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152. Steroids

Author

Scott, Ian C., Galloway, James B., Scott, David L., Scott, Ian C., Galloway, James B., and Scott, David L.

Published
2015
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155. Developments in time-reversal of electromagnetic fields using the transmission-line modelling method

Author

Scott, Ian

Subjects
502.85, TK7800 Electronics
Abstract

Inverse modelling methods are receiving significant interest, due to their simplicity and ease of use in the design of modern microwave components. This study investigates and further develops the technique of numerical time-reversal, in the context of automated component design, for modelling metal waveguide devices. The thesis demonstrates that time-reversal methods suffer from temporal truncation, evanescent wave decay and significant computational resource requirements and will investigate different methods to solve these problems. In order to reduce the runtime, the use of Prony’s method for temporal extrapolation of a discrete waveform is proposed. Lossy materials are investigated, with particular attention given to the loss of modal content from the reverse model due to material loss present in the forward phase of the time-reversal process. The memory and time requirements of a successful time-reversal design simulation are significant. Temporal, spatial and modal filtering are used to minimise the computational demands of time-reversal. Further, in order to accelerate convergence of the time-reversal design process, a number of linear acceleration methods are developed, notably successive over relaxation, conjugate gradients and generalised minimal residual. A convergence acceleration factor of two is achieved. It is shown that local evanescent content around optimised scattering elements is not always captured by the time-reversal process, and is dependant upon the component order, numerical sampling and machine precision. Internal mirrors are developed which capture the fast decaying fields around the metal features of a designed component and further increase the accuracy and speed of the time-reversal convergence. Their use for higher order component design is shown to be paramount in achieving convergence. Further, combined with the linear acceleration methods, the capture of local evanescent content is shown to greatly improve the viability of the time-reversal technique to practical microwave component design. The time-reversal methodology is implemented using the numerical transmission-line modelling (TLM) method for transverse magnetic polarisation in two-dimensions. A brief examination of the three-dimensional time-reversal using the symmetrical condensed TLM node is also given.

Published
2010

158. British clarinet concertos.

Author

Scott, Ian, 1958- Instrumentalist, Royal Ballet Sinfonia. Performer, Sutherland, Gavin. Conductor, Bush, Geoffrey. Rhapsody, clarinet, strings., Cruft, Adrian. Concertino, clarinet, string orchestra, op. 21., Horovitz, Joseph, 1926- Concertante, clarinet, strings, op. 1., MacDonald, Malcolm, 1916-1992. Cuban rondo., Paul, Alan, 1905-1968. Concerto, clarinet, orchestra., Ridout, Alan, 1934-1996. Concertinos, clarinet, string orchestra., and Woolfenden, Guy. Concertos, clarinet, orchestra.

Published
2002

160. Chromatin remodelling complex dosage modulates transcription factor function in heart development.

Author

Takeuchi, Jun K, Lou, Xin, Alexander, Jeffrey M, Sugizaki, Hiroe, Delgado-Olguín, Paul, Holloway, Alisha K, Mori, Alessandro D, Wylie, John N, Munson, Chantilly, Zhu, Yonghong, Zhou, Yu-Qing, Yeh, Ru-Fang, Henkelman, R Mark, Harvey, Richard P, Metzger, Daniel, Chambon, Pierre, Stainier, Didier YR, Pollard, Katherine S, Scott, Ian C, and Bruneau, Benoit G

Subjects
Heart, NIH 3T3 Cells, Animals, Zebrafish, Mice, Heart Defects, Congenital, Multiprotein Complexes, DNA Helicases, Adaptor Proteins, Signal Transducing, Homeodomain Proteins, T-Box Domain Proteins, Zebrafish Proteins, Nuclear Proteins, Transcription Factors, DNA Primers, Echocardiography, Electrocardiography, Microarray Analysis, Chromatin Immunoprecipitation, Morphogenesis, Gene Dosage, Haploinsufficiency, Homeobox Protein Nkx-2.5
Abstract

Dominant mutations in cardiac transcription factor genes cause human inherited congenital heart defects (CHDs); however, their molecular basis is not understood. Interactions between transcription factors and the Brg1/Brm-associated factor (BAF) chromatin remodelling complex suggest potential mechanisms; however, the role of BAF complexes in cardiogenesis is not known. In this study, we show that dosage of Brg1 is critical for mouse and zebrafish cardiogenesis. Disrupting the balance between Brg1 and disease-causing cardiac transcription factors, including Tbx5, Tbx20 and Nkx2-5, causes severe cardiac anomalies, revealing an essential allelic balance between Brg1 and these cardiac transcription factor genes. This suggests that the relative levels of transcription factors and BAF complexes are important for heart development, which is supported by reduced occupancy of Brg1 at cardiac gene promoters in Tbx5 haploinsufficient hearts. Our results reveal complex dosage-sensitive interdependence between transcription factors and BAF complexes, providing a potential mechanism underlying transcription factor haploinsufficiency, with implications for multigenic inheritance of CHDs.

Published
2011

164. RELEASE (REdressing Long-tErm Antidepressant uSE): Protocol for a 3-arm pragmatic cluster randomised controlled trial effectiveness-implementation hybrid type-1 in general practice

Author

Wallis, Katharine Ann, primary, Donald, Maria, additional, Horowitz, Mark, additional, Moncrieff, Joanna, additional, Ware, Robert, additional, Byrnes, Joshua, additional, Thrift, Karen, additional, Cleetus, Maryanne, additional, Panahi, Idin, additional, Zwar, Nicholas, additional, Morgan, Mark, additional, Freeman, Christopher, additional, and Scott, Ian, additional

Published
2023
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166. Cluster Analyses From the Real-World NOVELTY Study: Six Clusters Across the Asthma-COPD Spectrum

Author

Hughes, Rod, primary, Rapsomaniki, Eleni, additional, Bansal, Aruna T., additional, Vestbo, Jørgen, additional, Price, David, additional, Agustí, Alvar, additional, Beasley, Richard, additional, Fageras, Malin, additional, Alacqua, Marianna, additional, Papi, Alberto, additional, Müllerová, Hana, additional, Reddel, Helen K., additional, Olmo, Ricardo del, additional, Anderson, Gary, additional, Reddel, Helen, additional, Rabahi, Marcelo, additional, McIvor, Andrew, additional, Sadatsafavi, Mohsen, additional, Weinreich, Ulla, additional, Burgel, Pierre-Régis, additional, Devouassoux, Gilles, additional, Inoue, Hiromasa, additional, Rendon, Adrián, additional, van den Berge, Maarten, additional, García-Navarro, Alvar Agusti, additional, Faner, Rosa, additional, Olaguibel Rivera, José, additional, Janson, Christer, additional, Bilińska-Izydorczyk, Magdalena, additional, Fagerås, Malin, additional, Fihn-Wikander, Titti, additional, Franzén, Stefan, additional, Keen, Christina, additional, Ostridge, Kristoffer, additional, Chalmers, James, additional, Harrison, Timothy, additional, Pavord, Ian, additional, Azim, Adnan, additional, Belton, Laura, additional, Blé, Francois-Xavier, additional, Erhard, Clement, additional, Gairy, Kerry, additional, Hughes, Rod, additional, Lassi, Glenda, additional, Scott, Ian Christopher, additional, Chipps, Bradley, additional, Christenson, Stephanie, additional, Make, Barry, additional, Tomaszewski, Erin, additional, Benhabib, Gabriel, additional, Ruiz, Xavier Bocca, additional, Lisanti, Raul Eduardo, additional, Marino, Gustavo, additional, Mattarucco, Walter, additional, Nogueira, Juan, additional, Parody, Maria, additional, Pascale, Pablo, additional, Rodriguez, Pablo, additional, Silva, Damian, additional, Svetliza, Graciela, additional, Victorio, Carlos F., additional, Rolon, Roxana Willigs, additional, Yañez, Anahi, additional, Baines, Stuart, additional, Bowler, Simon, additional, Bremner, Peter, additional, Bull, Sheetal, additional, Carroll, Patrick, additional, Chaalan, Mariam, additional, Farah, Claude, additional, Hammerschlag, Gary, additional, Hancock, Kerry, additional, Harrington, Zinta, additional, Katsoulotos, Gregory, additional, Kim, Joshua, additional, Langton, David, additional, Lee, Donald, additional, Peters, Matthew, additional, Prassad, Lakshman, additional, Sajkov, Dimitar, additional, Santiago, Francis, additional, Simpson, Frederick Graham, additional, Tai, Sze, additional, Thomas, Paul, additional, Wark, Peter, additional, Cançado, José Eduardo Delfini, additional, Cunha, Thúlio, additional, Lima, Marina, additional, Cardoso, Alexandre Pinto, additional, FitzGerald, J. Mark, additional, Anees, Syed, additional, Bertley, John, additional, Bell, Alan, additional, Cheema, Amarjit, additional, Chouinard, Guy, additional, Csanadi, Michael, additional, Dhar, Anil, additional, Dhillon, Ripple, additional, Kanawaty, David, additional, Kelly, Allan, additional, Killorn, William, additional, Landry, Daniel, additional, Luton, Robert, additional, Mandhane, Piushkumar, additional, Pek, Bonavuth, additional, Petrella, Robert, additional, Stollery, Daniel, additional, Wang, Chen, additional, Chen, Meihua, additional, Chen, Yan, additional, Gu, Wei, additional, Christopher Hui, Kim Ming, additional, Li, Manxiang, additional, Li, Shiyue, additional, Lijun, Ma, additional, Qin, Guangyue, additional, Song, Weidong, additional, Tan, Wei, additional, Tang, Yijun, additional, Wang, Tan, additional, Wen, Fuqiang, additional, Wu, Feng, additional, Xiang, PingChao, additional, Xiao, Zuke, additional, Xiong, Shengdao, additional, Yang, Jinghua, additional, Yang, Jingping, additional, Zhang, Caiqing, additional, Zhang, Min, additional, Zhang, Ping, additional, Zhang, Wei, additional, Zheng, Xiaohe, additional, Zhu, Dan, additional, Bueno, Carlos Matiz, additional, Grimaldos, Fabio Bolivar, additional, Arboleda, Alejandra Cañas, additional, de Salazar, Dora Molina, additional, Bendstrup, Elisabeth, additional, Hilberg, Ole, additional, Kjellerup, Carsten, additional, Raherison, Chantal, additional, Bonniaud, Philippe, additional, Brun, Olivier, additional, Chouaid, Christos, additional, Couturaud, Francis, additional, de Blic, Jacques, additional, Debieuvre, Didier, additional, Delsart, Dominique, additional, Demaegdt, Axelle, additional, Demoly, Pascal, additional, Deschildre, Antoine, additional, Egron, Carole, additional, Falchero, Lionel, additional, Goupil, François, additional, Kessler, Romain, additional, Le Roux, Pascal, additional, Mabire, Pascal, additional, Mahay, Guillaume, additional, Martinez, Stéphanie, additional, Melloni, Boris, additional, Moreau, Laurent, additional, Riviere, Emilie, additional, Roux-Claudé, Pauline, additional, Soulier, Michel, additional, Vignal, Guillaume, additional, Yaici, Azzedine, additional, Bals, Robert, additional, Aries, Sven Philip, additional, Beck, Ekkehard, additional, Deimling, Andreas, additional, Feimer, Jan, additional, Grimm-Sachs, Vera, additional, Groth, Gesine, additional, Herth, Felix, additional, Hoheisel, Gerhard, additional, Kanniess, Frank, additional, Lienert, Thomas, additional, Mronga, Silke, additional, Reinhardt, Jörg, additional, Schlenska, Christian, additional, Stolpe, Christoph, additional, Teber, Ishak, additional, Timmermann, Hartmut, additional, Ulrich, Thomas, additional, Velling, Peter, additional, Wehgartner-Winkler, Sabina, additional, Welling, Juergen, additional, Winkelmann, Ernst-Joachim, additional, Barbetta, Carlo, additional, Braido, Fulvio, additional, Cardaci, Vittorio, additional, Clini, Enrico Maria, additional, Costantino, Maria Teresa, additional, Cuttitta, Giuseppina, additional, di Gioacchino, Mario, additional, Fois, Alessandro, additional, Foschino-Barbaro, Maria Pia, additional, Gammeri, Enrico, additional, Inchingolo, Riccardo, additional, Lavorini, Federico, additional, Molino, Antonio, additional, Nucera, Eleonora, additional, Patella, Vincenzo, additional, Pesci, Alberto, additional, Ricciardolo, Fabio, additional, Rogliani, Paola, additional, Sarzani, Riccardo, additional, Vancheri, Carlo, additional, Vincenti, Rigoletta, additional, Endo, Takeo, additional, Fujita, Masaki, additional, Hara, Yu, additional, Horiguchi, Takahiko, additional, Hosoi, Keita, additional, Ide, Yumiko, additional, Inomata, Minehiko, additional, Inoue, Koji, additional, Inoue, Sumito, additional, Kato, Motokazu, additional, Kawasaki, Masayuki, additional, Kawayama, Tomotaka, additional, Kita, Toshiyuki, additional, Kobayashi, Kanako, additional, Koto, Hiroshi, additional, Nishi, Koichi, additional, Saito, Junpei, additional, Shimizu, Yasuo, additional, Shirai, Toshihiro, additional, Sugihara, Naruhiko, additional, Takahashi, Ken-ichi, additional, Tashimo, Hiroyuki, additional, Tomii, Keisuke, additional, Yamada, Takashi, additional, Yanai, Masaru, additional, Rendon, Adrian, additional, Cerino Javier, Ruth, additional, Domínguez Peregrina, Alfredo, additional, Fernández Corzo, Marco, additional, Montano Gonzalez, Efraín, additional, Ramírez-Venegas, Alejandra, additional, Boersma, Willem, additional, Djamin, R.S., additional, Eijsvogel, Michiel, additional, Franssen, Frits, additional, Goosens, Martijn, additional, Graat-Verboom, Lidwien, additional, Veen, Johannes in 't, additional, Janssen, Rob, additional, Kuppens, Kim, additional, van de Ven, Mario, additional, Bakke, Per, additional, Brunstad, Ole Petter, additional, Einvik, Gunnar, additional, Høines, Kristian Jong, additional, Khusrawi, Alamdar, additional, Oien, Torbjorn, additional, Yoon, Ho Joo, additional, Chang, Yoon-Seok, additional, Cho, Young Joo, additional, Hwang, Yong Il, additional, Kim, Woo Jin, additional, Koh, Young-Il, additional, Lee, Byung-Jae, additional, Lee, Kwan-Ho, additional, Lee, Sang-Pyo, additional, Lee, Yong Chul, additional, Lim, Seong Yong, additional, Min, Kyung Hun, additional, Oh, Yeon-Mok, additional, Park, Choon-Sik, additional, Park, Hae-Sim, additional, Park, Heung-Woo, additional, Rhee, Chin Kook, additional, Yoon, Hyoung-Kyu, additional, García-Navarro, Alvar Agustí, additional, Andújar, Rubén, additional, Anoro, Laura, additional, Buendía García, María, additional, Mozo, Paloma Campo, additional, Campos, Sergio, additional, Casas Maldonado, Francisco, additional, Castilla Martínez, Manuel, additional, Cisneros Serrano, Carolina, additional, Comeche Casanova, Lorena, additional, Corbacho, Dolores, additional, Campo Matías, Felix Del, additional, Echave-Sustaeta, Jose, additional, Corral, Gloria Francisco, additional, Gamboa Setién, Pedro, additional, García Clemente, Marta, additional, Núñez, Ignacio García, additional, García Robaina, Jose, additional, García Salmones, Mercedes, additional, Marín Trigo, Jose Maria, additional, Fernandez, Marta Nuñez, additional, Palomo, Sara Nuñez, additional, Pérez de Llano, Luis, additional, Pueyo Bastida, Ana, additional, Rañó, Ana, additional, Rodríguez González-Moro, José, additional, Reig, Albert Roger, additional, Velasco Garrido, José, additional, Curiac, Dan, additional, Lif-Tiberg, Cornelia, additional, Luts, Anders, additional, Råhlen, Lennart, additional, Rustscheff, Stefan, additional, Adams, Frances, additional, Bradman, Drew, additional, Broughton, Emma, additional, Cosgrove, John, additional, Flood-Page, Patrick, additional, Fuller, Elizabeth, additional, Hartley, David, additional, Hattotuwa, Keith, additional, Jones, Gareth, additional, Lewis, Keir, additional, McGarvey, Lorcan, additional, Morice, Alyn, additional, Pandya, Preeti, additional, Patel, Manish, additional, Roy, Kay, additional, Sathyamurthy, Ramamurthy, additional, Thiagarajan, Swaminathan, additional, Turner, Alice, additional, Wedzicha, Wisia, additional, Wilkinson, Tom, additional, Wilson, Pete, additional, Al-Asadi, Lo’Ay, additional, Anholm, James, additional, Averill, Francis, additional, Bansal, Sandeep, additional, Baptist, Alan, additional, Campbell, Colin, additional, Campos, Michael A., additional, Crook, Gretchen, additional, DeLeon, Samuel, additional, Eid, Alain, additional, Epstein, Ellen, additional, Fritz, Stephen, additional, Harris, Hoadley, additional, Hewitt, Mitzie, additional, Holguin, Fernando, additional, Hudes, Golda, additional, Jackson, Richard, additional, Kaufman, Alan, additional, Kaufman, David, additional, Klapholz, Ari, additional, Krishna, Harshavardhan, additional, Lee, Daria, additional, Lin, Robert, additional, Maselli-Caceres, Diego, additional, Mehta, Vinay, additional, Moy, James N., additional, Nwokoro, Ugo, additional, Parikh, Purvi, additional, Parikh, Sudhir, additional, Perrino, Frank, additional, Ruhlmann, James, additional, Sassoon, Catherine, additional, Settipane, Russell A., additional, Sousa, Daniel, additional, Sriram, Peruvemba, additional, and Wachs, Richard, additional

Published
2023
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168. A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19: ACCORD-2

Author

Wilkinson, Tom, primary, De Soyza, Anthony, additional, Carroll, Miles, additional, Chalmers, James D., additional, Crooks, Michael G., additional, Griffiths, Gareth, additional, Shankar-Hari, Manu, additional, Ho, Ling-Pei, additional, Horsley, Alex, additional, Kell, Chris, additional, Lara, Beatriz, additional, Mishra, Biswa, additional, Moate, Rachel, additional, Page, Clive, additional, Pandya, Hitesh, additional, Raw, Jason, additional, Reid, Fred, additional, Saralaya, Dinesh, additional, Scott, Ian C., additional, Siddiqui, Salman, additional, Ustianowski, Andy, additional, van Zuydam, Natalie, additional, Woodcock, Ashley, additional, and Singh, Dave, additional

Published
2023
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169. Mettre fin au jeu du blâme générationnel

Author

Lavergne, M. Ruth, primary, Moravac, Catherine, additional, Scott, Ian, additional, McCracken, Rita K., additional, Hedden, Lindsay, additional, Grudniewicz, Agnes, additional, and Marshall, Emily Gard, additional

Published
2023
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170. Changes in comprehensiveness of services delivered by Canadian family physicians

Author

Lavergne, M. Ruth, primary, Rudoler, David, additional, Peterson, Sandra, additional, Stock, David, additional, Taylor, Carole, additional, Wilton, Andrew S., additional, Wong, Sabrina T., additional, Scott, Ian, additional, McGrail, Kimberlyn M., additional, McCracken, Rita K., additional, Marshall, Emily Gard, additional, MacKenzie, Adrian, additional, Katz, Alan, additional, Jamieson, Margaret, additional, Hedden, Lindsay, additional, Grudniewicz, Agnes, additional, Goldsmith, Laurie J., additional, Glazier, Richard H., additional, Burge, Fred, additional, and Blackie, Doug, additional

Published
2023
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171. Ending the generational blame game

Author

Lavergne, M. Ruth, primary, Moravac, Catherine, additional, Scott, Ian, additional, McCracken, Rita K., additional, Hedden, Lindsay, additional, Grudniewicz, Agnes, additional, and Marshall, Emily Gard, additional

Published
2023
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172. Oxidised IL-33 drives COPD epithelial pathogenesisviaST2-independent RAGE/EGFR signalling complex

Author

Strickson, Sam, primary, Houslay, Kirsty F., additional, Negri, Victor A., additional, Ohne, Yoichiro, additional, Ottosson, Tomas, additional, Dodd, Roger B., additional, Huntington, Catherine Chaillan, additional, Baker, Tina, additional, Li, Jingjing, additional, Stephenson, Katherine E., additional, O'Connor, Andy J., additional, Sagawe, J. Sophie, additional, Killick, Helen, additional, Moore, Tom, additional, Rees, D. Gareth, additional, Koch, Sofia, additional, Sanden, Caroline, additional, Wang, Yixin, additional, Gubbins, Elise, additional, Ghaedi, Mahboobe, additional, Kolbeck, Roland, additional, Saumyaa, Saumyaa, additional, Erjefält, Jonas S., additional, Sims, Gary P., additional, Humbles, Alison A., additional, Scott, Ian C., additional, Romero Ros, Xavier, additional, and Cohen, E. Suzanne, additional

Published
2023
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174. Biography and History in Film

Author

Scott, Ian

Subjects
Biography and History in Film (Essay collection) -- Freeman, Thomas S. -- Smith, David L., Books -- Book reviews, Humanities
Abstract

Biography and History in Film Thomas S. Freeman and David L. Smith, editors Palgrave Macmillan, 2019, xi + 336 pp. ISBN 9783319894072, $119.99 hardcover. In Thomas Freeman and David Smiths [...]

Published
2020

175. HpARI Protein Secreted by a Helminth Parasite Suppresses Interleukin-33

Author

Osbourn, Megan, Soares, Dinesh C., Vacca, Francesco, Cohen, E. Suzanne, Scott, Ian C., Gregory, William F., Smyth, Danielle J., Toivakka, Matilda, Kemter, Andrea M., le Bihan, Thierry, Wear, Martin, Hoving, Dennis, Filbey, Kara J., Hewitson, James P., Henderson, Holly, Gonzàlez-Cìscar, Andrea, Errington, Claire, Vermeren, Sonja, Astier, Anne L., Wallace, William A., Schwarze, Jürgen, Ivens, Alasdair C., Maizels, Rick M., and McSorley, Henry J.

Published
2017
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178. Genetic and Physiologic Dissection of the Vertebrate Cardiac Conduction System

Author

Chi, Neil C, Shaw, Robin M, Jungblut, Benno, Huisken, Jan, Ferrer, Tania, Arnaout, Rima, Scott, Ian, Beis, Dimitris, Xiao, Tong, Baier, Herwig, Jan, Lily Y, Tristani-Firouzi, Martin, and Stainier, Didier YR

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Cardiovascular, Heart Disease, Genetics, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Animals, Animals, Genetically Modified, Cardiac Electrophysiology, Connexin 43, Connexins, Embryo, Nonmammalian, Gene Expression Regulation, Developmental, Heart Conduction System, Hemodynamics, Mutation, Myocardium, Zebrafish, Agricultural and Veterinary Sciences, Medical and Health Sciences, Developmental Biology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

Vertebrate hearts depend on highly specialized cardiomyocytes that form the cardiac conduction system (CCS) to coordinate chamber contraction and drive blood efficiently and unidirectionally throughout the organism. Defects in this specialized wiring system can lead to syncope and sudden cardiac death. Thus, a greater understanding of cardiac conduction development may help to prevent these devastating clinical outcomes. Utilizing a cardiac-specific fluorescent calcium indicator zebrafish transgenic line, Tg(cmlc2:gCaMP)(s878), that allows for in vivo optical mapping analysis in intact animals, we identified and analyzed four distinct stages of cardiac conduction development that correspond to cellular and anatomical changes of the developing heart. Additionally, we observed that epigenetic factors, such as hemodynamic flow and contraction, regulate the fast conduction network of this specialized electrical system. To identify novel regulators of the CCS, we designed and performed a new, physiology-based, forward genetic screen and identified for the first time, to our knowledge, 17 conduction-specific mutations. Positional cloning of hobgoblin(s634) revealed that tcf2, a homeobox transcription factor gene involved in mature onset diabetes of the young and familial glomerulocystic kidney disease, also regulates conduction between the atrium and the ventricle. The combination of the Tg(cmlc2:gCaMP)(s878) line/in vivo optical mapping technique and characterization of cardiac conduction mutants provides a novel multidisciplinary approach to further understand the molecular determinants of the vertebrate CCS.

Published
2008

184. A Randomized Phase I Study of the Anti‐Interleukin‐33 Antibody Tozorakimab in Healthy Adults and Patients With Chronic Obstructive Pulmonary Disease.

Author

Reid, Fred, Singh, Dave, Albayaty, Muna, Moate, Rachel, Jimenez, Eulalia, Sadiq, Muhammad Waqas, Howe, David, Gavala, Monica, Killick, Helen, Williams, Adam, Krishnan, Surekha, Godwood, Alex, Shukla, Animesh, Hewitt, Lisa, Lei, Alejhandra, Kell, Chris, Pandya, Hitesh, Newcombe, Paul, White, Nicholas, and Scott, Ian C.

Subjects
CHRONIC obstructive pulmonary disease, MONOCLONAL antibodies, IMMUNOGLOBULINS, IMMUNE response
Abstract

Tozorakimab is a human monoclonal antibody that neutralizes interleukin (IL)‐33. IL‐33 is a broad‐acting epithelial "alarmin" cytokine upregulated in lung tissue of patients with chronic obstructive pulmonary disease (COPD). This first‐in‐human, phase I, randomized, double‐blind, placebo‐controlled study (NCT03096795) evaluated the safety, tolerability, pharmacokinetics (PKs), immunogenicity, target engagement, and pharmacodynamics (PDs) of tozorakimab. This was a 3‐part study. In part 1, 56 healthy participants with a history of mild atopy received single escalating doses of either intravenous or subcutaneous tozorakimab or placebo. In part 2, 24 patients with mild COPD received multiple ascending doses of subcutaneous tozorakimab or placebo. In part 3, 8 healthy Japanese participants received a single intravenous dose of tozorakimab or placebo. The safety data collected included treatment‐emergent adverse events (TEAEs), vital signs, and clinical laboratory parameters. Biological samples for PKs, immunogenicity, target engagement, and PD biomarker analyses were collected. No meaningful differences in the frequencies of TEAEs were observed between the tozorakimab and placebo arms. Three tozorakimab‐treated participants with COPD experienced treatment‐emergent serious adverse events. Subcutaneous or intravenous tozorakimab demonstrated linear, time‐independent PKs with a mean half‐life of 11.7–17.3 days. Treatment‐emergent anti‐drug antibody frequency was low. Engagement of tozorakimab with endogenous IL‐33 in serum and nasal airways was demonstrated. Tozorakimab significantly reduced serum IL‐5 and IL‐13 levels in patients with COPD compared with placebo. Overall, tozorakimab was well tolerated, with a linear, time‐independent serum PK profile. Additionally, biomarker studies demonstrated proof of mechanism. Overall, these data support the further clinical development of tozorakimab in COPD and other inflammatory diseases. [ABSTRACT FROM AUTHOR]

Published
2024
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185. Too much versus too little: looking for the "sweet spot" in optimal use of diagnostic investigations.

Author

Scott, Ian A, Crock, Carmel, and Twining, Matthew

Abstract

This article discusses the importance of finding the right balance in the use of diagnostic tests in healthcare. Failure to order tests when necessary or misinterpreting their results can lead to diagnostic errors and adverse outcomes, while overuse of tests can result in false positives, unnecessary labeling of diseases, and further unnecessary testing and treatment. The appropriateness of diagnostic investigations varies depending on the clinical setting, test choice, and study methodology. The article proposes strategies for achieving the "sweet spot" in using diagnostic tests, including questioning the role of testing, considering patient preferences and treatment options, understanding pre-test probability and test performance, avoiding misinterpretation of test results, using diagnostic decision support tools, ordering and sequencing tests appropriately, responding to diagnostic uncertainty, and applying system-level strategies for optimizing test use. [Extracted from the article]

Published
2024
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186. Systematic review and longitudinal analysis of implementing Artificial Intelligence to predict clinical deterioration in adult hospitals: what is known and what remains uncertain.

Author

Vegt, Anton H van der, Campbell, Victoria, Mitchell, Imogen, Malycha, James, Simpson, Joanna, Flenady, Tracy, Flabouris, Arthas, Lane, Paul J, Mehta, Naitik, Kalke, Vikrant R, Decoyna, Jovie A, Es'haghi, Nicholas, Liu, Chun-Huei, and Scott, Ian A

Abstract

Objective To identify factors influencing implementation of machine learning algorithms (MLAs) that predict clinical deterioration in hospitalized adult patients and relate these to a validated implementation framework. Materials and methods A systematic review of studies of implemented or trialed real-time clinical deterioration prediction MLAs was undertaken, which identified: how MLA implementation was measured; impact of MLAs on clinical processes and patient outcomes; and barriers, enablers and uncertainties within the implementation process. Review findings were then mapped to the SALIENT end-to-end implementation framework to identify the implementation stages at which these factors applied. Results Thirty-seven articles relating to 14 groups of MLAs were identified, each trialing or implementing a bespoke algorithm. One hundred and seven distinct implementation evaluation metrics were identified. Four groups reported decreased hospital mortality, 1 significantly. We identified 24 barriers, 40 enablers, and 14 uncertainties and mapped these to the 5 stages of the SALIENT implementation framework. Discussion Algorithm performance across implementation stages decreased between in silico and trial stages. Silent plus pilot trial inclusion was associated with decreased mortality, as was the use of logistic regression algorithms that used less than 39 variables. Mitigation of alert fatigue via alert suppression and threshold configuration was commonly employed across groups. Conclusions : There is evidence that real-world implementation of clinical deterioration prediction MLAs may improve clinical outcomes. Various factors identified as influencing success or failure of implementation can be mapped to different stages of implementation, thereby providing useful and practical guidance for implementers. [ABSTRACT FROM AUTHOR]

Published
2024
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187. O07: Haploinsufficiency of EIF3A and EIF3B cause a clinically variable phenotype characterized by neurodevelopmental abnormalities and congenital heart defects

Author

Somerville, Cherith, Erkut, Ersa, Schwartz, Marci, Chen, Xin, Manshaei, Roozbeh, Ding, Qiliang, Diderich, Karin, Herzig, Lisa, Dingmann, Bri, Quelin, Chloe, Pingault, Véronique, Dubourg, Christèle, Salgado, Joana Rosmaninho, Sousa, Sérgio, Koboldt, Daniel, Gosselin, Rachel, McBride, Kim, Arvio, Maria, Järvelä, Irma, Schrauwen, Isabelle, Conlin, Laura, Skraban, Cara, Reichert, Sara, Leonard, Jacqueline, Bedoukian, Emma, Kim, Raymond, Scott, Ian, and Jobling, Rebekah

Published
2024
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198. War

Author

Scott, Ian, primary and Thompson, Henry, additional

Published
2019
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200. Love

Author

Scott, Ian, primary and Thompson, Henry, additional

Published
2019
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