1,177 results on '"Byrne, K."'
Search Results
2. Insulin-like growth factor-1, insulin-like growth factor-binding protein-3, and breast cancer risk: observational and Mendelian randomization analyses with ∼430 000 women
- Author
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Murphy, N., Knuppel, A., Papadimitriou, N., Martin, R.M., Tsilidis, K.K., Smith-Byrne, K., Fensom, G., Perez-Cornago, A., Travis, R.C., Key, T.J., and Gunter, M.J.
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- 2020
- Full Text
- View/download PDF
3. Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis.
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Yarmolinsky, J, Robinson, JW, Mariosa, D, Karhunen, V, Huang, J, Dimou, N, Murphy, N, Burrows, K, Bouras, E, Smith-Byrne, K, Lewis, SJ, Galesloot, TE, Kiemeney, LA, Vermeulen, S, Martin, P, Albanes, D, Hou, L, Newcomb, PA, White, E, Wolk, A, Wu, AH, Le Marchand, L, Phipps, AI, Buchanan, DD, International Lung Cancer Consortium, PRACTICAL Consortium, Zhao, SS, Gill, D, Chanock, SJ, Purdue, MP, Davey Smith, G, Brennan, P, Herzig, K-H, Järvelin, M-R, Amos, CI, Hung, RJ, Dehghan, A, Johansson, M, Gunter, MJ, Tsilidis, KK, Martin, RM, Yarmolinsky, J, Robinson, JW, Mariosa, D, Karhunen, V, Huang, J, Dimou, N, Murphy, N, Burrows, K, Bouras, E, Smith-Byrne, K, Lewis, SJ, Galesloot, TE, Kiemeney, LA, Vermeulen, S, Martin, P, Albanes, D, Hou, L, Newcomb, PA, White, E, Wolk, A, Wu, AH, Le Marchand, L, Phipps, AI, Buchanan, DD, International Lung Cancer Consortium, PRACTICAL Consortium, Zhao, SS, Gill, D, Chanock, SJ, Purdue, MP, Davey Smith, G, Brennan, P, Herzig, K-H, Järvelin, M-R, Amos, CI, Hung, RJ, Dehghan, A, Johansson, M, Gunter, MJ, Tsilidis, KK, and Martin, RM
- Abstract
BACKGROUND: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear. METHODS: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,294 cancer cases and up to 1,238,345 controls. Genetic instruments for inflammatory markers were constructed using genome-wide significant (P < 5.0 × 10-8) cis-acting SNPs (i.e., in or ±250 kb from the gene encoding the relevant protein) in weak linkage disequilibrium (LD, r2 < 0.10). Effect estimates were generated using inverse-variance weighted random-effects models and standard errors were inflated to account for weak LD between variants with reference to the 1000 Genomes Phase 3 CEU panel. A false discovery rate (FDR)-corrected P-value ("q-value") <0.05 was used as a threshold to define "strong evidence" to support associations and 0.05 ≤ q-value < 0.20 to define "suggestive evidence". A colocalisation posterior probability (PPH4) >70% was employed to indicate support for shared causal variants across inflammatory markers and cancer outcomes. Findings were replicated in the FinnGen study and then pooled using meta-analysis. FINDINGS: We found strong evidence to support an association of genetically-proxied circulating pro-adrenomedullin concentrations with increased breast cancer risk (OR: 1.19, 95% CI: 1.10-1.29, q-value = 0.033, PPH4 = 84.3%) and suggestive evidence to support associations of interleukin-23 receptor concentrations with increased pancreatic cancer risk (OR: 1.42, 95% CI: 1.20-1.69, q-value = 0.055, PP
- Published
- 2024
4. Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis
- Author
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Yarmolinsky, J., Robinson, J.W., Mariosa, D., Karhunen, V., Huang, Jian, Dimou, N., Murphy, N., Burrows, K., Bouras, E., Smith-Byrne, K., Lewis, S.J., Galesloot, T.E., Kiemeney, B., Vermeulen, S., Martin, P., Albanes, D., Hou, L., Newcomb, P.A., White, E., Wolk, A., Wu, A.H., Marchand, L. Le, Phipps, A.I., Buchanan, D.D., Zhao, S.S., Gill, D., Chanock, S.J., Purdue, M.P., Smith, G. Davey, Brennan, P., Herzig, K.H., Järvelin, M.R., Amos, C.I., Hung, R.J., Dehghan, A., Johansson, M., Gunter, M.J., Tsilidis, K.K., Martin, R.M., Yarmolinsky, J., Robinson, J.W., Mariosa, D., Karhunen, V., Huang, Jian, Dimou, N., Murphy, N., Burrows, K., Bouras, E., Smith-Byrne, K., Lewis, S.J., Galesloot, T.E., Kiemeney, B., Vermeulen, S., Martin, P., Albanes, D., Hou, L., Newcomb, P.A., White, E., Wolk, A., Wu, A.H., Marchand, L. Le, Phipps, A.I., Buchanan, D.D., Zhao, S.S., Gill, D., Chanock, S.J., Purdue, M.P., Smith, G. Davey, Brennan, P., Herzig, K.H., Järvelin, M.R., Amos, C.I., Hung, R.J., Dehghan, A., Johansson, M., Gunter, M.J., Tsilidis, K.K., and Martin, R.M.
- Abstract
Contains fulltext : 304872.pdf (Publisher’s version ) (Open Access), BACKGROUND: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear. METHODS: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,294 cancer cases and up to 1,238,345 controls. Genetic instruments for inflammatory markers were constructed using genome-wide significant (P < 5.0 × 10(-8)) cis-acting SNPs (i.e., in or ±250 kb from the gene encoding the relevant protein) in weak linkage disequilibrium (LD, r(2) < 0.10). Effect estimates were generated using inverse-variance weighted random-effects models and standard errors were inflated to account for weak LD between variants with reference to the 1000 Genomes Phase 3 CEU panel. A false discovery rate (FDR)-corrected P-value ("q-value") <0.05 was used as a threshold to define "strong evidence" to support associations and 0.05 ≤ q-value < 0.20 to define "suggestive evidence". A colocalisation posterior probability (PPH(4)) >70% was employed to indicate support for shared causal variants across inflammatory markers and cancer outcomes. Findings were replicated in the FinnGen study and then pooled using meta-analysis. FINDINGS: We found strong evidence to support an association of genetically-proxied circulating pro-adrenomedullin concentrations with increased breast cancer risk (OR: 1.19, 95% CI: 1.10-1.29, q-value = 0.033, PPH(4) = 84.3%) and suggestive evidence to support associations of interleukin-23 receptor concentrations with increased pancreatic cancer risk (OR: 1.42, 95% CI: 1.20-1.69, q-value = 0
- Published
- 2024
5. IR-stimulated visible fluorescence in pink and brown diamond
- Author
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Byrne, K S, Chapman, J G, and Luiten, A N
- Subjects
Condensed Matter - Materials Science ,Physics - Optics - Abstract
Irradiation of natural pink and brown diamond by middle-ultraviolet light (photon energy > 4.1 eV) is seen to induce anomalous fluorescence phenomena at N3 defect centres (structure N3-V). When diamonds primed in this fashion are subsequently exposed to infrared light (even with a delay of many hours), a transient burst of blue N3 fluorescence is observed. The dependence of this IR-triggered fluorescence on pump wavelength and intensity suggest that this fluorescence phenomena is intrinsically related to pink diamond photochromism. An energy transfer process between N3 defects and other defect species can account for both the UV-induced fluorescence intensity changes, and the apparent optical upconversion of IR light. From this standpoint, we consider the implications of this N3 fluorescence behaviour for the current understanding of pink diamond photochromism kinetics., Comment: 6 pages, 6 figures
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- 2013
- Full Text
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6. Anaesthetic depth and complications after major surgery: an international, randomised controlled trial
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Shulman, M, Wallace, S, Farrington, C, Gallagher, W, Ditoro, A, Peyton, P, Baulch, S, Dalyell, A, Sidiropoulos, S, Reynolds, J, Rowley, J, Tan, N, McCallum, D, O'Loughlin, E, Wong, S, Owen, K, Sim, I-K, Glazov, L, Coutts, P, Pushpanathan, M, Findlay, V, Paech, M, Cavill, D, Chuan, A, Pope, L, Lucas, J, Robinson, B, Millard, A, Allen, S, Allen, M, McKeown, S, Sivalingam, P, Wilkes, T, Jowett, C, Kearney, A, Bennett, M, Favero, J-P, Sawhney, S, Drummond, K, Osborn, S, Wing, A, Taylor, J, Edwards, M, Reynolds, H, Town, C, Terblanche, N, Challis, M, Seale, R, Button, K, Cotter, R, Stewart, M, Zingerle, N, Hannon, S, Middleton, D, Edgley, C, March, S, McCulloch, T, Wong, G, Jeong, S, Connell, K, Kramer, K, Henderson, G, Ward, V, Buller, Y, Hird, N, Scott, D, Evered, L, Snyder, G, Silbert, B, Corcoran, P, Fitzgerald, E, Said, S, Watson, A, Baby, D, Bolsin, S, Marriott, A, Ives, K, Wakefeld, B-J, Jeffreys, A, Bates, S, Halliwell, R, Elliott, D, Cope, L, Paranthoiene, R, Peng, P, Liu, X, Zhou, X, Jin, X, Liu, H, An, L, Cui, W, Zhang, L, Jia, B, Fang, J, Koo, E, Lo, E, Fung, B, Tsang, M, Lam, L, Pang, E, Lau, V, Choi, G, Kwok, R, Yau, K, Cheng, B, Lam, C, Lee, E, Buggy, D, Keane, H, Byrne, K, Connolly, C, Ali, M, Cervantes, A, Kumar, K, Dandy, S, Ritchie, L, Kennedy, R, McKellow, M, Read, C, France, D, Truong, H, Chapman, C, Walker, S, Olliff, S, Houston, H, Scott, M, Minchin, I, Moniwa, A, McAlpine, J, Chaddock, M, Gray, L, Czepanski, C, Vinish, S, Buehner, U, Williams, E, Zhou, C, Goodman, L, Bermaat, J, Mans, G, Garden, A, Franks, R, Deiterle, J, Barrett, J, Roubos, S, van Lier, F, Verbrugge, S, Kalkman, C, Dieleman, J, Verdam-Veldkamp, J, van Kampen, A, Pai, A, Sevillano, A, Yeung, J, Melody, T, Atterbury, K, Hough, M, Dukes, S, Williams, S, Milan, Z, Kunst, G, Bhatia, K, MacNab, W, Weaver, E, Moulding, R, Doble, P, Klepsch, P, Self, J, Howes, T, Rees, B, Faulkner, B, Blackburn, J, Crombie, N, Cooper, L, Nair, A, Bell, G, Longfellow, R, Nicholas, C, Garratt, T, Pollard, M, Brown, G, Morrison, G, Lang, A, Dawson, H, MacDonald, M, Martin, T, Niebrzegowska, E, Dias, P, Rao Baikady, R, Jhanji, S, Siddaiah, N, Bird, L, Mittal, R, Nalawaya, P, Sonksen, J, Gidda, R, Wrench, I, Craw, N, Pippard, L, Davies, S, Wright, M, Turan, M, Maheshwari, K, Cohen, B, Saasouh, W, Singh, P, Govindarajan, S, Cuko, E, Marcano, F, Babazade, R, Leung, S, Raza, S, Reville, E, Hanline, C, Ayad, S, Buttar, M, Akhtar, Z, Niazi, A, Saha, P, Morris, A, Lokhande, C, Hassan, M, Honar, H, Bairacharya, G, Saxon, J, Chelnick, D, Carlson, R, Ruiz, J, Wilks, J, Williams, W, Dangler, L, Ifeanyi-Pillette, I, Suarez, J, Erfe, R, Perez, A, Veselis, R, Yang, G, Mehta, M, Pryor, K, Rubin, L, Malhotra, J, Steinkamp, M, Cooke, F, Friedlander, R, Short, Timothy G, Campbell, Douglas, Frampton, Christopher, Chan, Matthew T V, Myles, Paul S, Corcoran, Tomás B, Sessler, Daniel I, Mills, Gary H, Cata, Juan P, Painter, Thomas, Byrne, Kelly, Han, Ruquan, Chu, Mandy H M, McAllister, Davina J, and Leslie, Kate
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- 2019
- Full Text
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7. The role of plasma microseminoprotein-beta in prostate cancer: an observational nested case–control and Mendelian randomization study in the European prospective investigation into cancer and nutrition
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Smith Byrne, K., Appleby, P.N., Key, T.J., Holmes, M.V., Fensom, G.K., Agudo, A., Ardanaz, E., Boeing, H., Bueno-de-Mesquita, H.B., Chirlaque, M.D., Kaaks, R., Larrañaga, N., Palli, D., Perez-Cornago, A., Quirós, J.R., Ricceri, F., Sánchez, M.J., Tagliabue, G., Tsilidis, K.K., Tumino, R., Fortner, R.T., Ferrari, P., Riboli, E., Lilja, H., and Travis, R.C.
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- 2019
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8. Variability of outcrop magnetic susceptibility and its relationship to the porphyry Cu centers in the Highland Valley Copper district
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Byrne, K., Lesage, G., Morris, W.A., Enkin, R.J., Gleeson, S.A., and Lee, R.G
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- 2019
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9. Tranexamic acid in coronary artery surgery: One-year results of the Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) trial
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Myles, Paul, Smith, Julian, Cooper, D. James, Silbert, Brendan, McNeil, John, Marasco, Silvana, Esmore, Donald, Krum, Henry, Tonkin, A., Buxton, B., Heritier, S., Merry, A., Liew, D., McNeil, J., Forbes, A., Cooper, D.J., Wallace, S., Meehan, A., Myles, P., Galagher, W., Farrington, C., Ditoro, A., Wutzlhofer, L., Story, D., Peyton, P., Baulch, S., Sidiropoulos, S., Potgieter, D., Baker, R.A., Pesudovs, B., O'Loughlin J Wells, E., Coutts, P., Bolsin, S., Osborne, C., Ives, K., Smith, J., Hulley, A., Christie-Taylor, G., Painter, T., Lang, S., Mackay, H., Cokis, C., March, S., Bannon, P.G., Wong, C., Turner, L., Scott, D., Silbert, B., Said, S., Corcoran, P., de Prinse, L., Bussières, J.S., Gagné, N., Lamy, A., Semelhago, L., Chan, M.T.V., Underwood, M., Choi, G.S.Y., Fung, B., Landoni, G., Lembo, R., Monaco, F., Simeone, F., Marianello, D., Alvaro, G., De Vuono, G., van Dijk, D., Dieleman, J., Numan, S., McGuinness, S., Parke, R., Raudkivi, P., Gilder, E., Byrne, K., Dunning, J., Termaat, J., Mans, G., Jayarajah, M., Alderton, J., Waugh, D., Platt, M.J., Pai, A., Sevillano, A., Lal, A., Sinclair, C., Kunst, G., Knighton, A., Cubas, G.M., Saravanan, P., Millner, R., Vasudevan, V., Patteril, M., Lopez, E., Basu, R., Lu, J., Myles, Paul S., Smith, Julian A., Kasza, Jessica, Jayarajah, Mohandas, Painter, Thomas, Bussières, Jean S., McGuinness, Shay, Byrne, Kelly, Chan, Matthew T.V., Landoni, Giovanni, Wallace, Sophie, and Forbes, Andrew
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- 2019
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10. 43 Impact of administration of eapci patient video animation versus standard patient information leaflets on patient experience in the catheterization laboratory assessed using the patcath questionnaire
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Kenny Byrne, K, primary, Colleran, R, additional, Rai, H, additional, Fitzgerald, S, additional, Wilson, H, additional, Begossi, N, additional, MacDonnell, C, additional, McNaughton, E, additional, Coughlan, JJ, additional, and Byrne, RA, additional
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- 2023
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11. P‐BB‐43 | Impact of Irradiation on Quality of Conventional and Pathogen Reduced Platelets with 5‐day Storage
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Seifu, R., primary, Khoshi, M., additional, Skripchenko, A., additional, Byrne, K., additional, West‐Mitchell, K., additional, Flegel, W., additional, Villa, C., additional, Simak, J., additional, Vostal, J., additional, and Cantilena, K. Conry, additional
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- 2023
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12. P‐BB‐17 | Biochemical Parameters at Day 7 of Storage of Pathogen Reduced (UVA/Amotosalen) and Conventional Platelets in Additive Solution With or Without Irradiation
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Skripchenko, A., primary, Khoshi, M., additional, Seifu, R., additional, Byrne, K., additional, West‐Mitchell, K., additional, Cantilena, K. Conry, additional, Villa, C., additional, Simak, J., additional, and Vostal, J., additional
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- 2023
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13. Late Genitourinary Toxicity Outcomes in 300 Prostate Cancer Patients Treated With Dose-escalated Image-guided Intensity-modulated Radiotherapy
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Byrne, K., Hruby, G., Kneebone, A., Whalley, D., Guo, L., McCloud, P., and Eade, T.
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- 2017
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14. The effect of dabigatran on the kaolin-activated whole blood thromboelastogram
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Aho, A and Byrne, K
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- 2016
15. BLOOD PRESSURE AND RISK OF VALVULAR HEART DISEASE: A MENDELIAN RANDOMISATION STUDY
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Nazarzadeh, M., Pinho-Gomes, A.-C., Byrne, K. Smith, Raimondi, F., Solares, R.A., Salimi-Khorshidi, G., Tran, J., Zhu, Y., Otto, C.M., and Rahimi, K.
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- 2019
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16. Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis.
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Yarmolinsky, J, Robinson, JW, Mariosa, D, Karhunen, V, Huang, J, Dimou, N, Murphy, N, Burrows, K, Bouras, E, Smith-Byrne, K, Lewis, SJ, Galesloot, TE, Kiemeney, LA, Vermeulen, S, Martin, P, Albanes, D, Hou, L, Newcomb, PA, White, E, Wolk, A, Wu, AH, Marchand, LL, Phipps, AI, Buchanan, DD, International Lung Cancer Consortium, PRACTICAL consortium, Zhao, SS, Gill, D, Chanock, SJ, Purdue, MP, Smith, GD, Brennan, P, Herzig, K-H, Jarvelin, M-R, Dehghan, A, Johansson, M, Gunter, MJ, Tsilidis, KK, Martin, RM, Yarmolinsky, J, Robinson, JW, Mariosa, D, Karhunen, V, Huang, J, Dimou, N, Murphy, N, Burrows, K, Bouras, E, Smith-Byrne, K, Lewis, SJ, Galesloot, TE, Kiemeney, LA, Vermeulen, S, Martin, P, Albanes, D, Hou, L, Newcomb, PA, White, E, Wolk, A, Wu, AH, Marchand, LL, Phipps, AI, Buchanan, DD, International Lung Cancer Consortium, PRACTICAL consortium, Zhao, SS, Gill, D, Chanock, SJ, Purdue, MP, Smith, GD, Brennan, P, Herzig, K-H, Jarvelin, M-R, Dehghan, A, Johansson, M, Gunter, MJ, Tsilidis, KK, and Martin, RM
- Abstract
BACKGROUND: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear. METHODS: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,162 cancer cases and up to 824,556 controls. Genetic instruments for inflammatory markers were constructed using genome-wide significant (P < 5.0 x 10-8) cis-acting SNPs (i.e. in or ±250 kb from the gene encoding the relevant protein) in weak linkage disequilibrium (LD, r2 < 0.10). Effect estimates were generated using inverse-variance weighted random-effects models and standard errors were inflated to account for weak LD between variants with reference to the 1000 Genomes Phase 3 CEU panel. A false discovery rate (FDR)-corrected P-value ("q-value") < 0.05 was used as a threshold to define "strong evidence" to support associations and 0.05 ≤ q-value < 0.20 to define "suggestive evidence". A colocalisation posterior probability (PPH4) > 70% was employed to indicate support for shared causal variants across inflammatory markers and cancer outcomes. RESULTS: We found strong evidence to support an association of genetically-proxied circulating pro-adrenomedullin concentrations with increased breast cancer risk (OR 1.19, 95% CI 1.10-1.29, q-value=0.033, PPH4=84.3%) and suggestive evidence to support associations of interleukin-23 receptor concentrations with increased pancreatic cancer risk (OR 1.42, 95% CI 1.20-1.69, q-value=0.055, PPH4=73.9%), prothrombin concentrations with decreased basal cell carcinoma risk (OR 0.66, 95% CI
- Published
- 2023
17. The blood proteome of imminent lung cancer diagnosis
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Albanes, D, Alcala, K, Alcala, N, Amos, C, Arslan, AA, Bassett, JK, Brennan, P, Cai, Q, Chen, C, Feng, X, Freedman, ND, Guida, F, Hung, RJ, Hveem, K, Johansson, M, Koh, W-P, Langhammer, A, Milne, RL, Muller, D, Onwuka, J, Sorgjerd, EP, Robbins, HA, Sesso, HD, Severi, G, Shu, X-O, Sieri, S, Smith-Byrne, K, Stevens, V, Tinker, L, Tjonneland, A, Visvanathan, K, Wang, Y, Wang, R, Weinstein, S, Yuan, J-M, Zahed, H, Zhang, X, Zheng, W, Albanes, D, Alcala, K, Alcala, N, Amos, C, Arslan, AA, Bassett, JK, Brennan, P, Cai, Q, Chen, C, Feng, X, Freedman, ND, Guida, F, Hung, RJ, Hveem, K, Johansson, M, Koh, W-P, Langhammer, A, Milne, RL, Muller, D, Onwuka, J, Sorgjerd, EP, Robbins, HA, Sesso, HD, Severi, G, Shu, X-O, Sieri, S, Smith-Byrne, K, Stevens, V, Tinker, L, Tjonneland, A, Visvanathan, K, Wang, Y, Wang, R, Weinstein, S, Yuan, J-M, Zahed, H, Zhang, X, and Zheng, W
- Abstract
Identification of risk biomarkers may enhance early detection of smoking-related lung cancer. We measured between 392 and 1,162 proteins in blood samples drawn at most three years before diagnosis in 731 smoking-matched case-control sets nested within six prospective cohorts from the US, Europe, Singapore, and Australia. We identify 36 proteins with independently reproducible associations with risk of imminent lung cancer diagnosis (all p < 4 × 10-5). These include a few markers (e.g. CA-125/MUC-16 and CEACAM5/CEA) that have previously been reported in studies using pre-diagnostic blood samples for lung cancer. The 36 proteins include several growth factors (e.g. HGF, IGFBP-1, IGFP-2), tumor necrosis factor-receptors (e.g. TNFRSF6B, TNFRSF13B), and chemokines and cytokines (e.g. CXL17, GDF-15, SCF). The odds ratio per standard deviation range from 1.31 for IGFBP-1 (95% CI: 1.17-1.47) to 2.43 for CEACAM5 (95% CI: 2.04-2.89). We map the 36 proteins to the hallmarks of cancer and find that activation of invasion and metastasis, proliferative signaling, tumor-promoting inflammation, and angiogenesis are most frequently implicated.
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- 2023
18. Lung cancer risk discrimination of prediagnostic proteomics measurements compared with existing prediction tools
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Feng, X, Wu, WY-Y, Onwuka, JU, Haider, Z, Alcala, K, Smith-Byrne, K, Zahed, H, Guida, F, Wang, R, Bassett, JK, Stevens, V, Wang, Y, Weinstein, S, Freedman, ND, Chen, C, Tinker, L, Nost, TH, Koh, W-P, Muller, D, Colorado-Yohar, SM, Tumino, R, Hung, RJ, Amos, C, Lin, X, Zhang, X, Arslan, AA, Sanchez, M-J, Sorgjerd, EP, Severi, G, Hveem, K, Brennan, P, Langhammer, A, Milne, RL, Yuan, J-M, Melin, B, Johansson, M, Robbins, HA, Feng, X, Wu, WY-Y, Onwuka, JU, Haider, Z, Alcala, K, Smith-Byrne, K, Zahed, H, Guida, F, Wang, R, Bassett, JK, Stevens, V, Wang, Y, Weinstein, S, Freedman, ND, Chen, C, Tinker, L, Nost, TH, Koh, W-P, Muller, D, Colorado-Yohar, SM, Tumino, R, Hung, RJ, Amos, C, Lin, X, Zhang, X, Arslan, AA, Sanchez, M-J, Sorgjerd, EP, Severi, G, Hveem, K, Brennan, P, Langhammer, A, Milne, RL, Yuan, J-M, Melin, B, Johansson, M, and Robbins, HA
- Abstract
BACKGROUND: We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test. METHODS: We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models' sensitivity. All tests were 2-sided. RESULTS: The area under the curve for the protein-based risk model in the validation sample was 0.75 (95% confidence interval [CI] = 0.70 to 0.81) compared with 0.64 (95% CI = 0.57 to 0.70) for the PLCOm2012 model (Pdifference = .001). The EarlyCDT-Lung had a sensitivity of 14% (95% CI = 8.2% to 19%) and a specificity of 86% (95% CI = 81% to 92%) for incident lung cancer. At the same specificity of 86%, the sensitivity for the protein-based risk model was estimated at 49% (95% CI = 41% to 57%) and 30% (95% CI = 23% to 37%) for the PLCOm2012 model. CONCLUSION: Circulating proteins showed promise in predicting incident lung cancer and outperformed a standard risk prediction model and the commercialized EarlyCDT-Lung.
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- 2023
19. Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer: a collaborative analysis of 20 prospective studies and Mendelian randomization analysis
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Watts, EL, Perez-Cornago, A, Fensom, GK, Smith-Byrne, K, Noor, U, Andrews, CD, Gunter, MJ, Holmes, M, Martin, RM, Tsilidis, KK, Albanes, D, Barricarte, A, Bueno-de-Mesquita, HB, Cohn, BA, Deschasaux-Tanguy, M, Dimou, NL, Ferrucci, L, Flicker, L, Freedman, ND, Giles, GG, Giovannucci, EL, Haiman, CA, Hankey, GJ, Holly, JMP, Huang, J, Huang, W-Y, Hurwitz, LM, Kaaks, R, Kubo, T, Le Marchand, L, MacInnis, RJ, Mannisto, S, Metter, EJ, Mikami, K, Mucci, LA, Olsen, AW, Ozasa, K, Palli, D, Penney, KL, Platz, EA, Pollak, MN, Roobol, MJ, Schaefer, CA, Schenk, JM, Stattin, P, Tamakoshi, A, Thysell, E, Tsai, CJ, Touvier, M, Van Den Eeden, SK, Weiderpass, E, Weinstein, SJ, Wilkens, LR, Yeap, BB, Allen, NE, Key, TJ, Travis, RC, Watts, EL, Perez-Cornago, A, Fensom, GK, Smith-Byrne, K, Noor, U, Andrews, CD, Gunter, MJ, Holmes, M, Martin, RM, Tsilidis, KK, Albanes, D, Barricarte, A, Bueno-de-Mesquita, HB, Cohn, BA, Deschasaux-Tanguy, M, Dimou, NL, Ferrucci, L, Flicker, L, Freedman, ND, Giles, GG, Giovannucci, EL, Haiman, CA, Hankey, GJ, Holly, JMP, Huang, J, Huang, W-Y, Hurwitz, LM, Kaaks, R, Kubo, T, Le Marchand, L, MacInnis, RJ, Mannisto, S, Metter, EJ, Mikami, K, Mucci, LA, Olsen, AW, Ozasa, K, Palli, D, Penney, KL, Platz, EA, Pollak, MN, Roobol, MJ, Schaefer, CA, Schenk, JM, Stattin, P, Tamakoshi, A, Thysell, E, Tsai, CJ, Touvier, M, Van Den Eeden, SK, Weiderpass, E, Weinstein, SJ, Wilkens, LR, Yeap, BB, Allen, NE, Key, TJ, and Travis, RC
- Abstract
BACKGROUND: Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. METHODS: Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. RESULTS: In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I. CONCLUSIONS: These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.
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- 2023
20. Evaluation of pre-diagnostic blood protein measurements for predicting survival after lung cancer diagnosis
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Feng, X, Muller, DC, Zahed, H, Alcala, K, Guida, F, Smith-Byrne, K, Yuan, J-M, Koh, W-P, Wang, R, Milne, RL, Bassett, JK, Langhammer, A, Hveem, K, Stevens, VL, Wang, Y, Johansson, M, Tjonneland, A, Tumino, R, Sheikh, M, Robbins, HA, Feng, X, Muller, DC, Zahed, H, Alcala, K, Guida, F, Smith-Byrne, K, Yuan, J-M, Koh, W-P, Wang, R, Milne, RL, Bassett, JK, Langhammer, A, Hveem, K, Stevens, VL, Wang, Y, Johansson, M, Tjonneland, A, Tumino, R, Sheikh, M, and Robbins, HA
- Abstract
BACKGROUND: To evaluate whether circulating proteins are associated with survival after lung cancer diagnosis, and whether they can improve prediction of prognosis. METHODS: We measured up to 1159 proteins in blood samples from 708 participants in 6 cohorts. Samples were collected within 3 years prior to lung cancer diagnosis. We used Cox proportional hazards models to identify proteins associated with overall mortality after lung cancer diagnosis. To evaluate model performance, we used a round-robin approach in which models were fit in 5 cohorts and evaluated in the 6th cohort. Specifically, we fit a model including 5 proteins and clinical parameters and compared its performance with clinical parameters only. FINDINGS: There were 86 proteins nominally associated with mortality (p < 0.05), but only CDCP1 remained statistically significant after accounting for multiple testing (hazard ratio per standard deviation: 1.19, 95% CI: 1.10-1.30, unadjusted p = 0.00004). The external C-index for the protein-based model was 0.63 (95% CI: 0.61-0.66), compared with 0.62 (95% CI: 0.59-0.64) for the model with clinical parameters only. Inclusion of proteins did not provide a statistically significant improvement in discrimination (C-index difference: 0.015, 95% CI: -0.003 to 0.035). INTERPRETATION: Blood proteins measured within 3 years prior to lung cancer diagnosis were not strongly associated with lung cancer survival, nor did they importantly improve prediction of prognosis beyond clinical information. FUNDING: No explicit funding for this study. Authors and data collection supported by the US National Cancer Institute (U19CA203654), INCA (France, 2019-1-TABAC-01), Cancer Research Foundation of Northern Sweden (AMP19-962), and Swedish Department of Health Ministry.
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- 2023
21. Pre‐operative sciatic nerve block vs postoperative surgeon‐placed perineural stump catheter for prevention of phantom limb pain after below‐knee amputation
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Byrne, K., primary, Xu, W., additional, Termaat, J., additional, and Khashram, M., additional
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- 2023
- Full Text
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22. Long-term (180-day) outcomes in critically ill patients with COVID-19 in the REMAP-CAP randomized clinical trial
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Florescu, S, Stanciu, D, Zaharia, M, Kosa, A, Codreanu, D, Kidwai, A, Masood, S, Kaye, C, Coutts, A, MacKay, L, Summers, C, Polgarova, P, Farahi, N, Fox, E, McWilliam, S, Hawcutt, D, Rad, L, O’Malley, L, Whitbread, J, Jones, D, Dore, R, Saunderson, P, Kelsall, O, Cowley, N, Wild, L, Thrush, J, Wood, H, Austin, K, Bélteczki, J, Magyar, I, Fazekas, Á, Kovács, S, Szőke, V, Donnelly, A, Kelly, M, Smyth, N, O’Kane, S, McClintock, D, Warnock, M, Campbell, R, McCallion, E, Azaiz, A, Charron, C, Godement, M, Geri, G, Vieillard-Baron, A, Johnson, P, McKenna, S, Hanley, J, Currie, A, Allen, B, McGoldrick, C, McMaster, M, Mani, A, Mathew, M, Kandeepan, R, Vignesh, C, TV, B, Ramakrishnan, N, James, A, Elvira, E, Jayakumar, D, Pratheema, R, Babu, S, Ebenezer, R, Krishnaoorthy, S, Ranganathan, L, Ganesan, M, Shree, M, Guilder, E, Butler, M, Cowdrey, K-A, Robertson, M, Ali, F, McMahon, E, Duffy, E, Chen, Y, Simmonds, C, McConnochie, R, O’Connor, C, El-Khawas, K, Richardson, A, Hill, D, Commons, R, Abdelkharim, H, Saxena, M, Muteithia, M, Dobell-Brown, K, Jha, R, Kalogirou, M, Ellis, C, Krishnamurthy, V, O’Connor, A, Thurairatnam, S, Mukherjee, D, Kaliappan, A, Vertue, M, Nicholson, A, Riches, J, Maloney, G, Kittridge, L, Solesbury, A, Ramos, A, Collins, D, Brickell, K, Reid, L, Smyth, M, Breen, P, Spain, S, Curley, G, McEvoy, N, Geoghegan, P, Clarke, J, Silversides, J, McGuigan, P, Ward, K, O’Neill, A, Finn, S, Wright, C, Green, J, Collins, É, Knott, C, Smith, J, Boschert, C, Slieker, K, Ewalds, E, Sanders, A, Wittenberg, W, Geurts, H, Poojara, L, Sara, T, Nand, K, Reeve, B, Dechert, W, Phillips, B, Oritz-Ruiz de Gordoa, L, Affleck, J, Shaikh, A, Murray, A, Ramanan, M, Frakking, T, Pinnell, J, Robinson, M, Gledhill, L, Wood, T, Sanghavi, R, Bhonagiri, D, Ford, M, Parikh, HG, Avard, B, Nourse, M, McDonald, B, Edmunds, N, Hoiting, O, Peters, M, Rengers, E, Evers, M, Prinssen, A, Morgan, M, Cole, J, Hill, H, Davies, M, Williams, A, Thomas, E, Davies, R, Wise, M, Grimm, P, Soukup, J, Wetzold, R, Löbel, M, Starke, L, Lellouche, F, Lizotte, P, Declerq, P, Antoine, M, Stephanie, G, Jean-Pierre, E, François, B, Marion, B, Philippe, R, Pourcine, F, Monchi, M, Luis, D, Mercier, R, Sagnier, A, Verrier, N, Caplin, C, Richecoeu, J, Combaux, D, Siami, S, Aparicio, C, Vautier, S, Jeblaoui, A, Lemaire-Brunel, D, D'Aragon, F, Carbonneau, E, Leblond, J, Plantefeve, G, Leparco, C, Contou, D, Fartoukh, M, Courtin, L, Labbe, V, Voiriot, G, Salhi, S, Chassé, M, Carrier, F, Boumahni, D, Benettaib, F, Ghamraoui, A, Sement, A, Gachet, A, Hanisch, A, Haffiane, A, Boivin, A-H, Barreau, A, Guerineau, E, Poupblanc, S, Egreteau, P, Lefevre, M, Bocher, S, Le Loup, G, Le Guen, L, Carn, V, Bertel, M, Antcliffe, D, Templeton, M, Rojo, R, Coghlan, P, Smee, J, Barker, G, Finn, A, Kreb, G, Hoff, U, Hinrichs, C, Nee, J, Mackay, E, Cort, J, Whileman, A, Spencer, T, Spittle, N, Beavis, S, Padmakumar, A, Dale, K, Hawes, J, Moakes, E, Gascoyne, R, Pritchard, K, Stevenson, L, Cooke, J, Nemeth-Roszpopa, K, Gauli, B, Bastola, S, Muller, G, Nay, M-A, Kamel, T, Benzekri, D, Jacquier, S, Runge, I, Mathonnet, A, Barbier, F, Bretagnol, A, Carter, J, Van Der Heyden, K, Mehrtens, J, Morris, A, Morgan, S, Burke, T, Mercier, E, Chartier, D, Salmon, C, Dequin, P-F, Garot, D, Bellemare, D, Cloutier, È, Daher, R, Costerousse, O, Boulanger, M-C, Couillard-Chénard, É, Lauzier, F, Francoeur, C, Francois, B, Gay, A, Anne-Laure, F, Ramali, M, HC, O, Ghosh, A, Osagie, R, Arachchige, M, Hartley, M, Cheung, W, Wong, H, Seigne, P, Eustace, J, O'Callaghan, A-M, O'Brien, F, Bamford, P, Reid, A, Cawley, K, Faulkner, M, Pickering, C, Raj, A, Tsinaslanidis, G, Khade, R, Agha, G, Sekiwala, R, Smith, T, Brewer, C, Gregory, J, Limb, J, Cowton, A, O’Brien, J, Postlethwaite, K, Malakouti, S, Music, E, Ricketts, D, King, A, Clermont, G, Bart, R, Mayr, F, Schoenling, A, Andreae, M, Shetty, V, Brant, E, Malley, B, Donadee, C, Sackrowitz, R, Weissman, A, Yealy, D, Barton, D, Talia, N, Nikitas, N, Wells, C, Lankester, L, McMillan, H, Van den Oever, H, Kruisdijk-Gerritsen, A, Haidar, G, Bain, W, Barbash, I, Fitzpatrick, M, Franz, C, Kitsios, G, Moghbeli, K, Rosborough, B, Shah, F, Suber, T, Pulletz, M, Williams, P, Birch, J, Wiseman, S, Horton, S, Alegria, A, Turki, S, Elsefi, T, Crisp, N, Allen, L, Truman, N, Smith, M, Chukkambotla, S, Goddard, W, Duberley, S, Khan, M, Kazi, A, Simpson, J, Duke, G, Chan, P, Carter, B, Hunter, S, Voigt, I, Schueler, R, Blank, E, Hüning, V, Steffen, M, Goralski, P, Litton, E, Regli, A, Pellicano, S, Palermo, A, Eroglu, E, Bihari, S, Laver, RD, Jin, X, Brown, J, McIntyre, J, French, C, Bates, S, Towns, M, Yang, Y, McGain, F, McCullagh, I, Cairns, T, Hanson, H, Patel, B, Clement, I, Evetts, G, Touma, O, Holland, S, Hodge, C, Taylor, H, Alderman, M, Barnes, N, Da Rocha, J, Smith, C, Brooks, N, Weerasinghe, T, Sinclair, J-A, Abusamra, Y, Doherty, R, Cudlipp, J, Singh, R, Yu, H, Daebis, A, Ng, C, Kendrick, S, Saran, A, Makky, A, Greener, D, Rowe-Leete, L, Edwards, A, Bland, Y, Dolman, R, Foster, T, Laffey, J, McNicholas, B, Scully, M, Casey, S, Kernan, M, Brennan, A, Rangan, R, Tully, R, Corbett, S, McCarthy, A, Duffy, O, Burke, D, Linnett, V, Sanderson, A, Ritzema, J, Wild, H, Lucas, R, Marriott, Y, Andric, Z, Cviljevic, S, Br, R, Zapalac, M, Mirković, G, Khare, D, Pinder, M, Gopinath, A, Kannan, T, Dean, S, Vanmali, P, Depuydt, P, De Waele, J, De Bus, L, Fierens, J, Bracke, S, Vermassen, J, Vermeiren, D, Pugh, R, Lean, R, Qiu, X, Scanlan, J, Evans, A, Davies, G, Lewis, J, Plesnikova, Y, Khoud, A, Coetzee, S, Puxty, K, Cathcart, S, Rimmer, D, Bagot, C, Scott, K, Martin, L, Yusuff, H, Isgro, G, Brightling, C, Bourne, M, Craner, M, Boyles, R, Alexander, B, Roberts, T, Nelli, A, Rosenstein-Sisson, R, Speyer, R, Pech, Y, McCullough, J, Tallott, M, Vazquez-Grande, G, Marten, N, Liu, T, Siddiqui, A, Khanal, S, Amatya, S, Szakmany, T, Cherian, S, Williams, G, James, C, Waters, A, Prout, R, Stedman, R, Davies, L, Pegler, S, Kyeremeh, L, Moorhouse, L, Arbane, G, Marotti, M, Bociek, A, Campos, S, Van Nieuwkoop, K, Ottens, T, Visser, Y, Van den Berg, L, Van der Kraan-Donker, A, Brett, S, Arias, S, Hall, R, Paneru, H, Koirala, S, Paudel, P, Wilson, M, Vaara, S, Pettilä, L, Heinonen, J, Pettilä, V, Jain, S, Gupta, A, Holbrook, C, Antoine, P, Meziani, F, Allam, H, Cattelan, J, Clere-Jehl, R, Helms, J, Kummerlen, C, Merdji, H, Monnier, A, Rahmani, H, Studer, A, Schneider, F, Castelain, V, Morel, G, L’Hotellier, S, Ochin, E, Vanjak, C, Rouge, P, Bendjemar, L, Albert, M, Serri, K, Cavayas, A, Duplaix, M, Williams, V, Catorze, NJTADS, Pereira, TNAL, Ferreira, RMC, Bastos, JMPS, Batista, TMO, Badie, J, Berdaguer, F, Malfroy, S, Mezher, C, Bourgoin, C, Moneger, G, Bouvier, E, Muñoz-Bermúdez, R, Marin-Corral, J, Degracia, A, Gómez, F, López, M, Aceto, R, Aghemo, A, Badalamenti, S, Brunetta, E, Cecconi, M, Ciccarelli, M, Constantini, E, Greco, M, Folci, M, Selmi, C, Voza, A, Henning, J, Bonner, S, Hugill, K, Cirstea, E, Wilkinson, D, Jones, J, Altomy, M, Karlikowski, M, Sutherland, H, Wilhelmsen, E, Woods, J, North, J, Pletz, M, Hagel, S, Ankert, J, Kolanos, S, Bloos, F, Simons, K, Van Zuylen, T, Bouman, A, Kumar, N, Panwar, R, Poulter, A-L, Sunkara, K, Szigligeti, G, Leszkoven, J, Rochwerg, B, Karachi, T, Oczkowski, S, Centofanti, J, Millen, T, Sundaran, D, Hollos, L, Turns, M, Walsh, J, Al Qasim, E, Alswaidan, L, Hegazy, M, Arishi, H, Al Amri, A, AlQahtani, S, Naidu, B, Tlayjeh, H, Hussain, S, Al Enezi, F, Abdukahil, SA, Hopkins, P, Noble, H, O’Reilly, K, Mehta, R, Wong, O, Makanju, E, Rao, D, Sikondari, N, Saha, S, Corcoran, E, Pappa, E, Cockrell, M, Donegan, C, Balaie, M, Nickoleit-Bitzenberger, D, Schaaf, B, Meermeier, W, Prebeg, K, Azzaui, H, Hower, M, Brieger, K-G, Elender, C, Sabelhaus, T, Riepe, A, Akamp, C, Kremling, J, Klein, D, Landsiedel-Mechenbier, E, Laha, S, Verlander, M, Jha, A, Megarbane, B, Voicu, S, Deye, N, Malissin, I, Sutterlin, L, Mrad, A, Lehalleur, A, Naim, G, Nguyen, P, Ekhérian, J-M, Boué, Y, Sidéris, G, Vodovar, D, Guérin, E, Grant, C, Brain, M, Mineall, S, Paramasivam, E, Wilby, E, Ogg, B, Howcroft, C, Aspinwall, A, Charlton, S, Gould, R, Mistry, D, Awan, S, Bedford, C, Carr-Wilkinson, J, Hall, A, Gardiner-Hill, C, Maloney, C, Brunskill, N, Watchorn, O, Hardy, C, Qureshi, H, Flint, N, Nicholson, S, Southin, S, Ghattaoraya, A, Harding, D, O’Halloran, S, Collins, A, Smith, E, Trues, E, Borgatta, B, Turner-Bone, I, Reddy, A, Wilding, L, Wilson, C, Surti, Z, Aneman, A, Miller, J, White, H, Estensen, K, Morrison, L, Sutton, J, Cooper, M, Warnapura, L, Agno, R, Sathianathan, P, Shaw, D, Ijaz, N, Spong, A, Sabaretnam, S, Burns, D, Lang, E, Tate, M, Fischer, R, Biradar, V, Soar, N, Golden, D, Davey, M, Seaman, R, Osborne, A, Bannard-Smith, J, Clark, R, Birchall, K, Henry, J, Pomeroy, F, Quayle, R, Wylie, K, Sukuraman, A, John, M, Sibin, S, Leditschke, A, Finnis, M, Jongebloed, K, Khwaja, K, Campisi, J, Van Vonderen, M, Pietersma, M, Vrolijk, L, Kampschreur, L, Van Gulik, L, Makowski, A, Misztal, B, Haider, S, Liao, A, Squires, R, Oborska, A, Kayani, A, Kalchko-Veyssal, S, Prabakaran, R, Hadebe, B, KalchkoVeyssal, S, Williams, T, Song, R, Morpeth, S, Lai, V, Habraken, H, Stewart, R, Mwaura, E, Mew, L, Wren, L, Willams, F, Sutherland, S-B, Rebello, R, Shehabi, Y, Al-Bassam, W, Hulley, A, Kadam, U, Sathianathan, K, Innes, R, Doble, P, Graham, L, Shovelton, C, Dean, T, Salahuddin, N, Aryal, D, Koirala, K, Rai, N, Luitel, S, Seppelt, I, Whitehead, C, Lowrey, J, Gresham, R, Masters, K, Hamlyn, V, Hawkins, N, Roynon-Reed, A, Cutler, S, Lewis, S, Lazaro, J, Newman, T, Aravindan, L, Asghar, A, Bartholomew, J, Bayne, M, Beddows, S, Birch, C, Brend, M, Byrne, R, Campbell, D, Campbell, H, Chambers, E, Clinton, A, Collins, J, Crawshaw, S, Dawson, LA, Donaldson, K, Drake, C, Dyas, S, Ellis, Y, Gilmour, K, Goodwin, J, Halden, S, Hall, AS, Hanson, J, Harper, H, Harrison, S, Hayes, A, Hodgson, H, Hurford, S-A, Jackson, S, Levett, C, Lock, S, Lockett, T, Logan, M, Lomme, K, Luo, J, Marsh, E, Mguni, N, Monaghan, H, Murphy, S, Muzengi, N, Naz, M, O'Kell, E, Oliver, A, O'Reilly, J, Pearson, K, Porter, D, Potter, A, Rook, C, Rounds, C, Sheffield, J, Shirley, K, Siewersk, C, Skinner, T, Speight, H, Sutu, M, Unsworth, A, Van’t Hoff, W, Walker, S, Williams, H, Williamson, D, Williamson, JD, Duan, E, Tsang, J, Patterson, L, Austin, P, Chapman, S, Cabrelli, L, Fletcher, S, Nortje, J, Fottrell-Gould, D, Randell, G, Stammers, K, Healey, G, Pinto, M, Borrill, Z, Duncan, T, Ustianowski, A, Uriel, A, Eltayeb, A, Alfonso, J, Hey, S, Shaw, J, Fox, C, Lindergard, G, Charles, B, Blackledge, B, Connolly, K, Harris, J, Cuesta, J, Xavier, K, Purohit, D, Elhassan, M, Haldeos, A, Vincent, R, Abdelrazik, M, Jenkins, S, Ganesan, A, Kumar, R, Carter, D, Bakthavatsalam, D, Frater, A, Saleem, M, Everitt, R, Hacking, D, Zaman, M, Elmahi, E, Jones, A, Hall, K, Phillips, M, Terrill, L, Mills, G, Raithatha, A, Bauchmuller, K, Ryalls, K, Harrington, K, Bowler, H, Sall, J, Bourne, R, Gross, J, Massey, N, Adebambo, O, Long, M, Tony, K, Juffermans, N, Koopmans, M, Dujardin, R, Alderink, B, Rowland, M, Hutton, P, Bashyal, A, Davidson, N, Hird, C, Chhablani, M, Phalod, G, Kirkby, A, Archer, S, Netherton, K, Reschreiter, H, Camsooksai, J, Patch, S, Humphrey, C, Flynn, G, Harrington, C, Kruger, P, Walsham, J, Meyer, J, Harward, M, Jones, C, Sathe, S, Roche, L, Davies, E, Skinner, D, Gaylard, J, Newman, J, Pogson, D, Rose, S, Daly, Z, Brimfield, L, Nown, A, Parekh, D, Bergin, C, Bates, M, McGhee, C, Lynch, D, Bhandal, K, Tsakiridou, K, Bamford, A, Cooper, L, Whitehouse, T, Veenith, T, Forster, E, O'Connell, M, Sim, M, Hay, S, Henderson, S, Nygren, M, Valentine, E, Katary, A, Bell, G, Wilcox, L, Mataliotakis, M, Smith, P, Ali, M, Isguzar, A, Phull, M-K, Zaidi, A, Pogreban, T, Rosaroso, L, Harvey, D, Lowe, B, Meredith, M, Ryan, L, Schouten, J, Pickkers, P, Roovers, N, Klop-Riehl, M, Van der Eng, H, Sloots-Cuppen, S, Preijers, L, Van Oosten, N, Moine, P, Heming, N, Maxime, V, Bossard, I, Nicholier, T, Clair, B, Orlikowski, D, Bounab, R, Abdeladim, L, Baker, S, Duroux, M, Ratcliffe, M, Sy, E, Mailman, J, Lee, S, Gupta, C, Kassir, S, López, R, Rodríguez-Gómez, J, Cárcel, S, Carmona, R, De la Fuente, C, Rodriguez, M, Jan Hassing, R, Greven, F, Huijbens, D, Roebers, L, Verheij, H, Miles, H, Attokaran, A, Buehner, U, Williams, E, Chapman, M, O’Connor, S, Glasby, K, Rivett, J, Brown, N, Kutsogiannis, D, Thompson, P, Rooney, K, Rodden, N, Thomson, N, McGlynn, D, Abel, L, Gemmell, L, Sundaram, R, Hornsby, J, Walden, A, Keating, L, Frise, M, Rai, S, Bartley, S, Schuster-Bruce, M, Pitts, S, Miln, R, Purandare, L, Vamplew, L, Dempster, D, Gummadi, M, Dormand, N, Wang, S, Spivey, M, Bean, S, Burt, K, Moore, L, Hammonds, F, Richards, C, Campbell, L, Smyth, K, Day, C, Zitter, L, Benyon, S, Singh, J, Lynch, C, Mikusek, J, Deacon, B, Turner, K, Baker, E, Hickey, J, Champanerkar, S, Aitken, L, LewisProsser, L, Ahmad, N, Wiles, M, Willson, J, Grecu, I, Martin, J, Wrey Brown, C, Arias, A-M, Bevan, E, Westlake, S, Craven, T, Hope, D, Singleton, J, Clark, S, McCulloch, C, Biddie, S, Welters, I, Hamilton, D, Williams, K, Waugh, V, Mulla, S, Waite, A, Roman, J, Martinez, M, Johnston, B, Puthucheary, Z, Martin, T, Santos, F, Uddin, R, Fernandez, M, Seidu, F, Somerville, A, Pakats, M-L, Begum, S, Shahid, T, Presneill, J, Barge, D, Byrne, K, Janin, P, Yarad, E, Bass, F, Hammond, N, Vuylsteke, A, Chan, C, Victor, S, Waterson, S, McNamara, R, Boardman, M, Gattas, D, Buhr, H, Coles, J, Matsa, R, Gellamucho, M, Creagh-Brown, B, Marriot, C, Salberg, A, Zouita, L, Stone, S, Michalak, N, Donlon, S, Mtuwa, S, Mayangao, I, Verula, J, Burda, D, Harris, C, Jones, E, Bradley, P, Tarr, E, Harden, L, Piercy, C, Nolan, J, Kerslake, I, Cook, T, Simpson, T, Dalton, J, Demetriou, C, Mitchard, S, Ramos, L, White, K, Johnson, T, Headdon, W, Spencer, S, White, A, Howie, L, Reay, M, Watts, A, Traverse, E, Jennings, S, Anumakonda, V, Tuckwell, C, Harrow, K, Matthews, J, McGarry, K, Moore, V, Smith, L, Summerfield, A, Dark, P, Harvey, A, Doonan, R, McMorrow, L, Knowles, K, Pendlebury, J, Perez, J, Marsden, T, Taylor, M, Michael, A, Collis, M, Claxton, A, Habeichi, W, Horner, D, Slaughter, M, Thomas, V, Proudfoot, N, Keatley, C, Donnison, P, Casey, R, Irving, B, Matimba-Mupaya, W, Reed, C, Anthony, A, Trim, F, Cambalova, L, Robertson, D, Wilson, A, Hulme, J, Kannan, S, Kinney, F, Senya, H, Ratnam, V, Gill, M, Kirk, J, Shelton, S, Schweikert, S, Wibrow, B, Anstey, M, Rauniyar, R, Khoso, N, Asif, N, Taqdees, H, Frey, C, Scano, R, McKee, M, Murphy, P, Thomas, M, Worner, R, Faulkner, B, Gendall, E, Hayes, K, Blakemore, H, Borislavova, B, Deshpande, K, Van Haren, F, Konecny, P, Inskip, D, Tung, R, Hayes, L, Murphy, L, Neill, A, Reidy, B, O’Dwyer, M, Ryan, D, Ainscough, K, Hamilton-Davies, C, Mfuko, C, Abbass, H, Mandadapu, V, Leaver, S, Patel, K, Farnell-Ward, S, Saluzzio, R, Rawlins, S, Sicat, C, De Keulenaer, B, Ferrier, J, Fysh, E, Davda, A, Mevavala, B, Cook, D, Clarke, F, Banach, D, Fernández de Pinedo Artaraz, Z, Cabreros, L, Latham, V, Kruisselbrink, R, Brochard, L, Burns, K, Sandhu, G, Khalid, I, White, I, Croft, M, Holland, N, Pereira, R, Nair, P, Buscher, H, Reynolds, C, Newman, S, Santamaria, J, Barbazza, L, Homes, J, Smith, R, Zaki, A, Johnson, D, Garrard, H, Juhaz, V, Brown, L, Pemberton, A, Roy, A, Rostron, A, Woods, L, Cornell, S, Fowler, R, Adhikari, N, Kamra, M, Marinoff, N, Garrett, P, Murray, L, Brailsford, J, Fennessy, G, Mulder, J, Morgan, R, Pillai, S, Harford, R, Ivatt, H, Evans, D, Richards, S, Roberts, E, Bowen, J, Ainsworth, J, Kuitunen, A, Karlsson, S, Vahtera, A, Kiiski, H, Ristimäki, S, Albrett, J, Jackson, C, Kirkham, S, Tamme, K, Reinhard, V, Ellervee, A, Põldots, L, Rennit, P, Svitškar, N, Browne, T, Grimwade, K, Goodson, J, Keet, O, Callender, O, Udy, A, McCracken, P, Young, M, Board, J, Martin, E, Kasipandian, V, Patel, A, Allibone, S, Mary-Genetu, R, English, S, Watpool, I, Porteous, R, Miezitis, S, McIntyre, L, Brady, K, Vale, C, Shekar, K, Lavana, J, Parmar, D, Peake, S, Kurenda, C, Hormis, A, Walker, R, Collier, D, Kimpton, S, Oakley, S, Bhagani, S, De Neef, M, Garcia, S, Maharajh, A, Nandani, A, Dobson, J, Fernando, G, Eastgate, C, Gomez, K, Abdi, Z, Tatham, K, Jhanji, S, Black, E, Dela Rosa, A, Howle, R, Baikady, R, Drummond, A, Dearden, J, Philbin, J, Munt, S, Gopal, S, Pooni, J-S, Ganguly, S, Smallwood, A, Metherell, S, Naeem, A, Fagan, L, Ryan, E, Mariappa, V, Foulds, A, Revill, A, Bhattarai, B, De Jonge, E, Wigbers, J, Del Prado, M, Cremer, O, Mulier, J, Peters, A, Romberg, B, Schutgens, R, Troeman, D, Van Opdorp, M, Besten, H, Brakké, K, Barber, R, Hilldrith, A, Kluge, S, Nierhaus, A, Jarczak, D, Roedl, K, Kochanek, M, Rueß-Paterno, G, Mc-Kenzie, J, Eichenauer, D, Shimabukuro-Vornhagen, A, Wilcox, E, Del Sorbo, L, Abdelhady, H, Romagnuolo, T, Simpson, S, Maiden, M, Horton, M, Trickey, J, Krajinovic, V, Kutleša, M, Kotarski, V, Brohi, F, Jagannathan, V, Clark, M, Purvis, S, Wetherill, B, Brajković, A, Babel, J, Sever, H, Dragija, L, Kušan, I, Dushianthan, A, Cusack, R, De Courcy-Golder, K, Salmon, K, Burnish, R, Smith, S, Ruiz, W, Duke, Z, Johns, M, Male, M, Gladas, K, Virdee, S, Swabe, J, Tomlinson, H, Rohde, G, Grünewaldt, A, Bojunga, J, Petros, S, Kunz, K, Schütze, B, Weismann, D, Frey, A, Drayss, M, Goebeler, ME, Flor, T, Fragner, G, Wahl, N, Totzke, J, Sayehli, C, Hakak, S, Altaf, W, O'Sullivan, M, Murphy, A, Walsh, L, Rega La Valle, A, Bewley, J, Sweet, K, Grimmer, L, Johnson, R, Wyatt, R, Morgan, K, Varghese, S, Willis, J, Stratton, E, Kyle, L, Putensen, D, Drury, K, Skorko, A, Bremmer, P, Ward, G, Bassford, C, Sligl, W, Baig, N, Rewa, O, Bagshaw, S, Basile, K, Stavor, D, Burbee, D, McNamara, A, Wunderley, R, Bensen, N, Adams, P, Vita, T, Buhay, M, Scholl, D, Gilliam, M, Winters, J, Doherty, K, Berryman, E, Ghaffari, M, Marroquin, O, Quinn, K, Garrard, W, Kalchthaler, K, Beard, G, Skrtich, A, Bagavathy, K, Drapola, D, Bryan-Morris, K, Arnold, J, Reynolds, B, Hussain, M, Dunsavage, J, Saiyed, S, Hernandez, E, Goldman, J, Brown, C, Comp, S, Raczek, J, Morris, J, Vargas Jr., J, Weiss, D, Hensley, J, Kochert, E, Wnuk, C, Nemeth, C, Mowery, B, Hutchinson, C, Winters, L, McAdams, D, Walker, G, Minnier, T, Wisniewski, M, Mayak, K, McCreary, E, Bariola, R, Viehman, A, Daley, J, Lopus, A, Schmidhofer, M, Ambrosino, R, Keen, S, Toffalo, S, Stambaugh, M, Trimmer, K, Perri, R, Casali, S, Medva, R, Massar, B, Beyerl, A, Burkey, J, Keeler, S, Lowery, M, Oncea, L, Daugherty, J, Sevilla, C, Woelke, A, Dice, J, Weber, L, Roth, J, Ferringer, C, Beer, D, Fesz, J, Carpio, L, Colin, G, Zinzoni, V, Maquigneau, N, Henri-Lagarrigue, M, Pouplet, C, Reill, L, Distler, M, Maselli, A, Martynoga, R, Trask, K, Butler, A, Attwood, B, Parsons, P, Campbell, B, Smith, A, Page, V, Zhao, X, Oza, D, Abrahamson, G, Sheath, B, Young, P, Young, C, Lesona, E, Navarra, L, Cruz, R, Delaney, K, Aguilar-Dano, A, Gojanovic, M, Rhodes, J, Anderson, T, Morris, S, Nayyar, V, Bowen, D, Kong, J, Joy, J, Fuchs, R, Lambert, B, Tai, C, Thomas, A, Keen, A, Tierney, C, Omer, N, Bacon, G, Tridente, A, Shuker, K, Anders, J, Greer, S, Scott, P, Millington, A, Buchanan, P, Binnie, A, Powell, E, McMillan, A, Luk, T, Aref, N, Denmade, C, Sadera, G, Jacob, R, Hughes, D, Sterba, M, Geng, W, Digby, S, Southern, D, Reddy, H, Hulse, S, Campbell, A, Garton, M, Watkins, C, Smuts, S, Quinn, A, Simpson, B, McMillan, C, Finch, C, Hill, C, Cooper, J, Budd, J, Small, C, O’Leary, R, Collins, E, Holland, A, Alexander, P, Felton, T, Ferguson, S, Sellers, K, Ward, L, Yates, D, Birkinshaw, I, Kell, K, Scott, Z, Pearson, H, Hashmi, M, Hassan, N, Panjwani, A, Umrani, Z, Shaikh, M, Ain, Q, Kanwal, D, Van Bree, S, Bouw-Ruiter, M, Osinga, M, Van Zanten, A, McEldrew, R, Rashan, S, Singh, V, Azergui, N, Bari, S, Beltran, M, Brugman, C, Groeneveld, E, Jafarzadeh, M, Keijzer-Timmers, N, Kester, E, Koelink, M, Kwakkenbos-Craanen, M, Okundaye, C, Parker, L, Peters, S, Post, S, Rietveld, I, Scheepstra-Beukers, I, Schreuder, G, Smit, A, Brillinger, N, Markgraf, R, Eichinger, F, Doran, P, Anjum, A, Best-Lane, J, Barton, F, Miller, L, Richards-Belle, A, Saull, M, Sprinckmoller, S, Wiley, D, Darnell, R, Au, C, Lindstrum, K, Cheng, A, Forbes, A, Heritier, S, Trapani, T, Cuthbertson, B, Manoharan, V, Dondrop, A, Tolppa, T, Ehrmann, S, Hullegie, S, Povoa, P, Beasley, R, Daneman, N, McGloughlin, S, Paterson, D, Venkatesh, B, De Jong, M, Uyeki, T, Baillie, K, Netea, M, Orr, K, Patanwala, A, Tong, S, Cooper, N, Galea, J, Leavis, H, Ogungbenro, K, Patawala, A, Rademaker, E, Youngstein, T, Carrier, M, Fergusson, D, Hunt, B, Kumar, A, Laffan, M, Lother, S, Middeldorp, S, Stanworth, S, De Man, A, Masse, M-H, Abraham, J, Arnold, D, Begin, P, Charlewood, R, Chasse, M, Coyne, M, Daly, J, Gosbell, I, Harvala-Simmonds, H, MacLennan, S, McDyer, J, Menon, D, Pridee, N, Roberts, D, Thomas, H, Tinmouth, A, Triulzi, D, Walsh, T, Wood, E, Calfee, C, O’Kane, C, Shyamsundar, M, Sinha, P, Thompson, T, Young, I, Burrell, A, Ferguson, N, Hodgson, C, Orford, N, Phua, J, Baron, R, Epelman, S, Frankfurter, C, Gommans, F, Kim, E, Leaf, D, Vaduganathan, M, Van Kimmenade, R, Sanil, A, Van Beurden, M, Effelaar, E, Schotsman, J, Boyd, C, Harland, C, Shearer, A, Wren, J, Attanayaka, U, Darshana, S, Ishani, P, Udayanga, I, Higgins, AM, Berry, LR, Lorenzi, E, Murthy, S, McQuilten, Z, Mouncey, PR, Al-Beidh, F, Annane, D, Arabi, YM, Beane, A, Van Bentum-Puijk, W, Bhimani, Z, Bonten, MJM, Bradbury, CA, Brunkhorst, FM, Buzgau, A, Buxton, M, Charles, WN, Cove, M, Detry, MA, Estcourt, LJ, Fagbodun, EO, Fitzgerald, M, Girard, TD, Goligher, EC, Goossens, H, Haniffa, R, Hills, T, Horvat, CM, Huang, DT, Ichihara, N, Lamontagne, F, Marshall, JC, McAuley, DF, McGlothlin, A, McGuinness, SP, McVerry, BJ, Neal, MD, Nichol, AD, Parke, RL, Parker, JC, Parry-Billings, K, Peters, SEC, Reyes, LF, Rowan, KM, Saito, H, Santos, MS, Saunders, CT, Serpa-Neto, A, Seymour, CW, Shankar-Hari, M, Stronach, LM, Turgeon, AF, Turner, AM, Van de Veerdonk, FL, Zarychanski, R, Green, C, Lewis, RJ, Angus, DC, McArthur, CJ, Berry, S, Derde, LPG, Gordon, AC, Webb, SA, Lawler, PR, Comm REMAP-CAP Investigators, Apollo - University of Cambridge Repository, Intensive Care Medicine, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pittsburgh Foundation, PF, Amgen, Health Research Board, HRB: CTN 2014-012, Horizon 2020 Framework Programme, H2020: 101003589, Translational Breast Cancer Research Consortium, TBCRC, Canadian Institutes of Health Research, IRSC: 158584, Heart and Stroke Foundation of Canada, HSF, National Institute for Health and Care Research, NIHR, European Commission, EC, National Health and Medical Research Council, NHMRC: 1101719, APP194811, CS-2016-16-011, GNT2008447, RP-2015-06-18, Office of Health and Medical Research, OHMR, Health Research Council of New Zealand, HRC: 16/631, Eisai, Ministère des Affaires Sociales et de la Santé: PHRC-20-0147, Université Pierre et Marie Curie, UPMC, NIHR Imperial Biomedical Research Centre, BRC, Minderoo Foundation, Funding/Support : The Platform for European Preparedness Against (Re-) emerging Epidemics (PREPARE) consortium by the European Union, FP7-HEALTH-2013-INNOVATION-1 (#602525), the Rapid European COVID-19 Emergency Research response (RECOVER) consortium by the European Union’s Horizon 2020 research and innovation programme (#101003589), the Australian National Health and Medical Research Council (#APP1101719), the Australian Medical Research Future Fund (#APP2002132), the Health Research Council of New Zealand (#16/631), the Canadian Institutes of Health Research Strategy for Patient-Oriented Research Innovative Clinical Trials Program Grant (#158584) and the Canadian Institute of Health Research COVID-19 Rapid Research Funding (#447335), the UK National Institute for Health Research (NIHR) and the NIHR Imperial Biomedical Research Centre, the Health Research Board of Ireland (CTN 2014-012), the UPMC Learning While Doing Program, the Translational Breast Cancer Research Consortium, the French Ministry of Health (PHRC-20-0147), the Wellcome Trust Innovations Project (215522), the Minderoo Foundation, the EU Programme Emergency Support Instrument, the NHS Blood and Transplant Research and Development Programme, the Translational Breast Cancer Research Consortium, the NSW Office of Health and Medical Research, Amgen, Eisai, and the Pittsburgh Foundation. Dr Higgins is funded by an NHMRC Emerging Leadership Fellowship (GNT2008447). Dr McQuilten is funded by an NHMRC Emerging Leadership Fellowship (APP194811). Dr Gordon is funded by an NIHR Research Professorship (RP-2015-06-18) and Dr Shankar-Hari by an NIHR Clinician Scientist Fellowship (CS-2016-16-011). Dr Turgeon is the Chairholder of the Canada Research Chair in Critical Care Neurology and Trauma. Dr Lawler is supported by a career award from the Heart and Stroke Foundation of Canada., and European Project: 602525,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PREPARE(2014)
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Adult ,Male ,corticosteroid ,[SDV]Life Sciences [q-bio] ,Critical Illness ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,antiplatelet ,Lopinavir ,Adaptive platform trial randomized controlled trial intensive care, pneumonia COVID-19 antiplatelet immunoglobulin antiviral corticosteroid immune modulation anticoagulation ,All institutes and research themes of the Radboud University Medical Center ,Adrenal Cortex Hormones ,Humans ,anticoagulation ,intensive care, pneumonia ,COVID-19 Serotherapy ,Original Investigation ,Medicine(all) ,immune modulation ,Ritonavir ,SARS-CoV-2 ,COVID-19 ,Anticoagulants ,Bayes Theorem ,General Medicine ,Middle Aged ,antiviral ,Receptors, Interleukin-6 ,Adaptive platform trial ,randomized controlled trial ,Female ,Human medicine ,immunoglobulin ,Follow-Up Studies ,Hydroxychloroquine - Abstract
ImportanceThe longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown.ObjectiveTo determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes.Design, Setting, and ParticipantsPrespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022.InterventionsPatients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401).Main Outcomes and MeasuresThe main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83.ResultsAmong 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies.Conclusions and RelevanceAmong critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.
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- 2023
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23. PCR95 Functional Quality of Life Among People Living With Obesity: A Longitudinal Cohort of Patient Reported Outcomes
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Toliver, J, primary, Watkins, S, additional, Byrne, K, additional, and Oh, J, additional
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- 2022
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24. The Extent and Nature of Need for Mealtime Support among Adults with Intellectual Disabilities
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Ball, S. L., Panter, S. G., Redley, M., Proctor, C.-A, Byrne, K., Clare, I. C. H., and Holland, A. J.
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Background: For many adults with an intellectual disability (ID), mealtimes carry significant health risks. While research and allied clinical guidance has focused mainly on dysphagia, adults with a range of physical and behavioural difficulties require mealtime support to ensure safety and adequate nutrition. The extent of need for and nature of such support within the wider ID population has yet to be reported. Methods: In this study, we have estimated the prevalence of need for mealtime support among people with ID in the UK, using a population of 2230 adults known to specialist ID services (in Cambridgeshire, UK, total population 586 900). In a sample (n = 69, aged 19 to 79 years, with mild to profound ID), we characterised the support provided, using a structured proforma to consult support workers and carers providing mealtime support, and health and social care records. Results: Mealtime support was found to be required by a significant minority of people with ID for complex and varied reasons. Prevalence of need for such support was estimated at 15% of adults known to specialist ID services or 56 per 100 000 total population. Within a sample, support required was found to vary widely in nature (from texture modification or environmental adaptation to enteral feeding) and in overall level (from minimal to full support, dependent on functional skills). Needs had increased over time in almost half (n = 34, 49.3%). Reasons for support included difficulties getting food into the body (n = 56, 82.2%), risky eating and drinking behaviours (n = 31, 44.9%) and slow eating or food refusal (n = 30, 43.5%). These proportions translate into crude estimates of the prevalence of these difficulties within the known ID population of 11.9%, 6.6% and 6.4% respectively. Within the sample of those requiring mealtime support, need for support was reported to be contributed to by the presence of additional disability or illness (e.g. visual impairment, poor dentition and dementia; n = 45, 65.2%) and by psychological or behavioural issues (e.g. challenging behaviour, emotional disturbance; n = 36, 52.2%). Conclusions: These findings not only highlight the need for a multidisciplinary approach to mealtime interventions (paying particular attention to psychological and environmental as well as physical issues), but also signal the daily difficulties faced by carers and paid support workers providing such support and illustrate their potentially crucial role in managing the serious health risks associated with eating and drinking difficulties in this population.
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- 2012
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25. Cheating Behaviours, the Internet and Education Undergraduate Students
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Trushell, J., Byrne, K., and Simpson, R.
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This paper describes an illuminative small-scale study that piloted an initial survey instrument intended to investigate correspondences between 47 undergraduate Education final year students' use of information and communications technology (ICT), including the Internet, and--within the context of their adoption of tactics intended to impress lecturers or to exploit the hidden curriculum--students' engagement in cheating behaviours such as plagiarism. The study disclosed that 0.23 of the sample had reported single instances of cheating behaviours and that 0.21 of the sample had reported multiple instances of cheating behaviours. Analysis of data discerned correspondences between these cheating behaviours and personal factors. However, indicators of ICT capability and the Internet did not correlate significantly with cheating behaviours. Those students who had reported multiple instances of cheating behaviours were found to rate their ICT capabilities higher than their peers but had a tendency to report less frequent use of the Internet for coursework. Inferences are tentatively drawn for further research and for academic practices.
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- 2012
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26. P75 Evaluation of a complex home ventilation population before and after the advent of COVID-19 in the UK
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Ward, K, primary, Weir, M, additional, Campbell, L, additional, Faulkner-Byrne, K, additional, Jordan, J, additional, Hughes, A, additional, Angus, RM, additional, Chakrabarti, B, additional, Parker, R, additional, Nwosu, N, additional, Plant, PK, additional, and Manuel, A, additional
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- 2022
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27. EP05.01-023 Feasibility of Functional Lung Avoidance using Ga-68 4D Ventilation Perfusion PET/CT: The HI-FIVE Trial
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Bucknell, N.W., primary, Hardcastle, N., additional, Woon, B., additional, Bressel, M., additional, Byrne, K., additional, Selbie, L., additional, Callahan, J., additional, Hanna, G.G., additional, Hofman, M.S., additional, Ball, D., additional, Kron, T., additional, and Siva, S., additional
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- 2022
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28. MA11.05 The Blood Proteome of Imminent Lung Cancer
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Zahed, H., primary, Smith-Byrne, K., additional, Alcala, K., additional, Guida, F., additional, Johansson, M., additional, Stevens, V., additional, Langhammer, A., additional, Milne, R.L., additional, Yuan, J.-M., additional, and Robbins, H.A., additional
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- 2022
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29. P1.01-01 Comparison between Protein and Autoantibody Biomarkers for the Early Detection of Lung Cancer
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Feng, X., primary, Wu, W.Y.-Y., additional, Onwuka, J., additional, Alcala, K., additional, Smith-Byrne, K., additional, Zahed, H., additional, Guida, F., additional, Yuan, J.-M., additional, Wang, R., additional, Milne, R.L., additional, Bassett, J., additional, Langhammer, A., additional, Hveem, K., additional, Stevens, V.L., additional, Wang, Y., additional, Brennan, P., additional, Melin, B., additional, Johansson, M., additional, and Robbins, H.A., additional
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- 2022
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30. Genetic analysis of lung cancer and the germline impact on somatic mutation burden
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Gabriel, AAG, Atkins, JR, Penha, RCC, Smith-Byrne, K, Gaborieau, V, Voegele, C, Abedi-Ardekani, B, Milojevic, M, Olaso, R, Meyer, V, Boland, A, Deleuze, JF, Zaridze, D, Mukeriya, A, Swiatkowska, B, Janout, V, Schejbalová, M, Mates, D, Stojšić, J, Ognjanovic, M, consortium, ILCCO, Witte, JS, Rashkin, SR, Kachuri, L, Hung, RJ, Kar, S, Brennan, P, Sertier, A-S, Ferrari, A, Viari, A, Johansson, M, Amos, CI, Foll, M, McKay, JD, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), University of Oxford, Université Paris-Saclay, N.N. Blokhin Russian Cancer Research Center, Nofer Institute of Occupational Medicine (NIOM), Palacky University Olomouc, Charles University [Prague] (CU), National Institute of Public Health [Romania] (INSP), University Clinical Centre of Serbia, International Organisation for Cancer Prevention and Research, University of California [San Francisco] (UC San Francisco), University of California (UC), St Jude Children's Research Hospital, Centre for Systems Biology, Lunenfeld Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada, University of Bristol [Bristol], Fondation Synergie Lyon Cancer [Lyon], Centre Léon Bérard [Lyon], Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Inria Lyon, Institut National de Recherche en Informatique et en Automatique (Inria), Baylor College of Medicine (BCM), and Baylor University
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Cancer Research ,Germ Cells ,Lung Neoplasms ,Oncology ,[SDV]Life Sciences [q-bio] ,Mutation ,Humans ,Genetic Predisposition to Disease ,ICEP ,Polymorphism, Single Nucleotide ,Genome-Wide Association Study - Abstract
Background Germline genetic variation contributes to lung cancer (LC) susceptibility. Previous genome-wide association studies (GWAS) have implicated susceptibility loci involved in smoking behaviors and DNA repair genes, but further work is required to identify susceptibility variants. Methods To identify LC susceptibility loci, a family history-based genome-wide association by proxy (GWAx) of LC (48 843 European proxy LC patients, 195 387 controls) was combined with a previous LC GWAS (29 266 patients, 56 450 controls) by meta-analysis. Colocalization was used to explore candidate genes and overlap with existing traits at discovered susceptibility loci. Polygenic risk scores (PRS) were tested within an independent validation cohort (1 666 LC patients vs 6 664 controls) using variants selected from the LC susceptibility loci and a novel selection approach using published GWAS summary statistics. Finally, the effects of the LC PRS on somatic mutational burden were explored in patients whose tumor resections have been profiled by exome (n = 685) and genome sequencing (n = 61). Statistical tests were 2-sided. Results The GWAx–GWAS meta-analysis identified 8 novel LC loci. Colocalization implicated DNA repair genes (CHEK1), metabolic genes (CYP1A1), and smoking propensity genes (CHRNA4 and CHRNB2). PRS analysis demonstrated that these variants, as well as subgenome-wide significant variants related to expression quantitative trait loci and/or smoking propensity, assisted in LC genetic risk prediction (odds ratio = 1.37, 95% confidence interval = 1.29 to 1.45; P Conclusions This study has expanded the number of LC susceptibility loci and provided insights into the molecular mechanisms by which these susceptibility variants contribute to LC development.
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- 2022
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31. Body size at different ages and risk of six cancers: a Mendelian randomization and prospective cohort study
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Mariosa, D, Smith-Byrne, K, Richardson, TG, and Perez-Cornago, A
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It is unclear if body weight in early life affects cancer risk independently of adult body weight. To investigate this question for 6 obesity-related cancers, we performed univariable and multivariable analyses using 1) Mendelian randomization (MR) analysis and 2) longitudinal analyses in prospective cohorts. Both the MR and longitudinal analyses indicated that larger early life body size was associated with higher risk of endometrial (odds ratioMR = 1.61, 95% confidence interval = 1.23 to 2.11) and kidney (odds ratioMR = 1.40, 95% confidence interval = 1.09 to 1.80) cancer. These associations were attenuated after accounting for adult body size in both the MR and cohort analyses. Early life body mass index (BMI) was not consistently associated with the other investigated cancers. The lack of clear independent risk associations suggests that early life BMI influences endometrial and kidney cancer risk mainly through pathways that are common with adult BMI.
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- 2022
32. Reallocation of time between device-measured movement behaviours and risk of incident cardiovascular disease
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Walmsley, R, Chan, S, Smith-Byrne, K, Ramakrishnan, R ; https://orcid.org/0000-0002-6784-8319, Woodward, M ; https://orcid.org/0000-0001-9800-5296, Rahimi, K, Dwyer, T, Bennett, D, Doherty, A, Walmsley, R, Chan, S, Smith-Byrne, K, Ramakrishnan, R ; https://orcid.org/0000-0002-6784-8319, Woodward, M ; https://orcid.org/0000-0001-9800-5296, Rahimi, K, Dwyer, T, Bennett, D, and Doherty, A
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Objective To improve classification of movement behaviours in free-living accelerometer data using machine-learning methods, and to investigate the association between machine-learned movement behaviours and risk of incident cardiovascular disease (CVD) in adults. Methods Using free-living data from 152 participants, we developed a machine-learning model to classify movement behaviours (moderate-to-vigorous physical activity behaviours (MVPA), light physical activity behaviours, sedentary behaviour, sleep) in wrist-worn accelerometer data. Participants in UK Biobank, a prospective cohort, were asked to wear an accelerometer for 7 days, and we applied our machine-learning model to classify their movement behaviours. Using compositional data analysis Cox regression, we investigated how reallocating time between movement behaviours was associated with CVD incidence. Results In leave-one-participant-out analysis, our machine-learning method classified free-living movement behaviours with mean accuracy 88% (95% CI 87% to 89%) and Cohen’s kappa 0.80 (95% CI 0.79 to 0.82). Among 87 498 UK Biobank participants, there were 4105 incident CVD events. Reallocating time from any behaviour to MVPA, or reallocating time from sedentary behaviour to any behaviour, was associated with lower CVD risk. For an average individual, reallocating 20 min/ day to MVPA from all other behaviours proportionally was associated with 9% (95% CI 7% to 10%) lower risk, while reallocating 1 hour/day to sedentary behaviour from all other behaviours proportionally was associated with 5% (95% CI 3% to 7%) higher risk. Conclusion Machine-learning methods classified movement behaviours accurately in free-living accelerometer data. Reallocating time from other behaviours to MVPA, and from sedentary behaviour to other behaviours, was associated with lower risk of incident CVD, and should be promoted by interventions and guidelines.
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- 2022
33. Increasing use of post-mastectomy hypofractionated radiation therapy for breast cancer in Victoria
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Kim, S, Pitson, G, Koh, TL, Chao, M, Byrne, K, Hornby, C, Foroudi, F, Millar, J, Ong, WL, Kim, S, Pitson, G, Koh, TL, Chao, M, Byrne, K, Hornby, C, Foroudi, F, Millar, J, and Ong, WL
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INTRODUCTION: The aim of this study was to evaluate the use of post-mastectomy hypofractionationed radiation therapy (HFRT) for breast cancer in Victoria, Australia. METHODS: This is a population-based cohort of women with breast cancer who received post-mastectomy RT to the chest wall with or without nodal irradiation between 2012 and 2017. HFRT was defined as <25 fractions of RT. Data were captured in the Victorian Radiotherapy Minimum Dataset (VRMDS). The changing pattern of HFRT use was evaluated using the Cochran-Armitage test. Patient-, treatment- and institutional-related factors associated with HFRT use were evaluated using multivariable logistic regression. RESULTS: Two thousand and twenty-one women were included in this study, of which 238 (12%) received HFRT. This increased from 8% in 2012 to 18% in 2017 (P-trend < 0.001). Older women were more likely to have HFRT (26% in women above 70 years vs 6% in women under 50 years; P < 0.001). Women who did not have nodal irradiation were more likely to have HFRT than those who did (18% vs 9% respectively; P < 0.001). In multivariate analyses, the progressive increase in HFRT use over time remained statistically significant - women treated in 2017 were four times more likely to receive HFRT than those treated in 2012 (95% CI = 2.1-7.7; P < 0.001). Other factors independently associated with increased likelihood of HFRT use included increasing age at RT, and lack of nodal irradiation. CONCLUSION: In this first Australian study evaluating the use of post-mastectomy HFRT, we observed increasing HFRT use in Victoria over time. We anticipate this rising trend will continue in the coming years.
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- 2022
34. Recommendations for effective documentation in regional anesthesia: an expert panel Delphi consensus project
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Ahmed, HM, Atterton, BP, Crowe, GG, Barratta, JL, Johnson, M, Viscusi, E, Adhikary, S, Albrecht, E, Boretsky, K, Boublik, J, Breslin, DS, Byrne, K, Ch'ng, A, Chuan, A, Conroy, P, Daniel, C, Daszkiewicz, A, Delbos, A, Dirzu, DS, Dmytriiev, D, Fennessy, P, Fischer, HBJ, Frizelle, H, Gadsden, J, Gautier, P, Gupta, RK, Gurkan, Y, Hardman, HD, Harrop-Griffiths, W, Hebbard, P, Hernandez, N, Hlasny, J, Iohom, G, Ip, VHY, Jeng, CL, Johnson, RL, Kalagara, H, Kinirons, B, Lansdown, AK, Leng, JC, Lim, YC, Lobo, C, Ludwin, DB, Macfarlane, AJR, Machi, AT, Mahon, P, Mannion, S, McLeod, DH, Merjavy, P, Miscuks, A, Mitchell, CH, Moka, E, Moran, P, Ngui, A, Nin, OC, O'Donnell, BD, Pawa, A, Perlas, A, Porter, S, Pozek, J-P, Rebelo, HC, Roques, V, Schroeder, KM, Schwartz, G, Schwenk, ES, Sermeus, L, Shorten, G, Srinivasan, K, Stevens, MF, Theodoraki, K, Turbitt, LR, Valdes-Vilches, LF, Volk, T, Webster, K, Wiesmann, T, Wilson, SH, Wolmarans, M, Woodworth, G, Worek, AK, Moran, EML, Ahmed, HM, Atterton, BP, Crowe, GG, Barratta, JL, Johnson, M, Viscusi, E, Adhikary, S, Albrecht, E, Boretsky, K, Boublik, J, Breslin, DS, Byrne, K, Ch'ng, A, Chuan, A, Conroy, P, Daniel, C, Daszkiewicz, A, Delbos, A, Dirzu, DS, Dmytriiev, D, Fennessy, P, Fischer, HBJ, Frizelle, H, Gadsden, J, Gautier, P, Gupta, RK, Gurkan, Y, Hardman, HD, Harrop-Griffiths, W, Hebbard, P, Hernandez, N, Hlasny, J, Iohom, G, Ip, VHY, Jeng, CL, Johnson, RL, Kalagara, H, Kinirons, B, Lansdown, AK, Leng, JC, Lim, YC, Lobo, C, Ludwin, DB, Macfarlane, AJR, Machi, AT, Mahon, P, Mannion, S, McLeod, DH, Merjavy, P, Miscuks, A, Mitchell, CH, Moka, E, Moran, P, Ngui, A, Nin, OC, O'Donnell, BD, Pawa, A, Perlas, A, Porter, S, Pozek, J-P, Rebelo, HC, Roques, V, Schroeder, KM, Schwartz, G, Schwenk, ES, Sermeus, L, Shorten, G, Srinivasan, K, Stevens, MF, Theodoraki, K, Turbitt, LR, Valdes-Vilches, LF, Volk, T, Webster, K, Wiesmann, T, Wilson, SH, Wolmarans, M, Woodworth, G, Worek, AK, and Moran, EML
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BACKGROUND AND OBJECTIVES: Documentation is important for quality improvement, education, and research. There is currently a lack of recommendations regarding key aspects of documentation in regional anesthesia. The aim of this study was to establish recommendations for documentation in regional anesthesia. METHODS: Following the formation of the executive committee and a directed literature review, a long list of potential documentation components was created. A modified Delphi process was then employed to achieve consensus amongst a group of international experts in regional anesthesia. This consisted of 2 rounds of anonymous electronic voting and a final virtual round table discussion with live polling on items not yet excluded or accepted from previous rounds. Progression or exclusion of potential components through the rounds was based on the achievement of strong consensus. Strong consensus was defined as ≥75% agreement and weak consensus as 50%-74% agreement. RESULTS: Seventy-seven collaborators participated in both rounds 1 and 2, while 50 collaborators took part in round 3. In total, experts voted on 83 items and achieved a strong consensus on 51 items, weak consensus on 3 and rejected 29. CONCLUSION: By means of a modified Delphi process, we have established expert consensus on documentation in regional anesthesia.
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- 2022
35. Effects of brain tissue oxygen (PbtO2) guided management on patient outcomes following severe traumatic brain injury: A systematic review and meta-analysis
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Hays, LMC, Udy, A, Adamides, AA, Anstey, JR, Bailey, M, Bellapart, J, Byrne, K, Cheng, A, Cooper, DJ, Drummond, KJ, Haenggi, M, Jakob, SM, Higgins, AM, Lewis, PM, Hunn, MK, McNamara, R, Menon, DK, Murray, L, Reddi, B, Trapani, T, Vallance, S, Young, PJ, Diaz-Arrastia, R, Shutter, L, Murray, PT, Curley, GF, Nichol, A, Hays, LMC, Udy, A, Adamides, AA, Anstey, JR, Bailey, M, Bellapart, J, Byrne, K, Cheng, A, Cooper, DJ, Drummond, KJ, Haenggi, M, Jakob, SM, Higgins, AM, Lewis, PM, Hunn, MK, McNamara, R, Menon, DK, Murray, L, Reddi, B, Trapani, T, Vallance, S, Young, PJ, Diaz-Arrastia, R, Shutter, L, Murray, PT, Curley, GF, and Nichol, A
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Monitoring and optimisation of brain tissue oxygen tension (PbtO2) has been associated with improved neurological outcome and survival in observational studies of severe traumatic brain injury (TBI). We carried out a systematic review of randomized controlled trials to determine if PbtO2-guided management is associated with differential neurological outcomes, survival, and adverse events. Searches were carried out to 10 February 2022 in Medline (OvidSP), 11 February in EMBASE (OvidSP) and 8 February in Cochrane library. Randomized controlled trials comparing PbtO2 and ICP-guided management to ICP-guided management alone were included. The primary outcome was survival with favourable neurological outcome at 6-months post injury. Data were extracted by two independent authors and GRADE certainty of evidence assessed. There was no difference in the proportion of patients with favourable neurological outcomes with PbtO2-guided management (relative risk [RR] 1.42, 95% CI 0.97 to 2.08; p = 0.07; I2 = 0%, very low certainty evidence) but PbtO2-guided management was associated with reduced mortality (RR 0.54, 95% CI 0.31 to 0.93; p = 0.03; I2 = 42%; very low certainty evidence) and ICP (mean difference (MD) - 4.62, 95% CI - 8.27 to - 0.98; p = 0.01; I2 = 63%; very low certainty evidence). There was no significant difference in the risk of adverse respiratory or cardiovascular events. PbtO2-guided management in addition to ICP-based care was not significantly associated with increased favourable neurological outcomes, but was associated with increased survival and reduced ICP, with no difference in respiratory or cardiovascular adverse events. However, based on GRADE criteria, the certainty of evidence provided by this meta-analysis was consistently very low. MESH: Brain Ischemia; Intensive Care; Glasgow Outcome Scale; Randomized Controlled Trial; Craniocerebral Trauma.
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- 2022
36. 72 weeks post-partum follow-up of dolutegravir versus efavirenz initiated in late pregnancy (DolPHIN-2): an open-label, randomised controlled study
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Malaba, T.R., Nakatudde, I., Kintu, K., Colbers, A., Chen, T., Reynolds, H., Read, L., Read, J., Stemmet, L.A., Mrubata, M., Byrne, K., Seden, K., Twimukye, A., Theunissen, H., Hodel, E.M., Chiong, J., Hu, N.C., Burger, D.M., Wang, Duolao, Byamugisha, J., Alhassan, Y., Bokako, S., Waitt, C., Taegtmeyer, M., Orrell, C., Lamorde, M., Myer, L., Khoo, S., Malaba, T.R., Nakatudde, I., Kintu, K., Colbers, A., Chen, T., Reynolds, H., Read, L., Read, J., Stemmet, L.A., Mrubata, M., Byrne, K., Seden, K., Twimukye, A., Theunissen, H., Hodel, E.M., Chiong, J., Hu, N.C., Burger, D.M., Wang, Duolao, Byamugisha, J., Alhassan, Y., Bokako, S., Waitt, C., Taegtmeyer, M., Orrell, C., Lamorde, M., Myer, L., and Khoo, S.
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Item does not contain fulltext, BACKGROUND: Late initiation of antiretrovirals in pregnancy is associated with increased risk of perinatal transmission and higher infant mortality. We report the final 72-week postpartum results for efficacy and safety of dolutegravir-based compared with efavirenz-based regimens in mothers and infants. METHODS: DolPHIN-2 was a randomised, open-label trial. Pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating antiretroviral therapy in third trimester were eligible for inclusion. Eligible women were randomly assigned (1:1) to receive either dolutegravir-based (50 mg dolutegravir, 300 mg tenofovir disoproxil fumarate, and either 200 mg emtricitabine in South Africa or 300 mg lamivudine in Uganda) or efavirenz-based (fixed dose combination 600 mg tenofovir disoproxil fumarate plus either emtricitabine in South Africa or lamivudine in Uganda) therapy. The primary efficacy outcome was the time to a viral load of less than 50 copies per mL measured at 6, 12, 24, 48, and 72 weeks postpartum with a Cox model adjusting for viral load and CD4 cell count. Safety endpoints were summarised by the number of women and infants with events. This trial is registered with ClinicalTrials.gov, NCT03249181. FINDINGS: Between Jan 23 and Aug 15, 2018, 280 women were screened for inclusion, of whom 268 (96%) women were randomly assigned: 133 (50%) to the efavirenz group and 135 (50%) to the dolutegravir group. 250 (93%; 125 [50%] in the efavirenz group and 125 [50%] in the dolutegravir group) women were included in the intention-to-treat analysis of efficacy. Median time to viral load of less than 50 copies per mL was 4·1 weeks (IQR 4·0-5·1) in the dolutegravir group compared with 12·1 weeks (10·7-13·3) in the efavirenz group (adjusted hazard ratio [HR] 1·93 [95% CI 1·5-2·5]). At 72 weeks postpartum, 116 (93%) mothers in the dolutegravir group and 114 (91%) in the efavirenz gr
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- 2022
37. Prediagnosis Leisure-Time Physical Activity and Lung Cancer Survival: A Pooled Analysis of 11 Cohorts.
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Yang, JJ, Yu, D, White, E, Lee, DH, Blot, W, Robien, K, Sinha, R, Park, Y, Takata, Y, Gao, Y-T, Smith-Byrne, K, Monninkhof, EM, Kaaks, R, Langhammer, A, Borch, KB, Al-Shaar, L, Lan, Q, Sørgjerd, EP, Zhang, X, Zhu, C, Chirlaque, MD, Severi, G, Overvad, K, Sacerdote, C, Aune, D, Johansson, M, Smith-Warner, SA, Zheng, W, Shu, X-O, Yang, JJ, Yu, D, White, E, Lee, DH, Blot, W, Robien, K, Sinha, R, Park, Y, Takata, Y, Gao, Y-T, Smith-Byrne, K, Monninkhof, EM, Kaaks, R, Langhammer, A, Borch, KB, Al-Shaar, L, Lan, Q, Sørgjerd, EP, Zhang, X, Zhu, C, Chirlaque, MD, Severi, G, Overvad, K, Sacerdote, C, Aune, D, Johansson, M, Smith-Warner, SA, Zheng, W, and Shu, X-O
- Abstract
BACKGROUND: Little is known about the association between physical activity before cancer diagnosis and survival among lung cancer patients. In this pooled analysis of 11 prospective cohorts, we investigated associations of prediagnosis leisure-time physical activity (LTPA) with all-cause and lung cancer-specific mortality among incident lung cancer patients. METHODS: Using self-reported data on regular engagement in exercise and sports activities collected at study enrollment, we assessed metabolic equivalent hours (MET-h) of prediagnosis LTPA per week. According to the Physical Activity Guidelines for Americans, prediagnosis LTPA was classified into inactivity, less than 8.3 and at least 8.3 MET-h per week (the minimum recommended range). Cox regression was used to estimate hazard ratios (HRs) and 95% confidence interval (CIs) for all-cause and lung cancer-specific mortality after adjustment for major prognostic factors and lifetime smoking history. RESULTS: Of 20 494 incident lung cancer patients, 16 864 died, including 13 596 deaths from lung cancer (overall 5-year relative survival rate = 20.9%, 95% CI = 20.3% to 21.5%). Compared with inactivity, prediagnosis LTPA of more than 8.3 MET-h per week was associated with a lower hazard of all-cause mortality (multivariable-adjusted HR = 0.93, 95% CI = 0.88 to 0.99), but not with lung cancer-specific mortality (multivariable-adjusted HR = 0.99, 95% CI = 0.95 to 1.04), among the overall population. Additive interaction was found by tumor stage (Pinteraction = .008 for all-cause mortality and .003 for lung cancer-specific mortality). When restricted to localized cancer, prediagnosis LTPA of at least 8.3 MET-h per week linked to 20% lower mortality: multivariable-adjusted HRs were 0.80 (95% CI = 0.67 to 0.97) for all-cause mortality and 0.80 (95% CI = 0.65 to 0.99) for lung cancer-specific mortality. CONCLUSIONS: Regular participation in LTPA that met or exceeded the minimum Physical Activity Guidelines was associated wi
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- 2022
38. Circulating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortia
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Watts, EL, Perez-Cornago, A, Fensom, GK, Smith-Byrne, K, Noor, U, Andrews, CD, Gunter, MJ, Holmes, M, Martin, RM, Tsilidis, KK, Albanes, D, Barricarte, A, Bueno-de-Mesquita, B, Chen, C, Cohn, BA, Dimou, NL, Ferrucci, L, Flicker, L, Freedman, ND, Giles, GG, Giovannucci, EL, Goodman, GE, Haiman, CA, Hankey, GJ, Huang, J, Huang, W-Y, Hurwitz, LM, Kaaks, R, Knekt, P, Kubo, T, Langseth, H, Laughlin, G, Le Marchand, L, Luostarinen, T, MacInnis, RJ, Maenpaa, HO, Mannisto, S, Metter, JE, Mikami, K, Mucci, LA, Olsen, AW, Ozasa, K, Palli, D, Penney, KL, Platz, EA, Rissanen, H, Sawada, N, Schenk, JM, Stattin, P, Tamakoshi, A, Thysell, E, Tsai, CJ, Tsugane, S, Vatten, L, Weiderpass, E, Weinstein, SJ, Wilkens, LR, Yeap, BB, Allen, NE, Key, TJ, Travis, RC, Watts, EL, Perez-Cornago, A, Fensom, GK, Smith-Byrne, K, Noor, U, Andrews, CD, Gunter, MJ, Holmes, M, Martin, RM, Tsilidis, KK, Albanes, D, Barricarte, A, Bueno-de-Mesquita, B, Chen, C, Cohn, BA, Dimou, NL, Ferrucci, L, Flicker, L, Freedman, ND, Giles, GG, Giovannucci, EL, Goodman, GE, Haiman, CA, Hankey, GJ, Huang, J, Huang, W-Y, Hurwitz, LM, Kaaks, R, Knekt, P, Kubo, T, Langseth, H, Laughlin, G, Le Marchand, L, Luostarinen, T, MacInnis, RJ, Maenpaa, HO, Mannisto, S, Metter, JE, Mikami, K, Mucci, LA, Olsen, AW, Ozasa, K, Palli, D, Penney, KL, Platz, EA, Rissanen, H, Sawada, N, Schenk, JM, Stattin, P, Tamakoshi, A, Thysell, E, Tsai, CJ, Tsugane, S, Vatten, L, Weiderpass, E, Weinstein, SJ, Wilkens, LR, Yeap, BB, Allen, NE, Key, TJ, and Travis, RC
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Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet = .0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.
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- 2022
39. Machine-washable knitwear — Production routes
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Byrne, K. M. and Carr, C. M., editor
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- 1995
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40. MO-0711 Impact of operability and total metastatic ablation on outcomes after SABR for oligometastases
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Siva, S., primary, Bressel, M., additional, Sogono, P., additional, Shaw, M., additional, Chander, S., additional, Chu, J., additional, Plumridge, N., additional, Byrne, K., additional, Kothari, G., additional, Bucknell, N., additional, Hardcastle, N., additional, Kron, T., additional, Wheeler, G., additional, MacManus, M., additional, Hanna, G.G., additional, Ball, D.L., additional, and David, S., additional
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- 2022
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41. P578 Evolution of Crohnʼs disease treatment in clinical practice: a 25 year single centre cohort study
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Hartery, K., Moran, C., Sheridan, J., Keegan, D., Byrne, K., Horgan, G., Doherty, G., Cullen, G., Buckley, M., and Mulcahy, H.
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- 2017
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42. P370 A randomised controlled trial of acceptance and commitment therapy for the treatment of stress in inflammatory bowel disease
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Mulcahy, H., Wynne, B., McHugh, L., Rowan, C., Byrne, K., Keegan, D., Hartery, K., and Dooley, B.
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- 2017
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43. P261 Grading post-operative recurrence in Crohnʼs disease: a comparison between MRE and ileocolonoscopy
- Author
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Lavelle, A., Keegan, D., Byrne, K., Sheridan, J., Mulcahy, H., Cullen, G., Skehan, S., and Doherty, G.A.
- Published
- 2017
- Full Text
- View/download PDF
44. Posterodorsal Medial Amygdala Mediates Tail-Pinch Induced Food Intake in Female Rats
- Author
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Hu, M. H., Bashir, Z., Li, X. F., and OʼByrne, K. T.
- Published
- 2016
- Full Text
- View/download PDF
45. LUX-Lung 7: A Phase IIb, global, randomised, open-label trial of afatinib vs gefitinib as first-line treatment for patients (pts) with advanced non-small cell lung cancer (NSCLC) harbouring activating EGFR mutations: 140PD
- Author
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Park, K., Tan, E.-H., Zhang, L., Hirsh, V., OʼByrne, K., Boyer, M., Yang, J., Mok, T., Kim, M., and Paz-Ares, L.
- Published
- 2016
- Full Text
- View/download PDF
46. Impact of dose adjustment on the safety and efficacy of afatinib in patients (pts) with advanced EGFR mutation-positive non-small cell lung cancer (NSCLC): Post-hoc analyses of LUX-Lung 3 (LL3) and LUX-Lung 6 (LL6): 138PD
- Author
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Schuler, M., Yang, J., Sequist, L. V., Yamamoto, N., Zhou, C., OʼByrne, K., Hirsh, V., Mok, T., Shah, R., and Wu, Y.-L.
- Published
- 2016
- Full Text
- View/download PDF
47. XRCC6BP1: A key DNA repair gene in platinum-resistant NSCLC: 80P
- Author
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Barr, M. P., Foley, E., He, Y., Young, V., Ryan, R., Nicholson, S., Leonard, N., OʼByrne, K., Cuffe, S., and Finn, S.
- Published
- 2016
- Full Text
- View/download PDF
48. Inhibition and exploitation of aldehyde dehydrogenase 1 (ALDH1) as a cancer stem cell marker in cisplatin resistant NSCLC: 75P
- Author
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Barr, M. P., MacDonagh, L., Gray, S. G., OʼByrne, K., Cuffe, S., and Finn, S.
- Published
- 2016
- Full Text
- View/download PDF
49. Investigation of the interaction between non-small cell lung cancer cells and immortalised normal bronchial epithelial cells: 67P
- Author
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OʼByrne, K., Barr, M. P., Urquhart, A., Ryan, S.-L., Gray, S. G., Davies, A., Richard, D., Gately, K., and Baird, A.-M.
- Published
- 2016
- Full Text
- View/download PDF
50. Identification of a novel microRNA signature: Potential diagnostic biomarkers and predictors of cisplatin response?: 70P
- Author
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Barr, M. P., MacDonagh, L., Gray, S. G., Reidy, M., Sui, Sze Yin J., Nicholson, S., Leonard, N., OʼByrne, K., Cuffe, S., and Finn, S.
- Published
- 2016
- Full Text
- View/download PDF
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