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156. Moral Judgment

Author

Gallie, Roger D., Lehrer, Keith, editor, Cohen, Stewart, editor, and Gallie, Roger D.

Published
1998
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162. Global Retinoblastoma Treatment Outcomes

Author

Ekaterina Semenova, Kalle Nummi, Olga V Yugay, Carol P. S. Lam, Suganeswari Ganesan, Adriana Fandiño, Guillermo Chantada, Tero Kivelä, Elisa Carreras, Michala Burges, Phillipa Sharwood, V.G. Polyakov, Paula Schaiquevich, Vera Adobea Essuman, Quah Boon Long, Vera Yarovaya, Brenda L. Gallie, Rachel C. Brenna, Jaume Català, Paul T. Finger, Elena Kotova, Ashwin Mallipatna, Junyang Zhao, Winnie W. Y. Lau, Genoveva Correa-Llano, Tatiana L Ushakova, Ankit Singh Tomar, Jason C. S. Yam, Lorna Renner, Yacoub A. Yousef, Jonathan W. Kim, Elizabeth Esparza-Aguiar, Andrey A. Yarovoy, Vikas Khetan, Matthew W. Wilson, Sonia Moorthy, Marco A. Ramirez-Ortiz, and Chengyue Zhang

Subjects
Retinoblastoma, business.industry, Measures of national income and output, Treatment outcome, Outcome measures, Patient survival, World population, medicine.disease, Treatment failure, 3. Good health, 03 medical and health sciences, Ophthalmology, 0302 clinical medicine, 030220 oncology & carcinogenesis, 030221 ophthalmology & optometry, medicine, business, Demography, Cancer staging
Abstract

Purpose To compare metastasis-related mortality, local treatment failure, and globe salvage after retinoblastoma in countries with different national income levels. Design International, multicenter, registry-based retrospective case series. Participants Two thousand one hundred ninety patients, 18 ophthalmic oncology centers, and 13 countries on 6 continents. Methods Multicenter registry-based data were pooled from retinoblastoma patients enrolled between January 2001 and December 2013. Adequate data to allow American Joint Committee on Cancer staging, eighth edition, and analysis for the main outcome measures were available for 2085 patients. Each country was classified by national income level, as defined by the 2017 United Nations World Population Prospects, and included high-income countries (HICs), upper middle-income countries (UMICs), and lower middle-income countries (LMICs). Patient survival was estimated with the Kaplan-Meier method. Logistic and Cox proportional hazards regression models were used to determine associations between national income and treatment outcomes. Main Outcome Measures Metastasis-related mortality and local treatment failure (defined as use of secondary enucleation or external beam radiation therapy). Results Most (60%) study patients resided in UMICs and LMICs. The global median age at diagnosis was 17.0 months and higher in UMICs (20.0 months) and LMICs (20.0 months) than HICs (14.0 months; P Conclusions This international, multicenter, registry-based analysis of retinoblastoma management revealed that lower national income levels were associated with significantly higher rates of metastasis-related mortality, local treatment failure, and lower globe salvage.

Published
2021

165. List of Contributors

Author

Amaya, Luis, primary, Ashworth, Jane L, additional, Avery, Robert A, additional, Bartram, Jack, additional, Beres, Shannon J, additional, Binenbaum, Gil, additional, Biousse, Valérie, additional, Birch, Eileen E, additional, Biswas, Susmito, additional, Black, Graeme C M, additional, Black, Joanna, additional, Bowman, Richard J C, additional, Bradbury, John A, additional, Brodsky, Michael C, additional, Brosnahan, Donal, additional, de Alba, Alejandra, additional, Camuglia, Jayne E, additional, Carden, Susan M, additional, Castano, Giovanni, additional, Casteels, Ingele, additional, Chung, Yvonne, additional, Clarke, Michael P, additional, Coats, David K, additional, Collin, Richard, additional, Crompton, John, additional, Cunningham, Emmett T, additional, Demer, Joseph L, additional, Dollfus, Hélène, additional, Dolman, Peter J, additional, Donahue, Sean P, additional, Edelsten, Clive, additional, Fielder, Alistair R, additional, FitzPatrick, David R., additional, Fulton, Anne B, additional, Gallie, Brenda L, additional, Geloneck, Megan, additional, Gilbert, Clare E, additional, Giligson, Christy, additional, Gole, Glen A, additional, Good, William V, additional, Grigg, John R B, additional, Grossniklaus, Hans, additional, Hamel, Patrick, additional, Handler, Sheryl M, additional, Hansen, Ronald M, additional, Heidary, Gena, additional, Hertle, Richard W, additional, Hildebrand, Göran Darius, additional, Holder, Graham E, additional, Hoyt, Creig S, additional, Hubbard, G Baker, additional, Hutchinson, Amy K, additional, Jain, Saurabh, additional, Jamieson, Robyn V, additional, Jensen, Hanne, additional, Kadom, Nadja, additional, Kekunnaya, Ramesh, additional, Kersten, Robert C, additional, Kestelyn, Philippe, additional, Keunen, Jan E E, additional, Khaw, Peng Tee, additional, Kim, Chong Ae, additional, Koopman, Jan, additional, Kraft, Stephen P, additional, Kushner, Burton J, additional, Lambert, Scott R, additional, LaRoche, G Robert, additional, Larsen, Dorte Ancher, additional, Lee, Andrew G, additional, Lee, Barry, additional, Lenhart, Phoebe, additional, Liasis, Alki, additional, Liu, Grant T, additional, Lloyd, Christopher, additional, Lyons, Christopher J, additional, Matsuba, Carey A, additional, MacEwen, Caroline J, additional, McNab, Alan A, additional, Mehta, Vaishali, additional, Michaelides, Michel, additional, Mojon, Daniel, additional, Ulrik, Hans, additional, Moore, Anthony T, additional, Morris, Andrew A M, additional, Newman, Nancy J, additional, Nischal, Ken K, additional, O'Colmain, Una, additional, O'Connor, Anna R, additional, O'Keefe, Michael, additional, Olitsky, Scott E, additional, Ospina, Luis H, additional, Oystreck, Darren T, additional, Papadopoulos, Maria, additional, Park, Sunju, additional, Paysse, Evelyn A, additional, Peragallo, Jason H, additional, Pereira, Erika Mota, additional, Pilling, Rachel F, additional, Pineles, Stacy, additional, Prajna, Venkatesh, additional, Proudlock, Frank Antony, additional, Puvanachandra, Narman, additional, Quinn, Anthony G, additional, Quinn, Graham E, additional, Rahi, Jugnoo S, additional, Repka, Michael X, additional, Robinson, Joshua, additional, Russell, Buddy, additional, de Sá, Luis Carlos Ferreira, additional, Sachdeva, Virender, additional, Salchow, Daniel J, additional, Scawn, Richard L, additional, Schalij-Delfos, Nicoline, additional, van Schooneveld, Mary J, additional, Self, Jay, additional, Sergouniotis, Panagiotis I, additional, Shields, Carol L, additional, Shields, Jerry A, additional, Sloper, John J, additional, Snead, Martin P, additional, Soliman, Sameh E, additional, Sullivan, Timothy John, additional, Summers, C Gail, additional, Tan, Kimberley, additional, Taylor, David S, additional, Thompson, Dorothy A, additional, Traboulsi, Elias I, additional, Tuft, Stephen J, additional, Uddin, Jimmy M, additional, Vijayalakshmi, Perumalsamy, additional, Watts, Patrick, additional, Weakley, David R, additional, and Wells, Jill Razor, additional

Published
2017
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166. Stepwise Evolution of E. coli C and ΦX174 Reveals Unexpected Lipopolysaccharide (LPS) Diversity.

Author

Dherbey, Jordan Romeyer, Parab, Lavisha, Gallie, Jenna, and Bertels, Frederic

Subjects
ESCHERICHIA coli, BACTERIOPHAGES, BACTERIOPHAGE typing, BACTERIAL population, BACTERIAL diseases, LIPOPOLYSACCHARIDES, GENETIC mutation
Abstract

Phage therapy is a promising method for the treatment of multidrug-resistant bacterial infections. However, its long-term efficacy depends on understanding the evolutionary effects of the treatment. Current knowledge of such evolutionary effects is lacking, even in well-studied systems. We used the bacterium Escherichia coli C and its bacteriophage ΦX174, which infects cells using host lipopolysaccharide (LPS) molecules. We first generated 31 bacterial mutants resistant to ΦX174 infection. Based on the genes disrupted by these mutations, we predicted that these E. coli C mutants collectively produce eight unique LPS structures. We then developed a series of evolution experiments to select for ΦX174 mutants capable of infecting the resistant strains. During phage adaptation, we distinguished two types of phage resistance: one that was easily overcome by ΦX174 with few mutational steps ("easy" resistance) and one that was more difficult to overcome ("hard" resistance). We found that increasing the diversity of the host and phage populations could accelerate the adaptation of phage ΦX174 to overcome the hard resistance phenotype. From these experiments, we isolated 16 ΦX174 mutants that, together, can infect all 31 initially resistant E. coli C mutants. Upon determining the infectivity profiles of these 16 evolved phages, we uncovered 14 distinct profiles. Given that only eight profiles are anticipated if the LPS predictions are correct, our findings highlight that the current understanding of LPS biology is insufficient to accurately forecast the evolutionary outcomes of bacterial populations infected by phage. [ABSTRACT FROM AUTHOR]

Published
2023
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169. A White Retinal Lesion With Calcification in an 11-Year-Old Boy

Author

Leonardo Lando, Ashwin Mallipatna, and Brenda Gallie

Subjects
Male, Ophthalmology, Retinal Diseases, Humans, Calcinosis, Fluorescein Angiography, Child
Abstract

An 11-year-old boy was referred to assess a retinal mass in the left eye found on his first routine ophthalmic evaluation. A white, translucent solid lesion with calcification was noticeable in the inferonasal quadrant of the left eye. What would you do next?

Published
2022

170. Host-parasite coevolution promotes innovation through deformations in fitness landscapes

Author

Luis Zaman, Strobel Hm, Alita R. Burmeister, Jenna Gallie, Einat Shaer Tamar, Benjamin Kerr, Meyer, Roy Kishony, and Animesh Gupta

Subjects
Genotype, General Immunology and Microbiology, Fitness landscape, General Neuroscience, Novelty, General Medicine, Biology, Biological Evolution, General Biochemistry, Genetics and Molecular Biology, Host–parasite coevolution, Evolutionary biology, Mutation, Escherichia coli, Animals, Parasites, Coevolution
Abstract

During the struggle for survival, populations occasionally evolve new functions that give them access to untapped ecological opportunities. Theory suggests that coevolution between species can promote the evolution of such innovations by deforming fitness landscapes in ways that open new adaptive pathways. We directly tested this idea by using high-throughput gene editing-phenotyping technology (MAGE-Seq) to measure the fitness landscape of a virus, bacteriophage λ, as it coevolved with its host, the bacterium Escherichia coli. An analysis of the empirical fitness landscape revealed mutation-by-mutation-by-host-genotype interactions that demonstrate coevolution modified the contours of λ’s landscape. Computer simulations of λ’s evolution on a static versus shifting fitness landscape showed that the changes in contours increased λ’s chances of evolving the ability to use a new host receptor. By coupling sequencing and pairwise competition experiments, we demonstrated that the first mutation λ evolved en route to the innovation would only evolve in the presence of the ancestral host, whereas later steps in λ’s evolution required the shift to a resistant host. When time-shift replays of the coevolution experiment were run where host evolution was artificially accelerated, λ did not innovate to use the new receptor. This study provides direct evidence for the role of coevolution in driving evolutionary novelty and provides a quantitative framework for predicting evolution in coevolving ecological communities.

Published
2022

171. Evaluation of prognostic risk models for postoperative pulmonary complications in adult patients undergoing major abdominal surgery:a systematic review and international external validation cohort study

Author

Kouli, O, Murray, V, Bhatia, S, Cambridge, WA, Kawka, M, Shafi, S, Knight, SR, Kamarajah, SK, McLean, KA, Glasbey, JC, Khaw, RA, Ahmed, W, Akhbari, M, Baker, D, Borakati, A, Mills, E, Thavayogan, R, Yasin, I, Raubenheimer, K, Ridley, W, Sarrami, M, Zhang, G, Egoroff, N, Pockney, P, Richards, T, Bhangu, A, Creagh-Brown, B, Edwards, M, Harrison, EM, Lee, M, Nepogodiev, D, Pinkney, T, Pearse, R, Smart, N, Vohra, R, Sohrabi, C, Jamieson, A, Nguyen, M, Rahman, A, English, C, Tincknell, L, Kakodkar, P, Kwek, I, Punjabi, N, Burns, J, Varghese, S, Erotocritou, M, McGuckin, S, Vayalapra, S, Dominguez, E, Moneim, J, Salehi, M, Tan, HL, Yoong, A, Zhu, L, Seale, B, Nowinka, Z, Patel, N, Chrisp, B, Harris, J, Maleyko, I, Muneeb, F, Gough, M, James, CE, Skan, O, Chowdhury, A, Rebuffa, N, Khan, H, Down, B, Fatimah Hussain, Q, Adams, M, Bailey, A, Cullen, G, Fu, YXJ, McClement, B, Taylor, A, Aitken, S, Bachelet, B, Brousse de Gersigny, J, Chang, C, Khehra, B, Lahoud, N, Lee Solano, M, Louca, M, Rozenbroek, P, Rozitis, E, Agbinya, N, Anderson, E, Arwi, G, Barry, I, Batchelor, C, Chong, T, Choo, LY, Clark, L, Daniels, M, Goh, J, Handa, A, Hanna, J, Huynh, L, Jeon, A, Kanbour, A, Lee, A, Lee, J, Lee, T, Leigh, J, Ly, D, McGregor, F, Moss, J, Nejatian, M, O'Loughlin, E, Ramos, I, Sanchez, B, Shrivathsa, A, Sincari, A, Sobhi, S, Swart, R, Trimboli, J, Wignall, P, Bourke, E, Chong, A, Clayton, S, Dawson, A, Hardy, E, Iqbal, R, Le, L, Mao, S, Marinelli, I, Metcalfe, H, Panicker, D, R, HH, Ridgway, S, Tan, HH, Thong, S, Van, M, Woon, S, Woon-Shoo-Tong, XS, Yu, S, Ali, K, Chee, J, Chiu, C, Chow, YW, Duller, A, Nagappan, P, Ng, S, Selvanathan, M, Sheridan, C, Temple, M, Do, JE, Dudi-Venkata, NN, Humphries, E, Li, L, Mansour, LT, Massy-Westropp, C, Fang, B, Farbood, K, Hong, H, Huang, Y, Joan, M, Koh, C, Liu, YHA, Mahajan, T, Muller, E, Park, R, Tanudisastro, M, Wu, JJG, Chopra, P, Giang, S, Radcliffe, S, Thach, P, Wallace, D, Wilkes, A, Chinta, SH, Li, J, Phan, J, Rahman, F, Segaran, A, Shannon, J, Zhang, M, Adams, N, Bonte, A, Choudhry, A, Colterjohn, N, Croyle, JA, Donohue, J, Feighery, A, Keane, A, McNamara, D, Munir, K, Roche, D, Sabnani, R, Seligman, D, Sharma, S, Stickney, Z, Suchy, H, Tan, R, Yordi, S, Ahmed, I, Aranha, M, El Sabawy, D, Garwood, P, Harnett, M, Holohan, R, Howard, R, Kayyal, Y, Krakoski, N, Lupo, M, McGilberry, W, Nepon, H, Scoleri, Y, Urbina, C, Ahmad Fuad, MF, Ahmed, O, Jaswantlal, D, Kelly, E, Khan, MHT, Naidu, D, Neo, WX, O'Neill, R, Sugrue, M, Abbas, JD, Abdul-Fattah, S, Azlan, A, Barry, K, Idris, NS, Kaka, N, Mc Dermott, D, Mohammad Nasir, MN, Mozo, M, Rehal, A, Shaikh Yousef, M, Wong, RH, Curran, E, Gardner, M, Hogan, A, Julka, R, Lasser, G, Ní Chorráin, N, Ting, J, Browne, R, George, S, Janjua, Z, Leung Shing, V, Megally, M, Murphy, S, Ravenscroft, L, Vedadi, A, Vyas, V, Bryan, A, Sheikh, A, Ubhi, J, Vannelli, K, Vawda, A, Adeusi, L, Doherty, C, Fitzgerald, C, Gallagher, H, Gill, P, Hamza, H, Hogan, M, Kelly, S, Larry, J, Lynch, P, Mazeni, NA, O'Connell, R, O'Loghlin, R, Singh, K, Abbas Syed, R, Ali, A, Alkandari, B, Arnold, A, Arora, E, Azam, R, Breathnach, C, Cheema, J, Compton, M, Curran, S, Elliott, JA, Jayasamraj, O, Mohammed, N, Noone, A, Pal, A, Pandey, S, Quinn, P, Sheridan, R, Siew, L, Tan, EP, Tio, SW, Toh, VTR, Walsh, M, Yap, C, Yassa, J, Young, T, Agarwal, N, Almoosawy, SA, Bowen, K, Bruce, D, Connachan, R, Cook, A, Daniell, A, Elliott, M, Fung, HKF, Irving, A, Laurie, S, Lee, YJ, Lim, ZX, Maddineni, S, McClenaghan, RE, Muthuganesan, V, Ravichandran, P, Roberts, N, Shaji, S, Solt, S, Toshney, E, Arnold, C, Baker, O, Belais, F, Bojanic, C, Byrne, M, Chau, CYC, De Soysa, S, Eldridge, M, Fairey, M, Fearnhead, N, Guéroult, A, Ho, JSY, Joshi, K, Kadiyala, N, Khalid, S, Khan, F, Kumar, K, Lewis, E, Magee, J, Manetta-Jones, D, Mann, S, McKeown, L, Mitrofan, C, Mohamed, T, Monnickendam, A, Ng, AYKC, Ortu, A, Patel, M, Pope, T, Pressling, S, Purohit, K, Saji, S, Shah Foridi, J, Shah, R, Siddiqui, SS, Surman, K, Utukuri, M, Varghese, A, Williams, CYK, Yang, JJ, Billson, E, Cheah, E, Holmes, P, Hussain, S, Murdock, D, Nicholls, A, Patel, P, Ramana, G, Saleki, M, Spence, H, Thomas, D, Yu, C, Abousamra, M, Brown, C, Conti, I, Donnelly, A, Durand, M, French, N, Goan, R, O'Kane, E, Rubinchik, P, Gardiner, H, Kempf, B, Lai, YL, Matthews, H, Minford, E, Rafferty, C, Reid, C, Sheridan, N, Al Bahri, T, Bhoombla, N, Rao, BM, Titu, L, Chatha, S, Field, C, Gandhi, T, Gulati, R, Jha, R, Jones Sam, MT, Karim, S, Patel, R, Saunders, M, Sharma, K, Abid, S, Heath, E, Kurup, D, Patel, A, Ali, M, Cresswell, B, Felstead, D, Jennings, K, Kaluarachchi, T, Lazzereschi, L, Mayson, H, Miah, JE, Reinders, B, Rosser, A, Thomas, C, Williams, H, Al-Hamid, Z, Alsadoun, L, Chlubek, M, Fernando, P, Gaunt, E, Gercek, Y, Maniar, R, Ma, R, Matson, M, Moore, S, Morris, A, Nagappan, PG, Ratnayake, M, Rockall, L, Shallcross, O, Sinha, A, Tan, KE, Virdee, S, Wenlock, R, Donnelly, HA, Ghazal, R, Hughes, I, Liu, X, McFadden, M, Misbert, E, Mogey, P, O'Hara, A, Peace, C, Rainey, C, Raja, P, Salem, M, Salmon, J, Tan, CH, Alves, D, Bahl, S, Baker, C, Coulthurst, J, Koysombat, K, Linn, T, Rai, P, Sharma, A, Shergill, A, Ahmed, M, Ahmed, S, Belk, LH, Choudhry, H, Cummings, D, Dixon, Y, Dobinson, C, Edwards, J, Flint, J, Franco Da Silva, C, Gallie, R, Gardener, M, Glover, T, Greasley, M, Hatab, A, Howells, R, Hussey, T, Khan, A, Mann, A, Morrison, H, Ng, A, Osmond, R, Padmakumar, N, Pervaiz, F, Prince, R, Qureshi, A, Sawhney, R, Sigurdson, B, Stephenson, L, Vora, K, Zacken, A, Cope, P, Di Traglia, R, Ferarrio, I, Hackett, N, Healicon, R, Horseman, L, Lam, LI, Meerdink, M, Menham, D, Murphy, R, Nimmo, I, Ramaesh, A, Rees, J, Soame, R, Dilaver, N, Adebambo, D, Brown, E, Burt, J, Foster, K, Kaliyappan, L, Knight, P, Politis, A, Richardson, E, Townsend, J, Abdi, M, Ball, M, Easby, S, Gill, N, Ho, E, Iqbal, H, Matthews, M, Nubi, S, Nwokocha, JO, Okafor, I, Perry, G, Sinartio, B, Vanukuru, N, Walkley, D, Welch, T, Yates, J, Yeshitila, N, Bryans, K, Campbell, B, Gray, C, Keys, R, Macartney, M, Chamberlain, G, Khatri, A, Kucheria, A, Lee, STP, Reese, G, Roy choudhury, J, Tan, WYR, Teh, JJ, Ting, A, Kazi, S, Kontovounisios, C, Vutipongsatorn, K, Amarnath, T, Balasubramanian, N, Bassett, E, Gurung, P, Lim, J, Panjikkaran, A, Sanalla, A, Alkoot, M, Bacigalupo, V, Eardley, N, Horton, M, Hurry, A, Isti, C, Maskell, P, Nursiah, K, Punn, G, Salih, H, Epanomeritakis, E, Foulkes, A, Henderson, R, Johnston, E, McCullough, H, McLarnon, M, Morrison, E, Cheung, A, Cho, SH, Eriksson, F, Hedges, J, Low, Z, May, C, Musto, L, Nagi, S, Nur, S, Salau, E, Shabbir, S, Thomas, MC, Uthayanan, L, Vig, S, Zaheer, M, Zeng, G, Ashcroft-Quinn, S, Brown, R, Hayes, J, McConville, R, French, R, Gilliam, A, Sheetal, S, Shehzad, MU, Bani, W, Christie, I, Franklyn, J, Khan, M, Russell, J, Smolarek, S, Varadarassou, R, Ahmed, SK, Narayanaswamy, S, Sealy, J, Shah, M, Dodhia, V, Manukyan, A, O'Hare, R, Orbell, J, Chung, I, Forenc, K, Gupta, A, Agarwal, A, Al Dabbagh, A, Bennewith, R, Bottomley, J, Chu, TSM, Chu, YYA, Doherty, W, Evans, B, Hainsworth, P, Hosfield, T, Li, CH, McCullagh, I, Mehta, A, Thaker, A, Thompson, B, Virdi, A, Walker, H, Wilkins, E, Dixon, C, Hassan, MR, Lotca, N, Tong, KS, Batchelor-Parry, H, Chaudhari, S, Harris, T, Hooper, J, Johnson, C, Mulvihill, C, Nayler, J, Olutobi, O, Piramanayagam, B, Stones, K, Sussman, M, Weaver, C, Alam, F, Al Rawi, M, Andrew, F, Arrayeh, A, Azizan, N, Hassan, A, Iqbal, Z, John, I, Jones, M, Kalake, O, Keast, M, Nicholas, J, Patil, A, Powell, K, Roberts, P, Sabri, A, Segue, AK, Shah, A, Shaik Mohamed, SA, Shehadeh, A, Shenoy, S, Tong, A, Upcott, M, Vijayasingam, D, Anarfi, S, Dauncey, J, Devindaran, A, Havalda, P, Komninos, G, Mwendwa, E, Norman, C, Richards, J, Urquhart, A, Allan, J, Cahya, E, Hunt, H, McWhirter, C, Norton, R, Roxburgh, C, Tan, JY, Ali Butt, S, Hansdot, S, Haq, I, Mootien, A, Sanchez, I, Vainas, T, Deliyannis, E, Tan, M, Vipond, M, Chittoor Satish, NN, Dattani, A, De Carvalho, L, Gaston-Grubb, M, Karunanithy, L, Lowe, B, Pace, C, Raju, K, Roope, J, Taylor, C, Youssef, H, Munro, T, Thorn, C, Wong, KHF, Yunus, A, Chawla, S, Datta, A, Dinesh, AA, Field, D, Georgi, T, Gwozdz, A, Hamstead, E, Howard, N, Isleyen, N, Jackson, N, Kingdon, J, Sagoo, KS, Schizas, A, Yin, L, Aung, E, Aung, YY, Franklin, S, Han, SM, Kim, WC, Martin Segura, A, Rossi, M, Ross, T, Tirimanna, R, Wang, B, Zakieh, O, Ben-Arzi, H, Flach, A, Jackson, E, Magers, S, Olu abara, C, Rogers, E, Sugden, K, Tan, H, Veliah, S, Walton, U, Asif, A, Bharwada, Y, Bowley, D, Broekhuizen, A, Cooper, L, Evans, N, Girdlestone, H, Ling, C, Mann, H, Mehmood, N, Mulvenna, CL, Rainer, N, Trout, I, Gujjuri, R, Jeyaraman, D, Leong, E, Singh, D, Smith, E, Anderton, J, Barabas, M, Goyal, S, Howard, D, Joshi, A, Mitchell, D, Weatherby, T, Badminton, R, Bird, R, Burtle, D, Choi, NY, Devalia, K, Farr, E, Fischer, F, Fish, J, Gunn, F, Jacobs, D, Johnston, P, Kalakoutas, A, Lau, E, Loo, YNAF, Louden, H, Makariou, N, Mohammadi, K, Nayab, Y, Ruhomaun, S, Ryliskyte, R, Saeed, M, Shinde, P, Sudul, M, Theodoropoulou, K, Valadao-Spoorenberg, J, Vlachou, F, Arshad, SR, Janmohamed, AM, Noor, M, Oyerinde, O, Saha, A, Syed, Y, Watkinson, W, Ahmadi, H, Akintunde, A, Alsaady, A, Bradley, J, Brothwood, D, Burton, M, Higgs, M, Hoyle, C, Katsura, C, Lathan, R, Louani, A, Mandalia, R, Prihartadi, AS, Qaddoura, B, Sandland-Taylor, L, Thadani, S, Thompson, A, Walshaw, J, Teo, S, Ali, S, Bawa, JH, Fox, S, Gargan, K, Haider, SA, Hanna, N, Hatoum, A, Khan, Z, Krzak, AM, Li, T, Pitt, J, Tan, GJS, Ullah, Z, Wilson, E, Cleaver, J, Colman, J, Copeland, L, Coulson, A, Davis, P, Faisal, H, Hassan, F, Hughes, JT, Jabr, Y, Mahmoud Ali, F, Nahaboo Solim, ZN, Sangheli, A, Shaya, S, Thompson, R, Cornwall, H, De Andres Crespo, M, Fay, E, Findlay, J, Groves, E, Jones, O, Killen, A, Millo, J, Thomas, S, Ward, J, Wilkins, M, Zaki, F, Zilber, E, Bhavra, K, Bilolikar, A, Charalambous, M, Elawad, A, Eleni, A, Fawdon, R, Gibbins, A, Livingstone, D, Mala, D, Oke, SE, Padmakumar, D, Patsalides, MA, Payne, D, Ralphs, C, Roney, A, Sardar, N, Stefanova, K, Surti, F, Timms, R, Tosney, G, Bannister, J, Clement, NS, Cullimore, V, Kamal, F, Lendor, J, McKay, J, Mcswiggan, J, Minhas, N, Seneviratne, K, Simeen, S, Valverde, J, Watson, N, Bloom, I, Dinh, TH, Hirniak, J, Joseph, R, Kansagra, M, Lai, CKN, Melamed, N, Patel, J, Randev, J, Sedighi, T, Shurovi, B, Sodhi, J, Vadgama, N, Abdulla, S, Adabavazeh, B, Champion, A, Chennupati, R, Chu, K, Devi, S, Haji, A, Schulz, J, Testa, F, Davies, P, Gurung, B, Howell, S, Modi, P, Pervaiz, A, Zahid, M, Abdolrazaghi, S, Abi Aoun, R, Anjum, Z, Bawa, G, Bhardwaj, R, Brown, S, Enver, M, Gill, D, Gopikrishna, D, Gurung, D, Kanwal, A, Kaushal, P, Khanna, A, Lovell, E, McEvoy, C, Mirza, M, Nabeel, S, Naseem, S, Pandya, K, Perkins, R, Pulakal, R, Ray, M, Reay, C, Reilly, S, Round, A, Seehra, J, Shakeel, NM, Singh, B, Vijay Sukhnani, M, Brown, L, Desai, B, Elzanati, H, 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Subjects
Adult, Cohort Studies, Postoperative Complications, Health Information Management, Medicine (miscellaneous), COVID-19, Humans, Decision Sciences (miscellaneous), Health Informatics, Prospective Studies, Prognosis, Pandemics
Abstract

Background Stratifying risk of postoperative pulmonary complications after major abdominal surgery allows clinicians to modify risk through targeted interventions and enhanced monitoring. In this study, we aimed to identify and validate prognostic models against a new consensus definition of postoperative pulmonary complications. Methods We did a systematic review and international external validation cohort study. The systematic review was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched MEDLINE and Embase on March 1, 2020, for articles published in English that reported on risk prediction models for postoperative pulmonary complications following abdominal surgery. External validation of existing models was done within a prospective international cohort study of adult patients (≥18 years) undergoing major abdominal surgery. Data were collected between Jan 1, 2019, and April 30, 2019, in the UK, Ireland, and Australia. Discriminative ability and prognostic accuracy summary statistics were compared between models for the 30-day postoperative pulmonary complication rate as defined by the Standardised Endpoints in Perioperative Medicine Core Outcome Measures in Perioperative and Anaesthetic Care (StEP-COMPAC). Model performance was compared using the area under the receiver operating characteristic curve (AUROCC). Findings In total, we identified 2903 records from our literature search; of which, 2514 (86·6%) unique records were screened, 121 (4·8%) of 2514 full texts were assessed for eligibility, and 29 unique prognostic models were identified. Nine (31·0%) of 29 models had score development reported only, 19 (65·5%) had undergone internal validation, and only four (13·8%) had been externally validated. Data to validate six eligible models were collected in the international external validation cohort study. Data from 11 591 patients were available, with an overall postoperative pulmonary complication rate of 7·8% (n=903). None of the six models showed good discrimination (defined as AUROCC ≥0·70) for identifying postoperative pulmonary complications, with the Assess Respiratory Risk in Surgical Patients in Catalonia score showing the best discrimination (AUROCC 0·700 [95% CI 0·683–0·717]). Interpretation In the pre-COVID-19 pandemic data, variability in the risk of pulmonary complications (StEP-COMPAC definition) following major abdominal surgery was poorly described by existing prognostication tools. To improve surgical safety during the COVID-19 pandemic recovery and beyond, novel risk stratification tools are required. Funding British Journal of Surgery Society.

Published
2022

173. Different molecular routes to mat formation in environmental Pseudomonas isolates

Author

Anuradha Mukherjee and Jenna Gallie

Subjects
General Materials Science
Abstract

Many bacterial species secrete polymers and form mat-like structures. These mats can be useful (e.g., in bioremediation), or problematic (e.g., in hospital settings). The molecular bases of mat formation have been investigated in a number of species, including various pseudomonads. One well-characterized example is the plant symbiont Pseudomonas fluorescens SBW25. Laboratory populations of SBW25 readily acquire mutations in one of three regulatory loci (wsp, aws, mws), leading to the over-production of the secondary messenger cyclic-di-GMP. In turn, this activates the production of a cellulose-like polymer, the major structural component of the SBW25 mat. Here, we dissect and compare the molecular mechanisms of mat formation in two further plant-associated pseudomonads: P. simiae PICF7 and P. fluorescens A506. We find that both PICF7 and A506 are capable of mat formation in the laboratory, by distinct molecular routes. Mat formation in PICF7 involves mutations in wsp, aws, or mws that serve to activate the production of Pel (as opposed to cellulose in SBW25). Contrastingly, A506 mat formation does not require mutation of wsp, aws, or mws (despite their retention in the genome). Instead, our results are consistent with a readily reversible, non-mutational route to polymer production and mat formation in A506. Overall, our results demonstrate the presence of multiple molecular routes to mat formation among environmental, plant-associated pseudomonads. The presented work has since been published: Mukherjee A, Dechow-Seligmann G, Gallie J. 2022. Molecular Microbiology 117(2): 394-410.

Published
2022

176. Altered anterior visual system development following early monocular enucleation

Author

Krista R. Kelly, Larissa McKetton, Keith A. Schneider, Brenda L. Gallie, and Jennifer K.E. Steeves

Subjects
Retinoblastoma, Monocular enucleation, Anterior visual system development, Optic chiasm, Lateral geniculate nucleus, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract

Purpose: Retinoblastoma is a rare eye cancer that generally occurs before 5 years of age and often results in enucleation (surgical removal) of the cancerous eye. In the present study, we sought to determine the consequences of early monocular enucleation on the morphological development of the anterior visual pathway including the optic chiasm and lateral geniculate nucleus. Methods: A group of adults who had one eye enucleated early in life due to retinoblastoma was compared to binocularly intact controls. Although structural changes have previously been reported in late enucleation, we also collected data from one late enucleated participant to compare to our early enucleated participants. Measurements of the optic nerves, optic chiasm, optic tracts and lateral geniculate nuclei were evaluated from T1 weighted and proton density weighted images collected from each participant. Results: The early monocular enucleation group exhibited overall degeneration of the anterior visual system compared to controls. Surprisingly, however, optic tract diameter and geniculate volume decreases were less severe contralateral to the remaining eye. Consistent with previous research, the late enucleated participant showed no asymmetry and significantly larger volume decreases in both geniculate nuclei compared to controls. Conclusions: The novel finding of an asymmetry in morphology of the anterior visual system following long-term survival from early monocular enucleation indicates altered postnatal visual development. Possible mechanisms behind this altered development include recruitment of deafferented cells by crossing nasal fibres and/or geniculate cell retention via feedback from primary visual cortex. These data highlight the importance of balanced binocular input during postnatal maturation for typical anterior visual system morphology.

Published
2014
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178. Primary laser therapy as monotherapy for discrete retinoblastoma

Author

Brenda L. Gallie, Zhao Xun Feng, and Sameh E. Soliman

Subjects
medicine.medical_specialty, Retinal Neoplasms, medicine.medical_treatment, Brachytherapy, Less invasive, Vitreous seeding, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Laser therapy, Humans, Medicine, Retrospective Studies, Chemotherapy, business.industry, Retinoblastoma, Lasers, Infant, medicine.disease, Sensory Systems, Ophthalmology, 030221 ophthalmology & optometry, Laser Therapy, Radiology, Neoplasm Recurrence, Local, business, 030217 neurology & neurosurgery
Abstract

Background/aimLaser photocoagulation is less invasive than chemotherapy (systemic, intra-arterial or periocular) and brachytherapy. We studied the safety and efficacy of laser as primary monotherapy for discrete retinoblastoma with well-defined borders and attached retina.MethodsA single-institution retrospective non-comparative review (2004–2018) of discrete retinoblastoma tumours managed with primary laser (532 or 810 nm wavelength, 0.5–1 s duration and power titrated until desired tumour whitening). Efficacy was evaluated by tumour long-term stability avoiding non-laser therapies. Safety was evaluated by frequency of laser-related complications and uncontrollable tumour progression.ResultsEligible were 112 tumours in 55 eyes of 44 patients. Laser monotherapy (median 2 sessions) achieved initial remission in 95/112 (85%) tumour. Initial encircling only laser photocoagulation was associated with tumour progression (9/11, one tumour had vitreous seeding) compared with direct or combined photocoagulation techniques (0/94 and 0/7 tumours, respectively, p3 DD achieved long-term stability with laser monotherapy (pConclusionsDiscrete retinoblastoma ≤3 DD can be effectively and safely managed with laser monotherapy, sparing a significant proportion of patients/eyes from more invasive therapies.

Published
2021

186. Characterisation of retinoblastomas without RB1 mutations: genomic, gene expression, and clinical studies

Author

Rushlow, Diane E, Mol, Berber M, Kennett, Jennifer Y, Yee, Stephanie, Pajovic, Sanja, Thériault, Brigitte L, Prigoda-Lee, Nadia L, Spencer, Clarellen, Dimaras, Helen, Corson, Timothy W, Pang, Renée, Massey, Christine, Godbout, Roseline, Jiang, Zhe, Zacksenhaus, Eldad, Paton, Katherine, Moll, Annette C, Houdayer, Claude, Raizis, Anthony, Halliday, William, Lam, Wan L, Boutros, Paul C, Lohmann, Dietmar, Dorsman, Josephine C, and Gallie, Brenda L

Published
2013
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187. Mobilisation in the EveNing to TreAt deLirium (MENTAL): protocol for a mixed-methods feasibility randomised controlled trial

Author

David McWilliams, Elizabeth King, Peter Nydahl, Julie Lorraine Darbyshire, L Gallie, Dalia Barghouthy, C Bassford, and Owen Gustafson

Subjects
General Medicine
Abstract

IntroductionDelirium is common in critically ill patients and is associated with longer hospital stays, increased mortality and higher healthcare costs. A number of risk factors have been identified for the development of delirium in intensive care, two of which are sleep disturbance and immobilisation. Non-pharmacological interventions for the management of intensive care unit (ICU) delirium have been advocated, including sleep protocols and early mobilisation. However, there is a little published evidence evaluating the feasibility and acceptability of evening mobilisation.Methods and analysisMobilisation in the EveNing to TreAt deLirium (MENTAL) is a two-centre, mixed-methods feasibility randomised controlled trial (RCT). Sixty patients will be recruited from ICUs at two acute NHS trusts and randomised on a 1:1 basis to receive additional evening mobilisation, delivered between 19:00 and 21:00, or standard care. The underpinning hypothesis is that the physical exertion associated with evening mobilisation will promote better sleep, subsequently having the potential to reduce delirium incidence. The primary objective is to assess the feasibility and acceptability of a future, multicentre RCT. The primary outcome measures, which will determine feasibility, are recruitment and retention rates, and intervention fidelity. Acceptability of the intervention will be evaluated through semi-structured interviews of participants and staff. Secondary outcome measures include collecting baseline, clinical and outcome data to inform the power calculations of a future definitive trial.Ethics and disseminationEthical approval has been obtained through the Wales Research and Ethics Committee 6 (22/WA/0106). Participants are required to provide written informed consent. We aim to disseminate the findings through international conferences, international peer-reviewed journals and social media.Trial registration numberNCT05401461.

Published
2023

188. Work-Family Conflict and Working Conditions in Western Europe

Author

Gallie, Duncan and Russell, Helen

Abstract

This article explores the influence of working conditions on work-family conflict (WFC) among married/cohabiting employees across seven European countries. Using data from the European Social Survey, the paper first investigates the role of working conditions relative to household level characteristics in mediating work-family conflict at the individual level. It then considers whether perceived conflict is lower in countries with coordinated production regimes and where social policy is more supportive of combining paid work and care demands. For men the lowest rates of WFC occurred in Denmark, Sweden and Norway, so for men there was a distinct "Nordic" effect consistent with the welfare and production regime expectations. For women, we find paradoxically that "raw" levels of work-family conflict are particularly high in France, Denmark and Sweden where supports for reconciling work and family life are high. Our models show that the high conflict among French women can be explained by household composition factors and so is due to higher levels of family pressures. Higher levels of conflict among Danish and Swedish women appear to be associated with their longer hours of work. Work conditions are found to play a larger role than family characteristics in accounting for work-family conflict, both in the country level models and in the pooled models. While this partly reflects our focus on the spillover of work into family life, it is notable that family characteristics have little effect in mediating work pressures. The results suggest that a policy emphasis on improving work conditions is likely to have major leverage in reducing work-family conflict.

Published
2009
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190. Retinoblastoma

Author

Gallie, Brenda L., Trogadis, Judy, Han, Liping, Masters, John R. W., editor, and Palsson, Bernhard, editor

Published
2002
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191. Working Still Harder

Author

Alan Felstead, Francis Green, Duncan Gallie, and Golo Henseke

Subjects
Organizational Behavior and Human Resource Management, business.industry, Strategy and Management, Learning environment, 05 social sciences, 050209 industrial relations, Public relations, Work (electrical), Information and Communications Technology, Management of Technology and Innovation, 0502 economics and business, Work Intensity, Sociology, business, 050203 business & management, Self-employment
Abstract

The authors use data from the British Skills and Employment Surveys to document and to try to account for sustained work intensification between 2001 and 2017. They estimate the determinants of work intensity, first using four waves of the pooled cross-section data, then using a constructed pseudo-panel of occupation–industry cells. The latter approach suggests biases in cross-section models of work intensity, associated with unobserved fixed effects in specific occupations and industries. The pseudo-panel analysis can account for slightly more than half (51%) of work intensification using variables that measure effort-biased technological change, effort-biased organizational change, the growing requirement for learning new things, and the rise of self-employment. The authors interpret the work intensification and these effects within a power-resources framework.

Published
2021

193. DNA hypermethylation/boundary control loss identified in retinoblastomas associated with genetic and epigenetic inactivation of the RB1 gene promoter

Author

Helen Dimaras, Anthony Raizis, Brenda L. Gallie, P M George, H M Racher, and A Foucal

Subjects
0301 basic medicine, Cancer Research, Retinal Neoplasms, Ubiquitin-Protein Ligases, Epigenesis, Genetic, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Epigenetics, Genes, Retinoblastoma, E2F, Molecular Biology, Transcription factor, biology, Retinoblastoma, Promoter, DNA Methylation, Cell cycle, medicine.disease, Molecular biology, eye diseases, Retinoblastoma Binding Proteins, 030104 developmental biology, Histone, Child, Preschool, 030220 oncology & carcinogenesis, DNA methylation, biology.protein, Research Paper
Abstract

DNA hypermethylation events occur frequently in human cancers, but less is known of the mechanisms leading to their initiation. Retinoblastoma, an intraocular cancer affecting young children, involves bi-allelic inactivation of the RB1 gene (RB(−/-)). RB1 encodes a tumour suppressing, cell cycle regulating transcription factor (pRB) that binds and regulates the RB1 core and other E2F responsive promoters with epigenetic functions that include recruitment of histone deacetylases (HDACs). Evidence suggests that bi-allelic epigenetic inactivation/hypermethylation of the RB1 core promoter (Pr(E-/E-)), is specific to sporadic retinoblastomas (frequency~10%), whereas heritable RB1 promoter variants (Pr(−/+), frequency~1-2%) are not associated with known epigenetic phenomena. We report heritable Pr(−/-) retinoblastomas with the expected loss of pRB expression, in which hypermethylation consistent with distal boundary displacement (BD) relative to normal peripheral blood DNAs was detected in 4/4 cases. In contrast, proximal BD was identified in 16/16 RB(−/-) retinoblastomas while multiple boundaries distal of the core promoter was further identified in Pr(E-/E-)and Pr(E-/E+) retinoblastomas. However, weak or no DNA hypermethylation/BD in peripheral blood DNA was detected in 8/9 Pr(−/+) patients, with the exception, a carrier of a microdeletion encompassing several RB1 promoter elements. These findings suggest that loss of boundary control may be a critical step leading to epigenetic inactivation of the RB1 gene and that novel DNA methylation boundaries/profiles identified in the RB1 promoter of Pr(−/-) retinoblastomas, may be the result of epigenetic phenomena associated with epimutation in conjunction with loss of pRB expression/binding and/or RB1 promoter interactions with boundary control elements.

Published
2020

194. A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma

Author

Andrey A. Yarovoy, Jason C. S. Yam, Tero Kivelä, Brenda L. Gallie, Jonathan W. Kim, Ekaterina Semenova, Guillermo Chantada, Genoveva Correa-Llano, Adriana Fandiño, Matthew W. Wilson, Suganeswari Ganesan, Ashwin Mallipatna, Jaume Català, Sonia Moorthy, Elisa Carreras, Olga V Yugay, Ankit Singh Tomar, Junyang Zhao, Marco A. Ramirez-Ortiz, Tatiana L Ushakova, Michala Burges, Vikas Khetan, Vera Adobea Essuman, Chengyue Zhang, Winnie W. Y. Lau, V.G. Polyakov, Yacoub A. Yousef, Paula Schaiquevich, Kalle Nummi, Carol P. S. Lam, Phillipa Sharwood, Rachel C. Brenna, Paul T. Finger, Elena Kotova, Quah Boon Long, Vera Yarovaya, Lorna Renner, and Elizabeth Esparza-Aguiar

Subjects
0303 health sciences, Chemotherapy, medicine.medical_specialty, genetic structures, Retinoblastoma, business.industry, medicine.medical_treatment, Enucleation, Cancer, medicine.disease, Intraocular Retinoblastoma, eye diseases, Treatment failure, 3. Good health, Surgery, 03 medical and health sciences, Ophthalmology, 0302 clinical medicine, Treatment success, 030221 ophthalmology & optometry, medicine, sense organs, business, 030304 developmental biology, Cancer staging
Abstract

Purpose To evaluate the ability of the American Joint Committee on Cancer (AJCC) 8th edition to predict local tumor control and globe salvage for children with retinoblastoma (RB). Design International, multicenter, registry-based retrospective case series. Participants A total of 2854 eyes of 2097 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. Methods International, multicenter, registry-based data were pooled from patients enrolled between January 2001 and December 2013. All RB eyes with adequate records to allow tumor staging by the AJCC 8th edition criteria and follow-up to ascertain treatment outcomes were included. Main Outcome Measures Globe-salvage rates were estimated by AJCC clinical (cTNMH) categories and tumor laterality. Local treatment failure was defined as use of enucleation or external beam radiation therapy (EBRT), with or without plaque brachytherapy or intra-arterial chemotherapy (IAC). Results Unilateral RB occurred in 1340 eyes (47%). Among the 2854 eyes, tumor categories were cT1 to cT4 in 696 eyes (24%), 1334 eyes (47%), 802 eyes (28%), and 22 eyes (1%), respectively. Of these, 1275 eyes (45%) were salvaged, and 1179 eyes (41%) and 400 eyes (14%) underwent primary and secondary enucleation, respectively. The 2- and 5-year Kaplan–Meier cumulative globe-salvage rates without the use of EBRT by cTNMH categories were 97% and 96% for category cT1a tumors, 94% and 88% for cT1b tumors, 68% and 60% for cT2a tumors, 66% and 57% for cT2b tumors, and 32% and 25% for cT3 tumors, respectively. Risk of local treatment failure increased with increasing cT category (P Conclusions Multicenter, international, internet-based data sharing validated the 8th edition AJCC RB staging to predict globe-salvage in a large, heterogeneous, real-world patient population with RB.

Published
2020

195. A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma

Author

Kalle Nummi, Carol P. S. Lam, Phillipa Sharwood, Tero Kivelä, Brenda L. Gallie, Adriana Fandiño, Quah Boon Long, Vera Yarovaya, Guillermo Chantada, Sonia Moorthy, Jason C. S. Yam, Tatiana L Ushakova, Jaume Català, Matthew W. Wilson, Marco A. Ramirez-Ortiz, Winnie W. Y. Lau, Lorna Renner, Junyang Zhao, Ashwin Mallipatna, Chengyue Zhang, Ankit Singh Tomar, Vikas Khetan, V.G. Polyakov, Vera Adobea Essuman, Elizabeth Esparza-Aguiar, Suganeswari Ganesan, Jonathan W. Kim, Olga V Yugay, Genoveva Correa-Llano, Andrey A. Yarovoy, Paula Schaiquevich, Paul T. Finger, Elena Kotova, and Yacoub A. Yousef

Subjects
0303 health sciences, medicine.medical_specialty, Trilateral retinoblastoma, business.industry, Mortality rate, Enucleation, Cancer, medicine.disease, Confidence interval, 3. Good health, Metastasis, 03 medical and health sciences, Ophthalmology, 0302 clinical medicine, Internal medicine, 030221 ophthalmology & optometry, Medicine, business, Pathological, 030304 developmental biology, Cancer staging
Abstract

Purpose To evaluate the ability of the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual to estimate metastatic and mortality rates for children with retinoblastoma (RB). Design International, multicenter, registry-based retrospective case series. Participants A total of 2190 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. Methods Patient-specific data fields for RB were designed and selected by subcommittee. All patients with RB with adequate records to allow tumor staging by the AJCC criteria and follow-up for metastatic disease were studied. Main Outcome Measures Metastasis-related 5- and 10-year survival data after initial tumor staging were estimated with the Kaplan–Meier method depending on AJCC clinical (cTNM) and pathological (pTNM) tumor, node, metastasis category and age, tumor laterality, and presence of heritable trait. Results Of 2190 patients, the records of 2085 patients (95.2%) with 2905 eyes were complete. The median age at diagnosis was 17.0 months. A total of 1260 patients (65.4%) had unilateral RB. Among the 2085 patients, tumor categories were cT1a in 55 (2.6%), cT1b in 168 (8.1%), cT2a in 197 (9.4%), cT2b in 812 (38.9%), cT3 in 835 (40.0%), and cT4 in 18 (0.9%). Of these, 1397 eyes in 1353 patients (48.1%) were treated with enucleation. A total of 109 patients (5.2%) developed metastases and died. The median time (n = 92) from diagnosis to metastasis was 9.50 months. The 5-year Kaplan–Meier cumulative survival estimates by clinical tumor categories were 100% for category cT1a, 98% (95% confidence interval [CI], 97–99) for cT1b and cT2a, 96% (95% CI, 95–97) for cT2b, 89% (95% CI, 88–90) for cT3 tumors, and 45% (95% CI, 31–59) for cT4 tumors. Risk of metastasis increased with increasing cT (and pT) category (P Conclusions Multicenter, international, internet-based data sharing facilitated analysis of the 8th edition AJCC RB Staging System for metastasis-related mortality and offered a proof of concept yielding quantitative, predictive estimates per category in a large, real-life, heterogeneous patient population with RB.

Published
2020

198. EMPOWER Retinoblastoma: Engaging Patient Partners in Solving the Top 10 Priorities for Eye Cancer Research in Canada

Author

Ivana Ristevski, Jill Robert, Richelle Baddeliyanage, Roxanne Noronha, Maxwell Gelkopf, Kaitlyn Flegg, Leslie Low, Jennifer Steeves, Bruce Crooks, Brenda Gallie, and Helen Dimaras

Subjects
Canada, Health Priorities, Research, Retinal Neoplasms, Retinoblastoma, Humans, Research Personnel
Abstract

While it is recognized that research priorities should reflect and integrate the perspectives and needs of patients along with those of health professionals and researchers, it remains challenging to actualize such priorities into tangible research projects. Targeted dissemination is required to catalyze research on these priorities. To create awareness of and inspire action toward actualizing the top 10 retinoblastoma research priorities in Canada, Canadian Retinoblastoma Research Advisory Board (CRRAB) members developed a wide range of dissemination tools and processes. These resources, co-produced with patients, were instrumental to CRRAB sharing the top 10 priorities internationally to mobilize action toward solving them.

Published
2022

199. Asynchronous pineoblastoma is more likely after early diagnosis of retinoblastoma : a meta-analysis

Author

Charlotte J. Dommering, Brenda L. Gallie, Helen Dimaras, Sameh E. Soliman, Tero Kivelä, Wijnanda A. Kors, Robin W. Jansen, Marcus C. de Jong, Manohar Shroff, Furqan Shaikh, Pim de Graaf, Annette C. Moll, HUS Head and Neck Center, Silmäklinikka, Helsinki University Hospital Area, Radiology and nuclear medicine, Pediatric surgery, CCA - Cancer Treatment and quality of life, Human genetics, Ophthalmology, ACS - Diabetes & metabolism, APH - Quality of Care, and APH - Health Behaviors & Chronic Diseases

Subjects
Pediatrics, medicine.medical_specialty, PNET, MRI-BASED ASSESSMENT, Trilateral retinoblastoma, pineal gland, Retinal Neoplasms, Asymptomatic, retinoblastoma, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, magnetic resonance imaging, QUALITY, In patient, 3125 Otorhinolaryngology, ophthalmology, Stage (cooking), 10. No inequality, pineoblastoma, Pineoblastoma, AGED 0-5 YEARS, medicine.diagnostic_test, Brain Neoplasms, Retinoblastoma, business.industry, Infant, Magnetic resonance imaging, General Medicine, medicine.disease, Ophthalmology, Early Diagnosis, TRILATERAL RETINOBLASTOMA, PINEAL-GLAND, Meta-analysis, 030221 ophthalmology & optometry, medicine.symptom, LARGE POPULATION, business, CONSENSUS, Pinealoma, 030217 neurology & neurosurgery, MRI
Abstract

PURPOSE: To determine the risk of patients with an early diagnosis of heritable retinoblastoma being diagnosed with TRb (or pineoblastoma) asynchronously in a later stage and its effect on screening.METHODS: We updated the search (PubMed and Embase) for published literature as performed by our research group in 2014 and 2019. Trilateral retinoblastoma (TRb) patients were eligible for inclusion if identifiable as unique and the age at which TRb was diagnosed was available. The search yielded 97 new studies. Three new studies and eight new patients were included. Combined with 189 patients from the previous meta-analysis, the database included 197 patients. The main outcome was the percentage of asynchronous TRb in patients diagnosed before and after preset age thresholds of 6 and 12 months of age at retinoblastoma diagnosis.RESULTS: Seventy-nine per cent of patients with pineoblastoma are diagnosed with retinoblastoma before the age of 12 months. However, baseline MRI screening at time of retinoblastoma diagnosis fails to detect the later diagnosed pineal TRb in 89% of patients. We modelled that an additional MRI performed at the age of 29 months picks up 53% of pineoblastomas in an asymptomatic phase. The detection rate increased to 72%, 87% and 92%, respectively, with 2, 3 and 4 additional MRIs.CONCLUSIONS: An MRI of the brain in heritable retinoblastoma before the age of 12 months misses most pineoblastomas, while retinoblastomas are diagnosed most often before the age of 12 months. Optimally timed additional MRI scans of the brain can increase the asymptomatic detection rate of pineoblastoma.

Published
2022

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