Pitts, Sally, Miln, Rebecca, Purandare, Laura, Vamplew, Luke, Spivey, Michael, Bean, Sarah, Burt, Karen, Moore, Lorraine, Day, Christopher, Gibson, Charly, Gordon, Elizabeth, Zitter, Letizia, Keenan, Samantha, Baker, Evelyn, Cherian, Shiney, Cutler, Sean, Roynon-Reed, Anna, Harrington, Kate, Raithatha, Ajay, Bauchmuller, Kris, Ahmad, Norfaizan, Grecu, Irina, Trodd, Dawn, Martin, Jane, Wrey Brown, Caroline, Arias, Ana-Marie, Craven, Thomas, Hope, David, Singleton, Jo, Clark, Sarah, Rae, Nicola, Welters, Ingeborg, Hamilton, David Oliver, Williams, Karen, Waugh, Victoria, Shaw, David, Puthucheary, Zudin, Martin, Timothy, Santos, Filipa, Uddin, Ruzena, Somerville, Alastair, Tatham, Kate Colette, Jhanji, Shaman, Black, Ethel, Dela Rosa, Arnold, Howle, Ryan, Tully, Redmond, Drummond, Andrew, Dearden, Joy, Philbin, Jennifer, Munt, Sheila, Vuylsteke, Alain, Chan, Charles, Victor, Saji, Matsa, Ramprasad, Gellamucho, Minerva, Creagh-Brown, Ben, Tooley, Joe, Montague, Laura, De Beaux, Fiona, Bullman, Laetitia, Kersiake, Ian, Demetriou, Carrie, Mitchard, Sarah, Ramos, Lidia, White, Katie, Donnison, Phil, Johns, Maggie, Casey, Ruth, Mattocks, Lehentha, Salisbury, Sarah, Dark, Paul, Claxton, Andrew, McLachlan, Danielle, Slevin, Kathryn, Lee, Stephanie, Hulme, Jonathan, Joseph, Sibet, Kinney, Fiona, Senya, Ho Jan, Oborska, Aneta, Kayani, Abdul, Hadebe, Bernard, Orath Prabakaran, Rajalakshmi, Nichols, Lesley, Thomas, Matt, Worner, Ruth, Faulkner, Beverley, Gendall, Emma, Hayes, Kati, Hamilton-Davies, Colin, Chan, Carmen, Mfuko, Celina, Abbass, Hakam, Mandadapu, Vineela, Leaver, Susannah, Forton, Daniel, Patel, Kamal, Paramasivam, Elankumaran, Powell, Matthew, Gould, Richard, Wilby, Elizabeth, Howcroft, Clare, Banach, Dorota, Fernández de Pinedo Artaraz, Ziortza, Cabreros, Leilani, White, Ian, Croft, Maria, Holland, Nicky, Pereira, Rita, Zaki, Ahmed, Johnson, David, Jackson, Matthew, Garrard, Hywel, Juhaz, Vera, Roy, Alistair, Rostron, Anthony, Woods, Lindsey, Cornell, Sarah, Pillai, Suresh, Harford, Rachel, Rees, Tabitha, Ivatt, Helen, Sundara Raman, Ajay, Davey, Miriam, Lee, Kelvin, Barber, Russell, Chablani, Manish, Brohi, Farooq, Jagannathan, Vijay, Clark, Michele, Purvis, Sarah, Wetherill, Bill, Dushianthan, Ahilanandan, Cusack, Rebecca, de Courcy-Golder, Kim, Smith, Simon, Jackson, Susan, Attwood, Ben, Parsons, Penny, Page, Valerie, Zhao, Xiao Bei, Oza, Deepali, Rhodes, Jonathan, Anderson, Tom, Morris, Sheila, Xia Le Tai, Charlotte, Thomas, Amy, Keen, Alexandra, Digby, Stephen, Cowley, Nicholas, Southern, David, Reddy, Harsha, Campbell, Andy, Watkins, Claire, Smuts, Sara, Touma, Omar, Barnes, Nicky, Alexander, Peter, Felton, Tim, Ferguson, Susan, Sellers, Katharine, Bradley-Potts, Joanne, Yates, David, Birkinshaw, Isobel, Kell, Kay, Marshall, Nicola, Carr-Knott, Lisa, Writing Committee for the REMAP-CAP Investigators, Menon, David [0000-0002-3228-9692], Apollo - University of Cambridge Repository, Medical Microbiology and Infection Prevention, and AII - Infectious diseases

Subjects
Male, Hydrocortisone, Anti-Inflammatory Agents, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], 01 natural sciences, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Adrenal Cortex Hormones, Clinical endpoint, Medicine, 030212 general & internal medicine, Hydrocortisone/administration & dosage, Original Investigation, 2. Zero hunger, Mortality rate, Shock, Covid19, General Medicine, Middle Aged, Intensive care unit, 3. Good health, Intensive Care Units, Treatment Outcome, Early Termination of Clinical Trials, Corticosteroid, Female, Coronavirus Infections, medicine.drug, Adult, medicine.medical_specialty, Respiration, Artificial/statistics & numerical data, medicine.drug_class, Anti-Inflammatory Agents/administration & dosage, Pneumonia, Viral, UNCOVER, Adrenal Cortex Hormones/therapeutic use, 03 medical and health sciences, Betacoronavirus, All institutes and research themes of the Radboud University Medical Center, Internal medicine, Humans, 0101 mathematics, Adverse effect, Pandemics, business.industry, SARS-CoV-2, 010102 general mathematics, COVID-19, Odds ratio, Coronavirus Infections/drug therapy, Pneumonia, Viral/drug therapy, Respiration, Artificial, COVID-19 Drug Treatment, Shock/drug therapy, Human medicine, business
Abstract

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19.Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020.Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108).Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%).Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively.Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.

Published
2020
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30. IFITM3 restricts the morbidity and mortality associated with influenza

Author

Everitt, Aaron R., Clare, Simon, Pertel, Thomas, John, Sinu P., Wash, Rachael S., Smith, Sarah E., Chin, Christopher R., Feeley, Eric M., Sims, Jennifer S., Adams, David J., Wise, Helen M., Kane, Leanne, Goulding, David, Digard, Paul, Anttila, Verneri, Baillie, Kenneth J., Walsh, Tim S., Hume, David A., Palotie, Aarno, Xue, Yali, Colonna, Vincenza, Tyler-Smith, Chris, Dunning, Jake, Gordon, Stephen B., Everingham, K., Dawson, H., Hope, D., Ramsay, P., Walsh (Local Lead Investigator), T. S., Campbell, A., Kerr, S., Harrison, D., Rowan, K., Addison, J., Donald, N., Galt, S., Noble, D., Taylor, J., Webster (Local Lead Investigator), N., Taylor (Local Lead Investigator), I., Aldridge (Local Lead Investigator), J., Dornan, R., Richard, C., Gilmour, D., Simmons (Local Lead Investigator), R., White (Local Lead Investigator), R., Jardine, C., Williams (Local Lead Investigator), D., Booth (Local Lead Investigator), M., Quasim, T., Watson, V., Henry, P., Munro, F., Bell, L., Ruddy (Local Lead Investigator), J., Cole (Local Lead Investigator), S., Southward, J., Allcoat, P., Gray, S., McDougall (Local Lead Investigator), M., Matheson, J., Whiteside (Local Lead Investigator), J., Alcorn, D., Rooney (Local Lead Investigator), K., Sundaram, R., Imrie (Local Lead Investigator), G., Bruce, J., McGuigan, K., Moultrie (Local Lead Investigator), S., Cairns (Local Lead Investigator), C., Grant, J., Hughes, M., Murdoch (Local Lead Investigator), C., Davidson (Local Lead Investigator), A., Harris, G., Paterson, R., Wallis (Local Lead Investigator), C., Binning (Local Lead Investigator), S., Pollock, M., Antonelli, J., Duncan, A., Gibson, J., McCulloch, C., Murphy, L., Haley, C., Faulkner, G., Freeman, T., Hume, D. A., Baillie (Principal Investigator), J. K., Chaussabel, D., Adamson, W. E., Carman, W. F., Thompson, C., Zambon, M. C., Aylin, P., Ashby, D., Barclay, W. S., Brett, S. J., Cookson, W. O., Drumright, L. N., Dunning, J., Elderfield, R. A., Garcia-Alvarez, L., Gazzard, B. G., Griffiths, M. J., Habibi, M. S., Hansel, T. T., Herberg, J. A., Holmes, A. H., Hussell, T., Johnston, S. L., Kon, O. M., Levin, M., Moffatt, M. F., Nadel, S., Openshaw, P. J., Warner, J. O., Aston, S. J., Gordon, S. B., Hay, A., McCauley, J., OʼGarra, A., Banchereau, J., Hayward, A., Baillie, J. K., Simmonds, P., McNamara, P. S., Semple, M. G., Smyth, R. L., Nguyen-Van-Tam, J. S., Ho, L.-P., McMichael, A. J., Kellam, P., Smyth, Rosalind L., Openshaw, Peter J., Dougan, Gordon, Brass, Abraham L., and Kellam, Paul

Published
2012
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32. Capillary properties of model pores

Author

Walsh, Tim J.

Subjects
541, Surface chemistry
Abstract

Liquid menisci in small pores exhibit a curved surface across which there is a significant pressure difference. The capillary properties of such surfaces are important in many areas of science and technology. Pores of uniform section can be broadly classified according to whether the perimeter is smooth (as in cylindrical tubes) or angular (as in triangular tubes). A meniscus that is entirely bounded by the pore walls has a curvature that is inversely proportional to the tubes' hydraulic radius. A meniscus in an angular tube, however, has liquid wedges in the corners and this reduces the effective area of the pore. In the past it has been difficult to calculate the curvatures, of this class of menisci. Some recent studies have shown that a relatively straightforward, but hitherto neglected, method originated by Mayer & Stowe (1965) and Princen (1969a) can be applied to analyse wedging menisci. However, the method has lacked a comprehensive experimental verification. This investigation follows on from the previously limited studies. A standardised method for the application of the analysis is described, the results from which are compared to observations made using modified experimental procedures. The behaviour of the capillary surfaces formed in several model pores are analysed with the method. The model systems studied are rectangular ducts, the pores formed by a rod in an angled corner, by two contacting rods and a plate and the space between a rod and a plate. For the latter two shapes the analysis is extended to include systems of mixed wettability which have a particular bearing on enhanced oil recovery operations. Experiments in which curvatures are inferred from observations of capillary rise, are performed using two comparative techniques. An involved procedure confurns predictions of meniscus curvature to within 0.3%. Use of a more straightforward, though less accurate, technique enables variations of curvature with tube shape or contact angle(s) to be conveniently studied. Results obtained are excellent and confmn the theory within the determined experimental errors. In addition the analysis has been extended to predict more complex meniscus behaviour. The tubular space formed by three rods and a plate gives rise to a whole family of meniscus shapes. With certain geometries a capillary surface regards the tube as a pore doublet where the behaviour in one neighbouring pore depends on that in the other. The capillary properties of this model system shed light on the behaviour of adjacent pores in a porous medium undergoing drainage (ordesorption). Experiments show excellent agreement with predictions of meniscus shapes, curvatures and, most interestingly, points of spontaneous transition from one meniscus shape to another. The system also has a potential future application because one panicular arrangement of rods produces a meniscus with a curvature virtually independent of the geometry. This makes it suitable for producing a standard meniscus of known curvature.

Published
1989

39. GOES-R STATIONKEEPING AND MOMENTUM MANAGEMENT

Author

Chu, Donald, Chen, Sam, Early, Derrick, Freesland, Doug, Krimchansky, Alexander, Naasz, Bo, Reth, Alan, Tadikonda, Kumar, Tsui, John, and Walsh, Tim

Subjects
Space Communications, Spacecraft Communications, Command And Tracking
Abstract

The NOAA Geostationary Operational Environmental Satellites (GOES) fire thrusters to remain within a 1deg longitude-latitude box and to dump accumulated angular momentum. In the past, maneuvers have disrupted GOES imaging due to attitude transients and the loss of orbit knowledge. If the R-series of spacecraft to be launched starting in 2012 were to follow current practice, maneuvers would still fail to meet Image Navigation and Registration (INR) specifications during and after thruster firings. Although maneuvers and recovery take only one percent of spacecraft lifetime, they sometimes come at inopportune times, such as hurricane season, when coverage is critical. To alleviate this problem, thruster firings small enough not to affect imaging are being considered. Eliminating post-maneuver recovery periods increases availability and facilitates autonomous operation. Frequent maneuvers also reduce 1ongitudeAatitude variation and allow satellite co-location. Improved orbit observations come from a high-altitude GPS receiver, and improved attitude control comes from thruster torque compensation. This paper reviews the effects of thruster firings on position knowledge and pointing control and suggests that low-thrust burns plus GPS and feedforward control offer a less disruptive approach to GOES-R stationkeeping and momentum management.

Published
2006

41. Identification and proteomic profiling of exosomes in human cerebrospinal fluid

Author

Street Jonathan M, Barran Perdita E, Mackay C Logan, Weidt Stefan, Balmforth Craig, Walsh Tim S, Chalmers Rod TA, Webb David J, and Dear James W

Subjects
Exosomes, human, CSF, proteomics, Medicine
Abstract

Abstract Background Exosomes are released from multiple cell types, contain protein and RNA species, and have been exploited as a novel reservoir for disease biomarker discovery. They can transfer information between cells and may cause pathology, for example, a role for exosomes has been proposed in the pathophysiology of Alzheimer's disease. Although studied in several biofluids, exosomes have not been extensively studied in the cerebrospinal fluid (CSF) from humans. The objective of this study was to determine: 1) whether human CSF contains exosomes and 2) the variability in exosomal protein content across individuals. Methods CSF was collected from 5 study participants undergoing thoraco-abdominal aortic aneurysm repair (around 200 - 500 ml per participant) and low-density membrane vesicles were concentrated by ultracentrifugation. The presence of exosomes was determined by western blot for marker proteins, isopycnic centrifugation on a sucrose step gradient and transmission electron microscopy with immuno-labelling. Whole protein profiling was performed using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR). Results Flotillin 1 and tumor susceptibility gene 101 (TSG101), two exosomal marker proteins, were identified in the ultracentrifugation pellet using western blot. These markers localized to a density consistent with exosomes following isopycnic centrifugation. Transmission electron microscopy visualized structures consistent with exosomes in size and appearance that labelled positive for flotillin 1. Therefore, the pellet that resulted from ultracentrifugation of human CSF contained exosomes. FT-ICR profiling of this pellet was performed and 84-161 ions were detected per study participant. Around one third of these ions were only present in a single study participant and one third were detected in all five. With regard to ion quantity, the median coefficient of variation was 81% for ions detected in two or more samples. Conclusions Exosomes were identified in human CSF and their proteome is a potential new reservoir for biomarker discovery in neurological disorders such as Alzheimer's disease. However, techniques used to concentrate exosomes from CSF need refinement to reduce variability. In this study we used relatively large starting volumes of human CSF, future studies will focus on exosome isolation from smaller 'real life' clinical samples; a key challenge in the development of exosomes as translational tools.

Published
2012
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43. A smartphone-based test for the assessment of attention deficits in delirium: A case-control diagnostic test accuracy study in older hospitalised patients.

Author

Tieges, Zoë, Stott, David J., Shaw, Robert, Tang, Elaine, Rutter, Lisa-Marie, Nouzova, Eva, Duncan, Nikki, Clarke, Caoimhe, Weir, Christopher J., Assi, Valentina, Ensor, Hannah, Barnett, Jennifer H., Evans, Jonathan, Green, Samantha, Hendry, Kirsty, Thomson, Meigan, McKeever, Jenny, Middleton, Duncan G., Parks, Stuart, and Walsh, Tim

Subjects
AGE factors in cognition disorders, COGNITION disorders, DELIRIUM, RECEIVER operating characteristic curves, OLDER patients, DIAGNOSIS methods
Abstract

Background: Delirium is a common and serious acute neuropsychiatric syndrome which is often missed in routine clinical care. Inattention is the core cognitive feature. Diagnostic test accuracy (including cut-points) of a smartphone Delirium App (DelApp) for assessing attention deficits was assessed in older hospital inpatients. Methods: This was a case-control study of hospitalised patients aged ≥65 years with delirium (with or without pre-existing cognitive impairment), who were compared to patients with dementia without delirium, and patients without cognitive impairment. Reference standard delirium assessment, which included a neuropsychological test battery, was based on Diagnostic and Statistical Manual of Mental Disorders-5 criteria. A separate blinded assessor administered the DelApp arousal assessment (score 0–4) and attention task (0–6) yielding an overall score of 0 to 10 (lower scores indicate poorer performance). Analyses included receiver operating characteristic curves and sensitivity and specificity. Optimal cut-points for delirium detection were determined using Youden's index. Results: A total of 187 patients were recruited, mean age 83.8 (range 67–98) years, 152 (81%) women; n = 61 with delirium; n = 61 with dementia without delirium; and n = 65 without cognitive impairment. Patients with delirium performed poorly on the DelApp (median score = 4/10; inter-quartile range 3.0, 5.5) compared to patients with dementia (9.0; 5.5, 10.0) and those without cognitive impairment (10.0; 10.0, 10.0). Area under the curve for detecting delirium was 0.89 (95% Confidence Interval 0.84, 0.94). At an optimal cut-point of ≤8, sensitivity was 91.7% (84.7%, 98.7%) and specificity 74.2% (66.5%, 81.9%) for discriminating delirium from the other groups. Specificity was 68.3% (56.6%, 80.1%) for discriminating delirium from dementia (cut-point ≤6). Conclusion: Patients with delirium (with or without pre-existing cognitive impairment) perform poorly on the DelApp compared to patients with dementia and those without cognitive impairment. A cut-point of ≤8/10 is suggested as having optimal sensitivity and specificity. The DelApp is a promising tool for assessment of attention deficits associated with delirium in older hospitalised adults, many of whom have prior cognitive impairment, and should be further validated in representative patient cohorts. [ABSTRACT FROM AUTHOR]

Published
2020
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44. Synthesis of qualitative research studies regarding the factors surrounding UK critical care trial infrastructure.

Author

Pattison, Natalie, Arulkumaran, Nishkantha, O'Gara, Geraldine, Connolly, Bronwen, Humphreys, Sally, Walsh, Tim, Hopkins, Philip, and Dark, Paul

Abstract

Conducting clinical trials in critical care is integral to improving patient care. Unique practical and ethical considerations exist in this patient population that make patient recruitment challenging, including narrow recruitment timeframes and obtaining patient consent often in time-critical situations. Units currently vary significantly in their ability to recruit according to infrastructure and level of research activity. Aim To identify variability in the research infrastructure of UK intensive care units and their ability to conduct research and recruit patients into clinical trials. Design We evaluated factors related to intensive care patient enrolment into clinical trials in the UK. This consisted of a qualitative synthesis carried out with two datasets of in-depth interviews (distinct participants across the two datasets) conducted with 27 intensive care consultants (n=9), research nurses (n=17) and trial coordinators (n=1) from 27 units across the UK. Primary and secondary analyses of two datasets (one dataset had been analysed previously) were undertaken in the thematic analysis. Findings The synthesis yielded an overarching core theme of normalising research, characterised by motivations for promoting research and fostering research-active cultures within resource constraints, with six themes under this to explain the factors influencing critical care research capacity: organisational, human, study, practical resources, clinician and patient/family factors. There was a strong sense of integrating research in routine clinical practice, and recommendations are outlined. Conclusions The central and transferable tenet of normalising research advocates the importance of developing a culture where research is inclusive alongside clinical practice in routine patient care and is a requisite for all healthcare individuals from organisational to direct patient contact level. [ABSTRACT FROM AUTHOR]

Published
2019
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47. Effectiveness of a biomarker-based exclusion of ventilator-acquired pneumonia to reduce antibiotic use: protocol for a randomised controlled trial (VAPrapid-2):Study protocol for a randomised controlled trial

Author

Hellyer, Thomas P., Anderson, Niall H., Parker, Jennie, Dark, Paul, van den Broeck, Tina, Singh, Suveer, McMullan, Ronan, Agus, Ashley, Emerson, Lydia M., Blackwood, Bronagh, Gossain, Savita, Walsh, Tim, Perkins, Gavin, Conway Morris, Andre, McAuley, Daniel F., and Simpson, A. John

Subjects
respiratory tract diseases
Abstract

Background Ventilator-acquired pneumonia (VAP) is a common reason for antimicrobial therapy in the intensive care unit (ICU). Biomarker-based diagnostics could improve antimicrobial stewardship through rapid exclusion of VAP. Bronchoalveloar lavage (BAL) fluid biomarkers have previously been shown to allow the exclusion of VAP with high confidence. Methods/Design This is a prospective, multi-centre, randomised, controlled trial to determine whether a rapid biomarker-based exclusion of VAP results in fewer antibiotics and improved antimicrobial management. Patients with clinically suspected VAP undergo BAL, and VAP is confirmed by growth of a potential pathogen at > 104 colony-forming units per millilitre (CFU/ml). Patients are randomised 1:1, to either a ‘biomarker-guided recommendation on antibiotics’ in which BAL fluid is tested for IL-1β and IL-8 in addition to routine microbiology testing, or to ‘routine use of antibiotics’ in which BAL undergoes routine microbiology testing only. Clinical teams are blinded to intervention until 6 hours after randomisation, when biomarker results are reported to the clinician. The primary outcome is a change in the frequency distribution of antibiotic-free days (AFD) in the 7 days following BAL. Secondary outcome measures include antibiotic use at 14 and 28 days; ventilator-free days; 28-day mortality and ICU mortality; sequential organ failure assessment (SOFA) at days 3, 7 and 14; duration of stay in critical care and the hospital; antibiotic-associated infections; and antibiotic-resistant pathogen cultures up to hospital discharge, death or 56 days. A healthcare-resource-utilisation analysis will be calculated from the duration of critical care and hospital stay. In addition, safety data will be collected with respect to performing BAL. A sample size of 210 will be required to detect a clinically significant shift in the distribution of AFD towards more patients having fewer antibiotics and therefore more AFD. Discussion This trial will test whether a rapid biomarker-based exclusion of VAP results in rapid discontinuation of antibiotics and therefore improves antibiotic management in patients with suspected VAP.

Published
2016
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50. Sedation AND Weaning In Children (SANDWICH): protocol for a cluster randomised stepped wedge trial.

Author

Blackwood, Bronagh, Agus, Ashley, Boyle, Roisin, Clarke, Mike, Hemming, Karla, Jordan, Joanne, Macrae, Duncan, McAuley, Daniel Francis, McDowell, Clíona, McIlmurray, Lisa, Morris, Kevin P., Murray, Margaret, Parslow, Roger, Peters, Mark J., Tume, Lyvonne N., and Walsh, Tim

Abstract

Introduction Weaning from ventilation is a complex process involving several stages that include recognition of patient readiness to begin the weaning process, steps to reduce ventilation while optimising sedation in order not to induce distress and removing the endotracheal tube. Delay at any stage can prolong the duration of mechanical ventilation. We developed a multicomponent intervention targeted at helping clinicians to safely expedite this process and minimise the harms associated with unnecessary mechanical ventilation. Methods and analysis This is a 20-month cluster randomised stepped wedge clinical and cost-effectiveness trial with an internal pilot and a process evaluation. It is being conducted in 18 paediatric intensive care units in the UK to evaluate a protocol-based intervention for reducing the duration of invasive mechanical ventilation. Following an initial 8-week baseline data collection period in all sites, one site will be randomly chosen to transition to the intervention every 4 weeks and will start an 8-week training period after which it will continue the intervention for the remaining duration of the study. We aim to recruit approximately 10 000 patients. The primary analysis will compare data from before the training (control) with that from after the training (intervention) in each site. Full details of the analyses will be in the statistical analysis plan. Ethics and dissemination This protocol was reviewed and approved by NRES Committee East Midlands—Nottingham 1 Research Ethics Committee (reference: 17/EM/0301). All sites started patient recruitment on 5 February 2018 before randomisation in April 2018. Results will be disseminated in 2020. The results will be presented at national and international conferences and published in peer-reviewed medical journals. [ABSTRACT FROM AUTHOR]

Published
2019
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